Contribution of reduced skeletal muscle perfusion reserve to exercise intolerance in HFpEF

Abstract Methods Transthoracic echocardiography and skeletal muscle microvascular perfusion by contrast-enhanced ultrasound were performed at rest and immediately post exercise test in 77 HFpEF patients in NYHA class II and III, and in 20 age- and sex-matched individuals with a similar profile of comorbidities, but normal exercise tolerance. Exercise reserve of cardiac function parameters and skeletal muscle perfusion was calculated by subtracting resting value from exercise value. Results HFpEF patients demonstrated impairment of left ventricular (LV) and left atrial (LA) function reserve as reflected by lower exercise-induced increases in LV global longitudinal strain, LA reservoir strain, cardiac output and e’ mitral annular velocity, and higher increase in E/e’ ratio (Table). Similarly, skeletal muscle microvascular blood flow (MBF) reserve was lower in HFpEF patients than in the referents. There was no significant difference between the study group and the control group in resting MBF. MBF reserve was significantly associated with exercise capacity (r = 0.34; p = 0.004) and cardiac output reserve (r = 0.24; p = 0.04). In multivariable analysis including clinical and demographic variables, LV and LA components of cardiac functional reserve (LV global longitudinal strain, LA reservoir strain, cardiac output, e’ and E/e’) and MBF reserve, change from rest to exercise in MBF (beta 0.32, SE 0.10, p = 0.003) was in addition to patient age, sex and LV strain reserve among the independent correlates of exercise capacity. Conclusions Skeletal muscle perfusion reserve is impaired in HFpEF, and is associated with reduced exercise capacity independent of clinical, demographic and "central" cardiac factors. Accordingly, our results provide a rationale for extending the spectrum of pathophysiological milieu to be considered when planning patient management strategies in HFpEF over skeletal muscle-associated contributors to exercise intolerance.