title: Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: the Transthyretin Amyloidosis Cardiac Study (TRACS).
abstract: BACKGROUND
  TRACS sought to describe the clinical outcomes and disease progression of transthyretin (TTR) cardiac amyloidosis (ATTR) in an observational study. Clinical course is largely determined by disease type with ATTR categorized as wild-type (ATTRwt) or genetic-variant protein (ATTRm). Prospective data are lacking in the most common TTR mutation, V122I, present in approximately 3.5% of African Americans.
  
  
  METHODS
  Patients with ATTRwt (n = 18) and V122I ATTRm (n = 11) were longitudinally assessed every 6 months for up to 2 years by functional class assessments, biochemical markers, and echocardiography.
  
  
  RESULTS
  At baseline, no differences in clinical characteristics, biomarkers, or echocardiographic parameters were noted between patients with ATTRwt and patients with ATTRm. After 15.5 ± 8 months, there were 11 deaths and 1 cardiac transplant, with higher mortality (73% vs 22%, P = .03) and cardiovascular hospitalization (64% vs 28%, P = .02) among patients with ATTRm. The median survival from diagnosis was 25.6 months for ATTRm vs 43.0 months for ATTRwt (P = .04). Univariate predictors of mortality included disease duration, heart rate ≥ 70 beats/min, baseline stroke volume, left ventricular ejection fraction <50%, and ATTRm status. For each 6-month increment, the mean 6-minute walk distance declined by 25.8 m, N-terminal pro b-type natriuretic peptide increased by 1,816 pg/mL, and left ventricular ejection fraction fell by 3.2%, for the entire cohort.
  
  
  CONCLUSIONS
  In this prospective study, disease progression, morbidity, and mortality were observed in ATTR cardiomyopathy, particularly due to V122I, over a short duration. Given the prevalence of this mutation, further study of V122I in at-risk African American patients is warranted.
authors.affiliation: Amyloid Treatment and Research Program, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. frruberg@bu.edu
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ruberg
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Maurer
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.forename: Steven
authors.initials: S
authors.lastname: Zeldenrust
authors.forename: Martha
authors.initials: M
authors.lastname: Skinner
authors.forename: Antony Y
authors.initials: AY
authors.lastname: Kim
authors.forename: Rodney H
authors.initials: RH
authors.lastname: Falk
authors.forename: Kin N
authors.initials: KN
authors.lastname: Cheung
authors.forename: Ayan R
authors.initials: AR
authors.lastname: Patel
authors.forename: Arian
authors.initials: A
authors.lastname: Pano
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Packman
authors.forename: Donna Roy
authors.initials: DR
authors.lastname: Grogan
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid; D000686:Amyloidosis / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D009202:Cardiomyopathies / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009017:Morbidity; D009026:Mortality; D009154:Mutation; D011228:Prealbumin / Q000235:genetics*; D015995:Prevalence; D011446:Prospective Studies; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D000682:Amyloid; D011228:Prealbumin