Screening for features of advanced heart failure with reduced ejection fraction in stable outpatients - The SAINTS study

Introduction Timely identification of outpatients with heart failure (HF) with reduced ejection fraction (HFrEF) transitioning toward advanced HF is challenging, and the prevalence of advanced HF in this population is unknown. Methods Outpatients with chronic HF, an LVEF ≤30%, and NYHA class II–III symptoms despite medical therapy were identified from nine HF clinics by prescreening of electronic health records. Eligible patients were invited to undergo screening for features of advanced HFrEF defined as: (1) LVEF ≤30%; (2) NT-proBNP >2000 pg/mL; and (3) CPET with pVO 2 <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/m 2 and pulmonary capillary wedge pressure > 12mmHg. Results Among 1,020 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% CI 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 eGFR were associated with features of advanced HFrEF. A history of ventricular tachycardia or fibrillation, higher NT-proBNP, lower pVO 2 , KCCQ-OSS, and eGFR were associated with hemodynamic compromise. Conclusions 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. Study registration number NCT05299879