The effect of Cardiac Resynchronization Therapy (CRT) on functional capacity based on Cardiopulmonary Exercise Testing (CPET): a systematic review and meta-analysis

Abstract Aims Cardiac resynchronisation therapy (CRT) has a class 1a indication for patients with heart failure due to reduced ejection fraction (HFrEF) who also have conduction delay. Post-CRT management pathways are uncommon. Cardiopulmonary exercise testing (CPET) provides objective functional assessments and may serve as a valuable tool in assessing CRT response and guide device optimisation. This systematic review and meta-analysis aimed to assess the effect of CRT on key CPET parameters and identify patients who may benefit from further intervention. Methods A systematic search of MEDLINE, EMBASE, and Cochrane Central (May 2024) identified randomised controlled trials, non-randomised trials, and cohort studies evaluating changes in CPET post-CRT. Primary outcome was peak VO₂, with anaerobic threshold and ventilatory efficiency as secondary outcomes. Results were reported as standardised mean differences (SMD) and effect sizes using Cohen’s d. Results Fourteen studies (12 cohort studies and 2 RCTs) involving 858 patients were included. CRT was associated with significant improvements in peak VO₂ (SMD = 0.62, 95% CI 0.19–1.05, p < 0.001), anaerobic threshold (SMD = 0.70, 95% CI 0.03–1.36, p = 0.04), and ventilatory efficiency (SMD = -0.45, 95% CI -0.68 to -0.21, p < 0.001). Considerable heterogeneity was noted, likely reflecting differences in exercise protocols, patient characteristics, and device programming. Conclusions CRT improves exercise capacity and ventilatory efficiency, reinforcing its physiological benefits beyond cardiac remodelling. CPET may support personalised post-CRT care, including optimisation of device programming, medications, and rehabilitation. Worsening CPET parameters may help identify patients progressing to advanced heart failure, allowing for timely care planning.