Utility of preoperative troponin I to predict mortality in adult liver transplant recipients: Revisiting pretransplant cardiac risk in the current MELD-allocation era.

BACKGROUND: Preoperative risk assessment in liver transplant (LT) candidates, particularly related to cardiac risk, is an area of intense interest for transplant clinicians. Various cardiac testing methods are employed by transplant centers to characterize cardiac risk. Serum troponin is an established method for the detection of myocardial injury in a wide variety of clinical settings. Preoperative troponin screening has been reported to predict postoperative cardiac events and mortality in various surgical patient populations, however, the utility of preoperative troponin to predict posttransplant outcomes in current LT candidate populations requires further investigation. METHODS: We performed a prospective blinded study in a cohort of 275 consecutive LT recipients at a single transplant center to determine if preoperative serum troponin I (TnI) was predictive for postoperative 1-year mortality. RESULTS: Abnormal preoperative TnI levels (>.1 ng/mL) were found in 38 patients (14%). One-year mortality occurred in 19 patients (7%). There was no significant difference in mortality between patients with normal and abnormal troponin levels. Additionally, we found that there was no significant difference in early postoperative major adverse cardiac events between patient groups. CONCLUSIONS: Contrary to previous reports, elevated preoperative TnI was not significantly predictive of posttransplant mortality in LT recipients at our institution.

Diagnostic and predictive values of circulating tetrahydrobiopterin levels as a novel biomarker in patients with thoracic and abdominal aortic aneurysms.

We have previously shown that circulating levels of tetrahydrobiopterin (H4B) function as a robust biomarker for aortic aneurysms in several independent animal models. In the present study, we examined diagnostic and predictive values of circulating H4B levels in human patients of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) for the first time, while clinically applicable biomarkers for aortic aneurysms have never been previously available. Ninety-five patients scheduled for TAA repair surgeries and 53 control subjects were recruited at University of California Los Angeles (UCLA) Ronald Regan Medical Center, while 44 control subjects and 29 AAA patients were recruited through National Institute of Health (NIH) National Disease Research Interchange (NDRI) program. We had intriguing observations that circulating H4B levels were substantially lower in TAA and AAA patients, linearly correlated with aortic H4B levels (blood: R = 0.8071, p < 0.0001, n = 75; plasma: R = 0.7983, p < 0.0001, n = 75), and associated with incidence of TAA (blood: adjusted OR 0.495; 95% CI 0.379-0.647; p < 0.001; plasma: adjusted OR 0.501; 95% CI 0.385-0.652; p < 0.001) or AAA (blood: adjusted OR 0.329; 95% CI 0.125-0.868; p = 0.025) after adjustment for other factors. Blood or plasma H4B levels below 0.2 pmol/µg serve as an important threshold for prediction of aortic aneurysms independent of age and gender (for TAA risk - blood: adjusted OR 419.67; 95% CI 59.191-2975.540; p < 0.001; plasma: adjusted OR 206.11; 95% CI 40.956-1037.279; p < 0.001). This threshold was also significantly associated with incidence of AAA (p < 0.001 by Chi-square analysis). In addition, we observed previously unrecognized inverse association of Statin use with TAA, and an association of AAA with arrhythmia. Taken together, our data strongly demonstrate for the first time that circulating H4B levels can serve as a first-in-class, sensitive, robust and independent biomarker for clinical diagnosis and prediction of TAA and AAA in human patients, which can be rapidly translated to bedside to fundamentally improve clinical management of the devastating human disease of aortic aneurysms.

DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation.

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.

Intraoperative diastolic function assessed by TEE does not agree with preoperative diastolic function grade in CABG patients.

OBJECTIVE: To compare the agreement of the 2016 ASE/EACVI guidelines for grading diastolic dysfunction (DD) with the most commonly used intraoperative transesophageal echocardiography (TEE)-based diastolic function grading algorithm in cardiac surgical patients, and to describe the contribution of the echocardiographic variables used in the algorithms to any observed differences. DESIGN: Retrospective data analysis. SETTING: University tertiary medical center. PARTICIPANTS: Hundred and one patients undergoing coronary artery bypass grafting (CABG) at a single institution from June 2017 to February 2019. INTERVENTIONS: Preoperative transthoracic echocardiography (TTE) diastolic function grade determined by the 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) guidelines was compared to intraoperative diastolic function grade obtained by TEE. MEASUREMENTS AND MAIN RESULTS: Incidence of DD on preoperative TTE was only 19.8%, while 62.3% of patients were graded as having DD on the intraoperative TEE exam. There was grade agreement between TTE and TEE in only 47/101 patients (46.5%). The McNemar test showed poor agreement between the two algorithms (OR for disagreement = 15.33, CI = 4.77-49.30; p < 0.0001). Despite the low incidence of DD on preoperative TTE, mean lateral e' values were significantly lower on TTE compared to TEE (7.7 cm/s vs 9.5 cm/s; p = < 0.0001). CONCLUSIONS: There is strong disagreement between TTE and TEE-based DD grading algorithms. Due to the different echocardiographic variables used in each and the unique clinical settings in which they are applied, they produce fundamentally different results.

Combined Cardiothoracic Surgery and Liver Transplantation Versus Isolated Liver Transplantation.

OBJECTIVE: Combined cardiothoracic surgery and liver transplantation (cCSLT) recently increasingly has been used. Despite that, liver transplant immediately after cardiothoracic surgery has not been well-characterized. The authors aimed to compare perioperative management and postoperative outcomes between patients undergoing cCSLT and isolated liver transplantation (iLT). DESIGN: A retrospective study. SETTING: University tertiary medical center. PARTICIPANTS: Twenty-five cCSLT patients and 1091 iLT patients at a single institution from 2010 to 2017. INTERVENTIONS: Twenty-five cCSLT patients were compared with 100 randomly selected and 100 propensity-matched iLT patients. MEASUREMENTS AND MAIN RESULTS: All cCSLT patients underwent comprehensive preoperative evaluation by a multidisciplinary team. Of 25 cardiothoracic surgeries, heart transplant (n = 9) was most common, followed by coronary artery bypass grafting (n = 5) and lung transplant (n = 3). Intraoperative management of cCSLT was provided by 2 separate teams, one for cardiothoracic surgery and one for liver transplantation. Patients undergoing cCSLT often required cardiopulmonary bypass, an intra-aortic balloon pump, extracorporeal membrane oxygenation, or cardiac pharmacologic therapies and, additionally, needed more interventions including antifibrinolytic administration, venovenous bypass, massive blood transfusion, and platelet transfusions compared with iLT patients. Ninety-day survival rates were similar in the cCSLT (100%) and iLT groups (random iLT 87% and matched iLT 93%, log-rank test p = 0.089). CONCLUSIONS: Despite having end-stage liver disease and advanced cardiothoracic disorders and experiencing a complex intraoperative course, cCSLT patients had comparable 90-day survival to iLT patients. Comprehensive planning before transplant, optimal patient/donor selection, the multiple-team model, and meticulous intraoperative management are critical to the success of cCSLT.

Frequency and Outcomes of Elevated Perioperative Lactate Levels in Adult Congenital Heart Disease Patients Undergoing Cardiac Surgery.

OBJECTIVES: To assess whether lactate levels are associated with clinical outcomes in adult congenital heart disease patients who undergo cardiac surgery. DESIGN: Retrospective study. SETTING: Single quaternary academic referral center. PARTICIPANTS: Adult congenital heart disease patients (≥18 y old) with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Participants were classified into 3 groups according to their peak arterial lactate level within the first 48 hours of surgery. MEASUREMENTS AND MAIN RESULTS: In-hospital 30-day mortality, hospital and intensive care unit length of stay, duration of mechanical ventilation after surgery, acute kidney injury defined by Acute Kidney Injury Network criteria, and intensive care unit and hospital readmission within 30 days of surgery were examined. There was no significant difference among different lactate level groups in acute kidney injury, hospital length of stay, intensive care unit length of stay, hours of mechanical ventilation, need for redo surgery, or rates of hospital or intensive care unit readmission. In multivariable analysis, which included cardiopulmonary bypass time, redo surgery, nonelective case, and the adult congenital heart disease complexity score, lactate levels were not a significant predictor of either acute kidney injury or hospital length of stay. CONCLUSIONS: The appeal of using lactate levels to risk stratify-patients or to develop a model to predict mortality and morbidity has potential merit, but currently there is insufficient evidence to use lactate levels as a predictor of outcomes in adult patients with congenital heart disease undergoing cardiac surgery.

Preoperative Diastolic Dysfunction and Postoperative Outcomes after Noncardiac Surgery.

OBJECTIVE: To determine if diastolic dysfunction is independently associated with increased mortality, acute kidney injury, and hospital length of stay after noncardiac surgery. DESIGN: Retrospective observational cohort. SETTING: Academic referral center. PARTICIPANTS: All patients undergoing noncardiac and nonliver-transplant surgeries at University of California - Los Angeles between April 2013 and October 2017, who also had transthoracic echocardiograms performed within 6 months preceding their procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients' demographic, comorbidity, echocardiographic, and perioperative data were queried from the electronic health record. Diastolic dysfunction was graded by automated application of 2016 American Society of Echocardiography guidelines to queried echocardiographic measurements. During the study period, 12,871 eligible records were identified, of which 7,312 represented unique procedures with complete information. Twenty-three percent of patients had echocardiographic evidence of diastolic dysfunction (7.0% grade 1, 8.1% grade 2, 0.6% grade 3, and 7.5% nonspecific). Patients with diastolic dysfunction tended to be older and have higher American Society of Anesthesiologists scores with more comorbidities. Overall, 166 patients (2.3%) experienced an in-hospital death. After adjustment for potentially confounding variables, diastolic dysfunction was not significantly associated with increased in-hospital mortality, acute kidney injury, or hospital length of stay. CONCLUSIONS: Diastolic dysfunction does not appear to be associated with increased in-hospital mortality, acute kidney injury, or hospital length of stay in a cohort of noncardiac surgical patients at an academic medical center. These results highlight uncertainties in perioperative risk determination.

Regional Left Ventricular Myocardial Dysfunction After Cardiac Surgery Characterized by 3-Dimensional Strain.

BACKGROUND: Three-dimensional (3D) strain is an echocardiographic modality that can characterize left ventricular (LV) function with greater accuracy than ejection fraction. While decreases in global strain have been used to predict outcomes after cardiac surgery, changes in regional 3D longitudinal, circumferential, radial, and area strain have not been well described. The primary aim of this study was to define differential patterns in regional LV dysfunction after cardiac surgery using 3D speckle tracking strain imaging. Our secondary aim was to investigate whether changes in regional strain can predict postoperative outcomes, including length of intensive care unit stay and 1-year event-free survival. METHODS: In this prospective clinical study, demographic, operative, echocardiographic, and clinical outcome data were collected on 182 patients undergoing aortic valve replacement, mitral valve repair or replacement, coronary artery bypass graft, and combined cardiac surgery. Three-dimensional transthoracic echocardiograms were performed preoperatively and on the second to fourth postoperative day. Blinded analysis was performed for LV regional longitudinal, circumferential, radial, and area strain in the 17-segment model. RESULTS: Regional 3D longitudinal, circumferential, radial, and area strains were associated with differential patterns of myocardial dysfunction, depending on the surgical procedure performed and strain measure. Patients undergoing mitral valve repair or replacement had reduced function in the majority of myocardial segments, followed by coronary artery bypass graft, while patients undergoing aortic valve replacement had reduced function localized only to apical segments. After all types of cardiac surgery, segmental function in apical segments was reduced to a greater extent as compared to basal segments. Greater decrements in regional function were seen in circumferential and area strain, while smaller decrements were observed in longitudinal strain in all surgical patients. Both preoperative regional strain and change in regional strain preoperatively to postoperatively were correlated with reduced 1-year event-free survival, while postoperative strain was not predictive of outcomes. Only preoperative strain values were predictive of intensive care unit length of stay. CONCLUSIONS: Changes in regional myocardial function, measured by 3D strain, varied by surgical procedure and strain type. Differences in regional LV function, from presurgery to postsurgery, were associated with worsened 1-year event-free survival. These findings suggest that postoperative changes in myocardial function are heterogeneous in nature, depending on the surgical procedure, and that these changes may have long-term impacts on outcome. Therefore, 3D regional strain may be used to identify patients at risk for worsened postoperative outcomes, allowing early interventions to mitigate risk.

Preoperative Three-Dimensional Strain Imaging Identifies Reduction in Left Ventricular Function and Predicts Outcomes After Cardiac Surgery.

BACKGROUND: Echocardiography-based speckle-tracking strain imaging is an emerging modality to assess left ventricular function. The aim of this study was to investigate the change in left ventricular systolic function after cardiac surgery with 3-dimensional (3D) speckle-tracking strain imaging and to determine whether preoperative 3D strain is an independent predictor of acute and long-term clinical outcomes after aortic valve, mitral valve, and coronary artery bypass grafting operations. METHODS: In total, 163 adult patients undergoing aortic valve, mitral valve, and coronary artery bypass surgeries were enrolled prospectively and had complete data sets. Demographic, operative, and outcome data were collected. 3D transthoracic echocardiograms were preformed preoperatively and on second to fourth postoperative day. Blinded off-line analysis was performed for left ventricular 2-dimensional (2D) ejection fraction (EF2D) and 3D ejection fraction (EF3D) and global peak systolic area, longitudinal, circumferential, and radial strain. RESULTS: 3D global strain correlated well with EF3D. Ventricular function as measured by strain imaging decreased significantly after all types of cardiac surgery. When preoperative EF3D was used, receiver operating characteristic curves identified reference values for 3D global strain corresponding to normal, mildly reduced, and severely reduced ventricular function. Normal ventricular function (EF3D ≥ 50%) corresponded to 3D global area strain -25%, with area under curve = 0.86 (0.81-0.89). Patients with reduced preoperative 3D global area strain had worse postoperative outcomes, including length of intensive care unit stay (4 vs 3 days, P = .001), major adverse events (27% vs 11%, P = .03), and decreased 1-year event-free survival (69% vs 88%, P = .005). After we controlled for baseline preoperative risk models including European System for Cardiac Operative Risk Evaluation score and surgery type, preoperative strain was an independent predictor of both short- and long-term outcomes, including length of intensive care unit stay, postoperative inotrope score, and 1-year event-free survival. CONCLUSIONS: This study shows that cardiac surgery was associated with an acute reduction in postoperative left ventricular function, when evaluated with 3D strain imaging. In addition, preoperative 3D strain was demonstrated to be an independent predictor of acute and long-term clinical outcomes after cardiac surgery. The use of noninvasive 3D transthoracic echocardiogram strain imaging before cardiac surgery may provide added information to aid in perioperative risk stratification and management for these high-risk patients.

Left ventricular endocardial and epicardial strain changes with apical myocardial ischemia in an open-chest porcine model.

Early detection of acute myocardial ischemia is critical to prevent permanent myocardial damage. The impact of apical ischemia on global left ventricular (LV) function can be difficult to characterize using traditional volume-based echocardiography measures. Myocardial strain imaging is a sensitive, quantitative marker of myocardial deformation that can measure ventricular function. Recent advances allow layer-specific measurement of endo- and epicardial strain, enhancing the ability to evaluate myocardial ischemia. This study investigates the effects of apical ischemia on LV function using epi- and endocardial strain. We hypothesize that myocardial strain will identify changes in regional and global myocardial function associated with focal apical ischemia as compared to ejection fraction (EF), and that longitudinal strain will be a better indicator of myocardial dysfunction compared to circumferential or radial strain. In a porcine model (n = 9), acute ischemia was induced by left anterior descending coronary artery occlusion. Echocardiograms were performed at baseline, during 15-min ischemia, and after reperfusion. Global longitudinal strain decreased with acute focal ischemia of the left ventricular apical region (baseline: -16.4% vs. ischemia: -12.2%; P = 0.010), with no change observed in global circumferential and radial strain or EF Both endocardial and epicardial longitudinal strain decreased by 68% (P < 0.001) in the ischemic and peri-ischemic zone, while circumferential and radial strain only decreased in endocardium of the ischemic zone. Longitudinal strain was more sensitive to ischemia, being able to detect changes in global LV function and thus may confer clinical diagnostic advantage in the evaluation of acute LV apical ischemia.

Augmentation of cardiac sympathetic tone by percutaneous low-level stellate ganglion stimulation in humans: a feasibility study.

Modulation of human cardiac mechanical and electrophysiologic function by direct stellate ganglion stimulation has not been performed. Our aim was to assess the effect of low-level left stellate ganglion (LSG) stimulation (SGS) on arrhythmias, hemodynamic, and cardiac electrophysiological indices. Patients undergoing ablation procedures for arrhythmias were recruited for SGS. A stimulating electrode was placed next to the LSG under fluoroscopy and ultrasound imaging; and SGS (5-10 Hz, 10-20 mA) was performed. We measured hemodynamic, intracardiac and ECG parameters, and activation recovery intervals (ARIs) (surrogate for action potential duration) from a duodecapolar catheter in the right ventricular outflow tract. Five patients underwent SGS (3 males, 45 ± 20 years). Stimulating catheter placement was successful, and without complication in all patients. SGS did not change heart rate, but increased mean arterial blood pressure (78 ± 3 mmHg to 98 ± 5 mmHg, P < 0.001) and dP/dt max (1148 ± 244 mmHg/sec to 1645 ± 493 mmHg/sec, P = 0.03). SGS shortened mean ARI from 304 ± 23 msec to 283 ± 17 msec (P < 0.001), although one patient required parasympathetic blockade. Dispersion of repolarization (DOR) increased in four patients and decreased in one, consistent with animal models. QT interval, T-wave duration and amplitude at baseline and with SGS were 415 ± 15 msec versus 399 ± 15 msec (P < 0.001); 201 ± 12 msec versus 230 ± 28 msec; and 0.2 ± 0.09 mV versus 0.22 ± 0.08 mV, respectively. At the level of SGS performed, no increase in arrhythmias was seen. Percutaneous low-level SGS shortens ARI in the RVOT, and increases blood pressure and LV contractility. These observations demonstrate feasibility of percutaneous SGS in humans.

Increased red blood cell transfusions are associated with worsening outcomes in pediatric heart transplant patients.

BACKGROUND: Red blood cell (RBC) transfusions are associated with increased morbidity. Children receiving heart transplants constitute a unique group of patients due to their risk factors. Although previous studies in nontransplant patients have focused primarily on the effects of postoperative blood transfusions, a significant exposure to blood occurs during the intraoperative period, and a larger percentage of heart transplant patients require intraoperative blood transfusions when compared with general cardiac surgery patients. We investigated the relationship between clinical outcomes and the amount of blood transfused both during and after heart transplantation. We hypothesized that larger amounts of RBC transfusions are associated with worsening clinical outcomes in pediatric heart transplant patients. METHODS: A database comprising 108 pediatric patients undergoing heart transplantation from 2004 to 2010 was queried. Preoperative and postoperative clinical risk factors, including the amount of blood transfused intraoperatively and 48 hours postoperatively, were analyzed. The outcome measures were length of hospital stay, duration of tracheal intubation, inotrope score, and major adverse events. Bivariate and multivariate analyses were performed to control for simultaneous risk factors and determine outcomes in which the amount of blood transfused was an independent risk factor. RESULTS: Ninety-four patients with complete datasets were included in the final analysis. Eighty-eight percent received RBC transfusions, with a median transfusion amount of 38.7 mL/kg. A multivariate analysis correcting for 8 covariate risk factors, including the Index for Mortality Prediction After Cardiac Transplantation, age, weight, United Network for Organ Sharing status, warm and cold ischemia time, repeat sternotomy, and pretransplant hematocrit, showed RBC transfusions were independently associated with increased length of intensive care unit stay (means ratio = 1.34; 95% confidence interval, 1.03-1.76; P = 0.03), and increased inotrope score in the first postoperative 24 hour (mean ratio = 1.26; 95% confidence interval, 1.04-1.52; P = 0.04). Patients suffering major adverse events received significantly larger median amounts of blood RBC transfusions (P = 0.002). Transfusions >60 mL/kg were also associated with increased risk of major adverse events (accuracy 76%) including postoperative sepsis, extracorporeal membrane oxygenation, open chest, dialysis, and graft failure. CONCLUSION: The majority of pediatric patients undergoing orthotropic heart transplantation receive RBC transfusions, with the largest amount transfused in the operating room. Escalating amounts of RBC transfusions are independently associated with increased length of intensive care unit stay, inotrope scores, and major adverse events. Since heart allografts are a limited resource, improvement in the blood transfusion and conservation practices can enhance clinical outcomes in pediatric heart transplant patients.

Transthoracic echocardiography simulation is an efficient method to train anesthesiologists in basic transthoracic echocardiography skills.

BACKGROUND: The clinical utility of focused transthoracic echocardiography (TTE) is increasingly recognized in perioperative medicine. However its use is limited among anesthesiologists because of a lack of training. The most efficient training methods have not been determined. We hypothesized that simulation-based TTE training would be more effective than traditional lecture-based methods for teaching basic TTE skills to the anesthesiology residents. METHODS: In this prospective randomized study, 61 anesthesiology residents (in anesthesia clinical training years 1 to 3) were randomized to either control (n = 30) or simulation groups (n = 31) for TTE training. A standardized pretest was administered before TTE training sessions of 45 minutes each. The first training session used a lecture-based video didactic in the control group or a TTE simulator in the simulation group. Comprehension in both groups was then assessed using a written posttest and by performing a TTE examination on a volunteer subject. TTE examinations were graded on the ability to acquire the correct image, image quality, anatomy identification, and time required to attain proper imaging by 2 blinded experts. A second training session incorporating "hands-on" training with a volunteer subject was conducted in a subset of 21 residents (n = 11 control, n = 10 simulation). The simulation group included additional simulator training. After the second session, another posttest on a volunteer subject was administered. RESULTS: Pretest scores revealed similar preintervention knowledge among residents (56.0% ± 11.9% vs 59.3% ± 11.0%, P = 0.25; control versus simulator group, respectively). The simulation group scored higher on all criteria after the first training session: written posttest (57.9% ± 8.8% vs 68.2% ± 10.1%; P < 0.001), volunteer subject posttest image quality scores (0 to 25 scale) (6.4 ± 3.5 vs 12.4 ± 4.2; P = 0.003), anatomy identification scores (0 to 25 scale) (8.3 ± 6.6 vs 17.8 ± 6.6; P = 0.003), and percentage correct views (50 ± 19 vs 78 ± 21; P < 0.001). After the second session, all scores were again improved in the simulation group: volunteer subject posttest image quality scores (9.6 ± 3.3 vs 15.6 ± 2.8; P = 0.002), anatomy identification scores: (17.6 ± 3.8 vs 22.8 2.4; P = 0.003), and percentage correct views (80 ± 16 vs 96 ± 8; P = 0.007). DISCUSSION: This prospective randomized study demonstrated that anesthesiology residents trained with simulation acquired better skills in TTE image acquisition and anatomy identification on volunteer subjects. The educational benefit of simulation persisted even with introduction of hands-on instruction with volunteer subjects in both groups. The impact of these short-term educational approaches on longer-term retention and actual clinical application warrants further investigation.

NOX4-Dependent Hydrogen Peroxide Overproduction in Human Atrial Fibrillation and HL-1 Atrial Cells: Relationship to Hypertension.

BACKGROUND/OBJECTIVES: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia with patients dying frequently of stroke. In view of the unclear etiologies of AF and a potential role of oxidative stress, the present study examined cardiac reactive oxygen species production and NADPH oxidase (NOX) expression in AF patients. METHODS AND RESULTS: Patients with AF were older than those without (58.8 ± 11.7 vs. 47.8 ± 19.2, p = 0.047). Whereas total [Formula: see text] production (determined by electron spin resonance) was similar in patients with and without AF, H(2)O(2) production was more than doubled in AF patients (149.8 ± 26.28 vs. 66.9 ± 7.14 pmol/mg/min, p = 0.0055), which correlated well with a doubling in NOX isoform 4 (NOX4) expression. AF patients with co-existing hypertension had three-fold higher H(2)O(2) production compared to those without (239.0 ± 125.1 vs. 83.6 ± 51.3 pmol/mg/min, p = 0.003). Treatment of HL-1 atrial cells with angiotensin II, a known modulator of atrial structural remodeling, resulted in upregulation of NOX4 and H(2)O(2) production, further implicating a potential role of NOX4 in atrial remodeling. CONCLUSION: Our data represent the first implication that NOX4-derived H(2)O(2) may play an important role in the etiologies of AF.