NEW RESEARCH has shown that the coexistence of cardiac sarcoidosis (CS) and arrhythmogenic cardiomyopathy (ACM)-associated genetic variants presents distinct clinical features, including PR prolongation, atrioventricular block (AVB1°), septal involvement, and paroxysmal atrial fibrillation, necessitating refined diagnostic and management strategies.
Cardiac sarcoidosis is a chronic inflammatory disease characterised by non-caseating granulomas, while arrhythmogenic cardiomyopathy is a genetic condition primarily affecting desmosomal proteins. The overlap between these conditions remains poorly understood, leading to diagnostic and therapeutic challenges. This study aimed to describe the clinical, imaging, and genetic characteristics of patients with both CS and ACM-associated genetic variants to improve clinical decision-making.
This multicentre retrospective case-control study analysed three patient groups: those with biopsy-confirmed CS and pathogenic or likely pathogenic ACM-associated genetic variants (n=5), patients with genetic variants but no CS (n=5), and patients with CS without genetic variants (n=5). Clinical data were assessed, including symptoms, electrocardiographic findings, and imaging results from echocardiography, cardiac magnetic resonance, and positron-emission tomography. Patients with both CS and ACM-associated variants exhibited a significantly higher prevalence of atrioventricular block (100%), PR prolongation (204 ms vs 160 ms), and paroxysmal atrial fibrillation (80%) compared to those with genetic variants alone (0% for both). Imaging revealed septal involvement in 80% of those with both conditions, contrasting with 20% in those with only genetic variants. No significant differences were found between CS patients with and without ACM-associated variants. The identified genetic variants included PKP2 (40%), DSG2 (20%), DSP (20%), and TTN (20%).
These findings underscore the importance of assessing for CS in individuals with ACM-associated genetic variants who present with conduction abnormalities or septal involvement. The overlap of these conditions suggests a need for heightened clinical vigilance, particularly in patients exhibiting PR prolongation and AV block. Future research should explore the mechanistic relationship between inflammation and genetic predisposition to optimise diagnostic and treatment approaches. In clinical practice, early identification and targeted management strategies could improve patient outcomes, reinforcing the need for genetic screening and comprehensive cardiac evaluation in individuals at risk.
Katrina Thornber, EMJ
Reference
Rossi VA et al. Coexistence of cardiac sarcoidosis and arrhythmogenic cardiomyopathy-associated genetic variants: a multicentre case-control study. Heart. 2025;DOI:10.1136/heartjnl-2024-32452.
