Cardiogenetic Registry: Design and first Results on the prevalence of pathogenic variants in cardiomyopathies
N Panagiotides, S Prausmueller, H Arfsten, E Stix, S Stojkovic, M Huelsmann, N PavoAbstract
Background
In cardiomyopathies (CMP), structured genetic diagnostics improve risk stratification, guide family screening, and enable individualized therapy. Therefore, a dedicated cardiogenetic clinic and registry were established at our institution in 2024.
Purpose
To present the design of this Cardiogenetic Registry and report preliminary results.
Methods
This prospective, single-center registry includes adults with i) clinical phenotypes suggestive of inherited disease, ii) early-onset heart failure (HF) (<50 years), iii) familial clustering of HF or sudden cardiac death (SCD), iv) peripartum CMP or v) first grade relatives with pathogenic (P) or likely pathogenic (LP) variants irrespective of phenotype or any relatives with a genetic variant with suspected CMP. Whole exome sequencing (WES) is performed in index cases, while targeted carrier testing and cascade screening is offered to relatives in families with a P/LP variant.
Results
By September 2025, 126 (median age 41 [29-50], 64% male, median NT-proBNP was 616 pg/ml [114–2078]) patients had been included (113 index, 13 relatives). 64% had idiopathic CMP, 16% SCD/arrhythmia syndromes, 5% peripartum CMP and 15% other. To time, WES analysis was available for 58% (66/113) of index patients (Figure 1). Of these, 44 (67%) carried any reported variants [33, 7 and 4 for CMP/arrhythmia, non-cardiac disease or both]. 9 (14%) patients had more than one cardiac variant reported. In total, 21 (32%) patients had variants of uncertain significance (VUS) and 16 (25%) P/LP variants within the CMP/arrhythmia panel. The most common variants were found in the TTN gene.
Conclusions
The Cardiogenetic Registry provides structured, real-world data on inherited cardiac diseases in a specialized outpatient setting. First analyses indicate a comparably high diagnostic yield in patients of the Cardiogenetic Registry. The registry will contribute to optimized patient care, individualized therapeutic approaches, and integration into national and international research networks.Figure 1.Whole-exome sequencing analysisFor image description, please refer to the figure legend and surrounding text.Figure 2.Cardiac and non-cardiac genesFor image description, please refer to the figure legend and surrounding text.