Baseline assessment and comparison of arterial anatomy, hyperemic flow, and skeletal muscle perfusion in peripheral artery disease: The Cardiovascular Cell Therapy Research Network “Patients with Intermittent Claudication Injected with ALDH Bright Cells” (CCTRN PACE) study

Abstract

Background Peripheral artery disease (PAD) is important to public health as a major contributor to cardiovascular morbidity and mortality. Recent developments in MRI techniques permit improved assessment of PAD anatomy and physiology, and may serve as surrogate endpoints after pro-angiogenic therapies. Methods The “Patients with Intermittent Claudication Injected with ALDH Bright Cells” (PACE) study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the physiologic impact and potential clinical efficacy of autologous bone marrow-derived ALDHbr stem cells. The primary MRI endpoints of the study are; 1) total collateral count, 2) calf muscle plasma volume (a measure of capillary perfusion) by dynamic contrast-enhanced MRI, and 3) peak hyperemic popliteal flow by phase contrast MRI. Results The inter- and intra-reader and test-retest results demonstrated good-to-excellent reproducibility (ICC range: 0.61–0.98) for all MR measures. The PAD participants (n=82) had lower capillary perfusion measured by calf muscle plasma volume (3.8 vs 5.6%), and peak hyperemic popliteal flow (4.1 vs 13.5 ml/s) as compared to the normal participants (n=16), with a significant level of collateralization. Conclusions Reproducibility of the MRI primary endpoints in PACE was very good to excellent. The PAD participants exhibited decreased calf muscle capillary perfusion as well as arterial flow reserve when compared to normal participants. The MRI tools utilized in PACE may advance PAD science by enabling accurate measurement of PAD microvascular anatomy and perfusion before and after stem cell or other PAD therapies.

Leg blood flow and skeletal muscle microvascular perfusion responses to submaximal exercise in peripheral arterial disease

“…We found that calf muscle microvascular perfusion after 5 min of cuff occlusion was impaired in patients with PAD. Postocclusion time to peak acoustic intensity was longer in patients with PAD than control participants, which verifies the findings of a previous CEU study by Amarteifio et al (1) and is consistent with the perfusion limit reported in studies of patients with PAD using magnetic resonance imaging (19,31). In healthy individuals, postocclusion reactive hyperemia is predominantly determined by vascular resistance at the level of the microvessels (28), whereas in patients with PAD, the conduit artery resistance at the site of the arterial stenosis also likely contributes to the hyperemic response.…”

Peripheral arterial disease screening and diagnostic practice: A scoping review

“…Peak arterial blood velocity was reliable and valid as an outcome measure for clinical study effects of thermotherapy or prostacyclin plus peroneal nerve stimulation on patients with PAD. Collateral artery counts and capillary perfusion measured by MRA were reportedly reliable outcome measures in clinical studies, reflecting total vessel counts and lumen volumes …”

Every PACE Counts

“…The MRI-based assessment of collateral count, peak hyperemic flow, and capillary perfusion provide a refined picture of skeletal muscle blood flow as compared to hemodynamic measures such as ankle-brachial index. 8 But all three MRI-based measures were not associated with peak walking time at baseline or after treatment, suggesting a divergence of tissue blood flow and functional status in PAD. It is possible that a treatment that delivered a more profound effect on tissue perfusion would be needed to evaluate the relevance of these imaging metrics.…”