Introduction Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may cause stress-induced transient acute cardiac dysfunction through myocardial stunning, in the form of exacerbation-triggered Takotsubo syndrome (referred to as Takotsubo stunning). Although prior studies suggest an association between AECOPD and transient cardiac dysfunction, existing evidence is limited to retrospective cohorts, case reports and expert consensus. Therefore, the incidence and clinical impact of Takotsubo stunning with acute heart failure (AHF) during AECOPD remain unknown and may be overlooked due to overlapping clinical symptoms. Cardiac Assessment and Takotsubo-stunning among COPD-exacerbations in-Hospital (CATCH study) aims to determine the incidence of Takotsubo stunning during AECOPD and to evaluate its clinical implication.Methods and analysis CATCH is a prospective observational cohort study enrolling adults (≥18 years) admitted for AECOPD at Sahlgrenska University Hospital (Gothenburg, Sweden). Participants with chronic left ventricular systolic dysfunction (left ventricular ejection fraction <50%), pre-existing chronic regional wall motion abnormalities (RWMA) or prior type 1 myocardial infarction are excluded. Following informed consent, participants undergo echocardiographic screening for RWMA and/or systolic left ventricular dysfunction. Screening-positive patients have follow-up echocardiography at 24 hours (±6) and 30 days (±48 hours). Those with reversible dysfunction constitute the CATCH case group, while screening-negative participants serve as controls. Additional assessments include ECG, chest X-ray, N-terminal pro-B-type natriuretic peptide blood analysis and COPD severity. Primary outcomes include the incidence of reversible RWMA or left ventricular dysfunction (proxy for Takotsubo stunning) and in-hospital clinical signs of AHF (Killip class >1). A sample size of 150 patients is required for detecting AHF differences (α=0.05, 80% power).Ethics and dissemination The study received ethical approval from the Swedish Ethical Review Authority. All participants provided written informed consent. Results will be disseminated through peer-reviewed journals and scientific meetings.Registration details The CATCH study is registered at ClinicalTrials.gov (NCT06597331). The reference number for ethical approval is 2024-02071-01 (with addenda 2024-05448-02 and 2025-05861-02).

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.

BACKGROUND:Left ventricular diastolic dysfunction following Takotsubo syndrome (TS) and ST-elevation myocardial infarction (STEMI) is a marker of impaired myocardial relaxation and reduced ventricular compliance and is associated with adverse outcomes. We hypothesized that differences in diastolic function explain the better hemodynamic profile seen in TS compared to STEMI despite similar or more extensive cardiac systolic dysfunction. METHODS:Daily echocardiographic examinations including diastolic function parameters were made in women with TS (N = 69) or anterior STEMI (N = 43), starting on the day of symptom onset. The primary endpoints were a set of diastolic indices at 24 h after symptom onset. Women were also classified into diastolic subgroups based on the 2025ASE recommendations on evaluation of left ventricular diastolic function. RESULTS:TS and STEMI were balanced in age (69.4 ± 11.1 versus 69.5 ± 11.0), baseline risk factors and pre-admission cardiovascular medications. Women with TS had significantly lower S/D(p = 0.05), and higher E/é-lateral(p = 0.04), and LAVI(p = 0.05) compared to STEMI 24 h after admission. But there were no significant differences between the groups in diastolic grade, after 24 h. Longitudinal analyses of diastolic parameters over the course of the study period did not reveal any pattern suggestive of systematically worse or better diastolic function in TS than STEMI. Diastolic function parameters and diastolic function grade were similar also at 30-days follow-up in both groups. CONCLUSION:This study is the first to evaluate left ventricular diastolic function with repeated echocardiography. Because diastolic indices were similar or more impaired in TS than in STEMI, our findings do not support the hypothesis.

BACKGROUND:It is incompletely understood why patients with takotsubo syndrome (TS) have milder symptoms and a better hemodynamic profile than patients with ST-elevation myocardial infarction (STEMI) despite similar or more extensive cardiac dysfunction. We hypothesized that this discrepancy could be due to better global longitudinal and global radial strain (GLS and GRS) in TS patients that are not apparent using conventional echocardiography. METHODS:Daily echocardiograms were performed, starting on the day of symptom onset, to compare GLS and GRS over time in women with apical TS (n = 57), and women (n = 41), and men (n = 105) with anterior STEMI. We also assessed segmental longitudinal and radial strain of remote, apparently normal myocardial segments. RESULTS:At admission GLS was worse in women with TS than women and men with STEMI (GLS: -9.3 %(-10.4 %, -8.3 %) vs -11.9 %(-13.1 %, -10.6 %), and - 11.7 %(-12.5 %, -10.9 %), p = 0.002 and p = 0.001). GRS did not differ significantly between groups. Segmental longitudinal strain in remote segments was significantly worse in women with TS compared to women and men with STEMI (TS women -13.4(-14.8, -12.0), STEMI women -18.0(-19.9, 16.1), and STEMI men -16.9(-17.9, -15.9)). Both GLS and GRS improved within groups between day 0 and day 30. CONCLUSIONS:Contrary to our hypothesis, GLS and GRS are both depressed in the acute phase of apical TS to at least a similar extent as in anterior STEMI. Longitudinal strain appears to be affected to a greater extent in apical TS than in anterior STEMI, particularly in segments with normal radial strain that are remote to the akinetic segments.

Takotsubo syndrome (TS) and STEMI with timely reperfusion are both characterized by reversible acute myocardial dysfunction, often referred to as myocardial stunning. The natural course of cardiac functional recovery is incompletely understood in TS and STEMI. The aim of this study was to prospectively compare changes in cardiac function over the acute and subacute phases in women with TS versus anterior STEMI. The Stunning in Takotsubo versus Acute Myocardial Infarction (STAMI) study prospectively enrolled 61 women with TS and 41 women with STEMI. Echocardiography and blood sampling was performed within 4 h of admission and at 1, 2, 3, 7, 14, and 30 days after admission. The primary outcome was the proportion of reversible left ventricular akinesia (defined as extent of akinesia at baseline versus at 30 days) that resolved by 72 h. Secondary outcomes included LVEF, GLS, and TAPSE. Mixed effects linear regression or mixed effects tobit models with random intercepts were used to model echocardiographic parameters over time. At 72 h 40.4 https://clinicaltrials.gov/study/NCT04448639 . The stunning in Takotsubo versus acute myocardial infarction (STAMI) study compared the changes in cardiac function over time in 61 women with takotsubo syndrome (TS) versus 41 women with ST elevation myocardial infarction (STEMI) over a 30-day period. The time course of cardiac recovery was similar in takotsubo and anterior ST-elevation myocardial infarction. In both takotsubo and ST-elevation myocardial infarction, recovery of cardiac function takes on average longer than 7 days.

Compared to men, women have been reported to have increased morbidity and mortality after ST-elevation myocardial infarction (STEMI); but sex differences in cardiac function in the acute and subacute phases of STEMI are incompletely understood. The objective of this study was to prospectively compare changes in cardiac function over the acute and subacute phases after anterior STEMI with timely reperfusion in women versus men. The Stunning in Takotsubo versus Acute Myocardial Infarction (STAMI) study (NCT04448639) prospectively enrolled 105 men and 41 women with anterior STEMI. Echocardiography and blood sampling were performed within 4 hours of admission and at 1, 2, 3, 7, 14, and 30 days after admission. The primary outcome was akinesia recovery, defined as the difference in the percentage of akinesia observed at baseline versus follow-up. Secondary outcomes included wall motion score index (WMSI), left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). Mixed effects linear regression or zero-inflated tobit models with random intercepts were used to model echocardiographic parameters over time. Baseline patient characteristics were similar in both groups. The difference between women and men in akinesia recovery at 30 days was 8.3% (95% credible interval 0.8%, 15.5%). The covariate-adjusted posterior probability that akinesia recovery and WMSI improvement at 30 days are greater in women than men were 96.0% and 99.0% respectively. Similar but less pronounced trends towards greater improvement in women than men were observed for LVEF and GLS. In conclusion, cardiac dysfunction recovered to a greater extent in women than in men after anterior STEMI with timely reperfusion.

Background and aimsIschemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function.Methods and resultsRats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15 min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding.ConclusionIPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.

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.

Numerous roles for the Alk receptor tyrosine kinase have been described in Drosophila, including functions in the central nervous system (CNS), however the molecular details are poorly understood. To gain mechanistic insight, we employed Targeted DamID (TaDa) transcriptional profiling to identify targets of Alk signaling in the larval CNS. TaDa was employed in larval CNS tissues, while genetically manipulating Alk signaling output. The resulting TaDa data were analyzed together with larval CNS scRNA-seq datasets performed under similar conditions, identifying a role for Alk in the transcriptional regulation of neuroendocrine gene expression. Further integration with bulk and scRNA-seq datasets from larval brains in which Alk signaling was manipulated identified a previously uncharacterized Drosophila neuropeptide precursor encoded by CG4577 as an Alk signaling transcriptional target. CG4577, which we named Sparkly (Spar), is expressed in a subset of Alk-positive neuroendocrine cells in the developing larval CNS, including circadian clock neurons. In agreement with our TaDa analysis, overexpression of the Drosophila Alk ligand Jeb resulted in increased levels of Spar protein in the larval CNS. We show that Spar protein is expressed in circadian (clock) neurons, and flies lacking Spar exhibit defects in sleep and circadian activity control. In summary, we report a novel activity regulating neuropeptide precursor gene that is regulated by Alk signaling in the Drosophila CNS.

Development of the midgut visceral muscle of Drosophila crucially depends on Anaplastic Lymphoma Kinase (Alk) receptor tyrosine kinase (RTK) signalling, which is needed to specify founder cells (FCs) in the circular visceral mesoderm (VM). While activation of the Alk receptor by its ligand Jelly Belly (Jeb) is well characterized, only a small number of target molecules have been identified. Here, we assayed RNA polymerase II (Pol II) occupancy in VM cells by using the targeted DamID (TaDa) approach. To identify Alk targets we employed comparative analysis of embryos overexpressing Jeb versus embryos with abrogated Alk activity, revealing differential expression of a number of genes, including the Snail/Scratch family transcription factor Kahuli ( Kah ). Upon further in vivo validation, we confirmed that Alk signalling regulates Kah mRNA expression in the VM. We show that Kah mutants display defects in the formation of midgut constrictions, similar to that of pointed ( pnt ) mutants. Analysis of publicly available ChIP data defined a Kah target-binding site similar to that of Snail. In addition, we compared genes that were differentially expressed in Kah mutants with publicly available Kah- and Pnt-ChIP datasets identifying a set of common target genes putatively regulated by Kah and Pnt in midgut constriction. Taken together, we (i) report a rich dataset of Alk responsive loci in the embryonic VM, (ii) provide the first functional characterization of the Kah transcription factor, identifying a role in embryonic midgut constriction, and (iii) suggest a model in which Kah and Pnt cooperate in embryonic midgut morphogenesis.

Anaplastic lymphoma kinase (Alk) is an evolutionary conserved receptor tyrosine kinase belonging to the insulin receptor superfamily. In addition to its well-studied role in cancer, numerous studies have revealed that Alk signaling is associated with a variety of complex traits such as: regulation of growth and metabolism, hibernation, regulation of neurotransmitters, synaptic coupling, axon targeting, decision making, memory formation and learning, alcohol use disorder, as well as steroid hormone metabolism. In this study, we used BioID-based in vivo proximity labeling to identify molecules that interact with Alk in the Drosophila central nervous system (CNS). To do this, we used CRISPR/Cas9 induced homology-directed repair (HDR) to modify the endogenous Alk locus to produce first and next generation Alk::BioID chimeras. This approach allowed identification of Alk proximitomes under physiological conditions and without overexpression. Our results show that the next generation of BioID proteins (TurboID and miniTurbo) outperform the first generation BirA* fusion in terms of labeling speed and efficiency. LC-MS3-based BioID screening of AlkTurboID and AlkminiTurbo larval brains revealed an extensive neuronal Alk proximitome identifying numerous potential components of Alk signaling complexes. Validation of Alk proximitome candidates further revealed co-expression of Stardust (Sdt), Discs large 1 (Dlg1), Syntaxin (Syx) and Rugose (Rg) with Alk in the CNS and identified the protein-tyrosine-phosphatase Corkscrew (Csw) as a modulator of Alk signaling.