Arrhythmogenic Cardiomyopathy Diagnostics and Management

Arrhythmogenic cardiomyopathy is an inherited myocardial disorder distinguished by progressive fibrous and fatty replacement of the ventricular musculature and a propensity for life-threatening ventricular arrhythmias. Originally described as a right ventricular disease, recognition of left-dominant and biventricular phenotypes has prompted adoption of a broader term. Diagnosis relies on a synthesis of electrocardiographic abnormalities, structural and functional imaging findings, histopathological evidence, and genetic testing, as formalised in successive international consensus criteria. Cardiac magnetic resonance imaging, with its high spatial resolution and tissue-characterisation capabilities, now plays a central role in revealing subtle fibro-fatty scar patterns. Genetic analysis of desmosomal and non-desmosomal genes facilitates early identification of at-risk relatives and refines diagnostic certainty. Management aims to prevent sudden cardiac death through lifestyle modification, pharmacotherapy, catheter ablation and, in high-risk individuals, prophylactic implantable cardioverter-defibrillator (ICD) implantation. Risk stratification integrates clinical presentation, imaging markers, genotype, and arrhythmic burden to individualise therapeutic strategies. Emerging insights into molecular pathways and immune mechanisms promise to expand personalised approaches in the near future.

Research from Nature Portfolio

Foundational molecular studies have illuminated the pivotal role of desmosomal components in arrhythmogenesis. A seminal investigation demonstrated that loss of plakophilin-2 in cardiomyocytes disrupts transcription of key calcium-handling genes, leading to intracellular calcium imbalance and adrenergically induced arrhythmias, which may be mitigated by targeted use of antiarrhythmic agents. Complementary work has revealed systemic influences on myocardial remodelling, showing that altered expression of desmosomal proteins in adipose cells drives inflammatory and senescence pathways that may predispose to ventricular fibro-fatty infiltration. Together, these discoveries refine understanding of disease mechanisms and identify potential molecular targets for future diagnostic biomarkers and therapeutic interventions.

Arrhythmogenic Cardiomyopathy Diagnostics and Management publication trend

The graph below shows the total number of articles in arrhythmogenic cardiomyopathy diagnostics and management across all publications each year (not limited to Nature Index journals).

Technical terms

Desmosome: Cell-cell adhesion complex critical for mechanical coupling of cardiomyocytes.

Fibro-fatty replacement: Pathological substitution of myocardium with fibrous and adipose tissue.

Late-gadolinium enhancement (LGE): Magnetic resonance imaging technique that highlights myocardial scar.

Implantable cardioverter-defibrillator (ICD): Device implanted to detect and terminate life-threatening arrhythmias.

Risk stratification: Assessment of an individual’s probability of adverse events to guide therapy.

References

1. Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence. Nature Communications (2023).
2. NFĸB signaling drives myocardial injury via CCR2+ macrophages in a preclinical model of arrhythmogenic cardiomyopathy. Journal of Clinical Investigation (2024).
3. Plakophilin-2 is required for transcription of genes that control calcium cycling and cardiac rhythm. Nature Communications (2017).
4. Arrhythmogenic cardiomyopathy. Orphanet Journal of Rare Diseases (2016).
5. Arrhythmogenic right ventricular cardiomyopathy (ARVC): cardiovascular magnetic resonance update. Journal of Cardiovascular Magnetic Resonance (2014).
6. Importance of genotype for risk stratification in arrhythmogenic right ventricular cardiomyopathy using the 2019 ARVC risk calculator. European Heart Journal (2022).
7. Proposed diagnostic criteria for arrhythmogenic cardiomyopathy: European Task Force consensus report. International Journal of Cardiology (2023).