Myocardial ischemia-reperfusion (I/R) injury remains a major contributor to infarct expansion, adverse remodeling, and heart failure despite timely coronary revascularization. The repeated failure of cardioprotective interventions that were effective in animal models has exposed a persistent translational gap. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and engineered cardiac platforms preserve donor-specific human genetic backgrounds, provide scalable cell sources, and offer experimentally tractable systems for studying selected mechanisms of I/R injury. Recent advances in electrical, mechanical, metabolic, and endocrine maturation, together with engineered heart tissues (EHTs), cardiac organoids, and perfused heart-on-a-chip platforms, have improved the ability to model cardiomyocyte stress, calcium overload, mitochondrial dysfunction, oxidative injury, and multicellular crosstalk. Single-cell and spatial omics, CRISPR-based perturbation, and artificial intelligence (AI)-assisted high-content phenotyping further enable state-resolved and mechanistically testable analyses of vulnerable cardiac cell populations. In this narrative review, we synthesize recent progress in hiPSC-based myocardial I/R modeling, critically evaluate the strengths and limitations of current platforms, and discuss their use in mechanism-guided drug screening, cardiotoxicity assessment, and patient-specific preclinical modeling. We emphasize that these systems are not yet substitutes for clinical validation or whole-organ physiology. Their current value lies in providing controllable, human-relevant preclinical models that can prioritize mechanisms, identify candidate interventions, and support better-designed translational cardioprotection studies.

While studies have established the independent benefits of diet and exercise, comparatively few have assessed these modalities side by side, evaluating diet-only, exercise-only, and combined interventions under comparable conditions. This review focuses on randomized trials and meta-analyses that provide such direct comparisons, emphasizing outcome-specific differences and the circumstances in which combining both modalities yields added benefit.

Evidence indicates that the superiority of combined diet and exercise interventions is outcome-dependent rather than universal. Dietary interventions generally produce improvements in body weight, cholesterol, and fasting glucose, whereas exercise uniquely enhances cardiorespiratory fitness, muscular strength, endothelial function, and physical function. For cardiometabolic outcomes including insulin sensitivity and visceral adiposity, combined interventions frequently provide additive or synergistic benefits. However, for functional outcomes such as VO₂peak and muscular performance, exercise remains the primary determinant, and adding dietary modification confers limited additional benefit. Similarly, blood pressure responses to combined interventions vary widely and do not consistently exceed those produced by nutrient-focused dietary patterns alone. Diet and exercise exert complementary but nonredundant effects across cardiometabolic pathways, and their combined advantages depend on the specific clinical outcome targeted. While integrated lifestyle interventions offer the broadest overall benefit, implementing both simultaneously is often constrained by practical and behavioral barriers. A patient-centered, outcome-specific strategy prioritizing diet or exercise based on the individual's metabolic profile, functional status, and readiness may support adherence and provide a scalable path toward multimodal intervention. Such tailored sequencing has the potential to optimize cardiometabolic health and extend healthspan.

To characterize the clinical differences between pre- and postoperative congenital heart disease (CHD)-associated necrotizing enterocolitis (CHD-NEC) and to explore whether these entities represent distinct clinical phenotypes.

Patients with NEC episodes at our institution were retrospectively reviewed, and the NEC episodes were classified as classical NEC, preoperative CHD-NEC, or postoperative CHD-NEC. Clinical characteristics, clinical severity, laboratory data, detection triggers, and hemodynamic background at NEC onset were compared among groups. An exploratory subgroup analysis of postoperative CHD-NEC was performed.

This analysis included 55 NEC episodes in 47 infants, comprising 7 classical NEC, 15 preoperative CHD-NEC, and 33 postoperative CHD-NEC. Preoperative CHD-NEC was associated with a higher perforation rate (26.7% vs. 3.0%), a lower pH (7.35 vs. 7.44), higher lactate levels (26.5 vs. 11.5 mg/dL), and lower antithrombin III levels (51.0% vs. 81.0%) compared with postoperative CHD-NEC. Postoperative CHD-NEC was more often detected on imaging findings, including portal venous gas on ultrasonography (24.2% vs. 0.0%). Meanwhile, preoperative CHD-NEC was more often identified after the onset of a bloody stool (80.0% vs. 42.4%).

CHD-NEC may not be a uniform entity. However, preoperative CHD-NEC and postoperative CHD-NEC differ in terms of clinical severity, detection patterns, and hemodynamic background.

Calcitonin gene-related peptide (CGRP) pathway inhibitors are highly effective migraine preventives, but their long-term cerebrovascular and cardiovascular safety in patients with prior ischaemic events remains uncertain, as such individuals were largely excluded from clinical trials.

We analysed data from a prospective real-world registry of migraine patients treated with CGRP pathway inhibitors at our tertiary Headache Centre. Patients with a history of ischaemic stroke, transient cerebral ischaemic attack, or ischaemic heart disease were included. Clinical characteristics, treatment response, and vascular outcomes were assessed during follow-up.

Among 420 consecutive migraine patients treated with CGRP pathway inhibitors in our registry, 17 (4%) had a history of cerebrovascular and/or cardiovascular disease and met the inclusion criteria. These patients (median age 54.5 years, 76% female; 82% chronic migraine) contributed a total of 31 patient-years of exposure, with follow-up up to 5 years. Median time from event to treatment initiation was 5.0 years (IQR 4.5). 13 patients (76%) achieved ≥ 50% reduction in monthly migraine days (10/14 in chronic migraine; 3/3 in episodic migraine). No recurrent cerebrovascular events or worsening of underlying cardiac disease were observed during treatment. Serial neuroimaging, available in a subset, showed no new ischaemic lesions.

In this small real-world cohort patients with prior cerebrovascular and/or cardiovascular disease, the use of CGRP pathway inhibitors was not associated with new clinical or radiological ischaemic events over 31 patient‑years of follow‑up. These safety findings are reassuring but only exploratory and hypothesis-generating requiring further confirmation.

Audit and feedback (A&F) interventions are strategies used in different health care settings to monitor and improve professional practice and quality of assistance. However, when professional practice needs to be changed, barriers and enablers should be taken into account.

We conducted an online survey, a focus group, and a few interviews after disseminating two reports illustrating 61 key performance indicators (KPIs) describing the management of trauma, acute myocardial infarction and stroke in the Emergency Medical System of a Northeastern Italy Region. The study was conducted in the framework of the EASY-NET Project (NET-2016-02364191).

Novelty, perception, communication, change, data, and pandemics are the primary themes describing the attitude of health care professionals towards an A&F intervention using KPIs.

Improving collaborations and providing specific education should be a primary concern before investing further resources in developing indicators and disseminating results.

Out-of-hospital cardiac arrest (OHCA) is a major cause of mortality, and early bystander cardiopulmonary resuscitation (CPR) is critical for survival. This study assessed OHCA incidence and factors associated with bystander-initiated CPR in the Piedmont region of Northern Italy.

A retrospective cross-sectional analysis was conducted using 2022 administrative data from an Emergency Medical Dispatch Centre serving 851,538 residents. All confirmed OHCA cases were included. Demographic, clinical, and contextual variables were extracted. Descriptive statistics summarized case characteristics, and comparisons between events with and without bystander CPR were performed using chi-square or Fisher's exact tests.

Among 905 confirmed cases, the incidence was 106 per 100,000 inhabitants. Most patients were male (57%), with a mean age of 76 years, and arrests occurred predominantly at home (87%). Bystander CPR was documented in 644 cases, occurring in 39.9%, mainly independently. CPR was more frequent in rural areas (p=0.002) and public settings (p<0.001). Return of spontaneous circulation occurred in 6.4% and was strongly associated with bystander intervention (p<0.001).

Fewer than half of eligible patients received bystander CPR, highlighting gaps in community readiness. Strengthening public training and dispatcher-assisted CPR may improve outcomes.

Low levels of cardiorespiratory fitness are common after stroke and are associated with post-stroke disability and increased risk of secondary stroke. Cardiorespiratory training interventions aim to increase cardiorespiratory fitness, improve physical function, reduce disability, and help prevent future strokes. Clinical guidelines recommend exercise as part of lifestyle modification for secondary prevention, and strongly recommend exercise for rehabilitation. This review is one of three reviews that were originally a single review on physical fitness training for stroke.

The primary objective of this review was to determine whether cardiorespiratory training after stroke has an effect on death, disability, adverse events, risk factors, fitness, walking, and indices of physical function when compared to a non-exercise control.

In April 2025, we searched nine bibliographic databases and two trials registers to identify studies for inclusion in the review. We checked reference lists, tracked citations, and contacted experts.

We included randomised controlled trials comparing cardiorespiratory training interventions with usual care, no intervention, or a non-exercise intervention in people with stroke.

Our critical outcomes were death, disability, adverse events, risk factors, fitness, walking, and indices of physical function, assessed at the end of the intervention and the end of the longest follow-up.

We used the Cochrane RoB 1 tool to assess the risk of bias in the included studies.

The studies evaluated different comparisons (e.g. cardiorespiratory training versus no intervention/waiting list control or versus attention control or versus usual care), which we synthesised into a single comparison: cardiorespiratory training versus control. We used random-effects meta-analysis on arm-level data (risk difference (RD) for dichotomous data, and mean difference (MD) or standardised mean difference (SMD) for continuous data, with 95% confidence intervals (CIs)). For outcome data that we did not meta-analyse, we followed Synthesis Without Meta-analysis (SWiM) guidance. We used GRADE to assess the certainty of the evidence for critical outcomes.

We included 53 studies (2672 participants, with an average age of 61.9 years). Most studies recruited ambulatory participants in the early subacute (7 days to 3 months) or chronic (> 6 months) phases of recovery. Exercise duration recommendations were met in 49 studies, and frequency recommendations in 48. Twenty-eight studies lacked balanced exposure between groups. Programme duration was 12 weeks or more in 16 studies (maximum: 24 weeks). Sixteen studies had a post-intervention follow-up period (12 weeks to 12 months from baseline). One study planned a six-month follow-up but did not report it.

Cardiorespiratory training does not increase or decrease deaths at the end of intervention (RD 0.00, 95% CI -0.01 to 0.01; 36 studies, 1563 participants; high-certainty evidence) or the end of follow-up (RD -0.00, 95% CI -0.02 to 0.02; 10 studies, 713 participants; high-certainty evidence). Cardiorespiratory training may improve indices of disability slightly at the end of intervention (SMD 0.35, 95% CI 0.12 to 0.57; 17 studies, 1073 participants; very low-certainty evidence), but the evidence is very uncertain. Re-expressed using the Barthel Index (0 to 20), the equivalent effect is MD 1.68, 95% CI 0.59 to 2.74. It is unclear if the effect is clinically meaningful (the minimal clinically important difference (MCID) is +1.85). The effect is unclear at the end of follow-up (SMD -0.14, 95% CI -0.36 to 0.08; 5 studies, 347 participants; low-certainty evidence). Cardiorespiratory training does not increase or decrease the incidence of secondary cardiovascular or cerebrovascular events at the end of intervention (RD -0.00, 95% CI -0.03 to 0.02; 8 studies, 544 participants; high-certainty evidence) and probably does not affect them at the end of follow-up (RD -0.02, 95% CI -0.08 to 0.04; 4 studies, 412 participants; moderate-certainty evidence). It is very uncertain whether cardiorespiratory training affects systolic blood pressure (mmHg) at the end of intervention (MD -2.12, 95% CI -5.81 to 1.57; 9 studies, 535 participants; very low-certainty evidence) (MCID -2 mmHg) or follow-up (MD 0.93, 95% CI -4.30 to 6.16; 3 studies, 155 participants; very low-certainty evidence); the 95% CIs include the MCID. Cardiorespiratory training probably results in a slight improvement in cardiorespiratory fitness (VO₂ ml/kg/min) at the end of intervention (MD 2.37, 95% CI 1.39 to 3.36; 13 studies, 608 participants; moderate-certainty evidence); it is unclear if the effect is clinically meaningful (MCID +3.5 ml/kg/min). The effect may be similar at the end of follow-up (MD 2.76, 95% CI 1.36 to 4.16; 5 studies, 237 participants; low-certainty evidence). Subgroup analysis favoured longer interventions. Cardiorespiratory training probably results in a slight increase in comfortable walking speed (metres per second) at the end of intervention (MD 0.08, 95% CI 0.04 to 0.12; 16 studies, 647 participants; moderate-certainty evidence), but the effect is not clinically meaningful (MCID +0.13). The effect is unclear at the end of follow-up (MD 0.02, 95% CI -0.05 to 0.10; 3 studies, 182 participants; low-certainty evidence). Cardiorespiratory training may improve indices of balance at the end of intervention (SMD 0.31, 95% CI 0.15 to 0.47; 18 studies, 772 participants; very low-certainty evidence), but the evidence is very uncertain. Re-expressing using the Berg Balance Scale, the equivalent effect is MD 2.09, 95% CI 1.10 to 3.07; and it is unclear if it is clinically meaningful (MCID of +2). The effect is unclear at the end of follow-up (MD 0.90, 95% CI -1.32 to 3.12; 6 studies, 253 participants; low-certainty evidence). Overall, our certainty about the evidence is limited for most outcomes by imprecision (small number of studies and participants) or risks of bias (e.g. imbalanced exposure doses) or both.

Cardiorespiratory training after stroke does not affect mortality or the incidence of secondary events at the end of the aerobic exercise training programme or end of follow-up. It may increase fitness, reduce disability, increase walking speed, and improve balance at the end of intervention, but it is unclear if these improvements are clinically meaningful. Further well-designed randomised trials are needed to fully understand the potential benefits and long-term effects of cardiorespiratory training and the optimal exercise prescription.

No dedicated funding REGISTRATION: Protocol (and previous versions) available via DOI 10.1002/14651858.CD003316.

Kidney transplantation (KT) is optimal therapy for end-stage renal disease (ESRD), yet cardiovascular events (CVEs) are the top cause of morbidity and mortality in transplant recipients. We aimed to build a preoperative transthoracic echocardiography (TTE)-based predictive model combined with clinical and laboratory indicators to stratify post-transplant cardiovascular risk.

This single-center cohort enrolled 547 ESRD patients receiving KT from 2021 to 2022. Preoperative TTE, clinical and lab data were collected, with 1-year post-transplant CVEs as the primary endpoint. LASSO and multivariate logistic regression screened independent risk factors; ROC, calibration curves and decision curve analysis (DCA) validated model performance.

Overall 17.55% (96/547) patients developed 1-year CVEs. Interventricular septal thickness at end-diastole (IVSTd), pulmonary hypertension (PH), aortic valve calcification (AVC) and diabetes history were independent risk factors. The training set AUC reached 0.776 (sensitivity 61.8%, specificity 79.4%, 95%CI 0.711-0.841), and the testing set AUC was 0.749 (95%CI 0.618-0.880). Calibration curves showed favorable consistency, and DCA proved stable clinical net benefit within the 7%-68% threshold range.

One-year post-transplant CVE incidence remains high. IVSTd, PH, AVC and diabetes are independent predictors. This TTE-integrated model has reliable discrimination and clinical value for non-invasive cardiovascular risk stratification in KT candidates.

Left ventricular ejection fraction (LVEF) recovery after transcatheter aortic valve implantation (TAVI) varies among patients with severe aortic stenosis and reduced LVEF. We characterized serial changes in LVEF and examined their associations with ischemic heart disease (IHD) and baseline left ventricular end-diastolic diameter.

Among 685 patients who underwent TAVI between 2014 and 2024, 121 with native-valve severe aortic stenosis and baseline LVEF < 50% were analyzed. Echocardiography was performed before TAVI, early after TAVI (median, 3 days), and at 1, 6, and 12 months. Serial LVEF recovery was evaluated using linear mixed-effects models incorporating all available post-TAVI measurements.

LVEF improved significantly through 1 year, with a model-estimated increase of 12.3 percentage points (p < 0.001); left ventricular end-diastolic diameter, end-systolic diameter, and mass index also decreased. In multivariable mixed-effects models, IHD, baseline LVEF, baseline left ventricular end-diastolic diameter, and baseline mean aortic valve pressure gradient were associated with serial LVEF recovery. Adjusted recovery was greatest in patients without IHD and with smaller left ventricular end-diastolic diameter and most limited in those with IHD and larger left ventricular end-diastolic diameter.

TAVI was associated with serial LVEF improvement and left ventricular reverse remodeling. IHD and larger baseline left ventricular end-diastolic diameter were associated with limited LVEF recovery.

Echocardiographic assessment of right ventricular (RV) function remains challenging because conventional functional and deformation indices are strongly influenced by loading conditions. Right ventricular myocardial work (RVMW), derived by integrating myocardial deformation with ventricular pressure, has emerged as a potential framework for contextualizing RV mechanics according to afterload. However, its methodology, validation, clinical applications, and readiness for routine use have not been comprehensively mapped.

A scoping review was conducted in accordance with Joanna Briggs Institute methodology and reported according to PRISMA-ScR. MEDLINE via PubMed was systematically searched from inception through August 14, 2026. The search was supplemented by targeted terminology-based searches, backward and forward citation tracking, reference-list screening, and searches using individual RVMW indices. Original human studies quantitatively evaluating echocardiography-derived RVMW were eligible. Data were charted regarding study characteristics, RVMW methodology, pressure source, work indices, validation strategy, clinical application, prognostic value, reproducibility, and methodological limitations.

Thirty-nine studies met the eligibility criteria. The evidence encompassed several related but methodologically distinct RVMW constructs: 27 studies primarily used conventional non-invasive subpulmonary RV pressure-strain-loop analysis, three regional myocardial-work approaches, two systemic-RV myocardial work, two invasive-pressure-integrated approaches, two single-ventricle/Fontan approaches, and three emerging three-dimensional or volume-integrated pressure-strain-volume/pressure-volume methods. These constructs differ in pressure source, ventricular geometry, and mathematical derivation and are not numerically interchangeable. The literature evolved from early physiological and proof-of-concept investigations toward invasive validation, reference-value assessment, disease-specific phenotyping, interventional studies, and preliminary prognostic applications. Pulmonary hypertension represented the most extensively investigated clinical domain, while applications expanded to heart failure, congenital and systemic-RV physiology, mechanical circulatory support, structural interventions, pediatric populations, and physiological adaptation. Substantial heterogeneity remained in strain definition, RV segmentation, pressure estimation, pressure-curve construction, and analytical methodology.

Echocardiography-derived RVMW is a promising integrative framework that contextualizes RV deformation according to prevailing pressure load and may provide complementary information beyond conventional RV functional indices. Current evidence is strongest in pulmonary hypertension, while applications across other cardiovascular and systemic conditions are expanding. Nevertheless, methodological heterogeneity, limited multicenter validation, absence of universally accepted reference values and disease-specific thresholds, and uncertain incremental clinical utility currently preclude routine implementation. Standardized RV-specific methodology and prospective studies demonstrating management-relevant incremental value are required before RVMW can become a routinely actionable echocardiographic measure.