Risk Of Major Adverse Outcomes Research Articles

Cluster-specific predictors of early rhythm control in contemporary European cohort of patients with atrial fibrillation: The EHRA-PATHS Project

Abstract Background Early rhythm control (ERC) using antiarrhytmic drugs, electrical cardioversion or catheter ablation for AF within a year from first diagnosis of atrial fibrillation (AF) has been shown to reduce the risk of major adverse outcomes compared to usual care, and the effects of ERC have been suggested to be consistent across all AF subgroups with different risk profiles. We aimed to identify cluster-specific predictors of ERC in pre-defined AF clusters in contemporary European EHRA-PATHS AF cohort. Methods The EHRA-PATHS AF cohort was derived from the three prospective EurObservational Research Programme (EORP) AF registries - General Pilot, General Long-term, and AF III registry. A two-step cluster analysis was performed. A hierarchical cluster analysis with 18 variables was used to identify the optimal number of clusters, followed by a K-means cluster analysis to determine variable cluster association. Cluster-specific predictors of ERC were identified using univariate and multivariate logistic regression analyses. Results Of 18,799 patients, AF was diagnosed within 1 year in 8088 (43.0%), and 3913/8088 patients (48.4%) were treated with ERC. Among the three clusters - Cluster 1 (younger healthier AF patients) compared with Cluster 2 (Elderly with less comorbidity, mostly non-cardiovascular) and Cluster 3 (Elderly with more comorbidity, mostly cardiovascular), see Table, ERC was significantly more often used in Cluster 1 compared with Cluster 2 and Cluster 3 (both P<0.001), and in Cluster 2 compared with Cluster 3. Cluster-specific multivariable predictors of ERC are shown in Table. In all three clusters, asymptomatic AF (EHRA score I) and Northern Europe residence were inversely associated with ERC, while Western Europe residence was positively associated with ERC in Cluster 2 and 3. In Cluster 1, low stroke risk and hypertension were positively associated with ERC, while dilated left atrium (LA) and reduced left ventricular ejection fraction (LV EF) were negative predictors of ERC. In Cluster 2, age ≥80 years, enlarged LA, and CHA2DS2-VASc ≥2 for males and ≥3 for females were negatively associated with ERC. In Cluster 3, age ≥75 years, cardiomyopathy, liver disease, dementia and reduced LV EF were negative predictors of ERC. Conclusion Our study of a large European AF cohort showed that likelihood for ERC was greater in younger and healthier AF patients, as well as in elderly from Western Europe, while ERC was significantly less likely with increasing age and comorbidity (especially cardiovascular diseases). These findings likely reflect the lack of high-quality evidence supporting aggressive ERC in high-risk patients with AF. With increasing body of evidence favouring ERC such patients, a shift towards less selective consideration of ERC in daily practice may be expected.

Maternal, Fetal, and Labour Outcomes of Dupilumab Use for Atopic Dermatitis During Pregnancy: A Systematic Review.

Atopic dermatitis is a chronic complex inflammatory disease that significantly impacts maternal well-being and quality of life during pregnancy, warranting effective therapeutic interventions that prioritize maternal health and fetal safety. Dupilumab is approved for moderate-to-severe atopic dermatitis, but limited data exist regarding its safety during pregnancy. We conducted a systematic review to review and analyze maternal, fetal, and labour outcomes in patients receiving dupilumab for atopic dermatitis during pregnancy. Comprehensive searches were conducted using databases including OVID, Scopus, and Web of Science, covering studies published until May 2024. Our search yielded 285 studies, of which 13 met the eligibility criteria. These studies included 68 patients with 69 pregnancies, revealing 58 live births and 11 spontaneous abortions. Dupilumab therapy was administered continuously throughout pregnancy in 22.2% of cases, while 77.8% received intermittent treatment. Maternal atopic dermatitis outcomes showed significant improvement in disease severity. Most pregnancies (86.3%) progressed without complications. Labour-associated outcomes varied, with 82.4% of women undergoing vaginal deliveries. The majority of births occurred at full term (82.5%), with a mean gestational age of 38.4 weeks. Fetal outcomes demonstrated a normal birth weight in 92.3% of cases, with no reported congenital defects. Our review suggests that dupilumab use during pregnancy is associated with improvement of atopic dermatitis and low or minimal risk of major adverse outcomes in treated patients or their newborns. Prospective studies with long-term follow-up are warranted to confirm the safety of dupilumab in this population.

Cardiac magnetic resonance for ventricular arrhythmias: a systematic review and meta-analysis

BackgroundCardiac magnetic resonance (CMR) allows comprehensive myocardial tissue characterisation, revealing areas of myocardial inflammation or fibrosis that may predispose to ventricular arrhythmias (VAs). With this study, we aimed to estimate...

#2437 Association between iron deficiency and risk of major events in chronic kidney disease—CKD-REIN Cohort

Abstract Background and Aims Iron deficiency (ID) is common in patients with chronic kidney disease (CKD) but remains under-diagnosed and its prognosis poorly documented in the absence of anemia. Data from CKDopps showed low TSAT levels were associated with increased risk of all-cause mortality and incidence of major cardiovascular events in patients with moderate to advanced CKD, an effect that was not modified by the presence of anemia [1]. Additionally, patients with both low TSAT and high ferritin levels displayed the highest risk of all-cause mortality. The aim of the study was to assess the relationship between ID and the risk of major adverse outcomes in patients with CKD in France. Method Using data from the French CKD-REIN cohort which included and followed over 5 years, 3,033 nephrology outpatients with CKD stage 2 to 5 CKD [2], we estimated the prevalence of ID, defined by a ferritin level < 100 mg/L and/or a transferrin saturation (TSAT) < 20%, and associated hazard ratios (HR) of kidney failure with replacement therapy, kidney failure defined by an eGFR < 15 ml/min per 1.73 m2 or initiation of kidney replacement therapy, all-cause mortality, all-cause hospitalization and death or hospitalization for heart failure. The analysis was conducted using a Cox model in which ID was included as a time-dependent variable and adjusted for identified confounders (socio-demographic characteristics, comorbidities, and biological measures) and hemoglobin level. Results A total of 2 914 patients with at least one ferritin or TSAT measurement at baseline or during follow-up were included in the analysis. The majority were men (66%), with a mean age of 67 ± 13 years; 49.6%, 41.2%, and 9.2%, had CKD stage 2/3, 4, and 5, respectively. Baseline prevalence of ID in the cohort was 50% [48-52]. Mean hemoglobin was 13 ± 1.7 g/dL, and only 31% of patients with ID also had a hemoglobin < 12 g/dL. Of the 2 914 patients included in the analysis, 627 (22%) required dialysis or transplantation, and 382 (13%) died before kidney replacement therapy. The incidence rate of kidney failure with replacement therapy was 6.76 versus 3.53 per 100 person-years in patients with and without ID. ID was associated with significant increased risk of kidney failure with replacement therapy, with adjusted HRs for confounders and hemoglobin level of 1.51 [1.24-1.82] (Fig. 1). A total of 836 patients (29%) progressed to kidney failure during the study period, and 341 (12%) died before this stage. The incidence rate of kidney failure was 8.66 versus 6.43 per 100 person-years in patients with and without ID. ID was associated with significant increased risk of kidney failure, with adjusted HRs for confounders and hemoglobin level of 1.19 [1.02-1.38] (Fig. 1). Adjusted HRs for all-cause mortality, for all-cause hospitalization, and for hospitalization or death for heart failure, were 1.31 [1.04-1.66], 1.04 [0.93-1.15], and 1.38 [1.07-1.80], respectively (Fig. 2). Conclusion This study confirms that ID is common in patients with CKD and shows that ID is significantly associated with the risk for kidney failure, all-cause mortality, and heart failure, independent of the presence of anemia. An intervention trial would be needed to assess whether correction of this ID in CKD patients is associated with a reduction in associated risks.

Clinical importance of weight gain and associated factors in patients with moderate to severe ulcerative colitis: results from the MOSAIK cohort in Korea

BackgroundMany patients with ulcerative colitis (UC) gain weight after treatment. However, the clinical significance of weight gain in these patients remains unclear. This study aimed to evaluate body weight changes after treatment in patients newly diagnosed with moderate-to-severe UC and their effects on patients’ prognosis.MethodsThe change in weight between diagnosis and 1 year after treatment in 212 patients enrolled in the MOSAIK cohort (mean age, 40 years; males, 60%) was analyzed. Significant weight gain was defined as a weight increase of ≥ 5% from the baseline at 1 year. Factors associated with significant weight gain and the effect of significant weight gain on the risk of major adverse outcomes (clinical relapse, hospitalization, and new use of steroids or biologics) during a follow-up period of 20 months were evaluated.ResultsMean weight gain at 1 year was 1.7 ± 4.2 kg. The proportion of overweight/obese patients increased by 9.0% from 37.9% to 46.9%. Thirty-two percent had significant weight gain; extensive colitis at diagnosis was the only factor associated with significant weight gain (odds ratio 6.5, 95% confidence interval 1.4–31.0, p = 0.006). In multivariable analysis, significant weight gain was not associated with the risk of major adverse outcomes. Weight loss symptoms at diagnosis were associated with an increased risk for new steroid use after 1 year.ConclusionsApproximately one-third of patients with moderate-to-severe UC had significant weight gain after 1 year of treatment. However, significant weight gain was not associated with the patient’s prognosis.

Adverse outcomes according to metabolic status in obese and overweight patients with atrial fibrillation: a report from the GLORIA-AF Phase II and III Registry

Abstract Background The "obesity paradox" has been repeatedly described in atrial fibrillation (AF). Metabolic status has been proposed as a potential determinant of cardiovascular risk, particularly in overweight and obese patients, whereby ‘metabolically healthy’ and ‘metabolically unhealthy’ overweight/obesity subgroups can be defined. Purpose We aimed to explore the association between metabolic status, body mass index (BMI) and natural history of patients with recently diagnosed AF. Methods Eligible patients for GLORIA-AF registry Phases II and III were adults (age ≥18) with a recent diagnosis of AF (<3 months before enrolment, or <4.5 months in Latin America) and a CHA2DS2VASc score ≥1. For this analysis, we included patients with BMIs between 18.5 and 60 kg/m2 and with complete data on determinants of metabolic status (hypertension, diabetes mellitus (DM) and hyperlipidemia). We categorised patients according to BMI (normal weight [18.5-24.9 kg/m2], overweight [25.0-29.9 kg/m2], obesity [30.0-60.0 kg/m2]) and metabolic status (unhealthy status defined as the presence of at least one factors among hypertension, DM and hyperlipidemia; healthy status defined as having none of these three factors). We analysed the odds of receiving oral anticoagulant (OAC) and other treatments, as well as the risk of major adverse outcomes, using multivariable Cox regression analyses with a primary outcome of a composite of all-cause death and major adverse cardiovascular events (MACE). Results 24,828 (mean age 70.1±10.3, females 44.6%) patients were included. The most represented group was the overweight unhealthy (8,161, 32.9%), followed by obese unhealthy (7,485, 30.1%), normal weight unhealthy (5,115, 20.6%), normal weight healthy (1,778, 7.2%), overweight healthy (1,508, 6.1%), and obese healthy (781, 3.1%). Among the obese patients, females were mostly metabolically healthy (51.0% vs. 44.9%). Higher BMI was associated with metabolic unhealthy status, and higher odds of receiving OAC (Figure 1; OR (95%CI) for OAC prescription in obese vs. normal weight patients: 2.22 [2.00-2.45]) and other treatments. Compared to normal weight healthy patients, normal weight unhealthy patients showed a higher risk of the primary composite outcome (adjusted Hazard Ratio (aHR): 1.20, 95%CI: 1.01-1.42, p=0.039) and thromboembolism, while no significant difference for the risk of the primary outcome or thromboembolism was observed for the other groups (Figure 2). Metabolically healthy obese group was associated with a reduced risk of cardiovascular death (aHR: 0.35, 95%CI:0.14-0.88, p=0.026) and MACE (aHR:0.56, 95%CI:0.33-0.93, p=0.024). In all weight groups, unhealthy metabolic status was associated with an increased risk of major bleeding. Conclusions Increasing BMI was associated with poor metabolic status, and with more intensive therapeutic management. The risk of outcomes was heterogenous among BMI groups, with metabolically unhealthy subjects having a poorer prognosis.Odds of receiving OAC according to BMIAdjusted Cox regression analysis

Gendered Social Determinants of Health and Risk of Major Adverse Outcomes in Atrial Fibrillation: An Analysis from the ESC-EHRA EURObservational Research Programme in Atrial Fibrillation General Long-Term Registry

Gendered Social Determinants of Health and Risk of Major Adverse Outcomes in Atrial Fibrillation: An Analysis from the ESC-EHRA EURObservational Research Programme in Atrial Fibrillation General Long-Term Registry

Adherence to the Atrial Fibrillation Better Care (ABC) pathway and the risk of major outcomes in patients with atrial fibrillation: A post-hoc analysis from the prospective GLORIA-AF Registry.

The 'Atrial fibrillation Better Care' (ABC) pathway has been proposed to streamline a more holistic or integrated care approach to atrial fibrillation (AF) management. We aimed to analyse the impact of adherence to the ABC pathway on the risk of major adverse outcomes in a contemporary prospective global cohort of patients with AF. Patients enrolled Phase II and III of the GLORIA-AF Registry with complete data on ABC pathway adherence and follow-up were included in this post-hoc analysis between November 2011 and December 2014 for Phase II, and between January 2014 and December 2016 for Phase III. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Multivariable Cox-regression and delay of event (DoE) analyses were used to evaluate the association between adherence to the ABC pathway and the risk of outcomes. We included 24,608 patients in this analysis (mean age: 70.2 (10.3) years, 10,938 (44.4%) females). Adherence to the ABC pathway was associated with a significant risk reduction for the primary outcome, with greatest magnitude observed for full ABC pathway adherence (adjusted Hazard Ratio [aHR] 0.54, 95% Confidence Interval [CI]: 0.44-0.67, p<0.0001). ABC pathway adherence was also associated with reduced risk of mortality (aHR: 0.89, 95% CI: 0.79-1.00, p=0.048), thromboembolism (aHR: 0.78, 95% CI: 0.65-0.94, p=0.0078), and MACE (aHR: 0.82, 95% CI: 0.71-0.95, p=0.0071). An increasing number of ABC criteria attained was associated with longer event-free survival in the DoE analysis. Adherence to the ABC pathway in patients with AF was associated with a reduced risk of major adverse events, including mortality, thromboembolism and MACE. This underlines the importance of using the ABC pathway in the clinical care of patients with AF. This study was funded by Boehringer Ingelheim.

Abstract 12164: Gendered Social Determinants of Health and Risk of Major Adverse Outcomes in Atrial Fibrillation: An Analysis From the ESC-EHRA Eurobservational Research Programme in Atrial Fibrillation General Long-Term Registry

Introduction: Atrial fibrillation (AF) is associated with a high risk of adverse outcomes. Social determinants of health (SDOH) are gendered (unevenly distributed between females and males) and associated with outcomes in cardiovascular diseases. Little is known about their impact in AF. We evaluated the association between gendered SDOH and adverse outcomes in AF patients. Methods: Data came from the ESC-EHRA EORP-AF General Long-Term Registry, a European AF prospective registry. Gendered SDOH included: education, living alone vs not, smoking, alcohol use, gender inequality index (GII), physical activity and quality of life measures. Study outcome was a composite of major adverse cardiovascular events and all-cause death. SDOH main effect was tested in multivariate logistic regressions and for a sex/GII interaction. Results: We studied 11,096 patients (mean (SD) age 69.2 (11.4) years; 40.7% females, median [IQR] CHA 2 DS 2 -VASc score 3 [2-4]). Most had secondary education, did not live alone, did not smoke or use alcohol, were physically inactive, had moderate quality of life, and lived in countries with gender equity. Multivariate analyses showed that gendered SDOH together with traditional risk factors were associated with the outcome (Figure 1). Higher education level and quality of life were associated with lower risk of adverse outcomes. Conversely, living alone and higher GII (larger gender inequity) were associated with worse outcomes. Females were found at lower risk, however this protective effect was reversed in countries with higher GII (sex-GII p- interaction 0.048). Conclusions: Gendered SDOH are associated with adverse outcomes in AF. Notably, gender inequity confers poorer outcomes in females with AF.

Abstract 14328: The Impact of Peripheral Arterial Disease in Major Bleeding and Major Cardiac and Cerebrovascular Events in Patient Undergoing Percutaneous Coronary Intervention: A Contemporary Assessment

Introduction: Peripheral arterial disease (PAD) has been associated with adverse outcomes in patients undergoing percutaneous coronary intervention (PCI). However, there are controversial reports regarding its impact in the current era of radial interventions. Hypothesis: We assessed the hypothesis that patients with PAD and patients without PAD undergoing PCI have similar major bleeding complications and major adverse cardiac and cerebrovascular events (MACCE). Methods: This was a retrospective analysis of data collected from 6 New York metropolitan area tertiary care hospitals and submitted to the NCDR between 2010 and 2018. Major bleeding events were classified using Bleeding Academic Research Consortium (BARC) classification. Severe bleeding was defined as a BARC ≥3. Hierarchical logistic regression was utilized to assess the association of PAD with post-PCI adverse outcomes, as appropriate. Results: A total of 2,933 PAD patients (9.4%) underwent PCI (without PAD, n = 28,172). Results are shown in the Table. PAD patients had a significantly higher odds of MACCE and major bleeding complications, including blood transfusions and in-hospital mortality. Access site bleeding and the need for post PCI dialysis did not reach statistical significance. A multivariable analysis will be presented. Conclusions: In conclusion, PAD continues to be a major risk factor for patients undergoing PCI. When compared with patients without PAD, these patients are at an increased risk of major adverse outcomes, including a 67% increase in mortality risk and a 44% in major bleeding complications risk.

Red blood cell transfusion induces abnormal HIF-1\u03b1 response to cytokine storm after adult cardiac surgery

Patients undergoing cardiac surgery develop a marked postoperative systemic inflammatory response. Blood transfusion may contribute to disruption of homeostasis in these patients. We sought to evaluate the impact of blood transfusion on serum interleukin-6 (IL-6), hypoxia induced factor-1 alpha (HIF-1α) levels as well as adverse outcomes in patients undergoing adult cardiac surgery. We prospectively enrolled 282 patients undergoing adult cardiac surgery. Serum IL-6 and HIF-1α levels were measured preoperatively and on the first postoperative day. Packed red blood cells were transfused in 26.3% of patients (mean 2.93 ± 3.05 units) by the time of postoperative sampling. Postoperative IL-6 levels increased over 30-fold and were similar in both groups (p = 0.115), whilst HIF-1α levels (0.377 pg/mL vs. 0.784 pg/mL, p = 0.002) decreased significantly in patients who received red blood cell transfusion. Moreover, greater decrease in HIF-1α levels predicted worse in-hospital and 3mo adverse outcome. Red blood cell transfusion was associated with higher risk of major adverse outcomes (stroke, pneumonia, all-cause mortality) during the index hospitalization. Red blood cell transfusion induces blunting of postoperative HIF-1 α response and is associated with higher risk of adverse thrombotic and pulmonary adverse events after cardiac surgery.Clinical Trial Registration ClinicalTrials.gov Identifier: NCT03444259.

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

BackgroundEpidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients’ clinical phenotypes and analyse the differential clinical course.MethodsWe performed a hierarchical cluster analysis based on Ward’s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry.ResultsA total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients’ prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P < .001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27–3.62; HR 3.42, 95%CI 2.72–4.31; HR 2.79, 95%CI 2.32–3.35), and Cluster 1 (HR 1.88, 95%CI 1.48–2.38; HR 2.50, 95%CI 1.98–3.15; HR 2.09, 95%CI 1.74–2.51) reported a higher risk for the three outcomes respectively.ConclusionsIn European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes.

Adherence to the 'Atrial Fibrillation Better Care' Pathway in Patients with Atrial Fibrillation: Impact on Clinical Outcomes-A Systematic Review and Meta-Analysis of 285,000 Patients.

The 'Atrial fibrillation Better Care' (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with atrial fibrillation (AF). We performed a systematic review of current evidence for the use of the ABC pathway on clinical outcomes. We performed a systematic review and meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and EMBASE were searched for studies reporting the prevalence of ABC-pathway-adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Meta-analysis of odds ratio (OR) was performed with random-effects models; subgroup analysis and meta-regression were performed to account for heterogeneity. Among the eight studies included, we found a pooled prevalence of ABC-adherent management of 21% (95% confidence interval, CI: 13-34%), with a high grade of heterogeneity, explained by the increasing adherence to each ABC criterion. Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR: 0.42; 95% CI: 0.31-0.56), cardiovascular death (OR: 0.37; 95% CI: 0.23-0.58), stroke (OR: 0.55; 95% CI: 0.37-0.82) and major bleeding (OR: 0.69; 95% CI: 0.51-0.94), with moderate heterogeneity. Prevalence of comorbidities was moderators of heterogeneity for all-cause and cardiovascular death, while longer follow-up was associated with increased effectiveness for all outcomes. Adherence to the ABC pathway was suboptimal, being adopted in one in every five patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes.

The Atrial Fibrillation Better Care (ABC) pathway in atrial fibrillation: a systematic review and meta-analysis of 285,000 patients

Abstract Funding Acknowledgements Type of funding sources: None. Background The ‘Atrial Fibrillation Better Care’ (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with Atrial Fibrillation (AF), standing on three main pillars: ‘A’ Avoid stroke (with Anticoagulants); ‘B’ Better symptom management; ‘C’ Cardiovascular and Comorbidity management. The ABC pathway is now recommended in several clinical guidelines, including the recent European Society of Cardiology (ESC) AF management guidelines. We performed a systematic review of the current evidence for use of the ABC pathway on clinical outcomes. Methods We performed a systematic review and meta-analysis according to PRISMA Guidelines. Pubmed and EMBASE were searched for studies reporting the prevalence of ABC pathway adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Metanalysis of odds ratio (OR) was performed with random-effect models; subgroup analysis and meta-regression were performed to account for heterogeneity; a CHA2DS2-VASc-stratified sensitivity analysis was also performed. Results Among 2862 records retrieved from the literature search, 8 studies were included. The pooled prevalence of ABC adherent management was 21% (95% confidence intervals (CI), 13-34%), with a high grade of heterogeneity; in a multivariable meta-regression model, adherence to each criteria of the ABC pathway explained most part of the heterogeneity (R2 = 98.9%). Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR:0.42, 95%CI 0.31-0.56), cardiovascular death (OR:0.37, 95%CI 0.23-0.58), stroke (OR:0.55, 95%CI 0.37-0.82) and major bleeding (OR:0.69, 95%CI 0.51-0.94), with moderate heterogeneity. Meta-regressions showed that the increasing prevalence of diabetes mellitus, coronary artery disease, chronic heart failure and history of stroke were associated with a reduced effectiveness of the ABC pathway for all-cause and cardiovascular death; each comorbidity was able to explain a significant proportion of heterogeneity at univariate meta-regression. Conversely, longer follow-up time was associated with more effectiveness of the ABC pathway for all outcomes. Adherence to ABC pathway was associated with a progressively greater reduction of the all-cause death risk amongst patients with higher CHA2DS2-VASc scores; no difference in ABC pathway effectiveness was found across CHA2DS2-VASc strata for CV death and stroke occurrence. Conclusions Adherence to the ABC pathway was suboptimal, being adopted in 1 in every 5 patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes. Our data supports extensive application of the ABC pathway for the management of AF. Abstract Figure.

Impact on outcomes in Europe: a cluster analysis from the ESC-EHRA EORP AF general long-term registry

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf ESC-EHRA EORP AF General Long-Term Registry Investigators Introduction Data derived from recent observational studies in atrial fibrillation (AF) show how the complexity of the clinical phenotype, beyond baseline thromboembolic risk, can increase risk of major adverse outcomes. Importantly, risk factors tend to occur in clusters, rather than occur individually in isolation. Aims To describe AF patients’ clinical phenotypes among a large contemporary European AF cohort and to analyse the differential impact of these clinical phenotypes on the occurrence of major adverse outcomes. Methods We performed a hierarchical cluster analysis based on Ward’s Method and using Squared Euclidean Distance using 22 clinical covariates. All variables were considered as binary. Examining the distances between cluster coefficients and by visual inspection of the dendrogram produced we identified the optimal number of clusters. Patients with data available for all 22 variables were included. We considered occurrence of cardiovascular events and all-cause death. Results Among the original 11096 patients included, 9363 (84.4%) were available for this analysis. The cluster analysis identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients with prevalent noncardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients mainly admitted for first detected and paroxysmal AF with low prevalence of concomitant conditions; Cluster 3 (n = 2955; 31.6%) included patients with high prevalence of permanent AF, cardiac risk factors and comorbidities. Thromboembolic and bleeding risks were higher in Cluster 3 and progressively lower in Cluster 1 and Cluster 2 (both p &amp;lt; 0.001). Use of oral anticoagulant was significantly lower for Cluster 2 (83.2% vs. 86.5% and 86.7% in Cluster 1 and Cluster 3, respectively; p &amp;lt; 0.001). Over a mean follow-up of 22.5 (SD5.5) months, Cluster 3 had the highest rate of both cardiovascular events (10.0%) and all-cause death (13.2%), compared with Cluster 1 (6.6% and 9.4%, respectively) and Cluster 2 (3.7% and 3.8%, respectively) (both p &amp;lt; 0.001). Kaplan-Meier curves (Figure) show that Cluster 2 (green line) had the lowest cumulative risk of outcomes; risk was progressively higher in Cluster 1 (orange line) and Cluster 3 (yellow line). A Cox multivariable regression analysis, adjusted for type of AF, symptomatic status, CHA2DS2-VASc score and use of oral anticoagulants, showed that both Cluster 3 and Cluster 1 were associated with a significantly increased risk of cardiovascular events (HR: 1.80, 95%CI: 1.39-2.33 and HR: 1.40, 95%CI: 1.09-1.80, respectively) and all-cause death (HR: 1.80, 95%CI: 1.40-2.30 and HR: 1.66, 95%CI: 1.30-2.11) compared to Cluster 2. Conclusions In European AF patients, three main clinical clusters were identified, those with non-cardiac comorbidities, low risk and cardiac comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of cardiovascular events and all-cause death. Abstract Figure. Kaplan-Meier Curves for Outcomes

Deep Remission at 1 Year Prevents Progression of Early Crohn’s Disease

We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD). We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n= 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period. Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P= .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome. In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.

Frailty is Associated with an Increased Risk of Major Adverse Outcomes in Elderly Patients Following Surgical Treatment of Hip Fracture

We intended to explore the effect of level of frailty on, and relationship with, 1-, 3-, and 6-month postoperative emergency department visits, readmissions, and mortality. This is a prospective multicenter observational cohort study design. Patients aged 50 years or older treated for hip fracture (n = 245) were taken from Orthopedic wards in one medical center (n = 131) and one district hospital (n = 114) in Changhua County, Taiwan. Frailty was defined as measured by the validated Clinical Frailty Scale and categorized as robust, pre-frail, and frail. We used Kaplan-Meier analysis to estimate survival rates and Cox regression to estimate the risk of frailty associated with adverse outcomes. To examine the longitudinal associations between frailty and adverse outcome, the cross-lagged models were explored. Of the 245 patients, 55 (22.4%) were classified as frail, 113 (46.1%) as pre-frail, and 77 (31.4%) as robust. More cumulative events occurred for frail than for robust patients for each adverse outcome. Frailty has long-term effect on each adverse outcome after discharge, rather than the effect simultaneously. Targeting pre-frailty and frailty is essential for prevent adverse outcomes and improving the overall health of older adults after discharge for hip fracture.

P5656Heart failure clinical phenotypes and outcomes in patients with atrial fibrillation: an analysis from the eurobservational research programme in atrial fibrillation long-term general registry

Abstract Introduction Heart failure (HF) is a well-known risk factor for atrial fibrillation (AF). Moreover, HF is associated with worse clinical outcomes in patients with known AF. Recently, phenotypes of HF have been redefined according to the level of ejection fraction (EF). New data are needed to understand if a differential risk for outcomes exists according to the new phenotypes' definitions. Purpose To evaluate the risk of major adverse outcomes in patients with AF and HF according to HF clinical phenotypes. Methods We performed a subgroup analysis of AF patients enrolled in the EORP-AF Long-Term General Registry with a history of HF at baseline, available EF and follow-up data. Patients were categorized as follows: i) EF&lt;40%, i.e. HF reduced EF [HFrEF]; ii) EF 40–49%, i.e. HF mid-range EF [HFmrEF]; iii) EF ≥50%, i.e. HF preserved EF [HFpEF]. Any thromboembolic event (TE)/acute coronary syndrome (ACS)/cardiovascular (CV) death, CV death and all-cause death were recorded. Results A total of 3409 patients were included in this analysis: of these, 907 (26.6%) had HFrEF, 779 (22.9%) had HFmrEF and 1723 (50.5%) had HFpEF. An increasing proportion with CHA2DS2-VASc ≥2 was found across the three groups: 90.4% in HFrEF, 94.6% in HFmrEF and 97.3% in HFpEF (p&lt;0.001), while lower proportions of HAS-BLED ≥3 were seen (28.0% in HFrEF, 26.3% in HFmrEF and 23.6% in HFpEF, p=0.035). At discharge patients with HFpEF were less likely treated with antiplatelet drugs (22.0%) compared to other classes and were less prescribed with vitamin K antagonists (VKA) (57.0%) and with any oral anticoagulant (OAC) (85.7%). No differences were found in terms of non-vitamin K antagonist oral anticoagulant use. At 1-year follow-up, a progressively lower rate for all study outcomes (all p&lt;0.001), with an increasing cumulative survival, was found across the three groups, with patients with HFpEF having better survival (all p&lt;0.0001 for Kaplan-Meier curves). After full adjustment, Cox regression analysis showed that compared to HFrEF, HFmrEF and HFpEF were associated with risk of all study outcomes (Table). Cox Regression Analysis HR (95% CI) Any TE/ACS/CV Death CV Death All-Cause Death HFmrEF 0.65 (0.49–0.86) 0.53 (0.38–0.74) 0.55 (0.41–0.74) HFpEF 0.50 (0.39–0.64) 0.42 (0.31–0.56) 0.45 (0.35–0.59) ACS = Acute Coronary Syndrome; CI = Confidence Interval; CV = Cardiovascular; EF = Ejection Fraction; HF = Heart Failure; HR = Hazard Ratio. Conclusions In this cohort of AF patients with HF, HFpEF was the most common phenotype, being associated with a profile related to an increased thromboembolic risk. Compared to HFrEF, both HFmrEF and HFpEF were associated with a lower risk of all major adverse outcomes in AF patients.

P3784Impact of progressively impaired renal function on major adverse outcomes in European patients with atrial fibrillation: a report from the ESC EORP-AF long-term general registry

Abstract Background Renal function is an important predictor of major adverse outcomes in the general population. In the setting of atrial fibrillation (AF), renal dysfunction may act both as a risk factor and a proxy of vascular risk factors and comorbidities. Methods We analyzed the association of renal function, as estimated glomerular filtration rate (eGFR) using the CKD-EPI formula, with 1-year outcomes in a “real-world” cohort of European AF patients from the EORP-AF Long-Term General Registry. Results 7725 were available for this analysis. Of these, 1294 (16.7%) had normal renal function (≥90 mL/min/1.73 m2), 3848 (49.8%) mildly reduced renal function (60–89 mL/min/1.73 m2), 2311 (29.9%) moderately reduced renal function (30–59 mL/min/1.73 m2) and 272 (3.5%) severely reduced renal function (&lt;30 mL/min/1.73 m2). CHA2DS2-VASc and HAS-BLED scores values increased across eGFR strata (p&lt;0.0001). Among patients qualifying for oral anticoagulant (OAC) therapy, those with severely impaired renal function were less often prescribed with any OAC (79.8%, p&lt;0.0001), more likely with vitamin K antagonist (62.9%) than non-vitamin K antagonist oral anticoagulants (16.9%) (p&lt;0.0001). At 1-year follow-up the rates of any thromboembolic event (TE)/acute coronary syndrome (ACS)/cardiovascular (CV) death progressively increased with worsening renal function, up to 20.7% in patients with severe dysfunction (p&lt;0.0001). Rates of CV death and all-cause death were higher in severe renal dysfunction (16.9% and 21.3%; p&lt;0.0001). Cox regression analysis (adjusted for known predictors) showed that eGFR &lt;30 mL/min/1.73 m2, compared to normal renal function was associated with an increased risk of all the adverse outcomes (Table). eGFR decrease by 10 mL/min/1.73 m2 was associated with increased risks (Table). Any TE/ACS/CV Death CV Death All-Cause Death mL/min/1.73 m2 HR (95% CI) HR (95% CI) HR (95% CI) eGFR ≥90 (ref.) – – – eGFR 60–89 0.99 (0.67–1.46) 0.81 (0.44–1.51) 0.74 (0.47–1.19) eGFR 30–50 1.12 (0.74–1.69) 1.00 (0.53–1.89) 0.95 (0.59–1.54) eGFR &lt;30 2.47 (1.52–3.99) 2.73 (1.36–5.49) 2.16 (1.25–3.72) eGFR (by 10 mL/min/1.73 m2 decrease) 1.11 (1.05–1.17) 1.18 (1.10–1.27) 1.11 (1.03–1.18) ACS = Acute coronary syndrome; CI = Confidence interval; CV = Cardiovascular; eGFR = estimated Glomerular Filtration Rate; HR = Hazard ratio; TE = Thromboembolic event. Conclusions In AF patients, impaired renal function at baseline is associated with a progressive increase in the risk of major adverse outcomes during follow up. Severe renal dysfunction is an independent predictor of all the adverse outcomes.

B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial

BackgroundNatriuretic peptides are substrates of neprilysin; hence, B-type natriuretic peptide (BNP) concentrations rise with neprilysin inhibition. Thus, the clinical validity of measuring BNP in sacubitril/valsartan-treated patients has been questioned, and use of N-terminal pro–B-type natriuretic peptides (NT-proBNP) has been preferred and recommended. ObjectivesThe purpose of this study was to determine the prognostic performance of BNP measurements before and during treatment with sacubitril/valsartan. MethodsBNP and NT-proBNP were measured before and after 4 to 6 weeks, 8 to 10 weeks, and 9 months of treatment with sacubitril/valsartan in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. We assessed the association of levels of these natriuretic peptides with the subsequent risk of cardiovascular death or hospitalization for HF. ResultsMedian BNP concentration (before treatment: 202 ng/l [Q1 to Q3: 126 to 335 ng/l]) increased to 235 ng/l (Q1 to Q3: 128 to 422 ng/l) after 8 to 10 weeks of treatment. BNP concentrations doubled in 141 (18%) patients and tripled in 49 (6%) patients during the first 8 to 10 weeks of sacubitril/valsartan. In contrast, such striking increases in NT-proBNP following the use of the neprilysin inhibitor were extremely rare. Treatment with sacubitril/valsartan caused a rightward shift in the distribution of BNP when compared with NT-proBNP, but both peptides retained their prognostic accuracy (C-statistics of 63% to 67% for BNP and C-statistics of 64% to 70% for NT-proBNP) with no difference between the 2 biomarkers. Increases in both BNP and NT-proBNP during 8 to 10 weeks of sacubitril/valsartan were associated with worse outcomes (p = 0.003 and p = 0.005, respectively). ConclusionsCirculating levels of BNP may increase meaningfully early after initiation of sacubitril/valsartan. In comparison, NT-proBNP is not a substrate of neprilysin inhibition, and thus may lead to less clinical confusion when measured within 8 to 10 weeks of drug initiation. However, during treatment, either biomarker predicts the risk of major adverse outcomes in patients treated with angiotensin receptor-neprilysin inhibitors. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255)