Heart failure (HF) occurs when the heart muscle becomes too weak or stiff to pump blood efficiently enough to meet the body’s needs. This condition does not mean the heart has stopped working, but rather that it requires support to function correctly. While often associated with the effects of aging or poor lifestyle choices, the question of whether heart failure can be passed down through a family is complex and involves multiple genetic factors.
Acquired vs. Inherited Heart Failure
Heart failure can generally be divided into two categories: acquired and inherited. The majority of heart failure cases are acquired, meaning they develop over time due to external factors or other medical conditions. Common acquired causes include long-standing, uncontrolled high blood pressure, coronary artery disease which limits blood flow, and damage from a previous heart attack.
Inherited heart failure, in contrast, results from a genetic predisposition or a direct defect in the heart muscle structure or function. This genetic risk exists on a spectrum, from monogenic to polygenic inheritance. Monogenic risk involves a single, identifiable gene defect that causes the disease with a high degree of certainty, often following a clear pattern of inheritance.
Polygenic risk, however, involves the cumulative effect of many different common genetic variants, each contributing a small amount to the overall risk. Genetic factors may influence the development of acquired conditions, such as high blood pressure or diabetes, which then lead to heart failure.
Specific Genetic Conditions That Lead to Heart Failure
When heart failure is directly inherited, it is often caused by a group of conditions known as cardiomyopathies, which are diseases of the heart muscle. These conditions impair the heart’s ability to pump effectively. Two of the most common types are Hypertrophic Cardiomyopathy (HCM) and Dilated Cardiomyopathy (DCM).
Hypertrophic Cardiomyopathy is a condition where the heart muscle, typically the left ventricle, becomes abnormally thick and stiff, making it difficult for the heart to relax and fill with blood. This thickening is most often caused by mutations in genes that code for the sarcomere, the heart muscle’s contractile unit. Specifically, variants in the MYH7 and MYBPC3 genes, which code for beta-myosin heavy chain and myosin-binding protein C, account for a large percentage of HCM cases.
Dilated Cardiomyopathy is characterized by the enlargement and weakening of the heart chambers, preventing them from pumping blood forcefully. Truncating variants in the TTN gene, which codes for the giant protein titin, are the most frequent genetic cause of familial DCM, accounting for up to 25% of cases.
Other genetic disorders can also lead to heart failure, including inherited arrhythmia syndromes and infiltrative diseases. For example, certain mutations in genes like LMNA can cause an aggressive form of DCM often accompanied by electrical conduction problems. Familial amyloidosis, a condition where abnormal proteins are deposited in the heart tissue, stiffening the muscle and causing heart failure, is another example of a directly inherited cause.
Evaluating Family History and Genetic Risk
Healthcare providers typically recommend gathering a history spanning at least three generations to identify a potential inherited cause. Specific signs that suggest an inherited heart condition include unexplained sudden death in a young relative, an early diagnosis of heart failure before the age of 50, or multiple close relatives with a known cardiomyopathy.
If a genetic link is suspected, or if a specific mutation is found in the first affected family member, a process called cascade screening is initiated. Cascade screening involves offering clinical and genetic testing to at-risk first-degree relatives, such as parents, siblings, and children. Clinical screening usually includes an electrocardiogram (ECG) and an echocardiogram to look for subtle structural changes in the heart muscle before symptoms appear.
Genetic testing involves a blood test to look for the specific pathogenic variant identified in the affected relative. Management for these individuals often involves regular monitoring with cardiology specialists, which allows for the timely initiation of standard heart failure medications to slow disease progression. Knowing the specific gene mutation can sometimes guide treatment, such as the use of an implantable cardioverter-defibrillator for those with certain high-risk mutations.