Left Atrial Mechanical Dysfunction and the Risk for Ischemic Stroke in People Without Prevalent Atrial Fibrillation or Stroke : A Prospective Cohort Study.

BACKGROUND: Atrial myopathy-characterized by changes in left atrial function and size-may precede and promote atrial fibrillation (AF) and cardiac thromboembolism. In people without prior AF or stroke, whether analysis of left atrial function and size can improve ischemic stroke prediction is unknown. OBJECTIVE: To evaluate the association of echocardiographic left atrial function (reservoir, conduit, and contractile strain) and left atrial size (left atrial volume index) with ischemic stroke and determine whether these measures can improve the stroke prediction achieved by CHA2DS2-VASc score variables. DESIGN: Prospective cohort study. SETTING: ARIC (Atherosclerosis Risk in Communities) study. PARTICIPANTS: 4917 ARIC participants without prevalent stroke or AF. MEASUREMENTS: Ischemic stroke events (2011 to 2019) were adjudicated by physicians. Left atrial strain was measured using speckle-tracking echocardiography. RESULTS: Over 5 years, the cumulative incidences of ischemic stroke in the lowest quintiles of left atrial reservoir, conduit, and contractile strain were 2.99% (95% CI, 1.89% to 4.09%), 3.18% (CI, 2.14% to 4.22%), and 2.15% (CI, 1.09% to 3.21%), respectively, and that of severe left atrial enlargement was 1.99% (CI, 0.23% to 3.75%). On the basis of the Akaike information criterion, left atrial reservoir strain plus CHA2DS2-VASc variables was the best predictive model. With the addition of left atrial reservoir strain to CHA2DS2-VASc variables, 11.6% of the 112 participants with stroke after 5 years were reclassified to higher risk categories and 1.8% to lower risk categories. Among the 4805 participants who did not develop stroke, 12.2% were reclassified to lower and 12.7% to higher risk categories. Decision curve analysis showed a predicted net benefit of 1.34 per 1000 people at a 5-year risk threshold of 5%. LIMITATION: Underascertainment of subclinical AF. CONCLUSION: In people without prior AF or stroke, when added to CHA2DS2-VASc variables, left atrial reservoir strain improves stroke prediction and yields a predicted net benefit, as shown by decision curve analysis. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Abnormal P-wave terminal force in lead V1 is associated with low left atrial appendage ejection velocity.

BACKGROUND: Sinus P-wave abnormalities have been associated stroke in people with atrial fibrillation (AF). The majority of AF-related strokes occur from left atrial appendage (LAA) thromboembolism. Dysfunction of the left atrium (LA) and left atrial appendage (LAA) can increase rates of thromboembolic stroke. We studied whether abnormal P wave terminal force in V1 (aPTFV1) is associated with decreased LAA ejection velocity (LAAV) on transesophageal echocardiography (TEE). METHODS: We conducted a retrospective cross-sectional study reviewing patients at a tertiary care medical center who underwent TEE in sinus rhythm and had an interpretable sinus ECG within 12 months of TEE. Participants were excluded for complex congenital heart disease, age <18, cardiac transplantation, and chronic atrial pacing. Logistic regression analysis was used to estimate the odds ratios of LAAV<40 cm/s for aPTFV1. RESULTS: In our final cohort of 169 patients (28% of which had LAAV <40), the multivariate odds ratio of aPTFV1 for LAAV<40 cm/s after adjustment for CHA2DS2VASc variables, heart rate during TEE, history of atrial arrhythmias, and left atrial volume index was 2.24 (95% CI of 1.13-6.00). CONCLUSION: Abnromal P-wave terminal force in lead V1 is associated with low LAAV after adjustment for potential confounders. Future research is needed for validation of our findings and determination of clinical utility.

Refining Prediction of Atrial Fibrillation-Related Stroke Using the P2-CHA2DS2-VASc Score.

BACKGROUND: In people with atrial fibrillation (AF), periods of sinus rhythm present an opportunity to detect prothrombotic atrial remodeling through measurement of P-wave indices (PWIs)-prolonged P-wave duration, abnormal P-wave axis, advanced interatrial block, and abnormal P-wave terminal force in lead V1. We hypothesized that the addition of PWIs to the CHA2DS2-VASc score would improve its ability to predict AF-related ischemic stroke. METHODS: We included 2229 participants from the ARIC study (Atherosclerosis Risk in Communities) and 700 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with incident AF who were not on anticoagulants within 1 year of AF diagnosis. PWIs were obtained from study visit ECGs before development of AF. AF was ascertained using study visit ECGs and hospital records. Ischemic stroke cases were based on physician adjudication of hospital records. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of PWIs for ischemic stroke. Improvement in 1-year stroke prediction was assessed by C-statistic, categorical net reclassification improvement, and relative integrated discrimination improvement. RESULTS: Abnormal P-wave axis was the only PWI associated with increased ischemic stroke risk (hazard ratio, 1.84; 95% CI, 1.33-2.55) independent of CHA2DS2-VASc variables, and that resulted in meaningful improvement in stroke prediction. The ß estimate was approximately twice that of the CHA2DS2-VASc variables, and thus abnormal P-wave axis was assigned 2 points to create the P2-CHA2DS2-VASc score. This improved the C-statistic (95% CI) from 0.60 (0.51-0.69) to 0.67 (0.60-0.75) in ARIC and 0.68 (0.52-0.84) to 0.75 (0.60-0.91) in MESA (validation cohort). In ARIC and MESA, the categorical net reclassification improvements (95% CI) were 0.25 (0.13-0.39) and 0.51 (0.18-0.86), respectively, and the relative integrated discrimination improvement (95% CI) were 1.19 (0.96-1.44) and 0.82 (0.36-1.39), respectively. CONCLUSIONS: Abnormal P-wave axis-an ECG correlate of left atrial abnormality- improves ischemic stroke prediction in AF. Compared with CHA2DS2-VASc, the P2-CHA2DS2-VASc is a better prediction tool for AF-related ischemic stroke.

Abnormal P-Wave Axis and Ischemic Stroke: The ARIC Study (Atherosclerosis Risk In Communities).

BACKGROUND AND PURPOSE: Abnormal P-wave axis (aPWA) has been linked to incident atrial fibrillation and mortality; however, the relationship between aPWA and stroke has not been reported. We hypothesized that aPWA is associated with ischemic stroke independent of atrial fibrillation and other stroke risk factors and tested our hypothesis in the ARIC study (Atherosclerosis Risk In Communities), a community-based prospective cohort study. METHODS: We included 15 102 participants (aged 54.2±5.7 years; 55.2% women; 26.5% blacks) who attended the baseline examination (1987-1989) and without prevalent stroke. We defined aPWA as any value outside 0 to 75° using 12-lead ECGs obtained during study visits. Each case of incident ischemic stroke was classified in accordance with criteria from the National Survey of Stroke by a computer algorithm and adjudicated by physician review. Multivariable Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of aPWA with stroke. RESULTS: During a mean follow-up of 20.2 years, there were 657 incident ischemic stroke cases. aPWA was independently associated with a 1.50-fold (95% confidence interval, 1.22-1.85) increased risk of ischemic stroke in the multivariable model that included atrial fibrillation. When subtyped, aPWA was associated with a 2.04-fold (95% confidence interval, 1.42-2.95) increased risk of cardioembolic stroke and a 1.32-fold (95% confidence interval, 1.03-1.71) increased risk of thrombotic stroke. CONCLUSIONS: aPWA is independently associated with ischemic stroke. This association seems to be stronger for cardioembolic strokes. Collectively, our findings suggest that alterations in atrial electric activation may predispose to cardiac thromboembolism independent of atrial fibrillation.

Adding fuel to the fire: Coronary artery dissection complicating blunt chest trauma.

A 21year-old male presented to the emergency department with 6 h of atypical chest pain after suffering blunt chest trauma. His electrocardiogram revealed 1-1.5mm ST segment elevation in leads V1-V3 with reciprocal depressions in II, III, and aVF. Mid-anterior wall akinesis was observed on echocardiography associated with an estimated left ventricular ejection fraction of 40%. A left main coronary artery dissection was diagnosed and treated surgically with a bypass graft. Although rare, coronary dissections can be a catastrophic complication of chest trauma.

Development of technologies for placement of perineural catheters.

Continuous peripheral nerve block (CPNB) success is largely dependent on placement of the catheter close enough to the nerve to allow effective and sustained analgesia following painful surgeries with a minimum volume of local anesthetic. One of the most common problems associated with CPNB involves accurate placement of the catheter tip, migration, and dislodgement of the catheter. This is of increasing importance now that catheters are left in place for prolonged periods of time to provide postoperative analgesia, and patients with peripheral nerve catheters are being discharged home with ambulatory pumps. In response to the challenges of providing safe, effective, and consistently reliable analgesia, research and development in this field is expanding rapidly. This review article presents results from recent publications addressing the subject of peripheral nerve catheter localization.

Pulmonary vein isolation plus adjunctive therapy for the treatment of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Pulmonary vein isolation (PVI) is the primary technique for ablation of atrial fibrillation (AF). It is unclear whether adjunctive therapies in addition to PVI can reduce atrial arrhythmia recurrence (AAR) compared to PVI alone in patients with AF. METHODS: A meta-analysis of randomized controlled trials comparing PVI plus an adjunctive therapy (autonomic modulation, linear ablation, non-pulmonary vein trigger ablation, epicardial PVI [hybrid ablation], or left atrial substrate modification) to PVI alone was conducted. The primary outcome was AAR. Cumulative odd's ratios (OR) and 95% confidence intervals (CI) were calculated for each treatment type. RESULTS: Forty-six trials were identified that included 8,500 participants. The mean age (± standard deviation) was 60.2 (±4.1) years, and 27.2% of all patients were female. The mean follow-up time was 14.6 months. PVI plus autonomic modulation and PVI plus hybrid ablation were associated with a relative 53.1% (OR 0.47; 95% CI 0.32 to 0.69; p < 0.001) and 59.1% (OR 0.41; 95% CI 0.23 to 0.75; p = 0.003) reduction in AAR, respectively, compared to PVI alone. All categories had at least moderate interstudy heterogeneity except for hybrid ablation. CONCLUSION: Adjunctive autonomic modulation and epicardial PVI may improve the effectiveness of PVI. Larger, multi-center randomized controlled trials are needed to evaluate the efficacy of these therapies.

Pulmonary vein isolation with adjunctive left atrial ganglionic plexus ablation for treatment of atrial fibrillation: a meta-analysis of randomized controlled trials.

BACKGROUND: Adjunctive ganglionic plexus (GP) ablation may increase the efficacy of pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF). Prior meta-analyses examining PVI with adjunctive GP ablation have included non-randomized trials and have included trials evaluating thorascopic epicardial ablation. The objective of this study is to perform a meta-analysis of randomized controlled trials (RCTs) comparing endocardial catheter-based PVI to PVI with adjunctive GP ablation. METHODS: Summary odds ratio (OR) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed with I2 values. Sub-group analysis was performed comparing arrhythmia recurrence between patients with paroxysmal versus persistent AF at trial baseline. Meta-regressions were performed with mean left atrial diameter and left ventricular ejection fraction at trial baseline as the moderator variables. RESULTS: Five RCTs were identified including 814 patients: 406 PVI + GP ablation and 408 PVI alone. The mean age of participants was 56.5 years and 74.7% were male. Four of these trials evaluated catheter-based endocardial ablation for a total of 574 patients: 289 PVI + GP ablation and 285 PVI alone. The odds of arrhythmia recurrence in patients undergoing adjunctive GP ablation with PVI compared with PVI alone were a reduced: odds ratio (OR) 0.58, 95% confidence interval (CI) 0.41-0.82, I2 = 40.2%. In the subgroup analysis, the odds of arrhythmia recurrence with adjunctive GP ablation were reduced in those with paroxysmal AF (OR 0.396, 95% CI 0.23-0.69, I2 = 0%). A non-significant trend to reduced arrhythmia recurrence was also observed in those with persistent AF (OR 0.726, 95% CI 0.475-1.112, I2 = 0%). When performing the meta-regression, increased left atrial diameter was associated with decreased treatment effect of adjunctive GP ablation (R2 index = 1.0, I2 = 0%). CONCLUSIONS: The addition of GP ablation to PVI was associated with reduced arrhythmia recurrence. Adjunctive GP ablation was more effective in paroxysmal AF and in patients with smaller atria. Larger RCTs are needed to confirm the efficacy of GP + PVI ablation.

Role of magnesium alone or in combination with diltiazem and/or amiodarone in prevention of atrial fibrillation following off-pump coronary artery bypass grafting.

Objectives: In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation (AF) following off-pump coronary artery bypass grafting (CABG). Background: AF after CABG is common and contributes to morbidity and mortality. Various pharmacological preventive measures including magnesium, amiodarone, diltiazem, and combination therapy among others have been tried to lower the incidence of AF. Most of the studies have been performed in patients undergoing conventional on-pump CABG. In this uncontrolled trial, efficacy of magnesium alone or in combination with amiodarone and / or diltiazem has been studied in patients undergoing off-pump CABG. Methods: One hundred and fifty patients undergoing off-pump CABG were divided into 3 groups, Group M (n=21) received intraoperative magnesium infusion at 30mg/ kg over 1 hour after midline sternotomy; Group MD (n=78) received magnesium infusion in similar manner with diltiazem infusion at 0.05 µg/kg/hr throughout the intraoperative period; Group AMD (n=51) received preoperative oral amiodarone at a dose of 200 mg three times a day for 3 days followed by 200 mg twice daily for another 3 days followed by 200 mg once daily till the day of surgery along with magnesium and diltiazem infusion as in other groups. AF lasting more than 10 min or requiring medical intervention was considered as AF. Results: The overall incidence of postoperative AF was 12.6% with 11.7% in group AMD, 19% in group M, and 11.5% in group MD, which was not statistically significant. Conclusions: It is concluded that the use of amiodarone and/or diltiazem in addition to magnesium did not result in additional benefit of lowering the incidence of AF.

Non-pharmacologic autonomic neuromodulation for treatment of heart failure: A systematic review and meta-analysis of randomized controlled trials.

Treatment strategies that modulate autonomic tone through interventional and device-based therapies have been studied as an adjunct to pharmacological treatment of heart failure with reduced ejection fraction (HFrEF). The main objective of this study was to perform a meta-analysis of randomized controlled trials which evaluated the efficacy of device-based autonomic modulation for treatment of HFrEF. All randomized-controlled trials testing autonomic neuromodulation device therapy in HFrEF were included in this trial-level analysis. Autonomic neuromodulation techniques included vagal nerve stimulation (VNS), baroreflex activation (BRA), spinal cord stimulator (SCS), and renal denervation (RD). The prespecified primary endpoints included mean change and 95% confidence intervals (CI) of left ventricular ejection fraction (LVEF), NT pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QOL) measures including 6-minute hall walk distance (6-MHWD), and Minnesota Living with Heart Failure Questionnaire (MLHFQ). New York Heart Association (NYHA) functional class improvement was reported as odds ratios and 95% CI of improvement by at least 1 functional class. Eight studies were identified that included 1037 participants (2 VNS, 2 BRA, 1 SCS, and 3 RD trials). This included 6 open-label, 1 single-blind, and 1 sham-controlled, double-blind study. The mean age (±SD) was 61 (±9.3) years. The mean follow-up time was 7.9 months. Twenty percent of the total patients were female, and the mean BMI (±SD) was 29.86 (±4.12). Autonomic neuromodulation device therapy showed a statistically significant improvement in LVEF (4.02%; 95% CI 0.24,7.79), NT-proBNP (-219.80 pg/ml; 95% CI -386.56, -53.03), NYHA functional class (OR 2.32; 95% CI 1.76, 3.07), 6-MHWD (48.39 m; 95% CI 35.49, 61.30), and MLHFQ (-12.20; 95% CI -19.24, -5.16) compared to control. In patients with HFrEF, the use of autonomic neuromodulation device therapy is associated with improvement in LVEF, reduction in NT-proBNP, and improvement in patient-centered QOL outcomes in mostly small open-label trials. Large, double-blind, sham-controlled trials designed to detect differences in hard cardiovascular outcomes are needed before widespread use and adoption of autonomic neuromodulation device therapies in HFrEF.

External validation of Chronic Pancreatitis Prognosis Score (COPPS): A prospective cohort study.

BACKGROUND: Prognostic stratification in ChronicPancreatitis(CP) remains suboptimal and cumbersome. Chronic Pancreatitis Prognostic Score(COPPS) was recently developed to predict one-year hospitalisations in CP. AIM: External validation of COPPS in a geographically divergent patient population. METHODS: A single-center prospective cohort study, conducted on out-patients of a tertiary-care hospital. Consecutive adults with CP were assessed for COPPS risk predictors at baseline, similar to the original development cohort, and followed for one-year for: 1)hospitalisations; 2)development of pancreatitis-related complications; and 3)need for endoscopic and/or surgical interventions. Outcomes were compared by Kendall's tau-b(τb) and other statistical tests. Only those who had complete one-year follow-up were included in analysis. RESULTS: There were 177 patients(mean±SD age: 35.9 ± 11.2 years), 116(65%) males and 117(66%) with Idiopathic CP. Despite being younger, with significantly more females and Idiopathic CP, than the original development cohort, our cohort was similar to the latter regarding COPPS severity at baseline. Eight patients died over one-year; 169 were evaluated for outcomes. Increasingly severe COPPS categories correlated with increasing number of hospitalisations(both overall and pancreatitis-related) and increasing number of days spent in hospital(both overall and pancreatitis-related) irrespective of age at symptoms-onset(≤35 vs >35years), etiology(idiopathic vs alcohol) and smoking-status. CONCLUSIONS: COPPS is effective in a geographically distinct cohort having a different case-mix of CP patients(ClincialTrials.gov ID:NCT04907266).

Validation of the DeLiT Trial intravenous insulin infusion algorithm for intraoperative glucose control in noncardiac surgery: a randomized controlled trial.

PURPOSE: A safe and effective insulin infusion algorithm that achieves rigorous intraoperative glycemic control in noncardiac surgery has yet to be formally characterized and evaluated. We therefore report the validation of the DeLit Trial insulin infusion algorithm. METHODS: Patients scheduled for major noncardiac surgery were randomized to a target intraoperative blood glucose concentration of 4.4-6.1 mmoL·L(-1) (80-110 mg·dL(-1)) intensive group or 10-11.1 mmoL·L(-1) (180-200 mg·dL(-1)) conventional group. Glucose was managed with a dynamic intravenous insulin infusion algorithm. We compared the randomized groups on glucose time-weighted average (TWA), proportion of time spent within target, number of severe (< 2.2 mmoL·L(-1) or < 40 mg·dL(-1)) or moderate (< 2.8 mmoL·L(-1) or < 50 mg·dL(-1)) hypoglycemic episodes, and within-patient variability in glucose concentrations expressed as standard deviation from the patient mean. RESULTS: One hundred eighty-seven patients were assigned to intensive glucose control, and 177 patients were assigned to conventional glucose control. Median (lower quartile value [Q1], upper quartile value [Q3]) of intraoperative TWA for the intensive vs conventional groups was 6 [5.6, 6.7] mmoL·L(-1) vs 7.7 [6.9, 9.2] mmoL·L(-1), respectively; P < 0.001. The intensive group spent 49% (29, 71) of the time within target, substantially more time than the conventional group spent either within the intensive target or within its own target (both P < 0.001). The intensive group had slightly lower within-patient glucose variability than the conventional group (0.9 [0.7, 1.3] mmoL·L(-1) vs 1.3 [0.8, 1.8] mmoL·L(-1), respectively; P < 0.001). Three patients had moderate hypoglycemia (intensive group), but none experienced severe episodes. CONCLUSION: Tight intraoperative glucose control in noncardiac surgery can be maintained successfully without serious hypoglycemic episodes. (ClinicalTrials.gov number, NCT00433251).

Frequent Premature Atrial Contractions Are Associated With Poorer Cognitive Function in the Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: To evaluate the association of premature atrial contraction (PAC) frequency with cognitive test scores and prevalence of dementia or mild cognitive impairment (MCI). MATERIALS AND METHODS: We conducted a cross-sectional analysis using Atherosclerosis Risk in Communities study visit 6 (January 1, 2016, through December 31, 2017) data. We included 2163 participants without atrial fibrillation (AF) (age mean ± SD, 79±4 years; 1273 (58.9%) female; and 604 (27.97.0% Black) who underwent cognitive testing and wore a leadless, ambulatory electrocardiogram monitor for 14 days. We categorized PAC frequency based on the percent of beats: less than 1%, minimal; 1% to <5%, occasional; greater than or equal to 5%, frequent. We derived cognitive domain-specific factor scores (memory, executive function, language, and global z-score). Dementia and MCI were adjudicated. RESULTS: During a mean analyzable time of 12.6±2.6 days, 339 (15.7%) had occasional PACs and 107 (4.9%) had frequent PACs. Individuals with frequent PACs (vs minimal) had lower executive function factor scores by 0.30 (95% CI, -0.46 to -0.14) and lower global factor scores by 0.20 (95% CI, -0.33 to -0.07) after multivariable adjustment. Individuals with frequent PACs (vs minimal) had higher odds of prevalent dementia or MCI after multivariable adjustment (odds ratio, 1.74; 95% CI, 1.09 to 2.79). These associations were unchanged with additional adjustment for stroke. CONCLUSION: In community-dwelling older adults without AF, frequent PACs were cross-sectionally associated with lower executive and global cognitive function and greater prevalence of dementia or MCI, independently of stroke. Our findings lend support to the notion that atrial cardiomyopathy may be a driver of AF-related outcomes. Further research to confirm these associations prospectively and to elucidate underlying mechanisms is warranted.

Association of Ventricular Arrhythmias With Dementia: The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: We performed a cross-sectional analysis to determine whether nonsustained ventricular tachycardia (NSVT) and premature ventricular contractions (PVCs) were associated with dementia in a population-based study. METHODS: We included 2,517 (mean age 79 years, 26% Black) participants who wore a 2-week ambulatory continuous ECG recording device in 2016 to 2017. NSVT was defined as a wide-complex tachycardia ≥4 beats with a rate >100 bpm. We calculated NSVT and PVC burden as the number of episodes per day. Dementia was adjudicated by experts. We used logistic regression to assess the associations of NSVT and PVCs with dementia. RESULTS: The mean recording time of the Zio XT Patch was 12.6 ± 2.6 days. There were 768 (31%) participants with NSVT; prevalence was similar in White and Black participants. There were 134 (6.5%) dementia cases (5% in White, 10% in Black participants). After multivariable adjustment, there was no overall association between NSVT and dementia; however, there was a significant race interaction (p < 0.001). In Black participants, NSVT was associated with a 3.67 times higher adjusted odds of dementia (95% confidence interval [CI] 1.92-7.02) compared to those without NSVT, whereas in White participants NSVT was not associated with dementia (odds ratio [95% CI] 0.64 [0.37-1.10]). In Black participants only, a higher burden of PVCs was associated with dementia. CONCLUSIONS: Presence of NSVT and a higher burden of NSVT and PVCs are associated with dementia in elderly Black people. Further research to confirm this novel finding and to elucidate the underlying mechanisms is warranted.

Role of intraoperative and postoperative blood glucose concentrations in predicting outcomes after cardiac surgery.

BACKGROUND: Severe hyperglycemia is associated with adverse outcomes after cardiac surgery. Whether intraoperative and postoperative glucose concentrations equally impact outcomes is unknown. The objective of this investigation was to compare the ability of perioperative glucose concentrations and glycemic variability to predict adverse outcomes. Risk associated with decreasing increments of glucose concentrations, hypoglycemia, and diabetic status was also examined. METHODS: This retrospective analysis of prospectively collected data included 4,302 patients who underwent cardiac surgery between October 3, 2005 and May 31, 2007 at the Cleveland Clinic. Time-weighted mean intraoperative (GlcOR) and postoperative (GlcICU) glucose concentrations were calculated. Patients were categorized as follows: Glc more than 200, 171-200, 141-170, and less than or equal to 140 mg/dl. Coefficient of variation was used to calculate glycemic variability. Logistic regression model with backward selection assessed the relationship between glucose concentrations, variability, and adverse outcomes while adjusting for potential confounders. Another model assessed the predictability of GlcOR and GlcICU on adverse outcomes. RESULTS: Both GlcOR and GlcICU predicted risk for mortality and morbidity. Increased postoperative glycemic variability was associated with increased risk for adverse outcomes. Severe hyperglycemia (GlcOR and GlcICU > 200 mg/dl) was associated with worse outcomes; however, decreasing increments of GlcOR did not consistently reduce risk. GlcOR less than or equal to 140 mg/dl was not associated with improved outcomes compared with severe hyperglycemia, despite infrequent hypoglycemia. Diabetic status did not influence the effects of hyperglycemia. CONCLUSION: Perioperative glucose concentrations and glycemic variability are important in predicting outcomes after cardiac surgery. Incremental decreases of intraoperative glucose concentrations did not consistently reduce risk. Despite rare hypoglycemia, intraoperative glucose concentrations closest to normoglycemia were associated with worse outcomes.

Design and Organization of the Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT) Trial: a factorial trial evaluating the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery.

BACKGROUND: The perioperative period is characterized by an intense inflammatory response. Perioperative inflammation promotes postoperative morbidity and increases mortality. Blunting the inflammatory response to surgical trauma might thus improve perioperative outcomes. We are studying three interventions that potentially modulate perioperative inflammation: corticosteroids, tight glucose control, and light anesthesia. METHODS/DESIGN: The DeLiT Trial is a factorial randomized single-center trial of dexamethasone vs placebo, intraoperative tight vs. conventional glucose control, and light vs deep anesthesia in patients undergoing major non-cardiac surgery. Anesthetic depth will be estimated with Bispectral Index (BIS) monitoring (Aspect medical, Newton, MA). The primary outcome is a composite of major postoperative morbidity including myocardial infarction, stroke, sepsis, and 30-day mortality. C-reactive protein, a measure of the inflammatory response, will be evaluated as a secondary outcome. One-year all-cause mortality as well as post-operative delirium will be additional secondary outcomes. We will enroll up to 970 patients which will provide 90% power to detect a 40% reduction in the primary outcome, including interim analyses for efficacy and futility at 25%, 50% and 75% enrollment. DISCUSSION: The DeLiT trial started in February 2007. We expect to reach our second interim analysis point in 2010. This large randomized controlled trial will provide a reliable assessment of the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery. The factorial design will enable us to simultaneously study the effects of the three interventions in the same population, both individually and in different combinations. Such a design is an economically efficient way to study the three interventions in one clinical trial vs three. TRIAL REGISTRATION: This trial is registered at Clinicaltrials.gov #: NTC00433251.

The association between alcohol consumption and morbidity and mortality in patients undergoing coronary artery bypass surgery.

OBJECTIVE: Moderate alcohol consumption appears protective against cardiovascular events and mortality in community-based epidemiologic studies, but whether its consumption affects perioperative outcomes remains unknown. Therefore, the authors tested the hypothesis that alcohol consumption of 3 or more drinks per week improves postoperative outcomes in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN: A propensity-matched retrospective cohort study. SETTING: A major cardiovascular surgical institute, tertiary care teaching hospital. PARTICIPANTS: Data from 13,065 patients undergoing elective CABG surgery at the Cleveland Clinic were analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Propensity scores were used to match alcohol users with infrequent/nonusers. From the matched subset, the relationship between alcohol use and the composite outcome (any major cardiac, renal, respiratory, infectious, or neurologic morbidity and mortality) was determined univariably with the Pearson chi-square test and multivariably using stepwise logistic regression. Estimation of the relationship between such alcohol use and hospital length of stay was of secondary interest. Patients who reported consuming at least 3 drinks per week experienced similar odds of the composite outcome (adjusted odds ratio [95% confidence interval] of 1.13 [0.96-1.34], p = 0.14) to infrequent or nonusers. In a secondary analysis, the hospital length of stay was unrelated to alcohol use (adjusted hazard ratio [95% CI] of 1.03 [0.97-1.09], p = 0.28). CONCLUSION: The present results showed that alcohol consumption was not associated with the risk for postoperative complications in patients undergoing CABG surgery. Alcohol abusers could not be separated in this study, and, based on previous literature, this result might not be applied to them.