Explore the vast range of titles available.

Accumulating evidence suggests that modifications of gut function and microbiota composition might play a pivotal role in the pathophysiology of several cardiovascular diseases, including heart failure (HF). In this study we systematically analysed gut microbiota composition, intestinal barrier integrity, intestinal and serum cytokines and serum endotoxin levels in C57BL/6 mice undergoing pressure overload by transverse aortic constriction (TAC) for 1 and 4 weeks. Compared to sham-operated animals, TAC induced prompt and strong weakening of intestinal barrier integrity, long-lasting decrease of colon anti-inflammatory cytokine levels, significant increases of serum levels of bacterial lipopolysaccharide and proinflammatory cytokines. TAC also exerted effects on microbiota composition, inducing significant differences in bacterial genera inside Actinobacteria, Firmicutes, Proteobacteria and TM7 phyla as shown by 16S rDNA sequencing of fecal samples from TAC or sham mice. These results suggest that gut modifications represent an important element to be considered in the development and progression of cardiac dysfunction in response to TAC and support this animal model as a valuable tool to establish the role and mechanisms of gut-heart crosstalk in HF. Evidence arising in this field might identify new treatment options targeting gut integrity and microbiota components to face adverse cardiac events.

Controversial data exist regarding the impact of body mass index (BMI) on TAVI outcomes. Thirteen TAVI studies were included and analyzed for the incidence of procedural complications, 30-day, and long-term all-cause mortality. Three comparisons were executed: (1) underweight versus normal weight, (2) overweight versus normal weight, and (3) obese versus normal weight patients. Underweight patients (BMI <20 kg/m2) had similar 30-day all-cause mortality compared with the normal, although they displayed a significant worse survival at long-term follow-up (hazard ratio 1.68, 95% confidence interval (CI) 1.09 to 2.59, p = 0.02). Underweight patients showed a higher incidence of major and life-threatening bleedings (2,566 patients, odds ratio 1.64, 95% CI 1.10 to 2.45, p = 0.02) and of major vascular complications (2,566 patients, odds ratio 1.86, 95% CI 1.16 to 2.98, p = 0.01), compared with normal weight patients. Overweight patients (BMI ≥25 and <30 kg/m2) display similar 30-day and long-term all-cause mortality, as well as similar procedural complication rate compared with normal weight patients. Obese patients (BMI >30 kg/m2) had similar 30-day all-cause mortality rates compared with the normal weight category, whereas they displayed a significant better survival at long-term (hazard ratio 0.79, 95% CI 0.67 to 0.93, p = 0.004). Procedural complications did not differ between obese and normal body weight patients. In conclusion, a low BMI is linked to a significantly worse prognosis after TAVI. Therefore, BMI represents an important and handily tool that might be used in the risk prediction of patients to be addressed for TAVI.

In the past decades, percutaneous coronary intervention (PCI) has become the most common modality for myocardial revascularization in patients with coronary artery disease (CAD). Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is essential in all patients undergoing PCI to prevent thrombotic complications. A large proportion of patients undergoing PCI also have concomitant atrial fibrillation (AF), thus requiring an oral anticoagulant (OAC) to prevent ischemic stroke or systemic embolism. However, the association between OAC and DAPT further increases the risk of bleeding. Compared with a triple antithrombotic therapy (TAT), dual antithrombotic therapy (DAT) has shown to reduce bleeding events, but at the cost of higher risk of stent thrombosis. In this field, patients with AF undergoing PCI represent a special population with significant challenges, and several strategies are needed to reduce the risk for bleeding complications. In this review, we will discuss both the procedural and antithrombotic strategies to optimize ischemic and bleeding outcomes in patients with AF undergoing PCI.

Transcatheter aortic valve implantation (TAVI) is an effective alternative therapy in selected patients with severe aortic stenosis. The role and effects of coexistent moderate to severe mitral regurgitation (msMR) in patients who undergo TAVI remain unclear. Thirteen studies enrolling 4,839 patients who underwent TAVI, including patients with msMR, were considered in a meta-analysis and analyzed for all-cause-mortality; a further meta-analysis was performed to assess mitral regurgitation (MR) evolution after TAVI. In patients with msMR, all-cause-mortality after TAVI was significantly increased at 30-day (effect size [ES] −0.18, 95% confidence interval [CI] −0.31 to −0.04, I2 = 46.51, Q = 7.48), 1-year (ES −0.22, 95% CI −0.36 to −0.08, I2 = 56.20, Q = 11.41), and 2-year (ES −0.15, 95% CI −0.27 to −0.02, I2 = 0.00, Q = 2.64) follow-up compared with patients with absent or mild MR, independent of baseline left ventricular ejection fraction. Interestingly, the impact of msMR on outcomes was statistically stronger when the CoreValve system was used. TAVI was also associated with an improvement in MR entity at 3- and 6-month follow-up (overall ES −0.19, 95% CI −0.37 to −0.01, I2 = 61.52, Q = 10.39). In conclusion, the presence of preoperative msMR in patients with severe, symptomatic aortic stenosis who undergo TAVI negatively affects outcomes after TAVI. In addition, in the same group of patients, a trend toward a reduction in MR severity was observed. Whether the decrease in MR severity affects mortality after TAVI remains to be defined. •Moderate to severe MR in patients with severe AS negatively affects outcomes after TAVR.•This finding is particularly true when the CoreValve system is used.•TAVR is associated with a trend toward a reduction in MR severity.•Further studies including direct comparisons of different valves are warranted.•Whether MR recovery affects survival is still a matter of concern.

In Anderson–Fabry disease (AFD) the impact of left ventricular (LV) function on cardiac outcome is unknown. Noninvasive LV pressure–strain loop analysis is a new echocardiographic method to estimate myocardial work (MW). We aimed to evaluate whether LV function was associated with outcome and whether MW had a prognostic value in AFD. Ninety-six AFD patients (41.8 ± 14.7 years, 43.7% males) with normal LV ejection fraction were retrospectively evaluated. Inclusion criteria were sinus rhythm and ≥ 2-year follow-up. Standard echocardiography measurements, myocardial mechano-energetic efficiency (MEE) index, global longitudinal strain (GLS) and MW were evaluated. Adverse cardiac events were defined as composite of cardiac death, malignant ventricular tachycardia, atrial fibrillation and severe heart failure development. During a median follow-up of 63 months (interquartile range 37–85), 14 events occurred. Patient age, cardiac biomarkers, LV mass index, left atrium volume, E/Ea ratio, LV ejection fraction, MEE index, GLS and all MW indices were significantly related to adverse outcome at univariate analysis. After adjustment for clinical and echocardiographic parameters, which were significant at univariate analysis, GLS and MW resulted independent predictors of adverse events (p < 0.01). By ROC curve analysis, constructive MW ≤ 1513 mmHg% showed the highest sensitivity and specificity in predicting adverse outcome (92.9% and 86.6%, respectively). MW did not improve the predictive value of a model including clinical data, LV diastolic function and GLS. LV function impairment (both systolic and diastolic) is associated with adverse events in AFD. MW does not provide additive information over clinical features and systolic and diastolic function.

Despite improvements in the secondary prevention of atherothrombosis in patients with coronary artery disease during the past decade, it is estimated that approximately 19 million people annually die from cardiovascular diseases worldwide. Atherothrombosis remains the core pathobiology of acute complications including myocardial infarction (MI), and therefore, antithrombotic therapy plays a pivotal role in the strategies for major adverse cardiovascular event (MACE) prevention. Unlike early antithrombotic management after acute coronary syndrome, less evidence is available on long-term antithrombotic therapy in patients with chronic coronary syndrome (CCS). In addition, greater recognition of the impact of bleeding complications of such therapies has led to a more complex and personalized approach to their application. The purpose of this article is to review the available evidence on long-term antithrombotic therapy in patients with CCS including those with high-risk characteristics such as prior MI or polyvascular disease. A comprehensive literature review was performed in major databases including PubMed, Embase, and the Cochrane Library. The main focus of this narrative review was on available data from guidelines, meta-analysis, randomized controlled trials, and observational studies that assessed the efficacy and safety profile of long-term antithrombotic therapy in patients with CCS. Several studies suggest that long-term antithrombotic therapy is effective in reducing the risk of recurrent MACEs in patients with CCS. Current clinical guidelines recommend single antiplatelet therapy with aspirin as a first-line long-term strategy for patients without indication for oral anticoagulation. However, novel approaches focused on P2Y12 inhibitor monotherapy are emerging. More intensive antithrombotic strategies including long-term dual antiplatelet therapy and dual pathway inhibition further reduce ischemic risk but at the cost of increased bleeding. This review highlights the importance of close monitoring and regular reassessment of the risk-benefit balance of antithrombotic therapy in patients with CCS. Overall, long-term antithrombotic therapy with either single antiplatelet therapy or dual antiplatelet therapy/dual pathway inhibition is effective in reducing the risk of MACEs in patients with CCS. The choice of antithrombotic therapy should be individualized based on the patient's clinical profile, particularly for thrombohemorrhagic risk. Future research should focus on identifying the optimal antithrombotic regimen for specific subgroups of patients with prior MI particularly for those with high bleeding risk.

Background The long-term risk of cardiovascular (CV) events in individuals who develop new-onset type 2 diabetes (T2D) after having received statin therapy in primary prevention is mostly unknown. Methods We designed a population-based cohort study in individuals without T2D and atherosclerotic CV disease (ASCVD), divided in two groups according to the presence of statin therapy. We also balanced the study groups for demographic and clinical factors using propensity score matching. Results 119307 individuals without T2D and ASCVD were divided in statin users ( N  = 90906) or not ( N  = 28401) and followed-up for 70.1 ± 61.3 months. Yearly incidence of T2D rate was 0.3% in the control group and 2.2% in the statin treated group. A Cox regression analysis confirmed the association between incident T2D and statin therapy. In normotensive individuals, the presence of statin therapy led to a 2-fold risk to develop incident T2D (HR: 2.61;95% CI: 2.11–3.22, p  < 0.001). In the hypertensive population, statin therapy was associated with a HR of incident T2D of 4.62 (95% CI: 3.75–5.69, p  < 0.001). The rate of CV events, including coronary and cerebrovascular fatal and non-fatal events, was 1.9% in the statin group vs. 0.7% in the control group and a multiple regression analysis demonstrated an association between statin therapy and CV events. A further Cox regression performed only in the statin treated population revealed a significant association of CV events with age, serum creatinine levels, and incident T2D. Of note, the increased rate of new-onset T2D associated with statin use does not modify the class of CV risk of this population. All these findings were confirmed by propensity score matched analysis. Conclusions Statin therapy in primary prevention is associated with a higher risk of incident T2D, especially in hypertensive patients. However, since the final CV risk of those who develop T2D during statin treatment was lower than the one required for statin prescription according to the ESC guidelines, indicating that this phenomenon does not impair the benefit in CV prevention associated with the lipid lowering effect of statins.

Acute thrombotic events can unveil occult cancer, as they are its first manifestation in about 20 to 30% of all cases. Malignancy interacts in an intricate way with the hemostatic system, promoting both thrombosis and bleeding. The main pathway involved in these reactions involves the activation of tumor-associated procoagulant factors, which eventually results in clot formation. The clinical manifestation of cancer-related thrombotic events mainly involves the venous side, and manifests in a broad spectrum of conditions, including unusual sites of venous thrombosis. The selection of patients who have a balanced risk–benefit profile for management of anticoagulation is complex, given individual patient goals and preferences, different prognosis of specific cancers, common comorbidities, potential drug–drug interactions, underweight states, and the competing risks of morbidity and mortality. Anticoagulant treatment in cancer settings is broadly debated, considering the potential application of direct oral anticoagulants in both thromboprophylaxis and secondary prevention, having demonstrated its efficacy and safety compared to conventional treatment. This review aims to provide a brief overview of the pathophysiology and management of cancer-related thrombosis, summarizing the results obtained in recent clinical trials.

Background Statin therapy has been associated with increased risk of type 2 diabetes (T2D). We investigated the relationship between Low-Density Lipoprotein Cholesterol (LDL-C) plasma concentrations and incident T2D and evaluated the modifying effect of statin therapy in a large population-based cohort. Methods Individuals free of T2D and cardiovascular disease at baseline were followed longitudinally for the development of new-onset T2D. Cox proportional hazards models were applied to evaluate the associations of LDL-C levels and statin therapy with T2D risk. Results From a population of 202,545 individuals, we selected 13,674 participants free of T2D and cardiovascular disease (of whom 52% were on statins), who were followed for a median of 71.6 months (IQR 34.5–149.9), during which 1,819 (13%) developed incident T2D. Cox multiple regression analysis revealed a significant inverse association between LDL-C plasma levels and incident T2D ( p  < 0.001). When stratifying LDL-C into quartiles [i.e. low (< 84 mg/dL), medium (≥ 84 to < 107 mg/dL), high (≥ 107 to < 131 mg/dL), and very high (≥ 131 mg/dL)], we observed that patients with LDL-C < 84 mg/dL had the highest risk of developing T2D. The interaction between statin therapy and T2D incidence was significant only in the very high LDL-C group, where statin users had a greater risk than non-users (p = 0.018); in the other three LDL-C groups, statin therapy did not significantly modify the association between LDL-C and T2D risk. Conclusions Taken together, our findings demonstrate a strong inverse association between LDL-C and incident T2D in the general population. The increased risk of T2D at lower LDL-C levels appears to be independent of statin use, supporting the role of LDL-C as a potential biomarker of T2D susceptibility. Graphical Abstract

Background Prediabetes represents the final stage on the glycemic spectrum before the onset of type 2 diabetes mellitus (T2DM), and delaying its progression offers a unique opportunity to address the growing T2DM epidemic. Methods In this longitudinal cohort study, we investigated the effect of daily low-dose aspirin on the development of T2DM in individuals with prediabetes residing in Naples, Italy, who were followed by their primary care physicians between 2018 and 2022. Outcomes in the aspirin-treated group were compared with those in a control group not receiving aspirin, using data from the same database. Propensity score matching was employed to ensure comparability of covariates at baseline. Results The primary outcome was the onset of T2DM, defined as a new diagnosis accompanied by antidiabetic prescriptions lasting more than 30 days. Gastrointestinal bleeding was assessed as the safety endpoint. Over the follow-up period, 488 new cases of T2DM were documented (15.6% of the total population), with 174 cases occurring in the aspirin group (22.3 per 1000 person-years) and 314 in the non-aspirin group (40.2 per 1000 person-years), indicating a significantly lower incidence of diabetes among aspirin-treated individuals. Given the difference in comorbidity rates between groups, a Cox regression analysis was conducted across the entire follow-up period, showing that aspirin use was associated with a 47% reduction in the risk of developing T2DM (HR 0.53, 95% CI 0.44–0.64, p  < 0.001). However, aspirin use was also linked to an increased risk of gastrointestinal bleeding (4.9% vs 3.1%, p  < 0.05). Kaplan–Meier survival curves confirmed a significantly lower cumulative incidence of T2DM in the aspirin-treated group (log-rank test p  < 0.0001). Conclusions Daily treatment with 100 mg aspirin was associated with approximately a 50% reduction in the incidence of new-onset T2DM, but also with an increased risk of gastrointestinal bleeding, in elderly individuals with prediabetes. Graphical abstract