Multifactorial Determinants of Functional Capacity in Peripheral Arterial Disease

We aimed to investigate the pathophysiology of peripheral arterial disease (PAD) by examining magnetic resonance imaging (MRI) and spectroscopic (MRS) correlates of functional capacity. Despite the high prevalence, morbidity, and cost of PAD, its pathophysiology is incompletely understood. Eighty-five patients (age 68±10) with mild-to-moderate PAD (ankle brachial index (ABI) 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 31 P MRS phosphocreatine recovery time constant (PCr) were measured at peak exercise in calf muscle. All patients underwent MR angiography (MRA), treadmill testing with VO 2 max measurement and a 6-minute walk test. 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 sec −1 (normal, 0.065±0.013 sec −1 ), and PCr 87±54s (normal, 34±16s). MRA index, % wall volume, and ABI correlated with most functional measures. PCr was the best correlate of treadmill exercise time, whereas calf muscle perfusion was the best correlate of 6-minute walk distance. No correlation was noted between PCr and tissue perfusion. Functional limitations in PAD are multifactorial. As measured by magnetic resonance imaging and spectroscopy, atherosclerotic plaque burden, stenosis severity, and 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.