Muscle metaboreflex dysfunction in cardiovascular disease

Muscle metaboreflex dysfunction has emerged as a key contributor to autonomic imbalance and exercise intolerance across cardiovascular diseases. By amplifying or blunting reflex sympathetic, hemodynamic, and ventilatory responses to metabolite accumulation in contracting skeletal muscle, abnormal metaboreflex activity can worsen peripheral perfusion, impair the matching between oxygen delivery and utilization, and increase symptom burden during exertion. This review integrates physiological and clinical evidence linking metaboreflex dysregulation to impaired cardiopulmonary and skeletal muscle responses, summarizes key approaches used to assess this reflex function in humans, and discusses how cardiac rehabilitation and exercise training may recalibrate these pathways, particularly in heart failure. Sex and menopausal status may modify metaboreflex expression and vasoconstrictor transduction; therefore, we synthesize evidence in both sexes and highlight gaps in female representation and sex-stratified reporting. We appraise exercise modalities used in cardiac rehabilitation and highlight how aerobic exercise improves sympathovagal balance, ventilatory control, and metabolic efficiency, whereas resistance training and inspiratory muscle training provide complementary adaptations in peripheral muscle, vascular function, and respiratory reflex control. In selected stable patients, high-intensity interval training may be incorporated under supervision to potentiate cardiorespiratory gains. This targeted approach to metaboreflex modulation supports individualized, mechanism-driven prescriptions aligned with ventilatory thresholds and clinical status, with expected gains in functional capacity, prognostic markers, and patient-centered outcomes.