arrhythmogenic right ventricular cardiomyopathy

**Pathophysiology** - Mutations in genes encoding desmosomal proteins (plakoglobin [JUP; Naxos disease], desmoplakin [DSP; Carvajal syndrome], plakophilin-2 [PKP2; most common], desmoglein-2 [DSG2], desmocollin-2 [DSC2]). Most cases are autosomal dominant with incomplete penetrance and variable expression. Naxos disease is autosomal recessive. - Defective cell-cell adhesion causes myocyte detachment and death, especially under mechanical stress (exercise). Inflammation and repair then replace the myocardium with fibrofatty tissue. - Fibrofatty replacement begins in the "triangle of dysplasia" (RV inflow, outflow, and apex). It creates a substrate for reentrant ventricular arrhythmias. LV involvement is increasingly recognized (biventricular or left-dominant forms).

**Clinical presentation** - Typically age 20–40, with male predominance. It is a classic cause of sudden cardiac death in young athletes. - Palpitations, syncope, or exertional ventricular tachycardia. Late disease may cause RV failure (JVD, edema, hepatomegaly) and, less commonly, biventricular failure. - VT usually has a left bundle branch block (LBBB) morphology because it originates in the RV. - Naxos disease: cardiomyopathy plus palmoplantar keratoderma and woolly hair. Carvajal syndrome is similar, with LV predominance.

**Diagnosis (2010 Task Force criteria; updated Padua criteria include LV disease)** - ECG: - Epsilon wave (small deflection after the QRS at the start of the ST segment in V1–V3), the classic finding but not sensitive. - T-wave inversion in V1–V3 (in the absence of RBBB). - Prolonged terminal QRS activation. - Echo and cardiac MRI: RV dilation, regional wall-motion abnormalities, aneurysms. MRI may show late gadolinium enhancement and fatty infiltration. - Biopsy or histology: fibrofatty replacement (biopsy is limited by patchy involvement and the thin RV wall). - Family history and genetic testing.

**Management** - Restrict competitive and endurance exercise, because it accelerates disease progression. - Beta-blockers for arrhythmia suppression. Add sotalol or amiodarone, or do catheter ablation, for recurrent VT. - ICD for secondary prevention (prior VT, VF, or cardiac arrest) and for selected high-risk primary prevention (syncope, severe RV or LV dysfunction, NSVT). - Heart failure therapy as needed. Transplant for refractory disease. - Screen first-degree relatives with ECG, echo, and genetic testing.

**Differential and board pearls** - Differentiate from: - RV outflow tract VT: a benign idiopathic condition with a structurally normal heart. - Brugada syndrome: coved ST elevation in V1–V2 with RBBB-like pattern, SCN5A mutation. - Hypertrophic cardiomyopathy: another cause of sudden death in young athletes. - Sarcoidosis, myocarditis. - Gross pathology: thin, dilated RV wall with fat and fibrous replacement. Histology shows fibrofatty replacement of myocytes. - Buzzwords: "young athlete," "sudden death," "epsilon wave," "LBBB-morphology VT," "desmosome," "fibrofatty replacement."