Right ventricular–pulmonary arterial uncoupling predicts heart failure hospitalisation in transthyretin cardiac amyloidosis

Background Right ventricular (RV) involvement is common in transthyretin cardiac amyloidosis (ATTR-CM) and is associated with worse clinical outcomes. Echocardiographic assessment of RV function remains challenging. The relationship between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP), as well as S′TDI/PASP, have been proposed as markers of right ventricle–pulmonary artery (RV–PA) uncoupling, potentially better reflecting RV functional load. Purpose To assess the prognostic value of TAPSE/PASP and S′TDI/PASP in patients with ATTR-CM in relation to the risk of heart failure (HF) hospitalisation. Methods A retrospective analysis was performed in patients with confirmed ATTR-CM under outpatient follow-up at a specialised cardiomyopathy clinic. Clinical and echocardiographic data were collected at diagnosis, and HF hospitalisation events were recorded during follow-up. A total of 201 patients were identified; 46 were excluded due to echocardiographic assessment performed only during HF hospitalisation or incomplete data, resulting in 155 eligible patients. The primary endpoint was first HF hospitalisation after diagnosis. Follow-up time was defined from diagnosis to first hospitalisation or last clinical contact. Univariate and multivariate Cox regression analyses were performed, along with Kaplan–Meier survival analysis. Optimal cut-offs were determined using the Youden index. Results A total of 155 patients were included (mean age 79.3 ± 8.3 years, 88.2% male). Median left ventricular ejection fraction was 54% (IQR 43–62). RV functional parameters showed:TAPSE: median 18 mm (IQR 15–21)S′TDI: 9 cm/s (IQR 7–11) During a median follow-up of 368 days (IQR 109–785), 35% experienced at least one HF hospitalisation. Lower TAPSE/PASP ratio (continuous variable) was significantly associated with higher risk of hospitalisation (HR 0.18; 95% CI 0.04–0.74; p = 0.018), as were lower TAPSE values alone (HR 0.94 per mm; 95% CI 0.89–0.99; p = 0.021) and older age (HR 1.05 per year; 95% CI 1.03–1.08; p < 0.001). PASP alone was not significantly associated with outcome (HR 1.02; 95% CI 1.00–1.04; p = 0.071). The optimal cut-off for TAPSE/PASP was 0.5 (AUC 0.65; sensitivity 78%; specificity 56%). In multivariable analysis, TAPSE/PASP ≤ 0.5 was independently associated with increased HF hospitalisation risk (HR 2.13; 95% CI 1.21–3.74; p = 0.008). Age remained an independent predictor (HR 1.05 per year; 95% CI 1.04–1.07; p < 0.001). Event-free survival was significantly lower in patients with TAPSE/PASP ≤ 0.5. In contrast, S′TDI/PASP was not independently associated with outcome. Conclusions In patients with ATTR-CM, RV–PA uncoupling assessed by TAPSE/PASP ≤ 0.5 is associated with an increased risk of HF hospitalisation, independently of age. This simple and widely available echocardiographic index may serve as a complementary risk stratification tool in this population.RV-PA uncoupling in ATTR-CM