Right atrial and ventricular strain are correlated with variables of cardiopulmonary exercise testing in patients with arrhythmogenic cardiomyopathy and plakophilin-2 mutation

Abstract Background Arrhythmogenic cardiomyopathy (ACM) is a rare genetic condition with a high burden of potentially life-threatening ventricular arrhythmias and heart failure. Fractional area change (FAC) is an important variable for echocardiographic assessment of right ventricular function in patients with ACM, as impaired FAC is associated with future occurrence of arrhythmia and heart failure (Chen et al. 2025). Right atrial (RA) and ventricular (RV) strain may detect RV abnormalities earlier than FAC and may show promise in complementing echocardiographic assessment (Morris et al. 2017). Whether these echocardiographic variables are correlated with functional measures of cardiopulmonary exercise testing (CPET), which has been suggested to enrich risk stratification in ACM patients (Scheel et al. 2020), remains unknown. Purpose To assess whether FAC, RA and RV strain are correlated with functional CPET variables. Methods Fourteen non-sedentary patients with ACM and Plakophilin-2 (PKP-2) mutation and preserved systolic left ventricular function (≥50%) were included and underwent resting echocardiography, including assessment of FAC and semi-automated RA and RV strain. Incremental CPET using upright bicycle ergometry was performed within 24 hours. Spearman correlations of functional CPET variables as well as FAC, RA and RV strain were analyzed. Results Fourteen non-sedentary patients (9 men, 5 women; mean age 46.2 ± 12.0 years) were included. Mean predicted peak oxygen consumption (VO2peak) was 98.0% ± 28.0% indicating largely preserved cardiorespiratory fitness with considerable interindividual differences. FAC showed large variations (mean 39.0 ± 11.4%), with only three patients showing an FAC of 35.0% suggesting impaired RV function. In addition, mean RA reservoir (29.3 ± 13.7%) and RA contractile strain (-12.4 ± 8.1%) were severely reduced, while conduit strain (-16.9± 9.2%) was only slightly impaired (Krittanawong et al. 2023) in most patients. RV four chamber strain (-15.3 ± 5.3%) and free wall strain (-18.6 ± 8.3%) were also impaired (Morris et al. 2016) in most patients (Table 1). VO2peak showed significant correlations with FAC (r=0.72, p=0.004), RV free wall strain (r=-0.63, p=0.016) and RA conduit strain (r=-0.55, p=0.04). FAC and strain analyses displayed significant correlations with functional CPET variables (Figure 1). Conclusions FAC was largely preserved, while semi-automated RA and RV strain were reduced, indicating that these variables could be used as early markers to detect subclinical RA and RV dysfunction. Similarly to FAC, RA and RV strain were correlated with VO2peak and other functional CPET variables. Thus, holistic echocardiographic assessment of RA and RV function (including strain analysis) combined with CPET testing may facilitate early detection of subclinical dysfunction and help improve risk stratification in PKP-2 positive ACM patients.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.