INTRODUCTION:In heart failure (HF) patients, guidelines recommend scores for assessing outcomes and heart transplant (HTX) eligibility. However, scores use remains limited and cut-off values for HTX listing not well established.Among the available tools, MECKI score is easy to calculate and likely offers the best prognostic accuracy. Compare MECKI score-based survival with that of HTX recipients and identify a MECKI threshold above which survival is inferior to that of HTX recipients at 5-year. METHODS:Consecutive ambulatory HF patients enrolled in MECKI score programme between January 2010 and January 2022 were evaluated. Primary endpoint was a composite of cardiovascular death, HTX, or left ventricular assist device implantation. Heart transplant survival data were obtained from the International Society of Heart and Lung Transplantation registry updated through 2023. To identify the MECKI score threshold beyond which prognosis is worse than that of HTX recipients, patients were stratified by deciles of MECKI score. RESULTS:We analysed 3865 HF patients (mean age 62.4 ± 12.6 years). Peak VO₂ was 58.2 ± 18.3% predicted; VE/VCO₂ slope 33.2 ± 8.2, haemoglobin 13.5 ± 1.7 g/dL, Na⁺ 139 ± 3 mmol/L, LVEF 33.7 ± 10.4%, and eGFR 73 ± 26 mL/min/1.73 m². Periodic breathing occurred in 15.8% of patients. At 5 years, mean survival was 83.7%.The average 5-year survival of HTX recipients (71.2%) lies between the eighth and ninth MECKI score deciles suggesting a MECKI score value ≥0.1368 as the proper cut-off for HTX listing. CONCLUSION:MECKI score ≥0.1368 may warrant HTX listing, while lower scores support clinical deferral.

Climate change represents an escalating global health crisis that profoundly influences the risk factors for cardiovascular disease (CVD). Human-driven alterations in climate-including rising ambient temperatures, more frequent and severe heatwaves, air pollution, and extreme weather events-directly and indirectly exacerbate hypertension, diabetes, hyperlipidaemia, and physical inactivity. Exposure to high temperatures and pollution promotes vascular dysfunction, inflammation, and oxidative stress, leading to worsened blood pressure control, dysglycaemia, and disrupted lipid metabolism. Extreme weather events, floods, and wildfires trigger acute spikes in cardiovascular events through dehydration, myocardial ischaemia, and arrhythmias, while also disrupting healthcare delivery and medication adherence. Moreover, climate-driven changes in food systems and nutritional quality exacerbate unhealthy dietary behaviours, further amplifying cardiometabolic risk. Vulnerable populations-including older adults, racial and ethnic minorities, and those of lower socioeconomic status-bear a disproportionate burden of these effects. Mitigating the cardiovascular consequences of climate change requires integrated approaches that incorporate climate-sensitive risk stratification, targeted education of patients and clinicians, and adaptive health system responses. Primary care physicians play a central role in delivering anticipatory guidance and equitable care to at-risk individuals. This review synthesizes evidence linking climate change with CVD risk profiles. It outlines clinical and public health strategies to strengthen climate resilience in cardiovascular medicine.

Aims Cardiopulmonary exercise testing (CPET) parameters are used for heart failure (HF) prognostication. While the ventilation to carbon dioxide production (VE/VCO2) slope ≥34 identifies high risk, patients with intermediate values remain heterogeneous. The VE/VCO2 Y-intercept, reflecting dead space ventilation at rest and its changes during effort, may refine prognostication.Methods We retrospectively analysed 2642 HF. Follow-up was 26 (9–63) months. The study endpoint was the composite of all-cause death, urgent transplant or left ventricular assist device implantation.Results Median age was 62 (53–70) years and left ventricular ejection fraction (LVEF) 33% (27%–39%). 27% of patients were New York Heart Association class III–IV. During follow-up, 534 events occurred. Both VE/VCO₂ slope and peakVO₂ were associated with outcome in univariable and multivariable models (HR 1.04, 95% CI 1.03 to 1.06; HR 0.90, 95% CI 0.88 to 0.93, p<0.001, respectively). Y-intercept was not prognostic univariately but added independent value in multivariable models (HR 1.08, 95% CI 1.04 to 1.13, p<0.001). Prognosis and clinical profiles improved from group A (VE/VCO2 slope ≥34, n=858) to B (28–34, n=943) to C (<28, n=841). Group A versus C patients had lower LVEF (30% (25%–36%) vs 35% (30%–40%), ptrend<0.001), peakVO₂ (12.7 (10.06–15.3) vs 17.7 (14.6–21.6) mL/kg/min, ptrend<0.001) and higher N-terminal pro-B-type natriuretic peptide (1400 (572–3122) vs 454 (174–1081) pg/mL, ptrend<0.001). Only within group B, a high median Y-intercept (B1≥3.9 L/m) clearly identified patients with higher HF severity and worse survival than B2 (<3.9 L/m, log-rank p<0.001).Conclusion An increase in the VE/VCO2 slope is associated with a progressive lower survival. Y-intercept enhances risk assessment in HF with intermediate VE/VCO₂ slope values.

Cardiovascular disease remains the leading cause of mortality among women, whose risk is shaped by a complex interaction between biological characteristics and the social, reproductive, and environmental contexts in which they live. Beyond traditional cardiovascular risk factors, socioeconomic disadvantage, limited access to healthcare, caregiving responsibilities, psychosocial stress, discrimination, and neighbourhood deprivation can influence health behaviours, cardiometabolic profiles, and access to preventive care. These determinants also interact with reproductive health. Employment instability and economic uncertainty may affect fertility choices, while infertility, parity, assisted reproductive technology, and hypertensive disorders of pregnancy may provide clinically relevant information about subsequent cardiovascular risk. Environmental exposures - including air pollution, extreme heat, transportation noise, and limited access to green space - represent additional sources of cardiovascular vulnerability and are disproportionately concentrated in socioeconomically disadvantaged communities. Pregnancy and the menopausal transition may constitute periods of heightened susceptibility to these exposures. This narrative review examines how social, reproductive, and environmental determinants interact across the female life course to influence cardiovascular health. An integrated approach incorporating reproductive history, psychosocial conditions, socioeconomic circumstances, and environmental exposures into cardiovascular risk assessment may support more personalized prevention, reduce health inequalities, and inform clinical, community-based, and policy interventions.

Cardiovascular disease is the leading cause of mortality in women worldwide, yet the clinical and algorithmic infrastructure of cardiovascular medicine was constructed around a male prototype. The convergence of artificial intelligence, big data, wearable technologies and telemedicine, collectively termed Medicine 4.0, offers transformative potential for sex- and gender-specific cardiology. However, these tools risk perpetuating and algorithmically entrenching the sex and gender biases embedded in historical clinical datasets. This paper examines the mechanistic underpinnings of algorithmic sex/gender bias in cardiovascular artificial intelligence across six interacting bias categories, analyzes the epistemic risks of binary sex stratification in machine learning and proposes a structured operational framework comprising gender-aware clinical prompt engineering, a three-phase model for responsible artificial intelligence interaction and a coordinated agenda spanning data governance, algorithmic design, clinical education and regulatory oversight. Grounded in the Lancet Commission on Gender and Global Health's framing of gender distortion in health systems as a driver of structural injustice, this framework argues that precision cardiovascular medicine is scientifically meaningful only when it is equitable.

BACKGROUND:Current guidelines recommend evaluating patients with ambulatory heart failure (HF) for heart transplantation if their peak oxygen consumption (peak VO2) is <12 mL/kg/min. However, these recommendations are based on decades-old data. METHODS:We retrospectively analysed 8060 patients with ambulatory HF with cardiopulmonary exercise testing (CPET) data. The primary analysis focused on 1218 patients with left ventricular ejection fraction <40% and peak VO2 <12 mL/kg/min, enrolled between 2010 and 2022. Survival outcomes (composite of death/left ventricular assist device/heart transplantation) were compared with those of heart transplantation recipients from the International Society for Heart and Lung Transplantation registry. Patients were stratified by ventilatory efficiency (ventilation versus CO2 production slope (VE/VCO2) >34 vs ≤34) and presence of exercise oscillatory ventilation. Survival analyses were performed using Kaplan-Meier curves compared with log-rank tests and Cox proportional hazards models, with heart transplantation survival curves reconstructed from aggregate data. RESULTS:Patients with peak VO2 <12 mL/kg/min demonstrated better survival than heart transplantation recipients, with survival curves intersecting at approximately 2.7 years. Among those with VE/VCO2 ≤34, 10-year mortality risk was halved (p<0.01), with survival curves crossing those of heart transplantation recipients around year 4. Absence of exercise oscillatory ventilation was similarly associated with a 50% lower long-term mortality. Combining VE/VCO2 and exercise oscillatory ventilation identified four distinct risk groups with significantly different 10-year outcomes (p<0.01). Patients with peak VO2 <12 mL/kg/min, VE/VCO2 ≤34 and no exercise oscillatory ventilation exhibited survival comparable to heart transplantation recipients at year 5. CONCLUSIONS:In contemporary practice, a peak VO2 <12 mL/kg/min alone may not reliably identify patients with HF with sufficiently high short-term mortality to warrant heart transplantation referral. VE/VCO2 and exercise oscillatory ventilation provide important additional risk stratification, supporting re-evaluation of transplant referral criteria to reflect improved HF management and outcomes.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality among women, yet sex-specific and gender-specific differences in disease pathophysiology, clinical presentation, and treatment response are often underappreciated. This article presents the findings of a multidisciplinary expert consensus involving 59 specialists from cardiovascular and affine scientific societies. Experts were divided into 11 working groups, each focusing on distinct aspects of cardiovascular risk, prevention, diagnosis, and treatment in women. Utilizing a Delphi-like method, 71 key statements were developed, refined, and evaluated to establish a consensus on best practices for addressing sex-specific and gender-specific disparities in cardiovascular care. The findings underscore critical gaps in current guidelines, particularly regarding hormonal influences, pharmacological responses, and environmental and socioeconomic determinants of cardiovascular risk in women. The consensus highlights the need for improved screening strategies, individualized risk assessment models incorporating female-specific factors, and increased representation of women in cardiovascular research. Telemedicine and digital health tools offer promising solutions for bridging existing disparities. The study reinforces the necessity for a paradigm shift in cardiovascular medicine, advocating for gender-sensitive policies and clinical guidelines. Future research should focus on integrating gender-specific considerations into all facets of cardiovascular care to optimize outcomes for women.

BACKGROUND:Heatwaves are the deadliest extreme weather events, and their frequency and intensity are rising under anthropogenic climate change. In summer 2025 alone, an estimated 24,400 heat-related deaths occurred across 854 European cities, ∼68% attributable to human-induced warming. The cardiovascular system is disproportionately affected, yet the interplay between thermal stress, environmental pollutants, and individual autonomic vulnerability remains incompletely characterised. OBJECTIVES:To synthesise evidence on: (1) the epidemiological burden of heatwave-related cardiovascular mortality in Europe; (2) mechanistic pathways linking extreme heat and co-pollutants (PM2.5, ozone) to cardiac dysfunction; (3) autonomic dysregulation, via heart rate variability (HRV), as a marker of individual vulnerability; and (4) emerging wearable-based strategies for scalable risk monitoring. METHODS:Narrative review of primary literature and epidemiological reports from PubMed, Web of Science, and grey-literature repositories (WHO, EEA, Copernicus C3S), January 2000-June 2026. RESULTS:European heat-related excess deaths rose from ∼70,000 in 2003 to 61,672 in 2022, and an estimated 24,400 in just 10 weeks of 2025, despite two decades of heat-health action plans. Extreme heat acts synergistically with PM2.5 and ozone (interaction index SI 1.51 for cardiovascular mortality), potentiating sympathetic hyperactivation, myocardial ischaemia, arrhythmia, and thromboembolic risk. Reduced HRV (SDNN, RMSSD) amplifies risk in the elderly and in patients with heart failure, prior myocardial infarction, or ischaemic heart disease. Consumer-grade wearables now enable continuous, population-scale HRV surveillance. CONCLUSIONS:Heatwaves are cardiovascular emergencies requiring integrated epidemiological surveillance, mechanistic understanding, and precision monitoring. Population-wide wearable-based HRV monitoring, combined with personalised heat-health early warning systems, is a clinically actionable strategy to reduce excess cardiovascular mortality in a warming world.

Arterial hypertension (HTN) is a leading cause of morbidity and mortality in the general population, with significant sex and gender-related pathophysiological differences. Women face higher cardiovascular (CV) risk and unfavorable CV remodeling associated with HTN, as compared with men, and have specific risk factors for the development of HTN, i.e. reproductive factors and breast cancer status. Physical exercise (PE) represents a powerful, cost-effective, non-pharmacological treatment for the primary and secondary prevention of HTN. In this regard, much evidence highlighted the potential gender-related differences in terms of exercise-related CV adaptations, along with a significant gender gap concerning adherence to exercise protocols that is significantly lower in women for all age groups worldwide. However, to date, there are no specific, sex-focused recommendations in terms of exercise training in the female population with HTN or at risk of HTN. Given these premises, our review aims to summarize the role of exercise in the management of HTN in women, with a specific focus on pregnancy, menopause and breast cancer scenarios, as well as on cardiac rehabilitation. Our purpose is to underline the need for more sex-specific data to explore the best exercise protocols tailored on each participant’s characteristics, to get the greatest benefit and to improve adherence to exercise protocols.

BACKGROUND & AIMS:Breastfeeding is the optimal form of infant nutrition, conferring extensive benefits for both maternal and child health. Maternal physical activity likewise supports postpartum recovery, cardiometabolic health, and psychological well-being. Historical concerns have been raised about possible negative effects of exercise on breast milk composition, supply, and infant acceptance. This review synthesizes current evidence on the interplay between exercise and breastfeeding, with a focus on maternal and infant cardiometabolic health. METHODS:A structured literature search was conducted in PubMed and Scopus for the period January 2000-December 2024, using predefined keywords on breastfeeding, lactation, exercise, and maternal health. Eligible studies assessed maternal physical activity during lactation and reported outcomes on breast milk, maternal health, or infant development. Screening was performed independently by two reviewers following PRISMA guidelines. RESULTS:Moderate-intensity exercise (30-45 min per day) does not adversely affect milk volume, nutrient composition, or infant growth. Instead, it may enhance antioxidant levels in breast milk, improve lipid and hormonal profiles, and support maternal weight management. Transient lactate increases after strenuous exercise may alter milk taste, but normalize within an hour and have no clinical impact. Breastfeeding itself confers maternal cardiometabolic protection, lowering risks of hypertension, metabolic syndrome, and type 2 diabetes. Emerging data suggest maternal exercise during lactation may also influence infant metabolic programming, potentially reducing long-term risk of obesity and cardiovascular disease. CONCLUSIONS:Maternal exercise and breastfeeding are not mutually exclusive but synergistic in promoting maternal and child health. Accumulated evidence indicates that moderate maternal exercise does not compromise breast milk supply or its capacity to meet infant nutritional needs. IMPORTANCE:Healthcare providers should reassure postpartum women that moderate exercise is safe during lactation and encourage its integration into postpartum care. Future studies should explore high-intensity exercise, resistance training, and inter-individual variability to refine recommendations.

Inflammaging is a chronic, low-grade inflammation that accompanies aging and contributes to the development of age-related diseases. Recent research has increasingly focused on its impact in women, recognizing that aging and inflammatory processes differ between sexes. Estrogens, known for their anti-inflammatory effects, offer protection during reproductive years. However, their decline during menopause and the climacteric period is linked to increased inflammation and a higher risk of chronic diseases such as osteoporosis, cardiovascular disease, and arthritis. X-linked immune-related genes play a critical role in immune system regulation. Epigenetic changes associated with aging can affect the expression of inflammation-related genes, with hormonal and genetic differences contributing to sex-specific responses. Women generally exhibit stronger immune responses than men, which can enhance infection resistance but also increase susceptibility to autoimmune diseases and inflammaging. Lifestyle factors, including diet and physical activity, significantly influence inflammation. Due to metabolic differences, women may respond differently to these interventions. Postmenopausal women, for example, often exhibit higher levels of inflammatory markers like C-reactive protein (CRP) and interleukin-6 (IL-6), which are associated with elevated risks of cardiovascular and other age-related conditions. These findings suggest that strategies to reduce inflammation—such as anti-inflammatory diets or medications—should be tailored to the unique hormonal and physiological context of women. Understanding the distinct manifestations of inflammaging in women is essential for developing gender-specific approaches to promote healthier aging and reduce the burden of chronic disease in later life.

: Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart failure cases and is primarily characterized by impaired diastolic function, leading to increased ventricular filling pressures and symptoms like dyspnea and reduced exercise tolerance. Significant gender-specific differences are observed, with women, particularly post-menopausal, experiencing higher prevalence and distinct clinical profiles compared to men. Diastolic dysfunction in HFpEF involves altered cellular mechanisms such as reduced SERCA2a expression, impacting calcium handling and myocardial relaxation. Diagnostic strategies mainly employ echocardiography, including Doppler imaging, tissue Doppler imaging, and strain imaging, to assess ventricular relaxation and stiffness. However, early identification remains challenging, necessitating advanced tools like cardiac magnetic resonance and exercise stress testing for accurate diagnosis, especially in women who often present with subtle symptoms. Treatment options for HFpEF have traditionally been limited, but recent trials, notably EMPEROR-PRESERVED and DELIVER, demonstrated significant cardiovascular benefits using sodium–glucose cotransporter-2 (SGLT2) inhibitors. Additionally, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown promising results, particularly in obese patients. Despite these advances, gender differences in therapeutic response necessitate further research for personalized management strategies. Understanding sex-specific pathophysiological mechanisms and optimizing diagnostic criteria remain essential to improving prognosis and quality of life in HFpEF patients.

BackgroundCardiovascular disease (CVD) remains the leading cause of morbidity and mortality among women with type 2 diabetes (T2DM). The interplay between sex-specific biological factors, social determinants, and environmental exposures amplifies cardiometabolic risk across the female life course.ObjectivesThis manuscript explores how socioeconomic disparities, environmental pollution, chronic stress, food insecurity, and climate change synergistically increase the burden of T2DM and cardiovascular complications in women, and reviews potential preventive interventions including dietary strategies.MethodsA comprehensive narrative review was conducted, synthesizing current evidence on the exposome, social inequities, environmental insults, and evidence-based lifestyle interventions that contribute to or mitigate the development and progression of T2DM and CVD in women.ResultsLower socioeconomic status, limited education, housing instability, and inadequate access to healthcare and nutritious foods profoundly affect T2DM management and CVD prevention in women. Concurrently, exposure to air pollutants (PM2.5, NO2, O3), climate change-induced food insecurity, and heat-related stress further exacerbate insulin resistance, systemic inflammation, and vascular dysfunction. Life transitions such as gestational diabetes mellitus and menopause further magnify these risks. Current healthcare models insufficiently address these multilayered factors.ConclusionEffective cardiovascular prevention in women with T2DM requires a life-course approach that integrates biological transitions with environmental and social determinants to deliver sex-sensitive, stage-specific strategies.

Background: T wave amplitude and repolarization variability in ECG showed inverse correlations. Sympathetic activation, induced by head-up tilt, is associated to a reduced T wave amplitude. Methods: Noninvasive hemodynamic and ECG data from three healthy subjects' groups (Group 1: 10-19 years-old; Group 2: 40-49 years-old; Group 3: 80-89 years-old) were analyzed. Measurements were taken during controlled-breathing rest, and during head-up tilt. The mean and standard deviation ((SD)) were calculated for these ECG intervals: QT, STp (from S to Tpeak) and Te (from Tpeak to Tend). Results: During tilt, a significant decrease in T wave amplitude was observed in the younger groups (p < 0.001), but not in Group 3. At rest, Group 1 exhibited higher voltage compared to Group 2 (p < 0.05) and 3 (p < 0.001), as Group 2 compared to Group 3 (p < 0.05). A negative correlation was confirmed between T wave amplitude and QT(SD), STp(SD) and Te-SD (p < 0.001). Low-frequency normalized units (p < 0.05) and high-frequency normalized units (p < 0.001) were inversely related to T-wave amplitude. Conclusion: The findings suggest an age-dependent decline in T wave amplitude during tilt and elucidates the relationship between systolic function and T wave amplitude among healthy subjects. These insights warrant further investigations in clinical and research settings for cardiovascular diseases.

Type 2 myocardial infarction (T2MI) occurs due to an imbalance between coronary blood supply and myocardial oxygen demand, leading to ischemia without the rupture of an atherosclerotic plaque, distinguishing it from Type 1 myocardial infarction (T1MI). Although T2MI is frequently diagnosed in clinical practice and associated with a poor prognosis, there is limited understanding of the sex differences in this condition, despite women representing a higher proportion of T2MI cases compared to T1MI. This review explores the definitions, epidemiological aspects, and clinical scenarios that reveal significant differences in T2MI between men and women that contribute to disparities in outcomes. It examines the unique roles that sex and gender play in the development, presentation, and diagnosis of T2MI, emphasizing the need for greater awareness of these factors. Understanding how these differences contribute to this condition is essential for developing patient-tailored approaches to managing this often-undervalued disease and improving outcomes.

Appropriate interpretation of kidney function is essential for clinical and therapeutic management of heart failure (HF). We evaluated the prognostic accuracy of 6 glomerular filtration rate estimation (eGFR) formulas in HF patients with reduced ejection fraction (HFrEF) and their impact on the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score prognostic accuracy. We retrospectively analyzed 6,933 patients enrolled in the MECKI score database. GFR was estimated using: Modification of Diet in Renal Disease (MDRD); MRDR modified (MDRDm); Cockcroft-Gault (CG), CG modified (CGm); Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and the European Kidney Function Consortium (EKFC). Survival was assessed as the composite of cardiovascular death, left ventricular assist device implantation and urgent heart transplantation at 2 years. Each GFR estimation demonstrated similar but moderate prognostic capacity, with the area under the curve (AUC) for predicting survival ranging from 0.6271 (EKFC) to 0.635 (MDRD).. For cardiovascular death, the AUC values ranged from 0.668 to 0.677. The prevalence of severe CKD, defined as eGFR <30 ml/min/1.73 m², ranged from 3.2% (MDRD) to 4.5% (EKFC). When included in MECKI score, the 6 formulas showed a MECKI AUC for prognosis ranging from 0.7841 to 0.7883, with the EKFC and CKD-EPI showing the best performance. GFR estimations play a role in HFrEF prognosis without difference among the 6 most frequently used formulas. Furthermore, using eGFR calculated from the 6 different formulas in MECKI score did not significantly alter its strong prognostic power, highlighting MECKI reliability in risk stratification.

Ormoni sessuali e propensione al fumo ed ai suoi effetti nocivi sul sistema cardiovascolare della donna, La combinazione di ormoni sessuali e fumo crea un rischio aggravato di malattie cardiovascolari nelle donne. Gli effetti cardioprotettivi naturali degli estrogeni possono essere compromessi dal fumo, mentre il calo degli estrogeni durante la menopausa aumenta ulteriormente la vulnerabilità cardiovascolare. Il fumo accelera il danno ai vasi sanguigni, promuove l’infiammazione e lo stress ossidativo e peggiora i profili lipidici, tutti fattori che contribuiscono ad un elevato rischio di aterosclerosi, sindromi coronariche acute e ictus nelle donne. Pertanto, smettere di fumare e gestire i cambiamenti ormonali (ad esempio, con l’uso sicuro della terapia ormonale sostitutiva) sono strategie essenziali per ridurre i rischi cardiovascolari nelle donne.