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(Circulation. 2002;105:2605.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Heterogeneity in the Management and Outcomes of Patients With Acute Myocardial Infarction Complicated by Heart Failure

The National Registry of Myocardial Infarction

Frederick A. Spencer, MD; Theo E. Meyer, MD, PhD; Joel M. Gore, MD; Robert J. Goldberg, PhD

From the Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Mass.

Correspondence to Frederick A. Spencer, MD, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655. E-mail spencerf{at}ummhc.org

	Abstract

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Background— Heart failure (HF) is an important predictor of poor outcome after acute myocardial infarction (AMI). However, limited data exist about the clinical significance of HF in the coronary reperfusion era and the impact of its timing on hospital outcomes. The objective of this study was to determine the clinical impact of HF complicating AMI in the National Registry of Myocardial Infarction (NRMI). A secondary objective was to determine differences in demographic and clinical characteristics, treatment, and hospital death rates in patients presenting with HF compared with those developing HF after presentation.

Methods and Results— The study sample consisted of patients with AMI and without a history of HF included in the NRMI. Of 606 500 cases included from July 1, 1994 to June 30, 2000, 123 938 (20.4%) patients had HF at the time of hospital presentation and 52 220 (8.6%) developed HF thereafter. Patients with HF were older, more likely female, had more comorbidities, and were less likely to receive effective cardiac medications compared with patients without HF. The multivariable adjusted odds for in-hospital death were higher for patients with HF at presentation and thereafter (3.1 and 5.5, respectively) than those without HF.

Conclusions— Results from this nationwide registry suggest that the incidence and hospital death rates associated with HF complicating AMI remain high. Patients developing HF after hospital admission are at even greater risk than those presenting with HF. Effective cardiac therapies remain underutilized in these patients, and the reasons for this underutilization need to be explored.

Key Words: heart failure • myocardial infarction • prognosis

	Introduction

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The occurrence of heart failure (HF) in patients with acute myocardial infarction (AMI) has been consistently recognized as a strong predictor of increased morbidity and mortality since the 1960s.¹ Early descriptive studies also suggested that the development of HF in the setting of AMI was associated with larger infarct size and a greater prevalence of multivessel coronary disease.^2–4 The occurrence of HF complicating AMI has been perceived to be an important indication to proceed with cardiac catheterization and revascularization.

See p 2577

However, data from the population-based Worcester Heart Attack Study (WHAS) suggest that the clinical profile of patients with this syndrome has changed over the last 20 years.⁵ Increased use of modalities to restore antegrade flow in a timely manner and other adjuvant therapies have paralleled decreases in the incidence of HF complicating AMI.^5–8 Interestingly, data from the community-based WHAS also showed that patients with AMI complicated by HF in the 1990s were older, presented with more comorbidities, and were more likely to suffer a non–Q-wave myocardial infarction (MI) compared with patients hospitalized during earlier periods. These data suggest that HF after MI is an increasingly complex syndrome impacted by patient characteristics, success of reperfusion strategies, and use of adjuvant therapies. In addition, the timing of occurrence of HF in patients hospitalized with AMI may reflect varying interplay of these factors with different implications for subsequent prognosis. A systematic evaluation of the magnitude and clinical significance of HF complicating AMI in the present era is needed if we are to better understand and effectively treat this syndrome.

A primary goal of this study was to compare differences in demographic and clinical characteristics, use of treatment modalities, and hospital outcomes in patients with HF with those without HF during hospitalization for AMI. Given the importance of understanding how the timing of HF relative to the acute ischemic event influences prognosis and treatment, a secondary goal was to identify differences in demographic and clinical characteristics, use of medical therapies, and hospital case-fatality rates in patients who presented with HF on hospital admission compared with those who developed HF at a later time. The present data were obtained from a large multisite registry and, as such, may be more generalizable to the broader spectrum of AMI patients with HF seen in the community.

	Methods

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The National Registry of Myocardial Infarction (NRMI) is a cross-sectional observational database of patients hospitalized with AMI throughout the United States. The data collection process used in this study and quality-control features have been previously described.⁸ Data from 1 310 030 patients enrolled in NRMI-2 and NRMI-3 from July 1, 1994 to June 30, 2000 were used.

There were 1674 hospitals contributing data to NRMI-2 and 1553 hospitals contributing data to NRMI-3. These hospitals represent approximately one fourth of all acute medical-surgical hospitals in the United States. Participating hospitals were larger, more likely affiliated with a medical school, more likely certified by the Joint Commission on Accreditation of Health Care Organizations, and more likely to have facilities for cardiac catheterization, angioplasty, and surgery than nonregistry hospitals.⁶

Data Collection
Participation in the study was entirely voluntary, and hospitals were encouraged to enter consecutive patients with AMI irrespective of treatment strategy or outcome. Individual institutions participating in NRMI designated a local coordinator who was responsible for abstracting and forwarding data to the central registry. Completed case report forms were then sent to an independent data coordinating center.

To be included in NRMI, patients must have had an AMI before hospital discharge according to prespecified criteria. These included a supportive clinical history, increases in serial enzyme levels, or the presence of electrocardiographic findings consistent with AMI. Patients transferred to or from a nonregistry hospital were excluded for purposes of this study as were patients with a prior history of HF. Patients presenting with cardiogenic shock (n=9659) were also excluded. Cardiogenic shock was defined as the presence of pulmonary edema with evidence for hypoperfusion.

Patients with HF at the time of hospital presentation were defined as those having bibasilar rales, an S₃, or pulmonary edema at the time of initial evaluation (n=123 938). Patients who developed any of these clinical signs after initial evaluation were considered to have HF after hospital presentation (n=52 220).

Data Analysis
Differences in the distribution of demographic, clinical, and treatment characteristics between patients without HF, those with HF at presentation, and those who developed HF after presentation were examined using ² tests for categorized variables and ANOVA for continuous variables. Multivariable adjusted regression analyses controlling for age, sex, race, history of cardiovascular disease, history of cigarette smoking, and AMI associated characteristics (location, type, ECG findings, and size of the infarct) were performed to assess the likelihood of in-hospital death in patients with HF at the time of presentation and in those who developed HF after presentation compared with patients without HF. Because of the nonrandomized observational nature of this study, we did not control for the use of cardiac medications or interventional procedures in examining differences in hospital death rates according to timing of HF.

	Results

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Patient Characteristics
A total of 606 500 patients with AMI met our study criteria. Of these, 71% did not develop HF during hospitalization. In the remaining patients, 123 938 (20.4%) had HF at hospital presentation, whereas an additional 52 220 (8.6%) developed HF thereafter.

Patients with AMI complicated by HF were older, more likely female, and more likely to have a history of coronary artery disease, stroke, hypertension, or diabetes compared with patients who did not develop HF (Table 1). Patients with HF were more likely to present with an anterior MI and left bundle branch block and have an ejection fraction <50%.

View this table: [in this window] [in a new window]   Table 1. Characteristics of Patients With AMI According to Timing of Onset of HF: NRMI 2 and NRMI 3

Patients with HF on presentation were older, more often female, and more likely to have a history of MI, stroke, diabetes, or hypertension than those developing HF after presentation. However, they were less likely to have an anterior, ST-segment elevation, Q-wave, or large MI (creatinine phosphokinase >2x normal range).

Hospital Case-Fatality Rates
The crude in-hospital case fatality rate for patients with AMI complicated by HF was 24.0% compared with 6.2% in patients without HF. Of note, in-hospital death rate for patients excluded from the study because of cardiogenic shock at presentation was 68%. Patients with HF on presentation had a lower hospital death rate than patients developing HF after presentation (20.9% versus 31.5%) (Figure 1). After adjusting for demographic, clinical, and AMI-associated characteristics, the odds of dying for patients with HF remained significantly elevated (adjusted OR, 3.8; 95% CI, 3.7 to 3.9) compared with those without HF. The disparity in hospital mortality for patients with HF after presentation compared with patients with HF on presentation increased after adjustment, with adjusted odds ratios of 5.5 (95% CI, 5.4 to 5.7) and 3.1 (95% CI, 3.0 to 3.2), respectively, compared with those without HF.

View larger version (26K): [in this window] [in a new window]   Figure 1. Use of therapies within 24 hours of admission according to HF status: NRMI-2 and NRMI-3.

We carried out an additional analysis in which the characteristics of patients with HF surviving hospitalization were compared with those who died (Table 2). Patients presenting with HF who survived hospitalization were younger, more likely male, less likely to have a history of stroke, less likely to have an anterior, Q-wave MI, and less likely to present with left bundle-branch block or ST-segment elevation on their initial ECG. Similar findings were seen in patients developing HF after presentation. It is noteworthy that regardless of when HF occurred, survivors were much more likely to be treated with aspirin, ß-blockers, and ACE inhibitors compared with those who died during the acute hospitalization. Hospital survivors of HF were also much more likely to undergo percutaneous transluminal coronary angioplasty or coronary artery bypass graft (CABG) irrespective of the timing of onset of HF relative to AMI presentation.

View this table: [in this window] [in a new window]   Table 2. Characteristics of Patients With AMI Complicated by HF Surviving and Not Surviving Hospitalization: NRMI-2 and NRMI-3

Management Practices
Medication use differed substantially depending on the occurrence and timing of HF. Patients with HF were much less likely to be treated with aspirin, ß-blockers, intravenous heparin, or nitrates in the first 24 hours than those without HF (Figure 1). On the other hand, they were more likely to receive ACE inhibitors. A similar pattern was seen in patients presenting with HF compared with those developing HF at a later time. Patients with HF on initial evaluation were less likely to receive aspirin, heparin, nitrates, and ß-blockers than those developing HF at a later time. They were also more likely to receive ACE inhibitors during the first 24 hours of hospitalization.

At hospital discharge, patients who developed HF during hospitalization were much more likely to be treated with ACE inhibitors, digoxin, and diuretics but less likely to receive aspirin, ß-blockers, calcium antagonists, and nitrates than patients who did not develop HF. Differences in medication use at the time of hospital discharge in patients with HF according to time of presentation were much less striking (Figure 2).

View larger version (19K): [in this window] [in a new window]   Figure 2. Therapies at discharge in hospital survivors according to HF status: NRMI-2 and NRMI-3.

Angioplasty or CABG was performed in 40% of AMI patients without HF. In contrast, only 20% of those with HF at the time of presentation underwent revascularization compared with 36% of those who developed HF after presentation.

	Discussion

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In this analysis of more than 600 000 cases of AMI, HF developed in 30% of the study sample. This proportion is much lower than the incidence of 40% to 50% reported in earlier studies.^4,9,10 In the population-based WHAS, the percentage of patients with AMI developing HF during hospitalization declined from 38% in 1975 and 1978 to 33% in 1993 and 1995.⁵ These data suggest a gradual decline in the incidence of HF complicating AMI over the last several decades.

Despite suggestions of this encouraging decline, patients developing HF in the setting of AMI continue to have a poor outcome. In the present study, even after controlling for a variety of potentially confounding factors, patients developing HF were approximately four times more likely to die in hospital compared with those who did not develop HF. These results are in agreement with recent data from the WHAS that reported a significantly increased risk of dying for patients with, as compared with those without, HF.⁵ The hospital death rates observed in our study for patients with HF are relatively consistent with the hospital case-fatality rate of 18% noted in patients with HF enrolled in the WHAS in the mid-1990s. These death rates are substantially higher than those seen in clinical trials of patients with post-MI HF or left ventricular dysfunction. For example, overall 15-month mortality rate was 17% and 23% (in the treatment and placebo arms, respectively) in the landmark Acute Infarction Ramipril Efficacy trial, but only one fifth of these deaths occurred in hospital.¹¹ These data illustrate the importance of observational studies, because they provide a more representative picture of patterns of care and outcomes in the community setting.

We were able to identify subgroups of patients at increased risk for dying after HF. Elderly patients, those with a history of stroke, and patients with an anterior, Q-wave, or large MI were more likely to die than respective comparison groups. In addition, patients dying after HF were significantly less likely to be treated within the first 24 hours of hospitalization with agents shown to be effective in the management of patients with AMI. These results focus attention on the need for increased surveillance and treatment efforts in high-risk subgroups of patients with HF.

Timing of Onset of HF
Although much has been written about the prognostic significance of HF complicating AMI, there are limited data about the importance of timing of HF with regard to patient characteristics, treatment, and outcomes. A recent study documented the development of HF in 42% of 483 patients hospitalized with an initial AMI from 1992 to 1996.¹² Only 4% had HF on admission, whereas the rest developed HF later in their hospital course. This is in marked contrast to the results of our study in which 20% of study patients presented with HF and only 9% developed HF subsequently. These differences in the occurrence of early HF may be partially explained by the exclusion of patients with prior MI from the former study and attributable to differences in other demographic, clinical, and treatment characteristics. The marked discrepancy in the onset of HF after hospital admission may be partially attributable to different thresholds in the identification of HF between studies. Most notably, the inclusion of patients with radiologic evidence of pulmonary congestion in the study by Ali et al¹² would partially explain their increased incidence of HF in the late phase of MI.

In our study, patients with HF at the time of presentation were older, more likely to have a history of MI and other comorbidities, and less likely to have an anterior, ST-segment elevation or large MI compared with those developing HF at a later time. These data suggest that the early presence of HF may be strongly influenced by preexisting conditions and the ability to tolerate left ventricular dysfunction (systolic and diastolic) secondary to myocardial ischemia.

On the other hand, although still older and sicker than patients without HF, patients developing HF after hospital presentation were younger, had fewer comorbidities, and were more likely to have had an extensive infarct than those presenting to the hospital with HF. This patient profile suggests that extent of damage at the time of AMI is an important determinant of HF after presentation. In addition, many of these patients may have developed HF at a later time attributable to recurrent ischemia. Of concern was that patients in this group had the highest hospital death rates. In an analysis of data from the TAMI studies,¹³ patients developing HF after MI had both a reduced ejection fraction and significant multivessel disease that might have accounted for their marked increases in hospital and 1-year mortality compared with patients without HF. Based on the findings from our study and previous work in this area, the occurrence of HF after hospital presentation for AMI identifies a particularly high-risk subset of patients who warrant aggressive management.

Hospital Management Practices
The results of our study suggest significant underutilization of important cardiac therapies for patients with HF. The results of previous clinical trials do not support a conservative approach to the management of these patients. In fact, data from these trials suggest that patients developing HF in the setting of AMI have much to gain from aggressive treatment. The benefits associated with ACE inhibition after AMI are overwhelming.^11,14 Similarly, ß-blockers have been shown to be efficacious as both an early acute and chronic therapy for patients with AMI.^15,16 Presumably the reluctance to use ß-blockers in patients with HF stems from fear of precipitating recurrent episodes of HF. This reasoning is unfortunate, because the results of several studies indicate that these patients may benefit the most from ß-blockade. Analysis of data from the Beta Blocker Heart Attack trial suggests that treatment of patients with AMI complicated by HF with propanolol significantly reduced the risk of subsequent nonfatal MIs and sudden cardiac deaths.¹⁷ Interestingly, although patients with a history of HF who were randomized to propanolol experienced a higher incidence of recurrent HF in the first 30 days after trial enrollment than those taking placebo, recurrence rates were similar at the end of the 3-year follow-up.¹⁸ It should be noted that more recent trials of ß-blockade have used lower doses and more gradual titration, thereby minimizing exacerbations of HF. In the recently published CAPRICORN study, post-MI patients with ejection fractions <40% who were treated with carvedilol experienced a 27% reduction in all-cause mortality and nonfatal MI compared with placebo-treated patients.¹⁹

The reason for underutilization of other therapies shown to be effective in the management of patients with AMI in our study is even more perplexing. For example, only 70% of patients with AMI and HF on presentation received aspirin in the first 24 hours of hospitalization, and less than half of patients who developed HF at any time during hospitalization were discharged taking this agent. Early administration of aspirin can be difficult in the most critically ill patients with AMI, but its proven efficacy mandates that it be given even if alternative routes of administration are required.

Use of cardiac catheterization, angioplasty, or CABG was also decreased in patients with AMI complicated by HF, particularly in those presenting with HF. These findings are counterintuitive, because these patients clearly have an impaired short- and long-term prognosis, are more likely to have diminished left ventricular function or multivessel disease, and would have much to gain from coronary revascularization.

Study Limitations
As with any observational study, the present findings have several limitations. Although this registry involves >1600 hospitals throughout the United States, participating sites may not be representative of all United States hospitals. Another limitation of our study is the inability to additionally separate categories or classes of HF for more analysis. In the NRMI database, HF is classified using the Killip classification. Accordingly, patients with only radiologic evidence for HF were not included in this analysis. We were also unable to reliably identify patients with low cardiac output without pulmonary congestion. Because this was an observational study, we cannot make direct associations between therapy use (or nonuse) and hospital outcomes.

In conclusion, the results of this national registry suggest that, despite ongoing advances in the treatment of patients with AMI, the incidence and hospital death rates for HF complicating AMI remain high. Heart failure occurring after hospital presentation identifies a particularly high-risk subset of patients. Our data also suggest underutilization of effective cardiac therapies in patients with HF irrespective of the timing of this clinical syndrome. These findings reinforce the continued attention that needs to be devoted to the early identification of patients at risk for HF and the application of timely and effective preventive and treatment strategies.

Received February 4, 2002; revision received March 26, 2002; accepted March 26, 2002.

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