Diabetes and atrial fibrillation in hospitalized patients in the United States

BackgroundData on the burden of atrial fibrillation (AF) associated with diabetes among hospitalized patients are scarce. We assessed the AF‐related hospitalizations trends in patients with diabetes, and compared AF outcomes in patients with diabetes to those without diabetes.HypothesisAF‐related health outcomes differ between patient with diabetes and without diabetes.MethodsUsing the National Inpatient Sample (NIS) 2004–2014, we studied trends in AF hospitalization rate among diabetic patients, and compared in‐hospital case fatality rate, length of stay (LOS), cost and utilization of rhythm control therapies, and 30‐day readmission rate between patients with and without diabetes. Logistic or Cox regression models were used to assess the differences in AF outcomes by diabetes status.ResultsOver the study period, there were 4 325 522 AF‐related hospitalizations, of which 1 075 770 (24.9%) had a diagnosis of diabetes. There was a temporal increase in AF hospitalization rate among diabetic patients (10.4 to 14.4 per 1000 hospitalizations among patients with diabetes; +4.4% yearly change, p‐trend < .0001). Among AF patients, those with diabetes had a lower in‐hospital mortality (adjusted odds ratio [aOR]: 0.68; 95% CI: 0.65–0.72) and LOS (aOR: 0.95; 95% CI: 0.94–0.96), but no difference in costs (aOR: 0.95; 95% CI: 0.94–0.96) and a higher 30‐day rate of readmissions compared with no diabetes (aHR 1.05; 95% CI: 1.01–1.08), compared to individuals without diabetes.ConclusionAF and diabetes coexist among hospitalized patients, with rising trends over the last decade. Diabetes is associated with lower rates in‐hospital adverse AF outcomes, but a higher 30‐day readmission risk.     

Atrial Fibrillation After Ischemic Stroke Detected by Chest Strap-Style 7-Day Holter Monitoring and the Risk Predictors: EDUCATE-ESUS

Aim: This study aimed to investigate the diagnostic yield of 7-day Holter monitoring for detecting covert atrial fibrillation (AF) in patients with recent embolic stroke of undetermined source (ESUS) and to identify the pre-entry screening biomarkers that had significant associations with later detection of AF (clinicaltrials.gov. {"type":"clinical-trial","attrs":{"text":"NCT02801708","term_id":"NCT02801708"}}NCT02801708). Methods: A total of 206 patients who have recent ESUS without previously documented AF underwent Holter electrocardiography using a chest strap-style monitor. External validation of biomarkers predictive of AF was performed using 83 patients with ESUS who were implanted with insertable cardiac monitors. Results: The 7-day Holter monitoring started at a median of 13 days after the onset of stroke. AF was detected in 14 patients, and three of these showed a single AF episode lasting ＜2 min. The median time delay to the first documented AF was 50 h. Each of serum brain natriuretic peptide ≥ 66.0 pg/mL (adjusted odds ratio 5.23), atrial premature contractions (APCs) ≥ 345 beats (3.80), and APC short runs ≥ 13 (5.74) on 24-h Holter prior to the 7-day Holter showed a significant association with detection of AF, independent of age and physiological findings in this derivation cohort, and all of these showed a significant association in the validation cohort (adjusted odds ratio 6.59, 7.87, and 6.16, respectively). Conclusions: In recent ESUS patients, the detection rate of AF using the 7-day Holter monitoring was 6.8% (95% CI 4.1%–11.1%). Brain natriuretic peptide, APC count, and APC short runs in the standard clinical workup seemed to be predictors of covert AF.     

Improved procedural workflow for catheter ablation of paroxysmal AF with high‐density mapping system and advanced technology: Rationale and study design of a multicenter international study

BackgroundThe antral region of pulmonary veins (PV)s seems to play a key role in a strategy aimed at preventing atrial fibrillation (AF) recurrence. Particularly, low‐voltage activity in tissue such as the PV antra and residual potential within the antral scar likely represent vulnerabilities in antral lesion sets, and ablation of these targets seems to improve freedom from AF. The aim of this study is to validate a structured application of an approach that includes the complete abolition of any antral potential achieving electrical quiescence in antral regions.MethodsThe improveD procEdural workfLow for cathETEr ablation of paroxysmal AF with high density mapping system and advanced technology (DELETE AF) study is a prospective, single‐arm, international post‐market cohort study designed to demonstrate a low rate of clinical atrial arrhythmias recurrence with an improved procedural workflow for catheter ablation of paroxysmal AF, using the most advanced point‐by‐point RF ablation technology in a multicenter setting. About 300 consecutive patients with standard indications for AF ablation will be enrolled in this study. Post‐ablation, all patients will be monitored with ambulatory event monitoring, starting within 30 days post‐ablation to proactively detect and manage any recurrences within the 90‐day blanking period, as well as Holter monitoring at 3, 6, 9, and 12 months post‐ablation. Healthcare resource utilization, clinical data, complications, patients'' medical complaints related to the ablation procedure and patient''s reported outcome measures will be prospectively traced and evaluated.DiscussionThe DELETE AF trial will provide additional knowledge on long‐term outcome following a structured ablation workflow, with high density mapping, advanced algorithms and local impedance technology, in an international multicentric fashion. DELETE AF is registered at ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT05005143","term_id":"NCT05005143"}}NCT05005143).     

Indonesian registry on atrial fibrillation (OneAF)

Background:Data on the optimal therapeutic international normalized ratio (INR) for non-valvular and valvular atrial fibrillation (AF) in Indonesia is currently unavailable. Therefore, we designed the Indonesian Registry on Atrial Fibrillation (OneAF) registry in order to seek a safe and beneficial range of INR in Indonesian patients with non-valvular and valvular AF.Methods/design:The OneAF registry is a nationwide collaboration of the Indonesian Heart Rhythm Society (InaHRS) enrolling all hospitals with cardiac electrophysiologists in Indonesia. It is a prospective, multicentre, nationwide, observational study aiming to recruit non-valvular and valvular AF patients in Indonesia. The registry was started in January 2020 with a planned 2 years of recruitment. There are 2 respondents for this registry: non-cohort and cohort respondents. Non-cohort registry respondents are AF patients at hospitals who fulfill inclusion and exclusion criteria but did not consent for a 24 month follow up. Whereas patients who consented for a 24 month follow up were included as cohort registry respondents. Key data collected includes basic sociodemographic information, symptoms and signs, medical history, results of physical examination and laboratory test, details of diagnostics and treatment measures and events.Results:Currently, a total of 1568 respondents have been enrolled in the non-cohort registry, including 1065 respondents with non-valvular AF (67.8%) and 503 respondents with valvular AF (32.2%). We believe that the OneAF registry will provide insight into the regional variability of anticoagulant treatment for AF, the implementation of rhythm/rate control approaches, and the clinical outcomes concerning cardiocerebrovascular events.Trial registration:Registered at clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT04222868","term_id":"NCT04222868"}}NCT04222868).     

Effectiveness and safety of single transseptal ablation for atrial fibrillation in real‐word practice

BackgroundWe have previously reported that unilateral groin‐single transseptal (ST) ablation in patients with paroxysmal atrial fibrillation (AF) was safe and significantly reduced patient discomfort compared with bilateral groin‐double transseptal (DT) ablation.HypothesisIn the present study, we hypothesized that ST ablation would be as effective and safe as DT ablation in real‐world practice like previous study. Among the 1765 consecutive patients in the Yonsei AF ablation cohort from October 2015 to January 2020, 1144 patients who underwent radiofrequency ablation were included for the analysis. Among them, 450 underwent ST ablation and 694 underwent DT ablation.ResultsThe total procedure time, ablation time, and fluoroscopy time were longer in the ST group than in the DT group (p < .05 for all). The hospital stay after catheter ablation was 1.3 ± 1.1 days which was longer in DT group than ST group (p = .001). No significant difference was observed in the complication rate (p = .263) and AF‐free survival rate (log‐rank p = .19) between the groups. However, after excluding patients who used antiarrhythmic drugs when AF recurred, the AF‐free survival rates were lower in the DT group than in the ST group before and after propensity score matching (log‐rank p = .026 and .047, respectively).ConclusionAlthough the ST approach increases the procedure time compared with the DT approach owing to the need for more frequent catheter exchanges, the ST approach is a feasible and safe strategy for AF ablation in terms of rhythm outcomes and risk of complications.     

High‐density lipoprotein cholesterol levels are associated with major adverse cardiovascular events in male but not female patients with hypertension

BackgroundThe relationship between high‐density lipoprotein cholesterol (HDL‐C) levels and major adverse cardiovascular events (MACEs) in hypertensive patients of different sexes is unclear.HypothesisSex differences in the relationship between HDL‐C levels and the risk of MACEs among hypertensive patients.MethodsWe performed a post‐hoc analysis of data obtained from the Systolic Blood Pressure Intervention Trial (SPRINT) and explored sex‐based differences in the relationship between HDL‐C levels and MACEs among hypertensive patients using Cox proportional hazards regression.ResultsA total of 9323 hypertensive patients (6016 [64.53%] men and 3307 [35.47%] women) were assessed using SPRINT data. MACEs occurred in 395 (6.57%) men and 166 (5.02%) women after a mean follow‐up of 3.26 years. When HDL‐C levels were used as a continuous covariate, each 10 mg/dl increase in HDL‐C levels decreased the risk of MACEs in men (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.70–0.88; p < .0001). However, HDL‐C levels were not associated with MACEs in female hypertensive patients (HR, 1.02; 95% CI, 0.89–1.16; p = .7869). Compared with those in the first quartile, MACEs in the fourth quartile had the lowest risk among male patients (HR, 0.58; 95% CI, 0.41–0.82; p = .0023). Female patients in the fourth quartile of HDL‐C levels had an HR of 1.09 for MACEs (95% CI, 0.62–1.93; p = .7678). HDL‐C levels were not associated with the risk of MACEs among females.ConclusionAmong elderly hypertensive patients, higher HDL‐C levels were associated with a lower MACE incidence in men but not in women. Unique identifier: {"type":"clinical-trial","attrs":{"text":"NCT01206062","term_id":"NCT01206062"}}NCT01206062.     

Association of psychosocial factors with all‐cause hospitalizations in patients with atrial fibrillation

BackgroundA high burden of cardiovascular comorbidities puts patients with atrial fibrillation (AF) at high risk for hospitalizations, but the role of other factors is less clear.HypothesisTo determine the relationship between psychosocial factors and the risk of unplanned hospitalizations in AF patients.MethodsProspective observational cohort study of 2378 patients aged 65 or older with previously diagnosed AF across 14 centers in Switzerland. Marital status and education level were defined as social factors, depression and health perception were psychological components. The pre‐defined outcome was unplanned all‐cause hospitalization.ResultsDuring a median follow‐up of 2.0 years, a total of 1713 hospitalizations occurred in 37% of patients. Compared to patients who were married, adjusted rate ratios (aRR) for all‐cause hospitalizations were 1.28 (95% confidence interval [CI], 0.97‐1.69) for singles, 1.31 (95%CI, 1.06‐1.62) for divorced patients, and 1.02 (95%CI, 0.82‐1.25) for widowed patients. The aRRs for all‐cause hospitalizations across increasing quartiles of health perception were 1.0 (highest health perception), 1.15 (95%CI, 0.84‐1.59), 1.25 (95%CI, 1.03‐1.53), and 1.66 (95%CI, 1.34‐2.07). No different hospitalization rates were observed in patients with a secondary or primary or less education as compared to patients with a college degree (aRR, 1.06; 95%CI, 0.91‐1.23 and 1.05; 95%CI, 0.83‐1.33, respectively). Presence of depression was not associated with higher hospitalization rates (aRR, 0.94; 95%CI, 0.68‐1.29).ConclusionsThe findings suggest that psychosocial factors, including marital status and health perception, are strongly associated with the occurrence of hospitalizations in AF patients. Targeted psychosocial support interventions may help to avoid unnecessary hospitalizations.Trial registration ClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT02105844","term_id":"NCT02105844"}}NCT02105844.     

Diagnostic values of different ECG durations in paroxysmal AF diagnosis

ObjectiveTo evaluate the application value of different‐duration electrocardiograms (ECGs) in paroxysmal atrial fibrillation (AF) diagnosis.MethodsA total of 220 patients with paroxysmal atrial fibrillation diagnosed by 24‐h dynamic electrocardiogram in our hospital from January 2019 to December 2020 were selected as the study subjects. The patients were monitored for 10 s, 5 min, and 24 hr, respectively. The results of the three different‐duration ECGs were compared and analyzed in order to evaluate their paroxysmal AF diagnosis value.ResultsParoxysmal AF was detected in 18 patients (8.2%) with the 10‐s ECG; in 89 patients (40.5%) with the 5‐min ECG; and in 199 patients (90.5%) with the 24‐h dynamic ECG.ConclusionIn patients with paroxysmal AF, ECGs with longer detection times had higher detection rates.     

Impact of gender: Rivaroxaban for patients with atrial fibrillation in the XANTUS real-world prospective study

BackgroundThe XANTUS study ({"type":"clinical-trial","attrs":{"text":"NCT01606995","term_id":"NCT01606995"}}NCT01606995) demonstrated low rates of stroke and major bleeding in patients with atrial fibrillation (AF) receiving rivaroxaban in clinical practice for the prevention of thromboembolic events (N = 6784).HypothesisBecause previous real‐world studies have not reported gender‐dependent responses to rivaroxaban treatment, this sub‐analysis of the XANTUS study investigated the effect of gender on outcomes.MethodsThe centrally adjudicated outcomes were compared between genders. Primary outcomes were major bleeding and all‐cause death. Secondary outcomes included symptomatic thromboembolic events. Multivariable Cox regression analysis was performed to assess the effect of risk factors on outcomes between genders.ResultsA total of 2765 female and 4016 male patients were included in the analysis. Baseline characteristics were generally similar. No nominally significant interaction between gender and risk factors for the study outcomes was observed. Rates of major bleeding, all‐cause death and symptomatic thromboembolic events in patients with non‐valvular AF receiving rivaroxaban for stroke prevention were similar in men and women; no significant differences in risk factors for these outcomes were observed between genders.ConclusionsFurther research is needed to better characterize the relative importance of different risk factors on outcomes in men vs women and to determine whether gender differences exist in patients treated with non‐vitamin K antagonist oral anticoagulants.     

Predictors of rhythm outcomes after cardiac resynchronization therapy in atrial fibrillation patients: When should we use an atrial lead?

BackgroundCardiac resynchronization therapy (CRT) is widely used in atrial fibrillation (AF) patients and could impact rhythm stability.HypothesisWe aimed to identify predictors of sinus rhythm (SR) stability or AF progression in a real‐word cohort of CRT‐AF patients.MethodsFrom 330 consecutive implantable cardioverter‐defibrillator implantations due to ischemic or dilated cardiomyopathy, 65 (20%) patients with AF history (paroxysmal, n = 32) underwent a CRT implantation with an atrial electrode and were regularly followed every 4–6 months. Rhythm restoration was attempted for most AF patients based on symptoms, biventricular pacing (BP), and lack of thrombi.ResultsAfter 33 months, 18 (28%) patients progressed to permanent mode switch (MS≥99%) and 20 (31%) patients had stable SR (MS < 1%). Logistic regression showed that history of persistent AF (OR: 8.01, 95%CI: 2.0–31.7, p = .003) is associated with higher risk of permanent MS. In persistent AF patients, a bigger left atrium (OR: 1.2 per mm, 95%CI: 1.03–1.4, p = .025) and older age (OR: 1.15 per life‐year, 95%CI: 1.01–1.3, p = .032) were predictors of future permanent MS. Paroxysmal AF at implantation (OR: 5.96, 95%CI: 1.6–21.9, p = .007) and increased BP (OR: 1.4 per 1%, 95%CI: 1.05–1.89, p = .02) were associated with stable SR. In persistent AF patients, stable SR correlated with higher BP (98 ± 2 vs. 92 ± 8%, p < .001).ConclusionIn patients with AF undergoing CRT implantation, persistent AF, LA dilatation and advanced age relate to future permanent MS (AF), whereas high BP promotes SR stability. These findings could facilitate the management of CRT‐AF patients and guide therapy in order to maximize its effect on rhythm.     

The national burden of influenza‐like illness and severe respiratory illness overall and associated with nine respiratory viruses in South Africa, 2013–2015

BackgroundEstimates of the disease burden associated with different respiratory viruses are severely limited in low‐ and middle‐income countries, especially in Africa.MethodsWe estimated age‐specific numbers and rates of medically and non‐medically attended influenza‐like illness (ILI) and severe respiratory illness (SRI) that were associated with influenza, respiratory syncytial virus (RSV), rhinovirus, human metapneumovirus, adenovirus, enterovirus and parainfluenza virus types 1–3 after adjusting for the attributable fraction (AF) of virus detection to illness in South Africa during 2013–2015. The base rates were estimated from five surveillance sites and extrapolated nationally.ResultsThe mean annual rates per 100,000 population were 51,383 and 4196 for ILI and SRI, respectively. Of these, 26% (for ILI) and 46% (for SRI) were medically attended. Among outpatients with ILI, rhinovirus had the highest AF‐adjusted rate (7221), followed by influenza (6443) and adenovirus (1364); whereas, among inpatients with SRI, rhinovirus had the highest AF‐adjusted rate (400), followed by RSV (247) and influenza (130). Rhinovirus (9424) and RSV (2026) had the highest AF‐adjusted rates among children aged <5 years with ILI or SRI, respectively, whereas rhinovirus (757) and influenza (306) had the highest AF‐adjusted rates among individuals aged ≥65 years with ILI or SRI, respectively.ConclusionsThere was a substantial burden of ILI and SRI in South Africa during 2013–2015. Rhinovirus and influenza had a prominent disease burden among patients with ILI. RSV and influenza were the most prominent causes of SRI in children and the elderly, respectively.     

Substance Use Disorder Detection Rates Among Providers of General Medical Inpatients

BackgroundThe prevalence of substance use disorders is higher among medical inpatients than in the general population, placing inpatient providers in a prime position to detect these patients and intervene.ObjectiveTo assess provider detection rates of substance use disorders among medical inpatients and to identify patient characteristics associated with detection.DesignData drawn from a cluster randomized controlled trial that tested the effectiveness of three distinct implementation strategies for providers to screen patients for substance use disorders and deliver a brief intervention (Clinical Trials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01825057","term_id":"NCT01825057"}}NCT01825057).ParticipantsA total of 1076 patients receiving care from 13 general medical inpatient units in a large teaching hospital participated in this study.Main MeasuresData sources included patient self-reported questionnaires, a diagnostic interview for substance use disorders, and patient medical records. Provider detection was determined by diagnoses documented in medical records.Key ResultsProvider detection rates were highest for nicotine use disorder (72.2%) and lowest for cannabis use disorder (26.4%). Detection of alcohol use disorder was more likely among male compared to female patients (OR (95% CI) = 4.0 (1.9, 4.8)). When compared to White patients, alcohol (OR (95% CI) = 0.4 (0.2, 0.6)) and opioid (OR (95% CI) = 0.2 (0.1, 0.7)) use disorders were less likely to be detected among Black patients, while alcohol (OR (95% CI) = 0.3 (0.0, 2.0)) and cocaine (OR (95% CI) = 0.3 (0.1, 0.9)) use disorders were less likely to be detected among Hispanic patients. Providers were more likely to detect nicotine, alcohol, opioid, and other drug use disorders among patients with higher addiction severity (OR (95% CI) = 1.20 (1.08–1.34), 1.62 (1.48, 1.78), 1.46 (1.07, 1.98), 1.38 (1.00, 1.90), respectively).ConclusionsFindings indicate patient characteristics, including gender, race, and addiction severity impact rates of provider detection. Instituting formal screening for all substances may increase provider detection and inform treatment decisions.KEY WORDS: substance use disorder, detection, hospitalization, diagnosis     

Rhythm outcomes after aortic valve surgery: Treatment and evolution of new‐onset atrial fibrillation

BackgroundThe impact of new‐onset atrial fibrillation (AF) after aortic valve (AV) surgery on mid‐ and long‐term outcomes is under debate. Here, we sought to follow up heart rhythms after AV surgery, and to evaluate the mid‐term prognosis and effectiveness of treatment for patients with new‐onset AF.MethodsThis single‐center cohort study included 978 consecutive patients (median age, 59 years; male, 68.5%) who underwent surgical AV procedures between 2017 and 2018. All patients with postoperative new‐onset AF were treated with Class III antiarrhythmic drugs with or without electrical cardioversion (rhythm control). Status of survival, stroke, and rhythm outcomes were collected and compared between patients with and without new‐onset AF.ResultsNew‐onset AF was detected in 256 (26.2%) patients. For them, postoperative survival was comparable with those without new‐onset AF (1‐year: 96.1% vs. 99.3%; adjusted P = .30), but rate of stroke was significantly higher (1‐year: 4.0% vs. 2.2%; adjusted P = .020). With rhythm control management, the 3‐month and 1‐year rates of paroxysmal or persistent AF between patients with and without new‐onset AF were 5.1% versus 1.3% and 7.5% versus 2.1%, respectively (both P < .001). Multivariate models showed that advanced age, impaired ejection fraction, new‐onset AF and discontinuation of beta‐blockers were predictors of AF at 1 year.ConclusionsIn most cases, new‐onset AF after AV surgery could be effectively converted and suppressed by rhythm control therapy. Nevertheless, new‐onset AF predisposed patients to higher risks of stroke and AF within 1 year, for whom prophylactic procedures and continuous beta‐blockers could be beneficial.     

Rationale and design of a multi‐center,prospective randomized controlled trial on the effects of sacubitril–valsartan versus enalapril on left ventricular remodeling in ST‐elevation myocardial infarction: The PERI‐STEMI study

BackgroundAngiotensin receptor neprilysin inhibitor (ARNI) sacubitril‐valsartan has been recommended as one of the first‐line therapies in heart failure with reduced ejection fraction. However, whether ARNI could benefit patients with ST‐segment elevation myocardial infarction (STEMI) by improving left ventricular (LV) remodeling remains unknown. The primary objective of the PERI‐STEMI trial is to assess whether sacubitril‐valsartan is more effective in preventing adverse LV remodeling for patients with STEMI than enalapril.HypothesisWe hypothesize that sacubitril/valsartan is superior to enalapril in preventing adverse LV remodeling evaluated by cardiovascular magnetic resonance imaging at the 6‐month follow‐up.MethodsPERI‐STEMI is an investigator‐initiated, prospective, multi‐center, randomized, open‐label, superiority trial with blinded evaluation of outcomes. A total of 376 first‐time STEMI patients with primary percutaneous coronary intervention (PPCI) within 12 h after symptom onset will be randomized to sacubitril‐valsartan or enalapril treatment. All the patients will receive a baseline cardiovascular magnetic resonance (CMR) examination at 4–7 days post‐PPCI. The primary endpoint is the change of indexed LV mass at the 6‐month follow‐up CMR.ResultsEnrollment of the first patient is planned in November 2021. Recruitment is anticipated to last for 12–18 months and patients will be followed for 5 years after randomization. The study is expected to complete in June 2027.ConclusionsThe results of the PERI‐STEMI trial are expected to provide CMR evidence on whether ARNI could benefit patients with STEMI, so as to facilitate the strategy of CMR‐based risk stratification and therapy selection for these patients. PERI‐STEMI is registered at ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT04912167","term_id":"NCT04912167"}}NCT04912167).     

Role of antithymocyte globulin in matched sibling donor peripheral blood stem cell transplantation for hematologic malignancies

Background:High incidence of chronic graft-versus-host disease (GVHD) has been a major drawback of matched sibling donor peripheral blood stem cell transplantation (MSD -PBSCT). This study aimed to investigate the safety and efficacy of antithymocyte globulin (ATG) as a standardized part of GVHD prophylaxis in patients receiving MSD -PBSCT.Methods:A total of 72 patients with hematological malignancies receiving MSD -PBSCT who displayed similar baseline characteristics were either given rabbit ATG ( n = 42) or no ATG (n = 30), in addition to cyclosporine, methotrexate, and mycophenolate mofetil as a standard GVHD prophylaxis regimen. Either patients or donors aged ≥40 years were included in the study. Thymoglobulin was administered at a daily dose of 1.5 mg/kg on day −5 and 3.5 mg/kg on day −4 prior to transplant (the total dose was 5 mg/kg)Results:After a median follow-up of 874 days, the 3-year cumulative incidence of chronic GVHD (cGVHD) was 37.3% in the ATG group and 52.1% in the non -ATG group. The 3-year overall and disease-free survival probability were 71.0% and 62.0% (ATG versus non -ATG, P = .262) and 66.7% and 58.4% (ATG versus non -ATG, P = .334). No difference was found in the 2-year cumulative incidence of nonrelapse mortality and relapse between the ATG and non -ATG groups. This significant reduction in the incidence of cGVHD without increased relapse risk and nonrelapse mortality led to a 3-year GVHD-free, relapse-free survival probability of 66.7% and 40.0% in the ATG and non-ATG groups, respectively.Conclusions:These data suggested that rabbit antithymocyte globulin in the current protocol for GVHD prophylaxis was well tolerable and efficacious.The clinical trial was registered on January 1, 2016 (ClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT02677181","term_id":"NCT02677181"}}NCT02677181). https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02677181","term_id":"NCT02677181"}}NCT02677181.     

Predictive value of HMGB1 for atrial fibrillation recurrence after cryoballoon ablation in paroxysmal atrial fibrillation patients

BackgroundCryoballoon ablation (CBA) is recommended for patients with symptomatic drug refractory paroxysmal atrial fibrillation (pAF). However, substantial atrial fibrillation (AF) recurrence is common during follow‐up. Searching for a potential biomarker representing both myocardial injury and inflammation to identify patients at high risk of AF recurrence after CBA is very meaningful for postoperative management of AF patients.HypothesisTo evaluate the clinical efficacy of high‐mobility group box 1 (HMGB1) protein released from the left atrium to predict AF recurrence in pAF patients after CBA at 1‐year follow‐up.MethodsWe included 72 pAF patients who underwent CBA. To determine the expression levels of HMGB1, left atrial blood samples were collected from the patients before CBA and after the procedure through the transseptal sheath. Patients were followed up for AF recurrence for 1 year.ResultsA total of 19 patients of the 72 experienced AF recurrence. The level of postoperative HMGB1 (HMGB1post) was higher in the AF recurrence group than in the AF non recurrence group (p = .03). However, no differences were noted in the levels of other biomarkers such as preoperative high‐sensitivity C‐reactive protein (hs‐CRP), postoperativehs‐CRP, and preoperative HMGB1 between the two groups. Multiple logistic regression analysis revealed that a higher level of serum HMGB1post was associated with AF recurrence (odds ratio: 5.29 [1.17–23.92], p = .04). Receiver operating characteristic analysis revealed that HMGB1post had a moderate predictive power for AF recurrence (area under the curve: 0.68; sensitivity: 72%; and specificity: 68%). The 1‐year AF‐free survival was significantly lower in patients with a high HMGB1post level than in those with a low HMGB1post level (hazard ratio: 3.81 [1.49–9.75], p = .005).ConclusionIn pAF patients who under went CBA, the level of HMGB1 after CBA was associated with AF recurrence and demonstrated a moderate predictive power. Thus, we offer a potential biomarker to identify pAF patients at high risk of AF recurrence.     

Influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism

BackgroundVitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long‐term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla‐protein, an important vitamin K‐dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K‐dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT).MethodsThe influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial ({"type":"clinical-trial","attrs":{"text":"NCT02066662","term_id":"NCT02066662"}}NCT02066662) is a multicenter, prospective RCT with a two‐arm, open‐label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre‐existent coronary calcification. The development of CVC will be assessed by follow‐up CT at 12 and 24 months.ResultsIn total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.     

Prognostic value of lymphocyte-to-monocyte ratio previously determined to surgery in patients with non-metastatic renal cell carcinoma: A systematic review and a prisma-compliant meta-analysis

Background:The prognostic value of pretreatment lymphocyte to monocyte ratio in patients with renal cell carcinoma and, especially, in non-metastatic patients remains controversial.Methods:We conducted a PRISMA-compliant meta-analysis to systematically assess the prognostic value of LMR in patients with non-metastatic RCC. Overall survival, cancer-specific survival, and disease-free survival were analyzed. Pooled hazard ratios and 95% confidence intervals were calculated.Results:Seven studies comprising 4666 patients were included in the analysis. Unlike those observed in a previous meta-analysis, a lower lymphocyte to monocyte ratio was associated with poorer cancer-specific survival (fix-effect model, hazard ratio 3.04, 95% confidence intervals 2.05–4.51, P < .05). Heterogeneity Chi-squared value Q exp = 0. (P = .82) (I² = 0%). However, the association between a low lymphocyte to monocyte ratio and overall survival or disease-free survival did not obtain significance.Conclusion:A lower lymphocyte to monocyte ratio implied poor cancer-specific survival in patients with non-metastatic renal cell carcinoma. Prospective studies are required to confirm our findings.Registration number:ClinicalTrials.gov (identifier: {"type":"clinical-trial","attrs":{"text":"NCT04213664","term_id":"NCT04213664"}}NCT04213664)     

Kidney outcomes using a sustained ≥40% decline in eGFR: A meta‐analysis of SGLT2 inhibitor trials

BackgroundA recent meta‐analysis of sodium–glucose cotransporter 2 (SGLT2) inhibitor outcome trials reported that SGLT2 inhibitors were associated with reduction in the risk of adverse composite kidney outcomes, with moderate heterogeneity across the trials; however, the endpoints were defined differently across the trials.HypothesisThe apparent heterogeneity of the meta‐analysis of kidney composite outcomes of SGLT2 inhibitor trials will be substantially reduced by using a consistent assessment of sustained ≥40% decline in eGFR/chronic kidney dialysis/transplantation/renal death across trials.MethodsWe performed a meta‐analysis of kidney composite outcomes from the four SGLT2 cardiovascular outcome trial programs conducted in general type 2 diabetes mellitus populations, which included, as a surrogate of progression to kidney failure, a sustained ≥40% decline in eGFR along with kidney replacement therapy and kidney death. The trials assessed were VERTIS CV ({"type":"clinical-trial","attrs":{"text":"NCT01986881","term_id":"NCT01986881"}}NCT01986881), CANVAS Program ({"type":"clinical-trial","attrs":{"text":"NCT01032629","term_id":"NCT01032629"}}NCT01032629 and {"type":"clinical-trial","attrs":{"text":"NCT01989754","term_id":"NCT01989754"}}NCT01989754), DECLARE‐TIMI 58 ({"type":"clinical-trial","attrs":{"text":"NCT01730534","term_id":"NCT01730534"}}NCT01730534), and EMPA‐REG OUTCOME ({"type":"clinical-trial","attrs":{"text":"NCT01131676","term_id":"NCT01131676"}}NCT01131676).ResultsData from the trials comprised 42 516 individual participants; overall, 998 composite kidney events occurred. SGLT2 inhibition was associated with a significant reduction in the kidney composite endpoint (HR 0.58 [95% CI 0.51–0.65]) and with a highly consistent effect across the trials (Q statistic p = .64; I ² = 0.0%).ConclusionsOur meta‐analysis highlights the value of using similarly defined endpoints across trials and supports the finding of consistent protection against kidney disease progression with SGLT2 inhibitors as a class in patients with type 2 diabetes mellitus who either have established atherosclerotic cardiovascular disease or are at high cardiovascular risk with multiple cardiovascular risk factors.     

3-year Treatment of Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China

Background and AimsTenofovir alafenamide (TAF) has similar efficacy to tenofovir disoproxil fumarate (TDF) but with improved renal and bone safety in chronic hepatitis B patients studied outside of China. We report 3-year results from two phase 3 studies with TAF in China (Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT02836249","term_id":"NCT02836249"}}NCT02836249 and {"type":"clinical-trial","attrs":{"text":"NCT02836236","term_id":"NCT02836236"}}NCT02836236).MethodsChinese hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks (3 years). Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.ResultsOf the 334 patients (180 HBeAg-positive and 154 HBeAg-negative) randomized and treated, baseline characteristics were similar between groups. The overall mean age was 38 years and 73% were male. The mean HBV DNA was 6.4 log₁₀ IU/mL. The median alanine aminotransferase was 88 U/L, and 37% had a history of antiviral use. At week 144, the proportion with HBV DNA <29 IU/mL was similar among the two groups, with TAF at 83% vs. TDF at 79%, and TAF at 93% vs. TDF at 92% for the HBeAg-positive and -negative patients, respectively. In each study, higher proportions of TAF than TDF patients showed normalized alanine aminotransferase (via the American Association for the Study of Liver Diseases and the China criteria) and showed loss of HBsAg; meanwhile, the HBeAg seroconversion rates were similar. Treatment was well-tolerated among the TAF patients, who showed a smaller median decline in creatinine clearance (−0.4 vs. −3.2 mL/min; p=0.014) and less percentage change in bone mineral density vs. TDF at hip (−0.95% vs. −1.93%) and spine (+0.35% vs. −1.40%).ConclusionsIn chronic hepatitis B patients from China, TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.