Author(s): HSU, C., FU, T.C., WANG, C.H., WANG, J.S., Institution: KEELUNG CHANG GUNG MEMORIAL HOSPITAL, Country: TAIWAN, Abstract-ID: 132

INTRODUCTION:
Heart failure (HF) is a clinical syndrome resulting from structural or functional abnormalities of the heart. In addition, healthcare costs related to heart failure in the United States are projected to reach $30.7 billion by 2030. Consequently, the management of HF has become a significant challenge in modern medicine. Emerging evidence suggests that the serum microRNA (miRNA) profile is influenced by exercise. Therefore, the aim of this study is to identify changes in the serum miRNA profile induced by high-intensity interval training (HIIT) in patients with HF and to examine how these changes affect cardiomyocytes and cardiac fibroblasts.
METHODS:
We enrolled 40 HF patients with a mean age of approximately 60 years. All medication prescriptions were based on the guideline-directed medical therapy (GDMT) issued by the American Heart Association. Each participant underwent cardiopulmonary exercise testing (CPET), echocardiography, quality-of-life (QoL) assessment, and serum miRNA profiling. All participants were then randomly assigned to either a HIIT group or a GDMT-only group, with 20 patients in each arm. In addition to standard pharmacological treatment, HIIT participants performed supervised exercise sessions in the hospital, consisting of five cycles of 3 minutes at 80% peak oxygen consumption (VO₂peak) followed by 3 minutes at 40% VO₂peak, for a total of 30 minutes per session. The HIIT participants completed 36 sessions (three times per week), while the GDMT group underwent follow-up testing after 3–4 months using the same assessment protocol.
RESULTS:
Baseline characteristics were comparable between the two groups. HIIT significantly improved VO₂peak, oxygen uptake efficiency slope (OUES), heart rate reserve (HRR), and left ventricular ejection fraction (LVEF), while markedly reducing the ventilation–CO₂ slope (VE-VCO2 slope), left ventricular end-systolic volume (LVEDV), and left ventricular mass (LVM). HIIT also resulted in a meaningful reduction in serum levels of let-7e-5p, miR-106b-3p, miR-181a-5p, miR-29a-3p, miR-361-3p, miR-421, miR-425-5p, miR-6765-3p, and miR-93-3p. Subsequent in vitro experiments using serum collected before and after intervention in the HIIT group and at baseline and follow-up in the GDMT group revealed that only miR-29a-3p exhibited significant differential regulation: its mRNA expression decreased in cardiomyocytes but increased in cardiac fibroblasts.
CONCLUSION:
Pathological remodeling of the heart refers to structural and functional changes that occur following cardiac injury, such as ventricular dilation, myocardial wall thickening, or myocardial fibrosis. These alterations lead to impaired systolic and diastolic function and may ultimately progress to heart failure. Our findings indicate that high-intensity interval training (HIIT) can reverse pathological cardiac remodeling, an effect that appears to be mediated through the differential regulation of miR-29a-3p in cardiomyocytes and cardiac fibroblasts.