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These studies suggest that cardiomyopathy can be caused by genetic mutations, toxic effects of various drugs, and metabolic conditions such as diabetes.
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Cardiomyopathy is a complex and multifactorial disease characterized by the deterioration of the heart muscle, leading to impaired cardiac function. The causes of cardiomyopathy can be broadly categorized into genetic, metabolic, toxic, and other underlying conditions. This article synthesizes the key findings from recent research to provide a comprehensive overview of the causes of cardiomyopathy.
Hypertrophic cardiomyopathy is a common inherited cardiovascular disease caused by mutations in genes encoding proteins of the cardiac sarcomere. Over 1,400 mutations in at least 11 genes have been identified, with MYH7 and MYBPC3 mutations accounting for approximately 75% of cases . These mutations lead to thickened myocardium, impaired filling, and outflow obstruction, which can result in sudden cardiac death, particularly in young athletes.
Dilated cardiomyopathy is genetically heterogeneous, with mutations in over 50 genes linked to the condition. These genes encode proteins involved in the cytoskeleton, nucleoskeleton, mitochondria, and calcium handling . Mutations in sarcomere protein genes, such as beta-myosin heavy chain and troponin T, are also implicated, causing early-onset ventricular dilation and reduced contractile function. Genetic testing is increasingly used to identify patients at risk for rapid disease progression and heart failure.
Diabetes is a significant cause of cardiomyopathy, independent of hypertension and coronary artery disease. Diabetic cardiomyopathy (DCM) is characterized by impaired myocardial insulin signaling, mitochondrial dysfunction, and oxidative stress, leading to fibrosis, hypertrophy, and heart failure . Insulin resistance and hyperinsulinemia are key factors promoting this condition, with a higher prevalence observed in female patients.
Several drugs and environmental agents can cause toxic cardiomyopathy. Anticancer drugs like anthracyclines, trastuzumab, and imatinib interfere with myocardial cell bioenergetics and induce oxidative stress, leading to cardiotoxicity. Antiretroviral agents such as azidothymidine cause mitochondrial toxicity and increased reactive oxygen species (ROS) production. Thiazolidinedione antidiabetic drugs are also suspected to interfere with mitochondrial respiration and oxidative stress.
Substance abuse, including alcohol, cocaine, and methamphetamines, is a well-documented cause of cardiomyopathy. Alcohol-related cardiotoxicity involves multiple mechanisms, including apoptosis, mitochondrial dysfunction, and oxidative stress. Cocaine induces excessive sympathetic stimulation and increased myocardial oxygen consumption, while methamphetamines cause catecholamine-mediated toxicity.
Exposure to environmental toxins such as carbon monoxide, metals (cobalt, antimony, mercury), and scorpion venom can also lead to cardiomyopathy. These toxins interfere with mitochondrial function, induce oxidative stress, and disrupt calcium handling in myocardial cells.
Infiltrative myocardial diseases, such as amyloidosis and sarcoidosis, cause cardiomyopathy by depositing abnormal substances in the heart muscle, leading to impaired function and poor prognosis.
Myocarditis, often caused by viral infections, and connective tissue diseases can lead to cardiomyopathy through inflammatory damage to the heart muscle.
Peripartum cardiomyopathy occurs in women during the last month of pregnancy or within five months postpartum. It is associated with better survival rates compared to other forms of cardiomyopathy.
Cardiomyopathy is a multifactorial disease with diverse causes, including genetic mutations, metabolic disorders, toxic exposures, and other underlying conditions. Understanding these causes is crucial for early diagnosis, risk stratification, and the development of targeted therapies to improve patient outcomes.
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