HF With 'Recovered' LVEF: Distinct, Deserves More Scrutiny

Marlene Busko

July 14, 2016

ATLANTA, GA — Adult HF outpatients with improved or recovered left ventricular ejection fraction (LVEF) had better 3-year survival and less hospitalization than those with reduced LVEF (HFrEF) or preserved LVEF (HFpEF), in a new study[1].

Specifically, age- and sex-adjusted mortality was 4.8% in patients with heart failure with recovered ejection fraction (HFrecEF) vs 16.3% in patients with HFrEF and 13.2% in patients with HFpEF (P<0.001).

Thus, "heart failure with recovered ejection fraction should be treated as a distinct entity for clinical and research purposes," Dr Andreas P Kalogeropoulos (Emory University School of Medicine, Atlanta, GA) and colleagues advise, in an article published online July 6, 2016 in JAMA Cardiology.

In an accompanying editorial[2], Drs Jane E Wilcox and Clyde W Yancy (Northwestern University Feinberg School of Medicine, Chicago, IL) agree, saying, "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 HF has emerged."

Early Study of a New Phenotype: HFrecEF

Limited study has identified a subset of HF patients with preserved EF who had reduced EF in the past that improved or recovered over time, and now they had better outcomes than other HF patients.

To investigate this, Kalogeropoulos and colleagues reviewed medical records of adult outpatients with HF who were seen at Emory Healthcare cardiology clinics from January 2012 through April 2012 and had 3-year follow-up data.

They identified 2166 patients (41% women) with HF who had a median age of 65. About half were white (49%) or black (45%), and 63% had CAD.

The researchers defined preserved EF as LVEF >40%, according to guideline recommendations.

Of the 2166 patients, 1350 patients (62.3%) had HFrEF; 466 patients (21.5%) had HFpEF; and 350 patients (16.2%) had HFrecEF.

Compared with patients with HFpEF, patients with HFrecEF were younger (median age 65 vs 72), more likely to be male (52% vs 43%), and less likely to have CAD, diabetes, or kidney disease.

During the 3-year follow-up, 288 patients (13.3%) died. Mortality was similar in the three groups in the first year, but during years 2 and 3, mortality plateaued among patients with HFrecEF but continued to rise in the other groups.

During follow-up, there were 3813 hospitalizations, including 52.3% for cardiovascular causes and 39.4% specifically for HF.

Compared with patients with HFpEF, patients with HFrecEF were significantly less likely to die or be hospitalized during follow-up.

Risk of 3-Year Outcome, HFrecEF Group vs HFpEF Group*

Outcome HR (95% CI) P
Mortality 0.56 (0.34–0.92) 0.02
All-cause hospitalization 0.71 (0.55–0.91) 0.007
Cardiovascular hospitalization 0.50 (0.35–0.71) <0.001
HF hospitalization 0.48 (0.30–0.76) 0.002
*Adjusted for multiple variables

Patients with HFrecEF had lower rates of the combined outcomes commonly used in clinical trials.

Rates of 3-Year Combined Outcomes, %

Outcome HFrEF HFpEF HFrecEF
Death or all-cause hospitalization 58.8 52.7 41.4
Death or CV hospitalization 48.0 37.2 17.4
Death or HF hospitalization 40.1 28.9 11.8
*Adjusted for multiple variables

The study has several limitations, the authors acknowledge. The patients were seen at a single academic center and there may be selection bias. The researchers opted not to have a "borderline" LVEF category; instead, they performed a secondary analysis with HFpEF defined as LVEF >50%, which showed similar results. The editorialists also point out that study lacked information about the duration of HF.

Nevertheless, in this setting, 42.9% of the patients with current preserved EF had recovered rather than persistent preserved EF and more favorable outcomes than other patients, so they should be investigated separately, Kalogeropoulos and colleagues conclude.

Clinical trials, observational data, and current guidelines all support the existence of myocardial remodeling, Wilcox and Yancy note. Now we need "prospective studies . . . that include well-phenotyped inception cohorts to accurately identify the incidence of recovery and to discriminate those likely to recover and those likely to fail evidence-based medical and device therapy," they urge.

The authors and editorialists report that they have no relevant financial relationships.

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