A Review of Novel Agents and Clinical Considerations in Patients With ATTR Cardiac Amyloidosis

Benbrahim, Meissane; Norman, Kelsey P.; Sanchorawala, Vaishali; Siddiqi, Omar K.; Hughes, David

doi:10.1097/fjc.0000000000001004

Cited by 14 publications

(15 citation statements)

References 33 publications

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“…2 Clinical trials are also ongoing for investigational therapies for ATTR-CM, including the transthyretin stabilizer acoramidis, which may also prove to be beneficial against this progressive multisystem disease. 10,11 The growing preference for 99m Tc-PYP bone scintigraphy observed in this study is consistent with recent advances in diagnostic strategies 1,9 and expert consensus recommendations. 4−6 Increased recognition of the importance of this diagnostic tool has been accompanied by a raised awareness of 'red flag' sign/symptom patterns, such as heart failure with preserved ejection fraction, carpal tunnel syndrome, lumbar spinal stenosis, and spontaneous biceps tendon rupture, that may be early manifestations of ATTR-CM.…”

Section: Discussionsupporting

confidence: 86%

Temporal Trends in Diagnostic Testing Patterns for Wild-Type Transthyretin Amyloid Cardiomyopathy in the Medicare Fee-for-Service Population

Bourque

Schepart

Bhambri

et al. 2022

The American Journal of Cardiology

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Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is frequently misdiagnosed or diagnosed late in the disease course. ATTRwt-CM can be diagnosed invasively through tissue biopsy, but current diagnostic recommendations indicate technetium-99m pyrophosphate ( 99m Tc-PYP) bone scintigraphy is an acceptable noninvasive alternative. The relative use of these confirmatory diagnostic tests in routine clinical practice is unknown. A retrospective observational study assessed temporal trends in biopsy and 99m Tc-PYP scintigraphy and differences in patient characteristics using in/outpatient claims data from the US Medicare fee-for-service database. Claims prevalence for biopsy alone (≥1 claim for cardiac/extracardiac biopsy), imaging alone (≥1 claim for 99m Tc-PYP scintigraphy), and both tests and patient demographic, geographic, and clinical characteristics were examined. Of patients (n = 1226) receiving an ATTRwt-CM diagnostic code, 29%, 47%, and 24% were diagnosed by biopsy alone, 99m Tc-PYP scintigraphy alone, and both tests, respectively. Patients with claims for 99m Tc-PYP scintigraphy alone were older than those with claims for biopsy alone (79.9 vs 76.5; p <0.001). Fewer patients in the southern United States and more patients in the northeastern United States had claims for 99m Tc-PYP scintigraphy alone than biopsy alone (p <0.001). There was a temporal trend toward more claims for 99m Tc-PYP scintigraphy alone (odds ratio 1.21; p <0.001) and both tests (odds ratio 1.10; p = 0.008) versus biopsy alone. From 2017 to 2019, claims increased for 99m Tc-PYP scintigraphy alone. In conclusion, these data suggest a growing preference for the noninvasive imaging technique, which has high sensitivity/specificity, usability, and accessibility and may help facilitate earlier disease diagnosis. United States regional differences in the use of 99m Tc-PYP scintigraphy highlight the need for education initiatives.

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Section: Discussionsupporting

confidence: 86%

Temporal Trends in Diagnostic Testing Patterns for Wild-Type Transthyretin Amyloid Cardiomyopathy in the Medicare Fee-for-Service Population

Bourque

Schepart

Bhambri

et al. 2022

The American Journal of Cardiology

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“…Monoclonal antibodies developed against serum amyloid P (SAP) (constituent that contributes to aggregate stability) and TTR (including PRX004) have disclosed mixed results. While initial murine and human studies of anti-SAP led to clearance of amyloid tissue deposits, ongoing clinical trials have been suspended 90–92. A recent small phase I trial of PRX004 demonstrated safety and tolerability of anti-TTR treatment while reducing progression of neuropathy and cardiac disease (https://ir.prothena.com/static-files/ee65ab75-2e8b-4eae-989b-3de7c7bd9149).…”

Section: Ttr Fibril Removalmentioning

confidence: 99%

“…While initial murine and human studies of anti-SAP led to clearance of amyloid tissue deposits, ongoing clinical trials have been suspended. 90–92 A recent small phase I trial of PRX004 demonstrated safety and tolerability of anti-TTR treatment while reducing progression of neuropathy and cardiac disease ( https://ir.prothena.com/static-files/ee65ab75-2e8b-4eae-989b-3de7c7bd9149 ). Phase II studies of anti-TTR monoclonal antibodies are ongoing.…”

Section: Ttr Fibril Removalmentioning

confidence: 99%

Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis

Carroll

Dyck

Carvalho

et al. 2022

J Neurol Neurosurg Psychiatry

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Hereditary transthyretin amyloidosis (ATTRv) is a severe, adult-onset autosomal dominant inherited systemic disease predominantly affecting the peripheral and autonomic nervous system, heart, kidney and the eyes. ATTRv is caused by mutations of the transthyretin (TTR) gene, leading to extracellular deposition of amyloid fibrils in multiple organs including the peripheral nervous system. Typically, the neuropathy associated with ATTRv is characterised by a rapidly progressive and disabling sensorimotor axonal neuropathy with early small-fibre involvement. Carpal tunnel syndrome and cardiac dysfunction frequently coexist as part of the ATTRv phenotype. Although awareness of ATTRv polyneuropathy among neurologists has increased, the rate of misdiagnosis remains high, resulting in significant diagnostic delays and accrued disability. A timely and definitive diagnosis is important, given the emergence of effective therapies which have revolutionised the management of transthyretin amyloidosis. TTR protein stabilisers diflunisal and tafamidis can delay the progression of the disease, if treated early in the course. Additionally, TTR gene silencing medications, patisiran and inotersen, have resulted in up to 80% reduction in TTR production, leading to stabilisation or slight improvement of peripheral neuropathy and cardiac dysfunction, as well as improvement in quality of life and functional outcomes. The considerable therapeutic advances have raised additional challenges, including optimisation of diagnostic techniques and management approaches in ATTRv neuropathy. This review highlights the key advances in the diagnostic techniques, current and emerging management strategies, and biomarker development for disease progression in ATTRv.

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“…There are also clinical trials with the use of a specific monoclonal antibody PRX 004 affecting amyloid degradation. 61 In extreme cases, heart and liver transplants are performed.…”

Section: Therapeutic Proceduresmentioning

confidence: 99%

Updates for the diagnosis and management of cardiac amyloidosis

et al. 2022

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A substantial increase in the interest in transthyretin cardiac amyloidosis (ATTR-CA) is a result of the constantly growing number of patients, the use of clear diagnostic protocols and the availability of the first selective drug for these patients. This has also raised the awareness of the disease among physicians of all specialties. The topic is particularly relevant to cardiologists, who use non-invasive multimodal imaging in their daily practice.The differential diagnosis of the causes of myocardial hypertrophy includes arterial hypertension, hypertrophic cardiomyopathy, aortic stenosis (AS), athletic heart syndrome, Fabry disease, and cardiac amyloidosis (CA). It turns out that in patients with myocardial hypertrophy >15 mm, amyloidosis is the most common cause of left ventricular (LV) hypertrophy. In parallel, CA is one of the most common infiltrative diseases leading to a clinical picture that may mimic heart failure with preserved ejection fraction (HFpEF).The accumulation of amyloid in the extracellular space impairs the diastolic function of the myocardium, which is observed as the restrictive cardiomyopathy phenotype. In advanced cases, the LV systolic function is also impaired. Moreover, protein deposits contribute to the disturbances of calcium metabolism and cell metabolism as well as to cardiotoxicity, leading to edema and damage to cardiomyocytes.

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A Review of Novel Agents and Clinical Considerations in Patients With ATTR Cardiac Amyloidosis

Cited by 14 publications

References 33 publications

Temporal Trends in Diagnostic Testing Patterns for Wild-Type Transthyretin Amyloid Cardiomyopathy in the Medicare Fee-for-Service Population

Temporal Trends in Diagnostic Testing Patterns for Wild-Type Transthyretin Amyloid Cardiomyopathy in the Medicare Fee-for-Service Population

Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis

Updates for the diagnosis and management of cardiac amyloidosis

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