Pathophysiology and treatment of cardiac amyloidosis

Key Points

  • Cardiac amyloidosis should be suspected in any patient with heart failure and preserved ejection fraction or infiltrative cardiomyopathy

  • Histological diagnosis of amyloid requires further investigation to determine the protein subunit type, because the therapies vary widely

  • Preferred therapies for immunoglobulin light-chain amyloidosis involve standard-dose or high-dose chemotherapy with stem-cell rescue

  • Investigational therapies for transthyretin-related cardiomyopathy are diflunisal or tafamidis, and multiple new therapies for transthyretin-related amyloidosis and antibody therapy for immunoglobulin light-chain amyloidosis are being developed

Abstract

Amyloid cardiomyopathy should be suspected in any patient who presents with heart failure and preserved ejection fraction. In patients with echocardiographic evidence of ventricular thickening and without a clear history of hypertension, infiltrative cardiomyopathy should be considered. If imaging suggests the presence of amyloid deposits, confirmation by biopsy is required, although endomyocardial biopsy is generally not necessary. Assessment of aspirated subcutaneous fat and bone-marrow biopsy samples verifies the diagnosis in 40–80% of patients, dependent on the type of amyloidosis. Mass spectroscopy can be used to determine the protein subunit and classify the disease as immunoglobulin light-chain amyloidosis or transthyretin-related amyloidosis associated with mutant or wild-type TTR (formerly known as familial amyloid cardiomyopathy and senile cardiac amyloidosis, respectively). In this Review, we discuss the characteristics of cardiac amyloidosis, and present a structured approach to both the assessment of patients and treatment with emerging therapies and organ transplantation.

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Figure 1: Endomyocardial biopsy specimen.
Figure 2: Algorithm for diagnosis in patients with suspected amyloidosis.
Figure 3: Algorithm for diagnosis in patients with amyloidosis established by biopsy.

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M.A.G. researched data for the article, discussed its content, and wrote, reviewed, and edited the manuscript before submission. A.D. and T.S. also wrote the manuscript, and reviewed and edited it before submission.

Correspondence to Morie A. Gertz.

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Competing interests

M.A.G. declares that he has received honoraria from Celgene, ISIS, Millennium, Neotope, Novartis, and Onyx. A.D. declares that she has received research funding from Celgene, Janssen, Millennium, and Pfizer. T.S. declares no competing interests.

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Gertz, M., Dispenzieri, A. & Sher, T. Pathophysiology and treatment of cardiac amyloidosis. Nat Rev Cardiol 12, 91–102 (2015). https://doi.org/10.1038/nrcardio.2014.165

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