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Diflunisal for ATTR Cardiac Amyloidosis.
MedLine Citation:
PMID:  22747647     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Transthyretin (TTR) cardiac amyloidosis is an important, often under-recognized and potentially modifiable cause of heart failure with a preserved ejection fraction. The only proven treatment is liver or combined heart/liver transplantation, which, although effective, is not suitable for the vast majority of older adults with this condition. Diflunisal, a nonsteroidal anti-inflammatory drug, can stabilize the TTR tetramer in vitro and may prevent misfolding monomers and dimers from forming amyloid deposits in the heart. It is one of two small molecules assessed in animal safety studies and human clinical trials of TTR polyneuropathy. The authors conducted a single-arm, open-label investigation with a mean follow-up of 0.9±0.3 years to determine the safety and efficacy of diflunisal administration in a cohort of 13 patients with confirmed wild-type or mutant TTR cardiac amyloidosis. Diflunisal was well tolerated from a hematologic standpoint, although a 6% decline in estimated glomerular filtration rate was noted. Therapy was discontinued in one patient who rapidly developed volume overload. There was no significant mean change in cardiac structure (left ventricular mass: -53 g/m(2) change, P=.36), function (ejection fraction: -2% change, P=.61), or biomarkers (Troponin I: +0.03 ng/mL, P=.08; BNP: +93 pg/mL change, P=.52) during the course of therapy. These data suggest that at low dosages and with careful monitoring, diflunisal can be safely administered to compensated patients with cardiac TTR amyloidosis. Further study in a randomized placebo-controlled trial is warranted.
Authors:
Adam Castaño; Stephen Helmke; Julissa Alvarez; Susan Delisle; Mathew S Maurer
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-2
Journal Detail:
Title:  Congestive heart failure (Greenwich, Conn.)     Volume:  -     ISSN:  1751-7133     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9714174     Medline TA:  Congest Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Wiley Periodicals, Inc.
Affiliation:
From the Center for Advanced Cardiac Care, Division of Cardiology, Columbia College of Physicians and Surgeons, New York, NY.
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