Domenico Paparella

2014 ESC/EACTS Guidelines on myocardial revascularization The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Authors/Task Force members: Stephan Windecker* (ESC Chairperson) (Switzerland), Philippe Kolh* (EACTS Chairperson) (Belgium), Fernando Alfonso (Spain), Jean-Philippe Collet (France), Jochen Cremer (Germany), Volkmar Falk (Switzerland), Gerasimos Filippatos (Greece), Christian Hamm (Germany), Stuart J. Head (The Netherlands), Peter Jüni (Switzerland), A. Pieter Kappetein (The Netherlands), Adnan Kastrati (Germany), Juhani Knuuti (Finland), Ulf Landmesser (Switzerland), Günther Laufer (Austria), Franz-Josef Neumann (Germany), Dimitrios J. Richter (Greece), Patrick Schauerte (Germany), Miguel Sousa Uva (Portugal), Giulio G. Stefanini (Switzerland), David Paul Taggart (UK), Lucia Torracca (Italy), Marco Valgimigli (Italy), William Wijns (Belgium), and Adam Witkowski (Poland).

Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update

Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that has been implicated in the pathogenesis of several postoperative complications. Recent data indicate that a complex sequence of events leads to the final activation of leukocytes and endothelial cells (EC), which is responsible for cell dysfunction in different organs. Activation of the contact system, endotoxemia, ischemia and reperfusion injury and surgical trauma are all potential triggers of inflammation following CPB. Different pro- and anti-inflammatory mediators (cytokines, adhesion molecules) are involved and their release is mediated by intracellular transcription factors (nuclear factor-kappa B, NF-kappa B). In this review, we examine recent advances in the understanding of the pathophysiology of the CPB-induced acute phase reaction and evaluate the different pharmacological, technical and surgical strategies used to reduce its effects. Emphasis is given to the central role of transcription factor NF-kappa B in the complex mechanism of the inflammatory reaction and to the effects of compounds such as heparin and glycosaminoglycans, phosphodiesterase inhibitors and protease inhibitors whose role as anti-inflammatory agent has only recently been recognized.

Coagulation disorders of cardiopulmonary bypass: a review

BackgroundPostoperative bleeding is one of the most common complications of cardiac surgery.DiscussionExtensive surgical trauma, prolonged blood contact with the artificial surface of the cardiopulmonary bypass (CPB) circuit, high doses of heparin, and hypothermia are all possible triggers of a coagulopathy leading to excessive bleeding. Platelet activation and dysfunction also occur and are caused mainly by heparin, hypothermia, and inadequate protamine administration. Heparin and protamine administration based on heparin concentrations as opposed to fixed doses may reduce coagulopathy and postoperative blood loss.ConclusionsA better comprehension of the multifactorial mechanisms of activation of coagulation, inflammation, and fibrinolytic pathways during CPB may enable a more effective use of the technical and pharmaceutical options which are currently available.

Protective versus Conventional Ventilation for Surgery: A Systematic Review and Individual Patient Data Meta-analysis.

Background:Recent studies show that intraoperative mechanical ventilation using low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs). The aim of this individual patient data meta-analysis is to evaluate the individual associations between VT size and positive end–expiratory pressure (PEEP) level and occurrence of PPC. Methods:Randomized controlled trials comparing protective ventilation (low VT with or without high levels of PEEP) and conventional ventilation (high VT with low PEEP) in patients undergoing general surgery. The primary outcome was development of PPC. Predefined prognostic factors were tested using multivariate logistic regression. Results:Fifteen randomized controlled trials were included (2,127 patients). There were 97 cases of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957 patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63 cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose–response relationship was found between the appearance of PPC and VT size (R2 = 0.39) but not between the appearance of PPC and PEEP level (R2 = 0.08). Conclusions:These data support the beneficial effects of ventilation with use of low VT in patients undergoing surgery. Further trials are necessary to define the role of intraoperative higher PEEP to prevent PPC during nonopen abdominal surgery.

Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial

BACKGROUND Cardiopulmonary bypass initiates a systemic inflammatory response syndrome that is associated with postoperative morbidity and mortality. Steroids suppress inflammatory responses and might improve outcomes in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. We aimed to assess the effects of steroids in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. METHODS The Steroids In caRdiac Surgery (SIRS) study is a double-blind, randomised, controlled trial. We used a central computerised phone or interactive web system to randomly assign (1:1) patients at high risk of morbidity and mortality from 80 hospital or cardiac surgery centres in 18 countries undergoing cardiac surgery with the use of cardiopulmonary bypass to receive either methylprednisolone (250 mg at anaesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients were assigned with block randomisation with random block sizes of 2, 4, or 6 and stratified by centre. Patients aged 18 years or older were eligible if they had a European System for Cardiac Operative Risk Evaluation of at least 6. Patients were excluded if they were taking or expected to receive systemic steroids in the immediate postoperative period or had a history of bacterial or fungal infection in the preceding 30 days. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcomes were 30-day mortality and a composite of death and major morbidity (ie, myocardial injury, stroke, renal failure, or respiratory failure) within 30 days, both analysed by intention to treat. Safety outcomes were also analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00427388. FINDINGS Patients were recruited between June 21, 2007, and Dec 19, 2013. Complete 30-day data was available for all 7507 patients randomly assigned to methylprednisolone (n=3755) and to placebo (n=3752). Methylprednisolone, compared with placebo, did not reduce the risk of death at 30 days (154 [4%] vs 177 [5%] patients; relative risk [RR] 0·87, 95% CI 0·70-1·07, p=0·19) or the risk of death or major morbidity (909 [24%] vs 885 [24%]; RR 1·03, 95% CI 0·95-1·11, p=0·52). The most common safety outcomes in the methylprednisolone and placebo group were infection (465 [12%] vs 493 [13%]), surgical site infection (151 [4%] vs 151 [4%]), and delirium (295 [8%] vs 289 [8%]). INTERPRETATION Methylprednisolone did not have a significant effect on mortality or major morbidity after cardiac surgery with cardiopulmonary bypass. The SIRS trial does not support the routine use of methylprednisolone for patients undergoing cardiopulmonary bypass. FUNDING Canadian Institutes of Health Research.

Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data.

BACKGROUND Protective mechanical ventilation strategies using low tidal volume or high levels of positive end-expiratory pressure (PEEP) improve outcomes for patients who have had surgery. The role of the driving pressure, which is the difference between the plateau pressure and the level of positive end-expiratory pressure is not known. We investigated the association of tidal volume, the level of PEEP, and driving pressure during intraoperative ventilation with the development of postoperative pulmonary complications. METHODS We did a meta-analysis of individual patient data from randomised controlled trials of protective ventilation during general anesthaesia for surgery published up to July 30, 2015. The main outcome was development of postoperative pulmonary complications (postoperative lung injury, pulmonary infection, or barotrauma). FINDINGS We included data from 17 randomised controlled trials, including 2250 patients. Multivariate analysis suggested that driving pressure was associated with the development of postoperative pulmonary complications (odds ratio [OR] for one unit increase of driving pressure 1·16, 95% CI 1·13-1·19; p<0·0001), whereas we detected no association for tidal volume (1·05, 0·98-1·13; p=0·179). PEEP did not have a large enough effect in univariate analysis to warrant inclusion in the multivariate analysis. In a mediator analysis, driving pressure was the only significant mediator of the effects of protective ventilation on development of pulmonary complications (p=0·027). In two studies that compared low with high PEEP during low tidal volume ventilation, an increase in the level of PEEP that resulted in an increase in driving pressure was associated with more postoperative pulmonary complications (OR 3·11, 95% CI 1·39-6·96; p=0·006). INTERPRETATION In patients having surgery, intraoperative high driving pressure and changes in the level of PEEP that result in an increase of driving pressure are associated with more postoperative pulmonary complications. However, a randomised controlled trial comparing ventilation based on driving pressure with usual care is needed to confirm these findings. FUNDING None.

Rationale and design of the Left Atrial Appendage Occlusion Study (LAAOS) III

BACKGROUND Occlusion of the left atrial appendage (LAA) is a promising approach to stroke prevention in atrial fibrillation (AF). However, evidence of its efficacy and safety to date is lacking. We herein describe the rationale and design of a definitive LAA occlusion trial in cardiac surgical patients with AF. METHODS We plan to randomize 4,700 patients with AF in whom on-pump cardiac surgical procedure is planned to undergo LAA occlusion or no LAA occlusion. The primary outcome is the first occurrence of stroke or systemic arterial embolism over a mean follow-up of four years. Other outcomes include total mortality, operative safety outcomes (chest tube output in the first post-operative 24 hours, rate of post-operative re-exploration for bleeding in the first 48 hours post-surgery and 30-day mortality), re-hospitalization for heart failure, major bleed, and myocardial infarction. RESULTS Left Atrial Appendage Occlusion Study (LAAOS) III is funded in a vanguard phase by the Canadian Institutes for Health Research (CIHR), the Canadian Network and Centre for Trials Internationally, and the McMaster University Surgical Associates. As of September 9, 2013, 162 patients have been recruited into the study. CONCLUSIONS LAAOS III will be the largest trial to explore the efficacy of LAA occlusion for stroke prevention. Its results will lead to a better understanding of stroke in AF and the safety and efficacy of surgical LAA occlusion.

Gender-related differences in morbidity and mortality during combined valve and coronary surgery

BACKGROUND Gender-related differences in morbidity and mortality are well described for coronary artery bypass grafting but are not well understood for combined valve and bypass surgery. METHODS We reviewed retrospectively the morbidity and mortality of 1570 consecutive patients who underwent combined valve and bypass procedures at the Toronto General Hospital between January 1990 and October 2000. RESULTS There were 1073 men (68%) and 497 women (32%). The mean ages (+/- 1 SD) of women and men were 69 +/- 9 and 68 +/- 9 years, respectively (P =.02). Of the 1570 total patients, 973 patients (62%) underwent aortic valve and coronary bypass surgery, 481 patients (31%) had mitral valve and coronary bypass operations, and 116 (7%) patients had double or triple valve and coronary bypass operations. Preoperative hypertension (P =.002), diabetes (P =.001), and atrial fibrillation (P =.001) were seen more frequently in women. Body surface area was significantly lower in women (P =.0001). At presentation, more women were in congestive heart failure (69% vs 58%, P =.001) and in New York Heart Association functional class III or IV (25% vs 19%, P =.001). Although there was no difference in the number of women with three or more diseased vessels (32% vs 38%), only 35% of women received three or more grafts compared with 44% of men (P =.001). The use of left internal thoracic grafts, although uncommon in the whole study population (36%), was less common in women than in men (26% vs 41%, P =.001). Multivariable logistic analyses for morbidity and mortality showed female gender to be an independent risk factor. Mitral valve replacement, age, left ventricular dysfunction, New York Heart Association classes III and IV, and association of tricuspid valve disease, diabetes, peripheral vascular disease, and preoperative renal failure were found to be independent risk factors for mortality. CONCLUSION Female gender is an independent risk factor for combined morbidity and mortality during and after combined valve and coronary bypass surgery. As with isolated coronary artery bypass grafting, women undergoing combined procedures have more premorbid conditions, are more often in heart failure, had an equal incidence of triple vessel disease but received fewer grafts than men, and, therefore, were more frequently incompletely revascularized.

Protective Effects of Steroids in Cardiac Surgery: A Meta-Analysis of Randomized Double-Blind Trials

OBJECTIVE Cardiac surgery and cardiopulmonary bypass (CPB) induce an acute inflammatory response contributing to postoperative morbidity. The use of steroids as anti-inflammatory agents in surgery using CPB has been tested in many trials and has been shown to have good anti-inflammatory effects but no clear clinical advantages for the lack of an adequately powered sample size. The aim of this study was to evaluate the effects of steroid treatment on mortality and morbidity after cardiac surgery. DESIGN A systematic meta-analysis of randomized double-blind trials (RDBs). SETTING A university hospital. PARTICIPANTS Adult patients who underwent cardiac surgery. MEASUREMENTS AND MAIN RESULTS A trial search was performed through PubMed and Cochrane databases from 1966 to January 2009. Among 104 clinical trials reviewed, 31 RDB trials (1,974 patients) were considered suitable to be analyzed. A quality assessment of the trials was performed using the Jadad score. The types of steroid used in these trials were methylprednisolone (51.4%), dexamethasone (34.3%), hydrocortisone (5.7%), prednisolone (2.9%), or a combination of methylprednisolone and dexamethasone (5.7%). Steroid prophylaxis provided a protective effect preventing postoperative atrial fibrillation (odds ratio = 0.56; confidence interval [CI] 0.44-0.72, p < 0.0001), reducing postoperative blood loss (mean difference = -204.2 mL; CI from -287.4 to -121 mL; p < 0.0001), and reducing intensive care unit (mean difference = -6.6 hours; CI from -10.5 to -2.7 hours, p = 0.0007) and overall hospital stay (mean difference = -0.8 days; CI from -1.4 to -0.2 days, p = 0.01). Steroid prophylaxis had no effect on postoperative mortality, mechanical ventilation duration, re-exploration for bleeding, and postoperative infection. CONCLUSIONS A systematic review of RDB trials reveals that steroid prophylaxis may reduce morbidity after cardiac surgery and does not increase the risk of postoperative infections.

Mild to moderate mitral regurgitation in patients undergoing coronary bypass grafting: effects on operative mortality and long-term significance

BACKGROUND Patients undergoing bypass grafting (CABG) often present with mitral regurgitation (MR). While surgical strategy for patients with either trace or severe MR is well established, the need for a valve procedure with mild (2) to moderate (3+) mitral regurgitation is controversial. METHODS We reviewed 1,939 consecutive CABG patients (1987 to 1999). A preoperative echocardiogram performed when clinically indicated graded MR from 1 to 4+. Patient characteristics, hospital mortality, and long-term survival were compared between 167 patients with grade 2 to 3+ MR and controls. A multivariate analysis identified independent predictors for long-term mortality. RESULTS The MR patients were more often female and older; had increased comorbidities including hypertension, diabetes, and heart failure; had more extensive coronary disease and worse left ventricular (LV) function; and required urgent surgery more often. Operative mortality was 0.8% in no MR patients and 1.8% in MR patients (p not significant). Long-term survival for MR patients with poor LV function (LV grade 3 to 4) was significantly lower (53% versus 75% at 10 years, p = 0.001). Independent predictors of poor long-term survival were advanced age, LV dysfunction, heart failure, diabetes, prior cerebrovascular accident, peripheral vascular disease, and no left internal mammary artery use. CONCLUSIONS Coronary artery bypass graft patients with mild or moderate MR have worse baseline characteristics but operative mortality with CABG alone is not significantly increased. Long-term prognosis for MR patients with poor LV function is worse compared with patients with no MR but MR was not an independent predictor of long-term mortality. To determine whether surgical correction of MR would improve results, a prospective randomized trial seems warranted.