High‐Intensity Interval Training Is Associated With Improved 10‐Year Survival by Mediating Left Ventricular Remodeling in Patients With Heart Failure With Reduced and Mid‐Range Ejection Fraction

Background This study aimed to assess the left ventricular (LV) remodeling response and long‐term survival after high‐intensity interval training (HIIT) in patients with various heart failure (HF) phenotypes during a 10‐year longitudinal follow‐up. Methods and Results Among 214 patients with HF receiving guideline‐directed medical therapy, those who underwent an additional 36 sessions of aerobic exercise at alternating intensities of 80% and 40% peak oxygen consumption (V ̇ V̇ O 2peak) were considered HIIT participants (n=96). Patients who did not undergo HIIT were considered participants receiving guideline‐directed medical therapy (n=118). Participants with LV ejection fraction (EF) V ̇ V̇ O 2peak, serial LV geometry, and time to death were recorded. In all included participants, 10‐year survival was better (P =0. 015) for participants who underwent HIIT (80. 3%) than for participants receiving guideline‐directed medical therapy (68. 6%). An increased V ̇ V̇ O 2peak, decreased minute ventilation carbon dioxide production slope, and reduced LV end‐diastolic diameter were protective factors against all‐cause mortality. Regarding 138 patients with HF with reduced EF (P =0. 044) and 36 patients with HF with mid‐range EF (P =0. 036), 10‐year survival was better for participants who underwent HIIT than for participants on guideline‐directed medical therapy. Causal mediation analysis showed a significant mediation path for LV end‐diastolic diameter on the association between HIIT and 10‐year mortality in all included patients with HF (P <0. 001) and those with LV ejection fraction <50% (P =0. 006). HIIT also had a significant direct association with 10‐year mortality in patients with HF with LV ejection fraction <50% (P =0. 027) but not in those with LV ejection fraction ≥50% (n=40). Conclusions Reversal of LV remodeling after HIIT could be a significant mediating factor for 10‐year survival in patients with HF with reduced EF and those with HF with mid‐range EF.