Abstract 4137264: Subclassification of Peripheral Artery Disease Based on Muscle Force: Leg Failure with Reduced Muscle Force and Leg Failure with Preserved Muscle Force

Introduction: All claudicating patients with peripheral artery disease (PAD) exhibit leg failure, as evidenced by distinct walking impairment. However, based on a detailed evaluation of leg biomechanics, some claudicating patients maintain preserved leg muscle strength, while others demonstrate reduced strength. In this study, we aim to compare the clinical and physiological characteristics of the two groups. Methods: Fifty-four claudicating patients were categorized into two groups: leg failure with preserved muscle force (LEF-PF) versus leg failure with reduced muscle force (LEF-RF), based on the peak torque (PT) from performing maximum isometric plantar flexion contractions on a Biodex system. All patients underwent history and physical exam, measurement of leg hemodynamics, walking performance and quality of life, and gastrocnemius biopsy to evaluate the histology and biochemistry of the affected leg muscles. We used independent samples T test and chi-square test to compare the two groups. Results: LEF-PF (N=19, PT 92±15 Nm) and LEF-RF (N=35, PT 49±13 Nm) had similar demographic and comorbidity profiles. While ankle-brachial index didn't differ between the two groups, during the reactive hyperemia test, ankle pressure of LEF-RF dropped more significantly (p=0.021) upon occlusion release and took longer to recover (p=0.023). Both groups performed similarly on the Gardner Treadmill test, but LEF-PF performed better in the 6-Minute Walking test (p=0.062). LEF-PF also trended towards higher scores on the modified falls efficacy scale (p=0.056). Histologically, gastrocnemius muscle from LEF-PF had larger myofibers, while biochemically, they exhibited lower mitochondrial respiratory activity dependent on complex-II compared to LEF-RF. Conclusion: Our study presents a novel approach to understanding the physiology of claudication, focusing on the strength of the ischemic muscles. Despite comparable demographics and hemodynamics at rest, notable differences separate the two groups during stress-induced hemodynamics, walking performance, myofiber histology, and mitochondrial biochemistry. Further investigations are necessary to elucidate the underlying mechanisms behind the differences in muscle strength among patients with claudication. Such insights may enhance our understanding of PAD physiology and potentially correlate with variations in mortality rates, progression to more advanced PAD stages, and responses to different therapeutic interventions.