OBJECTIVES The main objective was to assess whether a composite coronary artery bypass grafting strategy including a saphenous vein graft bridge to distribute left internal mammary artery outflow provides non-inferior patency rates compared to conventional grafting surgery with separated left internal mammary artery to left anterior descending coronary graft and aorto-coronary saphenous vein grafts to other anterolateral targets.METHODS All patients underwent isolated grafting surgery with cardiopulmonary bypass and received = 2 grafts/patients on the anterolateral territory. The graft patency (i.e. non-occluded) was assessed using multislice spiral computed tomography at 1 year.RESULTS From 2012 to 2021, 208 patients were randomized to a bridge (n = 105) or conventional grafting strategy (n = 103). Patient characteristics were comparable between groups. The anterolateral graft patency was non-inferior in the composite bridge compared to conventional grafting strategy at 1 year [risk difference 0.7% (90% confidence interval -4.8 to 6.2%)]. The graft patency to the left anterior descending coronary was no different between groups (P = 0.175). Intraoperatively, the bridge group required shorter vein length for anterolateral targets (P < 0.001) and exhibited greater Doppler flow in the mammary artery pedicle (P = 0.004). The composite outcome of death, myocardial infarction or target vessel reintervention at 30 days was no different (P = 0.164).CONCLUSIONS Anterolateral graft patency of the composite bridge grafting strategy is non-inferior to the conventional grafting strategy at 1 year. This novel grafting strategy is safe, efficient, associated with several advantages including better mammary artery flow and shorter vein requirement, and could be a valuable alternative to conventional grafting strategies. Ten-year clinical follow-up is underway.

The main objective of the AMI-PONT trial was to assess whether a CABG strategy including a bridge to distribute the LIMA outflow provides non-inferior patency rates compared to conventional CABG surgery with separated LIMA graft to LAD and aorto-coronary SVG to other anterolateral targets. The bridge grafting strategy uses a short SVG interposed between the LAD and at least one other anterolateral target, with the LIMA grafted on the hood of the bridge just above the LAD anastomosis (almost direct LIMA-LAD connection). This technique is easy to implement and has several potential advantages including distribution of LIMA flow to a greater vascular bed, bridge convenience for angioplasty, easier anastomosis of the smaller/fragile LIMA graft on the bridge compared to diseased/intramyocardial LAD targets, and use of shorter SVG. The power analysis was based on a non-inferiority principle, considering the potential advantages of the bridge technique (unilateral 5% alpha, power 80%). From July 2012 to April 2021, 208 patients were randomized to a bridge (n=105) or conventional grafting strategy (n=103). Patients characteristics were comparable with a mean age of 65±8 years, 93% male, 34% diabetics, 22% recent myocardial infarction and LVEF of 57±9%. Patients underwent isolated CABG with cardiopulmonary bypass and received 4.2±0.9 grafts/patients including 2.2±0.4 grafts/patients on the anterolateral territory. There were three patient crossovers; data was assessed as intention-to-treat. The anterolateral graft patency index (i.e., non-occluded) was assessed using multislice spiral computed tomography at one year. The anterolateral graft patency index was no different at one year (bridge: 91.8% [145/158] vs conventional: 93.6% [160/171]) with a risk difference of 1.8% (90%CI -3.1% to 6.7%), which did not cross the specified boundary of -5%, demonstrating non-inferiority. The LIMA-to-LAD graft patency was no different (98.7% [74/75] vs 96.2% [75/78]; p=0.620). Intraoperatively, the bridge group exhibited greater Medistim doppler flow in the LIMA pedicle (75±48ml/min vs 56±33ml/min; p=0.002) and required shorter SVG length for the anterolateral targets (53±21mm vs 97±34mm; p<.001). The composite outcome of death, myocardial infarction or need for coronary intervention at 30 days was no different (2.9% [3/105] vs 6.8% [7/103]; p=0.212). The AMI-PONT trial shows non-inferiority of a composite grafting strategy compared to conventional CABG strategy for anterolateral graft patency at one year. The LSVB grafting strategy presents several technical advantages for cardiac surgeons faced with an aging patient population with diffusely diseased target vessels, limited availability of suitable conduits and diseased ascending aortas. Ten-year clinical follow-up is planned.

Despite highly encouraging animal studies, clinical trials have revealed marginal therapeutic efficacy of stem cell transplantation for ischemic cardiomyopathy (IC). Intracardiac delivery of unselected bone marrow cells have yielded inconsistent results in first-generation trials which indicated preference for use of selected stem cells in subsequent studies. Our team investigated the intra-cardiac delivery of autologous CD133+ cells in patients suffering from ischemic cardiomyopathy in COMPARE-AMI (recent infarct) and IMPACT-CABG (steady state cardiac insufficiency) phase II randomized trials respectively, counting in total 80 patients. While safety and feasibility endpoints were met, these studies demonstrate improvement of cardiac functional recovery in some but not in all patients. With available banked stem cells from these trials, our goal is to identify genomic signatures responsible for therapeutic efficacy in order to identify ideal allogeneic donor cell populations or novel pre-treatments ('pharmaco-optimization') that could replicate cellular phenotypes of functionally competent CD133+. Expression of 20,800 genes were analyzed in high-throughput AmpliSeq using CD133+ from patients classified as responders (≥3% LVEF) and non-responders according to cardiac fMRI comparing pre- and post-treatment changes. RNA-Seq differential expression analysis was performed using the package limma and gene set enrichment analysis was performed on Gene Ontology (GO) pathways using nominally significant genes. Heatmaps where produced using R on significantly associated GO terms. CD133+ from acute MI patients in COMPARE-AMI (n=13) compared to chronic MI patients in IMPACT-CABG (n=12) preferentially overexpress genes associated with cell cycle regulation, DNA synthesis/ repair, metabolic processes, telomere activity and cardiac development. Of these, cell cycle progression and cellular metabolism related genes are associated with COMPARE-AMI clinical responders (n=5). Moreover, FACS analysis revealed unaltered levels of surface markers for CD45+, CD34+, CD106+, CD184+, CD49d+ and CD105+ for responder and non-responder patients, whereas CD90+, a marker associated with different hematopoietic stem cell phenotypes including inhibition of proliferation and differentiation showed increased expression in non-responders (n=8). In this exploratory study we had the unique opportunity to use banked CD133+ cells to identify genes modulated during acute and chronic MI, as well as transcriptomic signatures associated with clinical response. Such signatures have guided our efforts in developing potent pharmaco-optimizers, and this data is used to query various databases containing large numbers of bioactive compounds to further refine stem cell optimization strategies for the purpose of replicating clinical responsiveness phenotypes in cells ex vivo prior to transplantation in our next-generation trials.

Background: Therapeutic benefits of cell therapy remain modest due to varying cell phenotypes from different patients and the poor survival of transplanted cells. IMPACT-CABG and COMPARE-AMI trials represent the first North American phase II randomized studies of autologous CD133+ stem cells delivered in the heart post myocardial infarction (MI). Cells were delivered in patients suffering from chronic ischemic cardiomyopathy through transepicardial injections during CABG procedure (IMPACT-CABG) and by intracoronary route during PCI and stenting <7 days following MI (COMPARE-AMI). With banked stem cells, we set out to identify the CD133+ expression phenotypes in both patient populations and identify transcriptomic signatures responsible for therapeutic effectiveness.

Therapeutic benefits of cell therapy remain mitigated due to factors including cell phenotypes and their poor survival and function in pathologic heart. Whereas first generation of advances focused on cell selection, delivery and a broad understanding of mechanisms involved in therapy success, the next advances will come from decoding complex biological pathways underpinning regenerative potential of cells from different patients. IMPACT-CABG trial represents the first North American phase II multicenter randomized study of intra-myocardial delivery of autologous CD133+ cells in chronic cardiomyopathy patients undergoing CABG. With banked stem cells from this trial, we have the opportunity to correlate the patient's clinical outcome with cellular gene expression profiles. Our goal is to identify genomic signatures responsible for therapeutic effectiveness and identify pre-treatments from our drug discovery platform that could activate cellular phenotypes replicating those of patients responding to cell therapy. In this exploratory study, expression of 20,800 human genes (Ion AmpliSeq) are analyzed in high-throughput format using CD133+ stem cells from 13 patients classified as responders (≥5% LVEF and/or ≤10% left ventricular volumes) vs non-responders according to cardiac fMRI comparing pre- and 6-month post-treatment changes. Differential expression and pathway analysis are performed using computational tools including DESeq2, GAGE (Generally Applicable GeneSet Enrichment for Pathways Analysis), PathView and R. Pathway analyses show significant association in responders with genes related to cytokine production, activity and receptor interaction, cell adhesion molecules, regulation of kinase cascades (p < 0.05). Several other comparisons were performed to characterize gene expression vs patient demographics. The general pattern of activity was replicated in human mesenchymal stem cells (hMSC) by short ex vivo pharmacological conditioning with Celastrol, an HSP90 targeting compound. Celastrol activates kinases PI3K/Akt and ERK1/2 within 5min, upregulates HSP70 and HO-1 mRNAs (>30-fold) as well as VEGF in cells maintained in normoxic (2.7-fold) or hypoxic condition (1.3-fold, p < 0.05). Celastrol improves hMSC viability during hypoxic or oxidative challenges. Proteomic analysis of culture conditioned-media shows upregulation (>2-fold) of over 100 proteins, including HSPs, growth factors, antioxidants, cytokines indicating improved paracrine potential. IMPACT-CABG responder's stem cells express gene sets associated with paracrine potential, cell engraftment and survival that can be mimicked by an ex vivo pharmacological pre-conditioning to improve stem cell therapeutic potential. Information gathered will be used in IMPACT-CABG II trial involving a first of its kind precision pharmaco-optimization strategy (USPTO62/350,258 patent pending) to harness the full potential of cellular cardiomyoplasty using CD133+ cells.

Purpose: A large multicenter randomized trial (RCT) is needed to assess off-pump coronary artery bypass graft (CABG) patency when performed by skilled surgeons. This prospective multicenter randomized pilot study compares graft patency after on-pump and off-pump techniques and addresses the feasibility of such an RCT. Materials and Methods: Consecutive patients were prospectively recruited for ≥64-slice computed tomography angiography graft patency assessment 1 year after randomization to off-pump or on-pump CABG. Blinded assessment of graft patency was performed, and the results were categorized as normal, ≥50% stenosis, or occlusion. A multilevel model with random effects on the patient was used to account for correlation of results in patients with multiple grafts. Results: A total of 157 patients (3 centers, 84 off-pump and 73 on-pump patients, 512 grafts, assessability rate 98.4%) were included. Patency index (% nonoccluded grafts) was 89% for the off-pump technique and 95% for the on-pump technique ( P =0.09). Patency was similar for arterial and vein grafts (both 92%; P =0.88), as well as between target territories (89% to 94%; P =0.53). Conclusions: In this pilot study, 1-year graft patency results after off-pump and on-pump surgery were similar. This feasibility trial demonstrates that a large multicenter RCT to compare CABG patency after on-pump with that after off-pump techniques is feasible and can be reliably undertaken using computed tomography angiography.

The CORONARY trial (NCT00463294, N=4752 patients randomly assigned to off- or on-pump CABG) demonstrated similar results between off-pump CABG compared with on-pump CABG at 1 year. As CABG aims to restore adequate blood supply to the ischemic heart, the success of the operation depends mainly on the patency of the grafts. The long-term patency, especially vein grafts, is limited and graft failure has consequences similar to those of native coronary artery disease: recurrent angina, myocardial infarct (MI), additional revascularization procedures, or death. It is still debated whether off-pump CABG surgery is associated with worse graft patency when performed by skilled surgeons in higher risk patients. The purpose of this study was to determine whether off-pump compared to on-pump is associated with lower CABG patency, and if there is an association between graft failure and clinical outcomes. PATENCY-CORONARY (NCT01414049) is a multicenter trial of a consecutive subset of patients from the CORONARY trial undergoing graft patency assessment using non-invasive ECG-gated computed tomography angiography (CTA). All CORONARY patients from 3 high volume off-pump CABG Canadian Centers reaching one-year follow-up (window of eligibility 9 months-24 months) were systematically approached to be included in the study. From the 335 patients eligible to participate in PATENCY-CORONARY (no kidney failure, no atrial fibrillation, NYHA<4) in three high CORONARY Canadian recruiting centers, 157 (47%) underwent CTA for graft patency assessment. Mean age was 69.0±6.3, 132 (84%) were men, 84 (54%) patients were operated off-pump. Patients received a number of 3.1±0.9 grafts versus 3.4±0.9 grafts in the off-pump and on-pump group, respectively (P=0.06). Out of 512 grafts segments, 504 (98.4%) were evaluable. Patency index (% of non-occluded grafts) was 89% in off-pump compared to 95% in on-pump (P=0.09); those 41 graft occlusions occurred in 29 patients. The overall patency index per graft types was no different for the arterial conduits and saphenous veins with 92% (175 /191segments) versus 92% (288 segments/313) respectively (P=0.88). Patency of grafts in different target coronary territories was no different, ranging from 89% to 94% (P=0.53). The occurrence of graft occlusion did not affect CORONARY outcomes (composite of death, myocardial infarct, stroke, renal failure requiring dialysis). PATENCY-CORONARY is one of the largest trials evaluating graft patency with CTA in off- vs on-pump surgery, and demonstrated the usefulness of this method after CABG. A high patency rate in veins and LIMA was observed, with few clinical events associated with graft failure.

OBJECTIVE:The objective was to assess, with computed tomography (CT) angiography, quantitative morphological parameters of a composite coronary artery bypass grafting (CABG) strategy and to correlate these with graft dysfunction. FINDINGS:Forty patients [median postoperative time, 32 (14-51) months] underwent CT angiography. Graft patency was assessed, and specific quantitative morphological parameters of the graft were collected. Graft segments had an overall patency rate of 93% (78/84). Two specific morphological parameters were found to be associated with graft dysfunction. CONCLUSION:A CT morphometric model can be used to identify quantitative 3D parameters associated with graft dysfunction. Such an approach could help in developing and improving CABG designs.

BackgroundCardiac surgeons in our center have designed a novel strategy involving a composite left internal mammary artery (LIMA) and saphenous vein graft (SVG) bridge to distribute the LIMA flow over a larger cardiac territory, thereby increasing flow through the LIMA. It involves a short saphenous vein segment (the bridge), interposed between the LAD and one anterolateral coronary targets (usually a diagonal artery). The LIMA is grafted on the hood of the SVG bridge directly above the LAD anastomosis. After demonstrating the feasibility and safety of the technique, we prospectively assessed graft patency in patients with multivessel disease treated with the composite LIMA-SVG bridge technique for the anterolateral territory and others aorto-coronary SVGs for the remaining coronary targets.MethodsGraft patency will be assessed in 110 patients with contrast-enhanced 256-slice CT with prospective ECG-gating at 12-18 months postoperatively. The primary security endpoint is to assess graft patency of the LIMA-LAD axis of the LIMA-SVG bridge, i.e. the percentage of graft non-occluded. The secondary endpoint involves intra-patient comparison of the distal target graft patency 1) in the LIMA-SVG bridge (i.e. diagonal arteries) versus 2) conventional aorto-coronary graft (i.e. circonflex or right coronary arteries). Generalized estimating equations were used to take into account the intra-patient comparison of graft patency.ResultsCT assessment was completed in 33 patients at a mean follow-up of 15±2 months. Mean age was 64±7 years with 88% males (n=29), 55% (n=18) in CCS angina class III-IV, 30% (n=10) with diabetes, 76% (n=25) with dyslipidemia, 66% (n=66) with hypertension and 45% (n= 15) with a history of smoking. Sequential aorto-coronary graft were used in 61% of patients (n=20). Graft patency was assessable in all but one patient (97%) due to artifact. LIMA-LAD axis patency was 100%. Distal target graft patency was 81% in the LIMA-SVG technique and 94% with the aorto-coronary SVG (p=0.152). Detailed graft lesion severity on a 4-point scale is provided in Table 1.ConclusionFRSQ BackgroundCardiac surgeons in our center have designed a novel strategy involving a composite left internal mammary artery (LIMA) and saphenous vein graft (SVG) bridge to distribute the LIMA flow over a larger cardiac territory, thereby increasing flow through the LIMA. It involves a short saphenous vein segment (the bridge), interposed between the LAD and one anterolateral coronary targets (usually a diagonal artery). The LIMA is grafted on the hood of the SVG bridge directly above the LAD anastomosis. After demonstrating the feasibility and safety of the technique, we prospectively assessed graft patency in patients with multivessel disease treated with the composite LIMA-SVG bridge technique for the anterolateral territory and others aorto-coronary SVGs for the remaining coronary targets. Cardiac surgeons in our center have designed a novel strategy involving a composite left internal mammary artery (LIMA) and saphenous vein graft (SVG) bridge to distribute the LIMA flow over a larger cardiac territory, thereby increasing flow through the LIMA. It involves a short saphenous vein segment (the bridge), interposed between the LAD and one anterolateral coronary targets (usually a diagonal artery). The LIMA is grafted on the hood of the SVG bridge directly above the LAD anastomosis. After demonstrating the feasibility and safety of the technique, we prospectively assessed graft patency in patients with multivessel disease treated with the composite LIMA-SVG bridge technique for the anterolateral territory and others aorto-coronary SVGs for the remaining coronary targets. MethodsGraft patency will be assessed in 110 patients with contrast-enhanced 256-slice CT with prospective ECG-gating at 12-18 months postoperatively. The primary security endpoint is to assess graft patency of the LIMA-LAD axis of the LIMA-SVG bridge, i.e. the percentage of graft non-occluded. The secondary endpoint involves intra-patient comparison of the distal target graft patency 1) in the LIMA-SVG bridge (i.e. diagonal arteries) versus 2) conventional aorto-coronary graft (i.e. circonflex or right coronary arteries). Generalized estimating equations were used to take into account the intra-patient comparison of graft patency. Graft patency will be assessed in 110 patients with contrast-enhanced 256-slice CT with prospective ECG-gating at 12-18 months postoperatively. The primary security endpoint is to assess graft patency of the LIMA-LAD axis of the LIMA-SVG bridge, i.e. the percentage of graft non-occluded. The secondary endpoint involves intra-patient comparison of the distal target graft patency 1) in the LIMA-SVG bridge (i.e. diagonal arteries) versus 2) conventional aorto-coronary graft (i.e. circonflex or right coronary arteries). Generalized estimating equations were used to take into account the intra-patient comparison of graft patency. ResultsCT assessment was completed in 33 patients at a mean follow-up of 15±2 months. Mean age was 64±7 years with 88% males (n=29), 55% (n=18) in CCS angina class III-IV, 30% (n=10) with diabetes, 76% (n=25) with dyslipidemia, 66% (n=66) with hypertension and 45% (n= 15) with a history of smoking. Sequential aorto-coronary graft were used in 61% of patients (n=20). Graft patency was assessable in all but one patient (97%) due to artifact. LIMA-LAD axis patency was 100%. Distal target graft patency was 81% in the LIMA-SVG technique and 94% with the aorto-coronary SVG (p=0.152). Detailed graft lesion severity on a 4-point scale is provided in Table 1. CT assessment was completed in 33 patients at a mean follow-up of 15±2 months. Mean age was 64±7 years with 88% males (n=29), 55% (n=18) in CCS angina class III-IV, 30% (n=10) with diabetes, 76% (n=25) with dyslipidemia, 66% (n=66) with hypertension and 45% (n= 15) with a history of smoking. Sequential aorto-coronary graft were used in 61% of patients (n=20). Graft patency was assessable in all but one patient (97%) due to artifact. LIMA-LAD axis patency was 100%. Distal target graft patency was 81% in the LIMA-SVG technique and 94% with the aorto-coronary SVG (p=0.152). Detailed graft lesion severity on a 4-point scale is provided in Table 1. ConclusionFRSQ FRSQ

Objectives Intraoperative assessment of coronary artery bypass grafts (CABG) anastomotic quality can be performed using transit-time flowmetry (TTF). The aim of this study was to compare on- versus off-pump coronary graft TTF and early postoperative outcomes. Materials and methods Between January 2009 and January 2010, 521 distal graft flows were assessed using TTF measurements in 253 consecutive patients undergoing primary isolated CABG surgery. Data were analyzed using multilevel models accounting for clustering among surgeons and grafts performed in the same patient. Results Mean age was 66 ± 10 years and 22% were female (n = 55) with 34% diabetics (n = 86) and 40% pre-operative myocardial infarction (MI) (n = 101). The surgeries were performed off-pump in 67% (n = 170) with sequential vein grafts in 57% (n = 144) of patients. Off-pump patients had higher pre-operative left ventricular ejection fractions (LVEF), fewer urgent surgeries, fewer distal anastomoses, and fewer sequential vein grafts (all p<0.001). Intra-operative coronary graft TTF measurements were lower in sequential vein grafts performed off-pump versus on-pump. More patients in the on-pump group needed milrinone or dobutamine 24-48 h postoperatively (p = 0.005). Independent predictors of lower TTF included female gender and off-pump surgery, whereas predictors of better TTF were pre-operative MI, larger coronary diameter at the site of the distal anastomosis, and sequential vein grafting. Conclusions Lower intra-operative TTF measurements were found in sequential vein grafts in offpump CABG. However, off-pump patients experienced similar short-term outcomes compared to on-pump patients.

Background: In severe coronary artery disease, coronary artery bypass grafting (CABG) surgery is indicated to re-establish an adequate blood supply to the ischemic myocardium. Effectiveness of CABG surgery for symptom relief and mortality decrease should therefore depend on bypass graft patency. As bypass using a left internal mammary artery (LIMA)-to-left anterior descending coronary artery (LAD) anastomosis allows the best results in terms of graft patency, we designed a new surgical technique using a saphenous vein graft as a venous bridge to distribute the LIMA flow to the cardiac anterolateral territory. This novel strategy could extend the patency benefits associated to the LIMA. Other potential benefits of this technique include easier surgical technique, possibility to use saphenous vein grafts as vein patch angioplasty, shorter saphenous vein grafts requirement and reduced or eliminated manipulations of the ascendant aorta (and associated stroke risk).Methods/Design: Between July 2012 and 2016, 200 patients undergoing a primary isolated CABG surgery using cardiopulmonary bypass with a LAD bypass graft and at least another target on the anterolateral territory will be randomized (1: 1) according to 1) the new composite strategy and 2) the conventional strategy with a LIMA-to-LAD anastomosis and revascularization of the other anterolateral target(s) with a separated aorto-coronary saphenous vein graft. The primary objective of the trial is to assess whether the composite strategy allows non-inferior anterolateral graft patency index (proportion of non-occluded CABGs out of the total number of CABGs) compared to the conventional technique. The primary outcome is the anterolateral graft patency index, evaluated at one year by 256-slice computed tomography angiography. Ten years of clinical follow-up is planned to assess clinical outcomes including death, myocardial infarction and need for revascularization.Discussion: This non-inferiority trial has the potential to advance the adult cardiac surgery field, given the potential benefits associated with the composite grafting strategy. Trial registration: ClinicalTrials.gov: NCT01585285.

OBJECTIVES: The aim of this pilot study was to describe and assess the safety of a novel composite graft technique for coronary artery bypass grafting (CABG) surgery. A saphenous vein is grafted to the left anterior descending artery (LAD) and other anterolateral coronary arteries, creating a saphenous vein bridge (SVB) and the left internal mammary artery (LIMA) is anastomosed to the SVB, distributing the blood flow distally (LIMA-SVB).METHODS: All patients who underwent CABG with the LIMA-SVB between 2005 and 2008 at our centre were enrolled in this study. Perioperative data were retrospectively collected from hospital charts, and the clinical follow-up was completed by telephone interview. Graft patency was assessed by computed tomography angiography (CTA) in patients with the longest follow-up time (n = 20).RESULTS: A total of 256 patients (mean age: 67 +/- 12 years; 79% male) received 4.0 +/- 1.0 grafts, including 2.2 +/- 0.4 distal grafts provided by the LIMA-SVB. Nine (3.5%) deaths and 4 (1.6%) myocardial infarctions (MIs) were noted in the perioperative period. With a median follow-up time of 36 months [inter-quartile range 31-44], 1 (0.5%) MI and 2 (1.0%) strokes were reported. At 51 months post-surgery [47-53], CTA demonstrated a LIMA pedicle (n = 20) and SVB (n = 42) patency rate of 100 and 93%, respectively. Specifically, the LIMA-SVB patency rate was 100% to the LAD and 85% to diagonal arteries. Aortocoronary vein grafts (n = 38) patency rate in the same patients was 87%.CONCLUSIONS: Revascularization of the anterolateral territory using the LIMA-SVB is a promising approach considering its clinical safety and favourable patency rate results. A prospective randomized clinical trial is underway to compare this technique to conventional CABG.

Cellular transplantation is a novel strategy to improve ischemic myocardium healing. Bone marrow CD133+ cells are distinct early progenitor group of hematopoietic stem cells that possess high engraftment, pluripotent and angiogenic capacity and appear valuable for cardiac repair by promoting neovascularization, cardiomyogenesis and inhibition of apoptosis. The aim is to report the feasibility, security and beneficial effects of intramyocardial injection of CD133+ stem cells. We report herein the 6 month follow-up on the first 5 patients treated in an open labeled fashion in the IMPACT-CABG study. This is a randomized-controlled phase II clinical trial aiming to assess the safety and effects of intramyocardial injections of autologous CD 133+ selected stem cells in coronary artery bypass grafting (CABG) patients with chronic ischemic cardiomyopathy (left ventricular ejection fraction (LVEF) below 45%). Cardiac function and myocardial viability was assessed by stress echocardiography and magnetic resonance imaging (MRI) before and 6 months after surgery. Bone marrow aspiration and cell selection, using the CliniMACS system, are performed the morning of the surgical procedure and cells are injected intramyocardially after completion of the distal anastomosis before weaning from cardiopulmonary bypass. Five males, mean age 65 ± 10 years, underwent CABG for 3 ± 1 bypasses. A total of 10 millions CD133+ cells were injected in 15 sites (total cell suspension volume 2.0 ml). Post-operative course was uneventful for each patient. There was no peri-operative complication related to this protocol, and no Major Adverse Cardiac Event (MACE) defined as cardiac death, myocardial infarction, repeated coronary revascularization or sustained ventricular arrhythmias. Pre- and 6 months post-operative LVEF were 34.0 ± 2.2 and 39.0 ± 11.9 respectively (P = ns). Moreover, MRI studies suggested that LV end-diastolic and end-systolic volumes decreased after cell implantation compared to baseline. Echocardiographic regional wall motion index for all patients in the ischemic stem cell-injected territories improve at 6 months of follow-up in all patients compared to baseline. The NYHA functional class improved for every patient from class III to class I. This work represents the first Canadian experience with CD133+ stem cells for the treatment of chronic ischemic cardiomyopathy and relies on state-of-the-art methods for assessing myocardial functional recovery and viability. These encouraging results support the safety and feasibility of intramyocardial injections of CD 133+ cells in addition to CABG. IMPACT-CABG trial with further double-blind randomization between CD 133+ cells vs. placebo will test the beneficial impact of this approach.

Various conduits and strategies are used to surgically bypass the coronary arteries. The aim of this study is to report the mid-term safety and patency follow-up of a novel strategy with a composite-sequential graft to bypass the left anterior descending artery (LAD) and other branches of the anterior territory using a saphenous vein (SV) bridge to distribute the outflow provided by the left internal mammary artery (LIMA). Between November 2004 and March 2008, 256 patients underwent CABG and received the LIMA-SV bridge (LSVB) to bypass the anterior coronaries. Perioperative data was prospectively collected and clinical follow-up was completed by telephone interview. Median age at operation was 68 years [quartiles 60, 76], 203 (79%) were male and median Parsonnet score was 12 [4, 17]. Mean number of distal bypasses performed was 4 ± 1, and 246 (96%) were complete revascularization. Surgical revascularization was performed off-pump in 134 patients (52%). Graft flow was evaluated intraoperatively in the LIMA pedicle using the Medi-Stim flowmeter (Medtronic) in a contemporary cohort and was significantly higher in the LSVB group (n = 142) compared to non-LSVB group (n = 199) with 67 ± 38 ml/min vs. 52 ± 30 ml/min, respectively (P < 0.001). At 30 days, out of 256 patients, death occurred in 10 (3.9%), cardiac death occurred in 5 (1.9%), myocardial infarction in 4 (1.5%) and stroke in 6 (2.3%). With a median follow up time of 36 months [31, 41], most patients had no or light exertional dyspnea (NYHA I-II; n = 178, 95%) and no or slight angina (CCS ≤I; n = 180, 96%). One patient (0.5%) had myocardial infarction, 2 (1.1%) underwent revascularization by PCI and 13 (6.1%) died, with 2 (0,9%) cardiac deaths. Long term graft patency was assessed with prospectively ECG-gated 256-slice computed tomography angiography in a random set of 20 patients with a median postoperative time of 51 months [47, 53]. All (100%) LIMA were patent, and 38 (90.5%) out of 42 LSVB distal anastomoses were patent. Revascularization of the anterior territory using LSVB is a feasible surgical strategy; this mid-term follow-up demonstrates its clinical safety. This novel technique has several potential advantages such as higher blood flow in the LIMA, avoidance of aortic manipulation and shorter vein grafts for anterior targets. In a 20 patient subgroup, LSVB showed a graft patency of 90.5% at 51 months, which compares favorably with traditional aortocoronary SV grafts. LSVB should be considered as a viable new tool in the armamentarium of cardiac surgeons.

Integrity of coronary artery bypass grafts (CABG) needs to be assessed intraoperatively. The aim of this study is to assess predictors of lower transit-time graft flow measurements. Between January 2009 to January 2010, 531 graft flows were measured using the transit-time flowmetry (Medistim) in 253 consecutive patients undergoing primary isolated CABG without intra-aortic balloon pump, for a total of 868 distal coronary grafts. Data was analyzed retrospectively using generalized estimating equations models accounting for clustering among surgeons. Mean age was 66 ± 10 years and 22% were female (n = 56) with 34% diabetics (n = 87), 40% preoperative myocardial infarction (MI) (n = 102) and 12% prior percutaneous coronary intervention (PCI) (n = 31). The left ventricular ejection fraction (LVEF) was 53%+/−13% with 17% of patients having a LVEF <40% (n = 42). The surgery was performed off-pump in 67% (n = 170), composite venous bridge for internal mammary artery (IMA) outflow distribution in 52% (n = 132), and sequential vein graft in 57% (n = 145) of patients. CABG transit-time flowmetry measurements were lower in the off-pump vs. on-pump patients for all revascularized territories. Among off-pump and on-pump patients, an increased mean arterial pressure was not associated with an improved flowmetry measure. Sequential vein grafts provided better flows in the marginal circumflex (53 ml/min [interquartile range: 34, 81] vs. 40 ml/min [24, 66]; P = 0.004) and right coronary or posterolateral (51 ml/min [34, 82] vs. 43 ml/min [30, 60]; P = 0.030) territories compared to non-sequential vein grafts. Independent predictor of lower flowmetry measure included female gender, higher LVEF, prior PCI and off-pump surgery, whereas predictors of better flows were preoperative MI, bigger coronary diameter at the site of the distal anastomosis, composite venous bridge for IMA outflow distribution and sequential vein graft. Lower flowmetry measure was associated with an increased incidence of low output syndrome (P = 0.018) and a trend for an increased operative mortality (P = 0.114). This study highlighted eight important predictors of higher and lower graft flow using the transit-time flowmetry. Those predictors should be kept in mind for intraoperative assessment of graft function and need for reintervention on the anastomoses.

The aneurysm of the sinus of Valsalva is rare and usually asymptomatic unless rupture occurs. A 72-year-old man presented with exertional dyspnoea due to an unruptured aneurysm of the right sinus of Valsalva compressing the right ventricular outflow tract (Fig. 1). Successful elective surgical repair was undertaken (Fig. 2). www.elsevier.com/locate/ejcts European Journal of Cardio-thoracic Surgery 38 (2010) 504

Background: Different solutions are possible for thoracic epidural analgesia in cardiac surgery. So far, local anesthetics alone or in combination with either clonidine or opioids have been used.

BACKGROUND:We present a 15-patient series of awake 'off-pump' [without cardiopulmonary bypass (CPB)] coronary artery bypass graft surgery, facilitated by thoracic epidural analgesia (TEA) and femoral nerve block.METHODS:Surgery was performed with a conventional median sternotomy. Analgesia was provided with TEA at T1-2 or 2-3 interspace, using bupivacaine 0.5% and sufentanil 1.66 microg ml(-1), initially at 20 ml litre(-1) until T1-10 dermatomal block was achieved, then maintained at 2-14 ml litre(-1) throughout surgery. Femoral nerve block was performed before operation with neuro-stimulation at the saphenous vein harvest site with 10 ml each of bupivacaine 0.25% and lidocaine 2%. Successful awake surgery, avoiding general anaesthesia (GA) with adequate surgical conditions, without CPB was the primary end point.RESULTS:Fifteen men, mean (sd) age of 63 (9) yr (range 49-81 yr), weight 78 (10) kg, underwent surgery. Three patients (20%) needed conversion to GA: one patient due to insufficient thoracic analgesia, another required initiation of CPB, and the third needed stabilization of the heart for graft suturing due to profound respiratory movements. All three were successfully extubated immediately after surgery. Awake surgery was successful and uneventful in 80% of cases.CONCLUSIONS:Combined TEA and femoral block is a novel anaesthetic technique, and is feasible, for cardiac surgery. However, certain technical limitations need to be overcome to evaluate the full potential of 'awake' cardiac surgery.