A 32-year-old man dies suddenly in his sleep. He had been experiencing easy fatigability for the past 6 months and mentioned that he was feeling tired "'all the time"' and needed to take naps during the day. He did not drink alcohol or use illicit drugs. He smoked a pack of cigarettes per day for 10 years. His father died from a "heart problem" at age 40. On autopsy, the heart appears grossly enlarged. A layered mural thrombus is seen in the left ventricular apex. Coronary atherosclerosis is present, with 20% narrowing of the mid-left anterior descending artery and 25% narrowing of the left circumflex artery. Which of the following is the most likely cause of death of this patient?

Question

A 32-year-old man dies suddenly in his sleep.  He had been experiencing easy fatigability for the past 6 months and mentioned that he was feeling tired "'all the time"' and needed to take naps during the day.  He did not drink alcohol or use illicit drugs.  He smoked a pack of cigarettes per day for 10 years.  His father died from a "heart problem" at age 40.  On autopsy, the heart appears grossly enlarged.  A layered mural thrombus is seen in the left ventricular apex.  Coronary atherosclerosis is present, with 20% narrowing of the mid-left anterior descending artery and 25% narrowing of the left circumflex artery.  Which of the following is the most likely cause of death of this patient?

Quizplus · Accepted Answer

This patient most likely died due to dilated cardiomyopathy (DCM). A primary insult to the myocardium leads to impaired myocardial contractile function with dilation of one or both ventricles. The structural changes to the ventricular myocardium places these patients at risk of sudden cardiac death from ventricular arrhythmia (ie, ventricular tachycardia, ventricular fibrillation). In addition, the global hypokinesis of the left ventricle leads to stagnation of blood flow and the possible development of LV mural thrombus and subsequent systemic embolization. Causes of DCM include infection (eg, viral myocarditis, Chagas disease), chemical toxicity (eg, alcohol), and inherited disease. The premature death of this patient's father from a heart problem suggests familial DCM, which is typically transmitted in an autosomal dominant inheritance pattern. Truncating mutations affecting the TTN gene, which encodes for the cardiac sarcomere protein titin, are the most common cause of familial DCM. (Choice A) Antiphospholipid antibody syndrome is an autoimmune disorder characterized by venous and/or arterial thrombosis. Cardiac manifestations can include valvular thickening, nonbacterial vegetations, and increased risk of coronary atherosclerosis; however, LV cavity enlargement and mural thrombus are not typical. (Choice C) Hypertrophic cardiomyopathy is an autosomal dominant genetic disorder caused by mutation in genes encoding for one of several cardiac sarcomere proteins (eg, beta-myosin heavy chain, myosin-binding protein C). It is a common cause of sudden cardiac death in young individuals, usually during exertion. Autopsy typically shows asymmetric septal hypertrophy of the left ventricle. (Choice D) Ischemic heart disease can lead to myocardial dysfunction and LV enlargement that mimics DCM; however, this patient's coronary arteries had only minor atherosclerotic narrowing (ie, 20% and 25%) that would not have caused clinically significant myocardial ischemia. (Choice E) Restrictive cardiomyopathy is typically the early cardiac manifestation of an infiltrative process (eg, amyloidosis, sarcoidosis) and is characterized by nondilated ventricles with enlargement of both atria. Educational objective: Dilated cardiomyopathy results from primary myocardial dysfunction leading to eccentric remodeling of the left ventricle. Patients can develop left ventricular mural thrombus and are at risk for sudden cardiac death due to ventricular arrhythmia. Familial dilated cardiomyopathy is typically inherited in an autosomal dominant pattern, and most commonly results from truncating mutations of the TTN gene that codes for the sarcomere protein titin. __________ References: Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. (http://www.ncbi.nlm.nih.gov/pubmed/17916581)

A 32-Year-Old Man Dies Suddenly in His Sleep