Project description:ImportanceDexmedetomidine is a widely used sedative in the intensive care unit (ICU) and has unique properties that may be associated with reduced occurrence of new-onset atrial fibrillation (NOAF).ObjectiveTo investigate whether the use of dexmedetomidine is associated with the incidence of NOAF in patients with critical illness.Design, setting, and participantsThis propensity score-matched cohort study was conducted using the Medical Information Mart for Intensive Care-IV database, which includes records of patients admitted to the ICU at Beth Israel Deaconess Medical Center in Boston dating 2008 through 2019. Included patients were those aged 18 years or older and hospitalized in the ICU. Data were analyzed from March through May 2022.ExposurePatients were divided into 2 groups according to dexmedetomidine exposure: those who received dexmedetomidine within 48 hours after ICU admission (dexmedetomidine group) and those who never received dexmedetomidine (no dexmedetomidine group).Main outcomes and measuresThe primary outcome was the occurrence of NOAF within 7 days of ICU admission, as defined by the nurse-recorded rhythm status. Secondary outcomes were ICU length of stay, hospital length of stay, and in-hospital mortality.ResultsThis study included 22 237 patients before matching (mean [SD] age, 65.9 [16.7] years; 12 350 male patients [55.5%]). After 1:3 propensity score matching, the cohort included 8015 patients (mean [SD] age, 61.0 [17.1] years; 5240 males [65.4%]), among whom 2106 and 5909 patients were in the dexmedetomidine and no dexmedetomidine groups, respectively. Use of dexmedetomidine was associated with a decreased risk of NOAF (371 patients [17.6%] vs 1323 patients [22.4%]; hazard ratio, 0.80; 95% CI, 0.71-0.90). Although patients in the dexmedetomidine group had longer median (IQR) length of stays in the ICU (4.0 [2.7-6.9] days vs 3.5 [2.5-5.9] days; P < .001) and hospital (10.0 [6.6-16.3] days vs 8.8 [5.9-14.0] days; P < .001), dexmedetomidine was associated with decreased risk of in-hospital mortality (132 deaths [6.3%] vs 758 deaths [12.8%]; hazard ratio, 0.43; 95% CI, 0.36-0.52).Conclusions and relevanceThis study found that dexmedetomidine was associated with decreased risk of NOAF in patients with critical illness, suggesting that it may be necessary and warranted to evaluate this association in future clinical trials.

Project description:Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF, but no molecular diagnostic exists to predict POAF based on pre-operative measurements. Such a tool would be of great value for perioperative planning to improve patient care and reduce healthcare costs. In this pilot study of epigenetic precision medicine in the perioperative period, we carried out bisulfite sequencing to measure DNA methylation status in blood collected from patients prior to cardiac surgery to identify biosignatures of POAF. Methods: We enrolled 221 patients undergoing cardiac surgery in this prospective observational study. DNA methylation measurements were obtained from blood samples drawn from awake patients prior to surgery. After controlling for clinical and methylation covariates, we analyzed DNA methylation loci in the discovery cohort of 110 patients for association with POAF. We also constructed predictive models for POAF using clinical and DNA methylation data. We subsequently performed targeted analyses of a separate cohort of 101 cardiac surgical patients to measure the methylation status solely of significant methylation loci in the discovery cohort. Results: A total of 47 patients in the discovery cohort (42.7%) and 43 patients in the validation cohort (42.6%) developed POAF. We identified 12 CpGs that were statistically significant in the discovery cohort after correcting for multiple hypothesis testing. Of these sites, 6 were amenable to targeted bisulfite sequencing and chr16:24640902 was statistically significant in the validation cohort. In addition, the methylation POAF prediction model had an AUC of 0.79 in the validation cohort. Conclusions: We have identified DNA methylation biomarkers that can predict future occurrence of POAF associated with cardiac surgery. This research demonstrates the use of precision medicine to develop models combining epigenomic and clinical data to predict disease.

Project description:BackgroundAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF, but no molecular diagnostic exists to predict POAF based on pre-operative measurements. Such a tool would be of great value for perioperative planning to improve patient care and reduce healthcare costs. In this pilot study of epigenetic precision medicine in the perioperative period, we carried out bisulfite sequencing to measure DNA methylation status in blood collected from patients prior to cardiac surgery to identify biosignatures of POAF.MethodsWe enrolled 221 patients undergoing cardiac surgery in this prospective observational study. DNA methylation measurements were obtained from blood samples drawn from awake patients prior to surgery. After controlling for clinical and methylation covariates, we analyzed DNA methylation loci in the discovery cohort of 110 patients for association with POAF. We also constructed predictive models for POAF using clinical and DNA methylation data. We subsequently performed targeted analyses of a separate cohort of 101 cardiac surgical patients to measure the methylation status solely of significant methylation loci in the discovery cohort.ResultsA total of 47 patients in the discovery cohort (42.7%) and 43 patients in the validation cohort (42.6%) developed POAF. We identified 12 CpGs that were statistically significant in the discovery cohort after correcting for multiple hypothesis testing. Of these sites, 6 were amenable to targeted bisulfite sequencing and chr16:24640902 was statistically significant in the validation cohort. In addition, the methylation POAF prediction model had an AUC of 0.79 in the validation cohort.ConclusionsWe have identified DNA methylation biomarkers that can predict future occurrence of POAF associated with cardiac surgery. This research demonstrates the use of precision medicine to develop models combining epigenomic and clinical data to predict disease.

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Clinical prediction scores and early anticoagulation therapy for new-onset atrial fibrillation in critical illness: a post-hoc analysis.

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