Stabilization of Cardiac Function With Diflunisal in Transthyretin (ATTR) Cardiac Amyloidosis

Lohrmann, Graham; Pipilas, Alexandra; Mussinelli, Roberta; Gopal, Daksha; Berk, John L.; Connors, Lawreen H.; Vellanki, Nirupama; Hellawell, Jennifer; Siddiqi, Omar K.; Fox, Jonathan; Maurer, Mathew S.; Ruberg, Frederick L.

doi:10.1016/j.cardfail.2019.11.024

Cited by 75 publications

(33 citation statements)

References 18 publications

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“…Diflunisal is a nonsteroidal anti-inflammatory drug with potent TTR stabilizing properties that is an inexpensive alternative to tafamidis. It has been effective in carefully select patients with TTR cardiac amyloidosis; however, it may predispose patients to congestive heart failure, chronic kidney disease, or gastrointestinal mucosal irritation/bleeding ( 9 ). Or, perhaps we should consider promising over-the-counter therapy with turmeric or epigallocatechin-3-gallate (green tea), although these have yet to be proven in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Spectrum of Transthyretin Cardiac Amyloidosis in a Family

Tushak¹,

Doshi²,

Trankle³

et al. 2021

JACC: CardioOncology

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Section: Discussionmentioning

confidence: 99%

Phenotypic Spectrum of Transthyretin Cardiac Amyloidosis in a Family

Tushak¹,

Doshi²,

Trankle³

et al. 2021

JACC: CardioOncology

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“…105 The authors noted renal dysfunction and fluid overload as major adverse events, which lead to study exclusion. Recent retrospective, longitudinal studies reported diflunisal treatment resulting in measurable differences in cardiac structure and function after only 1 year of administration (TTR concentration 19 vs. 33 mg/dL, P = 0.01; left atrial volume index +4.6 vs. À1.4 mL/m 2 , P = 0.002; cardiac troponin I +0.03 vs. À0.01 ng/mL; and GLS +1.2% vs. +0.1%, P = 0.03, in patients treated with placebo compared with diflunisal), 106 being well tolerated in both patients with ATTRv and ATTRwt; withdrawal due to side effects was related to gastrointestinal complaints, but most patients had no adverse events. 107…”

Section: Diflunisalmentioning

confidence: 96%

Progress and challenges in the treatment of cardiac amyloidosis: a review of the literature

et al. 2021

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Cardiac amyloidosis is a restrictive cardiomyopathy determined by the accumulation of amyloid, which is represented by misfolded protein fragments in the cardiac extracellular space. The main classification of systemic amyloidosis is determined by the amyloid precursor proteins causing a very heterogeneous disease spectrum, but the main types of amyloidosis involving the heart are light chain (AL) and transthyretin amyloidosis (ATTR). AL, in which the amyloid precursor is represented by misfolded immunoglobulin light chains, can involve almost any system carrying the worst prognosis among amyloidosis patients. This has however dramatically improved in the last few years with the increased usage of the novel therapies such as proteasome inhibitors and haematopoietic cell transplantation, in the case of timely diagnosis and initiation of treatment. The treatment for AL is directed by the haematologist working closely with the cardiologist when there is a significant cardiac involvement. Transthyretin (TTR) is a protein that is produced by the liver and is involved in the transportation of thyroid hormones, especially thyroxine and retinol binding protein. ATTR results from the accumulation of transthyretin amyloid in the extracellular space of different organs and systems, especially the heart and the nervous system. Specific therapies for ATTR act at various levels of TTR, from synthesis to deposition: TTR tetramer stabilization, oligomer aggregation inhibition, genetic therapy, amyloid fibre degradation, antiserum amyloid P antibodies, and antiserum TTR antibodies. Treatment of systemic amyloidosis has dramatically evolved over the last few years in both AL and ATTR, improving disease prognosis. Moreover, recent studies revealed that timely treatment can lead to an improvement in clinical status and in a regression of amyloid myocardial infiltration showed by imaging, especially by cardiac magnetic resonance, in both AL and ATTR. However, treating cardiac amyloidosis is a complex task due to the frequent association between systemic congestion and low blood pressure, thrombo-embolic and haemorrhagic risk balance, patient frailty, and generally poor prognosis. The aim of this review is to describe the current state of knowledge regarding cardiac amyloidosis therapy in this constantly evolving field, classified as treatment of the cardiac complications of amyloidosis (heart failure, rhythm and conduction disturbances, and thrombo-embolic risk) and the disease-modifying therapy.

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“…In a study of 130 patients with familial amyloid polyneuropathy who were randomized to 250 mg diflunisal twice daily or placebo for 2 years, diflunisal reduced the rate of progression of polyneuropathy (neuropathy impairment score plus 7 increased by 8.7 vs 25.0 points for diflunisal vs placebo, respectively; P < 0.001) and preserved quality of life ( 80 ). Furthermore, it appears to have therapeutic benefit in slowing the progression of ATTR-CA in stable HF patients ( 81 ). Treatment with diflunisal should include regular monitoring of renal function and clinical evaluation for worsening HF symptoms and gastrointestinal bleeding.…”

Section: Treatment Strategies and Specific Disease-modifying Therapeuticsmentioning

confidence: 99%