Transthyretin amyloidosis involves the deposition of transthyretin amyloid fibrils in the body. We report an unusual case of a young Afro-Caribbean woman harboring a Thr60Ala mutation who presented with clinical signs of heart failure and polyneuropathy confirmed with genetic testing and results of an abdominal fat pad biopsy. ().
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http://dx.doi.org/10.1016/j.jaccas.2020.08.030 | DOI Listing |
Biomedicines
December 2024
Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Cardiac amyloidosis (CA) is a progressive condition resulting from the deposition of amyloid fibrils in the heart, which leads to severe diastolic dysfunction and restrictive cardiomyopathy. The disease has two main subtypes: light-chain and transthyretin (TTR) CA, with the latter subdivided into wild-type and hereditary forms. Despite advances in diagnostic imaging, early detection remains a challenge due to non-specific symptoms that mimic other cardiac conditions.
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January 2025
Department of Cardiac Sciences, University of Calgary and Libin Cardiovascular Institute, Calgary, AB, Canada.
Purpose Of Review: This review evaluates recent advancements in Technetium-99 m pyrophosphate (99mTc-PYP) imaging for transthyretin amyloid cardiomyopathy (ATTR-CM). We summarize the advantages of single-photon emission computed tomography (SPECT) over planar imaging, the potential impact of quantitative methods, and emerging data for quantifying response to therapy.
Recent Findings: The current literature demonstrates the superior diagnostic accuracy of SPECT compared with planar imaging in 99mTc-PYP studies.
J Am Coll Cardiol
January 2025
Section of Cardiovascular Medicine, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, Massachusetts, USA. Electronic address:
J Am Coll Cardiol
December 2024
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address:
Background: Outpatient worsening heart failure (HF), defined by initiation or intensification of diuretics, is adversely prognostic for patients with either reduced or preserved ejection fraction.
Objectives: This study sought to investigate the prognostic value of outpatient worsening HF in transthyretin amyloidosis with cardiomyopathy and the effect of patisiran treatment.
Methods: Post hoc analyses of the APOLLO-B trial (NCT03997383) evaluated the associations between outpatient worsening HF (defined by oral diuretic initiation or intensification), measures of disease progression, and a composite endpoint of all-cause mortality and cardiovascular (CV) events.
Nat Struct Mol Biol
January 2025
Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.
Transthyretin (TTR) is a natively tetrameric thyroxine transporter in blood and cerebrospinal fluid whose misfolding and aggregation causes TTR amyloidosis. A rational drug design campaign identified the small molecule tafamidis (Vyndamax) as a stabilizer of the native TTR fold, and this aggregation inhibitor is regulatory agency approved for the treatment of TTR amyloidosis. Here we used cryo-EM to investigate the conformational landscape of this 55 kDa tetramer in the absence and presence of one or two ligands, revealing inherent asymmetries in the tetrameric architecture and previously unobserved conformational states.
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