What Causes Cardiomyopathy? Primary vs Secondary Cardiomyopathy

Cardiomyopathy is a group of disorders that affect the heart muscle. They are characterized by the presence of structural changes in the heart muscle — like changes in size, shape, or the thickness of the muscle walls. These changes can reduce the heart's ability to pump blood, or affect its electrical signaling and conduction.

What are the main types of cardiomyopathy?

Your heart is a muscular pump consisting of four chambers. The wwo upper chambers called atria collect the blood, while the lower chambers, called ventricles, pump the blood. Between the atrium and the ventricle, there is a valve that directs blood flow in one direction. The left and the right side of the heart are separated by a wall called the septum. Any of these parts can be impacted by cardiomyopathy, but the part that’s most commonly affected is the heart’s main pumping chamber — the left ventricle. When that happens, the heart can’t pump blood as effectively. That can manifest with symptoms like breathlessness, fatigue or swelling of the legs and feet.

There are four main types of cardiomyopathy:

• Dilated cardiomyopathy (DCM). DCM is thought to be the most common type of cardiomyopathy, in which one or both ventricles become enlarged (most commonly the left ventricle). Their walls stretch (dilate) and become thinner, making it harder for them to pump blood. The mitral valve that directs blood flow from the left atrium to the left ventricle can also be affected.
• Hypertrophic cardiomyopathy (HCM). HCM is the most common type of inherited cardiomyopathy. It usually affects the left ventricle and the septum, although the right ventricle and mitral valve can be affected as well. In this condition, the walls of the ventricle become thick and stiff. This means that the ventricle can hold less blood (the walls are thicker, so there is less space inside of the ventricle) and that it can’t relax or contract normally (because of the stiffness). If the valve is affected, blood might leak backward.
• Arrhythmogenic right ventricular cardiomyopathy (ARVC or arrhythmic cardiomyopathy). As the name says, the main symptom of this condition are arrhythmias or irregular heartbeats. Regular heartbeats depend on the electrical conductivity in the heart, which is interrupted in ARVC by deposits of fibrous scar tissue and fat cells. Myocytes (cells of the heart muscle) are joined together by protein structures called desmosomes. In ARVC, desmosomes don’t develop properly, causing myocytes to detach themselves and eventually die. They are replaced by fibrous scar tissue and fat cells. As the disease progresses the left ventricle might also be affected, but the atria (upper chambers) remain normal.
• Restrictive cardiomyopathy (RCM). RCM is the least common type of the four. The walls of the ventricles become stiff, and normal tissue is replaced with scar tissue. The size and shape of the ventricles usually stay normal. Because of the stiffness, the ventricles can’t fully relax and fill with blood.

You shouldn’t think of these types as single conditions with a single cause. Rather, they are a group of conditions that can have several different causes, often presenting with a different set of symptoms. For example, there are more than 27 known causes of RCM, and in all types of CM the cause can’t always be identified (those conditions are called idiopathic).

Classification of cardiomyopathy: primary vs secondary

In 2006, the American Heart Association (AHA) classified all cardiomyopathies in two major groups — primary and secondary, based on which organ is predominantly involved. In primary cardiomyopathy, the heart muscle is the sole (or the predominantly) affected organ, while secondary cardiomyopathy happens as a part of a generalized, multi-organ disorder in which the heart is one of the organs affected. However, this classification is imperfect, since the distinction can’t always be made, and the European Society of Cardiology recommends a different system.

What causes primary cardiomyopathy?

Depending on the cause, primary cardiomyopathy can be divided into three groups: genetic, acquired, and mixed (both genetic and non-genetic).

1. Genetic causes

Cardiomyopathies that can have a genetic cause include:

• Hypertrophic cardiomyopathy. HCM is a result of one or more mutations of the genes that code for proteins of the heart which are responsible for muscle contractions. So far, 11 genes have been associated with HCM, most commonly the genes for myosin heavy chain and myosin-binding protein C. There are more than 400 possible mutations of these genes. It is an autosomal dominant disease, which means that the mutated gene is found on the autosome (non-sex chromosome) and a child has a 50 percent chance of inheriting this condition from a parent.
• Arrhythmogenic right ventricular cardiomyopathy​. ARVC has been linked with mutations in four genes that are associated with the proteins that form the desmosome. It’s usually autosomal dominant.
• Left ventricular non-compaction (LVNC). In LVNC the walls of the left ventricle are non-compacted, creating a characteristic “spongy” look. Around 40 percent of the LVNC cases can be traced to a genetic origin.

2. Acquired causes

Conditions that may lead to primary cardiomyopathy include:

• Myocarditis. Myocarditis is an inflammation of the heart muscle, typically caused by viruses. When a virus enters the heart, the cells of the immune system enter the heart in an attempt to eliminate it. However, the immune response can sometimes damage the heart, either through molecules that some of these cells produce or by an attack on the heart cells instead of the virus (an autoimmune reaction.
• Stress. Broken heart syndrome is a common name for takotsubo cardiomyopathy that happens as a result of extreme psychological stress.
• Pregnancy. This happens very rarely and the exact cause is still unclear.

3. Mixed causes

Dilated cardiomyopathy and restrictive cardiomyopathy can be caused both by genetic and non-genetic causes.

In DCM around 25 to 35 percent of the cases are caused by mutations in the genes for different proteins in the heart. It can also be an acquired condition caused by myocarditis. The cause can be secondary as well, when DCM happens as a result of autoimmune disease, chemotherapy, endocrine disorders (hormone disorders) and many others.

What causes secondary cardiomyopathy?

A vast number of systemic diseases can affect the heart. They are different from primary conditions, because the heart is just one of several affected organs. They can be classified into several groups:

• Infiltrative. Amyloidosis (build-up of clumps of proteins), Gaucher disease(build-up of specific lipid called glucocerebroside), Hunter's disease (build-up of large sugar molecules called glycosaminoglycans), Hurler's disease (similar to Hunter's). In these conditions, abnormal substances accumulate between the heart muscle cells.
• Storage. Hemochromatosis (iron build-up), glycogen storage disease, Niemann-Pick disease (lipids build-up).
• Toxicity. Drugs, heavy metals, chemicals.
• Endocrine (hormonal and metabolic disorders). Diabetes mellitus, thyroid disorders, acromegaly (pituitary gland disorder).
• Nutritional deficiencies. Beri-beri (vitamin B₁ deficiency), scurvy (vitamin C deficiency).
• Autoimmune diseases (conditions in which the body attacks itself). Systemic lupus, scleroderma, rheumatoid arthritis.
• Cancer treatment.