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Objective: Postoperative delirium (POD) is common after cardiac surgery. We have previously identified plasma sodium concentration and the volume of infused fluids during surgery as possible risk factors. Both are linked to the selection and composition of the pump prime used for cardiopulmonary bypass (CPB). Present study aims to examine whether hyperosmolality increases the risk for POD. Design: Patients ≥65 years (n = 195) scheduled for cardiac surgery were prospectively enrolled into this double blinded randomised clinical trial. Study group received a pump prime containing mannitol and ringer-acetate (966 mOsmol) (n = 98) vs. ringer-acetate (388 mOsmol) (n = 97) in the control group. Postoperative delirium was defined according to DSM-5 criteria based on a test-battery pre- and postoperatively (days 1–3). Plasma osmolality was measured on five occasions and coordinated with the POD assessments. The primary outcome was the POD incidence related to hyperosmolality as the secondary outcome. Results: The incidence of POD was 36% in the study group and 34% in the control group, without intergroup difference (p=.59). The plasma osmolality was significantly higher in the study group, both on days 1 and 3 and after CPB (p

Treatable targets that hinder heart failure development following myocardial infarction remain limited. Through an unbiased transcriptional regulation study for ischemic heart disease, we identified the protein disrupted in schizophrenia 1 (DISC1), which has been almost solely characterized in the brain. Here, we show that loss of DISC1 is a major driver of heart disease and ischemic damage. Silencing of DISC1 sensitizes human cardiomyocyte cell lines to hypoxia, whereas DISC1 overexpression is cardioprotective. Mechanistically, we provide evidence that reduced DISC1 protein levels interrupt multiple signaling processes vital for cardiomyocyte survival whereas overexpression of DISC1 enhances pro survival signalling. The present study has implications for understanding scenarios where cardiomyocytes are unable to increase the levels of DISC1 during ischemia, e.g., in individuals with DISC1 genetic defects. Indeed, patients with severe mental illness display 20 years earlier mortality, with IHD as the greatest cause of death. The present study can thus shed light on this long-term enigma in epidemiology. Furthermore, the promising data showing activation of pro survival signalling processes with DISC1 overexpression opens new directions towards potential treatment strategies of patients suffering from ischemic heart disease.

IntroductionPostoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status.Methods and analysisThis five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery.Ethics and disseminationThis trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings.Trial registration numberNCT05029050.

OBJECTIVES Our goal was to investigate long-term mortality associated with red blood cell (RBC) transfusion among patients with anaemia undergoing cardiac surgery when adjusting for known risk factors. METHODS Adults with preoperative anaemia as defined by World Health Organization criteria undergoing open-heart surgery from 2000 through 2017 were included. Cox regression was performed for long-term mortality (30 days–5 years), comparing patients who received ≥1 unit of RBC with those who did not. Unadjusted and multivariable analyses adjusted for risk factors were performed. RESULTS The study included 1859 patients, 1525 (82%) of whom received RBC transfusion. A total of 370 (19.9%) deaths were registered between 30 days and 5 years; 88 patients (23.8%) died between 30 days and 1 year. The unadjusted hazard ratio (HR) associated with RBC transfusion was 2.09 (1.49–2.93, P CONCLUSIONS No statistically significant association between RBC transfusion and long-term mortality was found when we adjusted for known risk factors. This study suggests that the observed difference in mortality in this patient group is largely due to patient-related risk factors.

Background Complete embolization of a prosthetic heart valve is extremely rare and dangerous. This case reports a total embolization of a mechanical aortic valve and contributes to the literature regarding the diagnostic challenges related to infective endocarditis and follow-up after valvular surgery. Case summary A 28-year-old male 11.5 years status-post a mechanical aortic valve replacement presented with acute onset of chest pain and dyspnoea while jogging. The patient lost consciousness and went into cardiopulmonary arrest with acute pulmonary oedema and circulatory shock. An echocardiogram revealed an empty aortic annulus, and a chest radiograph showed an embolized valve in the aortic arch. The patient underwent emergent removal of the embolized valve and replacement with a new mechanical aortic valve. The patient survived with minimal sequelae. At a 3-month follow-up, he had resumed work, and the only sequelae were mild left ventricular dysfunction and minor vision loss. Although he experienced no warning signs or symptoms, the most likely aetiology for embolization of the valvular prosthesis was infective endocarditis, which was revealed by re-evaluation of an echocardiogram recorded 1 month before the presentation which demonstrated a subtle motion abnormality of the valve. Conclusions We present a case of a late complete embolization of a mechanical aortic valve most likely caused by asymptomatic infective endocarditis. The case illustrates the challenges in follow-up after valvular surgery and highlights the ultimate benefit of a well-functioning pre-hospital to hospital chain.

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care.

OBJECTIVESLow physical activity and cardiorespiratory fitness are known risk factors for coronary artery disease, but how they affect the risk of undergoing coronary artery bypass graft surgery is not established. We explored how physical activity and estimated cardiorespiratory fitness affect the risk of coronary surgery and postoperative outcome.METHODSParticipants with no history of coronary disease from the second wave of the Trøndelag Health Study (HUNT2) were cross-linked with the local heart surgery register and the Norwegian Cause of Death Registry. Cardiorespiratory fitness was estimated by a previously developed algorithm using clinical and self-reported information. Fine-Gray competing risk analyses were used to calculate the risk of undergoing isolated coronary surgery across physical activity groups and estimated cardiorespiratory fitness (mL/kg/min) as quintiles and per 1 metabolic equivalent of task (MET) (3.5 mL/kg/min).RESULTSWe included 45,491 participants. The mean population age was 46.0 [standard deviation (SD) 15.8] years, and the mean estimated fitness was 41.3 (SD 8.9) mL/kg/min. A total of 672 (1.5%) participants underwent coronary surgery during the follow-up period. The risk of undergoing isolated coronary surgery was 26% [95% confidence interval (CI) 3–44] lower for those classified as highly active compared to those classified as least active. Further, an 11% (95% CI 6–15) lower risk per 1-MET (3.5 mL/kg/min) of higher fitness. Finally, we observed a 15% (95% CI 5–23) lower mortality risk after surgery per 1-MET of higher fitness among those undergoing surgery.CONCLUSIONSHigh levels of physical activity and high estimated fitness levels were inversely associated with the risk of developing coronary disease requiring surgery and overall mortality after surgery.

Objective Investigate important clinical and operative variables associated with increases in cardiac troponin T (cTnT) as indicators of myocardial injury after coronary artery bypass grafting (CABG). Design Prospective cohort study. Setting Single university hospital. Participants The study comprised 626 patients undergoing isolated CABG from April 2008 through April 2010 with a validation cohort (n = 686) from 2015-2017. Interventions None. Measurements and Main Results Perioperative variables were registered prospectively. The extent of diffuse coronary atherosclerosis and significant stenoses were assessed with preoperative coronary angiography. Mixed model analysis was used to construct a statistical model explaining the course of cTnT concentrations. The model was adjusted for preoperative and intraoperative/postoperative myocardial infarction (MI) for independent assessment of additional variables. Clinical factors associated with increased cTnT concentrations during and after CABG were longer duration of cardiopulmonary bypass (p < 0.001), higher preoperative creatinine (p < 0.001), New York Heart Association functional classification IV (p = 0.006), reduced LVEF (p = 0.034), higher preoperative C-reactive protein (p = 0.049), and intraoperative/postoperative MI (p < 0.001). Factors associated with decreasing cTnT concentrations during CABG were higher BSA (p < 0.001) and a recent preoperative MI (p < 0.001). The extent of diffuse coronary atherosclerosis and significant stenoses were not associated with changes in cTnT (p = 0.35). Results were similar in the validation cohort. Conclusions Left ventricular ejection fraction, New York Heart Association classification, kidney function, inflammation status, duration of cardiopulmonary bypass, body surface area, and preoperative MI were associated with the cTnT rise-and-fall pattern related to myocardial injury after CABG. Information regarding these variables may be valuable when using cTnT in the diagnostic workup of postoperative MI. (C) 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/)Journal of Cardiothoracic and Vascular Anesthesia 33 (2019) 3309 3319Contents lists available atScienceDirectJournal of Cardiothoracic and Vascular Anesthesiajournal homepage:www.jcvaonline.com

Background: Patients with preoperative dual antiplatelet therapy prior to coronary artery bypass surgery are at risk of bleeding and blood component transfusion. We hypothesise that an optimised cardiopulmonary bypass strategy reduces postoperative blood loss and transfusions. Methods: In total, 60 patients admitted for coronary artery bypass grafting with ticagrelor and aspirin medication withdrawn ® heparin-coated circuit with low systemic heparinisation (activated clotting time ® coated open circuit, full systemic heparinisation (activated clotting time > 480 seconds) and conventional cardiotomy suction. This perfusion strategy was evaluated by the chest drain volume after 24 hours, perioperative haemoglobin and platelet loss accompanied by global coagulation assessments. Results: Patients in the study group demonstrated significantly better outcomes signified by lower blood loss 554 ± 224 versus 1,100 ± 989 mL (p 9/L (p = 0.001). Indices of rotational thromboelastometry indicated shorter clotting times within the internal and external pathways. Adenosine diphosphate activated platelet function was within normal range based on Multiplate® aggregometry, while ROTEM® platelet analyses indicated inhibited function both preoperatively and post-bypass. Platelet inhibition by aspirin was verified throughout the perioperative period. Platelet function showed no intergroup differences. Conclusion: A stringent perfusion strategy reduced blood loss and transfusions in dual antiplatelet therapy patients requiring urgent surgery.

Objectives. Two tools to categorize and present quality data, phase of care mortality analysis (POCMA) and failure to rescue (FTR) have been introduced in the cardiothoracic surgical environment, but not tested in Scandinavia. We aimed to investigate whether these tools could be used in a Norwegian patient population and to increase the understanding of why patients die after cardiac surgery. Design. A group of four, including one senior cardiothoracic surgeon and one senior anesthesiologist, scrutinized deaths within 30 days after cardiac surgery at the Clinic of Cardiothoracic Surgery, St. Olav's University Hospital, Norway between February 2012-October 2015 in line with the POCMA-methodology. We used the clinic's internal register to identify patients and utilized all available written information from each patient course. We decided whether each death was surgeon dependent, FTR or a result of a multifactorial etiology, and evaluated the strength of our decisions. Results. We identified 51 deaths out of 1983 operations in our study period, giving unadjusted mortality of 2.6%. Nine deaths were classified as surgeon dependent, 3 FTR and 39 multifactorial. Conclusions. POCMA- and FTR-analyses can be carried out in clinical data which is well documented. The operating surgeon is in many cases not responsible for operative mortality, very few die due to FTR, but most patients die due to a multifactorial etiology.

Patients with atrial fibrillation and atrial flutter scheduled to undergo open heart surgery can receive ablation treatment of arrhythmogenic foci during the same intervention. Sinus rhythm is restored in the majority in the short term, but the long-term results are more uncertain. This study, which is part of the international CURE-AF trial, evaluates results after Cox-Maze IV surgery for atrial fibrillation in Norway at six-year follow-up.Nineteen patients were included in this prospective cohort study. Atrial fibrillation had persisted for 40 months in the group with long-standing persistent atrial fibrillation (n = 12) and 6 months in the group with persistent atrial fibrillation (n = 7). Surgery for atrial fibrillation was performed according to the Cox-Maze IV procedure in the CURE-AF protocol. Follow-up in the first 12 months was strictly according to the CURE-AF protocol, thereafter conducted by the primary health service.Sinus rhythm was restored in 11 patients at the time of discharge and in 14 patients six months postoperatively. After 5-6 years of follow-up, all patients with long-standing persistent atrial fibrillation had experienced recurrence. Two achieved sinus rhythm after electroconversion. Six of the seven in the group with persistent atrial fibrillation had sinus rhythm after 5-6 years.The results were good initially, with restoration of sinus rhythm in more than two thirds of the patients after 6-9 months. Five years later, a high recurrence rate was found in patients with long-standing persistent atrial fibrillation. Several recurrences had not been detected by the public health service or treatment had not been attempted.

Background Patients with atrial fibrillation and atrial flutter scheduled to undergo open heart surgery can receive ablation treatment of arrhythmogenic foci during the same intervention. Sinus rhythm is restored in the majority in the short term, but the long-term results are more uncertain. This study, which is part of the international CURE-AF trial, evaluates results after Cox-Maze IV surgery for atrial fibrillation in Norway at six-year follow-up. Material and method Nineteen patients were included in this prospective cohort study. Atrial fibrillation had persisted for 40 months in the group with long-standing persistent atrial fibrillation (n = 12) and 6 months in the group with persistent atrial fibrillation (n = 7). Surgery for atrial fibrillation was performed according to the Cox-Maze IV procedure in the CURE-AF protocol. Follow-up in the first 12 months was strictly according to the CURE-AF protocol, thereafter conducted by the primary health service. Results Sinus rhythm was restored in 11 patients at the time of discharge and in 14 patients six months postoperatively. After 5-6 years of follow-up, all patients with long-standing persistent atrial fibrillation had experienced recurrence. Two achieved sinus rhythm after electroconversion. Six of the seven in the group with persistent atrial fibrillation had sinus rhythm after 5-6 years. Interpretation The results were good initially, with restoration of sinus rhythm in more than two thirds of the patients after 6-9 months. Five years later, a high recurrence rate was found in patients with long-standing persistent atrial fibrillation. Several recurrences had not been detected by the public health service or treatment had not been attempted.

OBJECTIVES Our goal was to study long-term observed and relative survival after first-time aortic valve replacement surgery with or without concomitant coronary artery bypass surgery with reference to valve morphology (i.e. bicuspid vs tricuspid). METHODS Consecutive patients (n = 5086) from 3 Swedish hospitals, operated on between 1 January 2005 and 31 December 2016, were included. The 30-day mortality (n = 116, 2.3%) was excluded from the analysis of long-term observed and relative survival (n = 4970). Observed survival was analysed using Cox regression. Relative survival was calculated as the ratio between observed and expected survival based on data from the general Swedish population, matched for age, sex and calendar year. Risk factors for death were explored using multivariable analysis. RESULTS During the follow-up (median 4.7 years) period, 1157 (23%) patients died. Observed survival excluding 30-day mortality was 96.6%, 82.7% and 57.6% after 1, 5 and 10 years. Compared with the general Swedish population, the relative 1-, 5- and 10-year survival rates were 99.0%, 97.5% and 89.0%. Bicuspid morphology was independently associated with higher observed and relative long-term survival. Renal dysfunction, diabetes, chronic obstructive pulmonary disease, heart failure, smoking and atrial fibrillation were associated with higher long-term mortality. Combined surgery was not associated with higher observed or relative mortality. CONCLUSIONS Patients with a bicuspid morphology had better prognosis, matching that of the general population. With increased age, long-term relative survival compared favourably with survival in the general Swedish population. Adding coronary artery bypass surgery to an aortic valve replacement procedure did not affect long-term outcome., Bicuspid aortic valve is the most common congenital heart condition and leads to premature valve failure in a significant number of patients [1].

Aims: Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end-stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca2+ handling in post-myocardial-infarction (MI) patients at mid-stage of HF. Methods and results: Nine MI patients and eight control patients without MI (non-MI) were included. Biopsies were taken from the left ventricular myocardium and processed for further measurements with epifluorescence and confocal microscopy. Cardiomyocyte function was progressively impaired in MI cardiomyocytes compared with non-MI cardiomyocytes when increasing electrical stimulation towards frequencies that simulate heart rates during physical activity (2 Hz); at 3 Hz, we observed almost total breakdown of function in MI. Concurrently, we observed impaired Ca2+ handling with more spontaneous Ca2+ release events, increased diastolic Ca2+, lower Ca2+ amplitude, and prolonged time to diastolic Ca2+ removal in MI (P < 0.01). Significantly reduced transverse-tubule density (−35%, P < 0.01) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase 2a (SERCA2a) function (−26%, P < 0.01) in MI cardiomyocytes may explain the findings. Reduced protein phosphorylation of phospholamban (PLB) serine-16 and threonine-17 in MI provides further mechanisms to the reduced function. Conclusions: Depressed cardiomyocyte contraction and relaxation were associated with impaired intracellular Ca2+ handling due to impaired SERCA2a activity caused by a combination of alteration in the PLB/SERCA2a ratio and chronic dephosphorylation of PLB as well as loss of transverse tubules, which disrupts normal intracellular Ca2+ homeostasis and handling. This is the first study that presents these mechanisms from viable and intact cardiomyocytes isolated from the left ventricle of human hearts at mid-stage of post-MI HF.

Authors/Task Force Members: Christa Boer (EACTA Chairperson)(Netherlands), Michael I. Meesters (Netherlands), Milan Milojevic (Netherlands), Umberto Benedetto (UK), Daniel Bolliger (Switzerland), Christian von Heymann (Germany), Anders Jeppsson (Sweden), Andreas Koster (Germany), Ruben L. Osnabrugge (Netherlands), Marco Ranucci (Italy), Hanne Berg Ravn (Denmark), Alexander B.A. Vonk (Netherlands), Alexander Wahba (Norway), Domenico Pagano (EACTS Chairperson)(UK),. Document Reviewers: Moritz W.V. Wyler von Ballmoos (USA), Mate Petricevic (Croatia), Arie Pieter Kappetein (Netherlands), Miguel Sousa-Uva (Portugal), Georg Trummer (Germany), Peter M. Rosseel (Netherlands), Michael Sander (Germany), Pascal Colson (France), Adrian Bauer (Germany).

Background Less-than-optimal long-term patency of the saphenous vein is one of the main obstacles for the success of coronary artery bypass grafting (CABG). Results from the IMPROVE-CABG trial has shown that harvesting the saphenous vein with a pedicle of perivascular tissue less than 5 mm while using manual distention provides comparable occlusion rates but significantly less intimal hyperplasia at early follow-up. The impact of pedicled veins on duration of operations, leg wound infections, and postoperative bleeding is unknown. Methods One hundred patients undergoing first-time elective CABG were randomly assigned to conventional or pedicled vein harvesting. Perioperative and postoperative data were collected prospectively during the hospital stay and at follow-up. Results Duration of extracorporeal circulation was significantly longer in the pedicled vein group (mean: 76 min versus 65 min, p = 0.006); however, no significant difference was found in the cross-clamp time. No significant difference was found in intraoperative vein graft flow, postoperative bleeding, or leg wound infections (4% in each group). No reoperations were due to vein graft bleeding. Conclusions Harvesting a pedicled vein provides comparable postoperative bleeding and leg wound infection rates in selected patients. The technique is associated with a slightly longer duration of extracorporeal circulation than harvesting conventional veins. Promising early results using the pedicled vein technique may contribute to a change in standard vein harvesting technique for CABG in selected patients.

Background Chronic postsurgical pain (CPSP) is a common complication after many surgical procedures, including cardiac surgery. The prevalence of CPSP after cardiac surgery ranges from 9.5% to 56%. Most studies on CPSP after cardiac surgery are retrospective and long-term prospective studies are scarce. The aim of this study was to follow CPSP and health-related quality of life (HRQOL) prospectively in a cohort of patients, emphasizing the prevalence from 12 months to 5 years. Methods A total of 534 patients (23% ≥75 years, 67% men) were consecutively included before surgery. Study-specific questionnaires and the Brief Pain Inventory (BPI) were used to measure CPSP at baseline, 12 months and 5-year follow-up. Short-Form Health Survey (SF-36) was used to measure HRQOL. Results Among 458 patients who were alive after 5 years, 82% responded (n = 373). The majority, 89.8% (335/373), did not report CPSP, neither 12 months nor 5 years after surgery. Among the 38 patients who reported CPSP after 12 months, 24 (63%) patients did not report CPSP after 5 years. The overall prevalence of CPSP after 5 years was 3.8% (14/373). Patients reporting CPSP and resolved CPSP had lower scores on HRQOL and more pain preoperatively than patients who did not report CPSP. Conclusions The prevalence of CPSP was lower in this study than previously reported. Among the patients reporting CPSP at 12 months, 63% did not report CPSP after 5 years. Hence, the observed decline in CPSP is in line with studies evaluating CPSP in noncardiac surgery. Significance The prevalence of chronic postsurgical pain (CPSP) at 5 years after surgery of 3.8% is lower than previously reported. The majority of patients reporting CPSP after 12 months did not report CPSP after 5 years.

Context Lung cancer surgery is among the surgical procedures associated with the highest prevalence of pain, but prospective longitudinal studies after the pain trajectory are scarce. Objectives We aimed to describe the pain trajectory in patients undergoing surgery for primary lung cancer and investigate whether distinct groups of patients could be identified based on different pain trajectories. Methods Patients (n = 264; 95% thoracotomies) provided data on the average and worst pain intensity, pain location, and comorbidities before, and at one month and five, nine, and 12 months after surgery. Pain profiles were analyzed by latent class mixed models. Results The occurrence of any pain increased from 40% before surgery to 69% after one month and decreased to 56%, 57%, and 55% at five, nine, and 12 months, respectively. Latent class mixed models identified two classes both for average and worst pain; one class started low with high ratings after one month, then returning to a level slightly higher than baseline. The other class started higher with similar scores through the trajectory. Patients reporting no pain (8%) were placed in a separate class. Higher comorbidity score, preoperative use of both pain and psychotropic medicine characterized the class with overall highest pain for average and/or worst pain. Conclusion Pain was highly prevalent after surgery, and subgroups could be identified based on different pain trajectories. Patients reported both postoperative pain and pain from chronic conditions. Knowledge about vulnerable patients and risk factors for pain is important to tailor interventions and information about pain.

Background Chylothorax is a rare clinical condition that results from thoracic duct damage with leakage of chyle from the lymphatic system to the pleural space. Rarely, constrictive pericarditis has been associated with chylothorax, but to our knowledge only in relation to secondary causes such as tuberculosis, HIV, or malignancy. Case summary A previously healthy 63-year-old man presented with effusive-constrictive pericarditis, recurrent right-sided pleural effusion, and chylothorax. There was no history of co-morbidities, surgical illness, or cardiac procedures. No single aetiologic factor was identified despite comprehensive assessment. Substantial immunosuppressive therapy was given without a sufficient clinical response. Pericardiectomy resulted in resolution of the constrictive haemodynamics and terminated chylous effusion. Discussion The hypothesized mechanisms for development of chylothorax in association with constrictive pericarditis are the increased effective capillary infiltration secondary to central venous hypertension and reduced lymphatic drainage due to high pressure in the left subclavian vein. Increased capillary filtration may result in excessive lymph formation. However, the mechanism is not completely understood.

Background Severe post-operative bleeding in cardiac surgery is associated with increased morbidity and mortality. We hypothesized that variation in genetic susceptibility contributes to post-operative bleeding in addition to clinical factors. Methods We included 1036 adults undergoing cardiac surgery with cardiopulmonary bypass. Two different endpoints for excessive post-operative bleeding were used, either defined as blood loss exceeding 2 ml/kg/h the first 4 h post-operatively or a composite including bleeding, transfusions, and reoperations. Twenty-two single nucleotide polymorphisms (SNPs) central in the coagulation and fibrinolysis systems or in platelet membrane receptors were genotyped, focusing on replication of earlier non-replicated findings and exploration of potential novel associations. Using logistic regression, significant SNPs were added to a model with only clinical variables to evaluate whether the genetic variables provided additional information. Results Univariate tests identified rs1799809 (located in the promoter region of the PROC gene), rs27646 and rs1062535 (in the ITGA2 gene), rs630014 (in the ABO gene), and rs6048 (in the F9 gene) as significantly associated with excessive post-operative bleeding (P

Objectives. We aimed to study the feasibility and reliability of focused ultrasound (US) examinations to quantify pericardial (PE)- and pleural effusion (PLE) by a pocket-size imaging device (PSID) performed by nurses in patients early after cardiac surgery. Design. After a 3-month training period, with cardiologists as supervisors, two nurses examined 59 patients (20 women) with US using a PSID at a median of 5 days after cardiac surgery. The amount of PE and PLE was classified in four categories by US (both) and chest x-ray (PLE only). Echocardiography, including US of the pleural cavities, by experienced cardiologists was used as reference. Results. Focused US by the nurses was more sensitive than x-ray to detect PLE. The correlations of the quantification of PE and PLE by the nurses and reference was r (95% confidence interval) 0.76 (0.46–0.89) and 0.81 (0.73–0.89), both p < 0.001. PE and PLE were drained in one and six (eight cavities) patients, all classified as large amount by the nurses. Conclusions. Cardiac nurses were able to obtain reliable measurements and quantification of both PE and PLE bedside by focused US and outperform the commonly used chest x-ray regarding PLE after cardiac surgery.

Aims Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end‐stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca2+ handling in post‐myocardial‐infarction (MI) patients at mid‐stage of HF. Methods and results Nine MI patients and eight control patients without MI (non‐MI) were included. Biopsies were taken from the left ventricular myocardium and processed for further measurements with epifluorescence and confocal microscopy. Cardiomyocyte function was progressively impaired in MI cardiomyocytes compared with non‐MI cardiomyocytes when increasing electrical stimulation towards frequencies that simulate heart rates during physical activity (2 Hz); at 3 Hz, we observed almost total breakdown of function in MI. Concurrently, we observed impaired Ca2+ handling with more spontaneous Ca2+ release events, increased diastolic Ca2+, lower Ca2+ amplitude, and prolonged time to diastolic Ca2+ removal in MI (P

OBJECTIVES The aim of this study was to compare long-term mortality in patients undergoing primary isolated coronary artery bypass grafting who received ≥1 units of red blood cells (RBCs) or no RBCs. We hypothesized that a possible difference in long-term mortality was due to preoperative morbidity and/or postoperative morbidity. METHODS This prospective cohort study, part of the Cardiac Surgery Outcome Study (CaSOS) at St. Olavs University Hospital, Trondheim, Norway, included patients operated on from 2000 through 2014 (n = 4014) and excluded those with large intra- or postoperative blood loss or 30-day mortality. Observed mortality from 30 days to 15 years postoperatively was compared between patients who received RBC transfusion and those who did not. Cox regression analysis was performed with unadjusted models, adjusting for pre- and intraoperative covariates, and with further adjustment for postoperative complications. Sensitivity analyses were performed with propensity score matching or including 30-day mortality. RESULTS The unadjusted hazard ratio (HR) for long-term mortality was 2.10 (1.81-2.43; P

OBJECTIVES During open-heart surgery, the myocardium experiences ischaemia-reperfusion injury. A single bout of moderate, 30-min exercise induces preconditioning and protects the heart from ischaemia-reperfusion injury in rats, but this has never been investigated in humans. We aimed to investigate whether 1 bout of moderate exercise 24 h prior to surgery protects against mitochondrial and cardiac damage. METHODS Patients scheduled for elective coronary artery bypass were eligible for this pilot study. Twenty were included and randomized to the treadmill exercise group (the EX group, n = 10) 24 h preoperatively or to standard presurgical procedures (control n = 10). Right atrial (RA) and left ventricular (LV) biopsies were collected immediately before and as long as possible after aortic cross-clamping to assess the primary outcome of mitochondrial respiration by respirometry, in addition to reactive oxygen species production by fluorometry and apoptotic transcripts. Cardiac troponin T and creatine kinase myocardial brain were measured in plasma at arrival, before surgery and 6 and 24 h postoperatively. RESULTS Mitochondrial respiration was lower in the EX group after surgery in the LV (Complex I -22%, P

Background Post-operative fluid overload following cardiac surgery is associated with increased morbidity and mortality. We hypothesised that genetic variations and pre-operative clinical factors predispose some patients to post-operative fluid overload. Methods Perioperative variables were collected prospectively for 1026 consecutive adults undergoing open-heart surgery at St. Olavs University Hospital, Norway from 2008–2010. Post-operative fluid overload was defined as a post-operative fluid balance/kg ≥ the 90th percentile of the study population. Genotyping was performed for 31 single-nucleotide polymorphisms related to inflammatory/vascular responses or previously associated with complications following open-heart surgery. Data were analysed using logistic regression modelling, and the findings were internally validated by bootstrapping (n = 100). Results Homozygous carriers of the common G allele of rs12917707 in the UMOD gene had a 2.2 times greater risk of post-operative fluid overload (P = 0.005) after adjustment for significant clinical variables (age, duration of cardiopulmonary bypass, and intraoperative red cell transfusion). A genetic risk score including 14 single-nucleotide polymorphisms was independently associated with post-operative fluid overload (P = 0.001). The number of risk alleles was linearly associated with the frequency of fluid overload (odds ratio per risk allele 1.153, 95 % confidence interval 1.056–1.258). Nagelkerke's R2 increased with 7.5% to a total of 25% for the combined clinical and genetic model. Hemofiltration did not reduce the risk. Conclusion A common variation in the UMOD gene previously shown to be related to renal function was associated with increased risk of post-operative fluid overload following cardiac surgery. Our findings support a genetic susceptibility to disturbed fluid handling following cardiac surgery.

Aim As few studies have presented a thorough analysis of the effect of levosimendan (LEV) on contractility, our purpose was to investigate in vivo cardiac function as well as in vitro cardiomyocyte function and calcium (Ca2+) handling following LEV treatment. Methods Rats with post-myocardial infarction heart failure (HF) induced by ligation of the left anterior descending coronary artery and sham-operated animals were randomized to the infusion of LEV (2.4 μg kg−1 min−1) or vehicle for 40 min. Echocardiographic examination was coupled to pressure-volume sampling in the left ventricle before (B) and after (40 min) infusion. Isolated left ventricular cardiomyocytes were studied in an epifluorescence microscope. Results HF LEV (n = 6), HF vehicle (n = 7), sham LEV (n = 5) and sham vehicle (n = 6) animals were included. LEV infusion compared to vehicle in HF animals reduced left ventricular end-diastolic pressure and mean arterial pressure (both P

Background Several models for predicting acute kidney injury following cardiac surgery have been published, and various end-point definitions have been used. Objectives Our aim was to investigate how acute kidney injury following cardiac surgery could be most accurately predicted. Design Single-centre prospective observational study. Setting St Olav's University Hospital, Trondheim, Norway, from 2000 to 2007. Patients All 5029 adult patients undergoing cardiac surgery were considered eligible for participation. Patients who required preoperative dialysis and patients with missing information on preoperative or maximum postoperative serum creatinine concentration were excluded (n=51). A total of 4978 patients were entered into the statistical analyses. Main outcome measures Logistic regression with bootstrapping methods was applied for model development and validation, together with the area under the receiver operating characteristic curve and Hosmer-Lemeshow test. We tested different end-points, exchanged serum creatinine concentration with creatinine clearance or estimated glomerular filtration rate and added intraoperative variables. The main end-point was at least 50% increase in serum creatinine concentration, an increase in concentration by at least 26.4 μmol l(-1) (0.3 mg dl(-1)) or a new requirement for dialysis after surgery. Results The final model consisted of 11 preoperative predictors of acute kidney injury: age, BMI, lipid-lowering treatment, hypertension, peripheral vascular disease, chronic pulmonary disease, haemoglobin concentration, serum creatinine concentration, previous cardiac surgery, emergency operation and operation type. The area under the receiver operating characteristic curve was 0.819 (95% confidence interval 0.801 to 0.837), and the Hosmer-Lemeshow test P value was 0.17. Exchanging serum creatinine concentration with glomerular filtration rate or creatinine clearance slightly reduced model discrimination and the addition of intraoperative variables improved discrimination somewhat. Slight end-point definition changes had little impact. Conclusion The risk of acute kidney injury can be accurately predicted using preoperative variables. Serum creatinine concentration was more accurate than estimated glomerular filtration rate or creatinine clearance. Intraoperative variables slightly improved the model, but did not seem to outweigh the advantages of a preoperative model.

OBJECTIVES: As survival after cardiac surgery has become very satisfactory even in elderly patients, more attention is being directed towards improved health-related quality of life (HRQOL). However, longitudinal prospective cohort studies describing HRQOL after cardiac surgery are still scarce. The purpose of this study was to explore HRQOL and survival in patients undergoing cardiac surgery after 5 years, emphasizing on older patients (≥75 years). METHODS: In a prospective population-based study, 534 patients (23% ≥75 years, 67% males) were consecutively included before surgery. HRQOL and medical and sociodemographic variables were measured by questionnaires at baseline, 6 and 12 months after surgery and again after 5 years. HRQOL was measured by the Short-Form 36 Health Survey (SF-36). RESULTS: Four hundred and fifty-eight patients were alive after 5 years, with a response rate of 82%. Older patients had lower 5-year survival than younger patients (P= 0.042), but it was similar to that of the general population. After 5 years, both older and younger patients had slightly lower scores on some SF-36 dimensions, compared with scores after 6 and 12 months. However, on seven of eight subscales of the SF-36, the scores after 5 years were still higher than before surgery. Older patients improved less from baseline to the follow-up, and had more profound reductions in scores from 12 months to 5 years on three subscales; physical functioning (P= 0.013), role physical (P< 0.001) and vitality (P= 0.036). CONCLUSIONS: HRQOL improved from baseline to 6 months postoperatively, and remained relatively stable 5 years after cardiac surgery even in elderly patients. The study showed that survival and HRQOL can match that of the general population.

OBJECTIVES Patients with lung cancer report sleep difficulties to be frequent and bothersome symptoms. This study describes the trajectory of sleep from before and up to 12 months after surgery for lung cancer. Further, it investigates possible associations between sleep disturbance, demographic and clinical characteristics before surgery. METHODS This study is part of a longitudinal multicentre study. Sleep disturbance was measured by The General Sleep Disturbance Scale (GSDS) that investigates frequencies of sleep difficulties (21 items) and a total sum score ≥43 indicates a clinically meaningful level of sleep disturbance (score range 0–147). Linear mixed models were used to study changes in sleep from baseline to 1, 5, 9 and 12 months after surgery. RESULTS The percentage of patients (n = 264) reporting sleep disturbances was 60.9% at baseline, 68.5% at Month 1, 55.4% at Month 5, 51.3% at Month 9 and 49.7% at Month 12. The increase to and decrease from Month 1 was the only significant alteration in the occurrence of sleep disturbance. The patients reported most problems within the subscales sleep quantity, early awakenings and sleep quality. Factors associated with sleep disturbance were lower age, use of pain medication and psychotropic medication and higher comorbidity score. CONCLUSIONS Lung cancer patients sleep poorly, before as well as after surgery. There is a need to address sleeping disturbance routinely in clinical practice and screening for sleeping problems is indicated. Further studies are warranted concerning factors that contribute to sleep disturbance and how they best can be treated. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Objective To investigate whether a multimarker strategy combining preoperative biomarkers representing distinct pathophysiologic pathways enhances preoperative risk assessment of acute kidney injury after cardiac surgery (CSA-AKI) and increases knowledge of underlying pathogenesis. Design Prospective, cohort study. Setting Single-center tertiary referral hospital. Participants The study comprised 1,015 adults undergoing cardiac surgery with cardiopulmonary bypass. Interventions CSA-AKI was defined as≥50% increase in serum creatinine concentration, absolute increase≥26 µmol/L, or new requirement for dialysis. Preoperative and perioperative information until hospital discharge was recorded. Preoperative plasma levels of C-reactive protein, terminal complement complex, neopterin, lactoferrin, N-terminal pro-brain natriuretic peptide, and cystatin C were determined using enzyme immunoassays. Biomarkers were selected based on causal hypotheses of underlying mechanisms and were related to inflammatory, hemodynamic, or renal signaling pathways. Measurements and Main Results One hundred patients (9.9%) developed CSA-AKI. Higher baseline plasma concentrations of neopterin and N-terminal pro-brain natriuretic peptide were associated independently with CSA-AKI (p = 0.04 and p

Objective To evaluate the effects of tranexamic acid on postoperative blood loss and transfusion requirements in elderly patients undergoing combined aortic valve replacement and coronary artery bypass graft surgery (CABG). Design A prospective, randomized, double-blinded, placebo-controlled, parallel-group trial. Setting A university hospital (single institution). Participants Sixty-four patients 70 years or older undergoing combined aortic valve replacement and CABG surgery were included. One patient was withdrawn from the study after randomization by the attending surgeon because of a change in the surgical procedure. The remaining 63 patients were analyzed as intention to treat. Interventions The included patients were randomized to treatment with either tranexamic acid, 10 mg/kg, as a bolus injection before surgery followed by 1 mg/kg/h as an infusion during surgery, or a corresponding volume of 0.9% sodium chloride. Measurements and Main Results Postoperative blood loss was recorded for 16 hours. The transfusion of blood products was recorded during the entire hospital stay. The number of packed red cell transfusions given to the patients was significantly lower in the tranexamic acid group compared with the placebo group (median, 3.0 [interquartile range, 2-5] v 5.0 [3-7], p = 0.049). Conclusion Tranexamic acid reduced the number of packed red cell transfusions given to patients 70 years or older undergoing combined aortic valve replacement and CABG surgery.

Context Cardiac dysfunction following open heart surgery is a major determinant of subsequent morbidity and mortality. Objectives To develop a specific risk prediction model for postoperative cardiac dysfunction based on preoperative variables, to investigate whether prediction could be improved by inclusion of selected intraoperative variables and to compare our model with five previously published risk scores. Design Single-centre prospectively collected data. Setting Tertiary care centre, Middle Norway. Patients Four thousand nine hundred and eighty-nine patients (all eligible) undergoing open cardiac surgery from 2000 to 2007. Main outcome measures Logistic regression models for postoperative cardiac dysfunction: predictive accuracy/calibration, discrimination as shown by area under the receiver operating characteristics curve, internal validity as indicated by bootstrapping, comparison of goodness-of-fit with predictions based on alternative risk scores. Results The preoperative model included chronic cardiac insufficiency, previous myocardial infarction, previous cardiac operation, pulmonary hypertension, renal dysfunction, low haemoglobin concentration, urgent operation and operation type other than isolated coronary artery bypass surgery. The area under the curve was 0.838 [95% confidence interval (CI) 0.812-0.864]. Risk prediction was accurate apart from a slight overestimation in the 2% of highest risk patients. Inclusion of a few intraoperative variables (inotropic or vasoconstrictor drugs, plasma or red cell transfusion) improved the model slightly, increasing the area under the curve to 0.875 (95% CI 0.854-0.896) or 0.890 (95% CI 0.863-0.902) for two equivalent models. On the basis of estimated shrinkage factors of 0.94, 0.97 and 0.98, respectively, the models should behave with 6% or less error in future datasets. Our preoperative model was significantly better than the previously published risk scores (P Conclusion The preoperative model including variables obtained easily in routine clinical work performed well and was improved only slightly by inclusion of intraoperative variables. Performance was better than those of the five previously published risk scores.

OBJECTIVES: Levosimendan is a novel inotropic agent claimed to improve myocardial contractility by a calcium-sensitizing effect. Our aim was to evaluate dose-dependent effects of levosimendan on left ventricular (LV) contractility and energetic properties in an acute, ischaemic heart failure porcine model. METHODS: Six pigs were used in an anaesthetized in vivo open-chest model. The time points of measurements were: baseline, after heart failure induction and after dose 1–4 (D1–D4). Heart failure was induced by microembolization of the left coronary artery before infusion of four different doses (D1: 2.5 µg/kg, D2: 10 µg/kg, D3: 40 µg/kg, D4: 80 µg/kg) of levosimendan. Haemodynamics were assessed by the pressure-conductance catheter technique. LV oxygen consumption was calculated from coronary flow measurements and coronary sinus blood gases. Mitochondrial respiration was studied in biopsies of the LV. RESULTS: Levosimendan had no significant, load-independent effect on contractile force (slope of preload recruitable stroke work was 34 mmHg immediately following failure and 39 (P = 0.406), 42 (P= 0.219), 46 (P = 0.067) and 41 (P= 0.267) at D1–D4), although the more load-dependent contractility indicator of dP/dtmax was slightly increased at dose 4 (P < 0.05). LV energy conversion efficiency (PVA–MVO2 relationship) remained unaltered at all doses. Maximal mitochondrial respiration decreased after induction of failure and remained at an unaltered low level during levosimendan infusion. CONCLUSIONS: Surprisingly, levosimendan had no significant effect on contractility, energy efficiency and mitochondrial respiration of the LV, in a porcine model of acute heart failure. At high doses, levosimendan induced vasodilatation and increased heart rate and cardiac output.

Background Prolonged ventilation is a serious complication after cardiac surgery, but few risk prediction models exist. Our objectives were to develop a specific risk prediction model based on pre-operative variables, to identify whether selected intraoperative variables could improve prediction, and to compare our model with the EuroSCORE. Methods Data from 5027 patients undergoing open-heart surgery in 2000–2007 were used for logistic regression model development. Internal validation was performed by bootstrapping. Discrimination and calibration were assessed with areas under the receiver operating characteristic curve (AUC) and the Hosmer–Lemeshow test. Our pre-operative model was compared with predictions based on the additive and logistic EuroSCORE. Results Age, previous cardiac surgery, peripheral arterial disease, left ventricular hypertrophy, chronic pulmonary disease, renal insufficiency, pre-operative hemoglobin concentration, urgent or emergency operation, and operation other than isolated coronary artery bypass grafting were identified as pre-operative predictors for prolonged ventilation (model I). Discrimination and accuracy were excellent (AUC: 0.848 and shrinkage factor: 94%). Calibration was good (Hosmer–Lemeshow test: P = 0.43). Inclusion of a few intraoperative variables somewhat improved the model, increasing shrinkage factors (96%) and discrimination ability (AUC model II = 0.870 and model III = 0.875 for two alternative such models). Our pre-operative model showed better performance than the logistic or additive EuroSCORE. Conclusions The pre-operative risk prediction model for prolonged ventilation with easily obtainable variables in routine clinical work performed well and was only slightly improved by inclusion of intraoperative variables. Performance was better than with the EuroSCORE.

Background Serotonin promotes pulmonary arterial vasoconstriction and pulmonary arterial smooth muscle cell proliferation, thereby having the potential to increase pulmonary arterial blood pressure. Although serotonin reuptake inhibitors (SRIs) might inhibit further deterioration in patients with manifest pulmonary arterial hypertension, they may induce pulmonary hypertension in healthy newborns after fetal exposure. As it is unclear whether treatment with SRIs affects pulmonary hemodynamics in adults without pulmonary hypertension, the aim of the present study was to investigate the effect of SRIs on pulmonary hemodynamics in such subjects. Methods Sixteen patients with stable angina pectoris scheduled for first time coronary artery bypass grafting were included in the study. Of these 8 were currently treated with an SRI (the SRI group) and 8 were not (the control group). Pulmonary arterial pressures were measured before induction of anesthesia by means of a pulmonary artery catheter. Serotonin transporter and 5-HT2A receptor gene polymorphisms and platelet 5-HT2A receptor expression were studied to elucidate their possible role as modifying factors. Results No patients in any of the groups had pulmonary arterial hypertension. Mean pulmonary artery pressure was 15.0 mmHg in the SRI group and 14.5 mmHg in the control group (P = 0.50; 95% confidence interval for the difference, -2.9 to +3.9 mmHg). Neither were there any significant differences between the groups for any of the other hemodynamic variables studied. The various gene polymorphisms and the extent of platelet 5-HT2A receptor expression did not influence the hemodynamic variables. Conclusions SRI treatment did not significantly influence pulmonary hemodynamics in patients without pulmonary hypertension. Keywords Serotonin; Selective serotonin reuptake inhibitors; Pulmonary hemodynamics; Pulmonary hypertension

Background: Several models for prediction of early mortality after open-heart surgery have been developed. Our objectives were to develop a local mortality risk prediction model, compare it with the European System for Cardiac Operative Risk Evaluation (EuroSCORE), and investigate whether the addition of intra-operative variables could enhance the accuracy of risk prediction. Methods: All 5029 patients undergoing open-heart surgery in 2000–2007 were included in the study. Logistic regression with bootstrap methods was used to develop a pre-operative risk prediction model for in-hospital mortality. Next, several intra-operative variables were added to the pre-operative model. Calibration and discrimination were assessed, and the model was internally validated for prediction in future datasets. We thereafter compared the pre-operative model with the additive and logistic EuroSCOREs. Results: Our pre-operative model included eight risk factors that are routinely registered in our department: age, gender, degree of urgency, operation type, previous cardiac surgery, and renal, cardiac, and pulmonary dysfunction. The model estimated mortality accurately throughout the dataset except in the 1% of patients at extremely high risk, in which mortality was somewhat overestimated. The estimated shrinkage factor was 0.930. The areas under the receiver operating characteristic curve for our pre-operative model and the logistic EuroSCORE were 0.857(0.823–0.891) and 0.821(0.785–0.857) (P=0.02). There was no significant difference in performance between the pre-operative and the intra-operative model (P>0.10). Conclusion: Our pre-operative model was simple and easy to use, and showed good predictive ability in our population. Internal validation indicated that it would accurately predict mortality in a future dataset.

Objectives Health-related quality of life (HRQOL) is an important end point after cardiac surgery, particularly in patients of older age. However, prospective long-term studies describing the trajectory of HRQOL after cardiac surgery are still scarce. Therefore, the aim was to assess survival, functional status, and trajectory of HRQOL 10 years after cardiac surgery. Methods In a prospective population-based study, 534 patients (23% aged 75 years or older, 67% male) were consecutively included before surgery. Functional status was measured according to self-assigned New York Heart Association (NYHA) classification. HRQOL was measured using the Short-Form Health Survey (SF-36). Questionnaires were given to the patients at baseline and sent by post at 6 and 12 months, and 5 and 10 years after surgery. Results Three hundred fifty-two patients were eligible after 10 years, 274 responded (77.8%). Total survival at 10 years was 67.8%. Patients aged 75 years or older at surgery had lower survival rates than younger patients (44.6% vs 74.6%, P Conclusions HRQOL and function improved from before to 10 years after cardiac surgery, also for older patients. These long-term results are of major importance when discussing the use of health care resources and patient-centered clinical decision-making.