Scally, C., Abbas, H., Ahearn, TS., Srivanasan, J., Rudd, A., Mezincescu, AM., Spath, N., Yucel-Finn, A., Yuecel, R., Dospinescu, C., Horgan, G.W., Broadhurst, P., Henning, A., Newby, DE., Semple, S., Wilson, HM. and Dawson, D.
||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
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.
Clinical Trial Registration: URL: https://clinicaltrials.gov Unique identifier: NCT02897739