Composite Outcome Research Articles

A very-low-calorie diet (VLCD) intervention for the management of prediabetes and early Type 2 diabetes mellitus in a multi-ethnic cohort in Aotearoa New Zealand: The PROGRESS NZ feasibility study.

Very-low calorie diets (VLCD) achieve weight loss and remission of Type 2 diabetes (T2DM), but efficacy and acceptability in non-European populations is less clear. This feasibility study examines the impact of 10% weight loss through VLCD on metabolic and body composition outcomes in a multi-ethnic cohort of Aotearoa New Zealand (AoNZ) men with prediabetes/early T2DM, and VLCD tolerability/cultural acceptability. Participants followed a VLCD intervention (mean energy 3033kJ/day) until achievement of 10% weight loss. An oral glucose tolerance test (OGTT), hyperinsulinaemic isoglycaemic clamp with stable isotopes, hood calorimetry and dual-energy Xray absorptiometry (DXA) were undertaken before and after intervention. Qualitative data on VLCD tolerability/cultural acceptability were collected. Fifteen participants were enrolled; nine achieved 10% weight loss. In this group, mean HbA1c reduced by 4.8mmol/mol (2.4-7.1) and reverted to normoglycaemia in n=5/9; mean body weight reduced by 12.0 kg (11.0-13.1) and whole-body glucose disposal improved by 1.5 mg kgFFM-1 min-1 (0.7-2.2). Blood pressure and fasting triglycerides improved significantly. No changes in hepatic glu-cose metabolism were found. In all participants who attended completion testing, HbA1c reduced by 3.4mmol/mol (SD 3.5) and total weight by 9.0kg (SD 5.7). The intervention was highly tolerable/culturally acceptable however challenges with fulfilment of cultural obligations were described. Results support VLCD use in AoNZ however further work to investigate ethnic differences in physiological response to VLCDs and to optimise protocols for multi-ethnic populations are required.

Hazard functioning modeling for dextrose fluids associated hemodilution; Cox-regressional analysis for patients’ Hematocrit Hemoglobin Ratio

Aims: This study looks at the cox-regressional relationships between hematocrit to hemoglobin ratio (HHR) and a group of outcomes of interest (cOI). These outcomes include death from any cause, acute myocardial infarction, stroke, and severe dilutional hyponatraemia incidence. Additionally other outcome of interest in this study will be prolongation of admission days, infection rate, acute kidney injury, and mandating the transition to the critical unit and mechanical ventilation intubation. The study also will investigate the performances of the tested ratio and will explore their sensitivity, specificity, and accuracy indexes. Methods: Between 2018 and 2022, a retrospective study was conducted at the King Hussein Medical Centre in Amman, Jordan, involving 926 patients. The study aimed to determine the potential risk of dilution of red blood cells in circulation caused by dextrose-containing fluids in patients with chronic kidney disease. The study aimed to determine the ideal threshold levels of the investigated ratio (HHR) to enhance clinical outcomes and safety margins, particularly in patients with severe renal impairment or chronic kidney disease in a hospital setting. The study included patients with fluctuating kidney function, renal replacement therapy, uncontrolled diabetes, and conditions necessitating specific fluid regimens. The study used binary logistic regression and cox-regression proportional hazard modelling to examine the correlation between the hematocrit to haemoglobin ratio and the composite outcomes of interest (cOI) in patients from Jordan. The findings suggest that higher cOI likelihood indicates a more advantageous condition, while lower values suggest a less advantageous condition. Results: A retrospective study at the KHMC in Amman, Jordan, involved 1306 patients from 2018 to 2022. The study focused on the hematocrit to haemoglobin ratio (HHR) and achieved correct classification rates of 70.8%. The best HHR was 2.555:1, with a 42.8% chance of occurring at this level. Cox-Regression Proportional Hazard Modelling revealed a censored percentage of 83.4% in HHR>2.555 stratum and 51.5% in HHR≤2.555 stratum. The study found a high percentage of HD patients processed in the analysis. Conclusion: Intravenous dextrose fluids associated hemodilutional state is linked to all-cause mortality in admitted medically and surgically patients and cardiovascular death. Low ratio increases the risk. Factors such as malnutrition and kidney function loss contribute to prognosis. Future studies should focus on mechanistic pathways, optimal targets, age, and sociodemographic factors.

GLP-1 Receptor Agonists and Cardiovascular Disease: What Do Clinicians Need to Know?

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are gaining importance due to their effects on cardiovascular parameters. This review discusses the findings of dedicated cardiovascular outcome trials of GLP-1RAs and summarizes their utility to help clinicians understand their role in cardiovascular disease. Patients with diabetes mellitus are at an increased risk of cardiovascular disease. Cardiovascular outcome trials have shown GLP-1RAs decrease the primary composite outcome of the first occurrence of major adverse cardiovascular events (MACE) in patients with diabetes. Additionally, select GLP-1RAs have also shown improved cardiovascular outcomes in patients without diabetes who are either overweight (BMI ≥ 27), or obese (BMI ≥ 30). There have also been encouraging results in patients with heart failure with preserved ejection fraction. There is increasing evidence showing GLP-1RAs are beneficial across the cardiometabolic spectrum of disease. Implementation of these therapeutics into clinical practice is important to improve cardiovascular risk.

Management of immunosuppression in lung transplant recipients and COVID-19 outcomes: an observational retrospective cohort-study

BackgroundThe aim of this study was to assess the impact of immunosuppression management on coronavirus disease 2019 (COVID-19) outcomes.MethodsWe performed a single-center retrospective study in a cohort of 358 lung transplant recipients (LTx) over the period from March 2020 to April 2022. All included symptomatic patients had at least one positive SARS-CoV-2 rt-PCR. We used a composite primary outcome for COVID-19 including increased need for oxygen since the hospital admission, ICU transfer, and in-hospital mortality. We assessed by univariate and multivariate analyses the risk factors for poor outcomes.ResultsOverall, we included 91 LTx who contracted COVID-19. The COVID-19 in-hospital mortality rate reached 4.4%. By hierarchical clustering, we found a strong and independent association between the composite poor outcome and the discontinuation of at least one immunosuppressive molecule among tacrolimus, cyclosporine, mycophenolate mofetil, and everolimus. Obesity (OR = 16, 95%CI (1.96; 167), p = 0.01) and chronic renal failure (OR = 4.6, 95%CI (1.4; 18), p = 0.01) were also independently associated with the composite poor outcome. Conversely, full vaccination was protective (OR = 0.23, 95%CI (0.046; 0.89), p = 0.047).ConclusionThe administration of immunosuppressive drugs such as tacrolimus, cyclocporine or everolimus can have a protective effect in LTx with COVID-19, probably related to their intrinsic antiviral capacity.

Association Between Changes in Smoking Habits and Incident Fracture After Acute Ischemic Stroke.

Survivors of stroke, particularly the older population, are at an increased risk of falls and incident fractures. Smoking is a widely recognized risk factor for fractures. However, the association between changes in smoking habits before and after an index stroke and increased risk of fracture remains unelucidated. Using the Korean National Health Insurance program, patients with ischemic stroke between 2010 and 2016 were enrolled. Individuals were classified by smoking habits: "never smoker," "former smoker," "smoking quitter," "new smoker," and "sustained smoker." The primary outcome was the composite outcome of the vertebral, hip, and any fractures. Multivariable Cox proportional hazards regression analysis was conducted, using the never-smoker group as the reference. Among 177 787 patients with health screening data within 2 years before and after ischemic stroke, 14 991 (8.43%) patients had any fractures. After multivariable adjustment, the sustained smokers had a significantly increased risk of composite primary outcomes of any, vertebral, and hip fractures (adjusted HR [aHR], 1.222 [95% CI, 1.124-1.329]; aHR, 1.27 [95% CI, 1.13-1.428]; aHR, 1.502 [95% CI, 1.218-1.853], respectively). Additionally, the new smoker group exhibited a similar or higher risk of any fractures and hip fractures (aHR, 1.218 [95% CI, 1.062-1.397]; aHR, 1.772 [95% CI, 1.291-2.431], respectively). Sustained smokers had a significantly increased risk of vertebral and hip fractures after an ischemic stroke. The risk of any hip fractures was higher in new smokers after ischemic stroke. As poststroke fractures are detrimental to the rehabilitation process of patients with stroke, physicians should actively advise patients to stop smoking.

Electroconvulsive therapy in the maintenance phase of psychotic unipolar depression.

To determine whether the rates of readmissions and suicide vary in psychotic unipolar depression based on whether patients receive maintenance electroconvulsive therapy (M-ECT) following the initial series of ECT, and to examine if there is an age-dependent association. We used Swedish national registries to identify hospitalized patients with psychotic unipolar depression, treated 2008-2019 who received ECT during their hospital stay. The patients who received subsequent M-ECT within 14 days after discharge were compared with those who did not. The primary composite outcome was time to readmission due to a psychiatric disorder, suicide attempt, or suicide within 2 years from discharge. Data were analyzed using Cox regression adjusted for previous psychiatric admissions, age, sex, comorbidity, and pharmacological treatment. We also conducted a within-individual analysis using the sign-test, with patients having ≥1 hospital episode followed by M-ECT and ≥1 hospital episode without M-ECT. A total of 1873 patients were included, of which 130 received M-ECT. There was no statistically significant group difference regarding the primary outcome in the whole sample. However, when stratified by age, there was a significant difference in favor of M-ECT for patients >65 years (adjusted hazard ratio 0.55, 95% confidence interval 0.35-0.87). The within-individual analysis, including 46 patients, significantly favored M-ECT. M-ECT was not associated with a differential risk of the composite of readmission and suicide in psychotic depression. Among patients >65 years, M-ECT was significantly associated with a decreased risk of the outcome. The possibility of residual confounding cannot be excluded.

Composite outcome measures in high-impact critical care randomised controlled trials: a systematic review

BackgroundThe use of composite outcome measures (COM) in clinical trials is increasing. Whilst their use is associated with benefits, several limitations have been highlighted and there is limited literature exploring their use within critical care. The primary aim of this study was to evaluate the use of COM in high-impact critical care trials, and compare study parameters (including sample size, statistical significance, and consistency of effect estimates) in trials using composite versus non-composite outcomes.MethodsA systematic review of 16 high-impact journals was conducted. Randomised controlled trials published between 2012 and 2022 reporting a patient important outcome and involving critical care patients, were included.Results8271 trials were screened, and 194 included. 39.1% of all trials used a COM and this increased over time. Of those using a COM, only 52.6% explicitly described the outcome as composite. The median number of components was 2 (IQR 2–3). Trials using a COM recruited fewer participants (409 (198.8–851.5) vs 584 (300–1566, p = 0.004), and their use was not associated with increased rates of statistical significance (19.7% vs 17.8%, p = 0.380). Predicted effect sizes were overestimated in all but 6 trials. For studies using a COM the effect estimates were consistent across all components in 43.4% of trials. 93% of COM included components that were not patient important.ConclusionsCOM are increasingly used in critical care trials; however effect estimates are frequently inconsistent across COM components confounding outcome interpretations. The use of COM was associated with smaller sample sizes, and no increased likelihood of statistically significant results. Many of the limitations inherent to the use of COM are relevant to critical care research.

Machine learning model for cardiovascular disease prediction in patients with chronic kidney disease

IntroductionCardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). This study aimed to develop CVD risk prediction models using machine learning to support clinical decision making and improve patient prognosis.MethodsElectronic medical records from patients with CKD at a single center from 2015 to 2020 were used to develop machine learning models for the prediction of CVD. Least absolute shrinkage and selection operator (LASSO) regression was used to select important features predicting the risk of developing CVD. Seven machine learning classification algorithms were used to build models, which were evaluated by receiver operating characteristic curves, accuracy, sensitivity, specificity, and F1-score, and Shapley Additive explanations was used to interpret the model results. CVD was defined as composite cardiovascular events including coronary heart disease (coronary artery disease, myocardial infarction, angina pectoris, and coronary artery revascularization), cerebrovascular disease (hemorrhagic stroke and ischemic stroke), deaths from all causes (cardiovascular deaths, non-cardiovascular deaths, unknown cause of death), congestive heart failure, and peripheral artery disease (aortic aneurysm, aortic or other peripheral arterial revascularization). A cardiovascular event was a composite outcome of multiple cardiovascular events, as determined by reviewing medical records.ResultsThis study included 8,894 patients with CKD, with a composite CVD event incidence of 25.9%; a total of 2,304 patients reached this outcome. LASSO regression identified eight important features for predicting the risk of CKD developing into CVD: age, history of hypertension, sex, antiplatelet drugs, high-density lipoprotein, sodium ions, 24-h urinary protein, and estimated glomerular filtration rate. The model developed using Extreme Gradient Boosting in the test set had an area under the curve of 0.89, outperforming the other models, indicating that it had the best CVD predictive performance.ConclusionThis study established a CVD risk prediction model for patients with CKD, based on routine clinical diagnostic and treatment data, with good predictive accuracy. This model is expected to provide a scientific basis for the management and treatment of patients with CKD.

Association between Neonatal Outcomes and Admission Hypothermia among Very Preterm Infants in Chinese Neonatal Intensive Care Units: A Multicenter Cohort Study.

We aimed to investigate the relationship between admission hypothermia and outcomes among very preterm infants (VPIs) in neonatal intensive care units (NICUs) in China. We also investigated the frequency of hypothermia in VPIs in China and the variation in hypothermia across Chinese Neonatal Network (CHNN) sites. This retrospective cohort study enrolled infants with 240/7 to 316/7 weeks of gestation with an admission body temperature ≤37.5 °C who were admitted to CHNN-participating NICUs between January 1 and December 31, 2019. A total of 5,913 VPIs were included in this study, of which 4,075 (68.9%) had hypothermia (<36.5 °C) at admission. The incidence of admission hypothermia varied widely across CHNN sites (9-100%). Lower gestational age (GA), lower birth weight, antenatal steroid administration, multiple births, small for GA, Apgar scores <7 at the 5th minute, and intensive resuscitation were significantly associated with admission hypothermia. Compared with infants with normothermia (36.5-37.5 °C), the adjusted odds ratios (ORs) for composite outcome among infants with admission hypothermia <35.5 °C increased to 1.47 (95% confidence interval [CI], 1.15-1.88). The adjusted ORs for mortality among infants with admission hypothermia (36.0-36.4 and <35.5 °C) increased to 1.41 (95% CI, 1.09-1.83) and 1.93 (95% CI, 1.31-2.85), respectively. Admission hypothermia was associated with a higher likelihood of bronchopulmonary dysplasia, but was not associated with necrotizing enterocolitis ≥stage II, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. Admission hypothermia remains a common problem for VPIs in a large cohort in China and is associated with adverse outcomes. Continuous quality improvement of admission hypothermia in the future may result in a substantial improvement in the outcomes of VPIs in China. · Admission hypothermia is common in VPIs.. · The incidence of admission hypothermia in VPIs remains high in China.. · Admission hypothermia is associated with adverse outcomes in VPIs..

Epinephrine vs. phenylephrine infusion for prophylaxis against maternal hypotension after spinal anesthesia for cesarean delivery: a randomized controlled trial.

The hemodynamic effects of relatively low-dose epinephrine and phenylephrine infusions during cesarean delivery under spinal anesthesia were compared. This randomized controlled trial included full-term pregnant women who underwent elective cesarean delivery. After spinal anesthesia, participants received either epinephrine (0.03mcg/kg/min) or phenylephrine (0.4mcg/kg/min) infusion that continued until 5min after delivery. The primary outcome was a composite outcome of the occurrence of any of hypotension, hypertension, bradycardia, and/or tachycardia. Neonatal outcomes, including umbilical artery blood gas and Apgar scores, were assessed. In total, 98 patients in each group were analyzed, and the number of patients with the composite outcome was comparable between the epinephrine and phenylephrine groups (30/98 [31%] vs. 31/98 [32%], respectively; P = 0.877). However, the incidence of hypotension was likely lower in the epinephrine group than in the phenylephrine group (P = 0.066), and the number of hypotensive episodes per patient was lower in the epinephrine group than in the phenylephrine group. On the other hand, the incidence of tachycardia was higher in the epinephrine group than that in the phenylephrine group. The incidence of hypertension was comparable between the two groups and none of the participants developed bradycardia. Neonatal outcomes were comparable between the two groups. Epinephrine and phenylephrine infusion produced comparable maternal hemodynamics and neonatal outcomes. Epinephrine was associated with a higher incidence of maternal tachycardia and likely lower incidence of maternal hypotension than phenylephrine. IRB number: MD-245-2022. This study was registered on May 31, 2023 at clinicaltrials.gov registry, NCT05881915, URL: https://classic. gov/ct2/show/NCT05881915term=NCT05881915&draw=2&rank=1.

Non-alcoholic fatty liver disease in patients with atrial fibrillation: a report from a global federated health network

Abstract Background Few data are available on the clinical course of patients with Atrial Fibrillation (AF) and Nonalcoholic Fatty Liver Disease (NAFLD). Purpose To evaluate the 1-year risk of all-cause death, thromboembolic events, and bleeding in AF patients with NAFLD. Methods Retrospective cohort study within the global TriNetX platform. Patients with AF were categorized into two groups: i) AF with NAFLD and ii) AF without liver diseases. The primary outcomes were the 1-year risks of a composite outcome of i) all-cause death and thrombotic events (all-cause death, acute myocardial infarction, ischemic stroke, systemic arterial thromboembolism, deep vein thrombosis, and pulmonary embolism), and hemorrhagic outcome (intracranial hemorrhage and gastrointestinal bleeding). Secondary outcomes were each component of the composite primary outcomes. Cox regression analysis before and after propensity-score-matching (PSM) was used to estimate HR and 95% confidence interval (95%CI). Sensitivity analyses were done to investigate the risk associated with cirrhosis and type of oral anticoagulant. Results We identified 22,636 AF patients with NAFLD (69±12 years, 46.7% females) and 391,014 AF patients without NAFLD (72±12 years, 42.7% females). Before PSM, AF patients with NAFLD were younger, and with a higher prevalence of cardiovascular risk factors than those without liver disease. After PSM, no difference was found between the two groups, but NAFLD patients showed a higher 1-year risk of thrombotic (HR 1.54, 95%CI 1.47-1.61) and hemorrhagic (HR 1.56, 95%CI 1.42-1.72) composite outcomes (Figure 1). The higher risk in NAFLD was consistent also for all the secondary outcomes (Figure 1). On the sensitivity analyses (Figure 2), a progressively increased risk of thrombotic and hemorrhagic events was found in non-cirrhotic and cirrhotic patients compared to patients without liver diseases, whereas non-vitamin-k antagonist (NOAC) seems to be safer and more effective than warfarin. Conclusion In AF patients, NAFLD is associated with a higher 1-year risk of all-cause death, thrombotic and hemorrhagic events. Further studies are needed to establish the best clinical approach to manage NAFLD in AF patients.Figure 1Figure 2

Impact of Elevated Gradients After Transcatheter Aortic Valve Implantation for Degenerated Surgical Aortic Valve Bioprostheses.

Elevated aortic valve gradients are common after transcatheter aortic valve implantation for degenerated surgical aortic valve replacement bioprostheses, but their clinical impact is uncertain. A total of 12 122 patients who underwent transcatheter aortic valve implantation-in-surgical aortic valve replacement from November 2011 to December 2019 in the Society of Thoracic Surgery/American College of Cardiology Transvalvular Therapeutics Registry were included. The primary outcome was a composite of 1-year all-cause mortality, stroke, myocardial infarction, or valve reintervention. Secondary outcomes included 1-year all-cause mortality, readmission, and change from baseline 12-question self-administered Kansas City Cardiomyopathy Questionnaire-Overall Summary Score. Due to nonlinearity observed with restricted cubic splines analysis, a Cox regression analysis with aortic valve mean gradient modeled as a spline-continuous variable (with 20 mm Hg as a cutoff) was used to study the 1-year composite outcome and mortality. The composite outcome occurred most frequently in patients with aortic valve mean gradient ≥30 and <10 mm Hg, as compared with those with 10 to 20 and 20 to 30 mm Hg ranges (unadjusted rates, 13.9%, 12.1%, 7.5%, and 6.5%, respectively; P=0.002). When the mean aortic valve gradient was ≥20 mm Hg, higher gradients were associated with greater risk of the 1-year composite outcome (adjusted hazard ratio, 1.02 [1.02-1.03] per mm Hg; P<0.001) and 1-year mortality (adjusted hazard ratio, 1.02 [1.00-1.03] per mm Hg; P=0.007). Whereas when the mean aortic valve gradient was <20 mm Hg, higher gradients were not significantly associated with the composite outcome (adjusted hazard ratio, 0.99 [0.98-1.003] per mm Hg; P=0.12) but were associated with lower 1-year mortality (adjusted hazard ratio, 0.98 [0.97-0.99] per mm Hg; P=0.007). The relationship between postprocedural aortic valve mean gradient after transcatheter aortic valve implantation-in-surgical aortic valve replacement and clinical outcomes is complex and nonlinear, with relatively greater adverse events occurring at low and high gradient extremes. Further study of factors mediating the relationship between postprocedural gradients and clinical outcomes, including low-flow states, is necessary.

Clinical impact of renal function changes in patients with atrial fibrillation receiving anticoagulation with marginal renal function

Abstract Background Renal function changes were frequently observed in patients with marginal renal function. Renal function is one of crucial components to determine the doses and types of oral anticoagulants in atrial fibrillation (AF) patients and also closely associated with the risk of stroke and bleeding. However, the incidence of renal function changes and its impact on the clinical outcomes were not well-elucidated in anticoagulated AF patients. Purpose To evaluate renal function changes during follow-up in anticoagulated AF patients with marginal renal function defined as estimated glomerular filtration rate (eGFR) 45 to &amp;lt;60 ml/min/1.73m2. We also analysed the association between renal function changes and clinical outcomes. Methods Using a Korean nationwide claims database, we included anticoagulated AF patients who underwent a national health examination from January 2014 to December 2018 and also had follow-up examination within 2-year. Patients with eGFR 45 to &amp;lt;60 ml/min/1.73m2 at baseline examination were included. Based on the follow-up eGFR values, patients were categorised into three groups according to the change in renal function: maintained group (maintaining follow-up eGFR ranges from eGFR 45 to &amp;lt;60 ml/min/1.73m2), improved group (eGFR &amp;gt;60 ml/min/1.73m2), and aggravated group (eGFR &amp;lt;45 ml/min/1.73m2). After follow-up examination, ischemic stroke, major bleeding, end-stage renal disease (ESRD), all-cause death, and the composite of all clinical outcomes were evaluated. Results A total of 5126 patients were included: 42.3 % of patients (n=2170) maintained their renal function at follow-up examination, renal function of 44.4 % of patients (n=2276) were improved, whereas 13.3% of patients (n=680) were aggravated at follow-up examination. The mean eGFR values at baseline of maintained, improved, and aggravated groups were 54.2±4.1, 55.5±3.7, and 52.2±4.3 ml/min/1.73m2, respectively (p&amp;lt;0.001). The aggravated group was older, had higher CHA2DS2-VASc scores, and had more prevalent comorbidities, including hypertension, diabetes, prior myocardial infarction, and heart failure, than other groups. After multivariable adjustment, the aggravated group was associated with significantly higher risks of major bleeding, ESRD, all-cause death, and the composite outcome (HR [95% confidence interval], 1.46 [1.03-2.07], p=0.035; 1.49 [1.24-1.80], p&amp;lt;0.001; 9.29 [4.92-17.6], p&amp;lt;0.001; 1.57 [1.36-1.83], p&amp;lt;0.001, respectively). Conclusion In the anticoagulated AF patients with marginal renal function, a substantial proportion of patients (13%) experienced renal function decline below eGFR 45 ml/min/1.73m2 within 2-year. Renal function decline was associated with higher risks of major bleeding, ESRD, all-cause death and the composite outcome than those maintained their baseline renal function. Performing regular check-ups of renal function and protecting renal function should be emphasised in anticoagulated patients with AF and marginal renal function.

Obesity paradox in atrial fibrillation patients on oral anticoagulation therapy: a Korean nationwide cohort study

Abstract Background The obesity paradox is a phenomenon that has been observed in specific pathological conditions, wherein individuals who are overweight or obese exhibit a survival advantage over those with a normal weight. This phenomenon has also been noted in patients diagnosed with atrial fibrillation (AF), although the impact of body mass index (BMI) on clinical outcomes in AF patients undergoing oral anticoagulant (OAC) therapy remains uncertain. Purpose The aim of this study was to investigate the potential relationship between obesity and cardiovascular outcomes in patients diagnosed with AF who were receiving OAC. Methods We utilized administrative claims data from the Korean National Health Insurance Service and the combined health check-up database of the National Health Insurance Corporation to conduct a retrospective national cohort study spanning from 2013 to 2020. The patients newly prescribed OAC for AF were included, between January 2015 and December 2019. We followed up with patients from their index date until each outcome event or the end of the study period. BMI was categorized into 5 groups based on the World Health Organization's recommended criteria for Asian populations. The predefined clinical outcomes included thromboembolism, major bleeding, all-cause death, and the composite outcome. Results A total of 35,333 patients were included in the study. The mean age was 69 ± 10 years, and 37.1% were female. During a median follow-up of 2.0 years (IQR, 0.4–3.3), there were 11,634 thromboembolic events, 1,521 major bleeding events, and 2,586 deaths. The adjusted hazard ratio (HR) for thromboembolism, major bleeding, all-cause death, and a composite outcome were lower in obese II group (HR 0.79, 95% CI 0.73–0.86; HR 0.99, 95% CI 0.79–1.24; HR 0.75, 95% CI 0.62–0.91; HR 0.81, 95% CI 0.75–0.88) compared to the normal range BMI group. Conclusions In AF patients undergoing OAC therapy, individuals classified as obese exhibited a reduced risk of thromboembolism, major bleeding, all-cause mortality, and composite outcome compared to patients with normal weight.Adjusted hazard ratio of outcomes by BMI

Impact of environment and ethnicity on prognosis in AF patients: does the 'where' matter more than the 'who'?

Abstract Background Atrial fibrillation (AF) is increasing worldwide and disparities are known between different geographically defined populations. However, populations are more and more multi-racial/multiethnic and less is known about the impact of geographical locations on various racial/ethnic populations. Purpose To study the influence of geographical location and race/ethnicity on the characteristics and the prognosis in AF patients. Methods From phase II/III of the GLORIA-AF registry, Asian and Caucasian patients from Western and Asian countries were included. The associations between geographical locations, race/ethnicity and a composite outcome composed of all-cause death, stroke and major bleeding were evaluated using Cox regression analyses. Results The study included 21,450 AF Caucasian and Asian patients from Western and Asian countries (mean±SD age 70.2±10; 44.3% female) with a median [IQR] follow-up of 3 years [2.3-3.1]. Among Caucasian patients, those living in Western countries (97.3%) were older, had less hypertension, congestive heart failure and coronary artery disease but more often lifestyle disorders (smoking, alcohol drinking) than those living in Asia (2.7%). Among Asian patients, those living in Western countries (2.6%) had more hypertension, diabetes mellitus, metabolic syndrome, coronary artery disease but less alcohol abuse than those living in Asia (2.6%). Regarding the composite outcome, Caucasian patients living in Asia had less adverse events than Asian patients living in Asia and Caucasian patients living in Western countries (adjusted hazard ratio on age, sex and CHA2DS2-VASc score (aHR): 0.53 (95% confidence interval (CI): 0.34-0.83), p=0.005) and aHR: 0.54 (95% CI: 0.35-0.83, p=0.005) respectively). Asian patients living in Asia had a better prognosis than Asian patients living in Western countries (aHR: 0.55 (95% CI: 0.35-0.85), p=0.007) and Caucasian patients living in Western countries when compared to Asian patients living in Western countries (aHR: 0.61 (95% CI: 0.40-0.94), p=0.025). Conclusion Geographical location has an impact on characteristics and prognosis of AF patients regardless of race/ethnicity. However, the gap in prognosis between Caucasian and Asian patients remains unchanged.Table 1.Baseline characteristics.Figure 1.Kaplan-Meier curves.

Incidence and predictors of heart failure events following cardiac surgery in patients with atrial fibrillation - insights from the LAAOS-III trial

Abstract Background Atrial fibrillation (AF) is a common comorbidity in patients undergoing cardiac surgery and further increases the risk of incident heart failure (HF). However, only limited data exist on HF events following surgery in patients with AF. Methods The Left Atrial Appendage Occlusion Study (LAAOS) III was a randomized trial evaluating concomitant left atrial appendage occlusion in patients with AF undergoing cardiac surgery. In this secondary analysis, we aimed to identify independent predictors of the composite outcome of HF hospitalization or HF-related death following discharge, using a multivariable Cox model – incorporating sex, age (≥65 vs &amp;lt;65 years), systolic blood pressure (≤140 vs &amp;gt;140 mmHg), body mass index (BMI; &amp;lt;25 vs 25-29.9 vs ≥30 kg/m2), diabetes mellitus (DM), prior HF diagnosis, prior stroke, ischemic heart disease (IHD), heart valve surgery, AF history duration, rhythm on discharge electrocardiogram, and trial allocation. Supplementary analyses were undertaken to further assess the continuous variables using cubic spline regression. Results Of 4770 patients enrolled, in-hospital death occurred in 201 (4.2%) and complete discharge data were available for 4564 (95.7%). During a median follow up of 3.9 years, 533 (11.7%) of 4564 patients were hospitalized for HF. In total, 873 (19.1%) died after discharge, including 95 HF-related deaths. The composite outcome of HF hospitalization or HF-related death occurred at an annualized event rate of 3.31%/year [95% confidence interval: 3.04-3.60]. The independent risk factors included age (event rate of 3.64%/year vs 2.03%/year for ≥65 vs &amp;lt;65 years; hazard ratio (HR) 1.71 [1.32-2.21]), DM (4.71%/year vs 2.71%/year for with vs without DM; HR 1.59 [1.34-1.90]), prior HF diagnosis (4.27%/year vs 2.17%/year for with vs without HF; HR 2.00 [1.66-2.41]), IHD (3.63%/year vs 2.85%/year for with vs without IHD; HR 1.26 [1.03-1.54]), AF history duration (3.81%/year vs 2.89%/year for &amp;gt;2 vs &amp;lt;0.5 years; HR 1.23 [1.01-1.50]), and AF rhythm at discharge (3.87%/year vs 2.68%/year for AF vs non-AF rhythm; HR 1.31 [1.09-1.58]). The supplementary spline analyses further revealed a positive correlation between BMI and the risk of the composite outcome (p-value 0.042). Conclusions In patients with AF undergoing cardiac surgery, post-discharge HF hospitalization and HF-related death occurred at a rate of 3.31% per year. Our study identified several significant risk factors including advanced age, higher BMI, DM, prior HF diagnosis, IHD, AF history &amp;gt;2 years, and AF rhythm at discharge.The associations of HF with age and BMI

Serial GLS assessments over time in patients with preserved ejection fraction undergoing permanent cardiac pacemaker placement

Abstract Background Chronic right-ventricular (RV) pacing can exacerbate heart failure in patients with a low ejection fraction (EF), but little is known about pacing-induced cardiomyopathy (PICM) in patients with preserved EF. We aimed to investigate risk factors of PICM in these patients during long-term follow-up. Methods The prospective registry at our University Hospital, South Korea, included de novo patients with preserved EF undergoing transvenous permanent pacemaker (PPM) implantation for atrioventricular blockage from 2018 to 2022. Patients with EF &amp;gt; 50% and expected ventricular pacing &amp;gt; 40% were included. All patients were followed with serial echocardiography (preimplant, post implant, 12 months). All patients enrolled in this study were seen as outpatients every 3–6 months. Composite outcomes were cardiac death (pump failure), hospitalization because of heart failure, PICM, and biventricular pacing (BVP) upgrade. Results 71 patients (28 men, 73.1 ± 9.5 years) were included. After PPM implantation, EF and GLS were significantly decreased. During three years of follow-up, 2 patient died, 6 were hospitalized, 7 suffered PICM, and 3 underwent BVP upgrade. Cox regression analysis identified reduced post-implant global longitudinal strain (GLS) (HR, 1.524; 95% CI, 1.149–2.021; P = 0.003) as independent predictors of PICM. Post-implant GLS showed high predictive accuracy for PICM, with an area under the curve of 0.92 (95% CI 0.829–0.971; P &amp;lt; 0.001) Conclusion Post-implant GLS, rather than pre-implant GLS could help identify individuals at high risk of PICM. After PPM implantation, it is important to measure GLS, and patients with reduced GLS should be monitored more frequently and echocardiographic surveillance, with a view to an upgrade to BVP.Serial EF and GLS assessmentGLS ROC curve

Phenotypes and outcomes in patients with atrial fibrillation: a global unsupervised cluster analysis from Phase II/III of the GLORIA-AF registry

Abstract Background Atrial fibrillation (AF) patients are characterized by a great clinical heterogeneity and complexity across the world. Usual classifications may not adequately characterize this population. Data-driven cluster analysis reveals different possible classifications of patients. Purpose To identify different clusters of AF patients who share similar clinical phenotypes and evaluate the association between identified clusters and clinical outcomes using cluster analysis. Methods An agglomerative hierarchical cluster analysis was performed in patients from phase II/III of the GLORIA-AF registry. Associations between clusters and a composite outcome composed of all-cause death, stroke and major bleeding were evaluated using Cox regression analyses. Results The study included 26,045 AF patients (mean±SD age 70.1±10; 44.8% female) with a median [IQR] follow-up of 3 years [2.3-3.1]. Five clusters were identified: Cluster 1 was composed of young males from North America with morbid obesity and cardiovascular (CV) risk factors; Cluster 2 included older Asian patients with lower body mass index (BMI), fewer CV risk factors, lower anticoagulation rate but the highest AF ablation rate; Cluster 3 identified European males with CV comorbidities and behavioral disorders (smoking, alcohol abuse); Cluster 4 was characterized by patients with the highest rate of permanent AF, cancer, anticoagulant therapy prescription ; Cluster 5 included older women from Europe with high CHA2DS2-VASc and HAS-BLED scores, the highest heart rate, lower BMI and high rate of previous stroke and transient ischemic attack. The incidence of the composite outcome increased a stepwise fashion among clusters from 3.2% patient-years (95% confidence interval (CI): 2.4-4.1) for Cluster 1 to 6% patient-years (95% CI: 5.6-6.4) for Cluster 5 (p&amp;lt;0.0001): Cluster 1 versus 2 hazard ratio (HR): 0.85 (95% CI 0.65–1.11); 2 versus 3 HR: 0.84 (95% CI 0.76–0.93); 3 versus 4 HR: 0.9 (95% CI 0.82–0.99) and 4 versus 5 HR: 0.82 (95% CI 0.74–0.91). Conclusion Cluster analysis identified five statistically-driven groups of AF patients, with distinct phenotype characteristics and associated with different risks for major clinical adverse events.Baseline characteristics.Dendrogram and Kaplan Meier-curves.

Risk of death, thrombotic and hemorrhagic events in patients with atrial fibrillation and systemic autoimmune diseases

Abstract Background Growing evidence showing that systemic autoimmune diseases (SAD) are associated with a high risk of incident atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown. Purpose To assess the risk of all-cause death, thrombotic events, and bleeding in AF patients with SAD. Methods Retrospective cohort study within a global health care network (TriNetx). Using ICD codes, AF patients were categorized into two groups: 1) AF patients with SAD (M32: Systemic Lupus Erythematosus; M33: Dermato-polymyositis; M34: Systemic Sclerosis; M35: Sjogren syndrome), and 2) AF controls (without systemic autoimmune, autoinflammatory, or rheumatic diseases). The primary outcomes were the 5-year risks of 1) all-cause death, 2) thrombotic events (ischemic stroke, transient ischemic attack, peripheral arterial thromboembolism, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and 3) hemorrhagic outcome (intracranial hemorrhage and gastrointestinal bleeding). Secondary outcomes were each component of the composite primary outcomes. Cox regression analysis before and after propensity-score-matching (PSM) was used to estimate HR and 95% confidence interval (95%CI). Sensitivity analyses were done to investigate the risk of primary outcomes associated with each systemic autoimmune disease and with different types of oral anticoagulant (OAC). Results We identified 22,371 AF patients with SAD (67.7±13.7 years, 72.2% females), and 1,478,693 AF controls (69.7±14.0, 42.6% females). Before PSM, AF patients with SAD were younger, more often females, and with a higher prevalence of cardiovascular risk factors; no differences were found after PSM. After PSM, AF patients with SAD showed a higher risk of all-cause death (HR 1.21, 95% 1.17-1.25), thrombotic events (HR 1.55, 95%CI 1.49-1.61), and hemorrhagic events (HR 1.39, 95%CI 1.32-1.46) compared to AF controls (Table 1). On sensitivity analyses, we found that the risk of primary outcomes in AF patients with SAD was independent from the OAC type, but NOAC was more effective than warfarin in reducing the risk of thrombotic events. The highest risk of all-cause death was associated with Systemic Sclerosis, while the highest risk of composite thrombotic events was associated with Systemic Lupus Erythematosus, and Dermato-polymyositis. The highest risk of stroke was associated with Sjogren syndrome; and myocardial infarction and deep vein thrombosis with Dermato-polymyositis, Systemic Lupus Erythematosus was associated with the highest risk of Intracranial hemorrhage, while Systemic Sclerosis to the highest risk of gastrointestinal bleeding (Table 2). Conclusion In AF patients the coexistence of SAD is associated with a high risk of all-cause death, thrombotic events, and bleeding. A personalized approach aimed to minimize the impact of SAD on the clinical course of AF patients is needed.Figure 1Figure 2

Outcomes of on-label reduced-dose edoxaban in octogenarian patients with atrial fibrillation

Abstract Background Non-vitamin K antagonist oral anticoagulants (NOACs) are effective in preventing thromboembolisms and reduce the risk of bleeding compared with warfarin. There are few reports on the outcomes of on-label reduced-dose NOACs. Purpose The aim of this study was to assess the safety and efficacy of on-label reduced-dose edoxaban in octogenarian patients with atrial fibrillation (AF). Methods This study is a multi-center, prospective, non-interventional study to evaluate the safety and efficacy of on-label reduced-dose edoxaban in patients with AF. We evaluated outcomes of major bleeding, stroke or systemic embolism, all-cause death, and composite clinical outcomes. Results A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study. 932 patients (38.1%) were octogenarians. Major bleeding events occurred at a rate of 1.69%/yr in octogenarian patients and 0.9%/yr in non-octogenarian patients. The event rate of strokes and systemic embolisms was 1.93%/yr in octogenarian patients and 0.66%/yr in non-octogenarian patients The overall net clinical outcomes occurred at a rate of 5.45%/yr in octogenarian patients and 2.24%/yr in non-octogenarian patients. Conclusions Reduced-dose edoxaban can be used safely in Asian patients with very elderly patients. Older age was associated with a higher risk of ischemic stroke and composite adverse events.