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    <title>Cokkinos, D.V.</title>
    <link>http://repub.eur.nl/res/aut/8221/</link>
    <description>List of Publications</description>
    <language>en</language>
    <image>
      <url>http://repub.eur.nl/static-eur/img/logo.png</url>
      <title>RePub, Erasmus University Rotterdam</title>
      <link>http://repub.eur.nl</link>
    </image>
    <item>
      <title>Transthoracic Doppler echocardiography assessment of left anterior descending artery flow in patients with previous anterior myocardial infarction (Article)</title>
      <link>http://repub.eur.nl/res/pub/30427/</link>
      <pubDate>2008-05-01T00:00:00Z</pubDate>
      <description>Aim: We tested the hypothesis that shortening of diastolic pressure half time (PHT) of left anterior descending (LAD) coronary flow in patients with old reperfused anterior myocardial infarction (MI) is related to the presence of permanent myocardial damage of the reperfused area. Methods and results: We studied 49 patients divided into: group A: 15 patients with previous anterior MI and evidence of myocardial scar; group B: 10 patients with previous anterior MI and no evidence of myocardial scar and group C: 24 patients without anterior MI. All patients underwent coronary angiography at least 6 months after an index event and any reperfusion procedure. Group A patients had lower PHT (199 ± 62 ms) than group C (377 ± 103 ms, p = 0.0001) and group B (316 ± 154 ms, p = 0.029) patients. No other LAD flow velocity parameter differed among the 3 groups. A PHT value of 265 ms discriminated patients with scarred anteriorwallwith a sensitivity of 79% and a specificity of 94% (0.88, p &lt; 0.001). Conclusion: Shortening of the LAD flow diastolic PHT in patients with remote, reperfused anterior MI reflects scarred myocardial tissue in the anteroapical wall while patients who maintain diastolic wall thickness after an acute coronary syndrome have PHT similar to patients without anterior MI. </description>
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      <title>Intermittent acute aortic valve regurgitation: A case report of a prosthetic valve dysfunction (Article)</title>
      <link>http://repub.eur.nl/res/pub/30440/</link>
      <pubDate>2008-03-01T00:00:00Z</pubDate>
      <description>Complications of any mechanical prosthesis include thrombus or pannus formation. In our case report we demonstrate that prosthetic aortic valve regurgitation due to pannus formation may be intermittent and non-cyclic in pattern and therefore not obvious at the time of original clinical examination. Under these conditions and as transesophageal echocardiography cannot be repeated promptly, transthoracic 2-D and Doppler echocardiography should be available at any time when symptoms occur and present the method of choice for acute patient evaluation. Thrombolysis seems to be the first treatment of choice in case of thrombus formation and re-do surgery in case of pannus formation. </description>
    </item> <item>
      <title>Prognostic significance of renal function in patients undergoing dobutamine stress echocardiography (Article)</title>
      <link>http://repub.eur.nl/res/pub/29898/</link>
      <pubDate>2008-02-01T00:00:00Z</pubDate>
      <description>Background. Dobutamine stress echocardiography (DSE) is used for risk stratification of patients with suspected coronary artery disease (CAD). However, the prognostic value of DSE among the entire strata of renal function has yet to be determined. We assessed the prognostic value of renal function relative to DSE findings. Methods. We studied 2292 patients, divided into 729 (32%) patients with normal renal function [creatinine clearance (CrCl) &gt;90 ml/min] and 1563 (68%) with renal dysfunction, classified as mild (CrCl: 60-90 ml/min) in 933, moderate (CrCl: 30-60 ml/min) in 502 and severe (CrCl &lt; 30ml/min) in 128 patients. All patients underwent DSE for the evaluation of known or suspected CAD and were followed for a mean of 8 years. Results. New wall motion abnormalities during DSE and mildly, moderately and severely abnormal CrCl were powerful independent predictors for all-cause mortality, cardiac death and hard cardiac events (cardiac death and non-fatal myocardial infarction). Kaplan-Meier curves demonstrated that patients with normal DSE and renal dysfunction have greater probability for cardiac death and hard cardiac events compared to those with normal renal function. The warranty of a normal DSE in the presence of moderate renal dysfunction was 15 and 36 months for 10 and 20% risk for cardiac death and hard cardiac events, respectively. Conclusions. The presence and severity of renal dysfunction has additional independent prognostic value over DSE findings. The low-risk warrantee period after a normal DSE is determined by the severity of renal dysfunction. </description>
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      <title>ACE inhibition with perindopril and biomarkers of atherosclerosis and thrombosis: Results from the PERTINENT study (Article)</title>
      <link>http://repub.eur.nl/res/pub/14542/</link>
      <pubDate>2008-01-01T00:00:00Z</pubDate>
      <description>The PERTINENT study measured biomarkers of atherosclerosis and thrombosis in a stable coronary artery disease population from EUROPA receiving ACE inhibition with perindopril 8 mg/day or placebo. Biomarkers of inflammation, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor-alpha (TNF-α), and a biomarker of thrombosis, d-dimer, were measured at baseline and 1 year. CRP was recorded in 1157 patients; fibrinogen, TNF-α, and d-dimer in 291 patients. There was no significant effect of treatment on CRP or fibrinogen. In contrast, there were significant reductions in TNF-α (27.60-25.20 pg/mL; P &lt; 0.05) and d-dimer (0.24-0.18 μg/mL; P &lt; 0.05) with perindopril over 1 year. Survival analysis of the prognostic significance of baseline CRP failed to detect a significant role for the prediction of cardiovascular events over 4 years (lower versus higher tertile: 1.54; 95% confidence interval 0.88-2.68; P = 0.16). In conclusion, in the PERTINENT trial, we observed significant effects of ACE inhibition on biomarkers of the atherothrombotic complications (d-dimer) and the proinflammatory cytokine TNF-α, but not on biomarkers of inflammation associated with atherosclerosis (CRP and fibrinogen).</description>
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      <title>ACE inhibition and endothelial function: Main findings of PERFECT, a sub-study of the EUROPA trial (Article)</title>
      <link>http://repub.eur.nl/res/pub/36429/</link>
      <pubDate>2007-08-01T00:00:00Z</pubDate>
      <description>Background: ACE inhibition results in secondary prevention of coronary artery disease (CAD) through different mechanisms including improvement of endothelial dysfunction. The Perindopril-Function of the Endothelium in Coronary artery disease Trial (PERFECT) evaluated whether long-term administration of perindopril improves endothelial dysfunction. Methods: PERFECT is a 3-year double blind randomised placebo controlled trial to determine the effect of perindopril 8 mg once daily on brachial artery endothelial function in patients with stable CAD without clinical heart failure. Endothelial function in response to ischaemia was assessed using ultrasound. Primary endpoint was difference in flow-mediated vasodilatation (FMD) assessed at 36 months. Results: In 20 centers, 333 patients randomly received perindopril or matching placebo. Ischemia-induced FMD was 2.7% (SD 2.6). In the perindopril group FMD went from 2.6% at baseline to 3.3% at 36 months and in the placebo group from 2.8 to 3.0%. Change in FMD after 36 month treatment was 0.55% (95% confidence interval -0.36, 1.47; p=0.23) higher in perindopril than in placebo group. The rate of change in FMD per 6 months was 0.14% (SE 0.05, p=0.02) in perindopril and 0.02% (SE 0.05, p=0.74) in placebo group (0.12% difference in rate of change p=0.07). Conclusion: Perindopril resulted in a modest, albeit not statistically significant, improvement in FMD. </description>
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      <title>Value of Myocardial Viability Estimation Using Dobutamine Stress Echocardiography in Assessing Risk Preoperatively Before Noncardiac Vascular Surgery in Patients With Left Ventricular Ejection Fraction &lt;35% (Article)</title>
      <link>http://repub.eur.nl/res/pub/35407/</link>
      <pubDate>2007-06-01T00:00:00Z</pubDate>
      <description>Patients with heart failure (HF) scheduled for vascular surgery have an increased risk of adverse postoperative outcome, and stratification usually depends on dichotomous risk factors. A quantitative prognostic model for patients with HF was developed using wall motion patterns during dobutamine stress echocardiography (DSE). A total of 295 consecutive patients (mean age 67 ± 12 years) with ejection fraction ≤35% were studied. During DSE, wall motion patterns of dysfunctional segments were scored as scar, ischemia, or sustained improvement. Cardiac death and myocardial infarction were noted perioperatively and during 5 years of follow-up. Of 4,572 dysfunctional segments; 1,783 (39%) had ischemia, 1,280 (28%) had sustained improvement, and 1,509 (33%) had scar. In 212 patients, ≥1 ischemic segment was present; 83 had only sustained improvement. Perioperative and late cardiac event rates were 20% and 30%, respectively. Using multivariate analysis, number of ischemic segments was associated with perioperative cardiac events (odds ratio per segment 1.6, 95% confidence interval 1.05 to 1.8), whereas number of segments with sustained improvement was associated with improved outcome (odds ratio per segment 0.2, 95% confidence interval 0.04 to 0.7). Multivariate independent predictors of late cardiac events were age and ischemia. Sustained improvement was associated with improved survival. In conclusion, DSE provides accurate risk stratification of patients with HF undergoing vascular surgery. </description>
    </item> <item>
      <title>The long prognostic value of wall motion abnormalities during the recovery phase of dobutamine stress echocardiography after receiving acute β-blockade (Article)</title>
      <link>http://repub.eur.nl/res/pub/36476/</link>
      <pubDate>2007-05-01T00:00:00Z</pubDate>
      <description>OBJECTIVE: To assess the prognostic value of wall motion abnormalities during the recovery phase of dobutamine stress echocardiography in addition to wall motion abnormalities at peak stress. METHODS: Wall motion abnormalities were assessed at peak and during recovery phase of dobutamine stress echocardiography in 187 consecutive patients, who were followed for occurrence of cardiac events. RESULTS: During follow-up (mean 36±28 months), 19 patients (10%) died from cardiac causes, 34 (18%) patients suffered nonfatal myocardial infarction, and 77 (41%) patients underwent late revascularization. Univariable predictors of cardiac events by Cox regression analysis were age (hazard ratio: 1.01; confidence interval: 1.00-1.03), dyslipidemia (hazard ratio: 1.41; confidence interval: 1.02-1.95), rest wall motion abnormalities (hazard ratio: 1.37; confidence interval: 1.14-1.64), new wall motion abnormalities (hazard ratio: 1.18; confidence interval: 0.95-1.45) at peak and new wall motion abnormalities (hazard ratio: 1.33; confidence interval: 1.11-1.59) at recovery phase of dobutamine stress echocardiography. The best multivariable model to predict cardiac events included new wall motion abnormality (hazard ratio: 5.34; confidence interval: 1.71-16.59) at recovery phase of dobutamine stress echocardiography, after controlling for clinical and peak dobutamine stress echocardiography data. CONCLUSIONS: Myocardial ischemia at recovery phase of dobutamine stress echocardiography is an independent predictor of cardiac events and has an incremental value when added to ischemia at peak. </description>
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      <title>Myocardial viability estimation during the recovery phase of stress echocardiography after acute beta-blocker administration (Article)</title>
      <link>http://repub.eur.nl/res/pub/36807/</link>
      <pubDate>2007-04-01T00:00:00Z</pubDate>
      <description>Background: Myocardial viability assessment in severely dysfunctional segments by dobutamine stress echocardiography (DSE) is less sensitive than nuclear scanning. Aim: To assess the additional value of using the recovery phase of DSE after acute beta-blocker administration for identifying viable myocardium. Methods: The study included 49 consecutive patients with ejection fraction (LVEF) ≤ 35%. All patients underwent DSE evaluation at low-high dose and during recovery phase, and dual-isotope single photon emission tomography (DISA-SPECT) evaluation for viability of severely dysfunctional segments. Patients with ≥ 4 viable segments were considered viable. Coronary revascularization followed within 3 months in all patients. Radionuclide evaluation of LVEF was performed before and 12 months after revascularization. Results: Viability with DISA-SPECT was detected in 463 (59%) segments, while 154 (19.7%) segments presented as scar. The number of viable segments increased from 415 (53%) at DSE to 463 (59%) at DSE and recovery, and the number of viable patients increased from 43 to 49 respectively. LVEF improved by ≥ 5% in 27 patients. Multivariate regression analysis showed that, DSE with recovery phase was the only independent predictor of ≥ 5% LVEF improvement after revascularization (OR 14.6, CI 1.4-133.7). Conclusion: In this study, we demonstrate that the recovery phase of DSE has an increased sensitivity for viability estimation compared to low-high dose DSE. </description>
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      <title>ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT (Article)</title>
      <link>http://repub.eur.nl/res/pub/35656/</link>
      <pubDate>2007-01-01T00:00:00Z</pubDate>
      <description>Objectives: EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease [EUROPA] demonstrates reduction in cardiovascular mortality and myocardial infarction for a possible vascular and antiatherosclerotic effect of angiotensin-converting enzyme (ACE) inhibition with perindopril. Our objective was to study the effect of perindopril on endothelial function and to verify its link to risk and occurrence of cardiovascular events. Methods: Blood from 1200 EUROPA patients was withdrawn at baseline and after 1 year of treatment with either perindopril or placebo to measure von Willebrand factor and from 45 healthy subjects and 87 EUROPA patients to study endothelial function at the cellular level by cultivating in vitro human umbilical vein endothelial cells. In this setting, we determined protein expression/activity of endothelial nitric oxide synthase and the rate of apoptosis. Plasma levels of angiotensin II, bradykinin, tumor necrosis factor α, and nitrite/nitrate were also measured. Results: The occurrence of cardiovascular events was related to von Willebrand factor at baseline (P = 0.013) that also significantly decreased after 1 year's treatment (P &lt; 0.001). Perindopril upregulated 19% and 27% protein expression/activity of endothelial nitric oxide synthase (P &lt; 0.05) as well as reduced the rate of apoptosis by 31% (P &lt; 0.05). There was also a significant reduction in levels of angiotensin II, increase in bradykinin, reduction in tumor necrosis factor α, and increase in nitrite/nitrate (P &lt; 0.05 for all). Conclusions: Abnormal endothelial function occurs in patients with coronary artery disease, and this can be counteracted by angiotensin-converting enzyme inhibition with perindopril. These effects could contribute, at least in part, to explaining the results of the main EUROPA Study. </description>
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      <title>Early percutaneous coronary intervention, platelet inhibition with eptifibatide, and clinical outcomes in patients with acute coronary syndromes. PURSUIT Investigators (Article)</title>
      <link>http://repub.eur.nl/res/pub/9261/</link>
      <pubDate>2000-01-01T00:00:00Z</pubDate>
      <description>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 (&lt;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.</description>
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