Diagnosis and Treatment of Cardiac Amyloidosis: ESC Position Statement

Garcia-Pavia P, Rapezzi C, Adler Y, et al.
Diagnosis and Treatment of Cardiac Amyloidosis: A Position Statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2021;Apr 7:[Epub ahead of print].

The following are key points to remember from the European Society of Cardiology (ESC) Working Group on Myocardial and Pericardial Diseases position statement on the diagnosis and treatment of cardiac amyloidosis:

Initial Considerations:

  1. Cardiac amyloidosis is often underdiagnosed. The majority of cases (>98%) are related to monoclonal immunoglobulin light chain (AL) or transthyretin (ATTR) deposition. ATTR amyloidosis can be hereditary or acquired/wild-type.
  2. Screening for cardiac amyloidosis can be considered when left ventricle wall thickness is ≥12 mm in the presence of any additional suggestive findings. These findings include but are not limited to:
    1. Family history of amyloidosis.
    2. Noncardiac: peripheral neuropathy, autonomic dysfunction, proteinuria, macroglossia, skin bruising, bilateral carpal tunnel syndrome, ruptured biceps tendon, lumbar spinal stenosis, known plasma cell dyscrasia.
    3. Cardiac: conduction disease, persistently elevated biomarkers, nondilated left ventricle with heart failure or aortic stenosis (particularly in the elderly), unexplained right heart failure.
    4. Typical electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging (MRI) findings.

Diagnostic Approach:

  1. Initial evaluation should include testing for monoclonal proteins (serum and urine electrophoresis with immunofixation, serum free light chain ratio) and a bone tracer cardiac scintigraphy scan (fairly specific for ATTR). Follow-up testing with cardiac MRI and tissue biopsy (cardiac or extracardiac) is used when indicated.
  2. The proposed diagnostic algorithm focuses on determining the presence/absence of AL and ATTR cardiac amyloidosis. The four key scenarios are:
    1. (-) monoclonal protein, (-) scintigraphy scan: unlikely to have cardiac amyloidosis, consider cardiac MRI and possible biopsy if suspicion is still high.
    2. (-) monoclonal protein, (+) scintigraphy scan: if grade 2 or 3 uptake on the scan then this is diagnostic for ATTR cardiac amyloidosis and no biopsy is needed, if grade 1 uptake then will need a biopsy to confirm diagnosis.
    3. (+) monoclonal protein, (-) scintigraphy scan: may have AL amyloidosis and will need a cardiac MRI, if MRI is negative then cardiac involvement is unlikely, if MRI is positive then will need a biopsy to confirm diagnosis.
    4. (+) monoclonal protein, (+) scintigraphy scan: may have AL or ATTR or combined amyloidosis, will need a cardiac biopsy to confirm diagnosis.
  3. For ATTR cardiac amyloidosis, referral to genetic counseling and testing should be completed. This will have an impact on prognostication, treatment choice, and screening of family members.

Prognosis and Management:

  1. Several scores based on biomarkers and clinical data are available for initial prognostication. However, the ability to predict disease trajectories in the era of new cardiac amyloidosis therapeutics is lacking. This is an area of future investigation.
  2. General management of cardiac amyloidosis:
    1. Be aware of managing common complications such as heart failure, atrial fibrillation, thromboembolism, conduction disorders, ventricular arrhythmias, and aortic stenosis.
    2. Use the following medications with caution: beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, digoxin.
    3. Organ transplantation, while not commonly performed, may be considered.
  3. Treatment for AL cardiac amyloidosis:
    1. Referral to hematology for consideration of chemotherapy or autologous stem cell transplant.
  4. Treatment for ATTR cardiac amyloidosis:
    1. Acquired/wild-type: tafamidis (TTR stabilizer, prevents protein misfolding).
    2. Hereditary: tafamidis (TTR stabilizer); if polyneuropathy is present then can also use patisiran (TTR gene silencer, prevents production).
    3. Tafamidis and patisiran have been shown to be effective in clinical trials. Additional indications for these drugs and other therapies, including agents that remove amyloid deposits, are under continued investigation or used off-label.
  5. Ideal follow-up and serial testing have not been established, though timing of testing and follow-up has been suggested. Referral to specialized centers is strongly encouraged.

Clinical Topics: Arrhythmias and Clinical EP, Cardio-Oncology, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Valvular Heart Disease, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Echocardiography/Ultrasound, Magnetic Resonance Imaging, Nuclear Imaging

Keywords: Amyloidosis, Amyloidosis, Familial, Aortic Valve Stenosis, Atrial Fibrillation, Cardiotoxicity, Diagnostic Imaging, Echocardiography, Geriatrics, Heart Failure, Immunoglobulin Light Chains, Magnetic Resonance Imaging, Pharmaceutical Preparations, Plaque, Amyloid, Prealbumin, Radionuclide Imaging, Spinal Stenosis, Stem Cell Transplantation, Thromboembolism

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