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Heart failure patients with recovered ejection fraction have better clinical courses, including lower mortality, than patients with permanently reduced or permanently preserved ejection fraction, researchers reported.

In a retrospective study from a single, academic medical center, close to 43% of heart failure patients with left ventricular ejection fraction (LVEF) exceeding 40% were found to have recovered LVEF, rather than persistently preserved LVEF, according to , of Emory University School of Medicine in Atlanta, and colleagues.

Among 2,166 patients in the cohort treated from January to April 2012, 350 (16.2%) had previously reduced (≤40%) LVEF that had increased above 40% and were classified as having recovered ejection fraction (HFrecEF), they wrote in .

The all-cause, adjusted death rate during at least 3 years of follow-up among patients with permanently reduced ejection fraction (HRrEF) was more than three-fold higher than among patients with recovered ejection fraction (16.3% versus 4.8%), they added.

The authors suggested that recovered ejection fraction should be considered a distinct heart failure phenotype.

In an interview with 番茄社区, Kalogeropoulos said it is increasingly clear that recovered ejection fraction is an important indicator of response to treatment among patients with heart failure.

"Patients and their families need to know that if ejection fraction improves, patients have a better prognosis moving forward," he said, adding that the next step is to determine how many patients achieve ejection fraction recovery with treatment.

In an accompanying editorial, , and , both of Northwestern University Feinberg School of Medicine in Chicago, wrote that myocardial recovery "is not the opposite of disease progression and likely represents more than reversal of already described pathophysiological models of LV dysfunction."

"This process may be quite intricate or may represent the benefit of timely interventions before an adverse burden of remodeling goes too far," they wrote. "Where this 'point of no return' lies in the natural history of heart failure is unknown and likely varies based on heart failure etiology."

Kalogeropoulos and colleagues noted that patients with consistently reduced and preserved ejection fractions have similar morbidity and mortality rates, but the prevalence and clinical course of patients with recovered ejection fraction has not been widely studied.

Their analysis excluded patients treated at their academic center during the inception period who had heart failure attributed to specific cardiomyopathies or other special causes. The mean age of the patients was 65 and 41.4% were female, while 48.7% were white and 45.2% were African American. Coronary artery disease was diagnosed in 63.2%.

Preserved (>40%) LVEF at inception was present in 37.7% of patients, and 16.2% had previously reduced (40%) LVEF and were classified as having HFrecEF. Also, 21.5% had no previous reduction in LVEF, and were classified as having preserved ejection fraction (HFpEF), while 62.3% of patients were classified as having HFrEF.

The analysis revealed that after 3 years, age and sex–adjusted mortality was 16.3% among patients with HFrEF, 13.2% among patients with HFpEF, and 4.8% among patients with HFrecEF (P<0.001 vs HFrEF or HFpEF).

Compared with patients with HFpEF and patients with HFrEF, patients with HFrecEF had fewer all-cause hospitalizations (adjusted rate ratio versus HFpEF 0.71, 95% CI 0.55-0.91, P=0.007), cardiovascular hospitalizations (RR 0.50, 95% CI 0.35-0.71, P<0.001), and heart failure-related hospitalizations (RR 0.48, 95% CI 0.30-0.76, P=0.002).

At 3 years, 55.2%, 41.1% and 33.6% of patients met the composite endpoints of death or all-cause hospitalization, death or cardiovascular hospitalization, and death or heart failure hospitalization, respectively, with HFrecEF patients less likely than patients in the other two groups to meet this endpoint.

Study limitations included the single-center, the possibility of heart failure misclassification, and a failure to obtain repeat LVEF assessments at prespecified time point for some patients with reduced LVEF. Survivor bias resulting in the overstatement of HFrecEF was also a possibility.

Wilcox and Yancy wrote that despite these and other potential limitations, the study makes a strong case for identifying and studying patients with recovered ejection fraction.

"It is our opinion that myocardial recovery exists, as evidenced by clinical trials, observational data, and recent integration into current guidelines," they wrote. "Now is the time to recognize recovery as a clinical reality for patients with HFrEF and to begin a deliberate pursuit of the underlying mechanisms and future clinical considerations. Indeed, a new phenotype of heart failure has emerged."

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