Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy.
cardiomyopathies
cytokines
inflammation
macrophages
monocytes
takotsubo cardiomyopathy
ultrasmall superparamagnetic iron oxide particles (USPIO)
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
26 03 2019
26 03 2019
Historique:
pubmed:
28
12
2018
medline:
31
12
2019
entrez:
28
12
2018
Statut:
ppublish
Résumé
Acute stress-induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable with that of myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy. In a multicenter study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age-, sex-, and comorbidity-matched control subjects. During the index event and at the 5-month follow-up, patients with takotsubo cardiomyopathy underwent multiparametric cardiac magnetic resonance imaging, including ultrasmall superparamagnetic particles of iron oxide (USPIO) enhancement for detection of inflammatory macrophages in the myocardium. Blood monocyte subpopulations and serum cytokines were assessed as measures of systemic inflammation. Matched control subjects underwent investigation at a single time point. Subjects were predominantly middle-aged (64±14 years) women (90%). Compared with control subjects, patients with takotsubo cardiomyopathy had greater USPIO enhancement (expressed as the difference between pre-USPIO and post-USPIO T2*) in both ballooning (14.3±0.6 milliseconds versus 10.5±0.9 milliseconds; P<0.001) and nonballooning (12.9±0.6 milliseconds versus 10.5±0.9 milliseconds; P=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 pg/mL versus 6.5±5.8 pg/mL; P<0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 pg/mL versus 1272±177 pg/mL; P=0.01) concentrations and classic CD14 We demonstrate for the first time that takotsubo cardiomyopathy is characterized by a myocardial macrophage inflammatory infiltrate, changes in the distribution of monocyte subsets, and an increase in systemic proinflammatory cytokines. Many of these changes persisted for at least 5 months, suggesting a low-grade chronic inflammatory state. URL: https://www.clinicaltrials.gov . Unique identifier: NCT02897739.
Sections du résumé
BACKGROUND
Acute stress-induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable with that of myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy.
METHODS
In a multicenter study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age-, sex-, and comorbidity-matched control subjects. During the index event and at the 5-month follow-up, patients with takotsubo cardiomyopathy underwent multiparametric cardiac magnetic resonance imaging, including ultrasmall superparamagnetic particles of iron oxide (USPIO) enhancement for detection of inflammatory macrophages in the myocardium. Blood monocyte subpopulations and serum cytokines were assessed as measures of systemic inflammation. Matched control subjects underwent investigation at a single time point.
RESULTS
Subjects were predominantly middle-aged (64±14 years) women (90%). Compared with control subjects, patients with takotsubo cardiomyopathy had greater USPIO enhancement (expressed as the difference between pre-USPIO and post-USPIO T2*) in both ballooning (14.3±0.6 milliseconds versus 10.5±0.9 milliseconds; P<0.001) and nonballooning (12.9±0.6 milliseconds versus 10.5±0.9 milliseconds; P=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 pg/mL versus 6.5±5.8 pg/mL; P<0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 pg/mL versus 1272±177 pg/mL; P=0.01) concentrations and classic CD14
CONCLUSIONS
We demonstrate for the first time that takotsubo cardiomyopathy is characterized by a myocardial macrophage inflammatory infiltrate, changes in the distribution of monocyte subsets, and an increase in systemic proinflammatory cytokines. Many of these changes persisted for at least 5 months, suggesting a low-grade chronic inflammatory state.
CLINICAL TRIAL REGISTRATION
URL: https://www.clinicaltrials.gov . Unique identifier: NCT02897739.
Identifiants
pubmed: 30586731
doi: 10.1161/CIRCULATIONAHA.118.037975
pmc: PMC6438459
mid: EMS80777
doi:
Substances chimiques
CXCL1 protein, human
0
Chemokine CXCL1
0
IL6 protein, human
0
Interleukin-6
0
Banques de données
ClinicalTrials.gov
['NCT02897739']
Types de publication
Clinical Trial
Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1581-1592Subventions
Organisme : British Heart Foundation
ID : FS/17/19/32641
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/15/108/31928
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT103782AIA
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/09/002
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/13/3/30183
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/09/002/26360
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Références
Circulation. 1998 May 5;97(17):1716-23
pubmed: 9591766
JAMA. 2017 Nov 21;318(19):1913-1924
pubmed: 29127948
Heart. 2012 Sep;98(17):1278-84
pubmed: 22791656
Expert Rev Cardiovasc Ther. 2012 Mar;10(3):271-3
pubmed: 22390796
J Am Soc Echocardiogr. 2017 Aug;30(8):745-755
pubmed: 28599831
JACC Basic Transl Sci. 2018 Dec 31;3(6):766-778
pubmed: 30623136
J Exp Med. 2017 Jul 3;214(7):1913-1923
pubmed: 28606987
Int J Cardiol. 2016 Apr 15;209:196-205
pubmed: 26896623
Immunobiology. 2015 Jul;220(7):924-33
pubmed: 25700973
Heart. 2018 Feb;104(4):300-305
pubmed: 28986407
Am J Cardiol. 2016 Mar 1;117(5):775-80
pubmed: 26782339
Circulation. 2001 Jan 23;103(3):415-22
pubmed: 11157694
Circulation. 2018 Mar 6;137(10):1039-1048
pubmed: 29128863
Lancet. 2015 Dec 19;386(10012):2481-8
pubmed: 26454362
Int J Cardiol. 2015 Apr 15;185:282-9
pubmed: 25818540
Herz. 2010 Jun;35(4):240-3
pubmed: 20582391
Eur J Heart Fail. 2016 Jan;18(1):8-27
pubmed: 26548803
J Clin Invest. 1995 Mar;95(3):1092-100
pubmed: 7883957
Am J Cardiol. 2015 Apr 15;115(8):1085-9
pubmed: 25724780
Circ Res. 2013 Jun 7;112(12):1624-33
pubmed: 23743228
J Cardiovasc Magn Reson. 2015 Jul 08;17:54
pubmed: 26152269
N Engl J Med. 2015 Sep 3;373(10):929-38
pubmed: 26332547
JACC Cardiovasc Imaging. 2015 Aug;8(8):985-7
pubmed: 25499134
Circulation. 2010 Jun 8;121(22):2437-45
pubmed: 20530020
J Am Coll Cardiol. 2016 Apr 26;67(16):1931-6
pubmed: 27102508
Heart. 2017 Oct;103(19):1528-1535
pubmed: 28642288
Eur J Radiol. 2010 Feb;73(2):255-9
pubmed: 19056193
Eur Heart J. 2007 Oct;28(20):2456-64
pubmed: 17395683
Circ Cardiovasc Imaging. 2012 Sep 1;5(5):559-65
pubmed: 22875883
Circulation. 2002 Jan 29;105(4):539-42
pubmed: 11815441
Cytokine. 2008 Aug;43(2):181-6
pubmed: 18579408
JAMA. 2011 Jul 20;306(3):277-86
pubmed: 21771988
Circulation. 2017 Jun 13;135(24):2426-2441
pubmed: 28606950
J Cardiovasc Magn Reson. 2011 Jan 11;13:4
pubmed: 21223554
Cytometry A. 2012 Oct;81(10):823-34
pubmed: 22837127
Am Heart J. 2012 Aug;164(2):215-21
pubmed: 22877807
Eur Heart J. 2013 Feb;34(6):462-75
pubmed: 23103659