Harry Suryapranata

Angiographic Assessment of Myocardial Reperfusion in Patients Treated With Primary Angioplasty for Acute Myocardial Infarction Myocardial Blush Grade

BACKGROUND The primary objective of reperfusion therapies for acute myocardial infarction is not only restoration of blood flow in the epicardial coronary artery but also complete and sustained reperfusion of the infarcted part of the myocardium. METHODS AND RESULTS We studied 777 patients who underwent primary coronary angioplasty during a 6-year period and investigated the value of angiographic evidence of myocardial reperfusion (myocardial blush grade) in relation to the extent of ST-segment elevation resolution, enzymatic infarct size, left ventricular function, and long-term mortality. The myocardial blush immediately after the angioplasty procedure was graded by two experienced investigators, who were otherwise blinded to all clinical data: 0, no myocardial blush; 1, minimal myocardial blush; 2, moderate myocardial blush; and 3, normal myocardial blush. The myocardial blush was related to the extent of the early ST-segment elevation resolution on the 12-lead ECG. Patients with blush grades 3, 2, and 0/1 had enzymatic infarct sizes of 757, 1143, and 1623 (P<0.0001), respectively, and ejection fractions of 50%, 46%, and 39%, respectively (P<0.0001). After a mean+/-SD follow-up of 1.9+/-1.7 years, mortality rates of patients with myocardial blush grades 3, 2, and 0/1 were 3%, 6%, and 23% (P<0.0001), respectively. Multivariate analysis showed that the myocardial blush grade was a predictor of long-term mortality, independent of Killip class, Thrombolysis In Myocardial Infarction grade flow, left ventricular ejection fraction (LVEF), and other clinical variables. CONCLUSIONS In patients after reperfusion therapy, the myocardial blush grade as seen on the coronary angiogram can be used to describe the effectiveness of myocardial reperfusion and is an independent predictor of long-term mortality.

Time Delay to Treatment and Mortality in Primary Angioplasty for Acute Myocardial Infarction Every Minute of Delay Counts

Background—Although the relationship between mortality and time delay to treatment has been demonstrated in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by thrombolysis, the impact of time delay on prognosis in patients undergoing primary angioplasty has yet to be clarified. The aim of this report was to address the relationship between time to treatment and mortality as a continuous function and to estimate the risk of mortality for each 30-minute delay. Methods and Results—The study population consisted of 1791 patients with STEMI treated by primary angioplasty. The relationship between ischemic time and 1-year mortality was assessed as a continuous function and plotted with a quadratic regression model. The Cox proportional hazards regression model was used to calculate relative risks (for each 30 minutes of delay), adjusted for baseline characteristics related to ischemic time. Variables related to time to treatment were age >70 years (P <0.0001), female gender (P =0.004), presence of diabetes mellitus (P =0.002), and previous revascularization (P =0.035). Patients with successful reperfusion had a significantly shorter ischemic time (P =0.006). A total of 103 patients (5.8%) had died at 1-year follow-up. After adjustment for age, gender, diabetes, and previous revascularization, each 30 minutes of delay was associated with a relative risk for 1-year mortality of 1.075 (95% CI 1.008 to 1.15; P =0.041). Conclusions—These results suggest that every minute of delay in primary angioplasty for STEMI affects 1-year mortality, even after adjustment for baseline characteristics. Therefore, all efforts should be made to shorten the total ischemic time, not only for thrombolytic therapy but also for primary angioplasty.

Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.

BACKGROUND The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre. METHODS We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297. FINDINGS 936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36). INTERPRETATION Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.

Symptom-onset-to-balloon time and mortality in patients with acute myocardial infarction treated by primary angioplasty

OBJECTIVES The aim of the study was to evaluate the relationship between symptom-onset-to-balloon time and one-year mortality in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary angioplasty. BACKGROUND Despite the prognostic implications demonstrated in patients with STEMI treated with thrombolysis, the impact of time-delay on prognosis in patients undergoing primary angioplasty has yet to be established. METHODS Our study population consisted of 1,791 patients with STEMI treated by primary angioplasty from 1994 to 2001. All clinical, angiographic and follow-up data were collected. Subanalyses were conducted according to patient risk profile at presentation and preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow. RESULTS A total of 103 patients (5.8%) had died at one year. Symptom-onset-to-balloon time was significantly associated with the rate of postprocedural TIMI 3 flow (p = 0.012), myocardial blush grade (p = 0.033), and one-year mortality (p = 0.02). A stronger linear association between symptom-onset-to-balloon time and one-year mortality was observed in non-low-risk patients (p = 0.006) and those with preprocedural TIMI flow 0 to 1 (p = 0.013). No relationship was found between door-to-balloon time and mortality. At multivariate analysis, a symptom-onset-to-balloon time >4 h was identified as an independent predictor of one-year mortality (p < 0.05). CONCLUSIONS This study shows that, in patients with STEMI treated by primary angioplasty, symptom-onset-to-balloon time, but not door-to-balloon time, is related to mortality, particularly in non-low-risk patients and in the absence of preprocedural anterograde flow. Furthermore, a symptom-onset-to-balloon time >4 h was identified as independent predictor of one-year mortality.

Randomized Comparison of Coronary Stenting With Balloon Angioplasty in Selected Patients With Acute Myocardial Infarction

BACKGROUND Although the benefits of primary angioplasty in acute myocardial infarction have been demonstrated, several areas for improvement remain. Therefore, a prospective randomized trial comparing primary stenting with balloon angioplasty in patients with acute myocardial infarction was conducted. METHODS AND RESULTS Patients with acute myocardial infarction were randomly assigned to undergo either primary stenting (n=112) or balloon angioplasty (n=115). The clinical end points were death, recurrent infarction, subsequent bypass surgery, or repeat angioplasty of the infarct-related vessel. The overall mortality rate at 6 months was 2%. Recurrent infarction occurred in 8 patients (7%) after balloon angioplasty and in 1 (1%) after stenting (P=0.036). Subsequent target-vessel revascularization was necessary in 19 (17%) and 4 (4%) patients, respectively (P=0.0016). The cardiac event-free survival rate in the stent group was significantly higher than in the balloon angioplasty group (95% versus 80%; P=0.012). CONCLUSIONS In selected patients with acute myocardial infarction, primary stenting can be applied safely and effectively, resulting in a lower incidence of recurrent infarction and a significant reduction in the need for subsequent target-vessel revascularization compared with balloon angioplasty.

Angiographic Assessment of Reperfusion in Acute Myocardial Infarction by Myocardial Blush Grade

Background—Angiographic successful reperfusion in acute myocardial infarction has been defined as TIMI 3 flow. However, TIMI 3 flow does not always result in effective myocardial reperfusion. Myocardial blush grade (MBG) is an angiographic measure of myocardial perfusion. We hypothesized that optimal angiographic reperfusion is defined by TIMI 3 flow and MBG 2 or 3. Methods and Results—In 924 consecutive patients with TIMI 3 flow after angioplasty for acute myocardial infarction, we prospectively studied the value of MBG. End points were death, MACE, enzymatic infarct size, and residual left ventricular ejection fraction. Follow-up was 16±11 months. Of the 924 patients, 101 (11%) patients had MBG 0 or 1. Mortality was significantly higher in patients with MBG 0 or 1 compared with patients with MBG 2 or 3 (relative risk, 4.7; 95% CI, 2.3 to 9.5;P <0.001). The combined incidence of MACE was higher in patients with MBG 0 or 1 compared with patients with MBG 2 or 3 (relative risk, 1.8; 95% CI, 1.1 to 2.8;P =0.009). Enzymatic infarct size was larger (1437±2388 versus 809±1672, P =0.001) and left ventricular ejection fraction was lower (37.7±10.6 versus 43.8±11.1, P <0.001) in patients with MBG 0 or 1 compared with patients with MBG 2 or 3. Conclusions—MBG is a strong angiographic predictor of mortality in patients with TIMI 3 flow after primary angioplasty. Enzymatic infarct size is larger and residual left ventricular ejection fraction is lower in patients with MBG 0 or 1 compared with MBG 2 or 3. Angiographic definition of successful reperfusion should include both TIMI 3 flow as well as MBG 2 or 3.

The Na+/H+exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction: Results of the evaluation of the safety and cardioprotective effects of eniporide in acute myocardial infarction (ESCAMI) trial

OBJECTIVES We conducted an international, prospective, randomized, double-blind, placebo-controlled phase 2 trial in patients undergoing thrombolytic therapy or primary angioplasty for acute ST-elevation myocardial infarction (MI) to investigate the effect of eniporide on infarct size and clinical outcome. BACKGROUND Experimental studies suggest that the activity of the Na(+)/H(+) exchange (NHE) plays an important role in the unfavorable sequels of myocardial ischemia and reperfusion. Eniporide specifically inhibits the NHE-1 isoform and has been shown to limit infarct size in experimental models. METHODS The primary efficacy end point was the infarct size measured by the cumulative release of alpha-hydroxybutyrate dehydrogenase (alpha-HDBH) (area under the curve [AUC] 0 to 72 h). In stage 1, 50, 100, 150 or 200 mg eniporide given as a 10-min infusion before start of reperfusion therapy were compared with placebo in 430 patients, and in stage 2, 100 and 150 mg eniporide were compared with placebo in 959 patients. RESULTS In stage 1, the administration of 100 mg and 150 mg eniporide resulted in smaller infarct sizes (mean alpha-HBDH AUC in U/ml x h, placebo: 44.2, 100 mg eniporide: 40.2, 150 mg eniporide: 33.9), especially in the angioplasty group. In contrast, in stage 2 there was no difference in the enzymatic infarct size between the three groups (placebo: 41.2, 100 mg eniporide: 43.0, 150 mg eniporide: 41.5). Overall there was no effect of eniporide on clinical outcome (death, cardiogenic shock, heart failure, life-threatening arrhythmias). However, there was a significant reduction of the incidence of heart failure in patients reperfused late (>4 h). CONCLUSIONS In this large study administration of the NHE-1 inhibitor eniporide, before reperfusion therapy in patients with acute ST elevation MI, did not limit infarct size or improve clinical outcome.

Reperfusion therapy in elderly patients with acute myocardial infarction: A randomized comparison of primary angioplasty and thrombolytic therapy

OBJECTIVES This study sought to determine the short- and long-term outcome of primary coronary angioplasty and thrombolytic therapy for acute myocardial infarction (AMI) in patients older than 75 years of age. BACKGROUND The benefit of reperfusion therapy in elderly patients with AMI is uncertain, although elderly people account for a large proportion of deaths. METHODS We randomly assigned a total of 87 patients with an AMI who were older than 75 years to treatment with angioplasty or intravenous (IV) streptokinase. Clinical outcome was measured by taking the end points of death and the combination of death, reinfarction or stroke during follow-up. RESULTS The primary end point, a composite of death, reinfarction or stroke, at 30 days had occurred in 4 (9%) patients in the angioplasty group as compared with 12 (29%) in the thrombolysis group (p = 0.01, relative risk [RR]: 4.3, 95% confidence interval [CI]: 1.2 to 20.0). At one year the corresponding figures were 6 (13%) and 18 (44%), respectively (p = 0.001, RR: 5.2, 95% CI: 1.7 to 18.1). CONCLUSIONS In this series of patients with AMI who were older than 75 years, primary coronary angioplasty had a significant clinical benefit when compared with IV streptokinase therapy.

Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction ☆: The glucose-insulin-potassium study: a randomized trial

OBJECTIVES In this study we considered the question of whether adjunction of glucose-insulin-potassium (GIK) infusion to primary coronary transluminal angioplasty (PTCA) is effective in patients with an acute myocardial infarction (MI). BACKGROUND A combined treatment of early and sustained reperfusion of the infarct-related coronary artery and the metabolic modulation with GIK infusion has been proposed to protect the ischemic myocardium. METHODS From April 1998 to September 2001, 940 patients with an acute MI and eligible for PTCA were randomly assigned, by open-label, to either a continuous GIK infusion for 8 to 12 h or no infusion. RESULTS The 30-day mortality was 23 of 476 patients (4.8%) receiving GIK compared with 27 of 464 patients (5.8%) in the control group (relative risk [RR] 0.82, 95% confidence interval [CI] 0.46 to 1.46). In 856 patients (91.1%) without signs of heart failure (HF) (Killip class 1), 30-day mortality was 5 of 426 patients (1.2%) in the GIK group versus 18 of 430 patients (4.2%) in the control group (RR 0.28, 95% CI 0.1 to 0.75). In 84 patients (8.9%) with signs of HF (Killip class > or =2), 30-day mortality was 18 of 50 patients (36%) in the GIK group versus 9 of 34 patients (26.5%) in the control group (RR 1.44, 95% CI 0.65 to 3.22). CONCLUSIONS Glucose-insulin-potassium infusion as adjunctive therapy to PTCA in acute MI did not result in a significant mortality reduction in all patients. In the subgroup of 856 patients without signs of HF, a significant reduction was seen. The effect of GIK infusion in patients with signs of HF (Killip class > or =2) at admission is uncertain.

The effect of completeness of revascularization on event-free survival at one year in the arts trial ☆

OBJECTIVES We sought to assess the relationship between completeness of revascularization and adverse events at one year in the ARTS (Arterial Revascularization Therapies Study) trial. BACKGROUND There is uncertainty to what extent degree of completeness of revascularization, using up-to-date techniques, influences medium-term outcome. METHODS After consensus between surgeon and cardiologist regarding the potential for equivalence in the completeness of revascularization, 1,205 patients with multivessel disease were randomly assigned to either bypass surgery or stent implantation. All baseline and procedural angiograms and surgical case-record forms were centrally assessed for completeness of revascularization. RESULTS Of 1,205 patients randomized, 1,172 underwent the assigned treatment. Complete data for review were available in 1,143 patients (97.5%). Complete revascularization was achieved in 84.1% of the surgically treated patients and 70.5% of the angioplasty patients (p < 0.001). After one year, the stented angioplasty patients with incomplete revascularization showed a significantly lower event-free survival than stented patients with complete revascularization (i.e., freedom from death, myocardial infarction, cerebrovascular accident and repeat revascularization) (69.4% vs. 76.6%; p < 0.05). This difference was due to a higher incidence of subsequent bypass procedures (10.0% vs. 2.0%; p < 0.05). Conversely, at one year, bypass surgery patients with incomplete revascularization showed only a marginally lower event-free survival rate than those with complete revascularization (87.8% vs. 89.9%). CONCLUSIONS Complete revascularization was more frequently accomplished by bypass surgery than by stent implantation. One year after bypass, there was no significant difference in event-free survival between surgically treated patients with complete revascularization and those with incomplete revascularization, but patients randomized to stenting with incomplete revascularization had a greater need for subsequent bypass surgery.