Epidemiology, pathophysiology and clinical outcomes for heart failure patients with a mid-range ejection fraction

Abstract

Aims: Heart failure (HF) patients with a mid-range ejection fraction (HFmrEF) are not well characterized. Accordingly, we examined the epidemiology, pathophysiology and clinical outcomes of HF patients with a left ventricular ejection fraction (LVEF) of 40-50%.

Methods and results: We identified 168 patients with an LVEF between 40-50% at enrollment into a HF registry, and determined whether LVEF was improved, worsened, or the same compared to a prior LVEF. Three subgroups of HFmrEF patients were identified: HFmrEF improved (prior LVEF <40%); HFmrEF deteriorated (prior LVEF >50%); HFmrEF unchanged (prior LVEF 40-50%). The majority of patients (73%) were HFmrEF improved, 17% were HFmrEF deteriorated, and 10% were HFmrEF unchanged. The demographics of the HFmrEF cohort were heterogeneous, with more coronary artery disease in the HFmrEF improved group and more hypertension and diastolic dysfunction in the HFmrEF deteriorated group. HFmrEF improved patients had significantly (P<0.001) better clinical outcomes relative to matched patients with HF and reduced ejection fraction, and significantly (P<0.01) improved clinical outcomes relative to HFmrEF deteriorated patients, whereas clinical outcomes of the HFmrEF deteriorated subgroup of patients were not significantly different from matched HF patients with preserved ejection fraction.

Conclusions: Patients with a mid-range LVEF are heterogeneous. Obtaining historical information with regard to prior LVEF allows one to identify a distinct pathophysiological substrate and clinical course for HFmrEF patients. Viewed together, these results suggest that in the modern era of HF therapeutics, the use of LVEF to categorize the pathophysiology of HF may be misleading, and argue for establishing a new taxonomy for classifying HF patients.

Keywords: Clinical outcomes; Ejection fraction; Heart failure.

Figure 1

Patient Selection. Consort diagram of the patients enrolled in the Washington University Heart Failure Registry. Patients with an LV ejection fraction from 40–50% (HFmrEF) subdivided into 3 different subgroups (see text for details). The numbers of patients are given in parenthesis.

Figure 2

Degree of Diastolic Dysfunction for HFmrEF patients based on origin ejection fraction. Among patients with diastolic dysfunction, the percentage of HFmrEF improved, HFmrEF unchanged, and HFmrEF deteriorated patients with Grade I, II, and III diastolic dysfunction is illustrated. Overall, there was a statistically significant increase in the degree of diastolic dysfunction in patients with more preserved ejection fractions at origin compared to those with reduced ejection fraction at origin (p<0.001 based on Fisher’s Exact Test).

Figure 3

Clinical Outcomes for HFmrEF, HFrEF, and HFpEF patients. Kaplan-Meier curves of the time to death/transplant/cardiac hospitalization for HFmrEF, HFrEF, HFpEF patients enrolled in the Washington University HF registry. A, Risk of death/transplant/cardiac hospitalization in HFmrEF patients (n= 102) compared with age and gender matched HFrEF patients (n=102). B, Risk of death/transplant/cardiac hospitalization in HFmrEF patients (n= 82) compared with age and gender matched HFpEF patients (n=82).

Figure 4

Outcomes for HFmrEF patients based on prior LV ejection fraction. A, Kaplan-Meier curves of the time to death/transplant/cardiac hospitalization for HFmrEF improved, HFmrEF unchanged, and HFmrEF deteriorated patients with significant difference for HFmrEF improved compared to HFmrEF deteriorated only (p = 0.011 based on log-rank test of pairwise comparisons with multiple testing adjustment). B, Kaplan-Meier curves of the time to first cardiac hospitalization for HFmrEF improved, HFmrEF unchanged, and HFmrEF deteriorated patients with significant difference for HFmrEF improved compared to HFmrEF deteriorated only (p = 0.029 based on log-rank test of pairwise comparisons with multiple testing adjustment).

Figure 5

Forest plot of clinical outcomes for HFmrEF patients compared to patients with HFrEF and HFmrEF. The hazard ratios and 95% confidence intervals comparing clinical outcomes of death, time to first cardiac hospitalization and the composite of time to death/cardiac transplantation/all cause hospitalization for: HFmrEF improved patients (n=71) compared to age and gender matched HFrEF patients (n=71); and HFmrEF deteriorated (n=16) patients compared to age and gender matched HFpEF patients (n=16). All p-values represent the significance of the hazard ratios for HFmrEF improved patients compared with matched HFrEF patients or for HFmrEF deteriorated patients compared with matched HFpEF patients.