Characterization of arrhythmogenic atrial cardiomyopathies

• Applicant: Sebastian Dittrich
• Subject Area: Cardiology, Angiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 525276126

Atrial fibrillation (AF) is the highest prevalent arrhythmia in adults. In the elderly, other cardiovascular comorbidities lead to persistent AF by complex pathophysiological mechanisms involving atrial myocardial fibrosis. A subset of patients however, often without typical comorbidities, presents with persistent AF related to myocardial fibrosis at younger age. Recent studies suggest, these patients may have a form of primary atrial myopathy (AM) with differences in pathogenesis and prognosis. Importantly, this primary AM can be an expression of dilated cardiomyopathy (DCM). DCM caused by disease causing (likely) pathogenic genetic mutations is often associated with a high atrial arrhythmia burden. Studies have shown that AF in DCM occurs frequently in patients below 50 years, despite a preserved LV function. It can be the only presenting symptom of the underlying disease, followed later in time by life-threatening ventricular arrhythmias or heart failure. Clinical decision making today regarding catheter ablation and risk-stratification for thromboembolic complications or ventricular arrhythmias does not reflect these differences in pathogenesis and prognosis between patients suffering from primary AM versus those with AF secondary to other cardiovascular disease. The general objective of this project is to characterize primary, arrhythmogenic atrial myopathies and improve diagnostic tools that target AM. While the applicant will be working full-time at Leiden University Medical Center supervising the associated studies, University Hospital Cologne (Germany) and Aarhus University Hospital (Denmark) will participate. Central is the establishment of a prospective, multicenter registry of young patients presenting with primary AM, undergoing assessment including imaging and genetic testing for rare, disease-causing mutations in cardiomyopathy genes. In a second part of the project, the atrial phenotype of different cardiomyopathy subtypes (DCM, HCM, ARVC), associated with high AF burdens, will be studied in a retrospective study. It analyzes outcome data of patients who suffer from one of these cardiomyopathies, previously diagnosed by genetic testing, and have been treated by catheter ablation. In the third part, a novel ablation catheter will be used to evaluate a reproducible electro-anatomical mapping strategy to identify areas of fibrosis and thus facilitate standardized diagnostic of AM. Results of mapping procedures will be correlated with CT imaging data. The aim is to improve substrate-based arrhythmia treatment and provide early risk-stratification for development of thromboembolic complications, ventricular arrhythmias, and heart failure in young patients presenting with primary AM. In patients suffering from primary AM as a manifestation of a genetic cardiomyopathy, we aim to evaluate a genotype-phenotype correlation to predict individual risk and allow for individualized treatment decisions.

• DFG Programme: WBP Fellowship
• International Connection: Netherlands
• Host: Professorin Dr. Katja Zeppenfeld