What are the unusual causes of dilated cardiomyopathy?

Unusual Causes of Dilated Cardiomyopathy

Beyond the common culprits of ischemia, hypertension, and idiopathic disease, dilated cardiomyopathy has several unusual etiologies that must be systematically considered to avoid missing reversible or specifically treatable conditions.

Neuromuscular Disorders

Myotonic Dystrophy

• Myotonic dystrophy type 1 (DM1) causes dilated cardiomyopathy in approximately 80% of patients, with cardiac manifestations being a leading cause of death alongside respiratory complications 1
• DM1 results from CTG trinucleotide repeat expansion in the DMPK gene, with longer repeats correlating with earlier onset and more severe disease 1
• The condition presents with progressive facial, neck, and distal limb weakness plus myotonia, cataracts, and neuropsychiatric deficits 1
• Cardiac involvement is particularly high-risk in younger patients aged 2-30 years, manifesting primarily as progressive conduction defects and tachyarrhythmias rather than dilated cardiomyopathy itself 1
• Myotonic dystrophy type 2 (DM2) shows less frequent cardiac involvement (10-20%) and dilated cardiomyopathy is uncommon, though sudden death can occur 1

Congenital Myopathies

• Congenital myopathies represent a heterogeneous group linked to >15 genes coding for sarcomeric or intracellular proteins, with RYR1 mutations being most prevalent 1
• These present with hypotonia and weakness from birth, prominent facial weakness with ptosis, generalized hypotonic posture, and proximal muscle weakness 1
• Prevalence is estimated at 1 in 26,000-28,000 births 1

Muscular Dystrophies

• X-linked dilated cardiomyopathy from dystrophin gene mutations typically presents in males during teen years to early 20s with elevated creatine kinase levels 2, 1
• Muscular dystrophies can produce dilated cardiomyopathy presenting with heart failure, arrhythmias, or sudden death 3

Infectious and Parasitic Causes

Chagas Disease

• Chagas cardiomyopathy from Trypanosoma cruzi infection causes progressive myocardial damage through parasite persistence and autoimmune responses 1
• The neurogenic hypothesis suggests cardiac parasympathetic neurons are irreversibly damaged during acute infection, leaving unopposed sympathetic activation that drives relentless myocardial damage 1
• Myocardial ischemia and coronary microcirculation abnormalities occur despite normal epicardial coronaries 1
• The conduction system is typically affected, resulting in right bundle-branch block, left anterior fascicular block, or complete atrioventricular block 1
• Prognosis is poor with 50% mortality within 4 years of heart failure onset; complete heart block, atrial fibrillation, LBBB, and complex ventricular ectopy indicate worse outcomes 1
• Benznidazole and nifurtimox achieve parasitologic cure in only ~50% of treated patients with substantial toxicity 1

HIV-Associated Cardiomyopathy

• HIV-associated cardiomyopathy occurs in approximately 8% of asymptomatic HIV-positive individuals 2, 3
• HIV screening should be performed in selected patients with unexplained dilated cardiomyopathy, particularly younger patients with risk factors 2

Autoimmune and Rheumatologic Disorders

Systemic Lupus Erythematosus

• Patients with SLE are 1-3 times more likely to be hospitalized with newly diagnosed heart failure than healthy cohorts, with highest risk in women <45 years of age 1
• Three main mechanisms cause SLE-induced heart failure: atherosclerosis (2-10 fold increased MI risk), myocarditis/inflammation, and drug-induced impairments 1
• Global LV dysfunction occurs in 5% of SLE patients, segmental wall-motion abnormalities in 4%, and RV enlargement in 4% 1
• Among 1249 newly diagnosed SLE patients followed for 8 years, confirmed heart failure occurred in only 2%, with ~20% having atherosclerosis as the primary cause 1
• Concomitant antiphospholipid antibodies further increase cardiovascular risk 1

Other Autoimmune Conditions

• Scleroderma, rheumatoid arthritis, dermatomyositis, and polyarteritis nodosa are well-described associations with heart failure through immune-mediated myocarditis, progressive fibrosis, and apoptosis 1, 4
• Sporadic case reports link ankylosing spondylitis, psoriatic arthritis, celiac sprue, vasculitis, and inclusion body myositis to heart failure 1

Arrhythmia-Induced Cardiomyopathy

PVC-Induced Cardiomyopathy

• PVC burden ≥24% is independently associated with cardiomyopathy, though the minimum threshold appears to be 10% 1
• Among 60 patients with idiopathic frequent PVCs (>10/hour), 22% had LV dysfunction, with greater PVC burden correlating with worse dysfunction 1
• Radiofrequency ablation resulted in normalization of ejection fraction in 82% of patients with LV dysfunction within 6 months 1
• The RV outflow tract is the most common PVC origin (52% of cases) 1
• Clues suggesting PVCs cause cardiomyopathy include: high PVC burden (>10-15% of total beats), epicardial origin (particularly RVOT), and improvement in EF with PVC suppression or ablation 2

Tachycardia-Induced Cardiomyopathy

• Tachycardia-induced cardiomyopathy was found in 6.8% of patients in a referral heart failure population 1
• Atrial fibrillation is the most common cause, but any sustained supraventricular or ventricular arrhythmia can be causative 1, 4
• Maintenance of sinus rhythm or control of ventricular rate is indicated in treating patients with tachycardia-induced cardiomyopathy (Level of Evidence B) 1
• Tachycardia can be present for a mean of 8 years before discovery of LV dysfunction, but with recurrent tachycardia, heart failure can develop within 6 months 1
• Chronic rapid pacing results in neurohormonal activation with reduction in serum sodium, activation of renin-angiotensin system, and increased plasma atrial natriuretic peptide, aldosterone, norepinephrine, and epinephrine 1

Pacing-Induced Cardiomyopathy

• Ventricular pacing at high rates can cause cardiomyopathy 1
• RV pacing alone can exacerbate heart failure symptoms, increase hospitalization, and increase mortality 1

Left Bundle Branch Block

• LBBB occurs in 25% of patients with heart failure 1
• The Framingham study demonstrated that 28% of subjects free of cardiovascular disease who developed LBBB subsequently developed heart failure 1

Metabolic and Endocrine Disorders

Hemochromatosis

• Measure fasting transferrin saturation to screen for hemochromatosis, as mutated alleles are common in Northern European descent 2, 3
• Hemochromatosis causes secondary cardiomyopathy as part of multiorgan systemic disease 4

Thyroid Disorders

• Both hyperthyroidism and hypothyroidism can cause or contribute to heart failure; measure thyroid-stimulating hormone in all patients 2, 3
• Thyroid disorders affect cardiac contractility and can be reversible with treatment 4

Nutritional Deficiencies

• Severe deficiencies of thiamine, carnitine, and selenium cause reversible dilated cardiomyopathy 4

Infiltrative Diseases

• Sarcoidosis can cause dilated cardiomyopathy, though characteristic changes are often missed on histological evaluation 3, 4
• Amyloidosis causes secondary cardiomyopathy as part of multiorgan systemic disease 4

Peripartum Cardiomyopathy

• Peripartum cardiomyopathy presents during the last month of pregnancy or within 5 months postpartum 4
• Risk factors include multiparity, advanced maternal age, obesity, and hypertension 4
• Incidence is 1 in 2,500-4,000 births in the United States 3

Stress-Induced (Takotsubo) Cardiomyopathy

• Stress-induced cardiomyopathy presents with acute, usually reversible LV dysfunction triggered by emotional or physical stress, mediated by catecholamine excess 4, 3
• Incidental coronary artery disease can be found in 10% of patients with stress-induced cardiomyopathy, complicating diagnosis 3

Critical Diagnostic Pitfalls

• A 3-generation family history is essential when assessing cardiomyopathy causes, as genetic mutations account for 30-50% of cases 2, 3
• Patients may underreport alcohol consumption; careful questioning about current and past use is necessary 2
• Recent viral syndrome preceding heart failure symptoms suggests myocarditis, though serum antibody titers have low yield and uncertain therapeutic implications 2
• Perfusion deficits and segmental wall-motion abnormalities can occur in nonischemic cardiomyopathy, mimicking ischemic disease on noninvasive testing 3
• Cardiac MRI should be considered at least once in every dilated cardiomyopathy patient for tissue characterization (fibrosis, edema, infiltration) to suggest underlying cause 2