fbpx Skip to main content

Medically reviewed by Dr. Shani S. Saks, D.O. on July 27, 2023

Diagnosing cardiac amyloidosis (CA) can be difficult due to its nonspecific presentation and overlapping clinical features. Clinical suspicion, cardiac biomarkers, monoclonal protein assessment, echocardiography, cardiac magnetic resonance findings, and bone scintigraphy are important in the diagnostic algorithm. Non-invasive techniques are preferred, but tissue and endomyocardial biopsies are still considered the gold standard for definitively diagnosing complex cases.

Cardiac amyloidosis (CA) diagnosis and subtyping are often missed or delayed due to its vague presentation, overlapping clinical picture, and diagnostic pitfalls. Advances in diagnostic techniques have improved the diagnostic approach of CA. A study in the Journal of Cardiovascular Development and Disease reviewed the current invasive and non-invasive diagnostic approaches for CA.

Clinical Suspicion

The most important factor in timely CA diagnosis is increased clinical suspicion, especially in the presence of “red flag” cardiac and extracardiac signs and symptoms.

Cardiac Biomarkers and Monoclonal Protein

Persistently elevated troponin and disproportionally raised N-terminal pro-brain natriuretic peptide, compared to the clinical presentation of heart failure, should raise the suspicion of CA. These biomarkers are currently recommended as the first steps of the CA diagnostic algorithm.

All patients with suspected CA should undergo serum and urine monoclonal protein assessment. A hematologist should be consulted for further evaluation if monoclonal protein is detected. A negative monoclonal protein assessment has a negative predictive value of 99% for light-chain (AL) amyloidosis and, therefore, will lead to a non-invasive algorithm to assess for transthyretin (ATTR) amyloidosis.  

Characteristic Echocardiography and Cardiac Magnetic Resonance Findings

Characteristic echocardiography findings suggestive of CA include left ventricular hypertrophy, impaired global longitudinal strain, left atrial dilatation and wall thickening, speckle-tracking echocardiography findings, etc. The current diagnostic criteria focus only on wall thickness and have limited sensitivity and specificity. Two scores inclusive of echocardiographic findings, amyloid level (AL) and increased wall thickness (IWT), have recently been proposed for diagnosing or ruling out CA. 

You May Also Like::  Study Refutes 'Fat but Healthy' Theory

Characteristic cardiac magnetic resonance (CMR) findings include diffuse or transmural late gadolinium enhancement, abnormal gadolinium kinetics, and high extracellular volume. CMR has higher sensitivity and specificity for CA than echocardiography. However, use of CMR is limited by the presence of renal disease. Both CMR and echocardiography are unable to differentiate between CA subtypes.

Bone Scintigraphy as a Cornerstone for CA Diagnosis and Subtyping

Recently, bone scintigraphy has become the cornerstone of CA diagnosis and subtyping. Technetium 99m bone scintigraphy should be performed in all patients with suspected CA. It should always be interpreted in combination with SPECT imaging and results of monoclonal protein screening to avoid false positive or false negative results.

Tissue and Endomyocardial Biopsy

In the case of positive scintigraphy uptake (Grade 2–3) and negative monoclonal protein assessment, a diagnosis of ATTR can be made without the need for invasive procedures. Any other clinical scenario requires a tissue biopsy, first with surrogate site sampling, and then with myocardial biopsy in the case of inconclusive results or the need for prompt diagnosis. Although the availability of other techniques limits the use of endomyocardial biopsy, it remains the gold standard for CA diagnosis. It is highly valuable for selected patients and is the only method for reliably establishing a diagnosis in challenging cases.


Kiotsekoglou, A., Saha, S. K., Nanda, N. C., & Lindqvist, P. (2020). Echocardiographic diagnosis of cardiac amyloidosis: Does the masquerader require only a “cherry on top”? Echocardiography-a Journal of Cardiovascular Ultrasound and Allied Techniques, 37(11), 1713–1715. https://doi.org/10.1111/echo.14952