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
Research background

In transthyretin cardiac amyloidosis (ATTR), protein deposition leads to myocardial thickening and heart failure, which is defined as ATTR cardiomyopathy (ATTR-CM). Recently, evidence was raised that inflammation might be associated with disease progression in ATTR polyneuropathy and heart failure. But until now little is known about the inflammatory state in ATTR-CM. Therefore, we measured IL-6 levels in ATTR-CM and analyzed its predictive value for cardiac outcome.

Research motivation

In ATTR-CM stable disease over several years as well as rapidly progressive disease courses are described. This discrepancy might results from differences in immunological response to myocardial protein deposits in ATTR-CM.

Research objectives

The objective of the study was to investigate differences in IL-6 levels and evaluate its predictive value for cardiovascular outcome (death/heart transplantation, decom-pensation or a combined endpoint).

Research methods

In this monocentric prospective study, 106 ATTR-CM patients were included, and IL-6 levels were measured using Luminex technology. Follow-up period was 12 mo, and statistical analysis was performed using parametric survival regression models.

Research results

IL-6 is associated with outcome in ATTR-CM but does not improve risk stratification in addition to established risk prediction parameters. The study thereby provides evidence that IL-6 axis might be involved in the pathogenesis of ATTR-CM. To investigate this hypothesis further, additional studies are needed.

Research conclusions

The study showed that IL-6 is associated with outcome in ATTR-CM but does not add further risk stratification potential to established risk prediction models.

Research perspectives

Further studies are needed to investigate inflammatory response in ATTR-CM.