From the Guidelines
A cardiac amyloid workup should begin with non-invasive testing, including serum and urine protein electrophoresis with immunofixation, serum free light chain assay, troponin, NT-proBNP, and comprehensive metabolic panel, as recommended by the most recent guidelines 1.
Initial Evaluation
The initial evaluation of a patient suspected of having cardiac amyloidosis should include:
- Serum and urine protein electrophoresis with immunofixation to detect monoclonal proteins
- Serum free light chain assay to assess for AL amyloidosis
- Troponin and NT-proBNP to evaluate for cardiac damage and dysfunction
- Comprehensive metabolic panel to assess for other potential causes of cardiac disease
Cardiac Imaging
Cardiac imaging is essential in the diagnosis of cardiac amyloidosis, including:
- Echocardiogram with strain analysis to evaluate for increased wall thickness, diastolic dysfunction, and characteristic apical sparing pattern
- Cardiac MRI with gadolinium to show distinctive late gadolinium enhancement patterns
- Nuclear imaging with technetium-99m pyrophosphate (99mTc-PYP) scan, which is particularly useful for diagnosing transthyretin amyloidosis (ATTR) with grade 2-3 uptake and a heart-to-contralateral lung ratio >1.5 being diagnostic 1
Genetic Testing
Genetic testing for TTR mutations should be performed to distinguish hereditary from wild-type ATTR, as management differs significantly between the two subtypes 1.
Treatment Planning
For treatment planning, it's crucial to determine the specific amyloid type (AL vs. ATTR) as management differs significantly, with AL requiring chemotherapy and ATTR potentially treated with tafamidis, patisiran, or inotersen depending on the subtype and clinical presentation 1.
Role of Endomyocardial Biopsy
While historically endomyocardial biopsy was the gold standard, it may now be avoided in cases where non-invasive testing is diagnostic, as recommended by recent guidelines 1. However, in cases of equivocal non-invasive findings, endomyocardial biopsy may still be necessary to establish a definitive diagnosis.
From the Research
Cardiac Amyloidosis Diagnosis
The diagnosis of cardiac amyloidosis can be challenging due to variable clinical manifestations and the perceived rarity of the disease 2, 3. However, advances in cardiovascular imaging have revealed a higher prevalence of cardiac amyloidosis in specific populations, leading to an increase in diagnosis, especially of transthyretin (ATTR) amyloidosis 2.
Diagnostic Techniques
Several diagnostic techniques are used to diagnose cardiac amyloidosis, including:
- Echocardiography: a noninvasive method for assessing cardiac morphology and function in cardiac amyloidosis 4
- Cardiac magnetic resonance (CMR): provides tissue characterization and can help diagnose cardiac amyloidosis 5
- Bone scintigraphy: a noninvasive method for assessing ATTR amyloidosis 5, 6
- Organ biopsy: may be required in some cases to confirm the diagnosis 2
Clinical Clues and Red Flags
Clinical clues and red flags can help raise suspicion for cardiac amyloidosis, including:
- Left ventricular wall thickening
- Heart failure
- Arrhythmia
- Variable clinical presentation 3
- Nonspecific symptoms, such as fatigue and shortness of breath 5
Importance of Early Diagnosis
Early diagnosis of cardiac amyloidosis is crucial, as timely treatment can significantly improve survival, especially in light chain amyloidosis 3. Effective treatment regimens are available, and death from cardiac causes can be prevented with early diagnosis and treatment 2.