RV-PA uncoupling is associated with increased mortality in transthyretin amyloid cardiomyopathy treated with tafamidis

Background The right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle's ability to adjust to an increased afterload. In case of transthyretin amyloid cardiomyopathy (ATTR-CM), impaired RV-PAc can result from increased left ventricular diastolic stiffness due to fibril deposition. Objectives While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unknown. We sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM. Methods In this multicentre 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 a TTR stabilizer. The primary outcome was all-cause mortality. Results Within a median time of 1.52 [IQR 0.72-2.56] years after diagnosis, 49 (11.7%) patients died. In multivariate Cox regression analysis impaired RV-PAc was a strong independent predictor of mortality (Hazard Ratio (HR) 2.16, 95% Confidence Interval (CI) 1.14-4.07, p = 0.018). RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382 mm/mmHg (area under the curve (AUC) 0.73, 95% CI 0.65-0.81). Patients with RV-PAc ratio <= 0.382 mm/mmHg exhibited significantly lower survival (HR 4.17, 95% CI 2.21-7.87, p < 0.001) within 3 years of follow up than those with RV-PAc ratio above the cut-off (Graphical Abstract). Conclusion Impaired adaptation 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. Therefore, the determination of RV-PAc could improve risk stratification for ATTR-CM patients.