Risk Difference Research Articles

Effectiveness of team-focused CPR on in-hospital CPR quality and outcomes

ObjectiveWe sought to identify changes in neurological outcome over time following initial training and subsequent implementation of team-focused CPR in an inpatient setting where responders practice specific roles with emphasis on minimally interrupted chest compressions and early defibrillation. MethodsThis retrospective pre- vs post-intervention study was conducted at an urban 900-bed teaching hospital and Level I Cardiac Resuscitation Center. We included adult patients suffering in-hospital cardiac arrest occurring in non-emergency department and non-intensive care unit areas who received CPR and/or defibrillation. We compared survival with good neurological outcome at time of hospital discharge in the one-year periods before and after implementation of team-focused CPR. To investigate skill degradation, we compared cumulative survival with good neurological outcome in 3-month intervals against the before team-focused CPR baseline. Trained research associates abstracted explicitly defined variables from electronic health records using a standardized form and data dictionary to achieve consistency between collaborators. ResultsOf 296 IHCAs, 207 patients met inclusion criteria and were analyzed. In 104 patients before team-focused CPR initiation, survival with good neurological outcome was 21%. In the 12-month period following team-focused CPR initiation, survival with good neurological outcome was 31% in 101 patients, risk difference 9.9% (95% CI −2 to 22%; p = 0.14). By quarterly time intervals, following team-focused CPR implementation, the cumulative survival with good neurological outcome at 3 months was 42%; at 6 months 37%; at 9 months 31%; and at 12 months 31%. ConclusionIn our single-institution implementation of team-focused CPR for in-hospital cardiac arrest, outcomes significantly improved at 6 months before declining towards baseline.

Sex and gender differences in hepatitis C virus risk, prevention, and cascade of care in people who inject drugs: systematic review and meta-analysis

People who inject drugs (PWID) are a priority population in HCV elimination programming. Overcoming sex and gender disparities in HCV risk, prevention, and the cascade of care is likely to be important to achieving this goal, but these have not yet been comprehensively reviewed. Systematic review and meta-analysis. We searched Pubmed, EMBASE and the Cochrane Database of Systematic Reviews 1 January 2012-22 January 2024 for studies of any design reporting sex or gender differences among PWID in at least one of: sharing of needles and/or syringes, incarceration history, injection while incarcerated, participation in opioid agonist treatment or needle and syringe programs, HCV testing, spontaneous HCV clearance, direct-acting antiviral (DAA) treatment initiation or completion, and sustained virological response (SVR). Assessment of study quality was based on selected aspects of study design. Additional data were requested from study authors. Data were extracted in duplicate and meta-analysed using random effects models. PROSPERO registration CRD42022342806. 9533 studies were identified and 92 studies were included. Compared to men, women were at greater risk for receptive needle and syringe sharing (past 6-12 months: risk ratio (RR) 1.12; 95% confidence interval (CI) 1.01-1.23; <6 months: RR 1.38; 95% CI 1.09-1.76), less likely to be incarcerated (lifetime RR 0.64; 95% CI 0.57-0.73) more likely to be tested for HCV infection (lifetime RR 1.07; 95% CI 1.01, 1.14), more likely to spontaneously clear infection (RR1.58; 95% CI 1.40-1.79), less likely to initiate DAA treatment (0.84; 95% CI 0.78-0.90), and more likely to attain SVR after completing DAA treatment (RR 1.02; 95% CI 1.01-1.04). There are important differences in HCV risk and cascade of care indicators among people who inject drugs that may impact the effectiveness of prevention and treatment programming. Developing and assessing the effectiveness of gender-specific and gender-responsive HCV interventions should be a priority in elimination programming. Réseau SIDA-MI du Québec.

Anticoagulation for post-operative atrial fibrillation after isolated coronary artery bypass grafting: a meta-analysis.

This study aimed to evaluate clinical outcomes in patients developing post-operative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) and characterize variations in oral anticoagulation (OAC) use, benefits, and complications. A systematic search identified studies on new-onset POAF after CABG and OAC initiation. Outcomes included risks of thromboembolic events, bleeding, and mortality. Furthermore, a meta-analysis was conducted on these outcomes, stratified by the use or non-use of OAC. The identified studies were all non-randomized. Among 1 698 307 CABG patients, POAF incidence ranged from 7.9% to 37.6%. Of all POAF patients, 15.5% received OAC. Within 30 days, thromboembolic events occurred at rates of 1.0% (POAF: 0.3%; non-POAF: 0.8%) with 2.0% mortality (POAF: 1.0%; non-POAF: 0.5%). Bleeding rates were 1.1% for POAF patients and 2.7% for non-POAF patients. Over a median of 4.6 years, POAF patients had 1.73 thromboembolic events, 3.39 mortality, and 2.00 bleeding events per 100 person-years; non-POAF patients had 1.14, 2.19, and 1.60, respectively. No significant differences in thromboembolic risks [effect size -0.11 (-0.36 to 0.13)] and mortality [effect size -0.07 (-0.21 to 0.07)] were observed between OAC users and non-users. However, OAC use was associated with higher bleeding risk [effect size 0.32 (0.06-0.58)]. In multiple timeframes following CABG, the incidence of complications in patients who develop POAF is low. The use of OAC in patients with POAF after CABG is associated with increased bleeding risk.

Racial/Ethnic differences in inflammation levels among older adults 56+: an examination of sociodemographic differences across inflammation measure.

Chronic inflammation is a key biological risk factor for many widespread adult health conditions. This study examines racial/ethnic differences in inflammation across several inflammatory markers, including selected cytokines that are identified as important for aging and age-related health outcomes. Data came from the 2016 Venous Blood Collection Subsample of the Health and Retirement Study. Using logistic regression models, we compared high-risk categories of C-reactive protein and cytokine markers (IL-6, IL-10, IL-1RA, TNFR1, and TGF-Beta), across race/ethnicity and whether these differences persisted among men and women. The findings provided evidence of significant race/ethnic differences in inflammatory measures, but the patterns differed across marker types. These findings emphasize that race/ethnic differences are not consistently captured across markers of inflammation and that researchers should proceed with caution when using individual markers of inflammation in an effort to not overlook potential racial/ethnic differences in biological risk.

Early vs Late Anticoagulation in Minor, Moderate, and Major Ischemic Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Whether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown. To assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation. Post hoc analysis of participants from the multinational (>100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis. Early vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined. A total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was -2.78% to 2.12% for minor stroke, -3.23% to 1.76% for moderate stroke, and -7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters. The treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke. ClinicalTrials.gov Identifier: NCT03148457.

Exploring the sex difference in cardiovascular risk during Growth Hormone Therapy in adults.

Given the previously identified sex differences in cardiovascular morbidity and mortality in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT), our aim is to investigate sex specific differences in the efficacy of (long-term) GHRT on cardiovascular (CV) risk profile and disease in subjects with GHD. Our hypothesis is that women will experience less beneficial effects than men. Retrospective nationwide cohort study. We compared all men (n = 1335) and women (n = 1251) with severe GHD registered in the Dutch National Registry of GH Treatment in Adults database with respect to cardiovascular risk profile and morbidity at baseline and during follow-up. Men had a more unfavourable CV risk profile at baseline. During the first years of GHRT, the reduction in waist circumference, waist-to-hip ratio, total cholesterol and triglyceride levels was greater in men than in women (all p < 0.05). Between-sex differences in effects during later follow-up were less clear. No sex differences were found in the risk of developing non-fatal cardio- or cerebrovascular disease during GHRT. Our results suggest that men with GHD did indeed experience more beneficial effects of GHRT on body composition and lipoprotein metabolism than women, at least in the early years of treatment. Also, the more unfavourable CV risk profile at baseline in men did not translate into a sex difference in the risk of developing cardiovascular and cerebrovascular morbidity during GHRT.

Physical frailty, genetic predisposition, and incident dementia: a large prospective cohort study.

Physical frailty and genetic factors are both risk factors for increased dementia; nevertheless, the joint effect remains unclear. This study aimed to investigated the long-term relationship between physical frailty, genetic risk, and dementia incidence. A total of 274,194 participants from the UK Biobank were included. We applied Cox proportional hazards regression models to estimate the association between physical frailty and genetic and dementia risks. Among the participants (146,574 females [53.45%]; mean age, 57.24 years), 3,353 (1.22%) new-onset dementia events were recorded. Compared to non-frailty, the hazard ratio (HR) for dementia incidence in prefrailty and frailty was 1.396 (95% confidence interval [CI], 1.294-1.506, P < 0.001) and 2.304 (95% CI, 2.030-2.616, P < 0.001), respectively. Compared to non-frailty and low polygenic risk score (PRS), the HR for dementia risk was 3.908 (95% CI, 3.051-5.006, P < 0.001) for frailty and high PRS. Furthermore, among the participants, slow walking speed (HR, 1.817; 95% CI, 1.640-2.014, P < 0.001), low physical activity (HR, 1.719; 95% CI, 1.545-1.912, P < 0.001), exhaustion (HR, 1.670; 95% CI, 1.502-1.856, P < 0.001), low grip strength (HR, 1.606; 95% CI, 1.479-1.744, P < 0.001), and weight loss (HR, 1.464; 95% CI, 1.328-1.615, P < 0.001) were independently associated with dementia risk compared to non-frailty. Particularly, precise modulation for different dementia genetic risk populations can also be identified due to differences in dementia risk resulting from the constitutive pattern of frailty in different genetic risk populations. In conclusion, both physical frailty and high genetic risk are significantly associated with higher dementia risk. Early intervention to modify frailty is beneficial for achieving primary and precise prevention of dementia, especially in those at high genetic risk.

Effects of whole-body vibration training on lower extremity muscle strength and physical function in elderly patients with sarcopenia

ABSTRACT Objectives To investigate the feasibility and benefits of WBV training in enhancing muscle strength and physical performance in older inpatients with sarcopenia. Methods We included 40 patients with sarcopenia (mean age 85 years; age range 80~90 years) and randomly separated into the WBV group or control (CON) group. The WBV group underwent 8 weeks of conventional rehabilitation training combined with WBV, whereas the CON group received 8 weeks of conventional rehabilitation training alone. The primary outcome was maximal isometric muscle strength. The secondary outcomes were the time-up-and-go test (TUGT), the five-times sit-to-stand test (FTSST), the 6-m gait speed test, and the Morse Fall Scale (MFS). Results After an 8-week intervention, only the quadriceps and tibialis anterior muscles in the CON group showed substantial gains in strength. In the WBV group, significant increases were observed in iliopsoas (P&lt;0.05), quadriceps (P&lt;0.01), hamstring(P&lt;0.01), and tibialis anterior muscle (P&lt;0.01) respectively. For all physical performance assessments, improvements were observed in both CON and WBV groups (P&lt;0.05), the improvement in the WBC group was greater than the CON group (P&lt;0.05). However, there was no significant difference in fall risk between the two groups (P&gt;0.05). Conclusion This result highlights a eight weeks of whole-body vibration training can increase the lower-limb muscular strength and physical performance of older inpatients with sarcopenia.

Role of dietary intake and physical activity in reducing weight social inequalities among adolescents: an application of G-formula to PRALIMAP-INÈS trial.

Interventions aiming to reduce social inequalities of weight status in adolescents usually focus on lifestyle behaviours, but their effectiveness is limited. This study analysed the effect of achieving levels of dietary intake (DI) and/or physical activity (PA) guidelines on reducing social inequalities in weight status among adolescents. We included adolescents from the PRomotion de l'ALIMentation et de l'Activité Physique - INÉgalité de Santé (PRALIMAP-INÈS) trial with weight status data available at baseline and 1-year follow-up (n=1130). PA and DI were measured using the International Physical Activity Questionnaire and a validated food frequency questionnaire, respectively. We estimated the likelihood of a 1-year reduction in body mass index z-score (BMIz) and population risk difference (PRD) under hypothetical DI and PA levels and socioeconomic status using the parametric G-formula. When advantaged and less advantaged adolescents maintained their baseline DI and PA, we found social inequalities in weight status, with a PRD of a 1-year reduction in BMIz of -1.6% (-3.0%; -0.5%). These inequalities were not observed when less advantaged adolescents increased their proportion of achieving DI guidelines by 30% (PRD=2.2% [-0.5%; 5.0%]) unlike the same increase in PA (PRD= -3.9% [-6.8%; -1.3%]). Finally, social inequalities of weight status were not observed when levels of achievement of both PA and DI guidelines increased by 30% (PRD= 2.2% [-0.5%; 4.0%]). Enhancing DI rather than PA could be effective in reducing social inequalities in weight status among adolescents. Future interventions aiming to reduce these inequalities should mostly target DI to be effective.

Sex Differences, Age, and Burn Size Contribute to Risk of PTSD and Depression After Burn Injury.

The prevalence of psychological symptoms in burn survivors has been well documented; however, the role of biological sex requires further investigation. This study explored sex differences among burn survivors and examined the impact of sex, age, and total body surface area (TBSA) of the burn injury on (1) the risk of developing PTSD and depression and, subsequently, (2) the influence of initial risk on symptom outcomes 30 days post-injury. Participants included 374 adult patients enrolled in the Burn Behavioral Health program at a regional Burn Center. T-tests and chi-square tests were conducted to determine differences between sexes on outcome measures. A path analysis was conducted to evaluate relationships between variables of interest. Findings revealed significant sex discrepancies in risk and symptom outcomes. Compared to men, women reported greater total risk scores of developing PTSD and depression (p = .005) early after their burn injury. A subscale analysis showed that women reported greater risk scores on depression (p < .001), but not on PTSD. Women did not report higher depression scores 30 days post-injury compared to men but did report higher PTSD scores than men (p = .020). When sex, age, and TBSA were included in a path analysis, female sex (p=.001), younger age (p<.001), and larger TBSA of the burn injury (p=.024) were associated with greater risk. Additionally, risk scores significantly predicted PTSD (p<.001) and depression (p<.001) symptoms 30 days post-injury. Our research shows how sex, age, and TBSA affect the risk of PTSD and depression among burn survivors. It underscores the importance of accounting for sex and age differences in mental health risk, especially in women and younger patients. This emphasizes the urgency of early screening and intervention.

Efficacy and safety evaluation of combined therapies incorporating whole-brain radiotherapy in patients with brain metastases: a systematic review and meta-analysis.

Whole-brain radiotherapy (WBRT) is a standard and effective approach for brain metastases, but it is linked to neurocognitive complications, specifically issues related to the hippocampus. Innovative strategies are being explored to enhance outcomes. However, a consensus is yet to be reached in this field. Our aim is to investigate the efficacy and safety of WBRT combined with simultaneous integrated boost (SIB), memantine, and hippocampal avoidance (HA) techniques in treatment of brain metastases. In this systematic review and meta-analysis, we comprehensively searched PubMed, MEDLINE, Embase, and Cochrane for studies reporting the efficacy and toxicity of WBRT-based combination therapies from inception to September 19, 2023. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) and risk differences (RDs) for dichotomous outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic. Among 2175 articles, 29 studies involving 3460 patients were included. The meta-analysis revealed that compared to WBRT alone, combination therapies significantly mitigated neurocognitive function decline (RD = -0.09, 95% CI [-0.18-0.01]; P = 0.03) and intracranial control failure (RR = 0.86, 95% CI [0.52-1.44]; P = 0.02), without increasing the risk of hippocampal recurrence or high-grade toxicities. Notably, HA-WBRT + SIB/memantine demonstrated improved neurocognitive outcomes and survival benefits. WBRT-based combination therapies demonstrate improved efficacy and comparable safety to WBRT alone, with specific emphasis on the effectiveness of HA-WBRT + Memantine and HA-WBRT + SIB in optimizing therapeutic outcomes for brain metastases.

Temporal order of atrial fibrillation and acute myocardial infarction and associated prognosis in the Danish Diet, Cancer, and Health cohort

Abstract Background Atrial fibrillation (AF) and acute myocardial infarction (AMI) share risk factors and are bidirectionally associated. Several studies found higher risks of outcomes in individuals with both conditions. Whether the risks of outcomes differ according to temporal order of AF and AMI is unclear. Purpose We aimed to assess the risks of heart failure (HF), ischemic stroke (IS) and all-cause mortality in individuals with both AF and AMI compared to only one. In addition, we assessed risks of outcome according to the temporal order of AF and AMI in individuals with both conditions. Methods The study was based on the Danish Diet, Cancer and Health cohort in which 57,053 men and women aged 50-64 years, with no diagnosis of cancer, participated. Assessment of AF, AMI and outcomes were based on diagnosis codes from the Danish National Patient Registry. We examined the risks of HF, IS and all-cause mortality during 10 years of follow-up in participants with both AF and AMI compared to only one and according to the temporal order of AF and AMI in participants with both conditions using Cox regression models. Results We identified 5,816 participants with newly diagnosed AF only, 3,448 with first AMI only, 348 with AF before AMI and 721 participants with AMI before AF. The multivariable-adjusted risks of HF, IS and all-cause mortality were higher among participants with both AF and AMI compared to participants with only AF or AMI (Figure 1). In participants with both AF and AMI, there was no difference in risk of HF (HR=0.92, 95% CI 0.72-1.17) or IS (HR=1.12, 95% CI 0.76-1.66) between participants with AF before AMI compared to AMI before AF. AMI before AF was associated with lower all-cause mortality compared to AF before AMI (HR=0.70, 95% CI 0.54-0.90) (Figure 2). Conclusions Risks of adverse outcomes were higher among participants with both AF and AMI compared to only AF or AMI. All-cause mortality, but not risk of HF or IS, differed according to temporal order with a lower mortality among participants with AMI before AF.Figure 1Figure 2

Time-trends of sex differences in stroke risk in atrial fibrillation: Are female patients still at higher risk today? A nationwide cohort study

Abstract Background Female sex is associated with higher risk of stroke in patients with atrial fibrillation (AF), particularly in the presence of other stroke risk factors. This has implications for oral anticoagulant treatment (OAC) decision-making, based on points of the CHA2DS2-VASc score. However, stroke rates have declined over recent years, and management has evolved over time towards a holistic approach that may have diminished the sex differences in AF-related stroke. Purpose To examine the changes in stroke risk over time in relation to risk differences between males and females not treated with oral anticoagulants in a nationwide cohort study. Methods This was an observational cohort study including patients with a hospital diagnosis of AF between 2007 and 2021. Data were obtained from the Danish nationwide registries. We identified a cohort of adult patients who were not receiving OAC treatment for up to 30 days after their AF diagnosis. Patients were followed up for thromboembolic events within one year after the AF diagnosis. Survival analysis was applied to describe the yearly rate of events and to estimate the risk ratio for females vs males of thromboembolism according to baseline risk levels, i.e., the CHA2DS2-VA score level (leaving out the ‘Sc’ sex criterion). Results A total of 188,704 AF patients (median age 75 years (IQR: 64 to 84); 49.7% female) who did not receive OAC treatment were included. The risk of thromboembolism during the entire study period was overall higher in females (3.5% in males vs. 4.7% among females). The overall one-year thromboembolic risk declined over time from 4.9% between 1997-2000 to 3.3% between 2017-2020, with male-female risk differences less evident in recent years (Figure 1a). The relative risk of stroke diminished from 1.22 (95%CI 1.10-1.34) in years 1997-2000 to 1.02 (95%CI 0.85-1.19) in years 2017-2020 for patients with a CHA2DS2-VA score of ≥2 (Figure 1b). For patients with a score of &amp;lt;2, the relative risk was lowest between 2005-2008 (1.02 (95%CI 0.63-1.42)) and was 1.18 (95%CI 0.54-1.83) in the latest time period. Formal statistical test for time trends according to score level revealed non-significant results (p-value=0.10 for score 0-1; p-value=0.17 for score levels of ≥2). Conclusion The risk of stroke among patients with AF has been declining over the last two decades. The excess stroke risk observed among females relative to males has also diminished, most evident among AF patients with ≥2 prevalent stroke risk factors.

Characteristics and incidence of peri-device leaks after left atrial appendage closure in patients with prior electrical isolation of left atrial appendage during catheter ablation

Abstract Background Patients who undergo electrical isolation of left atrial appendage (eLAAi) during atrial fibrillation (AF) ablation have a higher subsequent risk of thromboembolism. In post-ablation patients with eLAAi who undergo mechanical LAA closure (LAAC), there are limited data on imaging and clinical outcomes during follow-up, particularly peri-device leaks (PDLs). Purpose We investigated imaging outcomes on ~1 year follow up transesophageal echocardiography (TEE) for PDL and clinical outcomes in patients who had undergone LAAc after sustaining eLAAi from catheter ablation. Methods We analyzed data from TEEs at ~1 year follow up in patients who had undergone LAAC with either the Watchman or Watchman-FLX device. The images were analyzed for evidence of any discernible PDL which also which also included the absence of thrombosis/obliteration of the distal LAA. "Severe" PDL was categorized as the leak size of &amp;gt;5 mm on follow up TEE imaging. Baseline characteristics, imaging and clinical outcomes were compared with univariate comparison using Fisher’s exact test, between the two subgroups of LAAC patients stratified according to prior h/o eLAAi. Results A total of 532 patients underwent LAAC at our center between 03/2015 and 10/2022, with data available on ~1 year follow-up TEE imaging. Of these, 21 (3.9%) had undergone eLAAi during AF ablation prior to LAAC. At ~1 year follow up TEE imaging, the patients with prior h/o eLAAi had a numerically higher incidence of any PDL (42.9% vs 26.5%, p = 0.09). The incidence of severe PDL was significantly higher in the subgroup of patients with prior eLAAi as compared to patients without prior eLAAi (14.3% vs 3.3%, p = 0.04; Figure). There was no statistically-significant difference in the subsequent risk of thromboembolism between the eLAAi and control subgroups (4.8% vs 6.1%, p = 1.0) over an average follow-up of 577±331 days post-LAAC. Conclusions A prior history of eLAAi during AF ablation was associated with a higher risk of severe PDLs (&amp;gt;5mm) on follow up imaging after LAAC. The finding of severe PDL in the eLAAi subgroup might be attributable to ostial fibrosis as a result of ablation which might affect the LAA endocardial surface interaction with the device fabric. The occurrence of a higher risk of severe PDL in patients with prior eLAAi after LAAC might necessitate PDL closure or resumption of anticoagulation in such patients to mitigate the risk of subsequent thromboembolism.igure showing our study schema and compa

Systematic review and meta-analysis comparing cardiac resynchronization therapy with versus without defibrillation in patients with non-ischemic cardiomyopathy

Abstract Background Cardiac resynchronization therapy (CRT) stands as a notable medical breakthrough for individuals with heart failure and electrical desynchrony. This intervention aims to alleviate symptoms, diminish hospitalization rates, and enhance overall survival, both in conjunction with and without implantable cardioverter-defibrillator (ICD) therapy. Despite these advancements, the role of defibrillator therapy in addition with CRT for patients with non-ischemic cardiomyopathy (NICM) remains a topic of debate. Objective To assess and compare the outcomes of individuals diagnosed with NICM who have underwent CRT with implantable cardioverter-defibrillator (CRT-D) against those who received CRT with a pacemaker only (CRT-P). Methods We conducted a systematic search of PubMed, Embase and Cochrane database during August 2023 for studies comparing CRT-P and CRT-D in patients with nonischemic cardiomyopathy. Results Thirteen studies, including two randomized clinical trials, were incorporated, with a total of 61,326 patients providing 16,446 pooled death events (9,108 in CRT-D and 7,338 in CRT-P). The meta-analysis revealed that CRT-D was associated with a significantly lower risk of all-cause mortality compared to CRT-P (pooled HR 0.74; 95% CI: 0.62-0.88; I2=84%). Subgroup analysis focusing on propensity score-matched studies yielded consistent findings (pooled HR 0.82; 95% CI: 0.77-0.87; I² = 0%, P&amp;lt;0.001). However, subgroup analysis for patients older than 75 years suggested no statistically significant difference in mortality risk within this specific age group (pooled HR 0.96; 95% CI: 0.811-1.15; I² = 39%, P&amp;lt;0.001). Regarding the secondary endpoint of cardiovascular mortality, no significant risk reduction with CRT-D was observed (pooled HR 0.70; 95% CI: 0.49-1.01; I² = 92%), albeit with high heterogeneity. Conclusion Our study suggests that the addition of defibrillator therapy significantly reduces all-cause mortality in CRT-eligible patients with NICM, although results were not observed for patients older than 75 years.All-cause MortalityPatients older 75 years old

Stroke risk assessment in different atrial fibrillation subtypes: CHA2DS2-VASc score and beyond

Abstract Background Patients with atrial fibrillation (AF) have been known to have an inhomogeneous risk of stroke, with several well-documented risk factors including hypertension, history of stroke, and diabetes mellitus that have been incorporated into the CHA2DS2–VASc score to stratify risk levels. Accumulating evidence has suggested that AF subtype, namely persistent AF and paroxysmal AF, also have an impact on stroke development. Purpose This study focused on the impact of AF subtype on stroke risk in a large, long-term follow-up cohort as to provide insight of the impact on ischemic stroke risks. Such findings may play a role in future ischemic stroke risk stratification in selected patients. Methods A total of 7346 AF patients were followed up for 10 years from January 2010 to December 2020 (mean follow-up time 2.74 years). Among these patients, 2460 (33.5%) had persistent or permanent AF (PerAF) and 4886 (66.5%) had paroxysmal AF (PAF). The study evaluated the risk of ischemic stroke between the two groups using Cox models adjusting for all components of the CHA2DS2–VASc score. Analyses were further stratified into the usage of oral anticoagulation (OAC) or no OAC. Results Comparing AF patients based on subtype, it was found that PerAF patients were older, had a higher prevalence of previous stroke, congestive heart failure, PAD, DM, and were more often prescribed anticoagulants. Univariate analysis found patients with PerAF at a higher risk for ischemic stroke (HR 1.262, p&amp;lt;0.001). The results remained significant after multivariate analysis with factors of the CHA2DS2–VASc score (HR 1.234, p&amp;lt;0.001). After stratifying patients according to anticoagulation prescription, PerAF and PAF patients were found to have similar rates of developing ischemic stroke in patients under DOAC. Conclusions Patients with PerAF have a higher risk of stroke during follow-up independent of components of the CHA2DS2VASc score. In patients with OAC use, there was no difference in stroke risk between AF subtypes.Stroke Risk in OAC-naive patientsStroke Risk in OAC-experienced patients

Primary vs. secondary wound closure following transvenous system explantation in CIED infection

Abstract Background &amp; Introduction Patients undergoing an explantation of cardiac implantable electronic devices (CIED) receive either a primary or secondary wound closure or open wound treatment depending on departmental practice. To date, there is limited data on whether secondary wound closure or open wound treatment has any benefit in terms of future complications although it requires a more intensive wound care. Material &amp; Methods Patients who underwent CIED explantation for system infection at our institution between 2016 and 2022 were retrospectively reviewed. From this cohort, patients diagnosed with pocket infection were isolated and divided into two groups: (i) Patients who underwent primary wound closure with or without temporary use of a drain (PG), and (ii) patients who underwent secondary wound closure or open wound management (SG). Patients were followed up by telephone contact for short and long term complications. Results 387 patients underwent CIED explantation due to local or system infection at a heart centre. Of this cohort, 205 patients (135 female; 74.4 ±11.4 y.o.) had a pocket infection. In addition to local infection, 25.9% of all patients presented with a pocket perforation. The onset of infection was early (within 28 days) in 16.1%, intermediate (29 days - 1 year) in 50.2% and late (after 1 year) in 33.2%. Wound swabs and blood cultures were positive for pathogens in 61.0% and 14.1% respectively. 136 (65.9%) underwent primary wound closure, 69 (34.1%) underwent secondary wound closure or open wound management. Post-operative (p.o.) hematoma was present in 12.2% of the cases (6.6% of PG and 24.6% of SG). The risk of developing a p.o. hematoma was significantly more likely in the SG (OR=4.61; IC95%: 1.93 − 11.01). Re-implantation occurred in 70.2%, including 25.7% of leadless pacemakers an 1.5% subcutaneous defibrillators. In 13.7% re-implantation was not indicated, 4.4% refused and 1.0% had contraindications. Mean length of hospitalization was 12.4 ±8.9 days in the PG and 15.7 ±9.6 days in the SG (ρ = 0.0083). A total of 24 (34.8%) patients were discharged with an open wound with or without vacuum treatment (0.74% of PG; 34.8% of SG). Mean telephonic follow-up was 27 ±18 months in 147 cases (n1 = 99; n2 = 48). 91.8% of the cases had no pathological findings at follow-up. 2.7% developed a wound healing disorder (WHD) which was treated conservatively, 4.1% required revision, 0.7% explantation and 0.7% endocarditis. No statistical difference of complication risk between both groups was found (OR=1.8; IC95%: 0.51 - 6.17). Summary &amp; Conclusions Management of CIED pocket infection with primary wound closure compared to secondary wound closure showed a statistically significant shorter hospital stay and reduced likelihood of post-operative hematoma, with no increase in long-term complication rates.

#462 Initiation of SGLT2i vs GLP1-RA and incidence of AKI in persons with type 2 diabetes mellitus

Abstract Background and Aims Adverse kidney outcomes, including acute kidney injury (AKI), are frequent complications in people with diabetes mellitus type 2. In large placebo-controlled randomized trials, both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown efficacy in reducing the risk of kidney outcomes; however, no trial has compared the kidney protective effects of these drug classes head-to-head. We therefore conducted an emulated target trial to compare the effect of SGLT2i to that of GLP1-RA on the incidence of AKI. Method Using routinely collected data from nationwide Danish population-based registries, we included all adults with diabetes mellitus type 2 initiating SGLT2i or GLP1-RA in 2015-2020. Patients with prevalent kidney failure (defined as eGFR &amp;lt; 15 mL/min/1.73m2, dialysis, or kidney transplant), and patients initiating GLP1-RA marketed specifically for treatment of obesity were excluded. We assessed demographic and diabetes-related baseline characteristics along with comorbidities and comedication. We used propensity scores, estimated by logistic regression, to compute stabilized inverse probability of treatment weights, which were applied in all analyses to reduce confounding. Using an intention to treat approach, we followed patients from treatment initiation until the first of death, emigration, or end of follow-up (31 December 2021). Using creatinine measurements from in- and outpatient settings, we applied the KDIGO definition of AKI to record each episode of AKI during follow-up. We estimated the risk of a first AKI episode over time using the Aalen-Johansen estimator. Furthermore, to estimate the mean number of AKIs over time, i.e., including recurrent AKIs, we used the mean cumulative count estimator. Both estimators account for the competing risk of death. Comparing SGLT2i to GLP1-RA, we reported differences in risks and counts at 1, 3 and 5 years of follow-up. Finally, we estimated all-cause mortality using the Kaplan-Meier estimator. We used bootstrapping to obtain 95% confidence intervals (95% CI). Results We included 68 010 individuals, of which 44 034 (65%) initiated SGLT2i, and 23 976 (35%) initiated GLP1-RA. Initiators of SGLT2i were slightly older (median age 63 vs 62 years) and more often male (63% vs 56%) than initiators of GLP1-RA, but with similar diabetes duration (7 vs 7 years). The annual number of initiators of each drug in Denmark increased over the study period. Compared to GLP1-RA, initiators of SGLT2i generally had better estimated glomerular filtration rate (eGFR) at baseline (9% vs 18% had eGFR &amp;lt; 60 mL/min/1.73m2), more frequently used metformin (91% vs 84%), but less frequently insulin (11% vs 28%). Initiators of SGLT2i had a lower prevalence of hospital-diagnosed retinopathy (7% vs 9%), neuropathy (5% vs 6%), and obesity (13% vs 23%) than initiators of GLP1-RA. After inverse probability of treatment weighting, each variable was well balanced with absolute standardized mean differences below 0.02. During a median follow-up of 2.8 years, the weighted absolute risks of first time AKI at 1, 3, and 5 years were 4.8%, 11.2%, and 17.0% for initiators of SGLT2i, and 5.4%, 12.3%, and 19.1% for initiators of GLP1-RA, resulting in AKI risk differences of −0.6% (95% CI: −1.0% to −0.3%), −1.0% (95% CI: −1.7% to −0.5%), and −2.0% (95% CI: −3.0% to −1.1%). The mean cumulative counts showed a similar pattern, with SGLT2i initiators experiencing slightly fewer AKI episodes than GLP1-RA initiators on average (Fig. 1). After 5 years, an estimated 10.3% of SGLT2i initiators and 9.6% of GLP1-RA initiators had died, resulting in a risk difference of 0.7% (95% CI: -0.1% to 1.5%). Conclusion People with diabetes mellitus type 2 who initiated SGLT2i had slightly lower weighted incidence of AKI over 5 years than those initiating GLP1-RA.

#614 Identifying distinct patient phenotypes in patients with chronic kidney disease

Abstract Background and Aims Patients with chronic kidney disease (CKD) are heterogeneous in terms of age, causes of CKD, and comorbidities. Although individual risk factors greatly influence patients’ risk of clinical outcomes, this heterogeneity is rarely used to guide clinical decision-making. In this study we aimed to derive phenotypes in patients with CKD based on characteristics commonly available in routine clinical practice and evaluated whether these phenotypes were associated with clinical outcomes. Method Patients from the Utrecht Patient Oriented Database (UPOD) who were 18 years or older with CKD (defined as an eGFR &amp;lt;60 ml/min/1.73 m2 or an UACR &amp;gt; 3 mg/mmol present for &amp;gt;3 months) and visited one of the cardiovascular outpatient clinics of the University Medical Center Utrecht between 2012 and 2019 were included. Patient phenotypes were derived with latent class analyses based on age, sex, CKD stage, cause of kidney disease, and (cardiovascular) comorbidities. The incidence rate/100 person years (IR/100PY) for all-cause mortality and kidney failure (defined as initiation of kidney replacement therapy or a sustained eGFR &amp;lt;15) and 95% confidence interval (95% CI) was calculated for each phenotype. Results Overall 9005 patients were included (mean age 65 ± 14 years, 42% women, mean estimated glomerular filtration rate (eGFR) 49 ± 17 ml/min/1.73 m2). The median follow-up was 3.8 years [interquartile range 1.8–6.4]. Latent class analysis identified 7 phenotypes with the following characteristics: phenotype 1 were young patients with primary kidney disease (10%); phenotype 2 were patients with diabetes and a preserved eGFR (9%); phenotype 3 were patients with low comorbidity and inflammation (28%); phenotype 4 were older patients with a history of cardiovascular disease (27%); phenotype 5 were older patients with a history of cardiovascular disease and severe CKD (16%); phenotype 6 were younger patients with a kidney transplant and low comorbidity (6%); and phenotype 7 were older patients with a kidney transplant and cardiovascular disease (6%). The risk of all-cause mortality and kidney failure differed significantly between the identified phenotypes. The phenotypes of younger kidney transplant recipients, younger patients with primary kidney disease, and diabetes with preserved eGFR had the lowest risk for all-cause mortality (for all, IR/100 PY &amp;lt;5) (Fig. 1). The phenotypes with an intermediate incidence rate for all-cause mortality were the low comorbidity and inflammation phenotype (IR/100PY 7.4, 95% CI 6.9–8.0), the phenotype of older patients with cardiovascular disease (IR/100PY 7.2, 95% CI 6.7–7.8), and the phenotype of older patients with a kidney transplant and cardiovascular disease (IR/100PY 6.5, 95% CI 5.5–7.6). The phenotypes with highest incidence rate for all-cause mortality was the phenotype of older patients with cardiovascular disease and severe CKD (IR/100PY 12.5, 95% CI11.5–13.4). The phenotypes with the lowest risk for kidney failure were the diabetes phenotype, the low comorbidity and inflammation phenotype, and the phenotype of older patients with cardiovascular disease (all IR/100 PY &amp;lt;1). The phenotype of older patients with cardiovascular disease and severe CKD also had the highest risk to develop kidney failure (IR/100PY 5.8, 95% CI 5.1–6.6), followed by the phenotype of patients with primary kidney disease (IR/100PY 4.4, 95% CI 3.7 −5.5). Conclusion We identified 7 different phenotypes of patients with CKD including 2 phenotypes of patients with a kidney transplant with different clinical characteristics and prognosis. The differences in risk of all-cause mortality and kidney failure warrants a different monitoring and follow-up across the different phenotypes within the setting of CKD. Future studies should invest In evaluating the implementation of our identified phenotypes in routine clinical practice or clinical trial design with respect to differences in treatments.

#783 Individualized net benefit of intensive blood pressure lowering among older adults in SPRINT

Abstract Background and Aims The optimal blood pressure (BP) target for older adults remains controversial. This study aimed to determine whether results from the Systolic Blood Pressure Intervention Trial (SPRINT) could be tailored to individual trial participants using risk estimates and simulated preferences about the relative importance of multiple outcomes related to BP lowering. Method This analysis included 4,850 SPRINT participants age ≥65 years. Parsimonious Cox models were internally validated to predict the absolute difference in risk between intensive versus standard BP lowering in each SPRINT participant for all-cause death, cardiovascular outcomes, cognitive outcomes, and serious adverse events. Treatment effects were combined using simulated preference weights into an individualized net benefit, which represents the weighted sum of risk differences across outcomes. Individualized net benefits among older SPRINT participants were compared across categories of age (65-74 years vs. ≥ 75 years), frailty (fit, less fit, and frail), and polypharmacy status. Results When simulating preferences for older adults who view death, cardiovascular events, and cognitive impairment as much more important than the harms of BP lowering, the median (IQR) individualized net benefit was 5% (3%, 7%), and 100% had a net benefit that favoured intensive BP lowering. When simulating benefits and harms to have similar importance, the median (IQR) individualized net benefit was 2% (1%, 3%), and 95.4% had a positive net benefit. In subgroup analyses, the predicted net benefit of intensive BP lowering was significantly greater among those with advanced age, frailty, and polypharmacy compared with lower risk individuals (P&amp;lt;0.001 for all comparisons). Conclusion Almost all older participants in SPRINT had a predicted net benefit that favoured intensive BP control, but the degree of net benefit varied considerably. Personalizing BP targets for older adults according to each person's estimated risks and preferences may provide more refined BP target recommendations.