Arrhythmogenic cardiomyopathy: pathogenesis, pro-arrhythmic remodelling, and novel approaches for risk stratification...

Area of Science:

• Cardiology
• Genetics
• Molecular Biology

Background:

• Arrhythmogenic cardiomyopathy (ACM) is a life-threatening inherited heart disease.
• It results from genetic mutations affecting desmosomal proteins, altering the cardiac intercalated disc.
• ACM leads to fibrofatty tissue replacement of cardiomyocytes, ventricular dysfunction, and potentially sudden cardiac death (SCD).

Purpose of the Study:

• To review the etiology and pro-arrhythmic mechanisms of ACM, particularly in its early, concealed phase.
• To summarize potential novel biomarkers for risk stratification and disease progression prediction in ACM mutation carriers.
• To explore innovative therapeutic strategies for preventing arrhythmias and SCD in early-stage ACM.

Main Methods:

• Literature review focusing on genetic causes, molecular mechanisms, and clinical aspects of ACM.
• Analysis of current understanding of intercalated disc alterations in ACM.
• Synthesis of research on early disease detection, risk assessment, and emerging treatments.

Main Results:

• ACM pathogenesis involves desmosomal gene mutations leading to intercalated disc instability.
• Early ACM phases are often asymptomatic but carry a high risk of life-threatening arrhythmias and SCD.
• Disease severity and progression are highly variable among affected individuals.

Conclusions:

• Understanding early pro-arrhythmic mechanisms is crucial for managing ACM.
• Novel biomarkers are needed for accurate risk stratification and prediction of disease course.
• Targeted therapies hold promise for preventing arrhythmias and SCD in early-stage ACM.