Hugues Jeanmart

Comparative study of cyclosporine and tacrolimus vs newer immunosuppressants mycophenolate mofetil and rapamycin on coronary endothelial function

BACKGROUND Endothelial dysfunction contributes to the development of intimal hyperplasia in transplanted hearts by decreasing the protective effects of endothelial-derived nitric oxide. Immunosuppressive drugs may increase the dysfunction caused by rejection and further accelerate the development of graft coronary vasculopathy. This study compares the effect of cyclosporine and tacrolimus vs two newer immunosuppressive drugs, mycophenolate mofetil and rapamycin, on coronary endothelial function. METHODS An in vitro model of drug incubation in Krebs-bicarbonate solution (4(o)C, 48 hours) using porcine epicardial coronary arteries was developed. Coronary endothelial function studies were performed in organ chamber experiments after incubation with cyclosporine (10(-4), 10(-7) mol/liter), tacrolimus (10(-4), 10(-7) mol/liter), mycophenolate mofetil (10(-4), 10(-7) mol/liter), rapamycin (10(-7), 10(-11) mol/liter), and their vehicles to assess effects on G-protein-mediated vasorelaxations leading to the release of nitric oxide. RESULTS Exposure to cyclosporine and mycophenolate mofetil was associated with a dose-dependent decrease in endothelium-dependent relaxations to serotonin (an agonist that binds to 5-HT1D receptors coupled to Gi-protein) but no impairment of relaxations to bradykinin (an agonist that binds to B2 receptors coupled to Gq-proteins). Exposure to tacrolimus and rapamycin caused severe impairment of relaxations to serotonin and a lesser one to bradykinin. We observed alterations of relaxations to the calcium ionophore A23187 after exposure to mycophenolate mofetil and rapamycin. Exposure to rapamycin and mycophenolate mofetil vehicles impaired relaxation to all agonists. CONCLUSIONS These results suggest that cyclosporine and mycophenolate mofetil induce a dysfunction of the vasorelaxing properties of the endothelium that may lead to a decrease in the protective effects of nitric oxide on the vascular wall but that these drugs still have a more favorable vascular profile than do tacrolimus and rapamycin. Decreased endothelial function after mycophenolate mofetil and rapamycin exposure could be caused by their vehicles.

Retrospective cohort analysis of 926 tricuspid valve surgeries: Clinical and hemodynamic outcomes with propensity score analysis

BACKGROUND The objectives were to describe morbidity and mortality after tricuspid valve (TV) surgery, to compare outcomes after repair versus replacement, and to assess risk factors for mortality and tricuspid regurgitation (TR) recurrence. METHODS A retrospective cohort study including 926 consecutive cases of TV surgery (792 repairs and 134 replacements) performed at the Montreal Heart Institute was conducted. Median follow-up was 4.3 years (4,657 patient-years). Median age was 62 years (interquartile range 53-69 years), and 72% of patients were women. RESULTS Operative mortality was 14% (128 patients: 1977-1998 20%, 1999-2008 7%, P < .001). Independent risk factors for operative mortality in the 1999 to 2008 period were hypertension (odds ratio [OR] 6.03, P = .02), daily furosemide dose (by 10 mg) (OR 1.06, P = .05), weight (by 10 kg) (OR 0.36, P < .01), and cardiopulmonary bypass time (by 10 minutes) (OR 1.29, P < .001). Ten-year survival was 49% ± 2% and 38 ± 5% in the repair and replacement groups, respectively (P = .012). At discharge, severity of TR was ≥3/4 in 13% and 2% of patients in the repair and replacement groups, respectively (P = .01). Propensity score analysis showed that tricuspid repair was associated with higher rates of TR ≥3/4 at follow-up compared with replacement (hazard ratio 2.15, P = .02). Forty-eight reoperations (7% of patients at risk) were performed during follow-up (repair group, 6%; replacement group, 15%; P = .01). At last follow-up, New York Heart Association functional class was improved compared with baseline in both groups (P < .001). CONCLUSION Tricuspid valve surgery is associated with substantial early and late mortalities but with significant functional improvement. Replacement is more effective in early and late corrections of regurgitation, but it does not translate into better survival outcomes.

The Endovascular Coronary Sinus Catheter in Minimally Invasive Mitral and Tricuspid Valve Surgery: A Case Series

OBJECTIVES To determine the safety and efficacy of a standardized approach to the use of an endovascular coronary sinus (CS) catheter during minimally invasive cardiac surgery. DESIGN Case series. SETTING University hospital. PARTICIPANTS Patients undergoing mitral and/or tricuspid valve surgery using a minimally invasive cardiac surgery approach. INTERVENTIONS An endovascular CS catheter was placed to enable the administration of retrograde cardioplegia using transesophageal echocardiography (TEE), fluoroscopy, and CS pressure measurements. MEASUREMENTS AND MAIN RESULTS Data were collected from 96 patient records. A total of 95 (99.0%) endovascular coronary sinus catheters were positioned. The mean time to insert the catheter into the sinus ostium under TEE guidance was 6.3 ± 8.4 minutes. Confirmation of adequate positioning with fluoroscopy took an average of 9.1 ± 10.6 minutes for a mean total procedure time of 16.1 ± 14.1 minutes. Successful positioning, as defined by the ability to generate a perfusion pressure in the CS greater than 30 mmHg during surgery, was achieved in 87.5% of cases. During positioning, ventricularization of the CS pressure curve was observed in 86.0% of cases. The presence of ventricularization was associated with an increase in positioning success (odds ratio = 15.8; 95% confidence interval, 3.713-67.239). One patient developed extravasation of contrast agent after CS catheter placement, without evidence of CS rupture. CONCLUSIONS Endovascular CS catheter insertion can be performed with a high rate of success for positioning and a low complication rate. During positioning, obtaining ventricularization is associated with an increased success rate.

Statin treatment equalizes long-term survival between patients with single and bilateral internal thoracic artery grafts.

BACKGROUND The use of 2 internal thoracic artery (ITA) grafts increases survival 10 years after coronary artery bypass grafting (CABG) compared with single ITA grafting. Statin treatment was also shown to decrease development and progression of saphenous vein graft atherosclerosis. This study examined the effect of statin treatment on long-term survival after CABG. METHODS Operative, survival, and pharmacologic data of 6655 patients who underwent CABG with ITAs between 1995 and 2007 in our institution were obtained. RESULTS Patients with bilateral ITA grafts had an average 10-year-survival rate of 83% +/- 2% compared with 67% +/-1% in patients with single ITA grafts (p = 0.0001). Statin treatment caused a significant decrease in the long-term risk of death among patients who underwent single ITA grafting (hazard ratio [HR], 0.735, p = 0.0001). However, statin treatment had no effect on the risk of long-term death among patients who underwent bilateral ITA grafting (HR, 1.053; p = 0.7806). CONCLUSIONS Statin treatment initiated early after grafting improved long-term survival in patients with a single ITA graft but not in those with bilateral ITA grafts. Survival of statin-treated patients with single ITA grafts was similar to bilateral ITA patients.

Excellent outcomes for transcatheter aortic valve replacement within 1 year of opening a low-volume centre and consideration of requirements.

BACKGROUND After the approval of transcatheter aortic valve replacement (TAVR) for high-risk or inoperable patients with severe aortic stenosis (AS), many low- and moderate-volume TAVR programs were initiated. Contemporary outcomes from these newly initiated centres remain unknown. METHODS In March 2013, our institution was authorized by the Québec Ministry of Health to perform 30 TAVR procedures. After thorough clinical screening and imaging evaluation, suitable patients underwent transfemoral TAVR with the balloon-expandable SAPIEN XT (Edwards Lifesciences, Irvine, CA) transcatheter heart valve (THV). In-hospital and 30-day outcomes were prospectively collected and reported according to Valve Academic Research Consortium 2 guidelines. RESULTS From April 2013 to January 2014, 30 consecutive high-risk (n = 16 [53.3%]) or inoperable (n = 14 [46.7%]) patients (mean age, 84.6 years; mean Society of Thoracic Surgery score, 7) with symptomatic severe AS underwent transfemoral TAVR. No catastrophic intraprocedural complications such as annulus rupture, valve embolization, aortic dissection, or coronary occlusion occurred, and there were no deaths at 30 days. Disabling stroke occurred in 1 (3.3%) patient 48 hours after THV implantation. Major vascular complications and major bleeding occurred in 1 (3.3%) patient. No moderate or severe paravalvular leak was observed. The median length of stay was 2 (1-3) days, with 8 (26.7%) patients discharged within 24 hours after the procedure. CONCLUSIONS Excellent outcomes can be achieved in newly initiated relatively low-volume centres, which compares favorably to previously published large series. Important considerations include appropriate team training, rigorous patient screening, use of multimodality imaging techniques, a heart team approach, constant integration of lessons learned from larger published experiences, and maintaining a recommended minimum volume of 25 cases per year.

Arterial Balloon Catheter: A New Atraumatic Device for Dilating Arterial Grafts

BACKGROUND Harvesting of the internal mammary artery (IMA) for use in myocardial revascularization may result in spasm, which can impair early graft flow. Hydrostatic and mechanical dilatation can exert an intraluminal shear force, causing denudation of the IMA endothelium. A new long balloon dilatation technique (LB) has been developed to mechanically increase IMA diameter and flow without exerting any shear force on the endothelium. METHODS Vascular rings of porcine IMA were divided into four groups: no manipulation (control), metal dilators (MD), short balloon (SB), or LB intraluminal dilation. In situ flows after dilation and percentage of intact endothelium after silver nitrate staining were determined. Endothelium-dependent contractions with arachidonic acid, relaxations with acetylcholine, endothelium-independent contractions with norepinephrine, and relaxation with sodium nitroprusside were recorded in organ chamber experiments. RESULTS Increases in IMA flows were similar in all dilated groups. Endothelium-independent contractions and relaxations of IMA smooth muscle were unaffected by any type of mechanical dilation. However, endothelium-dependent contractions and relaxations were significantly impaired after MD and SB but preserved after LB dilation compared with control. Silver nitrate staining showed a greater preservation of the endothelial coverage after LB dilation. CONCLUSIONS IMA dilatation with the novel arterial LB catheter increases IMA flow and preserves endothelial cell integrity, making it an effective and atraumatic method to relieve IMA spasm before use for coronary artery bypass grafting.

DuraGraft vascular conduit preservation solution in patients undergoing coronary artery bypass grafting: rationale and design of a within-patient randomised multicentre trial

Introduction Saphenous vein grafts (SVGs) remain the most often used conduits in coronary artery bypass grafting (CABG). However, they are prone to vein graft disease (VGD) during follow-up, which may compromise clinical outcomes. Injury to the SVG endothelium during harvesting and storage promotes neointimal hyperplasia that can advance to atherosclerosis characterised by SVG failure. This trial investigates the potential benefit of DuraGraft, a novel, one-time intraoperative graft treatment developed to efficiently protect the structural and functional integrity of the vascular endothelium, on the development and progression of VGD in CABG patients. Methods and analysis This ongoing prospective randomised, double-blinded multicentre trial (NCT02272582/NCT02774824) includes patients undergoing isolated CABG requiring at least two SVGs. It compares the impact of DuraGraft, a novel treatment against VGD versus the standard-of-care (SOC; heparinised saline) using a within-patient randomisation (with one SVG treated with DuraGraft and the other treated with SOC). Besides clinical assessments, patients undergo longitudinal 64-slice or better multidetector CT (MDCT) angiography of paired grafts (within each patient) at 4–6 weeks, 3 months and 12 months. Primary endpoints will be the magnitude of change in mean wall thickness and lumen diameter (stenosis) of paired grafts, at 3 and 12 months, respectively. Besides the evaluation of overall safety, longitudinal assessment of each graft (secondary endpoint) is performed in order to obtain insight into graft behaviour after CABG. Enrolment of 119 patients was successfully completed, and analysis of MDCT angiography follow-up is ongoing with the completed analysis becoming available by end of first quarter of 2018. Ethics and dissemination The regional ethics committees have approved the trial. Results will be submitted for publication. Clinical trial identifier NCT02272582 and NCT02774824.

614 Coronary Artery Bypass Grafting in octogenarians: Results over the course of three 5-year periods

BACKGROUND: The incidence of CABG in the octogenarian population is rising, making it essential to explore ways to minimize morbidity and mortality in this population with inherent increased surgical risk. The aim of this study was to compare outcomes in octogenarians undergoing either conventional CABG (CCAB) with cardiopulmonary bypass (CPB) or offpump CABG (OPCAB) in three consecutive five-year cohorts METHODS: A retrospective chart review included all octogenarians who underwent isolated CABG between 2000-2004 (n 177), and 2005-2009 (n 231) in our institution. Comparison of these cohorts was performed and findings were then compared to the previously published 1995-1999 cohort (n 125). RESULTS: OPCAB was performed in 49.6% of patients in the 1995-1999 cohort, 49.2% in the 2000-2004, and only 20.8% in the 2005-2009 cohort. In the earlier cohorts no surgeon performed more than 30% of cases in either group, however, a single surgeon dedicated to the technique performed 70% of OPCAB surgeries in the recent cohort. Mortality was similar for OPCAB and CCAB in 2000-2004 (5.9% vs 5%, P 0.96) and 2005-2009 (6.3% vs 8.7%, P 0.77). This was markedly different from the 1995-1999 cohort’s results of 4.8% vs 15.9% (P 0.04). Stroke rates were also not significantly different between operative strategies in the 2 recent cohorts (2000-2004 1.2% vs 0%; 2005-2009 2.1% vs 3.2%), while CCAB was associated with a significantly increased stroke risk in the early cohort (6.3% vs 0%, P 0.04). Degree of aortic atherosclerosis was not identified in the early group because transesophageal echocardiography was not yet routine. Severe aortic atherosclerosis was significantly higher in the OPCAB group of the 2000-2004 cohort (53% vs 21%, P 0.01), while there was no difference between groups in the recent cohort. For the 2005-2009 cohort, when patients operated by the dedicated OPCAB surgeon were excluded, incidence of severe aortic atherosclerosis was higher with OPCAB (64% vs 31%, P 0.001). CONCLUSION: These results support the conclusion that CABG surgery in an octogenarian population can be performed safely and with similar mortality and stroke rates with or without CPB when patients are appropriately selected. OPCAB may be especially beneficial in the context of severe aortic atherosclerotic disease, and should be considered even by surgeons who do not routinely perform off-pump surgery. Improved outcome compared to the earliest cohort may be due to better screening for aortic atherosclerotic disease and improved perioperative care. 615 INHALED MILRINONE ADMINISTRATION IN CARDIAC SURGERY: SIMPLE JET OR ULTRASONIC NEBULISATION?