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.

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.

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.

Timing and mechanism of death determined clinically after primary angioplasty for acute myocardial infarction.

We reviewed the timing and mechanism of death in 1,184 consecutive patients with acute myocardial infarction (AMI) treated with primary angioplasty from 1984 to 1995. Of 98 deaths, 48 (49%) occurred early on day 0 or 1. The mechanisms of death were pump failure in 60 patients (61%), reinfarction in 7 patients (7.1%), left ventricular rupture in 5 patients (5.1%), arrhythmia in 3 patients (3.1%), other cardiac causes in 5 patients (5.1%), stroke in 6 patients (6.1%), anoxic encephalopathy in 7 patients (7.1%), and procedure-related deaths in 5 patients (5.1%). The strongest predictors of mortality were cardiogenic shock and unsuccessful reperfusion. Our data indicate that mortality after primary angioplasty, like thrombolytic therapy, is highest in the early hours and is usually due to pump failure. In contrast to thrombolytic therapy, the incidence of death from myocardial rupture and bleeding complications is low. Future treatment strategies will need to focus on the large number of patients with early death due to pump failure, especially patients with cardiogenic shock.

Benefit of late coronary reperfusion in patients with acute myocardial infarction and persistent ischemic chest pain.

The benefit of thrombolytic therapy given late after the onset of acute myocardial infarction (AMI) has been controversial because of low reperfusion rates and limited myocardial salvage. Persistent chest pain has been used as a criteria for late intervention, but there is little documentation to validate this practice. Clinical outcomes and myocardial salvage were evaluated in 74 patients with AMI and persistent chest pain who underwent late reperfusion (> 6 hours) with direct coronary angioplasty, and these were compared with outcomes in 460 patients with early reperfusion (< or = 6 hours). Patients with late reperfusion had a high infarct artery patency rate (96%), a low hospital mortality rate (5.4%), and a low incidence of reinfarction (1.4%) and recurrent ischemia that were similar to patients with early reperfusion. Patients with late reperfusion had surprisingly good recovery of left ventricular function with improvement in ejection fraction from 50% to 60% at follow-up angiography. Patients with late reperfusion had a greater incidence of collateral flow (45% vs 22%, p < 0.001) and a lower value of peak creatine kinase (1,357 vs 2,057 U/liter, p < 0.001) than patients with early reperfusion. This study emphasizes the importance of persistent chest pain as a marker of continued myocardial viability in patients who present late after AMI. These data suggest that the probable mechanism of continued viability is preserved flow to the infarct zone. Patients with AMI and persistent chest pain may benefit from reperfusion therapy beyond 6 to 12 hours.

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.

Intestinal transit and bacterial translocation in obstructive pancreatitis.

Pancreatic infection from gut-derived bacteria has emerged as the major cause of death in necrotizing pancreatitis. Bacterial overgrowth of indigenous enteric organisms as a consequence of guts stasis (ileus) represents a potential initial event in this process. The present study was designed to examine the interrelationships between intestinal transit, enteric bacteriology, and the translocation of bacteria from the gut lumen to mesenteric lymph nodes and splanchnic viscera during experimentally induced acute pancreatitis. Male rats underwent pancreaticobiliary duct ligation (PBDL) or sham surgery and were sacrificed after 24, 48, or 96 hr. Severity of pancreatitis was assessed with histology, tissue water content, and amylase and lipase levels. Intestinal transit was measured with fluorescent tracers. Blood, mesenteric lymph nodes (MLNs), splanchnic organs, and gut luminal contents were subjected to bacteriologic analysis. PBDL was followed by biochemical and histologic evidence of progressive pancreatic injury at each time interval. Enteric bacteria within the gut and in adjacent MLNs increased as intestinal transit decreased after PBDL-induced pancreatic inflammation. Surprisingly, all parameters returned to control levels by 96 hr in spite of progression of pancreatic inflammation.