Joost D.E. Haeck

Relation between the assessment of microvascular injury by cardiovascular magnetic resonance and coronary Doppler flow velocity measurements in patients with acute anterior wall myocardial infarction.

OBJECTIVES We studied the relation between presence and severity of microvascular obstruction (MO), measured by cardiovascular magnetic resonance (CMR) and intracoronary Doppler flow measurements, for assessment of myocardial reperfusion in patients with acute anterior myocardial infarction (MI) treated by primary percutaneous coronary intervention (PCI). BACKGROUND Cardiovascular magnetic resonance has been used to detect and quantify MO in patients after acute MI but has never been compared with coronary blood flow velocity patterns. METHODS Twenty-seven patients with first anterior ST-segment elevation MI successfully treated with primary PCI were included. Coronary blood flow velocity was measured during recatheterization 4 to 8 days after primary PCI. These measurements were related to MO determined by late gadolinium-enhanced (LGE) CMR performed the day before recatheterization. RESULTS Early systolic retrograde flow was observed in 0 of 8 patients without MO on LGE CMR and in 10 (53%) of 19 patients with MO (p = 0.01). The extent of MO correlated with the diastolic-systolic velocity ratio (r = 0.44; p = 0.02), diastolic deceleration time (r = -0.61; p = 0.001), diastolic deceleration rate (r = 0.75; p < 0.0001), and coronary flow velocity reserve of the infarct-related artery (r = -0.44; p = 0.02). Furthermore, multivariate regression analyses, including extent of MO, infarct size, and transmural necrosis on LGE CMR, revealed that extent of MO was the only independent factor related to early systolic retrograde flow and diastolic deceleration rate. CONCLUSIONS Assessment of microvascular injury by LGE CMR corresponds well to evaluation by intracoronary Doppler flow measurements. By means of CMR, quantification of myocardial function, infarct size, and microvascular injury can accurately be performed with a single noninvasive technique in patients with acute MI.

Randomized Comparison of Primary Percutaneous Coronary Intervention With Combined Proximal Embolic Protection and Thrombus Aspiration Versus Primary Percutaneous Coronary Intervention Alone in ST-Segment Elevation Myocardial Infarction: The PREPARE (PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-Elevation) Study

OBJECTIVES The purpose of this study was to evaluate the effectiveness of combined proximal embolic protection with thrombus aspiration (Proxis Embolic Protection System [St. Jude Medical, St. Paul, Minnesota]) in ST-segment elevation myocardial infarction patients. BACKGROUND Embolization during primary percutaneous coronary intervention (PCI) may result in microvascular obstruction, reduced myocardial perfusion, and impaired prognosis. METHODS Two hundred eight-four patients were randomized to primary PCI with the Proxis system versus primary PCI alone after angiography. The primary end point was the occurrence of complete (> or =70%) ST-segment resolution (STR) at 60 min measured by continuous ST-segment Holter. RESULTS There was no significant difference in the occurrence of the primary end point (80% vs. 72%, p = 0.14). However, immediate complete STR (at time of last contrast) occurred in 66% of Proxis-treated patients and 50% in control patients (absolute difference, 16.3%; 95% confidence interval: 4.3% to 28.2%; p = 0.009). A significant lower ST-segment curve area (0 to 3 h after primary PCI) was observed in the Proxis arm (5,192 microV/min vs. 6,250 microV/min, p = 0.037). Major adverse cardiac and cerebral events at 30 days occurred with similar frequency in both groups (6 vs. 10). CONCLUSIONS There was no significant difference in complete STR at 60 min in this proof-of-concept study. However, we observed a significant difference in immediate complete STR in Proxis-treated patients, better STR at later time points, and a reduction of electrocardiogram injury current over time, compared with control patients. The results suggest that primary PCI with the Proxis system may lead to better immediate microvascular flow in ST-segment elevation myocardial infarction patients. (The PREPARE Study; ISRCTN71104460).

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.

Feasibility and applicability of computer-assisted myocardial blush quantification after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction†

Objectives: The aim of the study was to evaluate whether the “Quantitative Blush Evaluator” (QuBE) score is associated with measures of myocardial reperfusion in patients with ST‐segment elevation myocardial infarction (STEMI) treated in two hospitals with 24/7 coronary intervention facilities. Background: QuBE is an open source computer program to quantify myocardial perfusion. Although QuBE has shown to be practical and feasible in the patients enrolled in the Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS), QuBE has not yet been verified on reperfusion outcomes of primary percutaneous coronary intervention (PCI) patients treated in other catheterization laboratories. Methods: Core lab adjudicated angiographic outcomes and QuBE values were assessed on angiograms of patients who were enrolled in the PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST‐Elevation (PREPARE) trial. ST‐segment resolution immediately after PCI measured by continuous ST Holter monitoring was calculated by a blinded core lab. Results: The QuBE score could be assessed on 229 of the 284 angiograms (81%) and was significantly associated with visually assessed myocardial blush grade (P < 0.0001). Patients with improved postprocedural Thrombolysis in Myocardial Infarction‐graded flow, myocardial blush grade, ST‐segment resolution immediately after PCI, or a small infarct size measured by peak CK‐MB had a significant better QuBE score. Conclusions: QuBE is feasible and applicable at angiograms of patients with STEMI recorded at other catheterization laboratories and is associated with measures of myocardial reperfusion.

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.

Recovery of Microcirculation After Intracoronary Infusion of Bone Marrow Mononuclear Cells or Peripheral Blood Mononuclear Cells in Patients Treated by Primary Percutaneous Coronary Intervention : The Doppler Substudy of the Hebe Trial

OBJECTIVES In the present substudy of the Hebe trial, we investigated the effect of intracoronary bone marrow mononuclear cell (BMMC) and peripheral blood mononuclear cell (PBMC) therapy on the recovery of microcirculation in patients with reperfused ST-segment elevation myocardial infarction (STEMI). BACKGROUND Several studies have suggested that cell therapy enhances neovascularization after STEMI. METHODS Paired Doppler flow measurements were available for 23 patients in the BMMC group, 18 in the PBMC group, and 19 in the control group. Coronary flow was assessed at 3 to 8 days after primary percutaneous coronary intervention (PCI) and repeated at 4-month follow-up, with intracoronary Doppler flow measurements. RESULTS At baseline, the coronary flow velocity reserve was reduced in the infarct-related artery and improved over 4 months in all 3 groups. The increase of coronary flow velocity reserve did not significantly differ between the 2 treatment groups and the control group (BMMC group: 2.0 ± 0.5 to 3.1 ± 0.7; PBMC group: 2.2 ± 0.6 to 3.2 ± 0.8; control group: 2.0 ± 0.5 to 3.4 ± 0.9). Additionally, the decrease in hyperemic microvascular resistance index from baseline to 4-month follow-up was not statistically different between the 2 treatment groups and the control group. CONCLUSIONS In STEMI patients treated with primary PCI in the Hebe trial, adjuvant therapy with BMMCs or PBMCs does not improve the recovery of microcirculation. Therefore, our data do not support the hypothesis of enhanced neovascularization after this mode of cell therapy. (Multicenter, randomised trial of intracoronary infusion of autologous mononuclear bone marrow cells or peripheral mononuclear blood cells after primary percutaneous coronary intervention [PCI]; ISRCTN95796863).

Early ST-segment recovery after primary percutaneous coronary intervention accurately predicts long-term prognosis after acute myocardial infarction

BACKGROUND Several ancillary studies reported on the prognostic value of ST-segment recovery (STR) with measurement at 30 to 240 minutes after primary percutaneous coronary intervention (PCI). We determined the long-term prognostic value of early STR, assessed at the end of primary PCI, in unselected patients after ST-segment elevation myocardial infarction (STEMI). METHODS We analyzed 12-lead electrocardiograms, recorded in the catheterization laboratory before arterial puncture and at the time of the end of PCI, from 2,124 STEMI patients who underwent primary PCI at our institution between 2000 and 2007. ST-segment recovery was categorized as complete (> or =70%), partial (30%-70%), or absent (<30%). Median follow-up was 4.1 years. RESULTS The estimated 5-year mortality was 8.3% in patients with complete STR, 14.4% in patients with partial STR, and 22.8% in patients with absent STR (P < .001). Multivariable-adjusted hazard ratios for 1-year death of patients with partial and absent STR, as compared with patients with complete STR, were 2.1 (95% CI 1.2-3.8, P = .014) and 3.2 (95% CI 1.8-5.8, P < .001), respectively. In a landmark analysis restricted to 1-year survivors, early STR was significantly predictive of 5-year mortality, even after multivariable adjustment. CONCLUSIONS Early STR assessment has strong, long-term prognostic properties in all-comer STEMI patients. Moreover, the prognostic power of early STR is not restricted to the early recovery phase after STEMI, but identifies high-risk subgroups among 1-year survivors.