Comparative efficacy of baroreflex activation therapy, cardiac contractility modulation, and cardiac resynchronization therapy in heart failure with reduced ejection fraction: a systematic review and network meta-analysis of randomized controlled trials

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) remains a major global health burden despite advances in guideline-directed medical therapy (GDMT). Device-based therapies-including baroreflex activation therapy (BAT), cardiac contractility modulation (CCM), and cardiac resynchronization therapy (CRT)-target distinct autonomic, contractile, and electrical mechanisms. However, their comparative effectiveness across structural, functional, and clinical outcomes remains uncertain. METHODS: We performed a systematic review and network meta-analysis of randomized controlled trials in accordance with PRISMA-NMA guidelines (PROSPERO CRD420251087472). PubMed, Embase, Scopus, and Google Scholar were searched for trials enrolling adults with HFrEF and left ventricular ejection fraction (LVEF) ≤40%. Random-effects frequentist models were used, with GDMT as the reference comparator. Outcomes included change in LVEF, health-related quality of life (HRQoL), exercise capacity, New York Heart Association (NYHA) functional class, heart failure-related hospitalization, and all-cause mortality. Treatment rankings were estimated using the surface under the cumulative ranking curve (SUCRA). RESULTS: Nineteen trials involving 10,125 participants were included. BAT ranked highest for improvement in LVEF, HRQoL, six-minute walk distance, and NYHA class. CRT demonstrated the greatest improvement in peak oxygen consumption, whereas CCM ranked best for reducing heart failure-related hospitalization. None of the device therapies significantly reduced all-cause mortality. Between-study heterogeneity was low to moderate, and sensitivity analyses confirmed the robustness of the findings. CONCLUSIONS: BAT, CCM, and CRT provide complementary benefits beyond GDMT, supporting a phenotype-guided approach to device therapy in patients with HFrEF.