Prognostic value of right ventricular systolic function markers in ATTR-CM

Introduction

Left ventricular (LV) dysfunction is a well-established prognostic factor in transthyretin cardiac amyloidosis (ATTR-CM). Amyloid deposition in ATTR-CM often leads to biventricular thickening and dysfunction, which may reflect amyloid burden. The clinical significance of right ventricular (RV) function, however, is not clearly defined.

Aims

To evaluate the added prognostic value of RV function in ATTR-CM.

Methods

Single-centre retrospective study including all consecutive patients with heart failure (HF) due to ATTR-CM followed from 2019 to 2025. ATTR-CM was diagnosed as per the recommended multi-step algorithm. Echocardiographic parameters were obtained from the first available transthoracic echocardiogram (TTE) performed at our institution. We proceeded with RV function analysis as per the EACVI/ASE recommendations. Fractional area change (FAC), was obtained in 2D ecochardiogram and easily executed. The primary endpoint was all-cause death. Survival analysis was performed using univariate and multivariate Cox regression models.

Results

Among 286 patients with ATTR-CM, 214 were identified to have a baseline TTE with RV-measurable functional data (mean age 85 ± 6 years, 81% male, 71% tafamidis). RV assessment showed a mean FAC of 34.6 ± 9.4% and free wall longitudinal strain (RV-FWLS) of -17.0 ± 5.2%. Median tricuspid annular plane systolic excursion (TAPSE) was 17 (13-19) mm and mean RV S’ (RVS) wave was 10 (8-13) cm/s. Among markers of RV systolic function, univariate analysis showed that FAC and FWLS were the only RV-related independent predictors.

After a median follow-up of 1.8 (1.0–2.9) years, the primary endpoint was reached in 62 patients (29.0%). In multivariate analysis – adjusted for NYHA, LV ejection fraction, NT-proBNP, creatinine, RV-FWLS and tafamidis– FAC remained as an independent predictor of all-cause mortality, while RV-FWLS did not. ROC curve analysis showed the optimal cut-off value for FAC <31% (present in 67% of the patients), with an area under the curve (AUC) of 0.729 (sensitivity 59% , specificity 81%). In a new multivariate model adjusted for the same variables, FAC <31% independently predicted the primary outcome with an HR 2.08 (95% CI 1.02-4.35; p=0.027).

Conclusion

In this ATTR-CM cohort, FAC provided independent prognostic information beyond well-established clinical, biomarkers, and echocardiographic parameters. A FAC < 31% was associated with a substantially higher risk of death — more than doubling the risk — highlighting its potential value for risk stratification.For image description, please refer to the figure legend and surrounding text.