What are the characteristic EKG (electrocardiogram) findings in a patient with suspected cardiac amyloidosis, particularly those with a history of multiple myeloma or chronic inflammatory diseases?

EKG Findings in Cardiac Amyloidosis

The most characteristic EKG finding in cardiac amyloidosis is low QRS voltage in limb leads (≤0.5 mV) despite increased left ventricular wall thickness on echocardiography—this voltage-to-mass discordance occurs in approximately 50% of AL amyloidosis and 25% of ATTR amyloidosis cases. 1, 2, 3

Primary Diagnostic EKG Features

Low Voltage Pattern

• Low QRS voltage in limb leads (amplitude ≤0.5 mV in each limb lead) is present in 54.5% of patients with cardiac amyloidosis, making it the most common EKG abnormality 3
• This finding is particularly significant when combined with increased left ventricular wall thickness (≥12 mm) on echocardiography—a discordance that is highly specific for cardiac amyloidosis 4, 1, 2
• Low voltage occurs in approximately 50% of AL amyloidosis patients and 25% of ATTR amyloidosis patients 1, 2
• The voltage-to-mass ratio has greater diagnostic accuracy than QRS voltage alone 5

Pseudo-Infarct Pattern

• Pathological Q waves in at least two contiguous leads without obstructive coronary artery disease occur in 40.2% of cardiac amyloidosis patients 3
• This pseudo-infarct pattern is significantly more common in cardiac amyloidosis compared to systemic amyloidosis without cardiac involvement (40.2% vs 4.6%, P < 0.001) 3
• The combination of low voltage on limb leads AND pseudo-infarct pattern has 96% positive predictive value and 98% specificity for cardiac amyloidosis 3

Secondary EKG Abnormalities

Arrhythmias

• Atrial arrhythmias (primarily atrial fibrillation) occur in 15.9% of cardiac amyloidosis patients compared to 3.4% in systemic amyloidosis without cardiac involvement 3
• Atrioventricular block is present in 14.8% of cardiac amyloidosis patients versus 1.1% in controls (P = 0.001) 3
• Conduction system infiltration by amyloid deposits can result in bundle branch blocks 5

Additional Findings

• Fragmented QRS complexes are significantly associated with the extent of late gadolinium enhancement on cardiac MRI and have independent prognostic value (hazard ratio: 2.034) 6
• QRS duration and the Sokolow index correlate with amyloid burden as measured by extracellular volume on cardiac MRI 6

Diagnostic Algorithm Using EKG

High Specificity Combination

• When both low voltage on limb leads AND pseudo-infarct pattern are present together (28% of cardiac amyloidosis cases), the specificity is 98% and positive predictive value is 96% 3
• This combination should immediately trigger comprehensive workup including monoclonal protein screening, echocardiography, and consideration of cardiac MRI or nuclear imaging 4, 1

Voltage-to-Mass Ratio in Bundle Branch Block

• In patients with bundle branch block, standard voltage criteria may not apply 5
• Total QRS score/left ventricular wall thickness ratio with a cutoff of 92.5 mV/cm is 100% sensitive and 83% specific for cardiac amyloidosis in patients with bundle branch block 5
• This indexed voltage measurement is superior to absolute voltage measurements when conduction abnormalities are present 5

Clinical Context and Pitfalls

Important Caveats

• Low voltage is NOT universally present—it can range from 20-74% depending on the series and amyloidosis subtype 5
• The absence of low voltage does NOT exclude cardiac amyloidosis 5
• In patients with chronic inflammatory diseases or multiple myeloma, the combination of increased wall thickness on echo with low voltage on EKG should raise immediate suspicion for cardiac amyloidosis 4, 7

Prognostic Value

• Fragmented QRS remains an independent predictor of mortality even after adjusting for clinical variables 6
• However, EKG characteristics lose independent prognostic value when cardiac MRI parameters (late gadolinium enhancement and extracellular volume) are included in analysis 6
• The Sokolow index also shows independent prognostic value in AL amyloidosis 6

Integration with Other Diagnostic Modalities

• EKG should be interpreted alongside echocardiography as the first-line diagnostic approach, with the voltage-to-mass discordance being the key diagnostic clue 4, 1, 2
• When EKG shows suggestive findings (low voltage, pseudo-infarct pattern, or their combination), proceed immediately with monoclonal protein screening (serum and urine immunofixation electrophoresis, serum free light chains) 4, 1
• Cardiac MRI is indicated when EKG and echocardiography are suggestive but not definitive, particularly for tissue characterization 4
• Nuclear imaging with 99mTc-PYP/DPD/HMDP can be diagnostic for ATTR amyloidosis without biopsy when grade 2-3 uptake is present and monoclonal protein screening is negative 4