A Monoclonal Human Alveolar Epithelial Cell Line ("Arlo") with Pronounced Barrier Function for Studying Drug Permeability and Viral Infections.

In the development of orally inhaled drug products preclinical animal models regularly fail to predict pharmacological as well as toxicological responses in humans. Models based on human cells and tissues are potential alternatives to animal experimentation allowing for the isolation of essential processes of human biology and making them accessible in vitro. Here, the generation of a novel monoclonal cell line "Arlo," derived from the polyclonal human alveolar epithelium lentivirus immortalized cell line hAELVi via single-cell printing, and its characterization as a model for the human alveolar epithelium as well as a building block for future complex in vitro models is described. "Arlo" is systematically compared in vitro to primary human alveolar epithelial cells (hAEpCs) as well as to the polyclonal hAELVi cell line. "Arlo" cells show enhanced barrier properties with high transepithelial electrical resistance (TEER) of ≈3000 Ω cm2 and a potential difference (PD) of ≈30 mV under air-liquid interface (ALI) conditions, that can be modulated. The cells grow in a polarized monolayer and express genes relevant to barrier integrity as well as homeostasis as is observed in hAEpCs. Successful productive infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a proof-of-principle study offers an additional, attractive application of "Arlo" beyond biopharmaceutical experimentation.

Partial Anomalous Pulmonary Venous Return Diagnosed by Central Catheter Misplacement.

Anomalous venous connections of the left lung can either affect all of the veins or only the upper lobe. They mostly drain into the innominate vein. We present the case of a patient who underwent a coronary bypass operation and was prepared with insertion of central lines including Swan-Ganz catheter through both the internal jugular veins. Blood gas analysis obtained from these catheters suggested the presence of a left-to-right shunt. CT (computed tomography) imaging confirmed a pulmonary venous anomaly with misplacement of the left-sided catheter in an abnormal pulmonary vein. Such a rare condition can be suspected by obtaining arterialized blood samples and measuring the mean pressure through central catheters.

Bronchial Fistula and Pneumomediastinum after EBUS-TBNA Following Mediastinoscopy.

Background Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a very useful diagnostic tool for the assessment of enlarged mediastinal and hilar lymph nodes. It is a safe procedure with a low risk of complications. Case Description We report a case of bronchial fistula and pneumomediastinum after EBUS-TBNA, which was performed shortly after a mediastinoscopy. Due to the extent of the bronchial lesion, a surgical closure of the bronchial fistula was necessary. The patient recovered completely. Conclusion The performance of EBUS-TBNA shortly after a mediastinoscopy should not be recommended to avoid possible procedure-related complications.

Safety of Simultaneous Coronary Artery Bypass Grafting and Carotid Endarterectomy Versus Isolated Coronary Artery Bypass Grafting: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: The optimal operative strategy in patients with severe carotid artery disease undergoing coronary artery bypass grafting (CABG) is unknown. We sought to investigate the safety and efficacy of synchronous combined carotid endarterectomy and CABG as compared with isolated CABG. METHODS: Patients with asymptomatic high-grade carotid artery stenosis ≥80% according to ECST (European Carotid Surgery Trial) ultrasound criteria (corresponding to ≥70% NASCET [North American Symptomatic Carotid Endarterectomy Trial]) who required CABG surgery were randomly assigned to synchronous carotid endarterectomy+CABG or isolated CABG. To avoid unbalanced prognostic factor distributions, randomization was stratified by center, age, sex, and modified Rankin Scale. The primary composite end point was the rate of stroke or death at 30 days. RESULTS: From 2010 to 2014, a total of 129 patients were enrolled at 17 centers in Germany and the Czech Republic. Because of withdrawal of funding after insufficient recruitment, enrolment was terminated early. At 30 days, the rate of any stroke or death in the intention-to-treat population was 12/65 (18.5%) in patients receiving synchronous carotid endarterectomy+CABG as compared with 6/62 (9.7%) in patients receiving isolated CABG (absolute risk reduction, 8.8%; 95% confidence interval, -3.2% to 20.8%; PWALD=0.12). Also for all secondary end points at 30 days and 1 year, there was no evidence for a significant treatment-group effect although patients undergoing isolated CABG tended to have better outcomes. CONCLUSIONS: Although our results cannot rule out a treatment-group effect because of lack of power, a superiority of the synchronous combined carotid endarterectomy+CABG approach seems unlikely. Five-year follow-up of patients is still ongoing. CLINICAL TRIAL REGISTRATION: URL: https://www.controlled-trials.com. Unique identifier: ISRCTN13486906.

Impact of frailty on short- and long-term morbidity and mortality after transcatheter aortic valve implantation: risk assessment by Katz Index of activities of daily living.

AIMS: Transcatheter aortic valve implantation (TAVI) represents a less invasive treatment option for elderly patients. Therefore, we aimed to determine the impact of frailty measured by the Katz Index of activities of daily living (ADL) on short- and long-term mortality after TAVI. METHODS AND RESULTS: Our study included 300 consecutive patients (mean age, 82±5 years) who had undergone TAVI at our institution (158 transapical, 142 transfemoral procedures). At baseline, 144 patients were impaired in at least one ADL and therefore defined as frail (Katz Index <6). Regarding in-hospital outcome, all serious complications except for stage 3 acute kidney injury were equally distributed in both groups, but early mortality was significantly higher in frail persons (5.5% vs. 1.3%, p=0.04 for immediate procedural mortality; 17% vs. 5.8%, p=0.002 for 30-day mortality; and 23% vs. 6.4%, p<0.0001 for procedural mortality). The risk-score-based 30-day mortality estimates (29% vs. 24% for log. EuroSCORE I, 9.5% vs. 7.5% for EuroSCORE II, and 8.8% vs. 5.9% for STS score) reflected neither the observed 30-day mortality in both groups nor the threefold risk elevation in frail patients. In contrast, the Katz Index <6 was identified as a significant independent predictor of long-term all-cause mortality by multivariate analysis (HR 2.67 [95% CI: 1.7-4.3], p<0.0001). During follow-up (median observation period 537 days) 56% of frail vs. 24% of non-frail patients died. CONCLUSIONS: Frailty status measured by the Katz Index represents a powerful predictor of adverse early and late outcome after TAVI, whereas commonly used risk scores lack calibration and discrimination in a TAVI-specific patient cohort. Therefore, we propose the incorporation of this simple and reproducible measure into pre-TAVI risk assessment.

Failure of acute procedural success predicts adverse outcome after percutaneous edge-to-edge mitral valve repair with MitraClip.

AIMS: MitraClip implantation is evolving as a potential alternative treatment to conventional surgery in high-risk patients with significant mitral regurgitation (MR). However, outcome predictors are under-investigated. The aim of this study was to identify predictors of midterm mortality and heart failure rehospitalisation after percutaneous mitral valve repair with MitraClip. METHODS AND RESULTS: A total of 150 consecutive patients were followed for a median of 463 days. Survival analyses were performed for baseline characteristics, risk scores and failure of acute procedural success (APS) defined as persisting MR grade 3+ or 4+. Univariate significant risk stratifiers were tested in multivariate analyses using a Cox proportional hazards model. Overall survival was 96% at 30 days, 79.5% at 12 months, and 62% at two years. Multivariate analysis identified APS failure (HR 2.13, p=0.02), NYHA Class IV at baseline (HR 2.11, p=0.01) and STS score ≥12 (HR 2.20, p<0.0001) as significant independent predictors of all-cause mortality, and APS failure (HR 2.31, p=0.01) and NYHA Class IV at baseline (HR 1.89, p=0.03) as significant independent predictors of heart failure rehospitalisation. Furthermore, a post-procedural significant decrease in hospitalisation rate could only be observed after successful interventions (0.89±1.07 per year before vs. 0.54±0.96 after implantation, p=0.01). Patients with severely dilated and overloaded ventricles who did not meet EVEREST II eligibility criteria were at higher risk of APS failure. CONCLUSIONS: The failure of acute procedural success proved to have the most important impact on outcome after MitraClip implantation.

Complete interventional heart repair of multiple concomitant cardiac pathologies in a staged approach.

OBJECTIVES AND BACKGROUND: The evidence of multiple percutaneous cardiac procedures in patients with numerous concomitant cardiac pathologies is limited. METHODS AND RESULTS: We report on the case of a 90-year-old male patient presenting with advanced heart failure because of degenerative aortic valve stenosis and degenerative mitral valve regurgitation. Moreover, significant coronary artery disease and intolerance of anticoagulation in atrial fibrillation were present. The patient was rejected from surgery because of age and frailty and underwent a staged interventional procedure with percutaneous coronary intervention, followed by transfemoral aortic valve implantation with Edwards Sapien XT, percutaneous mitral valve repair with MitraClip, and left atrial appendage closure with Amplatzer Cardiac Plug. The last procedure was complicated by pericardial tamponade necessitating pericardial drainage. Eight weeks later, the patient reported on the absence of dyspnea in activities of daily living and a significant gain in quality of live. CONCLUSIONS: The case demonstrates feasibility of a staged interventional approach in a select high-risk patient.

Prosthetic valve endocarditis after transcatheter aortic valve implantation: the incidence in a single-centre cohort and reflections on clinical, echocardiographic and prognostic features.

AIMS: Transcatheter aortic valve implantation (TAVI) has recently developed into an accepted alternative to conventional surgery in high-risk patients. According to current data, post-TAVI prosthetic valve endocarditis (PVE) seems to occur very rarely. METHODS AND RESULTS: We followed the first 180 consecutive patients who underwent TAVI at our institution to assess safety and efficacy of the procedure. During follow-up (median, 319 days), PVE was seen more frequently than expected. By applying modified Duke criteria five cases could be confirmed (four early-onset and one late-onset PVE, four cases with "definite diagnosis" and one with "possible diagnosis") representing an estimated PVE incidence of 3.4% at one year. Two patients died subsequently. Clinical summaries of all cases are reported and compared to previously published case reports. CONCLUSIONS: According to our hypothesis, PVE might be particularly difficult to diagnose after TAVI, whereas TAVI-specific elderly patients might be exceptionally vulnerable. There exists little experience of TEE interpretation in post-TAVI endocarditis which should possess unique characteristics regarding, e.g., valve dehiscence or abscess formation. Therefore, echocardiography as a diagnostic tool often remains initially inconclusive. Because of incongruence between prosthetic device and calcified native aortic valve, some degree of paravalvular leak is common after TAVI. These paravalvular leaks as a nidus for infection, advanced age and abundant comorbidities might predispose TAVI patients for infective endocarditis.

The risk-to-benefit ratio of transcatheter aortic valve implantation in specific patient cohorts: a single-centre experience.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has recently developed into an acceptable alternative to conventional surgery in high-risk patients. However, information on the identification of patients gaining most benefit from this procedure is still limited. The aim of this study was to evaluate safety and efficacy of TAVI in different patient cohorts. METHODS: Between August 2008 and December 2010, 180 high-risk patients underwent TAVI at our institution (97 transapical and 83 transfemoral approaches). Periprocedural complications as well as mortality and incidence of MACCE during follow-up were recorded. RESULTS: Mean age was 82 ± 5 years, and mean logistic EuroScore 27 ± 14%. In the total cohort, 30-day mortality was 8.9% and 12-month survival (according to Kaplan-Meier-analysis) 72%, with no significant differences between the two approaches. However, a significant difference in survival was obvious after stratification of patients according to logistic EuroScore mortality estimates. Survival proportions at 1 year were 62% in patients with logistic EuroScore >40%, 71% in patients with EuroScore 20-40% and 80% in octogenarians with EuroScore <20% (P = 0.009). Furthermore, the observed median event-free survival as an indicator for morbidity ranged between 315 days in the first, 442 days in the second and 710 days in the third group (P = 0.1). CONCLUSIONS: TAVI proved to be feasible with reproducible results. However, mortality and rehospitalization rates were considerably high in specific patient cohorts, suggesting that the risk-to-benefit ratio of TAVI should be validated individually. In the present study, octogenarians with logistic EuroScore <20% could be identified as candidates apparently gaining high benefit from the procedure.

Heart team approach for transcatheter aortic valve implantation procedures complicated by coronary artery occlusion.

We report on three out of 270 consecutive patients (1.1%) suffering from coronary artery obstruction or occlusion at the end of transcatheter aortic valve implantation (TAVI). The partial or total obstruction of the coronary artery seen in the post-implantation aortography was accompanied by haemodynamic instability and electrocardiographic changes typical for myocardial ischaemia. Immediate percutaneous coronary intervention with stent implantation was successful in two cases, while in the third case it was not possible to cross the occluded right coronary artery. Emergency coronary artery bypass grafting was performed resulting in uneventful myocardial recovery. All patients were discharged home. These cases highlight the awareness of this rare, life-threatening complication of TAVI, which is in need of a dedicated heart team involved not only in decision-making, but also in the procedure itself.

Impact of the learning curve on outcomes after percutaneous mitral valve repair with MitraClip and lessons learned after the first 75 consecutive patients.

AIMS: Mitral valve regurgitation plays a significant role in the aetiology and course of heart failure. We investigated the impact of the learning curve on outcomes after percutaneous mitral valve repair with MitraClip. METHODS AND RESULTS: Outcomes of the first 75 consecutive patients treated with MitraClip at our centre were stratified by subsequent treatment periods (25 patients each). Median total procedure time and device time decreased from 180 and 105 min in period 1 to 95 and 55 min in period 3 (P < 0.005 each). There was an excess of total safety events in period 1 (n = 16) that decreased in periods 2 and 3 (n = 6 and 3, P = 0.0003). Acute procedural success [APS; clip successfully placed and mitral regurgitation (MR) grade ≤2+ at discharge] was 80% in periods 1 and 2, but 92% in period 3 (P = 0.46). At 6 months, improvement in durability and completeness of mitral valve repair was evident: 89.4% of patients in period 3 and 65.0% in period 1 had MR ≤2+ at 6 months (P = 0.03). Within 30 days, no patient sustained myocardial infarction or stroke, and mortality was 2.7% for all patients without significant differences regarding periods. Furthermore, while treatment period did not affect mid-term survival and hospitalization for heart failure, failure of APS, STS (Society of Thoracic Surgeons) score ≥15%, and overt right heart failure at baseline predicted increased mortality. CONCLUSION: MitraClip showed a learning curve regarding mid-term durability and completeness of mitral valve repair, and APS predicted mortality. Recently published studies should be interpreted in consideration of these findings.

Intensified thermal management for patients undergoing transcatheter aortic valve implantation (TAVI).

BACKGROUND: Transcatheter aortic valve implantation via the transapical approach (TAVI-TA) without cardiopulmonary bypass (CPB) is a minimally invasive alternative to open-heart valve replacement. Despite minimal exposure and extensive draping perioperative hypothermia still remains a problem. METHODS: In this observational study, we compared the effects of two methods of thermal management on the perioperative course of core temperature. The methods were standard thermal management (STM) with a circulating hot water blanket under the patient, forced-air warming with a lower body blanket and warmed infused fluids, and an intensified thermal management (ITM) with additional prewarming using forced-air in the pre-operative holding area on the awake patient. RESULTS: Nineteen patients received STM and 20 were treated with ITM. On ICU admission, ITM-patients had a higher core temperature (36.4±0.7°C vs. 35.5±0.9°C, p=0.001), required less time to achieve normothermia (median (IQR) in min: 0 (0-15) vs. 150 (0-300), p=0.003) and a shorter period of ventilatory support (median (IQR) in min: 0 (0-0) vs. 246 (0-451), p=0.001). CONCLUSION: ITM during TAVI-TA reduces the incidence of hypothermia and allows for faster recovery with less need of ventilatory support.

Comparison of chromosomal aberrations in primary colorectal carcinomas to their pulmonary metastases.

Pulmonary metastases (PM) are frequent in colorectal carcinoma (CRC). However, little is known about the chromosomal imbalances in CRC that accompany metastatic pulmonary disease. We investigated tumor specimens of CRC (n=30) and their corresponding PM by comparative genomic hybridization (CGH). There were no substantial differences in the degree of chromosomal instability between CRC and PM, neither in average number of copy alterations (ANCA; 6.6 ± 0.8 and 7.7 ± 0.9) nor in gains (2.6 ± 0.5 and 2.6 ± 0.4), losses (3.6 ± 0.5 and 4.8 ± 0.6), or amplifications (0.4 ± 0.1 and 0.3 ± 0.1). Basically, similar patterns of chromosomal imbalances could be identified in both CRC and corresponding PM, most frequently including chromosomal gains at 7, 8q, 13q, and 20q, as well as losses at 4, 8p, 18q, and 20p. CRC and corresponding PM differed in frequencies for losses at chromosome arm 5q (3 vs. 26%; P=0.012). Losses at 4q and 11q in CRC were significantly associated with lower 5-year survival rates (80 vs. 24%, P=0.026 and 74 vs. 17%, P=0.007, respectively), and they may represent candidates for adverse prognostic markers in primary CRC.

Indications for reoperation late after correction of tetralogy of Fallot.

OBJECTIVE: Correction of tetralogy of Fallot has excellent long-term results. The present retrospective study investigates the indications for reoperation late after corrective surgery. METHODS: Data from 914 consecutive cases who underwent correction of tetralogy of Fallot in our department between 1960 and 2002 were retrospectively reviewed and analysed. In 91 patients, a total of 102 reoperations were performed late after repair. RESULTS: The mean time interval between corrective surgery and the first reoperation was 12.8 years. The main indication for reoperation was residual ventricular septal defect in nearly half of the cases, mostly isolated, but also in combination with a right ventricular outflow tract aneurysm or pulmonary stenosis. One-fourth of reoperated patients underwent a procedure on their pulmonary artery or pulmonary valve: replacement of pulmonary valve, replacement of primary implanted pulmonary artery conduits with or without concomitant surgery, and surgery for isolated peripheral pulmonary stenosis. The remaining indications were right ventricular outflow tract aneurysms and others. Aneurysms of the right ventricular outflow tract were seen mostly after the use of autologous - untreated - pericardial patch in 18 of 21 cases. CONCLUSION: The number of reoperations for residual ventricular septal defect decreased during the study period. The primary use of conduits led to an increased number of reoperations for conduit exchange due to degeneration or failure. Use of an untreated autologous pericardial patch for enlargement of the right ventricular outflow tract should be avoided due to increased risk for aneurysm formation.

Altered Na(+) currents in atrial fibrillation effects of ranolazine on arrhythmias and contractility in human atrial myocardium.

OBJECTIVES: We investigated changes in Na(+) currents (I(Na)) in permanent (or chronic) atrial fibrillation (AF) and the effects of I(Na) inhibition using ranolazine (Ran) on arrhythmias and contractility in human atrial myocardium. BACKGROUND: Electrical remodeling during AF is typically associated with alterations in Ca(2+) and K(+) currents. It remains unclear whether I(Na) is also altered. METHODS: Right atrial appendages from patients with AF (n = 23) and in sinus rhythm (SR) (n = 79) were studied. RESULTS: Patch-clamp experiments in isolated atrial myocytes showed significantly reduced peak I(Na) density ( approximately 16%) in AF compared with SR, which was accompanied by a 26% lower expression of Nav1.5 (p < 0.05). In contrast, late I(Na) was significantly increased in myocytes from AF atria by approximately 26%. Ran (10 mumol/l) decreased late I(Na) by approximately 60% (p < 0.05) in myocytes from patients with AF but only by approximately 18% (p < 0.05) in myocytes from SR atria. Proarrhythmic activity was elicited in atrial trabeculae exposed to high [Ca(2+)](o) or isoprenaline, which was significantly reversed by Ran (by 83% and 100%, respectively). Increasing pacing rates from 0.5 to 3.0 Hz led to an increase in diastolic tension that could be significantly decreased by Ran in atria from SR and AF patients. CONCLUSIONS: Na(+) channels may contribute to arrhythmias and contractile remodeling in AF. Inhibition of I(Na) with Ran had antiarrhythmic effects and improved diastolic function. Thus, inhibition of late I(Na) may be a promising new treatment option for patients with atrial rhythm disturbances and diastolic dysfunction.

CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation.

RATIONALE: Although research suggests that diastolic Ca(2+) levels might be increased in atrial fibrillation (AF), this hypothesis has never been tested. Diastolic Ca(2+) leak from the sarcoplasmic reticulum (SR) might increase diastolic Ca(2+) levels and play a role in triggering or maintaining AF by transient inward currents through Na(+)/Ca(2+) exchange. In ventricular myocardium, ryanodine receptor type 2 (RyR2) phosphorylation by Ca(2+)/calmodulin-dependent protein kinase (CaMK)II is emerging as an important mechanism for SR Ca(2+) leak. OBJECTIVE: We tested the hypothesis that CaMKII-dependent diastolic SR Ca(2+) leak and elevated diastolic Ca(2+) levels occurs in atrial myocardium of patients with AF. METHODS AND RESULTS: We used isolated human right atrial myocytes from patients with AF versus sinus rhythm and found CaMKII expression to be increased by 40+/-14% (P<0.05), as well as CaMKII phosphorylation by 33+/-12% (P<0.05). This was accompanied by a significantly increased RyR2 phosphorylation at the CaMKII site (Ser2814) by 110+/-53%. Furthermore, cytosolic Ca(2+) levels were elevated during diastole (229+/-20 versus 164+/-8 nmol/L, P<0.05). Most likely, this resulted from an increased SR Ca(2+) leak in AF (P<0.05), which was not attributable to higher SR Ca(2+) load. Tetracaine experiments confirmed that SR Ca(2+) leak through RyR2 leads to the elevated diastolic Ca(2+) level. CaMKII inhibition normalized SR Ca(2+) leak and cytosolic Ca(2+) levels without changes in L-type Ca(2+) current. CONCLUSION: Increased CaMKII-dependent phosphorylation of RyR2 leads to increased SR Ca(2+) leak in human AF, causing elevated cytosolic Ca(2+) levels, thereby providing a potential arrhythmogenic substrate that could trigger or maintain AF.

A three-group model to predict mortality in emergent coronary artery bypass graft surgery.

BACKGROUND: Emergent coronary artery bypass graft surgery (CABG) for acute myocardial infarction is associated with an increased operative risk. For estimation of mortality risk, the European System for Cardiac Operative Risk Evaluation (EuroSCORE) is appropriate up to a medium risk score (<6 points). To predict mortality risk more accurately in cases of higher EuroSCORE, additional cardiac data can be helpful. METHODS: Over a 3-year period, patient data including acute myocardial infarction and emergent CABG were retrospectively reviewed. Univariate and multivariate analysis for in-hospital mortality was performed. The EuroSCORE analysis and follow-up was investigated. RESULTS: Overall in-hospital mortality was 18.3%. Preoperative cardiac related predictors for in-hospital mortality were cardiogenic shock (p < 0.001), very poor left ventricular function (p = 0.001), and ST-segment elevation (p = 0.012). In multivariate regression analysis, age, cardiogenic shock, and pulmonary hypertension were independent preoperative risk factors. According to the EuroSCORE, we could define three statistically different groups: intermediate-risk, high-risk, and very high risk, with an observed mortality of 3.3%, 20.0%, and 63.2%, respectively. The EuroSCORE correlates with but overestimates the mortality risk. In subgroup analysis, the creatine kinase-myocardial band/hour ratio for the intermediate-risk group and ST-segment elevation for the high-risk group were additional cardiac risk factors. CONCLUSIONS: Patients with an acute myocardial infarction and emergency aortocoronary CABG have an elevated operative risk. Logistic EuroSCORE overestimates the mortality rate. Three different risk groups can be defined, in which creatine kinase-MB/h-ratio and ST-segment elevation can more accurately predict operative risk.

Myocardial ischemia with left ventricular outflow obstruction.

We report an unusual case of a 32-year old man who was treated for a hypertrophic obstructive cardiomyopathy (HOCM) with a DDD pacing with short AV delay reduction in the past. Without prior notice the patient developed ventricular fibrillation and an invasive cardiac diagnostic was performed, which revealed a myocardial bridging around of the left anterior descending artery (LAD). We suspected ischemia that could be either related to LAD artery compression or perfusion abnormalities due to AV delay reduction with related to diastolic dysfunction.

The eNOS 786C/T polymorphism in cardiac surgical patients with cardiopulmonary bypass is associated with renal dysfunction.

OBJECTIVE: Renal dysfunction is one of the most serious complications following cardiac surgery with cardiopulmonary bypass. The causes of renal dysfunction following cardiac surgery are poorly understood. We hypothesised that T-786C endothelial NO synthase (eNOS) polymorphism may lead to an increase in the occurrence of postoperative renal dysfunction following cardiac surgery with cardiopulmonary bypass. METHODS: A total of 497 patients undergoing cardiac surgery with cardiopulmonary bypass were included in the study. The T-786C eNOS polymorphism was detected by a polymerase chain reaction. The patients were grouped on the basis of whether they were homozygous or heterozygous for the C allele (TC+CC; n=289) or only homozygous for the T allele (TT; n=208). RESULTS: No significance was demonstrated in the preoperative risk factors, with the exclusion of smoking habits (p=0.04) for the C-allele carrier. The administration of anti-lipid agents (p=0.01) and anti-arrhythmics (p=0.01) was significantly lower in the TC/CC group. The TC+CC genotype group had a significantly greater decrease in creatine clearance (p=0.024), the lowest creatine clearance (p=0.004) and more C-allele carriers received acute renal replacement therapy (p=0.04). The usage of norepinephrine (p=0.02) and dobutamine (p=0.02) was significantly higher in C-allele carriers. In the TC+CC genotype group, cross-clamp time (p=0.02) and administration of red cell transfusion (p=0.04) achieved statistically significant difference. The overall in-hospital mortality rate was 8.2% for all patients and was not significant between genotypes. CONCLUSIONS: The present findings support the hypothesis that the T-786C eNOS polymorphism may play a role in the development of renal dysfunction and increase the occurrence of renal replacement therapy following cardiac surgery with cardiopulmonary bypass. This polymorphism may be useful in stratifying the risk for the development of postoperative renal dysfunction.