Screening for Features of Advanced Heart Failure with Reduced Ejection Fraction in Stable Outpatients

Timely identification of outpatients with heart failure with reduced ejection fraction (HFrEF) transitioning toward advanced heart failure (HF) is challenging, and the prevalence of advanced HF in this population is unknown.

Outpatients with chronic HF, left ventricular ejection fraction ≤30%, and New York Heart Association class II-III symptoms despite medical therapy were identified from 9 HF clinics by the prescreening of electronic health records. Eligible patients were invited to undergo screening for features of advanced HFrEF, defined as (1) left ventricular ejection fraction ≤30%; (2) N-terminal pro-B-type natriuretic peptide >2000 pg/mL; and (3) a cardiopulmonary exercise test with peak oxygen uptake <12 or 14 mL/kg/min or 6-minute walk distance <300 m. A subgroup underwent right heart catheterization. Logistic regression models were used to identify markers of advanced HF and hemodynamic compromise, defined as cardiac index <2.2 L/min/m² and pulmonary capillary wedge pressure >12 mm Hg.

Among 1020 identified patients, 424 accepted investigator contact, and 300 (median age 64 years, 21% women) were screened. Features of advanced HFrEF were identified in 19 patients (6.3%; 95% confidence interval 3.9%-9.7%). Hemodynamic compromise was present in 30% of the patients, including 83% and 23% of those meeting and not meeting the clinical advanced HF criteria, respectively. Lower systolic blood pressure, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), maximal workload, hemoglobin, and estimated glomerular filtration rate (eGFR) were associated with features of advanced HFrEF. A history of ventricular tachycardia or fibrillation, greater N-terminal pro-B-type natriuretic peptide, lower peak oxygen uptake, KCCQ-OSS, and eGFR were associated with hemodynamic compromise.

Screening outpatients with an ejection fraction ≤30% and mild-to-moderate symptoms identifies previously unrecognized features of advanced HFrEF in approximately 6%. Nearly one-third of the screened patients had hemodynamic compromise irrespective of whether they exhibited features of advanced HFrEF. Simple clinical markers such as eGFR, hemoglobin, or KCCQ-OSS may refine the screening process.