Author + information
- Received June 5, 2018
- Revision received August 20, 2018
- Accepted August 21, 2018
- Published online December 31, 2018.
- Heather M. Wilson, BSc, PhDa,∗ (, )
- Lesley Cheyne, BSca,
- Paul A.J. Brown, MBChB, PhDb,
- Keith Kerr, MBChBa,
- Andrew Hannah, MBChBc,
- Janaki Srinivasan, RDCSc,
- Natallia Duniak, MBChBb,
- Graham Horgan, BA, MSc, PhDa and
- Dana K. Dawson, DM, DPhila
- aSchool of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen, Scotland, United Kingdom
- bDepartment of Pathology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, Scotland, United Kingdom
- cDepartment of Cardiology NHS Grampian, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, Scotland, United Kingdom
- ↵∗Address for correspondence:
Dr. Heather M. Wilson, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, United Kingdom.
• Takotsubo cardiomyopathy is an acute heart failure syndrome often triggered by emotional or physical stress, where no treatment currently exists, and exact pathogenic mechanisms are unclear.
• Rats in which takotsubo-like cardiomyopathy was induced showed localized myocardial inflammatory changes, including progressive inflammatory infiltrates and myofiber atrophy, that persisted over the 14-day time course examined.
• Early neutrophil infiltrates were followed by clusters of myocardial macrophages, typically of an M1 proinflammatory phenotype, with no switch to M2 resolving macrophages; individual M2 macrophage levels, however, correlated with recovery in cardiac function. Human post-mortem myocardial tissue shared features of the experimental model demonstrating M1 macrophage clusters.
• The persistent clinical symptoms and long-term morbidity/mortality observed in takotsubo patients may, in part, relate to chronic nonresolving myocardial inflammation.
Takotsubo cardiomyopathy is an acute stress-induced heart failure syndrome for which the exact pathogenic mechanisms are unclear, and consequently, no specific treatment exists. In an experimental model of stress-induced takotsubo-like cardiomyopathy, the authors describe the temporal course of a chronic inflammatory response post-induction, with an initial early influx of neutrophils into myocardial tissue followed by macrophages that are typical of a proinflammatory M1 phenotype, and a nonsignificant increase in systemic inflammatory cytokines. Post-mortem myocardium from the more complex clinical takotsubo patients share features of the study’s experimental model. These findings suggest modulators of inflammation could be a potential therapeutic option.
This work was supported by grants from NHS Grampian Endowments and British Heart Foundation Project Grant no. PG/15/108/31928 The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received June 5, 2018.
- Revision received August 20, 2018.
- Accepted August 21, 2018.
- 2018 The Authors