title: Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers.
abstract: OBJECTIVE
  The aim of the study was to determine whether longitudinal left ventricular (LV) function provides prognostic information in a large cohort of patients with systemic light-chain (AL) amyloidosis.
  
  
  BACKGROUND
  AL amyloidosis is associated with a high incidence of cardiovascular events. Reduced myocardial longitudinal function is one of the hallmarks of myocardial involvement in this rare disease.
  
  
  METHODS
  Two hundred six consecutive patients with biopsy-proven AL amyloidosis were investigated in this prospective observational study. Echocardiographic imaging parameters, mean tissue Doppler-derived longitudinal strain (LS), and two-dimensional global longitudinal strain (2D-GLS) of the LV, cardiac serological biomarkers, and comprehensive clinical disease characteristics were assessed. The primary endpoint was all-cause mortality or heart transplantation.
  
  
  RESULTS
  After a median follow-up of 1207 days, LS and 2D-GLS were significant predictors of survival in AL amyloidosis. The cutoff values discriminating survivors from nonsurvivors were -10.65% for LS and -11.78% for 2D-GLS. In a multivariable echocardiographic Cox model, only diastolic dysfunction and 2D-GLS remained as independent predictors of survival. In comprehensive clinical models, 2D-GLS (p < 0.0001), diastolic dysfunction (p < 0.01), the pathologic free light chains (p < 0.05), cardiac troponin-T (cTnT) (p < 0.01), and the Karnofsky index (p < 0.001) remained as independent predictors. 2D-GLS delineated a superior prognostic value compared with that derived from pathologic free light chains or cTnT in patients evaluated before firstline chemotherapy (n = 113; p < 0.0001), and remained the only independent predictor besides the Karnofsky index in subjects with preserved LV ejection fraction (≥50%; n = 127; p < 0.01). LS and 2D-GLS both offered significant incremental information (p < 0.001) for the assessment of outcome compared with clinical variables (age, Karnofsky index, and New York Heart Association functional class) and serological biomarkers.
  
  
  CONCLUSIONS
  In the largest serial investigation reported so far, reduced LV longitudinal function served as an independent predictor of survival in AL amyloidosis and offered incremental information beyond standard clinical and serological parameters.
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Buss
authors.forename: Mostafa
authors.initials: M
authors.lastname: Emami
authors.forename: Derliz
authors.initials: D
authors.lastname: Mereles
authors.forename: Grigorios
authors.initials: G
authors.lastname: Korosoglou
authors.forename: Arnt V
authors.initials: AV
authors.lastname: Kristen
authors.forename: Andreas
authors.initials: A
authors.lastname: Voss
authors.forename: Dieter
authors.initials: D
authors.lastname: Schellberg
authors.forename: Christian
authors.initials: C
authors.lastname: Zugck
authors.forename: Christian
authors.initials: C
authors.lastname: Galuschky
authors.forename: Evangelos
authors.initials: E
authors.lastname: Giannitsis
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Schonland
authors.forename: Stefan E
authors.initials: SE
authors.lastname: Hardt
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D020107:Troponin T / Q000097:blood; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain