Since its first formal description in 1958, the medical understanding of and clinical approach toward hypertrophic cardiomyopathy (HCM) has evolved significantly. Not surprisingly, the terminology used to describe the condition has evolved as well. Once thought to be a rare, highly lethal and untreatable disease with an annual mortality rate as high as 6% per year, it is now known to be a common familial condition with only modest mortality (approximately 1%) in most cases.
In the January 1958 edition of the British Heart Journal, pathologist Donald Teare reported eight cases of sudden cardiac death in adolescents or young adults. Upon microscopic examination of the hearts at autopsy, all were found to have striking septal hypertrophy and a “bizarre arrangement of bundles of muscle fibres running in diverse directions and separated by connective tissue and clefts.”1 Teare postulated that the cause was a type of diffuse tumor that he called a “muscular hamartoma.”
Extensive research over the last 50 years, helped considerably by the development of echocardiography in the early 1970s, has provided a much broader and deeper understanding of this condition while validating many of Teare’s original observations. Rather than a tumor, this condition is now recognized as a genetically mediated primary disease of the myocardium – that is, a cardiomyopathy. Initially referred to by terms such as idiopathic hypertrophic subaortic stenosis (IHSS), hypertrophic obstructive cardiomyopathy (HOCM), muscular subaortic stenosis, and asymmetric septal hypertrophy (ASH), it has since been recognized that the condition can present in a variety of ways: not all cases affect the septum disproportionately, and about one-third of cases do not have obstruction to left ventricular outflow. Therefore the more general term “hypertrophic cardiomyopathy” (or HCM) is now preferred.
Definition, Epidemiology, and Cause
HCM is a disease found worldwide with a fairly consistent global prevalence of 0.2% (or 1 in 500). It is caused by pathogenic variations in at least one of the eight genes that encode for protein constituents of the sarcomere, which is the contractile unit of cardiac muscle. The disease is inherited in an autosomal dominant pattern; however, there is significant variation in expression even within families with the same mutation. At this point, more than 1,400 HCM-causing genetic mutations have been identified and novel mutations are common6.
The current generally accepted definition of HCM is a hypertrophied and nondilated left ventricle in the absence of other cardiac conditions (such as uncontrolled hypertension and aortic valve disease) that could also produce the findings. The hypertrophy may be quite focal or more generalized, and usually (but not always) has a wall thickness of ≥15 mm in adults (13-14 mm is considered borderline). In children, wall thickness of ≥2 standard deviations above the mean for age, sex, or body size meets the definition. MRI studies have shown that the left ventricular anterior free wall and contiguous basal anterior septum are the most frequently involved segments. A significant number of cases have involvement limited to areas of the left ventricle not well seen by echocardiography4.
The increased availability of genetic testing is identifying a growing population of individuals known to carry a pathogenic mutation (genotype-positive) but without clear clinical manifestations of the disease. These manifestations are referred to either as phenotype-negative or hypertrophy-negative. Research is also indicating that there are certain structural changes aside from hypertrophy that may indicate a “subclinical” or “preclinical” state.
HCM is often asymptomatic, especially when there is no obstruction to left ventricular outflow. When present, symptoms may include palpitations, dyspnea, fatigue, and syncope, particularly following exertion. Sudden cardiac death due to ventricular arrhythmia may be the initial manifestation of the disease. Atrial fibrillation, heart failure, and thromboembolic events are also potential complications. The ECG is usually abnormal with findings suggestive of left ventricular hypertrophy, such as increased QRS voltage and ST-T wave changes, but it may also be completely normal in a small minority of cases.
Echocardiography is the mainstay for diagnosis and risk stratification, although there
is an increasing role for MRI. In addition to a thickened, nondilated ventricle, the ejection fraction is often high despite evidence of diastolic dysfunction. There may be systolic anterior motion (SAM) of the mitral valve with eccentric mitral regurgitation and a dynamic left ventricular outflow tract gradient.
An MRI may enable a more accurate assessment of wall thickness in all areas of the ventricles and can also assess for fibrosis, which is an emerging marker for increased arrhythmia risk.
Clinical expression of HCM usually increases with age. Hypertrophy most often becomes apparent during adolescence, but a first appearance later in life is not uncommon. ECG changes, increased ejection fraction, and delayed myocardial relaxation may precede the onset of hypertrophy.
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