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Coexistence of cardiac sarcoidosis and arrhythmogenic cardiomyopathy-associated genetic variants: a multicentre

Valentina Alice Rossi^1,2, Matteo Palazzini³, Enrico Ammirati^3,4

¹Department of Cardiology, University Hospital Zurich, Zurich, Switzerland ardansaguner@gmail.com valereds@gmail.com.

Heart (British Cardiac Society)

|January 21, 2025

Insights

Cardiac sarcoidosis (CS) and arrhythmogenic cardiomyopathy (ACM) genetic variants coexist, presenting unique symptoms like AV block and PR prolongation. Early evaluation is crucial for patients with ACM variants showing conduction issues or septal involvement.

Area of Science:

Cardiology
Genetics
Immunology

Background:

Cardiac sarcoidosis (CS) is an inflammatory heart condition; arrhythmogenic cardiomyopathy (ACM) is a genetic disorder affecting desmosomal proteins.
The interplay between CS and ACM genetic variants presents diagnostic and management challenges.
This study investigates the clinical, imaging, and genetic profiles of patients with coexisting CS and ACM-associated genetic variants.

Purpose of the Study:

To characterize the clinical, imaging, and genetic features of patients with coexisting cardiac sarcoidosis and ACM-associated genetic variants.
To identify distinct patterns associated with the coexistence of these conditions.

Main Methods:

A multicentre retrospective case-control study.
Involved three groups: CS with ACM variants (n=5), ACM variants without CS (n=5), and CS without variants (n=5).
Analyzed clinical symptoms, ECG, echocardiography, cardiac MRI, and PET imaging data.

Main Results:

Patients with CS and ACM variants showed higher rates of atrioventricular block (100%), PR prolongation (204 ms), and atrial fibrillation (80%) compared to those with ACM variants alone.
Septal involvement was more prevalent in patients with both conditions (80%) versus ACM variants alone (20%).
Identified genetic variants included PKP2, DSG2, DSP, and TTN.

Conclusions:

Coexistence of CS and ACM genetic variants is linked to specific clinical features: PR prolongation, AV block, septal involvement, and atrial fibrillation.
Suggests evaluating for CS in individuals with ACM genetic variants presenting with conduction abnormalities or septal involvement.
Highlights the need for tailored diagnostic and therapeutic strategies for these complex cases.

Read full analysis

Abstract

Background:

Cardiac sarcoidosis (CS) is a chronic inflammatory disease characterised by non-caseating granulomas, while arrhythmogenic cardiomyopathy (ACM) is a genetic condition mainly affecting desmosomal proteins. The coexistence of CS and genetic variants associated with ACM is not well understood, creating challenges in diagnosis and management. This study aimed to describe the clinical, imaging and genetic features of patients with both conditions.

Methods:

This was a multicentre retrospective case-control study involving three groups of patients: those with biopsy-proven CS and pathogenic or likely pathogenic genetic variants linked to ACM (n=5); patients with genetic variants but no CS (n=5); and patients with CS without genetic variants (n=5). Clinical data, including symptoms, electrocardiographic findings and imaging results from echocardiography, cardiac magnetic resonance and positron-emission tomography, were analysed.

Results:

Patients with CS and genetic variants were more likely to exhibit atrioventricular block (100%), PR prolongation (204 ms vs 160 ms) and paroxysmal atrial fibrillation (80%) compared with those with genetic variants alone (0% for both). Imaging findings showed a higher prevalence of septal involvement in patients with both conditions (80%) than in those with genetic variants alone (20%). No significant differences were observed between patients with CS and genetic variants and those with CS without genetic variants. The genetic variants identified included variants in PKP2 (40%), DSG2 (20%), DSP (20%) and TTN (20%).

Conclusions:

The coexistence of CS and ACM-associated genetic variants is associated with distinct clinical features, including PR prolongation, AVB1°, septal involvement and paroxysmal atrial fibrillation. These findings emphasise the need to evaluate for CS in individuals with ACM and associated genetic variants who present with conduction abnormalities or septal involvement, guiding tailored diagnostic and therapeutic strategies.

Keywords:

Arrhythmogenic Right Ventricular Dysplasia Cardiomyopathies Cardiomyopathy, Dilated Myocarditis

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