Wichert J. Kuijt

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.

P2Y12 platelet inhibition in clinical practice

Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines.

Infarct size and left ventricular function in the PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-segment Elevation (PREPARE) trial: ancillary cardiovascular magnetic resonance study

Objectives The aim of the study was to evaluate whether primary percutaneous coronary intervention (PCI) with combined proximal embolic protection and thrombus aspiration results in smaller final infarct size and improved left ventricular function assessed by cardiovascular magnetic resonance (CMR) in ST-segment elevation myocardial infarction (STEMI) patients compared with primary PCI alone. Background Primary PCI with the Proxis system improves immediate microvascular flow post-procedure as measured by ST-segment resolution, which could result in better outcomes. Methods The ancillary CMR study included 206 STEMI patients who were enrolled in the PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-Elevation (PREPARE) trial. CMR imaging was assessed between 4 and 6 months after the index procedure. Results There were no significant differences in final infarct size (6.1 g/m2 vs 6.3 g/m2, p = 0.78) and left ventricular ejection fraction (50% vs 50%, p = 0.46) between both groups. Also, systolic wall thickening in the infarct area (44% vs 45%, p = 0.93) or the extent of transmural segments (8.3% of segments vs 8.3% of segments, p = 0.60) showed no significant differences. The incidence of major adverse cardiac and cerebral events at 6 months was similar in the Proxis and control group (8% vs 10%, respectively, p = 0.43). Conclusions Primary PCI with combined proximal embolic protection and thrombus aspiration in STEMI patients did not result in significant differences in final infarct size or left ventricular function at follow-up CMR. In addition, there was no difference in the incidence of major adverse cardiac and cerebral events at 6 months. Trial registration number ISRCTN71104460.

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.

Pressure-controlled intermittent coronary sinus occlusion (PICSO) in acute ST-segment elevation myocardial infarction: Results of the Prepare RAMSES safety and feasibility study

AIMS Pressure-controlled intermittent coronary sinus occlusion (PICSO) may improve myocardial perfusion after pPCI. We evaluated the safety and feasibility of PICSO after pPCI for STEMI, and explored its effects on infarct size and myocardial function. METHODS AND RESULTS Thirty patients were enrolled following successful pPCI of a left anterior descending coronary artery culprit lesion for anterior STEMI, in whom PICSO for 90 minutes was attempted. Infarct size and myocardial function were assessed by cardiovascular magnetic resonance (CMR) at two to five days and four months post pPCI. An independent core laboratory selected matched historical control patients with CMR data for comparison. PICSO was initiated in 19 patients (63%), and could be maintained for 90 (±2) minutes in 12 patients (40%). Major adverse safety events occurred in one patient (3%). Comparing all PICSO-treated patients to matched controls demonstrated no significant differences in infarct size or myocardial recovery. However, infarct size reduction from two to five days to four months was greater for patients successfully treated with PICSO compared with matched controls (41.6±8.2% vs. 27.7±9.9%, respectively; p=0.04). CONCLUSIONS PICSO is safe in the setting of STEMI, although feasibility was limited. Administration of sufficient PICSO therapy may be associated with enhanced myocardial recovery during follow-up, warranting further evaluation of this novel therapy.

Clinical outcome after surgical or percutaneous revascularization in coronary bypass graft failure.

Aims To describe long-term outcome following surgical and percutaneous revascularization in graft failure. Methods We analyzed consecutive patients with graft failure after heart-team assignment to percutaneous coronary intervention (PCI) or redo coronary artery bypass grafting (CABG) between 2003 and 2008. The primary endpoint was the composite of death, myocardial infarction (MI) or target vessel revascularization (TVR). Kaplan–Meier event rate estimates were calculated up to a 5-year follow-up. Independent predictors for outcomes were identified by backward selection in a multivariable Cox proportional hazard model. Results We identified 287 patients treated for graft failure: 243 with PCI and 44 with redo CABG. Patients undergoing PCI more frequently presented with ST-elevated myocardial infarction (STEMI) (P < 0.001), multivessel disease (P < 0.001), vein graft failure (P = 0.04), a history of MI (P < 0.001) and shorter time-to-graft failure (P = 0.001). Bare-metal stents (BMS) were used in 81.3% of the PCI-treated lesions and drug-eluting stents (DES) in 18.7%. The median follow-up was 3.9 years. Five-year rate of composite all-cause death, MI or TVR was 57.6% after PCI and 51% after CABG (P = 0.51). Repeat revascularization [TVR and target lesion revascularization (TLR)] was 30.7 and 21.3% after PCI, and 8.0 and 3.2% following CABG (P = 0.009; P = 0.008). In the PCI group, BMS was associated with higher rates of TVR (35.1 vs. 12.6%; P = 0.04) and TLR (24.8 vs. 7.6%; P = 0.04), but similar rate of death or MI compared with DES. Independent predictors for the primary outcome were creatinine [hazard ratio 1.008 per &mgr;mol/l, 95% confidence interval (CI) 1.005–1.011, P < 0.001] and peak creatine kinase MB (hazard ratio 1.001 per U/l, 95% CI 1.000–1.002, P = 0.027). Conclusion Clinical outcomes are similarly poor after heart-team triage for surgical or percutaneous intervention in patients with graft failure. Repeat revascularization occurred more frequent after PCI, particularly following BMS implantation.

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.

Percutaneous coronary intervention for acute coronary syndrome due to graft failure: use of bare-metal and drug-eluting stents and subsequent long-term clinical outcome.

Objectives: To describe clinical outcome after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) due to graft failure. Background: Limited data are available on outcome after PCI for graft failure‐induced ACS in the drug‐eluting stent (DES) era. Methods: Patients were identified who underwent PCI either with DES or BMS for ACS due to graft failure between January 2003 and December 2008. Follow‐up was performed at 1 year and April 2011. The primary endpoint was the composite of death, myocardial infarction (MI), or target vessel revascularization (TVR). Kaplan–Meier estimates were calculated at 1 and 5‐year follow‐up. Predictors were identified by backward selection in Cox proportional hazards models. Results: A total of 92 patients underwent PCI, of which 77 were treated with bare metal stents (BMS) and 15 with DES. Patient and procedural characteristics were similar in both groups. Mean follow‐up was 3.2 years. Five‐year composite event rate was 65.9% after BMS vs. 43.4% after DES implantation (P = 0.17). Individual endpoints were comparable in both groups. Recurrence of angina, hospitalization, and repeat interventions were similar. After multivariable adjustment, the use of DES was not associated with a significant reduction in the primary endpoint (HR = 0.44, 0.18–1.04, p = 0.06). Conclusion: In patients presenting with ACS due to acute graft failure, long‐term outcomes remain poor. In a nonrandomized comparison with BMS, DES use was not associated with significant improved long‐term clinical outcomes.

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.