Author + information
- Received February 24, 2019
- Revision received April 3, 2019
- Accepted April 9, 2019
- Published online June 3, 2019.
- Frederick L. Ruberg, MDa,
- Martha Grogan, MDb,
- Mazen Hanna, MDc,
- Jeffery W. Kelly, PhDd and
- Mathew S. Maurer, MDe,∗ (, )@ColumbiaMed
- aSection of Cardiovascular Medicine, Department of Medicine, Amyloidosis Center, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
- bDepartment of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
- cDepartment of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
- dDepartments of Chemistry and Molecular Medicine, Scripps Research Institute, La Jolla, California
- eDivision of Cardiology, Department of Medicine, Center for Advanced Cardiac Care, Columbia University Medical Center, New York, New York
- ↵∗Address for correspondence:
Dr. Mathew S. Maurer, Clinical Cardiovascular Research Laboratory for the Elderly, Columbia University Irving Medical Center, Allen Hospital of New York Presbyterian, 5141 Broadway, 3 Field West, Room 035, New York, New York 10034.
• ATTR-CM is an underdiagnosed condition.
• Diagnosing ATTR-CM requires a high index of suspicion and can be made noninvasively with nuclear scintigraphy when there is no evidence of a monoclonal protein.
• Emerging therapies that stabilize TTR have been shown to improve outcomes for patients with ATTR-CM, and TTR silencer therapies are entering late-phase clinical trials.
• Early diagnosis will be critical to afford the best efficacy of therapies.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) in older adults, resulting from myocardial deposition of misfolded transthyretin (TTR) or pre-albumin. Characteristic patterns of echocardiography and cardiac magnetic resonance can strongly suggest the disease but are not diagnostic. The diagnosis can be made with noninvasive nuclear imaging when there is no evidence of a monoclonal protein. Amyloid fibril formation results from a destabilizing mutation in hereditary ATTR amyloidosis (hATTR) or from an aging-linked process in wild-type ATTR amyloidosis (wtATTR). Recent studies have suggested that up to 10% to 15% of older adults with HF may have unrecognized wtATTR. Associated features, including carpal tunnel syndrome and lumbar spinal stenosis, raise suspicion and may afford a means for early diagnosis. Previously treatable only by organ transplantation, pharmaceutical therapy that slows or halts ATTR-CM progression and favorably affects clinical outcomes is now available. Early recognition remains essential to afford the best treatment efficacy.
Dr. Ruberg is supported by the National Institutes of Health (NIH) (grants HL139671-01 and AG 050206-02). Dr. Kelly is supported by the NIH (grant DK46335). Dr. Maurer is supported by the NIH (grants R01HL139671-01, R21AG058348 and K24AG036778). Dr. Ruberg has received support from Eidos Therapeutics; and has received consulting fees from Pfizer and GlaxoSmithKline. Dr. Grogan has taken part in clinical trials for Alnylam, Eidos, Pfizer, and Prothena; and has been a consultant to Alnylam, Eidos, Pfizer, Prothena, and Akcea. Dr. Kelly has received consulting, equity, and royalty fees from Pfizer linked to Tafamidis sales; is the founder of Fold Rx and Proteostasis Therapeutics; and has been a consultant, shareholder, and board member of Proteostasis Therapeutics. Dr. Hanna has taken part in clinical trials for Pfizer, Alnylam, and Akcea; and has been a consultant and a member of the Advisory Board for Pfizer, Alnylam, Akcea, and Eidos. Dr. Maurer has received consulting fees from Pfizer, GlaxoSmithKline, EIdos, Prothena, Akcea, and Alnylam; and has received clinical trial funding from Pfizer, Prothena, Eidos, and Alnylam.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received February 24, 2019.
- Revision received April 3, 2019.
- Accepted April 9, 2019.
- 2019 American College of Cardiology Foundation
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