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 ̇ $$ \dot{\mathrm{V}} $$ 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. V ̇ $$ \dot{\mathrm{V}} $$ 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 V ̇ $$ \dot{\mathrm{V}} $$ 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).

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.