Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs

Castaño, Adam; Drachman, Brian; Judge, Daniel P.; Maurer, Mathew S.

doi:10.1007/s10741-014-9462-7

Cited by 204 publications

(171 citation statements)

References 100 publications

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“…In the absence of treatment, the median survival is only 8 months [71] compared with 24-66 months in TTR cardiac amyloidosis [72]. This might be a result of a direct toxic effect of the LCs in AL amyloidosis [73], or the more widespread organ involvement associated with AL amyloidosis compared with other amyloidosis types.…”

Section: Prognosismentioning

confidence: 99%

Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy

et al. 2016

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Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, where the culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells. AL amyloidosis is an infrequent disease, and since presentation is variable and often nonspecific, diagnosis is often delayed. This results in cumulative organ damage and has a negative prognostic effect. AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained. Since as many as 31 known amyloidogenic proteins have been identified to date, determination of the amyloid type is required. While several typing methods are available, mass spectrometry has become the gold standard for amyloid typing. Upon confirming the diagnosis of amyloidosis, a pursuit for organ involvement is essential, with a focus on heart involvement, even in the absence of suggestive symptoms for involvement, as this has both prognostic and treatment implications. Details regarding initial treatment options, including stem cell transplantation, are provided in this review. AL amyloidosis management requires a multidisciplinary approach with careful patient monitoring, as organ impairment has a major effect on morbidity and treatment tolerability until a response to treatment is achieved and recovery emerges.

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Section: Prognosismentioning

confidence: 99%

Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy

et al. 2016

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“…Treatment and prognosis of cardiac amyloidosis vary greatly depending on the amyloid fibril precursor. Therefore, early detection and classification are important for the selection of appropriate therapeutic strategies such as chemotherapy, liver transplantation, and novel transthyretin‐modifying therapeutics 1, 2, 3, 4…”

Section: Introductionmentioning

confidence: 99%

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis

et al. 2017

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AimThe aim of this study was to evaluate the diagnostic utility of high‐sensitivity cardiac troponin T (hs‐cTnT) levels in discriminating cardiac amyloidosis from patients with cardiac hypertrophy caused by aetiologies other than cardiac amyloidosis.Methods and resultsSerum hs‐cTnT levels were measured in 96 patients with cardiac amyloidosis (light chain: 23, wild‐type transthyretin amyloidosis: 40, and mutated transthyretin amyloidosis: 33), and 91 patients with other causes of cardiac hypertrophy who were confirmed to have no cardiac amyloidosis by endomyocardial biopsy (control group). The diagnostic utility and cut‐off value of hs‐cTnT were evaluated by receiver operating characteristic analysis. The median hs‐cTnT levels were higher in cardiac amyloidosis than the control group [0.048 (0.029–0.073) vs. 0.016 (0.010–0.031) ng/mL; P < 0.001]. High levels of hs‐cTnT were suggestive of cardiac amyloidosis (cut‐off value: 0.0312 ng/mL, sensitivity: 0.74, specificity: 0.76, area under the curve: 0.788; 95% confidence interval: 0.723–0.854, P < 0.001), compared with brain natriuretic peptide and E/e′ ratio. The hs‐cTnT levels were also useful in differentiating each type of amyloidosis from the control group. Multivariate analysis identified log hs‐cTnT as an independent diagnostic factor for cardiac amyloidosis (odds ratio: 2.22; 95% confidence interval: 1.30–3.80; P = 0.004).ConclusionsHigh serum levels of hs‐cTnT are highly suggestive of cardiac amyloidosis, allowing its differentiation from cardiac hypertrophy of other aetiologies. Further refined diagnostic approaches that include imaging modalities and histopathological examination are needed for these patients to avoid underdiagnosis of cardiac amyloidosis.

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“…Over the past several years, however, a number of potentially disease-modifying treatment strategies have emerged and are now in human clinical trials for the treatment of ATTR cardiac amyloidosis. 3 …”

Section: Introductionmentioning

confidence: 99%

Serial scanning with technetium pyrophosphate (99mTc-PYP) in advanced ATTR cardiac amyloidosis

Castaño

DeLuca

Weinberg

et al. 2016

Journal of Nuclear Cardiology

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Background Development of noninvasive imaging modalities to quantify amyloid burden over time is an unmet clinical need. Technetium pyrophosphate (99mTc-PYP) scintigraphy is a simple and widely available radiotracer useful to differentiate transthyretin from light-chain amyloidosis in patients with advanced cardiac amyloidosis. We examined the utility of serial 99mTc-PYP scanning to quantify amyloid burden over time in TTR cardiac amyloidosis (ATTR-CA). Methods and Results Twenty subjects with ATTR-CA (10 wild type, 10 mutant) underwent serial 99mTc-PYP planar cardiac imaging. Cardiac retention was assessed both semiquantitatively (visual score 0, no uptake to 3, uptake greater than bone) and quantitatively (region of interest drawn over the heart, copied, and mirrored over the contralateral chest) to calculate a heart-to-contralateral (H/CL) ratio. Index scan mean visual score and H/CL were 3.0 ± 0.2 and 1.79 ± 0.2, respectively, and after an average 1.5 ± 0.5 years follow-up, did not differ, 3.0 ± 0.2, P = .33 and 1.76 ± 0.2, P = .44. H/CL change was minimal, 0.03 ± 0.17, did not correlate with time between scans, r = 0.19, P = .43, and was observed despite obvious clinical progression (increase in troponin ≥ 0.1 ng/mL, BNP ≥ 400 pg/mL, NYHA class, and/or death). Conclusions Serial 99mTc-PYP scanning in subjects with advanced ATTR-CA does not show significant changes over an average 1.5 years of follow-up despite obvious clinical progression.

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Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs

Cited by 204 publications

References 100 publications

Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy

Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis

Serial scanning with technetium pyrophosphate (99mTc-PYP) in advanced ATTR cardiac amyloidosis

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