Clinical profile, prognosis, and medical therapy of heart failure with mildly reduced ejection fraction in clinical practice

Background For 3 of 4 medication classes of guideline-directed medical therapy (GDMT), evidence is poor regarding benefit for those with heart failure with mildly-reduced ejection fraction (HFmrEF; defined as left ventricular ejection fraction 41-49%). Knowledge of how these medications are used in contemporary practice is essential to define the need for comparative effectiveness evidence for individuals with HFmrEF. Objectives To determine how medication prescription rates have recently changed for individuals with HFmrEF and to describe prognosis and clinical characteristics for individuals with HFmrEF in clinical practice. Methods This project used a novel clinical registry of individuals with left ventricular ejection fraction (LVEF) 41-49% on echocardiograms within a 12-hospital network and a 6-year period (July 2016-November 2022). In addition to data from echocardiography reports, the registry included laboratory values, diagnoses, and clinical notes at baseline HFmrEF recognition as well as medications and mortality over time. Study investigators manually reviewed clinical notes to characterize baseline symptoms. Descriptive statistics were used to describe the cohort and separate logistic regression models for each medication class were used to describe trends in utilization over time. Results 6517 individuals were included (66.8% male). Mean age was 68 (SD 16), 39.2% had atrial fibrillation and 25.8% had diabetes. At baseline, median creatinine was 1.0 mg/dL (SD 1.3 mg/dL) and median NT pro-BNP was 1913 pg/mL (SD 1454 pg/mL). Medication frequency for all 3 classes increased after 2016; the largest relative increase occurred for mineralocorticoid receptor antagonists (MRA) from 13% in 2016 to 25% in 2022. In 2022, 80% of individuals were prescribed beta-blockers and 64% were prescribed renin-angiotensin inhibitors. Median survival from the first recognition of HFmrEF was 4.7 years (SD 2.7 years). Conclusions Individuals with HFmrEF in a tertiary care integrated health network had high medical complexity and high rates of mortality. Medical therapy use in this population increased over a 6-year period but remained relatively lower than other reports for HFrEF. These results represent a major opportunity for improved treatment of HFmrEF. Better evidence is needed to define recommended therapies for affected individuals.