What is the initial workup for a patient presenting with cardiomegaly (enlarged heart)?

Workup for Cardiomegaly

For a patient presenting with cardiomegaly, begin immediately with a 12-lead ECG and transthoracic echocardiography (TTE), as a completely normal ECG makes heart failure highly unlikely (<10% probability), while echocardiography is essential to confirm cardiac dysfunction and determine left ventricular ejection fraction. 1

Initial Diagnostic Testing

Electrocardiogram (ECG)

• Perform a 12-lead ECG in all patients with suspected cardiomegaly 1
• A completely normal ECG has a negative predictive value exceeding 90% for excluding left ventricular systolic dysfunction 1
• Look specifically for: pathological Q-waves (suggesting prior myocardial infarction), left ventricular hypertrophy patterns, QRS duration ≥120 ms with LBBB morphology (indicating dyssynchrony), AV block, low QRS voltage (suggesting pericardial effusion, amyloidosis, or obesity), and atrial fibrillation 1

Transthoracic Echocardiography

• TTE is the preferred and recommended method for confirming cardiac dysfunction 1
• Echocardiography provides critical information on: left ventricular ejection fraction (distinguishing systolic dysfunction from preserved systolic function), wall thickness (≥15 mm suggests hypertrophic cardiomyopathy in adults), valvular function, diastolic filling patterns, left ventricular outflow tract obstruction, and mitral regurgitation 1
• For suspected hypertrophic cardiomyopathy, perform provocative maneuvers if resting gradient is <50 mm Hg 1

Chest X-ray

• Obtain chest X-ray in two planes to assess for cardiomegaly, pulmonary congestion, and pleural effusions 1
• Important caveat: cardiomegaly can be absent on chest X-ray even in chronic heart failure, and significant left ventricular systolic dysfunction may be present without radiographic cardiomegaly 1
• Chest X-ray is most useful for identifying alternative pulmonary explanations for symptoms and detecting pulmonary venous congestion or edema 1

Natriuretic Peptides

• Measure BNP or NT-proBNP to help exclude heart failure 1
• For non-acute presentations: BNP <35 pg/mL or NT-proBNP <125 pg/mL makes chronic heart failure unlikely 1
• For acute presentations: BNP <100 pg/mL or NT-proBNP <300 pg/mL has high negative predictive value 1
• Elevated levels can also indicate left ventricular hypertrophy, valvular disease, acute/chronic ischemia, or hypertension 1

Laboratory Evaluation

Routine Blood Tests

Obtain the following laboratory studies in all patients: 1, 2

• Complete blood count (hemoglobin, leukocytes, platelets)
• Serum electrolytes (sodium, potassium)
• Serum creatinine and estimated glomerular filtration rate
• Fasting blood glucose
• Liver function tests
• Urinalysis
• Thyroid-stimulating hormone (thyroid disease can mimic or aggravate heart failure) 1

Additional Testing Based on Clinical Suspicion

• Serum ferritin if iron storage disease suspected 3
• Troponins if myocardial ischemia/infarction suspected 1
• Consider screening for acromegaly (growth hormone levels) if patient has coarse facial features, spade-like hands/feet, or other suggestive features 4, 5

Advanced Imaging and Specialized Testing

Cardiac Magnetic Resonance (CMR)

• Consider CMR when echocardiography is inconclusive or technically limited 1
• CMR is particularly valuable for detecting myocardial fibrosis, assessing wall thickness in difficult-to-image segments, and evaluating for infiltrative diseases like amyloidosis 1

Cardiac CT

• Use cardiac CT when both echocardiography is limited and CMR is contraindicated or unavailable 1
• CT can assess coronary anatomy and measure cardiothoracic ratio (CTR <0.49 has low likelihood of left ventricular hypertrophy) 6

Genetic Testing and Family History

• Obtain a comprehensive 3-generation family history in all patients with suspected hypertrophic cardiomyopathy 1
• Genetic testing is recommended in patients fulfilling diagnostic criteria for HCM to enable cascade screening of relatives 1
• Consider genetic testing if wall thickness is 13-14 mm with other suggestive features (family history, ECG abnormalities) 1

Etiology-Specific Workup

For Hypertrophic Cardiomyopathy (wall thickness ≥15 mm)

• Perform systematic search for underlying cause including specialized laboratory testing 1
• Screen for: Fabry disease, Danon disease, amyloidosis (consider 99mTc-DPD scan and endomyocardial biopsy if suspected), mitochondrial disorders, and drug-induced causes (tacrolimus, hydroxychloroquine, anabolic steroids) 1
• 24-48 hour ambulatory ECG monitoring to assess for arrhythmias and sudden cardiac death risk 1

For Suspected Ischemic Cardiomyopathy

• Consider coronary angiography, stress echocardiography, or nuclear perfusion studies 1
• Coronary angiography is particularly important in acute or acutely decompensated heart failure not responding to initial treatment 1

Common Pitfalls to Avoid

• Do not rely solely on chest X-ray: Cardiomegaly may be absent on imaging despite significant cardiac dysfunction 1
• Do not dismiss the diagnosis with a normal echocardiogram alone: Consider diastolic dysfunction, which requires specific Doppler assessment of E/A ratio, deceleration time, and tissue Doppler imaging 1
• Do not overlook reversible causes: Screen for thyroid disease, anemia, and drug-induced cardiomyopathy, as these are potentially treatable 1
• Do not delay referral for complex cases: Consultation with or referral to a comprehensive HCM center is reasonable for complex disease-related management decisions 1