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)

J Am Soc Echocardiogr. 2011 Apr;24(4):444-54. doi: 10.1016/j.echo.2011.01.003. Epub 2011 Feb 18.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloidosis / complications*
  • Amyloidosis / genetics*
  • Amyloidosis / therapy*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Biomarkers / analysis
  • Echocardiography, Doppler*
  • Female
  • Genes, Immunoglobulin
  • Humans
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Variable Region / genetics*
  • Male
  • Melphalan / therapeutic use
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation
  • Proportional Hazards Models
  • Prospective Studies
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Transplantation, Autologous
  • Treatment Outcome
  • Ventricular Dysfunction, Left / diagnostic imaging*
  • Ventricular Dysfunction, Left / etiology*

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region
  • Melphalan