Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy

Caroline Scally, Hassan Abbas, Trevor Ahearn, Janaki Srinivasan, Alice Mezincescu, Amelia Rudd, Nicholas Spath, Alim Yucel-Finn, Raif Yuecel, Keith Oldroyd, Ciprian Dospinescu, Graham Horgan, Paul Broadhurst, Anke Henning, David E. Newby, Scott Semple, Heather M. Wilson, Dana K. Dawson

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Acute stress induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable to myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy. Methods: In a multi-centre study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age, sex and co-morbidity matched control subjects. During the index event and at 5 months 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 controls underwent investigation at a single time point. Results: Subjects were predominantly middle aged (64±14years) women (90%). When compared to 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 versus 10.5±0.9 ms, p<0.001) and non-ballooning (12.9±0.6 versus 10.5±0.9 ms, p=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 versus 6.5±5.8 pg/mL, p< 0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 versus 1272±177 pg/mL, p=0.01) concentrations, and classical CD14++CD16- monocytes (90±0.5 versus 87±0.9%, p=0.01) were also increased whilst intermediate CD14++CD16+ (5.4±0.3 versus 6.9±0.6%, p=0.01) and non-classical CD14+CD16++ (2.7±0.3% versus 4.2±0.5%, p=0.006) monocytes were reduced in patients with takotsubo cardiomyopathy. At 5 months, USPIO enhancement was no longer detectable in the left ventricular myocardium although there remained persistent elevations in serum interleukin-6 concentrations (p=0.009) and reductions in intermediate CD14++CD16+ monocytes (5.6±0.4 versus 6.9±0.6%, p=0.01). 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 pro-inflammatory cytokines. Many of these changes persisted for at least 5 months suggesting a low-grade chronic inflammatory state.
Original languageEnglish
Pages (from-to)1581-1592
Number of pages12
JournalCirculation
Volume139
Issue number13
Early online date11 Nov 2018
DOIs
Publication statusPublished - 26 Mar 2019

Fingerprint

Takotsubo Cardiomyopathy
Inflammation
Monocytes
Interleukin-6
Myocardium
Chemokine CXCL1
Serum
Macrophages
Cytokines
Heart Failure
Myocardial Infarction
Magnetic Resonance Imaging
ferumoxtran-10
Morbidity
Phenotype

Keywords

  • cardiomyopathies
  • cytokines
  • inflammation
  • macrophages
  • monocytes
  • takotsubo cardiomyopathy
  • ultrasmall superparamagnetic iron oxide particles (USPIO)
  • IRON-OXIDE NANOPARTICLES
  • MORTALITY
  • ULTRASMALL SUPERPARAMAGNETIC PARTICLES
  • HEART
  • RECOVERY
  • TAKO-TSUBO CARDIOMYOPATHY
  • INFARCTION
  • MONOCYTE
  • CARDIAC TROPONIN-I
  • ASSOCIATION

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy. / Scally, Caroline; Abbas, Hassan; Ahearn, Trevor; Srinivasan, Janaki; Mezincescu, Alice; Rudd, Amelia; Spath, Nicholas; Yucel-Finn, Alim; Yuecel, Raif; Oldroyd, Keith; Dospinescu, Ciprian; Horgan, Graham; Broadhurst, Paul; Henning, Anke; Newby, David E.; Semple, Scott; Wilson, Heather M.; Dawson, Dana K.

In: Circulation, Vol. 139, No. 13, 26.03.2019, p. 1581-1592.

Research output: Contribution to journalArticle

Scally, C, Abbas, H, Ahearn, T, Srinivasan, J, Mezincescu, A, Rudd, A, Spath, N, Yucel-Finn, A, Yuecel, R, Oldroyd, K, Dospinescu, C, Horgan, G, Broadhurst, P, Henning, A, Newby, DE, Semple, S, Wilson, HM & Dawson, DK 2019, 'Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy', Circulation, vol. 139, no. 13, pp. 1581-1592. https://doi.org/10.1161/CIRCULATIONAHA.118.037975
Scally, Caroline ; Abbas, Hassan ; Ahearn, Trevor ; Srinivasan, Janaki ; Mezincescu, Alice ; Rudd, Amelia ; Spath, Nicholas ; Yucel-Finn, Alim ; Yuecel, Raif ; Oldroyd, Keith ; Dospinescu, Ciprian ; Horgan, Graham ; Broadhurst, Paul ; Henning, Anke ; Newby, David E. ; Semple, Scott ; Wilson, Heather M. ; Dawson, Dana K. / Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy. In: Circulation. 2019 ; Vol. 139, No. 13. pp. 1581-1592.
@article{be465d5e3417474d8170518606146da1,
title = "Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy",
abstract = "Background: Acute stress induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable to myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy. Methods: In a multi-centre study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age, sex and co-morbidity matched control subjects. During the index event and at 5 months 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 controls underwent investigation at a single time point. Results: Subjects were predominantly middle aged (64±14years) women (90{\%}). When compared to 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 versus 10.5±0.9 ms, p<0.001) and non-ballooning (12.9±0.6 versus 10.5±0.9 ms, p=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 versus 6.5±5.8 pg/mL, p< 0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 versus 1272±177 pg/mL, p=0.01) concentrations, and classical CD14++CD16- monocytes (90±0.5 versus 87±0.9{\%}, p=0.01) were also increased whilst intermediate CD14++CD16+ (5.4±0.3 versus 6.9±0.6{\%}, p=0.01) and non-classical CD14+CD16++ (2.7±0.3{\%} versus 4.2±0.5{\%}, p=0.006) monocytes were reduced in patients with takotsubo cardiomyopathy. At 5 months, USPIO enhancement was no longer detectable in the left ventricular myocardium although there remained persistent elevations in serum interleukin-6 concentrations (p=0.009) and reductions in intermediate CD14++CD16+ monocytes (5.6±0.4 versus 6.9±0.6{\%}, p=0.01). 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 pro-inflammatory cytokines. Many of these changes persisted for at least 5 months suggesting a low-grade chronic inflammatory state.",
keywords = "cardiomyopathies, cytokines, inflammation, macrophages, monocytes, takotsubo cardiomyopathy, ultrasmall superparamagnetic iron oxide particles (USPIO), IRON-OXIDE NANOPARTICLES, MORTALITY, ULTRASMALL SUPERPARAMAGNETIC PARTICLES, HEART, RECOVERY, TAKO-TSUBO CARDIOMYOPATHY, INFARCTION, MONOCYTE, CARDIAC TROPONIN-I, ASSOCIATION",
author = "Caroline Scally and Hassan Abbas and Trevor Ahearn and Janaki Srinivasan and Alice Mezincescu and Amelia Rudd and Nicholas Spath and Alim Yucel-Finn and Raif Yuecel and Keith Oldroyd and Ciprian Dospinescu and Graham Horgan and Paul Broadhurst and Anke Henning and Newby, {David E.} and Scott Semple and Wilson, {Heather M.} and Dawson, {Dana K.}",
note = "The TERRIFIC study was funded by the British Heart Foundation Project Grant no. PG/15/108/31928 and a National Health Service Grampian Endowments Award (ES776/EA8177), both to Dr Dawson. Dr. Newby is supported by the British Heart Foundation (CH/09/002, RE/13/3/30183) and a Wellcome Trust Senior Investigator Award (WT103782AIA). DKD has a research agreement with Philips Healthcare. Ferumoxytol was initially purchased until November 2015 and after being withdrawn from the European market it was generously supplied through a Material Transfer Agreement from AMAG Pharmaceuticals, Waltham, MA, USA. The online-only Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/circulationaha.118.037975.",
year = "2019",
month = "3",
day = "26",
doi = "10.1161/CIRCULATIONAHA.118.037975",
language = "English",
volume = "139",
pages = "1581--1592",
journal = "Circulation",
issn = "0009-7322",
publisher = "American Heart Association",
number = "13",

}

TY - JOUR

T1 - Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy

AU - Scally, Caroline

AU - Abbas, Hassan

AU - Ahearn, Trevor

AU - Srinivasan, Janaki

AU - Mezincescu, Alice

AU - Rudd, Amelia

AU - Spath, Nicholas

AU - Yucel-Finn, Alim

AU - Yuecel, Raif

AU - Oldroyd, Keith

AU - Dospinescu, Ciprian

AU - Horgan, Graham

AU - Broadhurst, Paul

AU - Henning, Anke

AU - Newby, David E.

AU - Semple, Scott

AU - Wilson, Heather M.

AU - Dawson, Dana K.

N1 - The TERRIFIC study was funded by the British Heart Foundation Project Grant no. PG/15/108/31928 and a National Health Service Grampian Endowments Award (ES776/EA8177), both to Dr Dawson. Dr. Newby is supported by the British Heart Foundation (CH/09/002, RE/13/3/30183) and a Wellcome Trust Senior Investigator Award (WT103782AIA). DKD has a research agreement with Philips Healthcare. Ferumoxytol was initially purchased until November 2015 and after being withdrawn from the European market it was generously supplied through a Material Transfer Agreement from AMAG Pharmaceuticals, Waltham, MA, USA. The online-only Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/circulationaha.118.037975.

PY - 2019/3/26

Y1 - 2019/3/26

N2 - Background: Acute stress induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable to myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy. Methods: In a multi-centre study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age, sex and co-morbidity matched control subjects. During the index event and at 5 months 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 controls underwent investigation at a single time point. Results: Subjects were predominantly middle aged (64±14years) women (90%). When compared to 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 versus 10.5±0.9 ms, p<0.001) and non-ballooning (12.9±0.6 versus 10.5±0.9 ms, p=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 versus 6.5±5.8 pg/mL, p< 0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 versus 1272±177 pg/mL, p=0.01) concentrations, and classical CD14++CD16- monocytes (90±0.5 versus 87±0.9%, p=0.01) were also increased whilst intermediate CD14++CD16+ (5.4±0.3 versus 6.9±0.6%, p=0.01) and non-classical CD14+CD16++ (2.7±0.3% versus 4.2±0.5%, p=0.006) monocytes were reduced in patients with takotsubo cardiomyopathy. At 5 months, USPIO enhancement was no longer detectable in the left ventricular myocardium although there remained persistent elevations in serum interleukin-6 concentrations (p=0.009) and reductions in intermediate CD14++CD16+ monocytes (5.6±0.4 versus 6.9±0.6%, p=0.01). 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 pro-inflammatory cytokines. Many of these changes persisted for at least 5 months suggesting a low-grade chronic inflammatory state.

AB - Background: Acute stress induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable to myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy. Methods: In a multi-centre study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age, sex and co-morbidity matched control subjects. During the index event and at 5 months 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 controls underwent investigation at a single time point. Results: Subjects were predominantly middle aged (64±14years) women (90%). When compared to 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 versus 10.5±0.9 ms, p<0.001) and non-ballooning (12.9±0.6 versus 10.5±0.9 ms, p=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 versus 6.5±5.8 pg/mL, p< 0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 versus 1272±177 pg/mL, p=0.01) concentrations, and classical CD14++CD16- monocytes (90±0.5 versus 87±0.9%, p=0.01) were also increased whilst intermediate CD14++CD16+ (5.4±0.3 versus 6.9±0.6%, p=0.01) and non-classical CD14+CD16++ (2.7±0.3% versus 4.2±0.5%, p=0.006) monocytes were reduced in patients with takotsubo cardiomyopathy. At 5 months, USPIO enhancement was no longer detectable in the left ventricular myocardium although there remained persistent elevations in serum interleukin-6 concentrations (p=0.009) and reductions in intermediate CD14++CD16+ monocytes (5.6±0.4 versus 6.9±0.6%, p=0.01). 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 pro-inflammatory cytokines. Many of these changes persisted for at least 5 months suggesting a low-grade chronic inflammatory state.

KW - cardiomyopathies

KW - cytokines

KW - inflammation

KW - macrophages

KW - monocytes

KW - takotsubo cardiomyopathy

KW - ultrasmall superparamagnetic iron oxide particles (USPIO)

KW - IRON-OXIDE NANOPARTICLES

KW - MORTALITY

KW - ULTRASMALL SUPERPARAMAGNETIC PARTICLES

KW - HEART

KW - RECOVERY

KW - TAKO-TSUBO CARDIOMYOPATHY

KW - INFARCTION

KW - MONOCYTE

KW - CARDIAC TROPONIN-I

KW - ASSOCIATION

UR - http://www.scopus.com/inward/record.url?scp=85057329418&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/myocardial-systemic-inflammation-acute-stressinduced-takotsubo-cardiomyopathy

UR - http://europepmc.org/abstract/med/30586731

U2 - 10.1161/CIRCULATIONAHA.118.037975

DO - 10.1161/CIRCULATIONAHA.118.037975

M3 - Article

VL - 139

SP - 1581

EP - 1592

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 13

ER -