Exercise-induced mitral regurgitation and right ventricle to pulmonary circulation uncoupling across the heart failure phenotypes

Exercise-induced 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 was to describe functional phenotypes and cardiac response to exercise in HFrEF, HFmrEF, and HFpEF, according to Ex-MR prevalence. A total of 218 patients with HF [146 men, 68 (59-78) yr], 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 (≥2+/4+) regurgitation during exercise. Ex-MR was highly prevalent in the overall population (52%) although differed in the subgroups as follows: 82/137 (60%) in HFrEF, 17/41 (41%) in HFmrEF, and 14/40 (35%) in HFpEF (<i>P</i> < 0.05). 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), <i>P</i> = 0.004; 28.1 (24.5-31.9) vs. 34.4 (28.2-36.7), <i>P</i> = 0.01; 28.8 (26.6-32.4) vs. 32.2 (29.2-36.7), <i>P</i> = 0.01] and with lower peak VO₂ in HFrEF and HFmrEF. Exercise right ventricle to pulmonary circulation (RV-PC) uncoupling was observed in HFrEF and HFpEF patients with Ex-MR [peak TAPSE/SPAP: HFrEF 0.40 (0.30-0.57) vs. 0.29 (0.23-0.39), <i>P</i> = 0.006; HFpEF 0.44 (0.28-0.62) vs. 0.31 (0.27-0.33), <i>P</i> = 0.05]. HFpEF with Ex-MR showed a distinct phenotype characterized by better chronotropic reserve and peripheral O₂ extraction.<b>NEW & NOTEWORTHY</b> Ex-MR is a common mechanism across the spectrum of HF subtypes and combines with ventilatory inefficiency and RV-PC uncoupling. Interestingly, in HFpEF, Ex-MR emerged as unexpectedly prevalent and peculiarly associated with increased chronotropic response and peripheral O₂ extraction as potential adaptive mechanisms to backward flow redistribution.