Acute stress-induced (Takotsubo) cardiomyopathy is typically associated with a major stressful event and has a similar presentation to that of acute myocardial infarction, but its precise pathogenesis is unclear. A new study shows that this syndrome is characterized by macrophage infiltration in the myocardium, changes in circulating monocyte subsets and increased levels of pro-inflammatory cytokines in the blood, with some of these changes persisting for ≥5 months. “This study demonstrates for the first time that Takotsubo cardiomyopathy is accompanied by myocardial and systemic inflammatory activation,” says lead investigator Dana Dawson.

Credit: V. Summersby/Springer Nature Limited

The study included 55 patients with acute Takotsubo syndrome (mean age 64 years; 90% women) and 51 matched control individuals. To examine macrophage infiltration in the myocardium, Dawson and colleagues combined cardiac MRI with intravenous infusion of ultrasmall superparamagnetic particles of iron oxide (USPIO), which are phagocytosed mainly by activated macrophages. Systemic inflammation was measured by assessing monocyte subpopulations and cytokine levels in blood.

Takotsubo cardiomyopathy is accompanied by myocardial and systemic inflammatory activation

Myocardial uptake of USPIO was higher in patients in the acute phase of Takotsubo than in control individuals, suggesting a macrophage-driven cellular infiltration in the myocardium. Patients with acute Takotsubo also had elevated levels in the blood of the pro-inflammatory cytokines IL-6, IL-8 and CXCL1, an increase in pro-inflammatory monocytes (CD14++CD16–) and a decrease in intermediate (CD14++CD16+) and nonclassical (CD14+CD16++) monocytes. USPIO enhancement was no longer detectable after 5 months of the index event, but some of the systemic changes persisted, such as increased IL-6 levels and decreased number of intermediate monocytes. “These findings demonstrate that the acute inflammation evolves into a low-grade, chronic inflammatory state, which explains the lack of functional recovery seen in a proportion of patients with Takotsubo syndrome,” remarks Dawson. “It is, therefore, imperative that we search for therapeutic strategies to mitigate the clinical consequences of this condition and prevent recurrences,” she concludes.