http://repub.eur.nl/res/aut/30200/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/33970/ 2011-04-01T00:00:00Z Objective: To establish the prevalence of osteoporosis, vertebral fractures (VFs), and non-VFs in acromegaly patients with long-term controlled disease and factors potentially influencing fracture risk. Design: Case-control study. Patients and measurements: Eighty-nine patients (46% male, mean age: 58 years) were included. We studied VFs and non-VFs, bone mineral density (BMD), and markers of bone turnover. In 48 patients, BMD assessment was also obtained 7 years prior to the current study. To compare VF prevalence, data from a sample of the Dutch population (n=3469) were used. Results: VF prevalence was 59% (men 64% and women 54%), significantly increased when compared with controls (odds ratio up to 6.5), and independent of the duration of disease control, BMD, markers of bone turnover, and acromegalic disease characteristics. Mean number of VFs per patient was 3.4G0.3 (range 1-8). There was no relationship between the number and severity of fractures, parameters of bone turnover, and follow-up BMD measurements. BMD did not change during prolongation of follow-up by 7 years of controlled acromegaly. Conclusion: There is a very high prevalence of VFs in acromegaly patients with long-term controlled disease, independently of BMD. In view of the significant morbidity and mortality associated with VFs in general and the inability of BMD to predict fracture risk in acromegalic patients, we propose to include VF assessment, for example by lateral conventional radiographs of the spine in the screening of patients with acromegaly, both at diagnosis and during follow-up after establishment of disease control. 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/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/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/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/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/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/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/29836/ 2008-07-01T00:00:00Z Objective: It has been proposed that TSH has thyroid hormone-independent effects on bone mineral density (BMD) and bone metabolism. This concept is still controversial and has not been studied in human subjects in detail. We addressed this question by studying relationships between serum TSH concentration and indicators of bone turnover, after controlling for triiodothyronine (T3), free thyroxine (FT4), and non-thyroid factors relevant to BMD and bone metabolism. We also studied the contribution of the TSH receptor (TSHR)-Asp727Glu polymorphism to these relationships. Design: We performed a cross-sectional study with 148 patients, who had been thyroidectomized for differentiated thyroid carcinoma. Methods: We measured BMD of the femoral neck and lumbar spine. FT4, T3, TSH, bone-specific alkaline phosphatase, procollagen type 1 aminoterminal propeptide levels, C-cross-linking terminal telopeptide of type I collagen, and urinary N-telopeptide of collagen cross-links were measured. Genotypes of the TSHR-Asp727Glu polymorphism were determined by Taqman assay. Results: We found a significant, inverse correlation between serum TSH levels and indicators of bone turnover, which was independent of serum FT4and T3levels as well as other parameters influencing bone metabolism. We found that carriers of the TSHR-Asp727Glu polymorphism had an 8.1% higher femoral neck BMD, which was, however, no longer significant after adjusting for body mass index. Conclusion: We conclude that in this group of patients, serum TSH was related to indicators of bone remodeling independently of thyroid hormone levels. This may point to a functional role of the TSHR in bone in humans. Further research into this mechanism needs to be performed. http://repub.eur.nl/res/pub/35350/ 2007-07-01T00:00:00Z Objective: Therapy with the retinoid X receptor agonist bexarotene is associated with hypothyroidism caused by decreased pituitary TSH secretion. To evaluate the effects of bexarotene on peripheral thyroid hormone metabolism, we performed a study in athyreotic subjects on a fixed substitution dose with L-T4. Design: The design was an open prospective 6-wk intervention study. Methods: Ten athyreotic patients with pulmonary metastases of differentiated thyroid carcinoma received 6-wk redifferentiation treatment with 300 mg bexarotene/d. L-T4doses were kept stable. Before and in the sixth week of therapy, serum levels of total T4, free T4(FT4), T3, reverse T3(rT3), and TSH were measured. To study nondeiodinase-mediated thyroid hormone degradation, serum levels of T4sulfate (T4S) were measured. Recombinant human TSH was administered before and in the sixth week of bexarotene therapy. Results: Bexarotene induced profound decreases in total T4(56% of baseline), FT4(47%), T3(69%), rT3(51%), and T4S (70%) in all patients, whereas TSH levels were not affected. The T3/rT3ratio increased by 43%, and the T4S/FT4ratio increased by 48%. Serum TSH levels before and after recombinant human TSH were unaffected by bexarotene. Conclusions: In the present study, we demonstrate that increased peripheral degradation of thyroid hormones by a nondeiodinase-mediated pathway contributes to bexarotene induced-hypothyroidism. Copyright 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/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/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.