Magnus Dalén

Early and intermediate outcome after aortic valve replacement with a sutureless bioprosthesis: Results of a multicenter study

OBJECTIVE The aim of this study was to evaluate the outcome of aortic valve replacement with the sutureless Perceval S aortic valve bioprosthesis (Sorin Biomedica Cardio Srl, Saluggia, Italy). METHODS This is a retrospective analysis of 314 patients (mean age, 77.9 ± 5.0 years, mean European System for Cardiac Operative Risk Evaluation II, 9.0% ± 7.6%) who underwent aortic valve replacement with the Perceval S valve with (94 patients) or without (220 patients) concomitant coronary artery bypass surgery at 5 European centers. RESULTS The Perceval S valve was successfully implanted in all but 1 patient (99.7%). The mean aortic crossclamping time was 43 ± 20 minutes (isolated procedure, 39 ± 15 minutes; concomitant coronary surgery, 52 ± 26 minutes). Severe paravalvular leak occurred in 2 patients (0.6%). In-hospital mortality was 3.2% (1.4% after isolated procedure and 7.4% after concomitant coronary surgery). In-hospital mortality was 2.8% and 4.0% among patients with a European System for Cardiac Operative Risk Evaluation II less than 10% and 10% or greater, respectively (P = .558). Octogenarians had slightly higher in-hospital mortality (5.2% vs 2.0%, P = .125; after isolated procedure: 2.7% vs 0.7%, P = .223; after concomitant coronary surgery: 9.5% vs 5.8%, P = .491) compared with younger patients. Full sternotomy did not increase the in-hospital mortality risk compared with ministernotomy or minithoracotomy access (1.3% vs 1.4%, when adjusted for baseline covariates: P = .921; odds ratio, 0.886; 95% confidence interval, 0.064-12.346). One-year survival was 90.5%. Freedom from valve-related mortality, stroke, endocarditis, and reoperation was 99.0%, 98.1%, 99.2%, and 98.3%, respectively. CONCLUSIONS The sutureless Perceval S valve is associated with excellent early survival in high-risk patients, particularly among those undergoing an isolated procedure. Further studies are needed to prove the durability of this bioprosthesis.

European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG registry): Study Protocol for a Prospective Clinical Registry and Proposal of Classification of Postoperative Complications

BackgroundClinical evidence in coronary surgery is usually derived from retrospective, single institutional series. This may introduce significant biases in the analysis of critical issues in the treatment of these patients. In order to avoid such methodological limitations, we planned a European multicenter, prospective study on coronary artery bypass grafting, the E-CABG registry.DesignThe E-CABG registry is a multicenter study and its data are prospectively collected from 13 centers of cardiac surgery in university and community hospitals located in six European countries (England, Italy, Finland, France, Germany, Sweden). Data on major and minor immediate postoperative adverse events will be collected. Data on late all-cause mortality, stroke, myocardial infarction and repeat revascularization will be collected during a 10-year follow-up period. These investigators provided a score from 0 to 10 for any major postoperative adverse events and their rounded medians were used to stratify the severity of these complications in four grades. The sum of these scores for each complication/intervention occurring after coronary artery bypass grafting will be used as an additive score for further stratification of the prognostic importance of these events.DiscussionThe E-CABG registry is expected to provide valuable data for identification of risk factors and treatment strategies associated with suboptimal outcome. These information may improve the safety and durability of coronary artery bypass grafting. The proposed classification of postoperative complications may become a valuable research tool to stratify the impact of such complications on the outcome of these patients and evaluate the burden of resources needed for their treatment.Clinical Trials numberNCT02319083

In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome

Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties. However, many basic questions concerning their mechanisms of action after systemic infusion remain unanswered. We performed a detailed analysis of the immunomodulatory properties and proteomic profile of MSCs systemically administered to two patients with severe refractory acute respiratory distress syndrome (ARDS) on a compassionate use basis and attempted to correlate these with in vivo anti‐inflammatory actions. Both patients received 2 × 106 cells per kilogram, and each subsequently improved with resolution of respiratory, hemodynamic, and multiorgan failure. In parallel, a decrease was seen in multiple pulmonary and systemic markers of inflammation, including epithelial apoptosis, alveolar‐capillary fluid leakage, and proinflammatory cytokines, microRNAs, and chemokines. In vitro studies of the MSCs demonstrated a broad anti‐inflammatory capacity, including suppression of T‐cell responses and induction of regulatory phenotypes in T cells, monocytes, and neutrophils. Some of these in vitro potency assessments correlated with, and were relevant to, the observed in vivo actions. These experiences highlight both the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. The findings also suggest, but do not prove, a beneficial effect of lung protective strategies using adoptively transferred MSCs in ARDS. Appropriate randomized clinical trials are required to further assess any potential clinical efficacy and investigate the effects on in vivo inflammation.

Aortic valve replacement through full sternotomy with a stented bioprosthesis versus minimally invasive sternotomy with a sutureless bioprosthesis

OBJECTIVES The aim of this study was to analyse early postoperative outcomes and 2-year survival after aortic valve replacement (AVR) through a ministernotomy with a sutureless bioprosthesis implantation compared with a full sternotomy with implantation of a stented bioprosthesis. METHODS Patients who underwent primary isolated non-emergent AVR at six European centres were included in the study. Of these, 182 (32%) underwent a ministernotomy with a sutureless bioprosthesis (ministernotomy sutureless group) and 383 (68%) a full sternotomy with a stented bioprosthesis (full sternotomy stented group). Propensity score matching was used to reduce selection bias. RESULTS In the overall cohort, 30-day mortality was 1.6 and 2.1%, and 2-year survival was 92 and 92% in the ministernotomy sutureless group and in the full sternotomy stented group, respectively. Propensity score matching resulted in 171 pairs with similar characteristics and operative risk. Aortic cross-clamp (40 vs 65 min, P < 0.001) and cardiopulmonary bypass time (69 vs 87 min, P < 0.001) were shorter in the ministernotomy sutureless group. Patients undergoing ministernotomy received less packed red blood cells but the risk for postoperative permanent pacemaker implantation was higher. There were no differences regarding 30-day mortality or 2-year survival between the two groups. CONCLUSIONS AVR through a ministernotomy with implantation of a sutureless bioprosthesis was associated with shorter aortic cross-clamp and cardiopulmonary bypass time and less transfusion of packed red blood cells, but a higher risk for postoperative permanent pacemaker implantation compared with a full sternotomy with a stented bioprosthesis.

Ministernotomy Versus Full Sternotomy Aortic Valve Replacement With a Sutureless Bioprosthesis: A Multicenter Study

BACKGROUND The aim of this study was to analyze early postoperative outcomes and 2-year survival after aortic valve replacement (AVR) with the sutureless Perceval bioprosthesis (Sorin Biomedica Cardio Srl, Salluggia, Italy) performed through ministernotomy compared with full sternotomy. METHODS This was a study of 267 consecutive patients who underwent isolated AVR with the sutureless Perceval bioprosthesis between 2007 and 2014 at 6 European centers. Of these, 189 (70.8%) were performed through ministernotomy and 78 through a full sternotomy. Propensity score matching was used to reduce selection bias. RESULTS In the overall cohort of ministernotomy and full sternotomy patients, in-hospital mortality was 1.1% and 2.6% and 2-year survival was 92% and 91%, respectively. Propensity score matching resulted in 56 pairs with similar characteristics and operative risk. Aortic cross-clamp (44 minutes in both groups, p = 0.931) and cardiopulmonary bypass time (69 vs 74 minutes, p = 0.363) did not differ between the groups. Apart from higher values in the ministernotomy group for postoperative peak gradients (28.1 vs 23.3 mm Hg, p = 0.026) and mean aortic valve gradients (15.2 vs 11.7 mm Hg, p = 0.011), early postoperative outcomes did not differ in the propensity-matched cohort. There were no differences in the in-hospital mortality rate or 2-year survival between the groups. CONCLUSIONS AVR with the sutureless Perceval bioprosthesis through a ministernotomy was a safe and reproducible procedure that was not associated with prolonged aortic cross-clamp or cardiopulmonary bypass time compared with a full sternotomy. Early postoperative outcomes and 2-year survival were comparable between patients undergoing ministernotomy and full sternotomy.

Safety of Preoperative Use of Ticagrelor With or Without Aspirin Compared With Aspirin Alone in Patients With Acute Coronary Syndromes Undergoing Coronary Artery Bypass Grafting

Importance The optimal timing of discontinuation of ticagrelor before cardiac surgery is controversial. Objective To evaluate the safety of preoperative use of ticagrelor with or without aspirin in patients with acute coronary syndromes (ACS) undergoing isolated coronary artery bypass grafting (CABG) compared with aspirin alone. Design, Setting, and Participants This prospective, multicenter clinical trial was performed at 15 European centers of cardiac surgery. Participants were patients with ACS undergoing isolated CABG from the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) registry between January and September 2015. Exposures Before surgery, patients received ticagrelor with or without aspirin or aspirin alone. Main Outcomes and Measures Severe bleeding as defined by the Universal Definition of Perioperative Bleeding (UDPB) and E-CABG bleeding classification criteria. A propensity score-matched analysis was performed to adjust for differences in baseline and operative covariates. Results Of 2482 patients from the E-CABG registry, the study cohort included 786 (31.7%) consecutive patients with ACS (mean [SD] age, 67.1 [9.3] years; range, 32-88 years), and 132 (16.8%) were female. One-to-one propensity score matching provided 215 pairs, whose baseline and operative covariates had a standardized difference of less than 10%. Preoperative use of ticagrelor was associated with a similar risk of bleeding according to the UDPB and E-CABG bleeding classifications, but the incidence of platelet transfusion was higher in the ticagrelor group (13.5% [29 of 215] vs 6.0% [13 of 215]). Compared with those receiving aspirin alone, continuing ticagrelor up to the time of surgery or discontinuing its use less than 2 days before surgery was associated with a higher risk of platelet transfusion (22.7% [5 of 22] vs 6.4% [12 of 187]) and E-CABG bleeding grades 2 and 3 (18.2% [4 of 22] vs 5.9% [11 of 187]) and tended to have an increased risk of UDPB grades 3 and 4 (22.7% [5 of 22] vs 9.6% [18 of 187]). Among patients in whom antiplatelet drug use was discontinued at least 2 days before surgery, the incidence of platelet transfusion was 12.4% (24 of 193) in the ticagrelor group and 3.6% (1 of 28) in the aspirin-alone group. Conclusions and Relevance In propensity score-matched analyses among patients with ACS undergoing CABG, the use of preoperative ticagrelor with or without aspirin compared with aspirin alone was associated with more platelet transfusion but similar degree of bleeding; in patients receiving ticagrelor 1 day before or up until surgery, there was an increased rate of severe bleeding.

Correlation between point-of-care platelet function testing and bleeding after coronary artery surgery

Abstract Objectives. To investigate whether point-of-care platelet function testing immediately before coronary artery bypass grafting correlates to postoperative blood loss and transfusion requirements. Design. Blood samples from 50 patients on antiplatelet therapy were analysed by Plateletworks®. Thirty-three of the patients had received clopidogrel, 300–600 mg loading dose followed by 75 mg once daily, within 7 days. Postoperative chest drainage volume was recorded every hour. Results. Plateletworks® ADP-induced platelet aggregation correlated significantly to postoperative chest drainage volume at 5 hours (r = −0.83; p < 0.01) and 12 hours (r = −0.55; p < 0.01), and the tertile of patients with the lowest aggregation had higher postoperative transfusion requirements (p < 0.01) and about three times larger chest drainage volume than remaining patients during the first 5 hours after surgery (p < 0.01). Cessation of clopidogrel correlated to chest drainage volume at 5 hours (r = −0.48; p < 0.01) and 12 hours (r = −0.47; p < 0.01) after surgery. Conclusions. The significant correlation between Plateletworks® ADP-induced platelet aggregation and blood loss suggests that this test may be useful to predict risk of excessive bleeding and to guide timing of surgery and bleeding treatment in patients undergoing coronary artery bypass grafting.

Prediction of severe bleeding after coronary surgery: the WILL-BLEED Risk Score.

Severe perioperative bleeding after coronary artery bypass grafting (CABG) is associated with poor outcome. An additive score for prediction of severe bleeding was derived (n=2494) and validated (n=1250) in patients from the E-CABG registry. Severe bleeding was defined as E-CABG bleeding grades 2-3 (transfusion of >4 units of red blood cells or reoperation for bleeding). The overall incidence of severe bleeding was 6.4 %. Preoperative anaemia (3 points), female gender (2 points), eGFR <45 ml/min/1.73 m2 (3 points), potent antiplatelet drugs discontinued less than five days (2 points), critical preoperative state (5 points), acute coronary syndrome (2 points), use of low-molecular-weight heparin/fondaparinux/unfractionated heparin (1 point) were independent predictors of severe bleeding. The WILL-BLEED score was associated with increasing rates of severe bleeding in both the derivation and validation cohorts (scores 0-3: 2.9 % vs 3.4 %; scores 4-6: 6.8 % vs 7.5 %; scores>6: 24.6 % vs 24.2 %, both p<0.0001). The WILL-BLEED score had a better discriminatory ability (AUC 0.725) for prediction of severe bleeding compared to the ACTION (AUC 0.671), CRUSADE (AUC 0.642), Papworth (AUC 0.605), TRUST (AUC 0.660) and TRACK (AUC 0.640) bleeding scores. The net reclassification index and integrated discrimination improvement using the WILL-BLEED score as opposed to the other bleeding scores were significant (p<0.0001). The decision curve analysis demonstrated a net benefit with the WILL-BLEED score compared to the other bleeding scores. In conclusion, the WILL-BLEED risk score is a simple risk stratification method which allows the identification of patients at high risk of severe bleeding after CABG.

Coronary Artery Bypass Grafting in Patients 50 Years or Younger: A Swedish Nationwide Cohort Study

Background— There are limited data regarding long-term results after coronary artery bypass grafting (CABG) in young adults. We performed a nationwide population-based cohort study to analyze long-term survival, major adverse cardiovascular events, and factors associated with elevated risk in young adults undergoing CABG. Methods and Results— We included all adult patients ⩽50 years of age who underwent primary isolated CABG in Sweden between 1997 and 2013 from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) register. Patient data were linked from national Swedish health data registers to create a study database. We identified 4086 young adults with a mean age of 46 years and 18% women. During a median follow-up time of 10.9 years (interquartile range, 6.4–14.1) 490 (12%) patients died. Survival at 5, 10, and 15 years was 96% (95% CI, 95–96), 90% (95% CI, 89–91), and 82% (95%CI, 80–83), respectively, which was significantly better in comparison with patients aged 51 to 70 years and >70 years who underwent CABG during the same period. The cumulative incidence of death or a major adverse cardiovascular event during 17 years after CABG was mainly driven by myocardial infarction or the need for repeat revascularization. The most important risk factors for all-cause mortality were chronic kidney disease, reduced left ventricular ejection fraction, peripheral vascular disease, or chronic obstructive pulmonary disease. Conclusions— Long-term survival and freedom from major cardiovascular events after CABG was better in young adults than in older patients. Factors significantly associated with an elevated long-term risk of death or adverse outcome were similar to well-known risk factors for older age groups following CABG. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02276950.

Bilateral versus single internal mammary coronary artery bypass grafting in Sweden from 1997-2008.

Background Prior observational studies have suggested better outcomes in patients who receive bilateral internal mammary arteries (BIMA) during coronary artery bypass grafting (CABG) compared with patients who receive a single internal mammary artery (SIMA). The aim of this study was to analyze the association between BIMA use and long-term survival in patients who underwent primary isolated CABG. Methods and Results Patients who underwent primary isolated non-emergent CABG in Sweden between 1997 and 2008 were identified. The SWEDEHEART registry and other national Swedish registers were used to acquire information about patient characteristics and outcomes. Unadjusted and multivariable adjusted regression models were used to estimate the association between BIMA use and early mortality, long-term survival, and a composite of death from any cause or rehospitalization for myocardial infarction, heart failure, or stroke in the overall cohort and in a propensity score-matched cohort. The study population consisted of 49702 patients who underwent CABG with at least one internal mammary artery, and 559 (1%) of those had BIMA grafting. In the adjusted analyses, BIMA use was not associated with better survival compared with SIMA use in the overall cohort (hazard ratio (HR) for death: 1.16, 95% confidence interval (CI): 0.97 to 1.37) or in the matched cohort (HR: 1.04, 95% CI: 0.78 to 1.40). The results were similar for early mortality and the composite endpoint. Reoperation for sternal wound complications was more common among BIMA patients (odds ratio: 1.71, 95% CI: 1.01 to 2.88). Conclusions BIMA grafting was performed infrequently and was not associated with better outcomes compared with SIMA grafting in patients undergoing non-emergent primary isolated CABG in Sweden during 1997–2008.