Prospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Mar 26, 2021; 13(3): 55-67
Published online Mar 26, 2021. doi: 10.4330/wjc.v13.i3.55
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
Selina J Hein, Fabian Aus dem Siepen, Department of Cardiology, Pneumology and Angiology, University Hospital Heidelberg, Heidelberg, BW 69120, Germany
Maximilian Knoll, Department of Radiation Oncology, Heidelberg Ion-Beam Therapy Center, German Cancer Research Center, University Hospital Heidelberg, Heidelberg, BW 69120, Germany
Jennifer Furkel, Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, BW 69120, Germany
Stefan Schoenland, Department of Hematology, Oncology and Rheumatology, Amyloidosis Center, Heidelberg University Hospital, Heidelberg, BW 69120, Germany
Ute Hegenbart, Department of Hematology, Amyloidosis Center, Heidelberg University Hospital, Heidelberg, BW 69120, Germany
Hugo A Katus, Mathias Konstandin, Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, BW 69120, Germany
Arnt V Kristen, Department of Cardiology, Amyloidosis Center, University of Heidelberg, Heidelberg, BW 69120, Germany
Author contributions: Hein SJ was responsible for recruitment of the trial, data acquisition, conducting interleukin-6 measurements and drafted the manuscript; Knoll M was responsible for the statistical analyses of the data; Aus dem Siepen F was involved in recruitment for the trial and substantially revised the manuscript; Furkel J, Schönland S, Hegenbart U and Katus HA substantially revised the manuscript; Kristen AV and Konstandin MH were responsible for the funding, study design and substantially revised the manuscript.
Supported by The Alnylam Pharmaceuticals® under Grant, No. PO 4510001138, and the German Research Foundation and German Center for Cardiovascular Research Funding, No. KO-3900.
Institutional review board statement: The study was reviewed and approved by the ethical review committee Heidelberg (Approval No. S-485-2016).
Informed consent statement: All study participants, or their legal guardian, provided written consent prior to study enrollment.
Conflict-of-interest statement: Hegenbart U received honoraria of Pfizer, the other authors have nothing to declare.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 checklist, and the manuscript was prepared and revised according to the CONSORT 2010 checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Selina J Hein, MD, Consultant Physician-Scientist, Postdoc, Department on Cardiology, Pneumology and Angiology, University Hospital Heidelberg, In the Neuenheimer Field 410, Heidelberg, BW 69120, Germany.
Received: December 24, 2020
Peer-review started: December 25, 2020
First decision: January 11, 2021
Revised: January 19, 2021
Accepted: February 11, 2021
Article in press: February 11, 2021
Published online: March 26, 2021

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.


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.


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.


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.


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: Transthyretin amyloidosis, Inflammation, Heart failure, Interleukin-6, Outcome, Risk stratification

Core Tip: This was a monocentric prospective trial with 106 patients suffering from transthyretin cardiomyopathy (ATTR-CM) seeking to evaluate the prognostic value of interleukin-6 in ATTR-CM. Interleukin-6 is associated with outcome in ATTR-CM but did not further ameliorate existing risk prediction models.