Hypertrophic Cardiomyopathy

Updated: Apr 29, 2022
  • Author: Sandy N Shah, DO, MBA, FACC, FACP, FACOI; Chief Editor: Gyanendra K Sharma, MD, FACC, FASE  more...
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Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. This disorder is caused by a mutations in genes encoding cardiac sarcomere protein, resulting in variety of phenotypical expression and clinical course. HCM is the most common cause of sudden death in young people. 

Although HCM was written about and known as idiopathic hypertrophic subaortic stenosis (IHSS) or asymmetrical septal hypertrophy (ASH) decades ago, these terms were replaced by hypertrophic cardiomyopathy because the segmental hypertrophy can occur in any segment of the ventricle, not just the septum. Furthermore, this entity can present without subaortic obstruction to flow yet still carry the same ominous risk of arrhythmogenic sudden death and many of its clinical symptoms.

HCM can be separated into obstructive and nonobstructive types. Obstructive HCM is due to midsystolic obstruction of flow through the left ventricular outflow tract as a result of a Bernoulli effect–induced systolic anterior mitral valve movement toward the septum.

The significance of this obstruction, however, is highly controversial. Some investigators and experts believe the obstruction has less to do with the overall hemodynamic and pathophysiologic manifestations of this entity than it does with the inappropriate segmental hypertrophy, which, with its increased myocardial oxygen consumption and substrate for fatal ventricular arrhythmias, has much more significance in the overall clinical picture of this entity and in the treatment and prognosis of HCM.



Since the initial descriptions of hypertrophic cardiomyopathy (HCM), the feature that has attracted the greatest attention is the dynamic pressure gradient across the LV outflow tract. The pressure gradient appears to be related to further narrowing of an already small outflow tract (already narrowed by the marked asymmetrical septal hypertrophy and possibly by an abnormal location of the mitral valve) by the systolic anterior motion of the mitral valve against the hypertrophied septum.

Three explanations for the systolic anterior motion of the mitral valve have been offered, as follows: (1) the mitral valve is pulled against the septum by contraction of the papillary muscles, which occurs because of the valve's abnormal location and septal hypertrophy altering the orientation of the papillary muscles; (2) the mitral valve is pushed against the septum because of its abnormal position in the outflow tract; (3) the mitral valve is drawn toward the septum because of the lower pressure that occurs as blood is ejected at high velocity through a narrowed outflow tract (Venturi effect).

Most patients with HCM have abnormal diastolic function (whether or not a pressure gradient is present), which impairs ventricular filling and increases filling pressure, despite a normal or small ventricular cavity. These patients have abnormal calcium kinetics and subendocardial ischemia, which are related to the profound hypertrophy and myopathic process.



Abnormal calcium kinetics

Data link abnormal myocardial calcium kinetics to the cause of the inappropriate myocardial hypertrophy and specific features of hypertrophic cardiomyopathy (HCM), particularly in patients with diastolic functional abnormalities. Abnormal myocardial calcium kinetics and abnormal calcium fluxes from an increase in the number of calcium channels result in an increase in intracellular calcium concentration, which, in turn, may produce hypertrophy and cellular disarray.

Genetic causes

Familial HCM occurs as an autosomal dominant Mendelian-inherited disease in approximately 50% of cases. Some, if not all, of the sporadic forms of the disease may be caused by spontaneous mutations.

At least 6 different genes on at least 4 chromosomes are associated with HCM, with more than 50 different mutations discovered thus far. Familial HCM is a genetically heterogenous disease in that it can be caused by genetic defects at more than 1 locus.

In 1989, Seidman and collaborators first reported the genetic basis for HCM. They reported the existence of a disease gene located on the long arm of chromosome 14. Subsequently, they found this to be the gene encoding for beta cardiac myosin heavy chain.

Wide variation exists in the phenotypic expression of a given mutation of a given gene, with variability in clinical symptoms and the degree of hypertrophy expressed. Phenotypic variability is related to the differences in genotype, with specific mutations associated with particular symptoms, the degree of hypertrophy, and the prognosis. [1]

Other possible causes

Other possible causes of HCM include the following:

  • Abnormal sympathetic stimulation - Heightened responsiveness of the heart to the excessive production of catecholamines or the reduced neuronal uptake of norepinephrine might cause HCM

  • Abnormally thickened intramural coronary arteries - These do not dilate normally, which leads to myocardial ischemia; this progresses to myocardial fibrosis and abnormal compensatory hypertrophy

  • Subendocardial ischemia - This is related to abnormalities of the cardiac microcirculation that deplete the energy stores essential for the sequestration of calcium during diastole; subendocardial ischemia results in persistent interaction of the contractile elements during diastole and increased diastolic stiffness

  • Cardiac structural abnormalities - These include a catenoid configuration of the septum, which results in myocardial cell hypertrophy and disarray



Hypertrophic cardiomyopathy (HCM) is reported in 0.5% of the outpatient population referred for echocardiography. [2] The overall prevalence of HCM is low and has been estimated to occur in 0.05-0.2% of the population. [3] Morphologic evidence of disease is found by echocardiography in approximately 25% of first-degree relatives of patients with HCM. Genetic testing still is in the early stages of research development but can be used to identify asymptomatic family members with the same mutation as the proband (index case).

Sex-related demographics

HCM is slightly more common in males than in females. However, the genetic inheritance pattern is autosomal dominant, without sex predilection. Modifying genetic, hormonal, and environmental factors may lead to a higher likelihood of identification in males, increased symptomatology, or higher degrees of LV outflow obstruction, with more prominent findings upon physical examination.

HCM usually presents at a younger age in females. Females tend to be more symptomatic and are more likely to be disabled by their symptoms than males.

Age-related demographics

In general, HCM has a bimodal peak of occurrence. The most common presentation is in the third decade of life, but it may present in persons of any age, from newborns to elderly individuals.

In children, inherited cases are found in an age range from newborn (ie, stillborn babies) to adult. The peak incidence is in these cases is in the second decade of life.

In adults, the peak incidence is in the third decade of life, with the vast majority of cases occurring in the age range between the third and sixth decades of life.




Reported annual mortality rates in patients with hypertrophic cardiomyopathy (HCM) have ranged from less than 1% to 3-6%, and studies suggest that they have significantly improved over the past 40 years. [4]

A study by Elliott et al reported that published sudden death rates over the previous 10 years were lower than were previously published figures (median 1.0% (range 0.1–1.7) v 2.0% (0–3.5)). Nevertheless, HCM still carries a high risk for mortality and morbidity. [5]

One series of 46 patients with midventricular obstruction was found to have an increased risk of apical aneurysm formation, symptoms, and HCM-related death compared with those who did not have midventricular obstruction; the increased risk of symptoms and death was similar to that seen in patients with LV outflow obstruction. [6]

Most patients with HCM are asymptomatic. Unfortunately, the first clinical manifestation of the disease in such individuals may be sudden death, likely from ventricular tachycardia or fibrillation. Younger patients, particularly children, have a much higher mortality rate. Children have a much greater degree of ventricular hypertrophy and are much more symptomatic early on in the disease course, most likely because more malignant genotypes are present earlier in life.

The more benign mutations do not elicit a clinical or echocardiographic phenotype or symptoms in the pediatric population. Death often is sudden, unexpected, and typically is associated with sports or vigorous exertion. Early diagnosis is of prime importance in order to prescribe an appropriate level of safe activity. [1, 7, 8]

Screening of first-degree relatives is useful to identify additional affected family members prior to the onset of significant symptoms or sudden death.

Patients can have a myriad of arrhythmias, including atrial fibrillation, atrial flutter, ventricular ectopy, ventricular tachycardia, and ventricular fibrillation. These patients are among the highest-risk group for ventricular fibrillation and pose difficult therapeutic decisions for risk reduction.

Patients have a high likelihood of recurrent heart failure resulting from mitral regurgitation and profound diastolic dysfunction. HCM is a progressive condition that worsens over time, as does the gradient across the LV outflow tract if left untreated. Systolic function usually is well preserved until the late stages of the disease. Angina is rare in children but common in adults. Syncope and presyncope are common and may identify individuals at high risk for sudden death.


Complications of HCM may include the following:

  • Congestive heart failure

  • Ventricular and supraventricular arrhythmias

  • Infective mitral endocarditis

  • Atrial fibrillation with mural thrombus formation

  • Sudden death


Patient Education

Family members should learn cardiopulmonary resuscitation. In addition, refer the patient and family for psychosocial counseling. Refer children of patients with hypertrophic cardiomyopathy (HCM), especially those in the pediatric age range, for urgent echocardiography and genetic testing if an echocardiogram does not yet reveal overt disease.

Impose activity restrictions that include total abstinence from highly competitive athletic activities and very strenuous physical exertion, such as lifting heavy objects, lifting weights, and shoveling snow.

For patient education information, see the Heart Health Center, as well as Palpitations.