Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity

Area of Science:

• Cardiology
• Genetics
• Cardiovascular Imaging

Background:

• Arrhythmias and T-wave inversions are often misattributed to benign conditions or viral myocarditis.
• Left-dominant arrhythmogenic cardiomyopathy (LDAC) may present atypically, mimicking other cardiac disorders.
• The clinical and genetic underpinnings of LDAC require further elucidation.

Purpose of the Study:

• To investigate the clinical-genetic profile of left-dominant arrhythmogenic cardiomyopathy (LDAC).
• To identify characteristic features that distinguish LDAC from other cardiac conditions.
• To raise awareness among clinicians regarding the under-recognized LDAC subtype.

Main Methods:

• A cohort of 42 patients with unexplained inferolateral T-wave inversion, left ventricular (LV) arrhythmia, or a family history of LDAC/myocardial fibrosis was evaluated.
• Genetic analysis for desmosomal mutations was performed.
• Cardiac magnetic resonance imaging (MRI) and histopathology were utilized to assess LV myocardial changes.

Main Results:

• Patients presented with arrhythmias or chest pain, not heart failure, across a wide age range.
• Desmosomal mutations were found in a significant proportion of families (8/24) and patients (15/33).
• MRI revealed LV late enhancement in a subepicardial/midwall pattern, consistent with fibrofatty replacement; 50% were previously misdiagnosed with conditions like viral myocarditis or dilated cardiomyopathy (DCM).
• Significant arrhythmic events, including ventricular fibrillatory arrest and sudden cardiac death, occurred during follow-up.

Conclusions:

• Arrhythmogenic cardiomyopathy is characterized by a higher propensity for arrhythmia than ventricular dysfunction, differentiating it from DCM.
• LDAC is under-recognized due to misdiagnosis and lack of specific criteria.
• Clinicians should consider LDAC in patients with unexplained LV arrhythmias, T-wave inversions, apparent DCM, or myocarditis symptoms.