Table 1.

Practical Considerations in the Diagnosis and Management of Cardiac Amyloidosis

Modality	Screening	Diagnosis/Subtyping	Staging	Hallmark Findings	Advantages	Disadvantages
Electrocardiography	+	−	+	Low voltage Pseudoinfarct pattern Lack of precordial left ventricular hypertrophy, disproportionate to mass	Cheap and easily obtained	Lacks sensitivity
Echocardiography	+	−	+	Increased left and right ventricular wall thickness. Bi‐atrial enlargement Valvular thickening Impaired longitudinal strain with apical sparing	Widely available	Lacks sensitivity Cannot determine amyloid subtype Cannot reliably differentiate amyloid from other hypertrophic phenocopies
Cardiac magnetic resonance	+	−	+	Diffuse subendocardial or transmural LGE Markedly elevated extracellular volume (ECV) >40% Concentric left ventricular hypertrophy Abnormal longitudinal strain even when EF preserved Bi‐atrial enlargement Valvular thickening	Can differentiate amyloid from other hypertrophic phenocopies ECV correlates with amyloid burden Diagnostic versatility enables correct diagnosis when amyloidosis not present	Cannot differentiate amyloid subtype Need for gadolinium for LGE/ECV
Serum/urine light chain analysis	−	+	+	Presence of urine or plasma monoclonal protein K/λ ratio	Inexpensive and widely available Prognostic in AL‐CM	No role in ATTR cardiomyopathy
Tc‐PyP/DPD	+	+	−	Avid visual myocardial uptake equal to or greater than rib uptake Increased heart to contralateral lung (H/CL) ratio	Highly sensitive Able to noninvasively diagnose ATTR‐CM (in absence of light chain)	Radiation exposure Positive in up to 20% of cases of AL‐CM
Cardiac biomarkers (troponin, NT‐proBNP, etc)	+/−	−	+	Elevation in NT‐proBNP and troponin out of proportion with volume status	Cheap and easily obtained Useful for staging	Lacks sensitivity
Tissue biopsy	−	+	−	Apple green birefringence on Congo Red stain Presence of amyloid fibrils by mass spectroscopy or immunohistochemistry	Affected organ biopsy highly sensitive and specific (criterion standard) Able to determine amyloid subtype (regardless of light chain presence)	Invasive Fat pad biopsy may have lower diagnostic yield

AL‐CM, immunoglobulin light chain amyloidosis; ATTR, transthyretin amyloidosis; DPD, 3,3‐diphosphono‐1,2‐propanodicarboxylic acid; ECV, extracellular volume; EF, ejection fraction; LGE, late gadolinium enhancement; NT‐proBNP, N‐terminal pro‐brain‐type natriuretic peptide; PyP, pyrophosphate; and Tc, technetium.