Functional capacity improvement in patients with chronic heart failure treated with cardiac resynchronisation therapy is not associated with increased chronotropic reserve

Background Chronotropic incompetence is common in patients with chronic heart failure, but its causal relationship with exercise intolerance remains uncertain. The 6-minute walk test (6MWT) is a validated tool to assess functional capacity in this population. Purpose To evaluate changes in walked distance and maximum heart rate (MaxHR) during the 6MWT after 12 months of cardiac resynchronisation therapy (CRT). Methods We analysed data from a multicentre, randomised, non-inferiority trial (CRT-NEXT) enrolling patients with standard CRT-defibrillator (CRT-D) indication, no sinus node dysfunction under optimised medical therapy, and resting sinus rate ≥45 beats/min (bpm). Patients were randomised 1:1 to receive a CRT-DX system (capable of atrial sensing without atrial lead, programmed to VDD mode at 35 bpm) or conventional CRT-D system (programmed to DDD mode at 50 bpm). The 6MWT was performed before and 12 months after device implantation. Baseline and 12-month walked distance and the corresponding MaxHR values were compared between the two study arms using the linear mixed-effect models with random intercepts at the patient level. Results A total of 636 patients (age 68 ± 10 years, 71% male, LVEF 29% ± 6%) were randomised, and 585 (92%) completed the 12 month follow-up. The 6MWT distance increased significantly at 12 months compared with baseline (p<0.0001; CRT-DX: from 344 ± 120 m to 400 ± 116 m; CRT-D: from 347 ± 129 m to 398 ± 132 m), without between-group differences in change (p=0.41) (Figure). In contrast, MaxHR slightly decreased from baseline to 12-month follow-up (p=0.015; CRT-DX: from 92 ± 15 bpm to 90 ± 16 bpm; CRT-D: from 94 ± 16 bpm to 90 ± 17 bpm), without differences in change between groups (p=0.44). Conclusion In patients with chronic heart failure treated with CRT, functional capacity improves despite no increase in chronotropic reserve. These findings support the concept that chronotropic incompetence and resting heart rate are not causal factors of exercise intolerance in chronic heart failure patients with systolic dysfunction, as previously observed during acute testing (J Am Coll Cardiol 2016;67:1885-96).6MWT distance and MaxHR