Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin

Hanson, Jacquelyn; Arvanitis, Marios; Koch, Clarissa M.; Berk, John L.; Ruberg, Frederick L.; Prokaeva, Tatiana; Connors, Lawreen H.

doi:10.1161/circheartfailure.117.004000

Cited by 69 publications

(56 citation statements)

References 32 publications

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“…There was no difference in survival when stratified by AF type, paroxysmal (hazard ratio 1.04, P = 0.89) or long standing (hazard ratio 1.37, P = 0.29). We have recently reported that a TTR concentration of <180 mg/dL was associated with reduced survival in ATTRwt . Among patients with AF, we observed borderline significant survival differences with this threshold (hazard ratio 2.0, P = 0.059; Figure B ).…”

Section: Resultsmentioning

confidence: 66%

“…We have recently reported that a TTR concentration of <180 mg/dL was associated with reduced survival in ATTRwt. 17,18 Among patients with AF, we observed borderline significant survival differences with this threshold (hazard ratio 2.0, P = 0.059; Figure 2B). The primary cause of death with heart failure which was noted in 22 of 39 (56%) of desceased patients with AF, and 8 of 10 (80%) of deceased patients without AF.…”

Section: Survivalmentioning

confidence: 89%

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Features of atrial fibrillation in wild‐type transthyretin cardiac amyloidosis: a systematic review and clinical experience

et al. 2018

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AimsWild‐type transthyretin (ATTRwt) cardiac amyloidosis has emerged as an important cause of heart failure in the elderly. Atrial fibrillation (AF) commonly affects older adults with heart failure and is associated with reduced survival, but its role in ATTRwt is unclear. We sought to explore the clinical impact of AF in ATTRwt.Methods and resultsPatients with biopsy‐proven ATTRwt cardiac amyloidosis (n = 146) were retrospectively identified, and clinical, echocardiographic, and biochemical data were collected. Patients were classified as AF or non‐AF and followed for survival for a median of 41.4 ± 27.1 months. Means testing, univariable, and multivariable regression models were employed. A systematic review was performed. AF was observed in 70% (n = 102). Mean age was similar (AF, 75 ± 6 vs. non‐AF, 74 ± 5 years, P = 0.22). Anticoagulant treatment of patients with AF was as follows: 78% warfarin, 17% novel anticoagulant, and 6% no anticoagulation. Amiodarone was prescribed to 24%. There were no differences in left ventricular ejection fraction (P = 0.09) or left atrial volume (P = 0.87); however, mean diastolic dysfunction grade was higher in AF (mean 2.7 ± 0.5 vs. 2.4 ± 0.5, P = 0.01). While creatinine (P = 0.52) and B‐type natriuretic peptide (P = 0.48) were similar, patients with AF had lower serum transthyretin concentrations (221 ± 51 vs. 250 ± 52 μg/mL, P < 0.01). Survival between groups was similar (P = 0.46).ConclusionsThese data provide an evidence basis for clinical management and demonstrate that AF in ATTRwt does not negatively impact survival. Further analysis of the relationship between transthyretin concentration and AF development is warranted.

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Section: Resultsmentioning

confidence: 66%

Section: Survivalmentioning

confidence: 89%

Features of atrial fibrillation in wild‐type transthyretin cardiac amyloidosis: a systematic review and clinical experience

et al. 2018

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“…90 Survival was reduced if there was cardiac dysautonomia after LTX, or on MIBG-SPECT and no response to atropine. 44 Low TTR serum levels were an independent predictor of the outcome in these patients. 44 Low TTR serum levels were an independent predictor of the outcome in these patients.…”

Section: Predictors Of Survivalmentioning

confidence: 82%

“…TTR circulates in the blood as a soluble tetramer. Serum TTR levels were lower at the 1-year and 2-year follow-up after starting TTR-stabilizers in untreated patients with ATTRwt amyloidosis compared to treated patients 44. Reference limits for serum TTR are 20-40 mg/dL.…”

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confidence: 85%

“…44 In a 20-year retrospective study of 1379 patients having undergone LTX, survival was reduced with high body mass index, early-onset, long disease duration before LTX, and with Val30Met vs. non-Val30Met mutation. 44 In a 20-year retrospective study of 1379 patients having undergone LTX, survival was reduced with high body mass index, early-onset, long disease duration before LTX, and with Val30Met vs. non-Val30Met mutation.…”

Section: Predictors Of Survivalmentioning

confidence: 99%

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Hereditary transthyretin-related amyloidosis

et al. 2018

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Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early-and late-onset, rare, progressive disorder, predominantly manifesting as length-dependent, small fiber dominant, axonal polyneuropathy and frequently associated with cardiac disorders and other multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with the substitution Val30Met as the most frequent mutation. TTR mutations lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, and formation of amyloid fibrils, which are consecutively deposited extracellularly in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or the skin. Neuropathy may not only include large nerve fibers but also small fibers, and not only sensory and motor fibers but also autonomic fibers. Types of TTR variants, age at onset, penetrance, and clinical presentation vary between geographical areas. Suggestive of a ATTRm amyloidosis are a sensorimotor polyneuropathy, positive family history, autonomic dysfunction, cardiomyopathy, carpal tunnel syndrome, unexplained weight loss, and resistance to immunotherapy. If only sensory A-delta or C fibers are affected, small fiber neuropathy ensues. Diagnostic tests for small fiber neuropathy include determination of intraepidermal nerve fiber density, laser-evoked potentials, heat-and cold-detection thresholds, and measurement of the electrochemical skin conductance. Therapy currently relies on liver transplantation and TTR-stabilizers (tafamidis, diflunisal). K E Y W O R D Samyloid, neuropathy, small fiber, tafamidis, transplantation, transthyretin | 93 FINSTERER ET al. eyes, the gastrointestinal tract, the kidneys, and the skin. ATTRm amyloidosis is resistant to immunotherapy. Though ATTRm-related polyneuropathy or TTR-CA may occur without affection of another tissue, a variable combination of organ affection (multiorgan involvement) is the most frequent phenotype. This review aims at summarizing and discussing previous and recent findings concerning the clinical presentation, genetic background, pathogenesis, diagnosis, treatment, and outcome of ATTRm-related polyneuropathy. | ME THODSData for this review were identified by searches of MEDLINE for references of relevant articles. Search terms applied were "transthyretin," "gene," "TTR-FAP," or "mutation," combined with "neuropathy," "hereditary," "autonomic," "small fiber neuropathy," and "polyneuropathy." Results of the search were screened for potentially relevant studies by application of inclusion and exclusion criteria for the full texts of the relevant studies. Included were randomized controlled trials (RCTs), observational studies with controls, case series, and case reports. Only original articles about humans, and published between 1966 and 2018 were included. Reviews, editorials, and letters were not considered. Reference lists of retrieved studies were checked for reports of additional studies. Websites checked for additional, particularly geneti...

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Association of Low Plasma Transthyretin Concentration With Risk of Heart Failure in the General Population

et al. 2021

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IMPORTANCE Several lines of evidence support low plasma transthyretin concentration as an in vivo biomarker of transthyretin tetramer instability, a prerequisite for the development of both wild-type transthyretin cardiac amyloidosis (ATTRwt) and hereditary transthyretin cardiac amyloidosis (ATTRm). Both ATTRm and ATTRwt cardiac amyloidosis may manifest as heart failure (HF). However, whether low plasma transthyretin concentration confers increased risk of incident HF in the general population is unknown.OBJECTIVE To evaluate whether low plasma transthyretin concentration is associated with incident HF in the general population. DESIGN, SETTING, AND PARTICIPANTSThis study included data from 2 similar prospective cohort studies of the Danish general population, the Copenhagen General Population Study (CGPS; n = 9582) and the Copenhagen City Heart Study (CCHS; n = 7385). Using these data, first, whether low concentration of plasma transthyretin was associated with increased risk of incident HF was tested. Second, whether genetic variants in TTR associated with increasing tetramer instability were associated with lower transthyretin concentration and with higher risk of HF was tested.

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Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin

Cited by 69 publications

References 32 publications

Features of atrial fibrillation in wild‐type transthyretin cardiac amyloidosis: a systematic review and clinical experience

Features of atrial fibrillation in wild‐type transthyretin cardiac amyloidosis: a systematic review and clinical experience

Hereditary transthyretin-related amyloidosis

Association of Low Plasma Transthyretin Concentration With Risk of Heart Failure in the General Population

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