Mechanical and electrical uncoupling: the role of cardiac magnetic resonance imaging in arrhythmogenic cardiomyopathy proof of concept
Authors: Priego-Ranero A , Papaqui-Quitl M N , Ortega-Hernandez J A , Garcia Arias M R , Marquez-Murillo M F , Arguello Bolanos J , Gopar-Nieto R , Sierra Lara Martinez D 
Published: May 2024

Abstract

Funding Acknowledgements
None.

Introduction
Arrhythmogenic Cardiomyopathy (ACM) has a high risk of sudden cardiac death, especially under 60 years old (1:5,000 prevalence). ACM involves the replacement of normal heart tissue with fibro-adipose tissue in specific areas of the right ventricle (RV).
Cardiac Magnetic Resonance Imaging (CMR) is vital for ACM stratification and prognosis, focusing on RV volume and ejection fraction. Simulations suggest that ACM's abnormal deformation patterns are primarily due to mechanical changes like reduced contractility and increased stiffness, rather than electrical issues. Ventriculo-arterial coupling (VAC) is a valuable metric for assessing RV efficiency, with the TAPSE/sPAP index reflecting the RV's length-force relationship.
CMR assists in ACM stratification and prognosis, with VAC potentially serving as a key predictor of outcomes based on mechanical and structural abnormalities identified through CMR.

Purpose
Examine and establish a relationship between mechanical uncoupling, ventricular arrhythmias, and findings from CMR in patients with ACM.

Methods
We examined 25 ACM patients (median age 34, 72% men) using the 2019 Modified Task Force and Padua criteria. We investigated two key factors in ACM: Right ventricular-arterial coupling (TAPSE/SPAP ratio) and clinically relevant ventricular tachycardia (requiring cardioversion). We compared clinical, ECG, and imaging data (transthoracic echocardiogram and CMR as the gold standard).
We used Spearman rank tests for correlations, Fisher exact tests for nominal characteristics, and Mann-Whitney-U tests for group comparisons. In predefined regression models involving left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) function with VAC, we used flexible nonparametric regressions. A p-value &lt;0.05 was considered statistically significant. The analysis was conducted using SPSSv22 and SAS-University-Edition.

Results
A positive association of VAC with LVEF (ρ=0.472, p=0.023), RVEF (ρ=0.522, p=0.038) and RV indexed stroke volume (ρ=0.79, p&lt;0.001) was found. Low-rank regression splines showed a mainly positive association of LVEF (df=3 F=20.75 p&lt;0.001), RVEF (df=4 F=24.34 p&lt;0.001) and the RV indexed stroke volume, a positive linear association (df=1 F=31.67 p&lt;0.001).
In comparison with patients without crVT, those with crVT had a positive correlation with RV shortening, reduced RVEF (39.6 vs. 32.2%. p=0.025), higher LV mass (38.99 vs. 45.55, p=0.045), and LV end-diastolic volume (LVEDV) (56.99 vs. 68.15 ml/m2, p=0.045) by echocardiogram and CMR respectively; notwithstanding positive associations for VAC were seen with LVEDV (p=0.039), LV mass (p=0.039); and negative with RVEF by CMR (p=0.023), and RV shortening by echo (p=0.026).

Conclusions
We found that right VAC by echo correlates with RV and LV EF by CMR and RV stroke volume in patients with ACM. RVEF, LV mass, and end-diastolic volume correlate with clinically relevant arrhythmias.