Importance of time to reperfusion on outcomes with primary coronary angioplasty for acute myocardial infarction (results from the Stent Primary Angioplasty in Myocardial Infarction Trial).

The mortality benefit of thrombolytic therapy for acute myocardial infarction (AMI) is strongly dependent on time to treatment. Recent observations suggest that time to treatment may be less important with primary percutaneous transluminal coronary angioplasty (PTCA). Patients with AMI of <12 hours duration, without cardiogenic shock, who were treated with primary PTCA from the Stent PAMI Trial (n = 1,232) were evaluated to assess the effect of time to reperfusion on outcomes. Thrombolysis In Myocardial Infarction grade 3 flow was achieved in a high proportion of patients regardless of time to treatment. Improvement in ejection fraction from baseline to 6 months was substantial with reperfusion at <2 hours but was modest and relatively independent of time to reperfusion after 2 hours (<2 hours, 12.3% vs > or =2 hours, 4.2%, p = 0.004). There were no differences in 1- or 6-month mortality by time to reperfusion (6-month mortality: <2 hours [5.5%], 2 to <4 hours [4.6%], 4 to <6 hours [4.5%], >6 hours [4.2%], p = 0.97). There were also no differences in other clinical outcomes by time to reperfusion, except that reinfarction and infarct artery reocclusion at 6 months were more frequent with later reperfusion. The lack of correlation between time to treatment and mortality in patients without cardiogenic shock suggests that the survival benefit of primary PTCA may be related principally to factors other than myocardial salvage. These data may also have implications regarding the triage of patients with AMI for primary PTCA.

Quality of life after balloon angioplasty or stenting for acute myocardial infarction. One-year results from the Stent-PAMI trial.

OBJECTIVES: The goal of this study was to compare the impact of primary stenting or percutaneous transluminal coronary angioplasty (PTCA) on health-related quality of life (HRQOL) in patients undergoing direct angioplasty for acute myocardial infarction (AMI). BACKGROUND: Previous studies have demonstrated that coronary stenting reduces clinical and angiographic restenosis compared with PTCA. However, the impact of stenting on HRQOL from the patient's perspective remains unknown. METHODS: We administered the Seattle Angina Questionnaire and the Medical Outcomes Study Short-form Survey at 1, 6 and 12 months after initial treatment to all North American patients in the Stent-Primary Angioplasty for Myocardial Infarction trial (Stent-PAMI) (n = 509)-a randomized trial comparing primary stenting to conventional PTCA for patients with AMI. RESULTS: At one month, most HRQOL measures were similar for the two groups, but stent patients reported less bodily pain than PTCA patients (p = 0.03). At six-month follow-up, stenting resulted in significant improvements in several dimensions of HRQOL including reduced anginal frequency and bodily pain as well as improved disease perception (all p < or = 0.03) and a trend towards better anginal stability (p = 0.056). By 12-month follow-up, however, none of these differences remained statistically significant. These differences in HRQOL were largely explained by the greater need for ischemia-driven target-vessel repeat revascularization procedures in PTCA patients during the first six months (16.0% vs. 6.2%, p < 0.001). CONCLUSIONS: In patients undergoing revascularization for AMI, initial stent placement is associated with improvements in several dimensions of health status during the first six months of follow-up. In the absence of differences in mortality, these findings add to the overall argument in favor of initial stenting in patients treated with mechanical reperfusion for myocardial infarction.

Normal flow (TIMI-3) before mechanical reperfusion therapy is an independent determinant of survival in acute myocardial infarction: analysis from the primary angioplasty in myocardial infarction trials.

BACKGROUND: Whereas survival after lytic therapy for myocardial infarction is strongly dependent on early administration, it is unknown whether the otherwise excellent outcomes in patients undergoing primary PTCA for acute myocardial infarction, in whom TIMI-3 flow rates of >90% may be achieved, can be further improved by early reperfusion. METHODS AND RESULTS: Among 2507 patients enrolled in 4 PAMI trials undergoing primary PTCA, spontaneous reperfusion (TIMI-3 flow) was present in 16% at initial angiography. Compared with patients without TIMI-3 flow, those with TIMI-3 flow before PTCA had greater left ventricular ejection fraction (57+/-10% versus 53+/-11%, P=0.003) and were less likely to present in heart failure (7.0% versus 11.6%, P=0.009). Patients with initial TIMI-3 flow had significantly lower in-hospital rates of mortality, new-onset heart failure, and hypotension and had a shorter hospital stay. Cumulative 6-month mortality was 0.5% in patients with initial TIMI-3 flow, 2.8% with TIMI-2 flow, and 4.4% with initial TIMI-0/1 flow (P=0.009). By multivariate analysis, TIMI-3 flow before PTCA was an independent determinant of survival (odds ratio 2.1, P=0.04), even when corrected for by postprocedural TIMI-3 flow. CONCLUSIONS: Patients undergoing primary PTCA in whom TIMI-3 flow is present before angioplasty present with greater clinical and angiographic evidence of myocardial salvage, are less likely to develop complications related to left ventricular failure, and have improved early and late survival. These data warrant prospective randomized trials of pharmacological strategies to promote early reperfusion before definitive mechanical intervention in acute myocardial infarction.

Initial experience with multivessel percutaneous coronary intervention during mechanical reperfusion for acute myocardial infarction.

The feasibility and safety of simultaneous multivessel percutaneous coronary intervention during mechanical reperfusion for acute myocardial infarction was analyzed in a retrospective, case-controlled study. Patients who underwent multivessel coronary intervention had a higher risk of adverse clinical outcomes through 6 months compared with matched controls in whom coronary intervention was limited to the infarct-related artery.

Benefit of coronary reperfusion before intervention on outcomes after primary angioplasty for acute myocardial infarction.

Primary percutaneous transluminal coronary angioplasty has become the preferred reperfusion strategy for acute myocardial infarction in most institutions with interventional facilities and experienced operators. The benefit of establishing coronary reperfusion, with or without pharmacologic therapy, before primary angioplasty has not been established. Consecutive patients (n = 1,490) with acute myocardial infarction treated with aspirin and heparin followed by primary percutaneous transluminal coronary angioplasty were followed for 13 years. Follow-up angiography was obtained in 737 patients at 7.7 months. Thrombolysis In Myocardial Infarction (TIMI) 2 to 3 flow in the infarct artery at initial angiography was present in 18.3% of patients, and TIMI 0 to 1 flow in 81.7% of patients. Baseline variables were similar between the 2 groups, except patients with initial TIMI 2 to 3 flow had significantly less cardiogenic shock (1.7% vs 9.4%, p <0.0001) and a lower incidence of depressed ejection fraction <40% (12.6% vs 19.9%, p = 0.007). Procedural success was better in patients with initial TIMI 2 to 3 flow (97.4% vs 93.8%, p = 0.02), and catheterization laboratory events were less frequent. Patients with initial TIMI 2 to 3 flow had lower peak creatine kinase values (1,328 vs 2,790 IU/L, p <0.0001), higher acute ejection fraction (54.3% vs 51.6%, p = 0.05), higher late ejection fraction (59.2% vs 54.9%, p = 0.004), and lower 30-day mortality (4.8% vs 8.9%, p = 0.02). These data indicate that when reperfusion occurs before primary angioplasty, outcomes are strikingly better with less cardiogenic shock, improved procedural outcomes, smaller infarct size, better preservation of left ventricular function, and reduced mortality. This should encourage new strategies to establish reperfusion before "primary" angioplasty with "catheterization laboratory friendly" platelet inhibitors and/or low-dose thrombolytic drugs.

Angiographic and clinical characteristics associated with increased in-hospital mortality in elderly patients with acute myocardial infarction undergoing percutaneous intervention (a pooled analysis of the primary angioplasty in myocardial infarction trials).

Advanced age is associated with increased mortality in acute myocardial infarction (AMI) but the mechanism remains unclear. We performed a pooled analysis of 3,032 patients from the Primary Angioplasty in Myocardial Infarction (PAMI)-2, Stent-PAMI, and PAMI-No Surgery On Site trials to determine which clinical, hemodynamic, and angiographic characteristics in the elderly were associated with in-hospital death. There were 452 patients aged >/=75 years and 2,580 patients aged <75 years. Older patients had a lower number of risk factors for coronary artery disease but more comorbidities. Acute catheterization demonstrated more 3-vessel disease, higher left ventricular (LV) end-diastolic pressure, lower LV ejection fraction, and higher initial rates of Thrombolysis In Myocardial Infarction (TIMI) trial 2 or 3 flow. Elderly patients were equally likely to undergo percutaneous intervention but had a lower procedural success rate and lower rates of final TIMI 3 flow, and older patients were more likely to have post-AMI complications. In-hospital mortality was 10.2% and 1.8%, respectively (p = 0.001). Cardiac and noncardiac mortality was higher in elderly patients, and no significant differences in causes of death were identified. Multivariate analysis revealed that the strongest predictors of death were age >/=75 years, lower LV ejection fraction, lower final TIMI flow, higher Killip class, need for an intra-aortic balloon pump (IABP), and post-AMI stroke/transient ischemic attack, or significant arrhythmia. Despite avoiding thrombolysis, elderly patients remain at increased risk of bleeding, stroke, and other post-AMI complications, and death. Cardiac risk factor analysis and acute catheterization offer prognostic information but do not completely explain the mechanism of increased in-hospital mortality in the elderly.

Role of cardiac surgery in the hospital phase management of patients treated with primary angioplasty for acute myocardial infarction.

Although cardiac surgery is performed in approximately 10% of acute myocardial infarction (AMI) patients undergoing a primary percutaneous transluminal coronary angioplasty (PTCA) reperfusion strategy before discharge, the indications for and timing of operative revascularization, and the short- and long-term outcomes after surgery have not been characterized. In the prospective, controlled Primary Angioplasty in Myocardial Infarction-2 trial, cardiac catheterization was performed in 1,100 patients within 12 hours of onset of AMI at 34 centers, followed by primary PTCA when appropriate. Cardiac surgery was performed before hospital discharge in 120 patients (10.9%), electively in 42.6%, and on an urgent or emergent basis in 57.4%. Surgery was performed in 6.1% of 982 patients after primary PTCA (although emergently for failed PTCA in only 4 cases [0.4%]), and in 53 of 118 patients (44.9%) not undergoing primary PTCA. Patients requiring surgery were older, and more frequently had diabetes and 3-vessel disease than those managed nonoperatively. Internal mammary artery grafts were placed in only 31% of patients. In-hospital mortality was 6.4% in patients undergoing urgent/emergent surgery, 2.0% after elective surgery, and 2.6% in patients not undergoing surgery (p = NS). After multivariate correction for baseline risk factors, early and late survival free of reinfarction were similar in patients undergoing versus not undergoing in-hospital cardiac surgery. Thus, the appropriate use of coronary artery bypass graft surgery in the peri-infarction period is an integral component of the primary PTCA approach, and is frequently used to optimize the prognosis of a high-risk AMI cohort with unfavorable baseline features. The implications for the performance of primary PTCA in AMI at centers without on-site surgical facilities are discussed.

Influence of vessel size on early and late outcomes after primary angioplasty for acute myocardial infarction.

Small vessel size is associated with worse outcomes after elective angioplasty, but the effect of vessel size on outcomes after primary angioplasty for acute myocardial infarction has not been studied. We evaluated outcomes in 1,490 consecutive patients treated with primary angioplasty comparing patients with small (< 3.0 mm) versus large ( 3.0 mm) vessels. Outcomes were worse in patients with small vessels with lower procedural success rates (92% versus 96%; p = 0. 002), higher rates of reinfarction (5.5% vs. 3.4%; p = 0.07), more late reocclusion (12.5% vs. 4.1%; p = 0.002), less improvement in ejection fraction (1.8% vs. 4.2%; p = 0.04), lower follow-up ejection fraction (53.7% vs. 56.5%; p = 0.03), and higher 30-day and late mortality (12.5% vs. 6.4%; p = 0.0002). The higher mortality can be explained by a higher baseline risk profile combined with worse procedural results and higher rates of reocclusion and reinfarction. These data stress the importance of developing new strategies to improve procedural and late outcomes after primary angioplasty in patients with small vessels.

Clinical and angiographic outcomes in patients with previous coronary artery bypass graft surgery treated with primary balloon angioplasty for acute myocardial infarction. Second Primary Angioplasty in Myocardial Infarction Trial (PAMI-2) Investigators.

OBJECTIVES: We sought to characterize the presenting characteristics of patients with previous coronary artery bypass graft surgery (CABG) and acute myocardial infarction (AMI) and to determine the angiographic success rate and clinical outcomes of a primary percutaneous transluminal coronary angioplasty (PTCA) strategy. BACKGROUND: Patients who have had previous CABG and AMI comprise a high risk group with decreased reperfusion success and increased mortality after thrombolytic therapy. Little is known about the efficacy of primary PTCA in AMI. METHODS: Early cardiac catheterization was performed in 1,100 patients within 12 h of onset of AMI at 34 centers in the prospective, controlled Second Primary Angioplasty in Myocardial Infarction trial (PAMI-2), followed by primary PTCA when appropriate. Data were collected by independent study monitors, end points were adjudicated and films were read at an independent core laboratory. RESULTS: Of 1,100 patients with AMI, 58 (5.3%) had undergone previous CABG. The infarct-related vessel in these patients was a bypass graft in 32 patients (55%) and a native coronary artery in 26 patients. Compared with patients without previous CABG, patients with previous CABG were older and more frequently had a previous myocardial infarction and triple-vessel disease. Coronary angioplasty was less likely to be performed when the infarct-related vessel was a bypass graft rather than a native coronary artery (71.9% vs. 89.8%, p = 0.001); Thrombolysis in Myocardial Infarction trial (TIMI) flow grade 3 was less frequently achieved (70.2% vs. 94.3%, p < 0.0001); and in-hospital mortality was increased (9.4% vs. 2.6%, p = 0.02). As a result, mortality at six months was 14.3% versus 4.1% in patients with versus without previous CABG (p = 0.001). By multivariate analysis, independent determinants of late mortality in the entire study group were advanced age, triple-vessel disease, Killip class and post-PTCA TIMI flow grade <3. CONCLUSIONS: Reperfusion success of a primary PTCA strategy in patients with previous CABG, although favorable with respect to historic control studies, is reduced as compared with that in patients without previous CABG. New approaches are required to treat patients with previous CABG and AMI, especially when the infarct-related vessel is a diseased saphenous vein graft.

Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent Primary Angioplasty in Myocardial Infarction Study Group.

BACKGROUND: Coronary-stent implantation is frequently performed for treatment of acute myocardial infarction. However, few studies have compared stent implantation with primary angioplasty alone. METHODS: We designed a multicenter study to compare primary angioplasty with angioplasty accompanied by implantation of a heparin-coated Palmaz-Schatz stent. Patients with acute myocardial infarction underwent emergency catheterization and angioplasty. Those with vessels suitable for stenting were randomly assigned to undergo angioplasty with stenting (452 patients) or angioplasty alone (448 patients). RESULTS: The mean (+/-SD) minimal luminal diameter was larger after stenting than after angioplasty alone (2.56+/-0.44 mm vs. 2.12+/-0.45 mm, P<0.001), although fewer patients assigned to stenting had grade 3 blood flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) (89.4 percent, vs. 92.7 percent in the angioplasty group; P=0.10). After six months, fewer patients in the stent group than in the angioplasty group had angina (11.3 percent vs. 16.9 percent, P=0.02) or needed target-vessel revascularization because of ischemia (7.7 percent vs. 17.0 percent, P<0.001). In addition, the combined primary end point of death, reinfarction, disabling stroke, or target-vessel revascularization because of ischemia occurred in fewer patients in the stent group than in the angioplasty group (12.6 percent vs. 20.1 percent, P<0.01). The decrease in the combined end point was due entirely to the decreased need for target-vessel revascularization. The six-month mortality rates were 4.2 percent in the stent group and 2.7 percent in the angioplasty group (P=0.27). Angiographic follow-up at 6.5 months demonstrated a lower incidence of restenosis in the stent group than in the angioplasty group (20.3 percent vs. 33.5 percent, P<0.001). CONCLUSIONS: In patients with acute myocardial infarction, routine implantation of a stent has clinical benefits beyond those of primary coronary angioplasty alone.

Intra-aortic balloon counterpulsation before primary percutaneous transluminal coronary angioplasty reduces catheterization laboratory events in high-risk patients with acute myocardial infarction.

The benefit of intra-aortic balloon counterpulsation (IABC) before primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction in high-risk patients has not been well documented. Consecutive patients (n = 1,490) with acute myocardial infarction treated with primary PTCA from 1984 to 1997 were prospectively enrolled in an ongoing registry. Catheterization laboratory events occurred during or after intervention in 88 patients (5.9%), including ventricular fibrillation in 59 patients (4.0%), cardiopulmonary arrest in 46 patients (3.1%), and prolonged hypotension in 33 patients (2.2%). Cardiogenic shock was the strongest predictor of catheterization laboratory events (odds ratio [OR] 2.18, 95% confidence intervals [CI] 1.58 to 3.02) followed by low ejection fraction (<30%) (OR 1.51, 95% CI 1.06 to 2.15) and congestive heart failure (CHF) (OR 1.45, 95% CI 1.01 to 2.07). IABC used before intervention was associated with fewer catheterization laboratory events in patients with cardiogenic shock (n = 1 19) (14.5% vs. 35.1%, p = 0.009), in patients with CHF or low ejection fraction (n = 119) (0% vs. 14.6%, p = 0.10), and in all high-risk patients combined (n = 238) (1 1.5% vs. 21.9%, p = 0.05). IABC was a significant independent predictor of freedom from catheterization laboratory events (OR 0.48, 95% CI 0.29 to 0.79). These data support the use of IABC before primary PTCA for acute myocardial infarction in all patients with cardiogenic shock, and suggest that prophylactic IABC may also be beneficial in patients with CHF or depressed left ventricular function.

Clinical and angiographic follow-Up after primary stenting in acute myocardial infarction: the Primary Angioplasty in Myocardial Infarction (PAMI) stent pilot trial.

BACKGROUND: Restenosis has been reported in as many as 50% of patients within 6 months after PTCA in acute myocardial infarction (AMI), which necessitates repeat target-vessel revascularization (TVR) in approximately 20% of patients during this time period. Routine (primary) stent implantation after PTCA has the potential to further improve late outcomes. METHODS AND RESULTS: Primary stenting was performed as part of a prospective study in 236 consecutive patients without contraindications who presented with AMI of <12 hours' duration at 9 international centers. A mean of 1.4+/-0.7 stents were implanted per patient (97% Palmaz-Schatz) at 17.3+/-2.4 atm. During a clinical follow-up period of 7.4+/-2.6 months, death occurred in 4 patients (1.7%), reinfarction occurred in 5 patients (2.1%), and TVR was required in 26 patients (11.1%). By Cox regression analysis, small reference-vessel diameter and the number of stents implanted were the strongest determinants of TVR. Angiographic restenosis occurred in 27.5% of lesions. By multiple logistic regression analysis, the number of stents implanted and the absence of thrombus on the baseline angiogram were independent determinants of binary restenosis. CONCLUSIONS: A strategy of routine stent implantation during mechanical reperfusion of AMI is safe and is associated with favorable event-free survival and low rates of restenosis compared with primary PTCA alone.

Importance of time to reperfusion for 30-day and late survival and recovery of left ventricular function after primary angioplasty for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the importance of time to reperfusion for outcomes after primary angioplasty for acute myocardial infarction. BACKGROUND: Survival benefit of thrombolytic therapy for acute myocardial infarction is strongly dependent on time to treatment. Recent observations suggest that time to treatment may be less important for survival with primary angioplasty. METHODS: Consecutive patients (n=1,352) with acute myocardial infarction treated with primary angioplasty were followed for up to 13 years. Paired acute and follow-up ejection fraction data were obtained at cardiac catheterization in 606 patients. RESULTS: Reperfusion was achieved within 2 h in 164 patients (12%). Thirty-day mortality was lowest with early reperfusion (4.3% at <2 h vs. 9.2% at > or = 2 h, p=0.04) and was relatively independent of time to reperfusion after 2 h (9.0% at 2 to 4 h, 9.3% at 4 to 6 h, 9.5% at >6 h). Thirty-day-plus late cardiac mortality was also lowest with early reperfusion (9.1% at <2 h vs. 16.3% at > or = 2 h, p=0.02) and relatively independent at time to reperfusion after 2 h (16.4% at 2 to 4 h, 16.9% at 4 to 6 h, 15.6% at >6 h). Improvement in left ventricular ejection fraction was greatest in the early reperfusion group and relatively modest after 2 h (6.9% at <2 h vs. 3.1% at > or =2 h, p=0.007). CONCLUSIONS: Time to reperfusion, up to 2 h, is important for survival and recovery of left ventricular function. After 2 h, recovery of left ventricular function is modest and survival is relatively independent of time to reperfusion. These data suggest that factors other than myocardial salvage may be responsible for survival benefit in patients treated with primary angioplasty after 2 h.

Prospective, multicenter study of the safety and feasibility of primary stenting in acute myocardial infarction: in-hospital and 30-day results of the PAMI stent pilot trial. Primary Angioplasty in Myocardial Infarction Stent Pilot Trial Investigators.

OBJECTIVES: The goals of this study were to examine the safety and feasibility of a routine (primary) stent strategy in acute myocardial infarction (AMI). BACKGROUND: Limitations of reperfusion by primary percutaneous transluminal coronary angioplasty (PTCA) in AMI include in-hospital recurrent ischemia or reinfarction in 10% to 15% of patients, restenosis in 37% to 49% and late infarct-related artery reocclusion in 9% to 14%. By lowering the residual stenosis and sealing dissection planes created by PTCA, primary stenting may further improve short- and long-term outcomes after mechanical reperfusion. METHODS: Three hundred twelve consecutive patients treated with primary PTCA for AMI at nine international centers were prospectively enrolled. After PTCA, stenting was attempted in all eligible lesions (vessel size 3.0 to 4.0 mm; lesion length < or = 2 stents; and the absence of giant thrombus burden after PTCA, major side branch jeopardy or excessive proximal tortuosity or calcification). Patients with stents were treated with aspirin, ticlopidine and a 60-h tapering heparin regimen. RESULTS: Stenting was attempted in 240 (77%) of 312 patients, successfully in 236 (98%), with Thrombolysis in Myocardial Infarction grade 3 flow restored in 230 patients (96%). Patients with stents had low rates of in-hospital death (0.8%), reinfarction (1.7%), recurrent ischemia (3.8%) and predischarge target vessel revascularization for ischemia (1.3%). At 30-day follow-up, no additional deaths or reinfarctions occurred among patients with stents, and target vessel revascularization was required in only one additional patient (0.4%). CONCLUSIONS: Primary stenting is safe and feasible in the majority of patients with AMI and results in excellent short-term outcomes.