The following are key points to remember from this review of the basic pathophysiology, clinical presentation, diagnosis, and management of the most common forms of cardiac amyloidosis:

1. Amyloidosis is a disease, which may be systemic or localized, characterized by deposition of abnormal protein that accumulates in tissues, resulting in damaging fibrous deposits.
2. Cardiac amyloidosis is an underrecognized cause of heart failure (HF), particularly diastolic. It is usually associated with depositions of immunoglobulin light-chain aggregations (AL) or transthyretin (ATTR).
3. In AL, a plasma cell clone secretes excess light chain immunoglobulins prone to misfolding. It may be associated with plasma cell dyscrasias such as multiple myeloma.
4. Two types of ATTR include mutant ATTR, due to a genetic mutation, and wild-type ATTR, related to an acquired defect.
5. Various extracardiac manifestations may occur. Bilateral carpal tunnel syndrome is a common manifestation of ATTR.
6. Cardiac amyloidosis causes biventricular wall thickening and stiffness, HF, and restrictive cardiomyopathy. Poor ventricular filling may cause orthostasis or syncope.
7. Differential diagnosis includes other cardiomyopathies like hypertrophic, restrictive from radiation, infiltrative, and high-output HF.
8. Echocardiogram and cardiac magnetic resonance imaging can support a diagnosis of infiltrative cardiomyopathy but cannot diagnose amyloidosis or distinguish types of amyloidosis.
9. Laboratory studies showing plasma cell dyscrasia suggest AL.
10. With AL, biopsy is mandatory for diagnosis. If confirmed, use mass spectrometry to identify the specific amyloid type.
11. ATTR can be diagnosed with pyrophosphate nuclear scan. If strongly positive, DNA sequencing should be performed to determine the transthyretin subtype.
12. Treatment goals are to manage cardiac symptoms/complications and to suppress amyloid formation and deposition.
13. Sodium restriction, daily weights, and education regarding orthostatic hypotension and support stockings should be encouraged.
14. Loop diuretics are often used, but patients may develop hypotension and orthostasis. Conventional HF therapies are often poorly tolerated and should be avoided.
15. Cardiac transplantation may be considered, but extracardiac amyloid organ dysfunction may preclude candidacy. Left ventricular assist devices are contraindicated in patients with small ventricular cavities.
16. To suppress amyloid formation and deposition, AL is treated with chemotherapy with/without autologous stem cell transplantation.
17. Drugs such as transthyretin silencer therapies and RNA interference approaches are in development. Tafamidis, a transthyretin stabilizer that reduces mortality and cardiac hospitalizations, was recently approved by the US Food and Drug Administration for ATTR.
18. Clinicians should have a high index of suspicion for amyloidosis in patients with HF with preserved ejection fraction without hypertension or ischemia or who do not tolerate guideline-directed medical therapy.
19. Clinicians should refer patients with suspected amyloidosis to high-volume amyloid centers for consultation.
20. Rapid diagnosis and treatment of AL is needed. Following HF diagnosis, median survival is 4-6 months.

Clinical Topics: Heart Failure and Cardiomyopathies, Vascular Medicine, Acute Heart Failure

Keywords: Amyloidosis, Amyloid, Prealbumin, Immunoglobulin Light Chains, Cardiomyopathy, Restrictive, Heart Failure, Multiple Myeloma, Diagnosis, Differential, Sodium Potassium Chloride Symporter Inhibitors, Pharmaceutical Preparations

< Back to Listings