Early restoration of normal coronary perfusion after myocardial infarction (MI) limits infarct size, preserves left ventricular (LV) function and reduces mortality. The primary objective of reperfusion therapy is not only to restore epicardial vessel patency, but also to reperfuse tissue in order to maintain myocyte viability and, thus, LV function. Although primary percutaneous coronary intervention (PCI) is the most effective method of reperfusion for acute MI, significant LV contractile dysfunction is still evident months after the index event in a significant number of patients.^1–3 While convalescent LV function is the strongest determinant of late survival after MI, the predictors of myocardial recovery in patients who are treated by contemporary PCI techniques have been incompletely characterized.^4–6 In addition, despite multiple trials demonstrating the efficacy of current guideline-based medical therapy post-MI, evidence shows that a large gap exists in the effective application of guideline-compliant care to many patients in clinical practice.^7–9 Currently, conflicting data exist with regard to prevention strategies for sudden cardiac arrest (SCA) following MI. While it is clear that SCA occurs more often in the first 30 days following MI, early implantable cardioverter-defibrillator (ICD) implantation in the DINAMIT trial did not reduce overall mortality.^10,11 Thus, patient selection is of paramount importance when applying device therapies to prevent SCA post-MI. In order to further clarify the natural history of patients presenting with acute MI in the setting of contemporary revascularization techniques and pharmacologic treatment, we examined a prospective database of MI patients with clinical and echocardiographic data to 6 months post-initial presentation.

Methods
The Ohio Pacing Infarct Study (OPIS) database is a prospective registry of over 600 patients presenting with acute MI. The current report comprises 75 consecutive patients with first acute MI and severe LV systolic dysfunction with a left ventricular ejection fraction (LVEF) of less than or equal to 30%. Initial demographic and clinical data were collected during the hospitalization and at 1-, 3- and 6-month follow up. Baseline echocardiography evaluation of LVEF was obtained during the initial hospitalization and assessed at 1-, 3- and 6-month follow up. Baseline demographic and clinical characteristics, as well as LV function and medication use, are expressed using descriptive statistics as percentages or means ± standard deviation (SD). Differences in LV function over time were compared using the paired t-test, with statistical significance at a p-value of < 0.05.

Results
Baseline demographics and clinical characteristics are shown in Table 1. Seventy-one percent of the patients were male, with a mean age of 65 ± 14 years. Thirty-six percent were diabetic and 51% had a previous history of coronary artery disease (CAD). ST-segment elevation MI (STEMI) patients made up 72% of the study population, while non-ST-segment elevation MI (NSTEMI) patients contributed 28%. Fibrinolysis was administered to 33% of the STEMI patients at an outside facility prior to transfer for PCI. Average door-to-balloon time (DTB) for PCI, including patients transferred from an outside facility (includes time of presentation at the outside hospital), was 135 ± 91 minutes for STEMI patients, and 125 minutes to 2.1 days for NSTEMI patients. Platelet glycoprotein (GP) IIb/IIIa inhibitors were administered more often to STEMI than NSTEMI patients (70% vs. 38%, respectively). The average length of stay for survivors of hospitalization was 5.7 ± 3.1 days for STEMI (CPK range 424–5,250; troponin range 0.25–75.7), and 2.4 ± 1.2 days for NSTEMI (CPK range 175–705; troponin range 0.10–5.68) patients.
Eighty-seven percent (65/75) of patients underwent successful revascularization during the initial hospitalization (62 PCI, 3 surgical); revascularization was not performed in 10 patients, but these were included in the analysis. At hospital discharge, 84% of patients were treated with a beta-blocker, 73% with an ACE-inhibitor, 81% with a statin, 88% with aspirin and 84% with clopidogrel (Table 2). The mean LVEF was 25.7 ± 5.9% in-hospital, 36.6 ± 11.8% at 1–3 months (p < 0.01), and 37.6 ± 9.3% at 6 months (p < 0.01) (Table 2 and Figure 1). By 1- to 3-month follow up, 63% of patients had improved LVEF, 24% were unchanged and 14% were worse (Table 3). Fifty-one percent of all patients had an ejection fraction at 1–3 month follow up that was above 35%. Repeat hospitalization to 6-month follow up occurred in 24% of patients (4.2% coronary artery bypass graft surgery [CABG], 5.6% PCI, 14% congestive heart failure [CHF]) (Table 4). One patient died in-hospital and 3 died by the 6-month follow up for a cumulative mortality rate of 5.3% (Table 4).

Discussion
The principal finding of the present study is that a strategy of early revascularization and guideline-compliant medical management with neurohormonal modulators (beta adrenergic receptor-blockers, angiotensin-converting enzyme [ACE] inhibitors/ angiotensin receptor-blockers [ARB]), statin therapy and platelet inhibitor therapy, favorably impacts LV function and short-term prognosis in patients who present with acute MI and severe LV systolic dysfunction. The majority of these patients (> 60%) demonstrated significant improvement in LVEF at 1–3 months that was sustained to 6-month follow up. In addition, the cumulative mortality to 6-month follow up was lower (5.3%) than previously reported for similar high-risk patient cohorts.
The prognostic value of convalescent LVEF measured days to months after MI is well established.^4,5 In addition, LV function measured during the index PCI procedure has been demonstrated to be a strong determinant of survival after primary PCI.⁶ These relationships, however, have not been well defined in the contemporary era of early, aggressive mechanical revascularization and strict compliance with guideline-adherent medical management. Previous studies have found no clear association between time to mechanical reperfusion and LVEF at baseline, primarily when time to reperfusion is > 3 hours.^12,13 The demonstration that spontaneous reperfusion before PCI improves baseline LVEF and enhanced survival underlies the rationale for facilitated PCI currently being investigated in randomized trials.^6,14 Additional studies have demonstrated that very early reperfusion (within 2 hours) is associated with enhanced recovery of LVEF and increased survival.^12,15 The relatively short DTB times (135 ± 91 minutes for STEMI) for mechanical reperfusion in the present study may help explain the beneficial effect demonstrated on LVEF.
Previous reports have also demonstrated the beneficial effect of adherence to ACC/AHA guidelines for patients with acute coronary syndromes (ACS). Recent data from NRMI (National Registry of Myocardial Infarction) of acute STEMI patients, and CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines) including NSTEMI patients both demonstrated improved outcomes at hospitals with greater adherence to the guidelines.^7–9 The early revascularization strategy in our current study, combined with greater than or equal to 80% compliance with recommended medications at discharge, likely provided the beneficial outcomes reported. Indeed, recent reports have documented an incremental survival advantage at 6- to 12-month follow up in acute coronary syndrome patients, particularly STEMI, with each additional guideline-compliant medication (antiplatelet, beta-blocker, ACE-inhibitor, lipid-lowering agent) prescribed at hospital discharge.^16,17
Two other observations from the current study have significant clinical therapeutic ramifications. First, the above therapeutic strategy led to significant improvement in LVEF at 1- to 3-month follow up. This has direct implications for the timing of implantable cardioverter-defibrillator (ICD) implantation following MI. Prophylactic ICD therapy did not reduce overall mortality in patients when implanted 6 to 40 days following MI in the DINAMIT trial.11 This was due to an increase in the rate of death from nonarrhythmic causes among patients assigned to receive an ICD that counterbalanced the reduction in arrhythmia-related death provided by ICD therapy. Mean LVEF was low (28%) and did not significantly improve to 6-week follow up, however longer-term assessment of LV recovery was not performed. These findings led to the current consensus that early after an MI, patients may be too clinically unstable for ICD therapy and decisions about implantation should be delayed for 30–40 days post-MI. Current ACC/AHA guidelines recommend ICD implantation in patients with reduced LVEF (< 30%) 1 month after STEMI and 3 months after coronary revascularization.¹⁸ Our present study supports waiting 1–3 months following MI and reassessment of LVEF prior to consideration of ICD therapy.
Second, the degree of improvement in LVEF seen in our current study is consistent with what has been demonstrated in cell-based therapies for MI patients. Intracoronary injection of progenitor cells in 59 patients with acute MI increased LVEF from 50 ± 10% to 58 ± 10% in the nonrandomized TOPCARE-AMI trial.¹⁹ The randomized BOOST trial enrolled 60 patients with STEMI to post-infarction therapy (4.8 ± 1.3 days post-PCI) with intracoronary autologous bone marrow cells (BMC). The control group demonstrated an absolute increase of 0.7% and 3.1% after 6 and 18 months, respectively; while the BMC transfer group increased by 6.7% and 5.9%.^20,21 The difference in LVEF between groups was significant at 6 months, but not after 18 months. Our results demonstrate the importance of the control group in cell-based therapy trials, assigned to early revascularization combined with guideline based medical therapy. Thus, a contemporary comparator “control” group is required when interpreting results of clinical trials utilizing cell-based therapies for acute MI.

Conclusion
In conclusion, a strategy of early, aggressive revascularization combined with guideline based medical therapy favorably impacts LV function and short-term prognosis in MI patients who present with severe LV systolic dysfunction. With contemporary treatment strategies, the majority (> 60%) of these patients demonstrate improvement in LVEF (comparable to data from cell-based therapy) and mortality is lower (5.3%) than has previously been reported. These findings emphasize the need for contemporary control groups when interpreting the results of trials utilizing cell transplantation, and the importance of appropriate timing when selecting patients for ICD therapy post-MI.