Abstract 15548: Rare Association of Arrhythmogenic Left Ventricular Cardiomyopathy Phenotype of Titin Mutation of Uncertain Significance

Case Presentation: A 67-year-old female presented to the office with exertional dyspnea, atypical chest pain, palpitations, and dizziness. She had a past medical history of hypertension, hyperlipidemia, mitral valve prolapse, and moderate mitral regurgitation. Her EKG identified multiple PVCs requiring the placement of a Holter monitor, a PVC burden of 31,441 beats (15%) was captured with variable morphology. TTE showed mild global hypokinesis of the left ventricle and ejection fraction (EF) of 40%. Coronary arteries were normal on cardiac catheterization. Cardiac magnetic resonance revealed epicardial late gadolinium enhancement suggestive of fatty infiltration of the distal lateral wall of the left ventricle (LV) indicative of Arrhythmogenic left ventricular cardiomyopathy (ALVC). The basal anterolateral wall of the LV appeared thin and dyskinetic, and the right ventricle was normal in size and function. Optimal medical therapy was initiated with metoprolol, sacubitril/valsartan, dapagliflozin, and spironolactone. A dual-chamber ICD was placed for primary prevention. Over time with medical management, her PVC burden reduced, and LVEF improved to 50%. A multigene panel for cardiomyopathies identified a mutation in titin (TTN) gene variant of unknown significance. Discussion: Previously thought to affect only the right ventricle, arrhythmogenic cardiomyopathy (ACM) is a rare genetic disease characterized by fibrofatty replacement of the ventricular myocardium. ALVC refers to the predominant LV dominant phenotype of this disease. The most frequent genetic mutations occur in the genes plakophilin (PKP2), desmoplakin (DSP), and desmoglein (DSG2). However, we report a case of ALVC in the setting of titin (TTN) gene variant, which is a gene usually implicated in dilated cardiomyopathy. However, the clinical significance of the TTN gene variant identified in our patient remains unclear as more studies are needed to link it to the phenotypic findings.