This article discusses HCM and its causes, including genetics and risk factors for complications.
Genetics of Hypertrophic Cardiomyopathy
While mutations that cause HCM are usually passed down from a family member, usually in an autosomal dominant way, they can also be sporadic in some cases, meaning the mutation occurs randomly, without a parent being affected.
Adding to the complexity, however, is the fact that several different types of mutations exist. And even people who have inherited a mutation that causes HCM may not develop it or its complications, a phenomenon known as variable penetrance.
Furthermore, someone with HCM may have more or less severe symptoms than a family member, which is known as variable expression.
Mutations That Cause Hypertrophic Cardiomyopathy
Sarcomere Mutations
The most common type of mutations that cause HCM are mutations in sarcomeric proteins in the heart.
Sarcomeres are proteins found in muscle cells. Mutations in sarcomeres that cause HCM result in thickening of the heart muscle, disorganized muscle fibers, and scarring.
The following is a list of mutations in sarcomeric proteins known to cause HCM:
MYH7: β-Myosin Heavy ChainMYBPC3: Myosin binding protein C3TNNT2: Cardiac troponin TTNNI3: Cardiac troponin ITPM1: α-TropomyosinMYL2: Regulatory myosin light chainMYL3: Essential myosin light chainACTC1: Cardiac α-actinCSRP3: Cysteine- and glycine-rich protein 3
In people who have a sarcomere mutation, mutations in beta myosin heavy chain and myosin binding protein C3 are the most common causes. They are found in about 70% of cases. The other sarcomere mutations each account for only 1%–5% of HCM mutations.
Genetic testing is performed in people whose imaging tests reveal signs of HCM. It is particularly useful after a diagnosis of HCM to test family members for the gene mutation.
Variants of Uncertain Significance
Not everyone with HCM has an identified mutation that has been shown to cause HCM. Some people may have variants in the related genes, but it remains unclear if they are the cause of HCM. These are known as “variants of uncertain significance.”
As our understanding of genetics in HCM evolves, these variants may be further clarified.
Risk Factors for Sudden Cardiac Death
Heart muscle thickening, disorganization, and scarring in HCM can lead to arrhythmias and sudden cardiac death. In fact, HCM is the most commonly identified cause of sudden death in athletes younger than 30 years old.
Healthcare providers use risk factors to determine the risk of sudden death and make recommendations about exercise restrictions and implantable cardioverter defibrillators (ICDs). These devices monitor the heart rhythm and provide a shock of electricity to stop dangerous arrhythmias.
The following are factors found to be associated with increased risk of SCD.
Sudden Cardiac Death in a Family Member
The risk of sudden death is increased if a family member has experienced SCD. This is particularly true when the family member is a close relative (first or second degree relative) and was less than 50 years of age at the time of death.
Findings on Heart Imaging
The left ventricle is the main muscular chamber of the heart that pumps blood to the body. Noninvasive imaging tests, such as echocardiogram and cardiac magnetic resonance imaging (MRI), give information about the left ventricle that can predict who is at higher risk of SCD.
Findings that may indicate HCM include:
Thickness of the left ventricular wall: Normally, the left ventricle is less than 1 centimeter thick. In HCM, however, the left ventricle is thicker. Those with HCM who have left ventricular wall thickness of 3 centimeters or more are at high risk of sudden cardiac death. Left ventricular dysfunction: The ejection fraction (EF) is a measure of the heart’s pumping function. The EF is the proportion of blood pumped out with each heartbeat. In HCM, when the EF is below 50%, risk of SCD is higher. Apical aneurysm: People with HCM sometimes have a small out-pouching of the ventricular wall, known as an apical aneurysm. Having an apical aneurysm also increases risk of SCD in HCM. Extensive scarring: Cardiac MRI can reveal scarring of the heart. When less than 15% of the heart is scarred, risk of SCD is higher.
History of Unexplained Syncope
Those with HCM who have had recent unexplained fainting spells are also at risk of SCD. “Unexplained” syncope, or fainting, means that there was no obvious cause of loss of consciousness, such as a vasovagal event (for example, passing out when getting blood drawn).
Findings on Heart Rhythm Monitoring
People with HCM undergo heart rhythm monitoring to evaluate for arrhythmias. Those whose rhythm monitoring show an arrhythmia called nonsustained ventricular tachycardia (NSVT) that are frequent, long, or very fast, are at higher risk of SCD.
Summary
Hypertrophic cardiomyopathy is an inherited disease that can be caused by several different genetic mutations. Having a genetic mutation increases risk, but does not mean that your heart will necessarily be severely affected. Genetic testing is particularly useful for evaluating family members.
Beta-blockers Calcium channel blockers Disopyramide Mavacamten (recently approved by the Food and Drug Administration) Septal reduction therapy Implantable cardioverter defibrillator
If hypertrophic cardiomyopathy runs in your family, you should have an evaluation by a cardiologist, who will evaluate your symptoms, family history, and order any necessary testing.
A Word From Verywell
Finding out that you have a genetic mutation for hypertrophic cardiomyopathy can provoke anxiety, especially if other family members have experienced problems from thickened heart muscle. Know that not everyone with the mutation goes on to have detectable heart problems, and there are many promising treatments for people with HCM. Cardiac testing will help you and your healthcare provider determine a treatment and follow-up plan.
