Cardiopulmonary exercise testing following conduction system versus biventricular pacing in heart failure: a substudy of the PhysioSync-HF randomized trial

Background Cardiac resynchronization therapy (CRT) improves clinical outcomes and functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB). Conduction system pacing (CSP) has emerged as a physiological alternative to conventional biventricular pacing (BiVP), but important gaps remain regarding cardiorespiratory fitness outcomes following CRT, particularly with CSP strategies. Purpose To compare changes in cardiorespiratory fitness between CSP and BiVP in patients with HFrEF and LBBB undergoing CRT. Methods This prespecified substudy was nested within the PhysioSync-HF trial, which randomized adults with symptomatic HFrEF (NYHA II–III), LVEF <35%, and LBBB to CSP or BiVP. Cardiopulmonary exercise test (CPET) was performed at baseline and repeated at 6 and 12 months after the procedure. All patients were clinically stable and on optimized medical therapy at enrollment. The primary endpoint of this substudy was the change in peak oxygen uptake (VO2 peak) up to 12 months. Secondary endpoints included relative VO2 peak, % predicted VO2, VE/VCO2 slope, and oxygen uptake efficiency slope (OUES). Linear regression models adjusted for baseline values were used to compare groups and assess longitudinal changes. Patients who underwent the index procedure were analyzed according to the randomization assignment (modified intention-to-treat). Results A total of 30 participants underwent CPET at baseline and follow-up with valid measurements. At baseline, mean age was 64.7 ± 8.7 years; 55% were female; BMI was 29 ± 6; LVEF was 27.6 ± 6.5%; and QRS duration was 183 ± 20ms. Peak VO2 improved significantly from baseline to 12 months in both groups (each within-group p < 0.05), with no significant differences between CSP and BiVP (+0.14; 95% CI −0.03 to 0.32; p = 0.11) (Figure). Similar improvements over time were observed for relative VO2 peak, % predicted VO2, OUES, and VE/VCO2 slope with both therapies, with no significant between-group differences (p > 0.05 for all comparisons) (Table). Conclusion In patients with symptomatic HFrEF and LBBB, randomization to either CSP or BiVP resulted in significant improvements in cardiorespiratory fitness and prognostic indicators up to 12 months, with no significant differences between pacing strategies. Given the limited power of this substudy, between-group findings should be interpreted with caution.