Multifactorial Determinants of Functional Capacity in Peripheral Arterial Disease. Uncoupling of Calf Muscle Perfusion and Metabolism

Objectives: We aimed to investigate the pathophysiology of peripheral arterial disease (PAD) by examining magnetic resonance imaging (MRI) and spectroscopic (MRS) correlates of functional capacity. Background: Despite the high prevalence, morbidity, and cost of PAD, its pathophysiology is incompletely understood. Methods: Eighty-five patients (age 68 ± 10 years) with mild-to-moderate PAD (ankle-brachial index 0.69 ± 0.14) had their most symptomatic leg studied by MRI/MRS. Percent wall volume in the superficial femoral artery was measured with black blood MRI. First-pass contrast-enhanced MRI calf muscle perfusion and ³¹P MRS phosphocreatine recovery time constant (PCr) were measured at peak exercise in calf muscle. All patients underwent magnetic resonance angiography (MRA), treadmill testing with maximal oxygen consumption measurement, and a 6-min walk test. Results: Mean MRA index of number and severity of stenoses was 0.84 ± 0.68 (normal 0), % wall volume 74 ± 11% (normal 46 ± 7%), tissue perfusion 0.039 ± 0.015 s^-1 (normal 0.065 ± 0.013 s^-1), and PCr 87 ± 54 s (normal 34 ± 16 s). MRA index, % wall volume, and ankle-brachial index correlated with most functional measures. PCr was the best correlate of treadmill exercise time, whereas calf muscle perfusion was the best correlate of 6-min walk distance. No correlation was noted between PCr and tissue perfusion. Conclusions: Functional limitations in PAD are multifactorial. As measured by MRI and spectroscopy, atherosclerotic plaque burden, stenosis severity, tissue perfusion, and energetics all play a role. However, cellular metabolism is uncoupled from tissue perfusion. These findings suggest a potential role for therapies that regress plaque, increase tissue perfusion, and/or improve cellular metabolism. (Comprehensive Magnetic Resonance of Peripheral Arterial Disease; NCT00587678).