Molecular Partners (Switzerland)

Purpose To determine whether baseline clinical characteristics and cardiac MRI parameters predict major adverse cardiac events (MACEs) in participants with angiographically confirmed spontaneous coronary artery dissection (SCAD). Materials and Methods This prospective single-center study included participants with SCAD who were angiographically diagnosed between March 2018 and November 2023. Cardiac MRI was performed after a median of 4 days (IQR, 1.5-7) from symptom onset. SCAD types were classified according to the Yip-Saw system. Follow-up evaluation was performed at a median of 5.5 months after discharge, and MACEs were recorded. The primary outcome was the occurrence of MACEs. Secondary analyses included extent of late gadolinium enhancement (LGE). Statistical analysis included binary logistic and Cox proportional hazards regression. Results Overall, 59 participants (mean age, 49 years ± 10; 40 female participants [68%]) were included. ST-elevation myocardial infarction at presentation was diagnosed in 24 of 59 (41%). Angiographically, 41 of 59 (69.5%) were SCAD type 2. Baseline cardiac MRI demonstrated acute injury in 48 of 59 (81%) and LGE in 54 of 59 (93%), typically moderate (median, three segments [IQR, two to five]). In the adjusted model, ST-elevation myocardial infarction manifestation independently predicted greater LGE extent (P = .02; odds ratio, 7.00; 95% CI: 2.00, 24.00). After multivariable adjustment, SCAD type 1 was significantly associated with MACEs (P = .002; hazard ratio, 10.00; 95% CI: 2.00, 23.00), as was transmural LGE (P = .006; hazard ratio, 1.50; 95% CI: 1.10, 2.10). A threshold of greater than or equal to four LGE segments identified a critical risk zone. Conclusion In SCAD, SCAD type 1 and involvement of more than three transmural LGE segments at acute cardiac MRI independently predicted MACEs. Keywords: MR Perfusion, Cardiac, Arteries, Cardiomyopathies, Ischemia/Infarction Supplemental material is available for this article. © RSNA, 2026.

The obesity paradox has been described in different cardiovascular conditions. Data on the association between obesity and outcomes in patients with Takotsubo syndrome (TTS) are lacking. The aim of this study was to determine the relationship between body weight and mortality in TTS patients. Patients enrolled in the International Takotsubo Registry from January 2011 to July 2021 and with available data on body mass index (BMI) were included in the analysis. Patients were stratified according to BMI (underweight, <18.5 kg/m2; normal weight, 18.5-24.9 kg/m2; overweight, 25.0-29.9 kg/m2; obese, 30.0-34.9 kg/m2; and very obese, ≥35.0 kg/m2). The primary endpoint was mortality at 1 year. Of the 2707 patients, 222 (8.2%) were underweight, 1340 (49.5%) of normal weight, 759 (28.0%) overweight, 268 (9.9%) obese and 118 (4.4%) very obese (p=0.02). Rates of mortality at 1 year were 11.3%, 6.9%, 5.5%, 4.9% and 9.3% in underweight, normal weight, overweight, obese and very obese patients (p=0.02). Being overweight or obese was significantly associated with a lower mortality rate at 1 year (HR 0.70, 95% CI 0.51 to 0.96, p=0.03), and this association remained significant after multivariable adjustments (adjusted HR 0.67, 95% CI 0.46 to 0.97, p=0.03). A U-shaped mortality curve across BMI categories was observed in TTS patients, with the highest mortality rates observed in underweight and the lowest rates observed in obese patients. These observations provide the first evidence for the existence of the obesity paradox in TTS. NCT01947621.

Background: Current US and European guidelines recommend targeting a systolic blood pressure (SBP) below 130 mmHg in patients at high cardiovascular (CV) risk, such as those with a history of acute coronary syndrome (ACS), though these recommendations are largely extrapolated from trials in the general hypertensive population. Aims: Our aim was to evaluate the prognostic significance of SBP measured one year after an ACS event on subsequent CV outcomes. Methods: The SPUM-ACS cohort prospectively enrolled patients with ACS between 2009 and 2017 across four Swiss tertiary care centers. We included patients who were alive at one-year post-enrollment and had available SBP measurements at that time point. The association between continuous SBP, measured one year post ACS (marking the start of the follow-up period) and the risk of the composite outcome of 3-point major adverse CV events (MACE) —including CV death, non-fatal stroke or transient ischemic stroke, and non-fatal myocardial infarction—was assessed using restricted cubic spline modeling. Outcomes were monitored up to five years after the index ACS event. Analyses were adjusted for age, sex, established CV risk factors and antihypertensive medication classes. Results: A total of 2,731 patients (mean age 63±12 years; 82% male; mean SBP 132±19 mmHg; 55.1% ST elevation myocardial infarction) were included in the analysis. During a median follow-up of 4.0 years, 273 patients experienced a MACE. The association between SBP at 1 year and the risk of 3-point MACE demonstrated a nonlinear, J-shaped pattern ( Figure 1, P non-linearity =0.05) The lowest risk was observed for SBP values between ~125 and 135 mmHg (23.7% of the cohort), with a progressive increase in risk for SBP levels above 135 mmHg (40.4% of the cohort). Specifically, for SBP values above 135 mmHg, each 5 mmHg-increase was associated with a higher risk of MACE (adjusted hazard ratio: 1.09; 95% confidence interval: 1.01–1.18). In analyses stratified by age and sex, the J-shaped relationship remained consistent, with no significant interaction observed (P interaction for age =0.80; P interaction for sex =0.66; Figure 2 ). Conclusions: In this large and well-characterized cohort of post-ACS patients, the lowest risk of CV events was observed with SBP levels between ~125 and 135 mmHg, without evidence of differences by age and sex. Our data support the recommendations of targeting SBP within a reasonable range after an ACS while avoiding both over- and undertreatment.

Aging is associated with enhanced platelet activation and inflammatory responses, contributing to an increased risk of thrombotic and cardiovascular events. However, how megakaryocytes (Mk) change with age or between sexes is still unclear.We performed single-cell RNA sequencing to profile bone marrow from young (3-month-old) and old (> 24-month-old) C57BL/6 mice, as well as from young and middle-aged human donors. In parallel, platelet activation was assessed by CD62P expression using flow cytometry in isolated and washed mouse platelets from young and old donors. Single-cell clustering in mouse bone marrow revealed five distinct Mk subpopulations. The age-dependent shift was more pronounced for subpopulations associated with platelet activation (mMk3) and immune/inflammatory responses (mMk4). mMk3 cells were more abundant in females, whereas mMk4 predominated in males. An increased platelet activation phenotype in old mice was confirmed in both sexes by CD62P expression analyses. Differential gene expression analyses showed that aging alters gene expression patterns related to platelet activation and aggregation via receptor signaling, granule formation, and inflammation. Aged males exhibited enrichment in genes linked to mitochondrial function, oxidative stress, lipid metabolism and membrane dynamics, whereas aged females showed upregulation of serotonin receptor genes. Human transcriptomic data support our murine findings, exhibiting increased expression of genes involved in mitochondrial electron transport and immune signaling in middle-aged individuals. Our study reveals a complex, sex-specific remodeling of Mk subpopulations in the aging organisms, characterized by distinct pro-thrombotic and pro-inflammatory transcriptional profiles. These observations suggest potential targets for developing age- and sex-tailored antithrombotic therapies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40364-025-00830-x.

First‐line therapy for ischemic stroke relies on the systemic administration of thrombolytics for dissolving clots affecting brain perfusion. However, because conservative dosages are used to avoid off‐target toxicity and side effects, the systemic route is often unable to deal with large clots in a timely manner. Targeted delivery of thrombolytics could be the solution if microrobots carrying the drugs could be navigated through the patient's neurovascular network to locally administer them directly to the clot. Herein, the steering of magnetic microrobots along a patient‐specific neurovascular network is numerically studied, for optimizing the navigation of the microrobots to target vessels often obstructed in ischemic stroke. It is found that spatially constant magnetic gradients can be used to navigate the microrobots to the target vessels and describe various navigation strategies that can be used by health professionals to reach different positions in the vasculature. Equations are developed to predict the required magnetic gradients as a function of the microrobot diameter, which are key for the development of magnetic navigation systems that can autonomously navigate microrobots through neurovascular networks. These findings open exciting possibilities for exploring targeted drug delivery approaches in clinical settings.

Triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) are the most aggressive molecular subtypes of breast cancer. Poor clinical outcomes highlight the pressing need to discover novel targets for the effective treatment of these diseases. LMP7 (β5i/PSMB8), a proteolytic subunit of the immunoproteasome, is implicated in the pathogenesis of multiple myeloma, autoimmune and inflammatory diseases, and inflammation-related cancers. However, the role of LMP7 in TNBC and IBC remains poorly characterized. Here, we evaluated the function of LMP7 in TNBC and IBC using the selective LMP7 inhibitor M3258. In human TNBC patient samples, LMP7 expression correlated strongly with CD8+ T cell infiltration and activation markers. M3258 inhibited LMP7 activity, reduced viability, and induced apoptosis in TNBC/IBC cell lines in vitro. In a novel immunocompetent in vivo model of TNBC/IBC, M3258 reduced tumor growth and the tumor abundance of M2 macrophages. Additionally, M3258 activated tumor-infiltrating CD8+ T cells and suppressed the expression of specific inflammatory pathway gene signatures in immune cells. Co-culture with M2 macrophages enhanced the invasiveness of TNBC/IBC cells, which was effectively suppressed by M3258 treatment. Our results demonstrate for the first time that LMP7 shapes the pro-tumorigenic microenvironment of TNBC/IBC, in part by modulating the pathogenic role of M2 macrophages. These findings suggest that LMP7 may represent a novel target for therapeutic intervention in TNBC/IBC.

Due to its peculiar structure and function, the cardiovascular system is particularly vulnerable to the detrimental effects of ageing. Current knowledge about the molecular mechanisms of ageing revealed the processes actively promoting ageing, e.g. progressive telomere shortening, and the mechanisms opposing it, e.g. endogenous production of antioxidant substances. This knowledge can be used to measure biological age at cellular and molecular levels and to interfere with it by pharmacological or non-pharmacological interventions. Biological ageing is determined by the simultaneous occurrence of independent hallmarks, which encompass a wide range of biological processes, from genomic changes to systemic inflammation and dysbiosis. This narrative review will summarize the role of ageing hallmarks in the cardiovascular system, how they can be measured, and what are the possible interventions to counteract their effects.