Incremental Value of Bi-Ventricular Ejection Fraction (BiVEF) Phenotyping for the Discrimination of Heart Failure Symptoms and Clinical Outcomes: A Cardiovascular Magnetic Resonance Study of 9,437 Patients

Background Left ventricular ejection fraction (LVEF) continues to be employed as the principle phenotypic marker for the classification, prognostication, and management of cardiovascular disease. However, expanding evidence identifies similarly important roles for right ventricular ejection fraction (RVEF) across multiple referral cohorts, raising the consideration of bi-ventricular ejection fraction (BiVEF) based phenotyping in broader clinical practice. We assessed the value of cardiovascular magnetic resonance (CMR)-based BiVEF phenotyping versus conventional LVEF-only phenotyping for the prediction of NYHA functional class and future heart failure (HF) outcomes. Methods 9,437 consecutively enrolled adult patients clinically referred for CMR were evaluated for NYHA class ≥II at time of imaging and a future composite outcome of HF hospitalization, HF death, and need for cardiac transplantation or LV assist device. Results Median age was 57 years (Q1, Q3 44-66, 62% male). Across all LVEF strata, RVEF<45% was independently associated with NYHA ≥II after comprehensive adjustment for baseline clinical and imaging characteristics. Respective adjusted odds ratios for RVEF <45% versus ≥45% were 2.30 (1.79-2.97), 1.58 (1.13-2.20), and 2.01 (1.44-2.79) for LVEF <40%, 40-50, and >50% categories (p<0.001, =0.007, and <0.001; respectively). Over a median follow-up of 3.9 years, 766 patients (8%) experienced the HF outcome. In a multivariable Fine-Gray model, the respective adjusted HR sub for LVEF <40% and 40-50% were 2.13 (1.64-2.77) and 1.70 (1.33-2.17); p<0.001) relative to LVEF >50%. In this model, RVEF <45% was associated with 1.52 (1.25-1.86) greater hazard for future HF outcome versus RVEF ≥45% (p<0.001). Conclusions RV contractile health is independently associated with HF symptoms and identifies patients at elevated risk of future HF outcomes. Incremental prognostic value from BiVEF phenotyping is delivered versus LVEF-only phenotyping.