In a 50‑year‑old man with a markedly dilated left ventricle and left atrium, generalized hypokinesia, an ejection fraction of about 27 % and a normal coronary angiogram, what are the possible causes of his non‑ischemic cardiomyopathy?

Causes of Non-Ischemic Cardiomyopathy in This Patient

In this 50-year-old man with dilated cardiomyopathy, normal coronary arteries, and severe left ventricular dysfunction (EF 27%), the most likely causes include idiopathic dilated cardiomyopathy (which may have an undetected genetic basis), alcohol-induced cardiomyopathy, viral myocarditis, tachycardia-induced cardiomyopathy from uncontrolled atrial fibrillation or frequent PVCs, thyroid disorders, or toxic exposures including chemotherapeutic agents and recreational drugs. 1, 2

Primary Diagnostic Considerations

Idiopathic/Genetic Dilated Cardiomyopathy

• Genetic mutations account for 30-50% of dilated cardiomyopathy cases, with even higher rates in younger patients 2
• Up to 30% of "idiopathic" cases demonstrate familial clustering when first-degree relatives undergo echocardiographic screening 2
• A 3-generation family history is essential to identify inherited patterns of cardiomyopathy, arrhythmias, or sudden death 1
• Most patients without identifiable causes have idiopathic dilated cardiomyopathy, which often represents undiagnosed genetic disease 3

Alcohol-Induced Cardiomyopathy

• Particularly common in men aged 30-55 years with heavy drinking history and probable genetic susceptibility 1, 2
• Patients frequently underreport alcohol consumption, requiring careful questioning about current and past use 2
• This is a critical reversible cause if alcohol cessation occurs early 1

Viral Myocarditis

• Viral myocarditis accounts for up to 75% of patients presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA) and may evolve into dilated cardiomyopathy 1, 2
• Recent viral syndrome preceding heart failure symptoms suggests this diagnosis 2
• Bacterial, fungal, tuberculosis, and Chagas disease (if endemic exposure) should also be considered 1

Tachycardia-Induced Cardiomyopathy

• Persistently elevated ventricular rate during atrial fibrillation (≥130 bpm) can produce dilated cardiomyopathy 3
• The dilated left atrium in this patient raises suspicion for chronic atrial fibrillation as a contributing factor 3
• High PVC burden (>10-15% of total beats), particularly from the right ventricular outflow tract, can cause reversible cardiomyopathy 2
• Rate control may lead to reversal with median LVEF increasing from 25% to 52% in one study 3

Secondary Etiologies to Systematically Exclude

Toxic/Substance-Related

• Chemotherapeutic agents (anthracyclines, tyrosine kinase inhibitors, trastuzumab, interferons) 1
• Recreational drugs (cocaine, methamphetamine) 1, 2
• Detailed medication and substance exposure history is mandatory 1

Metabolic/Endocrine Disorders

• Thyroid disorders (both hyperthyroidism and hypothyroidism) can cause or contribute to heart failure—measure TSH in all patients 1, 2
• Hemochromatosis—screen with fasting transferrin saturation, as mutated alleles are common in Northern European descent 1, 2
• Diabetes mellitus and obesity increase cardiomyopathy risk 1
• Acromegaly and pheochromocytoma are rare but reversible causes 1

Autoimmune/Inflammatory

• Sarcoidosis can cause cardiomyopathy, though characteristic changes are often missed on histological evaluation 1
• Systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue disorders 2

Infectious

• HIV-associated cardiomyopathy occurs in approximately 8% of asymptomatic HIV-positive individuals—screen in selected patients with unexplained dilated cardiomyopathy, particularly younger patients with risk factors 1, 2

Neuromuscular Disorders

• Muscular dystrophies can produce dilated cardiomyopathy presenting with heart failure, arrhythmias, or sudden death 1
• X-linked dilated cardiomyopathy (dystrophin gene mutations) typically presents in males during teen years to early 20s with elevated creatine kinase levels 2

Diagnostic Approach

Essential Initial Workup

• Detailed alcohol and substance use history (current and past) 2
• Three-generation family history focusing on cardiomyopathy, heart failure, arrhythmias, and sudden death 1
• Thyroid-stimulating hormone measurement 1, 2
• Fasting transferrin saturation for hemochromatosis screening 1, 2
• HIV screening in appropriate risk populations 1, 2
• 24-hour Holter monitoring to assess for high PVC burden or paroxysmal atrial fibrillation 2
• Creatine kinase if muscular dystrophy suspected 2

Role of Endomyocardial Biopsy

• Endomyocardial biopsy is NOT indicated in routine evaluation of cardiomyopathy, as most patients show nonspecific changes (hypertrophy, cell loss, fibrosis) 3, 1
• The overall usefulness is unclear, and it has not been established how biopsy findings affect patient management 3
• May be considered only when specific treatable conditions are strongly suspected based on other clinical data 3

Advanced Imaging

• Cardiac MRI should be considered at least once for tissue characterization (fibrosis, edema, infiltration) and to suggest underlying cause 2
• CMR can detect myocardial edema suggesting active myocarditis, infiltrative patterns, or fibrosis patterns that suggest specific etiologies 2, 4

Critical Clinical Pitfalls

• Approximately 50% of heart failure patients with reduced ejection fraction have normal or near-normal coronary arteries on angiography 3, 1
• Perfusion deficits and segmental wall-motion abnormalities can occur in nonischemic cardiomyopathy, mimicking ischemic disease on noninvasive testing 3, 1
• Patients may underreport alcohol consumption—direct, nonjudgmental questioning is essential 2
• The dilated left atrium suggests chronic atrial fibrillation may be both consequence and contributor to ventricular dysfunction 3
• Serum viral antibody titers have low yield and uncertain therapeutic implications 2