Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes

Abstract

Background: We hypothesized that patients with heart failure (HF) who recover left ventricular function (HF-Recovered) have a distinct clinical phenotype, biology, and prognosis compared with patients with HF with reduced ejection fraction (HF-REF) and those with HF with preserved ejection fraction (HF-PEF).

Methods and results: The Penn Heart Failure Study (PHFS) is a prospective cohort of 1821 chronic HF patients recruited from tertiary HF clinics. Participants were divided into 3 categories based on echocardiograms: HF-REF if EF was <50%, HF-PEF if EF was consistently ≥50%, and HF-Recovered if EF on enrollment in PHFS was ≥50% but prior EF was <50%. A significant portion of HF-Recovered patients had an abnormal biomarker profile at baseline, including 44% with detectable troponin I, although in comparison, median levels of brain natriuretic factor, soluble fms-like tyrosine kinase receptor-1, troponin I, and creatinine were greater in HF-REF and HF-PEF patients. In unadjusted Cox models over a maximum follow-up of 8.9 years, the hazard ratio for death, transplantation, or ventricular assist device placement in HF-REF patients was 4.1 (95% confidence interval, 2.4-6.8; P<0.001) and in HF-PEF patients was 2.3 (95% confidence interval, 1.2-4.5; P=0.013) compared with HF-Recovered patients. The unadjusted hazard ratio for cardiac hospitalization in HF-REF patients was 2.0 (95% confidence interval, 1.5-2.7; P<0.001) and in HF-PEF patients was 1.3 (95% confidence interval, 0.90-2.0; P=0.15) compared with HF-Recovered patients. Results were similar in adjusted models.

Conclusions: HF-Recovered is associated with a better biomarker profile and event-free survival than HF-REF and HF-PEF. However, these patients still have abnormalities in biomarkers and experience a significant number of HF hospitalizations, suggesting persistent HF risk.

Keywords: heart failure; myocardium; ventricular remodeling.

Figure 1

Flow diagram of patient classification. HOCM, hypertrophic obstructive cardiomyopathy; LVAD, left ventricular assist device; ECHO, echocardiogram; EF, ejection fraction; HF-PEF, heart failure with preserved ejection fraction; HF-RECOVERED, heart failure with recovered ejection fraction; HF-REF, heart failure with reduced ejection fraction.

Figure 2

Probability of all-cause death, cardiac transplantation, or VAD placement for all participants (A) and probability of cardiac hospitalization for all participants (B) from time of referral to an outpatient HF specialty care center.

Figure 2

Probability of all-cause death, cardiac transplantation, or VAD placement for all participants (A) and probability of cardiac hospitalization for all participants (B) from time of referral to an outpatient HF specialty care center.