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

Am Heart J. 2017 Jan;183:24-34. doi: 10.1016/j.ahj.2016.09.013. Epub 2016 Oct 2.

Abstract

Background: Peripheral artery disease (PAD) is important to public health as a major contributor to cardiovascular morbidity and mortality. Recent developments in magnetic resonance imaging (MRI) techniques permit improved assessment of PAD anatomy and physiology, and may serve as surrogate end points after proangiogenic therapies.

Methods: The 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 end points of the study are as follows: (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 (PC-MRI).

Results: The interreader and intrareader and test-retest results demonstrated good-to-excellent reproducibility (interclass correlation coefficient range 0.61-0.98) for all magnetic resonance 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 13.5mL/s) as compared with the healthy participants (n=16), with a significant level of collateralization.

Conclusions: Reproducibility of the MRI primary end points in PACE was very good to excellent. The PAD participants exhibited decreased calf muscle capillary perfusion as well as arterial flow reserve when compared with healthy participants. The MRI tools used 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Autografts
  • Double-Blind Method
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Injections, Intramuscular
  • Intermittent Claudication / physiopathology
  • Intermittent Claudication / therapy*
  • Leg / blood supply*
  • Leg / diagnostic imaging
  • Magnetic Resonance Angiography
  • Magnetic Resonance Imaging
  • Male
  • Muscle, Skeletal / blood supply
  • Peripheral Arterial Disease / physiopathology*
  • Peripheral Arterial Disease / therapy*
  • Regional Blood Flow