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Improvement of risk assessment in systemic light-chain amyloidosis using human placental growth factor

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Abstract

Background

Vascular amyloid deposition is common in light-chain amyloidosis resulting in endothelial dysfunction. Human placental growth factor (PlGF), a member of the vascular endothelial growth factor family was found to be altered in diverse pathological conditions, e.g. endothelial dysfunction. This study evaluated the clinical role of PlGF in light-chain amyloidosis.

Methods

PlGF (cobas-PlGF, Roche Diagnostics, Mannheim, Germany) was analyzed in 125 consecutive patients with AL and correlated with diverse clinical parameters including mortality.

Results

Kidney (n = 76) and heart (n = 57) were predominantly affected by amyloid deposition. Median PlGF was 26.3 (21.1–42.1) ng/L, NT-proBNP 3649 (1124–8581) pg/mL, and hs-TnT 42 (21–107) ng/L. PlGF increased with number of organs involved and with deterioration of renal function. A significant correlation of PlGF with hs-TnT (ρ = 0.306; p = 0.0007) and NT-proBNP (ρ = 0.315; p = 0.0006) was observed, but no correlation was observed with clinical, echocardiography, and electrocardiography parameters of cardiac involvement. In this cohort 1-year all-cause mortality was 19.2 %. The best cutoff discriminating survivors and non-survivors was 28.44 ng/L (sensitivity 66.7 %; specificity 78.1 %). A three-step risk model including hs-TnT and NT-proBNP revealed a better discrimination if patients at intermediary risk were additionally stratified by PlGF. Net reclassification index was 37.2 % (p = 0.002). Multivariate analysis revealed PlGF, difference of involved and uninvolved light chain, number of organs involved and risk class according to troponin T and NT-proBNP as independent predictors of mortality.

Conclusion

Plasma PlGF values in AL are invariably associated with the number of involved organs, but not with clinical, echocardiography, and electrocardiography parameters of cardiac involvement. PlGF provide useful information for risk stratification of patients at intermediary risk according to hs-TnT and NT-proBNP.

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Acknowledgments

The brilliant technical assistance of Heidi Deigentasch, Melanie Magin, and Christa Dewald is gratefully acknowledged. Many thanks are to Winfried Koch for his excellent statistical support.

Conflict of interest

EG has received financial support for clinical trials from Roche Diagnostics, Germany. He is consultant to Roche Diagnostics and receives honoraria for lectures from Roche Diagnostics. HAK has developed the cTnT assay and holds a patent jointly with Roche Diagnostics. He has received grants and research support from several companies, and has received honoraria for lectures from Roche Diagnostics. The remaining authors do not have any disclosures.

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Authors and Affiliations

  1. Department of Cardiology, Angiology, and Respiratory Medicine, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Arnt V. Kristen, Johannes Rinn, David Lindenmaier, Corina Merkle, Stefan Hardt, Evangelos Giannitsis & Hugo A. Katus

  2. Department of Haematology and Oncology, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Ute Hegenbart

  3. Institute of Pathology, Kiel University, Arnold-Heller-Straße 3/14, 24105, Kiel, Germany

    Christoph Röcken

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  1. Arnt V. Kristen
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Correspondence to Arnt V. Kristen.

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Kristen, A.V., Rinn, J., Hegenbart, U. et al. Improvement of risk assessment in systemic light-chain amyloidosis using human placental growth factor. Clin Res Cardiol 104, 250–257 (2015). https://doi.org/10.1007/s00392-014-0779-y

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  • DOI: https://doi.org/10.1007/s00392-014-0779-y

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