Cardiovascular disease (CVD) is the leading cause of mortality worldwide. The healthy adult heart depends on flexible energy use, but a diseased or injured heart is associated with a loss of flexibility and metabolic remodeling. Since metabolism plays a central role in cardiac health and disease, there is a growing need to understand how metabolic reprogramming contributes to cardiac dysfunction and impaired CM maturation. Human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) are widely used as a platform to study human cardiac development and disease mechanisms. However, current models are limited by metabolic and structural immaturity. This review provides an overview of the dynamic shifts in cardiac metabolic states from fetal development to senescence, while delineating the metabolic signatures of healthy versus disease states. These metabolic switches are orchestrated by a complex interplay of upstream signals driven by variations in substrate availability, post-translational modifications and key transcriptional regulatory networks, which ultimately regulate downstream cardiac remodeling and pathological cascades. As cardiac metabolic function is affected by a coordinated multicellular network, this review also includes the metabolic crosstalk between CMs and non-CMs, including fibroblasts, endothelial cells and immune cells. In addition, various strategies to further mature hiPSC-CMs are summarized to enhance their metabolic profiles. Investigating cardiac metabolic shifts bridges developmental biology, stem cell biology, and regenerative cardiology by revealing how energy metabolism governs cellular identity, maturation, and regenerative potential. These insights are essential for improving stem-cell-derived CMs for disease modeling, drug discovery, and heart repair.

Chronic coronary syndromes (CCSs) are increasingly recognized as complex immunometabolic vascular disorders in which coronary microvascular dysfunction (CMD), persistent low-grade inflammation, oxidative stress, and maladaptive cellular remodeling contribute to ischemic symptoms and adverse outcomes beyond epicardial stenosis. CMD represents a heterogeneous condition comprising both functional and structural endotypes and constitutes a major determinant of myocardial ischemia, heart failure progression, and adverse cardiovascular outcomes, even in the absence of obstructive coronary artery disease. Emerging evidence indicates that immunometabolic reprogramming of endothelial cells, vascular smooth muscle cells, and immune cells sustains microvascular dysfunction in CCSs. Metabolic shifts toward glycolysis, mitochondrial dysfunction, redox imbalance, and dysregulated lipid metabolism promote chronic inflammatory activation within the coronary microenvironment. Convergent mitochondrial stress (including NAD⁺ decline) and redox injury promote endothelial senescence and increase susceptibility to regulated cell death, progressively limiting vasodilatory reserve and predisposing to microvascular rarefaction. Pyroptosis and ferroptosis-like lipid peroxidation further exacerbate endothelial barrier disruption and inflammatory amplification. In parallel, inflammasome activation, iron-dependent lipid peroxidation, impaired autophagy, and endoplasmic reticulum stress form interconnected molecular networks that amplify vascular injury through self-reinforcing mechanisms. This narrative review integrates mechanistic and translational evidence linking immunometabolic dysregulation, mitochondrial stress, thromboinflammatory signaling, endothelial senescence, and regulated cell death to distinct CMD endotypes. We propose a systems-level framework in which coronary microvascular dysfunction is conceptualized as an immunometabolic vascular network disorder, with reduced coronary flow reserve (CFR)-often termed myocardial flow reserve (MFR) in PET studies-emerging as the integrative functional endpoint of these interacting molecular perturbations and a robust predictor of major cardiovascular events.

Fear of falling is a common and serious psychological challenge after stroke, yet its longitudinal patterns remain poorly understood. Current evidence often fails to capture individual heterogeneity in recovery trajectories. This study aimed to identify distinct longitudinal trajectories of fear of falling and explore associated factors to inform targeted rehabilitation strategies in post-stroke patients.

A prospective longitudinal study.

From August 2023 to December 2024, we enrolled 166 stroke patients from the neurology wards of two hospitals in Lanzhou, China, forming a hospital-based sample within an urban healthcare setting. Fear of falling was assessed using a single-item question and the Short Falls Efficacy Scale-International at four time points: 2 weeks, 1 month, 3 months, and 6 months post-stroke. Data were analyzed using latent class growth modeling in Mplus 8.0.

The prevalence of fear of falling was 48.8%, 49.4%, 45.8%, and 34.3% at 2 weeks, 1 month, 3 months, and 6 months, respectively. Mean Short Falls Efficacy Scale-International scores were 11.30 (±4.74), 9.84 (±3.40), 9.61 (±3.13), and 8.00 (±1.22) at these time points. Three distinct fear of falling trajectories were identified: high-level continuous decline (20.48%), medium-level steady decline (26.51%), and low-level fear (53.01%). Age, anxiety levels, and depression levels were significant factors associated with these trajectories.

Fear of falling after stroke demonstrates heterogeneous longitudinal trajectories that are significantly influenced by age, anxiety, and depression. These findings highlight the importance of individualized assessment and targeted psychological support during stroke rehabilitation.

Fear of falling is a dynamic psychological challenge during stroke recovery. Routine screening for fear of falling, anxiety, and depression may help nurses identify patients at risk for persistent fear trajectories. Tailored rehabilitation and psychological interventions may improve rehabilitation participation and recovery outcomes.

No patient or public engagement.

Central venous catheterization in neonates presents unique challenges due to transitional circulatory physiology and potential persistence of fetal vascular structures. We describe a rare intraoperative observation in a 4-day-old baby boy weighing 1.8 kg, diagnosed with a large retroperitoneal mass causing abdominal compartment syndrome. The patient underwent emergency exploratory laparotomy. During ultrasound-guided internal jugular vein catheterization in the setting of an open abdomen, the guidewire was unexpectedly visualized emerging through the umbilical vein. This unusual finding indicated the presence of a patent ductus venosus, a fetal vessel that normally closes soon after birth but may remain patent for days or weeks in some neonates. The patent ductus venosus provided an anomalous communication between the umbilical and systemic venous systems, creating a potential pathway for guidewire misdirection. This case highlights the importance of understanding neonatal vascular anatomy, especially the persistence of fetal circulatory structures that may alter expected catheter trajectories. Awareness of such variations, coupled with real-time ultrasound and fluoroscopic confirmation, is essential to prevent inadvertent catheter misplacement and associated complications. This observation reinforces the need for heightened vigilance and imaging guidance during central venous access in critically ill neonates with altered hemodynamics and developmental vascular anomalies.

Intra-arterial thrombolysis (IAT) following successful mechanical thrombectomy (MT) in patients with anterior circulation large-vessel occlusion (LVO) improves cerebral tissue reperfusion and consequently clinical outcome, but has to be validated in non-Asian populations. We hypothesised that IAT with alteplase versus no IAT leads to a better clinical outcome in patients with anterior circulation LVO stroke who have successful angiographic recanalisation.

Intra-Arterial thrombolysis after SUCCESSful angiographic recanalization in acute large-vessel occlusion stroke of the anterior circulation (IA-SUCCESS) trial is a phase 3 investigator-initiated, multicentre, randomised, open-label, blinded-endpoint (PROBE) clinical trial with a health economic evaluation conducted in France. Patients with acute ischaemic stroke due to anterior circulation LVO within 24 h of stroke onset and successful angiographic reperfusion (defined as extended Thrombolysis in Cerebral Infarction score 2b-3) after intravenous thrombolysis alone, MT alone or both will be randomised in two balanced parallel groups (1:1) to receive either IAT with alteplase (0.225 mg kg-1 and a maximum of 20 mg) injected in the ipsilateral internal carotid artery or no IAT. A total of 626 patients will be included.

The primary outcome is the functional outcome on the modified Rankin Scale at 90 (±15) days. Standard secondary clinical outcomes are assessed at 24 (±6) h, 5-7 days, 90 (±15) days and 12 (±1) months. Safety outcomes include mortality at 90 (±15) days and intracranial haemorrhage.

The IA-SUCCESS trial will provide high-quality randomised data on the clinical efficacy and safety of intra-arterial alteplase following successful angiographic recanalisation in European patients with ischaemic stroke due to anterior circulation LVO intended for MT.

ClinicalTrials.gov NCT06768138.

Thrombolysis has been shown to reduce disability after acute ischaemic stroke in randomised trials. Our study sought to compare the benefit from thrombolysis observed in a comprehensive national stroke registry with that expected from the clinical trials.

Data from a total of 168,347 ischaemic stroke patients who attended one of 118 emergency stroke hospitals in England and Wales from 2016 to 2021 were extracted from the Sentinel Stroke National Audit Programme. We constructed a machine learning model, designed to isolate the effect of thrombolysis, using explainable machine learning (XGBoost with SHapley Additive exPlanations [SHAP]).

Thrombolysis was found to be associated with a statistically significant improvement in the odds of achieving a better outcome (modified Rankin scale [mRS] threshold). Regression analysis predicted a maximum 2.5-fold improvement in odds of achieving mRS 0-1, with a decline to no treatment effect at 5 h 28 min post-onset.

Our results confirm a beneficial effect of thrombolysis in a large prospective national stroke registry, and align closely with meta-analyses of clinical trials of thrombolysis both in terms of magnitude of effect and decline over time. This work also demonstrates the potential to apply explainable machine learning to observational data to assist in understanding how clinical trials are implemented in real-world settings.

Thrombolysis, in practice, has the same observed benefit as in the clinical trials.

Clinical monitoring of patients with heart failure or cardiomyopathy is facilitated by detailed assessment of cardiac loading conditions. Specifically, alterations in preload and afterload may unmask pathology through effects on ventricular pressure-volume (PV) relations. Therefore, the aim was to assess non-invasive PV loops during left ventricular load manipulation in healthy participants and in patients with hypertrophic cardiomyopathy (HCM).

In total, n = 46 participants were studied in paired experiments at baseline and during load manipulation. Controls (n = 24) and patients with HCM (n = 14) were assessed at baseline and during intravenous infusion of 1.5-2 L isotonic saline, and another group of volunteers (n = 8) was assessed at baseline and during infusion of glyceryl trinitrate (GTN). Non-invasive PV loops were calculated from cardiovascular magnetic resonance (CMR) and concurrent brachial blood-pressure measurements.

Saline infusion brought about increased end-diastolic and decreased end-systolic volumes in controls, but not in HCM. Concurrently, PV loops revealed mechanistic differences, where controls but not HCM exhibited decreased arterial elastance and potential energy during load manipulation. In both groups, ventricular-arterial coupling (VAC) decreased, and ventricular efficiency and cardiac output increased. Infusion of GTN resulted in decreased ventricular volumes. Contrary to saline infusion, volunteers receiving GTN retained unchanged arterial elastance, VAC, ventricular efficiency and cardiac output.

Non-invasive PV analysis from CMR detects cardiac response to altered loading conditions in healthy participants and in patients with HCM. Our findings support the use of CMR-derived PV loops for detailed assessment of cardiac thermodynamic performance in relation to interventions affecting preload and afterload.

In Tanzania, many people living with HIV have uncontrolled hypertension, yet integration of hypertension management into HIV care remains limited. The Community Health Worker Optimization of Antihypertensive Care in HIV (COACH) intervention was developed to integrate standardized hypertension management into HIV clinic workflows.

A single-arm pilot trial was conducted from December 2024 to September 2025 at 2 public HIV clinics in Moshi, Tanzania.

COACH included 6 monthly community health worker-delivered hypertension education sessions within HIV clinic visits, monthly blood pressure (BP) checks, care coordination, subsidized antihypertensive medications, a standardized treatment algorithm, and provider training. The primary effectiveness outcome was BP control at 6 months (<140/<90 mm Hg). Secondary effectiveness outcomes included systolic and diastolic BP, Hypertension Knowledge Level Scale score, medication adherence, body mass index, and 5-year cardiovascular risk. Paired t tests and McNemar tests compared baseline and follow-up values.

Of 100 participants, 96 completed follow-up. Six-month BP control was achieved in 73 participants (76%). Mean systolic BP decreased from 159.6 mm Hg at baseline to 130.8 mm Hg at follow-up (-28.9 mm Hg, P < 0.001); diastolic BP decreased from 100.8 to 85.5 mm Hg (-15.4 mm Hg, P < 0.001). Hypertension Knowledge Level Scale scores increased from 15.0 to 20.4 (P < 0.001), and self-reported adherence improved from 14.0% to 95.0% (P < 0.001). Mean body mass index decreased from 27.0 to 26.6 kg/m2 (P = 0.019), and the proportion with ≥20% 5-year cardiovascular risk declined from 33% to 7% (P < 0.001).

COACH resulted in substantial improvements in BP control, hypertension knowledge, medication adherence, and cardiovascular risk among people living with HIV in Tanzania.

Emerging technologies enable continuous monitoring of temporal exposures to disease risk factors, leading to complex exposure processes characterized by subject-specific numbers and durations of exposure episodes. A key scientific question is how the number and duration of such episodes influence disease risk. Existing methods typically rely on scalar summaries or time-indexed representations and are not naturally suited to model duration-dependent risk accumulation at the episode level. We introduce the FLexible Accumulation ModEl (FLAME), a semiparametric model for risk accumulation at the level of individual exposure episodes, with duration as the primary driver of risk. FLAME is motivated by and applied to quantifying the association between the duration of intraoperative hypotension and acute kidney injury (AKI) following cardiac surgery. The estimated risk accumulation function reveals that, although 60 one-minute hypotensive episodes are associated with an AKI probability of 0.24, a single sustained 60-minute episode increases that probability to 0.33, representing a 38% increase despite identical total duration. These findings provide actionable insights for intraoperative hemodynamic management and demonstrate the importance of accounting for episodic exposure patterns. While motivated by cardiac surgery, FLAME is broadly applicable to other settings involving high-resolution temporal exposures. An R package, flameRisk, is provided to facilitate the application of the method in practice.

Gastrin-17 (G-17) and serum pepsinogen (PG) are indicators that reflect the structure and function of the stomach mucosa. Although they have been linked to upper gastrointestinal bleeding (UGIB) in peptic ulcer disease, it is unknown how they relate to the risk of UGIB in patients with acute coronary syndrome (ACS) after dual antiplatelet treatment (DAPT) following percutaneous coronary intervention (PCI).

This single-center, retrospective study aims to evaluate whether PG and G-17 as gastric mucosal assessment markers, are potentially associated with UGIB during DAPT following PCI in patients with ACS.

This study employed a retrospective analysis design and included 334 patients with ACS (2021-2023) from Xuzhou Medical University Affiliated Hospital, divided into UGIB group (69 patients) and non-UGIB group (265 patients). Clinical and laboratory data were collected. Multivariate logistic regression and ROC curve analysis were used to evaluate the associations of G-17, PRECISE-DAPT scores, ACS subtype, and P₂Y₁₂ receptor antagonist used for UGIB after DAPT.

Compared with the non-UGIB group, G-17 levels and PRECISE-DAPT scores in the UGIB group were markedly higher, and ticagrelor was prescribed more commonly (p < 0.001). The area under the curve (AUC) of G-17, PRECISE-DAPT scores alone, and in combination were 0.734, 0.794, and 0.844, respectively; the AUC further increased to 0.878 after incorporating ticagrelor exposure, indicating that the combined assessment with ticagrelor exposure has superior exploratory value in identifying high-risk patients with UGIB (p < 0.05). Furthermore, the combined use of PPIs during DAPT reduced the incidence of UGIB (34.78% vs. 65.22%, p < 0.05), which serves as an important interfering factor for G-17 assessment.

Higher G-17 levels and PRECISE-DAPT scores were associated with UGIB during DAPT after PCI. Combined assessment with ticagrelor exposure showed exploratory value for identifying patients at higher bleeding risk, although PPIs use influenced model performance. Given the retrospective single-center design and limited sample size, these findings remain preliminary and require prospective multicenter validation.