Why Cardiac Amyloidosis Causes Low Voltage QRS Complexes
Low voltage QRS complexes occur in cardiac amyloidosis because extracellular amyloid protein deposits in the myocardial interstitium physically disrupt normal electrical conduction through the myocardium, reducing the amplitude of electrical signals despite paradoxically increased ventricular wall thickness. 1
Pathophysiological Mechanism
The fundamental explanation lies in the infiltrative nature of the disease:
Amyloid fibrils deposit in the extracellular space between myocytes, creating a non-conductive barrier that interrupts normal electrical signal propagation through the heart muscle 2, 3
These protein deposits act as electrical insulators, preventing the normal transmission of depolarization waves across the myocardium, which reduces the voltage amplitude recorded on surface ECG 4
The amyloid infiltration causes direct myocyte damage through oxidative stress and mechanical disruption, further impairing the generation and conduction of electrical impulses 2
Despite causing ventricular wall thickening (which would normally increase QRS voltage), the non-conductive amyloid material paradoxically reduces electrical signal amplitude 1
The Classic Diagnostic Discordance
This creates the pathognomonic finding that should trigger suspicion for cardiac amyloidosis:
Low QRS voltage in limb leads occurs in approximately 50% of patients with cardiac amyloidosis 2
This appears paradoxical when echocardiography shows increased left ventricular wall thickness (≥14 mm), creating a voltage-to-mass discordance 1
This discordance between wall thickness on echocardiogram and QRS voltage on ECG is specifically highlighted in the 2022 AHA/ACC/HFSA guidelines as a key diagnostic clue that should prompt evaluation for cardiac amyloidosis 1
Additional ECG Manifestations
Beyond low voltage, the amyloid infiltration causes other characteristic ECG abnormalities:
Pseudo-infarction patterns appear in precordial leads due to loss of anterior forces from septal infiltration 2, 4
Conduction abnormalities including atrioventricular blocks and sinus node dysfunction result from amyloid deposition in the conduction system 2, 4, 5
Atrial fibrillation occurs in up to 70% of patients at diagnosis due to atrial infiltration and stretch 5
Clinical Pitfall to Avoid
Do not dismiss the possibility of cardiac amyloidosis simply because QRS voltage appears normal or even high in some leads. 2 While low voltage in limb leads is common (50% of cases), it is not universal. The diagnosis requires integrating multiple findings including:
- Clinical context (heart failure symptoms, carpal tunnel syndrome, spinal stenosis, polyneuropathy) 1
- Echocardiographic features (increased wall thickness, apical sparing pattern) 1
- Laboratory markers (elevated BNP/NT-proBNP, troponin) 1
- Advanced imaging (late gadolinium enhancement on cardiac MRI, positive Tc-99m PYP scan) 1, 6
The low voltage QRS is a supportive finding that increases diagnostic suspicion but does not confirm or exclude the diagnosis by itself 1.