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.

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 (V̇$$ \dot{\mathrm{V}} $$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) <40%, ≥40% and <50%, and ≥50% were considered to have HF with reduced EF, HF with mid‐range EF, and HF with preserved EF, respectively. V̇$$ \dot{\mathrm{V}} $$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 V̇$$ \dot{\mathrm{V}} $$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).

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.