Diflunisal tolerability in transthyretin cardiac amyloidosis: a single center’s experience

Agrebi, I.; Donnelly, J.P.; Sperry, Brett W.; Samaras, Christy; Valent, Jason; Hanna, Mazen

doi:10.1080/13506129.2018.1519507

Cited by 55 publications

(29 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Worsening of heart failure led to discontinuation of diflunisal in one patient (1.5%) in the study by Berk and colleagues, but was not encountered in other studies . In regard to cardiac function, administration of diflunisal appeared to be safe overall, even in patients diagnosed with ATTR‐associated cardiomyopathy …”

Section: Clinical Efficacy – What Do We Know So Far?mentioning

confidence: 87%

“…In particular, diflunisal induced gastrointestinal injury that led to bleeding in one patient (1.5%), while it caused gastric intolerance in 13% of patients in another study . However, the risk of gastrointestinal injury can be reduced by proton pump inhibitors or histamine type 2 receptor antagonists …”

Section: Clinical Efficacy – What Do We Know So Far?mentioning

confidence: 94%

“…Additionally, some patients experienced a deterioration of renal function that aggravated over time and improved shortly after diflunisal was discontinued . Hence, close renal monitoring is recommended.…”

Section: Clinical Efficacy – What Do We Know So Far?mentioning

confidence: 99%

“…18 In particular, diflunisal induced gastrointestinal injury that led to bleeding in one patient (1.5%), 18 while it caused gastric intolerance in 13% of patients in another study. 99 However, the risk of gastrointestinal injury can be reduced by proton pump inhibitors or histamine type 2 receptor antagonists. 85,88 Worsening of heart failure led to discontinuation of diflunisal in one patient (1.5%) in the study by Berk and colleagues, but was not encountered in other studies.…”

Section: Safety Profilesmentioning

confidence: 99%

“…18,85 In regard to cardiac function, administration of diflunisal appeared to be safe overall, even in patients diagnosed with ATTR-associated cardiomyopathy. 88,99 Additionally, some patients experienced a deterioration of renal function that aggravated over time and improved shortly after diflunisal was discontinued. 85,88,99 Hence, close renal monitoring is recommended.…”

Section: Safety Profilesmentioning

confidence: 99%

See 4 more Smart Citations

Emerging therapies in transthyretin amyloidosis – a new wave of hope after years of stagnancy?

Müller

Butler

Heidecker

2020

European J of Heart Fail

View full text Add to dashboard Cite

Transthyretin amyloidosis (ATTR) is a rare, yet underdiagnosed disease characterized by progressive impairment of neurologic and cardiac function due to deposition of misfolded transthyretin. Despite great efforts, such as the introduction of orthotopic liver transplant, the devastating prognosis for both variant and wild‐type ATTR patients remained unchanged over the last decades, mainly due to a lack of specific therapies. Fortunately, recent years saw the introduction of promising targeted therapies, which aim to interfere with the deposition of misfolded transthyretin (TTR) at various stages of the cascade underlying ATTR progression. These include TTR tetramer stabilizers (tafamidis, diflunisal, epigallocatechin‐3‐gallate), TTR silencers (inotersen, patisiran) and fibril disruptors (monoclonal antibodies, doxycycline and tauroursodeoxycholic acid). In the context of this review we explain their mechanisms of action, analyse their efficacy on neurologic and cardiac function based on all clinical trials conducted to date and discuss their clinical applicability. Eventually suggestions for future clinical research into the field are provided.

show abstract

Section: Clinical Efficacy – What Do We Know So Far?mentioning

confidence: 87%

Section: Clinical Efficacy – What Do We Know So Far?mentioning

confidence: 94%

Section: Clinical Efficacy – What Do We Know So Far?mentioning

confidence: 99%

Section: Safety Profilesmentioning

confidence: 99%

Section: Safety Profilesmentioning

confidence: 99%

See 3 more Smart Citations

Emerging therapies in transthyretin amyloidosis – a new wave of hope after years of stagnancy?

Müller

Butler

Heidecker

2020

European J of Heart Fail

View full text Add to dashboard Cite

show abstract

Diagnosis and treatment of transthyretin‐related amyloidosis cardiomyopathy

Teng

Bae

et al. 2020

Clinical Cardiology

View full text Add to dashboard Cite

Transthyretin-related amyloidosis (ATTR) is a subgroup of amyloidosis that results from extracellular misassembled and toxic amyloid deposits affecting multiple organ systems, and cardiac tissues in particular. Because ATTR often presents as heart failure with preserved ejection fraction (HFpEF), it has been largely underdiagnosed. Once considered incurable with a grave prognosis, ATTR cardiomyopathy has seen the development of promising alternatives for diagnosis and treatment, with early diagnosis and treatment of ATTR cardiomyopathy highly beneficial due to its high mortality rate. For instance, diagnosing ATTR cardiomyopathy previously required a cardiac biopsy, but new modalities, such as cardiac magnetic resonance imaging and radionuclide bone scans, show promise in accurately diagnosing ATTR cardiomyopathy. Ongoing research and clinical trials have focused on identifying new treatments which primarily target amyloid fiber formation by inhibiting TTR gene expression, stabilizing the TTR tetramer, preventing oligomer aggregation, or affecting degradation of amyloid fibers. In this review, we describe the advances made in the diagnosis and treatment of ATTR in order to increase awareness of the disease and encourage a lower threshold for ATTR workup. Our review also highlights the need for improving the screening, diagnosis, and treatment guidelines for ATTR cardiomyopathy. K E Y W O R D S heart disease, physical diagnosis/cardiovascular, treatment 1 | BACKGROUND Transthyretin (TTR)-related amyloidosis (ATTR), a rare and underdiagnosed disease, mainly affects the cardiac and peripheral nerves and is fatal if not treated in time. 1 Primarily synthesized in the liver, TTR is a protein that transports vitamin A and thyroxine in plasma and cerebrospinal fluid. 2 The mechanism of transportation involves four oligomers that attach to each other to form two dimers, which in turn form a TTR tetramer that contains the hormone binding site. 2 Through gene mutation or aging of the protein, TTR can become unstable and break up into oligomers, which aggregate into insoluble fibrils called TTR amyloid that deposit into extracellular space or tissues, causing ATTR. 3 Based on the type of precursor and misfolded protein amyloids, there are different types of amyloid diseases from ATTR to light chain amyloidosis (AL), which is caused by aggregation of immunoglobulin light chains produced by plasma cells in the bone marrow. 4 Depending on the type of precursor protein, different protein amyloids target Catherine Teng and Pengyang Li contributed equally to this review article.

show abstract

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Diflunisal tolerability in transthyretin cardiac amyloidosis: a single center’s experience

Cited by 55 publications

References 25 publications

Emerging therapies in transthyretin amyloidosis – a new wave of hope after years of stagnancy?

Emerging therapies in transthyretin amyloidosis – a new wave of hope after years of stagnancy?

Diagnosis and treatment of transthyretin‐related amyloidosis cardiomyopathy

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

Contact Info

Product

Resources

About