No-touch saphenous vein grafts in coronary artery surgery (SWEDEGRAFT): Rationale and design of a multicenter, prospective, registry-based randomized clinical trial.

The SWEDEGRAFT study (ClinicalTrials.gov Identifier: NCT03501303) tests the hypothesis that saphenous vein grafts (SVGs) harvested with the "no-touch" technique improves patency of coronary artery bypass grafts compared with the conventional open skeletonized technique. This article describes the rationale and design of the randomized trial and baseline characteristics of the population enrolled during the first 9 months of enrollment. The SWEDEGRAFT study is a prospective, binational multicenter, open-label, registry-based trial in patients undergoing first isolated nonemergent coronary artery bypass grafting (CABG), randomized 1:1 to no-touch or conventional open skeletonized vein harvesting technique, with a planned enrollment of 900 patients. The primary end point is the proportion of patients with graft failure defined as SVGs occluded or stenosed >50% on coronary computed tomography angiography at 2 years after CABG, earlier clinically driven coronary angiography demonstrating an occluded or stenosed >50% vein graft, or death within 2 years. High-quality health registries and coronary computed tomography angiography are used to assess the primary end point. The secondary end points include wound healing in the vein graft sites and the composite outcome of major adverse cardiac events during the first 2 years based on registry data. Demographics of the first 200 patients enrolled in the trial and other CABG patients operated in Sweden during the same time period are comparable when the exclusion criteria are taken into consideration. RCT# NCT03501303.

Validity of the Swedish Cardiac Surgery Registry.

OBJECTIVES: Our goal was to validate the Swedish Cardiac Surgery Registry by reviewing the reported cardiac operations to assess the completeness and quality of the registered data and the EuroSCORE II variables. METHODS: A total of 5837 cardiac operations were reported to the Swedish Cardiac Surgery Registry in Sweden during 2015. A randomly selected sample of 753 patient records (13%) was scrutinized by 3 surgeons at all 8 units in Sweden performing open cardiac surgery in adults. RESULTS: Coverage was excellent with 99% [95% confidence interval (CI) 98-99%] of the performed procedures found in the registry. Reported waiting times for surgery were correct in 78% (95% CI 76-79%) of the cases. The main procedural code was correctly reported in 96% (95% CI 95-97%) of the cases. The correlation between reported and monitored logistic EuroSCORE II had a coefficient of 0.79 (95% CI 0.76-0.82), and the median difference in EuroSCORE II was 0% (interquartile range -0.4% to 0.4%). The majority of EuroSCORE II variables had good agreement and coherence; however, New York Heart Association functional class, preoperative renal dysfunction, left ventricular ejection fraction, Canadian Cardiovascular Society Class IV angina and poor mobility were less robust. Postoperative complications were rare and in general had a high degree of completeness and agreement. CONCLUSIONS: The reliability of the variables in the national Swedish Cardiac Surgery Registry was excellent. Thus, the registry is a valuable source of data for quality studies and research. Some EuroSCORE II variables require improved and stricter definitions to obtain uniform reporting and high validity.

Pulmonary artery dissection in a patient with undiagnosed pulmonary hypertension--A case report and review of literature.

Pulmonary artery dissection is rare and highly lethal and most reports in the literature are from autopsies. We describe a patient with undiagnosed primary pulmonary hypertension suffering from pulmonary artery dissection that subsequently underwent surgical repair and in addition review the current literature on this topic.

A structured blood conservation programme reduces transfusions and costs in cardiac surgery.

OBJECTIVES: Transfusions of blood products can be lifesaving, but they are also associated with considerable risks and adverse effects, including immune response and infections. In cardiac surgery, transfusions have also been associated with increased mortality. We prospectively studied the effects of a structured programme to reduce transfusions and transfusion-associated costs in cardiac surgery. METHODS: The programme included: (i) education of all staff about the risks and benefits of blood transfusions; (ii) revised guidelines for transfusions; and (iii) a transfusion log where indication for transfusion, status of the patient and prescribing physician were registered. Transfusion prevalence, complications and costs for blood products were registered for all acute and elective cardiac operations during a 12-month period before (n = 1128) and after (n = 1034) the programme was started. The two time periods were compared. In addition, the prevalence of transfusions was registered for 2 more years after the programme was initiated. RESULTS: The first year after the programme was initiated the proportion of patients transfused with red blood cell concentrate decreased by 21.8% (from 58.2 to 45.5%, P <0.001), plasma by 37.4% (from 30.8 to 19.3%, P <0.001) and platelets by 21.0% (from 20.5 to 16.2%, P = 0.010). Reoperations for bleeding (5.8 vs 5.0%), early complication rate and 30-day mortality (2.5 vs 2.6%) were not significantly different before and after the start date. Based on the 2009 institutional prices for red blood cell concentrate (102 €/unit), plasma (35 €/unit) and platelets (290 €/unit), the savings on blood products were €161,623 during the first 12 months after the programme was launched. The proportion of patients transfused with any blood product was 60.9% before the programme was started and 48.3, 54.0 and 50.7% 1-3 years after its start (all P <0.001), respectively. CONCLUSIONS: A structured blood conservation programme reduces transfusions and costs for blood products in cardiac surgery, without any signs of compromised medical safety. The effects of introducing such a programme are maintained over at least 3 years.

Sustained heparin effect contributes to reduced plasma thrombin generation capacity early after cardiac surgery.

INTRODUCTION: Thrombin is a key component in the coagulation cascade, and impaired thrombin generation has been linked to increased bleeding after surgical procedures. The aim was to evaluate postoperative thrombin generation capacity in plasma after cardiac surgery, and its potential associations to activity of individual coagulation factors and heparin. MATERIAL AND METHODS: Forty-eight coronary artery bypass grafting patients were included in a prospective observational cohort study. Thrombin generation capacity was analysed in plasma with calibrated automated thrombogram with tissue factor as activator before (baseline), and 2 h and 24 h after surgery. In addition, plasma activity of coagulation factors II, V, VII, VIII, IX, X, XI, XIII, were determined. Heparin effect was assessed by anti-Xa activity, APTT and thrombin time. RESULTS: Thrombin generation was markedly reduced 2h after surgery compared to baseline. Peak levels decreased with median 74% (interquartile range 52-90), p<0.001, and endogenous thrombin generation potential decreased with 65% (43-86), p<0.001. Postoperative changes in endogenous thrombin generation potential correlated inversely to changes in anti-Xa activity (r=-0.51, p=0.010) and to changes in thrombin time (r=-0.51, p=0.009), but there were no correlations to changes in individual coagulation factor activity. CONCLUSIONS: A marked reduction in thrombin generation potential was observed in the early postoperative phase after cardiac surgery. The decrease was independent of reductions in individual coagulation factor activity but correlated to heparin effects. The results indicate that a sustained heparin effect contributes to the postoperative reduction in thrombin generation capacity.

Prophylactic fibrinogen infusion in cardiac surgery patients: effects on biomarkers of coagulation, fibrinolysis, and platelet function.

OBJECTIVE: We have recently reported that prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass grafting (CABG) surgery. Because fibrinogen for the first time was administered to patients without hereditary fibrinogen deficiency or ongoing bleeding, a detailed analysis of the effects of fibrinogen concentrate on biomarkers of coagulation, fibrinolysis, and platelet function was performed. METHODS: Twenty CABG patients with preoperative plasma fibrinogen levels <3.8 g/L were included in a prospective study. Patients were randomized to preoperative infusion of 2 g fibrinogen concentrate (fibrinogen group) or no infusion (control group). Activated partial thromboplastin time (aPTT), prothrombin time, activated clotting time, and plasma concentrations of fibrinogen, antithrombin, thrombin-antithrombin complex, prothrombin fragment 1.2, and D-dimer, thromboelastometry, platelet count, and platelet aggregometry were analyzed before and 15 minutes after infusion, and 2 and 24 hours after surgery. RESULTS: Fifteen minutes after infusion of fibrinogen concentrate, fibrinogen plasma levels increased by 0.6 ± 0.2 g/L (P < .001 between groups), and induced minimal changes in aPTT and plasma levels of antithrombin, while remaining variables remained unchanged. After surgery, fibrinogen levels no longer differed between groups. D-dimer was significantly higher after surgery in the fibrinogen group (P = .03), while none of the other markers were statistically different between groups. CONCLUSIONS: Infusion of 2 g fibrinogen to cardiac surgery patients, without hereditary or acquired fibrinogen deficiency or ongoing bleeding, results in no or minimal changes in biomarkers reflecting coagulation and platelet function. An increased release of fibrin degradation products was detected after surgery in fibrinogen-treated patients.

Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery: a prospective observational study.

BACKGROUND: Hemodilution and consumption of coagulation factors during cardiopulmonary bypass has been suggested to contribute to bleeding complications after cardiac surgery. The aim was to describe the activity of individual coagulation factors after CABG in relation to hemodilution and postoperative bleeding. MATERIALS AND METHODS: Plasma concentrations of fibrinogen and plasma activity of FII, FV, FVII, FVIII, FIX, FX, FXI and FXIII adjusted for hemodilution were analysed in 57 CABG patients before, and 2h and 24h after surgery. Postoperative bleeding was registered and correlations to coagulation factor activity were calculated. RESULTS: Adjusted plasma concentration of fibrinogen (-14+/-6%), and plasma activity of FII (-9+/-6%), FV (-13+/-8%), FX (-13+/-7%) and FXIII (-9+/-14%) were reduced two hours after surgery compared to baseline (all p<0.001). FVII (+3+/-12%, p=0.34) and FXI (+1+/-19%, p=0.50) were unchanged, while FVIII (+23+/-44%, p=0.006) and FIX (+23+/-17%, p<0.001) increased. Twenty-four hours after surgery fibrinogen (+45+/-27%), FVIII (+93+/-66%) and FIX (+33+/-26%) were all increased (all p<0.001), while FVII (-37+/-14%, p<0.001), FXI (-4+/-18%, p=0.02) and FXIII (-6+/-15%, p=0.004) were decreased. Median postoperative blood loss was 380 ml/12h. There were significant inverse correlations between postoperative blood loss and fibrinogen concentration 2h after surgery (r=-0.33, p=0.019) and between postoperative blood loss and pre- and postoperative FXIII activity (r=-0.34, p=0.009 and r=-0.41, p=0.003, respectively), but not between blood loss and any of the other factors. CONCLUSIONS: There is a marked dissociation in plasma activity of individual coagulation factors after CABG. Plasma concentration of fibrinogen and factor XIII activity correlates inversely to postoperative blood loss after CABG.

Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery. A prospective randomised pilot study.

It has been suggested that preoperative fibrinogen plasma concentration is independently associated to postoperative blood loss after cardiac surgery. Theoretically, prophylactic infusion of fibrinogen concentrate may thus reduce postoperative bleeding, but this has not previously been investigated. Twenty elective coronary artery bypass graft (CABG) patients with preoperative plasma fibrinogen levels <3.8 g/l were included in a prospective randomised pilot study. Patients were randomised to receive an infusion of 2 g fibrinogen concentrate (FIB group) or no infusion before surgery (control group). Primary endpoint was safety with clinical adverse events and graft occlusion assessed by multi-slice computed tomography. Predefined secondary endpoints were postoperative blood loss, blood transfusions, haemoglobin levels 24 hours (h) after surgery, and global haemostasis assessed with thromboelastometry, 2 and 24 hours after surgery. Infusion of 2 g fibrinogen concentrate increased plasma levels of fibrinogen by 0.6 +/- 0.2 g/l. There were no clinically detectable adverse events of fibrinogen infusion. Computed tomography revealed one subclinical vein graft occlusion in the FIB group. Fibrinogen concentrate infusion reduced postoperative blood loss by 32% (565 +/- 150 vs. 830 +/- 268 ml/12 h, p=0.010). Haemoglobin concentration was significantly higher 24 h after surgery in the FIB group (110 +/- 12 vs. 98 +/- 8 g/l, p=0.018). Prophylactic fibrinogen concentrate infusion did not influence global postoperative haemostasis as assessed by thromboelastometry. In conclusion, in this pilot study preoperative fibrinogen concentrate infusion reduced bleeding after CABG without evidence of postoperative hypercoagulability. Larger studies are necessary to ensure safety and confirm efficacy of prophylactic fibrinogen treatment in cardiac surgery.

Plasma fibrinogen level, bleeding, and transfusion after on-pump coronary artery bypass grafting surgery: a prospective observational study.

BACKGROUND: Early identification of patients with increased risk of excessive bleeding and transfusion after cardiac surgery offers the possibility to initiate countermeasures. Fibrinogen is a key protein in the coagulation cascade and thus a potential biomarker for bleeding. We investigated the relationship between preoperative fibrinogen plasma concentration and postoperative bleeding and transfusion after coronary artery bypass grafting (CABG). STUDY DESIGN AND METHODS: A total of 170 patients (mean age, 67 +/- 9 years; 75% men) undergoing isolated CABG were included in a prospective observational study. Patient variables (age, sex, operation time, anticoagulation therapy), preoperative laboratory variables (platelet [PLT] count, activated partial thromboplastin time, prothrombin time, and fibrinogen), postoperative bleeding volume, and transfusions during hospital stay were registered. Independent predictors of bleeding volume and transfusion were identified with multiple regression models. RESULTS: Postoperative bleeding volume correlated univariately with preoperative fibrinogen concentration (r = -0.53, p < 0.001) and PLT count (r = -0.26, p = 0.001) but only preoperative fibrinogen concentration was an independent predictor of postoperative bleeding volume. Twenty-nine of the 170 patients (17%) received transfusions with blood products. Independent predictors of transfusion were preoperative fibrinogen concentration (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.7 per 1-unit decrease; p = 0.027), female sex (OR, 5.0; 95% CI, 1.8-14.7; p = 0.002), and aortic cross-clamp time (OR, 1.03; 95% CI, 1.01-1.06 per minute; p = 0.013). CONCLUSION: The results indicate that preoperative fibrinogen concentration (even within the normal range) is a limiting factor for postoperative hemostasis. Preoperative measurement of fibrinogen concentration provides information about bleeding volume and transfusion requirements after CABG.

Tumor necrosis factor gene polymorphism and cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after cardiac transplantation. Tumor necrosis factor-alpha (TNF-alpha) may be a key factor in the development of CAV. Two bi-allelic polymorphisms associated with high TNF-alpha production have been identified in the TNF gene locus, TNFA1/2, at position -308 and TNFB1/2 at +252. We hypothesized that recipient TNFA2 and TNFB2 homozygosity is associated with the development of CAV after heart transplantation. METHODS: TNF gene polymorphisms were analyzed by multiplex fluorescent solid-phase mini-sequencing in 70 cardiac transplant recipients. Recipients homozygous for TNFA2 or TNFB2 (Group A, n = 29) were compared with recipients heterozygous or homozygous for TNFA1 and TNFB1 (Group B, n = 41). Coronary arteriography was performed annually or when indicated. Cumulative freedom from CAV and survival was calculated according to the Kaplan-Meier test. RESULTS: Mean follow-up was 3.8 +/- 0.3 years. In Group A, 11 of 29 recipients (38%) developed CAV compared with 9 of 41 (22%) in Group B (p = 0.12). Cumulative freedom from CAV at 3 years was 42% in Group A and 80% in Group B (p = 0.043). In Group A, 11 of 29 recipients (38%) died during follow-up compared with 4 of 41 (10%) in Group B (p = 0.006). Cumulative survival at 3 years was 72% in Group A and 93% in Group B (p = 0.003). CONCLUSIONS: The results suggest that TNFA2 and TNFB2 allele homozygosity is associated with cardiac allograft vasculopathy and mortality in heart transplant recipients.