Background: ST-elevation myocardial infarction (STEMI) and Takotsubo syndrome (TS) are two distinct cardiac conditions that both result in sudden loss of cardiac dysfunction and that are difficult to distinguish clinically. This study compared plasma protein changes in 24 women with STEMI and 12 women with TS in the acute phase (days 0–3 post symptom onset) and the stabilization phase (days 7, 14, and 30) to examine the molecular differences between these conditions. Methods: Plasma proteins from STEMI and TS patients were extracted during the acute and stabilization phases and analyzed via quantitative proteomics. Differential expression and functional significance were assessed. Data are accessible on ProteomeXchange, ID PXD051367. Results: During the acute phase, STEMI patients showed higher levels of myocardial inflammation and tissue damage proteins compared to TS patients, along with reduced tissue repair and anti-inflammatory proteins. In the stabilization phase, STEMI patients exhibited ongoing inflammation and disrupted lipid metabolism. Notably, ADIPOQ was consistently downregulated in STEMI patients in both phases. When comparing the acute to the stabilization phase, STEMI patients showed increased inflammatory proteins and decreased structural proteins. Conversely, TS patients showed increased proteins involved in inflammation and the regulatory response to counter excessive inflammation. Consistent protein changes between the acute and stabilization phases in both conditions, such as SAA2, CRP, SAA1, LBP, FGL1, AGT, MAN1A1, APOA4, COMP, and PCOLCE, suggest shared underlying pathophysiological mechanisms. Conclusions: This study presents protein changes in women with STEMI or TS and identifies ADIPOQ, SAA2, CRP, SAA1, LBP, FGL1, AGT, MAN1A1, APOA4, COMP, and PCOLCE as candidates for further exploration in both therapeutic and diagnostic contexts.

Aims: Current experimental models of Takotsubo syndrome (TTS) do not readily distinguish intrinsic myocardial responses from systemic neurohumoral influences. We sought to establish and comprehensively characterize a primary isolated heart TTS model, in which the complete TTS-like phenotype is induced entirely within a Langendorff-perfused rat heart, enabling mechanistic investigation and preclinical therapeutic testing under controlled conditions. Methods and results: Male Sprague-Dawley rat hearts were perfused, and TTS was induced by controlled intra-aortic isoprenaline infusion, while control hearts received vehicle alone. Haemodynamic function and coronary flow were monitored continuously for 6 h. The primary endpoint was the group-by-time interaction for left ventricular developed pressure, analysed using generalized additive mixed models. Prespecified exploratory analyses included principal component analysis, Gaussian mixture modelling, and machine-learning-based feature analysis. Echocardiography, cardiac troponin release, and representative histology were used for multimodal phenotypic validation. Primary isolated TTS hearts developed progressive systolic and diastolic dysfunction characterized by reductions in left ventricular developed pressure, rate-pressure product, and coronary flow together with prolongation of surrogate isovolumic relaxation constant (TAU) (primary endpoint: P = 0.001; q = 0.002). Temporal modelling identified three reproducible physiological phases: hyperactivation, transition, and functional nadir. Echocardiography demonstrated characteristic apical ballooning, reduced ejection fraction, impaired global longitudinal strain, and increased left ventricular akinesia index. Progressive cardiac troponin release and representative histological alterations provided supportive biochemical and structural corroboration of the functional phenotype. Conclusion: We describe the first primary isolated heart model reproducing the core functional phenotype of TTS entirely within an isolated heart preparation. Thus, intrinsic myocardial responses to acute catecholaminergic stress are sufficient to generate regional dysfunction of TTS in the absence of systemic neurohumoral input.

Background: Both Takotsubo syndrome (TS) and ST-elevation myocardial infarction (STEMI) are conditions characterised by the acute onset of left ventricular (LV) dysfunction. While LV thrombus is a known complication of LV dysfunction, its epidemiology in these two patient groups remains poorly understood. Methods: We used data from the Stunning in Takotsubo versus Acute Myocardial Infarction (STAMI) study, which prospectively enrolled patients with TS and STEMI at Sahlgrenska University Hospital. Serial echocardiography was performed on admission and on days 1, 2, 3, 7, 14 and 30. Predictors of LV thrombus were identified using Cox regression analyses. Results: 314 patients were included; 68 with TS, 148 with anterior STEMI and 98 with non-anterior STEMI. Mean LV ejection fraction (LVEF) at admission was 39% (95% CI 35.8 to 42.2) in TS, 46.7% (95% CI 43.3 to 50.1) in anterior STEMI and 52.8% (95% CI 48.9 to 56.7) in non-anterior STEMI. LV thrombus occurred in 20 of 246 (8.1%) STEMI patients but in none of the TS patients. All but one LV thrombus was found in anterior STEMI. All LV thrombi in anterior STEMI were detected within 7 days, while the single non-anterior LV thrombus was found on day 30. All patients with LV thrombi received anticoagulation. Predictors of LV thrombus included lower LVEF and higher troponin levels. Conclusions: Despite more severe LV dysfunction in TS compared with STEMI, LV thrombus was exclusively found in STEMI patients. Almost all LV thrombi were found in anterior STEMI within the first week and showed a high-resolution rate at 30 days. Our findings highlight pathophysiological differences between these two conditions, warranting further investigation and implications for differing surveillance needs after TS and STEMI.