Cardiomyopathies

Definition and ClassificationTop

Cardiomyopathies are myocardial disorders in which the myocardium is structurally and functionally abnormal in the absence of significant coronary artery disease, hypertension, valvular heart disease, or congenital heart disease. These 4 conditions can cause left ventricular dysfunction from ischemia, infarction, volume overload, or pressure overload and are excluded from the classification scheme of cardiomyopathies by the European Society of Cardiology and the American Heart Association.

While classification schemes vary, cardiomyopathies are typically classified according to morphologic phenotypes, which can be further divided into familial or nonfamilial forms.

Classification:

1) Dilated cardiomyopathy.

2) Hypertrophic cardiomyopathy.

3) Restrictive cardiomyopathy.

4) Arrhythmogenic ventricular cardiomyopathy.

5) Unclassified cardiomyopathy.

Each of the above 5 types of cardiomyopathy can be further classified as:

1) Familial (genetic) cardiomyopathy: Occurrence in more than one family member of a phenotype caused by the same genetic mutation or a de novo mutation in an index patient that can be transmitted to offspring.

2) Nonfamilial (nongenetic) cardiomyopathy: Either idiopathic (of an unknown cause) or acquired (associated with toxins, infections, other diseases).

South Asia Perspective

The etiology of cardiomyopathies is complex but frequently has a genetic component. Of the common cardiomyopathies, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are genetic disorders. Dilated and restrictive cardiomyopathies are also associated with genetic mutations in a substantial number of patients. They are usually inherited as autosomal dominant disorders, although X-linked autosomal recessive and mitochondrial inheritance may also be present. Hundreds of mutations involving genes encoding sarcomeric and cytoskeletal proteins have been identified so far and the number is still growing. 

The pattern of these mutations varies in different ethnic groups, including South Asians. Although the genes involved remain the same, individual mutations differ. The reason for this variation is the founder effect—the effect of the first individual in whom the mutation occurred. Recent mutations may be restricted to a family, whereas those that occurred in the more remote past may be more prevalent in the population. A typical example is a 25 basepair deletion in intron 32 of the MyBPC3 gene that occurred in a South Asian individual ~23,000 to 33,000 years back. Over this long period, this sequence variation has spread to involve millions of the founder descendants. This is the most common sequence variation in South Asians (~4% of India’s population) that increases the risk of cardiomyopathies.

Novel sequence variations in South Asians may have important clinical implications but there is a paucity of clinical data on many of these. However, genetic counseling is an important part of cardiomyopathy management.