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Genetic Considerations for Cardiomyopathy

What is Cardiomyopathy?

Cardiomyopathy is a progressive heart muscle disease that can be acquired or inherited. This condition makes it increasingly difficult for the heart to pump blood throughout the body due to the weakening heart muscle. As cardiomyopathy progresses, patients might experience symptoms of fatigue, irregular heartbeats (arrhythmia), syncope, etc.

Genetic Considerations for Cardiomyopathy

Varying factors cause many types of cardiomyopathy; the most common type is dilated cardiomyopathy (DCM). DCM makes up 55% of cardiomyopathies, and its etiology is usually idiopathic or unknown. People with DCM have enlarged and thinned out ventricles. DCM can be inherited or occur due to coronary heart disease. Researchers have found that around 30-50% of patients have familial DCM resulting from mutations in up to 40 genes.

In most cases, DCM is inherited through an autosomal dominant pattern. This signifies that one copy of the mutated gene is enough to cause a child to inherit DCM. The affected genes encode for sarcomeric and cytoskeletal (desmin) in cardiac muscle cells called cardiomyocytes.

Scientists have determined that 25% of familial DCM is caused by truncating variants of the titin gene (TTN). Titin is the largest-known protein that plays essential roles in skeletal and cardiac muscles, and TTN provides instructions for making it. These TTN gene mutations have been found to result in shortened or truncated titin proteins that affect muscle cell functions, mainly sarcomere function. It is still unknown how exactly mutations in sarcomeric genes such as TTN cause familial DCM. Instead, it’s thought that cardiomyocyte function is impaired, resulting in the thinning and debilitation of the cardiac muscle.

A family history of heart disease and related conditions such as high blood pressure leads to an increased chance of heart diseases such as cardiomyopathy by around 6- to 400-fold. This statistic is affected based on the number of individuals with afflictions in your family, age, and even gender.

Genetic Screening for Cardiomyopathy

Genetic screening is an essential tool for early prognosis and diagnosis to establish possible preventative measures and treatments for afflicted humans and their possible asymptomatic relatives. Possible preventive measures or primary prevention strategies include cardiac monitoring, heart failure medications, and implantable cardioverter-defibrillators (ICDs). Affected individuals benefit from genetic counseling, which includes lifestyle changes such as limiting alcohol intake, eating a healthy diet, and more.

Genetic testing for cardiomyopathy involves collecting blood samples and looking for mutations in the genes known to cause cardiomyopathy, such as the TTN gene. Our research from early 2023 “Cardiomyopathy prevalence exceeds 30% in individuals with TTN variants and early atrial fibrillation”, on TTN variants in cardiology, performed in partnership with the Desert Research Institute, found a direct genetic association between atrial fibrillation and cardiomyopathy. The study showed that combining phenotypic information with population genomic screening can identify patients at a higher risk for progressing to symptomatic heart failure. To be able to have population-level screening for this gene, health systems must incorporate genomics into the routine management of heart disease.

After genetic screening is done, treatments are discussed with genetic professionals and depend on the complications at hand. For instance, severe cases often need cardiac transplantation, while more manageable cases with worsening symptoms can be ameliorated through oral diuretics, angiotensin-converting enzyme (ACE) inhibitors, etc.

Cardiomyopathy Outlook

Generally, cardiomyopathy will shorten your lifespan, whether inherited or acquired. The life expectancy for individuals with cardiomyopathy depends on the type and cause of it. On average, almost 50% of patients are dead within five years. Being able to identify the genetic risk of cardiomyopathy is critical to health systems providing preventative care, and population genomics provides an avenue for systems to start to engage in proactive, precision care. Get in touch with our team to learn more about how a turn-key population genomics program could improve care, reduce costs and drive innovation at your organization.