Histology · Year 1 · from Histology
Case 2: Arrhythmogenic Right Ventricular Cardiomyopathy
Clinical Image
Source: Wikipedia - Arrhythmogenic Right Ventricular Cardiomyopathy - CC BY-SA 3.0
Case Presentation
A 32-year-old man presents after an episode of palpitations and near-syncope during jogging. His ECG shows T-wave inversions in leads V1-V3 and an "epsilon wave" (small positive deflection at the end of the QRS complex). Cardiac MRI reveals fatty and fibrous replacement of the right ventricular free wall with regional wall motion abnormalities. Genetic testing identifies a mutation in PKP2, the gene encoding plakophilin-2, a desmosomal protein. He is diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC). The pathophysiology is explained: desmosomal proteins (plakophilin, desmoplakin, desmoglein, desmocollin) are essential components of the intercalated disc, specifically the desmosomes that provide mechanical adhesion between cardiomyocytes. When defective, cardiomyocytes detach and die during the mechanical stress of contraction, being replaced by fibro-fatty tissue. This creates a substrate for life-threatening ventricular arrhythmias. He receives an ICD and is restricted from competitive sports.
Key Learning Points
- ARVC results from mutations in desmosomal proteins of the intercalated disc
- Intercalated discs contain three junction types: fascia adherens (anchors actin), desmosomes (mechanical strength via intermediate filaments), and gap junctions (electrical coupling)
- Defective desmosomes cause cardiomyocyte detachment and death with fibro-fatty replacement
- The fibro-fatty tissue disrupts normal electrical conduction, creating re-entry circuits and arrhythmias
- This disease demonstrates the critical importance of intercalated disc integrity for cardiac function