title: Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis.
abstract: BACKGROUND
  Immunoglobulin amyloid light-chain (AL)-related cardiac amyloidosis (CA) has a worse prognosis than either wild-type (ATTRwt) or mutant (ATTRm) transthyretin (TTR) CA. Detailed echocardiographic studies have been performed in AL amyloidosis but not in TTR amyloidosis and might give insight into this difference. We assessed cardiac structure and function and outcome in a large population of patients with CA and compared findings in TTR and AL-related disease.
  
  
  RESULTS
  We analyzed 172 patients with CA (AL amyloidosis, n=80; ATTRm, n=36; ATTRwt, n=56) by standard echocardiography and 2-dimensional speckle-tracking imaging-derived left ventricular (LV) longitudinal (LS), radial, and circumferential strains. Despite a preserved LV ejection fraction (55±12%), LS was severely impaired in CA. Standard measures of LV function and speckle-tracking imaging worsened as wall thickness increased, whereas apical LS was preserved regardless of the pathogenesis of CA and the degree of wall thickening. Compared with ATTRm and AL amyloidosis, ATTRwt was characterized by greater LV wall thickness and lower ejection fraction. LS was more depressed in both ATTRwt and AL amyloidosis (-11±3% and -12±4%, respectively, P=0.54) than in ATTRm (-15±4%, P<0.01 versus AL amyloidosis and ATTRwt). TTR-related causes were favorable predictors of survival, whereas LS and advanced New York Heart Association class were negative predictors.
  
  
  CONCLUSIONS
  In patients with CA, worsening LV function correlated with increasing wall thickness regardless of pathogenesis. Patients with ATTRwt had a statistically greater wall thickness but lesser mortality than those with AL amyloidosis, despite very similar degrees of LS impairment. This paradox suggests an additional mechanism for LV dysfunction in AL amyloidosis, such as previously demonstrated light-chain toxicity.
authors.affiliation: Cardiovascular Division (C.C.Q., S.D.S., I.U.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Institute of Cardiology (C.C.Q., S.L., M.F., C.G., A.M., C.R.), University of Bologna and S.Orsola-Malpighi Hospital, Bologna, Italy; Department of Cardiology (J.K., R.H.F.), Harvard Vanguard Medical Associates, Boston, MA; and Brigham and Women's Hospital Cardiac Amyloidosis Program (R.H.F), Harvard Medical School, Boston, MA.
authors.forename: Candida Cristina
authors.initials: CC
authors.lastname: Quarta
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Imran
authors.initials: I
authors.lastname: Uraizee
authors.forename: Jenna
authors.initials: J
authors.lastname: Kruger
authors.forename: Simone
authors.initials: S
authors.lastname: Longhi
authors.forename: Marinella
authors.initials: M
authors.lastname: Ferlito
authors.forename: Christian
authors.initials: C
authors.lastname: Gagliardi
authors.forename: Agnese
authors.initials: A
authors.lastname: Milandri
authors.forename: Claudio
authors.initials: C
authors.lastname: Rapezzi
authors.forename: Rodney H
authors.initials: RH
authors.lastname: Falk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D000686:Amyloidosis / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000378:metabolism / Q000401:mortality*; D003971:Diastole / Q000502:physiology; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011228:Prealbumin / Q000378:metabolism*; D015995:Prevalence; D011379:Prognosis; D013599:Systole / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D007147:Immunoglobulin Light Chains; D011228:Prealbumin
keywords: amyloid; amyloidosis, hereditary, transthyretin-related; cardiomyopathies; echocardiography; transthyretin