Cardiac Rehabilitation in the Era of CRT and ARNI: A Missing Link in Heart Failure with Reduced Ejection Fraction Care

Heart failure with reduced ejection fraction (HFrEF) continues to impose a high burden of morbidity and mortality despite significant advances in pharmacologic and device-based therapy. Cardiac resynchronization therapy (CRT) and angiotensin receptor-neprilysin inhibitors (ARNIs) have independently demonstrated substantial benefits in symptoms, health-related quality of life (HRQoL), and survival. Cardiac rehabilitation (CR), incorporating structured exercise, education, and lifestyle optimization, is well established as an effective intervention in HFrEF, yet its role in the era of combined CRT and ARNI therapy remains insufficiently characterized. This literature review synthesizes current evidence on CR in HFrEF populations receiving CRT, ARNI, or both, highlighting its impact on HRQoL, exercise capacity, and functional outcomes. Across diverse study designs-including randomized trials, observational cohorts, and meta-analyses-CR consistently yielded clinically meaningful improvements in patient-reported HRQoL and objective measures such as six-minute walk distance (6MWD) and peak oxygen uptake. Data directly evaluating CR in patients concurrently receiving both CRT and ARNI are lacking; indirect evidence suggests CR is compatible with, and may add to, contemporary device and drug therapy. However, referral rates remain low, indicating an implementation gap despite strong evidence of benefit. The review underscores the importance of integrating CR into contemporary HFrEF care and identifies a pressing need for targeted prospective studies to define its role in patients receiving dual device-pharmacologic therapy.