title: Utility of Doppler myocardial imaging, cardiac biomarkers, and clonal immunoglobulin genes to assess left ventricular performance and stratify risk following peripheral blood stem cell transplantation in patients with systemic light chain amyloidosis (Al).
abstract: BACKGROUND
  Cardiac dysfunction is a well-recognized complication of light chain amyloidosis (AL). Autologous stem cell transplant (auto-SCT) has emerged as a successful treatment modality for AL patients. In this study, we examined the effect of clonal immunoglobulin light chain genes (VL), which encodes the immunoglobulin light chain protein that ultimately forms amyloid, on cardiac function, in the context of auto-SCT and its impact on overall survival.
  
  
  METHODS
  Longitudinal Doppler myocardial imaging parameters along with cardiac biomarkers were used to assess for cardiac function pre and post auto-SCT.
  
  
  RESULTS
  VL gene analysis revealed that Vl genes, in particular VlVI, were associated with worse cardiac function parameters than Vk genes. Clonal VL genes appeared to have an impact on left ventricular (LV) function post-transplant and also influenced mortality, with specific VL gene families associated with lower survival. Another key predictor of mortality in this report was change in tricuspid regurgitant flow velocity following auto-SCT. Correlations were also observed between systolic strain rate, systolic strain and VL genes associated with amyloid formation.
  
  
  CONCLUSIONS
  Clonal VL gene usage influences global cardiac function in AL, with patients having VlVI and VlII-III-associated amyloid more severely affected than those having Vk or VlI amyloid. Pulsed wave tissue Doppler imaging along with immunoglobulin gene analysis offers novel insights into prediction of mortality and cardiac dysfunction in AL after auto-SCT.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Bellavia
authors.forename: Roshini S
authors.initials: RS
authors.lastname: Abraham
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Pellikka
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.forename: Ghormallah B
authors.initials: GB
authors.lastname: Al-Zahrani
authors.forename: Tammy D
authors.initials: TD
authors.lastname: Green
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Manske
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: Fletcher A
authors.initials: FA
authors.lastname: Miller
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Abraham
mesh_terms: D000686:Amyloidosis / Q000150:complications* / Q000235:genetics* / Q000628:therapy*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D015150:Echocardiography, Doppler; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000209:etiology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D008558:Melphalan