PO87
Uncovering the LMNA mutation behind a 2:1 atrioventricular block

A 58-year-old female patient with a medical history of dyslipidemia and pleural tuberculosis and a significant family history of cardiovascular disease, presented to the Emergency Department with a two-week history of dizziness. She denied syncope, angina, heart failure symptoms, or use of any medications. Her family history included a brother with dilated cardiomyopathy with biventricular involvement, who underwent heart transplantation at the age of 40; a first-degree cousin with a history of sudden cardiac death (not autopsied); and both parents with heart failure.

Initial evaluation revealed a sinus rhythm electrocardiogram with a heart rate of 40 bpm and a 2:1 atrioventricular block. Transthoracic echocardiography showed preserved global systolic function (left ventricular ejection fraction of 63% by biplane Simpson). The patient was admitted to the Cardiology Department for pacemaker implantation. Given the patient’s relatively young age, significant family history, and symptomatic atrioventricular block without any identifiable secondary cause, further investigation was conducted during hospitalization and follow-up. Autoimmune screening was negative. Cardiac magnetic resonance imaging showed preserved biventricular systolic function, no segmental wall motion abnormalities and a small area of mid-myocardial fibrosis in the basal anterior interventricular septum. Genetic testing in the patient identified a variant of uncertain significance, while subsequent testing in her brother revealed a probably pathogenic gene mutation, both in the Lamin (LMNA) gene. Over a follow-up period of approximately one year and a half, serial echocardiograms showed progressive left ventricular systolic dysfunction. The latest assessment demonstrated a slightly dilated left ventricle with normal wall thickness, abnormal septal motion, and mildly reduced left ventricular ejection fraction (45% by biplane Simpson, 46% by 3D). The patient was referred for cardiac resynchronization therapy – defibrillator implantation.

This case describes a 58-year-old woman with significant family history of dilated cardiomyopathy with a probably pathogenic LMNA gene mutation in her brother and sudden cardiac death, who initially presented with symptomatic 2:1 atrioventricular block, requiring pacemaker implantation, followed by progressive left ventricular dysfunction and genetic confirmation of a LMNA mutation, identified per now as variant of uncertain significance. The LMNA gene is associated with dilated cardiomyopathy and conduction system disease, conferring a high risk of sudden cardiac death. This case highlights the importance of a high index of suspicion and timely genetic testing, as well as the correlation with clinical findings, that allow an early diagnosis and tailored management of these patients.