Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is one of the oldest known causes of sudden death. It was first described in 1958. It has been called HOCM (hypertrophic obstructive cardiomyopathy) and also IHSS (idiopathic hypertrophic subaortic stenosis), despite the fact that some patients do not have a sizeable resting outflow gradient. It is a relatively common genetic cause of sudden death, particularly in young athletes.

Epidemiology

Hypertrophic cardiomyopathy is actually the most common genetically-associated form of sudden cardiac death. It is estimated that 1 in 500 people (0.2% of the general population) carry an HCM genetic mutation. However, the phenotypic presentation or clinical penetrance of the disease is much lower. Most patients with an HCM mutation will not show signs of the disease during life.

Pathophysiology

Syncope in these subjects may occur due to arrhythmias or from an obstruction due to ventricular hypertrophy and cavitary obliteration. Dehydration can trigger a syncopal event in such patients. Sudden death is thought to occur in HCM due to a primary electrical abnormality by ventricular arrhythmias. In support of this view, one large study of HCM patients in whom defibrillators were implanted demonstrated that nearly 25% of the patients had documented ventricular arrhythmias over a three-year follow-up period. The disease may be progressive in some patients. The myocyte hypertrophy continues over years in a clinically silent manner and may lead ultimately to an end-stage, dilated cardiomyopathic picture. Depending upon the time frame during which the patient is evaluated, the HCM-affected heart could appear grossly normal, markedly hypertrophied, or even dilated, making the diagnosis difficult.

Clinical Features

When present, the hallmark feature of hypertrophic cardiomyopathy is myocyte disarray. The clinical diagnosis of HCM during life is made most reliably by echocardiography. Severe ventricular wall thickening can be seen. A normal left ventricular wall thickness is generally 30 mm are not unusual in severe cases of HCM. This marked septal hypertrophy is often an age-dependent effect, and may not be seen initially in young patients. In most cases, the left ventricle may be affected diffusely or may demonstrate asymmetric septal hypertrophy (ASH). In contrast, in the Japanese variant of HCM, the apical left ventricle is primarily affected and shows abnormal thickening. At autopsy using detailed pathologic examination, one can frequently see hypertrophied myocytes with bizarre shapes, chaotic cellular alignment, and gross cellular disarray in the left ventricle. Patchy areas of myocardial scarring and fibrosis can sometimes be noted, which is felt due to abnormal intramural coronary arteries.

Genetics

The polygenic and multicellular nature of HCM makes it a frustratingly complicated disease to diagnose unless gross histopathologic abnormalities are found on echocardiogram or at autopsy. At least 10 different genes encoding the cardiac sarcomere have been implicated in HCM. Over 150 unique mutations have been reported to date since the first genetic cause for HCM was identified in 1990. Most such mutations are missense mutations found in the proteins of the cardiac sarcomere and are located in the b-myosin heavy chain, cardiac troponin T, or myosin binding protein-C. Although the disease is autosomal dominant, a family history of syncope or sudden death may be lacking, and the disease has widely variable clinical penetrance. Within the b-myosin heavy chain gene (MYH7), numerous mutations have been described as malignant mutations associated with a poor clinical prognosis. These particular mutations seemed to be associated with a severe clinical phenotype including progression to end-stage heart failure or sudden death, a relatively high penetrance of the disease, and extreme left ventricular wall thickness.

Treatment

There are no formal guidelines for treating asymptomatic patients with hypertrophic cardiomyopathy. In those patients with symptoms of shortness of breath, medical therapy with medications that reduce the outflow gradient remain the mainstay of therapy. Such medications include beta-blockers or calcium channel blockers. In very symptomatic patients with a large (> 50 mm) gradient, the outflow gradient can be reduced by surgical myomectomy or by catheter-based alcohol ablation. The latter is a relatively new technique which causes a controlled myocardial infarction and thus reduces the outflow gradient. There was initial enthusiasm for placing dual chamber pacemakers to pace and try to decrease the outflow gradient. However, follow-up studies have shown that the long-term clinical benefit of this therapy is minimal. In those patients deemed high-risk for an arrhythmic event, an ICD may be implanted to avert sudden death. EP studies are not considered useful at identifying patients at risk for sudden death.