Phosphocreatine recovery time constant (PCr) at peak exercise as a potential endpoint for clinical trials in PAD
Journal of Cardiovascular Magnetic Resonance volume 18, Article number: P352 (2016)
Patients with PAD who have intermittent claudication have reduced exercise tolerance, however, the mechanisms are not well understood. Ankle-brachial index (ABI) correlates neither with walking distance nor the degree of claudication or functional limitation as it is only able to measure flow at the macrovascular level. 31phosphocreatine (31p) is a non-invasive marker of mitochondrial capacity in the skeletal muscle providing an insight into muscle metabolism and tissue perfusion. We sought to analyze the relationship of 31p recovery time constant (PCr) and exercise capacity in a population with PAD.
Twenty-three (23) patients with PAD (ABI < 0.9) were prospectively enrolled. All performed supine plantar flexion exercise at 50 rpm using a pedal ergometer until exhaustion or limiting symptoms. PCr was measured by 31p MR spectroscopy using a 3 T Siemens Trio MR scanner during recovery after peak exercise. A single-pulse, surface coil localized 512 msec free induction decay acquisition with 20 averages centered on the midcalf was used. A standard 31p surface coil in the patient table is employed. PCr was then calculated using a monoexponential fit of phosphocreatine concentration versus time, beginning at cessation of exercise. Patients later exercised on a treadmill (Gardner exercise protocol) and completed a 6 min-walk protocol. Peak VO2 (peak oxygen consumption) was measured. METS (Metabolic equivalents), total distance (feet), total exercise time and start of claudication time were also recorded.
The mean age was 67 ± 11 years, 63% were male, 63% were Caucasian, the mean ABI was 0.69 ± 0.09. The mean logPCr was 1.68 ± 0.25, 6-min walk distance 1024.7 ± 351.9 feet, 6-min walk start of claudication 330.0 ± 274.2 feet, peak VO2 13.4 ± 3.7 (ml/kg/min), METS 3.8 ± 1.1, treadmill exercise time 5.8 ± 4.4 min. PCr correlated with 6-min walk total distance (Pearson's r: 0.43, p = 0.04), total METS (r = 0.49, p = 0.02) and peak VO2 (r = 0.49, p = 0.02). No correlation was seen between PCr and claudication distance (p = 0.27) nor start of leg discomfort (p = 0.24). ABI did not correlate with any of these exercise parameters.
PCr recovery time constant correlates significantly with total distance, METS and peak VO2 in patients with PAD whereas ABI does not. PCr recovery kinetics could be used a therapeutic target in novel interventions in patients with PAD as it correlates better with exercise parameters than ABI.
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Gonzalez, J.A., Li, Y., Shaw, P.W. et al. Phosphocreatine recovery time constant (PCr) at peak exercise as a potential endpoint for clinical trials in PAD. J Cardiovasc Magn Reson 18 (Suppl 1), P352 (2016). https://doi.org/10.1186/1532-429X-18-S1-P352