Niels J.W. Verouden

Genous™ endothelial progenitor cell capturing stent vs. the Taxus Liberté stent in patients with de novo coronary lesions with a high-risk of coronary restenosis: a randomized, single-centre, pilot study

Aims The purpose of this study was to evaluate the GenousTM endothelial progenitor cell capturing stent vs. the Taxus Liberté paclitaxel-eluting stent in patients with de novo coronary lesions with a high-risk of coronary restenosis. Methods and results We randomly assigned 193 patients with lesions carrying a high risk of restenosis to have the Genous stent or the Taxus stent implanted. Lesions were considered high risk of restenosis if one of the following applied: chronic total occlusion, lesion length >23 mm, vessel diameter <2.8 mm, or any lesion in a diabetic patient. At 1-year, the rate of the primary end point, target vessel failure (TVF), was 17.3% in the Genous stent group when compared with 10.5% in the Taxus stent group [risk difference (RD) 6.8%, 95% CI −3.1 to 16.7%], a difference predominantly due to a higher incidence of repeat revascularization in patients treated with the Genous stent. In contrast, no stent thrombosis was observed in the Genous stent group compared to 4 stent thromboses in the Taxus stent group (RD −4.2%; 95% CI −10.3 to 0.3%). Repeat angiography between 6 and 12 months in a subgroup of patients showed a significantly higher late loss in the Genous stent compared with the Taxus stent (1.14 ± 0.64 and 0.55 ± 0.61 mm). Conclusion In patients with lesions carrying a high risk of restenosis, the Genous stent resulted in a non-significant higher rate of TVF compared with the Taxus stent mainly due to more repeat revascularizations in the Genous stent group. There were four stent thromboses with Taxus stent, none with the Genous stent.

Multiple Biomarkers at Admission Significantly Improve the Prediction of Mortality in Patients Undergoing Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction

OBJECTIVES We investigated whether multiple biomarkers improve prognostication in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention. BACKGROUND Few data exist on the prognostic value of combined biomarkers. METHODS We used data from 1,034 STEMI patients undergoing primary percutaneous coronary intervention in a high-volume percutaneous coronary intervention center in the Netherlands and investigated whether combining N-terminal pro-brain natriuretic peptide, glucose, C-reactive protein, estimated glomerular filtration rate, and cardiac troponin T improved the prediction of mortality. A risk score was developed based on the strongest predicting biomarkers in multivariate Cox regression. The additional prognostic value of the strongest predicting biomarkers to the established prognostic factors (age, body weight, diabetes, hypertension, systolic blood pressure, heart rate, anterior myocardial infarction, and time to treatment) was assessed in multivariable Cox regression. RESULTS During follow-up (median, 901 days), 120 of the 1,034 patients died. In Cox regression, glucose, estimated glomerular filtration rate, and N-terminal pro-brain natriuretic peptide were the strongest predictors for mortality (p < 0.05, for all). A risk score incorporating these biomarkers identified a high-risk STEMI subgroup with a significantly higher mortality when compared with an intermediate- or low-risk subgroup (p < 0.001). Addition of the 3 biomarkers to established prognostic factors significantly improved prediction for mortality, as shown by the net reclassification improvement (0.481, p < 0.001) [corrected] and integrated discrimination improvement (0.0226, p = 0.03) [corrected]. CONCLUSIONS Our data suggest that addition of a multimarker to a model including established risk factors improves the prediction of mortality in STEMI patients undergoing primary percutaneous coronary intervention. Furthermore, the use of a simple risk score based on these biomarkers identifies a high-risk subgroup.

Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

BackgroundIn the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events.Methods/DesignThe Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction (EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years.DiscussionThe ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome.Trial registrationtrialregister.nl NTR1108.

Persistent precordial “hyperacute” T-waves signify proximal left anterior descending artery occlusion

Objective: To describe patients with a distinct electrocardiogram (ECG) pattern without ST-segment elevation in the presence of an acute occlusion of the proximal left anterior descending (LAD) artery. Design: Single-centre observational study. Patients: Patients with acute anterior wall myocardial infarction who were referred for primary percutaneous coronary intervention (PCI) between 1998 and 2008. Results: We identified patients with a static, distinct ECG pattern without ST-segment elevation and an occlusion of the proximal LAD artery during urgent coronary angiography before PCI. Of 1890 patients who underwent primary PCI of the LAD artery, we could identify 35 patients (2%) with this distinct ECG pattern. The ECG showed ST-segment depression at the J-point of at least 1 mm in precordial leads with upsloping ST-segments continuing into tall, symmetrical T-waves. Patients with this distinct ECG pattern were younger, more often male and more often had hypercholesterolaemia compared to patients with anterior myocardial infarction and ST-segment elevation. Conclusions: In patients presenting with chest pain, ST-segment depression at the J-point with upsloping ST-segments and tall, symmetrical T-waves in the precordial leads of the 12-lead ECG signifies proximal LAD artery occlusion. It is important for cardiologists and emergency care physicians to recognise this distinct ECG pattern, so they can triage such patients for immediate reperfusion therapy.

Comparison of long-term mortality after percutaneous coronary intervention in patients treated for acute ST-elevation myocardial infarction versus those with unstable and stable angina pectoris.

Data remain limited regarding the comparative long-term mortality across the spectrum of patients with different indications for percutaneous coronary intervention (PCI). We evaluated early and late mortality in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary PCI compared with early and late mortality in patients undergoing PCI for unstable angina (UA) or non-STEMI (NSTEMI) and stable angina. A total of 10,549 consecutive patients undergoing PCI from 1997 to 2005 at a single institution were followed up prospectively (median 3.2 years, interquartile range 1.5 to 5.6) to assess all-cause mortality. The indication for PCI was STEMI in 28%, UA/NSTEMI in 32%, and stable angina in 40%. The mortality rate at 6 years was 18.9% in patients with STEMI, 16.2% in patients with UA/NSTEMI, and 11.7% in those with stable angina. During the initial 6 months, patients with STEMI had an increased risk of death compared with patients with UA/NSTEMI (relative risk [RR] 3.09, 95% confidence interval [CI] 2.46 to 3.89) and stable angina (RR 5.82, 95% CI 4.45 to 7.62). However, between 6 months and 6 years, mortality accrued at an almost similar rate among patients with STEMI and those with stable angina (RR 1.06, 95% CI 0.86 to 1.32) and mortality was greatest in patients with UA/NSTEMI (UA/NSTEMI vs stable angina: RR 1.33, 95% CI 1.11 to 1.58; STEMI vs UA/NSTEMI: RR 0.80, 95% CI 0.65 to 0.99). In conclusion, we have demonstrated that the inferior survival rates in patients with STEMI after primary PCI are mainly attributed to greater mortality in the first months after the event. These observations highlight that new adjunctive therapeutic strategies should aim at mortality reduction in the first months after primary PCI.

Histopathology of aspirated thrombus and its association with ST-segment recovery in patients undergoing primary percutaneous coronary intervention with routine thrombus aspiration.

Background: In patients with ST‐segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with thrombus aspiration, the histopathology of aspirated thrombus was previously related to long‐term mortality. In this study, we sought to investigate the association between histopathology of aspirated thrombus and ST‐segment recovery, a marker of microvascular dysfunction, immediately at the end of the PCI procedure. Methods: We included 892 STEMI patients who underwent primary PCI with routine thrombus aspiration and for whom combined data on histopathology of aspirated thrombus and ST‐segment recovery were available. Patients were categorized according to histopathology of aspirated thrombus: fresh only (<1 day), older (>1 day), or no material aspirated. ST‐segment recovery was defined as incomplete if <50%. Results: Incomplete ST‐segment recovery occurred in 134 of 363 patients (37%) with fresh thrombus, in 104 of 238 patients (44%) with older thrombus, and in 142 of 291 patients (49%) with no material. Unadjusted odds ratios for incomplete ST‐segment recovery of patients with older thrombus and no material, when compared with patients with fresh thrombus, were 1.33 (95% CI, 0.95–1.85; P = 0.097) and 1.63 (95% CI 1.19–2.23; P = 0.002), respectively. Both associations were unchanged after multivariable adjustment for clinical predictors of ST‐segment recovery. ST‐segment recovery was a strong predictor of long‐term mortality, independent of the histopathology of aspirated thrombus. Conclusions: This study shows that ST‐segment recovery immediately at the end of the PCI procedure was a significant prognosticator, independent of the histopathology of aspirated thrombus. We found that the histopathology of aspirated thrombus (fresh, older, no material) was associated with ST‐segment recovery in STEMI patients undergoing primary PCI with thrombus aspiration.

Prediction of 1-Year Mortality With Different Measures of ST-Segment Recovery in All-Comers After Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction

Background—Post hoc analyses from several randomized, controlled trials have established the prognostic importance of different measures of ST-segment recovery in highly selected patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction (STEMI). In this single-center registry, we investigated whether various measures of ST-segment recovery can be applied to unselected STEMI patients undergoing primary PCI. Methods and Results—We analyzed 12-lead ECGs from 2124 consecutive STEMI patients who underwent primary PCI at our institution between November 1, 2000, and January 1, 2007. ECGs were recorded at the catheterization laboratory immediately before arterial puncture and at the end of PCI. We examined measures assessing ST-segment recovery on the postprocedural ECG and measures comparing both ECGs and related these to 1-year, all-cause mortality. Cumulative ST-segment recovery (∑ST-D resolution) at a 50% cutoff had the highest unadjusted accuracy (C statistic, 0.646; 95% confidence interval, 0.602 to 0.689; P<0.001) as compared with the other 8 measures evaluated. Furthermore, ∑ST-D resolution was the strongest contributor to both the net reclassification and integrated discrimination improvement. Conclusions—Although each measure of ST-segment recovery provided univariable prognostic information, the ∑ST-D resolution measure comparing summed ST-segment deviations on the preprocedural and postprocedural ECG was the best independent predictor of 1-year mortality in all-comer STEMI patients after primary PCI.

Comparison of the usefulness of N-terminal pro-brain natriuretic peptide to other serum biomarkers as an early predictor of ST-segment recovery after primary percutaneous coronary intervention.

Data on the ability of serum biomarkers to predict microvascular obstruction by ST-segment recovery after primary percutaneous coronary intervention (PCI) is largely absent. Therefore, we determined the association between 5 serum biomarkers, obtained before emergency coronary angiography, and immediate ST-segment recovery in patients who had undergone primary PCI for ST-segment elevation myocardial infarction. We measured N-terminal pro-brain natriuretic peptide (NT-pro-BNP), cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and serum creatinine from blood samples obtained through the arterial sheath at the start of primary PCI. Serial 12-lead electrocardiograms were recorded in the catheterization laboratory before arterial puncture and at the end of the PCI. ST-segment recovery was defined as incomplete if <50%. Of 662 included patients with ST-segment elevation myocardial infarction, 338 (51%) had incomplete ST-segment recovery. An elevated NT-pro-BNP level (> or = 608 ng/L) was the strongest predictor of incomplete ST-segment recovery (adjusted odds ratio 2.6, 95% confidence interval 1.6 to 4.1; p <0.001) compared to other serum biomarkers and clinical predictors. An elevated NT-pro-BNP level was more strongly predictive in patients without a history of coronary artery disease or hypertension (adjusted odds ratio 4.7, 95% confidence interval 2.4 to 9.2; p <0.001). NT-pro-BNP was the best contributor to both net reclassification (0.43; p <0.001) and integrated discrimination improvement (0.04; p <0.001) when added to a multivariate model with clinical predictors of incomplete ST-segment recovery. In conclusion, NT-pro-BNP was the strongest independent predictor of ST-segment recovery at the end of primary PCI for ST-segment elevation myocardial infarction compared to the other serum biomarkers reflecting myocardial cell damage, renal function, and inflammation.

Clinical and angiographic predictors of ST-segment recovery after primary percutaneous coronary intervention.

Important determinants of incomplete ST-segment recovery in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) have been incompletely characterized. Early risk stratification could identify patients with STEMI and incomplete ST-segment recovery who may benefit from adjunctive therapy. For the present study, we analyzed 12-lead electrocardiograms from 2,124 patients with STEMI who underwent primary PCI at our institution from 2000 to 2007. ST-segment recovery was defined as percent change in cumulative ST-segment deviation between preprocedural and immediately postprocedural electrocardiograms and categorized as incomplete when <50%. A total of 1,032 patients (49%) had incomplete ST-segment recovery. After multivariable adjustment, age >60 years (adjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.06 to 1.54, p = 0.011), diabetes mellitus (OR 1.36, 95% CI 1.02 to 1.82, p = 0.034), left anterior descending coronary artery-related STEMI (OR 1.92, 95% CI 1.61 to 2.30, p<0.001), and multivessel disease (OR 1.34, 95% CI 1.10 to 1.63, p = 0.004) were independent predictors of incomplete ST-segment recovery. Current smoking (OR 0.79, 95% CI 0.65 to 0.95, p = 0.013) and a preprocedural Thrombolysis In Myocardial Infarction grade <3 flow (OR 0.70, 95% CI 0.53 to 0.93, p = 0.014) were inversely related to ST-segment recovery. Incomplete ST-segment recovery was a strong predictor of long-term mortality (hazard ratio 2.07, 95% CI 1.59 to 2.69, p <0.001) in addition to identified characteristics that independently predicted incomplete ST-segment recovery. In conclusion, incomplete ST-segment recovery at the end of PCI occurred significantly more often in the presence of an age >60 years, nonsmoking, diabetes mellitus, left anterior descending coronary artery-related STEMI, multivessel disease, and preprocedural Thrombolysis In Myocardial Infarction grade 3 flow. Patients with STEMI and these clinical features are at increased risk of impaired myocardial salvage and are appropriate candidates for adjunctive therapy.

Impact of early, late, and no ST-segment resolution measured by continuous ST Holter monitoring on left ventricular ejection fraction and infarct size as determined by cardiovascular magnetic resonance imaging

BACKGROUND The goal of this study is to determine the predictive value of ST-segment resolution (STR) early after percutaneous coronary intervention (PCI), late STR, and no STR for left ventricular ejection fraction (LVEF) and infarct size (IS) by cardiovascular magnetic resonance (CMR) at follow-up in patients with ST-segment elevation myocardial infarction. METHODS The analysis included 199 patients who were enrolled in the PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-Elevation trial and in whom both continuous ST Holter and CMR at follow-up were available. Patients were stratified into 3 groups: (1) early complete (≥70%) STR measured immediately after last contrast injection (n = 113); (2) late complete STR (n = 52), defined as complete STR from 30 to 240 minutes after PCI; and (3) no complete STR after 240 minutes (n = 34). RESULTS Patients with early STR had more preserved LVEF and smaller IS compared to patients with late STR or no STR (LVEF: early STR, 54% ± 8%; late STR, 46% ± 13%; no STR, 43% ± 11%; and IS: 3.9 ± 3.3 g/m(2); 8.0 ± 6.9 g/m(2); 12.0 ± 6.0 g/m(2); respectively; all P < .0001). Early STR was independently predictive for LVEF (β = 8.5; P = .0005) and IS (β = -7.0; P < .0001). Late STR was not predictive for LVEF (β = 1.6; P = .51) but predictive for IS (β = -3.5; P = .003). CONCLUSIONS Patients with early complete STR after primary PCI have better preserved LVEF and smaller IS. Patients with late complete STR do not have better preserved LVEF but do have smaller IS. ST-segment resolution is a strong, independent predictor of LVEF and IS as assessed by CMR.