Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug;8(4):3348-3353.
doi: 10.1002/ehf2.13376. Epub 2021 May 2.

Adaptive anti-myocardial immune response following hospitalization for acute heart failure

Caroline Morbach  1   2 , Niklas Beyersdorf  3 , Thomas Kerkau  3 , Gustavo Ramos  1   2 , Floran Sahiti  1   2 , Judith Albert  1   2 , Roland Jahns  4 , Georg Ertl  1 , Christiane E Angermann  1 , Stefan Frantz  1   2 , Ulrich Hofmann  1   2 , Stefan Störk  1   2
Affiliations

Adaptive anti-myocardial immune response following hospitalization for acute heart failure

Caroline Morbach et al. ESC Heart Fail. 2021 Aug.

Abstract

Aims: It has been hypothesized that cardiac decompensation accompanying acute heart failure (AHF) episodes generates a pro-inflammatory environment boosting an adaptive immune response against myocardial antigens, thus contributing to progression of heart failure (HF) and poor prognosis. We assessed the prevalence of anti-myocardial autoantibodies (AMyA) as biomarkers reflecting adaptive immune responses in patients admitted to the hospital for AHF, followed the change in AMyA titres for 6 months after discharge, and evaluated their prognostic utility.

Methods and results: AMyA were determined in n = 47 patients, median age 71 (quartiles 60; 80) years, 23 (49%) female, and 24 (51%) with HF with preserved ejection fraction, from blood collected at baseline (time point of hospitalization) and at 6 month follow-up (visit F6). Patients were followed for 18 months (visit F18). The prevalence of AMyA increased from baseline (n = 21, 45%) to F6 (n = 36, 77%; P < 0.001). At F6, the prevalence of AMyA was higher in patients with HF with preserved ejection fraction (n = 21, 88%) compared with patients with reduced ejection fraction (n = 14, 61%; P = 0.036). During the subsequent 12 months after F6, that is up to F18, patients with newly developed AMyA at F6 had a higher risk for the combined endpoint of death or rehospitalization for HF (hazard ratio 4.79, 95% confidence interval 1.13-20.21; P = 0.033) compared with patients with persistent or without AMyA at F6.

Conclusions: Our results support the hypothesis that AHF may induce patterns of adaptive immune responses. More studies in larger populations and well-defined patient subgroups are needed to further clarify the role of the adaptive immune system in HF progression.

Keywords: Acute heart failure; Adaptive immune response; Anti-myocardial; Autoantibody; Inflammation.

PubMed Disclaimer

Conflict of interest statement

C.M. reports research cooperation with the University of Würzburg and TOMTEC Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany; advisory and speaker honoraria as well as travel grants from Amgen, TOMTEC, Orion Pharma, Alnylam, Akcea, Pfizer, Boehringer Igelheim, and EBR Systems; principal investigator in trials sponsored by Alnylam and AstraZeneca; and financial support from the interdisciplinary centre for clinical research—IZKF Würzburg (advanced clinician–scientist programme). N.B. declares reception of a travel grant from Roche Diagnostics GmbH. T.K. and G.R. have nothing to disclose. F.S. receives financial support from IZKF Würzburg (MD/PhD programme scholarship). J.A. reports financial support from the interdisciplinary centre for clinical research—IZKF Würzburg (UNION CVD clinician–scientist programme). R.J. reports several research grants from the German Federal Ministry of Education and Research BMBF FKZ 01ES0816 und FKZ 01EY1712, and the Interdisciplinary Centre of Research (IZKF), University Hospital Würzburg (Z‐9). G.E. reports significant honoraria for trial leadership from Abbott and Novartis; has been a consultant for Abbott, Boehringer Ingelheim, Novartis, ResMed, and Vifor (modest); and received significant grant support from Boehringer Ingelheim, Thermo Fisher, Siemens Healthineers, Vifor, and German Federal Ministry of Education and Research. C.E.A. reports honoraria for trial leadership from Abbott, Boehringer Ingelheim, and Novartis; has been a consultant for and/or received speaker honoraria from Abbott, Boehringer Ingelheim, Novartis, ResMed, Springer, and Vifor; and received grant support from Boehringer Ingelheim, Thermo Fisher, Siemens Healthineers, Vifor, and German Federal Ministry of Education and Research. S.F. reports advisory and speaker honoraria as well as travel grants from Amgen Europe, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol Meyers Squibb GmbH, Daiichi Sankyo, MSD, Novartis, Pfizer, Sanofi, Servier, and Vifor. U.H. reports advisory and speaker honoraria as well as travel grants from AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol Meyers Squibb GmbH, Daiichi Sankyo, MSD, Novartis, Pfizer, and Sanofi. S.S. reports research grants from the German Federal Ministry of Education and Research, European Union, and University Hospital Würzburg; participation in data safety monitoring or event adjudication in studies sponsored by Roche and Medtronic; participation in advisory boards for Novartis, Bayer, Boehringer Ingelheim, Thermo Fisher, and Boston Scientific; principal investigator in trials (co‐)sponsored by Boehringer Ingelheim, Novartis, Bayer, and Lundbeck; and speaker honoraria by Boehringer Ingelheim, Servier, Novartis, AstraZeneca, Pfizer, Bayer, and Thermo Fisher.

Figures

Figure 1
Figure 1
Study flow. N = 47 patients hospitalized for acute heart failure were analysed for the presence of anti‐myocardial antibodies (AMyA). The red drop symbol indicates the time points of venous blood sampling. Twenty patients provided pairs of venous samples at index hospitalization (i.e. baseline). Out of those, n = 12 were AMyA negative at Day 3; none of these patients exhibited altered AMyA titres during the index hospitalization. However, 15 patients who had been AMyA negative at baseline had generated new AMyA titres 6 months later (F6). All patients were followed for 18 months (F18) to collect endpoint information. The lower part of the figure illustrates the qualitative course of AMyA (positive +; negative −) from baseline to F6 in the total study population.
Figure 2
Figure 2
Status of expression of anti‐myocardial antibodies at baseline (BL) and at the 6 month follow‐up visit (F6) in patients with acute heart failure and reduced (HFrEF, n = 23) vs. preserved (HFpEF, n = 24) left ventricular ejection fraction. +/+, anti‐myocardial antibodies (AMyA) titre positive at BL and F6; −/−, AMyA titre negative at BL and F6; −/+, AMyA titre newly developed between BL and F6.
Figure 3
Figure 3
Event‐free survival (hospitalization for heart failure or death) observing the 12 month period between 6 (F6) and 18 months (F18) after discharge from the index hospitalization. Groups composed by the presence of anti‐myocardial autoantibodies (AMyA) at baseline (BL) and F6 in n = 47 patients, who had been hospitalized for acute heart failure (AHF) at baseline (index hospitalization). HR, hazard ratio.
See this image and copyright information in PMC

References

    1. Sabbah HN. Pathophysiology of acute heart failure syndrome: a knowledge gap. Heart Fail Rev 2017; 22: 621–639. - PubMed
    1. Frantz S, Falcao‐Pires I, Balligand JL, Bauersachs J, Brutsaert D, Ciccarelli M, Dawson D, de Windt LJ, Giacca M, Hamdani N, Hilfiker‐Kleiner D, Hirsch E, Leite‐Moreira A, Mayr M, Thum T, Tocchetti CG, van der Velden J, Varricchi G, Heymans S. The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC. Eur J Heart Fail 2018; 20: 445–459. - PMC - PubMed
    1. Caforio AL, Tona F, Bottaro S, Vinci A, Dequal G, Daliento L, Thiene G, Iliceto S. Clinical implications of anti‐heart autoantibodies in myocarditis and dilated cardiomyopathy. Autoimmunity 2008 2008; 41: 35–45. - PubMed
    1. Kaya Z, Leib C, Katus HA. Autoantibodies in heart failure and cardiac dysfunction. Circ Res 2012; 110: 145–158. - PubMed
    1. Keppner L, Heinrichs M, Rieckmann M, Demengeot J, Frantz S, Hofmann U, Ramos G. Antibodies aggravate the development of ischemic heart failure. Am J Physiol Heart Circ Physiol 2018. 1; 315: H1358–H1367. - PubMed

Publication types