title: Heart Failure Resulting From Age-Related Cardiac Amyloid Disease Associated With Wild-Type Transthyretin: A Prospective, Observational Cohort Study.
abstract: BACKGROUND
  Heart failure caused by wild-type transthyretin amyloidosis (ATTRwt) is an underappreciated cause of morbidity and mortality in the aging population. The aims of this study were to examine features of disease and to characterize outcomes in a large ATTRwt cohort.
  
  
  RESULTS
  Over 20 years, 121 patients with ATTRwt were enrolled in a prospective, observational study. Median age at enrollment was 75.6 years (range, 62.6-87.8 years); 97% of patients were white. The median survival, measured from biopsy diagnosis, was 46.69 months (95% confidence interval, 41.95-56.77); 78% of deaths were attributable to cardiac causes. By Kaplan-Meier analysis, 5-year survival was 35.7% (95% confidence interval, 25-46). Impaired functional capacity (mean Vo2max, 13.5 mL·kg(-1)·min(-1)) and atrial fibrillation (67%) were common clinical features. Multivariate predictors of reduced survival were elevated serum brain natriuretic peptide (482 ± 337 pg/mL) and uric acid (8.2 ± 2.6 mg/dL), decreased left ventricular ejection fraction (50% median; range, 10%-70%), and increased relative wall thickness (0.75 ± 0.19).
  
  
  CONCLUSIONS
  In this series of patients with biopsy-proven ATTRwt, poor functional capacity and atrial arrhythmias were common clinical features. Elevated brain natriuretic peptide and uric acid, decreased left ventricular ejection fraction, and increased relative wall thickness were associated with limited survival of only 35.7% at 5 years for the group as a whole. These data establish the natural history of ATTRwt, provide statistical basis for the design of future interventional clinical trials, and highlight the need for more sensitive diagnostic tests and disease-specific treatments for this disease.
authors.affiliation: From Amyloidosis Center (L.H.C., F. Sam, M.S., F. Salinaro, F.L.R., J.L.B., D.C.S.), Department of Pathology and Laboratory Medicine (L.H.C), and Department of Medicine (F. Sam, M.S., F.L.R., J.L.B., D.C.S.), Boston University School of Medicine, MA; Department of Medicine, University of Pavia, Italy (F. Salinaro); and Department of Biostatistics, Boston University School of Public Health, MA (F. Sun). lconnors@bu.edu.
authors.forename: Lawreen H
authors.initials: LH
authors.lastname: Connors
authors.affiliation: From Amyloidosis Center (L.H.C., F. Sam, M.S., F. Salinaro, F.L.R., J.L.B., D.C.S.), Department of Pathology and Laboratory Medicine (L.H.C), and Department of Medicine (F. Sam, M.S., F.L.R., J.L.B., D.C.S.), Boston University School of Medicine, MA; Department of Medicine, University of Pavia, Italy (F. Salinaro); and Department of Biostatistics, Boston University School of Public Health, MA (F. Sun).
authors.forename: Flora
authors.initials: F
authors.lastname: Sam
authors.affiliation: From Amyloidosis Center (L.H.C., F. Sam, M.S., F. Salinaro, F.L.R., J.L.B., D.C.S.), Department of Pathology and Laboratory Medicine (L.H.C), and Department of Medicine (F. Sam, M.S., F.L.R., J.L.B., D.C.S.), Boston University School of Medicine, MA; Department of Medicine, University of Pavia, Italy (F. Salinaro); and Department of Biostatistics, Boston University School of Public Health, MA (F. Sun).
authors.forename: Martha
authors.initials: M
authors.lastname: Skinner
authors.affiliation: From Amyloidosis Center (L.H.C., F. Sam, M.S., F. Salinaro, F.L.R., J.L.B., D.C.S.), Department of Pathology and Laboratory Medicine (L.H.C), and Department of Medicine (F. Sam, M.S., F.L.R., J.L.B., D.C.S.), Boston University School of Medicine, MA; Department of Medicine, University of Pavia, Italy (F. Salinaro); and Department of Biostatistics, Boston University School of Public Health, MA (F. Sun).
authors.forename: Francesco
authors.initials: F
authors.lastname: Salinaro
authors.affiliation: From Amyloidosis Center (L.H.C., F. Sam, M.S., F. Salinaro, F.L.R., J.L.B., D.C.S.), Department of Pathology and Laboratory Medicine (L.H.C), and Department of Medicine (F. Sam, M.S., F.L.R., J.L.B., D.C.S.), Boston University School of Medicine, MA; Department of Medicine, University of Pavia, Italy (F. Salinaro); and Department of Biostatistics, Boston University School of Public Health, MA (F. Sun).
authors.forename: Fangui
authors.initials: F
authors.lastname: Sun
authors.affiliation: From Amyloidosis Center (L.H.C., F. Sam, M.S., F. Salinaro, F.L.R., J.L.B., D.C.S.), Department of Pathology and Laboratory Medicine (L.H.C), and Department of Medicine (F. Sam, M.S., F.L.R., J.L.B., D.C.S.), Boston University School of Medicine, MA; Department of Medicine, University of Pavia, Italy (F. Salinaro); and Department of Biostatistics, Boston University School of Public Health, MA (F. Sun).
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ruberg
authors.affiliation: From Amyloidosis Center (L.H.C., F. Sam, M.S., F. Salinaro, F.L.R., J.L.B., D.C.S.), Department of Pathology and Laboratory Medicine (L.H.C), and Department of Medicine (F. Sam, M.S., F.L.R., J.L.B., D.C.S.), Boston University School of Medicine, MA; Department of Medicine, University of Pavia, Italy (F. Salinaro); and Department of Biostatistics, Boston University School of Public Health, MA (F. Sun).
authors.forename: John L
authors.initials: JL
authors.lastname: Berk
authors.affiliation: From Amyloidosis Center (L.H.C., F. Sam, M.S., F. Salinaro, F.L.R., J.L.B., D.C.S.), Department of Pathology and Laboratory Medicine (L.H.C), and Department of Medicine (F. Sam, M.S., F.L.R., J.L.B., D.C.S.), Boston University School of Medicine, MA; Department of Medicine, University of Pavia, Italy (F. Salinaro); and Department of Biostatistics, Boston University School of Public Health, MA (F. Sun).
authors.forename: David C
authors.initials: DC
authors.lastname: Seldin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D028227:Amyloid Neuropathies, Familial / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends
keywords: amyloidosis; heart failure; prognosis; survival