'The imitation game': a heart failure case report with a great diagnostic twist

Area of Science:

• Cardiology
• Genetics
• Molecular Biology

Background:

• Arrhythmogenic ventricular cardiomyopathy (AVC) is a hereditary heart muscle disease linked to genetic defects in cardiac desmosome components.
• Mutations in the desmoglein-2 (DSG-2) gene are implicated in the pathogenesis of AVC.

Observation:

• A 49-year-old male presented with heart failure and ventricular arrhythmias, exhibiting imaging findings suggestive of cardiac sarcoidosis.
• Initial treatment for presumed cardiac sarcoidosis led to inflammation resolution, but subsequent genetic testing revealed a pathogenic DSG-2 variant.
• The patient presented with clinical and imaging features mimicking cardiac sarcoidosis, including myocardial inflammation detected by FDG-PET.

Findings:

• Genetic analysis identified a pathogenic variant in the DSG-2 gene, establishing a diagnosis of DSG-2 associated AVC.
• DSG-2 mutations are associated with significant left ventricular (LV) involvement and heart failure in AVC patients.
• The case demonstrates that DSG-2 cardiomyopathy can present with clinical and imaging characteristics similar to inflammatory cardiomyopathies like cardiac sarcoidosis.

Implications:

• This case underscores the importance of considering genetic testing for desmoglein-2 (DSG-2) associated AVC in patients with unexplained heart failure and arrhythmias, even when inflammatory conditions are suspected.
• Clinicians should maintain a high index of suspicion for inflammatory cardiomyopathies as a differential diagnosis in patients presenting with decompensated heart failure, arrhythmias, and evidence of active myocardial inflammation.
• The findings expand the clinical spectrum of DSG-2 cardiomyopathy and highlight the diagnostic challenges in differentiating it from other inflammatory heart conditions.