RV-PA uncoupling is a strong predictor of 3-year all-cause mortality in transthyretin amyloid cardiomyopathy

Abstract Background Right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle's ability to adjust to an increased afterload which, in case of transthyretin amyloid cardiomyopathy (ATTR-CM), can result from increased left ventricular diastolic stiffness due to fibril deposition. While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unclear. This study sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM. Methods In this two-centre study, RV-PAc was investigated by the echocardiographic surrogate of ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP) in 418 ATTR-CM patients, all treated with TTR stabilizer. The primary outcome was all-cause mortality. Receiver operation curves and Youden’s J analysis were applied to identify an optimal cut-off value of RV-PAc ratio. Results Within a median time of 631 (IQR 361-983) days after diagnosis, 14.4% of patients died. RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382mm/mmHg (area under the curve (AUC) 0.746, 95% CI 0.68-0.82). Patients with RV-PAc ratio ≤0.382mm/mmHg (impaired RV-PAc, n=158) exhibited significantly lower survival (HR 4.07, 95% CI 2.26-7.33, p<0.001) within 3 years of follow up than those with RV-PAc ratio > 0.382mm/mmHg. In multivariate Cox regression analysis, incorporating a range of known prognostic variables, reduced RV-PAc was a strong echocardiographic predictor of mortality (Hazard Ratio (HR) 2.99, 95% Confidence Interval (CI) 1.63-5.51, p <0.001). Conclusion Impaired adaption of the RV to increased afterload is associated with worse outcome in ATTR-CM patients. RV-PAc ratio can serve as an echocardiographic predictor for all-cause mortality within three years after diagnosis. Therefore, determination of RV-PAc could improve risk stratification for ATTR-CM patients.Figure_1_Kaplan-Meier curves