Elevated interleukin-6 levels are associated with impaired outcome in cardiac transthyretin amyloidosis

Selina J Hein; Maximilian Knoll; Fabian Aus dem Siepen; Jennifer Furkel; Stefan Schoenland; Ute Hegenbart; Hugo A Katus; Arnt V Kristen; Mathias Konstandin

doi:10.4330/wjc.v13.i3.55

Elevated interleukin-6 levels are associated with impaired outcome in cardiac transthyretin amyloidosis

World J Cardiol. 2021 Mar 26;13(3):55-67. doi: 10.4330/wjc.v13.i3.55.

Authors

Selina J Hein¹, Maximilian Knoll², Fabian Aus dem Siepen³, Jennifer Furkel⁴, Stefan Schoenland⁵, Ute Hegenbart⁶, Hugo A Katus⁷, Arnt V Kristen⁸, Mathias Konstandin⁷

Affiliations

¹ Department of Cardiology, Pneumology and Angiology, University Hospital Heidelberg, Heidelberg, BW 69120, Germany. selina.hein@med.uni-heidelberg.de.
² Department of Radiation Oncology, Heidelberg Ion-Beam Therapy Center, German Cancer Research Center, University Hospital Heidelberg, Heidelberg, BW 69120, Germany.
³ Department of Cardiology, Pneumology and Angiology, University Hospital Heidelberg, Heidelberg, BW 69120, Germany.
⁴ Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, BW 69120, Germany.
⁵ Department of Hematology, Oncology and Rheumatology, Amyloidosis Center, Heidelberg University Hospital, Heidelberg, BW 69120, Germany.
⁶ Department of Hematology, Amyloidosis Center, Heidelberg University Hospital, Heidelberg, BW 69120, Germany.
⁷ Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, BW 69120, Germany.
⁸ Department of Cardiology, Amyloidosis Center, University of Heidelberg, Heidelberg, BW 69120, Germany.

Abstract

Background: Elevated interleukin (IL)-6-levels have been described in familial variant transthyretin amyloidosis (ATTRv) associated polyneuropathy and heart failure. However, IL-6 in cardiac ATTR amyloidosis (ATTR-CM) and its prognostic value have not been investigated yet.

Aim: We aim to study the correlation between IL-6 levels with clinical presentation (Gillmore-class) and outcome [heart transplantation or death (htx/death)], or the combined endpoint of cardiac decompensation or htx/death in ATTR-CM.

Methods: IL-6 levels of 106 ATTR-CM patients [54 wild-type ATTRwt, 52 ATTRv-CM], 15 asymptomatic carriers of ATTR mutations (aATTRv-CM) and 27 healthy donors were quantified using Luminex technology. Statistical analysis was performed using parametric survival regression models.

Results: We found that IL-6 levels from wild-type ATTR patients were significantly elevated compared to healthy controls, while aATTRv-CM carriers and ATTRv-CM patients did not show a significant difference. IL-6 levels showed significantly higher values in increasing Gillmore classes. Univariate analyses revealed association of low IL-6 levels with cardiac decompensation and htx/death [odds ratio: 0.26 (0.09-0.72), P = 0.01] and htx/death [odds ratio: 0.15 (0.04-0.58), P = 0.006]. However, in the multivariate model, no significant improvement of risk prediction was seen for IL-6, while established prognostic factors were significantly associated with outcome.

Conclusion: Raised IL-6 levels correlate with clinical presentation and are associated with worse outcome in ATTR-CM but do not improve stratification in addition to established risk factors.

Keywords: Heart failure; Inflammation; Interleukin-6; Outcome; Risk stratification; Transthyretin amyloidosis.