By Van Selby, MD

Assistant Professor of Medicine, University of California, San Francisco, Cardiology Division, Advanced Heart Failure Section

Dr. Selby reports no financial relationships relevant to this field of study.

SYNOPSIS: Patients suffering from systolic heart failure who subsequently improve their ejection fraction experience a more favorable clinical course compared to those presenting with persistently reduced ejection fraction or heart failure with preserved ejection fraction.

SOURCE: Kalogeropoulos AP, Fonarow GC, Georgiopoulou V, et al. Characteristics and outcomes of adult outpatients with heart failure and improved or recovered ejection fraction. JAMA Cardiol 2016;1:510-518.

Patients presenting with chronic heart failure (HF) typically are divided into those with preserved (HFpEF) or reduced left ventricular ejection fraction (HFrEF). Although the management of the two conditions differs significantly, overall prognosis is relatively similar for the two diagnoses. However, it is recognized that some HFpEF patients initially presented with HFrEF and experienced significant improvement in ejection fraction. The characteristics and outcomes of these patients with “recovered” ejection fraction have not been well described.

Kalogeropoulos et al retrospectively evaluated the medical records of all patients who were treated at the Emory University cardiology practice for a diagnosis of chronic heart failure between Jan. 1 and April 30, 2012. Patients were assigned to one of three groups: HFrEF (defined as EF < 40%), HFpEF (defined as current and all previous EF measurements > 40%), or heart failure with recovered ejection fraction (HFrecEF, defined as EF > 40% but any previously documented EF < 40%).

Of 2,166 patients with chronic HF, 350 (16.2%) had HFrecEF, 466 (21.5%) had HFpEF, and 1,350 (62.3%) had HFrEF. Those with recovered EF predominantly were male and featured significantly lower rates of diabetes, coronary artery disease, and hypertension (P < 0.01 for all). Over three years of follow-up, age- and sex-adjusted mortality was significantly lower among patients with HFrecEF (4.8%) compared to those with HFrEF or HFpEF (16.3% and 13.2%, respectively; P < 0.001). Patients with HFrecEF also experienced significantly fewer all-cause hospitalizations, cardiovascular hospitalizations, and HF-related hospitalizations.

The authors concluded that outpatients with HFrecEF experience a different clinical course than patients with HFpEF or HFrEF, with lower mortality and less frequent hospitalizations, and should be investigated separately in future clinical trials.

COMMENTARY

Data from large clinical trials and registries support the concept that appropriate use of evidence-based therapies for systolic HF, such as beta-blockers and ACE inhibitors, leads to improvement in ejection fraction for a significant portion of patients presenting with HFrEF. These patients often are diagnosed with HFpEF. In their single-center cohort, Kalogeropoulos et al found HFrecEF patients represented approximately 43% of all patients with HF and an EF > 40%. The authors also demonstrated fairly convincingly that these patients have different clinical characteristics and substantially better outcomes than those with persistently reduced EF or true HFpEF.

Although it is clear myocardial recovery is possible, the exact underlying mechanisms remain poorly understood. Patients suffering from HFrecEF may experience reverse remodeling, leading to improvements in neurohormonal activation and therefore better outcomes. The lower frequency of coronary artery disease (and presumably myocardial scar) in the HFrecEF group may have improved their ability to reverse remodel. Refining our ability to identify HFrEF patients with potential for remodeling and recovering systolic function would improve risk stratification and guide clinical decision making.

This study has important limitations. As a single-center, academic cohort, the findings may not be generalizable to broader clinical practice. Categorization was based solely on available clinical echocardiographic data, and may have led to misclassification of cases. The authors used a strict EF cutpoint of 40% to differentiate HFpEF and HFrEF, instead of including a “borderline EF” category, as some have recommended. One question that arises frequently in HFrecEF is how long to continue medical therapy for HFrEF once the ejection fraction has recovered. Unfortunately, there is minimal evidence to guide these decisions, and a retrospective study such as this cannot be used to make recommendations regarding clinical management.

From here, prospective studies are needed to determine predictors of improvement in EF, and the optimal treatment strategies for these patients once the EF has recovered. As the authors suggested, patients presenting with HFrecEF may need to be studied as a distinct group in future HF clinical trials. For now, the findings guide the way we categorize patients with HF and are especially useful when discussing prognosis in patients with HFrEF who subsequently recover systolic function.