Impact of right ventricle to pulmonary artery coupling on outcomes in patients with primary mitral regurgitation

Abstract Background In patients with significant primary mitral regurgitation (MR), both elevated pulmonary pressure and right ventricular (RV) dysfunction have been shown to be associated with adverse outcomes. However, the adaptation of the RV to increasing pulmonary pressures can vary, even within ranges of RV function that are considered normal. The concept of coupling the RV to pulmonary artery (PA) has therefore been introduced to better describe the match between the RV contractility and the opposing afterload, but has not been assessed so far in primary MR patients. Purpose To evaluate the association of RV-PA coupling with outcome in primary MR patients undergoing mitral valve surgery. Methods RV-PA coupling was measured before surgery as the ratio of tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (sPAP) in 499 patients with primary MR and elevated sPAP (≥ 30 mmHg by echocardiography). The study outcome was all-cause mortality. Results Based on age and sex adjusted spline curve analysis (Fig 1A), TAPSE/sPAP values <0.48 mm/mmHg indicated RV/PA uncoupling and were associated with mortality hazard ratios >1. Compared to patients with a coupled RV, those with RV/PA uncoupling (192; 38.5%) were significantly older (mean age 70 vs 65 years; P<0.001), more symptomatic (88% vs 68%; P<0.001) and had higher rates of atrial fibrillation (54% vs 31%; P<0.001). After a median follow-up of 8.3 years, 98 (19.6%) patients died. Kaplan-Meier analysis showed significantly lower survival in patients with RV/PA uncoupling (70.8% vs 86.3%; P<0.001) (Fig 1B). On multivariable analysis, impaired TAPSE/sPAP was independently associated with mortality (HR: 1.97; P=0.015) after adjustment for significant clinical and echocardiographic covariates (Fig 2A). To compare the predictive value of TAPSE/sPAP vs TAPSE or sPAP alone, these variables were added separately to the same base model (Fig 2B). Adding the TAPSE/sPAP ratio to the base model resulted in a significant net reclassification improvement (NRI: 0.475; 95% CI: 0.102 to 0.846), while TAPSE or sPAP alone did not. Even in a subgroup of patients with only mildly elevated sPAP (30–50 mmHg, n = 355; 71%), RV-PA uncoupling was independently associated with mortality (HR: 2.1; P = 0.028). Conclusion In patients with primary MR and elevated pulmonary pressure, RV-PA uncoupling was independently associated with post-surgical mortality, and resulted in better risk stratification of these patients than TAPSE or sPAP alone. TAPSE/sPAP ratio remained independently associated with mortality even in a subgroup of patients with only mildly increased pulmonary pressure. This highlights the importance of assessing RV function in the context of the opposing afterload.Figure 1:TAPSE/SPAP cutoff and survival Figure 2:Multivariable Cox models

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