What are the causes of non-ischemic cardiomyopathy?

Causes of Non-Ischemic Cardiomyopathy

Non-ischemic cardiomyopathy (NICM) encompasses a broad spectrum of myocardial disorders characterized by ventricular dysfunction in the absence of coronary artery disease, with approximately 50% of cases being idiopathic, particularly in younger patients. 1

Major Etiological Categories

Toxin-Induced

• Alcohol-induced cardiomyopathy - common in men aged 30-55 years with heavy drinking history and probable genetic susceptibility 1
• Chemotherapeutic agents - including anthracyclines, tyrosine kinase inhibitors, trastuzumab, and interferons 1
• Recreational drugs - cocaine and methamphetamine use 1

Genetic/Familial

• Inherited cardiomyopathies - approximately 40% of dilated cardiomyopathies have genetic etiology 2
• Muscular dystrophies - various types can produce dilated cardiomyopathy presenting with heart failure, arrhythmias, or sudden death 1
• Family history - a 3-generation family history is recommended when assessing cardiomyopathy causes 1

Inflammatory/Infectious

• Viral myocarditis - accounts for up to 75% of patients presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA) 1
• Bacterial, fungal, or tuberculosis infections 1
• Chagas disease - caused by Trypanosoma cruzi, endemic in Central and South America 1
• HIV-associated cardiomyopathy - occurs in approximately 8% of asymptomatic HIV-positive individuals 1

Autoimmune/Rheumatologic

• Systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis 1
• Other autoimmune conditions affecting cardiac function 1

Metabolic/Endocrine

• Thyroid disorders, acromegaly, pheochromocytoma 1
• Diabetes mellitus and obesity 1
• Hemochromatosis and other metabolic storage diseases 1

Infiltrative Disorders

• Cardiac amyloidosis - characterized by amyloid protein deposition in myocardium 1
• Sarcoidosis - granulomatous inflammation affecting the myocardium 1
• Hemochromatosis - iron overload affecting cardiac function 1, 2

Specific Clinical Entities

Peripartum Cardiomyopathy

• Occurs in late pregnancy or within 5 months postpartum 1
• Incidence of 1 in 2,500-4,000 births in the United States 1
• Risk factors include age >30 years, non-white ethnicity, multiparity, poor socioeconomic status, hypertension, preeclampsia, and prolonged tocolytic therapy 1

Stress-Induced (Takotsubo) Cardiomyopathy

• Characterized by transient left ventricular systolic dysfunction 1
• Triggered by emotional or physical stressors with catecholamine surge 3
• Predominantly affects postmenopausal women (90% of cases), with 96% occurring in women ≥50 years 3
• Presents similarly to acute myocardial infarction with chest pain, ST-segment elevation, and elevated cardiac enzymes 1
• Accounts for approximately 2% of myocardial infarction with non-obstructive coronary arteries 1

Left Ventricular Non-Compaction

• Characterized by prominent trabeculations due to persistent embryonic sinusoids 1
• Leads to left ventricular failure, thromboembolism, and arrhythmias 1

Arrhythmia-Related Cardiomyopathy

• Tachycardia-mediated cardiomyopathy 1
• Frequent premature ventricular contractions 1
• Right ventricular pacing-induced cardiomyopathy 1

Diagnostic Considerations

Imaging Findings

• Echocardiography typically shows dilated ventricle and global systolic dysfunction in dilated cardiomyopathy 1
• Cardiac MRI can identify specific patterns of myocardial involvement, including edema in "hot phases" of cardiomyopathies 4
• Endomyocardial biopsy may be necessary in certain cases, particularly to exclude myocarditis 1

Clinical Presentation

• May present with heart failure, arrhythmias, or sudden death 1
• Acute presentations can include chest pain, worsening dyspnea, or palpitations 4
• "Hot phases" of cardiomyopathies characterized by troponin elevation, myocardial edema, and arrhythmic instability 4

Prognostic Implications

• Non-ischemic cardiomyopathy generally has better prognosis than ischemic cardiomyopathy 5
• Response to medical therapy differs between ischemic and non-ischemic etiologies 5
• Patients with non-ischemic cardiomyopathy account for >40% of those receiving mechanical circulatory support and are the leading indication for heart transplantation 2
• Specific genetic backgrounds (e.g., lamin A/C mutations) may predict high risk of progressive dysfunction and sudden death 2

Clinical Pitfalls and Caveats

• Approximately 50% of patients with heart failure and reduced ejection fraction have normal or near-normal coronary arteries on angiography 1
• Endomyocardial biopsy findings may be nonspecific (hypertrophy, cell loss, fibrosis) and may not always affect management decisions 1
• Incidental coronary artery disease can be found in 10% of patients with stress-induced cardiomyopathy, complicating diagnosis 1
• Early recognition of potentially reversible causes (tachycardia-induced, alcohol, iron overload) is crucial as correction can lead to clinical improvement 2