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

• Published in: Circulation (New York, N.Y.) Vol. 139; no. 13; pp. 1581 - 1592
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States by the American College of Cardiology Foundation and the American Heart Association, Inc 26.03.2019
• Subjects: Acute Disease; Aged; Chemokine CXCL1 - blood; Female; Follow-Up Studies; Humans; Inflammation; Interleukin-6 - blood; Magnetic Resonance Imaging; Male; Middle Aged; Myocarditis - blood; Myocarditis - diagnostic imaging; Myocarditis - physiopathology; Prospective Studies; Takotsubo Cardiomyopathy - blood; Takotsubo Cardiomyopathy - diagnostic imaging; Takotsubo Cardiomyopathy - physiopathology; monocytes; macrophages; takotsubo cardiomyopathy; inflammation; ultrasmall superparamagnetic iron oxide particles (USPIO); cytokines; cardiomyopathies
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.118.037975

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 CD14CD16 monocytes (90±0.5% versus 87±0.9%; P=0.01) were also increased whereas intermediate CD14CD16 (5.4±0.3% versus 6.9±0.6%; P=0.01) and nonclassic CD14CD16 (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 persistent elevations in serum interleukin-6 concentrations (P=0.009) and reductions in intermediate CD14CD16 monocytes (5.6±0.4% versus 6.9±0.6%; P=0.01) remained. 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:URLhttps://www.clinicaltrials.gov. Unique identifierNCT02897739.