The diagnosis of cardiac amyloidosis involves a combination of clinical history, imaging studies, and tissue biopsy.
Clinical history
- The ARC 2019 guidelines recommend recognizing certain clinical features as diagnostic clues for ATTR cardiomyopathy. These include evidence of right-sided heart failure, heart failure with preserved ejection fraction (HFpEF), intolerance to ACE inhibitors or β-blockers, bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, unexplained peripheral neuropathy, unexplained atrial arrhythmias, or conduction system disease
Imaging studies
- Echocardiography with longitudinal left ventricular strain measurement or cardiac MRI with late gadolinium enhancement and T1 mapping are recommended by the CCS/CHFS 2020 guidelines for all patients with suspected cardiac amyloidosis to evaluate for characteristic features of the disease or alternative causes of heart failure
- Radionuclide imaging, specifically bone scintigraphy, is recommended by both the ARC 2019 and CCS/CHFS 2020 guidelines to confirm the presence of transthyretin cardiac amyloidosis in patients with high clinical suspicion for cardiac amyloidosis without evidence of serum or urine monoclonal light chains
- Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is a reference standard for the diagnosis of cardiac amyloidosis and can provide incremental information on outcome even after adjustment for known prognostic factors
Tissue biopsy
- The ARC 2019 guidelines recommend performing a tissue biopsy from a clinically affected organ, such as an endomyocardial biopsy if the heart is clinically affected, or an abdominal fat or bone marrow biopsy if a monoclonal protein is detected, depending on availability and expertise at the clinic
- Endomyocardial biopsy is recommended by the CCS/CHFS 2020 guidelines for diagnosis and subtyping with mass spectrometry or immunohistochemistry/immunofluorescence, if available, when the existing diagnostic workup for cardiac amyloidosis is equivocal or discordant with clinical suspicion
Genetic testing
- The ACC/AHA/HFSA 2022 guidelines recommend obtaining genetic testing with transthyretin gene sequencing to differentiate hereditary variant from wild-type transthyretin cardiac amyloidosis in patients diagnosed with transthyretin cardiac amyloidosis
In summary, the diagnosis of cardiac amyloidosis involves recognizing clinical features that suggest the disease, utilizing imaging studies to identify characteristic cardiac involvement, performing tissue biopsy when necessary to confirm the diagnosis and determine the amyloid type, and conducting genetic testing to distinguish between hereditary and wild-type forms of transthyretin amyloidosis.