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

Figures

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  Figure 1. Flow diagram of participant selection and follow‐up. Patients with stable heart failure (HF) signs and symptoms were primarily included and further screened by exclusion criteria. Cardiopulmonary exercise test and 2‐dimensional (2D) echocardiographic examination were assessed for the high‐intensity interval training (HIIT) participants within 1 week after completing 36 sessions of exercise trainings (immediate physiological adaptations to HIIT in red transparent panel). The same guideline‐directed medical therapy (GDMT) program was applied for HIIT participants after ceasing HIIT and GDMT participants during follow‐up. Serial 2D echocardiographic examinations were performed for all included patients with HF during the 10‐year follow‐up to evaluate the chronic clinical outcomes after HIIT (green transparent panel) on patients with HF. HFmrEF indicates heart failure with mid‐range ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; and LVEF, left ventricular ejection fraction.

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  Figure 2. Left ventricular (LV) remodeling responses to high‐intensity interval training (HIIT) and guideline‐directed medical therapy (GDMT) for participants with different heart failure (HF) phenotypes. Heatmaps show the changes in LV ejection fraction (ΔLVEF), LV end‐diastolic diameter (ΔLVEDD), and LV end‐systolic diameter (ΔLVESD) as the differences in parameters measured during the longitudinal follow‐up to the baseline assessments for different HF phenotypes. HFmrEF indicates heart failure with mid‐range ejection fraction; HFpEF, heart failure with preserved ejection fraction; and HFrEF, heart failure with reduced ejection fraction.

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  Figure 3. Survival for all included participants according to different heart failure (HF) phenotypes. A, Ten‐year survival for all patients with HF who underwent high‐intensity interval training (HIIT) versus guideline‐directed medical therapy (GDMT). B, Patients with HF with reduced ejection fraction (HFrEF). C, Patients with HF with mid‐range ejection fraction (HFmrEF). D, Patients with HF with preserved ejection fraction (HFpEF).

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  Figure 4. Relative risk of all‐cause mortality in all included patients with heart failure during the 10‐year follow‐up. Age, peak oxygen consumption (V˙O2peak), minute ventilation (V˙ E) minute carbon dioxide production (V˙ CO2) slope, and left ventricular end‐diastolic diameter (LVEDD) in red dots were significant risk factors for all‐cause mortality. aHR indicates adjusted hazard ratio; BMI, body mass index; and COex, peak cardiac output during exercise.

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  Figure 5. Causal mediation analysis was assessed by adjusted multiple linear regression for the association between high‐intensity interval training (HIIT) and 10‐year all‐cause mortality in all included patients with heart failure (HF) (red) and patients with HF with left ventricular ejection fraction (LVEF) <50% (blue). The direct association between HIIT and mortality was observed in patients with HF with an LVEF <50%, but not in all included patients with HF. The associations between HIIT and mortality were mediated by left ventricular end‐diastolic diameter (LVEDD) in the above patient classification. IA indicates indirect association; m1, pathway coefficient (95% CI) between HIIT and the mediating factor; and m2, pathway coefficient (95% CI) between the mediating factor and long‐term mortality.