Women are less likely to have a stroke compared with men, but certain sex-specific risk factors can increase their risk for ischemic or hemorrhagic stroke later in life. The 2024 American Heart Association and American Stroke Association guideline for primary prevention of stroke emphasizes female-specific factors that increase risk for stroke, including adverse pregnancy outcomes, premature and early menopause, endometriosis, and certain hormone therapies (eg, combined hormonal contraceptives). This review explores these sex-specific risk enhancers and highlights the importance of a detailed gynecologic and obstetric history when assessing stroke risk in women.

Pregnancy is generally well tolerated in patients with arrhythmogenic cardiomyopathy (AC), but there are limited data comparing right-dominant AC (ARVC) and left-dominant AC (ALVC), as well as gene-positive but phenotype-negative (G+/P-) individuals. Recent guidelines have also introduced the non-dilated left ventricular cardiomyopathy (NDLVC).

This study examines disease expression in pregnant women with AC and family members with pathogenic genetic variants but a negative phenotype (G+/P-). We also included those with NDLVC.

We reviewed data from 22 patients diagnosed with definite AC and 9 G+/P- patients. Four patients meeting criteria for NDLVC were also analyzed. Each underwent at least one cardiovascular evaluation during pregnancy, which included a 12-lead ECG, echocardiography, and 24-h ambulatory monitoring. Events were defined as new or worsening arrhythmias, heart failure, or thromboembolic events.

All AC patients, including those with ARVC and ALVC, tolerated pregnancy well. None of the G+/P- patients was diagnosed with AC during pregnancy. One G+/P- patient had ECG changes, while three with PKP2 mutations experienced mild left ventricular dysfunction but fully recovered postdelivery. Among the four NDLVC patients, only one developed left ventricular dysfunction. There was no increase in arrhythmias, and 31% of the cases required caesarean sections. All pregnancies resulted in live births, and no major maternal complications were reported.

Pregnancy is typically safe for women with AC and G+/P- individuals, provided that they are hemodynamically stable. Patients with NDLVC also manage pregnancy well. However, careful monitoring during and after pregnancy is essential, even without obvious clinical signs of the disease.

Dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin offers superior ischemic protection compared with single-agent therapy in patients with peripheral artery disease (PAD). However, its real-world adoption remains limited. We aimed to determine the proportion of revascularized PAD patients eligible for DPI, and to explore reasons for ineligibility and associated clinical outcomes.

Consecutive patients undergoing lower limb revascularization for PAD between May 2021 and May 2023 were prospectively enrolled in the RAPID (RivAroxaban for PerIpheral artery Disease) registry and followed up for a median time of 283 (interquartile range 142-445) days. VOYAGER PAD eligibility criteria were applied. The primary outcome was eligibility for DPI. Exploratory clinical outcomes included major adverse limb events (MALE) - defined as the composite of cardiovascular death, acute limb ischemia, or repeat limb revascularization - and major bleeding.

A total of 196 patients were enrolled during the study period. Among them, 98 (50.0%) met DPI eligibility criteria; however, DPI was administered only to 4.1% of eligible patients. The most frequent exclusion factors were high bleeding risk (99.0%), low hemoglobin (48.8%), and age at least 75 years (36.7%). MALE occurred in 35 patients (28%), driven by recurrent revascularization (20%), while major bleeding occurred in nine patients (5%). DPI eligibility was associated with a lower risk of MALE (hazard ratio 0.42; 95% confidence interval 0.20-0.85), but this association faded out after statistical adjustment. Major bleeding did not differ between eligible and noneligible patients.

In a contemporary population of PAD patients undergoing revascularization, only half met the VOYAGER PAD eligibility criteria. Bleeding-related exclusions prevailed, highlighting the need for systematic anemia correction and bleeding avoidance strategies to broaden eligibility for DPI and improve clinical outcomes.

ST-elevation myocardial infarction (STEMI) in very elderly patients (≥85 years) poses a major clinical challenge due to frailty and comorbidities. In the general population, left anterior descending (LAD) artery involvement predicts adverse outcomes, but data in the very elderly are limited. We aimed to evaluate the impact of LAD culprit lesions on 30-day mortality in this population.

In this multicenter registry (six Italian Hub hospitals, 2010-2023), 586 consecutive STEMI patients aged ≥85 years undergoing coronary angiography and percutaneous coronary intervention (PCI) were retrospectively analyzed. Patients were stratified by culprit vessel: LAD (n = 288) vs. non-LAD (n = 298). Demographic, clinical, procedural characteristics, and 30-day outcomes, including mortality and major adverse cardiovascular events, were collected. Multivariable analysis identified independent predictors of mortality.

Baseline differences included prior myocardial infarction (MI) (9.4% vs. 18.5%, P < 0.01), prior CABG (0.3% vs. 4.7%, P < 0.01), and dyslipidemia (35.4% vs. 45.6%, P = 0.02), less frequent in LAD STEMI. Single-vessel disease was more common in LAD STEMI (42.0% vs. 31.5%, P = 0.01). Overall, 30-day mortality was 19.3% (113/586), higher in the LAD group [hazard ratio (HR) 1.57; 95% confidence interval (CI) 1.06-2.33; P = 0.024]. In LAD STEMI, cardiogenic shock at presentation was the strongest independent predictor of death (HR 6.10; 95% CI 3.70-10.35; P = 0.01), while dyslipidemia was associated with lower mortality (HR 0.51; 95% CI 0.28-0.92; P = 0.03).

In very elderly STEMI patients, LAD culprit lesions are associated with higher short-term mortality. Cardiogenic shock at presentation and absence of dyslipidemia identify a high-risk subgroup, emphasizing the need for tailored risk stratification and careful procedural planning in this vulnerable population.

Transcatheter aortic valve implantation (TAVI) is the standard of care for elderly (≥70 years) or high-risk patients with severe aortic stenosis, yet current guidelines recommend its performance only in Heart Valve Centres with on-site cardiac surgery. This study evaluated procedural safety and long-term outcomes of TAVI performed in selected non-surgical centres.

We retrospectively analysed 186 consecutive patients undergoing TAVI at 'F. Miulli' Hospital between 2016 and 2024, enrolled in the MURGIA-TAVI Registry. The programme operated without institutional on-site cardiac surgery, supported by a structured Heart Team approach and a visiting surgical back-up. Outcomes were assessed according to Valve Academic Research Consortium-3 definitions and survival was evaluated up to 5 years.

Among 186 patients (mean age 82 years; STS score 7%), transfemoral access was used in 93%. Technical success was 98.9%, with no intraprocedural deaths. Conversion to emergent cardiac surgery occurred in two patients (1.1%); both survived at 30 days. In-hospital mortality was 1.6%, never valve-related. Major complications included cardiac tamponade (1.6%), major bleeding (2.2%) and major vascular complications (1.1%). At 1 year, mortality was 15.6% with no valve-related deaths, and valve dysfunction occurred in 1.9% of patients. Five-year survival reached 52.5%. Outcomes, including rates of emergent cardiac surgery, were comparable to those reported in published registries from centres without institutional on-site cardiac surgery.

Our findings suggest that TAVI can be safely performed in selected hospitals without on-site cardiac surgery within a structured Heart Team framework and a visiting surgical back-up, potentially expanding access, shortening waiting times, and meeting the growing demand for TAVI.

Cardiovascular diseases is the most common cause of mortality in the world. B vitamins (B₁-B₁₂) control how mitochondria make energy, how nitric oxide is made, how one-carbon is used, and how genes work. A deficiency leads to hyperhomocysteinemia, oxidative stress, and endothelial dysfunction, all of which are important to vascular disease. Observational studies consistently associate low B-vitamin levels with an elevated risk of cardiovascular diseases; nevertheless, randomized supplementation trials have demonstrated only modest reductions in significant events.

This narrative review summarizes molecular, epidemiological, and clinical evidence on the role of B vitamins in cardiovascular health. Special focus was paid to functional biomarkers and gene-nutrient interactions that affect how well a therapy works. The literature was identified through targeted searches of PubMed, Scopus, and Google Scholar. Priority was given to high-quality evidence, including mechanistic studies, observational cohorts, randomized controlled trials, meta-analyses, and major review articles relevant to cardiovascular outcomes.

Functional indicators, such as methylmalonic acid and holotranscobalamin, offer superior accuracy compared to blood levels in assessing vitamin status. Nutrigenetic interactions, particularly the effects of folate and riboflavin on methylenetetrahydrofolate reductase polymorphisms, exhibit blood pressure-lowering and stroke-preventive advantages. The clinical efficacy of B-vitamin supplementation is highly dependent on baseline nutritional status and regional food fortification policies. For example, folic acid supplementation significantly reduces stroke incidence in populations who lack mandatory folate fortification, whereas trials conducted in folate-sufficient cohorts generally demonstrated no added cardiovascular benefit. Recognizing this population-specific variability helps explain the historical discrepancy between the strong mechanistic potential of B-vitamins and the mixed results observed in large-scale clinical trials.

While adequate B-vitamin status remains mechanistically essential for cardiovascular homeostasis, the clinical benefits of routine supplementation are nuanced and highly population-dependent. Consequently, ubiquitous supplementation is unlikely to produce extensive advantages. A precision strategy that combines biomarkers, genotype stratification, and population context can help find their therapeutic potential. Future methods should integrate diet with precision cardiology to enhance vascular prevention.

Residual atherosclerotic cardiovascular disease (ASCVD) risk often remains even after low-density lipoprotein cholesterol (LDL-C) levels have been brought down to target levels. Remnant cholesterol (RC) and inflammation have been increasingly linked to the residual risk. We aimed to investigating whether the discriminative value of RC the ability of RC to discriminate and its claimed interactions with LDL-C are due to a real clinical phenotype or are affected by formula-dependent biases between the Friedewald and Sampson-NIH equations.

We performed a cross-sectional analysis of consecutively tested adults (n = 3,342) using residual serum samples from routine clinical monitoring. To reduce analytical variability, all lipid profiles were analyzed using a single, dedicated reagent lot. We contrasted risk models with Friedewald-calculated versus Sampson-NIH-calculated LDL-C to assess equation-dependent differences. Lipid parameters, hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and C-reactive protein (CRP) were measured. ASCVD was defined using International Classification of Diseases, 10th Edition (ICD-10) codes. Missing covariate data were handled using multiple imputation by chained equations (m = 50), with additional complete-case sensitivity analyses for CRP-related models. To reduce bias, the observed ASCVD status was included as an auxiliary variable; the outcome itself was not imputed. The discriminative performance of nested logistic regression models was assessed through the pooled area under the receiver operating characteristic curve (AUC) and pooled DeLong p-values.

The primary clinical focus was the presence of documented pre-existing ASCVD diagnoses, identified in 11.4% of the cohort, while 9.4% of participants met the criteria for atherogenic dyslipidemia (AD). In the primary analysis with Friedewald LDL-C, we detected a statistically significant (p < 0.001) negative interaction between LDL-C and RC, while logCRP remained an independent correlate in the adjusted model. Interestingly, when we verified this using the more accurate Sampson-NIH equation to minimize the possibility that the result would be solely due to calculation bias, the paradoxical interaction was still statistically significant (p = 0.003) along with a strong model performance (AUC: 0.729). This indicates that the interaction is not entirely explained by the mathematical artifact of the Friedewald formula, but rather represents a consistent statistical pattern in this cohort.

RC adds statistically significant value to risk discrimination. The continuous inverse relationship of LDL-C with high RC identifies a statistical pattern consistent with persistent atherogenic burden despite apparently optimal calculated LDL-C levels. Awareness of this potential suppressor effect may aid in refining risk stratification in tertiary-care settings.

Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular wall thickening, while right ventricular involvement in HCM is also common and has been identified to relate to worse prognosis. Right ventricular outflow tract (RVOT) obstruction is a rare clinical disorder with diverse etiologies, among which HCM is one of the most prevalent specific causes. Currently, severe RVOT obstruction caused by HCM remains rarely reported. Its phenotypic and genetic characteristics remains uncharacterized, warranting more attention.

This case presented a 33-year-old woman who had a unique cardiac manifestation of HCM characterized by severe RVOT obstruction, apical hypertrophy, a membranous ventricular septal aneurysm and an atrial septal aneurysm. Her genetic tests reported three novel mutation sites associated with cardiomyopathy. The diagnosis of HCM was supported by imaging, genetic and histological findings. The patient underwent RVOT myectomy to relieve the obstruction. Follow-up echocardiography at four months showed gradual recovery of right ventricular function and a marked reduction in the pressure gradient of RVOT.

Isolated, severe RVOT obstruction caused by HCM is very rare. It requires careful differentiation from congenital heart diseases and actively individualized management in line with guidelines for left ventricular involvement. The unique cardiac features in our case exhibited phenotypic heterogeneity of HCM. The novel reported mutation sites indicated genetic heterogeneity of cardiomyopathy. With more clinical evidence available, we will have a deeper understanding of genotype-phenotype correlations across different cardiomyopathies.

The study is not a clinical trial. The registration details (registry, trial registration number, and data of registration) are not needed.

To prevent hypertension and cardiovascular diseases, many studies have aimed to develop a convenient formula for estimating 24-hour sodium excretion. However, previous formulas that use regression analysis based on spot urine samples have been criticized for several evaluation metric problems including adjusted coefficient of determination, correlation coefficient, mean bias, and systematic bias, and being not suitable for individual-level predictions. This study aimed to address these limitations by developing a new formula with higher predictive accuracy in a population. We hypothesized that more accurate predictions could be achieved by incorporating additional individual-specific information into the regression model. Specifically, we proposed that four refinements would improve prediction accuracy: accounting for sex differences, including voided volume, considering the time elapsed since the last meal at the time of spot urine collection, and categorizing participants into two groups based on predicted sodium salt excretion. To test these hypotheses, we provided low- and high-salt meals to 104 young healthy volunteers over 3 days. We collected all urine samples from the participants and measured sodium and creatinine levels. Using these data, we refined the Tanaka formula to provide a more accurate estimate of 24-hour sodium excretion in young people. The four refinements significantly improved the performance of previous formulas, leading to better correlation between predicted and observed sodium excretion values, reduced systematic bias, and overall enhanced accuracy. Although our refined formula has improved accuracy in predicting the average sodium excretion of a population, there may be still room for improvement in the future.

Restoring cardiac function after myocardial infarction remains a major challenge, as current pharmacological and interventional therapies primarily mitigate symptoms and slow disease progression without addressing the irreversible loss of functional myocardium. Although a diverse range of biologically active agents has been developed to modulate inflammation, angiogenesis, fibrosis, and cardiomyocyte survival, their therapeutic impact is frequently limited by delivery strategies that fail to match the dynamic and heterogeneous nature of post-infarction healing. Advances in biomaterials, nanotechnology, and device engineering have enabled drug delivery systems capable of spatiotemporally programmed therapeutic engagement. By responding to injury-associated cues, recreating key features of the myocardial microenvironment, and incorporating programmable release architectures, these systems coordinate localization, release kinetics, and duration of action with distinct phases and regions of cardiac repair. When combined with appropriate delivery interfaces, including nanocarriers, injectable depots, structured platforms, and biologically derived vehicles, spatiotemporal drug delivery transforms therapy from passive administration into an active determinant of biological outcome. This Review synthesizes recent mechanistic and engineering advances to frame spatiotemporal precision as a unifying principle for cardiac drug delivery. Aligning therapeutic action with the intrinsic biology of myocardial healing provides a rational pathway toward more effective, durable, and biologically informed strategies for cardiac repair and, where biology permits, regeneration.