Ischaemic heart disease shows important differences between men and women, requiring an understanding of sex and gender dissimilarities to improve outcomes. This Scientific Statement provides an updated review of the current knowledge from risk factors to prognosis. It discusses the unequal impact of certain traditional risk factors between men and women, along with additional factors, such as hormonal changes and treatments (including those for transgender people and cancer), pregnancy-related complications, and autoimmune diseases, which contribute to the sex-specific risk profiles. Moreover, it outlines functional and structural sex differences in the pathophysiology (e.g. coronary atheroma plaques and burden, coronary dissection, vasospasm, and microvascular disease) with women being more prone to microvascular disease and endothelial dysfunction, while paradoxically experiencing less severe myocardial ischaemia at similar levels of coronary stenosis. The document further addresses the evaluation of diagnostic tools, which often have a male-centric bias, resulting in underdiagnosis in women who also tend to receive less guideline-recommended treatment. Additionally, women can have different responses and side effects to various preventive and therapeutic treatments, potentially contributing to the worse prognosis documented in acute coronary syndromes with obstructive coronary artery disease, particularly at a young age. Considering all these sex and gender differences and the low enrolment of women in randomized controlled trials, questions arise regarding the optimal treatment for women. Addressing sex differences requires conducting sex-specific research to close the knowledge gap. Overall, the Scientific Statement highlights all relevant sex- and gender-specific dissimilarities to advance clinical practice and identify directions for future research to improve guideline recommendations for equitable care.

Background: Disparities exist in the representation of genders in cardiovascular clinical trials. Atrial fibrillation (AF) is associated with significant morbidity and mortality; however, understanding regarding the representation of women in AF-related clinical trials remains limited. Therefore, this systematic review sought to evaluate the representation of women in AF-related clinical trials. Methods: We conducted a systematic review of clinical trials using the PubMed, Scopus, and EMBASE databases from 1996 to January 1st, 2024, focusing on AF-related lifestyle interventions, pharmacological treatments, catheter ablation, and device therapies for AF. Data extraction and analysis encompassed trial characteristics, participant demographics, and funding sources. The primary outcome was the prevalence of female enrollees, quantified through participation-to-prevalence ratios (PPRs). This was estimated overall and stratified by funding source, intervention type, and enrollment region. Results: Of the 103 clinical trials involving 218,322 participants (39.5% female), the PPR ranged from 0.00 to 1.73, with an average PPR of 1.03. Meanwhile, 43% of the trials exhibited female under-representation (PPR, <0.8). University-funded trials showed higher female enrollment (mean PPR, 0.951) compared to industry/government-funded trials (mean PPR, 0.800). No differences were observed in the representation of women when comparing enrollment regions or intervention types. Conclusions: Despite advancements in AF management, gender disparities persist in AF-related clinical trial representation, particularly in industry/government-funded studies compared to university-funded trials. Thus, addressing implicit biases and enforcing sex equality guidelines are critical steps toward more inclusive cardiovascular research.

Background:Females with severe aortic stenosis present with distinct anatomical and clinical characteristics compared to males, which may influence outcomes following transcatheter aortic valve replacement (TAVR). We sought to investigate the prognostic impact of sex-specific differences on short- and long-term outcomes following TAVR. Methods:PubMed, Embase, Scopus, and Web of Science were searched through August 2025 for randomized and observational studies reporting sex-specific outcomes after TAVR. Reconstructed individual patient data from published Kaplan-Meier (KM) curves were used to estimate long-term survival outcomes. Results:Overall, 71 studies involving 481,353 patients were included. Compared with males, females demonstrated a higher short-term risk of adverse outcomes, including 30-day all-cause mortality (hazard ratio [HR]: 1.064, 95% CI: 1.005-1.127; p = 0.033) and stroke/transient ischemic attack (HR: 1.511, 95% CI: 1.317-1.734; p < 0.001). Females were also more likely to experience life-threatening bleeding (risk ratio [RR]: 1.29, 95% CI: 1.03-1.62; p = 0.028), major bleeding (RR: 1.26, 95% CI: 1.13-1.41; p < 0.001), and major vascular complications (RR: 1.66, 95% CI: 1.53-1.81; p < 0.001). Despite these higher periprocedural risks, females demonstrated superior long-term outcomes, with lower all-cause mortality (HR: 0.812, 95% CI: 0.794-0.831; p < 0.001) and cardiovascular mortality (HR: 0.837, 95% CI: 0.784-0.893; p < 0.001) during follow-up extending to 10 years, whereas risks of stroke/transient ischemic attack and myocardial infarction were comparable between sexes. Conclusions:Females undergoing TAVR experience higher early risks of mortality, stroke, bleeding, and vascular complications, but exhibit a sustained long-term survival advantage compared with males, highlighting the need for sex-centered periprocedural management strategies.

AIMS:The growing population of adults with congenital heart disease (ACHD) has prompted global initiatives to define standards of care, training pathways, and institutional requirements for catheter-based interventions. High-quality care and effective training rely on specialized, multidisciplinary centres integrating paediatric and adult cardiologists, surgeons, and anaesthesiologists with congenital expertise, supported by advanced catheter labs and hybrid theatres. This work outlines essential elements for optimal ACHD catheterization training, emphasizing a structured, competency-based curriculum covering theory, procedural skills, and post-procedural care. METHODS AND RESULTS:Collaboration between paediatric and adult cardiologists is highlighted as vital for comprehensive care. To meet national and regional needs, a two-tier model of 'level 1' and 'level 2' centres-each with specific capacities-is proposed. Scientific societies play a key role in establishing guidelines, certifications, and facilitating trainee mobility and international collaboration. Emerging tools such as augmented reality and virtual case libraries can improve accessibility and quality of training. The framework also addresses global equity, considering regional and socio-economic differences. Proctorships and partnerships with industry are integral for introducing innovations and maintaining skills in evolving techniques. CONCLUSION:By fostering collaboration, harmonized standards, and multidisciplinary expertise, this model aims to improve ACHD training and meet growing patient needs.

Background/Objectives: Ultrasound-assisted catheter-directed thrombolysis (USAT) and mechanical thrombectomy (MT) are increasingly used for intermediate-high-risk pulmonary embolism (PE), but real-world comparisons are scarce. We compare 30-day all-cause, cardiovascular, non-cardiovascular, PE-related, and major bleeding events between intermediate-high-risk patients with acute PE treated with USAT or MT. Methods: We analyzed 286 patients with acute intermediate-high-risk PE enrolled in the multicenter USAT IH-PE registry (March 2019-October 2025). Patients underwent USAT (EKOS™, Boston Scientific, Marlborough, MA, USA) or MT (FlowTriever, Inari Medical, Irvine, CA, USA or Indigo, Penumbra, Inc., Alameda, CA, USA) during index hospitalization. Primary endpoints were 30-day all-cause, cardiovascular, and PE-related mortality. Propensity score matching (1:1) balanced baseline characteristics. Kaplan-Meier analyses with log-rank testing assessed time-to-event outcomes. Results: After matching (69 patients per group), baseline clinical and hemodynamic variables were well balanced. Both USAT and MT significantly improved RV/LV ratio, tricuspid annular plane systolic excursion (TAPSE), and PASP (all p < 0.001). Thirty-day all-cause mortality was similar between USAT and MT (13.0% vs. 11.5%; p = 0.78), with no differences in cardiovascular or PE-related mortality (8.6% vs. 1.4%, p = 0.58 and 5.7% vs. 1.4%, p = 0.17, respectively). Major bleeding was infrequent and observed only in the USAT group (4.3%). Conclusions: In this real-world multicenter cohort, USAT and MT showed comparable short-term mortality, safety, and echocardiographic recovery, supporting individualized catheter-based reperfusion strategies for intermediate-high-risk PE.

Aims Despite an overall decline in cardiovascular mortality in recent years and advances in diagnosis and treatment, acute coronary syndromes (ACS) remain a leading cause of morbidity and mortality among women worldwide. Sex-specific risk factors and mechanisms remain under-recognized and complicate early diagnosis and management.Methods and results The GEDI-ACS registry (PNRR-MCNT2-2023-12377431; NCT06441942) is a prospective, multicentre, non-randomized clinical study aiming to identify the phenotypic and genetic profiles of women with ACS. The study is enrolling 100 consecutive women presenting with ACS (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, or unstable angina) in Northern and Southern Italy. In these patients, comprehensive clinical, imaging, biochemical, and molecular phenotyping (including whole exome sequencing, transcriptomics, proteomics, and metabolomics) will be performed. Data on socioeconomic status, health literacy, and awareness of cardiovascular risk factors will be collected through standardized questionnaires. Follow-up, scheduled at 1 and 12 months, will assess clinical outcomes, quality of life, adherence to therapies, and lifestyle modifications.Conclusion The GEDI-ACS registry will provide novel insights into the sex-specific profile of ACS by integrating clinical, genetic, molecular, and socioeconomic data from female patients. The results may support the development of personalized interventions that account for gender diversity.

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.

Background The optimal revascularisation strategy for patients undergoing percutaneous coronary intervention (PCI) after transcatheter aortic valve implantation (TAVI) remains undefined. In particular, the prognostic impact of complete revascularisation (CR) versus incomplete revascularisation (ICR) in this setting is unknown. Aims To evaluate the long-term clinical outcomes of CR versus ICR in patients undergoing PCI after TAVI. Methods We analysed 447 patients from the multicentre, international Revascularization After Transcatheter Aortic Valve Implantation (REVIVAL) registry who underwent PCI after TAVI between 2008 and 2023. Patients were classified as CR or ICR according to the presence of residual significant stenosis following PCI. The primary endpoint was the 4-year incidence of major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction or stroke. The Kaplan-Meier method was used to estimate cumulative event rates, and a weighted Cox regression model employing an entropy balance approach was used to adjust for possible confounders. Results ICR was achieved in 132 patients (29.5%) and CR in 315 patients (70.5%). The mean follow-up after PCI was 1065±904 days (1213±938 in the ICR group; 1002±883 in the CR group). The crude 4-year incidence of MACE was 35.0% with ICR and 34.7% with CR (HR 0.93, 95% CI 0.62 to 1.39, p=0.710). Adjusted analysis confirmed no significant difference (32.5% vs 34.1%; HR 1.01, 95% CI 0.62 to 1.64, p=0.971). Conclusion In this registry, CR after TAVI was common but not associated with improved outcomes compared with ICR. These results support a selective rather than systematic pursuit of CR in elderly, high-risk post-TAVI patients.

High-risk percutaneous coronary interventions (HR-PCI) are increasingly common, and mechanical circulatory support (MCS) has emerged as a potential adjunct to improve patient outcomes. However, data comparing MCS to standard care remain limited. This study evaluates the impact of microaxial flow pump (m-AFP)-supported HR-PCI in left main (LM) disease on achievement of complete revascularization and on mortality at follow-up. The standard-of-care (SOC) cohort was derived from the Delta (Drug Eluting Stent for Left Main Coronary Artery) 2 Registry and included all patients with distal LM bifurcation disease and left ventricular ejection fraction (LVEF) <40%. The m-AFP population was extracted from the IMP-IT (IMPella Mechanical Circulatory Support Device in Italy) Registry and comprised patients with severe LM stenosis who underwent HR-PCI with m-AFP support. Baseline characteristics were compared to assess key differences between the two populations. The primary endpoint was complete revascularization, defined as treatment of all identified diseased vessels. Mortality was assessed at follow-up using Kaplan-Meier analysis. A total of 414 patients were included in the analysis (332 form the Delta 2 and 82 from the IMP-IT Registry). Baseline characteristics such as age, body mass index, hypertension, dyslipidemia and diabetes were comparable between the two cohorts. Baseline creatinine and LVEF did not differ (1.38±1.5 vs 1.63±1.7mg/dl and 32.3±11.4 vs 32.3±7%). SOC patients had more frequently suffered from myocardial infarction (36.5 vs 52.7%, p=0.009). Upon coronary angiography, the rate of three-vessel disease was higher among the m-AFP patients (71.6 vs 34.0%, p<0.001). Despite a higher burden of coronary artery disease, patients in the m-AFP cohort were more likely to achieve complete revascularization, and this association remained significant after adjusting for prior MI (45.6% vs. 23.9%, OR 2.71, 95% CI 1.62–4.55, p<0.001). At a comparable median follow-up, the m-AFP cohort showed a numerical trend toward lower mortality (15.4% vs. 25.3%, HR 1.70, 95% CI 0.93–3.13, p=0.087). In HR-PCI for LM disease, m-AFP support was associated with a higher likelihood of achieving complete revascularization. A numerical trend towards lower mortality was also observed.

BACKGROUND:Despite rapid percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), large infarcts contribute to heart failure and mortality. Left ventricular (LV) wall tension and load are major determinants of infarct size. Preclinical studies identified that delaying reperfusion to permit LV unloading with a transvalvular microaxial flow pump (TV-mAFP) reduces infarct size. We tested whether this combination reduces infarct size compared with reperfusion alone in patients with anterior STEMI without cardiogenic shock. OBJECTIVES:The STEMI-Door to Unload (DTU) pivotal trial tested the central hypothesis that the combination of mechanical LV unloading plus a 30-minute delay before PCI reduces infarct size compared with immediate PCI alone in patients with anterior STEMI without cardiogenic shock. METHODS:We conducted an open-label, randomized controlled trial at 55 hospitals in the United States, Germany, Italy, United Kingdom, Switzerland, and Canada. Adults aged 18 to 85 years with no prior myocardial infarction and presenting with acute anterior STEMI within 1 to 6 hours of symptom onset before hospital arrival were eligible for inclusion. Patients were randomly assigned (1:1) by study site personnel to either LV unloading with a TV-mAFP for 30 minutes before PCI (treatment group) or PCI alone (control group). The primary outcome was infarct size normalized to LV mass (IS/LVM) evaluated by cardiac magnetic resonance imaging 3 to 5 days after PCI and was evaluated in all randomized patients. The trial is closed to new participants. RESULTS:Between December 12, 2019 and September 3, 2024, 527 patients were randomized; 262 patients were assigned to the treatment group and 265 to the control group. Mean patient age was 61 ± 11 years, and 417 patients (79.1%) were men. Total ischemic time was longer in the treatment arm. IS/LVM was 30.8% ± 16.2% in the treatment group and 31.9% ± 16.9% in the control group (mean difference: -1.1%; 95% CI: -4.2 to 2.0; P = 0.50). Major bleeding or vascular complications at 30-day follow-up occurred more frequently in the treatment group when compared with either a prespecified performance goal or the control group. CONCLUSIONS:Combination of a TV-mAFP plus delayed PCI did not reduce infarct size in patients with anterior STEMI without cardiogenic shock compared with PCI alone. (Primary Unloading and Delayed Reperfusion in ST-Elevation Myocardial Infarction: The STEMI-DTU Trial [DTU-STEMI]; NCT03947619).

Cardiovascular disease is the leading cause of death in women, yet significant disparities persist in diagnosis, treatment, and research representation. This clinical consensus statement outlines the rationale and framework for establishing women's heart centres (WHCs) in Europe. Women's heart centres are proposed as hub-and-spoke reference networks embedded within existing cardiovascular systems, delivering multidisciplinary, sex-sensitive care across the life course. The document defines referral pathways, operational standards, and core and advanced training competencies in women's cardiovascular health. Key domains include ischaemia/myocardial infarction with non-obstructive coronary arteries, cardio-obstetrics, cardio-oncology, autoimmune disease, mental health, and cardiac rehabilitation. Implementation strategies emphasize scalable models, integration with primary care, telemedicine, quality improvement, and research engagement. Although long-term outcome data remain limited, available evidence suggests improved diagnostic precision, risk factor control, and patient-reported outcomes. Establishing WHC offers a structured approach to reduce inequities and strengthen cardiovascular care for women across Europe.

Conventional risk factors do not completely explain the burden of atherosclerotic cardiovascular disease (ASCVD) in women. Obesity and chronic low-grade inflammation are recognized as important contributors to atherosclerotic risk. This viewpoint explains the role of obesity-driven inflammation in the development and management of atherosclerosis in women. Abdominal obesity promotes a proinflammatory and prothrombotic environment that accelerates atherogenesis. Women with higher inflammatory biomarker levels and experience sex-specific risk-modifying stages, such as polycystic ovary syndrome, pregnancy-related conditions, and menopause, have higher risk for cardiovascular events, including atherosclerosis. We review evidence for antiobesity and anti-inflammatory therapies. Integrating obesity and inflammation into ASCVD care in women requires targeted screening, risk assessment, and sex-stratified research approaches. This viewpoint highlights the relation between obesity and atherosclerosis.

Aims:Patients with cancer have an increased risk of cardiovascular (CV) events, although there is limited data on future trends in cancer prevalence amongst patients with an acute cardiovascular admission. The aim of this study was to evaluate trends in cancer prevalence among CV admissions with an attempt to predict future cancer and CV co-morbidity over the next 20 years. Methods and results:The analysis included all hospital admissions with a primary CV diagnosis from the US National Inpatient Sample (NIS), from 2016 to 2020. The sample was stratified by specific CV admission and by cancer status and type. The chi-square and the Kruskal-Wallis tests were used to compare categorical and continuous data, respectively, across the years. A Poisson regression model was used to predict the prevalence of overall and specific cancer types through 2040, based on the 5-year baseline period. Among 4.79 million CV admissions from 2016 to 2020, there was a significant increase in cancer prevalence from 4.8% to 5.4% (P < 0.001). This upward trend was observed across all CV diagnoses. Predictive modelling estimates that cancer prevalence in CV inpatients will increase from a 4.8% baseline in 2016 to 11.9% by 2040, with the most pronounced rate of growth seen in liver (IRR 1.069; P < 0.001), breast (IRR 1.056; P < 0.001), and renal cancer (IRR 1.055; P < 0.001). Nevertheless, haematological and lung cancers show the highest prevalence, both at baseline and in 2040. Conclusion:The prevalence of cancer among patients hospitalized with CV disease is predicted to increase 2.48-fold by 2040. This trend highlights the importance of integrated cardio-oncology and multidisciplinary care models.