Right ventricular to pulmonary artery uncoupling: the diagnostic value in distinguishing hypertrophic cardiomyopathy and wild-type transthyretin cardiac amyloidosis
E Mata, A M Pinto, L Pinheiro, T Pereira, M Castro, B Lage Garcia, D Ferreira, M Lourenco, F Cordeiro, M Fernandes, O Azevedo, A LourencoAbstract
Background
Right ventricular (RV) to pulmonary artery (PA) coupling reflects how effectively the RV adapts to the afterload imposed by the pulmonary circulation. Emerging evidence suggests that disruption of this relationship (RV-PA uncoupling) may occur differently across cardiomyopathies. Hypertrophic cardiomyopathy (HCM) typically features primary myocardial hypertrophy with preserved RV function until advanced stages, whereas wild-type transthyretin cardiac amyloidosis (ATTR-CM) is marked by progressive RV infiltration and earlier impairment of RV mechanics.
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 RV-FWS/PASP (Right Ventricular Free Wall Strain) - have diagnostic utility in differentiating HCM from ATTR-CM.
Methods
This retrospective study included HCM (n=30) and ATTR-CM (n=30) patients evaluated between 2014 and 2021. Two blinded observers assessed RV structure and function using echocardiography and 2D-STE. Receiver operating characteristic (ROC) analysis assessed the diagnostic performance of RV-PA coupling indices, with DeLong’s test used for comparison.
Results
ATTR-CM patients were older than HCM patients (83.4±4.8 vs 59.8±13.6 years, p<0.001), had higher NT-proBNP levels (11001±15080 vs 1117±1103pg/ml, p<0.001) and similar septal wall thickness (18.9±2.7 vs 18.7±2.3, p=0.769). ATTR-CM patients also presented lower TAPSE/PASP ratio (0.428±0.199 vs 0.754±0.219, p<0.001), FAC/PASP ratio (0.855±0.358 vs 1.420±0.367, p<0.001) and RV-FWS/PASP ratio (0.246±0.120 vs 0.434±0.143, p<0.001). In ROC curve analysis, TAPSE/PASP ratio had an area under the curve (AUC) of 0.865 [0.752-0.939] (p<0.0001) with an associated cutoff of ≤0.537 for identifying ATTR-CM (sensitivity: 70%; specificity: 86.7%). FAC/PASP ratio showed an AUC of 0.857 [0.742-0.934] (p<0.0001) with an associated cutoff of ≤1.03 for identifying ATTR-CM (sensitivity: 73.33%; specificity: 83.33%). The RV-FWS/PASP ratio had an AUC of 0.849 [0.739-0.929] (p<0.0001) with an associated cutoff of ≤0.275 for identifying ATTR-CM (sensitivity: 60%; specificity: 93.33%). Pairwise comparisons showed no significant difference between TAPSE/PASP, FAC/PASP or RV-FWS/PASP ratios in distinguishing ATTR-CM from HCM. When compared to the RV function parameters not normalized to load, the AUCs for TAPSE and FAC were numerically lower than those of the load-normalized parameters (AUC: 0.740 for TAPSE, AUC: 0.709 for FAC and AUC: 0.894 for RV-FWS).
Conclusion
Overall, RV-PA coupling indices were all significantly lower in ATTR-CM compared with HCM and demonstrated good diagnostic accuracy for distinguishing between the two conditions, and two of them outperformed the parameters not normalized to load. All three measures showed consistent discriminatory value, supporting RV-PA coupling assessment as a useful adjunct in differentiating ATTR-CM from HCM.