Atrial fibrillation (AF) is frequent in dialysis patients and associates with a substantial increase in stroke, cardiovascular events, and mortality, yet the net clinical benefit of oral anticoagulation (OAC) in this setting remains uncertain. Dialysis patients were excluded from pivotal vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) trials, and observational data are conflicting. The PRO position argues that in carefully selected patients with very high thromboembolic risk and acceptable bleeding risk, thromboembolic prophylaxis-pharmacological with OAC or non-pharmacological with left atrial appendage closure (LAAC)-can reduce stroke and possibly mortality. This view is supported by several cohort studies suggesting lower ischemic events and improved survival when OAC is maintained, and international normalized ratio control is good, and by emerging data that LAAC may offer similar stroke protection with less bleeding and lower mortality than OAC or no prophylaxis. The CON position stresses that many large studies show no clear stroke reduction and consistently higher major bleeding with warfarin versus no OAC, that small randomized controlled trials of DOACs versus VKAs reveal very high absolute bleeding without clear efficacy gains, and that VKAs may aggravate vascular calcification. Both positions agree on the need for individualized, shared decision-making and for adequately powered randomized trials comparing OAC and LAAC with no specific therapy in dialysis AF.

Introduction:Cyclophosphamide (CYC) and rituximab (RTX), alone or combined, are the mainstays of induction therapy in antineutrophil cytoplasmic autoantibody (ANCA)-glomerulonephritis. It is unknown whether the response to induction is differentially affected by kidney histopathology. Methods:This is a retrospective, multicenter study including patients with biopsy-proven ANCA-glomerulonephritis. Cases were grouped according to the Berden nephropathology classification. Estimated glomerular filtration rate (eGFR) recovery at 6 months was defined as eGFR increase ≥ 15 ml/min per 1.73 m2 or discontinuation of kidney replacement therapy (KRT); kidney failure was defined as sustained eGFR < 15 ml/min per 1.73 m2 or long-term KRT. Multivariable regression models were used to explore independent predictors of kidney outcomes across Berden classes. Results:The cohort included 304 patients; median baseline eGFR was 20 ml/min per 1.73 m2 (interquartile range [IQR]: 11-35). Induction immunosuppression was with CYC in 59%, with RTX in 17%, and with RTX-CYC in 24%. Overall, 50% recovered kidney function and 19.4% had kidney failure over a median follow-up of 42 months (IQR: 18-72). In the crescentic class, the RTX group had lower chances of eGFR recovery than CYC (odds ratio [OR]: 0.23, 95% confidence interval [CI]: 0.05-0.98, P = 0.047); the trend was similar in comparison with RTX-CYC (OR: 0.20, 95% CI: 0.03-1.19, P = 0.077). In the crescentic class, RTX monotherapy was marginally associated with increased risk of kidney failure, compared with both CYC (hazard ratio [HR]: 3.42, 95% CI: 1.03-11.35, P = 0.045) and RTX-CYC (HR: 5.33, 95% CI: 0.91-31.18, P = 0.063). No significant differences were observed in the other Berden classes. Conclusion:Patients with crescentic class ANCA-glomerulonephritis receiving RTX monotherapy may have worse kidney outcomes than those treated with CYC-based regimens. Further studies are needed to validate these results and better understand how to personalize treatment.

BACKGROUND AND AIM:Familial hypercholesterolemia (FH) is a common genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) from early life, significantly increasing lifetime risk of atherosclerotic cardiovascular disease. Early identification and initiation of lipid-lowering therapy (LLT) are crucial. This study aimed to describe the timing, pharmacological approach, and early outcomes of LLT initiation in children and adolescents with FH from the Italian LIPIGEN registry. METHODS:We analysed 341 paediatric FH patients who were untreated at baseline and had follow-up data within 3 years. Data included clinical features, LDL-C levels, genetic testing results, and treatment patterns. Outcomes included time to LLT initiation, type of therapy, LDL-C reduction, and achievement of guideline-recommended goals. RESULTS:Mean age at baseline was 10.8 years. At the end of the first year of follow-up, 51.6% initiated LLT, increasing to 78.9% after 3 years (mean age at treatment initiation: 10.9 years), with earlier initiation among those with higher baseline LDL-C. Statins were the most used agents (43.9%), especially in children ≥8 years, followed by combination statin-ezetimibe (11.5%). Nutraceuticals were more common in children <8 years. LLT was associated with a mean LDL-C reduction of 25.7%, reaching 50.2% with statin-ezetimibe. Only 26.1% achieved LDL-C goals, with highest rates among those on combination therapy. CONCLUSIONS:Despite increased use of pharmacological therapy, therapeutic inertia remains common in paediatric FH, resulting in few children reaching recommended LDL-C targets. These findings highlight the need for earlier intervention, closer follow-up, and optimization of treatment strategies to improve long-term cardiovascular outcomes.

Atherogenic dyslipidemia is a condition characterized by high lipid levels that promote the development of atherosclerosis. While the clinical manifestations of atherosclerosis typically manifest in adulthood, early vascular damage can be identified in children and adolescents. Dyslipidemia is not uncommon in childhood and adolescence, and its development depends on the interaction between genetic and environmental factors. Forms caused by genetic defects tend to manifest earlier and usually require drug treatment. Forms caused by unhealthy lifestyles and eating habits tend to manifest later and often only require dietary and behavioural treatment. The review describes the most common primary forms, diagnostic criteria and treatment options, both pharmacological and non-pharmacological, emphasizing the differences and specificities of dyslipidemia in children compared to adults. The review’s objective is also to provide a clinically focused summary of the current evidence on atherogenic dyslipidemia in children and adolescents.

Atrial fibrillation (AF) is highly prevalent in patients with kidney failure (KF) who are undergoing hemodialysis (HD). All patients with AF and a thromboembolic risk score (CHA2DS2-VA) of two or more should be prescribed oral anticoagulant therapy (OAC), according to cardiology guidelines. However, there are no randomized controlled trials (RCTs) demonstrating that OAC protects against thromboembolic events in HD patients. Furthermore, evidence from observational studies is insufficient to demonstrate the benefits of OAC for preventing thromboembolism in HD patients with AF. Instead, it suggests that OAC is associated with an increased risk of bleeding in these patients. Left atrial appendage closure (LAAC) has been proposed as a means of preventing thromboembolic events in patients with AF. RCTs conducted in populations with preserved kidney function have demonstrated that the procedure is not inferior to OAC in terms of efficacy, and is associated with greater safety. Although no RCTs have tested the safety and efficacy of LAAC in KF patients undergoing HD, some observational studies suggest that LAAC has a similar efficacy profile in patients with and without KF. However, a higher incidence of peri-procedural complications has been reported. Observational studies comparing the efficacy and safety of LAAC with OAC in KF patients have shown a similar or reduced incidence of thromboembolism and bleeding in patients undergoing the procedure. The purpose of this Position Paper is to provide comprehensive, evidence-based information on the advantages and limitations of LAAC in KF patients with AF undergoing HD.

In most patients with atrial fibrillation (AF), effective stroke prevention necessitates long-term (often lifelong) oral anticoagulant therapy (OAC). However, the effectiveness of OAC therapy in a clinical setting (i.e. outside the controlled environment of randomized clinical trials) is strongly influenced by patients' adherence and persistence with prescribed therapy. However, suboptimal adherence to OAC remains a substantial problem in routine practice-available evidence suggests that patients do not take their OAC one out of every four days, and approximately one in three to four patients is poorly adherent to OAC. In addition, around 15% of high-risk OAC-eligible patients with AF refuse to take OAC for a variety of patient-specific reasons. Poor adherence to OAC therapy is associated with adverse clinical outcomes [such as stroke or systemic embolism, hospitalization, mortality, bleeding (particularly with vitamin K antagonist therapy)] and increased economic costs. In this overview, we summarize important aspects of the adherence to medication concept, including the definition and measurement of adherence, the determinants and prevalence of OAC non-adherence, the clinical importance of achieving and maintaining good adherence, strategies to improve adherence to OAC, and alternative treatment options for effective thromboprophylaxis in patients with AF who are non-adherent to OAC therapy.

BACKGROUND:The American Academy of Pediatrics, the European Society of Hypertension, and the European Society of Cardiology propose distinct hypertension classification criteria for children and adolescents based on 2 percentile derivations and different fixed blood pressure thresholds at different ages, leading to potential confusion in clinical and research settings. METHODS:We developed 2 Shiny apps and 1 mobile app that allow simultaneous calculation of blood pressure percentiles using both methods and classify hypertension according to each guideline. The first Shiny app was designed for research purposes, offering an efficient tool for handling large pediatric data sets. The second Shiny app and the mobile app are designed for clinical use, presenting the same relevant outcomes for individual patients in a user-friendly interface. The research-focused app was tested on 3 data sets varying in age, blood pressure, and weight distributions. RESULTS:When comparing the 3 hypertension classifications across the samples, the American Academy of Pediatrics and European Society of Cardiology criteria consistently identified more individuals as hypertensive than the European Society of Hypertension across all age and weight groups, resulting in discordance rates from 2.3% to 21.1%. In contrast, the American Academy of Pediatrics and the European Society of Cardiology showed high agreement, with minimal or absent discordance ranging from 0.0% to 4.4%. An exception was seen in ages of 13 to 16 years, where differing criteria led to greater and unpredictable discordance. CONCLUSIONS:These apps offer researchers and clinicians powerful tools to calculate blood pressure percentiles and hypertension classifications based on different guidelines. This marks an important first step toward identifying which classification best predicts clinical outcomes.

Sudden cardiac death is an important cause of mortality in patients with kidney failure undergoing renal replacement therapy, either hemodialysis or peritoneal dialysis. The risk factors associated with sudden cardiac death in these patients only partly overlap with those in the general population. Kidney failure per se and hemodialysis therapy expose these patients to an increased risk of sudden cardiac death compared with individuals with preserved renal function. Studies of the implantable cardioverter defibrillator for primary prevention of sudden cardiac death in patients with kidney failure have failed to demonstrate its usefulness. Moreover, the incidence of complications associated with cardiac electronic device implantation in this population is extremely high. This review aims to provide an update on the available studies on the pathophysiology and prevention of sudden cardiac death in patients with kidney failure undergoing dialysis and to propose the adoption of clinical practices to reduce its incidence.

AIMS:Patients with end-stage renal disease (ESRD) and atrial fibrillation present a challenge for thromboembolic prevention, given their elevated risks of both thromboembolism and bleeding. Anticoagulants carry a higher bleeding risk in this population without clear evidence of thromboembolic benefit. This study aims to define the role of left atrial appendage occlusion (LAAO) as a preventive strategy for patients with ESRD. METHODS AND RESULTS:A systematic literature review was conducted to identify studies reporting outcomes in patients with ESRD who underwent LAAO. Meta-analyses of aggregate and individual patient data were performed to evaluate acute and long-term outcomes and compare them with those of patients without ESRD. Seventeen studies reporting data from 24 127 patients, including 1047 with ESRD, were included. Procedural complications were more common in patients with ESRD (RR 2.23; P = 0.02), with a pooled rate of 4% (95% CI, 1-9%). There was no significant difference in thromboembolic event rates during follow-up between the groups (IRR 1.44; P = 0.16), but major bleeding incidence was higher among patients with ESRD (IRR 1.84; P < 0.01). Individual patient-level data from seven studies comprising 4745 patients (268 with ESRD) were obtained and analysed. Similarly, there was no significant association between ESRD and stroke/TIA incidence (HR, 1.22; 95% CI, 0.66-2.26), but major bleeding was higher on patients with ESRD (HR, 1.65; 95% CI, 1.01-2.69). CONCLUSION:LAAO represents a feasible option for thromboembolic prevention in patients with ESRD, although these patients have an increased risk of complications and bleeding.

Cardiovascular and cerebrovascular diseases (CVDs), primarily driven by atherosclerosis, remain the leading cause of mortality worldwide and represent a major healthcare burden. Mounting evidence demonstrates that atherosclerotic processes begin in childhood, with lipid streaks detectable as early as the first decade of life. The increasing prevalence of obesity, hypertension, dyslipidemia, insulin resistance, and other modifiable cardiovascular risk factors (CVRFs) in children and adolescents highlights the urgent need for prevention strategies starting early in life. This document, jointly produced by the Italian Society of Pediatrics (SIP), the Italian Society of Hypertension (SIIA), the Italian Society for the Study of Atherosclerosis (SISA), and the Italian Society for Cardiovascular Prevention (SIPREC), emphasizes that atherosclerosis should be considered a disease with its roots in childhood and that true primary prevention must begin from pregnancy and birth. Two possible and complementary levels of intervention should be considered: (1) population-wide promotion of healthy diets, lifestyles, and supportive environments; and (2) early identification and management of specific CVRFs in children and adolescents. The involvement of multiple stakeholders—families, pediatricians, schools, healthcare professionals, policymakers, patient associations, and the media—is crucial to ensure the effectiveness of prevention interventions. Particular attention must be given to obesity, as both an independent risk factor and a driver of additional metabolic and vascular risks. Fighting CVDs requires a paradigm shift: preventive action must start early, be comprehensive, and mobilize all sectors of society. Only by addressing cardiovascular risk during childhood can the future burden of CVDs be effectively reduced.

Background: Awareness, diagnosis, and treatment of familial hypercholesterolemia (FH) starting from childhood are a cornerstone of cardiovascular disease prevention. The LIPIGEN Paediatric Group, a network of specialised centres for the diagnosis and management of familial genetic dyslipidemia, is an active part of this mission. Materials and Methods: This is the second exploratory survey organised within the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) paediatric centres. A digital questionnaire consisting of 16 questions was proposed to the principal investigators of 35 LIPIGEN centres in September 2023. We analysed the main FH screening strategies implemented in Italy, which are the referral characteristics to the lipid clinics and clinical and biochemical criteria considered to diagnose FH in paediatric patients. Results: Centres frequently reported conducting cascade screening (88.6%) and reverse screening (57.1%), whereas 28.6% of respondents indicated using selective screening and only 5.7% reported employing child–parent screening. We documented a detailed biochemical characterisation of paediatric patients (62.9% of respondents usually perform full lipoprotein profile and 80% determine lipoprotein(a) for each patient) and a high percentage of genetic analysis (82.9%). We have also highlighted a quite low awareness of FH as a genetic condition involving paediatric patients among primary care paediatricians and general practitioners. Conclusions: The results of our survey show that specialised lipid centres usually have good diagnostic competence when dealing with paediatric patients with hypercholesterolemia. However, FH awareness and the importance of early diagnosis and treatment initiation in childhood still need to be further improved.

Rationale & Objective: Atrial fibrillation (AF) is highly prevalent among patients receiving maintenance hemodialysis (HD) and patients with ST elevation myocardial infarction (STEMI). We investigated the association of AF with in-hospital mortality, 1-year mortality, and 1-year readmission for acute myocardial infarction (AMI) in HD patients admitted with STEMI. Study Design: Retrospective cohort study based on a large administrative database. Setting & Participants: 138,939 patients admitted with STEMI from 2003-2018, of whom 1,185 (8.5%)receiving HD, followed from the date of admission until death, migration, or 1 year after discharge. Exposures: STEMI (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] 410.x) as the primary discharge diagnosis, maintenance HD (ICD-9-CM 39.95; 54.98; V560; V563.1; V563.2), and AF (ICD-9-CM 427.31). Outcomes: In-hospital all-cause mortality (primary outcome), 1-year all-cause mortality, and 1-year readmission for AMI (secondary outcomes). Analytical Approach: Multivariable logistic regression and multivariable Cox regression. Results: One hundred and ninety-five out of 1,185 (16.5%) patients had AF at admission or developed AF during hospitalization. After adjusting for possible confounders, AF versus sinus rhythm was associated with higher in-hospital mortality (odds ratio [OR] = 1.57; 95% confidence interval [CI], 1.11-2.22). AF was associated with higher 1-year mortality (hazard ratio [HR] = 1.45; 95% CI, 1.18-1.76), whereas it was not associated with higher 1-year readmission for AMI (HR = 1.05; 95% CI, 0.72-1.53). Less than 20% of patients with AF discharged alive were prescribed oral anticoagulant therapy. In this subgroup, oral anticoagulant therapy was associated with lower 1-year mortality (HR = 0.46; 95% CI, 0.24-0.89). Limitations: Potential bias due to incorrect or incomplete coding, retrospective design, incidence of thromboembolic events after discharge, and cause of 1-year mortality unknown. Conclusions: AF is highly prevalent and associated with adverse short- and long-term outcomes in HD patients admitted with STEMI. Plain-Language Summary: Atrial fibrillation (AF) is common both in patients with kidney failure receiving hemodialysis (HD) and in those with acute myocardial infarction. We investigated retrospectively the impact of AF on 1,185 patients receiving HD admitted for ST elevation myocardial infarction (STEMI). We examined the incidence of in-hospital mortality, 1-year mortality, and 1-year readmission for acute myocardial infarction in patients with AF compared with patients without AF. AF was associated with increased in-hospital mortality and an increased risk of death at 1-year follow-up. In patients who survived the STEMI episode, treatment with oral anticoagulants was associated with a lower risk of death at 1-year follow-up. This study shows a heavy prognostic impact of AF on HD patients who underwent STEMI.

The prevalence of pediatric excess weight has reached such levels that there are fears of a sharp increase in associated noncommunicable diseases when today’s children become adults [...]

Introduction: Chronic kidney disease (CKD) increases cardiovascular risk through mechanisms such as oxidative stress and the accumulation of advanced glycation end products (AGEs). Glycated albumin (GA) is associated with cardiovascular risk in CKD patients, but its relationship with AGEs and systemic inflammation remains unclear. This study investigated these associations in old patients with severe CKD, with and without diabetes. Methods: We conducted a cross-sectional analysis in 122 patients aged ≥ 65 years with CKD stages G3a–G5, including 67 diabetics and 55 non-diabetics. Patients with confounding comorbidities were excluded. We measured GA, AGEs, various AGEs receptors (RAGE) isoforms, and inflammatory cytokines (CRP, IL-6, TNFα, and MCP-1) using standardized assays. Statistical analyses included group comparisons, correlation coefficients, and multivariate regression. Results: Of 122 patients (mean age 77.7 ± 11.3 years), diabetics had higher GA percentages than non-diabetics (22.0 ± 7.1% vs. 17.5 ± 5.4%, p = 0.0001), while AGEs (2931 ± 763 vs. 3156 ± 809 AU; p = 0.118) and inflammatory markers (CRP 0.240[0.380] vs. 0.200[0.280] mg/dL; p = 0.142; IL-6 3.4[4.0] vs. 3.0[3.8] pg/mL; p = 0.238) were similar between groups. Overall, GA was inversely correlated with estimated glomerular filtration rate (eGFR) (ρ = −0.189, p = 0.037) and positively with glycated hemoglobin (HbA1c) (ρ = 0.525, p < 0.0001), but showed no significant correlation with AGEs, RAGE isoforms, or inflammatory cytokines. In multivariate analysis, only HbA1c remained independently associated with GA (β = 0.222, p = 0.005). Conclusions: In old patients with severe CKD, GA appears to be a more useful marker of glycemic control than glycation stress, the latter of which is the result of multiple factors, including impaired kidney function and systemic inflammation.