From the Guidelines
Patients with heart failure and monoclonal gammopathy suspected of having amyloidosis should undergo a comprehensive evaluation including serum free light chain assay, serum and urine immunofixation, cardiac biomarkers (troponin and NT-proBNP), and advanced cardiac imaging, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
Evaluation Approach
The evaluation approach should include:
- Initial assessment with echocardiography with strain imaging to identify characteristic patterns such as increased left ventricular wall thickness and reduced global longitudinal strain with relative apical sparing
- Cardiac MRI with gadolinium enhancement to reveal distinctive late gadolinium enhancement patterns
- Nuclear scintigraphy using technetium-labeled tracers (99mTc-PYP, 99mTc-DPD, or 99mTc-HMDP) for diagnosing transthyretin amyloidosis, as outlined in the ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis 1
Diagnostic Criteria
Diagnostic criteria for cardiac amyloidosis include:
- Abnormal NT-proBNP and Troponin T levels
- Abnormal free light chains (FLCs) defined by an abnormal serum Kappa and Lambda immunoglobulin FLC ratio
- Presence of a monoclonal light chain, which requires hematology-oncology consultation and consideration of heart or other biopsy
Management
Management depends on the type of amyloidosis identified:
- For light chain (AL) amyloidosis, prompt referral to hematology for chemotherapy regimens (such as bortezomib, cyclophosphamide, and dexamethasone) is essential
- For transthyretin (ATTR) amyloidosis, tafamidis (20 or 80 mg daily) is approved to reduce cardiovascular mortality and hospitalization, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1
Heart Failure Management
Heart failure management should be tailored carefully, as standard therapies like beta-blockers and ACE inhibitors may be poorly tolerated. Diuretics are the mainstay for congestion management, while anticoagulation should be considered due to increased thromboembolism risk, particularly with atrial fibrillation. Early diagnosis is critical as treatment outcomes are significantly better when initiated before advanced cardiac damage occurs.
From the FDA Drug Label
VYNDAQEL and VYNDAMAX are transthyretin stabilizers indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization (1)
The evaluation and management approach for patients with heart failure and monoclonal gammopathy suspected of having amyloidosis is not directly addressed in the provided drug labels.
- Key points:
- The labels discuss the treatment of transthyretin-mediated amyloidosis, but do not provide information on the evaluation of amyloid in the setting of heart failure and monoclonal gammopathy.
- The labels do not mention monoclonal gammopathy as a specific condition to be evaluated or managed in the context of amyloidosis 2, 2, 2. Therefore, no conclusion can be drawn about the evaluation and management approach for these patients based on the provided information.
From the Research
Evaluation Approach
The evaluation of patients with heart failure and monoclonal gammopathy suspected of having amyloidosis involves several steps:
- Diagnosis can be made using serum free light chain assay and immunofixation electrophoresis to exclude light chain amyloidosis combined with cardiac nuclear scintigraphy to detect radiotracer uptake in a pattern consistent with amyloidosis 3
- It is essential to determine the precursor protein, as the clinical course and treatment of AL (light-chain amyloid protein) and ATTR amyloidosis are distinct 4
- Mass spectrometry-based proteomic analysis can be used to determine the validity of tests to predict amyloid type 5
Management Approach
The management of patients with heart failure and monoclonal gammopathy suspected of having amyloidosis involves:
- Loop diuretics, such as furosemide, torsemide, and bumetanide, are the primary treatment for fluid overload and symptomatic relief of patients with ATTR heart failure 3
- An ATTR-directed therapy that inhibited misfolding of the TTR protein (tafamidis, a protein stabilizer) can reduce mortality, hospitalizations, and is most effective when administered early in the disease course 3
- In patients with both monoclonal gammopathy and a TTR variant, it is imperative to discern the tissue type of the amyloid to deduce the correct diagnosis 6
- Novel treatment strategies, including gene-silencing therapies and monoclonal antibodies, are being developed to target and remove amyloid fibrils that have deposited in the myocardium 7
Importance of Accurate Diagnosis
Accurate diagnosis is crucial in patients with heart failure and monoclonal gammopathy suspected of having amyloidosis:
- The prevalence of coexistent monoclonal gammopathy of undetermined significance (MGUS) with ATTR amyloidosis is high, with an MGUS rate that is higher than the general population 4
- Blood and urine monoclonal protein studies are not, by themselves, robust predictors of cardiac amyloid type in patients undergoing endomyocardial biopsy 5
- In patients with amyloidosis who have both monoclonal gammopathy and a TTR variant, it is imperative to discern the tissue type of the amyloid to deduce the correct diagnosis 6