Thrombelastographic hypercoagulability and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): a randomized controlled trial.

A hypercoagulable state has, in observational studies, been associated with increased risk of thromboembolic events. The aim of this trial was to study whether dual antiplatelet therapy (DAPT) with clopidogrel in addition to aspirin could reduce the rate of graft occlusions, thromboembolic events, and death compared to aspirin monotherapy in hypercoagulable patients undergoing coronary artery bypass surgery. A total of 1683 patients were screened for eligibility, among which 165 patients were randomized and 133 patients underwent multislice computed tomography scan to evaluate their grafts. Thrombelastography (TEG) and multiplate aggregometry were performed before and after surgery, and again at three months follow up. TEG hypercoagulability was defined as the maximum amplitude above 69 mm. At three months follow up, 17 out of 66 (25.7%) DAPT patients and 15 of 67 (22.4%) aspirin patients had significant graft stenosis or occlusions (p = 0.839). Saphenous vein grafts (SVGs) were stenosed or occluded in 15 (22.7%) patients in the DAPT group and 7 (10.4%) in the aspirin group (p = 0.167). Thromboembolic events and death after the second postoperative day (when clopidogrel was started) were numerically, but not statistically, lower in the DAPT group, 3 (3.8%) vs. 8 (9.9%), p = 0.211. In univariate logistic regression analysis, only postoperative day 4 platelet response to aspirin measured with multiplate was correlated with graft occlusion, OR 1.020 [1.002-1.039], p = 0.033. This is the first trial to test the hypothesis of intensified antiplatelet therapy in hypercoagulable patients. Due to the low enrollment and high loss to follow up, our results can only be viewed as hypothesis generating. We found a high rate of graft occlusions in this patient population. Our results were not suggestive of that DAPT improved saphenous vein graft patency. A trend was observed in patients on DAPT toward fewer MI and deaths. Postoperative response to aspirin therapy was found to be associated with early SVG occlusion.

Survival after aortic root replacement with a stentless xenograft is determined by patient characteristics.

OBJECTIVES: Our objective was to examine intermediate-term survival and reinterventions in unselected patients, stratified according to indication, who received a Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis as a full aortic root replacement. METHODS: Data from medical records were retrospectively collected for patients who had aortic root replacement using Freestyle bioprostheses between 1999 and 2018 at 6 North-Atlantic centers. Survival status was extracted from national registries and results stratified according to indication for surgery. RESULTS: We included 1030 implantations in 1008 patients with elective indications for surgery: aneurysm (39.8%), small root (8.3%), and other (13.8%), and urgent/emergent indications: endocarditis (26.7%) and Stanford type A aortic dissection (11.4%). Across indications, 46.3% were nonelective cases and 34.0% were reoperations. Median age was 66.0 (interquartile range, 58.0-71.8) years and median follow-up was 5.0 (interquartile range, 2.6-7.9) years. Thirty-day mortality varied from 2.9% to 27.4% depending on indication. Intermediate survival for 90-day survivors with elective indications were not different from the general population standardized for age and sex (P = .95, .83, and .16 for aneurysms, small roots, and other, respectively). In contrast, patients with endocarditis and type A dissection had excess mortality (P < .001). Freedom from valve reinterventions was 95.0% and 94.4% at 5 and 8 years, respectively. In all, 52 patients (5.2%) underwent reinterventions, most because of endocarditis. CONCLUSIONS: At intermediate term follow-up this retrospective study provides further support for the use of the Freestyle bioprosthesis in the real-world setting of diverse, complex, and often high-risk aortic root replacement and suggests that outcome is determined by patient and disease, rather than by prosthesis, characteristics.

No major differences in 30-day outcomes in high-risk patients randomized to off-pump versus on-pump coronary bypass surgery: the best bypass surgery trial.

BACKGROUND: Off-pump coronary artery bypass grafting compared with coronary revascularization with cardiopulmonary bypass seems safe and results in about the same outcome in low-risk patients. Observational studies indicate that off-pump surgery may provide more benefit in high-risk patients. Our objective was to compare 30-day outcomes in high-risk patients randomized to coronary artery bypass grafting without or with cardiopulmonary bypass. METHODS AND RESULTS: We randomly assigned 341 patients with a EuroSCORE > or = 5 and 3-vessel coronary disease to undergo coronary artery bypass grafting without or with cardiopulmonary bypass. Patients were followed through the Danish National Patient Registry. The primary outcome was a composite of adverse cardiac and cerebrovascular events (ie, all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and coronary reintervention). An independent adjudication committee blinded to treatment allocation assessed the outcomes. Baseline characteristics were well balanced between groups. The mean number of grafts per patient did not differ significantly between groups (3.22 in off-pump group and 3.34 in on-pump group; P=0.11). Fewer grafts were performed to the lateral part of the left ventricle territory during off-pump surgery (0.97 versus 1.14 after on-pump surgery; P=0.01). No significant differences in the composite primary outcome (15% versus 17%; P=0.48) or the individual components were found at 30-day follow-up. CONCLUSIONS: Both off- and on-pump coronary artery bypass grafting can be performed in high-risk patients with low short-term complications. CLINICAL TRIAL REGISTRATION- clinicaltrials.gov. Identifier: NCT00120991.

Graft patency after off-pump versus on-pump coronary artery surgery in high-risk patients.

OBJECTIVE: To compare angiographic graft patency in high-risk patients randomly allocated to off-pump vs. on-pump coronary artery bypass grafting (CABG). DESIGN: From a randomised, single-centre clinical trial including patients undergoing isolated first-time coronary bypass surgery a subgroup of patients were scheduled to 1-year coronary angiographic follow-up. Patients had 3-vessel disease and a EuroSCORE > or =5. We evaluated graft patency using a patency index (percentage of patent grafts out of the total number of grafts in each patient). RESULTS: One-year angiography was performed in 34 patients undergoing off-pump surgery and 35 patients undergoing on-pump surgery. The mean number of distal anastomoses was 3.38+/-0.65 in the off-pump group versus 3.46+/-0.61 in the on-pump group (NS). The number of patients without graft failure was 22 in the off-pump group and 24 in the on-pump group (NS). The overall patency index was 85% in the off-pump group versus 87% in the on-pump group with a mean difference of -2.1%, 95% confidence interval -12.9 to 8.7 (NS). CONCLUSIONS: In patients with 3-vessel disease and a high-risk profile we found no statistically significant difference in graft patency between off-pump and on-pump CABG at 1-year coronary angiographic follow-up.

One-year results of total arterial revascularization vs. conventional coronary surgery: CARRPO trial.

AIMS: To investigate clinical and angiographic outcomes after coronary surgery using total arterial revascularization (TAR). METHODS AND RESULTS: We randomized 331 patients with multivessel or isolated left main disease to TAR [internal thoracic (ITA) and radial arteries] vs. conventional revascularization (CR) using left ITA and vein grafts. The primary angiographic outcome was the patency index: number of patent grafts (<50% stenosed) divided by number of constructed grafts. One-year angiography was complete for 83% of patients. Mean patency index (+/-SD) was 87 +/- 22% in the TAR group and 88 +/- 18% in the conventional group (P = 0.52). In 72% of TAR patients and 67% of the conventional group, all grafts were patent (P = 0.45). Multiple imputation of missing angiographic data did not influence on results. Within 1 year, 37 (23%) TAR patients and 43 (25%) conventional group patients suffered cardiac events (HR 1.09, 95% CI 0.70-1.69, P = 0.70). One patient (0.6%) in the TAR group and two (1.2%) in the conventional group died (P = 1.00). CONCLUSION: Within 1 year post-operatively, TAR seems at least as safe and effective as CR. Prolonged follow-up will reveal whether this is sustained or superior results of TAR can justify a more general use.

The Best Bypass Surgery Trial: rationale and design of a randomized clinical trial with blinded outcome assessment of conventional versus off-pump coronary artery bypass grafting.

BACKGROUND: Recent trials suggest that off-pump coronary artery bypass grafting (OPCAB) reduces the risk of mortality and morbidity compared with conventional coronary artery bypass grafting (CCAB) using cardiopulmonary bypass. Patients with a moderate- to high-risk of complications after CCAB may have additional benefit from OPCAB. METHODS: The Best Bypass Surgery Trial is a randomized, single center trial comparing the effects of OPCAB versus CCAB. The inclusion criteria are 3 vessel coronary heart disease affecting one of the marginal arteries, age>54 years, and EuroSCORE>or=5. The primary composite outcome measure consists of all-cause mortality, myocardial infarction, stroke, cardiac arrest, cardiogenic shock, and cardiac revascularization procedure. Follow up involves collection of data of mortality and morbidity via linkage to public registers, quality of life assessment at 3 and 12 months postoperatively and angiographic control at 12 months. The sample size of 330 patients was based on an estimated 75% one-year event free rate of the primary outcome measure in the OPCAB arm and 60% in the control arm with alpha=.05 and beta=.20. Accordingly, the trial will be able to detect an absolute risk reduction of 15% or a relative risk reduction of 37.5%. The median follow-up time is scheduled to 3 years. RESULTS: Enrollment started in April 2002 and ended March 2006. CONCLUSION: The results may have implications on the treatment modality of moderate- to high-risk patients scheduled for coronary artery bypass grafting.

Complete arterial coronary revascularisation using radial artery conduit for double thoracic artery inlet flow: arterial sling operation.

BACKGROUND: Coronary artery bypass graft surgery with arterial revascularisation of all diseased coronary vessels is considered highly efficient because arterial grafts have an excellent long-term patency compared with venous grafts. However, problems to reach the infero-lateral wall with the in situ internal thoracic arteries usually require alternative techniques. We present the first results of a new surgical principle using a free radial artery segment to complete the arterial coronary revascularisation and concomitantly connect the internal thoracic arteries. METHODS: In patients referred for coronary bypass surgery and three-vessel disease an end-to-end anastomosis of the right internal thoracic artery and the radial artery segment preceded cardiopulmonary bypass, during which side-to-side anastomoses of the radial artery segment were used to revascularise stenotic branches of the right coronary and circumflex arteries. The left internal thoracic artery was used for revascularisation of stenotic branches of the left anterior descending artery, and finally an end-to-side anastomosis of the radial artery segment to the left internal thoracic artery was performed. Coronary artery blood flow was measured in 41 patients with Doppler flow probe. RESULTS: One hundred and ninety-two coronary anastomoses (an average of 4.2 per patient) were performed in 46 patients. We measured a mean total blood flow in the arterial sling graft of 104ml/min (range 35-221ml/min), compared with 69 and 68ml/min of the single inlet right and left internal thoracic arteries, respectively (P<0.01). Flow capacities of 104 and 120ml/min of the right and left internal thoracic arteries were measured during clamp of both the aorta and the contralateral internal thoracic artery. The mean crossclamp duration was 77min (range 51-113min). Postoperative angiography demonstrated patent graft anastomoses to all coronary arteries. There were no perioperative deaths or myocardial infarctions. One patient had a minor postoperative stroke. DISCUSSION: Complete arterial revascularisation can be achieved by the arterial sling operation with an acceptable crossclamp time and a high early rate of graft patency. The double arterial inlet provides a 50% higher blood flow to the beating heart and two-fold increase in the flow reserve compared with a single inlet. Although further research including long-term follow-up of this new principle is required, the present findings seem promising and suggest that the arterial sling operation has a potential role for complete arterial coronary revascularisation.

Aortic valve bypass: experience from Denmark.

OBJECTIVES: In aortic valve bypass (AVB) a valve-containing conduit is connecting the apex of the left ventricle to the descending aorta. Candidates are patients with symptomatic aortic valve stenosis rejected for conventional aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI). During the last one and a half year, 10 patients otherwise left for medical therapy have been offered this procedure. We present the Danish experiences with the AVB procedure with a focus on patient selection, operative procedure and short-term results. METHODS: AVB is performed through a left thoracotomy. A 19-mm Freestyle(®) valve (Medtronic) is anastomosed to a vascular graft and an apex conduit. The anastomosis to the descending aorta is made prior to connecting the conduit to the apex. In 1 patient, we used an automated coring and apical connector insertion device (Correx(®)). The device results in a simultaneous coring and insertion of an 18-mm left ventricle connector in the apical myocardium. AVB is routinely performed without circulatory assistance. RESULTS: Ten patients have been operated on since April 2011: eight females and 2 males with a median age of 76 (65-91) years. Seven patients had a severely calcified ascending aorta. Three of these had previously had a sternotomy, but did not have an AVR because of porcelain aorta. Six patients had a very small left ventricle outflow tract (<18 mm). The median additive EuroSCORE was 12 (10-15). Seven patients were operated on without circulatory assistance. Two patients had a re-exploration for bleeding and 1 developed a ventricle septum defect 1 month postoperatively and was treated with surgical closure. The median follow-up was 7 (2-15) months and was without mortality. New York Heart Association class was reduced from 2.5 to 2 at the follow-up, but some patients were still in the recovery period. The total valve area (native plus conduit) was 2.2 (1.9-2.5) cm(2) and 1.34 (1.03-1.46) cm(2)/m(2), indexed to the body surface area. There was no AV block or stroke. CONCLUSIONS: AVB can be performed with low mortality and acceptable results in selected patients. The procedure can be offered to patients rejected for conventional aortic valve replacement and TAVI and results in a larger total valve area than by insertion of standard bioprosthesis.

Decreased mitochondrial oxidative phosphorylation capacity in the human heart with left ventricular systolic dysfunction.

AIMS: Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is associated with a shift in substrate utilization and a compromised energetic state. Whether these changes are connected with mitochondrial dysfunction is not known. We hypothesized that the cardiac phenotype in LVSD could be caused by reduced mitochondrial oxidative phosphorylation (OXPHOS) capacity and reduced mitochondrial creatine kinase (miCK) capacity. The study aim was to test mitochondrial OXPHOS capacity in LVSD myocardium compared with OXPHOS capacity in a comparable patient group without LVSD. METHODS AND RESULTS: Myocardial biopsies were obtained from the left ventricle during cardiac valve or left ventricular assist device (LVAD) surgery. Patients were stratified according to left ventricular ejection fraction (LVEF) into LVSD (LVEF <45%, n = 14) or CONTROL (LVEF >45%, n = 15). Mitochondrial respiration was measured in muscle fibres with addition of non-fatty acid substrates or octanoyl-l-carnitine, a medium chain fatty acid (MCFA). The in situ enzyme capacity of miCK was determined from APD titrations in the presence or absence of creatine. Maximal OXPHOS capacity with non-fatty acid substrates was lower in the LVSD group compared with the CONTROL group (P ≤ 0.05). ADP sensitivity always increased significantly (P ≤ 0.05) with the addition of creatine, after which the sensitivity was highest (P ≤ 0.05) in LVSD compared with CONTROL. The stimulation of OXPHOS from octanoyl-l-carnitine titrations elicited ∼40% lower respiration in LVSD compared with CONTROL (P ≤ 0.05). CONCLUSION: Human LVSD is associated with markedly diminished OXPHOS capacity, particularly in MCFA oxidation. This offers a candidate mechanism for a compromised energetic state and decreased reliance on fatty acid utilization in HF.

Comparably improved health-related quality of life after total arterial revascularization versus conventional coronary surgery--Copenhagen arterial revascularization randomized patency and outcome trial.

OBJECTIVE: We compared health-related quality of life up to 11 months after coronary artery bypass grafting using total arterial revascularization versus conventional coronary surgery. METHODS: In this randomized single-center trial, 161 patients underwent total arterial revascularization using single or bilateral internal thoracic artery (ITA) and radial artery grafts versus 170 patients conventionally revascularized using left ITA and saphenous vein grafts. Preoperatively, and at 3 and 11 months, postoperatively, patients filled in the generic questionnaire Short Form-36 (SF-36). RESULTS: The mean age was 59±8 years and 39 were women (12%). Median EuroSCORE (European System for Cardiac Risk Evaluation) was 2 (interquartile range 1-4). More than 90% of patients filled in the questionnaire at all three time points. Preoperatively, all scores were lower (P<0.001) than for a sample of the general Danish population. On all scales of the SF-36, there was statistically significant improvement at 3 and 11 months in both groups. For 'social functioning', the improvement following total arterial revascularization was significantly higher than following conventional revascularization (P=0.01). For total arterial revascularization, there were also not statistically significant improvements for 'physical component summary' (P=0.09), 'bodily pain' (P=0.07) and 'vitality' (P=0.08). CONCLUSION: Health-related quality of life up to 1 year after total arterial revascularization is equal or slightly better than results after conventional coronary surgery.

Three-year follow-up in a subset of high-risk patients randomly assigned to off-pump versus on-pump coronary artery bypass surgery: the Best Bypass Surgery trial.

OBJECTIVE: To evaluate off-pump versus on-pump coronary artery bypass grafting (CABG) in patients with three-vessel disease and a high-risk operative profile. DESIGN: A randomised clinical trial. SETTING: Rigshospitalet, University Hospital, Copenhagen, Denmark. PARTICIPANTS: 341 patients with three-vessel disease and a EuroSCORE of 5 or greater. Main exclusion criteria were previous heart surgery, poor left ventricular function (ejection fraction <30%), or unstable preoperative condition. INTERVENTION: CABG performed with versus without cardiopulmonary bypass. MAIN OUTCOME MEASURE: The primary outcome was a composite of major adverse cardiac and cerebrovascular events (MACCE) including all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke and coronary reintervention. RESULTS: MACCE occurred in 69 (40%) patients allocated to off-pump versus 54 (33%) patients allocated to on-pump CABG during the median 3.7 years of follow-up (HR 1.22; 95% CI 0.86 to 1.75; p=0.26). All-cause mortality was significantly increased in the off-pump group (24% vs 15%; HR 1.66, 95% CI 1.02 to 2.73; p=0.04), but cardiac-related death was not significantly different (10% vs 7%; HR 1.30, 95% CI 0.64 to 2.66; p=0.47). An insignificant trend towards a reduction in myocardial infarction after off-pump CABG was observed (7% vs 14%; HR 0.53, 95% CI: 0.27 to 1.04; p=0.06). CONCLUSIONS: No significant difference in the primary outcome of MACCE was found between off-pump and on-pump CABG. However, mortality seemed higher after off-pump CABG. TRIAL REGISTRATION: http://clinicaltrials.gov/number, NCT00120991.

A novel nonsense variant in Nav1.5 cofactor MOG1 eliminates its sodium current increasing effect and may increase the risk of arrhythmias.

BACKGROUND: The protein MOG1 is a cofactor of the cardiac sodium channel, Nav1.5. Overexpression of MOG1 in Nav1.5-expressing cells increases sodium current markedly. Mutations in the genes encoding Nav1.5 and its accessory proteins have been associated with cardiac arrhythmias of significant clinical impact. We sought to investigate whether MOG1 is implicated in cardiac arrhythmias. METHODS: We performed a genetic screening of the MOG1-encoding gene (gene symbol RANGRF, alias MOG1) in 220 Danish patients with cardiac arrhythmia. Of the 220, 197 were young patients with lone atrial fibrillation and 23 were patients with Brugada syndrome. The effect of one variant was investigated functionally by patch-clamping CHO-K1 cells coexpressing Nav1.5 with MOG1. RESULTS: We uncovered a novel heterozygous nonsense variant, c.181G>T (p.E61X), that, however, was also present in control subjects, albeit at a lower frequency (1.8% vs 0.4%, P = 0.078). Electrophysiological investigation showed that the p.E61X variant completely eliminates the sodium current-increasing effect of MOG1 and thereby causes loss of function in the sodium current. When mimicking heterozygosity by coexpression of Nav1.5 with wild-type MOG1 and p.E61X-MOG1, no current decrease was seen. CONCLUSIONS: Our screening of Nav1.5 cofactor MOG1 uncovered a novel nonsense variant that appeared to be present at a higher frequency among patients than control subjects. This variant causes MOG1 loss of function and therefore might be disease causing or modifying under certain conditions.

Comparable three months' outcome of total arterial revascularization versus conventional coronary surgery: Copenhagen Arterial Revascularization Randomized Patency and Outcome trial.

OBJECTIVE: The in-hospital safety of total arterial revascularization for coronary artery bypass surgery seems to be comparable to conventional revascularization, but randomized trials evaluating this are few and data on complications in the postoperative months are sparse. METHODS: In a randomized single-center trial, 331 patients underwent total arterial revascularization using single or bilateral internal thoracic and radial arteries versus conventional revascularization using the left internal thoracic artery and saphenous vein grafts. We report the results from 3 months' follow-up. RESULTS: The mean age of patients was 59 +/- 8 years, and 39 were women (12%). The median EuroSCORE was 2 (interquartile range 1-4). The arterial group comprised 161 patients, and the conventional group comprised 170 patients. The mean number of bypasses in the arterial group was 2.9 +/- 0.9 versus 3.2 +/- 0.9 in the conventional group (P = .004). Three months' follow-up for the arterial versus conventional groups showed the following: deaths: 1 (0.6%) versus 0; stroke: 3 (1.9%) versus 3 (1.8%); myocardial infarction: 6 (3.7%) versus 4 (2.4%); sternal wound reoperation: 4 (2.5%) versus 0 (P = .054); arm and leg wound complications requiring hospitalization: 3 (1.9%) versus 6 (3.5%) (P = .50), respectively. CONCLUSION: These results confirm previous reports that total arterial revascularization can be performed with low in-hospital morbidity and mortality. Further, in the 3 postoperative months, total arterial revascularization did not lead to more complications or admissions than conventional surgery. Arterial grafting was performed with significantly fewer bypasses, but no differences in anginal status were seen after 3 months. A tendency toward more sternal complications after arterial grafting was observed, but clinical outcomes were comparable to conventional grafting.

Another pitfall in minimally invasive mitral valve repair.

We report a case of severe systolic anterior motion (SAM) and dynamic left ventricular outflow obstruction after repair of a flail posterior leaflet of the mitral valve. The reason for SAM was found to be due to traction on the pericardial stay sutures placed to expose the surgical field. The SAM and the outflow obstruction were completely resolved by cutting these sutures. Our case demonstrates the contribution of geometric factors in the development of SAM and left ventricular outflow obstruction and emphasizes the need to evaluate the heart in its natural position within the mediastinum.

The arterial sling operation: one-year follow-up.

BACKGROUND: Coronary artery bypass graft surgery with total arterial revascularization, particularly the use of bilateral in situ internal thoracic arteries, is considered an improved treatment of patients with ischemic heart disease. The sling operation connects the internal thoracic arteries with the radial artery, creating an arterial arcade with double inlet of blood to the peripheral vascular bed. In this paper we present 1-year follow up of angiographic and clinical results of the arterial sling operation. METHODS: The arterial sling operation was performed in 28 patients in the period from October 2000 to September 2001, and all patients were offered an angiographical and clinical examination 1 year postoperatively. All angiograms were systematically reviewed by an interventional cardiologist and a cardiac surgeon. RESULTS: Twenty-three patients participated in the 1-year angiographic follow up. Of these 3 patients had a fully open arterial sling, 15 patients had stenosis or occlusion of one segment, and 5 patients had occlusion or stenosis of 2 segments of the radial artery. Eight of the total 93 peripheral anastomoses were occluded. The 1-year graft patency rate was 91.4%. CONCLUSIONS: The arterial sling operation is safe and the one year patency rate is high. Although one or two segments of the arterial sling may degenerate due to competitive blood flow, this does not affect blood flow in the vascular bed in patients without disease progression. However, arterial revascularization should be performed in a way to minimize competitive flow.

Trauma to the heart and thoracic aorta: the Copenhagen experience.

Injuries of the heart and thoracic aorta (traumatic aortic rupture, TAR) remain amongst the most challenging of all injuries seen in the field of trauma and cardiothoracic surgery. The aim herein was to present our experience of such lethal injuries treated at Denmark's busiest hospital. We found 11 patients with cardiac injuries and nine patients with TAR. Five patients with cardiac injuries presented in shock of which two died. Eight patients with TAR were operated on using bypass without paraplegia. The Danish experience of heart trauma is limited but with satisfactory results. We recommend left heart bypass to prevent paraplegia in TAR.