Henrik Bjursten

Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study

Abstract Aims Excessive bleeding impairs outcome after coronary artery bypass grafting (CABG). Current guidelines recommend withdrawal of clopidogrel and ticagrelor 5 days (120 h) before elective surgery. Shorter discontinuation would reduce the risk of thrombotic events and save hospital resources, but may increase the risk of bleeding. We investigated whether a shorter discontinuation time before surgery increased the incidence of CABG-related major bleeding complications and compared ticagrelor- and clopidogrel-treated patients. Methods and results All acute coronary syndrome patients in Sweden on dual antiplatelet therapy with aspirin and ticagrelor (n = 1266) or clopidogrel (n = 978) who underwent CABG during 2012–13 were included in a retrospective observational study. The incidence of major bleeding complications according to the Bleeding Academic Research Consortium-CABG definition was 38 and 31%, respectively, when ticagrelor/clopidogrel was discontinued <24 h before surgery. Within the ticagrelor group, there was no significant difference between discontinuation 72–120 or >120 h before surgery [odds ratio (OR) 0.93 (95% confidence interval, CI, 0.53–1.64), P = 0.80]. In contrast, clopidogrel-treated patients had a higher incidence when discontinued 72–120 vs. >120 h before surgery (OR 1.71 (95% CI 1.04–2.79), P = 0.033). The overall incidence of major bleeding complications was lower with ticagrelor [12.9 vs. 17.6%, adjusted OR 0.72 (95% CI 0.56–0.92), P = 0.012]. Conclusion The incidence of CABG-related major bleeding was high when ticagrelor/clopidogrel was discontinued <24 h before surgery. Discontinuation 3 days before surgery, as opposed to 5 days, did not increase the incidence of major bleeding complications with ticagrelor, but increased the risk with clopidogrel. The overall risk of major CABG-related bleeding complications was lower with ticagrelor than with clopidogrel.

Incidence, dynamics, and prognostic value of acute kidney injury for death after cardiac surgery.

OBJECTIVE This study relates long-term mortality after cardiac surgery to different methods of measuring postoperative renal function, classified according to the Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. The dynamics of acute kidney injury during hospital stay were studied by comparing renal function preoperatively, at its poorest measurement, and at discharge. METHODS A total of 5746 patients undergoing coronary artery bypass grafting were studied in a Cox analysis, over a median follow-up time of 6.0 years (range, 2.5-9.5 years). Renal function was determined using the highest and discharge levels of plasma creatinine by Cockroft-Gault and Modification of Diet in Renal Disease formulae. Acute kidney injury was classified according to the RIFLE criteria. Renal recovery was studied in a 2-dimensional matrix, and the impact of renal function at different time points was related to survival. RESULTS Although the p-creatinine classified most patients in the nonacute kidney injury and Risk class; the Cockroft-Gault and Modification of Diet in Renal Disease formulae classified more patients in Injury and Failure classes; and higher Risk, Injury, and Failure classes were associated with increased long-term mortality. The effect of renal recovery on long-term survival was only in part associated with improved outcome. In addition, the poorest renal function was a stronger predictor of mortality compared with preoperative and discharge levels. CONCLUSIONS Classification using RIFLE criteria seems to be useful because it detects patients with renal impairment that affects long-term survival. The Modification of Diet in Renal Disease method seems to be the most robust method when predicting outcome, and the poorest renal function was the best predictor of outcome. Renal recovery was generally associated with better outcome.

S100B Profiles and Cognitive Function at High Altitude

Exposure to high altitude can lead to acute mountain sickness (AMS) and high altitude cerebral edema (HACE). In this study we investigated the effect of high altitude on neurocognitive function and S100B release. Increased S100B release has been hypothesized to signify a loss of integrity in the blood-brain barrier (BBB). Seven healthy volunteers trekked to Capanna Regina Margherita (4554 m above sea level) in the Monte Rosa massif. During ascent and descent, five test events were undertaken; participants underwent neurocognitive testing, Lake Louise scoring (LLS), and blood sampling to measure levels of S100B. The blood tests revealed that S100B levels increased 42% to 122% from baseline, and mean LLS increased from 0.57 to 2.57. A significant correlation was observed between both S100B levels and LLS and S100B and some neurocognitive scores. The study indicates that S100B can be released by a mild hypoxia during AMS. Moreover, an observed correlation between S100B and a lower score on neurocognitive tests suggests that the pathogenetic mechanisms may be linked. The study indicates that a decline in cognitive function is associated with symptoms of AMS.

Erythropoietin and protection of renal function in cardiac surgery (the EPRICS Trial).

Background:To date, there are no known methods for preventing acute kidney injury after cardiac surgery. Increasing evidence suggests that erythropoietin has renal antiapoptotic and tissue protective effects. However, recent human studies have shown conflicting results. The authors aimed to study the effect of a single high-dose erythropoietin preoperatively on renal function after coronary artery bypass grafting in patients with preoperative impaired renal function. Methods:This single-center, randomized, double-blind, placebo-controlled study included 75 patients scheduled for coronary artery bypass grafting with preexisting renal impairment estimated glomerular filtration rate based on p-cystatin C (<60 and >15 ml/min). The patients either received a single high-dose erythropoietin (400 IU/kg) or placebo preoperatively. The primary endpoint was renal protection evaluated by p-cystatin C at the third postoperative day compared to the preoperative values. Incidence of acute kidney injury and other renal biomarker changes were among secondary endpoints. Results:There was no statistically significant difference on the third postoperative day for relative p-cystatin C level changes from baseline between the groups, 131 ± 31% (mean ± SD) for the study group and 125 ± 24% for the control group (P = 0.31; 95% CI, −0.6 to 20% for the difference). There were no statistically significant differences in other renal biomarkers or measures between the groups (p-neutrophil gelatinase–associated lipocalin, p-creatinine, p-urea, and estimated glomerular filtration rate). There were no other differences in outcome variables between the groups. Conclusion:Intravenous administration of a single high-dose (400 IU/kg) erythropoietin did not have a renal protective effect on patients with reduced kidney function undergoing coronary artery bypass surgery.

Blood transfusion after cardiac surgery: is it the patient or the transfusion that carries the risk?

Background: The transfusion of red blood cells (RBCs) after cardiac surgery has been associated with increased long‐term mortality. This study reexamines this hypothesis by including pre‐operative hemoglobin (Hb) levels and renal function in the analysis.

Efficacy and safety of the Lotus Valve System for treatment of patients with severe aortic valve stenosis and intermediate surgical risk: Results from the Nordic Lotus-TAVR registry

BACKGROUND Transcatheter aortic valve replacement (TAVR) has become an established therapeutic option for patients with symptomatic, severe aortic valve stenosis (AS) who are ineligible or at high risk for conventional valvular surgery. In Northwestern Europe, the TAVR technology is also increasingly used to treat patients with an intermediate risk profile. METHODS AND RESULTS The study was designed as an independent Nordic multicenter registry of intermediate risk patients treated with the Lotus Valve System (Boston Scientific, MA, USA; N=154). Valve Academic Research Consortium (VARC)-defined device success was obtained in 97.4%. A Lotus Valve was successfully implanted in all patients. There was no valve migration, embolization, ectopic valve deployment, or TAV-in-TAV deployment. The VARC-defined combined safety rate at 30days was 92.2%, with a mortality rate of 1.9% and stroke rate of 3.2%. The clinical efficacy rate after 30days was 91.6% - only one patient had moderate aortic regurgitation. When considering only those patients in the late experience group (N=79), the combined safety and clinical efficacy rates were 93.7% and 92.4%, respectively. The pacemaker implantation rate was 27.9% - this rate was 12.8% in case of a combined implantation depth <4mm and a device/annulus ratio<1.05. CONCLUSIONS The present study demonstrates the efficacy and safety of the repositionable, retrievable Lotus Valve System in intermediate risk patients with AS. The VARC-defined device success rate was 97.4% with a 30-day patient safety and clinical efficacy rate of more than 90%. Less than moderate aortic regurgitation was obtained in 99.4% of patients.

Evaluation of cystatin C with iohexol clearance in cardiac surgery.

Background: Post‐operative renal dysfunction after cardiac surgery is not uncommon and can lead to adverse outcome. The ability to accurately monitor renal function is therefore important. Cystatin C is known to be a sensitive marker of the glomerular filtration rate (GFR), but it has not been fully evaluated in cardiac surgery. Iohexol clearance is considered a reliable reference method for the determination of GFR. The aim of this study is to, for the first time, evaluate the diagnostic accuracy of plasma cystatin C compared with iohexol clearance in cardiac surgery.

Shrunken Pore Syndrome is associated with a sharp rise in mortality in patients undergoing elective coronary artery bypass grafting.

Abstract Shrunken Pore Syndrome was recently suggested for the pathophysiologic state in patients characterized by an estimation of their glomerular filtration rate (GFR) based upon cystatin  C, which is lower or equal to 60% of their estimated GFR based upon creatinine, i.e. when eGFRcystatin  C ≤ 60% of eGFRcreatinine. Not only the cystatin  C level, but also the levels of other low molecular mass proteins are increased in this condition. The preoperative plasma levels of cystatin  C and creatinine were measured in 1638 patients undergoing elective coronary artery bypass grafting. eGFRcystatin  C and eGFRcreatinine were calculated using two pairs of estimating equations, CAPA and LMrev, and CKD-EPIcystatin  C and CKD-EPIcreatinine, respectively. The Shrunken Pore Syndrome was present in 2.1% of the patients as defined by the CAPA and LMrev equations and in 5.7% of the patients as defined by the CKD-EPIcystatin  C and CKD-EPIcreatinine equations. The patients were studied over a median follow-up time of 3.5 years (2.0–5.0 years) and the mortality determined. Shrunken Pore Syndrome defined by both pairs of equations was a strong, independent, predictor of long-term mortality as evaluated by Cox analysis and as illustrated by Kaplan-Meier curves. Increased mortality was observed also for the subgroups of patients with GFR above or below 60 mL/min/1.73 m2. Changing the cut-off level from 60 to 70% for the CAPA and LMrev equations increased the number of patients with Shrunken Pore Syndrome to 6.5%, still displaying increased mortality.

Acute Kidney Injury Assessed by Cystatin C after Transcatheter Aortic Valve Implantation and Late Renal Dysfunction.

OBJECTIVE The aim of the present study was to evaluate acute kidney injury (AKI) with cystatin C following transcatheter aortic valve implantation (TAVI) and to assess the impact of postoperative AKI on outcome and late renal function. DESIGN A prospective study. SETTING Single, tertiary referral center. PARTICIPANTS Sixty-eight consecutive patients with severe aortic stenosis and advanced comorbidity. INTERVENTIONS Blood samples were collected on 4 occasions pre- and postoperatively to determine levels of s-creatinine and cystatin C. Additionally, a sample was collected at followup 12 months postoperatively for the determination of s-creatinine. MEASUREMENTS AND MAIN RESULTS The mean preoperative eGFR (s-creatinine) was 67±24 mL/min/1.73 m² compared to 45±21 mL/min/1.73 m² with eGFR (cystatin C) (p<0.001). Postoperative AKI was diagnosed in 25 patients (39%) with eGFR (cystatin C), compared to 21 patients (33%) with GFR (s-creatinine) and the RIFLE criteria. The 90-day mortality was 14.3% for the AKI+group and 2.3% for the AKI-group (p = 0.099). At 12 months followup, renal function remained impaired in patients with postoperative AKI and deteriorated in patients without. CONCLUSIONS The risk of postoperative AKI is considerable following TAVI, with an increased risk of early mortality for AKI+patients. Cystatin C may be a valuable adjunct to the established biomarker s-creatinine for preoperative risk assessment and for early postoperative diagnosis of AKI. The acute postoperative renal impairment in patients with AKI does not fully recover in the long term. There is a progressive renal impairment in both groups postoperatively, the etiology probably being multifactorial.

Fondaparinux or enoxaparin: A comparative study of postoperative bleeding in coronary artery bypass grafting surgery.

Abstract Objectives. Preoperative treatment with anti-coagulants for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) exposes patients undergoing surgical revascularization to a higher risk of perioperative bleeding. The aim of this study was to compare the effect on bleeding and transfusion needs during cardiac surgery for patients treated with enoxaparin or fondaparinux. Design. Using a combined retrospective and prospective approach, we studied the outcome of 147 patients with NSTE-ACS referred to coronary artery bypass grafting in terms of bleeding, blood transfusions and other complications. Results. Eighty patients were treated preoperatively with enoxaparin, and 67 patients with fondaparinux. There was no significant difference in postoperative bleeding (532 ± 355 for enoxaparin group vs. 580 ± 300 ml for fondaparinux group, p = ns) or transfusion needs for the two groups. A subgroup analysis of the fondaparinux group showed a significantly higher amount of postoperative bleeding after 12 h for patients when preoperative treatment with fondaparinux was discontinued less than 36 h prior to surgery compared to more than 36 h. Discussion. This study suggests that preoperative treatment with fondaparinux for NSTE-ACS is as safe as enoxaparin in terms of postoperative bleeding and transfusion needs. Findings support discontinuation of fondaparinux at 36 h prior to surgery.