The objective of this study is to determine the association of clinically prescribed, on-label, TTR stabilizing therapy (e.g. tafamidis or acoramidis) with levels of circulating transthyretin amyloid aggregates (TAAs, a surrogate for amyloid disease activity) measured serially over time in patients with transthyretin cardiac amyloidosis (ATTR-CA). To accomplish this objective, the hypothesis that TTR stabilizing therapy will be associated lower circulating TAAs over time will be tested. Completion of this study will advance the understanding of the influence of ATTR-CA treatments on circulating evidence of amyloidosis and justify the role of blood testing to monitor treatment response in patients with ATTR-CA.
Men and women ages 30-80 who have symptomatic ATTR-CA as determined by a history of HF (this will be assessed by study personnel and defined as : 1) history of hospitalization within the previous 12 months for management of HF; 2) an elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or 3) a clinical diagnosis of HF from a treating clinician)
ATTR-CA previously diagnosed histologically by amyloid staining and tissue typing with immunohistochemistry or mass spectrometry or by bone scintigraphy in without abnormal M-protein
TTR gene sequencing confirming the TTR genotype has resulted or is pending
Enrollment will be stratified by n/N=30/50 starting on-label TTR-stabilizing therapy (e.g. tafamidis) within 5 days after enrollment or by n/N=20/50 of those currently taking TTR-stabilizing therapy
Other known causes of cardiomyopathy
History of light-chain cardiac amyloidosis
Cardiac transplantation
Liver transplantation
ATTR-CA patients with a diagnosis of heart failure.
Cohort
Prospective
Not listed
Serial blood levels of circulating TTR amyloid aggregates (TAAs)
The primary hypothesis is that TTR stabilizing therapy will lower circulating evidence of amyloidosis in patients with ATTR-CA from baseline to 3 months. In addition, the study team expects that there will be a time\*treatment interaction identifying that treatment initiation will have a differential effect on serial levels of circulating s over time than those currently on treatment. These observations will support the role for measuring circulating TAAs to monitor treatment response in ATTR-CA.
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University of Texas Southwestern Medical Center
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
