Right ventricular-pulmonary artery coupling: a functional approach to distinguishing fabry disease from wild-type transthyretin cardiac amyloidosis

Background

Fabry disease (FD) and wild-type transthyretin cardiac amyloidosis (wtATTR-CM) can both present similar patterns of left ventricular hypertrophy, which may complicate their distinction during routine evaluation. As right ventricular adaptation to afterload has emerged as a sensitive marker of early myocardial involvement, right ventricular-pulmonary artery (RV-PA) coupling metrics have gained interest as potential diagnostic indicators.

Aim

To evaluate the diagnostic utility of RV-PA coupling indices-TAPSE/PASP (Tricuspid Annular Plane Systolic Excursion/Pulmonary Artery Systolic Pressure), FAC/PASP (Fractional Area Change), and RV-FWS/PASP (Right Ventricular Free Wall Strain) in differentiating FD from ATTR-CM.

Methods

This retrospective study included 30 patients with FD and 30 with wtATTR-CM, evaluated between 2014 and 2021. RV structure and function were independently assessed by two blinded observers using echocardiography and 2D speckle-tracking echocardiography (2D-STE). The diagnostic performance of coupling indices was evaluated using receiver operating characteristic (ROC) analysis, with DeLong’s test applied for comparison of AUCs.

Results

Patients with ATTR-CM were older than those with FD (83.4±4.8 vs 64.6±10.7years, p<0.001), had higher NT-proBNP levels (11,001±15,080 vs 899±1,016 pg/ml, p<0.001), and greater septal wall thickness (18.9±2.7 vs 17.4±2.7mm, p=0.036). ATTR-CM patients also exhibited lower RV-PA coupling indices, including TAPSE/PASP (0.428±0.199 vs 0.871±0.252, p<0.001), FAC/PASP (0.855±0.358 vs 1.608±0.435, p<0.001), and RV-FWS/PASP (0.246±0.120 vs 0.507±0.171, p<0.001).

In ROC curve analysis, all three indices demonstrated good diagnostic performance for identifying ATTR-CM. TAPSE/PASP ratio had an area under the curve (AUC) of 0.924 [0.826–0.976] (p<0.0001) with an associated cutoff of ≤0.679 for identifying ATTR-CM (sensitivity: 93%; specificity: 77%). FAC/PASP ratio showed an AUC of 0.917 [0.817–0.973] (p<0.0001) with an associated cutoff of ≤1.25 for identifying ATTR-CM (sensitivity: 80%; specificity: 87%). The RV-FWS/PASP ratio had an AUC of 0.916 [0.815-0.972] (p<0.0001) with an associated cutoff of ≤0.375 for identifying ATTR-CM (sensitivity: 90%; specificity: 83%). Pairwise comparisons showed no significant differences among the three ratios, suggesting that each index offers similar diagnostic value in differentiating ATTR-CM from FD. When compared to the right ventricular function parameters not normalized to load, the AUCs were always numerically lower than those of the load-normalized parameters (AUC 0.836 for TAPSE, AUC of 0.829 for FAC and AUC of 0.888 for RV-FWS).

Conclusion

RV-PA coupling indices were more impaired in wtATTR-CM than in FD, with all ratios showing strong diagnostic performance. Although no single index was superior, RV-PA coupling assessment may add value in the differentiation of wtATTR-CM from FD.