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Background Patients with recent coronary artery bypass graft (CABG) surgery are at risk for early graft failure, which is associated with a risk of myocardial infarction and death. In the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced the primary major adverse cardiovascular events (MACE) outcome of cardiovascular death, stroke, or myocardial infarction. Rivaroxaban 5 mg twice daily alone did not significantly reduce MACE. Objectives This pre-planned substudy sought to determine whether the COMPASS treatments are more effective than aspirin alone for preventing graft failure and MACE after CABG surgery. Methods The substudy randomized 1,448 COMPASS trial patients 4 to 14 days after CABG surgery to receive the combination of rivaroxaban plus aspirin, rivaroxaban alone, or aspirin alone. The primary outcome was graft failure, diagnosed by computed tomography angiogram 1 year after surgery. Results The combination of rivaroxaban and aspirin and the regimen of rivaroxaban alone did not reduce the graft failure rates compared with aspirin alone (combination vs. aspirin: 113 [9.1%] vs. 91 [8.0%] failed grafts; odds ratio [OR]: 1.13; 95% confidence interval [CI]: 0.82 to 1.57; p = 0.45; rivaroxaban alone vs. aspirin: 92 [7.8%] vs. 92 [8.0%] failed grafts; OR: 0.95; 95% CI: 0.67 to 1.33; p = 0.75). Compared with aspirin, the combination was associated with fewer MACE (12 [2.4%] vs. 16 [3.5%]; hazard ratio [HR]: 0.69; 95% CI: 0.33 to 1.47; p = 0.34), whereas rivaroxaban alone was not (16 [3.3%] vs. 16 [3.5%]; HR: 0.99, CI: 0.50 to 1.99; p = 0.98). There was no fatal bleeding or tamponade within 30 days of randomization. Conclusions The combination of rivaroxaban 2.5 mg twice daily plus aspirin or rivaroxaban 5 mg twice daily alone compared with aspirin alone did not reduce graft failure in patients with recent CABG surgery, but the combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE, as observed in the larger COMPASS trial. (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS [COMPASS]; NCT01776424)

BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.

Background: Hybrid ablation [thoracoscopic ablation (TA) of atrial fibrillation (AF) followed by catheter ablation (CA)] is an increasingly common method of the treatment for patients with AF. The aim of this study was to assess the response to ganglionated plexi (GP) ablation in patients with a previous TA (i.e., to assess whether TA had resulted in damage to the GP. Heart rate variability (HRV) was used as a marker of the autonomic response. Methods: Twenty AF patients underwent pulmonary vein isolation (PVI) plus GP ablation (GP group) and 18 AF patients underwent CA including GP ablation as a part of hybrid ablation (i.e., all patients had undergone a previous TA; Hybrid group). In each group, a 5 min electrocardiogram (ECG) obtained before and after the CA were analyzed. Time and frequency domain parameters were evaluated. Results: Vagal responses (VR) during CA were observed in 12 (60%) patients in the GP group; however, in the Hybrid group, VR was not observed in any of the patients during CA. The change in normalized power in the low frequency (LF) component and the ratio between the LF and high frequency (LF/HF ratio) components of the HRV spectra, before and after ablation, were statistically significant in the GP group (3.3±2.6 before vs. 1.8±1.9 after ablation) but unchanged, before or after CA, in the Hybrid group. Conclusions: GP ablation in patients subsequent to TA has a little influence on HRV parameters, which could be explained by GP damage during the preceding TA.

BackgroundWe previously reported that there was no significant difference at 30 days or at 1 year in the rate of the composite outcome of death, stroke, myocardial infarction, or renal failure between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report the results at 5 years (the end of the trial). MethodsA total of 4752 patients (from 19 countries) who had coronary artery disease were randomly assigned to undergo off-pump or on-pump CABG. For this report, we analyzed a composite outcome of death, stroke, myocardial infarction, renal failure, or repeat coronary revascularization (either CABG or percutaneous coronary intervention). The mean follow-up period was 4.8 years. ResultsThere were no significant differences between the off-pump group and the on-pump group in the rate of the composite outcome (23.1% and 23.6%, respectively; hazard ratio with off-p...

Aims: Off-pump coronary artery bypass graft surgery (OPCAB) is an established alternative to on-pump surgical revascularization. Previous studies in patients with low or intermediate risk showed no significant differences between off-pump and on-pump surgical revascularization. The aim of this study was to compare the two techniques in patients with high operative risk. Methods: PRAGUE-6 is a prospective randomized single-center study of 206 patients, with an additive EuroSCORE ≥ 6, scheduled for isolated coronary surgery: Group A - on-pump (n = 108) versus Group B - off-pump (n = 98). The primary outcome was a combined endpoint of all-cause deaths, stroke, myocardial infarction, or renal failure requiring new hemodialysis, within 30 days and 1 year after randomization. All data were analyzed using the "intention-to-treat" principle. Results: Early postoperative myocardial infarction was detected in 12.1% (A) vs. 4.1% (B) of patients ( P = 0.048, hazard ratio 0.32, 95% CI 0.11-0.99). There was a significantly higher incidence of primary combined end-point in group A (20.6% vs. 9.2%, P = 0.028, HR 0.41, 95% CI 0.19-0.91) in the first 30 days, but not after 1 year (30.8% vs. 21.4%, P = 0.117, HR 0.65, CI 0.37-1.12). Conclusion: Off-pump surgical revascularization in patients with high operative risks can significantly reduce the incidence of major postoperative complications during the first 30 days. There was no statistically significant difference in the incidence of these complications after 1 year.

This study was designed to investigate the distribution of vasa vasorum in walls of failed aorto-coronary venous grafts. Fifty-one diseased venous grafts harvested from 39 patients underwent qualitative histological evaluation. The morphology of the grade of the pathological changes and the extent of the vascularisation were examined, and related to the length of the interval between the primary surgery and the explantation. The obtained results were placed into five groups, substantially differing one from the other in morphology and vascularisation. The intervals between grafts implantation and explantation ranged from 1 day to 35 years. The onset of arterialization of the graft media was observed on average at 1 month after bypass implantation. During this same time period massive intimal hyperplasia and atherosclerosis occurred. Vasa vasorum proliferation from the adventitia to the outer layers of the media was first apparent between 7 and 24 months after implantation. Proliferation of the vasa vasorum throughout the entire atherosclerotic media and hyperplastic intima continued for a much longer time interval. No correlation between neoangiogenesis and age, sex or type of bypassed coronary branch was proven. Regarding the given findings, the authors believe that changes in hemodynamic conditions and endothelial trauma are primarily responsible for the development of graft disease and that vasa vasorum proliferation is only a secondary reaction to the structural changes of the graft wall. To what extent the frequently present pre-existing intimal hyperplasia of venous bypass grafts play in the development of graft disease remains questionable.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.

A case of macro-reentrant tachycardia associated with a box lesion after thoracoscopis left atrial surgical atrial fibrillation (AF) ablation yet to be described. The goal was to clarify the mechanisms and electrophysiological characteristics of this type of tachycardia.A patient was admitted for an EP study following surgical thoracoscopic AF ablation (box lexion formation by right-sided Cobra thoracoscopic ablation). Thoracoscopic ablation was done as the first step of the hybrid ablation approach to the persistent AF; the second step was the EP study. At the EP study, he presented with incessant regular tachycardia (cycle length of 226 ms). An EP study with conventional, 3D activation and entrainment mapping was done to assess the tachycardia mechanism. Two conduction gaps in the superior line (roofline) between the superior pulmonary veins were discovered. The tachycardia was successfully treated with a radiofrequency application near the gap close to the left superior pulmonary vein; however, following tachycardia termination, pulmonary vein isolation was absent. A second radiofrequency application, close to the roof of the right superior pulmonary, vein closed the gap in the box and led to the isolation of all 4 pulmonary veins. No atrial tachycardia recurred during the 6-month follow-up.Conduction gaps in box lesion created by thoracospcopic ablation can present as a novel type of man-made tachycardia after surgical ablation of atrial fibrillation. Activation and entrainment mapping is necessary for an accurate diagnosis.

Objectives Thoracoscopic occlusion of the left atrial appendage (LAA) has become a routine part of thoracoscopic ablation for the treatment of atrial fibrillation (AF). Evaluation of residual findings of the occluded LAA by echocardiography has yet to be described. Methods Patients with AF indicated for hybrid ablation (thoracoscopic procedure followed by catheter ablation) were enrolled in this study. LAA was occluded as a routine part of the thoracoscopic procedure. Follow-up transoesophageal echocardiography was performed at the end of the procedure, 2-5 days and 2-3 months after the procedure (before the endocardial stage). The residual pouches of the LAA were measured in the mitral valve view (30-110°) and in the perpendicular view. The depth of the residual pouch was measured from the ostial plane (connecting the Coumadin ridge and the circumflex artery) to the deepest part of the residuum. The volume of the residual pouch and the distance from the circumflex artery to the proximal and the distal ends of the AtriClip were measured using computed tomography. Results Forty patients were enrolled in this study. The success rate for the occlusion of the LAA, assessed on transoesophageal echocardiography 2-5 days after surgery, was 97.5%. Regarding the residual findings, no reperfused LAAs were found, and only residual stumps remained. The depth of the stump was 12.9 ± 5.9 mm, the area was 2.2 ± 1.1 cm2, and the volume was 3.6 ± 1.9 ml (all data are shown as mean ± standard deviation). Conclusions The occlusion of the LAA using an AtriClip PRO device was a clinically safe procedure with high efficacy and was associated with the presence of a small residual pouch after occlusion. Clinical trial registration NCT02832206.

OBJECTIVES Hybrid ablation of atrial fibrillation (AF) is a promising treatment strategy; however, data regarding its efficacy and safety are still limited. METHODS Patients with non-paroxysmal AF were enrolled. First, a thoracoscopic, epicardial isolation of pulmonary veins and the left atrial posterior wall ('box lesion') was performed; a novel unipolar/bipolar radiofrequency device was used. Moreover, in 12 patients enrolled thereafter, the left atrial appendage was occluded. Electrophysiological evaluation and catheter ablation were performed 2-3 months later, with the goal of verifying or completing (if needed) the box lesion and ablation of the ganglionated plexi and the cavotricuspid isthmus. Outcomes were assessed using 1-week and 24-h Holter monitoring, repeated echocardiography and laboratory measurements. RESULTS Thirty-eight patients (13 persistent and 25 long-standing persistent AF) were enrolled with a mean AF duration of 33 ± 32.9 months. The procedure was successfully completed in 35 patients; 3 patients underwent only the surgical part because of a postoperative left atrial appendage thrombus (2 patients) and perioperative stroke (1 patient). After 6 months, 30 (86%) patients were arrhythmia-free, whereas 80% were also off antiarrhythmics. After 1 year, 28 (82%) patients were arrhythmia-free, 79% were off anti-arrhythmics and 47% were off anticoagulation treatment. Four (10.5%) serious postoperative complications occurred, including 1 stroke, 1 right phrenic nerve palsy and 2 pneumothoraxes with a need for drainage. Significant improvements were observed in echocardiographic, functional and serological parameters. CONCLUSIONS Hybrid ablation is an effective treatment strategy for patients with persistent or long-standing persistent AF. Over 80% of patients were arrhythmia-free 1 year after the procedure. Sinus rhythm restoration was accompanied by improvements in functional, echocardiographic and serological markers.

Hybrid ablation of atrial fibrillation (AF) is a promising treatment strategy for patients with non-paroxysmal AF, although, data regarding mid-term outcomes are limited. Patients with persistent or long-standing persistent AF were enrolled. Initially, a thoracoscopic, right-sided, epicardial ablation was performed, with a goal of creating a box lesion on the posterior wall of the left atrium; a novel versapolar radiofrequency (RF) catheter was used. In patients enrolled later, occlusion of the left atrial appendage was also performed. An endocardial procedure was performed 2–4 months later, with the goal of confirming/completing the box lesion and ablating the ganglionated plexi and cavotricuspid isthmus. Efficacy was assessed using multiple 24-h and 1-week Holter monitoring. Analysis was performed to search for variables associated with procedure’s failure. Forty-one patients (14 persistent and 27 long-standing persistent AF) were enrolled with a mean AF duration of 33.5 ± 33.1 months. Mean follow-up was 507.2 ± 201.1 days (180–731). At the last follow-up visit, 27(65%) patients were arrhythmia-free, without anti-arrhythmics or need for re-ablation. Additional 4 patients (9.8%) were in sinus rhythm (SR) following re-ablation of postprocedural peri-mitral flutter and 4 (9.8%) were in SR on anti-arrhythmics. Longer periods of preoperative AF were independently associated with worse arrhythmia-free survival (p = 0.015). Serious postoperative complications occurred in 3 (7.3%) patients; only 1 (2.4%) patient had clinical consequences after 6 months. Hybrid ablation of non-paroxysmal AF using a novel, versapolar RF device yields promising mid-term results. Better arrhythmia-free survival rates were found in AF patients with shorter AF duration.

Background Catheter and surgical ablation of atrial fibrillation (AF) can be associated with a risk of thromboembolic events. The goal of this study was to assess optimal anticoagulation management during thoracoscopic ablation of AF. Methods Fifty-two patients with persistent or long-standing persistent AF underwent hybrid ablation consisting of thoracoscopic ablation followed by electrophysiologic (EP) evaluation and consecutive ablation if indicated. The thoracoscopic ablation was performed using three different anticoagulation protocols: (1) without periprocedural heparin and without occlusion of the left atrial appendage; (2) with periprocedural heparin but without left atrial appendage occlusion; and (3) with periprocedural heparin and left atrial appendage occlusion. Transesophageal echocardiography (TEE) was obligatorily used to screen for intraatrial thrombi before the surgical and EP procedure and before hospital discharge for patients in protocols 2 and 3. Results In group 1 (n = 20), 1 patient (5%) had a postoperative stroke with persistent neurologic deficit, and 6 other patients (30%) had a new thrombus in the left atrial appendage seen on the pre-EP TEE. In group 2 (n = 6), 3 left atrial appendage thrombi occurred (50%; 2 on predischarge TEE and 1 on pre-EP TEE). In group 3 (n = 26), no intracardiac thrombi were found on predischarge and pre-EP TEE, and there were no strokes in this group of patients, namely, the rates of thrombus or stroke were significantly reduced when compared with groups 1 and 2 ( p = 0.001). Conclusions Thoracoscopic ablation of AF can be associated with a risk of left atrial appendage thrombus formation and possibly also stroke. With administration of heparin during the ablation, followed by occlusion of the left atrial appendage as a part of the procedure, this risk can be effectively reduced.

Background Hybrid ablation (a combination of thoracoscopic epicardial ablation and catheter ablation) has become a new technique for atrial fibrillation treatment. Objective The goal of this study was to evaluate the success and electrophysiological follow-up after using the COBRA Fusion device to deliver a circumferential lesion set anterior to the pulmonary veins in an attempt to isolate the posterior left atrium (box isolation). Methods Surgical ablation was carried out via a thoracoscopic approach using the COBRA Fusion radiofrequency catheter. An electrophysiology study was done 2–3 months later to verify box isolation (and to complete it, if needed) and to perform right-sided isthmus ablation. Fat thickness along the presumed box lesion line was measured using preprocedural computed tomography. Results Thirty patients (mean age 60.0 ± 11.6 years; 22 men; 8 with long-standing persistent AF and 22 with persistent atrial fibrillation) were enrolled. The duration of the EP study was 216.3 ± 64.2 minutes. Box isolation, based on the EP study, was complete in 12 patients (40%) and incomplete in 18 patients (60%). Successful box isolation was achieved with catheter ablation in 16 of 18 patients (89%). A total of 39 gaps in these 16 patients were identified. Typical gap locations were the anterior-superior part of the superior pulmonary veins and the roofline. Fat thickness along the roofline was substantially higher than that along the inferior line (4.58 ± 1.61 mm vs 2.37 ± 0.76 mm; P Conclusion There is a relatively low rate of complete isolation using the COBRA catheter ablation system. The superior line and anterior parts of superior pulmonary veins have most conduction gaps.

BACKGROUND: The relative benefits and risks of performing coronary-artery bypass grafting (CABG) with a beating-heart technique (off-pump CABG), as compared with cardiopulmonary bypass (on-pump CABG), are not clearly established. METHODS: At 79 centers in 19 countries, we randomly assigned 4752 patients in whom CABG was planned to undergo the procedure off-pump or on-pump. The first coprimary outcome was a composite of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days after randomization. RESULTS: There was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG (9.8% vs. 10.3%; hazard ratio for the off-pump group, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P=0.59) or in any of its individual components. The use of off-pump CABG, as compared with on-pump CABG, significantly reduced the rates of blood-product transfusion (50.7% vs. 63.3%; relative risk, 0.80; 95% CI, 0.75 to 0.85; P

The study was performed to examine a possible augmentation of systemic administration of tranexamic acid by the additional topical application during heart valve surgery in the post-aprotinin era. One-hundred patients were enrolled in the study and all the patients were given tranexamic acid intravenously. The participants were randomized into two groups (A, n = 49; B, n = 51), and before commencing the sternal suturing, the study solution (group A: 250 ml of normal saline + tranexamic acid 2.5 g, placebo group B: 250 ml of normal saline) was poured into the pericardial cavity. The cumulative blood loss (geometric means [95% confidence intervals]) 4 h after the surgery was 86.1 [56.1, 132.2] ml in group A, and 135.4 [94.3, 194.4] in group B, test for equality of geometric means P = 0.107, test for equality of variances P = 0.059. Eight hours after the surgery, the blood loss was 199.4 [153.4, 259.2] ml in group A, 261.7 [205.1, 334.0] ml in group B, P = 0.130 and P = 0.050, respectively. Twenty-four hours postoperatively the blood loss was 504.2 [436.0, 583.0] ml in group A, 569.7 [476.0, 681.7] ml in group B, P = 0.293 and P = 0.014, respectively. The proportion of patients transfused postoperatively by fresh frozen plasma differed significantly between the two study groups (group A: n = 21, group B: n = 36, P = 0.008). Our hypothesis is supported by a significant difference in the inter-group variance of blood loss and the proportion of patients requiring fresh frozen plasma; however evident differences in mean postoperative blood loss were not statistically significant.

Objectives Changes in hemostasis after off-pump coronary artery bypass grafting are still being discussed. There is a lack of information about platelet activity and aspirin efficacy after coronary artery bypass grafting. The aim of this study was to assess and compare platelet activity and aspirin efficacy early and late after off-pump and on-pump coronary artery bypass grafting. Methods Eighty patients were enrolled in a prospective randomized study. Platelet activity was determined based on membrane expression of antigen CD62P (P-selectin) by means of flow cytometric analysis. Aspirin efficacy was assessed by using arachidonic acid–induced platelet aggregation. Blood samples were collected before the operation, immediately postoperatively, and on days 1, 2, 5, and 30. Results In the off-pump group expression of P-selectin was markedly increased in comparison with preoperative values, with a maximum difference observed on day 2 (+53%, P = .02), and it was significantly higher compared with that seen in the on-pump group on days 2 and 5 (+53% vs +4%, P = .004, and +20% vs −16%, P = .005). On day 30, P-selectin expression was similar both between the groups and in comparison with the preoperative values. Arachidonic acid–induced platelet aggregation was gradually decreasing until day 30, but on day 2, there was an unexpected increase in aggregation that was more expressed in the off-pump group. Conclusions The platelet activity is higher in the early postoperative period in off-pump compared with on-pump coronary artery bypass grafting. The present aspirin strategy seems to be insufficient in the early postoperative period, irrespective of the surgical technique used.

Background: The question whether the primary increase of vasa vasorum (VV) of venous wall (i) plays an initial role in varicogenesis or (ii) is an expression of impairment of the nutritional conditions in superficial veins of lower extremities is not unambiguously solved yet. The aim of the study was to describe the arrangement of the VV within the wall of the human great saphenous vein (GSV) qualitatively, and of its tributaries at different stages of varicosis and in other pathological states like thrombophlebitis or phlebosclerosis. Material and methods: 22 patients deserving an aorto-coronary bypass surgery or GSV surgery were subdivided into three groups according to the staging of their varices and other pathology. The harvested GSV were prepared for light and scanning electron microscopy. One cadaverous specimen of GSV was injected with India ink. Results: In specimens from reticular and primary large varices local intimal hyperplasia was regularly found, partially accompanied with a mild increase of VV. Tortuosities and irregular dilations of adventitial veins were also found. In patients with recurrent primary varices or thrombophlebitis severe intimal and medial hyperplasia, thrombosis and a striking increase of VV were found. The intima remained avascular in all cases. Conclusions: Remarkable increase of VV accompanies the most severe forms of varices as well as all cases of the extreme grades of phlebosclerosis, medial hyperplasia and thrombosis. We hypothesize that this increase in VV is rather a secondary vascular reaction to the impaired metabolic conditions within the venous wall than a primary varicogenic factor.

Although in many cardiac surgery centers pharmacological strategies based on fibrinolytic inhibitors are used on a routine basis, detailed knowledge of fibrinolysis during various settings of coronary surgery is still limited. Sixty-five patients scheduled for coronary surgery were randomized into 3 groups: group A--conventional coronary artery bypass grafting, group B--off-pump surgery, and group C--coronary artery bypass grafting with modified, rheoparin coated cardiopulmonary bypass with the avoidance of reinfusion of cardiotomy blood into the circuit. The sampling time points for rotation thromboelastographic evaluations were as follows: preoperatively, 15 minutes after sternotomy, on the completion of peripheral bypass anastomoses, at the end of the procedures, and 24 hours after the end of surgery. D-dimer levels were evaluated before surgery, at the end of procedures, and 24 hours after surgery. Thromboelastographic signs of fibrinolysis (evaluated by Lysis Onset Time-intergroup differences at 60 and 150 minutes of assessment: P = 0.003 and P < 0.001, respectively) were clearly detectable during cardiopulmonary bypass in group A, but not at any time in groups B and C. At the other sampling times all thromboelastographic parameters were similar in all groups. In group A, no exceptional bleeding tendency (during 24 hours), as compared to groups B and C (geometric means and 95% confidence intervals: group A: 686.7 [570.8; 826.1] mL, group B: 555.3 [441.3; 698.9] mL, group C: 775.6 [645.1; 932.3] mL, P = 0.157), and no significant correlations between Lysis Onset Time, postoperative blood loss, and D-dimer levels were found. No significant differences in postoperative blood loss related to cardiac surgeons and assistant surgeons were detected. Thromboelastographic signs of increased fibrinolysis were detectable in the important proportion of coronary surgery patients operated on with the use of conventional cardio-pulmonary bypass, but not in off-pump patients and those operated on with the biocompatible surface-modified circuit without reinfusion of cardiotomy suction blood. These signs resolved spontaneously at the end of surgery and were not associated with increased postoperative bleeding. No significant correlation with D-dimer levels was found.

The aim of this preliminary, prospective, randomized study was to compare rotation thromboelastography (roTEG) results and D-dimer levels in off-pump versus on-pump coronary surgery in order to identify the activation of fibrinolysis. Twenty patients scheduled for coronary bypass grafting were assessed (off-pump group A, n = 10; on-pump group B, n = 10). Blood samples for roTEG examination were taken preoperatively (t0), 15 minutes after sternotomy (t1), on the completion of peripheral bypass anastomoses (t2), and at the end of procedures (t3). The time points for D-dimer levels analyses were before operation, at the end of procedures, and 24 hours later. A certain degree of roTEG signs of fibrinolysis was noticed at time t2 in both groups and in group B these marks were quite widely, but not significantly expressed (P for intergroup differences for Lysis on Set Time at 60 and 150 minutes were P = 0.190 and P = 0.122, respectively), borderline differences were found for Maximum Clot Firmness (P = 0.082) with a lower mean value for group B (arithmetic means [95% confidence intervals] - 57.7 [54.2; 61.2] mm). Completely expressed roTEG signs of hyperfibrinolysis were observed in 2 patients from group B. In group B also the highest geometric means of D-dimers (1326.0 [943.5; 1863.6] ng mL-1) and thus a dramatic intergroup difference (P < 0.001) were observed at the end of surgery; 24 hours later the significantly elevated D-dimer levels in both groups (A: 1070.0 [723.5; 1582.6] versus B: 1093.3 [732.0; 1632.9] ng mL-1) were equalized (P = 0.932). Our roTEG results display a slightly greater, but fairly subtle activation of fibrinolysis during the course of cardiopulmonary bypass, compared to off-pump cardiac surgery.

Off-pump coronary artery bypass surgery is becoming increasingly popular despite the lack of sufficient evidence from randomized trials. The aim of our prospective, randomized, single-center study was to examine the role of off-pump revascularization among nonselected patients.A total of 400 consecutive nonselected patients (mean age 63 years) scheduled for isolated coronary revascularization were randomized by a cardiologist into two groups: A (on-pump) and B (off-pump). The cardiac surgeon was allowed to change the operative technique at any time after randomization. The only exclusion criterion was an emergency procedure. The primary end point was any of the following within 30 days: death, myocardial infarction, stroke, or new renal failure requiring hemodialysis. The study was analyzed on the intention-to-treat principle.The primary end point occurred in 4.9% of patients in group A versus 2.9% in group B (not significant). Mortality was 1.1% in group A versus 2.0% in group B (not significant). Preoperative crossover occurred in 5.4% of patients in each group (not significant). Intraoperative conversion was necessary in 9.8% of patients in group B versus 1.1% of patients in group A (p0.001). Group B patients had fewer distal anastomoses (2.3 versus 2.7 in group A; p0.001), less blood loss (560 versus 680 mL; p0.001), lower postoperative creatine kinase MB levels (0.15 versus 0.56 microkat/L; p0.001) and lower total hospital costs (3,451 versus 4,387; p0.001).In our study off-pump technique was applicable in 85% of nonselected patients and is at least as clinically safe and effective as on-pump surgery.

Surgical ablation (SA) is commonly used in atrial fibrillation (AF) patients undergoing cardiac surgery. However, its effect has been established in few randomized studies. To assess the complete atrial fibrillation free (AF-free) survival in randomized study assessing the effects of additional concomitant SA of AF in patients primarily indicated for other cardiac surgery.The PRAGUE-12 study was a prospective randomized study comparing the effect of adding SA to other cardiac surgery. We examined the data from the PRAGUE-12 trial and grouped patients according to complete AF-free survival. All patients had regular check-ups at 3, 6, 9 months, some of them with Holter recordings, and a final check-up at 12 months with Holter recording.One hundred ninety-four patients were analyzed; 104 originally randomized to surgery with adding SA (SA group) and 90 without it (non-SA group). Complete AF-free status was found in 46 patients from the SA group (44.2%) and 25 patients (27.8%) from the non-SA group (p0.05). In a multivariate logistic regression, the SA group was associated with a greater chance for complete AF-free survival (OR 1.87, p0.05). In the multivariate analysis of the SA group, history of myocardial infarction (OR 0.2, p0.05) and a higher EuroSCORE (OR 0.9, p 0.05) were independently associated with a lower probability of AF-free survival.Complete AF-free survival following SA was present in almost one half of patients. Patients with a history of myocardial infarction and higher EuroSCOREs were less likely to benefit from an add-on SA procedure.

BACKGROUND: Previously, we reported that there was no significant difference at 30 days in the rate of a primary composite outcome of death, myocardial infarction, stroke, or new renal failure requiring dialysis between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report results on quality of life and cognitive function and on clinical outcomes at 1 year. METHODS: We enrolled 4752 patients with coronary artery disease who were scheduled to undergo CABG and randomly assigned them to undergo the procedure off-pump or on-pump. Patients were enrolled at 79 centers in 19 countries. We assessed quality of life and cognitive function at discharge, at 30 days, and at 1 year and clinical outcomes at 1 year. RESULTS: At 1 year, there was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG (12.1% and 13.3%, respectively; hazard ratio with off-pump CABG, 0.91; 95% confidence interval [CI], 0.77 to 1.07; P=0.24). The rate of the primary outcome was also similar in the two groups in the period between 31 days and 1 year (hazard ratio, 0.79; 95% CI, 0.55 to 1.13; P=0.19). The rate of repeat coronary revascularization at 1 year was 1.4% in the off-pump group and 0.8% in the on-pump group (hazard ratio, 1.66; 95% CI, 0.95 to 2.89; P=0.07). There were no significant differences between the two groups at 1 year in measures of quality of life or neurocognitive function. CONCLUSIONS: At 1 year after CABG, there was no significant difference between off-pump and on-pump CABG with respect to the primary composite outcome, the rate of repeat coronary revascularization, quality of life, or neurocognitive function. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294.).

Background Uncertainty remains regarding the benefits and risks of the technique of operating on a beating heart (off pump) for coronary artery bypass grafting (CABG) surgery versus on-pump CABG. Prior trials had few events and relatively short follow-up. There is a need for a large randomized, controlled trial with long-term follow-up to inform both the short- and long-term impact of the 2 approaches to CABG. Methods We plan to randomize 4,700 patients in whom CABG is planned to undergo the procedure on pump or off pump. The coprimary outcomes are a composite of total mortality, myocardial infarction (MI), stroke, and renal failure at 30 days and a composite of total mortality, MI, stroke, renal failure, and repeat revascularization at 5 years. We will also undertake a cost-effectiveness analysis at 30 days and 5 years after CABG surgery. Other outcomes include neurocognitive dysfunction, recurrence of angina, cardiovascular mortality, blood transfusions, and quality of life. Results As of May 3, 2011, CORONARY has recruited >3,884 patients from 79 centers in 19 countries. Currently, patient's mean age is 67.6 years, 80.7% are men, 47.0% have a history of diabetes, 51.4% have a history of smoking, and 34.4% had a previous MI. In addition, 20.9% of patients have a left main disease, and 96.6% have double or triple vessel disease. Conclusions CORONARY is the largest trial yet conducted comparing off-pump CABG to on-pump CABG. Its results will lead to a better understanding of the safety and efficacy of off-pump CABG.

Atrial fibrillation is associated with the activation of inflammatory processes [e.g. higher concentrations of pro-inflammatory cytokines interleukin-6 (IL-6), C-reactive protein (CRP)], as well as a pro-thrombotic state [e.g. increased concentration of serum pro-thrombotic markers P-selectin and CD40 ligand (CD40L)]. The aim of the present study was to establish, whether successful epicardial ablation of AF leads to decreased concentrations of traditional inflammatory and thrombotic markers.Twenty-five patients with symptomatic paroxysmal or persistent AF were prospectively studied. All underwent epicardial isolation of pulmonary veins. The success of the ablation was assessed clinically and with three Holter recordings. Blood samples were drawn before, three and six months after surgery. Serum concentrations of IL-6, interleukin-10 (IL-10), CRP, CD40L and P-selectin were measured using ELISA.AF was successfully ablated in 15 patients (SR group). In the other 10 patients (AF group), AF re-occurred during follow-up. Neither group differed with respect to age, gender, left ventricular ejection fraction, or preoperative concentrations of measured molecules. The concentrations of IL-6, CRP and CD40L decreased in successfully ablated patients; however, there was no change in the concentrations of these molecules in the AF group. The concentrations of IL-10 and P-selectin were unchanged in both groups during follow-up.Successful ablation of AF, with sinus rhythm restoration and maintenance, is associated with decreased serum levels of markers of inflammation.

Objectives: Increased apoptotic processes in tissue samples from hearts in atrial fibrillation (AF) have been previously documented in animals. Whether the restoration of sinus rhythm is associated with decreased apoptosis is not known. The aim of the present study was to establish whether successful epicardial ablation of AF leads to changes in the concentration of serum markers of apoptosis. Methods: Twenty-five patients with AF were prospectively studied. All underwent epicardial isolation of pulmonary veins. The success of the ablation was assessed clinically and with 3 Holter recordings. Blood samples were drawn before surgery, and at 3 and 6 months after. Serum concentrations of Fas (apoptosis-stimulating fragment) and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) were measured using ELISA. Results: AF was successfully ablated in 15 patients (SR group). In the other 10 patients (AF group), AF recurred during follow-up. Neither group differed with respect to age, sex, left ventricular ejection fraction, or preoperative concentrations of measured molecules. While Fas decreased in successfully ablated patients, there was no change in the Fas concentration in the AF group. Similarly, the concentrations of TRAIL decreased in the SR group, but remained unchanged in the AF group. Conclusion: The ablation of AF is associated with decreased serum markers for apoptosis.

Heart valve surgery carries a high risk of renal insufficiency as an independent risk factor due to prolonged cardiopulmonary bypass. Multiple causes of cardiopulmonary bypass-associated renal damage have been described, and haemoglobin-induced renal injury is presently being investigated. Forty-three patients scheduled for heart valve surgery (mostly combined) were enrolled in the prospective study. Plasma free haemoglobin (PFH) levels were evaluated by photocolorimetric measurement at the start of procedures ( t0) and before the end of extracorporeal circulation ( t1). A statistically significant increase in PFH levels during cardiopulmonary bypass was detected [median values (interquartile range) - t0: 62.0 (53.4) mg/L, t1: 320.4 (352.2) mg/L], P < 0.001. A significant regression relationship between the duration of cardiopulmonary bypass and the increased PFH was found (Spearman’s correlation coefficient 0.628, P < 0.001). In some elderly patients, the tendency towards a high release of PFH during cardiopulmonary bypass was more pronounced, but the overall association between age and PFH levels was of borderline significance (P = 0.077). The correlation between PFH and post-operative serum creatinine was low and non-significant, but the latter correlated highly with the pre-operative serum creatinine values (Spearman’s correlation coefficient reached values of 0.6-0.7, P < 0.001). Patients were classified according to the Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage renal failure (RIFLE) classification for acute renal dysfunction during post-operative days 1 — 4; the influence of PFH levels at t1 on the consequent RIFLE classification was not proven (P=0.648), but 4 patients in the Injury category had shown a higher median value of PFH (433.6 mg/L) in comparison with the others (29 patients with no acute renal dysfunction - 313.7 mg/L, 10 patients at Risk - 330.1 mg/L).

Although in many cardiac surgery centers pharmacological strategies based on fibrinolytic inhibitors are used on a routine basis, detailed knowledge of fibrinolysis during various settings of coronary surgery is still limited. Sixty-five patients scheduled for coronary surgery were randomized into 3 groups: group A--conventional coronary artery bypass grafting, group B--off-pump surgery, and group C--coronary artery bypass grafting with modified, rheoparin coated cardiopulmonary bypass with the avoidance of reinfusion of cardiotomy blood into the circuit. The sampling time points for rotation thromboelastographic evaluations were as follows: preoperatively, 15 minutes after sternotomy, on the completion of peripheral bypass anastomoses, at the end of the procedures, and 24 hours after the end of surgery. D-dimer levels were evaluated before surgery, at the end of procedures, and 24 hours after surgery. Thromboelastographic signs of fibrinolysis (evaluated by Lysis Onset Time-intergroup differences at 60 and 150 minutes of assessment: P = 0.003 and P0.001, respectively) were clearly detectable during cardiopulmonary bypass in group A, but not at any time in groups B and C. At the other sampling times all thromboelastographic parameters were similar in all groups. In group A, no exceptional bleeding tendency (during 24 hours), as compared to groups B and C (geometric means and 95% confidence intervals: group A: 686.7 [570.8; 826.1] mL, group B: 555.3 [441.3; 698.9] mL, group C: 775.6 [645.1; 932.3] mL, P = 0.157), and no significant correlations between Lysis Onset Time, postoperative blood loss, and D-dimer levels were found. No significant differences in postoperative blood loss related to cardiac surgeons and assistant surgeons were detected. Thromboelastographic signs of increased fibrinolysis were detectable in the important proportion of coronary surgery patients operated on with the use of conventional cardio-pulmonary bypass, but not in off-pump patients and those operated on with the biocompatible surface-modified circuit without reinfusion of cardiotomy suction blood. These signs resolved spontaneously at the end of surgery and were not associated with increased postoperative bleeding. No significant correlation with D-dimer levels was found.

a Cardiocenter, Department of Cardiology, 3rd Medical School, Charles University and University Hospital Kralovske Vinohrady Prague, Czech Republic b Cardiocenter, Department of Cardiac Surgery, 3rd Medical School, Charles University and University Hospital Kralovske Vinohrady Prague, Czech Republic c Department of Clinical Hematology, University Hospital Kralovske Vinohrady Prague, Czech Republic

Background— Off-pump coronary bypass surgery has become a widely used technique during recent years. However, limited data are available with regard to 1-year patency of bypass grafts implanted on the beating heart in unselected consecutive bypass surgery candidates. The aim of this study was to compare 1-year angiographic patency of bypass grafts done on the beating heart (off pump) with those done classically (on pump). Methods and Results— The PRAGUE-4 trial randomized 400 consecutive nonselected cardiac surgery candidates into group A (on pump; n=192) and group B (off pump; n=208). One-year follow-up coronary angiography was done in 255 patients. The arterial graft patency after 1 year was 91% in both groups. Saphenous graft patency was 59% (on pump) versus 49% (off pump; P =NS). Saphenous graft patency per patient was lower in the off-pump group: 0.7 patent anastomosis per patient versus 1.1 patent anastomosis in the on-pump group ( P P =NS). Grafts anastomosed distally to collateralized chronic total occlusions of native coronary arteries remained patent in 100% on the left anterior descending artery compared with 23% on other arteries ( P Conclusions— The patency of arterial coronary bypass grafts done on the beating heart is excellent and equal to grafts done on pump. The off-pump procedure in the unselected patient population results in fewer patent saphenous grafts per patient.

Experience gained with administration of supranormal-therapeutic doses (90 microg/kg) of recombinant activated factor VII in 7 cardiac surgery patients is presented. The patients were given recombinant activated factor VII postoperatively for intractable bleeding, 5 of them after surgical revision. Administration of recombinant activated factor VII was associated with significant reduction in blood loss (P0.05) and shortening of INR and aPTT in laboratory tests. None of the patients needed reoperation. Administration of recombinant activated factor VII proved highly effective in management of massive hemorrhage in cardiac surgery.

A new "less invasive" technique avoiding thoracic epidural analgesia has be en tested for suitability as a routine procedure for cardiac anesthesia. Early postoperative extubation is an important step in this fasttrack procedure.Consecutive patients (n = 547; age, 35-82 years; mean age, 64 year s; male to female ratio, 3.5) underwent general anesthesia with ultra-short-acting opiates and then underwent coronary surgery (n = 465), valve surgery (n = 38), or combined and other procedures (n = 44) a r;. In 51.4% cases, coronary artery bypass grafting was performed off pump. The percentage of patients extubated within 10 minutes after skin closure was the primary end point. In addition, we attempted to identify the limiting factors of the procedure tested.Of the 547 patients, 499 (91%) were extubated within 10 minutes after skin closure. Early extubation failed in 48 (9%) of the patients. The mortality rate was 1.5%. One (0.2%) of the patients needed early reintubation because of pneumothorax. Postoperative myocardial ischemia was recorded in 10 (1.8%) of the patients. Ninetysix (17.5%) of the patients were treated pharmacologically for newly developed atrial fibrillation. None of the patients needed hemodialysis. Transient neurological disorders were recorded in 10 (1.8%) of the patients. The early extubation failure group showed statistically significantly higher rates of preoperative lung dysfunction, use of extracorporeal circulation, administration of inotropic drugs in the operating room, and statistically significantly longer duration of surgery.Early extubation proved suitable as a routine procedure for the vast majority of patients. With a good postoperative analgetic protocol, there is no need for thoracic epidural analgesia. Such avoidance of thoracic epidural analgesia is a further step in minimizing invasiveness in cardiac surgery.

In this prospective study, we monitored two laboratory parameters, C-reactive protein (CRP) and fibronectin (FIN) levels, in 30 patients undergoing elective surgery for ischemic heart disease. These patients were divided into three groups according to the surgical procedure used: group A, approach through a median sternotomy with the use of extracorporeal circulation; group B, approach through a median sternotomy without the use of extracorporeal circulation; and group C, approach through a left anterior small thoracotomy (LAST) without the use of extracorporeal circulation. Peak CRP levels were found in all three groups on the second postoperative day, with the mean levels being statistically significantly higher in group C. This group also showed the highest mean CRP levels on the third and fourth postoperative days, with the difference being statistically nonsignificant. These findings can be explained by an enhanced production of cytokines, which in turn trigger CRP synthesis, induced by postoperative pain due to the LAST procedure. No statistically significant correlation between preoperative CRP levels and their postoperative development was found. None of the groups studied showed any statistically significant decrease in FIN plasma levels, either prior to adjustment for hemodilution or after adjustment for hematocrit and serum albumin.

Thoracic epidural anesthesia without intubation was used in 10 patients undergoing off-pump coronary artery reconstruction performed through median sternotomy. Considering the preoperative finding of impaired pulmonary function, all were moderate-risk patients for surgery using conventional general anesthesia with intubation. All patients had an uneventful postoperative course. In indicated cases, we regard thoracic epidural anesthesia as a suitable method again modifying the term ‘minimally invasive’ in cardiac surgery. q 2001 Elsevier Science B.V. All rights reserved.