What are the possible causes of low voltage QRS (electrocardiogram abnormality) in a patient?

Causes of Low Voltage QRS

Low voltage QRS on ECG most commonly results from cardiac amyloidosis (present in up to 50% of AL amyloidosis and 20% of ATTR amyloidosis), pericardial effusion, infiltrative cardiomyopathies, obesity, COPD/emphysema, and hypothyroidism, with the voltage-to-wall thickness discordance being particularly diagnostic for distinguishing amyloidosis from other causes of left ventricular hypertrophy. 1

Cardiac Causes

Infiltrative Cardiomyopathies

• Cardiac amyloidosis is the most critical cardiac cause, occurring in approximately 50% of patients with AL amyloidosis and 20% with TTR amyloidosis 1
• The ratio between QRS voltages and LV wall thickness is particularly useful—low voltage despite increased wall thickness strongly suggests amyloidosis rather than hypertrophic cardiomyopathy 1, 2
• Storage diseases including Pompe disease, PRKAG2 mutations, and Danon disease can present with low voltage, though these typically show extreme LVH with Sokolow scores ≥50 mm 1
• End-stage hypertrophic cardiomyopathy in its burnout phase may develop low voltage, though this is rare and limited to advanced disease 1, 2

Pericardial Disease

• Pericardial effusion with or without tamponade is a life-threatening cause that requires immediate recognition 1, 3
• Constrictive pericarditis can present with low QRS voltage, generalized T-wave inversion/flattening, and atrial abnormalities 1
• Low voltage in myocarditis occurs particularly when accompanied by pericardial effusion and heart failure 1

Myocardial Disease

• Dilated cardiomyopathy with extensive myocardial fibrosis or atrophy reduces voltage generation 1, 4
• Acute myocardial infarction, particularly anterior STEMI with multi-vessel disease, shows low voltage in 19% of cases and predicts need for CABG 5
• Myocardial edema from any cause (myocarditis, takotsubo syndrome) can transiently reduce voltage 1, 6

Extracardiac Causes

Body Habitus and Fluid Status

• Obesity increases the distance between the heart and recording electrodes, attenuating voltage 1, 4
• Peripheral edema of any etiology induces reversible low voltage and also reduces P wave and T wave amplitudes 6
• Anasarca from any cause creates a similar voltage attenuation effect 6

Pulmonary Disease

• COPD/emphysema causes hyperinflation that increases the distance between heart and chest wall, reducing precordial voltages 1, 4
• Lung disease in general should be excluded before attributing low voltage to cardiac causes 1

Endocrine and Metabolic

• Hypothyroidism causes myxedematous infiltration and pericardial effusion, both contributing to low voltage 4

Diagnostic Approach Algorithm

Step 1: Confirm Low Voltage Definition

• Limb leads: QRS amplitude <0.5 mV in all limb leads 2, 7
• Precordial leads: QRS amplitude <1.0 mV in all precordial leads 2

Step 2: Immediate Life-Threatening Exclusions

• Echocardiography to evaluate for pericardial effusion/tamponade, which requires urgent pericardiocentesis 1, 4, 3
• Assess for acute heart failure with hemodynamic compromise 1

Step 3: Calculate Voltage-to-Wall Thickness Ratio

• If LV wall thickness >12 mm with low voltage, strongly suspect cardiac amyloidosis 1, 8
• This discordance has 88% sensitivity and near 100% specificity for distinguishing amyloidosis from HCM 1, 8

Step 4: Screen for Cardiac Amyloidosis

• Serum and urine immunofixation electrophoresis plus serum free light chains 1, 2
• NT-proBNP and troponin levels (disproportionately elevated in amyloidosis) 1, 2
• Nuclear imaging with 99mTc-PYP/DPD/HMDP if monoclonal protein negative (grade 2-3 uptake diagnostic for ATTR) 1, 8, 2
• Cardiac MRI if echo suggestive but equivocal, looking for diffuse subendocardial late gadolinium enhancement 8, 2

Step 5: Evaluate Extracardiac Causes

• Chest X-ray for emphysema, lung hyperinflation 1
• TSH to exclude hypothyroidism 4
• Clinical assessment for obesity, peripheral edema, anasarca 1, 6

Step 6: Additional Cardiac Evaluation

• Review for systemic symptoms: bilateral carpal tunnel syndrome, lumbar spinal stenosis, spontaneous biceps tendon rupture, peripheral neuropathy (all suggest amyloidosis) 1, 8, 2
• Assess for conduction abnormalities: progressive AV block suggests storage diseases, mitochondrial disorders, or amyloidosis 1, 2
• Look for other ECG clues: pseudoinfarct Q waves, abnormally deep Q waves in inferolateral leads, giant negative T waves suggesting apical involvement 1

Critical Pitfalls to Avoid

• Do not dismiss low voltage as benign without excluding amyloidosis and pericardial effusion—both have significant mortality implications 1, 3
• Do not rely on voltage criteria alone for diagnosing LVH in patients with limb lead low voltage, as this significantly underestimates true LVH prevalence 9
• Do not assume normal pericardial thickness excludes constrictive pericarditis—18% of surgically proven cases have normal thickness 1
• Recognize that low voltage may be the only ECG finding in early or atypical presentations of serious disease 1
• In anterior STEMI with low voltage, suspect multi-vessel disease and consider early surgical revascularization 5

Management Based on Etiology

• Cardiac amyloidosis: Immediate referral to specialized amyloidosis center; avoid calcium channel blockers and digoxin; implement disease-specific therapy (tafamidis for ATTR, chemotherapy for AL) 4, 2
• Pericardial effusion/tamponade: Urgent pericardiocentesis 1, 4
• Myocarditis: Restrict from exercise 3-6 months; standard heart failure management 1
• Dilated cardiomyopathy: Standard heart failure management with guideline-directed medical therapy 4
• Extracardiac causes: Treat underlying condition (thyroid replacement, COPD management, weight reduction) 4