Independent prognostic value of ejection fraction, resting coronary flow, coronary flow reserve, myocardial viability, and inducible ischemia in heart failure with a reduced ejection fraction

Abstract

Abstract Background and Aims Patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF) have a heterogeneous prognosis, and assessment of coronary physiology with coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) may complement established predictors based on wall motion. Methods and results In a prospective multicenter study design, we enrolled 1,408 HF patients (age 66±12 years, 1,035 men), with EF <50%, 743 (53%) with coronary artery disease, and 665 (47%) with normal coronary arteries. Recruitment (years 2004-2022) involved 8 accredited laboratories, with inter-observer variability <10% for CFV measurement. Baseline CFV (abnormal value >31 cm/s) was obtained by pulsed-wave Doppler in mid-distal LAD. Coronary flow velocity reserve (CFVR, abnormal value ≤2.0) was assessed with exercise (n=99), dobutamine (n=100), and vasodilator stress (dipyridamole in 1,149, adenosine in 60). Inducible myocardial ischemia was identified with wall motion score index (WMSI) stress> rest (cut-off ∆≥0.12). LV contractile reserve (CR) was identified with WMSI stress< rest (cutoff ∆≥0.25). Test response ranged from score 0 (EF>30%, CFV ≤31 cm/s, CFVR >2.0, LVCR present, ischemia absent) to score 5 (all steps abnormal). All-cause death was the only end-point. Results During a median follow-up of 990 days, 253 patients died. Independent predictors of death were EF (HR: 0.956, 95% CI: 0.943-0.968, p<0.0001), CFV (HR: 2.407, 95% CI: 1.871-3.096, p<0.001), CFVR (HR: 3.908, 95% CI: 2.903-5.260, p<0.001), stress-induced ischemia (HR: 2.223, 95% CI: 1.642-3.009, p<0.001), and LVCR (HR: 0.524, 95% CI: 0.324-.647, p=0.008). The annual mortality rate was lowest (1.2%) in patients with a score of 0 (n=61) and highest (31.9%) in patients with a score of 5 (n=15, p<0.001). Conclusion High resting CFV predicts worse survival in ischemic and nonischemic HF with reduced EF. The value is independent and additive to resting EF, CFVR, LVCR, and inducible ischemia.