Munir Boodhwani

Repair-oriented classification of aortic insufficiency: impact on surgical techniques and clinical outcomes.

OBJECTIVE Valve repair for aortic insufficiency requires a tailored surgical approach determined by the leaflet and aortic disease. Over the past decade, we have developed a functional classification of AI, which guides repair strategy and can predict outcome. In this study, we analyze our experience with a systematic approach to aortic valve repair. METHODS From 1996 to 2007, 264 patients underwent elective aortic valve repair for aortic insufficiency (mean age - 54 +/- 16 years; 79% male). AV was tricuspid in 171 patients bicuspid in 90 and quadricuspid in 3. One hundred fifty three patients had type I dysfunction (aortic dilatation), 134 had type II (cusp prolapse), and 40 had type III (restrictive). Thirty six percent (96/264) of the patients had more than one identified mechanism. RESULTS In-hospital mortality was 1.1% (3/264). Six patients experienced early repair failure; 3 underwent re-repair. Functional classification predicted the necessary repair techniques in 82-100% of patients, with adjunctive techniques being employed in up to 35% of patients. Mid-term follow up (median [interquartile range]: 47 [29-73] months) revealed a late mortality rate of 4.2% (11/261, 10 cardiac). Five year overall survival was 95 +/- 3%. Ten patients underwent aortic valve reoperation (1 re-repair). Freedoms from recurrent Al (>2+) and from AV reoperation at 5 years was 88 +/- 3% and 92 +/- 4% respectively and patients with type I (82 +/- 9%; 93 +/- 5%) or II (95 +/- 5%; 94 +/- 6%) had better outcomes compared to type III (76 +/- 17%; 84 +/- 13%). CONCLUSION Aortic valve repair is an acceptable therapeutic option for patients with aortic insufficiency. This functional classification allows a systematic approach to the repair of Al and can help to predict the surgical techniques required as well as the durability of repair. Restrictive cusp motion (type III), due to fibrosis or calcification, is an important predictor for recurrent Al following AV repair.

Skeletonized Internal Thoracic Artery Harvest Reduces Pain and Dysesthesia and Improves Sternal Perfusion After Coronary Artery Bypass Surgery: A Randomized, Double-Blind, Within-Patient Comparison

Background— Observational studies suggest that skeletonization of the internal thoracic artery (ITA) can improve conduit flow and length and reduce deep sternal infections and postoperative pain. We performed a randomized, double-blind, within-patient comparison of skeletonized and nonskeletonized ITAs in patients undergoing coronary surgery. Methods and Results— Patients (n=48) undergoing bilateral ITA harvest were randomized to receive 1 skeletonized and 1 nonskeletonized ITA. Intraoperatively, ITA flow was assessed directly and with a Doppler flow probe before and after topical application of papaverine. ITA harvest time and conduit length were recorded. A blinded assessment of pain (visual analog scale) and dysesthesia (physical examination) was performed at discharge, at 2 weeks, and at a 3-month follow-up. Sternal perfusion was assessed with nuclear imaging (n=7). Skeletonization required longer ITA harvest times (27±1 versus 24±1 minutes; P=0.04). There was a trend toward increased ITA length in the skeletonized group (18.2±0.3 versus 17.7±0.3 cm; P=0.09). In situ ITA flow was lower in skeletonized arteries (7.4±0.9 versus 10.1±1.0 mL/min; P=0.01) and increased significantly after ITA division and papaverine application. Postanastomotic flows were similar between groups. Skeletonization was associated with decreased pain at the 3-month follow-up and a reduction in major sensory deficits at the 4-week and 3-month (17% versus 50%; P=0.002) follow-ups. Baseline adjusted sternal perfusion was significantly greater by 17±6% (P=0.03) on the skeletonized side. Conclusions— Skeletonization results in reduced postoperative pain and dysesthesia and increased sternal perfusion at follow-up but does not produce increased conduit flow. ITA skeletonization may be a strategy for reducing morbidity after CABG.

Repair of regurgitant bicuspid aortic valves: A systematic approach

OBJECTIVE Patients with bicuspid aortic valves can present with aortic insufficiency caused by cusp disease or the aortic root pathology. We present our 13-year experience with a functional and systematic approach to bicuspid aortic valve repair. METHODS Between 1995 and 2008, 122 consecutive patients (mean age, 44 +/- 11 years) with bicuspid aortic valves underwent non-emergency valve repair for isolated aortic insufficiency (43%), aortic root dilatation (14%), or both (43%). Preoperative echocardiography identified aortic dilatation (n = 75), cusp prolapse (n = 96), and cusp restriction (n = 45) as mechanisms of aortic insufficiency. Raphé repair (n = 98) was performed by shaving (21%) or resection with primary closure (60%) or pericardial patch (18%). Functional aortic annuloplasty was performed using subcommissural annuloplasty (n = 51), ascending aortic replacement (n = 17), or aortic root replacement (n = 54) using a reimplantation (76%) or remodeling technique (24%). RESULTS There was no operative mortality. Five patients underwent early aortic valve reoperation (3 re-repairs). At discharge, 93% of patients had aortic insufficiency grade 0/1 and 7% of patients had grade 2. Seven additional patients underwent aortic valve reoperation during follow-up (2 re-repairs). Overall survival was 97% +/- 3% at 8 years. At 5 and 8 years follow-up, freedom from aortic valve reoperation was 94% +/- 2% and 83% +/- 5%, respectively, and freedom from aortic valve replacement was 96% +/- 2% and 90% +/- 5%, respectively. Freedom from recurrent aortic insufficiency (>2+) was 94% +/- 3% at 5 years. Freedom from thromboembolism and bleeding was 96% +/- 2% at 8 years. CONCLUSION A systematic approach to bicuspid aortic valve repair yields good early and midterm results. Repair of bicuspid valves for aortic insufficiency is a feasible and attractive alternative to mechanical valve replacement in young patients.

The Cardiotomy Trial: A Randomized, Double-Blind Study to Assess the Effect of Processing of Shed Blood During Cardiopulmonary Bypass on Transfusion and Neurocognitive Function

Background— Reinfusion of unprocessed cardiotomy blood during cardiac surgery can introduce particulate material into the cardiopulmonary bypass circuit, which may contribute to postoperative cognitive dysfunction. On the other hand, processing of this blood by centrifugation and filtration removes coagulation factors and may potentially contribute to coagulopathy. We sought to evaluate the effects of cardiotomy blood processing on blood product use and neurocognitive functioning after cardiac surgery. Methods and Results— Patients undergoing coronary and/or aortic valve surgery using cardiopulmonary bypass were randomized to receive unprocessed blood (control, n=134) or cardiotomy blood that had been processed by centrifugal washing and lipid filtration (treatment, n=132). Patients and treating physicians were blinded to treatment assignment. A strict transfusion protocol was followed. Blood transfusion data were analyzed using Poisson regression models. The treatment group received more intraoperative red blood cell transfusions (0.23±0.69 U versus 0.08±0.34 U, P=0.004). Both red blood cell and nonred blood cell blood product use was greater in the treatment group and postoperative bleeding was greater in the treatment group. Patients were monitored intraoperatively by transcranial Doppler and they underwent neuropsychometric testing before surgery and at 5 days and 3 months after surgery. There was no difference in the incidence of postoperative cognitive dysfunction in the 2 groups (relative risk: 1.16, 95% CI: 0.86 to 1.57 at 5 days postoperatively; relative risk: 1.05, 95% CI: 0.58 to 1.90 at 3 months). There was no difference in the quality of life nor was there a difference in the number of emboli detected in the 2 groups. Conclusions— Contrary to expectations, processing of cardiotomy blood before reinfusion results in greater blood product use with greater postoperative bleeding in patients undergoing cardiac surgery. There is no clinical evidence of any neurologic benefit with this approach in terms of postoperative cognitive function.

Resveratrol Improves Myocardial Perfusion in a Swine Model of Hypercholesterolemia and Chronic Myocardial Ischemia

Background— Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia. Methods and Results— Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d orally, HCRV, n=7). Four weeks later, an ameroid constrictor was placed on the left circumflex artery. Animals underwent cardiac MRI and coronary angiography 7 weeks later before euthanasia and tissue harvest. Total cholesterol was lowered about 30% in HCRV animals (P<0.001). Regional wall motion analysis demonstrated a significant decrease in inferolateral function from baseline to 7 weeks in HCC swine (P=0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks (P=0.32). Tissue blood flow during stress was 2.8-fold greater in HCRV swine when compared with HCC swine (P=0.04). Endothelium-dependent microvascular relaxation response to Substance P was diminished in HCC swine, which was rescued by resveratrol treatment (P=0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC and HCRV swine versus control swine (P=0.02). Immunoblot analysis demonstrated significantly greater expression in HCRV versus HCC swine of the following markers of angiogenesis: VEGF (P=0.002), peNOS (ser1177) (P=0.04), NFkB (P=0.004), and pAkt (thr308) (P=0.001). Conclusions— Supplemental resveratrol attenuates regional wall motion abnormalities, improves myocardial perfusion in the collateral dependent region, preserves endothelium-dependent coronary vessel function, and upregulates markers of angiogenesis associated with the VEGF signaling pathway.

Serologic Markers of Brain Injury and Cognitive Function After Cardiopulmonary Bypass

Objective:To examine the association between biochemical markers of brain injury (MBI) and the inflammatory response in relation to neurocognitive deficiency (NCD) after cardiopulmonary bypass (CPB). Summary Background Data:In cardiac surgery, NCD is a common but underdiagnosed complication with an unclear pathophysiology leading to significant morbidity. Despite extensive investigation, identification of a MBI for clinical use and clarifying the pathophysiology of NCD have not been achieved. Methods:Forty patients undergoing CABG and/or valve procedures using CPB were administered a validated neurocognitive battery preoperatively and postoperatively at day 4 and 3 months. S-100b, neuron specific enolase (NSE), and tau protein were assayed as MBIs preoperatively and postoperatively at 6 hours and day 4. C-reactive protein (CRP), interleukin (IL)-6, C3a, and total peroxide levels were also quantified from serum. Impact of cardiotomy suction and antifibrinolytics on markers of brain injury was assessed. Results:The incidence of early NCD was 40% (16 of 40). NSE and tau protein at the 6-hour time point were both significantly elevated in the presence of NCD (NCD group) compared with those without NCD (NORM group) (8.69 ± 0.82 vs. 5.98 ± 0.61; P = 0.018 and 68.8 vs. 29.2%; P = 0.015; respectively). S-100b increase was not different between the NCD and NORM groups. Cardiotomy suction significantly elevated S-100b levels, whereas NSE and tau were not significantly influenced. Aprotinin did not have an effect on NCD or levels of MBIs. Also, the NCD group had significantly elevated CRP and peroxide levels compared with the NORM group at postoperative day 4 while C3a was significantly elevated at 6 hours. Conclusion:NSE and tau are better associated with NCD and less influenced by cardiotomy suction compared with S-100β. Inflammatory and oxidative stress is associated with NCD post-CPB.

Functional, Cellular, and Molecular Characterization of the Angiogenic Response to Chronic Myocardial Ischemia in Diabetes

Background— Ischemic heart disease is the most common cause of mortality in diabetic patients. Although therapeutic angiogenesis is an attractive option for these patients, they appear to have reduced collateral formation in response to myocardial ischemia. The aims of this study were to establish a large animal model of diabetes and chronic myocardial ischemia, evaluate the effects of diabetes on the angiogenic response, and elucidate the molecular pathways involved. Methods and Results— Diabetes was induced in male Yucatan miniswine using a pancreatic β-cell specific toxin, alloxan (150 mg/kg; n=8). Age-matched swine served as controls (n=8). Eight weeks after induction, chronic ischemia was induced by ameroid constrictor placement around the circumflex coronary artery. Myocardial perfusion and function were assessed at 3 and 7 weeks after ameroid placement using isotope-labeled microspheres. Endothelial cell density and myocardial expression of angiogenic mediators was evaluated. Diabetic animals exhibited significant endothelial dysfunction. Collateral dependent perfusion and LV function were significantly impaired in diabetic animals. Diabetic animals also demonstrated reduced endothelial cell density (173±14 versus 234±23 cells/hpf, P=0.03). Expression of VEGF, Ang-1, and Tie-2 was reduced, whereas antiangiogenic proteins, angiostatin (4.4±0.9-fold increase, P<0.001), and endostatin (2.9±0.4-fold increase, P=0.03) were significantly elevated in the diabetic myocardium. Conclusions— Diabetes results in a profound impairment in the myocardial angiogenic response to chronic ischemia. Pro- and antiangiogenic mediators identified in this study offer novel targets for the modulation of the angiogenic response in diabetes.

A randomized evaluation of simulation training on performance of vascular anastomosis on a high-fidelity in vivo model: The role of deliberate practice

OBJECTIVES There is mounting evidence supporting the benefit of surgical skills practice in a simulated environment. However, the use of simulation in cardiac surgical training has been limited. The purpose of the current trial was to examine the effect of independent and deliberate simulator practice, during nonclinical time, on the performance of an end-to-side microvascular anastomosis in an in vivo model. METHODS This single-blinded, randomized controlled trial received institutional review board approval. Thirty-nine first- and second-year surgical trainees were randomized to an expert-guided tutorial on a procedural trainer or to the expert-guided tutorial combined with self-directed practice on the same procedural trainer. Self-directed practice consisted of 10 anastomoses performed on the procedural trainer: a low-fidelity, commercially available bench model using 4-mm polytetrafluoroethylene graft as simulated blood vessel. Two weeks after the tutorial, subjects performed an end-to-side anastomosis in a live porcine model, under realistic operating room conditions. Assessment of outcomes was performed by 2 blinded, expert observers, uings validated measurements of technical skill. The primary outcome was the score on the Objective Structured Assessment of Technical Skill (OSATS) scale. Secondary outcomes included an anastomosis-specific end-product evaluation and time to completion. Statistical analysis was conducted using nonparametric, univariate techniques. RESULTS Compared with residents who received expert-guided simulator training alone, those who in addition practiced on a simulator independently after hours scored significantly higher on the OSATS scale (23.7 ± 4.7 vs 18.5 ± 3.9, P = .003). Residents who practiced independently also scored significantly higher on the end-product evaluation (11.4 ± 3.2 vs 8.9 ± 2.1, P = .02) and performed the anastomosis significantly faster (777 seconds vs 977 seconds, P = .04). Interrater reliability was high between the expert observers (intraclass correlation coefficient = 0.8). CONCLUSIONS Residents who had the opportunity for self-directed simulator practice performed an end-to-side anastomosis more adeptly, more quickly, and with a higher quality end product. The results of this randomized trial suggest that independent training on a procedural trainer did transfer to improved performance in an operating room environment. Simulator training should be incorporated into cardiovascular surgical curricula and residents should have access to this modality for independent after-hours practice to improve operating room performance.

Endostatin and angiostatin are increased in diabetic patients with coronary artery disease and associated with impaired coronary collateral formation

Coronary artery disease (CAD) is the leading cause of mortality in diabetic patients. Because of the diffuse nature of their disease, diabetic patients may be at risk for incomplete revascularization, highlighting a potential role for proangiogenic therapy in this group. This study investigates molecular mechanisms of angiogenesis in diabetic patients. Myocardial tissue was harvested from patients undergoing coronary artery bypass grafting [nondiabetic (ND) 11, type 2 diabetic (DM) 10]. Expression of angiostatin, endostatin, their precursors (plasminogen and collagen XVIII, respectively), enzymes leading to their production [matrix metalloprotease (MMP)-2 and -9, cathepsin L], and an inhibitor of MMPs (tissue inhibitor of metalloproteinase) was assessed with Western blotting. MMP activity was assessed. Coronary collateralization was graded by Rentrop scoring of angiograms. Plasminogen and collagen XVIII expression were similar between groups. Angiostatin expression trended to increase 1.24-fold (P = 0.07), and endostatin expression increased 2.02-fold in DM patients relative to ND (P = 0.02). MMP-9 expression was no different between groups, whereas MMP-2 expression decreased 1.8-fold in diabetics (P = 0.003). MMP-2 and -9 activity decreased 1.33-fold (P = 0.03) and 1.57-fold (P = 0.04), respectively, in diabetic patients. Cathepsin L expression was 1.38-fold higher in diabetic patients (P = 0.02). Coronary collateralization scores were ND 2.1 +/- 0.37 vs. DM 1.0 +/- 0.4 (P = 0.05). Myocardial endostatin expression correlated strongly with the percentage of hemoglobin A(1c) (r = 0.742, P = 0.0001). Myocardial expression of angiostatin and endostatin demonstrated significant negative linear correlations with coronary collateralization (angiostatin r = -0.531, P = 0.035, endostatin r = -0.794, P = 0.0002). Diabetic patients with CAD exhibit increased levels of the antiangiogenic proteins angiostatin and endostatin and differential regulation of the enzymes governing their production relative to ND patients. Myocardial levels of these proteins show significant correlation to coronary collateralization. These findings offer potential new therapeutic targets for enhancing proangiogenic therapy and insight into the angiogenic impairments seen in diabetes.

Canadian Cardiovascular Society Position Statement on the Management of Thoracic Aortic Disease

This Canadian Cardiovascular Society position statement aims to provide succinct perspectives on key issues in the management of thoracic aortic disease (TAD). This document is not a comprehensive overview of TAD and important elements of the epidemiology, presentation, diagnosis, and management of acute aortic syndromes are deliberately not discussed; readers are referred to the 2010 guidelines published by the American Heart Association, American College of Cardiology, American Association for Thoracic Surgery, and other stakeholders. Rather, this document is a practical guide for clinicians managing adult patients with TAD. Topics covered include size thresholds for surgical intervention, emerging therapies, imaging modalities, medical and lifestyle management, and genetics of TAD. The primary panel consisted of experts from a variety of disciplines that are essential for comprehensive management of TAD patients. The methodology involved a focused literature review with an emphasis on updates since 2010 and the use of Grading of Recommendations Assessment, Development, and Evaluation methodology to arrive at specific recommendations. The final document then underwent review by a secondary panel. This document aims to provide recommendations for most patients and situations. However, the ultimate judgement regarding the management of any individual patients should be made by their health care team.