From the Guidelines
Kappa (κ) and lambda (λ) free light chains are essential for diagnosing cardiac amyloidosis, particularly for identifying light chain (AL) amyloidosis, and should be performed in all patients with suspected cardiac amyloidosis as part of the initial diagnostic workup, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
Role of Kappa and Lambda Free Light Chains
The test measures the levels of unbound light chains in the blood and calculates the κ/λ ratio. In AL amyloidosis, there is typically an abnormal κ/λ ratio (normal range is approximately 0.26-1.65), with one light chain type being elevated due to production by a clonal plasma cell population.
- An abnormal ratio suggests AL amyloidosis, while a normal ratio points toward other types like transthyretin amyloidosis (ATTR).
- The magnitude of light chain elevation correlates with disease severity and can be used for monitoring treatment response.
- Additionally, urine protein electrophoresis with immunofixation should be performed alongside serum testing to detect Bence Jones proteinuria.
Diagnostic Approach
It's important to note that some patients with AL amyloidosis may have subtle light chain abnormalities, so both serum and urine testing are recommended for comprehensive evaluation.
- Early detection is critical as AL amyloidosis has a poorer prognosis than ATTR but responds to targeted plasma cell therapies.
- The 2019 expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis also support the use of biomarkers and imaging to build suspicion for ATTR-CM 1.
Clinical Considerations
In patients with high clinical suspicion for cardiac amyloidosis, without evidence of serum or urine monoclonal light chains, bone scintigraphy should be performed to confirm the presence of transthyretin cardiac amyloidosis, as recommended by the 2022 AHA/ACC/HFSA guideline 1.
- Genetic testing should be performed to differentiate hereditary variant from wild-type transthyretin cardiac amyloidosis.
- A comprehensive diagnostic approach, including serum and urine free light chain assays, urine protein electrophoresis with immunofixation, and bone scintigraphy, is necessary for accurate diagnosis and treatment of cardiac amyloidosis.
From the Research
Role of Kappa and Lambda Free Light Chains in Diagnosing Cardiac Amyloidosis
- The diagnosis of cardiac amyloidosis can be aided by the analysis of serum free light chain kappa and lambda values, which can help differentiate between immunoglobulin light chain amyloid (AL) amyloidosis and other forms of amyloidosis 2.
- A study found that the serum free light chain kappa/lambda ratios were non-overlapping for the three major groups: AL-lambda, non-AL, and AL-kappa, with a kappa/lambda ratio value between 0.5 and 5.0 having 100% sensitivity and 100% specificity for distinguishing AL amyloidosis from non-AL amyloidosis 2.
- However, cases have been reported where the serum kappa/lambda free light chain ratio was normal or negative, despite the presence of cardiac amyloidosis, highlighting the importance of combining multiple diagnostic techniques, including immunofixation electrophoresis, bone marrow biopsy, and echocardiography 3, 4.
- Echocardiography can play a crucial role in the non-invasive diagnosis of cardiac amyloidosis, with specific findings such as thickened right and left ventricular myocardium, normal or small LV cavity size, and diffuse hyper-refractile 'granular sparkling' appearance 5.
- Advanced imaging modalities, such as tissue Doppler, Doppler-based strain, speckle tracking imaging, and three-dimensional echocardiography, can provide additional information on left ventricular dysfunction, but may not be able to provide a non-invasive diagnosis of cardiac amyloidosis 5.
- Rare cases of isolated light chain amyloid cardiomyopathy with negative immunofixation and normal free light chain ratio have been reported, highlighting the importance of considering even slight increases in serum lambda or kappa FLCs as abnormal in suspected cardiac amyloidosis 4.
- The involvement of heavy and light chain (AHL)-type cardiac amyloidosis has been illustrated in a case report, with immunofluorescence microscopy showing positive expression for IgG heavy chain and kappa light chain, and negative staining for IgM and IgA heavy chains and lambda light chain 6.