PURPOSE:The aim of this study was to examine the incremental value of three-dimensional transesophageal echocardiography (3DTEE) versus two-dimensional transesophageal echocardiography (2DTEE) in the detection of prosthetic valve endocarditis (PVE), its prognostic value, and its peculiar diagnostic features compared to native valve endocarditis (NVE). METHODS:One hundred and twenty-nine patients with infective endocarditis (64 PVE and 65 NVE), selected from a population of one hundred and ninety-five patients with suspected PVE or NVE, were studied using 3DTEE and 2DTEE. Presence, location and size of vegetations, new or progressive valve regurgitation, perivalvular extension, and new dehiscence of valve prosthesis were assessed. RESULTS:A definite diagnosis of infective endocarditis was obtained by using 2023 Duke-ESC criteria. Significant improvement in global χ2 value was noted with the addition of 3DTEE parameters compared with 2DTEE alone for PVE detection (from 81.7 to 92.3, p=0.002) and for prediction of in-hospital mortality (from 79.3 to 86.7, p=0.01). In patients with prosthetic valves and surgical confirmation of the diagnosis, 2DTEE and 3DTEE showed a sensitivity of 84.8% and 90.1%, a specificity of 74.2% and 84.3% (p=0.001), a positive predictive value of 89.6% and 93.4%, and a negative predictive value of 76.3% and 85.6% (p=0.003) for PVE detection. Regarding the detection of PVE- and NVE-related valvular and perivalvular lesions according to surgery findings, Receiver Operating Characteristic (ROC) curve analysis showed similar diagnostic performance of three-dimensional transesophageal echocardiography (3DTEE) for valvular complications (AUC = 0.727 vs. 0.897, p = 0.704) and superior diagnostic performance for perivalvular complications, both in mechanical and biological prostheses (AUC = 0.831 vs. 0.516, p = 0.012, and AUC = 0.836 vs. 0.697, p = 0.026, respectively). These results were particularly marked in early PVE compared to late PVE (AUC = 0.883 vs. 0.478, p = 0.001). CONCLUSIONS:Our results suggest that 3DTEE provides additional diagnostic and prognostic information for patients with PVE and higher diagnostic performance for perivalvular complications compared to NVE.

BACKGROUND:Transcatheter aortic valve implantation (TAVI) is increasingly performed in younger and lower-risk patients. Since many of these patients will outlive their transcatheter heart valve (THV), redo-TAVI procedures are expected to rise in number. Yet, real-world evidence on the procedural safety and efficacy of redo-TAVI remains limited. AIMS:We aimed to evaluate the 30-day procedural and clinical outcomes of redo-TAVI using the balloon-expandable SAPIEN 3 platform. METHODS:The ReTAVI registry is a prospective, international study enrolling consecutive patients with a failed aortic THV undergoing redo-TAVI with a balloon-expandable SAPIEN 3 THV. Data were collected across 59 international centres. All imaging was centrally analysed, and major clinical events were adjudicated by an independent committee. RESULTS:â¨A total of 143 patients (median age 84 years; 40.6% female; median Society of Thoracic Surgeons risk score 7.0%) were enrolled. The predominant failing THVs were balloon-expandable SAPIEN 3 (30.1%), self-expanding CoreValve/Evolut (53.1%), and ACURATE (14.0%) platforms. The most common failure mode was isolated regurgitation (48.6%), followed by stenosis (35.2%) and a mixed pathology (16.2%). The replacement valve was successfully implanted in 95.1% of patients, with a 30-day mortality rate of 3.5%. The 30-day stroke and pacemaker implantation rates were 0.7% and 6.3%, respectively. Redo-TAVI significantly improved valve haemodynamics, with mean gradients decreasing overall (Δ=-12.0 mmHg), and a more pronounced reduction in stenotic failures (Δ=-29.0 mmHg). Coronary obstruction was observed in 1.4% of cases. CONCLUSIONS:Redo-TAVI with a balloon-expandable SAPIEN 3 THV platform is a safe and effective reintervention strategy across diverse failed THV types, when guided by the Heart Team, standardised procedural planning, and comprehensive imaging. CLINICALTRIALS:gov: NCT05601453.

Heart failure (HF) is a complex systemic syndrome for which the HLM staging system has been proposed to better capture disease complexity. This study investigated the prognostic role of HLM staging according to SGLT2i status and the impact of in-hospital SGLT2i therapy across different stages of HF severity. In this prospective, multicenter, observational study, consecutive patients hospitalized for HF between November 2022 and August 2025 were enrolled and stratified according to HLM stage and according to SGLT2i status at discharge. The primary endpoint was the composite of cardiovascular (CV) death or HF hospitalization at 6-month follow-up. A total of 711 patients were included. The primary endpoint occurred in 82 patients with a significant increase across HLM stages (p < 0.001). Increasing HLM stage was associated with higher risk of adverse outcomes (HR = 1.40; 95% CI 1.02-1.90; p = 0.03), regardless of SGLT2i status. SGLT2i therapy initiation within the index hospitalization was independently associated with a lower risk of the composite endpoint (HR = 0.59; 95% CI 0.38-0.92; p = 0.02) across the HLM severity stages. In this cohort of HF patients, the HLM staging system provided potential clinically meaningful risk stratification irrespective of SGLT2i therapy, and SGLT2i therapy was associated with improved outcomes irrespective of HLM severity. These observations suggest a potential role for integrated pathophysiological staging in risk assessment and therapeutic evaluation.

The prognostic role of high-risk plaque (HRP) features, including high coronary calcium scores detected by CT, beyond traditional cardiovascular risk factors and obstructive coronary artery disease (CAD), remains uncertain. This study evaluated the prognostic value of a combined HRP definition in stable chest pain patients with low-to-intermediate pretest probability of CAD. This prespecified analysis included participants randomized to the CT arm of the pragmatic, prospective 26-center European DISCHARGE trial (NCT02400229). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, nonfatal myocardial infarction, or stroke); the secondary endpoint was expanded MACE (transient ischemic attack and major procedure-related complications). Our combined HRP definition was any coronary plaque with positive remodeling, napkin-ring sign, low attenuation, or total calcium score ≥ 400 Agatston units. Among 1745 participants (age: 60 ± 10 years, 990 female), 35 MACE and 47 expanded MACE occurred at a median follow-up of 3.5 years (IQR: 2.9–4.2). After risk factor adjustment, the combined HRP definition was associated with a higher risk of MACE (HR: 3.81; 95

BACKGROUND:Long-term oral anticoagulation remains the standard of care for patients with atrial fibrillation, despite the non-negligible risk of bleeding. Percutaneous left atrial appendage closure (LAAC) has emerged as an alternative strategy for preventing stroke with inconclusive modern data. AIMS:Our aim was to evaluate the comparative efficacy and safety of LAAC vs. medical therapy in patients with atrial fibrillation. METHODS:A systematic search of PubMED, Scopus and EMBASE was conducted up to April 2026 to identify randomized controlled trials comparing LAAC with medical therapy. The primary endpoint was overall stroke. The secondary endpoints were ischemic stroke, hemorrhagic stroke, systemic embolism, mortality, major bleeding and non-procedural bleeding. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model with restricted maximum likelihood estimation and Hartung-Knapp adjustment. RESULTS:Six randomized controlled trials, encompassing 7004 patients globally (device group: 3681 patients; medical therapy group: 3323 patients), were included in the analysis. LAAC was associated with a similar risk of stroke to medical therapy (OR, 0.92; 95% CI, 0.65-1.3; P = 0.55) at a median 39 (interquartile range 36-47) months of follow-up. No significant differences were observed in ischemic stroke, hemorrhagic stroke, systemic embolism, all-cause mortality or cardiovascular mortality. Rates of major bleeding were comparable (OR, 1.13; 95% CI, 0.90-1.43; P = 0.23). However, medical therapy was associated with a significantly higher risk of non-procedural bleeding compared with LAAC (OR, 1.95; 95% CI, 1.67-2.27; P <0.001). These findings were consistent across subgroup analyses. CONCLUSIONS:LAAC provides thromboembolic protection comparable to medical therapy while reducing non-procedural bleeding. These findings support its role as an alternative strategy in selected patients at increased bleeding risk.

Background The optimal duration of antiplatelet therapy (APT) after patent foramen ovale (PFO) device closure remains uncertain. Objectives This study aimed to evaluate the impact of APT duration on long-term outcomes after PFO closure. Methods PROLONG (PFO Transcatheter Occlusion Long-Term Outcomes National Group; NCT06504121) is a multicenter retrospective registry of patients who underwent PFO device closure between 1999 and 2013 at 12 Italian centers. This analysis included patients with successful PFO closure, no significant residual shunt, and no other indication for long-term antithrombotic therapy. Patients were categorized by APT duration after PFO closure in the discontinuation group (≤12 months) or the continuation group (>12 months). The primary outcome was net adverse clinical events (NACE), a composite of ischemic events (ischemic stroke, transient ischemic attack, or systemic embolism) and major bleeding (Bleeding Academic Research Consortium ≥3). Inverse probability of treatment weighting was applied for baseline confounders. Results Among 940 patients (mean age 47 ± 12 years; 55% women) followed for 14.0 ± 3.1 years, the cumulative incidence of NACE was 3.6% in the APT discontinuation group and 7.2% in the APT continuation group (adjusted HR [aHR]: 0.71; 95% CI: 0.38-1.37; P = 0.31). Ischemic events were similar (3.1% vs 4.3%; P = 0.66), while major bleeding was lower in the APT discontinuation group (0.9% vs 2.8%; P = 0.014). APT discontinuation was associated with lower NACE in patients with Risk of Paradoxical Embolism (RoPE) score ≥7 (aHR: 0.32; 95% CI: 0.11-0.90; P = 0.039), but not in those with RoPE <7 (aHR: 1.07; 95% CI: 0.49-2.35; P = 0.89; P for interaction = 0.089). Conclusions In patients with a RoPE score ≥7, early discontinuation of APT after effective PFO closure was associated with a lower incidence of NACE at long-term follow-up.

OBJECTIVES:Failed transradial approach (TRA) in patients undergoing percutaneous coronary procedures is associated with higher rates of vascular complications. While female sex is associated with an increased risk of failed TRA, it is unknown if females are also exposed to an increased risk of adverse events after access crossover. The authors compared the outcomes of males and females experiencing crossover following a failed TRA. METHODS:The REPEAT study prospectively enrolled patients undergoing coronary procedures through TRA with access failure. In this subanalysis, patients were stratified according to sex. Propensity score matching for major confounders was used to generate comparable groups. The primary outcome was a composite of vascular complication and significant bleeding. RESULTS:Of 462 patients experiencing TRA failure, 245 were male and 217 female. Female patients were older and showed fewer comorbidities. TRA failure was more commonly related to radial tortuosity in females and subclavian tortuosity in males. After propensity score matching, 123 pairs were selected. Females showed higher rates of femoral crossover compared with males, in whom a contralateral radial access is mostly preferred. The incidence of the primary outcome was comparable between the 2 groups (males: 8.1% vs females: 12.2%; odds ratio [OR], 1.57; 95% CI, 0.68-3.64; P = .294). Consistent results were evident in a sensitivity analysis on patients undergoing cross over to femoral access (males: 14.5% vs females: 13.0%; OR, 0.8; 8 95% CI, 0.33-2.33; P = .805). CONCLUSIONS:In patients experiencing a failed TRA, no statistically significant differences were evident in terms of vascular complications or bleeding between females and males.

Interindividual variability in response to aspirin remains a major challenge in antiplatelet therapy. Identification of patients with high (HPR), optimal (OPR) or low platelet reactivity (LPR) remains challenging and may be influenced by both biological and methodological factors, including interlaboratory variability. We report results of a large cohort of aspirin-treated patients to assess the gold standard light transmission aggregometry (LTA). We retrospectively analyzed 3,065 patients treated with aspirin (ASA; 75-150 mg/day) who sequentially underwent LTA assessment using multiple agonists (ADP 2μM, collagen 2 μg/mL, arachidonic acid [AA] 0.75 mM, epinephrine 10μM). Patients were stratified according to AA-induced platelet aggregation using a 16% cut-off (third quartile). Patients with AA >16% showed significantly higher platelet aggregation across all agonists (p<0.0001). However, a substantial proportion of patients with AA ≤16%, consistent with effective COX-1 inhibition, still exhibited high platelet reactivity when stimulated with ADP, epinephrine or collagen. Collagen-induced aggregation was particularly informative in identifying residual platelet reactivity. Sex-related differences were observed, with females showing higher platelet reactivity, especially to ADP and collagen. Platelet reactivity in aspirin-treated patients is highly heterogeneous, with hyper- or hypo-reactive phenotype potentially affecting the safety and efficacy of antiplatelet therapy. AA-induced aggregation alone is insufficient to fully characterize platelet responsiveness. A multiagonist approach, particularly including collagen, may improve identification of patients with residual platelet reactivity and support personalized antiplatelet strategies. These data support ongoing strategies of guided selection of antiplatelet therapy in patients with cardiovascular disease.

BACKGROUND:Intravascular imaging modalities such as optical coherence tomography (OCT), intravascular ultrasound (IVUS) and near-infrared spectroscopy allow the detection of vulnerable coronary plaques, which may predict the risk of future major adverse cardiovascular events (MACEs). However, the prognostic relevance of specific plaque characteristics remains incompletely defined. OBJECTIVES:This updated meta-analysis aimed to identify the most reliable intracoronary imaging-derived parameters for predicting MACE in untreated coronary lesions. METHODS:A systematic search of PubMed, Scopus and Google Scholar was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines to identify adjusted observational studies reporting the prognostic impact of plaque vulnerability features assessed by OCT or IVUS. The primary outcome was study-defined MACE. HRs were pooled using random-effects or fixed-effects models depending on heterogeneity. Subgroup and sensitivity analyses were conducted to explore the impact of imaging modality and plaque feature definitions. RESULTS:12 studies including 8453 patients and 22 319 lesions were analysed. All investigated plaque features were significantly associated with an increased risk of MACE. Among predictors, thin-cap fibroatheroma (TCFA) demonstrated the lower positive association (HR 3.06, 95% CI 1.97 to 4.77), while plaque burden showed the highest (HR 3.92, 95% CI 1.45 to 10.59). IVUS-derived parameters (minimum lumen area and high-risk plaque definition) were superior to their OCT counterparts, whereas OCT better discriminated prognostic TCFA. The combination of minimum lumen area, TCFA and lipid arc yielded the strongest predictive performance for MACE risk. CONCLUSIONS:Intracoronary imaging-derived plaque features are significantly associated with future cardiovascular events. Multiparametric models integrating compositional and morphological features apparently enhance risk stratification compared with single parameters. PROSPERO REGISTRATION NUMBER:CRD420251047286.

BACKGROUND:Complete revascularization is recommended for patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, the optimal timing of non-culprit lesion percutaneous coronary intervention (PCI) remains controversial, ranging from treatment during the initial procedure to several weeks after the acute event. AIMS:We systematically searched MEDLINE, Scopus, and EMBASE through September 2025 for randomized controlled trials comparing immediate vs. staged complete revascularization with drug-eluting stents in patients presenting with STEMI and multivessel coronary artery disease undergoing primary PCI. METHODS:The primary endpoint was death from cardiac causes at a median follow-up of 12 months. Secondary endpoints were all-cause mortality, recurrent non-fatal myocardial infarction (MI), any unplanned revascularization, target-vessel revascularization, target-lesion revascularization, major bleeding, acute kidney injury, and stroke. RESULTS:Six randomized controlled trials including 2837 patients (1441 immediate and 1446 staged) were analyzed. At 12 months, death from cardiac cause occurred at comparable rates between strategies (risk ratio [RR], 0.99; 95% confidence interval [CI], 0.98-1.01; P = 0.33). No significant differences were observed for all-cause mortality (RR, 0.99; 95% CI, 0.97-1.00; P = 0.13), non-fatal MI (RR. 1.01; 95% CI, 0.99-1.04; P = 0.17), target vessel revascularization (RR, 1.00; 95% CI, 0.98-1.01; P = 0.48), or target lesion revascularization (RR, 1.00; 95% CI, 0.99-1.02; P = 0.34). Similarly, no differences were found for stroke (RR, 1.00; 95% CI, 0.99-1.01; P = 0.75), major bleeding (RR, 1.01; 95% CI, 0.99-1.03; P = 0.21), or AKI (RR, 1.00; 95% CI, 0.99-1.03; P = 0.79). Immediate complete revascularization may be associated with a trend towards lower rates of unplanned revascularization compared with staged PCI (RR, 0.97; 95% CI, 0.93-1.01; P = 0.09). CONCLUSIONS:In patients with STEMI and multivessel coronary disease, an immediate complete revascularization strategy showed comparable rates of death from cardiac cause and non-fatal MI as compared with staged complete revascularization at a median of 12 months of follow-up.

Aims:To compare outcomes of patients with severe mitral regurgitation (MR) after m-TEER and surgery. Methods and results:PubMed, Scopus, and Google Scholar databases were searched for randomized controlled trials and propensity score matching studies comparing mid-term outcomes of m-TEER vs. surgical valve repair. All-cause of death, rehospitalization for heart failure, mitral reintervention, NYHA class at clinical follow-up and grade ≥ 3 at echocardiographic follow-up were the outcomes of interest. Additional sensitivity analyses were performed to account for heterogeneity. Nine studies (2 RCT and 7 propensity score matching studies) with a total of 23 825 patients (m-TEER group = 11 970; surgery group = 11 855) were included. Surgery and m-TEER were associated with comparable rates of all-cause mortality at a median follow-up of 18 months (RR 1.02, 95%CI 0.77-1.37, P-value 0.87). Surgical repair was associated with a reduced risk of rehospitalization for heart failure (RR 1.70, 95%CI 1.47-1.98, P value < 0.01) and mitral reintervention (RR 3.27, 95%CI 2.49-4.30, P value < 0.01), due to a reduced at least moderate residual MR (RR 6.35, 95%CI 1.43-28.22, P value 0.02). Conclusion:In patients with severe MR, m-TEER resulted in comparable outcomes for all-cause deaths compared to surgery, although the latter was associated with reductions in heart failure rehospitalization, reintervention and MR residual rates at a median 18-month follow-up.

AIMS:Emerging evidence suggests sex-specific differences in platelet biology and clinical responses to antiplatelet agents. Light transmission aggregometry (LTA) represents the historical gold standard for the assessment of platelet reactivity but is influenced by pre-analytical and analytical variables. We analysed a large dataset of patients undergoing LTA using a standardized methodology to investigate the impact of sex on platelet reactivity with or without antiplatelet therapy. METHODS AND RESULTS:Between 2004 and 2022, 11,913 patients sequentially underwent LTA assessments following stimulation with adenosine diphosphate (ADP) (2 µM), collagen (2 µg/mL), arachidonic acid (AA, 0.5 mM), and epinephrine (10 µM). After applying study entry criteria, 5687 patients were included: 428 healthy volunteers (HV, F = 273; M = 155), 1055 controls (CTR; F = 725; M = 330), 3289 aspirin-treated patients (ASA; F = 2058; M = 1231), 430 clopidogrel-treated patients (CLOP; F = 272; M = 158), and 485 patients on dual antiplatelet therapy (DAPT; F = 166; M = 319). Within each group, results were analysed and compared between males and females.Females exhibited significantly greater platelet reactivity in response to ADP compared to males in the HV (P = 0.004), CTR (P < 0.0001), ASA (P < 0.0001), and CLOP (P < 0.018) groups, but not in the DAPT group. Among aspirin-treated patients, females showed increased platelet reactivity (P < 0.0001) in response to collagen, compared with males. CONCLUSION:Females exhibit heightened baseline ADP-dependent platelet reactivity and a diminished response to aspirin and clopidogrel monotherapy compared to males.

Abstract Background Although most patients with early repair of an isolated atrial septal defect (ASD) have resolution of right ventricular (RV) dilatation, some studies show persistent RV dysfunction and reduced maximal exercise capacity in long-term follow-up in a considerable subgroup of patients. Purpose Right ventricular myocardial work (RVMW) is a novel method for non-invasive assessment of right ventricular (RV) function using RV pressure-strain loops. We sought to evaluate RV function by RVMW indexes in adult patients with atrial septal defect (ASD) before and six months after transcatheter closure in order to assess their value compared to RV three-dimensional(3D) volumetric indexes and two-dimensional(2D)-Doppler parameters. Methods Fifteen ASD patients before and after percutaneous closure were studied using a commercially available cardiovascular ultrasound system (Vivid E95, GE Vingmed Ultrasound, Norway). 15 healthy age- and sex-matched subjects were selected as controls. RV volumes and ejection fraction (3D-RVEF) were obtained using a software package (4D Auto RVQ). 2D-Doppler parameters of RV function (fractional area change -FAC-, tricuspid annular plane systolic excursion -TAPSE-, myocardial performance index -MPI-) were calculated. RV global longitudinal strain (RVGLS) was evaluated by tracing the RV free wall and interventricular septum. Pulmonary artery systolic pressure (PASP) was estimated by tracing the tricuspid regurgitation velocity-time integral. RV global work index (RVGWI), RV global constructive work (RVGCW), RV global wasted work (RVGWW), and RV global work efficiency (RVGWE) were analysed. Datasets were digitally stored and analyzed offline using GE EchoPAC Version-R6. Peak oxygen consumption(VO2) derived from symptom-limited treadmill tests was obtained. Results Overall, 3D-RVEF, RVGWI and RVGWE were significantly higher than control group in open ASD (p=0.02) and decreased significantly six months after closure (p=0.03). NYHA class improved from 1.9±0.4 before to 1.2±0.5 after closure (p<0.05). In 5 patients (33%) 3D-RVEF was reduced and RV was dilated compared to controls six months after closure (p=0.04 and p=0.02, respectively). RVGWI was significantly correlated with RVGLS (p<0.001), PASP (p=0.002), and TAPSE (p=0.014). By multivariate analysis RVGWE and 3D-RVEF were independent predictors of functional class. ROC analysis showed RVGWE and 3D-RVEF (AUC 0.8917 and 0.8869, respectively) to be more sensitive predictors of unfavorable outcome after defect closure (VO2 ≤16mL/min/kg) compared to FAC, TAPSE, and MPI (AUC 0.7586, 0.7824, and 0.7963, respectively). Conclusions In ASD patients before and after closure, right ventricular myocardial work provides useful insights into the quantitative assessment of RV function. RVMW findings are comparable to RV-3D volumetric parameters as predictors of impaired exercise impairment and more accurate than 2D parameters.