Abstract 11196: Germline Mutation in Plakophilin 2 and Associated Hypertrophic Cardiomyopathy: Clinical Debate of Nascent Pleomorphism and Pleotropism

Abstract

Introduction: Arrhythmogenic cardiomyopathy(ACM) is often not seen until adolescence or early childhood. Electric abnormalities usually precede the structural remodeling visible on cardiac imaging. Clinical case: 31-year-old male with asthma and hypertension presented to the ED with palpitations and was in atrial fibrillation with rapid ventricular response. He was treated with diltiazem and converted to sinus rhythm. TTE performed showed basal septal hypertrophy with hypercontractile LV. He was discharged on beta-blocker and anticoagulation. Few days after, he reported lightheadedness and syncopal spells after starting on beta-blocker therapy, and orthostatic by nature. ECG revealed sinus rhythm, left ventricular hypertrophy and inferolateral deep T wave inversions. Family history was revealing for HCM in father and grandmother, but no genetic conditions or sudden cardiac deaths. Stress TTE with diltiazem use showed no LVOT obstruction at rest or after exercise. Cardiac MRI revealed asymmetric basal septal hypertrophy with max thickness of 1.5 cm. Dynamic LVOT obstruction was seen with anomalous insertion of papillary muscle into mid-anterior portion of anterior mitral leaflet. LV was hypercontractile with EF 85%, and no evidence of fibrosis. RV was normal in size/function without abnormal wall motion. Holter monitoring was unremarkable. Cardiomyopathy/arrhythmia multigene panel testing surprisingly showed a heterozygous plakophilin-2(PKP2) pathogenic germline mutation c.1689-1G>C, pathogenic for ARVC. Conclusion: Based on current guidelines, he would not have ACM and begs the question of management in patients with positive ACM genetics, but no ACM-related disease expression. The underlining question would be the clinical significance and evolution of such detected mutations, and given the current paucity in evidence, we share your enthusiasm in learning more about this patient’s future clinical trajectory.