Effects of a 12-week supervised multicomponent training on skeletal muscle mitochondrial function in patients with heart failure with preserved ejection fraction
A Martinez-Dominguez, M Gutierrez-Garcia, S Oscoz-Ochandorena, M Izquierdo, R Ramirez-VelezAbstract
Background/Introduction
Heart failure with preserved ejection fraction (HFpEF) is the most prevalent heart failure phenotype and is marked by profound exercise intolerance. Peripheral skeletal muscle abnormalities, particularly impaired mitochondrial oxidative capacity, may contribute to limited functional capacity in HFpEF, yet mitochondrial adaptations to exercise training remain insufficiently characterized.
Purpose
To evaluate the effects of a 12-week supervised multicomponent training program on skeletal muscle mitochondrial respiratory function in patients with HFpEF compared with a contemporaneous HFpEF control group.
Methods
This is a secondary analysis of 25 patients with HFpEF (mean [SD] age, 66 [9.7] years) underwent vastus lateralis muscle biopsies at baseline and after a 12-week intervention period (exercise group, n = 16; control group n = 9). Mitochondrial respiratory function (pmol O₂·s⁻¹·mg⁻¹ tissue) was quantified in permeabilized muscle fibers using high-resolution respirometry with a standardized substrate–inhibitor titration protocol. Body composition was evaluated by dual-energy X-ray absorptiometry. Between-group differences in postintervention outcomes were evaluated using ANCOVA, with adjustment for baseline values, age, sex, and baseline leg lean mass.
Results
After adjusting for covariates, mitochondrial respiration was significantly higher in the exercise group compared with controls across multiple respiratory states. Compared with control group, complex I–linked respiration increased by 24.1 pmol O₂·s⁻¹·mg⁻¹ (95% CI, 8.4–39.8; Cohen’s d = 1.66), and complex II–linked respiration increased by 10.5 pmol O₂·s⁻¹·mg⁻¹ (95% CI, 2.3–18.7; Cohen’s d = 1.36). Oxidative phosphorylation–supported respiration increased by 25.9 pmol O₂·s⁻¹·mg⁻¹ (95% CI, 7.5–44.4; Cohen’s d = 1.49), and maximal electron transport system capacity increased by 20.9 pmol O₂·s⁻¹·mg⁻¹ (CI 1.7–40.2; Cohen’s d = 1.13).
Conclusion(s)
In patients with HFpEF, a 12-week supervised multicomponent exercise training program was associated with clinically relevant improvements in skeletal muscle mitochondrial oxidative capacity. These findings support peripheral mitochondrial plasticity as a plausible mechanism underlying exercise-related functional benefits and reinforce supervised exercise training as a key non-pharmacological therapeutic strategy for HFpEF. ClinicalTrials.gov ID NCT07251361