Evaluation of Thromboelastography 6s prognostication of fibrinogen supplementation in pediatric cardiac surgery.

BACKGROUND: Implementation of point-of-care tests is recommended to provide tailored substitution during cardiac surgery. The measurement and substitution of fibrinogen have gained particular interest since it is the first coagulation factor to become depleted during cardiac surgery. However, the prognostic ability of thromboelastography (TEG) 6s has not been evaluated in pediatric patients. The aim of the present study was to describe patient characteristics of infants receiving fibrinogen substitution during cardiac surgery and evaluate the prognostic ability of TEG6s after weaning off cardiopulmonary bypass (CPB). METHODS: Infants undergoing congenital cardiac surgery with CPB were retrospectively included (n = 279) between January 2017 to July 2019. Patient and perioperative data were collected on the day of surgery until 6:00 AM the next morning. Hemostatic capacity was assessed with TEG6s. The efficacy of TEG-functional fibrinogen-maximal amplitude (TEG-FF-MA) measurements for the prediction of intraoperative bleeding, and thereby cryoprecipitate need, was evaluated by a sensitivity and specificity analysis. RESULTS: Among 174 children with TEG-FF-MA data, 147 (84%) received cryoprecipitate intraoperatively. Cryoprecipitate administration was associated with younger age 66 (10-132) versus 98 (45-204) days (p = .044), higher RACHS-1 classification, and intraoperative bleeding 21 (11-47) versus 5 (3-13) ml/kg (p < .001, mean difference 29 ml/kg [CI: 8-50]). Median TEG-FF-MA values were lower in transfused children 7.6 (5.3-11.0) versus 10.5 (7.3-13.4) mm (p = .004, mean difference - 2.4 mm [CI: -4.1 to - 0.73]). The volume of cryoprecipitate was associated with bypass time, TEG-FF-MA values, and in particular intraoperative bleeding volumes. A TEG-FF-MA threshold of 10.0 mm, resulted in sensitivity: 74%, specificity: 56%, positive predictive value: 80%, and a negative predictive value of 47% for the prediction of intraoperative bleeding (>10 ml/kg) and consequently a need of cryoprecipitate transfusion. CONCLUSION: Fibrinogen substitution in infants was associated with younger age and higher RACHS-1 category. The prognostic value of TEG6s was evaluated, and cryoprecipitate transfusion was related to TEG-FF-MA values, but also CPB-time, surgical complexity, and in particular excessive intraoperative bleeding. A clear-cut threshold for TEG-FF-MA is difficult to establish in infants undertaken congenital heart surgery.

Ethics in extracorporeal life support: a narrative review.

During 50 years of extracorporeal life support (ECLS), this highly invasive technology has left a considerable imprint on modern medicine, and it still confronts researchers, clinicians and policymakers with multifarious ethical challenges. After half a century of academic discussion about the ethics of ECLS, it seems appropriate to review the state of the argument and the trends in it. Through a comprehensive literature search on PubMed, we identified three ethical discourses: (1) trials and evidence accompanying the use of ECLS, (2) ECLS allocation, decision-making and limiting care, and (3) death on ECLS and ECLS in organ donation. All included articles were carefully reviewed, arguments extracted and grouped into the three discourses. This article provides a narrative synthesis of these arguments, evaluates the opportunities for mediation and substantiates the necessity of a shared decision-making approach at the limits of medical care.

Five-Year Clinical and Echocardiographic Outcomes From the NOTION Randomized Clinical Trial in Patients at Lower Surgical Risk.

BACKGROUND: The NOTION trial (Nordic Aortic Valve Intervention) was designed to compare transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) in patients ≥70 years old with isolated severe aortic valve stenosis. Clinical and echocardiographic outcomes are presented after 5 years. METHODS: Patients were enrolled at 3 Nordic centers and randomized 1:1 to TAVR using the self-expanding CoreValve prosthesis (n=145) or SAVR using any stented bioprostheses (n=135). The primary composite outcome was the rate of all-cause mortality, stroke, or myocardial infarction at 1 year defined according to Valve Academic Research Consortium-2 criteria. RESULTS: Baseline characteristics were similar. The mean age was 79.1±4.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 3.0%±1.7%. After 5 years, there were no differences between TAVR and SAVR in the composite outcome (Kaplan-Meier estimates 38.0% versus 36.3%, log-rank test P=0.86) or any of its components. TAVR patients had larger prosthetic valve area (1.7 cm2 versus 1.2 cm2, P<0.001) with a lower mean transprosthetic gradient (8.2 mm Hg versus 13.7 mm Hg, P<0.001), both unchanged over time. More TAVR patients had moderate/severe total aortic regurgitation (8.2% versus 0.0%, P<0.001) and a new pacemaker (43.7% versus 8.7%, P<0.001). Four patients had prosthetic reintervention and no difference was found for functional outcomes. CONCLUSIONS: These are currently the longest follow-up data comparing TAVR and SAVR in lower risk patients, demonstrating no statistical difference for major clinical outcomes 5 years after TAVR with a self-expanding prosthesis compared to SAVR. Higher rates of prosthetic regurgitation and pacemaker implantation were seen after TAVR. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01057173.

Accepting the avoidable death: The philosophy of limiting intensive care.

Limiting intensive care is paid increasing attention. In the echoing call for physicians' ethical self-restriction, it is easily overlooked, however, that ethics needs a critical epistemological analysis before it can suffice as an emergency brake to futile treatment. This analysis is provided by the present essay. The authors suggest that the difficulties of resolving moral dilemmas related to limiting intensive care may just be due to the unclarified epistemological status of moral claims. Even if normative ethics cannot prescribe right decisions, but only draw conclusions from defined premises, the premises may or may not be true. Their intertwined descriptive and normative evidence is endorsed in an academic and political discourse. There will necessarily be various demands for rationality in prudent decisions between physicians, their patients and society. These demands are formulated dialogically through critical questions and justified answers. A good argument is the convincing one that, finally and ideally, leads to the absence of open objections. Thus, in the end the rightness of a given decision does not depend on axiomatic moral principles, but is comparative and conditional, as it is given in an omnilateral argument. Neither is it the democratic process of shared decision making that we should evaluate, but rather the argumentative state itself, when we judge the morality of health politics and clinical practice.

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Valve Stenosis: 1-Year Results From the All-Comers NOTION Randomized Clinical Trial.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an option in certain high-risk surgical patients with severe aortic valve stenosis. It is unknown whether TAVR can be safely introduced to lower-risk patients. OBJECTIVES: The NOTION (Nordic Aortic Valve Intervention Trial) randomized clinical trial compared TAVR with surgical aortic valve replacement (SAVR) in an all-comers patient cohort. METHODS: Patients ≥ 70 years old with severe aortic valve stenosis and no significant coronary artery disease were randomized 1:1 to TAVR using a self-expanding bioprosthesis versus SAVR. The primary outcome was the composite rate of death from any cause, stroke, or myocardial infarction (MI) at 1 year. RESULTS: A total of 280 patients were randomized at 3 Nordic centers. Mean age was 79.1 years, and 81.8% were considered low-risk patients. In the intention-to-treat population, no significant difference in the primary endpoint was found (13.1% vs. 16.3%; p = 0.43 for superiority). The result did not change in the as-treated population. No difference in the rate of cardiovascular death or prosthesis reintervention was found. Compared with SAVR-treated patients, TAVR-treated patients had more conduction abnormalities requiring pacemaker implantation, larger improvement in effective orifice area, more total aortic valve regurgitation, and higher New York Heart Association functional class at 1 year. SAVR-treated patients had more major or life-threatening bleeding, cardiogenic shock, acute kidney injury (stage II or III), and new-onset or worsening atrial fibrillation at 30 days than did TAVR-treated patients. CONCLUSIONS: In the NOTION trial, no significant difference between TAVR and SAVR was found for the composite rate of death from any cause, stroke, or MI after 1 year. (Nordic Aortic Valve Intervention Trial [NOTION]; NCT01057173).

Multimodal analgesia versus traditional opiate based analgesia after cardiac surgery, a randomized controlled trial.

BACKGROUND: To evaluate if an opiate sparing multimodal regimen of dexamethasone, gabapentin, ibuprofen and paracetamol had better analgesic effect, less side effects and was safe compared to a traditional morphine and paracetamol regimen after cardiac surgery. METHODS: Open-label, prospective randomized controlled trial. 180 patients undergoing cardiac procedures through median sternotomy, were included in the period march 2007-August 2009. 151 patients were available for analysis. Pain was assessed with the 11-numeric rating scale (11-NRS). RESULTS: Patients in the multimodal group demonstrated significantly lower average pain scores from the day of surgery throughout the third postoperative day. Extensive nausea and vomiting, was found in no patient in the multimodal group but in 13 patients in the morphine group, p < 0.001. Postoperative rise in individual creatinine levels demonstrated a non-significant rise in the multimodal group, 33.0±53.4 vs. 19.9±48.5, p = 0.133. Patients in the multimodal group suffered less major in-hospital events in crude numbers: myocardial infarction (MI) (1 vs. 2, p = 0.54), stroke (0 vs. 3, p = 0.075), dialysis (1 vs. 2, p = 0.54), and gastrointestinal (GI) bleeding (0 vs. 1, p = 0.31). 30-day mortality was 1 vs. 2, p = 0.54. CONCLUSIONS: In patients undergoing cardiac surgery, a multimodal regimen offered significantly better analgesia than a traditional opiate regimen. Nausea and vomiting complaints were significantly reduced. No safety issues were observed with the multimodal regimen. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01966172.

The Nordic aortic valve intervention (NOTION) trial comparing transcatheter versus surgical valve implantation: study protocol for a randomised controlled trial.

BACKGROUND: Degenerative aortic valve (AV) stenosis is the most prevalent heart valve disease in the western world. Surgical aortic valve replacement (SAVR) has until recently been the standard of treatment for patients with severe AV stenosis. Whether transcatheter aortic valve implantation (TAVI) can be offered with improved safety and similar effectiveness in a population including low-risk patients has yet to be examined in a randomised setting. METHODS/DESIGN: This randomised clinical trial will evaluate the benefits and risks of TAVI using the transarterial CoreValve System (Medtronic Inc., Minneapolis, MN, USA) (intervention group) compared with SAVR (control group) in patients with severe degenerative AV stenosis. Randomisation ratio is 1:1, enrolling a total of 280 patients aged 70 years or older without significant coronary artery disease and with a low, moderate, or high surgical risk profile. Trial outcomes include a primary composite outcome of myocardial infarction, stroke, or all-cause mortality within the first year after intervention (expected rates 5% for TAVI, 15% for SAVR). Exploratory safety outcomes include procedure complications, valve re-intervention, and cardiovascular death, as well as cardiac, cerebral, pulmonary, renal, and vascular complications. Exploratory efficacy outcomes include New York Heart Association functional status, quality of life, and valve prosthesis and cardiac performance. Enrolment began in December 2009, and 269 patients have been enrolled up to December 2012. DISCUSSION: The trial is designed to evaluate the performance of TAVI in comparison with SAVR. The trial results may influence the choice of treatment modality for patients with severe degenerative AV stenosis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01057173.

[Percutaneous aortic valve replacement - initial experience and results]. / Perkutan indsaettelse af aortaklap - initiale erfaringer og resultater.

INTRODUCTION: Aortic stenosis (AS) is the most common heart valvular disease and with progressive disease morbidity and mortality are substantial. The standard treatment in symptomatic patients is surgical valve replacement. However, one third of the patients with severe AS are inoperable due to advanced age and comorbidity. The aim of this study was to evaluate the results of percutaneous aortic valve replacement - a new treatment modality for patients with inoperable AS. MATERIAL AND METHODS: A total of 20 patients were treated with CoreValve ReValving System valve prosthesis at the Copenhagen University Hospital in the period November 2007 to September 2008. RESULTS: The procedural success was 100% and 30-day mortality was 5%, none of which was due to cardiac death. The treatment resulted in a considerable relief of symptoms. The aortic valve area showed a significant increase from 0.8 +/- 0.2 cm(2) to 1.9 +/- 0.6 cm(2) (p < 0.01). There was a significant decrease in the peak pressure gradient across the aortic valve from 75 +/- 38 mm Hg to 18 +/- 8 mm Hg (p < 0.01). Permanent pacemaker due to AV block was the most common complication with an incidence of 25% during the 30-day follow-up. CONCLUSION: Implantation of a percutaneous aortic valve can be achieved in patients with inoperable AS and may become a very important therapeutic modality for this group of patients. These first results from Copenhagen University Hospital are promising and in concordance with international experience.

[Transcatheter replacement of the aortic valve--a novel treatment modality for high-risk patients]. / Transkateterindsaettelse af aortaklap--en ny behandlingsmodalitet til højrisikopatienter.

Aortic stenosis is the most common valve disease and in line with the rising life expectancy, the population of patients with this disease is expected to rise in years to come. About one third of the patients evaluated for conventional surgical replacement of the aortic valve are dismissed due to high risk of complication as a result of age and occurrence of comorbidity. For this group of inoperable patients, a new treatment can be offered in the form of transcatheter replacement of the aortic valve. This article describes the method and the current experiences.

Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery.

OBJECTIVES: Cardiac surgery and cardiopulmonary bypass (CPB) induce an inflammatory reaction that may lead to tissue injury. Experimental studies suggest that recombinant human erythropoietin (EPO) independent of its erythropoietic effect may be used clinically as an anti-inflammatory drug. This study tested the hypothesis that 2 large doses of EPO administered shortly before CPB ameliorate the systemic inflammatory response to CPB. DESIGN AND SETTING: A prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital. PARTICIPANTS: Patients scheduled for coronary artery bypass graft surgery with CPB. INTERVENTIONS: EPO (epoetin alfa, 500 IU/kg intravenously, n = 22) or placebo (n = 21) was administered 12 to 18 hours preoperatively and again at the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: CPB in both groups greatly increased plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-1beta receptor antagonist, IL-6, IL-10, and N-terminal probrain natriuretic peptide (NT-proBNP). Compared with placebo, EPO at day 3 after CPB augmented the TNF-alpha response (p < 0.05) and at 2 hours after CPB increased NT-proBNP (p < 0.05). Also, EPO tended to enhance the CPB-induced increase in IL-1beta receptor antagonist (p = 0.057). Otherwise, EPO had no effect on pro- and antiinflammatory mediators compared with placebo. CONCLUSIONS: Two large doses of EPO given shortly before CPB do not reduce perioperative release of inflammatory cytokines. In contrast, EPO may augment the TNF-alpha and NT-proBNP response. Although the long-term clinical impact remains unknown, the findings do not support use of EPO as an anti-inflammatory drug in patients undergoing cardiac surgery.

The Best Bypass Surgery Trial: rationale and design of a randomized clinical trial with blinded outcome assessment of conventional versus off-pump coronary artery bypass grafting.

BACKGROUND: Recent trials suggest that off-pump coronary artery bypass grafting (OPCAB) reduces the risk of mortality and morbidity compared with conventional coronary artery bypass grafting (CCAB) using cardiopulmonary bypass. Patients with a moderate- to high-risk of complications after CCAB may have additional benefit from OPCAB. METHODS: The Best Bypass Surgery Trial is a randomized, single center trial comparing the effects of OPCAB versus CCAB. The inclusion criteria are 3 vessel coronary heart disease affecting one of the marginal arteries, age>54 years, and EuroSCORE>or=5. The primary composite outcome measure consists of all-cause mortality, myocardial infarction, stroke, cardiac arrest, cardiogenic shock, and cardiac revascularization procedure. Follow up involves collection of data of mortality and morbidity via linkage to public registers, quality of life assessment at 3 and 12 months postoperatively and angiographic control at 12 months. The sample size of 330 patients was based on an estimated 75% one-year event free rate of the primary outcome measure in the OPCAB arm and 60% in the control arm with alpha=.05 and beta=.20. Accordingly, the trial will be able to detect an absolute risk reduction of 15% or a relative risk reduction of 37.5%. The median follow-up time is scheduled to 3 years. RESULTS: Enrollment started in April 2002 and ended March 2006. CONCLUSION: The results may have implications on the treatment modality of moderate- to high-risk patients scheduled for coronary artery bypass grafting.

Acute fatal pulmonary vein occlusion after catheter ablation of atrial fibrillation.

BACKGROUND: In treatment of atrial fibrillation (AF) catheter radiofrequency isolation of the pulmonary veins (PVs) has proved to be highly successful. There have been several case reports regarding PV stenosis, however none of these have reported a fatal outcome. METHODS AND RESULTS: A 31-year-old man was referred to us for treatment of complications related to catheter ablation. According to the documentation from the hospital, the patient underwent segmental ostial PV isolation for treatment of AF. A few hours after the procedure, the patient developed dyspnoea, hemoptysis, and a high fever. The patient was first diagnosed as having pneumonia but five days later transesophageal echocardiography and pulmonal angiography revealed total occlusion of the left superior and inferior PVs. When we received the patient he underwent open-heart surgery, which showed thrombi in the orifices of the left sided PVs protruding into the left atrium. In each of the left sided PVs severe stenosis was seen in the bifurcation area. Thrombus material was removed followed by placement of two stents in each of the left sided pulmonary veins at the first bifurcations. However, the patient died 14 days after the ablation procedure. Selective autopsy of the left lung revealed diffuse alveolar damage, disseminated intravascular coagulation, multiple thrombi formation, and haemorrhagic infarctions. CONCLUSIONS: PV stenosis may occur very early after the ablation procedure. Delayed diagnosis can be fatal. The early stenosis may result in thrombus formation in the left atrium and PVs and in this case surgery should be considered.