What are the non‑ischemic causes of dilated cardiomyopathy?

Non-Ischemic Causes of Dilated Cardiomyopathy

Non-ischemic dilated cardiomyopathy results from genetic mutations (30-50% of cases), viral myocarditis, cardiotoxic substances (alcohol, chemotherapy, recreational drugs), endocrine/metabolic disorders, peripartum state, tachyarrhythmias, autoimmune diseases, nutritional deficiencies, and infiltrative diseases. 1

Genetic and Familial Causes

• Genetic mutations account for 30-50% of all DCM cases, with 30-40% attributable to identifiable pathogenic variants in specific protein genes affecting cytoskeletal and sarcomeric proteins. 1
• A 3-generation family history should be obtained when evaluating DCM, as familial patterns are common. 2
• Several inherited muscular dystrophies produce DCM, presenting with heart failure, arrhythmias, or sudden death. 3

Infectious and Inflammatory Causes

• Viral myocarditis represents a well-established pathway from acute inflammation to chronic DCM, with cell-mediated autoimmune mechanisms triggered by viral infection driving progression. 1
• Viral myocarditis accounts for up to 75% of patients presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA). 2
• Bacterial, fungal, or tuberculosis infections can cause cardiomyopathy. 2
• Chagas disease (Trypanosoma cruzi) is endemic in Central and South America and leads to cardiomyopathy. 2
• HIV-associated cardiomyopathy occurs in approximately 8% of asymptomatic HIV-positive individuals. 2

Cardiotoxic Substances

Alcohol

• Alcohol is a common and reversible cause of DCM when consumption is stopped early, particularly affecting men aged 30-55 years with heavy drinking history and probable genetic susceptibility. 1, 2

Chemotherapeutic Agents

• Anthracyclines and other cancer treatments cause direct myocyte injury leading to DCM. 1
• Tyrosine kinase inhibitors, trastuzumab, and interferons can also cause cardiomyopathy. 2

Recreational Drugs

• Cocaine and methamphetamine lead to cardiomyopathy through direct cardiotoxic effects. 2

Endocrine and Metabolic Disorders

• Diabetes mellitus contributes to secondary cardiomyopathy through metabolic derangements. 1
• Thyroid disorders (both hypo- and hyperthyroidism) affect cardiac contractility and can cause or contribute to heart failure. 1, 2
• Acromegaly and pheochromocytoma are associated with cardiomyopathy. 2
• Nutritional deficiencies (thiamine, carnitine, selenium) cause reversible DCM when severe. 1
• Hemochromatosis and other metabolic storage diseases lead to cardiomyopathy through iron deposition and should be screened with fasting transferrin saturation. 2

Pregnancy-Related

• Peripartum cardiomyopathy presents during the last month of pregnancy or within 5 months postpartum, with an incidence of 1 in 2,500-4,000 births in the United States. 1, 3
• Risk factors include multiparity, advanced maternal age (>30 years), obesity, nonwhite background, poor socioeconomic status, prolonged tocolytic therapy, hypertension, preeclampsia, and cocaine use. 1, 3
• Endomyocardial biopsy may be needed to exclude myocarditis in these patients. 3

Arrhythmia-Induced

• Tachycardia-induced cardiomyopathy results from chronic supraventricular or ventricular arrhythmias with rapid rates, causing reversible systolic dysfunction. 1

Autoimmune and Inflammatory Disorders

• Systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, scleroderma, and polyarteritis nodosa all associate with DCM through immune-mediated myocardial damage. 1
• Sarcoidosis can cause cardiomyopathy, though characteristic changes are often missed on histological evaluation. 2

Infiltrative Diseases

• Amyloidosis, hemochromatosis, and sarcoidosis cause secondary cardiomyopathy as part of multiorgan systemic disease. 1

Stress-Related

• Stress-induced (Takotsubo) cardiomyopathy presents with acute, usually reversible LV dysfunction triggered by emotional or physical stress, mediated by catecholamine excess. 1, 3
• It presents similarly to acute myocardial infarction with chest pain, ST-segment elevation on ECG, and elevated cardiac enzymes. 3
• Diagnosis is made based on Mayo Clinic or InterTAK diagnostic criteria. 3
• Important caveat: Incidental coronary artery disease is found in 10% of patients with stress-induced cardiomyopathy, complicating diagnosis. 3, 2

Hypertensive Heart Disease

• Long-standing uncontrolled hypertension leads to "burned-out" dilated cardiomyopathy after initial concentric hypertrophy, with progressive chamber dilation and declining ejection fraction. 1

Cirrhosis-Related

• Cardiomyopathy can be seen in cirrhotic patients, independent of alcohol exposure. 3

Unclassified Entities

• LV non-compaction is characterized by prominent trabeculations due to persistent embryonic sinusoids, leading to LV failure, thromboembolism, and arrhythmias. 3, 2

Critical Diagnostic Pitfall

Approximately 50% of patients with heart failure and reduced ejection fraction have normal or near-normal coronary arteries on angiography, making systematic evaluation for non-ischemic causes essential. 2 Endomyocardial biopsy may be necessary in certain cases, particularly to exclude myocarditis, though it is not indicated in routine evaluation. 2