A cardiovascular-motor axis framework for perfusion-mediated motor impairment

Abstract

Cardiovascular disease is the leading cause of death worldwide, and among survivors of heart failure, peripheral arterial disease, valvular disease, and atrial fibrillation many develop motor impairment: weakness, slow gait, sarcopenia, frailty. These deficits are usually attributed to deconditioning or coexisting conditions. This narrative review advances a different hypothesis: that reduced arterial blood delivery, from a failing pump or a narrowed artery, itself drives motor impairment at every level of the motor pathway, from cortex to muscle fibre. We group cardiovascular conditions into systemic models of low blood flow (heart failure with reduced or preserved ejection fraction, low-flow aortic stenosis, atrial fibrillation) and regional models of arterial obstruction (carotid, subclavian, and vertebral stenosis; peripheral arterial disease), quantifying the perfusion deficit where haemodynamic data exist. We then examine mechanisms: cerebral hypoperfusion that thins the motor cortex and weakens motor planning; vulnerability of the cerebellum, basal ganglia, and spinal motor neurons, impairing coordination and gait; ischaemic peripheral nerve damage that denervates muscle; loss of muscle capillaries, mitochondrial injury, and failed regeneration; amplified feedback from underperfused muscle that suppresses central motor drive; and gating of corticospinal excitability by the cardiac cycle. Causality is supported by within-patient comparisons, in which a lateralised ischaemic limb or hypoperfused hemisphere weakens while the opposite side, under identical systemic conditions, does not; by graded perfusion-to-outcome relationships; and by recovery after cardiac transplantation, ventricular assist device support, valve replacement, and revascularisation. Deconditioning amplifies these effects rather than causing them, so treatment should restore blood flow and rebuild muscle together.