What are the clinical and echocardiographic characteristics of AL amyloidosis‑related cardiac disease?

Clinical and Echocardiographic Characteristics of AL Amyloid Cardiac Disease

Clinical Presentation

AL cardiac amyloidosis predominantly affects middle-aged men (mean age 53 years) and most commonly presents with congestive heart failure (59%), though 37% of patients may have no cardiac symptoms at initial diagnosis. 1

Cardinal Clinical Features

• Heart failure with preserved ejection fraction (HFpEF) is the typical presentation, with symptoms of dyspnea, peripheral edema, and pleural effusions 2, 3
• Chest pain may occur due to microcirculatory dysfunction, occasionally mimicking acute coronary syndrome despite normal coronary arteries 4, 5
• Disproportionately elevated NT-proBNP relative to the degree of heart failure (sensitivity 93%, specificity 90%) is a key biomarker finding 3, 6
• Elevated troponin levels (troponin T, I, or high-sensitivity) are commonly present and persistently elevated 2, 6, 5

Extracardiac Manifestations

• Macroglossia and periorbital purpura are pathognomonic physical findings when present 5
• Bilateral carpal tunnel syndrome without rheumatoid arthritis or trauma is a significant red flag 2, 3
• Autonomic or sensory polyneuropathy may be present 3

Prognosis

• Median survival is approximately 13 months from diagnosis, but drops dramatically to 4-6 months once congestive heart failure symptoms appear 6, 1
• Cardiac involvement is the cause of death in 76% of cases 1

Electrocardiographic Characteristics

Voltage-Mass Discordance

The hallmark ECG finding is low QRS voltage (<0.5 mV in limb leads) despite increased ventricular wall thickness on imaging—this voltage-to-mass discordance occurs in approximately 50% of AL amyloidosis patients. 2, 3, 6

Additional ECG Abnormalities

• Pseudoinfarct pattern (Q waves in precordial leads unrelated to prior myocardial infarction) is actually more common than low voltage in cardiac amyloidosis 2
• Absence of left ventricular hypertrophy voltage criteria despite significant wall thickening on imaging 7
• Atrial fibrillation and atrioventricular conduction abnormalities are frequent arrhythmic manifestations 1, 4
• Right bundle branch block may be present 5

The ECG is abnormal in 86% of patients with cardiac involvement 1

Echocardiographic Characteristics

Structural Abnormalities

Diffuse ventricular wall thickening (≥12 mm) with a small left ventricular cavity is the primary structural finding, occurring in 70% of patients, while isolated septal thickening occurs in 30%. 8, 3, 1

• Biatrial enlargement disproportionate to ventricular dysfunction (27% of patients) 1, 9
• Increased atrial septal thickness is a characteristic feature 2, 8
• Thickened cardiac valves (mitral and/or aortic) without significant stenosis (13% of patients) 8, 1
• Granular sparkling appearance of the myocardium (27% of patients), though this is neither sensitive nor specific 1, 7
• Pericardial effusion in 40% of patients 1, 9

Functional Abnormalities

Restrictive transmitral Doppler filling pattern with elevated left-sided filling pressures occurs in 57% of patients and is the hallmark of diastolic dysfunction. 2, 1, 9

• Preserved left ventricular ejection fraction until late stages of disease (73% maintain normal systolic function initially) 1, 7
• Impaired systolic function develops in 27% as disease progresses 1

Advanced Strain Imaging

Reduced global longitudinal strain with apical sparing pattern (apical-to-basal strain ratio >2.1) is highly suggestive of cardiac amyloidosis and should be assessed in all suspected cases. 2, 8, 7

• LV ejection fraction-to-strain ratio >4 is a notable diagnostic feature 2, 8
• Decreased longitudinal strain with preserved apical function creates the characteristic "bulls-eye" appearance on strain mapping 2, 7
• 2D or 3D speckle-tracking echocardiography is more useful than conventional echo for screening and should be utilized when cardiac amyloidosis is suspected 8, 7

Diagnostic Algorithm Integration

When echocardiography shows these suggestive findings, immediately proceed with monoclonal protein screening (serum and urine immunofixation electrophoresis plus serum free light chain assay) to confirm AL amyloidosis. 2, 3, 5

Key Diagnostic Pitfalls

• Echocardiography cannot distinguish AL from ATTR amyloidosis—monoclonal protein screening is mandatory for subtype determination 8, 3
• Neither ECG nor echocardiography alone is sufficient for diagnosis—they serve to "rule in" suspicion and prompt further evaluation 7
• Cardiac MRI should be performed when echo is suggestive but equivocal, showing diffuse subendocardial late gadolinium enhancement (88% sensitivity, 100% specificity for AL) and elevated native T1 values 2, 8, 9
• Endomyocardial biopsy remains definitive when non-invasive methods are equivocal, with Congo red staining showing apple-green birefringence under polarized light 3

Monitoring Asymptomatic Patients

Patients with histologically proven amyloidosis should undergo echocardiography even without cardiac symptoms, as 72% of initially asymptomatic patients with echocardiographic evidence of cardiac involvement will develop cardiac symptoms. 1