Prognostic value of right ventricular to pulmonary artery coupling in transthyretin amyloid cardiomyopathy

Introduction

Right ventricular-pulmonary artery (RV-PA) uncoupling has emerged as an important prognostic marker in several cardiopulmonary diseases, but its relevance in Transthyretin Amyloid Cardiomyopathy (ATTR-CM) remains underexplored.

Purpose

To determine whether RV-PA coupling indices - TAPSE/PASP (Tricuspid Annular Plane Systolic Excursion/Pulmonary Artery Systolic Pressure), FAC/PASP (Fractional Area Change), and RVGLS/PASP (Right Ventricular Global Longitudinal Strain) - predict a composite outcome of all-cause mortality and heart failure hospitalization (HFH) in patients with ATTR-CM.

Methods

We conducted a retrospective observational study including patients with confirmed ATTR-CM who underwent transthoracic echocardiography. RV-PA coupling was evaluated using TAPSE/PASP, FAC/PASP, and RVGLS/PASP. Non-coupled RV parameters were also assessed. Clinical follow-up included the composite of all-cause mortality and HFH. Cox proportional hazards models were used to identify independent predictors. Prognostic performance was estimated with ROC curve analysis. Kaplan-Meier survival curves were constructed using the optimal ROC-derived cut-off values, and differences were evaluated using the log-rank test.

Results

A total of 52 patients were included (mean age 82 years, 69% male). Among the parameters evaluated, FAC/PASP (HR 0.42 [0.17-0.998] p=0.049) and FAC (HR 0.97 [0.93-0.997] p=0.037) were the only independent predictors of the composite outcome. TAPSE/PASP (HR 0.19 [0.03-1.35] p=0.096), RVGLS/PASP (HR 0.15 [0.02-1.43] p=0.098), TAPSE (HR 0.94 [0.87-1.02] p=0.139), and RVGLS (HR 0.94 [0.88-1.02] p=0.139) were not statistically significant.

At 1-year follow-up, ROC analysis showed: FAC/PASP area under the curve (AUC) of 0.654 [0.508-0.782], TAPSE/PASP AUC of 0.592 [0.447-0.726], and RVGLS/PASP AUC of 0.569 [0.424-0.706]. The optimal FAC/PASP cut-off was ≤0.6, with sensitivity of 39% and a specificity of 92%. Kaplan-Meier analysis stratifing patients using the ROC-derived FAC/PASP threshold of 0.6 %/mmHg identified patients with RV-PA uncoupling. demonstrated significantly higher event rates in patients below this threshold, confirmed by the log-rank test (p = 0.0002).

Conclusion

In patients with cardiac amyloidosis, RV-PA uncoupling (particularly FAC/PASP) may be associated with adverse outcomes. More robust studies are needed to confirm FAC/PASP as a potential marker for risk stratification and help guide clinical decision-making in this population.