Exercise-Related Mitral Regurgitation and Right Ventricle to Pulmonary Circulation Uncoupling Across the Heart Failure Phenotypes

Exercise-related mitral regurgitation (Ex-MR) is one of the mechanisms that contribute to reduced functional capacity in heart failure (HF). Its prevalence is not well defined across different HF subtypes. The aim of the present study is to describe functional phenotypes and cardiac response to exercise in HFrEF, HFmrEF and HFpEF, according with Ex-MR prevalence. A total of 218 HF patients (146 men, 68[59-78] years), 137 HFrEF, 41 HFmrEF, 40 HFpEF and 23 controls were tested with cardiopulmonary exercise test combined with exercise-echocardiography. Ex-MR was defined as development of at least moderate (³2+/4+) regurgitation during exercise. Ex-MR was highly prevalent in the overall population (52%) although the prevalence differed as follows: 82/137(60%) in HFrEF, 17/41(41%) in HFmrEF and 14/40(35%) in HFpEF (p< .05). Ex-MR was associated with a high rate of ventilation (VE) to carbon dioxide production (VCO2) in all HF subtypes (31.2[26.6-35.6] vs 33.4[29.6-40.5], p=0.004; 28.1[24.5-31.9] vs 34.4[28.2-36.7], p=0.01; 28.8[26.6-32.4] vs 32.2[29.2-36.7], p=0.01) and with lower peakVO2 in HFrEF and HFmrEF. Right ventricle to pulmonary circulation (RV-PC) uncoupling was observed during exercise in HFrEF and HFpEF patients (peak TAPSE/SPAP: HFrEF 0.40[0.30-0.57]vs0.29[0.23-0.39],p=0.006; HFpEF 0.44[0.28-0.62]vs0.31[0.27-0.33],p=0.05). HFpEF with Ex-MR showed a distinct phenotype characterized by better chronotropic reserve and peripheral O2 extraction. The Ex-MR is a common mechanism across all HF subtypes, associated with ventilatory inefficiency and RV-PC uncoupling. In HFpEF, Ex-MR is unexpectedly prevalent and associated with increased chronotropic response and peripheral O2 extraction as potential adaptive mechanisms to backward flow redistribution.