The Mechanism of Effort Intolerance in Patients with Peripheral Arterial Disease: a Combined Stress Echocardiography and Cardiopulmonary Exercise Test

Background Data to delineate exercise intolerance in patients with peripheral arterial disease (PAD) are scarce. We used a combined stress echocardiography and cardiopulmonary exercise test (CPET) to explore effort intolerance in PAD. Methods Twenty-eight patients who had both PAD and coronary artery disease (CAD) were compared with sex and age-matched 31 CAD patients and 15 normal controls using a symptom-limited ramp bicycle CPET on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation: (VO2)/(echocardiography-calculated cardiac output) at each activity level. Results Along stages of exercise (unloaded; anaerobic threshold; peak), in PAD+CADF patients compared with CAD or controls: diastolic function worsened (E/e’ 13.2±3.1 vs 9.3±2.4 vs 9.6±4; 16.6±4.3 vs 10.4±2.5 vs 9.1±3.8; 15.8±4 vs 11.9±2.9 vs 9.1±4.1), and oxygen consumption (6.1±1.4 vs 5.8±1.9 vs 6.5±2.5;14.2±1.8 vs 17.1±2.9 vs 18.1±3.3; 14.9±2 vs 19.3±2.5 vs 22±3.6 ml/kg/min) and oxygen pulse (6.5±1.9 vs 6.5±2 vs 6.6±2.3; 8.2±1.8 vs 10±2.4 vs 8.1±2.3; 8.1±2.2 vs 11.1±2 vs 11.7±2.6ml/beat) were reduced. Notably, oxygen pulse was blunted due to an insufficient increase in both stroke volume (89±11 vs 92±11 vs 92±13; 95±10 vs 104±9 vs 103±11; 86±10 vs 97±10 vs 98±11ml) and oxygen extraction (0.06±0.03 vs 0.07±0.03 vs 0.07±0.03; 0.09±0.03 vs 0.12±0.03 vs 0.12±0.03; 0.09±0.03 vs 0.13±0.03 vs 0.13±0.03l/l). Chronotropic incompetence was more prevalent in PAD patients and persisted after correction for beta-blockers use (62% vs 42% and 11% respectively). Reduced ventilatory efficiency (peak VE/VCO2 36.8±4.9 vs 31.5±4 vs 30.5±5l/l) and reduced mechanical efficiency (slope of oxygen consumption/work rate 8.96±0.42 vs 10.37±0.41 vs 10.8±0.49l/W) were found. Conclusion Exercise limitation is affected by diastolic dysfunction, chronotropic incompetence and peripheral factors in PAD patients. Clinical perspectives Peripheral arterial disease (PAD) is characterized by exercise intolerance. Yet, the mechanism behind this limitation is not well characterized. We show here that effort limitation in PAD is caused by a combination of central and peripheral cardiovascular factors including diastolic dysfunction, chronotropic incompetence and insufficient peripheral muscle oxygen extraction. These data may assist targeting future therapeutic measures.