CHF, systolic function, and mortality

From the Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark

Congestive heart failure (CHF) is a major cause of morbidity and mortality in the Western world, and the incidence is rising. It is well known that patients with heart failure due to low ejection fraction of the left ventricle have a poor prognosis. Approximately one half of the patients admitted to the hospital with CHF, however, have normal systolic function of the left ventricle.1,2 Large studies on the long-term prognosis of patients with heart failure and preserved systolic function are few. The aim of the present study was to determine long-term survival in a consecutive cohort of patients admitted to the hospital with CHF and to explore the importance of left ventricular systolic function.

Methods

The Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND)-CHF registry included consecutive heart failure patients admitted to 34 Danish hospitals between November 1993 and July 1996.3,4 To be included in the registry, a clinical diagnosis of CHF was mandatory. At least one episode of shortness of breath, either on minimal exertion or at rest (New York Heart Association [NYHA] functional class III or IV) within the preceding month, was also required. Patients with acute myocardial infarction (MI) within the previous 7 days were excluded from the

DIAMOND-CHF screening registry.

Patients were screened using a clinical history, a physical examination, and an electrocardiogram. Left ventricular systolic function was evaluated by means of wall motion index.5 An estimate of left ventricular ejection fraction can be calculated from wall motion index by multiplying the wall motion index by 0.3. Hence, a wall motion index of 1.2 is approximately equivalent to an ejection fraction of 0.35, the value we used in our study to define significant left ventricular systolic dysfunction. Follow-up time ranged from

5 to 8 years. A total of 5,548 patients were screened, but 57 patients were lost to follow-up, resulting in a study population of 5,491 patients. Relative risk ratios were calculated using a Cox proportional hazards model.

Results

Patient characteristics are shown in table 1. As expected, patients were elderly and more than one half had a history of ischemic heart disease. Most patients (63%) were admitted for dyspnea. Comorbid conditions were common, most often chronic obstructive pulmonary disease (COPD; 22%), hypertension (24%), and diabetes (16%). Normal or near-normal systolic function (wall motion index > 1.6) was found in 37% of patients. Patients with significantly depressed systolic function (wall motion index < 1.2) were younger, more frequently men, and had a higher prevalence of previous MI. At discharge, 77% of the patients with significant systol-

ic dysfunction (wall motion index

< 1.2) were treated with an angiotensin-converting enzyme (ACE) inhibitor and more than 60% were treated with digoxin. Only 13% were treated with a beta blocking agent.

A total of 3,955 patients (72%) died during follow-up, and the crude 1-year mortality rate was 24%. Declining systolic function was clearly associated with increased mortality (figure).

To determine if this association was a result of bias, we conducted a multivariate analysis of survival using all the characteristics shown in table 1, except medications. Patients were not randomly assigned to treatment, therefore medications were not included because their presence in the model would have been a potential source of bias. The results of the multivariate analysis are shown in table 2. In this model, decreasing left ventricular systolic function (low wall motion index), male sex, valve disease, impaired renal function, COPD, and duration of heart failure had an independent negative influence on survival. The relative risk associated with increasing wall motion index was 0.6, which can be interpreted as a 40% higher risk of death in patients with a wall motion index of 1.0 (equal to an ejection fraction of 30%) compared with patients who had a wall motion index of 2.0 (normal systolic function). Mortality among patients without significantly depressed systolic function (wall motion index

> 1.6), however, was high as well

(1-year mortality rate, 19%).

We found a significant interaction (P < .001) between wall motion index and age; wall motion index was of less importance for patients ages 80 years and older (relative risk, 0.80 [0.69—0.92]) compared with younger patients. Furthermore, wall motion index interacted with history of MI. The risk ratio for patients with previous MI was 0.49 (0.43–0.56), whereas for patients without such a history, the relative risk was 0.65 (0.60–0.72). A similar interaction was found between wall motion index and a history of ischemic heart

disease, such as MI, angina, or both. Despite the interaction, systolic function was an independent predictor of death for patients without a history of myocardial ischemia.

Discussion

The patients in our study were elderly and most often men, which is in accordance with most other epidemiologic studies of patients hospitalized with CHF. Myocardial ischemia appeared to be the underlying cause of CHF in more than one half of the patients, which is a general finding in heart failure populations in Western Europe and in the United States. Patients were infrequently treated with ACE inhibitors at admission (26%), but the treatment rate in the group with wall motion indexes below 1.2 at discharge (77%) was comparable with that reported in contemporary registries.6,7 Few patients were treated with beta blocking agents, probably because the data were collected before firm evidence of the benefit of beta blockade in CHF had emerged.

Our study confirms that patients hospitalized with CHF have a poor prognosis. After 1 year, nearly one quarter of the patients had died. This finding is similar to mortality rates reported previously.8-10 It is different from most randomized clinical CHF trials, however, in which approximately 10% of patients in the placebo arm die.11 This finding underscores the difference between consecutive CHF patients in a registry and patients selected for a CHF trial.

We found that left ventricular systolic function was a potent predictor of death in hospitalized CHF patients. Although others have reported this, several investigators found no difference in mortality between CHF patients with normal and decreased systolic function.1,2,8,12-15 The reason for this discrepancy is not entirely clear. In some studies that showed no difference in mortality between patients with normal and low ejection fractions, however, information about systolic function was missing for a substantial number of patients (50%), which could have been a major source of bias.

In other studies, patients were selected on the basis of a low ejection fraction. In this subgroup, it may be difficult to detect a prognostic effect of left ventricular systolic function.

In our study, information about left ventricular systolic function was available for 95% of patients. Thus, our analysis provides solid evidence that left ventricular systolic function contributes important prognostic information for hospitalized CHF patients.

Although low wall motion index predicted a high mortality rate, a grave prognosis was also found in the group of patients with normal or near-normal ejection fractions. After 1 year, nearly one in five patients with wall motion indexes above

1.6 had died, indicating that nonsystolic heart failure is highly lethal. Unlike the case for systolic heart failure, little evidence is available on how to improve the prognosis of patients with nonsystolic heart failure, and this should be an area of major interest in the future.

We found a clinically significant interaction between coronary heart disease and systolic function with regard to survival in CHF. Left ventricular systolic function was of greater importance for patients with angina or previous MI. One explanation for this observation is that patients with a history of ischemia are at high risk for a new ischemic episode or MI. It could also be speculated that a new ischemic event may be better tolerated in CHF patients with preserved contractile reserve than in patients who already have a low ejection fraction. Thus, a low ejection fraction could be more dangerous to the patient with a history of ischemic heart disease than the patient with a lower risk of ischemia, such as those with idiopathic dilated cardiomyopathy.

We also found an interaction between age and systolic function. Wall motion index was of less importance for patients ages 80 years and older. This may be because elderly patients are at higher risk of dying of noncardiac causes, implying that the prognostic effect of wall motion index may be diluted in this population.

Conclusion

Our study shows that left ventricular systolic function is an important predictor of survival for patients hospitalized with CHF. The effect of left ventricular systolic function on prognosis is, to some extent, modified by age and by the presence or absence of myocardial ischemia. Although the survival of CHF patients with preserved systolic function is superior to that of patients with low ejection fraction, patients with nonsystolic heart failure also carry a dismal prognosis.