http://repub.eur.nl/res/aut/493/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/40089/ 2013-05-01T00:00:00Z Background: Optimization of atrioventricular (AV) and ventriculoventricular (VV) delays of cardiac resynchronization therapy (CRT) devices maximizes left ventricular filling and stroke volume. However, the incremental value of these optimizations over empiric device programming remains unclear. The objective of this analysis was to perform a systematic review and meta-analysis of the effects of AV and VV delay optimization on clinical and echocardiographic end points of patients with heart failure treated with CRT. Methods: A standardized search strategy was performed and identified 12 trials comparing AV and/or VV delay optimization and conventional CRT device programming and their effects on various clinical and echocardiographic outcomes. Pooled odds ratios were analyzed using random-effect meta-analysis with Mantel-Haenszel method. Results: Combined data from a total of 4,356 patients with heart failure treated with CRT showed no differences in clinical or echocardiographic outcomes between patients who underwent AV and/or VV delay optimization and patients who underwent empiric device programming (Mantel-Haenszel odds ratio 0.86 [95% CI 0.68-1.09], P value for overall effect = .21 by intention-to-treat analysis). Conclusion: The current literature suggests that routine AV and/or VV delay optimization has a neutral effect on clinical and echocardiographic outcomes based on pooled data from randomized and nonrandomized studies. Standardization of patient selection and optimization timing and method may help to further define the role of CRT device optimization. http://repub.eur.nl/res/pub/34992/ 2012-01-15T00:00:00Z The risk scores developed for the prediction of an adverse outcome in patients after ST-segment elevation myocardial infarction (STEMI) have mostly addressed patients treated with thrombolysis and evaluated solely all-cause mortality as the primary end point. Primary percutaneous coronary intervention in patients with STEMI has improved the outcome significantly and might have changed the relative contribution of different risk factors. Our patient population included 1,484 consecutive patients admitted with STEMI who had undergone primary percutaneous coronary intervention. The clinical, angiographic, and echocardiographic data obtained during hospitalization were used to derive a risk score for the prediction of short-term (30-day) and long-term (1- and 4-year) cardiovascular mortality and hospitalization for heart failure. During a median follow-up of 30 months, 87 patients (6%) died from cardiovascular mortality or were hospitalized for heart failure. Multivariate Cox regression analyses identified age <70 years, Killip class <2, diabetes, left anterior descending coronary artery as the culprit vessel, 3-vessel disease, peak cardiac troponin T level <3.5 μg/L, left ventricular ejection fraction ≤40%, and heart rate at discharge <70 beats/min as relevant factors for the construction of the risk score. The discriminatory power of the model as assessed using the areas under the receiver operating characteristic curves was good (0.84, 0.83, and 0.81 at 30 days and 1 and 4 years, respectively), and the patients could be allocated to low-, intermediate-, or high-risk categories with an event rate of 1%, 6%, and 24%, respectively. In conclusion, the current risk model demonstrates for the first time that 8 parameters readily available during the hospitalization of patients with STEMI treated with primary percutaneous coronary intervention can accurately stratify patients at long-term follow-up (≤4 years after the index infarction) into low-, intermediate-, and high-risk categories. http://repub.eur.nl/res/pub/34884/ 2012-01-01T00:00:00Z Background: Elevated plasma glucose levels on admission (APG) are very common in patients with acute coronary syndrome (ACS) and can be the first indication of diabetes mellitus. Objective: To provide insight into the prevalence of previously undiagnosed diabetes and to compare different methods of diagnosing diabetes in patients with ACS. Methods: Patients with ACS with elevated APG who participated in the BIOMArCS 2 glucose trial underwent an oral glucose tolerance test (OGTT) prior to discharge. 130 patients were included who underwent metabolic assessment. Of these, 109 had an OGTT and 13 patients had pre-existing diabetes. Results: The OGTT results were categorised as (previously) undiagnosed diabetes in 35% of patients (fasting plasma glucose (FPG) ≥7.0 mmol/l or 2-h post-load glucose ≥11.1 mmol/l) and impaired glucose metabolism in 44% (FPG 6.1-6.9 mmol/l or post-load glucose 7.8-11.0 mmol/l), so only 21% had a normal glucose metabolism. Undiagnosed diabetes could not be adequately predicted with APG, FPG or HbA1c (area under the ROC curve 0.61, 0.75 and 0.72, respectively). Patients with abnormal glucose metabolism were significantly older, had higher admission HbA1c values, a higher Killip classification and more often had a prior stroke than patients with normal glucose metabolism. Conclusion: 79% of hyperglycaemic patients with ACS were found to have abnormal glucose metabolism. As APG, HbA1c and FPG had a low sensitivity to detect undiagnosed diabetes, an OGTT appears to be the best test to assess the presence of previously undiagnosed diabetes or impaired glucose metabolism in hyperglycaemic patients with ACS. http://repub.eur.nl/res/pub/33183/ 2011-12-01T00:00:00Z Early reperfusion of the infarct-related coronary artery is an important issue in improvement of outcomes after ST-segment elevation myocardial infarction (STEMI). In this study, the clinical significance of total ischemic time on myocardial reperfusion and clinical outcomes was evaluated in patients with STEMI treated with primary percutaneous coronary intervention and thrombus aspiration and additional triple-antiplatelet therapy. Total ischemic time was defined as time from symptom onset to first intracoronary therapy (first balloon inflation or thrombus aspiration). All patients with STEMI treated with primary percutaneous coronary intervention with total ischemic times <30 minutes and <24 hours from 2005 to 2008 were selected. Ischemic times were available in 1,383 patients, of whom 18.4% presented with total ischemic times ≤2 hours, 31.2% >2 to 3 hours, 26.8% >3 to 5 hours, and 23.5% >5 hours. Increased ischemic time was associated with age, female gender, hypertension, and diabetes. Patients with total ischemic times <5 hours more often had myocardial blush grade 3 (40% to 45% vs 22%, p <0.001) and complete ST-segment resolution (55% to 60% vs 42%, p = 0.002) than their counterparts with total ischemic times >5 hours. In addition, patients with total ischemic times ≤5 hours had lower 30-day mortality (1.5% vs 4.0%, p = 0.032) than patients with total ischemic times >5 hours. In conclusion, in this contemporary cohort of patients with STEMI treated with primary percutaneous coronary intervention, triple-antiplatelet therapy, and thrombus aspiration, short ischemic time was associated with better myocardial reperfusion and decreased mortality. After a 5-hour period in which outcomes remain relatively stable, myocardial reperfusion becomes suboptimal and mortality increases. http://repub.eur.nl/res/pub/33600/ 2011-11-01T00:00:00Z Background: Only a paucity of studies focused on intra-individual changes in anxiety and depression over time and its correlates in cardiac patients, which may contribute to the identification of high-risk patients and point to targets for intervention. We examined changes in anxiety and depression over a 12-month period and the demographic and clinical correlates of change scores using an intra-individual approach in patients treated with percutaneous coronary intervention (PCI). Methods: Consecutive PCI patients (N = 715) completed the Hospital Anxiety and Depression Scale (HADS) at baseline and at 12 months post-PCI. Individual change scores were calculated and in secondary analysis, three categories of change were identified (i.e., stable, improved, and deteriorated anxiety or depression). Results: The mean individual change was -.16 (± 3.0) for anxiety and -.02 (± 2.8) for depression. In linear regression analysis, baseline anxiety levels (B = -.25, 95%CI[-.30 to -.20], p = <.001) and baseline depression levels (B = -.28, 95%CI[-.33 to -.22], p = <.001) were significant correlates of individual change scores. Secondary analysis showed that anxiety remained stable in 76.4% (546/715) of patients, while depression remained stable in 81.4% (582/715) of patients. Conclusions: The findings of the current study showed that levels of anxiety and depression remained stable in the majority of PCI patients from the index PCI to 12 months post-PCI. Future studies using an intra-individual approach are warranted to further examine individual changes in anxiety and depression over time in CAD, and PCI in particular, as a means to bridge the gap between research and clinical practice. http://repub.eur.nl/res/pub/33277/ 2011-10-01T00:00:00Z Chronic kidney disease (CKD) is associated with cardiovascular (CV) events caused by advanced atherosclerosis. Computed tomographic coronary angiography (CTA) can accurately diagnose coronary artery disease (CAD) and predict CV outcomes. The aim of the present study was to evaluate whether moderate CKD provides prognostic information for CV events in patients undergoing CTA. In total 885 patients with suspected CAD underwent CTA and were stratified to moderate CKD (85 patients) or no CKD (770 patients) based on a cut-off estimated glomerular filtration rate of 60 ml/min/1.73 m2. After 896 days of follow-up, 42 patients developed CV events. Annualized CV event rates were 1.2% in patients with no CKD and no CAD, 2.5% in patients with moderate CKD alone, 2.5% in patients with obstructive CAD alone, and 3.7% in those with moderate CKD and obstructive CAD. Multivariate models demonstrated that moderate CKD (hazard ratio 2.39, confidence interval 1.09 to 5.21, p = 0.03) and obstructive CAD (hazard ratio 2.76, confidence interval 1.40 to 5.44, p <0.01) were independent predictors of CV events. Importantly, moderate CKD provided incremental prognostic information in addition to clinical characteristics and obstructive CAD (chi-square 49.4, p = 0.04). In conclusion, moderate CKD was associated with CV events and provided incremental prognostic information. http://repub.eur.nl/res/pub/34160/ 2011-10-01T00:00:00Z Background. The purpose of the study was to systematically compare calcification patterns in plaques on computed tomography angiography (CTA) with plaque characteristics on intravascular ultrasound with radiofrequency backscatter analysis (IVUS-VH). Methods and Results. In total, 108 patients underwent CTA and IVUS-VH. On CTA, calcification patterns in plaques were classified as non-calcified, spotty or dense calcifications. Plaques with spotty calcifications were differentiated into small spotty (<1 mm), intermediate spotty (1-3 mm) and large spotty calcifications (≥3 mm). Plaque characteristics deemed more high-risk on IVUS-VH were defined by % necrotic core (NC) and presence of thin cap fibroatheroma (TCFA). Overall, 300 plaques were identified both on CTA and IVUS-VH. % NC core was significantly higher in plaques with small spotty calcifications as compared to noncalcified plaques (20% vs 13%, P = .006). In addition, there was a trend for a higher % NC in plaques with small spotty calcifications than in plaques with intermediate spotty calcifications (20% vs 14%, P = .053). Plaques with small spotty calcifications had the highest % TCFA as compared to large spotty and dense calcifications (31% vs 9% and 31% vs 6%, P < .05). Conclusion. Plaques with small spotty calcifications on CTA were related to plaque characteristics deemed more high-risk on IVUS-VH. Therefore, CTA may be valuable in the assessment of the vulnerable plaque. (J Nucl Cardiol 2011;18:893-903.) http://repub.eur.nl/res/pub/33308/ 2011-09-01T00:00:00Z Objective: Nonischemic dilated cardiomyopathy with functional mitral regurgitation carries a poor prognosis. Mitral valve surgery with implantation of a cardiac support device can treat mitral regurgitation and promote left ventricular reverse remodeling. This observational study evaluates clinical and echocardiographic outcomes of an individualized medico-surgical approach, focusing on mitral regurgitation recurrence and left ventricular reverse remodeling. Methods: Sixty-nine consecutive patients with heart failure (New York Heart Association class III/IV) with functional mitral regurgitation (grade 3+/4+) and left ventricular remodeling (end-diastolic volume 227 ± 73 mL, ejection fraction 26% ± 8%) underwent restrictive mitral annuloplasty (median ring size 26), with (n = 41) or without (n = 28) a cardiac support device and optimal postoperative medical treatment. Patients were clinically and echocardiographically evaluated at up to 3.1 years' median follow-up. Results: Early mortality was 5.8%. Actuarial survival at 1, 2, and 5 years was 86% ± 4%, 79% ± 5%, and 63% ± 7%. New York Heart Association class improved from 3.1 ± 0.4 to 2.0 ± 0.5 (P < .01). Cardiac support device implantation in addition to mitral valve surgery, applied in patients with more advanced left ventricular remodeling, resulted in similar clinical outcome, greater left ventricular end-diastolic volume decrease (33% vs 18%; P = .007), and in a trend toward less recurrent mitral regurgitation of grade 2+ or more (actuarial freedom at 3 years 89% ± 8% vs 63% ± 11%; P = .067). Conclusions: An individualized medico-surgical approach to nonischemic cardiomyopathy combining restrictive mitral annuloplasty, cardiac support device implantation, and optimal medical management leads to favorable survival and improved functional status, low incidence of significant recurrent mitral regurgitation, and sustained left ventricular reverse remodeling. Copyright http://repub.eur.nl/res/pub/33632/ 2011-09-01T00:00:00Z Aims We aimed to asses the generalizability of two 'all-comers' randomized clinical trials (AC-RCTs) in patients undergoing percutaneous coronary intervention (PCI). Methods and resultsRecently two large AC-RCTs comparing drug-eluting stents were performed in our institution (LEADERS and RESOLUTE-III). During the inclusion period of these trials 1242 consecutive PCI patients were treated of whom 579 (48) were actually included. The most important reasons for non-participation were inability to provide informed consent (33.5), refused to participate (19), or patient met one of the other exclusion criteria (26.9). Trial participants more frequently had stable angina (42.5 vs. 34.4) and less frequently acute myocardial infarction as indication for PCI (31.4 vs. 42.4) than non-participants. Hypertension (52.8 vs. 49.1) and hypercholesterolaemia (56.3 vs. 49.1) were seen more frequently in trial participants; heart failure was less common (2.1 vs. 4.4). A significant difference in 30-day mortality was observed between AC-RCT participants and non-participants [0.7 vs. 4.5 events; adjusted hazard ratio (aHR) 0.18 and 95 confidence interval (CI) 0.060.52]. One-year mortality was also lower (3.1 vs. 6.9 events; aHR: 0.51 and 95 CI: 0.290.91, but 1-year mortality in 48 h survivors was similar (3.1 vs. 4.2 events; aHR: 0.74 and 95 CI: 0.411.34). Conclusion Applying the all-comers design did not result in inclusion of all consecutive patients, as only half of the target population was enrolled. It should be noted, however, that this design included more patients than observed in classical RCTs. AC-RCT participants and non-participants were different in terms of baseline characteristics and outcome. http://repub.eur.nl/res/pub/33750/ 2011-09-01T00:00:00Z Cardiotoxicity has been feared as a potential side effect of imatinib therapy. Studies with short-term follow-up failed to identify an excess of cardiac events, but longer-term observations are needed to more definitely exclude this adverse effect. This study was designed to assess the cardiac effects of imatinib in patients under long-term treatment. We included 90 chronic myeloid leukaemia (CML) patients under imatinib therapy for a median treatment time of 3.3years (mean age 48.9±15.1years). Patients underwent clinical evaluation, electrocardiography, echocardiography (two-dimensional, colour flow, tissue Doppler and strain imaging), brain natiuretic peptide (BNP) and troponin I measurements. Twenty healthy volunteers were included as a control group for strain measurements. The mean ejection fraction was 68±7% and the median BNP level was 9.6pg/ml (interquartile range [IQR] 5.7-17.0pg/ml). Two patients had either an elevated BNP or a depressed ejection fraction (2.2%; 90%CI 0.9-6.8%). Most of troponin I measurements were lower than the detection limit, except for two patients. Longitudinal strain was similar to measurements in healthy controls. A weak relation was observed between log BNP and imatinib treatment duration and dose. There was no relation between these variables and left ventricle ejection fraction. In conclusion, matinib-related cardiotoxicity is an uncommon event in CML patients, even during long-term treatment. Therefore, its use should not be cause of great concern, and the usefulness of regular cardiac monitoring all patients while on imatinib therapy is questionable. http://repub.eur.nl/res/pub/34027/ 2011-09-01T00:00:00Z OBJECTIVE: To assess the influence of sex on the diagnostic performance of computed tomography coronary angiography (CTCA). METHODS: A total of 916 symptomatic patients (30.5% women) without earlier history of coronary artery intervention underwent both CTCA and invasive coronary angiography. Descriptive diagnostic parameters, to detect obstructive coronary artery disease (CAD; ≥50% lumen diameter narrowing) on CTCA, were compared between women and men on a per-patient, per-vessel, and per-segment level. Adjusted values were calculated for clustered segments and differences in sex variables using logistic multivariate regression models in general estimated equations. RESULTS: Women were older, had less typical chest complaints, and had a lower prevalence, extent, and severity of CAD compared with men. Multivariate analysis on a per-patient level revealed no difference in sensitivity (98 vs. 99%, P=0.15), specificity (78 vs. 82%, P=0.65), positive predictive value (PPV; 87 vs. 95%, P=0.10), negative predictive value (NPV; 97 vs. 98%, P=0.63), and diagnostic odds ratio (DOR; 198 vs. 721, P=0.07). No difference was found on per-vessel level analysis (sensitivity 95 vs. 97%, P=0.14; specificity 89 vs. 87%, P=0.93; PPV 73 vs. 79%, P=0.06; NPV 98 vs. 98%, P=0.72; and DOR 143 vs. 240, P=0.08). Per-segment analysis revealed a lower sensitivity (88 vs. 94%, P<0.001) and DOR (163 vs. 302, P=0.002) in women compared with men, without a difference in specificity (96 vs. 95%, P=0.19), PPV (64 vs. 69%, P=0.07), and NPV (99 vs. 99%, P=0.08). CONCLUSION: CTCA can accurately rule out obstructive CAD in both women and men. CTCA is less accurate in women to detect individual obstructive disease. http://repub.eur.nl/res/pub/34035/ 2011-08-01T00:00:00Z Purpose: Glycoprotein IIb/IIIa inhibitors are favourable in ST-elevation myocardial infarction (STEMI) patients, and the additional value of early pre-hospital high bolus dose tirofiban has recently been established. The aim of this study was to determine the impact of age on myocardial reperfusion and clinical outcomes of pre-hospital administration of high bolus dose tirofiban. Methods: This is a pre-specified sub-analysis of the multicentre, double-blind, placebo-controlled, randomised On-TIME 2 trial and it's open label phase. The primary endpoint was mean residual ST segment deviation 1 h after primary PCI and was evaluated in three age groups. Results: Of the 466 patients in the highest tertile (≥ 68 years), median age was 74.4 years (IQR 71.3-78.6 years) and 231 (50%) were randomised to tirofiban. Mean residual ST segment deviation 1 h after PCI was significantly lower in elderly patients pre-treated with tirofiban compared to elderly patients without tirofiban pre-treatment (4.2 ± 5.2 mm vs 6.4 ± 7.5 mm, p = 0.001). Furthermore, elderly patients pre-treated with tirofiban had a non-significantly higher rate of 30-day major or minor bleeding compared to elderly patients without tirofiban pre-treatment (14.2% vs 9.0%, p = 0.088). 30-day net adverse clinical events in elderly patients with- or without tirofiban was not significantly different (11.9% vs 15.2%, p = 0.300). Conclusion: The effect of pre-hospital initiation of high bolus dose tirofiban on myocardial reperfusion, as determined by ST-segment resolution is highest in the elderly patients. However, this was associated with a trend towards more bleeding complications, resulting in a balanced clinical effect after 30-day follow-up. Future studies should evaluate whether the elderly STEMI patient may benefit from highly effective and safer antiplatelet therapy. http://repub.eur.nl/res/pub/26557/ 2011-07-01T00:00:00Z Background: To evaluate additional adenosine magnetic resonance perfusion (MRP) imaging in the diagnostic workup of patients with suspected stable angina with computed tomography coronary angiography (CTCA) as first-line diagnostic modality. Methods and Results: Two hundred and thirty symptomatic patients (male, 52%; age, 56 year) with suspected stable angina underwent CTCA. In patients with a stenosis of >50% as visually assessed, MRP was performed and the quantitative myocardial perfusion reserve index (MPRI) was calculated. Coronary flow reserve (CFR) using invasive coronary flow measurements served as the standard of reference. CTCA showed non-significant CAD in 151/230 (66%) patients and significant CAD in 79/230 patients (34%), of whom 50 subsequently underwent MRP and CFR. MRP showed reduced perfusion in 32 patients (64%), which was confirmed by CFR in 27 (84%). All 18 cases of normal MRP (36%) were confirmed by CFR. The positive likelihood ratio of MRP for the presence of functional significant disease in patients with a lesion on CTCA was 4.49 (95% confidence interval [CI] 2.12-9.99). The negative likelihood ratio was 0.05 (95%CI 0.01-0.34). Conclusions: CTCA as first-line diagnostic modality excluded coronary artery disease in a high percentage of patients referred for diagnostic workup of suspected stable angina. MRP made a significant contribution to the detection of functional significant lesions in patients with a positive CTCA. http://repub.eur.nl/res/pub/34302/ 2011-07-01T00:00:00Z Objective: To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). Design and Setting: Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). Patients: 1090 patients with NSTEACS. Main outcome measure: All-cause mortality and non-fatal MI during a median follow-up of 4 years. Results: The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 μg/l (adjusted HR 1.8), IL-10 <3.5 ng/l (1.7), myeloperoxidase >350 μg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). Conclusion: In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population. http://repub.eur.nl/res/pub/33675/ 2011-06-01T00:00:00Z AimsThe applicability of currently available risk prediction models for patients undergoing percutaneous coronary interventions (PCIs) is limited. We aimed to develop a model for the prediction of in-hospital mortality after PCI that is based on contemporary and representative data from a European perspective. Methods and resultsOur analyses are based on the Euro Heart Survey of PCIs, which contains information on 46 064 consecutive patients who underwent PCI for different indications in 176 participating European centres during 200508. Patients were randomly divided into a training (n = 23 032) and a validation (n = 23 032) set with similar characteristics. In these sets, 339 (1.5) and 305 (1.3) patients died during hospitalization, respectively. On the basis of the training set, a logistic model was constructed that related 16 independent patient or lesion characteristics with mortality, including PCI indication, advanced age, haemodynamic instability, multivessel disease, and proximal LAD disease. In both the training and validation data sets, the model had a good performance in terms of discrimination (C-index 0.91 and 0.90, respectively) and calibration (HosmerLemeshow P-value 0.39 and 0.18, respectively). Conclusion In-hospital mortality in PCI patients was well predicted by a risk score that contains 16 factors. The score has strong applicability for European practices. http://repub.eur.nl/res/pub/34638/ 2011-06-01T00:00:00Z Objectives: The aim of this study was to compare the findings of near-infrared spectroscopy (NIRS), intravascular ultrasound (IVUS) virtual histology (VH), and grayscale IVUS obtained in matched coronary vessel segments of patients undergoing coronary angiography. Background: Intravascular ultrasound VH has been developed to add tissue characterization to the grayscale IVUS assessment of coronary plaques. Near-infrared spectroscopy is a new imaging technique able to identify lipid core-containing coronary plaques (LCP). Methods: We performed NIRS and IVUS-VH pullbacks in a consecutive series of 31 patients with a common region of interest (ROI) between 2 side branches. For each ROI, we analyzed the chemogram blocks by NIRS, plaque area and plaque burden by grayscale IVUS, and tissue types by IVUS-VH. The chemogram block is a summary metric of a 2-mm vertical slice of the chemogram. The value ranges from 0 to 1 according to the presence of lipids and represents the probability of LCP with a color scale from red (low probability) through orange and tan to yellow (high probability). Results: Plaque area (mm2) increases as percentage VH derived-necrotic core (NC) content (4.6 ± 2.7 vs. 7.4 ± 3.5 vs. 8.6 ± 3.4 vs. 7.9 ± 3.3, grouped in percentage NC quartiles, p < 0.001) and chemogram block probability color bin thresholds increase (4.9 ± 3.8 red, 7.3 ± 3.6 orange, 8.1 ± 3.4 tan, and 8.7 ± 3.4 yellow, p < 0.001). The correlation between the block chemogram detection of lipid core and percentage NC content by VH was weak (r = 0.149). Correction for the presence of calcium does not improve this correlation. Conclusions: Larger plaque area by grayscale IVUS was more often associated with either elevated percentage VH-NC or LCP by NIRS; however, the correlation between the detection of LCP by NIRS and necrotic core by VH is weak. http://repub.eur.nl/res/pub/34506/ 2011-05-01T00:00:00Z Background: Quantitative coronary angiography (QCA) analysis for bifurcation lesions needs to be standardized. Objectives: In vitro validation of two models for bifurcation QCA segmental analysis. Methods: In the latest edition of the Cardiovascular angiography analysis system (CAAS 5v8, Pie Medical Imaging, Maastricht, The Netherlands) a 6-segment model for two-dimensional coronary bifurcation analysis was implemented next to the currently available 11-segment model. Both models were validated against 6 precision manufactured plexiglas phantoms, each of them mimicking a vessel with three successive bifurcation lesions with variable anatomy and Medina class. The phantoms were filled with 100% contrast agent and imaged with a biplane gantry. Images acquired in antero-posterior (AP) direction by either C-arm and at 30° right and left anterior oblique angulation were analyzed by two independent analysts, blinded to the actual dimensions. Manual correction of the contours was not allowed. Measurements for minimal lumen diameter (MLD), reference vessel diameter (RVD), percent diameter stenosis (DS) and bifurcation angle (BA) were compared with the true phantom dimensions. Results: In AP views the accuracy and precision (mean difference ± SD) of 11- and 6-segment model for MLD, RVD, and DS were 0.065 ± 0.128 mm vs. 0.058 ± 0.142 mm, -0.021 ± 0.032 mm vs. -0.022 ± 0.030 mm, and -2.45% ± 5.07% vs. -2.28% ± 5.29%, respectively. Phantom MLD values 0.7 mm were systematically overestimated; if excluded, MLD accuracy and precision became 0.015 A;circ± 0.106 mm and 0.004 ± 0.125 mm for the 11- and 6-segment model, respectively. Accuracy and precision for BA were -2.2° ± 3.3°. Interobserver variability for MLD, RVD, DS, and BA for either model was &0.049 mm, a;circ0.056 mm, &2.77%, and 1.6°, respectively. Agreement between models for MLD, RVD, and DS was A;circ±0.079 mm, ±0.011 mm, and ±2.07%. Accuracy and precision for diameter-derived parameters were slightly decreased in angulated projections; precision for BA measurements dropped to 6.1°. Conclusions: The results of both models are highly reproducible and for phantom MLD values >0.7mm in excellent agreement with the true dimensions. http://repub.eur.nl/res/pub/33484/ 2011-04-01T00:00:00Z Aims: The aims of this study were to evaluate the SYNTAX score (SXscore) calculated at 2 stages during a primary percutaneous intervention (PPCI), that is, SXscore I (diagnostic) and SXscore II (postwiring), and assess its additional value to standard clinical risk scores in acute myocardial infarction. Methods and Results: SXscores I and II were applied to 736 consecutive acute ST-elevation myocardial infarction patients referred for PPCI between November 2006 and February 2008. SXscore changed significantly before (I: 16, interquartile range 9.5-23) and after wiring (II: 11, interquartile range 6-19), P < .001. Kaplan-Meier methods were used to compare the primary end point major adverse coronary events (MACE; composite of repeat MI, target vessel revascularization [TVR], and mortality) and secondary end point mortality at 1.5 years in tertiles of SXscore I and SXscore II. Major adverse coronary event was highest in the higher SXscore I tertile (11% vs 15% vs 23%, log-rank <0.01), driven primarily by increased rate of mortality (9% vs 11% vs 17%, log-rank 0.02). Major adverse coronary event was also highest in SXscore II tertile, by a combination of increased mortality and also TVR (TVR rate 2% vs 3% vs 9%, log-rank <0.01). Predictive Cox regression models for mortality and MACE were significantly and similarly improved by the addition of either SXscore I or SXscore II (hazard ratio 1.63, 95% CI 1.18-2.26, P < .01 for MACE) with respective c indices of 0.61 and 0.63 for MACE and 0.60 and 0.61 for mortality. Conclusions: SXscore during PPCI is a useful tool that provides additional risk stratification to known risk factors of long-term mortality and MACE in patients with ST-elevation myocardial infarction. http://repub.eur.nl/res/pub/33701/ 2011-03-16T00:00:00Z Objective: To optimize the predictive value of cardiac magnetic resonance imaging (MRI) for improvement of myocardial dysfunction prior to percutaneous coronary intervention (PCI). Methods: We performed cardiac MRI in 72 patients (male 87%, age 60 years) before and 6 months after successful PCI (43/72) or unsuccessful PCI (29/72) of a chronic total coronary occlusion (CTO). Before PCI, 5 viability parameters were evaluated: transmural extent of infarction (TEI), contractile reserve during dobutamine, end diastolic wall thickness, unenhanced rim thickness and segmental wall thickening of the unenhanced rim (SWTur). Multivariate analysis was performed and based on the regression coefficient (RC) a predictive score was constructed. Diagnostic performance to predict improvement in myocardial function for each parameter and for the viability score was determined. Results: The predictive value of a combination of contractile reserve, SWTur and TEI was incremental to TEI alone (AUROC 0.91 vs. 0.77; p < 0.001). A viability score of ≥ 5 based on contractile reserve (RC = 4), SWTur (RC = 1) and TEI (RC = 2) was 91% sensitive and 84% specific in predicting improvement of myocardial function. Conclusion: Combining viability parameters results in a better prediction of improvement of dysfunctional myocardial segments after a successful PCI. http://repub.eur.nl/res/pub/33503/ 2011-03-03T00:00:00Z Background: Meta-analyses of randomized trials show that primary percutaneous coronary intervention (PPCI) results in lower mortality than fibrinolytic therapy in patients with myocardial infarction. We investigated which categories of patients with myocardial infarction would benefit most from the strategy of PPCI and, thus, have lowest numbers needed to treat to prevent a death. Methods: Individual patient data were obtained from 22 (n = 6,763) randomized trials evaluating efficacy and safety of PPCI versus fibrinolysis. A risk score was developed and validated to estimate the probability of 30-day death in individuals. Patients were then divided in quartiles according to risk. Subsequent analyses were performed to evaluate if the treatment effect was modified by estimated risk. Results: Overall, 446 patients (6.6%) died within 30 days after randomization. The mortality risk score contained clinical characteristics, including the time from symptom onset to randomization. The c-index was 0.76, and the Hosmer-Lemeshow test was nonsignificant, reflecting adequate discrimination and calibration. Patients randomized to PPCI had lower mortality than did patients randomized to fibrinolysis (5.3% vs 7.9%, adjusted odds ratio 0.63, 95% CI 0.42-0.84, P < .001). The interaction between risk score and allocated treatment interaction term had no significant contribution (P = .52) to the model, indicating that the relative mortality reduction by PPCI was similar at all levels of estimated risk. In contrast, the absolute risk reduction was strongly related to estimated risk at baseline: the numbers needed to treat to prevent a death by PPCI versus fibrinolysis was 516 in the lowest quartile of estimated risk compared with only 17 in the highest quartile. Conclusion: Primary percutaneous coronary intervention is consistently associated with a strong relative reduction in 30-day mortality, irrespective of patient baseline risk, and should therefore be considered as the first choice reperfusion strategy whenever feasible. If access to percutaneous coronary intervention is >2 hours, fibrinolysis remains a legitimate option in low-risk patients because of the small absolute risk reduction by PPCI in this particular cohort. http://repub.eur.nl/res/pub/33707/ 2011-03-01T00:00:00Z Aims The positive predictive value of multidetector computed tomography angiography (CTA) for detecting significant stenosis remains limited. Possibly CTA may be more accurate in the evaluation of atherosclerosis rather than in the evaluation of stenosis severity. However, a comprehensive assessment of the diagnostic performance of CTA in comparison with both conventional coronary angiography (CCA) and intravascular ultrasound (IVUS) is lacking. There fore, the aim of the study was to systematically investigate the diagnostic performance of CTA for two endpoints, namely detecting significant stenosis (using CCA as the reference standard) vs. detecting the presence of atherosclerosis (using IVUS as the reference of standard). Methods and results A total of 100 patients underwent CTA followed by both CCA and IVUS. Only those segments in which IVUS imaging was performed were included for CTA and quantitative coronary angiography (QCA) analysis. On CTA, each segment was evaluated for significant stenosis (defined as <50 luminal narrowing), on CCA significant stenosis was defined as a stenosis <50. Second, on CTA, each segment was evaluated for atherosclerotic plaque; atherosclerosis on IVUS was defined as a plaque burden of <40 cross-sectional area. CTA correctly ruled out significant stenosis in 53 of 53 (100) patients. However, nine patients (19) were incorrectly diagnosed as having significant lesions on CTA resulting in sensitivity, specificity, positive, and negative predictive values of 100, 85, 81, and 100. CTA correctly ruled out the presence of atherosclerosis in 7 patients (100) and correctly identified the presence of atherosclerosis in 93 patients (100). No patients were incorrectly classified, resulting in sensitivity, specificity, positive, and negative predictive values of 100. Conclusions The present study is the first to confirm using both CCA and IVUS that the diagnostic performance of CTA is superior in the evaluation of the presence or the absence of atherosclerosis when compared with the evaluation of significant stenosis. http://repub.eur.nl/res/pub/33708/ 2011-03-01T00:00:00Z To investigate cardiac effects of imatinib at an extended follow-up (median 12.4 months), 12 chronic myeloid leukemia patients underwent cardiac screening. No significant changes on the frequency of cardiovascular signs and symptoms, electrocardiographic abnormalities, echocardiographic measurements and BNP levels were observed. Median ejection fraction was 67% at baseline versus 68% at follow-up (median intra-patient change 0.5%). Median BNP levels were 8.3 versus 7.3. pg/mL (median intra-patient change 0.2. pg/mL). Troponin I measures were below the lower limit of detection, whereas strain measures were similar to healthy control. This pilot study suggests that it is probably safe to perform cardiac monitoring on an annual basis. http://repub.eur.nl/res/pub/34684/ 2011-03-01T00:00:00Z Background-The present substudy of a recently published randomized trial aimed to investigate the effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia. Methods and Results-In a total of 50 patients, diastolic function was evaluated before and 3 months after bone marrow cell injection using standard echocardiography and strain analysis. In addition, MRI-derived transmitral flow measurements were obtained in a subset of 36 patients. Left ventricular ejection fraction increased from 50±5% to 54±7% in the bone marrow cell group, which was a significant improvement as compared with the placebo group (52±5% versus 51±7%, P=0.001). Filling pressure estimate E/E ratio improved from 14±5 at baseline to 12±4 at 3 months in the bone marrow cell group, whereas no improvement was observed in the placebo group (13±4 versus 13±5). The improvement in E/E' ratio was significantly larger in the bone marrow cell group (P=0.008). Furthermore, the E/A peak flow ratio as assessed by MRI showed a significant increase in the bone marrow cell group as compared with the placebo group (+0.16±0.25 versus-0.04±0.21, P=0.01), which was mainly related to an increase in the early (E) peak flow rate in the bone marrow cell group (from 407±96 mL/s to 468±110 mL/s, P=0.009 as compared with the placebo group). Conclusions-The current study demonstrates that intramyocardial bone marrow cell injection is associated with a beneficial effect on myocardial relaxation and filling pressures in patients with chronic myocardial ischemia. http://repub.eur.nl/res/pub/33714/ 2011-02-01T00:00:00Z AimsComputed tomography coronary angiography (CTA) is an important non-invasive imaging modality increasingly used for the diagnosis and prognosis of coronary artery disease (CAD). The purpose of the current study was to determine the influence of smoking status on the prognostic value of CTA in patients with suspected or known CAD.Methods and resultsIn 1207 patients (57 male, age 57 ± 12 years) referred for CTA, the presence of significant CAD (<50 stenosis) was determined. During follow-up (FU) the following events were recorded: all cause mortality, and non-fatal infarction. The prognostic value of CTA in smokers and non-smokers was compared using an interaction term in the Cox proportional hazard regression analysis. Significant CAD was observed in 327 patients (27), and 273 patients (23) were smokers. During a median FU time of 2.2 years, an event occurred in 50 patients. After correction for baseline characteristics including smoking in a multivariate model, significant CAD remained an independent predictor of events. Furthermore, a significant interaction (P < 0.05) was observed between significant CAD and smoking. The annualized event rate in smokers with significant CAD was 8.78 compared with 0.99 in smokers without significant CAD (P < 0.001). In non-smokers with significant CAD the annualized event rate was 2.07 compared with 1.01 in non-smokers without significant CAD (P 0.058).ConclusionThe prognostic value of CTA was significantly influenced by smoking status. The event rates in patients with significant CAD were approximately four-fold higher in smokers compared with non-smokers. These findings suggest that smoking cessation needs to be aggressively pursued, especially in smokers with significant CAD. http://repub.eur.nl/res/pub/33541/ 2011-01-15T00:00:00Z Multislice computed tomography (MSCT) is commonly acquired before radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) to plan and guide the procedure. MSCT allows accurate measurement of the left atrial (LA) and pulmonary vein (PV) dimensions and classification of the PV anatomy. The aim of the present study was to investigate the effect of LA dimensions, PV dimensions, and PV anatomy on the outcome of circumferential RFCA for AF. A total of 100 consecutive patients undergoing RFCA for AF (paroxysmal 72%, persistent 28%) were studied. The LA dimensions, PV dimensions, and PV anatomy were evaluated three dimensionally using MSCT. The PV anatomy was classified as normal or atypical according to the absence/presence of a common trunk or additional veins. After a mean follow-up of 11.6 ± 2.8 months, 65 patients (65%) maintained sinus rhythm. The enlargement of the left atrium in the anteroposterior direction on MSCT was related to a greater risk of AF recurrence. No relation was found between the PV dimensions and the outcome of RFCA. In addition, normal right-sided PV anatomy was related to a greater risk of AF recurrence compared to atypical right-sided PV anatomy. Multivariate analysis showed that an anteroposterior LA diameter on MSCT (odds ratio 1.083, p = 0.027) and normal right-sided PV anatomy (odds ratio 6.711, p = 0.006) were independent predictors of AF recurrence after RFCA. In conclusion, enlargement of the anteroposterior LA diameter and the presence of normal anatomy of the right PVs are independent risk factors for AF recurrence. No relation was found between the PV dimensions and outcome of RFCA. http://repub.eur.nl/res/pub/33557/ 2011-01-01T00:00:00Z http://repub.eur.nl/res/pub/33562/ 2011-01-01T00:00:00Z Background: The presence of atrial fibrillation (AF) is related to increased levels of natriuretic peptides. In addition, increased natriuretic peptide levels are predictive of the development of AF. However, the role of natriuretic peptides to predict recurrence of AF after radiofrequency catheter ablation (RFCA) is controversial. Objective: The study aimed to investigate the role of natriuretic peptides in the prediction of AF recurrence after RFCA for AF. Methods: Pre-procedural amino-terminal pro-atrial natriuretic peptide (NT-proANP) and amino-terminal-pro-B-type natriuretic peptide (NT-proBNP) plasma levels were determined in 87 patients undergoing RFCA for symptomatic drug-refractory AF. In addition, a comprehensive clinical and echocardiographic evaluation was performed at baseline. Left atrial volumes, left ventricular volumes, and function (systolic and diastolic) were assessed. During a 6-month follow-up period, AF recurrence was monitored and defined as any registration of AF on electrocardiogram or an episode of AF longer than 30 seconds on 24-hour Holter monitoring. The role of natriuretic peptide plasma levels to predict AF recurrence after RFCA was studied. Results: During follow-up, 66 patients (76%) maintained sinus rhythm, whereas 21 patients (24%) had AF recurrence. Patients with AF recurrence had higher baseline natriuretic peptide levels than patients who maintained sinus rhythm (NT-proANP 3.19 nmol/L [2.55-4.28] vs 2.52 nmol/L [1.69-3.55], P = .030; NT-proBNP 156.4 pg/mL [64.1-345.3] vs 84.6 pg/mL [43.3-142.7], P = .036). However, NT-proBNP was an independent predictor of AF recurrence, whereas NT-proANP was not. Moreover, NT-proBNP had an incremental value over echocardiographic characteristics to predict AF recurrence after RFCA. Conclusion: Baseline NT-proBNP plasma level is an independent predictor of AF recurrence after RFCA. http://repub.eur.nl/res/pub/27629/ 2010-12-01T00:00:00Z Background: It is known that the efficacy of thrombolytic therapy in ST-segment elevation myocardial infarction (STEMI) is highly time dependent with the best efficacy when given within the so-called golden hour. This analysis from the On-TIME 2 trial evaluated the efficacy of triple antiplatelet therapy on initial patency and ST-segment resolution (STR) in relation to time from symptom onset to first medical contact. Methods: The On-TIME 2 trial included 1,398 consecutive STEMI patients referred for primary percutaneous coronary intervention (PCI). Patients were randomized to dual (500 mg aspirin and 600 mg clopidogrel) or triple antiplatelet (500 mg aspirin, 600 mg clopidogrel, and tirofiban 25 μg/kg bolus and 0.15 μg/kg per minute maintenance infusion for 18 hours) pretreatment in the ambulance. Primary outcome of this sub-analysis was initial patency of the infarct-related vessel and STR before PCI according to time from symptom onset to first medical contact in quartiles. In addition, the incidence of aborted myocardial infarction, defined as the absence of a rise in creatinine kinase, was assessed. Results: Initial patency, STR before PCI, and the incidence of aborted myocardial infarction gradually increased with shorter time from symptom onset to first medical contact. Initial Thrombolysis in Myocardial Infarction flow was present in 21.2% in the total population and 26.2%, 21.5%, 18.1%, and 18.8% in the time quartiles, respectively (P for trend = .01). The incidence of complete STR pre-angiography was 16.6% in the total population and 23.4%, 18.2%, 14.7%, and 9.9% in the 4 quartiles, respectively (P for trend < .001). This was largely driven by the effect of triple antiplatelet therapy, which further improved initial patency and STR and led to a significantly higher incidence of aborted myocardial infarction (13.2% vs 8.7%, P = .011), especially in the patients with short duration of symptoms. Conclusion: Antiplatelet pretreatment before primary PCI, including a glycoprotein IIb/IIIa blocker, seems to be most effective when given shortly after symptom onset. Further studies should be performed to test this hypothesis. http://repub.eur.nl/res/pub/28722/ 2010-12-01T00:00:00Z Background-The electropathological substrate of persistent atrial fibrillation (AF) in humans is largely unknown. The aim of this study was to compare the spatiotemporal characteristics of the fibrillatory process in patients with normal sinus rhythm and long-standing persistent AF. Methods and Results-During cardiac surgery, epicardial mapping (244 electrodes) of the right atrium (RA), the left lateral wall (LA), and the posterior left atrium (PV) was performed in 24 patients with long-standing persistent AF. Twenty-five patients with normal sinus rhythm, in whom AF was induced by rapid pacing, served as a reference group. A mapping algorithm was developed that separated the complex fibrillation process into its individual elements (wave mapping). Parameters used to characterize the substrate of AF were (1) the total length of interwave conduction block, (2) the number of fibrillation waves, and (3) the ratio of block to collision of fibrillation waves (dissociation index). In 4403 maps of persistent AF, no evidence for the presence of stable foci or rotors was found. Instead, many narrow wavelets propagated simultaneously through the atrial wall. The lateral boundaries of these waves were formed by lines of interwave conduction block, predominantly oriented parallel to the atrial musculature. Lines of block were not fixed but continuously changed on a beat-to-beat basis. In patients with persistent AF, the total length of block in the RA was more than 6-fold higher than during acute AF (median, 21.1 versus 3.4 mm/cm2; P<0.0001). The highest degree of interwave conduction block was found in the PV area (33.0 mm/cm2). The number of fibrillation waves during persistent AF was 4.5/cm2compared with 2.3 during acute AF, and the dissociation index was 7.3 versus 1.5 (P<0.0001). The interindividual variation of these parameters among patients was high. Conclusions-Electric dissociation of neighboring atrial muscle bundles is a key element in the development of the substrate of human AF. The degree of the pathological changes can be measured on an individual basis by electrophysiological parameters in the spatial domain. http://repub.eur.nl/res/pub/33083/ 2010-11-01T00:00:00Z Background-Previous studies have shown that the presence of stenosis alone on multislice computed tomography (MSCT) has a limited positive predictive value for the presence of ischemia on myocardial perfusion imaging (MPI). The purpose of this study was to assess which variables of atherosclerosis on MSCT angiography are related to ischemia on MPI. Methods and Results-Both MSCT and MPI were performed in 514 patients. On MSCT, the calcium score, degree of stenosis (≥50% and ≥70% stenosis), and plaque extent and location were determined. Plaque composition was classified as noncalcified, mixed, or calcified. Ischemia was defined as a summed difference score (≥2 on a per-patient basis. Ischemia was observed in 137 patients (27%). On a per-patient basis, multivariate analysis showed that the degree of stenosis (presence of (≥70% stenosis, odds ratio=3.5), plaque extent and composition (mixed plaques (≥3, odds ratio=1.7; calcified plaques ≥3, odds ratio=2.0), and location (atherosclerotic disease in the left main coronary artery and/or proximal left anterior descending coronary artery, odds ratio=1.6) were independent predictors for ischemia on MPI. In addition, MSCT variables of atherosclerosis, such as plaque extent, composition, and location, had significant incremental value for the prediction of ischemia over the presence of ge;70% stenosis. Conclusions-In addition to the degree of stenosis, MSCT variables of atherosclerosis describing plaque extent, composition, and location are predictive of the presence of ischemia on MPI. http://repub.eur.nl/res/pub/27521/ 2010-10-26T00:00:00Z BACKGROUND-: During persistent atrial fibrillation (AF), waves with a focal spread of activation are frequently observed. The origin of these waves and their relevance for the persistence of AF are unknown. METHODS AND RESULTS-: In 24 patients with longstanding persistent AF and structural heart disease, high-density mapping of the right and left atria was performed during cardiac surgery. In a reference group of 25 patients, AF was induced by rapid pacing. For data analysis, a mapping algorithm was developed that separated the fibrillatory process into its individual wavelets and identified waves with a focal origin. During persistent AF, the incidence of focal fibrillation waves in the right atrium was almost 4-fold higher than during acute AF (median, 0.46 versus 0.12 per cycle per 1 cm (25th to 75th percentile, 0.40 to 0.77 and 0.01 to 0.27; P<0.0001). They were widely distributed over both atria and were recorded at 46±18% of all electrodes. A large majority (90.5%) occurred as single events. Repetitive focal activity (>3) happened in only 0.8%. The coupling interval was not more than 11 ms shorter than the average AF cycle length (P=0.04), and they were not preceded by a long interval. Unipolar electrograms at the site of origin showed small but clear R waves. These data favor epicardial breakthrough rather than a cellular focal mechanism as the underlying mechanism. Often, conduction from a site of epicardial breakthrough was blocked in 1 or more directions. This generated separate multiple wave fronts propagating in different directions over the epicardium. CONCLUSIONS-: Focal fibrillation waves are due to epicardial breakthrough of waves propagating in deeper layers of the atrial wall. In patients with longstanding AF, the frequency of epicardial breakthroughs was 4 times higher than during acute AF. Because they provide a constant source of independent fibrillation waves originating over the entire epicardial surface, they offer an adequate explanation for the high persistence of AF in patients with structural heart disease. http://repub.eur.nl/res/pub/28688/ 2010-09-17T00:00:00Z Background: Catheter-related bloodstream infection (CRBSI) results in significant attributable morbidity and mortality. In this randomized, double-blind, placebo-controlled trial, we studied the efficacy and safety of a daily ethanol lock for the prevention of CRBSI in patients with a tunnelled central venous catheter (CVC). Methodology: From 2005 through 2008, each lumen of the CVC of adult hematology patients was locked for 15 minutes per day with either 70%-ethanol or placebo, where after the lock solution was flushed through. As a primary endpoint, the incidence rates of endoluminal CRBSI were compared. Principal Findings: The intent-to-treat analysis was based on 376 patients, accounting for 448 CVCs and 27,745 catheter days. For ethanol locks, the incidence of endoluminal CRBSI per 1000 CVC-days was 0.70 (95%-CI, 0.4-1.3), compared to 1.19 (95% confidence interval, 0.7-1.9) for placebo (incidence rate-ratio, 0.59; 95% confidence interval, 0.27-1.30; P = .19). For endoluminal CRBSI according to the strictest definition (positive hub culture and identical bacterial strain in blood), a 3.6-fold, non-significant, reduction was observed for patients receiving ethanol (2 of 226 versus 7 of 222; P = .103). No lifethreatening adverse events were observed. More patients receiving ethanol discontinued lock-therapy (11 of 226 versus 1 of 222; P = .006) or continued with decreased lock-frequency (10 of 226 versus 0 of 222; P = .002), due to non-severe adverse events. Conclusions: In this study, the reduction in the incidence of endoluminal CRBSI using preventive ethanol locks was nonsignificant, although the low incidence of endoluminal CRBSI precludes definite conclusions. Therefore, the lack of statistical significance may partially reflect a lack of power. Significantly more patients treated with ethanol locks discontinued their prophylactic treatment due to adverse effects, which were non-severe but reasonably ethanol related. Additional studies should be performed in populations with higher incidence of (endoluminal) CRBSI. Alternative sources of bacteremia, like exoluminal CRBSI or microbial translocation during chemotherapy-induced mucositis may have been more important in our patients. Trial Registration: ClinicalTrials.gov NCT00122642. http://repub.eur.nl/res/pub/27586/ 2010-09-15T00:00:00Z Because right ventricular (RV) dysfunction predicts a poor outcome in patients with congenital heart disease (CHD), regular monitoring of RV function is indicated. To date, cardiac magnetic resonance (CMR) imaging has been the reference method. A more practical, more accessible, and accurate tool would be preferred. We defined normality regarding RV systolic function using healthy controls and tested the ability of real-time 3-dimensional echocardiographic (RT3DE) findings to identify patients with CHD with RV dysfunction. The cutoff values for the RV volumes and ejection fraction (EF) were derived from the CMR imaging findings from 41 healthy controls (mean age 27 ± 8 years, 56% men). In 100 patients with varying CHDs (mean age 27 ± 11 years, 65% men), both RT3DE data sets (iE33) and short-axis CMR imaging (1.5 T) were obtained within 2 hours. The RT3DE and CMR RV volumes and EF were calculated using commercially available software. Receiver operating characteristic curves were created to obtain the sensitivity and specificity of the RT3DE data to identify RV dysfunction. Applying the cutoff values derived from the healthy controls using the CMR data of patients with CHD, we identified 23 patients with an enlarged indexed end-diastolic volume, 29 patients with an enlarged indexed end-systolic volume, and 21 patients with an impaired RVEF. The best cutoff values predicting RV dysfunction using the RT3DE findings were identified (indexed end-diastolic volume >105 ml/m2, indexed end-systolic volume >54 ml/m2, and EF <43%). The RT3DE findings revealed 23 patients with impaired RVEF, with 95% sensitivity, 89% specificity, and a negative predictive value of 99%. In conclusion, real-time 3-dimensional echocardiography is a very sensitive tool to identify RV dysfunction in patients with CHD and could be applied clinically to rule out RV dysfunction or to indicate additional quantitative analysis of RV function. http://repub.eur.nl/res/pub/27304/ 2010-09-01T00:00:00Z Background: It is uncertain if elevated admission plasma glucose (APG) remains an independent determinant of longer-term mortality in myocardial infarction (MI) patients with early restoration of coronary reperfusion by primary percutaneous coronary intervention. The objective of the study was to describe the relation between elevated APG and long-term mortality in MI patients undergoing invasive management. Methods: We studied 1,185 consecutive MI patients treated in the Medical Center Alkmaar in the separate years 1996 and 1999 (preinvasive era) and 2003 and 2006 (invasive era). In both eras, APG was derived according to a standard protocol. A multivariate Cox regression model was created to study the relation between APG, reperfusion era, and 5-year mortality. Results: During a median follow-up of 63 months, 261 patients had died. Mortality was lower in the invasive (19%) than in the preinvasive era (28%). Increased APG was associated with increased mortality, irrespective of the initial reperfusion strategy, although the relation was more pronounced in the preinvasive era (P value for heterogeneity of effects < .001). Each millimole-per-liter APG increase corresponded to a 7% increased mortality (adjusted hazard ratio 1.07, 95% CI 1.04-1.10). Patients with an APG >11 mmol/L had nearly 2-fold higher mortality (hazard ratio 1.9, 95% CI 1.3-2.7) than those with lower values. Conclusion: Elevated APG remains a determinant of long-term mortality in MI patients, irrespective of the advances that have been made in reperfusion therapy. http://repub.eur.nl/res/pub/27472/ 2010-09-01T00:00:00Z Background: Major vascular surgery patients are at high risk for developing asymptomatic perioperative myocardial ischemia reflected by a postoperative troponin release without the presence of chest pain or electrocardiographic abnormalities. Long-term prognosis is severely compromised and characterized by an increased risk of long-term mortality and cardiovascular events. Current guidelines on perioperative care recommend single antiplatelet therapy with aspirin as prophylaxis for cardiovascular events. However, as perioperative surgical stress results in a prolonged hypercoagulable state, the postoperative addition of clopidogrel to aspirin within 7 days after perioperative asymptomatic cardiac ischemia could provide improved effective prevention for cardiovascular events. Study design: DECREASE-VII is a phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial designed to evaluate the efficacy and safety of early postoperative dual antiplatelet therapy (aspirin and clopidogrel) for the prevention of cardiovascular events after major vascular surgery. Eligible patients undergoing a major vascular surgery (abdominal aorta or lower extremity vascular surgery) who developed perioperative asymptomatic troponin release are randomized 1:1 to clopidogrel or placebo (300-mg loading dose, followed by 75 mg daily) in addition to standard medical treatment with aspirin. The primary efficacy end point is the composite of cardiovascular death, stroke, or severe ischemia of the coronary or peripheral arterial circulation leading to an intervention. The evaluation of long-term safety includes bleeding defined by TIMI criteria. Recruitment began early 2010. The trial will continue until 750 patients are included and followed for at least 12 months. Summary: DECREASE-VII is evaluating whether early postoperative dual antiplatelet therapy for patients developing asymptomatic cardiac ischemia after vascular surgery reduces cardiovascular events with a favorable safety profile. http://repub.eur.nl/res/pub/27764/ 2010-09-01T00:00:00Z Aims:Data regarding pregnancy outcome in women with congenital heart disease (CHD) are limited.Methods and results: In 1802 women with CHD, 1302 completed pregnancies were observed. Independent predictors of cardiac, obstetric, and neonatal complications were calculated using logistic regression. The most prevalent cardiac complications during pregnancy were arrhythmias (4.7) and heart failure (1.6). Factors independently associated with maternal cardiac complications were the presence of cyanotic heart disease (corrected/uncorrected) (P < 0.0001), the use of cardiac medication before pregnancy (P < 0.0001), and left heart obstruction (P < 0.0001). New characteristics were mechanical valve replacement (P = 0.0014), and systemic (P = 0.04) or pulmonary atrioventricular valve regurgitation related with the underlying (moderately) complex CHD (P = 0.03). A new risk score for cardiac complications is proposed. The most prevalent obstetric complications were hypertensive complications (12.2). No correlation of maternal characteristics with adverse obstetric outcome was found. The most prevalent neonatal complications were premature birth (12), small for gestational age (14), and mortality (4). Cyanotic heart disease (corrected/uncorrected) (P = 0.0003), mechanical valve replacement (P = 0.03), maternal smoking (P = 0.007), multiple gestation (P = 0.0014), and the use of cardiac medication (P = 0.0009) correlated with adverse neonatal outcome.Conclusion: In our tertiary CHD cohort, cardiac, obstetric, and neonatal complications were frequently encountered, and (new) correlations of maternal baseline data with adverse outcome are reported. A new risk score for adverse cardiac complications is proposed, although prospective validation remains necessary. http://repub.eur.nl/res/pub/27797/ 2010-08-01T00:00:00Z Aims Multidetector computed tomography coronary angiography (CTA) has emerged as a feasible imaging modality for non-invasive assessment of coronary artery disease (CAD). Recently, 320-row CTA systems were introduced, with 16 cm anatomical coverage, allowing image acquisition of the entire heart within a single heart beat. The aim of the present study was to assess the diagnostic accuracy of 320-row CTA in patients with known or suspected CAD. Methods and resultsA total of 64 patients (34 male, mean age 61 ± 16 years) underwent CTA and invasive coronary angiography. All CTA scans were evaluated for the presence of obstructive coronary stenosis by a blinded expert, and results were compared with quantitative coronary angiography. Four patients were excluded from initial analysis due to non-diagnostic image quality. Sensitivity, specificity, and positive and negative predictive values to detect ≥50 luminal narrowing on a patient basis were 100, 88, 92, and 100, respectively. Moreover, sensitivity, specificity, and positive and negative predictive values to detect ≥70 luminal narrowing on a patient basis were 94, 95, 88, and 98, respectively. With inclusion of non-diagnostic imaging studies, sensitivity, specificity, and positive and negative predictive values to detect ≥50 luminal narrowing on a patient basis were 100, 81, 88, and 100, respectively. Conclusion The current study shows that 320-row CTA allows accurate non-invasive assessment of significant CAD. http://repub.eur.nl/res/pub/20646/ 2010-07-01T00:00:00Z Objective: Local anatomy and the patient's risk profile independently affect the expansion rate of an abdominal aortic aneurysm. We describe a hybrid method that combines finite element modelling and statistical methods to predict patient-specific aneurysm expansion. Methods: The 3-D geometry of the aneurysm was imaged with computed tomography. We used finite element methods to calculate wall stress and aneurysm expansion. Expansion rate was adjusted by risk factors obtained from a database of 80 patients. Aneurysm diameters predicted with and without the risk profiles were compared with diameters measured with ultrasound for 11 patients. Results: For this specific group of patients, local anatomy contributed 62% and the risk profile 38% to the aneurysmal expansion rate. Predictions with risk profiles resulted in smaller root mean square errors than predictions without risk profiles (2.9 vs. 4.0 mm, p < 0.01). Conclusions: This hybrid approach predicted aneurysmal expansion for a period of 30 months with high accuracy. http://repub.eur.nl/res/pub/28702/ 2010-07-01T00:00:00Z Objectives: This study sought to demonstrate the feasibility of a dedicated algorithm for automated quantification of stenosis severity on multislice computed tomography in comparison with quantitative coronary angiography (QCA). Background: Limited information is available on quantification of coronary stenosis, and previous attempts using semiautomated approaches have been suboptimal. Methods: In patients who had undergone 64-slice computed tomography and invasive coronary angiography, the most severe lesion on QCA was quantified per coronary artery using quantitative coronary computed tomography (QCCTA) software. Additionally, visual grading of stenosis severity using a binary approach (50% stenosis as a cutoff) was performed. Diameter stenosis (percentage) was obtained from detected lumen contours at the minimal lumen area, and corresponding reference diameter values were obtained from an automatic trend analysis of the vessel areas within the artery. Results: One hundred patients (53 men; 59.8 ± 8.0 years) were evaluated, and 282 (94%) vessels were analyzed. Good correlations for diameter stenosis were observed for vessel-based (n = 282; r = 0.83; p < 0.01) and patient-based (n = 93; r = 0.86; p < 0.01) analyses. Mean differences between QCCTA and QCA were -3.0% ± 12.3% and -6.2% ± 12.4%. Furthermore, good agreement was observed between QCCTA and QCA for semiquantitative assessment of diameter stenosis (accuracy of 95%). Diagnostic accuracy for assessment of <50% diameter stenosis was higher using QCCTA compared with visual analysis (95% vs. 87%; p = 0.08). Moreover, a significantly higher positive predictive value was observed with QCCTA when compared with visual analysis. http://repub.eur.nl/res/pub/28031/ 2010-06-15T00:00:00Z Objectives: The purpose of this study was to evaluate whether 123-iodine metaiodobenzylguanidine (123-I MIBG) imaging predicts ventricular arrhythmias causing appropriate implantable cardioverter-defibrillator (ICD) therapy (primary end point) and the composite of appropriate ICD therapy or cardiac death (secondary end point). Background: Although cardiac sympathetic denervation is associated with ventricular arrhythmias, limited data are available on the predictive value of sympathetic nerve imaging with 123-I MIBG on the occurrence of arrhythmias. Methods: Before ICD implantation, patients underwent 123-I MIBG and myocardial perfusion imaging. Early and late 123-I MIBG (planar and single-photon emission computed tomography [SPECT]) imaging was performed to assess cardiac innervation (heart-to-mediastinum ratio, cardiac washout rate, and 123-I MIBG SPECT defect score). Stress-rest myocardial perfusion imaging was performed to assess myocardial infarction and perfusion abnormalities (perfusion defect scores). During follow-up, appropriate ICD therapy and cardiac death were documented. Results: One-hundred sixteen heart failure patients referred for ICD therapy were enrolled. During a mean follow-up of 23 ± 15 months, appropriate ICD therapy (primary end point) was documented in 24 (21%) patients and appropriate ICD therapy or cardiac death (secondary end point) in 32 (28%) patients. Late 123-I MIBG SPECT defect score was an independent predictor for both end points. Patients with a large late 123-I MIBG SPECT defect (summed score >26) showed significantly more appropriate ICD therapy (52% vs. 5%, p < 0.01) and appropriate ICD therapy or cardiac death (57% vs. 10%, p < 0.01) than patients with a small defect (summed score ≤26) at 3-year follow-up. Conclusions: Cardiac sympathetic denervation predicts ventricular arrhythmias causing appropriate ICD therapy as well as the composite of appropriate ICD therapy or cardiac death. http://repub.eur.nl/res/pub/28007/ 2010-06-01T00:00:00Z Objectives: The purpose of this trial was to study the effect of a high bolus dose (HBD) of tirofiban on clinical outcome in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). Background: The On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2) placebo-controlled, double-blind, randomized trial showed that early administration of HBD tirofiban in the ambulance improves ST-segment resolution in patients with STEMI undergoing primary percutaneous coronary intervention. The effect of early tirofiban treatment on clinical outcome is unclear. Methods: The On-TIME 2 trial consisted of 2 phases: an open-label phase, followed by a double-blind, placebo-controlled phase. STEMI patients were randomized to either HBD tirofiban or no tirofiban (phase 1) or placebo (phase 2) in addition to aspirin, heparin, and high-dose clopidogrel. The protocol pre-specified a pooled analysis of the 2 study phases to assess the incidence of major adverse cardiac events at the 30-day follow-up and on total mortality at the 1-year follow-up. Results: During a 3-year period, 1,398 patients were randomized, 414 in phase 1 and 984 in phase 2. Major adverse cardiac events at 30 days were significantly reduced (5.8% vs. 8.6%, p = 0.043). There was a strong trend toward a decrease in mortality (2.2% vs. 4.1%, p = 0.051) in patients who were randomized to tirofiban pre-treatment, which was maintained during the 1-year follow-up (3.7% vs. 5.8%, p = 0.08). No clinically relevant difference in bleeding was observed. Conclusions: Early, pre-hospital initiation of HBD tirofiban, in addition to high-dose clopidogrel, improves the clinical outcome after primary percutaneous coronary intervention in patients with STEMI. (Ongoing 2b/3a inhibition In Myocardial infarction Evaluation; ISRCTN06195297). http://repub.eur.nl/res/pub/27585/ 2010-05-01T00:00:00Z BACKGROUND: Few data are available that systematically describe rates and trends of postoperative mortality for fairly large, unselected patient populations. METHODS: This population-based study uses a registry of 3.7 million surgical procedures in 102 hospitals in The Netherlands during 1991-2005. Patients older than 20 yr who underwent an elective, nonday case, open surgical procedure were enrolled. Patient data included main (discharge) diagnosis, secondary diagnoses, dates of admission and discharge, death during admission, operations, age, sex, and a limited number of comorbidities classified according to the International Classification of Diseases 9th revision Clinical Modification. The main outcome measure was postoperative all-cause mortality. Univariable and multivariable logistic regression analyses were applied to evaluate the relationship between type of surgery and the main outcome. RESULTS: Postoperative all-cause death was observed in 67,879 patients (1.85%). In a model based on a classification into 11 main surgical categories, breast surgery was associated with lowest mortality (adjusted incidence, 0.07%), and vascular surgery was associated with highest mortality (adjusted incidence, 5.97%). In a model based on 36 surgical subcategories, the adjusted mortality ranged from 0.07% for hernia nuclei pulposus surgery to 18.5% for liver transplant. The c-index of the 36-category model was 0.88, which was significantly (P < 0.001) higher than the c-index that was associated with the simple surgical classification (low vs. high risk) in the commonly used Revised Cardiac Risk Index (c-index, 0.83). CONCLUSIONS: This population-based study provided a detailed and contemporary overview of postoperative mortality for the entire surgical spectrum, which may act as reference standard for surgical outcome in Western populations. Copyright http://repub.eur.nl/res/pub/28442/ 2010-05-01T00:00:00Z Objective To compare the risks of pregnancy complications in women with repaired and unrepaired isolated ventricular septal defect (VSD). Design A retrospective multicentre study. Setting Tertiary centres in the Netherlands and Belgium. Methods Women were identified using two congenital heart disease registries. Eighty-eight women were identified who had experienced 202 pregnancies, including 46 miscarriages and nine terminations of pregnancy. Information on each completed pregnancy (n = 147; unrepaired VSD, n = 104; repaired VSD, n = 43) was obtained using medical records and telephone interviews. Data from the Generation R database (prospective cohort study; n = 9667) were used to determine the background risk (controls). Odds ratios and 95% CI were estimated using general estimation equation analysis adjusted for multiple pregnancies per woman, maternal age and parity status. Main outcome measures Adjusted odds ratios (AORs) for developing pregnancy complications in relation to corrective status. Results Pregnancies in women with an unrepaired VSD were associated with a higher risk of pre-eclampsia (AOR 4.59, 95% CI 2.01-10.5, P < 0.001) compared with controls. No differences were observed when comparing women with repaired VSD and controls. Pregnancies in women with repaired VSD were associated with a higher risk of premature labour (AOR 4.02, 95% CI 1.12-14.4, P = 0.03) and small-for-gestational-age (SGA) births (AOR 4.09, 95% CI 1.27-13.2, P = 0.02) compared with women with unrepaired VSD. Conclusions Women with unrepaired VSD are at increased risk of pre-eclampsia, which suggests that it is not a benign condition. In addition, women with repaired VSD are at increased risk of premature labour and SGA births compared with women with unrepaired VSD. http://repub.eur.nl/res/pub/28683/ 2010-05-01T00:00:00Z Background-Data on the association between right ventricular (RV) function and adverse events after acute myocardial infarction (AMI) are scarce. The purpose of the current study was to evaluate the relation between RV function and adverse events in patients treated with primary percutaneous coronary intervention for AMI. Methods and Results-Consecutive patients admitted with AMI treated with primary percutaneous coronary intervention underwent echocardiography within 48 hours of admission to assess left ventricular and RV function. RV function was quantified with RV fractional area change (RVFAC), tricuspid annular plane systolic excursion, and RV strain. The end point was defined as a composite of all-cause mortality, reinfarction, and hospitalization for heart failure. All patients (n=621) were followed prospectively, and during a mean follow-up of 24 months, 86 patients reached the composite end point. RVFAC, tricuspid annular plane systolic excursion, and RV strain were all univariable predictors of worse outcome. After multivariable analysis, only RVFAC (hazard ratio, 0.96; 95% CI, 0.92 to 0.99) and RV strain (hazard ratio, 1.08; 95% CI, 1.03 to 1.13) independently predicted the composite end point. In addition, RV strain provided incremental value to clinical information, infarct characteristics, left ventricular function, and RVFAC. Conclusions-RV function provides strong prognostic information in patients treated with primary percutaneous coronary intervention for AMI. http://repub.eur.nl/res/pub/27333/ 2010-04-01T00:00:00Z http://repub.eur.nl/res/pub/28313/ 2010-04-01T00:00:00Z Objectives: This study aims to compare the outcome of the two co-existing modifications of staged total cavopulmonary connection (TCPC) - the intra-atrial lateral tunnel (ILT) and the extracardiac conduit (ECC). Methods: We included 209 patients after staged TCPC (102 ILT and 107 ECC), operated on between 1988 and 2008. Medical and surgical records were reviewed for (1) patient demographics and cardiac anatomy; (2) pre-Fontan procedures; (3) pre-Fontan haemodynamics and cardiac functional status; (4) operative details; (5) postoperative hospital course; (6) follow-up information on arrhythmias and thrombo-embolic events; (7) post-Fontan interventions; and (8) clinical status at last follow-up until June 2008. Results: Median follow-up duration was 4.3 years (interquartile range 1.5-7.4 years). At 6-year follow-up, freedom from Fontan failure (i.e., mortality or re-operations for Fontan failure) was 83% for the ILT and 79% for the ECC groups (p = 0.6); freedom from late re-operations (other than re-operations for Fontan failure) was 79% for the ILT and the ECC groups and freedom from arrhythmias was 83% for the ILT, and 92% for the ECC groups (p = 0.022). Multivariable Cox regression analysis identified intensive care unit stay and cardiopulmonary bypass time as risk factors for Fontan failure, but they were not strong predictors. Right ventricular morphology was identified as a risk factor for arrhythmias. The occurrence of thrombo-embolic events was low with no difference between the ILT and the ECC groups, and irrespective of the postoperative use of anticoagulant or anti-platelet aggregation therapy. At most recent follow-up, sinus rhythm was present in 70% of patients; in 23% of the patients, ventricular function was found to be moderately or severely impaired at echocardiography. Conclusions: Outcome after staged ILT- and ECC-type Fontan operations is good, with comparable freedom from late re-operations and freedom from Fontan failure at 6-year follow-up. The incidence of arrhythmias was significantly lower in the ECC group. Right ventricular morphology was identified as a risk factor for arrhythmias. http://repub.eur.nl/res/pub/28704/ 2010-03-01T00:00:00Z Objectives: The aim of this study was to obtain a valid estimate of the clinical effects of primary percutaneous coronary intervention (PPCI) in relation to age. Background: Treatment with PPCI is most beneficial in high-risk myocardial infarction patients. Paradoxically, elderly patients, who are at increased risk of adverse outcome, are often withheld PPCI. Methods: Individual patient data were obtained from 22 randomized trials (n = 6,763) evaluating the clinical effects of PPCI versus fibrinolysis (FL). Differences in 30-day death, repeat myocardial infarction, and stroke between patients randomized to FL and PPCI were determined in 5 age-strata: ≤50, >50 to 60, >60 to 70, >70 to 80, and >80 years. Treatment effects are reported as odds ratios (ORs) and 95% confidence intervals (CI). Multivariable logistic regression analyses, which included age × treatment interaction, were applied to examine evidence of heterogeneity in age-specific ORs. Results: Thirty-day death increased with increasing age and ranged from 1.1% (FL) and 1.8% (PPCI) in patients ≤50 years to 26.4% and 18.3% in patients >80 years of age. The point estimate of treatment effect (overall adjusted OR: 0.65; 95% CI: 0.52 to 0.79) was compatible with a mortality reduction favoring PPCI in all age-strata (except in patients ≤50 years of age), and 95% CIs were largely overlapping. There was no evidence of heterogeneity in ORs between age categories. Similar results were observed for repeat myocardial infarction and stroke. Conclusions: In this analysis of randomized trials, the reduction in clinical end points by PPCI was not influenced by age. Hence, age per se should not be considered an exclusion criterion for the application of PPCI. http://repub.eur.nl/res/pub/28730/ 2010-03-01T00:00:00Z Objectives: The aim of this study was to investigate the effect of complete, incomplete, and unsuccessful revascularization by percutaneous coronary intervention (PCI) on left ventricular ejection fraction (EF) in patients with multivessel disease and impaired left ventricular function and assess the diagnostic accuracy of cardiac magnetic resonance imaging (MRI) for improvement in EF. Background: The effect of PCI for multivessel coronary artery disease on long-term myocardial function and the predictive value of cardiac MRI on global function are incompletely investigated. Methods: Cardiac MRI was performed in patients with multivessel disease before and 6 months after complete revascularization (n = 34) or incomplete revascularization (n = 22) or in patients without successful revascularization (n = 15). For the prediction of recovery of EF, wall thickening was quantified on cine images at rest and during 5- and 10-μg/kg/min dobutamine. The transmural extent of infarction was quantified on delayed enhancement cardiac MRI. Results: The EF improved significantly after complete revascularization (46 ± 12% to 51 ± 13%; p < 0.0001) but did not change after incomplete (49 ± 11% to 49 ± 10%; p = 0.88) or unsuccessful revascularization (49 ± 13% to 47 ± 13%; p = 0.11). Sensitivity, specificity, positive and negative predictive value for the prediction of improvement in EF of >4% after PCI were 100%, 75%, 74%, and 100%, respectively, for dobutamine-cardiac MRI and 70%, 77%, 70%, and 77%, respectively, for delayed enhancement-cardiac MRI. Conclusions: Complete revascularization for multivessel coronary artery disease improves EF, whereas EF did not change in patients after incomplete or unsuccessful revascularization. Improvement in EF can be predicted by performing cardiac MRI before PCI. http://repub.eur.nl/res/pub/27600/ 2010-02-15T00:00:00Z Data evaluating gender- and age-specific differences in plaque observations on multislice computed tomography (MSCT) are scarce. Accordingly, the aim of this study was to evaluate coronary plaque patterns in men and women in relation to age using MSCT. The findings were compared to observations on grayscale intravascular ultrasound (IVUS) and virtual histology (VH) IVUS. In total, 93 patients (59 men, 34 women) underwent 64-slice MSCT followed by conventional coronary angiography with IVUS. Plaque extent and composition were assessed on MSCT, grayscale IVUS, and VH IVUS. Coronary plaque patterns were compared between men and women in 2 age groups (<65 and ≥65 years old). In patients aged <65 years, more plaques were observed on MSCT in men (6 ± 4 vs 2 ± 2 in women, p <0.001). Also, a larger plaque burden was observed on grayscale IVUS in men (45.7 ± 11.4% vs 36.3 ± 11.6% in women, p <0.001). Similarly, more mixed plaques were observed in men (3 ± 3 vs 1 ± 1 in women, p = 0.003), whereas a larger arc of calcium was detected on grayscale IVUS in men (91.7 ± 93.5° vs 25.7 ± 51.0° in women, p <0.001). On VH IVUS, the prevalence of thin-cap fibroatheroma was higher in men (31% vs 0%) compared to women. In patients aged ≥65 years old, no important differences in plaque patterns were observed between men and women. In conclusion, more extensive atherosclerosis and more calcified lesions were observed in men than in women. These differences were predominantly present in patients aged <65 years and were lost in those aged ≥65 years. http://repub.eur.nl/res/pub/27301/ 2010-02-01T00:00:00Z Background: Surgical risk scores, such as the logistic EuroSCORE (LES) and Society of Thoracic Surgeons Predicted Risk of Mortality (STS) score, are commonly used to identify high-risk or "inoperable" patients for transcatheter aortic valve implantation (TAVI). In Europe, the LES plays an important role in selecting patients for implantation with the Medtronic CoreValve System. What is less clear, however, is the role of the STS score of these patients and the relationship between the LES and STS. Objective: The purpose of this study is to examine the correlation between LES and STS scores and their performance characteristics in high-risk surgical patients implanted with the Medtronic CoreValve System. Methods: All consecutive patients (n = 168) in whom a CoreValve bioprosthesis was implanted between November 2005 and June 2009 at 2 centers (Bern University Hospital, Bern, Switzerland, and Erasmus Medical Center, Rotterdam, The Netherlands) were included for analysis. Patient demographics were recorded in a prospective database. Logistic EuroSCORE and STS scores were calculated on a prospective and retrospective basis, respectively. Results: Observed mortality was 11.1%. The mean LES was 3 times higher than the mean STS score (LES 20.2% ± 13.9% vs STS 6.7% ± 5.8%). Based on the various LES and STS cutoff values used in previous and ongoing TAVI trials, 53% of patients had an LES ≥15%, 16% had an STS ≥10%, and 40% had an LES ≥20% or STS ≥10%. Pearson correlation coefficient revealed a reasonable (moderate) linear relationship between the LES and STS scores, r = 0.58, P < .001. Although the STS score outperformed the LES, both models had suboptimal discriminatory power (c-statistic, 0.49 for LES and 0.69 for STS) and calibration. Conclusions: Clinical judgment and the Heart Team concept should play a key role in selecting patients for TAVI, whereas currently available surgical risk score algorithms should be used to guide clinical decision making. http://repub.eur.nl/res/pub/27877/ 2010-02-01T00:00:00Z The disclosure forms of all the authors and reviewers are available on the ESC website www.escardio.org/guidelines. http://repub.eur.nl/res/pub/27470/ 2010-01-15T00:00:00Z Even after successful repair, hypertension is one of the main determinants of cardiovascular morbidity and mortality in patients with aortic coarctation (CoA). We compared the effect of candesartan (angiotensin II receptor blockade) and metoprolol (β-adrenergic receptor blockade) on blood pressure, large artery stiffness, and neurohormonal status in hypertensive patients after repair of CoA. In the present open-label, crossover study, hypertensive patients after CoA repair were first randomly assigned to treatment with candesartan 8 mg or metoprolol 100 mg once per day. After 8 weeks of treatment with one of the drugs, the other treatment was given for 8 weeks. The treatment effects were assessed with 24-hour ambulatory blood pressure monitoring, measurement of large artery stiffness, and neurohormonal plasma levels at baseline and after 8 weeks of either treatment. Sixteen patients (mean age 37 ± 12 years, 26 ± 15 years after repair, 63% men) completed the study. The 24-hour mean arterial pressure at baseline was 97.7 ± 6.2 mm Hg. Metoprolol (mean dose 163 ± 50 mg/day) decreased the mean arterial pressure (7.0 ± 4.2 and 4.1 ± 3.6 mm Hg, respectively) more than did candesartan (mean dose 13 ± 4 mg/day; p = 0.018, 95% confidence interval 0.6 to 5.5). Large artery stiffness did not change with either treatment. With metoprolol, plasma B-type natriuretic peptide increased and plasma renin decreased. With candesartan, the plasma renin and noradrenaline levels increased and aldosterone levels decreased. In conclusion, in adult hypertensive patients after CoA repair, metoprolol had more of an antihypertensive effect than did candesartan. Moreover, the neurohormonal outcome did not support a significant role for the renin-angiotensin system in the causative mechanism of hypertension after CoA. http://repub.eur.nl/res/pub/27584/ 2010-01-01T00:00:00Z Background: Routine predictions made by surgeons or historical mean durations have only limited capacity to predict operating room (OR) time. The authors aimed to devise a prediction model using the surgeon's estimate and characteristics of the surgical team, the operation, and the patient. Methods: Seventeen thousand four hundred twelve consecutive, elective operations from the general surgical department in an academic hospital were analyzed. The outcome was OR time, and the potential predictive factors were surgeon's estimate, number of planned procedures, number and experience of surgeons and anesthesiologists, patient's age and sex, number of previous hospital admissions, body mass index, and eight cardiovascular risk factors. Linear mixed modeling on the logarithm of the total OR time was performed. Results: Characteristics of the operation and the team had the largest predictive performance, whereas patient characteristics had a modest but distinct effect on OR time: operations were shorter for patients older than 60 yr, and higher body mass index was associated with longer OR times. The surgeon's estimate had an independent and substantial contribution to the prediction, and the final model explained 27% of the residual variation in log (OR time). Using the prediction model instead of the surgeon's prediction based on historical averages would reduce shorter-than-predicted and longer-than-predicted OR time by 2.8 and 6.6 min per case (a relative reduction of 12 and 25%, respectively), assessed on independent validation data. Conclusions: Detailed information on the operative session, the team, and the patient substantially improves the prediction of OR times, but the surgeon's estimate remains important. The prediction model may be used in OR scheduling. http://repub.eur.nl/res/pub/28416/ 2010-01-01T00:00:00Z Background: Anecdotal evidence suggests that transcatheter aortic valve implantation (TAVI) is being used beyond pre-market label indications. Methods: To assess the frequency and outcomes associated with "off-label" use of TAVI, we conducted a retrospective study, examining adherence to patient selection criteria in 63 patients undergoing implantation with the 18F CoreValve ReValving System (CRS). Label status (on-label vs off-label) was determined by following (1) inclusion/exclusion criteria indicated in the 18F CRS safety and efficacy trial and (2) a patient selection matrix indicating anatomical boundaries to guide patient selection. Off-label use was defined as the presence of at least one exclusion criterion or "non-acceptable" criteria based on the patient selection matrix. Results: Off-label implantation was identified in 42 patients (67%)-40% had one, 19% had two and 8% had three or more off-label criteria. Baseline demographics were similar between the groups except for a higher logistic EuroSCORE in the on-label group (19.8 (11.2) vs 14.5 (7.3), p=0.029). There was no significant difference in the procedural success rates between the on-label and off-label groups (91% vs 95%, respectively, p=0.47). The frequency of angiographic moderatesevere aortic regurgitation, post-implant dilatation or implantation of a second valve was also similar between the groups. At 30 days, the cumulative death rate was 10%; there were four deaths in the "on-label" and three deaths in the "off-label" group. Conclusion: In this study we found that "off-label" implantation of the CRS was common. Further studies are needed to evaluate the consequences of "label status" for patients undergoing TAVI. http://repub.eur.nl/res/pub/28723/ 2010-01-01T00:00:00Z Background-The extent of viable myocardial tissue is recognized as a major determinant of recovery of left ventricular (LV) function after myocardial infarction. In the current study, the role of global LV strain assessed with novel automated function imaging (AFI) to predict functional recovery after acute infarction was evaluated. Methods and Results-A total of 147 patients (mean age, 61 ±11 years) admitted for acute myocardial infarction were included. All patients underwent 2D echocardiography within 48 hours of admission. Significant relations were observed between baseline AFI global LV strain and peak level of troponin T (r=0.64), peak level of creatine phosphokinase (r=0.62), wall motion score index (r=0.52), and viability index assessed with single-photon emission computed tomography (r=0.79). At 1-year follow-up, LV ejection fraction was reassessed. Patients with absolute improvement in LV ejection fraction ≥5% at 1-year follow-up (n=70; 48%) had a higher (more negative) baseline AFI global LV strain (P<0.0001). Baseline AFI global LV strain was a predictor for change in LV ejection fraction at 1-year follow-up. A cutoff value for baseline AFI global LV strain of-13.7% yielded a sensitivity of 86% and a specificity of 74% to predict LV functional recovery at 1-year follow-up. Conclusions-AFI global LV strain early after acute myocardial infarction reflects myocardial viability and predicts recovery of LV function at 1-year follow-up. http://repub.eur.nl/res/pub/24249/ 2009-12-01T00:00:00Z Drug-eluting stents (DES) reduce restenosis rates compared to bare-metal stents. Most trials using DES enrolled selected patient and lesion subtypes, and primary endpoint focused on angiographic metrics or relatively short-term outcomes. When DES are used in broader types of lesions and patients, important differences may emerge in long-term outcomes between stent types, particularly the incidence of late stent thrombosis. PROTECT is a randomized, open-label trial comparing the long-term safety of the zotarolimus-eluting stent and the sirolimus-eluting stent. The trial has enrolled 8,800 patients representative of those seen in routine clinical practice, undergoing elective, unplanned, or emergency procedures in native coronary arteries in 196 centers in 36 countries. Indications for the procedure and selection of target vessel and lesion characteristics were at the operator's discretion. Procedures could be staged, but no more than 4 target lesions could be treated per patient. Duration of dual antiplatelet therapy was prespecified to achieve similar lengths of treatment in both study arms. The shortest predefined duration was 3 months, as per the manufacturer's instructions. The primary outcome measure is the composite rate of definite and probable stent thrombosis at 3 years, centrally adjudicated using Academic Research Consortium definitions. The main secondary end points are 3-year all-cause mortality, cardiac death, large nonfatal myocardial infarction, and all myocardial infarctions. This large, international, randomized, controlled trial will provide important information on comparative rates of stent thrombosis between 2 different DES systems and safety as assessed by patient-relevant long-term clinical outcomes. http://repub.eur.nl/res/pub/24265/ 2009-12-01T00:00:00Z The aim of this study was to investigate the value of coronary calcium detection by computed tomography compared to computed tomographic angiography (CTA) and exercise testing to detect obstructive coronary artery disease (CAD) in patients with stable chest pain. A total of 471 consecutive patients with new stable chest complaints were scheduled to undergo dual-source multislice computed tomography (Siemens, Germany; coronary calcium score [CCS] and coronary CTA) and exercise electrocardiography (XECG). Clinically driven invasive quantitative angiography was performed in 98 patients. Only 3 of 175 patients (2%) with a negative CCS had significant CAD on CT angiogram, with only 1 confirmed by quantitative angiography. In patients with a high calcium score (Agatston score >400), CTA could exclude significant CAD in no more than 4 of 65 patients (6%). In patients with a low-intermediate CCS, CTA more often yielded diagnostic results compared to XECG and could rule out obstructive CAD in 56% of patients. For patients with CAD on CT angiogram, those with abnormal exercise electrocardiographic results more often showed severe CAD (p <0.034). In patients with diagnostic results for all tests, the sensitivity and specificity to detect >50% quantitative angiographic diameter stenosis were 100% and 15% for CCS >0, 82% and 64% for CCS >100, 97% and 36% for CTA, and 70% and 76% for XECG, respectively. In conclusion, nonenhanced computed tomography for calcium detection is a reliable means to exclude obstructive CAD in stable, symptomatic patients. Contrast-enhanced CTA can exclude significant CAD in patients with a low-intermediate CCS but is of limited value in patients with a high CCS. http://repub.eur.nl/res/pub/25252/ 2009-12-01T00:00:00Z Purpose: To investigate the effect of heart rate frequency (HRF) and heart rate variability (HRV) on radiation exposure, image quality, and diagnostic performance to help detect significant stenosis (≥50% lumen diameter reduction) by using adaptive electrocardiographic (ECG) pulsing at dual-source (DS) spiral computed tomographic (CT) coronary angiography. Materials and Methods: Institutional review committee approval and informed consent were obtained. No prescan β-blockers were applied. Unenhanced CT and CT coronary angiography with adaptive ECG pulsing were performed in 927 consecutive patients (600 men, 327 women; mean age, 60.3 years ± 11.0 [standard deviation]) divided in three HRF groups: low, intermediate, and high (≤65, 66-79, and ≥80 beats/min, respectively), and four HRV groups given mean interbeat difference (IBD) during CT coronary angiography: normal, minor, moderate, and severe (IBDs of 0-1, 2-3, 4-10, and >10, respectively). Radiation exposure and image quality were also evaluated. In 444 of these, diagnostic performance was presented as sensitivity, specificity, positive predictive values (PPVs), and negative predictive values and likelihood ratios with corresponding 95% confidence intervals by using quantitative coronary angiography as the reference standard. Results: CT coronary angiography yielded good image quality in 98% of patients and no significant differences in image quality were found among HRF and HRV groups. Radiation exposure was significantly higher in patients with low versus high HRF and in patients with severe versus normal HRV. No significant differences among HRF and HRV groups in image quality and diagnostic performance were found. A nonsignificant trend was found toward a lower specificity and PPV in patients with a high HRF or severe HRV when compared with low HRF or normal HRV in patients with a low calcium score (Agatston score <100). Conclusion: DS spiral CT coronary angiography performed with adaptive ECG pulsing results in preserved diagnostic image quality and performance independent of HRF or HRV at the cost of limited dose reduction in arrhythmic patients. http://repub.eur.nl/res/pub/26973/ 2009-12-01T00:00:00Z http://repub.eur.nl/res/pub/17900/ 2009-11-01T00:00:00Z Objectives: This study sought predictors of mortality in patients aged ≥75 years with a first ST-segment elevation myocardial infarction (STEMI) and evaluated the validity of the GUSTO-I and TIMI risk models. Methods: Clinical variables, treatment and mortality data from 433 consecutive patients were collected. Univariable and multivariable logistic regression analyses were applied to identify baseline factors associated with 30-day mortality. Subsequently a model predicting 30-day mortality was created and compared with the performance of the GUSTO-I and TIMI models. Results: After adjustment, a higher Killip class was the most important predictor (OR 16.1; 95% CI 5.7-45.6). Elevated heart rate, longer time delay to admission, hyperglycemia and older age were also associated with increased risk. Patients with hypercholesterolemia had a significantly lower risk (OR 0.46; 95% CI 0.24-0.86). Discrimination (c-statistic 0.79, 95% CI 0.75-0.84) and calibration (Hosmer-Lemeshow 6, p = 0.5) of our model were good. The GUSTO-I and TIMI risk scores produced adequate discrimination within our dataset (c-statistic 0.76, 95% CI 0.71-0.81, and c-statistic 0.77, 95% CI 0.72-0.82, respectively), but calibration was not satisfactory (HL 21.8, p = 0.005 for GUSTO-I, and HL 20.6, p = 0.008 for TIMI). Conclusions: Short-term mortality in elderly patients with a first STEMI depends most importantly on initial clinical and hemodynamic status. The GUSTO-I and TIMI models are insufficiently adequate for providing an exact estimate of 30-day mortality risk. http://repub.eur.nl/res/pub/24652/ 2009-11-01T00:00:00Z AimsThe purpose of this study was to assess the relationship between calcium scoring (CS) and multi-slice computed tomography coronary angiography (MSCTA) and to determine if MSCTA has an incremental prognostic value to CS.Methods and resultsIn 432 patients (59 male, age 58 ± 11 years) referred for cardiac evaluation owing to suspected coronary artery disease (CAD), CS and 64-slice MSCTA were performed. The following events were combined in a composite endpoint: all-cause mortality, non-fatal infarction, and unstable angina requiring revascularization. CS was 0 in 147 (34) patients, CS 1-99 was present in 122 (28), CS 100-399 in 75 (17), CS 400-999 in 56 (13), and CS ≥ 1000 in 32 (7). MSCTA was normal in 133 (31) patients, MSCTA 30-50 stenosis was observed in 190 (44), and MSCTA ≥50 stenosis in 109 (25). During follow-up [median 670 days (25th-75th percentile: 418-895)], an event occurred in 21 patients (4.9). After multivariate correction for CS, MSCTA ≥ 50 stenosis, the number of diseased segments, obstructive segments, and non-calcified plaques were independent predictors with an incremental prognostic value to CS.ConclusionMSCTA provides additional information to CS regarding stenosis severity and plaque composition. This additional information was shown to translate into incremental prognostic value over CS. http://repub.eur.nl/res/pub/24964/ 2009-11-01T00:00:00Z INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts adverse cardiac outcome in patients undergoing vascular surgery. However, several conditions might influence this prognostic value, including anemia. In this study, we evaluated whether anemia confounds the prognostic value of NT-proBNP for predicting cardiac events in patients undergoing vascular surgery. METHODS:: A detailed cardiac history, resting echocardiography, and hemoglobin and NT-proBNP levels were obtained in 666 patients before vascular surgery. Anemia was defined as serum hemoglobin <13 g/dL for men and <12 g/dL for women. Troponin T measurements and 12-lead electrocardiograms were performed on postoperative days 1, 3, 7, and 30 and whenever clinically indicated. The primary end point of the study was the composite of 30-day postoperative cardiovascular death, nonfatal myocardial infarction, and troponin T release. Receiver operating characteristic curve analysis was used to assess the optimal cutoff value of NT-proBNP for the prediction of the composite end point. Multivariable regression analysis was used to assess the additional value of NT-proBNP for the prediction of postoperative cardiac events in nonanemic and anemic patients. RESULTS:: Anemia was present in 206 patients (31%) before surgery. Hemoglobin level was inversely related with the NT-proBNP levels (β coefficient = -2.242; P = 0.025). The optimal predictive cutoff value of NT-proBNP for predicting the composite cardiovascular outcome was 350 pg/mL. After adjustment for clinical cardiac risk factors, both anemia (odds ratio [OR] 1.53; 95% confidence interval [CI]: 1.07-2.99) and increased levels of NT-proBNP (OR 4.09; 95% CI: 2.19-7.64) remained independent predictors for postoperative cardiac events. However, increased levels of NT-proBNP were not predictive for the risk of adverse cardiac events in the subgroup of anemic patients (OR 2.16; 95% CI: 0.90-5.21). CONCLUSIONS:: Both anemia and NT-proBNP are independently associated with an increased risk for postoperative cardiac events in patients undergoing vascular surgery. NT-proBNP has less predictive value in anemic patients. Copyright http://repub.eur.nl/res/pub/26995/ 2009-11-01T00:00:00Z Background: Clinical characteristics of patients, angiographic referral bias, and several technical factors may all affect the reported diagnostic accuracy of tests. The aim of this study was to assess their influence on the diagnostic accuracy of dobutamine stress echocardiography (DSE). Methods: The medical literature from 1991 to 2006 was searched for diagnostic studies using DSE and meta-analysis was applied to the 62 studies thus retrieved, including 6881 patients. These studies were analyzed for patient characteristics, angiographic referral bias, and several technical factors. Results: The sensitivity of DSE was significantly related to the inclusion of patients with prior myocardial infarctions (0.834 vs 0.740, P < .01) and defining the results of DSE as already positive in case of resting wall motion abnormalities rather than obligatory myocardial ischemia (0.786 vs 0.864, P < .01). Specificity tended to be lower when patients with resting wall motion abnormalities were included in a study (0.812 vs 0.877, P < .10). The presence of referral bias adversely affected the specificity of DSE (0.771 vs 0.842, P < .01). Conclusion: This analysis suggests that the reported sensitivity of DSE is likely higher and the specificity lower than expected in routine clinical practice because of the inappropriate inclusion of patients with prior myocardial infarctions, the definition of positive results on DSE, and the negative influence of referral bias. However, in the patient subset that will be sent to coronary angiography, the opposite results can be expected. http://repub.eur.nl/res/pub/17948/ 2009-10-01T00:00:00Z Aim To assess the relative value of a novel measure of left ventricular (LV) dyssynchrony derived from magnetic resonance imaging (MRI) and the extent of scar tissue for prediction of response to cardiac resynchronization therapy (CRT).Methods and resultsThirty-five heart failure patients scheduled for CRT were included. Left ventricular dyssynchrony was defined as the standard deviation of 16 segment time-to-maximum radial wall thickness (SDt-16) obtained from a cine-set of short-axis slices. Delayed-enhanced MRI was performed for scar analysis. Echocardiography was used to determine response to CRT (reduction ≥15% in LV end-systolic volume 6 months after implantation). At follow-up, 21 patients (60%) were classified as responders. On MRI, SDt-16 was significantly higher in responders compared with non-responders (median 97 vs. 60 ms, P < 0.001), whereas the total extent of scar was larger in non-responders (median 35% vs. 3% in responders, P < 0.001). At the logistic regression analysis, SDt-16 was directly associated (OR = 6.3, 95% CI 3.1-9.9, P < 0.001) and the total extent of scar was inversely associated (OR = 0.52, 95% CI 0.43-0.87, P < 0.001) with response to CRT.ConclusionMagnetic resonance imaging offers the unique opportunity to assess LV dyssynchrony and scar extent in a single session. Both these parameters are important predictors of echocardiographic response to CRT. http://repub.eur.nl/res/pub/24895/ 2009-10-01T00:00:00Z Objective: To compare the diagnostic performance of CT angiography (CTA) and exercise electrocardiography (XECG) in a symptomatic population with a low-intermediate prevalence of coronary artery disease (CAD). Design: Prospective registry. Setting: Tertiary university hospital. Patients: 471 consecutive ambulatory patients with stable chest pain complaints, mean (SD) age 56 (10), female 227 (48%), pre-test probability for significant CAD >5%. Intervention: All patients were intended to undergo both 64-slice, dual-source CTA and an XECG. Clinically driven quantitative catheter angiography was performed in 98 patients. Main outcome measures: Feasibility and interpretability of, and association between, CTA and XECG, and their diagnostic performance with invasive coronary angiography as reference. Results: CTA and XECG could not be performed in 16 (3.4%) vs 48 (10.2%, p<0.001), and produced nondiagnostic results in 3 (0.7%) vs 140 (33%, p<0.001). CTA showed ≥1 coronary stenosis (≥50%) in 140 patients (30%), XECG was abnormal in 93 patients (33%). Results by CTA and XECG matched for 185 patients (68%, p=0.63). Catheter angiography showed obstructive CAD in 57/98 patients (58%). Sensitivity, specificity, positive and negative predictive value of CTA to identify patients with ≥50% stenosis was 96%, 37%, 67% and 88%, respectively; compared with XECG: 71%, 76%, 80% and 66%, respectively. Quantitative CTA slightly overestimated diameter stenosis: 6 (21)% (R=0.71), compared with QCA. Of the 312 patients (66%) with a negative CTA, 44 (14%) had a positive XECG, but only 2/17 who underwent catheter angiography had significant CAD. Conclusion: CTA is feasible and diagnostic in more patients than XECG. For interpretable studies, CTA has a higher sensitivity, but lower specificity for detection of CAD. http://repub.eur.nl/res/pub/24239/ 2009-09-18T00:00:00Z Background: The aim of this study was to assess the prognostic value of technetium-99m tetrofosmin gated SPECT imaging in women using quantitative gated single photon emission computed tomography (SPECT) imaging. Methods: We followed 453 consecutive female patients. Average follow-up was 1.33 years (max. 2.55). Hard endpoints were cardiac death, acute myocardial infarction, or documented ventricular fibrillation. Event-free survival curves were obtained. Optimal cutoff values for left ventricular (LV) volumes, LV ejection fraction (LVEF), and perfusion data to predict outcome were determined by ROC curve analysis. Results: A total of 236 patients had an abnormal study, of whom 27 patients experienced hard events (16 deaths) and 47 patients soft events. For hard events summed stress score (SSS) and LVEF, and for any cardiac event SSS showed independent incremental prognostic value. The survival curves were maximally separated when using cutoff values for SSS of ≥ 22 and LVEF < 52% (P < 0.001, HR 4.61 and P < 0.001 HR 5.24 for SSS and LVEF resp.), and SSS ≥ 14 (P < 0.001 HR 3.76) for any cardiac event. Conclusion: In women, perfusion and functional parameters derived from quantitative gated technetium-99m tetrofosmin SPECT imaging can adequately be used for cardiac risk assessment. Using quantitative gated SPECT, female patients with an LVEF < 52% or an SSS ≥ 22 are at increased risk for subsequent hard events. Furthermore, patients with an SSS ≥ 14 are at increased risk for any cardiac events. http://repub.eur.nl/res/pub/32665/ 2009-09-03T00:00:00Z BACKGROUND: Adverse cardiac events are common after vascular surgery. We hypothesized that perioperative statin therapy would improve postoperative outcomes. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned patients who had not previously been treated with a statin to receive, in addition to a beta-blocker, either 80 mg of extended-release fluvastatin or placebo once daily before undergoing vascular surgery. Lipid, interleukin-6, and C-reactive protein levels were measured at the time of randomization and before surgery. The primary end point was the occurrence of myocardial ischemia, defined as transient electrocardiographic abnormalities, release of troponin T, or both, within 30 days after surgery. The secondary end point was the composite of death from cardiovascular causes and myocardial infarction. RESULTS: A total of 250 patients were assigned to fluvastatin, and 247 to placebo, a median of 37 days before vascular surgery. Levels of total cholesterol, low-density lipoprotein cholesterol, interleukin-6, and C-reactive protein were significantly decreased in the fluvastatin group but were unchanged in the placebo group. Postoperative myocardial ischemia occurred in 27 patients (10.8%) in the fluvastatin group and in 47 (19.0%) in the placebo group (hazard ratio, 0.55; 95% confidence interval [CI], 0.34 to 0.88; P=0.01). Death from cardiovascular causes or myocardial infarction occurred in 12 patients (4.8%) in the fluvastatin group and 25 patients (10.1%) in the placebo group (hazard ratio, 0.47; 95% CI, 0.24 to 0.94; P=0.03). Fluvastatin therapy was not associated with a significant increase in the rate of adverse events. CONCLUSIONS: In patients undergoing vascular surgery, perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome. (Current Controlled Trials number, ISRCTN83738615.) Copyright http://repub.eur.nl/res/pub/24243/ 2009-08-01T00:00:00Z Purpose: Failed conversion of epidural labor analgesia (ELA) to epidural surgical anesthesia (ESA) for intrapartum Cesarean delivery (CD) has been observed in clinical practice. However, spinal anesthesia (SA) in parturients experiencing failed conversion of ELA to ESA has been associated with an increased incidence of serious side effects. In this retrospective cohort analysis, we examined our routine clinical practice of removing the in situ epidural, rather than attempting to convert to ESA, prior to administering SA for intrapartum CD. Methods: Hemodynamic data, frequencies of either high or total spinal block, and maternal and neonatal outcome data were gathered from the anesthesia records of all parturients at the Amphia Hospital, undergoing intrapartum CD between January 1, 2001 and May 1, 2005. Results: Complete data were available for 693 patients (97.6%) of the 710 medical records that were identified. Of the 693 patients, 508 (73.3%) had no ELA and received SA, 128 patients (18.5%) received SA following epidural anesthesia for labor, 19 (2.7%) underwent conversion of ELA to ESA, and 38 (5.5%) received general anesthesia. When comparing both SA groups, no clinically relevant differences were observed regarding the incidence of total spinal block (0% in both groups) or high spinal block (0.2 vs 0.8%, P = 0.36). The number of hypotensive episodes, the total amount of ephedrine administered, and the Apgar scores recorded at 5 and 10 min were similar amongst groups. Conclusions: The incidence of serious side effects associated with SA for intrapartum CD following ELA is low and not different compared to SA only. http://repub.eur.nl/res/pub/24263/ 2009-08-01T00:00:00Z The incidence of postoperative stroke ranges from 0.08% to 0.7% in noncardiac surgery. Recently, the PeriOperative ISchemic Evaluation (POISE) study reported an incidence of postoperative stroke of 1% in patients scheduled for noncardiac surgery when β blockers were initiated immediately before surgery. To assess the association between chronic β-blocker use and postoperative stroke in noncardiac surgery, we undertook a case-control study among 186,779 patients who underwent noncardiac surgery from 2000 to 2008 at the Erasmus Medical Centre. Patients who were undergoing intracerebral surgery or carotid surgery or who had head and/or carotid trauma were excluded. The case subjects were 34 patients (0.02%) who had experienced a stroke within 30 days after surgery. Of the remaining patients, 2 controls were selected for each case and were stratified according to calendar year, type of surgery, and age. For cases and controls, information was obtained regarding β-blocker use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. The use of β blockers was as common in the cases as in the controls (29% vs 29%; p = 1.0). The adjusted odds ratio for postoperative stroke among β-blocker users compared with nonusers was 0.4 (95% confidence interval 0.1 to 1.5). Similar results were obtained in the subgroups of patients stratified according to the use of cardiovascular therapy and the presence of cardiac risk factors. In conclusion, the present case-control study has shown no increased risk of postoperative stroke in patients taking chronic β-blocker therapy. http://repub.eur.nl/res/pub/24894/ 2009-08-01T00:00:00Z Background: In patients with ischaemic cardiomyopathy and viable myocardium, left ventricular ejection fraction (LVEF) does not always improve after revascularisation. Whether this may affect prognosis is unclear. Objective: To evaluate the prognosis of viable patients with and without improvement of LVEF after coronary revascularisation. Methods: Before revascularisation, radionuclide ventriculography (RNV) and dobutamine stress echocardiography were performed to assess LVEF and myocardial viability, respectively. Nine to 12 months after revascularisation, LVEF improvement was assessed by RNV. Patients were divided into three groups: group 1, viable patients with LVEF improvement (n=27); group 2, viable patients without LVEF improvement (n=15), group 3, non-viable patients (n=48). Cardiac events were evaluated during a 4-year follow-up. Results: After revascularisation, the mean (SD) LVEF improved from 32 (9)% to 42 (10)% in group 1, but did not change significantly in group 2 and in group 3, p<0.001 by analysis of variance (ANOVA). Heart failure symptoms improved in both groups 1 (mean (SD) NYHA class from 3.1 (0.9) to 1.7 (0.7)) and 2 (from 3.2 (0.7) to 1.7 (0.9)), but not in group 3 (from 2.8 (1.0) to 2.7 (0.5)), p<0.001 by ANOVA. During follow-up, the cardiac event rate was low (4%) in group 1, intermediate (21%) in group 2 and high (33%) in group 3 (p=0.01). Conclusion: The best prognosis after revascularisation may be expected in those viable patients whose LVEF improves. Conversely, viable patients without functional improvement have an intermediate prognosis. http://repub.eur.nl/res/pub/25425/ 2009-08-01T00:00:00Z OBJECTIVE - It is unclear whether the coronary atherosclerotic plaque burden is similar in patients with type 1 and type 2 diabetes. By using multislice computed tomography (MSCT), the presence, degree, and morphology of coronary artery disease (CAD) in patients with type 1 and type 2 diabetes were compared. RESEARCH DESIGN AND METHODS - Prospectively, coronary artery calcium (CAC) scoring and MSCT coronary angiography were performed in 135 asymptomatic patients (65 patients with type 1 diabetes and 70 patients with type 2 diabetes). The presence and extent of coronary atherosclerosis as well as plaque phenotype were assessed and compared between groups. RESULTS - No difference was observed in average CAC score (217 ± 530 vs. 174 ± 361) or in the prevalence of coronary atherosclerosis (65% vs. 71%) in patients with type 1 and type 2 diabetes. However, the prevalence of obstructive atherosclerosis was higher in patients with type 2 diabetes (n = 24; 34%) compared with that in patients with type 1 diabetes (n = 11; 17%) (P = 0.02). In addition, a higher mean number of atherosclerotic and obstructive plaques was observed in patients with type 2 diabetes. In addition, the percentage of noncalcified plaques was higher in patients with type 2 (66%) versus type 1 diabetes (27%) (P < 0.001), resulting in a higher plaque burden for each CAC score compared with that in type 1 diabetic patients. CONCLUSIONS - Although CAC scores and the prevalence of coronary atherosclerosis were similar between patients with type 1 and type 2 diabetes, CAD was more extensive in the latter. Also, a relatively higher proportion of noncalcified plaques was observed in patients with type 2 diabetes. These observations may be valuable in the development of targeted management strategies adapted to diabetes type. http://repub.eur.nl/res/pub/24451/ 2009-07-01T00:00:00Z Objective: This study assessed clinical condition at midterm follow-up after total cavopulmonary connection for a functionally univentricular heart performed on children younger than 5 years. Methods: Thirty-four Fontan patients (median age 10.4 years, range 6.8-20.7 years, 22 boys, median follow-up 7.8 years, 5.0-17.8 years) underwent electrocardiography, Holter monitoring, bicycle exercise testing, cardiac magnetic resonance imaging, and N-terminal prohormone brain natriuretic peptide (NT-pro-BNP) analysis. Results: Twenty-three patients (68%) were in sinus rhythm. Holter monitoring demonstrated normal mean heart rate, low maximal heart rate, and no clinically significant arrhythmias or sinus node dysfunction. With maximal bicycle ergometry (n = 19), maximum workload (60% of normal), maximum heart rate (90% of normal), and maximal oxygen uptake (69% of normal) were all significantly lower in the Fontan group than in a control group (P < .001). Variables of submaximal exercise indicated less efficient oxygen uptake during exercise in all Fontan patients. Ejection fraction was lower than in control subjects (59% ± 13% vs 69% ± 5%, P < .001). Mean end-diastolic and end-systolic volumes and ventricular mass were higher than in control subjects (P < .001). Mean NT-pro-BNP levels were increased relative to reference values, but only 8 patients had levels above the upper reference limit. Conclusion: At midterm follow-up, Fontan patients were in acceptable clinical condition, with preserved global ventricular function, moderately decreased exercise capacity, and NT-pro-BNP levels within reference range. Systemic ventricular mass was elevated, however, suggesting contractility-afterload mismatch. Long-term consequences for ventricular function merit further investigation. http://repub.eur.nl/res/pub/24650/ 2009-07-01T00:00:00Z Aims to assess the long-term rate of mortality and the recurrence of potentially life-threatening ventricular arrhythmias in secondary prevention implantable cardioverter defibrillator (ICD) patients and to construct a model for baseline risk stratification.Methods and resultsSince 1996, all patients with ischaemic heart disease, receiving ICD therapy for secondary prevention of sudden death, were included in the current study. Patients were evaluated at implantation and during long-term follow-up. A total of 456 patients were included in the analysis and followed for 54 ± 35 months. During follow-up, 100 (22) patients died and ICD therapy was noted in 216 (47) patients, of which 138 (30) for fast, potentially life-threatening ventricular arrhythmia. Multivariate analysis revealed a history of atrial fibrillation or flutter (AF), ventricular tachycardia as presenting arrhythmia, and wide QRS and poor left ventricular ejection fraction as independent predictors of life-threatening ventricular arrhythmias. The strongest predictor was AF with a hazard ratio of 2.1 (95 confidence interval 1.3-3.2). On the basis of the available clinical data, it was not possible to identify a group which exhibited no risk on recurrence of potentially life-threatening ventricular arrhythmias.ConclusionIschaemic secondary prevention ICD recipients exhibit a high recurrence rate of potentially life-threatening ventricular arrhythmias. Factors that increase risk can be identified but, even with these factors, it was not possible to distinguish a recurrence-free group. http://repub.eur.nl/res/pub/17145/ 2009-06-01T00:00:00Z Hyperglycemia is common among patients admitted with acute coronary syndromes (ACS) and is associated with less favorable clinical outcomes. Guidelines for the treatment of hyperglycemia in myocardial infarction are confusing, partly because of lack of sufficient evidence. Neither do we know what the everyday practice on hyperglycemia in ACS is. Therefore the aim of our study is to describe current glucose management in ACS patients in The Netherlands. We designed a multiple-choice questionnaire that was emailed to all 94 independent cardiology departments of each of the 114 hospitals within The Netherlands. We interviewed cardiologists about their specific hospital setting, the presence, content, and actual use of a dedicated hyperglycemia protocol in the setting of ACS. Ninety-four questionnaires were returned (response rate 100%). Only 32% of the respondents reported to have a routinely applied, dedicated hyperglycemia protocol in the setting of ACS. An admission glucose of 13.0 mmol/L is considered a stress value by 60% of respondents. Treatment of hyperglycemia is postponed until after the acute phase (ie, after >6 hours) in 41% of the cardiology departments and in 76% HbA1c is not routinely measured before discharge. Only a minority of Dutch cardiology departments have a routinely applied, dedicated hyperglycemia protocol for patients admitted with ACS. Different views exist on the interpretation of admission hyperglycemia in patients without previously diagnosed diabetes. Dedicated protocols with well-established treatment goals allow early treatment and are mandatory to improve timely metabolic regulation. © 2009 Lippincott Williams & Wilkins, Inc. http://repub.eur.nl/res/pub/24648/ 2009-06-01T00:00:00Z AimsAngiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using individual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of perindopril-based regimen in patients with vascular disease or at high risk of vascular disease.Methods and resultsWe studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a perindopril-based treatment regimen or placebo. The perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89; 95 confidence interval (CI) 0.82-0.96; P = 0.006], cardiovascular mortality (HR 0.85; 95 CI 0.76-0.95; P = 0.004), non-fatal myocardial infarction (HR 0.80; 95 CI 0.71-0.90; P < 0.001), stroke (HR 0.82; 95 CI 0.74-0.92; P = 0.002), and heart failure (HR 0.84; 95 CI 0.72-0.96; P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure.ConclusionThis study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (perindopril-indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease. http://repub.eur.nl/res/pub/24745/ 2009-06-01T00:00:00Z Objective: This study evaluated the effectiveness and safety of beta-blockers and statins for the prevention of perioperative cardiovascular events in intermediate-risk patients undergoing noncardiovascular surgery. SUMMARY BACKGROUND DATA:: Beta-blockers and statins reduce perioperative cardiac events in high-risk patients undergoing vascular surgery by restoring the myocardial oxygen supply/demand balance and/or stabilizing coronary plaques. However, their effects in intermediate-risk patients remained ill-defined. METHODS:: In this randomized open-label 2 × 2 factorial design trial 1066 intermediate cardiac risk patients were assigned to bisoprolol, fluvastatin, combination treatment, or control therapy before surgery (median: 34 days). Intermediate risk was defined by an estimated risk of perioperative cardiac death and myocardial infarction (MI) of 1% to 6%, using clinical data and type of surgery. Starting dose of bisoprolol was 2.5 mg daily, titrated to a perioperative heart rate of 50 to 70 beats per minute. Fluvastatin was prescribed in a fixed dose of 80 mg. The primary end point was the composite of 30-day cardiac death and MI. This study is registered in the ISRCTN registry and has the ID number ISRCTN47637497. RESULTS:: Patients randomized to bisoprolol (N = 533) had a lower incidence of perioperative cardiac death and nonfatal MI than those randomized to bisoprolol-control (2.1% vs. 6.0% events; hazard ratios: 0.34; 95% confidence intervals: 0.17-0.67; P = 0.002). Patients randomized to fluvastatin experienced a lower incidence of the end point than those randomized to fluvastatin-control therapy (3.2% vs. 4.9% events; hazard ratios: 0.65; 95% confidence intervals: 0.35-1.10), but statistical significance was not reached (P = 0.17). CONCLUSION:: Bisoprolol was associated with a significant reduction of 30-day cardiac death and nonfatal MI, while fluvastatin showed a trend for improved outcome. Copyright http://repub.eur.nl/res/pub/25170/ 2009-05-20T00:00:00Z Context Previous studies have suggested that bone marrow cell injection may improve myocardial perfusion and left ventricular (LV) function in patients with chronic myocardial ischemia. Objective To investigate the effect of intramyocardial bone marrow cell injection on myocardial perfusion and LV function in patients with chronic myocardial ischemia. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial at a Netherlands university hospital, May 1, 2005-March 3, 2008 (6-month follow-up ended September 2008) of 50 patients with chronic myocardial ischemia (mean age [SD], 64 [8] years; 43 men). Inclusion criteria: severe angina pectoris despite optimal medical therapy and myocardial ischemia. All patients were ineligible for conventional revascularization. Interventions Intramyocardial injection of 100X 106autologous bone marrowderived mononuclear cells or placebo solution. Main Outcome Measures Primarily, the summed stress score, a 17-segment score for stress myocardial perfusion assessed by Tc-99m tetrofosmin single-photon emission computed tomography (SPECT), Secondary included LV ejection fraction (LVEF), Canadian Cardiovascular Society (CCS) class, and Seattle Angina Questionnaire qualityof-life score (mean difference >5% considered clinically significant). Results After 3-month follow-up, the summed stress score (mean [SD]) improved from 23.5 (4.7) to 20,1 (4,6) (P < .001) in the bone marrow cell group, compared with a decrease from 24.8 (5.5) to 23.7 (5.4) (P=.004) in the placebo group. In the bone marrow cell-treated patients who underwent magnetic resonance imaging (MRI), a 3% absolute increase in LVEF was observed at 3 months (95% CI, 0.5% to 4.7%; n=18), but the placebo group showed no improvement. CCS angina score improved significantly in the bone marrow cell group (6-month absolute difference, -0.79; 95% CI, -1.10 to -0.48; P<.001) compared with no significant improvement in the placebo group. Qualityof-life score increased from 56% (9%) to 64% (12%) at 3 months and 69% (12%) at 6 months in bone marrow cell-treated patients, compared with a smaller increase in the placebo group from 57% (11 %) to 61 % (14%) to 64% (17%). The improvements in CCS class and quality of life score were significantly greater in bone marrow cell-treated patients than in place bo-treated patients (P=.03 and P=.04, respectively). Conclusions In this short-term study of patients with chronic myocardial ischemia refractory to medical treatment, intramyocardial bone marrow cell injection resulted in a statistically significant but modest improvement in myocardial perfusion compared with placebo. Further studies are required to assess long-term results and efficacy for mortality and morbidity. Trial Registrations trialregister.nl Identifier: NTR400 and isrctn.org Identifier: ISRCTN58194927 http://repub.eur.nl/res/pub/24343/ 2009-05-01T00:00:00Z Objective: Advanced ischemic heart failure can be treated with surgical ventricular restoration (SVR). While numerous risk factors for mortality and recurrent heart failure have been identified, no plain predictor for identifying SVR patients with left ventricular damage beyond recovery is yet available. We tested echocardiographic wall motion score index (WMSI) as a predictor for mortality or poor functional result. Methods: One hundred and one patients electively operated between April 2002 and April 2007 were included for analysis. All patients had advanced ischemic heart failure (NYHA-class ≥ III and LVEF ≤ 35%). Mean logistic EuroSCORE was 10 ± 8. All patients were evaluated at 1-year follow-up. Risk factors for poor outcome, defined as mortality or poor functional result (NYHA class ≥ III) at 1-year follow-up were identified by univariable logistic regression analysis. Preoperatively, a 16-segment echocardiographic WMSI was calculated and receiver operating characteristic curve analysis was used to identify cut-off values for WMSI in predicting poor outcome. Results: Early mortality was 9.9%, late mortality 6.6%. NYHA class improved from 3.2 ± 0.4 to 1.5 ± 0.7. At 1-year follow-up, 10 patients (12%) were in NYHA class III and the remaining patients were in NYHA class I or II (75 patients, 88%). WMSI was found to be the only statistically significant predictor for poor outcome (odds ratio 139, 95% confidence interval (CI) 17-1116, p < 0.0001). The optimal cut-off value for WMSI in predicting mortality or poor functional result was 2.19 with a sensitivity and specificity of 82% (95% CI 81.5-82.5% and 81.4-82.6%). The area under the curve was 0.94 (95% CI 0.90-0.99). Positive and negative predictive values were 67% and 92% respectively (95% CI 66.4-67.6% and 91.4-92.6%). Conclusions: Sufficient residual remote myocardium is necessary to recover from a SVR procedure and to translate the surgically induced morphological changes into a functional improvement. Preoperative WMSI is a surrogate measure of residual remote myocardial function and is a promising tool for better patient selection to improve results after SVR procedures for advanced ischemic heart failure. http://repub.eur.nl/res/pub/25433/ 2009-05-01T00:00:00Z The significance of left ventricular (LV) dyssynchrony for the prediction of response to cardiac resynchronization therapy (CRT) has been demonstrated. Parameters reflecting LV dyssynchrony (phase SD, histogram bandwidth) can be derived from gated myocardial perfusion SPECT (GMPS) using phase analysis. The feasibility of LV dyssynchrony assessment with phase analysis on GMPS using Quantitative Gated SPECT (QGS) software has not been demonstrated in patients undergoing CRT. The aim of the present study was to validate the QGS algorithm for phase analysis on GMPS in a direct comparison with echocardiography using tissue Doppler imaging (TDI) for LV dyssynchrony assessment. Also, prediction of response to CRT using GMPS and phase analysis was evaluated. Methods: Patients (n = 40) with severe heart failure (New York Heart Association class III-IV), an LV ejection fraction of no more than 35%, and a QRS complex greater than or equal to 120 ms were evaluated for LV dyssynchrony using GMPS and echocardiography with TDI. At baseline and after 6 mo of CRT, clinical status, LV volumes, and LV ejection fraction were evaluated. Patients with functional improvement were classified as CRT responders. Results: Both histogram bandwidth (r = 0.69, r2= 0.48, SEE = 25.4, P < 0.01) and phase SD (r = 0.65, r2= 0.42, SEE = 26.8, P < 0.01) derived from GMPS correlated significantly with TDI for assessment of LV dyssynchrony. At baseline, CRT responders showed a significantly larger histogram bandwidth (94° ± 23° vs. 68° ± 21°, P < 0.01) and a larger phase SD (26° ± 6° vs. 18° ± 5°, P < 0.01) than did nonresponders. Receiver-operating-characteristic curve analysis identified an optimal cutoff value of 72.5° for histogram bandwidth to predict CRT response, yielding a sensitivity of 83% and a specificity of 81%. For phase SD, sensitivity and specificity similar to those for histogram bandwidth were obtained at a cutoff value of 19.6°. Conclusion: QGS phase analysis on GMPS correlated significantly with TDI for the assessment of LV dyssynchrony. Moreover, a high accuracy for prediction of response to CRT was obtained using either histogram bandwidth or phase SD. Copyright http://repub.eur.nl/res/pub/27139/ 2009-05-01T00:00:00Z OBJECTIVES: High-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with the presence of coronary artery disease. The aim of this study was to assess the prognostic value of hs-CRP and NT-proBNP for postoperative cardiac events in noncardiac vascular surgery patients. METHODS: In 592 patients, cardiac history, hs-CRP, and NT-proBNP levels were assessed preoperatively. Levels of hs-CRP of at least 6.5 mg/l and NT-proBNP of at least 350 pg/ml were defined as the optimal cut-off values for the prediction of postoperative cardiac events. The end point was the composite of 30-day cardiovascular death, Q-wave myocardial infarction, and troponin T release. Multivariable regression analysis was used to evaluate the association between hs-CRP, NT-proBNP and the end point. The performance of the risk models based on cardiac risk factors alone and the addition of both biomarkers was determined using C statistics. RESULTS: After adjustment for cardiac risk factors, site of surgery and type of procedure, elevated levels of hs-CRP (odds ratio 2.54; 95% confidence interval 1.50-4.30) and NT-proBNP (odds ratio 4.78; 95% confidence interval 2.71-8.42) remained independent predictors for postoperative cardiac events. When hs-CRP and NT-proBNP were added to the cardiac risk score, the C statistic improved from 0.79 to 0.84. A combined elevation of hs-CRP and NT-proBNP provided a seven-fold higher risk for postoperative cardiac events. CONCLUSION: Both hs-CRP and NT-proBNP have additional value in the prediction of postoperative cardiac events in vascular surgery patients. Their integrated use improves cardiac risk stratification. http://repub.eur.nl/res/pub/16232/ 2009-04-03T00:00:00Z Background: Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are alternative treatments for multivessel coronary disease. Although the procedures have been compared in several randomised trials, their long-term effects on mortality in key clinical subgroups are uncertain. We undertook a collaborative analysis of data from randomised trials to assess whether the effects of the procedures on mortality are modified by patient characteristics. Methods: We pooled individual patient data from ten randomised trials to compare the effectiveness of CABG with PCI according to patients' baseline clinical characteristics. We used stratified, random effects Cox proportional hazards models to test the effect on all-cause mortality of randomised treatment assignment and its interaction with clinical characteristics. All analyses were by intention to treat. Findings: Ten participating trials provided data on 7812 patients. PCI was done with balloon angioplasty in six trials and with bare-metal stents in four trials. Over a median follow-up of 5·9 years (IQR 5·0-10·0), 575 (15%) of 3889 patients assigned to CABG died compared with 628 (16%) of 3923 patients assigned to PCI (hazard ratio [HR] 0·91, 95% CI 0·82-1·02; p=0·12). In patients with diabetes (CABG, n=615; PCI, n=618), mortality was substantially lower in the CABG group than in the PCI group (HR 0·70, 0·56-0·87); however, mortality was similar between groups in patients without diabetes (HR 0·98, 0·86-1·12; p=0·014 for interaction). Patient age modified the effect of treatment on mortality, with hazard ratios of 1·25 (0·94-1·66) in patients younger than 55 years, 0·90 (0·75-1·09) in patients aged 55-64 years, and 0·82 (0·70-0·97) in patients 65 years and older (p=0·002 for interaction). Treatment effect was not modified by the number of diseased vessels or other baseline characteristics. Interpretation: Long-term mortality is similar after CABG and PCI in most patient subgroups with multivessel coronary artery disease, so choice of treatment should depend on patient preferences for other outcomes. CABG might be a better option for patients with diabetes and patients aged 65 years or older because we found mortality to be lower in these subgroups. Funding: Agency for Healthcare Research and Quality. http://repub.eur.nl/res/pub/24212/ 2009-04-01T00:00:00Z Background: Angiotensin-converting enzyme (ACE) inhibitors reduce clinical symptoms and improve outcome in patients with hypertension, heart failure, and stable coronary artery disease (CAD) and are among the most frequently used drugs in these patient groups. For hypertension, treatment is guided by the level of blood pressure. In the secondary prevention setting, there are no means of guiding therapy. Prior attempts to target ACE-inhibitors to those patients that are most likely to benefit have not been successful, mainly due to the consistency in the treatment effect in clinical subgroups. Still, for prolonged prophylactic treatment with ACE-inhibitors it would be best to target treatment to only those patients most likely to benefit, which would considerably lower the number needed to treat and increase cost-effectiveness. A new approach for such "tailored-therapy" may be to integrate information on the genetic variation between patients. Until now, pharmacogenetic research of the efficacy of ACE-inhibitor therapy in CAD patients is still in a preliminary stage. Methods: The PERindopril GENEtic association study (PERGENE) is a substudy of the EUROPA trial, a randomized double-blind placebo-controlled multicentre clinical trial which demonstrated a beneficial effect of the ACE-inhibitor perindopril in reducing cardiovascular morbidity and mortality in 12.218 patients with stable coronary artery disease (mean follow-up 4.2 years). Blood tubes were received from patients at the beginning of the EUROPA trial and buffy coats were stored at -40°C at the central core laboratory. Candidate genes were selected in the renin-angiotensin-system and bradykinin pathways. Polymorphisms were selected based on haplotype tagging principles using the HapMap genome project, Seattle and other up-to-date genetic database platforms to comprehensively cover all common genetic variation within the genes. Selection also took into consideration the functionality of SNP's, location within the gene (promoter) and existing relevant literature. The main outcome measure of PERGENE is the effect of genetic factors on the treatment benefit with ACE-inhibitors. The size of this pharmacogenetic substudy allows detection with a statistical power of 98% to detect a difference in hazard ratios (treatment effect) of 20% between genotypes with minor allele frequency of 0.20 (two-sided alpha 0.05). Conclusion: The PERGENE study is a large cardiovascular pharmacogenetic study aimed to assess the feasibility of pharmacogenetic profiling of the treatment effect of ACE-inhibitor use with the perspective to individualize treatment in patients with stable coronary artery disease. http://repub.eur.nl/res/pub/24259/ 2009-04-01T00:00:00Z Prophylactic coronary revascularization in vascular surgery patients with extensive coronary artery disease was not associated with an improved immediate postoperative outcome. However, the potential long-term benefit was unknown. This study was performed to assess the long-term benefit of prophylactic coronary revascularization in these patients. Of 1,880 patients scheduled for major vascular surgery, 430 had ≥3 risk factors (age >70 years, angina pectoris, myocardial infarction, heart failure, stroke, diabetes mellitus, and renal failure). All underwent cardiac testing using dobutamine echocardiography or nuclear stress imaging. Patients with extensive stress-induced ischemia (≥5 segments or ≥3 walls) were randomly assigned to additional revascularization. In total, 101 patients showed extensive ischemia and were assigned to revascularization (n = 49) or no revascularization (n = 52). After 2.8 years, the overall survival rate was 64% for patients randomly assigned to no preoperative coronary revascularization versus 61% for patients assigned to preoperative coronary revascularization (hazard ratio [HR] 1.18, 95% confidence interval [CI] 0.63 to 2.19, p = 0.61). Rates for survival free of all-cause death, nonfatal myocardial infarction, and coronary revascularization were similar in both groups at 49% and 42% for patients allocated to medical treatment or coronary revascularization, respectively (HR 1.51, 95% CI 0.89 to 2.57, p = 0.13). Only 2 patients assigned to medical treatment required coronary revascularization during follow-up. Also, in patients who survived the first 30 days after surgery, there was no apparent benefit of revascularization on cardiac events (HR 1.35, 95% CI 0.72 to 2.52, p = 0.36). In conclusion, preoperative coronary revascularization in high-risk patients undergoing major vascular surgery was not associated with improved postoperative or long-term outcome compared with the best medical treatment. http://repub.eur.nl/res/pub/25239/ 2009-04-01T00:00:00Z Diagnosing catheter-related bloodstream infection (CRBSI) still often involves tip culture. The conventional method is the semiquantitative roll plate method. However, the use of a quantitative sonication technique could have additional value, as it may detect endoluminal microorganisms more easily. Because endoluminal infection tends to occur in long-term central venous catheters, we compared both techniques for patients with long-term tunnelled catheters. For 313 consecutive Hickman catheter tips from 279 hematological patients, colonization detection rates were compared by performing both techniques in a random order, using conventional detection cutoffs. Additionally, for the subgroup of patients with clinical suspicion of CRBSI (n = 89), the diagnostic values of both techniques were compared. The overall tip colonization rate was 25%. For each technique, the detection rate tended to be better if that technique was performed first. The diagnostic performance for the subgroup of patients with clinical suspicion of CRBSI was limited and not different for both methods. Sensitivity and specificity were 45% and 84%, respectively, for sonication versus 35% and 90%, respectively, for the roll plate technique. The fact that 35 of 40 patients with CRBSI received antimicrobial therapy before catheter removal and tip culture, in an attempt to salvage the catheter, may partly explain this poor performance. No differences were observed when catheters were stratified according to in situ time below or above the median of 4 weeks. The sonication culture technique was not better than the roll plate method to diagnose tip colonization or CRBSI in patients with long-term tunnelled catheters. Copyright http://repub.eur.nl/res/pub/16173/ 2009-03-20T00:00:00Z Rede, In verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar Klinische epidemiologie van hart- en vaatziekten aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 20 maart 2009. De leidende gedachte binnen het vakgebied Klinische epidemiologie is dat medisch handelen gebaseerd dient te zijn op het best beschikbare bewijs van zijn werkzaamheid en doeltreffendheid. Dat bewijs is niet gegrond op de persoonlijke ervaring van patiënten, noch op de klinische expertise van individuele artsen, hoe waardevol deze elementen ook zijn. Maar het bewijs voor de effectiviteit van het klinisch handelen is bij voorkeur afkomstig van wetenschappelijk onderzoek onder groepen patiënten, waarin theoretische concepten worden getoetst, en waarbij gezocht wordt naar relaties tussen het optreden en het beloop van ziekten enerzijds, en verklarende factoren of determinanten daarvan anderzijds.|1 Deze determinanten kunnen zowel oorzakelijke als niet-oorzakelijke factoren zijn. Vanzelfsprekend dient onderzoek naar determinant-uitkomst relaties te worden opgezet en uitgevoerd in overeenstemming met kwalitatief hoogstaande standaarden. http://repub.eur.nl/res/pub/24098/ 2009-03-01T00:00:00Z Purpose: To assess normal values for biventricular function, volumes, and mass with current cardiovascular magnetic resonance (CMR) imaging sequences in children. Materials and Methods: Included in the study were 60 healthy children aged 8-17 years. A short axis set of contiguous slices was acquired with CMR imaging employing steady-state free precession. Biventricular end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), and mass were determined. Uni- and multivariate linear regression analyses were performed to study the interrelation of age, gender, and body surface area (BSA) on biventricular volumes and mass. The coefficient of variation was calculated for intra- and interobserver variability. Results: EF did not differ between boys and girls (mean LV-EF 69 ± (SD) 5%, mean RV-EF 65 ± 5%). BSA had good (EDV, mass) and modest (ESV) correlation with biventricular measurements. Gender appeared a significant modifier of these relations, whereas age had no independent contribution. The intra- and interobserver coefficient of variation was in the range 2.1%-13.9°/o for biventricular EDV, ESV,and mass. Conclusion: This study reveals gender-specific normative data for biventricular function, volumes, and mass in children age 8-17 years that can be used as reference data in the follow-up of pediatric cardiac patients. http://repub.eur.nl/res/pub/27217/ 2009-03-01T00:00:00Z Drugs that modulate the renin-angiotensin-aldosterone system (RAAS) play an important role in modern cardiovascular prevention strategies. Inhibitors of the RAAS, in particular angiotensin-converting enzyme (ACE) inhibitors, have been proven to be beneficial in specific patient groups, including patients with hypertension, heart failure, diabetes mellitus and stable coronary artery disease. Although clinical trials demonstrated a rather consistent beneficial effect of ACE inhibitors across groups of patients based on clinical characteristics, the variability in treatment response on the individual patient level is extensive. Recent publications suggest that genetic polymorphisms in the RAAS are related to cardiovascular risk. Genetic variability also seems associated with the response to ACE inhibitor therapy, and can probably be used to tailor treatment. This review discusses several approaches to guide ACE inhibitor therapy in patients with coronary artery disease. In addition, the potential impact of pharmacogenetics regarding this particular topic is highlighted. Copyright http://repub.eur.nl/res/pub/24400/ 2009-02-17T00:00:00Z Objectives: This study was designed to determine whether multislice computed tomography (MSCT) coronary angiography has incremental prognostic value over single-photon emission computed tomography myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD). Background: Although MSCT is used for the detection of CAD in addition to MPI, its incremental prognostic value is unclear. Methods: In 541 patients (59% male, age 59 ± 11 years) referred for further cardiac evaluation, both MSCT and MPI were performed. The following events were recorded: all-cause death, nonfatal infarction, and unstable angina requiring revascularization. Results: In the 517 (96%) patients with an interpretable MSCT, significant CAD (MSCT ≥50% stenosis) was detected in 158 (31%) patients, and abnormal perfusion (summed stress score [SSS]: ≥4) was observed in 168 (33%) patients. During follow-up (median 672 days; 25th, 75th percentile: 420, 896), an event occurred in 23 (5.2%) patients. After correction for baseline characteristics in a multivariate model, MSCT emerged as an independent predictor of events with an incremental prognostic value to MPI. The annualized hard event rate (all-cause mortality and nonfatal infarction) in patients with none or mild CAD (MSCT <50% stenosis) was 1.8% versus 4.8% in patients with significant CAD (MSCT ≥50% stenosis). A normal MPI (SSS <4) and abnormal MPI (SSS ≥4) were associated with an annualized hard event rate of 1.1% and 3.8%, respectively. Both MSCT and MPI were synergistic, and combined use resulted in significantly improved prediction (log-rank test p value <0.005). Conclusions: MSCT is an independent predictor of events and provides incremental prognostic value to MPI. Combined anatomical and functional assessment may allow improved risk stratification. http://repub.eur.nl/res/pub/24399/ 2009-02-10T00:00:00Z Objectives: The aim of the current study was to evaluate the relation between the extent of left ventricular (LV) reverse remodeling and clinical/echocardiographic improvement after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome. Background: Despite the current selection criteria, individual response to CRT varies significantly. Furthermore, it has been suggested that reduction in left ventricular end-systolic volume (LVESV) after CRT is related to outcome. Methods: A total of 302 CRT candidates were included. Clinical status and echocardiographic evaluation were performed before implantation and after 6 months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Results: Based on different extents of LV reverse remodeling, 22% of patients were classified as super-responders (decrease in LVESV ≥30%), 35% as responders (decrease in LVESV 15% to 29%), 21% as nonresponders (decrease in LVESV 0% to 14%), and 22% negative responders (increase in LVESV). More extensive LV reverse remodeling resulted in more clinical improvement, with a larger increase in LV function and more reduction in mitral regurgitation. In addition, more LV reverse remodeling resulted in less heart failure hospitalizations and lower mortality during long-term follow-up (22 ± 11 months); 1- and 2-year hospitalization-free survival rates were 90% and 70% in the negative responder group compared with 98% and 96% in the super-responder group (log-rank p value <0.001). Conclusions: The extent of LV reverse remodeling at midterm follow-up is predictive for long-term outcome in CRT patients. http://repub.eur.nl/res/pub/30138/ 2008-12-01T00:00:00Z Background: Invasive pulmonary aspergillosis (IPA) is a leading cause of mortality in immunocompromised patients, with the highest risk observed in patients with acute leukaemia or lung transplantation. IPA-prophylactic strategies include administration of aerosolized amphotericin-B. Liposomal amphotericin-B (L-AmB) is one of the formulations available, although few data exist on safety and tolerability. Methods: Data on tolerability, systemic toxicity and effects of aerosolized L-AmB on pulmonary function were recorded in a subgroup out of 271 haematological patients enrolled in a placebo-controlled trial on the efficacy of aerosolized L-AmB for the prevention of IPA. Using an adaptive aerosol-delivery system, nebulization of L-AmB or placebo was performed during chemotherapy-induced neutropenia for 30 min/day on 2 consecutive days/week with a maximum of 6 weeks. Results: Thirty-eight patients (41 episodes) received L-AmB, 39 patients (49 episodes) received placebo. Proportions of patients with >20% post-nebulization decline in forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) did not differ between groups. Also 26/38 L-AmB patients (68%) versus 31/39 patients (79%) on placebo had no significant decline during the entire treatment (p=0.20). Coughing was significantly more reported in L-AmB patients (p<0.0001). No differences were observed when baseline and post-nebulization serum levels of renal function and hepatic enzymes were compared. Conclusions: Short-term prophylactic nebulization of L-AmB was well tolerated and not associated with decline in pulmonary function or systemic adverse effects. http://repub.eur.nl/res/pub/29372/ 2008-11-12T00:00:00Z http://repub.eur.nl/res/pub/14657/ 2008-10-21T00:00:00Z Objectives: The aim of the current study was to evaluate echocardiographic parameters after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome in patients with the left ventricular (LV) lead positioned at the site of latest activation (concordant LV lead position) as compared with that seen in patients with a discordant LV lead position. Background: A nonoptimal LV pacing lead position may be a potential cause for nonresponse to CRT. Methods: The site of latest mechanical activation was determined by speckle tracking radial strain analysis and related to the LV lead position on chest X-ray in 244 CRT candidates. Echocardiographic evaluation was performed after 6 months. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Results: Significant LV reverse remodeling (reduction in LV end-systolic volume from 189 ± 83 ml to 134 ± 71 ml, p < 0.001) was noted in the group of patients with a concordant LV lead position (n = 153, 63%), whereas patients with a discordant lead position showed no significant improvements. In addition, during long-term follow-up (32 ± 16 months), less events (combined for heart failure hospitalizations and death) were reported in patients with a concordant LV lead position. Moreover, a concordant LV lead position appeared to be an independent predictor of hospitalization-free survival after long-term CRT (hazard ratio: 0.22, p = 0.004). Conclusions: Pacing at the site of latest mechanical activation, as determined by speckle tracking radial strain analysis, resulted in superior echocardiographic response after 6 months of CRT and better prognosis during long-term follow-up. http://repub.eur.nl/res/pub/14551/ 2008-10-01T00:00:00Z Real-time 3-dimensional echocardiography (RT3DE) can provide a unique combination of accurate left atrial (LA) volume quantification and rapid, automatic assessment of LA function. The aim of the study was to evaluate the changes in LA volumes and function in patients with atrial fibrillation (AF) undergoing radiofrequency catheter ablation (RFCA) using RT3DE; 57 consecutive patients referred for RFCA were studied. Paroxysmal AF was present in 43 patients (75%) and persistent AF in 14 (25%). After a mean follow-up of 7.9 ± 2.7 months, patients were divided into 2 groups: successful RFCA (SR group) and recurrence of AF (AF group). RT3DE was performed before, within 3 days, and 3 months after RFCA to assess LA volumes (maximum, minimum, and preA) and LA functions (passive, active, and reservoir). A total of 38 patients (67%) had successful RFCA (SR group). Immediately after RFCA, no significant changes in LA volumes and function were observed. After 3 months, a significant reduction in LA volumes (maximum: 26 ± 8 to 23 ± 7 ml/m2, p <0.01) was noted only in the SR group, with a significant improvement in LA active (22 ± 8% to 33 ± 9%, p <0.01) and reservoir functions (116 ± 45% to 152 ± 54%, p <0.01). Conversely, the AF group showed a trend towards a deterioration of LA volumes and function. In conclusion, in patients who maintain sinus rhythm after RFCA, a significant reverse remodeling and functional improvement of the left atrium is observed using RT3DE. http://repub.eur.nl/res/pub/14686/ 2008-10-01T00:00:00Z Aims: Atherosclerotic plaque characteristics play an important role in the development of coronary events. We investigated coronary plaque characteristics on multi-slice computed tomography (MSCT) and virtual histology intravascular ultrasound (VH IVUS) in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). Methods and results: Fifty patients (25 with ACS, 25 with stable CAD) underwent 64-slice MSCT followed by VH IVUS in 48 (96%) patients. In ACS patients, 32% of plaques were non-calcified on MSCT and 59% were mixed [corresponding odds ratio (95% confidence intervals): 3.9 (1.6-9.5), P = 0.003 and 3.4 (1.6-6.9), P = 0.001, respectively]. In patients with stable CAD, completely calcified lesions were more prevalent (61%). On VH IVUS, the percentage of necrotic core was higher in the plaques of ACS patients (11.16 ± 6.07 vs. 9.08 ± 4.62% in stable CAD, P = 0.02). In addition, thin cap fibroatheroma was more prevalent in ACS patients (32 vs. 3% in patients with stable CAD, P < 0.001) and was most frequently observed in mixed plaques on MSCT. Plaque composition both on MSCT and VH IVUS was identical between culprit and non-culprit vessels of ACS patients. Conclusion: On MSCT, differences in plaque characterization were demonstrated between patients with ACS and stable CAD. Plaques of ACS patients showed features of vulnerability to rupture on VH IVUS. Potentially, MSCT may be useful for non-invasive identification of atherosclerotic plaque patterns associated with higher risk. http://repub.eur.nl/res/pub/29765/ 2008-09-30T00:00:00Z Objectives: We sought to determine the risk of late stent thrombosis (ST) during long-term follow-up beyond 3 years, searched for predictors, and assessed the impact of ST on overall mortality. Background: Late ST was reported to occur at an annual rate of 0.6% up to 3 years after drug-eluting stent (DES) implantation. Methods: A total of 8,146 patients underwent percutaneous coronary intervention with a sirolimus-eluting stent (SES) (n = 3,823) or paclitaxel-eluting stent (PES) (n = 4,323) and were followed up to 4 years after stent implantation. Dual antiplatelet treatment was prescribed for 6 to 12 months. Results: Definite ST occurred in 192 of 8,146 patients with an incidence density of 1.0/100 patient-years and a cumulative incidence of 3.3% at 4 years. The hazard of ST continued at a steady rate of 0.53% (95% confidence interval [CI]: 0.44 to 0.64) between 30 days and 4 years. Diabetes was an independent predictor of early ST (hazard ratio [HR]: 1.96; 95% CI: 1.18 to 3.28), and acute coronary syndrome (HR: 2.21; 95% CI: 1.39 to 3.51), younger age (HR: 0.97; 95% CI: 0.95 to 0.99), and use of PES (HR: 1.67; 95% CI: 1.08 to 2.56) were independent predictors of late ST. Rates of death and myocardial infarction at 4 years were 10.6% and 4.6%, respectively. Conclusions: Late ST occurs steadily at an annual rate of 0.4% to 0.6% for up to 4 years. Diabetes is an independent predictor of early ST, whereas acute coronary syndrome, younger age, and PES implantation are associated with late ST. http://repub.eur.nl/res/pub/29131/ 2008-09-09T00:00:00Z Background - Randomized trials that studied clinical outcomes after percutaneous coronary intervention (PCI) with bare metal stenting versus coronary artery bypass grafting (CABG) are underpowered to properly assess safety end points like death, stroke, and myocardial infarction. Pooling data from randomized controlled trials increases the statistical power and allows better assessment of the treatment effect in high-risk subgroups. Methods and Results - We performed a pooled analysis of 3051 patients in 4 randomized trials evaluating the relative safety and efficacy of PCI with stenting and CABG at 5 years for the treatment of multivessel coronary artery disease. The primary end point was the composite end point of death, stroke, or myocardial infarction. The secondary end point was the occurrence of major adverse cardiac and cerebrovascular accidents, death, stroke, myocardial infarction, and repeat revascularization. We tested for heterogeneities in treatment effect in patient subgroups. At 5 years, the cumulative incidence of death, myocardial infarction, and stroke was similar in patients randomized to PCI with stenting versus CABG (16.7% versus 16.9%, respectively; hazard ratio, 1.04, 95% confidence interval, 0.86 to 1.27; P=0.69). Repeat revascularization, however, occurred significantly more frequently after PCI than CABG (29.0% versus 7.9%, respectively; hazard ratio, 0.23; 95% confidence interval, 0.18 to 0.29; P<0.001). Major adverse cardiac and cerebrovascular events were significantly higher in the PCI than the CABG group (39.2% versus 23.0%, respectively; hazard ratio, 0.53; 95% confidence interval, 0.45 to 0.61; P<0.001). No heterogeneity of treatment effect was found in the subgroups, including diabetic patients and those presenting with 3-vessel disease. Conclusions - In this pooled analysis of 4 randomized trials, PCI with stenting was associated with a long-term safety profile similar to that of CABG. However, as a result of persistently lower repeat revascularization rates in the CABG patients, overall major adverse cardiac and cerebrovascular event rates were significantly lower in the CABG group at 5 years. http://repub.eur.nl/res/pub/29764/ 2008-08-19T00:00:00Z Objectives: We sought to determine the diagnostic accuracy of noninvasive visual (computed tomography coronary angiography [CTCA]) and quantitative computed tomography coronary angiography (QCT) to predict the hemodynamic significance of a coronary stenosis, using intracoronary fractional flow reserve (FFR) as the reference standard. Background: It has been demonstrated that CTCA provides excellent diagnostic sensitivity for identifying coronary stenoses, but may lack accurate delineation of the hemodynamic significance. Methods: We investigated 79 patients with stable angina pectoris who underwent both 64-slice or dual-source CTCA and FFR measurement of discrete coronary stenoses. CTCA and conventional coronary angiography (CCA), and QCT and quantitative coronary angiography (QCA), were performed to determine the severity of a stenosis that was compared with FFR measurements. A significant anatomical or functional stenosis was defined as ≥50% diameter stenosis or an FFR <0.75. Stented segments and bypass grafts were not included in the analysis. Results: A total of 89 stenoses were evaluated of which 18% (16 of 89) had an FFR <0.75. The diagnostic accuracy of CTCA, QCT, CCA, and QCA to detect a hemodynamically significant coronary lesion was 49%, 71%, 61%, and 67%, respectively. Correlation between QCT and QCA with FFR measurement was weak (R values of -0.32 and -0.30, respectively). Correlation between QCT and QCA was significant, but only moderate (R = 0.53; p < 0.0001). Conclusions: The anatomical assessment of the hemodynamic significance of coronary stenoses determined by visual CTCA, CCA, or QCT or QCA does not correlate well with the functional assessment of FFR. Determining the hemodynamic significance of an angiographically intermediate stenosis remains relevant before referral for revascularization treatment. http://repub.eur.nl/res/pub/29532/ 2008-07-01T00:00:00Z PURPOSE OF REVIEW: Several trials demonstrated that angiotensin-converting enzyme inhibitors reduce the incidence of cardiovascular events during long-term follow-up in high-risk and low-risk patients. Clinical treatment guidelines propose that angiotensin-converting enzyme inhibitors should be considered in the routine secondary prevention in the broad group of coronary artery disease patients. This review discusses several approaches to guide angiotensin- converting enzyme-inhibition therapy to more specific groups of patients that are most likely to benefit. RECENT FINDINGS: The beneficial effect of angiotensin-converting enzyme inhibition has been shown to be consistent across subgroups in stable coronary artery disease. Still, large interindividual variability in blood pressure response is well documented. It should also be realized that the absolute treatment effects are modest. The efficiency and cost-effectiveness of this prolonged prophylactic treatment would be significantly enhanced if those patients can be distinguished who benefit most. Recently, it was suggested that markers of an activated renin-angiotensin- aldosterone system might be used to guide angiotensin-converting enzyme-inhibition therapy. SUMMARY: At the start of treatment, clinical characteristics are not sufficient to distinguish between patients who will and will not benefit from angiotensin-converting enzyme inhibitors. Although pharmacogenetic research in coronary artery disease is still in a premature stage, it may be expected to provide a useful tool in optimizing and individualizing the management of angiotensin-converting enzyme-inhibitor therapy in coronary artery disease patients. http://repub.eur.nl/res/pub/29382/ 2008-06-23T00:00:00Z Aims: To describe smoking habits in adults with congenital heart disease (ACHD) and to assess the relationship between smoking exposure and cardiovascular mortality. Methods: Data on smoking history and cardiovascular mortality were extracted from the Euro Heart Survey on adult congenital heart disease - a retrospective cohort study, that included patients diagnosed with 1 of 8 subgroups of ACHD (Atrial Septal Defects, Ventricular Septal Defects, Marfan Syndrome, Aortic Coarctation, Tetralogy of Fallot (ToF), Transposition of the Great Arteries (TGA), Fontan circulation, and Cyanotic disease). Results: Complete data of 3375 ACHD patients (median age 28 years) were available for analysis. At inclusion, 9.3% (n = 314) were current smokers and 4.2% (n = 142) of the patients had smoked in the past. During a median follow-up of 5.1 years, 101 patients (3%) died. In the majority of cases the cause of death was cardiovascular (n = 81; 80%). Kaplan-Meier and Cox survival analysis for each of the defects separately showed a significantly increased age and sex-adjusted cardiovascular mortality associated with smoking exposure in TGA patients (Hazard ratio 4.2 (95% CI 1.0-16.8); P = 0.044). Also in ToF mortality was higher amongst smokers, though not significantly (HR 3.4 (95% CI 0.6-18.5); P = 0.15). In the remaining defects no relationship between smoking and cardiovascular mortality was observed. Conclusion: The prevalence of smoking amongst ACHD patients is relatively low. Smoking exposure is associated with increased cardiovascular mortality in patients with TGA. Prospective long-term follow-up studies are necessary. http://repub.eur.nl/res/pub/29319/ 2008-06-06T00:00:00Z Background: There is a lack of evidence regarding treatment options for adults with an atrial septal defect (ASD) who present with an open defect or with sequelae after closure of the defect. The aim of this study was to describe the clinical characteristics and treatment of a large cohort of adult patients born with an ASD type II. Methods and results: Data on the clinical characteristics of 882 ASD II patients (mean follow-up of 4.2 years) included in the Euro Heart Survey on adult congenital heart disease were analysed. At baseline, the defects of 377 patients (mean age 39.2 (16.1) years; 65% females) had been closed, leaving 505 patients (mean age 41.1 (16.4) years; 68% females) with an open ASD. Hemodynamic abnormalities were more prevalent among patients with an open compared to those with a closed defect at baseline: pulmonary arterial hypertension 35% versus13%; right ventricular (RV) dysfunction 31% versus 8%; and severe RV volume overload 18% versus 1% (all P-values < 0.001). These prevalences increased with age, but hemodynamic parameters remained stable during follow-up in nearly all patients with a small defect. Also functional limitations were more common in those with open defects at baseline compared to those with closed defects (54% versus 25%). There was no difference in the prevalence of arrhythmia's. The best independent predictors of functional limitations appeared to be PAH (odds ratio 25.2 (5.8-109.6); P < 0.001)) and RV volume overload (odds ratio 2.3 (1.5-3.4; P < 0.001)) in a multivariable model. During follow-up, 9 patients died and in 294 patients the defect was closed, in 180 patients surgically, and in 114 patients by device. Among the latter group there were relatively more females (78% vs 66%; P = 0.035). In the surgically closed group defects were more "severe". There were substantial differences according to country in the relative frequency of device closure versus surgical closure, as well as the size and hemodynamic severity of the defects closed. Conclusion: The data from this study provide a cross-section of the kind of adult patients with an ASD that are seen at outpatient clinics for adult congenital heart disease throughout Europe. Taken together, non-operated patients fared significantly worse in all aspects of hemodynamics studied than the patients whose defects had been closed. In moderate or large defects, when not-operated, clinical parameters tend to worsen with time, and closure of such a defect-the sooner the better-seems always to be the preferred treatment option. In the majority of small defects, operation is not necessarily indicated. http://repub.eur.nl/res/pub/29271/ 2008-06-01T00:00:00Z Aims: Studies reporting improved left ventricular (LV) function of percutaneous skeletal myoblast (SkM) injection in patients with ischaemic cardiomyopathy had follow-up not exceeding 12 months, and did not include a control group. Our group has reported evidence for myoblast efficacy in the first five out of the 14 treated patients. The objective of the present evaluation was to assess if these effects were sustained at long-term follow-up. We compared function of patients treated with SkM 4 years earlier with a matched control group. Secondary endpoints included mortality, NYHA class, N-terminal pro-B-natriuretic peptide levels, incidence of arrhythmias, and quality of life. Methods and results: Fourteen patients with ischaemic cardiomyopathy who underwent SkM injection were compared with 28 non-randomized control patients matched for age, sex, location, and extent of myocardial infarction. Contrast echocardiography and tissue Doppler imaging (TDI) was performed to compare global and regional LV function. At 4-year follow-up, three patients (21%) had died in the treated group and 11 patients (39%) in the control group (P = 0.8). In the survivors, LV ejection fraction (EF) was 35 ± 10% and 37 ± 9% in the SkM group and 36 ± 8% and 36 ± 6% in the controls at baseline and 4 years follow-up, respectively (P = 0.96 between groups at follow-up). TDI-derived systolic velocity in the injected sites was 5.4 ± 1.8 cm/s in the SkM group when compared with 5.1 ± 1.6 cm/s in corresponding sites in the control group (P = 0.47). None of the secondary endpoints showed a difference between the groups. However, in the patients fitted with an internal cardioverter defibrillator, more arrhythmias leading to interventions occurred in the treated group than in the control group, 87% and 13%, respectively (P = 0.015). Conclusion: Percutaneous intramyocardial SkM injection in ischaemic cardiomyopathy has no sustained positive effect on resting global or regional LV function, respectively, at 4-year follow-up. Moreover, the procedure may induce a higher risk of developing serious arrhythmias, but larger patient series are required before more precise characterization of the safety and efficacy profile of the procedure is possible. http://repub.eur.nl/res/pub/29432/ 2008-04-25T00:00:00Z Introduction: A proposed benefit of dual-chamber arrhythmia discrimination is a reduction in inappropriate therapy in implantable cardioverter-defibrillators (ICDs). The aim of this meta-analysis was to establish whether dual-chamber arrhythmia discrimination algorithms reduce inappropriate device therapy. Methods and results: Public domain databases, MEDLINE, EMBASE, and Cochrane Register of Controlled Trials, were searched from 1996 to 2006. Two investigators abstracted data independently. Pooled estimates were calculated using both fixed-effects and random-effects models. We retrieved 5 prospective studies comparing dual-chamber with single-chamber arrhythmia discrimination, accumulating data on 748 patients. Pooled per-patient based analysis demonstrated that the number of patients receiving inappropriate ICD therapy was not different between single- and dual-chamber devices (odds ratio [OR] 1.23; 95% CI, 0.83 to 1.81; p = 0.31). Per-episode based analysis demonstrated a favoring benefit for dual-chamber arrhythmia discrimination (OR 0.64; 95% CI, 0.52 to 0.78; p < 0.001). A mean reduction of 1.1 inappropriately treated atrial episodes per patient was observed with dual-chamber arrhythmia discrimination (p < 0.001). Conclusions: Dual-chamber arrhythmia discrimination is associated with a reduction in the number of inappropriate treated episodes. The number of patients who experience inappropriate therapy is not reduced by dual-chamber discrimination. http://repub.eur.nl/res/pub/32402/ 2008-04-01T00:00:00Z http://repub.eur.nl/res/pub/11676/ 2008-03-14T00:00:00Z Objective: To investigate whether the beneficial and harmful effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST elevation acute coronary syndromes (NSTE-ACS) depend on age. Methods: A meta-analysis of six trials of platelet glycoprotein IIb/IIIa receptor blockers in patients with NSTE-ACS (PRISM, PRISM-PLUS, PARAGON-A, PURSUIT, PARAGON-B, GUSTO IV-ACS; n = 31 402) was performed. We applied multivariable logistic regression analyses to evaluate the drug effects on death or non-fatal myocardial infarction at 30 days, and on major bleeding, by age subgroups (<60, 60–69, 70–79, >=80 years). We quantified the reduction of death or myocardial infarction as the number needed to treat (NNT), and the increase of major bleeding as the number needed to harm (NNH). Results: Subgroups had 11 155 (35%), 9727 (31%), 8468 (27%) and 2049 (7%) patients, respectively. The relative benefit of platelet glycoprotein IIb/IIIa receptor blockers did not differ significantly (p = 0.5) between age subgroups (OR (95% CI) for death or myocardial infarction: 0.86 (0.74 to 0.99), 0.90 (0.80 to 1.02), 0.97 (0.86 to 1.10), 0.90 (0.73 to 1.16); overall 0.91 (0.86 to 0.99). ORs for major bleeding were 1.9 (1.3 to 2.8), 1.9 (1.4 to 2.7), 1.6 (1.2 to 2.1) and 2.5 (1.5–4.1). Overall NNT was 105, and overall NNH was 90. The oldest patients had larger absolute increases in major bleeding, but also had the largest absolute reductions of death or myocardial infarction. Patients >=80 years had half of the NNT and a third of the NNH of patients <60 years. Conclusions: In patients with NSTE-ACS, the relative reduction of death or non-fatal myocardial infarction with platelet glycoprotein IIb/IIIa receptor blockers was independent of patient age. Larger absolute outcome reductions were seen in older patients, but with a higher risk of major bleeding. Close monitoring of these patients is warranted. http://repub.eur.nl/res/pub/29185/ 2008-03-01T00:00:00Z http://repub.eur.nl/res/pub/29314/ 2008-03-01T00:00:00Z Aims: The aim of the current study was to evaluate the relationship between the presence of left ventricular (LV) dyssynchrony at baseline and acute vs. late improvement in mitral regurgitation (MR) after cardiac resynchronization therapy (CRT). Methods and results: Sixty eight patients consecutive (LV ejection fraction 23 ± 8%) with at least moderate MR (≥grade 2+) were included. Echocardiography was performed at baseline, 1 day after CRT initiation and at 6 months follow-up. Speckle tracking radial strain was used to assess LV dyssynchrony at baseline. The majority of patients improved in MR after CRT, with 43% improving immediately after CRT, and 20% improving late (after 6 months) after CRT. Early and late responders had similar extent of LV dyssynchrony (209 ± 115 ms vs. 190 ± 118 ms, P = NS); however, the site of latest activation in early responders was mostly inferior or posterior (adjacent to the posterior papillary muscle), whereas the lateral wall was the latest activated segment in late responders. Conclusion: Current data suggest that the presence of baseline LV dyssynchrony is related to improvement in MR after CRT. LV dyssynchrony involving the posterior papillary muscle may lead to an immediate reduction in MR, whereas LV dyssynchrony in the lateral wall resulted in late response to CRT. http://repub.eur.nl/res/pub/29767/ 2008-03-01T00:00:00Z Aims: Cardiac morbidity and mortality is high in patients undergoing high-risk surgery. This study investigated whether impaired glucose regulation and elevated glycated haemoglobin (HbA1c) levels are associated with increased cardiac ischaemic events in vascular surgery patients. Methods: Baseline glucose and HbA1cwere measured in 401 vascular surgery patients. Glucose < 5.6 mmol/l was defined as normal. Fasting glucose 5.6-7.0 mmol/l or random glucose 5.6-11.1 mmol/l was defined as impaired glucose regulation. Fasting glucose ≥ 7.0 or random glucose ≥ 11.1 mmol/l was defined as diabetes. Perioperative ischaemia was identified by 72-h Holter monitoring. Troponin T was measured on days 1, 3 and 7 and before discharge. Cardiac death or Q-wave myocardial infarction was noted at 30-day and longer-term follow-up (mean 2.5 years). Results: Mean (± sd) level for glucose was 6.3 ± 2.3 mmol/l and for HbA1c6.2 ± 1.3%. Ischaemia, troponin release, 30-day and long-term cardiac events occurred in 27, 22, 6 and 17%, respectively. Using subjects with normal glucose levels as the reference category, multivariate analysis revealed that patients with impaired glucose regulation and diabetes were at 2.2- and 2.6-fold increased risk of ischaemia, 3.8- and 3.9-fold for troponin release, 4.3- and 4.8-fold for 30-day cardiac events and 1.9- and 3.1-fold for long-term cardiac events. Patients with HbA1c> 7.0% (n = 63, 16%) were at 2.8-fold, 2.1-fold, 5.3-fold and 5.6-fold increased risk for ischaemia, troponin release, 30-day and long-term cardiac events, respectively. Conclusions: Impaired glucose regulation and elevated HbA1care risk factors for cardiac ischaemic events in vascular surgery patients. http://repub.eur.nl/res/pub/28903/ 2008-02-15T00:00:00Z Patients scheduled for major vascular surgery are screened for cardiac risk factors using standardized risk indexes, including diabetes mellitus (DM). Screening in patients without a history of DM includes fasting glucose measurement. However, an oral glucose tolerance test (OGTT) could significantly improve the detection of DM and impaired glucose tolerance (IGT) and the prediction of perioperative cardiac events. In a prospective study, 404 consecutive patients without signs or histories of IGT or DM were included and subjected to OGTT. The primary study end point was the composite of perioperative myocardial ischemia, assessed by 72-hour Holter monitoring using ST-segment analysis and troponin release. The primary end point was noted in 21% of the patients. IGT was diagnosed in 104 patients (25.7%), and new-onset DM was detected in 43 patients (10.6%). The OGTT detected 75% of the patients with IGT and 72% of the patients with DM. Preoperative glucose levels significantly predicted the risk for perioperative cardiac ischemia; odds ratios for DM and IGT were, respectively, 3.2 (95% confidence interval 1.3 to 8.1) and 1.4 (95% confidence interval 0.7 to 3.0). In conclusion, the prevalence of undiagnosed IGT and DM is high in vascular patients and is associated with perioperative myocardial ischemia. Therefore, an OGTT should be considered for all patients who undergo elective vascular surgery. http://repub.eur.nl/res/pub/28926/ 2008-02-01T00:00:00Z Background: Restrictive mitral annuloplasty with revascularization is considered the best approach to ischemic mitral regurgitation with heart failure, but late results are controversial. We report late outcome in relation to preoperative left ventricular end-diastolic diameter (LVEDD) cutoff values, previously identified to predict intermediate-term left ventricular reverse remodeling. Methods: One hundred consecutive ischemic mitral regurgitation patients underwent restrictive mitral annuloplasty (stringent downsizing by two ring sizes; median size, 26) and coronary revascularization. Survivors were clinically and echocardiographically assessed at intermediate (18 months) and late (mean, 46 months) follow-up. Results: Early mortality was 8%, and late mortality was 18%. Actuarial 1-, 3-, and 5-year survival rates were 87% ± 3.4%, 80% ± 4.1%, and 71% ± 5.1%. Mortality predictors (Cox regression) were preoperative inotropic support (hazard ratio, 6.2; 95% confidence interval, 2.3 to 16.9) and preoperative LVEDD greater than 65 mm (hazard ratio, 4.5; 95% confidence interval, 1.9 to 10.9). Five-year survival rate for patients with LVEDD of 65 mm or less was 80% ± 5.2%, versus 49% ± 11% for LVEDD greater than 65 mm (p = 0.002). At 4.3 years' follow-up, New York Heart Association functional class had improved from 2.9 ± 0.8 to 1.6 ± 0.6 (p < 0.01). Mitral regurgitation grade was 0.8 ± 0.7, and was less than grade 2+ in 85% of patients. Left ventricular reverse remodeling was sustained with time for the LVEDD of 65 mm or less group. Late deaths did not show intermediate-term systolic left ventricular reverse remodeling, indicating a more extensive intrinsic left ventricular abnormality. Conclusions: At 4.3 years' follow-up, intermediate-term cutoff values for left ventricular reverse remodeling proved to be predictors for late mortality. For patients with preoperative LVEDD of 65 mm or less, restrictive mitral annuloplasty with revascularization provides a cure for ischemic mitral regurgitation and heart failure; however, when LVEDD exceeds 65 mm, outcome is poor and a ventricular approach should be considered. http://repub.eur.nl/res/pub/28761/ 2008-01-01T00:00:00Z N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is related to stress-induced myocardial ischemia and/or volume overload, both common in patients with renal dysfunction. This might compromise the prognostic usefulness of NT-pro-BNP in patients with renal impairment before vascular surgery. We assessed the prognostic value of NT-pro-BNP in the entire strata of renal function. In 356 patients (median age 69 years, 77% men), cardiac history, glomerular filtration rate (GFR, ml/min/1.73 m2), and NT-pro-BNP level (pg/ml) were assessed preoperatively. Troponin T and electrocardiography were assessed postoperatively on days 1, 3, 7, and 30. The end point was the composite of cardiovascular death, Q-wave myocardial infarction, and troponin T release. Multivariate analysis was used to evaluate the interaction between GFR, NT-pro-BNP and their association with postoperative outcome. Median GFR was 78 ml/min/1.73 m2and the median concentration of NT-pro-BNP was 197 pg/ml. The end point was reached in 64 patients (18%); cardiac death occurred in 7 (2.0%), Q-wave myocardial infarction in 34 (9.6%), and non-Q-wave myocardial infarction in 23 (6.5%). After adjustment for confounders, NT-pro-BNP levels and GFR remained significantly associated with the end point (p = 0.005). The prognostic value of NT-pro-BNP was most pronounced in patients with GFR ≥90 (odds ratio [OR] 1.18, 95% confidence interval [CI] 0.80 to 1.76) compared with patients with GFR 60 to 89 (OR 1.04, 95% CI 1.002 to 1.07), and with GFR 30 to 59 (OR 1.12, 95% CI 1.03 to 1.21). In patients with GFR <30 ml/min/1.73 m2, NT-pro-BNP levels have no prognostic value (OR 1.00, 95% CI 0.99 to 1.01). In conclusion, the discriminative value of NT-pro-BNP is most pronounced in patients with GFR ≥90 ml/min/1.73 m2and has no prognostic value in patients with GFR <30 ml/min/1.73 m2. http://repub.eur.nl/res/pub/30273/ 2008-01-01T00:00:00Z Objective: To compare the diagnostic accuracy of 64-slice multislice computed tomography (MSCT) coronary angiography between female and male patients using conventional coronary angiography as the reference standard. Design: Diagnostic accuracy study. Setting: University hospital. Patients: 103 consecutive patients (51 men, 52 women, mean (SD) age 60 (10) years) with known and suspected coronary artery disease underwent 64-slice MSCT. Main outcome measures: Diagnostic accuracy of 64-slice MSCT to detect obstructive (≥50% luminal narrowing) stenoses in men and women. Results: One male and two female patients were excluded from the analysis owing to non-diagnostic MSCT scans as a result of increased heart rate and breathing during the scan. Accordingly, on segmental level, 728/762 coronary segments were of sufficient quality in women (96% (95% CI 95% to 97%)) and 704/723 segments were interpretable in men (97% (95% CI 96% to 98%)). In the remaining 100 patients included in the further analyses, the sensitivity and specificity on a segmental level in women and men were 85% (95% CI 75% to 95%) vs 85% (95% CI 78% to 92%) and 99% (95% CI 98% to 100%) vs 99% (95% CI 98% to 100%), respectively. On a patient level, the sensitivity in women and men was 95% (95% CI 87% to 100%) vs 100%, specificity 93% (95% CI 83% to 100%) vs 89% (95% CI 74% to 100%), positive predictive value 91% (95% CI 79% to 100%) vs 94% (95% CI 86% to 100%), and negative predictive value 96% (95% CI 89% to 100%) vs 100%, respectively. Conclusion: The findings confirm the high diagnostic accuracy of 64-slice MSCT coronary angiography in both male and female patients. http://repub.eur.nl/res/pub/30454/ 2008-01-01T00:00:00Z Aim: The in vivo comparison of the accuracy of two 3-dimensional quantitative coronary angiography (QCA) systems. Methods: Precision-drilled plexiglass phantoms with five different luminal diameters (0.5-1.9 mm) were percutaneously inserted into the coronary arteries of four Yorkshire pigs. Twenty-one angiographic images of these stenotic phantoms were acquired for in vivo validation testing. Quantitative assessments of the minimum, maximum, and mean luminal diameters together with the minimum luminal area were determined using two 3D QCA systems, the CardiOp-B® and CAAS 5. Results: The CardiOp-B system significantly underestimated the minimum luminal diameter MLD whilst both systems significantly overestimated the maximum luminal diameter at the minimal luminal area (MLA) over the phantom's true value. The CAAS 5 system had a greater degree of accuracy/mm (mean difference = 0.01 vs. 0.03) and precision/mm (SD = 0.09 vs. 0.23) than the CardiOp-B in assessing the minimal LD. An increased precision/mm (SD = 0.01 vs. 0.29) and accuracy/mm (mean difference = 0.03 vs. 0.11) in the mean LD was observed with the CAAS 5. In comparing the MLA/mm2the CAAS 5 was more precise/mm2(SD = 0.14 vs. 0.55) and accurate/mm2(mean difference = 0.12 vs. 0.02) to the true phantom MLA compared to the CardiOp-B system. Conclusions: In a 21 phantom study, the CAAS 5 3D QCA system had a greater degree of accuracy and precision in both the luminal and area measurements than the CardiOp-B 3D QCA system. http://repub.eur.nl/res/pub/35052/ 2007-12-10T00:00:00Z Background: Prognostic information in peripheral arterial disease (PAD) may provide the basis for optimal management strategies at an early stage. This study aimed to develop a prognostic risk index for long-term mortality in patients with PAD. Methods: In a single-center observational cohort study, 2642 patients with an ankle-brachial index of 0.90 or lower were randomly divided into derivation (n=1332) and validation (n=1310) cohorts. Cox regression analysis with stepwise backward elimination identified predictors of 1-year, 5-year, and 10-year mortality in the derivation cohort. Weighted points were assigned to each predictor. Index discrimination was determined in both the derivation and validation cohorts. Results: During 10 years of follow-up, 42.2% and 40.4% of patients died in the derivation and validation cohorts, respectively. The risk index for 10-year mortality (+points) included renal dysfunction (+12), heart failure (+7), ST-segment changes (+5), age greater than 65 years (+5), hypercholesterolemia (+5), ankle-brachial index lower than 0.60 (+4), Q-waves (+4), diabetes (+3), cerebrovascular disease (+3), and pulmonary disease (+3). Statins (-6), aspirin (-4), and β-blockers (-4) were associated with reduced 10-year mortality. Patients were stratified into low (<0 points), low-intermediate (0-5 points), high-intermediate (6-9 points), and high (>9 points) risk categories, according to risk score. Ten-year mortality rates were 22.1%, 32.2%, 45.8%, and 70.4%, respectively (P < .001) and comparable to mortality in the validation cohort. C statistics demonstrated good discrimination in both the derivation (0.72) and validation cohorts (0.73). Conclusions: A prognostic risk index for long-term mortality stratified patients with PAD into different risk categories. This may be useful for risk stratification, patient counseling, and medical decision making. http://repub.eur.nl/res/pub/36160/ 2007-11-27T00:00:00Z Objectives: This study sought to examine whether the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitor therapy by perindopril are modified by renal function in patients with stable coronary artery disease. Background: A recent study reported that an impaired renal function identified a subgroup of patients with stable coronary artery disease more likely to benefit from ACE inhibition therapy. In light of the growing interest in tailored therapy for targeting medications to specific subgroups, remarks on the consistency of the treatment effect by ACE inhibitors are highly important. Methods: The present study involved 12,056 patients with stable coronary artery disease without heart failure randomized to perindopril or placebo. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease equation. Cox regression analysis was used to estimate multivariable-adjusted hazard ratios. Results: The mean eGFR was 76.2 (±18.1) ml/min/1.73 m2. During follow-up, the primary end point (cardiovascular death, nonfatal myocardial infarction, or resuscitated cardiac arrest) occurred in 454 of 5,761 patients (7.9%) with eGFR ≥75 and in 631 of 6,295 patients (10.0%) with eGFR <75. Treatment benefits of perindopril were apparent in both patient groups either with eGFR ≥75 (hazard ratio 0.77; 95% confidence interval 0.64 to 0.93) or eGFR <75 (hazard ratio 0.84; 95% confidence interval 0.72 to 0.98). We observed no significant interaction between renal function and treatment benefit (p = 0.47). Using different cutoff points of eGFR at the level of 60 or 90 resulted in similar trends. Conclusions: The treatment benefit of perindopril is consistent and not modified by mild to moderate renal insufficiency. http://repub.eur.nl/res/pub/36170/ 2007-10-23T00:00:00Z Objectives: This study sought to examine whether higher statin doses and lower low-density lipoprotein (LDL) cholesterol are associated with improved cardiac outcome in vascular surgery patients. Background: Statins may have cardioprotective effects during major vascular surgery. Methods: In a prospective study of 359 vascular surgery patients, statin dose and cholesterol levels were recorded preoperatively. Myocardial ischemia and heart rate variability were assessed by 72-h 12-lead electrocardiography starting 1 day before to 2 days after surgery. Troponin T was measured on postoperative day 1, 3, 7, and before discharge. Cardiac events included cardiac death or nonfatal Q-wave myocardial infarction at 30 days and follow-up (mean 2.3 years). Results: Perioperative myocardial ischemia, troponin T release, 30-day events, and late cardiac events occurred in 29%, 23%, 4%, and 18%, respectively. In multivariate analysis, lower LDL cholesterol (per 10 mg/dl) correlated with lower myocardial ischemia (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.80 to 0.95), troponin T release (OR 0.89, 95% CI 0.82 to 0.96), and 30-day (OR 0.89, 95% CI 0.78 to 1.00) and late cardiac events (hazard ratio 0.91, 95% CI 0.84 to 0.96). Higher statin doses (per 10% of maximum recommended dose) correlated with lower myocardial ischemia (OR 0.85, 95% CI 0.76 to 0.93), troponin T release (OR 0.84, 95% CI 0.76 to 0.93), and 30-day (OR 0.62, 95% CI 0.40 to 0.96) and late cardiac events (hazard ratio 0.76, 95% CI 0.65 to 0.89), even after adjusting for LDL cholesterol. Significantly higher perioperative heart rate variability was observed in patients with higher statin doses. Conclusions: Higher statin doses and lower LDL cholesterol correlate with lower perioperative myocardial ischemia, perioperative troponin T release, and 30-day and late cardiac events in major vascular surgery. http://repub.eur.nl/res/pub/36172/ 2007-10-16T00:00:00Z Objectives: We sought to identify predictors of left ventricular (LV) remodeling after acute myocardial infarction. Background: Left ventricular remodeling after myocardial infarction is associated with an adverse long-term prognosis. Early identification of patients prone to LV remodeling is needed to optimize therapeutic management. Methods: A total of 178 consecutive patients presenting with acute myocardial infarction who underwent primary percutaneous coronary intervention were included. Within 48 h of intervention, 2-dimensional echocardiography was performed to assess LV volumes, LV ejection fraction (LVEF), wall motion score index, left atrial dimension, E/E′ ratio, and severity of mitral regurgitation. Left ventricular dyssynchrony was determined using speckle-tracking radial strain analysis. At 6-month follow-up, LV volumes, LVEF, and severity of mitral regurgitation were reassessed. Results: Patients showing LV remodeling at 6-month follow-up (20%) had comparable baseline characteristics to patients without LV remodeling (80%), except for higher peak troponin T levels (p < 0.001), peak creatine phosphokinase levels (p < 0.001), wall motion score index (p < 0.05), E/E′ ratio (p < 0.05), and a larger extent of LV dyssynchrony (p < 0.001). Multivariable analysis demonstrated that LV dyssynchrony was superior in predicting LV remodeling. Receiver-operating characteristic curve analysis demonstrated that a cutoff value of 130 ms for LV dyssynchrony yields a sensitivity of 82% and a specificity of 95% to predict LV remodeling at 6-month follow-up. Conclusions: Left ventricular dyssynchrony immediately after acute myocardial infarction predicts LV remodeling at 6-month follow-up. http://repub.eur.nl/res/pub/36173/ 2007-10-09T00:00:00Z Objectives: We assessed the usefulness of 64-slice computed tomography coronary angiography (CTCA) to detect or rule out coronary artery disease (CAD) in patients with various estimated pretest probabilities of CAD. Background: The pretest probability of the presence of CAD may impact the diagnostic performance of CTCA. Methods: Sixty-four-slice CTCA (Sensation 64, Siemens, Forchheim, Germany) was performed in 254 symptomatic patients. Patients with heart rates ≥65 beats/min received beta-blockers before CTCA. The pretest probability for significant CAD was estimated by type of chest discomfort, age, gender, and traditional risk factors and defined as high (≥71%), intermediate (31% to 70%), and low (≤30%). Significant CAD was defined as the presence of at least 1 ≥50% coronary stenosis on quantitative coronary angiography, which was the standard of reference. No coronary segments were excluded from analysis. Results: The estimated pretest probability of CAD in the high (n = 105), intermediate (n = 83), and low (n = 66) groups was 87%, 53%, and 13%, respectively. The diagnostic performance of the computed tomography (CT) scan was different in the 3 subgroups. The estimated post-test probability of the presence of significant CAD after a negative CT scan was 17%, 0%, and 0% and after a positive CT scan was 96%, 88%, and 68%, respectively. Conclusions: Computed tomography coronary angiography is useful in symptomatic patients with a low or intermediate estimated pretest probability of having significant CAD, and a negative CT scan reliably rules out the presence of significant CAD. Computed tomography coronary angiography does not provide additional relevant diagnostic information in symptomatic patients with a high estimated pretest probability of CAD. http://repub.eur.nl/res/pub/35155/ 2007-10-01T00:00:00Z BACKGROUND: The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for Perioperative Cardiovascular Evaluation for Noncardiac Surgery recommend an algorithm for a stepwise approach to preoperative cardiac assessment in vascular surgery patients. The authors' main objective was to determine adherence to the ACC/AHA guidelines on perioperative care in daily clinical practice. METHODS: Between May and December 2004, data on 711 consecutive peripheral vascular surgery patients were collected from 11 hospitals in The Netherlands. This survey was conducted within the infrastructure of the Euro Heart Survey Programme. The authors retrospectively applied the ACC/AHA guideline algorithm to each patient in their data set and subsequently compared observed clinical practice data with these recommendations. RESULTS: Although 185 of the total 711 patients (26%) fulfilled the ACC/AHA guideline criteria to recommend preoperative noninvasive cardiac testing, clinicians had performed testing in only 38 of those cases (21%). Conversely, of the 526 patients for whom noninvasive testing was not recommended, guidelines were followed in 467 patients (89%). Overall, patients who had not been tested, irrespective of guideline recommendation, received less cardioprotective medications, whereas patients who underwent noninvasive testing were significantly more often treated with cardiovascular drugs (β-blockers 43% vs. 77%, statins 52% vs. 83%, platelet inhibitors 80% vs. 85%, respectively; all P < 0.05). Moreover, the authors did not observe significant differences in cardiovascular medical therapy between patients with a normal test result and patients with an abnormal test result. CONCLUSION: This survey showed poor agreement between ACC/AHA guideline recommendations and daily clinical practice. Only one of each five patients underwent noninvasive testing when recommended. Furthermore, patients who had not undergone testing despite recommendations received as little cardiac management as the low-risk population. http://repub.eur.nl/res/pub/36184/ 2007-09-18T00:00:00Z Objectives: Speckle-tracking strain analysis was used to assess the effects of permanent right ventricular (RV) pacing on the heterogeneity in timing of regional wall strain and left ventricular (LV) dyssynchrony. Background: Recent studies have shown detrimental effects of RV pacing, possibly related to the induction of LV dyssynchrony. Methods: Fifty-eight patients treated with His bundle ablation and pacemaker implantation were studied. To assess the effect of RV pacing on time-to-peak radial strain of different LV segments, we applied speckle-tracking analysis to standard LV short-axis images. In addition, New York Heart Association (NYHA) functional class, LV volumes, and systolic function were assessed at baseline and after long-term RV pacing. Results: At baseline, similar time-to-peak strain for the 6 segments was observed (mean 371 ± 114 ms). In contrast, after a mean of 3.8 ± 2.0 years of RV pacing, there was a marked heterogeneity in time-to-peak strain of the 6 segments. In 33 patients (57%), LV dyssynchrony, represented by a time difference ≥130 ms between the time-to-peak strain of the (antero)septal and the posterolateral segments, was present. In these patients, a deterioration of LV systolic function and NYHA functional class was observed. In 11 patients, an "upgrade" of the conventional pacemaker to a biventricular pacemaker resulted in partial reversal of the detrimental effects of RV pacing. Conclusions: Speckle-tracking analysis revealed that permanent RV pacing induced heterogeneity in time-to-peak strain, resulting in LV dyssynchrony in 57% of patients, associated with deterioration of LV systolic function and NYHA functional class. Biventricular pacing may reverse these adverse effects of RV pacing. http://repub.eur.nl/res/pub/35199/ 2007-09-15T00:00:00Z Currently, left ventricular (LV) ejection fraction (EF) and/or LV volumes are the established predictors of mortality in patients with coronary artery disease (CAD) and severe LV dysfunction. With contrast-enhanced magnetic resonance imaging (MRI), precise delineation of infarct size is now possible. The relative merits of LVEF/LV volumes and infarct size to predict long-term outcome are unknown. The purpose of this study was to determine the predictive value of infarct size assessed with contrast-enhanced MRI relative to LVEF and LV volumes for long-term survival in patients with healed myocardial infarction. Cine MRI and contrast-enhanced MRI were performed in 231 patients with healed myocardial infarction. LVEF and LV volumes were measured and infarct size was derived from contrast-enhanced MRI. Nineteen patients (8.2%) died during a median follow-up of 1.7 years (interquartile range 1.1 to 2.9). Cox proportional hazards analysis revealed that infarct size defined as spatial extent (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.1 to 1.6, chi-square 6.7, p = 0.010), transmurality (HR 1.5, 95% CI 1.1 to 1.9, chi-square 8.9, p = 0.003), or total scar score (HR 6.2, 95% CI 1.7 to 23, chi-square 7.4, p = 0.006) were stronger predictors of all-cause mortality than LVEF and LV volumes. In conclusion, infarct size on contrast-enhanced MRI may be superior to LVEF and LV volumes for predicting long-term mortality in patients with healed myocardial infarction. http://repub.eur.nl/res/pub/36984/ 2007-09-01T00:00:00Z Background: Reverse remodeling of the left ventricle (LV) is one of the advantageous mechanisms of cardiac resynchronization therapy (CRT). Substantial LV dyssynchrony seems mandatory for echocardiographic response to CRT. Conversely, LV dyssynchrony early after acute myocardial infarction may result in LV dilatation during follow-up. Objective: The purpose of this study was to evaluate the relation between LV dyssynchrony early after acute myocardial infarction and the occurrence of long-term LV dilatation. Methods: A total of 124 consecutive patients presenting with acute myocardial infarction who underwent primary percutaneous coronary intervention were included. Within 48 hours of intervention, two-dimensional echocardiography was performed to assess LV volumes, LV ejection fraction (LVEF), and wall motion score index (WMSI). LV dyssynchrony was quantified using color-coded tissue Doppler imaging (TDI). At 6-month follow-up, LV volumes and LVEF were reassessed. Results: Patients with substantial LV dyssynchrony (≥65 ms) at baseline (18%) had comparable baseline characteristics to patients without substantial LV dyssynchrony (82%), except for a higher prevalence of multivessel coronary artery disease (P = .019), higher WMSI (P = .042), and higher peak levels of creatine phosphokinase (P = .021). During 6 months of follow-up, 91% of the patients with substantial LV dyssynchrony at baseline developed LV remodeling, compared with 2% in the patients without substantial LV dyssynchrony. LV dyssynchrony at baseline was strongly related to the extent of long-term LV dilatation at 6 months of follow-up. Conclusion: Most patients with substantial LV dyssynchrony immediately after acute myocardial infarction develop LV dilatation during 6 months of follow-up. http://repub.eur.nl/res/pub/35306/ 2007-08-01T00:00:00Z Background: Although relationships between chronic Chlamydia pneumoniae (Cpn) infection and the risk of coronary events in stable coronary artery disease patients have been reported, a similar link in acute coronary syndrome (ACS) patients has not been consistently observed. Methods: In a nested case-control substudy of the Global Utilization of Strategies to Open Occluded Arteries IV Acute Coronary Syndromes trial, 295 cases (30-day death/myocardial infarction [MI]) were matched by age, sex, baseline creatine kinase-myocardial kinase, and smoking status with 295 control subjects. To test the hypothesis on 1-year mortality, another subset (n = 276) was drawn from the 590-patient cohort; 138 patients who died at 1 year plus the matching controls who survived at 1 year. We measured Cpn IgG and IgA antibody titers in baseline serum with microimmunofluorescence. Conditional logistic regression was used to quantify the prognostic relevance seropositivity (IgG ≥1:32; IgA ≥1:16) and elevated titer levels. Results: The prevalence of Cpn IgG and IgA was similar between cases and controls (30-day death/MI: IgG, 80% vs 85%, P = .126; IgA, 45% vs 37%, P = .079), and were not statistically significant predictors of 30-day death/MI after baseline adjustment. Likewise, the 1-year death cohort had comparable proportions of Cpn IgG and IgA among cases and controls (86% vs 91% [P = .265] and 49% vs 43% [P = .334], respectively), and did not add prognostic value. Conclusions: These findings are in concert with study results suggesting that chronic Cpn infection is not associated with 30-day death/MI or 1-year mortality in non-ST elevation ACS. http://repub.eur.nl/res/pub/35764/ 2007-08-01T00:00:00Z Aims: To determine the adjunctive value of CT coronary angiography (CTCA) in the diagnostic work-up of patients with typical angina pectoris. Methods and results: CTCA was performed in 62 consecutive patients (45 male, mean age 58.8 ± 7.7 years) with typical angina undergoing diagnostic work-up including exercise-ECG and conventional coronary angiography. Only patients with sinus heart rhythm and ability to breath hold for 20 s were included. Patients with initial heart rates ≥70 beats/min received β-blockers. We determined the post-test likelihood ratios, to detect or exclude patients with significant (≥50% lumen diameter reduction) stenoses, of exercise-ECG and CTCA separately, and of CT performed after exercise-ECG testing. The prevalence of patients with significant coronary artery disease (CAD) was 74%. Positive and negative likelihood ratios for exercise-ECG were 2.3 [95% confidence interval (CI): 1.0-5.3] and 0.3 (95% CI: 0.2-0.7) and for CTCA 7.5 (95% CI: 2.1-27.1) and 0.0 (95% CI: 0.0-8), respectively. CTCA increased the post-test probability of significant CAD after a negative exercise-ECG from 58 to 91%, and after a positive exercise-ECG from 89 to 99%, while CT correctly identified patients without CAD (probability 0%). Conclusion: Non-invasive CTCA is a potentially useful tool, in the diagnostic work-up of patients with typical angina pectoris, both to detect and to exclude significant CAD. http://repub.eur.nl/res/pub/36609/ 2007-08-01T00:00:00Z Background: Peripheral arterial disease (PAD) is a risk factor for cardiovascular events. This study assessed the prognostic significance of repeated ankle-brachial index (ABI) measurements at rest and after exercise in patients with PAD receiving conservative treatment. Methods: In a cohort study of 606 patients (mean age 62 ± 12 years, 68% male), ABI at rest and after exercise was measured at baseline and after 1 year. Patients with reductions in ABI were divided into three equally-sized groups (minor, intermediate and major reductions) and were compared to patients without reductions. During a mean follow-up of 5 ± 3 years, all-cause mortality, cardiac events, stroke and progression to kidney failure were noted. Results: Death was recorded in 83 patients (14%) of which 49% were due to cardiac causes. Non-fatal myocardial infarction occurred in 38 patients (6%), stroke in 46 (8%) and progression to kidney failure in 35 (6%). By multivariate analysis, patients with major declines in resting (>20%) and post-exercise (>30%) ABI were at increased risk of all-cause mortality (HR: 3.3, 95% CI: 1.5-7.2, HR: 3.0, 95% CI: 1.4-6.4, respectively), cardiac events (HR: 3.1, 95% CI: 1.3-7.2, HR: 2.4, 95% CI: 1.1-5.6, respectively), stroke (HR: 4.2, 95% CI: 1.6-10.4, HR: 3.9, 95% CI: 1.4-10.2, respectively) and kidney failure (HR: 2.7, 95% CI: 1.1-7.5, HR: 6.9, 95% CI: 1.5-31.5, respectively), compared to patients with no declines in ABI. Conclusions: This study shows that major 1-year declines in resting and post-exercise ABI are associated with all-cause mortality, cardiac events, stroke and kidney failure in patients with PAD. http://repub.eur.nl/res/pub/35314/ 2007-07-09T00:00:00Z Background: There is growing evidence for a clinical benefit of primary percutaneous coronary intervention (PCI) compared with fibrinolysis; however, whether the treatment effect is consistent among patients with diabetes mellitus is unclear. We compared PCI with fibrinolysis for treatment of ST-segment elevation myocardial infarction in patients with diabetes mellitus. Methods: A pooled analysis of individual patient data from 19 trials comparing primary PCI with fibrinolysis for treatment of ST-segment elevation myocardial infarction was performed. Trials that enrolled at least 50 patients with ST-segment elevation myocardial infarction and randomized patients to receive either primary PCI or fibrinolysis were considered for inclusion in our study. Clinical end points were total deaths, recurrent infarction, death or nonfatal recurrent infarction, and stroke, measured 30 days after randomization. Results: Of 6315 patients, 877 (14%) had diabetes. Thirty-day mortality (9.4% vs 5.9%; P<.001) was higher in patients with diabetes. Mortality was lower after primary PCI compared with fibrinolysis in both patients with diabetes (unadjusted odds ratio, 0.49; 95% confidence interval, 0.31-0.79; P=.004) and without diabetes (unadjusted odds ratio, 0.69; 95% confidence interval, 0.54-0.86, P=.001), with no evidence of heterogeneity of treatment effect (P=.24 for interaction). Recurrent infarction and stroke were also reduced after primary PCI in both patient groups. After multivariable analysis, primary PCI was associated with decreased 30-day mortality in patients with and without diabetes, with a point estimate of greater benefit in diabetic patients. Conclusions: Diabetic patients with ST-segment elevation myocardial infarction treated with reperfusion therapy have increased mortality compared with patients without diabetes. The beneficial effects of primary PCI compared with fibrinolysis in diabetic patients are consistent with effects in nondiabetic patients. http://repub.eur.nl/res/pub/36792/ 2007-06-01T00:00:00Z Aim: To investigate the role of pulmonary arterial hypertension (PAH) in adult patients born with a cardiac septal defect, by assessing its prevalence and its relation with patient characteristics and outcome. Methods and results: From the database of the Euro Heart Survey on adult congenital heart disease (a retrospective cohort study with a 5-year follow-up), the relevant data on all 1877 patients with an atrial septal defect (ASD), a ventricular septal defect (VSD), or a cyanotic defect were analysed. Most patients (83%) attended a specialised centre. There were 896 patients with an ASD (377 closed, 504 open without and 15 with Eisenmenger's syndrome), 710 with a VSD (275, 352 and 83, respectively), 133 with Eisenmenger's syndrome owing to another defect and 138 remaining patients with cyanosis. PAH was present in 531 (28%) patients, or in 34% of patients with an open ASD and 28% of patients with an open VSD, and 12% and 13% of patients with a closed defect, respectively. Mortality was highest in patients with Eisenmenger's syndrome (20.6%). In case of an open defect, PAH entailed an eightfold increased probability of functional limitations (New York Heart Association class > 1), with a further sixfold increase when Eisenmenger's syndrome was present. Also, in patients with persisting PAH despite defect closure, functional limitations were more common. In patients with ASD, the prevalence of right ventricular dysfunction increased with systolic pulmonary artery pressure (OR= 1.073 per mm Hg; p<0.001). Major bleeding events were more prevalent in patients with cyanosis with than without Eisenmenger's syndrome (17% vs 3%; p<0.001). Conclusion: In this selected population of adults with congenital heart disease, PAH was common and predisposed to more symptoms and further clinical deterioration, even among patients with previous defect closure and patients who had not developed Eisenmenger's physiology. http://repub.eur.nl/res/pub/36204/ 2007-05-29T00:00:00Z Objectives: The purpose of this study was to investigate the appropriateness of stenting a functionally nonsignificant stenosis. Background: Percutaneous coronary intervention (PCI) of an intermediate stenosis without evidence of ischemia is often performed, but its benefit is unproven. Coronary pressure-derived fractional flow reserve (FFR) is an invasive index used to identify a stenosis responsible for reversible ischemia. Methods: In 325 patients scheduled for PCI of an intermediate stenosis, FFR was measured just before the planned intervention. If FFR was ≥0.75, patients were randomly assigned to deferral (Defer group; n = 91) or performance (Perform group; n = 90) of PCI. If FFR was <0.75, PCI was performed as planned (Reference group; n = 144). Clinical follow-up was 5 years. Results: There were no differences in baseline clinical characteristics between the 3 groups. Complete follow-up was obtained in 98% of the patients. Event-free survival was not different between the Defer and Perform groups (80% and 73%, respectively; p = 0.52), but was significantly worse in the Reference group (63%; p = 0.03). The composite rate of cardiac death and acute myocardial infarction in the Defer, Perform, and Reference groups was 3.3%, 7.9%, and 15.7%, respectively (p = 0.21 for Defer vs. Perform group; p = 0.003 for the Reference vs. both other groups). The percentage of patients free from chest pain at follow-up was not different between the Defer and Perform groups. Conclusions: Five-year outcome after deferral of PCI of an intermediate coronary stenosis based on FFR ≥0.75 is excellent. The risk of cardiac death or myocardial infarction related to this stenosis is <1% per year and not decreased by stenting. http://repub.eur.nl/res/pub/36205/ 2007-05-01T00:00:00Z Objectives: The purpose of this research was to perform a feasibility study of prophylactic coronary revascularization in patients with preoperative extensive stress-induced ischemia. Background: Prophylactic coronary revascularization in vascular surgery patients with coronary artery disease does not improve postoperative outcome. If a beneficial effect is to be expected, then at least those with extensive coronary artery disease should benefit from this strategy. Methods: One thousand eight hundred eighty patients were screened, and those with ≥3 risk factors underwent cardiac testing using dobutamine echocardiography (17-segment model) or stress nuclear imaging (6-wall model). Those with extensive stress-induced ischemia (≥5 segments or ≥3 walls) were randomly assigned for additional revascularization. All received beta-blockers aiming at a heart rate of 60 to 65 beats/min, and antiplatelet therapy was continued during surgery. The end points were the composite of all-cause death or myocardial infarction at 30 days and during 1-year follow-up. Results: Of 430 high-risk patients, 101 (23%) showed extensive ischemia and were randomly assigned to revascularization (n = 49) or no revascularization. Coronary angiography showed 2-vessel disease in 12 (24%), 3-vessel disease in 33 (67%), and left main in 4 (8%). Two patients died after revascularization, but before operation, because of a ruptured aneurysm. Revascularization did not improve 30-day outcome; the incidence of the composite end point was 43% versus 33% (odds ratio 1.4, 95% confidence interval 0.7 to 2.8; p = 0.30). Also, no benefit during 1-year follow-up was observed after coronary revascularization (49% vs. 44%, odds ratio 1.2, 95% confidence interval 0.7 to 2.3; p = 0.48). Conclusions: In this randomized pilot study, designed to obtain efficacy and safety estimates, preoperative coronary revascularization in high-risk patients was not associated with an improved outcome. http://repub.eur.nl/res/pub/36207/ 2007-05-01T00:00:00Z Background: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are associated with improved outcome in patients with peripheral arterial disease. Statins may also have beneficial properties beyond their lipid-lowering effect. Methods: A prospective, observational cohort study was conducted at a university hospital from 1990 to 2005 to examine whether higher doses of statins and lower low-density lipoprotein (LDL) cholesterol levels are both independently associated with improved outcome in peripheral arterial disease. Enrolled were 1374 consecutive patients (age, 61 ± 10 years, 73% male) with peripheral arterial disease (ankle-brachial index ≤0.90). They were screened for clinical risk factors, statin therapy, and LDL cholesterol levels. Serial LDL cholesterol levels were measured at 6 months and yearly after enrollment. The mean follow-up time was 6.4 ± 3.6 years, and no patients were lost to follow-up. The primary end points were all-cause and cardiac mortality. The secondary end point was the progression to kidney failure. Results: Overall mortality, cardiac death, and progression to kidney failure occurred in 29%, 20%, and 5% of patients, respectively. Multivariate analysis revealed that higher doses of statins (per 10% increase) and lower 6-month LDL cholesterol levels (per 10 mg/dL decrease) were both independently associated with lower all-cause mortality (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.62 to 0.80; and HR, 0.96; 95% CI, 0.93 to 0.98, respectively) and cardiac death (HR, 0.76; 95% CI, 0.67 to 0.86; and HR, 0.95; 95% CI, 0.92 to 0.98, respectively). Higher high-density lipoprotein cholesterol levels also correlated significantly with lower all-cause and cardiac mortality. Higher doses of statins (per 10% increase) were associated with less progression to kidney failure (HR, 0.69; 95% CI, 0.54 to 0.89). Conclusions: Higher doses of statins and lower LDL cholesterol levels are both independently associated with improved outcome in patients with peripheral arterial disease. These results support the view that statins have beneficial effects beyond their lipid-lowering properties and should be considered in all patients with PAD, irrespective of LDL cholesterol levels. http://repub.eur.nl/res/pub/35810/ 2007-05-01T00:00:00Z OBJECTIVE - Cardiovascular events are high in patients with type 2 diabetes, whereas their risk stratification is more difficult. The higher risk may be related to differences in coronary plaque burden and composition. The purpose of this study was to evaluate whether differences in the extent and composition of coronary plaques in patients with and without diabetes can be observed using multislice computed tomography (MSCT). RESEARCH DESIGN AND METHODS - MSCT was performed in 215 patients (86 [40%] with type 2 diabetes). The number of diseased coronary segments was determined per patient; each diseased segment was classified as showing obstructive (≥50% luminal narrowing) disease or not. In addition, plaque type (noncalcified, mixed, and calcified) was determined. Plaque characteristics were compared in patients with and without diabetes. Regression analysis was performed to assess the correlation between plaque characteristics and diabetes. RESULTS - Patients with diabetes showed significantly more diseased coronary segments than nondiabetic patients (4.9 ± 3.5 vs. 3.9 ± 3.2, P = 0.03) with more nonobstructive (3.7 ± 3.0 vs. 2.7 ± 2.4, P = 0.008) plaques. Relatively more noncalcified (28 vs. 19%) and calcified (49 vs. 43%) and less mixed (23 vs. 38%) plaques were observed in patients with diabetes (P < 0.0001). Diabetes correlated with the number of diseased segments and nonobstructive, noncalcified, and calcified plaques. CONCLUSIONS - Differences in coronary plaque characteristics on MSCT were observed between patients with and without diabetes. Diabetes was associated with higher coronary plaque burden. More noncalcified and calcified plaques and less mixed plaques were observed in diabetic patients. Thus, MSCT may be used to identify differences in coronary plaque burden, which may be useful for risk stratification. http://repub.eur.nl/res/pub/36211/ 2007-04-24T00:00:00Z Objectives: The purpose of this study was to compare left ventricular (LV) dyssynchrony assessment by gated myocardial perfusion single-photon emission computed tomography (SPECT) (GMPS) and tissue Doppler imaging (TDI). Background: Recently, it has been suggested that LV dyssynchrony is an important predictor of response to cardiac resynchronization therapy (CRT); dyssynchrony is predominantly assessed by TDI with echocardiography. Information on LV dyssynchrony can also be provided by GMPS with phase analysis of regional LV maximal count changes throughout the cardiac cycle, which tracks the onset of LV thickening. Methods: In 75 patients with heart failure, depressed LV function, and wide QRS complex, GMPS and 2-dimensional echocardiography, including TDI, were performed as part of clinical screening for eligibility for CRT. Clinical status was evaluated with New York Heart Association functional classification, 6-min walk distance, and quality-of-life score. Different parameters (histogram bandwidth, phase SD, histogram skewness, and histogram kurtosis) of LV dyssynchrony were assessed from GMPS and compared with LV dyssynchrony on TDI with Pearson's correlation analyses. Results: Histogram bandwidth and phase SD correlated well with LV dyssynchrony assessed with TDI (r = 0.89, p < 0.0001 and r = 0.80, p < 0.0001, respectively). Histogram skewness and kurtosis correlated less well with LV dyssynchrony on TDI (r = -0.52, p < 0.0001 and r = -0.45, p < 0.0001, respectively). Conclusions: The LV dyssynchrony assessed from GMPS correlated well with dyssynchrony assessed by TDI; histogram bandwidth and phase SD showed the best correlation with LV dyssynchrony on TDI. These parameters seem most optimal for assessment of LV dyssynchrony with gated SPECT. Outcome studies after CRT are needed to further validate the use of GMPS for assessment of LV dyssynchrony. http://repub.eur.nl/res/pub/35471/ 2007-04-15T00:00:00Z The Syntax score (SXscore) was recently developed as a comprehensive angiographic scoring system aiming to assist in patient selection and risk stratification of patients with extensive coronary artery disease undergoing contemporary revascularization. A validation of this angiographic classification scheme is lacking. We assessed its predictive value in patients who underwent percutaneous intervention (PCI) for 3-vessel disease and explored its performance in comparison with the modified lesion classification system of the American Heart Association/American College of Cardiology. The SXscore, applied to 1,292 lesions in 306 patients who underwent PCI for 3-vessel disease in the Arterial Revascularization Therapies Study Part II, was 4 to 54.5, and after a median of 370 days (range 274 to 400) predicted the rate of major adverse cardiac and cerebrovascular events (hazard ratio 1.08/U increase, 95% confidence interval 1.05 to 1.11, p <0.0001), with patients in the highest SXscore tertile having a significantly higher event rate (27.9%) than patients in the lowest tertile (8.7%, hazard ratio 3.5, 95% confidence interval 1.7 to 7.4, p = 0.001). By multivariable analyses, SXscore independently predicted outcome with an almost fourfold adjusted increase in the risk of major adverse cardiac and cerebrovascular events in patients with high versus low values based on the discrimination level provided by classification and regression tree analysis. Compared with the modified lesion classification scheme of the American Heart Association/American College of Cardiology, SXscore showed a greater discrimination ability (c-index 0.58 ± 0.08 vs 0.67 ± 0.08, respectively, p <0.001) and a better goodness of fit with the Hosmer-Lemeshow statistic. In conclusion, the SXscore is a promising tool to risk stratify outcome in patients with extensive coronary artery disease undergoing contemporary PCI. http://repub.eur.nl/res/pub/35492/ 2007-04-01T00:00:00Z Background: Intervention is advised in selected asymptomatic patients with aortic valve disease. However, little is known regarding their actual management. Methods: The Euro Heart Survey was designed to evaluate practices. Severe isolated aortic stenosis (AS) was defined by a valve area ≤0.6 cm2/m2body surface area or mean gradient ≥50 mm Hg. Severe aortic regurgitation (AR) was defined by a grade ≥3/4. Patients were classified as asymptomatic when they were in New York Heart Association class I and were without angina. Decision to operate was analyzed by comparing patient characteristics with the American College of Cardiology/American Heart Association recommendations. Results: Of the 5001 patients, 136 had severe, isolated, and asymptomatic aortic valve disease (84 with AS and 52 with AR). Stress testing was performed in only 6 patients (4%). A decision to operate was taken in 45 patients (54%) with AS and 21 (40%) with AR. Indications for surgery were in accordance with the American College of Cardiology/American Heart Association guidelines in 57 patients (68%) with AS and in 41 (83%) with AR. However, the decision to operate was frequently based on class IIb recommendations in patients with AS. Intervention was "overused" in 18 patients with AS (21%) and in 5 (9%) with AR. Intervention was "underused" in 9 patients (11%) with AS and in 4 (8%) with AR. Conclusions: In asymptomatic patients with severe aortic valve disease, a decision to operate is frequently taken; and it is most often in agreement with guidelines, although often based on low-level recommendations. http://repub.eur.nl/res/pub/35532/ 2007-03-08T00:00:00Z BACKGROUND: Although randomized studies have shown a beneficial effect of drug-eluting stents in reducing the risk of repeated revascularization, these trials were underpowered to compare rates of death and myocardial infarction. The long-term safety of drug-eluting stents has been questioned recently. METHODS: We performed a pooled analysis of 1748 patients in four randomized trials evaluating the safety of sirolimus-eluting stents as compared with bare-metal stents. Patient-level data were obtained and analyzed by independent statisticians at two academic institutions. The primary safety end point was survival at 4 years. We tested for heterogeneities in treatment effect in patient subgroups. RESULTS: The survival rate at 4 years was 93.3% in the sirolimus-stent group, as compared with 94.6% in the bare-metal-stent group (hazard ratio for death, 1.24; 95% confidence interval [CI], 0.84 to 1.83; P=0.28). In the 428 patients with diabetes, a significant difference in the survival rate was observed in favor of the bare-metal-stent group over the sirolimus-stent group (95.6% vs. 87.8%; hazard ratio for death in the sirolimus-stent group, 2.9; 95% CI, 1.38 to 6.10; P=0.008). The lower survival rate among patients with diabetes who were treated with sirolimus-eluting stents was due to increased numbers of deaths from both cardiovascular and noncardiovascular causes. No difference in survival rate was detected among the patients without diabetes. Rates of myocardial infarction and stent thrombosis were similar in the two groups. CONCLUSIONS: In a pooled analysis of data from four trials comparing sirolimus-eluting stents and bare-metal stents, no significant differences were found between the two treatments in rates of death, myocardial infarction, or stent thrombosis. Copyright http://repub.eur.nl/res/pub/36812/ 2007-03-01T00:00:00Z Objective: Self-perceived health status may be helpful in identifying patients at high risk for adverse outcomes. The Euro Heart Survey on Coronary Revascularization (EHS-CR) provided an opportunity to explore whether impaired health status was a predictor of 1-year mortality in patients with coronary artery disease (CAD) undergoing angiographic procedures. Methods: Data from the EHS-CR that included 5619 patients from 31 member countries of the European Society of Cardiology were used. Inclusion criteria for the current study were completion of a self-report measure of health status, the EuroQol Questionnaire (EQ-5D) at discharge and information on 1-year follow-up, resulting in a study population of 3786 patients. Results: The 1-year mortality was 3.2% (n = 120). Survivors reported fewer problems on the five dimensions of the EQ-5D as compared with non-survivors. A broad range of potential confounders were adjusted for, which reached a p<0.10 in the unadjusted analyses. In the adjusted analyses, problems with self-care (OR 3.45; 95% CI 2.14 to 5.59) and a low rating (≤ 60) on health status (OR 2.41; 95% CI 1.47 to 3.94) were the most powerful independent predictors of mortality, among the 22 clinical variables included in the analysis. Furthermore, patients who reported no problems on all five dimensions had significantly lower 1-year mortality rates (OR 0.47; 95% CI 0.28 to 0.81). Conclusions: This analysis shows that impaired health status is associated with a 2-3-fold increased risk of all-cause mortality in patients with CAD, independent of other conventional risk factors. These results highlight the importance of including patients' subjective experience of their own health status in the evaluation strategy to optimise risk stratification and management in clinical practice. http://repub.eur.nl/res/pub/36816/ 2007-03-01T00:00:00Z http://repub.eur.nl/res/pub/35842/ 2007-02-24T00:00:00Z Background: Stent thrombosis is a safety concern associated with use of drug-eluting stents. Little is known about occurrence of stent thrombosis more than 1 year after implantation of such stents. Methods: Between April, 2002, and Dec, 2005, 8146 patients underwent percutaneous coronary intervention with sirolimus-eluting stents (SES; n=3823) or paclitaxel-eluting stents (PES; n=4323) at two academic hospitals. We assessed data from this group to ascertain the incidence, time course, and correlates of stent thrombosis, and the differences between early (0-30 days) and late (>30 days) stent thrombosis and between SES and PES. Findings: Angiographically documented stent thrombosis occurred in 152 patients (incidence density 1·3 per 100 person-years; cumulative incidence at 3 years 2·9%). Early stent thrombosis was noted in 91 (60%) patients, and late stent thrombosis in 61 (40%) patients. Late stent thrombosis occurred steadily at a constant rate of 0·6% per year up to 3 years after stent implantation. Incidence of early stent thrombosis was similar for SES (1·1%) and PES (1·3%), but late stent thrombosis was more frequent with PES (1·8%) than with SES (1·4%; p=0·031). At the time of stent thrombosis, dual antiplatelet therapy was being taken by 87% (early) and 23% (late) of patients (p<0·0001). Independent predictors of overall stent thrombosis were acute coronary syndrome at presentation (hazard ratio 2·28, 95% CI 1·29-4·03) and diabetes (2·03, 1·07-3·83). Interpretation: Late stent thrombosis was encountered steadily with no evidence of diminution up to 3 years of follow-up. Early and late stent thrombosis were observed with SES and with PES. Acute coronary syndrome at presentation and diabetes were independent predictors of stent thrombosis. http://repub.eur.nl/res/pub/35615/ 2007-02-01T00:00:00Z BACKGROUND - Atherosclerosis is considered an inflammatory disease. Recent studies provided evidence for a predominant upstream location of plaque inflammation. The present study introduces a novel technique that evaluates the underlying mechanism of this spatial organization. METHODS AND RESULTS - In hypercholesterolemic rabbits, atherosclerosis of the infrarenal aorta was induced by a combination of endothelial denudation and a high-cholesterol diet (2% cholesterol for 2 months). At the time of death, aortic vessel segments were dissected and reconstructed with a new technique that preserved the original intravascular ultrasound-derived lumen geometry. This enabled us to study the spatial relation of histological markers like macrophages, smooth muscle cells, lipids, gelatinolytic activity, and oxidized low-density lipoprotein. Results showed a predominant upstream localization of macrophages and gelatinase activity. Colocalization studies indicated that gelatinase activity was associated with macrophages and smooth muscle cells. Further analysis revealed that this was caused by subsets of smooth muscle cells and macrophages, which were associated with oxidized low-density lipoprotein accumulation. CONCLUSIONS - Upstream localization of a vulnerable plaque phenotype is probably due to an accumulation of oxidized low-density lipoprotein, which activates/induces subsets of smooth muscle cells and macrophages to gelatinase production. http://repub.eur.nl/res/pub/36506/ 2007-02-01T00:00:00Z BACKGROUND: Patients undergoing noncardiac, nonvascular surgery are at risk for perioperative mortality owing to underlying (a)symptomatic coronary artery disease. We hypothesized that β-blocker and statin use are associated with reduced perioperative mortality. METHODS: We performed a case-control study in 75 581 patients who underwent 108 593 noncardiac, nonvascular surgery at the Erasmus Medical Center between 1991 and 2001. Cases were the 989 patients who died during hospital stay after surgery. From the remaining patients, 1879 matched controls (age, sex, calendar year and type of surgery) were selected. Information was then obtained regarding the use of β-blockers and statins and the presence of cardiac risk factors. RESULTS: The median age of the study population was 63 years; 61% were men. β-blockers were less often used in cases than in controls (6.2 vs. 8.2%; P=0.05), as were statins (2.4 vs. 5.5%; P<0.001). After adjustment for the propensity of β-blocker use and cardiovascular risk factors, β-blockers were associated with a 59% mortality reduction (odds ratio 0.41; 95% confidence interval 0.28-0.59). Statins were associated with a 60% mortality reduction (adjusted odds ratio 0.40; 95% confidence interval 0.24-0.68). A significant interaction between β-blockers and statins was observed (P<0.001). In the presence of each other, statins and β-blockers were not associated with reduced mortality (adjusted odds ratio 2.0 and 95% confidence interval 0.74-5.7 and adjusted odds ratio 1.3 and 95% confidence interval 0.52-3.2). It should be, however, noted that only nine cases and 29 controls used both agents simultaneously. CONCLUSION: This case-control study provides evidence that β-blockers and statins are individually associated with a reduction of perioperative mortality in patients undergoing noncardiac, nonvascular surgery. http://repub.eur.nl/res/pub/36510/ 2007-02-01T00:00:00Z OBJECTIVE: Evaluation of contrast-enhanced magnetic resonance imaging to assess right ventricular infarction in patients with acute inferior myocardial infarction. BACKGROUND: Contrast-enhanced magnetic resonance imaging has been used for assessing scar tissue after left ventricular infarction. The value of contrast-enhanced magnetic resonance imaging to assess right ventricular infarction is unknown and was evaluated. METHODS: Consecutive patients (n=18) with first acute inferior infarction were included. Resting electrocardiogram and right-sided electrocardiogram were acquired to assess right ventricular involvement. Resting cine magnetic resonance imaging was performed to evaluate right ventricular function and volumes, whereas the extent of right ventricular scar tissue was assessed by contrast-enhanced magnetic resonance imaging. Cine magnetic resonance imaging was repeated at 6-months follow-up to re-assess right ventricular function and volumes. RESULTS: Sensitivity and specificity of magnetic resonance imaging were 100 and 78%, respectively, to detect right ventricular infarction (using the right-sided electrocardiogram as the gold standard). At 6 months follow-up, patients with scar tissue on contrast-enhanced magnetic resonance imaging showed right ventricular dilatation. Moreover, the extent of right ventricular scar tissue was linearly related to the severity of right ventricular dilatation. CONCLUSIONS: Contrast-enhanced magnetic resonance imaging permits accurate assessment of right ventricular scar tissue. Patients with extensive right ventricular infarction demonstrate right ventricular dilatation at 6 months follow-up. http://repub.eur.nl/res/pub/36825/ 2007-02-01T00:00:00Z Background: Repeat coronary artery bypass grafting (redo-CABG) in patients with ischaemic cardiomyopathy is associated with high perioperative risk and worse long-term outcome compared with patients undergoing their first CABG. Objective: To assess whether patients with viable myocardium undergoing redo-CABG have a better outcome. Methods: 18 patients with ischaemic cardiomyopathy underwent redo-CABG and 34 underwent their first CABG; all had substantial viability (≥25% of the left ventricle) on dobutamine stress echocardiography (DSE). Left ventricular ejection fraction (LVEF) and heart failure symptoms were assessed before and 9-12 months after revascularisation. Cardiac event rate was assessed during the follow-up period (median 4 years, 25-75th centile 2.8-4.9 years). Results: The extent of viable myocardium on DSE was comparable in the two groups (11.3 (3.9) segments in patients who underwent redo-CABG v 12.8 (3.0) in patients who underwent their first CABG; p = NS). LVEF improved from 32% (9%) to 39% (12%); p = 0.01, in patients who underwent redo-CABG and from 30% (7%) to 36% (7%); p<0.01, in those who underwent their first CABG; New York Heart Association class improved from 2.5 (1.1) to 1.9 (0.8); p = 0.03, and from 2.7 (1.0) to 1.8 (0.70); p<0.01, respectively. In patients who underwent redo-CABG, the perioperative mortality was 0, post-surgery inotropic support was needed in 11% of the patients and mid-term (4-year) survival was 100%, with a total event rate of 28%. All these variables were not statistically different from patients who underwent their first CABG (p = 0.50, 0.90, 0.08 and 0.81, respectively). Conclusion: Patients with ischaemic cardiomyopathy and substantial viability undergoing redo-CABG benefit from revascularisation in terms of improvement in LVEF, heart failure symptoms, angina and mid-term prognosis. http://repub.eur.nl/res/pub/36829/ 2007-02-01T00:00:00Z Objective: To assess the long-term prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) after major vascular surgery. Design: A single-centre prospective cohort study. Patients: 335 patients who underwent abdominal aortic aneurysm repair or lower extremity bypass surgery. Interventions: Prior to surgery, baseline NT-proBNP level was measured. Patients were also evaluated for cardiac risk factors according to the Revised Cardiac Risk Index. Dobutamine stress echocardiography (DSE) was performed to detect stress-induced myocardial ischaemia. Main outcome measures: The prognostic value of NT-proBNP was evaluated for the endpoints all-cause mortality and major adverse cardiac events (MACE) during long-term follow-up. Results: In this patient cohort (mean age: 62 years, 76% male), median NT-proBNP level was 186 ng/l (interquartile range: 65-444 ng/l). During a mean follow-up of 14 (SD 6) months, 49 patients (15%) died and 50 (15%) experienced a MACE. Using receiver operating characteristic curve analysis for 6-month mortality and MACE, NT-proBNP had the greatest area under the curve compared with cardiac risk score and DSE. In addition, an NT-proBNP level of 319 ng/l was identified as the optimal cut-off value to predict 6-month mortality and MACE. After adjustment for age, cardiac risk score, DSE results and cardioprotective medication, NT-proBNP ≥319 ng/l was associated with a hazard ratio of 4.0 for all-cause mortality (95% CI: 1.8 to 8.9) and with a hazard ratio of 10.9 for MACE (95% CI: 4.1 to 27.9). Conclusion: Preoperative NT-proBNP level is a strong predictor of long-term mortality and major adverse cardiac events after major non-cardiac vascular surgery. http://repub.eur.nl/res/pub/35644/ 2007-01-01T00:00:00Z M-mode echocardiography (using the septal-to-posterior wall motion delay [SPWMD]) and color-coded tissue Doppler imaging (TDI; using the septal-to-lateral delay in peak systolic velocity) have been proposed for assessment of left ventricular (LV) dyssynchrony and prediction of response to cardiac resynchronization therapy (CRT). In this study, a head-to-head comparison between M-mode echocardiography and color-coded TDI was performed for assessment of LV dyssynchrony and prediction of response to CRT. Consecutive (n = 98) patients with severe heart failure (New York Heart Association class III/IV), LV ejection fraction ≤35%, and QRS duration >120 ms underwent CRT. Before pacemaker implantation, LV dyssynchrony was assessed by M-mode echocardiography (SPWMD) and color-coded TDI (septal-to-lateral delay). At baseline and 6 months after implantation, clinical and echocardiographic parameters were evaluated. SPWMD measurement was not feasible in 41% of patients due to akinesia of the septal and/or posterior walls or poor acoustic windows. Conversely, the septal-to-lateral delay could be assessed in 96% of patients. At 6-month follow-up, 75 patients (77%) were classified as responders to CRT (improvement ≥1 New York Heart Association class). The sensitivity and specificity of SPWMD were lower compared with those of septal-to-lateral delay (66% vs 90%, p <0.05; 50% vs 82%, p = NS, respectively). In conclusion, LV dyssynchrony assessment was feasible in 59% of patients with M-mode echocardiography compared with 96% (p <0.05) when color-coded TDI was used. Color-coded TDI was superior to M-mode echocardiography for prediction of response to CRT. http://repub.eur.nl/res/pub/35872/ 2007-01-01T00:00:00Z Aims: At present, 20-30% of patients do not respond to cardiac resynchronization therapy (CRT). In this study, the relation between the extent of viable myocardium and scar tissue vs. response to CRT was evaluated. In addition, the presence of scar tissue in the left ventricular (LV) lead position was specifically related to response to CRT. Methods and results: A total of 51 consecutive patients with ischaemic heart failure and substantial LV dyssynchrony undergoing CRT were included. All patients underwent gated SPECT before CRT implantation to determine the extent of scar tissue and viable myocardium. Clinical and echocardiographic parameters were assessed at baseline and after 6 months of CRT. The results demonstrated direct relations between the response to CRT and the extent of viable myocardium and scar tissue. In addition, the 15 patients (29%) with transmural scar tissue (< 50% tracer activity) in the region of the LV pacing lead showed no improvement after 6 months of CRT. Conclusion: The extent of scar tissue and viable myocardium were directly related to the response to CRT. Furthermore, scar tissue in the LV pacing lead region may prohibit response to CRT. Evaluation for viability and scar tissue may be considered in the selection process for CRT. http://repub.eur.nl/res/pub/36344/ 2007-01-01T00:00:00Z Objective: To determine the relationship between preoperative glucose levels and perioperative mortality in noncardiac, nonvascular surgery. Research design and methods: We performed a case-control study in a cohort of 108 593 patients who underwent noncardiac surgery at the Erasmus MC during 1991-2001. Cases were 989 patients who underwent elective noncardiac, nonvascular surgery and died within 30 days during hospital stay. From the remaining patients, 1879 matched controls (age, sex, calendar year, and type of surgery) were selected. Information was obtained regarding the presence of cardiac risk factors, medication, and preoperative laboratory results. Preoperative random glucose levels < 5.6 mmol/l (110 mg/dl) were normal. Impaired glucose levels in the range of 5.6-11.1 mmol/l were prediabetes. Glucose levels ≥ 11.1 mmol/l (200 mg/dl) were diabetes. Results: Preoperative glucose levels were available in 904 cases and 1247 controls. A cardiovascular complication was the primary cause of death in 207 (23%) cases. Prediabetes glucose levels were associated with a 1.7-fold increased mortality risk compared with normoglycernic levels (adjusted odds ratio (OR) 1.7 and 95% confidence interval (CI) 1.4-2.1; P<0.001). Diabetes glucose levels were associated with a 2.1-fold increased risk (adjusted OR 2.1 and 95% CI 1.3-3.5; P<0.001). In cases with cardiovascular death, prediabetes glucose levels had a threefold increased cardiovascular mortality risk (adjusted OR 3.0 and 95% CI 1.7-5.1) and diabetes glucose levels had a fourfold increased cardiovascular mortality risk (OR 4.0 and 95% CI 1.3-12). Conclusions: Preoperative hyperglycemia is associated with increased (cardiovascular) mortality in patients undergoing noncardiac, nonvascular surgery. http://repub.eur.nl/res/pub/36715/ 2007-01-01T00:00:00Z Objectives: To assess the relation between beta-blocker use, underlying cardiac risk, and 1-year outcome in vascular surgery patients, including the effect of beta-blocker withdrawal. Design: Prospective survey. Materials: 711 consecutive peripheral vascular surgery patients from 11 hospitals in the Netherlands between May and December 2004. Methods: Patients were evaluated for cardiac risk factors, beta-blocker use and 1-year mortality. Low and high risk was defined according to the Revised Cardiac Risk Index. Propensity scores for the likelihood of beta-blocker use were calculated and regression models were used to study the relation between beta-blocker use and mortality. Results: 285 patients (40%) received beta-blockers throughout the perioperative period (continuous users). Only 52% of the 281 high risk patients received continuous beta-blocker therapy. Beta-blocker therapy was started in 29 and stopped in 21 patients, respectively. One-year mortality was 11%. After adjustment for potential confounders and the propensity of its use, continuous beta-blocker use remained significantly associated with a lower 1-year mortality compared to non-users (HR = 0.4; 95%CI = 0.2-0.7). In contrast, beta-blocker withdrawal was associated with an increased risk of 1-year mortality compared to non-users (HR = 2.7; 95%CI = 1.2-5.9). Conclusions: We demonstrated an under-use of beta-blockers in vascular surgery patients, even in high-risk patients. Perioperative beta-blocker use was independently associated with a lower risk of 1-year mortality compared to non-use, while perioperative withdrawal of beta-blocker therapy was associated with a higher 1-year mortality. http://repub.eur.nl/res/pub/36717/ 2007-01-01T00:00:00Z Background: The aim of this study was to assess the prognostic value of quantitative gated technetium 99m tetrofosmin single photon emission computed tomography (SPECT) imaging in patients with left bundle branch block (LBBB). Methods and Results: We followed up 101 consecutive patients with LBBB using Tc-99m tetrofosmin gated SPECT imaging. The mean follow-up was 1.24 years (maximum, 2.48 years). Hard endpoints were all-cause death and acute myocardial infarction. Event-free survival curves were obtained. Optimal cutoff points for left ventricular (LV) volumes and LV ejection fraction (EF) to predict outcome were determined by receiver operating characteristic curve analysis. Of the patients, 94 had an abnormal study. Fifteen hard events occurred (thirteen deaths). Perfusion abnormalities were similar for patients with or without events. For LV function parameters, the survival curves were maximally separated when we used cutoff values of 160 mL or greater for end-diastolic volume (P = .019 and hazard ratio [HR] of 1.04 for hard events, P = .024 and HR of 1.04 for all-cause death), 100 mL or greater for end-systolic volume (P = .043 and HR of 1.04 for hard events, P = .062 and HR of 1.04 for all-cause death), and lower than 35% for LVEF (P = .013 and HR of 0.81 for hard events, P = .047 and HR of 0.81 for all-cause death). Conclusion: By use of quantitative gated SPECT imaging, LBBB patients with an end-diastolic volume of 160 mL or greater, end-systolic volume of 100 mL or greater, or LVEF lower than 35% are at increased risk for subsequent cardiac events. http://repub.eur.nl/res/pub/13907/ 2005-10-01T00:00:00Z AIMS: Plaque rupture has been associated with a high matrix metalloproteinase (MMP) activity. Recently, regional temperature variations have been observed in atherosclerotic plaques in vivo and ascribed to the presence of macrophages. As macrophages are a major source of MMPs, we examined whether regional temperature changes are related to local MMP activity and macrophage accumulation. METHODS AND RESULTS: Plaques were experimentally induced in rabbit (n=11) aortas, and at the day of sacrifice, a pull-back was performed with a thermography catheter. Hot (n=10), cold (n=10), and reference (n=11) regions were dissected and analysed for smooth muscle cell (SMC), lipids (L), collagen (COL), and macrophage (MPhi) cell densities (%); a vulnerability index (VI) was calculated as VI=MPhi+L/(SMC+COL). In addition, accumulation and activity of MMP-2 and MMP-9 were determined with zymography. Ten hot regions were identified with an average temperature of 0.40+/-0.03 degrees C (P<0.05 vs. reference) and 10 cold regions with 0.07+/-0.03 degrees C (P<0.05 vs. hot). In the hot regions, a higher macrophage density (173%), less SMC density (77%), and a higher VI (100%) were identified. In addition, MMP-9 (673%) activity was increased. A detailed regression analysis revealed that MMP-9 predicted hot regions better than macrophage accumulation alone. CONCLUSION: In vivo temperature measurements enable to detect plaques that contain more macrophages, less SMCs, and a higher MMP-9 activity. http://repub.eur.nl/res/pub/13702/ 2005-06-01T00:00:00Z AIMS: To study recovery of segmental wall thickening (SWT), ejection fraction (EF), and end-systolic volume (ESV) after acute myocardial infarction (AMI) in patients who underwent primary stenting with drug-eluting stents. Additionally, to evaluate the predictive value of magnetic resonance imaging (MRI)-based myocardial perfusion and delayed enhancement (DE) imaging. METHODS AND RESULTS: Twenty-two patients underwent cine-MRI, first-pass perfusion, and DE imaging 5 days after successful placement of a drug-eluting stent in the infarct-related coronary artery. Regional myocardial perfusion and the transmural extent of DE were evaluated. A per patient perfusion score was calculated and consisted of a summation of all segmental scores. Myocardial infarct size was quantified by measuring the volume of DE. At 5 months after AMI, cine-MRI was performed and SWT, EF, and ESV were quantified. EF increased from 48+/-11 to 55+/-9% (P<0.01). SWT at 5 months was inversely related to baseline segmental DE scores (P<0.001) and segmental perfusion scores (P<0.001). EF and ESV at 5 months were related to acute infarct size (R(2)=0.65; P<0.001 and R(2)=0.78; P<0.001, respectively) and the calculated perfusion score (R(2)=0.23; P=0.02 and R(2)=0.14; P=0.09, respectively) at baseline. CONCLUSION: Marked recovery of left ventricular function was observed in patients receiving a drug-eluting stent for AMI. DE imaging appears to be a better prognosticator than perfusion imaging. http://repub.eur.nl/res/pub/13747/ 2005-06-01T00:00:00Z AIMS: The purpose of the Euro Heart Survey Programme of the European Society of Cardiology is to evaluate to which extent clinical practice endorses existing guidelines as well as to identify differences in population profiles, patient management, and outcome across Europe. The current survey focuses on the invasive diagnosis and treatment of patients with established coronary artery disease (CAD). METHODS AND RESULTS: Between November 2001 and March 2002, 7769 consecutive patients undergoing invasive evaluation at 130 hospitals (31 countries) were screened for the presence of one or more coronary stenosis >50% in diameter. Patient demographics and comorbidity, clinical presentation, invasive parameters, treatment options, and procedural techniques were prospectively entered in an electronic database (550 variables+29 per diseased coronary segment). Major adverse cardiac events (MACE) were evaluated at 30 days and 1 year. Out of 5619 patients with angiographically proven coronary stenosis (72% of screened population), 53% presented with stable angina while ST elevation myocardial infarction (STEMI) was the indication for coronary angiography in 16% and non-ST segment elevation myocardial infarction or unstable angina in 30%. Only medical therapy was continued in 21%, whereas mechanical revascularization was performed in the remainder [percutaneous coronary intervention (PCI) in 58% and coronary artery bypass grafting (CABG) in 21%]. Patients referred for PCI were younger, were more active, had a lower risk profile, and had less comorbid conditions. CABG was performed mostly in patients with left main lesions (21%), two- (25%), or three-vessel disease (67%) with 4.1 diseased segments, on average. Single-vessel PCI was performed in 82% of patients with either single- (45%), two- (33%), or three-vessel disease (21%). Stents were used in 75% of attempted lesions, with a large variation between sites. Direct PCI for STEMI was performed in 410 cases, representing 7% of the entire workload in the participating catheterization laboratories. Time delay was within 90 min in 76% of direct PCI cases. In keeping with the recommendations of practice guidelines, the survey identified under-use of adjunctive medication (GP IIb/IIIa receptor blockers, statins, and angiotensin-converting enzyme-inhibitors). Mortality rates at 30 days and 1 year were low in all subgroups. MACE primarily consisted of repeat PCI (12%). CONCLUSION: The current Euro Heart Survey on coronary revascularization was performed in the era of bare metal stenting and provides a global European picture of the invasive approach to patients with CAD. These data will serve as a benchmark for the future evaluation of the impact of drug-eluting stents on the practice of interventional cardiology and bypass surgery. http://repub.eur.nl/res/pub/8380/ 2005-01-01T00:00:00Z STUDY OBJECTIVE: International variation in the outcomes of patients with acute coronary syndromes (ACS) has been well reported. The relative contributions of patient, hospital, and country level factors on clinical outcomes, however, remain unclear, and thus, was the objective of this study. DESIGN: Multilevel logistic regression models were developed for death/(re)infarction (MI) at 30 days and death in one year, with patients (1st level) nested in hospitals (2nd level) and hospitals in countries (3rd level).Settings: The GUSTO IV ACS clinical trial was carried out at 458 hospital sites in 24 countries. PATIENTS: 7800 non-ST segment elevation (NSTE) ACS patients. MAIN RESULTS: There were substantial variations among countries in the processes and outcomes of care at 30 days, ranging from 5.4% to 50.0% for percutaneous coronary intervention, 4.3% to 21.2% for coronary artery bypass graft surgery, 5.0% to 13.9% for 30 day death/(re)MI, and 4.9% to 14.8% for one year mortality. However, the residual inter-country variations in 30 day death/(re)MI and one year mortality became non-significant and nearly disappeared (p > 0.500 for both) after adjusting for key baseline patient characteristics and hospital factors, which became significant (p < 0.01 for both). Patient level factors accounted for 96%-99% of total variation in these end points, leaving the remaining 1% and 4% of variance attributable to hospital level factors. CONCLUSION: The international differences in clinical outcomes in this study of NSTE ACS are primarily accounted for by the patient level factors, with hospital level factors playing a minor part, and the country level factors a negligible one. These findings have significant policy and research implications involving international collaboration and comparisons. http://repub.eur.nl/res/pub/13489/ 2004-09-01T00:00:00Z BACKGROUND: Immediate, as well as early, revascularisation is of benefit in patients with acute coronary syndromes (ACS) presenting with ST elevation. However, trials comparing invasive versus medical treatment in patients with an acute coronary syndrome without ST elevation do not consistently show improvement in survival after revascularisation. Accordingly, additional data are warranted. METHODS: The effect of revascularisation within 30 days on one-year survival in the GUSTO IV ACS trial was investigated. A total of 7800 patients were included with an acute coronary syndrome without ST elevation, documented by either elevated cardiac troponin or transient or persistent ST-segment depression. In this trial, comparing abciximab versus placebo as initial medical therapy, coronary angiography within 60 h after randomisation was discouraged. In 30-day survivors, those who underwent revascularisation were compared with 30-day survivors without revascularisation. Adjustments were made for patient characteristics, and for a propensity score that was adjusted for covariates associated with the likelihood of early revascularisation. FINDINGS: Of the 7496 patients who survived at least 30 days, 2265 (30%) underwent coronary revascularisation within 30 days: 789 patients CABG, 1450 PCI and 26 both CABG and PCI. Procedure-related mortality was low at 1.8%. Patients with revascularisation had a lower one-year mortality compared to medically treated patients (2.3% vs. 5.6%, p < 0.001). After multivariable analyses, patients with revascularisation had a relative risk of subsequent mortality within 1 year of 0.53 (95% CI 0.37-0.77) compared to patients without revascularisation. CONCLUSIONS: Revascularisation within 30 days is associated with an improved prognosis in ACS without ST-segment elevation. The relative high mortality in medically treated patients may be related in part to patient selection, but warrants further studies to improve outcome of these patients. http://repub.eur.nl/res/pub/13444/ 2004-07-01T00:00:00Z AIMS: Due to a lack of clinical trials, scientific evidence regarding the management of patients with chronic heart failure and preserved left ventricular function (PLVF) is scarce. The EuroHeart Failure Survey provided information on the characteristics, treatment and outcomes of patients with PLVF as compared to patients with a left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: We performed a secondary analysis using data from the EuroHeart Failure Survey, only including patients with a measurement of LV function (n = 6806). We selected two groups: patients with LVSD (54%) and patients with a PLVF (46%). Patients with a PLVF were, on average, 4 years older and more often women (55% vs. 29%, respectively, p < 0.001) as compared to LVSD patients, and were more likely to have hypertension (59% vs. 50%, p < 0.001) and atrial fibrillation (25% vs. 23%, p = 0.01). PLVF patients received less cardiovascular medication compared to PLVF patients, with the exception of calcium antagonists. Multivariate analysis revealed that LVSD was an independent predictor for mortality, while no differences in treatment effect on mortality between the two groups was observed. A sensitivity analysis, using different thresholds to separate patients with and without LVSD revealed comparable findings. CONCLUSIONS: In the EuroHeart Failure Survey, a high percentage of heart failure patients had PLVF. Although major clinical differences were seen between the groups, morbidity and mortality was high in both groups. http://repub.eur.nl/res/pub/5731/ 2004-05-01T00:00:00Z BACKGROUND: The glycoprotein IIb/IIIa receptor antagonist abciximab reduces the risk of thrombotic complications with percutaneous coronary intervention, but also has been associated with higher bleeding rates. METHODS: In the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO IV-ACS) trial, abciximab (either a 24-hour or 48-hour infusion) was compared with placebo in 7800 patients with an acute coronary syndrome. During study drug administration, 2% of the patients underwent a revascularization procedure. RESULTS: In 1507 patients (19.3%), bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) classification was observed while they were hospitalized or within 7 days. Ninety-eight patients (1.2%) had a major bleed, including 8 with intracranial hemorrhages. In 215 patients (2.8%), a minor bleed was reported, and in 1194 patients (15.3%), an insignificant bleed was reported. Bleeding was more frequent in patients receiving a 48-hour infusion of abciximab. Spontaneous bleeding was seen in 911 patients (11.7%). The other 596 patients had a bleeding event in conjunction with a procedure. The most significant predictors for bleeding with multivariable analysis were: use of low-molecular weight heparin, duration of abciximab infusion, region of hospitalization, performance of coronary artery bypass grafting or percutaneous coronary intervention (PCI), advanced age, and female sex. For major bleeding, the predictors were performance of coronary artery bypass grafting or PCI, long duration of abciximab administration, and advanced age. CONCLUSION: Treatment with abciximab in patients with non-ST-elevation acute coronary syndromes is safe because major bleeding and stroke are rare, and most events are clinically manageable or have few clinical consequences. Guidelines for use of abciximab in combination with other antithrombotic agents developed for PCI should also be respected in acute coronary syndromes. Specific dosing guidelines for combination with low-molecular weight heparin must be developed for patients who subsequently will undergo a PCI. http://repub.eur.nl/res/pub/5722/ 2004-01-01T00:00:00Z Guidelines for the management of patients with cardiovascular disease are designed to assist cardiologists and other physicans in their practice. Surveys are conducted to assess whether guidelines are followed in practice. The results of surveys on acute coronary syndromes, coronary revascularisation, secondary prevention, valvular heart disease and heart failure are presented. Comparing surveys conducted between 1995 and 2002, a gradual improvement in use ofsecondary preventive therapy is observed. Nevertheless, important deviations from established guidelines are noted, with a significant variation among different hospitals in the Netherlands and in other European countries. Measures for fiuther improvement of clinical practice indude more rapid treatment of patients with evolving myocardial infarction, more frequent use of clopidogrel and glycoprotein IIb/IIIa receptor blockers in patients with acute coronary syndromes, more frequent use of 5-blockers in patients with heart failure and more intense measures to encourage patients to stop smoking. Targets for the proportion ofpatients who might receive specific therapies are presented. http://repub.eur.nl/res/pub/5733/ 2004-01-01T00:00:00Z Doel. Beschrijven of richtlijnen voor de behandeling van acuut coronair syndroom (ACS) in de dagelijkse praktijk worden toegepast, en op welke punten de behandeling verschilt tussen Nederland en de overige lidstaten van de European Society of Cardiology (ESC). Opzet. Prospectief observationeel onderzoek. Methode. In de periode 4 september 2000-15 mei 2001 werden in Nederland in 6 ziekenhuizen, en in 24 andere ESC-lidstaten in 97 ziekenhuizen, patiënten met een bevestigde diagnose van ACS geïncludeerd. Gegevens werden verzameld over de acute behandeling en secundaire preventie bij patiënten met ST-elevatie en over medicamenteuze behandeling, risicostratificatie en secundaire preventie bij patiënten zonder ST-elevatie. De bevindingen werden vergeleken met de aanbevelingen in de richtlijnen van de ESC. Resultaten. In Nederland werden 223 patiënten met ST-elevatie geïncludeerd en 198 zonder, en in de overige Europese landen respectievelijk 4208 en 5169 patiënten. De mediane leeftijd was 64-67 jaar. Het percentage mannen was 64-73. Van de patiënten met ST-elevatie die binnen 12 uur na het ontstaan van de symptomen in het ziekenhuis arriveerden, ontving 35% noch trombolyse, noch primaire percutane coronaire interventie. Zowel in Nederland als in de andere Europese landen onderging de helft van de patiënten met ST-elevatie trombolyse later dan 40 minuten en primaire percutane coronaire interventie later dan 90 minuten, na binnenkomst in het ziekenhuis. Risicoschatting door een troponinebepaling werd in Nederland vaker toegepast. Van de hoogrisicopatiënten zonder ST-elevatie onderging ruim 50% in zowel Nederland als de rest van Europa coronairangiografie. Bijna 70% en 80% van de laag-risicopatiënten zonder ST-elevatie onderging een inspanningstest en/of coronairangiografie. In Nederland werden clopidogrel, glycoproteïne-IIb/IIIa-antagonisten en statinen vaker voorgeschreven en ACE-remmers minder vaak. Conclusie. Richtlijnen voor de behandeling van ACS werden zowel in Nederland als in de rest van Europa matig gevolgd. De behandeling verschilde op diverse punten tussen Nederland en de andere landen. http://repub.eur.nl/res/pub/13253/ 2003-11-25T00:00:00Z BACKGROUND: In vivo detection of vulnerable plaques is presently limited by a lack of diagnostic tools. Intravascular ultrasound elastography is a new technique based on intravascular ultrasound and has the potential to differentiate between different plaques phenotypes. However, the predictive value of intravascular elastography to detect vulnerable plaques had not been studied. METHODS AND RESULTS: Postmortem coronary arteries were investigated with intravascular elastography and subsequently processed for histology. In histology, a vulnerable plaque was defined as a plaque consisting of a thin cap (<250 microm) with moderate to heavy macrophage infiltration and at least 40% of atheroma. In elastography, a vulnerable plaque was defined as a plaque with a high strain region at the surface with adjacent low strain regions. In 24 diseased coronary arteries, we studied 54 cross sections. In histology, 26 vulnerable plaques and 28 nonvulnerable plaques were found. Receiver operator characteristic analysis revealed a maximum predictive power for a strain value threshold of 1.26%. The area under the receiver operator characteristic curve was 0.85. The sensitivity was 88%, and the specificity was 89% to detect vulnerable plaques. Linear regression showed high correlation between the strain in caps and the amount of macrophages (P<0.006) and an inverse relation between the amount of smooth muscle cells and strain (P<0.0001). Plaques, which are declared vulnerable in elastography, have a thinner cap than nonvulnerable plaques (P<0.0001). CONCLUSIONS: Intravascular elastography has a high sensitivity and specificity to detect vulnerable plaques in vitro. http://repub.eur.nl/res/pub/5716/ 2003-09-01T00:00:00Z Objective: The objective of this observational study was to assess time from electrocardiogram diagnosis to treatment and time from pain onset to treatment with double bolus reteplase compared to current therapy with streptokinase or bolus anistreplase in 2 cities (Rotterdam and Nijmegen) in the Netherlands, where prehospital thrombolysis is an established way of treatment of acute myocardial infarction. Methods: Prehospital thrombolysis is performed using electrocardiogram diagnosis by the ambulance service as well as bolus anistreplase for treatment in Nijmegen, and streptokinase infusion in Rotterdam. Reteplase or anistreplase/streptokinase was assigned open label to patients according to order of presentation on a 1-to-1 basis. All patients were treated with nitrates sublingually and aspirin orally. Time intervals were recorded by the ambulance staff. Results: In total, 250 patients were treated between April 1, 1999 and August 1, 2000. Reteplase was used in 120 patients and anistreplase/streptokinase in 130 patients. Using double bolus reteplase resulted in a significantly shorter time to treatment: a median of 81 minutes compared to a median of 104 minutes with the established therapy (P < .0001). There were no differences in mortality, aborted myocardial infarction, hemorrhagic stroke or the need for rescue angioplasty between the groups. Conclusion: In prehospital thrombolysis, double bolus reteplase is associated with a shorter time to treatment than bolus anistreplase or infusion of streptokinase. http://repub.eur.nl/res/pub/10128/ 2003-05-01T00:00:00Z Stress echocardiography and myocardial perfusion imaging are commonly used noninvasive imaging modalities for the evaluation of ischaemic heart disease. Both modalities have proved clinically useful in the entire spectrum of coronary artery disease. Both techniques can detect coronary artery disease and provide prognostic information. Both techniques can identify low-risk and high-risk subsets among patients with known or suspected coronary artery disease and thus guide patient management decisions. In patients with acute myocardial infarction, both techniques have been used to identify residual viable tissue and predict improvement of function over time. In patients with chronic ischaemic left ventricular (LV) dysfunction, viability assessment with either modality can be used to predict improvement of function after revascularisation and thus guide patient treatment. http://repub.eur.nl/res/pub/13148/ 2003-04-29T00:00:00Z BACKGROUND: Convincing evidence suggests that atherosclerosis is an inflammatory disease. The inflammatory response is an important determinant of atherosclerotic plaque instability. Therefore, we investigated the prognostic impact of key inflammatory players, namely the inflammatory marker C-reactive protein (CRP) and the antiinflammatory cytokine interleukin-10 (IL-10), in patients with acute coronary syndromes. METHODS AND RESULTS: IL-10, CRP, and troponin T were measured at baseline and before discharge in 547 patients enrolled in the placebo group of the c7E3 Anti Platelet Therapy in Unstable Refractory angina (CAPTURE) trial. Death and nonfatal myocardial infarction were recorded during 6-month follow-up. IL-10 levels did not correlate with troponin T concentrations but were inversely correlated with CRP levels (P<0.001). Patients with elevated IL-10 levels (>3.5 pg/mL; n=276) were at significantly lower risk compared with patients with elevated IL-10 levels (hazard ratio, 0.33; 95% confidence interval [CI], 0.25 to 0.76; P=0.002). The predictive value of IL-10 was independent of myocardial necrosis but significantly interacted with CRP levels. CRP-positive patients with IL-10 serum levels above the calculated threshold value of 3.5 pg/mL were protected from the increased cardiac risk of CRP-positive patients with low IL-10 levels (adjusted hazard ratio, 0.25; 95% CI, 0.10 to 0.63; P=0.003). Moreover, discharge IL-10 levels >2.5 pg/mL were associated with lower cardiac risk during 6-month follow-up (hazard ratio, 0.38; 95% CI, 0.19 to 0.83; P=0.005). CONCLUSIONS: Elevated IL-10 serum levels are associated with a more favorable prognosis in patients with acute coronary syndromes and elevated CRP levels. These data demonstrate the importance of the balance between proinflammatory and antiinflammatory markers as a major determinant of patients' outcome in acute coronary syndromes. http://repub.eur.nl/res/pub/13153/ 2003-04-15T00:00:00Z BACKGROUND: Patients undergoing major vascular surgery are at increased risk of perioperative mortality due to underlying coronary artery disease. Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (statins) may reduce perioperative mortality through the improvement of lipid profile, but also through the stabilization of coronary plaques on the vascular wall. METHODS AND RESULTS: To evaluate the association between statin use and perioperative mortality, we performed a case-controlled study among the 2816 patients who underwent major vascular surgery from 1991 to 2000 at the Erasmus Medical Center. Case subjects were all 160 (5.8%) patients who died during the hospital stay after surgery. From the remaining patients, 2 controls were selected for each case and were stratified according to calendar year and type of surgery. For cases and controls, information was obtained regarding statin use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. A vascular complication during the perioperative phase was the primary cause of death in 104 (65%) case subjects. Statin therapy was significantly less common in cases than in controls (8% versus 25%; P<0.001). The adjusted odds ratio for perioperative mortality among statin users as compared with nonusers was 0.22 (95% confidence interval 0.10 to 0.47). Similar results were obtained in subgroups of patients according to the use of cardiovascular therapy and the presence of cardiac risk factors. CONCLUSIONS: This case-controlled study provides evidence that statin use reduces perioperative mortality in patients undergoing major vascular surgery. http://repub.eur.nl/res/pub/5701/ 2003-03-08T00:00:00Z Acute myocardial infarction is a common disease with serious consequences in mortality, morbidity, and cost to the society. Coronary atherosclerosis plays a pivotal part as the underlying substrate in many patients. In addition, a new definition of myocardial infarction has recently been introduced that has major implications from the epidemiological, societal, and patient points of view. The advent of coronary-care units and the results of randomised clinical trials on reperfusion therapy, lytic or percutaneous coronary intervention, and chronic medical treatment with various pharmacological agents have substantially changed the therapeutic approach, decreased in-hospital mortality, and improved the long-term outlook in survivors of the acute phase. New treatments will continue to emerge, but the greatest challenge will be to effectively implement preventive actions in all high-risk individuals and to expand delivery of acute treatment in a timely fashion for all eligible patients. http://repub.eur.nl/res/pub/10115/ 2003-03-01T00:00:00Z AIMS: To investigate the clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting (coronary plaque sealing, i.e. dilatation of angiographically non-significant lesions) compared to moderate and severe stenoses. METHODS AND RESULTS: Patients with chronic stable angina and a single de novo lesion in a native coronary vessel scheduled to undergo percutaneous coronary intervention (PCI) were selected from 14 different studies. Off-line analysis of angiographic outcomes was assessed in all patients using identical and standardised methods of data acquisition, analysis and definitions. Clinical endpoints were adjudicated by independent clinical events committees. All quantitative coronary angiographic (QCA) analyses were performed in the same core laboratory. Stenosis severity prior to PCI was categorised into three groups: <50% diameter stenosis (DS), 50-99%DS and >99%DS pre. A total of 3812 patients were included in this study; 1484 patients (39%) were successfully treated with balloon angioplasty (BA) only and stented angioplasty was performed in 2328 patients (61%).One-year mortality and rate of non-fatal myocardial infarction (MI) (Kaplan-Meier) did not differ between BA and stented angioplasty for any of the stenosis severity categories. Following BA, the combined event rate (death and non-fatal MI) was 4.8, 4.6 and 0% in the <50, 50-99 and >99%DS categories, respectively. Following stented angioplasty, the combined event rate was 3.1, 4.4 and 4.8% in the same categories. The need for repeat revascularisation corrected for stenosis severity in the Cox proportional-hazards regression model was reduced by 20% after stented angioplasty (hazard ratio (HR) 0.80, 95%CI 0.69-0.93). CONCLUSION: The concept of plaque sealing is appealing from the theoretical point of view. However, with current technology, plaque sealing cannot prevent death and future non-fatal MIs in the long-term because 1-year event rates after PCI of non-significant stenoses remain unacceptably elevated when compared with the estimated 1-year probability of a non-fatal MI in lesions with a <50%DS. Moreover, major adverse cardiac events at 1-year after PCI are not directly related to the degree of pre-procedural stenosis severity. http://repub.eur.nl/res/pub/10087/ 2003-02-04T00:00:00Z BACKGROUND: In patients with acute coronary syndromes, compensatory processes are initiated, including angiogenesis and endothelial regeneration of ruptured or eroded plaques. Angiogenic growth factors like vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and basic fibroblast growth factor (bFGF) are upregulated during ischemia. However, it is unknown whether their serum levels are related to clinical outcome. METHODS AND RESULTS: We measured VEGF, HGF, and bFGF levels in 1090 patients with acute coronary syndromes. Angiographic evaluation was performed at baseline as well as death, and nonfatal myocardial infarctions were recorded during 6-month follow-up. HGF and VEGF, but not bFGF, were significantly and independently associated with the patients' outcome. Patients with elevated VEGF serum levels suffered from adverse outcome (adjusted hazard ratio, 2.50 [1.52 to 4.82]; P=0.002). VEGF elevation was associated with evidence of ischemia and was a significant predictor of the effect of glycoprotein IIb/IIIa inhibition. In contrast, patients with high HGF levels had a significantly lower event rate compared with patients with low HGF levels (adjusted hazard ratio, 0.33 [0.21 to 0.51]; P<0.001). HGF levels did not correlate with evidence of ischemia and did not predict the effect of abciximab. Intriguingly, however, HGF levels significantly correlated with angiographically visible collateralization of the target vessel (22.4% versus 10.5%; P<0.001). CONCLUSIONS: The angiogenic growth factors VEGF and HGF are independent predictors of the patients' prognosis in acute coronary syndromes. Whereas VEGF elevation correlated with the evidence of myocardial ischemia and indicated an adverse outcome, HGF elevation was independent of ischemia and associated with improved collateralization as well as a favorable prognosis. http://repub.eur.nl/res/pub/10082/ 2003-01-28T00:00:00Z BACKGROUND: This study was designed to investigate long-term effects of the glycoprotein IIb/IIIa inhibitor abciximab in patients with acute coronary syndrome without ST elevation who were not scheduled for coronary intervention. METHODS AND RESULTS: A total of 7800 patients were included with an acute coronary syndrome without ST elevation, documented by either elevated cardiac troponin or transient or persistent ST-segment depression. They were randomized to abciximab bolus and 24-hour infusion, abciximab bolus and 48-hour infusion, or matching placebo. The overall 1-year mortality rate was 8.3% (649 patients). One-year mortality was 7.8% in the placebo group and 8.2% in the 24-hour and 9.0% in the 48-hour abciximab infusion group. Compared with placebo, the hazard ratio for the 24-hour infusion of abciximab was 1.1 (95% CI 0.86 to 1.29), and for the 48-hour infusion, it was 1.2 (95% CI 0.95 to 1.41). The lack of benefit of abciximab was observed in every subgroup studied. Patients with negative troponin or elevated C-reactive protein had a higher mortality rate after treatment with abciximab for 48 hours than with placebo: 8.5% versus 5.8% in those with negative troponin (P=0.02), 16.3% versus 12.1% in those with elevated C-reactive protein (P=0.04). CONCLUSIONS: Compared with placebo, abciximab did not provide any survival benefit at 1 year in patients admitted with an acute coronary syndrome with ST depression and/or elevated troponin who were not scheduled to undergo early coronary revascularization. In subgroups of patients, in particular those with low cardiac troponin or elevated C-reactive protein, abciximab was associated with excess mortality. http://repub.eur.nl/res/pub/10085/ 2003-01-01T00:00:00Z AIMS: Treatment with the glycoprotein IIb/IIIa receptor antagonist abciximab before and during coronary intervention in refractory unstable angina improves early outcome. We collected 4-year follow-up data to assess whether this benefit is sustained. Additionally, we investigated the predictive value of baseline troponin T and CRP for long-term cardiovascular events. METHODS AND RESULTS: Of 1265 patients enrolled in the CAPTURE trial follow-up was available in 94% of the patients alive after 6 months (median 48 months). Survival was similar in both groups. Both elevated troponin T and CRP were associated with impaired outcome, independently of other established risk factors, but with a different time course. Elevated troponin was associated with increased procedure related risk, and elevated CRP with increased risk for subsequent events. Lower rates of the composite end-point of death or myocardial infarction with abciximab vs. placebo were sustained during long-term follow up: 15.7% vs 17.2% at 4 years (P=ns), particularly in patients with elevated troponin T: 16.9% with abciximab vs 28.4% with placebo: P=0.015. Elevated CRP was not associated with specific benefit of abciximab. CONCLUSION: Troponin T as a marker of thrombosis and CRP as a marker of inflammation are independent predictors of impaired outcome at 4 years follow-up. The initial benefit from abciximab with regard to death and myocardial infarction was preserved at 4 years. No specific benefit with abciximab was observed for patients with elevated CRP, suggesting that a chronic inflammatory process is not affected by abciximab. In contrast the benefit of treatment in patients with elevated troponin T implies that the acute thrombotic process in refractory unstable angina is treated effectively. http://repub.eur.nl/res/pub/8299/ 2003-01-01T00:00:00Z OBJECTIVE: To evaluate the discriminatory value and compare the predictive performance of six non-invasive tests used for perioperative cardiac risk stratification in patients undergoing major vascular surgery. DESIGN: Meta-analysis of published reports. METHODS: Eight studies on ambulatory electrocardiography, seven on exercise electrocardiography, eight on radionuclide ventriculography, 23 on myocardial perfusion scintigraphy, eight on dobutamine stress echocardiography, and four on dipyridamole stress echocardiography were selected, using a systematic review of published reports on preoperative non-invasive tests from the Medline database (January 1975 and April 2001). Random effects models were used to calculate weighted sensitivity and specificity from the published results. Summary receiver operating characteristic (SROC) curve analysis was used to evaluate and compare the prognostic accuracy of each test. The relative diagnostic odds ratio was used to study the differences in diagnostic performance of the tests. RESULTS: In all, 8119 patients participated in the studies selected. Dobutamine stress echocardiography had the highest weighted sensitivity of 85% (95% confidence interval (CI) 74% to 97%) and a reasonable specificity of 70% (95% CI 62% to 79%) for predicting perioperative cardiac death and non-fatal myocardial infarction. On SROC analysis, there was a trend for dobutamine stress echocardiography to perform better than the other tests, but this only reached significance against myocardial perfusion scintigraphy (relative diagnostic odds ratio 5.5, 95% CI 2.0 to 14.9). CONCLUSIONS: On meta-analysis of six non-invasive tests, dobutamine stress echocardiography showed a positive trend towards better diagnostic performance than the other tests, but this was only significant in the comparison with myocardial perfusion scintigraphy. However, dobutamine stress echocardiography may be the favoured test in situations where there is valvar or left ventricular dysfunction. http://repub.eur.nl/res/pub/8335/ 2003-01-01T00:00:00Z OBJECTIVE: To investigate the incidence of clinical problems related to a bicuspid valve (aortic stenosis and regurgitation) and the incidence of ascending aorta and aortic arch pathology in combination with coarctation repair. PATIENTS: 124 adult patients after surgical correction of aortic coarctation were studied. The incidence of aortic valve, ascending aorta, and aortic arch pathology was determined using echocardiography and magnetic resonance imaging. The median age at coarctation repair was 9 years and at last follow up 28 years. RESULTS: Three patients died from aorta pathology. Aortic valve disease was found in 63% of the patients, requiring an intervention in 22%, at a median of 13 years after coarctation repair. Ascending aorta dilatation was observed in 28% and aortic arch abnormalities in 23%, among whom kinking of the aortic arch was found in 12%. Antihypertensive medication was used in 24%. In the patients with hypertension the age at operation and age at follow up were significantly higher (p = 0.0001 and p < 0.0001, respectively). CONCLUSION: In addition to the well known problems of hypertension and recoarctation, aortic valve and aortic arch pathology are commonly encountered in patients with previous coarctation repair. Aortic abnormalities may predispose to dilatation and dissection, thus necessitating careful lifelong attention in all patients with coarctation. http://repub.eur.nl/res/pub/8460/ 2003-01-01T00:00:00Z BACKGROUND: CD40 ligand is expressed on platelets and released from them on activation. We investigated the predictive value of soluble CD40 ligand as a marker for clinical outcome and the therapeutic effect of glycoprotein IIb/IIIa receptor inhibition in patients with acute coronary syndromes. METHODS: Serum levels of soluble CD40 ligand were measured in 1088 patients with acute coronary syndromes who had previously been enrolled in a randomized trial comparing abciximab with placebo before coronary angioplasty and in 626 patients with acute chest pain. RESULTS: The levels of soluble CD40 ligand were elevated (above 5.0 microg per liter) in 221 patients with acute coronary syndromes (40.6 percent). Among patients receiving placebo, elevated soluble CD40 ligand levels indicated a significantly increased risk of death or nonfatal myocardial infarction during six months of follow-up (adjusted hazard ratio as compared with patients with low levels of the ligand [< or =5.0 microg per liter], 2.71; 95 percent confidence interval, 1.51 to 5.35; P=0.001). The prognostic value of this marker was validated in the patients with chest pain, among whom elevated soluble CD40 ligand levels identified those with acute coronary syndromes who were at high risk for death or nonfatal myocardial infarction (adjusted hazard ratio as compared with those with low levels of the ligand, 6.65; 95 percent confidence interval, 3.18 to 13.89; P<0.001). The increased risk in patients with elevated soluble CD40 ligand levels was significantly reduced by treatment with abciximab (adjusted hazard ratio as compared with those receiving placebo, 0.37; 95 percent confidence interval, 0.20 to 0.68; P=0.001), whereas there was no significant treatment effect of abciximab in patients with low levels of soluble CD40 ligand. CONCLUSIONS: In patients with unstable coronary artery disease, elevation of soluble CD40 ligand levels indicated an increased risk of cardiovascular events. Elevation of soluble CD40 ligand identifies a subgroup of patients at high risk who are likely to benefit from antiplatelet treatment with abciximab. http://repub.eur.nl/res/pub/5696/ 2002-12-01T00:00:00Z BACKGROUND: The 6-month clinical outcome of patients with multivessel disease enrolled in PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) is described. Patients with complete angiography data were included; multivessel disease was stratified according to the treatment strategy applied early during hospitalization, i.e. medical treatment, percutaneous coronary intervention (PCI) (balloon), PCI (stent), or coronary artery bypass grafting (CABG). METHODS: Patients were divided into three groups according to the treatment strategy applied during the first 30 days of enrolment. Patients who did not undergo a percutaneous or surgical coronary intervention were classified as medically treated. Patients who underwent a PCI (prior to a possible CABG) were separated from those who underwent a CABG (prior to a possible PCI). The PCI group was further subdivided: patients receiving >/=1 coronary stents were separated from those in whom no stents were used. RESULTS: The mortality rate at 30 days was 6.7, 3.9, 2.4 and 4.8% for the medical treatment, PCI (balloon), PCI (stent) and CABG groups, respectively (p value = 0.002). Differences as observed at 30 days were still present at 6-month follow-up with 11.1, 5.8, 5.5 and 6.5% mortality event rates for the aforementioned groups (p value = 0.002). The 30-day myocardial infarction (MI) rate according to the opinion of the Clinical Events Committee was lower among medically than non-medically treated patients, with the highest event rate observed in the CABG group (27.7%). Approximately half of the MIs in the PCI and CABG subgroups occurred within 48 h after the procedure. CONCLUSIONS: The observed differences in clinical outcomes are explained by an imbalance in baseline characteristics and comorbid conditions between the analyzed groups of patients. http://repub.eur.nl/res/pub/4771/ 2002-09-01T00:00:00Z The purpose of this study was to compare measurements by MetriCath to intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA). The MetriCath system consists of a low-pressure (200 mm Hg) balloon catheter connected to a pressure transducer and infusion pump linked to a computer that records pressure-volume curves. Cross-sectional area of blood vessels is obtained directly from the unrestrained and in-stent pressure-volume measurements. We compared stent cross-sectional area measurements by MetriCath, IVUS, and QCA in a porcine stented coronary artery model. Comparison of area measurements in 14 stents showed no significant differences between the three methods (P = 0.66). On average, values differed 0.37 ± 0.60mm2 between MetriCath and QCA, 0.13 ± 0.55 mm2 between MetriCath and IVUS, and 0.22 ± 0.80 mm2 between IVUS and QCA. This corresponds to 6.2% ± 10%, 3.0% ± 9.0%, and 3.1% ± 12.9% relative difference from the average of two corresponding measurements. Linear regression analysis showed excellent correlation between measurements (r ± 0.99 for all comparisons). The differences in in-stent area measurements between MetriCath and both QCA and IVUS were small. Considering the ease and rapidity of obtaining MetriCath results, this technique may form an alternative to the others in evaluating stent expansion. Based on these findings, clinical evaluation seems warranted. http://repub.eur.nl/res/pub/9937/ 2002-08-01T00:00:00Z The building blocks come together, finally! Already three decades ago we were dreaming of the complete Cardiology Information System. However, at that time the computer programmers explained that it was too early. In the subsequent year information tech- nology (IT) specialists, replacing the programmers, gave similar messages. Business interests of medical equipment industries seemed not to support data exchange; however this has changed in recent years. Now, finally the pieces come together. The bricks have been laid, the blocks have been made, and the system can be built. http://repub.eur.nl/res/pub/9938/ 2002-08-01T00:00:00Z AIMS: To better delineate the characteristics, treatments, and outcomes of patients with acute coronary syndromes (ACS) in representative countries across Europe and the Mediterranean basin, and to examine adherence to current guidelines. METHODS AND RESULTS: We performed a prospective survey (103 hospitals, 25 countries) of 10484 patients with a discharge diagnosis of acute coronary syndromes. The initial diagnosis was ST elevation ACS in 42.3%, non-ST elevation ACS in 51.2%, and undetermined electrocardiogram ACS in 6.5%. The discharge diagnosis was Q wave myocardial infarction in 32.8%, non-Q wave myocardial infarction in 25.3%, and unstable angina in 41.9%. The use of aspirin, beta-blockers, angiotensin converting enzyme inhibitors, and heparins for patients with ST elevation ACS were 93.0%, 77.8%, 62.1%, and 86.8%, respectively, with corresponding rates of 88.5%, 76.6%, 55.8%, and 83.9% for non-ST elevation ACS patients. Coronary angiography, percutaneous coronary interventions, and coronary bypass surgery were performed in 56.3%, 40.4%, and 3.4% of ST elevation ACS patients, respectively, with corresponding rates of 52.0%, 25.4%, and 5.4% for non-ST elevation ACS patients. Among patients with ST elevation ACS, 55.8% received reperfusion treatment; 35.1% fibrinolytic therapy and 20.7% primary percutaneous coronary interventions. The in-hospital mortality of patients with ST elevation ACS was 7.0%, for non-ST elevation ACS 2.4%, and for undetermined electrocardiogram ACS 11.8%. At 30 days, mortality was 8.4%, 3.5%, and 13.3%, respectively. CONCLUSIONS: This survey demonstrates the discordance between existing guidelines for ACS and current practice across a broad region in Europe and the Mediterranean basin and more extensively reflects the outcomes of ACS in real practice in this region http://repub.eur.nl/res/pub/4785/ 2002-05-01T00:00:00Z http://repub.eur.nl/res/pub/13020/ 2002-03-01T00:00:00Z http://repub.eur.nl/res/pub/9838/ 2002-02-05T00:00:00Z BACKGROUND: The relevance of the adverse prognostic implications of CK-MB elevation after percutaneous coronary intervention (PCI) remains controversial. Therefore, we compared the relationship between the level of postprocedural CK-MB elevation and 6-month mortality in patients undergoing PCI with the relationship between the level of spontaneous, non-PCI-related CK-MB elevation and 6-month mortality in patients with acute coronary syndromes (ACS) treated medically. METHODS AND RESULTS: In the PURSUIT trial, 5583 of 9461 patients who presented with a non-ST-elevation ACS did not undergo PCI or CABG and had at least 1 CK-MB sample collected during index-hospitalization. There was a gradual increase in 6-month mortality with higher CK-MB levels: 4.1%, 8.6%, 9.0%, 14.3%, 15.5% for CK-MB ratios 0 to 1, >1 to 3, >3 to 5, >5 to 10, and >10 times the upper limit of normal. A combined analysis in 8838 patients undergoing PCI in 5 large, clinical trials revealed a proportional relationship between postprocedural CK-MB levels (</= 48 hours after PCI) and 6-month mortality. In patients with CK-MB ratios 0 to 1, >1 to 3, >3 to 5, >5 to 10, and >10, the risk of death was 1.3%, 2.0%, 2.3%, 4.3%, and 7.4%, respectively. The absolute mortality rates were lower after procedure-related infarcts compared with spontaneous infarcts. Yet, the relative increase in 6-month mortality with each increase in peak CK-MB level was similar for PCI-related myocardial necrosis and spontaneous myocardial necrosis, as all tests for heterogeneity of the odds ratios were nonsignificant. CONCLUSIONS: The present analysis indicates that the adverse prognostic implications of periprocedural myocardial necrosis should be considered similar to the adverse consequences of spontaneous myocardial necrosis. http://repub.eur.nl/res/pub/13008/ 2002-02-01T00:00:00Z BACKGROUND: Many patients with acute coronary syndromes are offered percutaneous coronary intervention. However, the appropriate indications for, and optimal timing of, such procedures are uncertain. We analysed timing of intervention and associated events (death and myocardial infarction) in the PURSUIT trial in which 9461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide, or placebo for 72 h. Other treatment was left to the investigators. 2430 patients underwent percutaneous coronary intervention within 30 days. Four groups were distinguished, who underwent percutaneous coronary intervention on day 1; on days 2 or 3; at 4 to 7 days; or between 8 until 30 days, for eptifibatide- and placebo-treated patients. RESULTS: The four groups treated with placebo demonstrated total 30-day events of 15.9% for day 1 percutaneous coronary intervention, 17.7%, 15.0% and 18.2%, respectively, for successive intervals of later intervention. Later intervention was associated with more pre-procedural events (2.2% to 13.7%, P=0.001) which was balanced by a decrease in procedure-related events (12.1 to 3.1%, P=0.001), while the overall 30-day event rates were similar. Eptifibatide-treated patients with percutaneous coronary intervention on day 1 had the lowest rate of 30-day events (9.2%, P<0.05 vs other groups). In this group, pre-procedural risk was only 0.3%, while percutaneous coronary intervention on eptifibatide treatment was associated with low procedural risk (7.2%). The total 30-day event rate for later percutaneous coronary intervention in patients receiving eptifibatide was 14.0 on days 2 and 3, 15.0% for days 4 to 7 and 17.4% for days 7 to 30, respectively. CONCLUSION: Patients treated with a platelet glycoprotein IIb/IIIa receptor blocker, and early percutaneous coronary intervention (within 24 h) had the lowest event rate in this post hoc analysis. Thus 'watchful waiting' may not be the optimal strategy. Rather an early invasive strategy with percutaneous coronary intervention under protection of a platelet glycoprotein IIb/IIIa receptor blocker should be considered in selected patients. Randomized trials are warranted to verify this issue. http://repub.eur.nl/res/pub/5676/ 2002-01-19T00:00:00Z BACKGROUND: Platelet glycoprotein IIb/IIIa inhibitors have been shown to reduce cardiac complications in patients undergoing percutaneous coronary intervention. The clinical efficacy of these drugs in acute coronary syndromes, however, is still unclear. We did a meta-analysis of all large randomised trials designed to study the clinical efficacy and safety of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes who were not routinely scheduled to undergo early coronary revascularisation. METHODS: Inclusion criteria were: randomisation of patients with acute coronary syndromes but without persistent ST elevation; comparison of a glycoprotein IIb/IIIa inhibitor with placebo or control therapy; non-recommendation of early coronary revascularisation during study-drug infusion; and enrollment of at least 1000 patients. Data on individual patients were obtained from all participants in these trials. FINDINGS: Six trials, enrolling 31402 patients, fulfilled the inclusion criteria. 30 days after randomisation, 3530 (11.2%) patients died or developed a myocardial infarction. At 30 days, a 9% reduction in the odds of death or myocardial infarction was seen with glycoprotein IIb/IIIa inhibitors compared with placebo or control (10.8% [1980/18297] vs 11.8% [1550/13105] events; odds ratio 0.91 [95% CI 0.84-0.98]; p=0.015). The relative treatment benefit was similar in subgroups of patients according to important clinical baseline characteristics; hence, the absolute treatment benefit was largest in high-risk patients. An unexpected and significant interaction was seen between sex and allocated treatment, with a treatment benefit in men (0.81 [0.75-0.89] but not in women (1.15 [1.01-1.30]). However, once patients were stratified according to troponin concentration, there was no evidence of a sex difference in treatment response, and a risk reduction was seen in men and women with raised troponin concentrations. Major bleeding complications were increased by glycoprotein IIb/IIIa inhibitors (2.4% [445/18297] vs 1.4% [180/13105]; p<0.0001), but intracranial bleeding was not (16 [0.09%] vs 8 [0.06%]; p=0.40). INTERPRETATION: Glycoprotein IIb/IIIa inhibitors reduce the occurrence of death or myocardial infarction in patients with acute coronary syndromes not routinely scheduled for early revascularisation. The event reduction is greatest in patients at high risk of thrombotic complications. Treatment with a glycoprotein IIb/IIIa inhibitor might therefore be considered especially in such patients early after admission, and continued until a decision about early coronary revascularisation has been made. http://repub.eur.nl/res/pub/13002/ 2002-01-01T00:00:00Z AIMS: This study was conducted to analyse flow velocity parameters and predictors of a suboptimal coronary flow reserve (<2.5) following balloon angioplasty. METHODS: Two hundred and twenty-five patients underwent sequential intracoronary Doppler as part of the DEBATE I study. Of these, 183, with complete angiography and Doppler at the 6-month follow-up, were included. Univariate and multivariate logistic analysis was performed to identify independent predictors of post-procedural suboptimal coronary flow reserve, defined as coronary flow reserve <2.5. RESULTS: Forty-eight per cent (n=88) of the patients achieved a suboptimal coronary flow reserve. These patients had higher baseline velocities (cm.s(-1)) before balloon angioplasty (18+/-9 vs 14+/-6, P=0.004), after balloon angioplasty (22+/-11 vs 14+/-5, P<0.001) and at follow-up (19+/-9 vs 16+/-6, P=0.011) than the optimal coronary flow reserve group. Although the suboptimal group had lower hyperaemic velocities (cm.s(-1)) after balloon angioplasty than the optimal group (42+/-17 vs 49+/-16, P=0.008), these velocities became similar at follow-up. Increasing age (odds ratio, OR 1.071, P=0.0002), female gender (OR 2.52, P=0.014) and increasing pre-procedural baseline average peak velocities (OR 1.056, P<0.001) were found to be independent predictors of a suboptimal coronary flow reserve following balloon angioplasty. CONCLUSION: A suboptimal coronary flow reserve was associated with (1) a chronically elevated baseline average peak velocity (2) a transient deficit in the hyperaemic average peak velocity (3) the elderly, and female gender. http://repub.eur.nl/res/pub/8329/ 2002-01-01T00:00:00Z OBJECTIVE: To assess the prevalence of myocardial viability by technetium-99m (Tc-99m)-tetrofosmin/fluorine-18-fluorodeoxyglucose (FDG) single photon emission computed tomography (SPECT) in patients with ischaemic cardiomyopathy. DESIGN: A retrospective observational study. SETTING: Thoraxcenter Rotterdam (a tertiary referral centre). PATIENTS: 104 patients with chronic coronary artery disease and severely depressed left ventricular function presenting with heart failure symptoms. MAIN OUTCOME MEASURES: Prevalence of myocardial viability as evaluated by Tc-99m-tetrofosmin/FDG SPECT imaging. Two strategies for assessing viability in dysfunctional myocardium were used: perfusion imaging alone, and the combination of perfusion and metabolic imaging. RESULTS: On perfusion imaging alone, 56 patients (54%) had a significant amount of viable myocardium, whereas 48 patients (46%) did not. Among the 48 patients with no significant viability by perfusion imaging alone, seven additional patients (15%) had significantly viable myocardium on combined perfusion and metabolic imaging. Thus with a combination of perfusion and metabolic imaging, 63 patients (61%) had viable myocardium and 41 (39%) did not. CONCLUSIONS: On the basis of the presence of viable dysfunctional myocardium, 61% of patients with chronic coronary artery disease and depressed left ventricular ejection fraction presenting with heart failure symptoms may be considered for coronary revascularisation. The combination of perfusion and metabolic imaging identified more patients with significant viability than myocardial perfusion imaging alone. http://repub.eur.nl/res/pub/9882/ 2002-01-01T00:00:00Z BACKGROUND: Because heterogeneous results have been reported, we assessed coronary flow velocity changes in individuals who underwent percutaneous transluminal coronary angioplasty (PTCA) and examined their impact on clinical outcome. METHODS AND RESULTS: As part of the Doppler Endpoints Balloon Angioplasty Trial Europe (DEBATE) II study, 379 patients underwent Doppler flow-guided angioplasty. All patients were evaluated according to their coronary flow velocity reserve (CFVR) results (> or =2.5 or < 2.5) at the end of the procedure. A CFVR < 2.5 after angioplasty was associated with an elevated baseline blood flow velocity in both the target artery and reference artery. CFVR before PTCA and CFVR in the reference artery were independent predictors of an optimal CFVR after balloon angioplasty (CFVR before PTCA: odds ratio [OR], 2.26; 95% confidence interval [CI], 1.57 to 3.24; CFVR in reference artery: OR, 1.90; 95% CI, 1.21 to 2.98; both P<0.001) and stent implantation (before PTCA: OR, 2.54; 95% CI, 1.47 to 4.36; reference artery: OR, 1.97; 95% CI, 1.07 to 3.87; both P<0.05). A low CFVR at the end of the procedure was an independent predictor of major adverse cardiac events (MACE) at 30 days (OR, 4.71; 95% CI, 1.14 to 25.92; P=0.034) and at 1 year (OR, 2.06; 95% CI, 1.16 to 3.66; P=0.014). After excluding MACE at 30 days, no difference in MACE at 1 year was observed between the patients with and without a CFVR < 2.5 at the end of the procedure. CONCLUSIONS: A low postprocedural CFVR was associated with a worse periprocedural outcome (which was related to microcirculatory disturbances), but there was no significant difference at late follow-up. http://repub.eur.nl/res/pub/4823/ 2001-09-22T00:00:00Z Abstract OBJECTIVES: We sought to assess whether coronary stents have modified the predictive value of demographic, clinical and quantitative coronary angiographic (QCA) predictors of coronary restenosis. BACKGROUND: A systematic analysis in a large cohort of registries and randomized trials of the percutaneous transluminal coronary angioplasty (PTCA) and stent era has never been performed. METHODS: A total of 9,120 treated lesions in 8,156 patients included in nine randomized trials and 10 registries, with baseline, post-procedural and six-month follow-up QCA analyses, were included in this study. Predictors of restenosis were identified with univariate and multivariate logistic regression analyses. Interaction terms were introduced in the regression equation to evaluate whether the predictors of restenosis were common to both eras or specific for either one of the revascularization techniques. RESULTS: The restenosis rate was 35% after PTCA and 19% after angioplasty with additional stenting. In the univariate analysis, favorable predictors were previous coronary artery bypass graft surgery (CABG), stent use, stent length and a large pre-procedural minimal lumen diameter (pre-MLD); unfavorable predictors were weight, body mass index, diabetes mellitus, multi-vessel disease, lesion length and a high residual post-procedural diameter stenosis (post-DS). Predictors specific for the PTCA population were a large post-procedural MLD (post-MLD) as favorable and a severe pre-procedural DS (pre-DS) as unfavorable. Favorable predictors specific for the stent population were a large post-MLD and a large pre-procedural reference diameter (pre-RD). In the multivariate analysis, the best model included the following favorable predictors: stent use, a large post-MLD, previous CABG and the interaction term between stent use and a large post-MLD; unfavorable predictors were lesion length and diabetes mellitus. CONCLUSIONS: There are no major differences in demographic and clinical predictors of coronary restenosis between PTCA and stent populations. In the modern (stent) era, a severe pre-DS is no longer an unfavorable predictor of restenosis. Still important, but more so in the stent population, is a large post-MLD (optimal result). Finally, a larger pre-RD became a favorable predictor with the advent of stenting. http://repub.eur.nl/res/pub/12947/ 2001-09-01T00:00:00Z BACKGROUND: There are limited data regarding the immediate and long-term effect of balloon angioplasty on the coronary flow reserve evaluated in a multicentre setting. METHODS AND RESULTS: A total of 86 patients with one-vessel disease and normal left ventricular function were analysed before and after optimal balloon angioplasty (diameter stenosis <35%) and at 6-month follow-up. Coronary flow reserve was assessed with a Doppler guide wire. A low coronary flow reserve (<or=2.5) after PTCA, due to an increased baseline blood flow velocity, was encountered in 42 of the 86 patients (49%). Recurrence of angina and target lesion revascularization were more frequent in these patients than in patients with a coronary flow reserve >2.5 (46% vs 23% and 36% vs 16%, respectively; P<0.05) due to a trend towards restenosis (29% vs 16%; P=0.15) or a low coronary flow reserve at follow-up due to persistent elevated baseline blood flow velocity. Patients without restenosis showed a decrease or increase of coronary flow reserve during follow-up, determined by alterations of hyperaemic blood flow velocity. CONCLUSIONS: Patients with an impaired coronary flow reserve directly after optimal balloon angioplasty showed a higher target lesion revascularization rate compared to patients with a coronary flow reserve >2.5. This patient group consists of patients prone to develop restenosis, while other patients are characterized by a persistently low coronary flow reserve, probably secondary to disturbed autoregulation and/or diffuse mild coronary atherosclerosis. Coronary flow reserve alterations in patients without restenosis were related to changes in hyperaemic blood flow velocity, suggesting that this phenomenon relates to epicardial remodelling. http://repub.eur.nl/res/pub/12934/ 2001-08-22T00:00:00Z AIM: To assess the long-term cardioprotective effect of bisoprolol in a randomized high-risk population after successful major vascular surgery. High-risk patients were defined by the presence of one or more cardiac risk factor(s) and a dobutamine echocardiography test positive for ischaemia. METHODS: 1351 patients were screened prior to surgery, 846 patients had one or more risk factor(s), and 173 of these patients also had ischaemia during dobutamine echocardiography. One hundred and twelve patients could be randomized for additional bisoprolol therapy or standard care. Eleven patients died in the peri-operative period (up to 1 month after surgery). Randomized patients continued bisoprolol or standard care after surgery. During follow-up of 101 survivors (median 22 months, range 11-30) cardiac death or myocardial infarction was noted. No patient was lost during follow-up.Results The incidence of cardiac events during follow-up in the bisoprolol group was 12% vs 32% in the standard care group (P=0.025). Cardiac death occurred in 15 patients, nine patients in the standard care and in six in the bisoprolol group; myocardial infarction occurred in six patients, five in the standard care and one in the bisoprolol group. The odds ratio for cardiac death or myocardial infarction after surgery in high-risk patients with additional bisoprolol therapy was 0.30 (0.11-0.83). CONCLUSIONS: Bisoprolol significantly reduced long-term cardiac death and myocardial infarction in high-risk patients after successful major cardiac vascular surgery. http://repub.eur.nl/res/pub/4831/ 2001-07-01T00:00:00Z Background The coronary flow velocity acceleration at the stenotic site (SVA), defined as a ≥50% increase in resting stenotic velocity when compared with the reference segment, has been shown to be highly sensitive and specific for the diagnosis of a hemodynamically significant stenosis. In this study, we describe the value of postprocedural SVA for the prediction of a lack of improvement in functional activity at long-term follow-up balloon angioplasty (BA). Methods We investigated the improvement in functional activity in patients undergoing single native vessel angioplasty and intracoronary Doppler (before BA, after BA, and again at 6-month follow-up) as part of the Doppler Endpoints Balloon Angioplasty Trial Europe (DEBATE) I trial. Lack of improvement was defined as no change in Duke Activity Status Index (DASI) at 6-month follow-up, whereas SVA was defined as ≥50% elevation in resting velocity at the treated area compared with the distal measurement. Results SVA was found more frequently in patients without improvement in DASI (45% vs 31%, P = .03). Similar percent diameter stenosis and coronary flow velocity reserve were observed in patients with and those without improvement in DASI at follow-up. By multivariate regression analysis, the presence of SVA (P = .029; odds ratio, 1.97; 95% confidence interval, 1.07 to 3.63) and an elevated DASI at baseline (P < .001; odds ratio, 1.05; 95% confidence interval, 1.03 to 1.07) were associated with a lack of improvement at follow-up. Conclusions The detection of SVA was associated with failure of improvement in functional activity at follow-up after coronary intervention. http://repub.eur.nl/res/pub/5660/ 2001-05-15T00:00:00Z Patients with coronary artery disease frequently have elevated antibody titers against Chlamydia pneumoniae, but whether antichlamydial antibody titers are correlated with prognosis in unstable angina remains unclear. We therefore investigated the sera of 1,096 patients with unstable angina regarding immunoglobulin (Ig) IgG, IgA, and IgM antibody titers against chlamydial lipopolysaccharides (LPS) and the concentrations of C-reactive protein (CRP) and troponin T (TnT). Anti-LPS IgG titers were increased in 45% of patients at enrollment and in 48% of patients at discharge (p <0.0001). Anti-LPS IgA titers were increased in 27% of patients at enrollment and in 33% of patients at discharge (p <0.0001). Patients who subsequently died had significantly lower IgM titers at enrollment than patients without events (p = 0.016). IgG, IgA, or IgM titers did not correlate with concentrations of CRP or TnT. In this large-scale study of patients with unstable angina, we frequently found elevated antichlamydial antibody titers. Patients with low IgM anti-LPS titers were at risk for subsequent death. However, there was no correlation between antichlamydial antibody titers and CRP or TnT. http://repub.eur.nl/res/pub/5666/ 2001-01-01T00:00:00Z OBJECTIVE: To describe the results of thrombolysis prior to hospitalisation in patients with evolving myocardial infarction. DESIGN: Prospective cohort study. METHOD: The 'Reperfusion for acute infarcts Rotterdam' (Dutch acronym: REPAIR) programme aims to minimise treatment delay in patients with evolving myocardial infarction by the initiation of thrombolytic therapy prior to hospital admission. For patients with symptoms that indicate a developing myocardial infarction, treatment is initiated immediately by the ambulance personnel at the patient's home, once the diagnosis has been confirmed with the help of a portable 12-lead ECG system. The interval between the onset of symptoms and the thrombolysis infusion was recorded for all patients, as well as any complications which occurred during transportation. The long-term survival was determined using data from the municipal registration. RESULTS: In the period 1988-2000, 1487 patients were treated using the REPAIR protocol, 80% of these within two hours after the onset of symptoms. In 9 cases (0.6%) a thrombolytic treatment had been initiated, whereas the diagnosis 'myocardial infarction' was not confirmed at the hospital. During transport 40 patients (2.7%) experienced ventricle fibrillation, 25 (1.7%) severe hypotension, and 2 patients (0.1%) died. Mortality at 30 days and at one, five, and ten years was 4.9%, 7.3%, 16.2% en 30.1%, respectively. Patients treated within two hours after the onset of symptoms had lower mortality rates than those treated later: at one year 6.7% versus 9.7%, and at 5 years 14.0% versus 25.1% (Kaplan-Meier estimates; log rank test: p = 0.001). CONCLUSION: Immediate thrombolytic treatment of patients with a developing myocardial infarction which could be safely initiated by ambulance personnel, resulted in excellent short-term and long-term survival. http://repub.eur.nl/res/pub/8301/ 2001-01-01T00:00:00Z OBJECTIVE: To study the relation between moderate coronary dissections, coronary flow velocity reserve (CFVR), and long term outcome. METHODS: 523 patients undergoing balloon angioplasty and sequential intracoronary Doppler measurements were examined as part of the DEBATE II trial (Doppler endpoints balloon angioplasty trial Europe). After successful balloon angioplasty, patients were randomised to stenting or no further treatment. Dissections were graded at the core laboratory by two observers and divided into four categories: none, mild (type A-B), moderate (type C), severe (types D to F). Patients with severe dissections (n = 128) or without available reference vessel CFVR (n = 139) were excluded. The remaining 256 patients were divided into two groups according to the presence (group A, n = 45) or absence (group B, n = 211) of moderate dissection. RESULTS: Following balloon angioplasty, there was no difference in CFVR between the two groups. At 12 months follow up, a higher rate of major adverse cardiac events was observed overall in group A than in group B (10 (22%) v 23 (11%), p = 0.041). However, the risk of major adverse events was similar in the subgroups receiving balloon angioplasty (group A, 6 (19%) v group B, 16 (16%), NS). Among group A patients, the adverse events risk was greater in those randomised to stenting (odds ratios 6.603 v 1.197, p = 0.046), whereas there was no difference in risk if the group was analysed according to whether the CFVR was < 2.5 or >/= 2.5 after balloon angioplasty. CONCLUSIONS: Moderate dissections left untreated result in no increased risk of major adverse cardiac events. Additional stenting does not improve the long term outcome. http://repub.eur.nl/res/pub/9569/ 2001-01-01T00:00:00Z STUDY OBJECTIVE: To assess the long-term prognostic value of dobutamine stress echocardiography (DSE) for cardiac events (cardiac death, myocardial infarction, and late revascularization) in patients with atrial fibrillation (AF). METHODS: Baseline ECGs were studied in patients undergoing DSE between 1989 and 1998. Sixty-nine patients had AF before DSE. Prognostic value of DSE in these patients was compared with a control group who had sinus rhythm (n = 1,664). The presence of stress-induced ischemia was noted for every patient. The mean follow-up period was 35 months (range, 6 to 84 months). Data are presented as hazards ratio (HR) with 95% confidence interval (CI). RESULTS: Heart rate at rest was higher in patients with AF (77 +/- 15 beats/min vs 73 +/- 14 beats/min; p = 0.04); however, double product at peak stress was not different between patients with AF and sinus rhythm (17,602 vs 17,169, respectively; p = 0.46). In patients with AF, target heart rate was achieved at a lower dobutamine dose (33 +/- 8 microg/kg/min vs 35 +/- 9 microg/kg/min; p = 0.01). Cardiac arrhythmias occurred more frequently (12% vs 5%; p = 0.001) in patients with AF during DSE. During a follow-up period of 7 years, cardiac death occurred in 5 patients, myocardial infarction in 2 patients, and late revascularization in 10 patients. Prognostic value of DSE for all late cardiac events was similar in patients with AF (HR, 3.0; 95% CI, 0.9 to 9.5) and sinus rhythm (HR, 3.4; 95% CI, 2.7 to 4.3; p = 0.85). CONCLUSION: The prognostic value of DSE for late cardiac events is maintained in patients with AF. http://repub.eur.nl/res/pub/9625/ 2001-01-01T00:00:00Z CONTEXT: Patients who undergo major vascular surgery are at increased risk of perioperative cardiac complications. High-risk patients can be identified by clinical factors and noninvasive cardiac testing, such as dobutamine stress echocardiography (DSE); however, such noninvasive imaging techniques carry significant disadvantages. A recent study found that perioperative beta-blocker therapy reduces complication rates in high-risk individuals. OBJECTIVE: To examine the relationship of clinical characteristics, DSE results, beta-blocker therapy, and cardiac events in patients undergoing major vascular surgery. DESIGN AND SETTING: Cohort study conducted in 1996-1999 in the following 8 centers: Erasmus Medical Centre and Sint Clara Ziekenhuis, Rotterdam, Twee Steden Ziekenhuis, Tilburg, Academisch Ziekenhuis Utrecht, Utrecht, and Medisch Centrum Alkmaar, Alkmaar, the Netherlands; Ziekenhuis Middelheim, Antwerp, Belgium; and San Gerardo Hospital, Monza, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Italy. PATIENTS: A total of 1351 consecutive patients scheduled for major vascular surgery; DSE was performed in 1097 patients (81%), and 360 (27%) received beta-blocker therapy. MAIN OUTCOME MEASURE: Cardiac death or nonfatal myocardial infarction within 30 days after surgery, compared by clinical characteristics, DSE results, and beta-blocker use. RESULTS: Forty-five patients (3.3%) had perioperative cardiac death or nonfatal myocardial infarction. In multivariable analysis, important clinical determinants of adverse outcome were age 70 years or older; current or prior angina pectoris; and prior myocardial infarction, heart failure, or cerebrovascular accident. Eighty-three percent of patients had less than 3 clinical risk factors. Among this subgroup, patients receiving beta-blockers had a lower risk of cardiac complications (0.8% [2/263]) than those not receiving beta-blockers (2.3% [20/855]), and DSE had minimal additional prognostic value. In patients with 3 or more risk factors (17%), DSE provided additional prognostic information, for patients without stress-induced ischemia had much lower risk of events than those with stress-induced ischemia (among those receiving beta-blockers, 2.0% [1/50] vs 10.6% [5/47]). Moreover, patients with limited stress-induced ischemia (1-4 segments) experienced fewer cardiac events (2.8% [1/36]) than those with more extensive ischemia (>/=5 segments, 36% [4/11]). CONCLUSION: The additional predictive value of DSE is limited in clinically low-risk patients receiving beta-blockers. In clinical practice, DSE may be avoided in a large number of patients who can proceed safely for surgery without delay. In clinically intermediate- and high-risk patients receiving beta-blockers, DSE may help identify those in whom surgery can still be performed and those in whom cardiac revascularization should be considered. http://repub.eur.nl/res/pub/9668/ 2001-01-01T00:00:00Z CONTEXT: Abciximab, a potent inhibitor of the platelet glycoprotein IIb/IIIa receptor, reduces thrombotic complications in patients undergoing percutaneous coronary intervention (PCI). Because of its potent inhibition of platelet aggregation, the effect of abciximab on risk of stroke is a concern. OBJECTIVE: To determine whether abciximab use among patients undergoing PCI is associated with an increased risk of stroke. DESIGN: Combined analysis of data from 4 double-blind, placebo-controlled, randomized trials (EPIC, CAPTURE, EPILOG, and EPISTENT) conducted between November 1991 and October 1997 at a total of 257 academic and community hospitals in the United States and Europe. PATIENTS: A total of 8555 patients undergoing PCI with or without stent deployment for a variety of indications were randomly assigned to receive a bolus and infusion of abciximab (n = 5476) or matching placebo (n = 3079). One treatment group in EPIC received a bolus of abciximab only. MAIN OUTCOME MEASURE: Risk of hemorrhagic and nonhemorrhagic stroke within 30 days of treatment among abciximab and placebo groups. RESULTS: No significant difference in stroke rate was observed between patients assigned abciximab (n = 22 [0.40%]) and those assigned placebo (n = 9 [0.29%]; P =.46). Excluding the EPIC abciximab bolus-only group, there were 9 strokes (0.30%) among 3023 patients who received placebo and 15 (0.32%) in 4680 patients treated with abciximab bolus plus infusion, a difference of 0.02% (95% confidence interval [CI], -0.23% to 0.28%). The rate of nonhemorrhagic stroke was 0.17% in patients treated with abciximab and 0.20% in patients treated with placebo (difference, -0.03%; 95% CI, -0.23% to 0.17%), and the rates of hemorrhagic stroke were 0.15% and 0.10%, respectively (difference, 0.05%; 95% CI, -0.11% to 0.21%). Among patients treated with abciximab, the rate of hemorrhagic stroke in patients receiving standard-dose heparin in EPIC, CAPTURE, and EPILOG was higher than in those receiving low-dose heparin in the EPILOG and EPISTENT trials (0.27% vs 0.04%; P =.057). CONCLUSIONS: Abciximab in addition to aspirin and heparin does not increase the risk of stroke in patients undergoing PCI. Patients undergoing PCI and treated with abciximab should receive low-dose, weight-adjusted heparin. http://repub.eur.nl/res/pub/9781/ 2001-01-01T00:00:00Z BACKGROUND: Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called "edge effect." To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side. METHODS AND RESULTS: Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P< 0.01). CONCLUSIONS: The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff. http://repub.eur.nl/res/pub/12895/ 2000-12-01T00:00:00Z AIMS: We investigated the influence of tensile stress on plaque growth after balloon angioplasty with and without beta-radiation therapy. METHODS AND RESULTS: Thirty-one consecutive patients successfully treated with balloon angioplasty were analysed qualitatively and quantitatively by means of an ECG-gated three-dimensional intravascular ultrasound post-procedure and at follow-up. Eighteen patients were irradiated with catheter-based beta-radiation ((90)Sr/(90)Y source) and 13 were not (control). Studied segments were divided into 2 mm subsegments. Thus 184 irradiated and 111 non-irradiated subsegments were included. Tensile stress was calculated according to Laplace's law. The radiation dose was calculated by means of dose-volume histograms. Plaque growth was positively correlated to tensile stress in both the radiation and control groups (r=0.374, P=0.0001 and r=0.305, P=0.001). Low-dose subsegments (<6 Gy) had a significant correlation (r=0.410, P=0.0001) whereas no correlation was observed in the effective-dose subsegments (> or = 6 Gy). Multivariate analysis identified tensile stress as the only independent predictor of plaque increase in non-irradiated subsegments, whereas actual dose and plaque morphology were stronger predictors in irradiated subsegments. CONCLUSION: The results of this study suggest that plaque growth is related to tensile stress after balloon angioplasty. Intracoronary brachytherapy may alter the biophysical process on plaque growth when the prescribed dose is effectively delivered. http://repub.eur.nl/res/pub/12877/ 2000-07-01T00:00:00Z BACKGROUND: Both nuclear imaging with F18-fluorodeoxyglucose and dobutamine stress echocardiography have been used to identify viable myocardium, although dobutamine-stress echocardiography has been demonstrated to be the less sensitive of the two. AIM: To compare the accuracy of pulsed-wave Doppler tissue sampling with dobutamine-stress echocardiography for the detection of viable myocardium, using F18-fluorodeoxyglucose imaging as a reference. Methods Forty patients with chronic coronary artery disease and left ventricular dysfunction (mean ejection fraction 33+/-11%), underwent F18-fluorodeoxyglucose imaging, dobutamine-stress echocardiography and pulsed-wave Doppler tissue sampling. Evaluation was performed using a six-segment model. RESULTS: Visual assessment by resting echo was feasible in 230 out of 240 segments (96%); 177 (77%) segments showed severe dyssynergy at rest. F18-fluorodeoxyglucose imaging showed viability in 95 (54%) segments while 82 (46%) were non-viable. Ejection phase velocity at rest was not significantly different; ejection velocities during low-dose and peak-dose dobutamine, however, were significantly higher in viable myocardium (8.6+/-2.9 vs 6.0+/-1.8 and 9.3+/-3.1 vs 6.2+/-2.1 cm x s(-1)). Using receiver operating characteristic curves the optimal cut-off value for viability assessment was an increase in the ejection phase velocity low-dose of 1+/-0.5 cm x s(-1), while 0+/-0.5 cm x s(-1)predicted non-viability. The sensitivity and specificity (95%CI) of pulsed-wave Doppler tissue sampling and dobutamine-stress echocardiography for the prediction of viability was respectively 87% (82-92) vs 75% (67-81) (P<0.05) and 52% (44-59) vs 51% (45-59) (P=ns). CONCLUSIONS: The sensitivity of pulsed-wave Doppler tissue sampling is superior to dobutamine-stress echocardiography for the assessment of myocardial viability. http://repub.eur.nl/res/pub/5618/ 2000-06-15T00:00:00Z Aims To identify, without additional investigation, a large group of myocardial infarction patients at low risk who would qualify for early discharge. Methods The decision rule was developed in 647 unselected patients with consecutively admitted myocardial infarction, and validated in 825 others. Daily event-rates were calculated for major (death, ventricular fibrillation, recurrent infarction, heart failure, advanced AV-block) and minor (unstable angina and rhythm-abnormalities) cardiac complications. Results Patients free from major complications until day 7 (44% of all patients) were found to constitute a very low risk group and thus would qualify for discharge at day 7. Of the 39% of patients with an uncomplicated infarction (low risk) in the validation group, 31% were discharged at day 7, while 8% stayed longer because of non-cardiac co-morbidity, for social reasons or logistic problems. No major adverse event occurred within 7 days after hospital discharge and only 1·8% developed complications within 1 month. The median duration of hospital stay for all in-hospital survivors was 7 days compared to 10 days in the control group. Conclusion Prospective application of the early discharge decision rule, based upon simple clinical variables and without the need for additional non-invasive and/or invasive tests, resulted in a significant reduction of hospital stay. The decision rule correctly classified patients into high and low risk groups and appeared feasible and safe. Its efficacy was demonstrated by its ability to identify a large group of post infarction survivors at low risk for complications during follow-up. http://repub.eur.nl/res/pub/12838/ 2000-03-15T00:00:00Z AIMS: Evaluation of angiographical and intracoronary Doppler-derived parameters of coronary stenosis severity. METHODS AND RESULTS: A total of 225 patients with one-vessel disease were studied before PTCA and at 6 months follow-up. Exercise electrocardiography was performed to document presence (n = 157) or absence (n = 138) of an ST segment shift (> or =0.1 mV). Intracoronary blood flow velocity analysis was performed to determine the proximal/distal flow velocity ratio, the distal diastolic/systolic flow velocity ratio and coronary flow velocity reserve. Receiver operator characteristic curves were calculated to assess the predictive value of these variables compared with the exercise test. The distal coronary flow velocity reserve demonstrated the best linear correlation for both percentage diameter stenosis and minimum lumen diameter (r = 0.67 and r = 0.66; P<0.01), compared to the diastolic/systolic flow velocity ratio (r = 0.19 and r = 0.14; P<0.01) and the proximal/distal flow velocity ratio (r = 0.03 and r = 0.07; not significant). The areas under the curve were 0. 84+/-0.02; 0.82+/-0.03 and 0.83+/-0.03 for diameter stenosis, minimum lumen diameter and coronary flow velocity reserve, respectively. Logistic regression analysis revealed that the percentage diameter stenosis or minimum lumen diameter and coronary flow velocity reserve were independent predictors for the result of stress testing. CONCLUSIONS: The distal coronary flow velocity reserve is the best intracoronary Doppler parameter for evaluation of coronary narrowings. Angiographical estimates of coronary lesion severity and distal coronary flow velocity reserve are good and independent predictors for the assessment of functional severity of coronary stenosis, emphasizing the complementary role of these parameters for clinical decision making. http://repub.eur.nl/res/pub/12827/ 2000-03-04T00:00:00Z AIMS: Variations in outcome of patients from different geographic regions have been observed in many large international trials. We analysed the factors that might contribute to the geographic variations in patient outcome and treatment effect as observed in the PURSUIT trial. METHODS: In PURSUIT, 9461 patients with acute coronary syndromes without persistent ST-elevation were randomized to the platelet inhibitor eptifibatide or placebo for 72 h in 27 countries in four geographic regions: Western (n=3697) and Eastern Europe (n=1541) as well as North (n=3827) and Latin America (n=396). The primary end-point was the 30-day composite of death or myocardial infarction. In the initial univariate analysis, the treatment effect appeared greater in N. America than in W. Europe, while no benefit was apparent in L. America and E. Europe. However, the confidence intervals were wide and overlapping. To study these differences, a subdivision in an early and late patient outcome and treatment effect was made. Accordingly, we analysed the rate of death or infarction at 72 h censored for percutaneous coronary intervention and the rate between 3 and 30 days, respectively. Additional analyses were performed with different definitions of myocardial infarction using progressively higher thresholds of CK(-MB) elevation. Multivariable analysis was used to evaluate the relation between region and outcome and to determine the adjusted odds ratios for the eptifibatide treatment effect. RESULTS: Major differences in baseline demographics were apparent among the four regions; in particular, more patients from E. Europe had characteristics associated with impaired outcome. Interventional treatment also varied considerably, with more patients from N. America undergoing revascularization. Despite differences in the 72 h event rate, eptifibatide showed a consistent trend towards a reduction in the composite end-point among all four regions and for all definitions of infarction. Relative reductions ranged from 17-42% in W. Europe, 23-35% in N. America, 0-33% in E. Europe, and 55-82% in L. America. After multivariable adjustment, the pattern of benefit with eptifibatide was consistent among the regions. In patients undergoing percutaneous coronary intervention during study drug infusion in W. Europe (n=266) and N. America (n=931), the relative reduction in myocardial infarction during medical therapy ranged from 56-75% in W. Europe and 14-67% in N. America, while the reduction in procedure-related events ranged from 12-44% and 25-61% for different definitions of infarction. After multivariable adjustment neither benefit nor rebound were apparent after study drug discontinuation, or after 3 days in all regions, except in L. America. In general, the differences in outcome and treatment effect were greatest when the protocol definition of myocardial infarction (CK(-MB) >1 upper normal limit) was applied. Under stricter definitions, these differences became smaller and disappeared with the investigator's assessment. CONCLUSION: The analysis suggests that the apparent differences in patient outcome and eptifibatide treatment effect can be explained largely by differences in baseline demographics and adjunctive treatment strategies as well as by the methodology of myocardial infarction definition and the adjudication process. http://repub.eur.nl/res/pub/4888/ 2000-01-01T00:00:00Z Background—Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with ß-radiation after BA. Methods and Results—Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a ß-emitting 90Sr/90Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (Dv90Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). Dv90Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r=0.71; P=0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, Dv90Adv, and type of plaque. Conclusions—Residual plaque burden, delivered dose, and tissue composition play a fundamental role in the volumetric outcome at 6-month follow-up after ß-radiation therapy and BA. http://repub.eur.nl/res/pub/9261/ 2000-01-01T00:00:00Z BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists prevent the composite end point of death or myocardial infarction (MI) in patients with acute coronary syndromes. There is uncertainty about whether this effect is confined to patients who have percutaneous coronary interventions (PCIs) and whether PCIs further prevent death or MI in patients already treated with GP IIb/IIIa antagonists. METHODS AND RESULTS: PURSUIT patients were treated with the GP IIb/IIIa antagonist eptifibatide or placebo; PCIs were performed according to physician practices. In 2253 of 9641 patients (23.4%), PCI was performed by 30 days. Early (<72 hours) PCI was performed in 1228 (12.7%). In 34 placebo patients (5.5%) and 10 treated with eptifibatide (1.7%) (P=0.001), MI preceded early PCI. In patients censored for PCI across the 30-day period, there was a significant reduction in the primary composite end point in eptifibatide patients (P=0.035). Eptifibatide reduced 30-day events in patients who had early PCI (11.6% versus 16.7%, P=0.01) and in patients who did not (14.6% versus 15.6%, P=0.23). After adjustment for PCI propensity, there was no evidence that eptifibatide treatment effect differed between patients with or without early PCI (P for interaction=0.634). PCI was not associated with a reduction of the primary composite end point but was associated with a reduced (nonspecified) composite of death or Q-wave MI. This association disappeared after adjustment for propensity for early PCI. CONCLUSIONS: Eptifibatide reduced the composite rates of death or MI in PCI patients and those managed conservatively. http://repub.eur.nl/res/pub/9374/ 2000-01-01T00:00:00Z BACKGROUND: Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with beta-radiation after BA. METHODS AND RESULTS: Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a beta-emitting (90)Sr/(90)Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (D(v90)Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). D(v90)Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r = 0.71; P = 0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, D(v90)Adv, and type of plaque. CONCLUSIONS: Residual plaque burden, delivered dose, and tiss composition play a fundamental role in the volumetric outcome at 6-month follow-up after beta-radiation therapy and BA. http://repub.eur.nl/res/pub/9378/ 2000-01-01T00:00:00Z BACKGROUND: Appropriate treatment policies should include an accurate estimate of a patient's baseline risk. Risk modeling to date has been underutilized in patients with acute coronary syndromes without persistent ST-segment elevation. METHODS AND RESULTS: We analyzed the relation between baseline characteristics and the 30-day incidence of death and the composite of death or myocardial (re)infarction in 9461 patients with acute coronary syndromes without persistent ST-segment elevation enrolled in the PURSUIT trial [Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy]. Variables examined included demographics, history, hemodynamic condition, and symptom duration. Risk models were created with multivariable logistic regression and validated by bootstrapping techniques. There was a 3.6% mortality rate and 11.4% infarction rate by 30 days. More than 20 significant predictors for mortality and for the composite end point were identified. The most important baseline determinants of death were age (adjusted chi(2)=95), heart rate (chi(2)=32), systolic blood pressure (chi(2)=20), ST-segment depression (chi(2)=20), signs of heart failure (chi(2)=18), and cardiac enzymes (chi(2)=15). Determinants of mortality were generally also predictive of death or myocardial (re)infarction. Differences were observed, however, in the relative prognostic importance of predictive variables for mortality alone or the composite end point; for example, sex was a more important determinant of the composite end point (chi(2)=21) than of death alone (chi(2)=10). The accuracy of the prediction of the composite end point was less than that of mortality (C-index 0.67 versus 0.81). CONCLUSIONS: The occurrence of adverse events after presentation with acute coronary syndromes is affected by multiple factors. These factors should be considered in the clinical decision-making process. http://repub.eur.nl/res/pub/9552/ 2000-01-01T00:00:00Z BACKGROUND: Coronary stenting improves outcomes compared with balloon angioplasty, but it is costly and may have other disadvantages. Limiting stent use to patients with a suboptimal result after angioplasty (provisional angioplasty) may be as effective and less expensive. METHODS AND RESULTS: To analyze the cost-effectiveness of provisional angioplasty, patients scheduled for single-vessel angioplasty were first randomized to receive primary stenting (97 patients) or balloon angioplasty guided by Doppler flow velocity and angiography (523 patients). Patients in the latter group were further randomized after optimization to either additional stenting or termination of the procedure to further investigate what is "optimal." An optimal result was defined as a flow reserve >2.5 and a diameter stenosis <36%. Bailout stenting was needed in 129 patients (25%) who were randomized to balloon angioplasty, and an optimal result was obtained in 184 of the 523 patients (35%). There was no significant difference in event-free survival at 1 year between primary stenting (86.6%) and provisional angioplasty (85.6%). Costs after 1 year were significantly higher for provisional angioplasty (EUR 6573 versus EUR 5885; P:=0.014). Results after the second randomization showed that stenting was also more effective after optimal balloon angioplasty (1-year event free survival, 93.5% versus 84.1%; P:=0. 066). CONCLUSIONS: After 1 year of follow-up, provisional angioplasty was more expensive and without clinical benefit. The beneficial value of stenting is not limited to patients with a suboptimal result after balloon angioplasty. http://repub.eur.nl/res/pub/5608/ 1999-12-01T00:00:00Z Although it is well known that smoking is strongly associated with coronary heart disease, many patients continue or resume smoking after being diag- nosed with coronary heart disease and even after an important event such as a myocardial infarction, angio- plasty or coronary bypass surgery. The evidence that smoking causes cardiovascular disease and new events in patients with coronary heart disease, among other serious disorders such as lung cancer and emphysema, justifies the promotion of smoking cessation. All rec- ommendations on the prevention of coronary heart dis- ease emphasize the importance of smoking cessation in the reduction of the risk of coronary death and non-fatal coronary events[3,4]. The recent EUROASPIRE study on the status of secondary prevention of coronary heart disease in nine European countries has shown, however, that success in smoking cessation among coronary heart disease patients is far from satisfactory[5]. In this era of evidence-based medicine, information from systematic reviews of published studies should guide physicians and other health professionals advising patients in smoking cessation. With this in mind, we have carried out a systematic review of published observational studies on the impact of smoking cessation on the prognosis and on smoking intervention trials in patients with coronary heart disease. http://repub.eur.nl/res/pub/12816/ 1999-11-01T00:00:00Z AIMS: To establish to what extent smoking status and its management is recorded in coronary patients' medical records, and to investigate their motivation to change smoking behaviour. METHODS: In EUROASPIRE, a survey on secondary prevention in 21 hospitals in the Czech Republic, Finland, France, Germany, Hungary, Italy, the Netherlands, Slovenia and Spain, data were collected from records of 4863 consecutive patients =<70 years of age, with previous (>6 months) admission for coronary bypass operation, angioplasty, myocardial infarction or ischaemia. Of these, 3569 patients were interviewed 1.6 years following their index hospitalization. RESULTS: Of the 82% of patients whose pre-hospitalization smoking behaviour was known, 34% were smokers. Documentation was significantly better in younger patients, in males and patients requiring angioplasty or bypass operation. In only 35% of 1364 smokers was the smoking habit recorded again after discharge from hospital At the time of the interview, 554 of the interviewed patients were still smoking. In over 90% of the smokers, advice to quit smoking was reported at interview. A positive relationship was found between receiving advice and seeking help to stop smoking, between receiving advice to stop smoking and attempting to stop, as well as between seeking help and attempting to stop. CONCLUSION: In almost 20% of coronary patients, smoking habits are not documented in medical records, and in only 35% of the smoking patients is smoking status documented at the follow-up. After a cardiac event requiring hospitalization as many as 50% of patients continue their smoking habit and so there is further potential to reduce the risk of recurrent coronary disease. Advice to stop smoking motivates patients to seek help and to attempt to stop smoking. Physicians repeated advice to stop smoking is important and smoking status should always be documented at follow-up. http://repub.eur.nl/res/pub/12808/ 1999-08-01T00:00:00Z AIMS: Thrombin plays a key role in the clinical syndrome of unstable angina. We investigated the safety and efficacy of five dose levels of efegatran sulphate, a direct thrombin inhibitor, compared to heparin in patients with unstable angina. METHODS: Four hundred and thirty-two patients with unstable angina were enrolled. Five dose levels of efegatran were studied sequentially, ranging from 0.105 mg. kg(-1). h(-1)to 1.2 mg. kg(-1). h(-1)over 48 h. Safety was assessed clinically, with reference to bleeding and by measuring clinical laboratory parameters. Efficacy was assessed by the number of patients experiencing any episode of recurrent ischaemia as measured by computer-assisted continuous ECG ischaemia monitoring. Clinical end-points were: episodes of recurrent angina, myocardial infarction, coronary intervention (PTCA or CABG), and death. RESULTS: Efegatran demonstrated dose dependent ex-vivo anticoagulant activity with the highest dose level of 1.2 mg. kg(-1). h(-1)resulting in steady state mean activated partial thromboplastin time values of approximately three times baseline. Thrombin time was also increased. Neither of the efegatran doses studied were able to suppress myocardial ischaemia during continuous ECG ischaemia monitoring to a greater extent than that seen with heparin. There were no statistically significant differences in clinical outcome or major bleeding between the efegatran and heparin groups. Minor bleeding and thrombophlebitis occurred more frequently in the efegatran treated patients. CONCLUSION: Administration of efegatran sulphate at levels of at least 0.63 mg. kg(-1). h(-1)provided an anti-thrombotic effect which is at least comparable to an activated partial thromboplastin time adjusted heparin infusion. There was no excess of major bleeding. The level of thrombin inhibition by efegatran, as measured by activated partial thromboplastin time, appeared to be more stable than with heparin. Thus, like other thrombin inhibitors, efegatran sulphate is easier to administer than heparin. However, no clinical benefits of efegatran over heparin were apparent. http://repub.eur.nl/res/pub/5597/ 1999-08-01T00:00:00Z AIMS: Studies on the glycoprotein IIb-IIIa receptor blocker abciximab in patients undergoing percutaneous coronary intervention consistently show a reduction in procedure-related myocardial infarction. Some such infarcts are characterized by elevated creatine kinase or creatine kinase-MB, without apparent clinical symptoms. The clinical relevance of such 'creatine kinase leaks' has been questioned. Therefore we investigated the relationship between post-procedural creatine kinase-MB elevation and outcome at the 6 month follow-up. METHODS AND RESULTS: Creatine kinase-MB, or total creatine kinase values were analysed in 5025 out of 6156 patients enrolled in the CAPTURE, EPIC and EPILOG studies. A consistent gradual increase in 6 month mortality was observed as creatine kinase-MB or creatine kinase levels increased: 1.1%, 2.1%, 1.8%, 3. 6% and 6.7% for creatine-MB or creatine ratios (relative to upper limit of normal) <1, 1-3, 3-5, 5-10 and >/=10, respectively. Also the incidence of death or (recurrent) myocardial infarction was related to creatine kinase-MB or creatine kinase ratios. Subsequent revascularization was not related to periprocedural myocardial infarction. By multivariable analysis, correcting for clinical and angiographic characteristics, mortality at 6 months was related to the enzyme (creatine kinase, creatine kinase-MB) ratio, a history of heart failure and age. The combined end-point of death and myocardial infarction was also related to these factors, as well as to a history of bypass surgery and unstable angina. CONCLUSION: Modest elevation of cardiac enzymes (creatine kinase-MB, creatine kinase) after percutaneous coronary intervention is associated with an increased risk of mortality and reinfarction during the 6 month follow-up. Measures to reduce such periprocedural infarcts are warranted. http://repub.eur.nl/res/pub/5588/ 1999-01-01T00:00:00Z Background—The purpose of this study was to assess the long-term value of dobutamine-atropine stress echocardiography (DSE) for prediction of late cardiac events in patients with proven or suspected coronary artery disease. Methods and Results—Clinical data and DSE results were analyzed in 1734 consecutive patients undergoing DSE between 1989 and 1997. Seventy-four patients who underwent revascularization within 3 months of DSE and 1 patient lost to follow-up were excluded; the remaining 1659 (median age, 62 years; range, 14 to 99 years) were followed up for 36 months (range, 6 to 96 months). Wall motion abnormalities at rest and the presence and extent of stress-induced wall motion abnormalities (ischemia) were scored for each patient. Cardiac events were related to clinical and ECG data and DSE results. Four hundred twenty-eight cardiac events occurred in 366, documented cardiac death in 108 (total death, 247), nonfatal infarction in 128, and late revascularization in 192 patients. In a multivariable Cox proportional-hazards model, the ratio of documented cardiac death or (re)infarction was increased in the presence of stress-induced ischemia (hazard ratio, 3.3; 95% CI, 2.4 to 4.4) and extensive rest wall motion abnormalities (hazard ratio, 1.9; 95% CI, 1.3 to 2.6). The number of ischemic segments was predictive for late cardiac events. A normal DSE carried a relatively good prognosis, with an annual event rate of cardiac death or infarction of 1.3% over a 5-year period. Conclusions—In a large group of patients, DSE has an added value for predicting late cardiac events during long-term follow-up, improving the separation between high- risk and very-low-risk patients. http://repub.eur.nl/res/pub/9019/ 1999-01-01T00:00:00Z BACKGROUND--The purpose of this study was to assess the long-term value of dobutamine-atropine stress echocardiography (DSE) for prediction of late cardiac events in patients with proven or suspected coronary artery disease. METHODS AND RESULTS--Clinical data and DSE results were analyzed in 1734 consecutive patients undergoing DSE between 1989 and 1997. Seventy-four patients who underwent revascularization within 3 months of DSE and 1 patient lost to follow-up were excluded; the remaining 1659 (median age, 62 years; range, 14 to 99 years) were followed up for 36 months (range, 6 to 96 months). Wall motion abnormalities at rest and the presence and extent of stress-induced wall motion abnormalities (ischemia) were scored for each patient. Cardiac events were related to clinical and ECG data and DSE results. Four hundred twenty-eight cardiac events occurred in 366, documented cardiac death in 108 (total death, 247), nonfatal infarction in 128, and late revascularization in 192 patients. In a multivariable Cox proportional-hazards model, the ratio of documented cardiac death or (re)infarction was increased in the presence of stress-induced ischemia (hazard ratio, 3.3; 95% CI, 2.4 to 4.4) and extensive rest wall motion abnormalities (hazard ratio, 1.9; 95% CI, 1.3 to 2.6). The number of ischemic segments was predictive for late cardiac events. A normal DSE carried a relatively good prognosis, with an annual event rate of cardiac death or infarction of 1.3% over a 5-year period. CONCLUSIONS--In a large group of patients, DSE has an added value for predicting late cardiac events during long-term follow-up, improving the separation between high- risk and very-low-risk patients. http://repub.eur.nl/res/pub/9193/ 1999-01-01T00:00:00Z BACKGROUND: Glycoprotein (GP) IIb/IIIa receptor blockers prevent life-threatening cardiac complications in patients with acute coronary syndromes without ST-segment elevation and protect against thrombotic complications associated with percutaneous coronary interventions (PCIs). The question arises as to whether these 2 beneficial effects are independent and additive. METHODS AND RESULTS: We analyzed data from the CAPTURE, PURSUIT, and PRISM-PLUS randomized trials, which studied the effects of the GP IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban, respectively, in acute coronary syndrome patients without persistent ST-segment elevation, with a period of study drug infusion before a possible PCI. During the period of pharmacological treatment, each trial demonstrated a significant reduction in the rate of death or nonfatal myocardial infarction in patients randomized to the GP IIb/IIIa inhibitor compared with placebo. The 3 trials combined showed a 2.5% event rate in this period in the GP IIb/IIIa inhibitor group (N=6125) versus 3.8% in placebo (N=6171), which implies a 34% relative reduction (P<0.001). During study medication, a PCI was performed in 1358 patients assigned GP IIb/IIIa inhibition and 1396 placebo patients. The event rate during the first 48 hours after PCI was also significantly lower in the GP IIb/IIIa inhibitor group (4. 9% versus 8.0%; 41% reduction; P<0.001). No further benefit or rebound effect was observed beyond 48 hours after the PCI. CONCLUSIONS: There is conclusive evidence of an early benefit of GP IIb/IIIa inhibitors during medical treatment in patients with acute coronary syndromes without persistent ST-segment elevation. In addition, in patients subsequently undergoing PCI, GP IIb/IIIa inhibition protects against myocardial damage associated with the intervention. http://repub.eur.nl/res/pub/9207/ 1999-01-01T00:00:00Z BACKGROUND: Cardiovascular complications are the most important causes of perioperative morbidity and mortality among patients undergoing major vascular surgery. METHODS: We performed a randomized, multicenter trial to assess the effect of perioperative blockade of beta-adrenergic receptors on the incidence of death from cardiac causes and nonfatal myocardial infarction within 30 days after major vascular surgery in patients at high risk for these events. High-risk patients were identified by the presence of both clinical risk factors and positive results on dobutamine echocardiography. Eligible patients were randomly assigned to receive standard perioperative care or standard care plus perioperative beta-blockade with bisoprolol. RESULTS: A total of 1351 patients were screened, and 846 were found to have one or more cardiac risk factors. Of these 846 patients, 173 had positive results on dobutamine echocardiography. Fifty-nine patients were randomly assigned to receive bisoprolol, and 53 to receive standard care. Fifty-three patients were excluded from randomization because they were already taking a beta-blocker, and eight were excluded because they had extensive wall-motion abnormalities either at rest or during stress testing. Two patients in the bisoprolol group died of cardiac causes (3.4 percent), as compared with nine patients in the standard-care group (17 percent, P=0.02). Nonfatal myocardial infarction occurred in nine patients given standard care only (17 percent) and in none of those given standard care plus bisoprolol (P<0.001). Thus, the primary study end point of death from cardiac causes or nonfatal myocardial infarction occurred in 2 patients in the bisoprolol group (3.4 percent) and 18 patients in the standard-care group (34 percent, P<0.001). CONCLUSIONS: Bisoprolol reduces the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction in high-risk patients who are undergoing major vascular surgery. http://repub.eur.nl/res/pub/16993/ 1998-02-04T00:00:00Z Myocardial infarction is one of the leading causes of death among adults in the Western World. In The Netherlands, yearly approximately 20,000 men and 10,000 women are admitted with this disease, which is responsible for circa 12% of annual mortality (figure). Myocardial infarction is an acute coronary syndrome, which may happen during the chronic process of coronary atherosclerosisp· At a certain stage in this process fissuring and disruption of the growing atherosclerotic plaque may occur, initiating intraluminal thrombus formation. Such thrombi may cause total occlusion of the coronary artery, so that oxygen delivery to the myocardium is blocked. IE th is situation persists for more than 30 minutes, irreversible damage to the myocardium, i.e. myocardial infarction, will occur. Prolonged duration of coronary occlusion results in a progressive increase of the infarcted area, until the whole area at risk becomes necrotic. Generally, after approximately six hours of continuous occlusion the infarct has reached its full extension. Although the notion that myocardial infarction is caused by acute coronary thrombosis was already advanced in the beginning of this century, the correctness of this idea was demonstrated only in the early 1980s, by studies of DeWood et al. Since that time, treatment strategies have been introduced that aimed at rapid and lasting restoration of the coronary blood circulation. The overall benefits of these 'reperfusion' strategies have been established unequivocally. http://repub.eur.nl/res/pub/4973/ 1997-01-01T00:00:00Z Background The aim of this prospective, multicenter study was the identification of Doppler flow velocity measurements predictive of clinical outcome of patients undergoing single-vessel balloon angioplasty with no previous Q-wave myocardial infarction. Methods and Results In 297 patients, a Doppler guidewire was used to measure basal and maximal hyperemic flow velocities proximal and distal to the stenosis before and after angioplasty. In 225 patients with an angiographically successful percutaneous transluminal coronary angioplasty (PTCA), postprocedural distal coronary flow reserve (CFR) and percent diameter stenosis (DS%) were correlated with symptoms and/or ischemia at 1 and 6 months, with the need for target lesion revascularization, and with angiographic restenosis (defined as DS 50% at follow-up). Logistic regression and receiver operator characteristic curve analyses were applied to determine the prognostic cutoff value of CFR and DS separately and in combination. Optimal cutoff criteria for predictors of these clinical events were DS, 35%; CFR, 2.5. A distal CFR after angioplasty >2.5 with a residual DS 35% identified lesions with a low incidence of recurrence of symptoms at 1 month (10% versus 19%, P=.149) and at 6 months (23% versus 47%, P=.005), a low need for reintervention (16% versus 34%, P=.024), and a low restenosis rate (16% versus 41%, P=.002) compared with patients who did not meet these criteria. Conclusions Measurements of distal CFR after PTCA, in combination with DS%, have a predictive value, albeit modest for the short- and long-term outcomes after PTCA, and thus may be used to identify patients who will or will not benefit from additional therapy such as stent implantation. http://repub.eur.nl/res/pub/4988/ 1997-01-01T00:00:00Z Background Demonstration and quantification of site-specific intracoronary administration of compounds has been confined thus far to the experimental animal laboratory. The aim of this study was to describe a scintigraphic method to demonstrate site-specific intracoronary drug delivery in humans. The methods allow on-line visualization and off-line quantification of site-specifically infused -emitting compounds. Methods and Results In 12 patients after balloon angioplasty, 99mTc-labeled heparin was administered at the site of dilatation by use of a coil balloon. Both the infusion period and the washout period after the end of infusion were monitored with a -camera. A curve of counts per pixel as a function of time was derived that showed an accumulation phase during infusion followed by a washout phase after the end of infusion. Both phases were fitted by regression analysis and showed a linear accumulation pattern and a biexponential washout pattern. After correction for background counts, 99mTc decay, and body attenuation, peak heparin amount and regional bioavailability were calculated. Peak amount was defined as the initial point of the slow washout component of the biexponential curve (elimination component), and regional bioavailability was defined as the area under the curve of accumulation and washout phase. Half-life and retention time, defined as seven half-lives, were obtained by use of the elimination component after correction for 99mTc decay. Mean peak delivered amount was 45±44 IU (236±228 µg), corresponding to an efficiency of delivery ranging from 1% to 8% of the totally infused dose. Total regionally bioavailable heparin reached 244±194 IU·h (1.28±1.01 mg·h). Retention time varied from 12 to 90 hours (mean, 50:33±22:50 hours:minutes). Conclusions Site-specific intracoronary heparin delivery after angioplasty by means of the coil balloon was demonstrated in humans, and regional pharmacokinetics was quantified by use of a radioisotopic technique. http://repub.eur.nl/res/pub/5554/ 1997-01-01T00:00:00Z http://repub.eur.nl/res/pub/8730/ 1997-01-01T00:00:00Z In anesthetized pigs, we investigated whether asynchrony (delta T) and nonuniformity (regional differences) in contractility (delta E) could describe the interaction between normal and stunned myocardium. Mechanical interaction was evaluated by regional postsystolic work (PSW) before and after production of stunning by a 5-min occlusion of the left circumflex coronary artery [LCX (LCX stunning)] and a subsequent 10-min occlusion of the left anterior descending coronary artery [LAD (LAD stunning)]. delta T and delta E were intensified by intracoronary (LAD) infusions of dobutamine. From regional end-systolic pressure-segment length relationships, systolic segment shortening (SS), end-systolic elastance (E), external work (EW), and PSW were determined. LCX stunning decreased SSLCX from 14 +/- 2 (mean +/- SE, n = 9) to 10 +/- 2% and ELCX from 103 +/- 25 to 52 +/- 7 mmHg/mm, whereas the LAD region was unaffected. EWLCX decreased from 165 +/- 16 to 138 +/- 20 mmHg.mm, whereas PSWLCX increased from -4 +/- 6 to 8 +/- 3 mmHg.mm. Additional LAD stunning reduced SSLAD from 16 +/- 2 to 9 +/- 3% and ELAD from 79 +/- 10 to 31 +/- 6 mmHg/mm, without affecting SSLCX and ELCX. In the normal myocardium, PSWLAD increased and PSWLCX decreased, but, during local LAD dobutamine infusions after stunning, both PSWLCX and PSWLAD increased. In normal myocardium, the changes in PSWLCX could be described by delta T (65 +/- 11%) and delta E (37 +/- 15%). After stunning of the LAD area, the contribution of delta E increased to 55 +/- 14% at the expense of delta T (37 +/- 15%). Similar contributions of delta E (54 +/- 13%) and delta T (57 +/- 13%) were found when both the LCX and LAD distribution areas were stunned. In normal myocardium, both delta T and delta E modulate mechanical interaction, with the contribution of delta T exceeding that of delta E. In stunned myocardium, both factors contribute, but the contribution shifts in favor of delta E. http://repub.eur.nl/res/pub/5044/ 1996-03-01T00:00:00Z The ABC classification of the American College of Cardiology and the American Heart Association is a commonly used categorization to estimate the risk and success of intracoronary intervention, as well as the probability of restenosis. To evaluate the reliability of qualitative angiogram readings, we randomly selected 200 films from single lesion angioplasty procedures. A repeated visual assessment (> or = 2 months interval) by two independent observers resulted in kappa values of inter and intra-observer variability for the ABC lesion classification and for all separate items that compile it. Variability in assessment is expressed in percentage of total agreement, and in kappa value, which is a parameter of the agreement between two or more observations in excess of the chance agreement. Percentage of total agreement and kappa value was 67.8% and 0.33 respectively for the ABC classification, indicating a poor agreement. Probably this is due to the deficiency of strict definitions. Further investigation has to demonstrate whether improvement can be achieved using complete and detailed definitions without ambiguity, and consensus after panel assessment. http://repub.eur.nl/res/pub/5046/ 1996-01-01T00:00:00Z Background The use of stents improves the result after balloon coronary angioplasty. Thrombogenicity of stents is, however, a concern. In the present study, we compared stents with an antithrombotic coating with regular stents. Methods and Results Regular stents were placed in coronary arteries of pigs receiving no aspirin (group 1; n=8) or aspirin over 4 weeks (group 2, n=10) or 12 weeks (group 3, n=9). Stents coated with heparin (antithrombin III uptake, 5 pmol/stent) were placed in 7 pigs that did not receive aspirin (group 4). The other animals received aspirin and coated stents with a heparin activity of 12 pmol antithrombin III/stent (group 5, n=10) or 20 pmol/stent (group 6, n=10; group 7, n=10). Quantitative arteriography was performed at implantation and after 4 (groups 1, 2, and 4 through 6) or 12 weeks (groups 3 and 7). In an additional 5 animals, five regular and five coated stents (20 pmol/stent) were placed and explanted after 5 days for examination of the early responses to the implants. Thrombotic occlusion of the regular stent occurred in 9 of 27 in groups 1 through 3. However, in 0 of 30 of the animals receiving high-activity heparin-coated stents (groups 5 through 7), thrombotic stent occlusion was observed (P<.001). Histological analysis at 4 weeks showed that the neointima in group 6 was thicker compared with its control group 2 (259±104 and 117±36 µm, P<.01), but at 12 weeks the thickness was similar (152±61 and 198±49 µm, respectively). Comparison at 5 days suggested delayed endothelialization of the coating. http://repub.eur.nl/res/pub/5518/ 1996-01-01T00:00:00Z Currently several modes of reperfusion therapy for acute myocardial infarction are available. Streptokinase, accelerated alteplase and direct angioplasty are the most frequently used. These options are increasingly effective, but are also increasingly complex and costly. Since, unfortunately, physicians are often restricted by budget limitations, choices must be made in clinical practice to provide optimal therapy to individual patients. In order to guide such decision making, we developed a model to predict the expected benefit of therapy in terms of gain in life expectancy. Patients' life expectancy will decrease after infarction. Part of this loss can be prevented by early reperfusion therapy. The clinical benefit of therapy ranges from negligible gain in patients with small infarcts treated relatively late to an expected gain of more than 2 years in patients with extensive infarction treated within 3 h of onset of symptoms. The expected benefits are presented in a set of tables and depend on age, previous infarction, estimated infarct size, treatment delay and intracranial bleeding risk. With the help of these table, resources will be allocated in such a manner that patients who will benefit the most will receive the most effective therapy. Patients with similar expected treatment benefit will be offered the same mode of therapy. Future life years were discounted at 5% per year. The arbitrary thresholds currently applied for decision making at the Thoraxcenter are: no reperfusion therapy when the estimated gain in discounted life expectancy was < 1 month, streptokinase for 1-4 months and accelerated alteplase for a gain >or = 5 months. Direct angioplasty is recommended in patients with an estimated gain > or = 12 months, and in patients with an increased risk of intracranial bleeding. In this way, approximately 80% of our patients will be treated with thrombolytics (40% streptokinase and 40% accelerated alteplase), while in 10% direct angioplasty will be initiated. Patients with small infarcts presenting late will not receive reperfusion therapy. These threshold values have been chosen arbitrarily, and different thresholds may be selected in other centres. However, the developed model would guarantee that treatment decisions are made in a consistent manner, to provide optimal therapy for patients with evolving myocardial infarction, in spite of limited resources. http://repub.eur.nl/res/pub/5519/ 1996-01-01T00:00:00Z OBJECTIVE: To improve pre-hospital triage of patients with suspected acute cardiac disease. DESIGN: Prospective study. SUBJECTS. Patients with symptoms suggestive of acute cardiac pathology, who were seen by a general practitioner, for whom acute admission into hospital was requested, and in whom a pre-hospital electrocardiogram was recorded by the ambulance service. METHODS: The study consisted of two phases. In the first phase, a decision rule was developed based on clinical characteristics and electrocardiographic findings in 1005 patients with suspected acute cardiac pathology. In the second phase, the decision rule was prospectively validated. Symptoms were recorded by a standardized questionnaire by the general practitioner and a computerized electrocardiogram was made by the ambulance nurses at the patient's home. Three electrocardiographic outcomes were available: 'normal electrocardiogram', 'possible myocardial infarction' or 'extensive myocardial infarction'. By use of the predictive model, the general practitioner could decide if hospitalization was necessary or not. MAIN OUTCOME MEASUREMENTS: Identification of patients at low (stable angina, atypical chest pain, other pathology) and high (myocardial infarction, unstable angina) probability of acute cardiac pathology. RESULTS: Among 977 patients with a complete pre-hospital evaluation in the validation phase of the study, the decision rule recommended 'no hospitalization' in 227 patients (23%). The general practitioner followed this advice in 44% of these patients. Although seven of them developed a non-Q wave myocardial infarction, no complications occurred in patients not admitted. In addition, the general practitioner did not hospitalize 19 (2%) of 750 patients for whom the decision rule recommended admission. Pre-hospital triage by the general practitioner resulted in a 12% (118 of 977 patients) reduction of the number of patients admitted to the Coronary Care Units. CONCLUSIONS: Pre-hospital triage by the general practitioner was facilitated using a standardized questionnaire and pre-hospital electrocardiography, and resulted in a reduction in the number of patients admitted to the Coronary Care Unit, and proved to be safe. http://repub.eur.nl/res/pub/5488/ 1995-07-04T00:00:00Z http://repub.eur.nl/res/pub/5064/ 1995-01-01T00:00:00Z Background Inefficacy of systemic drug administration for restenosis prevention may partially relate to insufficient local drug concentration. This study aimed to evaluate the acute feasibility and long-term outcome of using an infusion-perfusion coil balloon, Dispatch. Methods and Results In 22 patients after balloon angioplasty, the coil balloon was studied for (1) feasibility of local heparin delivery, (2) symptoms and signs of ischemia during prolonged deployment compared with angioplasty balloon occlusion, (3) coronary pressure and flow distal to the inflated device, and (4) long-term clinical and angiographic results. During prolonged intracoronary deployment of the coil balloon (29±8 minutes), 5 of 22 patients developed mild chest pain versus 20 of 22 during angioplasty (275±283 seconds). Neither hemodynamic nor vectorcardiographic signs of ischemia were detected, in contrast to angioplasty balloon occlusion. Baseline flow across the coil balloon was 44±31 mL/min, increasing by a factor of 1.8±0.7 during pharmacologically induced hyperemia. A mean volume of 14.2±6.1 mL containing 1416±608 IU of heparin was infused locally at a pressure of 122±54 mm Hg. At 7±1-month follow-up, 1 asymptomatic patient had died, and of the remaining 21, 17 (81%) were asymptomatic. Angiographic follow-up was obtained in 15 of 21 patients (71%), including all 4 symptomatic patients. Mean minimal luminal diameter after the procedure was 2.16±0.49 mm and at follow-up, 1.89±0.45 mm, which corresponds to a restenosis rate (diameter stenosis 50%) of 7% (1/15). Conclusions Intracoronary use of the coil balloon after balloon angioplasty proved to be feasible and subjectively as well as objectively well tolerated during prolonged deployment by virtue of its perfusion properties. High volumes of heparin solution can be infused locally at very low pressure. No unfavorable clinical or angiographic long-term effects were observed. http://repub.eur.nl/res/pub/4603/ 1994-01-01T00:00:00Z OBJECTIVES. The purpose of this study was to determine the predictive value of quantitative coronary angiography in the assessment of the functional significance of coronary stenosis as judged from the development of left ventricular wall motion abnormalities during dobutamine-atropine stress echocardiography. BACKGROUND. Coronary angiography is the reference method for assessment of the accuracy of noninvasive diagnostic imaging techniques to detect the presence of significant coronary stenosis. However, use of arbitrary cutoff criteria for the interpretation of angiographic data may considerably influence the true diagnostic accuracy of the technique investigated. METHODS. Thirty-four patients without previous myocardial infarction and with single-vessel coronary stenosis were studied with both quantitative angiography and dobutamine-atropine stress echocardiography. Two different techniques of quantitative angiographic analysis--edge detection and videodensitometry--were used for measurement of minimal lumen diameter, percent diameter stenosis and percent area stenosis. Two-dimensional echocardiographic images were collected during incremental doses of intravenous dobutamine and later analyzed using a 16-segment left ventricular model. Angiographic cutoff criteria were derived from receiver-operating curves to define the functional significance of coronary stenosis on the basis of dobutamine-atropine stress echocardiography. RESULTS. The angiographic cutoff values with the best predictive value for the development of left ventricular wall motion abnormalities during dobutamine-atropine stress echocardiography were minimal lumen diameter of 1.07 mm, percent diameter stenosis of 52% and percent area stenosis of 75%. Minimal lumen diameter was found to have the best predictive value for a positive dobutamine stress test (odds ratio 51, sensitivity 94%, specificity 75%). CONCLUSIONS. Automated quantitative angiographic measurement of minimal lumen diameter is a practical and useful index for determining both the anatomic and functional significance of coronary stenosis, and a value of 1.07 mm is the best predictor for a positive dobutamine stress test. http://repub.eur.nl/res/pub/4619/ 1994-01-01T00:00:00Z OBJECTIVES. This study was designed to examine whether restenosis is related to the extent or mechanism of lumen improvement and to explore angiographic determinants of optimal atherectomy. BACKGROUND. Directional atherectomy induces a greater extent of immediate gain and late loss but has not been found to yield a better late angiographic lumen than angioplasty in randomized trials. The difference in lumen renarrowing may be related to either the extent or the mechanism of immediate gain. The design of previous studies has precluded the detection of a device-specific effect on restenosis. METHODS. A retrospective analysis was based on matching a prospectively collected series of 80 native coronary arteries successfully treated with atherectomy with a prospectively collected series of 80 native coronary arteries successfully treated with balloon angioplasty. Angiographic analysis was performed in 160 lesions to explore whether a specific device-related effect exists. Multivariate analyses were performed to determine the correlates of minimal lumen diameter at follow-up and late lumen loss and to identify the procedural characteristics for optimal atherectomy. RESULTS. Matching resulted in two comparable groups with equivalent baseline clinical and stenosis characteristics. By study design, atherectomy and angioplasty resulted in similar mean (+/- SD) immediate lumen gain (1.15 +/- 0.44 vs. 1.10 +/- 0.40 mm, p = 0.50). However, lumen loss was more pronounced after atherectomy, and, thus, the minimal lumen diameter at follow-up differed significantly between the two groups (1.78 +/- 0.57 vs. 2.00 +/- 0.56 mm, p = 0.001). Device type was retained in the multivariate analysis as an independent predictor of late minimal lumen diameter and lumen loss. Multivariate analysis identified vessel size and immediate gain as determinants of optimal atherectomy. CONCLUSIONS. Restenosis is a consequence not only of the extent of lumen improvement but also of the mechanism of vessel wall injury (debulking vs. dilating). While performing atherectomy, the operator should strive for an optimal procedural result to accommodate an increased intimal hyperplastic response.