CONGRESS ABSTRACT

Background and aims: heart failure with preserved ejection fraction (HFpEF) is frequent and challeging clinical syndrome among patients with diabetes whose pathophysiology remains relatively poorly characterized; we aimed at analyzing the effects of diabetes on cardiopulmonary and metabolic determinants of effort intolerance in HFpEF. Methods: patients with effort intolerance underwent cardiopulmonary exercise testing (CPET) with concomitant stress echocardiography; we applied indirect calorimetry to breath-by-breath gas exchange to analyze lipid and glucose oxidation rates to a subgroup of 16 vs 16 matched patients. Patients with HFpEF and type 2 diabetes (T2D) were compared to matched patients with HFpEF and normal glucose tolerance. Results. We analyzed 66 patients with diabetes and 130 patients with normal glucose tolerance, matched for age (78±4 vs 77±10 years, p=0.7857), sex (males 59 vs 54%, p=0.4849), and BMI (27.3±4.4 vs 26.8±4.4 kg/mq, p=0.3711). Patients with diabetes had lower peak VO2 (12.4±2.8 vs 13.6±4.4, p=0.0095) with respect to controls, despite having identical hemodynamic response (cardiac output, vascular systemic resistance, peripheral extraction), systolic function (ejection fraction, TAPSE, global longitudinal strain 15.1±3.4 ±4.4 vs 15.0±3.5, p=8753) and systolic reserve, as well as ventilatory function (all p>0.5). Lipid oxidation rates were reduced in patients with T2D, including maximal fat oxidation (MFO, 0.14±0.04 vs 0.19±0.07 g/min, p=0.0430) with early reliance on glucose oxidation (Figure, panel A). Of note, MFO and peak VO2 were directly correlated (p=0.0151, see Figure panel B). Conclusions. Among patients with HFpEF, T2D is associated to worse cardiopulmonary performance with reduced peak VO2 despite similar ventilatory and hemodynamic responses. In an exploratory analysis, patients with T2D displayed reduced lipid oxidation rates that are strongly correlated to peak VO2, suggesting that diabetes-related impairments in muscle oxidative capacity might contribute to reducing functional capacity in this population.