Antonino S. Rubino

Off-pump coronary artery bypass surgery versus standard linear or pulsatile cardiopulmonary bypass: endothelial activation and inflammatory response

OBJECTIVE Poor outcomes after coronary artery bypass grafting (CABG) have been linked to perioperative endothelial activation and systemic inflammatory responses. The use of pulsatile cardiopulmonary bypass (PCPB) or off-pump CABG (OPCABG) may minimise these phenomena. We compared biochemical and clinical outcomes among patients who underwent CABG with PCPB, CABG with linear CPB (LCPB) or OPCABG. METHODS Sixty consecutive patients undergoing isolated elective CABG were prospectively randomised trial to receive pulsatile CPB (group A, 20 patients), linear CPB (group B, 20 patients) or OPCABG (group C, 20 patients). Levels of proinflammatory cytokines (interleukins-2, -6, and -8), anti-inflammatory cytokines (interleukin-10) and endothelial markers (vascular endothelial growth factor (VEGF), monocyte chemo-attractant protein (MCP)-1) were measured before, during and after surgery. RESULTS VEGF and MCP-1 levels increased significantly during surgery in all groups, but they increased the least and were the lowest overall with OPCABG. They rose most and peaked overall with LCPB. Interleukin-2 levels remained stable during OPCABG but decreased equally during PCPB and LCPB. Interleukin-6 and -8 levels rose significantly during both types of CPB versus OPCABG. Interleukin-10 levels increased significantly in all groups during surgery, but they rose least and were the lowest overall with OPCABG and rose most and were the highest overall with PCPB. Intubation times, intensive care unit (ICU) stay and hospital stay were significantly longer in the LCPB group than the other two groups. CONCLUSIONS LCPB appears to promote endothelial activation and cytokine secretion, which may delay recovery. OPCABG was associated with slight endothelial activation and cytokine response. PCPB significantly attenuates endothelial/cytokine leakage, resulting in hospital outcomes comparable with those after OPCABG.

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.

Impact of clonidine administration on delirium and related respiratory weaning after surgical correction of acute type-A aortic dissection: results of a pilot study

Delirium and transient neurologic dysfunctions (TND) often complicate the postoperative course after surgery for acute type-A aortic dissection (AAD). We evaluated the role of clonidine on neurological outcome and respiratory function in 30 consecutive patients undergoing surgery for AAD. Patients were prospectively randomized to receive either clonidine (0.5 microg/kg bolus, followed by continuous infusion at 1-2 microg/kg/h) or placebo (NaCl 0.9%) in on starting and throughout the weaning period from the mechanical ventilation. Incidence of delirium and TND, Delirium Detection Score (DDS), weaning parameters [respiratory rate to tidal volume ratio - f/VT; pressure-frequency product (PFP); partial pressure of arterial oxygen to fractional inspired oxygen concentration (PaO(2)/FiO(2)); partial pressure of carbon dioxide (PaCO(2))], weaning duration and intensive care unit (ICU) length of stay were recorded. The two groups were similar for preoperative and operative variables and also for the incidence of postoperative complications. DDS was lower in the clonidine group (P<0.001). Patients weaned with clonidine showed lower f/VT and PFP, higher PaO(2)/FiO(2) and PaCO(2), lower DDS, weaning period and the related ICU length of stay (P<0.001). This was further confirmed in patients developing delirium/TND. Intravenous clonidine after surgery for AAD reduces the severity of delirium, improves the respiratory function, shortens the weaning duration and the ICU length of stay.

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

Midterm clinical and echocardiographic results and predictors of mitral regurgitation recurrence following restrictive annuloplasty for ischemic cardiomyopathy

OBJECTIVE Although mitral restrictive annuloplasty plus coronary artery bypass grafting are considered the best therapeutic strategies for ischemic cardiomyopathy with chronic mitral regurgitation, some recurrences are still reported. We evaluated predictors for late recurrence of ischemic cardiomyopathy with chronic mitral regurgitation. METHODS Hospital outcome and serial clinical and echocardiographic (preoperative, discharge, 6 months, end of follow-up) follow-up assessments were recorded for 82 consecutive patients with ischemic cardiomyopathy with chronic mitral regurgitation having coronary artery bypass grafting + mitral restrictive annuloplasty (2 sizes ring downsizing). Recurrent ischemic cardiomyopathy with chronic mitral regurgitation was defined by grade >or= 2 at echocardiography. RESULTS Hospital mortality was 4.9%; 17.7 +/- 1.7 (standard error) months (range 1-55) survival was 95.5% +/- 2.5%. Two-year Kaplan-Meier freedom from reintervention was 94.2% +/- 4.2%; from rerevascularization, 87.5% +/- 11.7%; from congestive heart failure, 83.8% +/- 5.7%; from ischemic cardiomyopathy with chronic mitral regurgitation grade >or= 2, 46.5% +/- 11.2%. Recurrence of ischemic cardiomyopathy with chronic mitral regurgitation gave lower 2-year Kaplan-Meier freedom from death (P = .03) and lower 2-year freedom from congestive heart failure (P = .0001), reintervention (P = .034), and tricuspid insufficiency (P = .0001). Ischemic cardiomyopathy with chronic mitral regurgitation recurrence correlated with worsened New York Heart Association class (P = .0001), left ventricular ejection fraction (P = .024), pulmonary arterial pressures (P = .0001), left ventricular end-diastolic diameter (P = .004), left ventricular end-systolic diameter (P = .014), indexed left ventricular mass (P = .008), and coaptation depth (P = .0001). Independent predictors for recurrent ischemic cardiomyopathy with chronic mitral regurgitation were previous anterior + posterior myocardial infarction (odds ratio 3.70; confidence interval 2.93-5.41; P = .001), preoperative left ventricular end-diastolic diameter >or= 70 mm (odds ratio 3.91; confidence interval 2.65-5.22; P = .001), and coaptation depth at discharge >or= 0.5 cm (odds ratio 11.9; confidence interval 5.91-21.34; P = .0001). Preoperative left ventricular end-diastolic diameter >or= 70 mm correlated with higher congestive heart failure (P = .002), recurrent ischemic cardiomyopathy with chronic mitral regurgitation (P = .0001), worsened New York Heart Association class (P = .0001), and higher diuretics (P = .0001). Coaptation depth < 0.5 cm at discharge accounted for better survival (P = .010), lower incidence of congestive heart failure (P = .0001), lower need for diuretics (P = .0001), and improved New York Heart Association class (P = .0001). CONCLUSIONS Failure of mitral restrictive annuloplasty is responsible for follow-up mortality and congestive heart failure and correlates with absence of cardiac reverse remodeling. Prognosis of patients having mitral restrictive annuloplasty for ischemic cardiomyopathy with chronic mitral regurgitation is good, as long as a low postoperative coaptation depth is achieved. Patients with significant left ventricular dilation should be considered for different surgical strategies.

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.

Intra-aortic balloon pump induced pulsatile perfusion reduces endothelial activation and inflammatory response following cardiopulmonary bypass §

OBJECTIVE Intra-aortic balloon pump (IABP)-induced pulsatile perfusion has demonstrated that it can preserve organ function during cardiopulmonary bypass (CPB). We evaluated the role of IABP pulsatile perfusion on endothelial response. METHODS Forty consecutive isolated CABG undergoing preoperative IABP were randomized to receive IABP pulsatile CPB during aortic cross-clamping (group A, 20 patients) or standard linear CPB (group B, 20 patients) during cross-clamp time. Hemodynamic results were analyzed by Swan-Ganz catheter [mean arterial pressure (MAP), cardiac index (CI), indexed systemic vascular resistances (ISVR), indexed pulmonary vascular resistances (IPVR), wedge pressure (PCWP)]. Inflammatory/endothelial response was analyzed by pro-inflammatory (IL-2, IL-6, IL-8), anti-inflammatory cytokines (IL-10), and endothelial markers [vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1)]. All measurements were recorded preoperatively (T0), before aortic declamping (T1), at the end of surgery (T2), 12h (T3) and 24h (T4) postoperatively. ANOVA for repeated measures was used to evaluate the differences of means. RESULTS Hemodynamic response was comparable except for higher MAP (p=0.01 at T1) and lower ISVR (p=0.001 at T1, p=0.003 at T2) in group A. No differences were found in perioperative leakage of IL-2, IL-6, and IL-8 between the two groups (within-group p=0.0001 either in group A and group B; between-groups p=NS at 2-ANOVA). Group A showed significantly lower VEGF (between-groups p=0.001 at 2-ANOVA, p=0.001 at T1, T2) and MCP-1 (between-groups p=0.001 at 2-ANOVA, p=0.001 at T1, T2) with higher IL-10 secretion (between-groups p=0.001 at 2-ANOVA, p=0.01 at T1, T2, T3). CONCLUSIONS IABP-induced pulsatile perfusion allows lower endothelial activation during CPB and higher anti-inflammatory cytokines secretion.

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.

Leukocyte Depletion During Extracorporeal Circulation Allows Better Organ Protection but Does Not Change Hospital Outcomes

BACKGROUND Leukocyte filtration has been reported to reduce inflammatory damage during cardiopulmonary bypass. We evaluated the role of leukocyte filtration on hospital outcome and postoperative morbidity. METHODS Eighty-two consecutive patients who underwent isolated coronary artery bypass grafting were randomly assigned (1:1) to receive leukocyte filters on both arterial and cardioplegia lines or standard arterial filters during cardiopulmonary bypass. Hospital outcome, postoperative markers of morbidity, and biochemical assays were compared. Data were collected preoperatively, intraoperatively, and postoperatively. Costs for patients receiving intraoperative leukofiltration were compared with control patients getting standard arterial filters. RESULTS Hospital mortality and intensive care unit and hospital length of stay were similar. Although duration of ventilation and incidence of pneumonia were comparable, leukocyte-depleted patients showed a higher ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (p = 0.008) and lower need for postoperative noninvasive ventilation (p = 0.041). Control patients showed higher need for continuous furosemide infusion (p = 0.013) and for renal replacement therapy (p = 0.014), in association with higher serum creatinine (p = 0.038) and blood urea (p = 0.18) and lower glomerular filtration rate (p = 0.038). Leukocyte-depleted patients required lower doses of inotropic agents (p = 0.56), whereas troponin I leakage and incidence of postoperative atrial fibrillation were comparable. No differences were found in terms of postoperative cerebral dysfunction or neutrophil and platelet counts, as well as postoperative bleeding and need for transfusions. Finally, leukodepletion proved significantly cost-beneficial, with a 37% cost reduction. CONCLUSIONS Although hospital outcomes were similar in terms of mortality and length of stay, the improvements in pulmonary, renal, and myocardial function, in association with the cost benefit, justify the use of leukocyte-depletion filters in the clinical practice.

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.