Mortality and reoperations in survivors operated on for acute type A aortic dissection and implications for catheter-based or hybrid interventions.

OBJECTIVE: This study investigated late outcomes (mortality, reoperations) and their associated predictors after operations for acute type A aortic dissection. The role catheter-based and hybrid interventions is discussed. METHODS: All hospital survivors operated on for acute type A aortic dissection from 1990 through 2009 were reviewed, with cross-sectional follow-up. Mortality (overall and aortic) and freedom from reoperations (proximal and distal) were estimated using actuarial methods. Preoperative, intraoperative, and postoperative variables (n = 44) associated with late outcomes were analyzed with univariable and multivariable (Cox) statistical methods. RESULTS: Of 360 operated-on patients, 291 hospital survivors (81%) were monitored for a median of 5.5 years (1864 patient-years). Total late mortality was 30% (n = 86), with estimated (standard error) survival of 82% (3%), 64% (4%), and 48% (6%) at 5, 10, and 15 years, respectively. Aortic events accounted for at least 27% (up to 42% including unknown causes) of late deaths. In Cox analysis, variables independently related (hazard ratios [95% confidence limits]) to late mortality were increased age (1.6 per 10 years [1.3, 2.0]), earlier operation (<2005; 2.3 [1.2, 4.6]), permanent neurologic damage (2.6 [1.6, 4.2]), and respiratory insufficiency (3.4 [1.8, 6.4]). Thirty-four patients underwent 46 reoperations, 21 on the proximal and 25 on the distal aorta, up to 19 years after the primary operation; respective in-hospital reoperative mortality was 14% and 12%. Estimated freedom (standard error) from aortic reoperation was 95% (2%), 87% (4%), and 61% (5%) at 5, 10, and 15 years, respectively. In multivariable Cox analysis (hazard ratios [95% confidence limits]), use of surgical adhesive at the primary operation (4.2 [1.6, 11]) and temporary neurologic damage (3.2l [1.2, 8.9]) were independently related to proximal reoperation, and DeBakey type I dissection (10.5 [1.4, 80]) was related to late distal reoperation. Catheter-based (endovascular, percutaneous) or hybrid procedures were not used in any patients but could have been used in up to 74% of reoperations, including in four of six of those that resulted in in-hospital death and putatively in 10 of 17 patients who sustained lethal aortic events without reoperation. CONCLUSIONS: Despite close follow-up, aortic-related death after a successful operation for acute type A aortic dissection is prevalent, and overall mortality remains substantial. Reoperations are not uncommon, may be indicated very late as well as repeatedly in the same patient, and are associated with a significant mortality. Increased use of applicable but seemingly under-used catheter-based or hybrid treatment approaches could benefit this growing patient population by offering repeat intervention to more patients and as substitute for reoperative open surgery in selected cases.

Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE) study.

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10(-27 and-30)). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2-deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research.

Deep hypothermia and aortic regurgitation without left ventricular venting, an animal model.

OBJECTIVE: Omitting ventricular decompression in resternotomy during cardiopulmonary bypass with deep hypothermia and circulatory arrest in patients with aortic regurgitation (AR) has recently been reported. The consequences of the dilated and non-dilated heart in conjunction with rapid and profound cooling were further studied in this randomized animal model. METHODS: In five pigs (group A) AR was induced before cooling to 15°C and circulatory arrest of 30 minutes without left ventricular decompression. The animals were rewarmed with a competent valve, and weaning off bypass was attempted. In another five pigs (group B) the protocol was repeated with left ventricular decompression. Hemodynamics and the extent of myocardial infarction were evaluated. RESULTS: During cooling in group A mean arterial and left atrial pressures were equalized and all animals suffered massive pulmonary edema. Only one animal could be weaned off bypass. The remaining four suffered considerable biventricular failure and succumbed when weaned off bypass. The animals in group B were stable throughout the experiment and easily weaned off bypass. Myocardial infarction was significantly more extensive in group A, 22 (6-36)% of left ventricular area, compared to group B; 3 (3-11)%, p = 0.016. CONCLUSIONS: In our experimental model aortic regurgitation without left ventricular venting in deep hypothermia and circulatory arrest has damaging effects on the myocardium.

Resternotomy using hypothermic arrest.

BACKGROUND: Resternotomy during closed chest cardiopulmonary bypass in hypothermia with or without circulatory arrest has been the preferred method for cardiac reoperations with adherent structures to the sternum. Here, we report our experience with this method and the effects of omitting ventricular decompression during the cooling procedure. METHODS: Twenty reoperations were performed in 19 patients. In half (n = 10) of the procedures aortic regurgitation was present. Cardiopulmonary bypass was instituted in all patients before resternotomy, and the re-entry into the chest was performed either under hypothermic low-flow cardiopulmonary bypass or circulatory arrest. The reason for this choice of technique was adherent structures to the sternum posing a substantial risk for rupture during resternotomy in all patients. RESULTS: Rupture upon re-entry into the chest occurred in five operations. No patient died due to re-entry injury. The overall hospital mortality was 15%. No differences in postoperative outcomes including heart failure, biochemical markers indicating myocardial damage, and three-month follow-up assessment of cardiac function were found between patients with aortic regurgitation and patients without aortic regurgitation. CONCLUSIONS: Based on our experience, omitting ventricular decompression in resternotomy in hypothermia and arrested circulation or low-flow cardiopulmonary bypass can be safely used, and the presence of aortic regurgitation does not seem to influence the outcome.

Management of the emergency response to the SARS-CoV-2 (COVID-19) outbreak in Stockholm, Sweden, and winter preparations.

INTRODUCTION Sweden is unique in adopting a 'no-lockdown' public health approach to the SARS-CoV-2 (COVID-19) outbreak. There were fears that health services would not be able to care for high numbers of COVID-19 patients. AIM To describe and review the emergency response of a public primary and community health-care organisation in Stockholm, Sweden, to the demand for care for COVID-19 and non-COVID-19 patients during March-July 2020, and summarise preparations for the months to follow. METHODS This was a rapid implementation action research case study, which also draws on one author's experience as Chief Executive Officer and other members' experience in an emergency management group. RESULTS Sweden experienced similar mortality per million population to the UK, despite the different public health strategy used to address the COVID-19 outbreak. The Stockholm-integrated public primary and community health-care service, serving a population of 2.3 million, made many changes quickly. One change included coordinating non-acute private health-care services, following the local government emergency directive to do so. DISCUSSION It is possible that the fast and effective response by management and services in primary and community health care reduced infection and hospital demand, which contributed to a lower mortality than otherwise expected. The actions and preparations described for Stockholm's response may provide ideas for other health-care systems. The partnership research approach between the Karolinska Medical University and the Region Stockholm health-care system used in this project shows that rapid research methods have advantages for both partners in an emergency situation.

Guideline on antiplatelet and anticoagulation management in cardiac surgery.

This document presents a professional view of evidence-based recommendations around the issues of antiplatelet and anticoagulation management in cardiac surgery. It was prepared by the Audit and Guidelines Committee of the European Association for Cardio-Thoracic Surgery (EACTS). We review the following topics: evidence for aspirin, clopidogrel and warfarin cessation prior to cardiac surgery; perioperative interventions to reduce bleeding including the use of aprotinin and tranexamic acid; the use of thromboelastography to guide blood product usage; protamine reversal of heparin; the use of factor VIIa to control severe bleeding; anticoagulation after mechanical, tissue valve replacement and mitral valve repair; the use of antiplatelets and clopidogrel after cardiac surgery to improve graft patency and reduce thromboembolic complications and thromboprophylaxis in the postoperative period. This guideline is subject to continuous informal review, and when new evidence becomes available. The formal review date will be at 5 years from publication (September 2013).

Splanchnic metabolism during gut ischemia and short-term endotoxin and hemorrhagic shock as evaluated by intravasal microdialysis.

The splanchnic area is of considerable interest in different types of shock. To characterize the metabolic changes in the splanchnic region in response to different types of shock we used a model where shock-induced metabolic changes in the splanchnic region were studied by the use of intravasal microdialysis. 23 anesthetized domestic pigs were randomized into four groups: Group I, serving as controls (n = 5); Group II, mesenteric ischemia for 180 followed by 120 min of reperfusion (n = 5); Group III, endotoxin shock for 5 h (n = 5); and Group IV, hemorrhagic shock for 180 min followed by re-transfusion of shed blood (n = 8). Microdialysis catheters were placed in the left femoral artery, portal vein and a small ileal mesenteric vein. Samples of the perfusate were continuously collected in micro-vials and analyzed for glucose, lactate, pyruvate and glycerol. In gut ischemia and endotoxin shock the outflow-pattern of lactate, lactate/pyruvate ratio and glucose in the mesenteric vein differed significantly from controls and hemorrhage whereas an increase in glycerol was only noted in the ischemic group. The most prominent differences were detected in lactate/pyruvate ratio, a marker of tissue ischemia with the most pronounced changes during mesenteric ischemia/reperfusion. During endotoxin shock increases in microdialysate metabolites were only noted in the splanchnic region suggesting a specific vulnerability in the region. Studying the lactate/pyruvate ratio may provide additional information when interpreting increased blood lactate levels. In addition glycerol may prove to be a useful marker of splanchnic ischemia. Intravasal microdialysis represents a potentially useful method for monitoring regional metabolic events.

Cardiac outflow of amino acids and purines during myocardial ischemia and reperfusion.

A novel application of microdialysis was studied, in which myocardial outflow of amino acids and purines was monitored by intravasal microdialysis in the myocardial venous outflow during ischemia and reperfusion. Microdialysis catheters were introduced into the great cardiac vein, pulmonary artery, and external jugular vein in 20 anesthetized pigs. The left anterior descending artery was occluded in four groups of pigs for 0, 10, 15, and 60 min. Ischemia was followed by 120 min of reperfusion. Microdialysis samples were analyzed for taurine, aspartate, glutamate, hypoxanthine, inosine, and guanosine. Myocardial infarction developed when ischemia exceeded 10 min. Taurine, aspartate, inosine, and guanosine increased early in the great cardiac vein during ischemia. We found the outflow patterns of amino acids and purines to be graded in response to different lengths of ischemia. In this study we have demonstrated a graded outflow of amino acids and purines in response to ischemia and a positive correlation between infarct size and myocardial outflow of amino acids and purines. This could be of value in a clinical setting to quantify the extent of myocardial damage.

Is there a role for endothelin-blockade early after coronary artery bypass grafting?

BACKGROUND: Diverse results exist regarding myocardial release of endothelin after coronary artery bypass grafting. Because endothelin may be involved in regulation of coronary blood flow, postoperative endothelin-blockade could influence the surgical outcome. In this study, we have evaluated the cardiac outflow of endothelin and effects on coronary flow by endothelin-blockade immediately after completion of the coronary bypass grafting. METHODS: Thirty patients were subjected to infusions of endothelinA blocker (BQ-123, 260 nmoL/min for up to 30 minutes) or endothelinA blocker and endothelinB blocker (BQ-123 and BQ-788, 260 and 250 nmol/min, respectively, for up to 30 minutes) into a veingraft anastomosed to a coronary vessel, and the coronary blood flow was measured. Plasma levels of endothelin from the coronary sinus and the periphery were determined. RESULTS: There were no significant changes in flow caused by endothelinA blockade alone or in combination with endothelinB blockade. There were no immediately increased levels of endothelin after surgery or after infusions of the endothelin blockers. CONCLUSIONS: Endothelin blockade does not influence the immediate perioperative myocardial blood flow after coronary bypass grafting. There is no significantly increased myocardial outflow of endothelin, and endothelin does not have any influence on the basal tone of the coronary vessels in the early phase after coronary bypass grafting.

Plasma levels and vascular effects of endothelin and big endothelin in patients with stable and unstable angina pectoris undergoing coronary bypass grafting.

OBJECTIVES: The aim of this study was to determine the plasma and pericardial levels of endothelin-1 (ET-1) and its precursor big endothelin-1 (Big ET-1) in patients with unstable and stable angina prior to and following coronary bypass surgery. To further investigate the content of ET-1, tissue levels were studied in the internal mammary artery (IMA) in patients with stable and unstable angina pectoris. Finally, the difference in reactivity of the IMA to ET-1 and Big ET-1 in stable and unstable patients was evaluated. METHODS: Plasma and pericardial levels of ET-1 and Big ET-1 were determined with radioimmunoassay in 81 patients (33 unstable) immediately before coronary bypass surgery, and at 6, 14, 40 and 64 h following the procedure. Specimens of the distal IMA from 12 patients (six unstable) were collected at the beginning of surgery for determination of tissue levels of ET-1. Additionally, distal internal mammary arteries were obtained from another 24 patients (12 unstable). These vessels were mounted in organ baths for functional studies on vascular reactivity to ET-1 and Big ET-1. RESULTS: The peripheral plasma levels of ET-1 in unstable patients were significantly lower in patients with unstable angina compared with patients with stable angina pectoris at all points of measurement. The levels of Big ET-1 were significantly higher pre-operatively in the unstable group, but decreased to similar levels to those of stable patients following coronary bypass grafting. There was no difference in ET-1 tissue content in the IMA between the patients. ET-1 and Big ET-1 caused an endothelin(A) (ET(A))-receptor blocker sensitive, concentration-dependent contraction of the IMA obtained from stable as well as unstable patients. CONCLUSIONS: It is concluded that unstable angina pectoris is associated with an increased ET-1 turnover. This increased turnover may participate in the local regulation of coronary vascular tone with subsequent influence of the condition of the patients. The present investigation also implies that ET(A)-blockade may be useful as an additional pharmacological principal in the treatment of unstable angina pectoris prior to revascularization, as well as to prevent post-operative arterial graft spasm.

Guideline for the surgical treatment of atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and its prevalence is ∼1-2% of the general population, but higher with increasing age and in patients with concomitant heart disease. The Cox-maze III procedure was a groundbreaking development and remains the surgical intervention with the highest cure rate, but due to its technical difficulty alternative techniques have been developed to create the lesions sets. The field is fast moving and there are now multiple energy sources, multiple potential lesion sets and even multiple guidelines addressing the issues surrounding the surgical treatment of AF both for patients undergoing this concomitantly with other cardiac surgical procedures and also as stand-alone procedures either via sternotomy or via videothoracoscopic techniques. The aim of this document is to bring together all major guidelines in this area into one resource for clinicians interested in surgery for AF. Where we felt that guidance was lacking, we also reviewed the evidence and provided summaries in those areas. We conclude that AF surgery is an effective intervention for patients with all types of AF undergoing concomitant cardiac surgery to reduce the incidence of AF, as demonstrated in multiple randomized studies. There is some evidence that this translates into reduced stroke risk, reduced heart failure risk and longer survival. In addition, symptomatic patients with AF may be considered for surgery after failed catheter intervention or even as an alternative to catheter intervention where either catheter ablation is contraindicated or by patient choice.

EuroSCORE II.

OBJECTIVES: To update the European System for Cardiac Operative Risk Evaluation (EuroSCORE) risk model. METHODS: A dedicated website collected prospective risk and outcome data on 22,381 consecutive patients undergoing major cardiac surgery in 154 hospitals in 43 countries over a 12-week period (May-July 2010). Completeness and accuracy were validated during data collection using mandatory field entry, error and range checks and after data collection using summary feedback confirmation by responsible officers and multiple logic checks. Information was obtained on existing EuroSCORE risk factors and additional factors proven to influence risk from research conducted since the original model. The primary outcome was mortality at the base hospital. Secondary outcomes were mortality at 30 and 90 days. The data set was divided into a developmental subset for logistic regression modelling and a validation subset for model testing. A logistic risk model (EuroSCORE II) was then constructed and tested. RESULTS: Compared with the original 1995 EuroSCORE database (in brackets), the mean age was up at 64.7 (62.5) with 31% females (28%). More patients had New York Heart Association class IV, extracardiac arteriopathy, renal and pulmonary dysfunction. Overall mortality was 3.9% (4.6%). When applied to the current data, the old risk models overpredicted mortality (actual: 3.9%; additive predicted: 5.8%; logistic predicted: 7.57%). EuroSCORE II was well calibrated on testing in the validation data subset of 5553 patients (actual mortality: 4.18%; predicted: 3.95%). Very good discrimination was maintained with an area under the receiver operating characteristic curve of 0.8095. CONCLUSIONS: Cardiac surgical mortality has significantly reduced in the last 15 years despite older and sicker patients. EuroSCORE II is better calibrated than the original model yet preserves powerful discrimination. It is proposed for the future assessment of cardiac surgical risk.

EACTS guidelines for the use of patient safety checklists.

The Safety Checklist concept has been an integral part of many industries that face high-complexity tasks for many decades and in industries such as aviation and engineering checklists have evolved from their very inception. Investigations of the causes of surgical deaths around the world have repeatedly pointed to medical errors that could be prevented as an important cause of death and disability. As a result, the World Health Organisation developed and evaluated a three-stage surgical checklist in 2007 demonstrating that complications were significantly reduced, including surgical infection rates and even mortality. Together with the results from other large cohort studies into the utility of the surgical checklist, many countries have fully implemented the use of surgical checklists into routine practice. A key factor in the successful implementation of a surgical checklist is engagement of the staff implementing the checklist. In surgical specialties such as our own it was quickly seen that there were many important omissions in the generic checklist that did not cover issues particular to our specialty, and thus the European Association for Cardio-Thoracic Surgery embarked on a process to create a version of the checklist that might be more appropriate and specific to cardiothoracic surgery, including checks on preparations for excessive bleeding, perfusion arrangements and ICU preparations, for example. The guideline presented here summarizes the evidence for the surgical checklist and also goes through in detail the changes recommended for our specialty.

Mortality in acute type A aortic dissection: validation of the Penn classification.

BACKGROUND: Intraoperative and in-hospital mortality after surgery for acute type A dissection depends largely on preoperative conditions, specifically the presence of localized or generalized ischemia. Recently, the Penn classification of patients with acute type A aortic dissection has been described. The primary aim was to validate the Penn classification and to investigate preoperative variables related to mortality. METHODS: All consecutive patients operated for acute type A aortic dissection, 1990 to 2009 (n = 360), were included in a retrospective observational study. Univariate and multivariable analyses were used to identify variables related to intraoperative and in-hospital mortality. Propensity scoring was used to adjust for treatment selection bias. RESULTS: Overall intraoperative mortality was 7% (24 of 360) and in-hospital mortality was 19% (69 of 360). Two hundred nineteen patients (61%) were Penn class Aa (14% in-hospital mortality), 51 (14%) class Ab (24% mortality), 63 (18%) class Ac (24% mortality), and 27 (8%) class Abc (44% mortality), p =0.007. In multivariable analysis, Penn class Ac and Abc were independently related to intraoperative death (odds ratio 5.0 and 5.4, respectively), and Penn class Abc and non-Aa were independently related to in-hospital mortality (odds ratio 3.4 and 2.3, respectively). Concomitant coronary artery bypass grafting, older age, DeBakey type I dissection, and prolonged periods of cardiopulmonary bypass and hypothermic circulatory arrest were also independently associated with mortality. CONCLUSIONS: The Penn classification of acute type A aortic dissection is purposeful and its continued usage encouraged. Penn class indicating localized or generalized ischemia is independently related to intraoperative and in-hospital mortality.

Guideline for resuscitation in cardiac arrest after cardiac surgery.

The Clinical Guidelines Committee of the European Association for Cardio-Thoracic Surgery provides this professional view on resuscitation in cardiac arrest after cardiac surgery. This document was created using a multimodal methodology for evidence generation including the extrapolation of existing guidelines from the International Liaison Committee on Resuscitation where possible, our own structured literature reviews on issues particular to cardiac surgery, an international survey on resuscitation hosted by CTSNet and manikin simulations of potential protocols. This protocol differs from existing generic guidelines in a number of areas, the most import of which are the following: successful treatment of cardiac arrest after cardiac surgery is a multi-practitioner activity with six key roles that should be allocated and rehearsed on a regular basis; in ventricular fibrillation, three sequential attempts at defibrillation (where immediately available) should precede external cardiac massage; in asystole or extreme bradycardia, pacing (where immediately available) should precede external cardiac massage; where the above measures fail, and in pulseless electrical activity, early resternotomy is advocated; adrenaline should not be routinely given; protocols for excluding reversible airway and breathing complications and for safe emergency resternotomy are given. This guideline is subject to continuous informal review, and when new evidence becomes available.

If a patient arrests after cardiac surgery is it acceptable to delay cardiopulmonary resuscitation until you have attempted either defibrillation or pacing?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether it is acceptable to delay cardiopulmonary resuscitation if a patient arrests after cardiac surgery in order to attempt defibrillation or pacing, prior to performing external cardiac massage. Altogether 550 papers were found in Medline and 990 in Embase using the reported search, of which 22 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that current resuscitation guidelines state that there is no evidence to support or refute external cardiac massage prior to defibrillation in-hospital, although a benefit has been shown for patients out-of-hospital if the response time is over 4-5 min. In addition, four large studies including the AHA National Registry of Cardiopulmonary Resuscitation, who reported the findings of 6789 in-hospital arrests, emphasise the importance of early defibrillation within 1-2 min. More concerning in patients post-cardiac surgery are four case reports after cardiothoracic surgery and five in the non-surgical literature where significant harm has been caused from external cardiac massage, although equally we found cohort studies of cardiac surgical patients who had external cardiac massage followed by re-sternotomy and found no trauma due to external cardiac massage. We recommend that guidelines for immediate external massage should be adhered to currently as the evidence that these guidelines may do harm is not yet strong enough to recommend a change in practice. However, we acknowledge that there are no in-hospital data to support very short periods of external massage prior to defibrillation and there have been examples of damage to the myocardium due to external massage. This should be borne in mind when external massage is being performed on a patient after cardiac surgery.