OPCAB surgery: a critical review of two different categories of pre-operative ejection fraction.

OBJECTIVE: Literature review found little information on off-pump coronary artery bypass (OPCAB) procedure in patients with poor left ventricular function and there was no information comparing the low EF and normal EF patients undergoing OPCAB procedure. METHODS: Between 1/1/1998 and 6/30/1999, 387patients had surgery performed utilizing the off-pump technique and 45 of these patients had pre-operative left ventricular function of equal to or less than 30% (LVEF < or =30). The two groups (LVEF < or =30 and LVEF>30) were compared using univariate analysis. Patients in LVEF < or =30 were older and more female gender. LVEF< 30 had more NYHA class IV patients (64 vs. 50%) and more symptoms related to depressed left ventricular function. The mean pre-operative left ventricular function was 25% in LVEF < or =30 and 56% in LVEF>30. Pre-operative predicted risk was 6.4+/-5.5% in LVEF < or =30 and 2.7+/-4.5% in LVEF>30 (P< 0.001). Most (> 95%) of the patients in both groups were elective status, and LVEF < or =30 patients had increased incidence of redo (11 vs. 6%, P=0.2). In LVEF>30, 84% of the patients had stable angina while only 69% in LVEF < or =30 (P=0.009). RESULTS: Intra-operatively no significant differences were measured in number of grafts per patient (2.7 vs. 2.8), amount of blood loss, peak CK-MB, skin-to-skin time, or OR time. Patients with LVEF < or =30 have more frequent utilization IABP during pre, intra and post-operative period. The statistical analysis yields no significance in post-operative major neurological deficit between these two groups; and are comparative to the nationally reported incidence of neurological deficit for on-pump patients. The operative mortality in the low EF group was 4.4 and 1.8% in LVEF>30 group (P=0.23). CONCLUSIONS: Given the clinical presentation of the low EF group, higher prediction risk, longer pre-operative stay, and length of ventilation (24 vs. 8 h P=0.12) a longer surgery to discharge stay (8 vs. 6 days, P=0.02) is anticipated. Short-term clinical outcomes for both groups of OPCAB patients encouraged us to continue to offer this approach to this broad base of patient population.

A review of 1,582 consecutive Octopus off-pump coronary bypass patients.

BACKGROUND: Off-pump coronary bypass may provide a safer form of surgical revascularization by avoiding the unwanted complications of cardiopulmonary bypass, particularly in the increasingly complex patients being referred for operation. This study reviews the entire experience of the Medtronic Octopus System (Medtronic, Minneapolis, MN) for beating heart bypass from 7 surgeons. Demographics, operative procedures, early outcomes, and trends in usage were examined. METHODS: Patients were selected for off-pump procedures by the individual surgeons. Data were entered prospectively into locally maintained databases and then collected for collation and analysis. RESULTS: A total of 1,582 consecutive Octopus patients were entered, representing the entire Octopus experience of each surgeon. Proportions of off-pump procedures relative to standard bypass increased over time, as did the percentage of patients receiving three or more grafts, 24.6% in 1997 and 55.9% in 1999. A total of 3,653 anastomoses were performed, 1,905 to the left anterior descending system, 837 to the circumflex distribution, and 911 to the right coronary territory. Morbidity was low. Few patients required conversion to cardiopulmonary bypass (2.6%; 0.2% urgently). Permanent stroke occurred in 0.6% and myocardial infarction in 1.2%. Operative mortality was 1%. CONCLUSIONS: Octopus off-pump bypass was demonstrated to be a safe procedure with widening applicability. With experience surgeons tend to apply the system to increasing proportions of their patients and are able to revascularize all coronary territories.

Is low ejection fraction safe for off-pump coronary bypass operation?

BACKGROUND: Does the manipulation of the heart during off-pump coronary artery bypass (OPCAB) procedure further compromise the hemodynamic stability of a patient with depressed left ventricular function compared with the conventional coronary artery bypass (CCAB) approach? Does this manipulation induce a more dramatic hypoperfused state that may contribute to an increase in the incidence of related complications or mortality? This retrospective review of data attempted to answer the above concern. METHODS: Between January 1, 1998, and June 30, 1999, 177 patients with ejection fractions of 30% or less underwent full sternotomy coronary artery bypass grafting at our institution. Of these patients, 45 underwent OPCAB procedures and 132 patients underwent CCAB. Pre-, intra-, and postoperative variables as identified by The Society of Thoracic Surgeons National Cardiac Surgery Database were compared using univariate and logistical regression analysis. RESULTS: Despite recognized hemodynamic derangement during cardiac displacement, these groups of OPCAB patients appeared to tolerate the procedure well. Univariate analysis of cardiac enzyme leak and blood loss was statistically significant in the OPCAB patients. Utilizing regression analysis, cardiopulmonary bypass was the only predictor for all postoperative complications. CONCLUSIONS: Multivessel coronary artery bypass utilizing the OPCAB approach in patients with depressed left ventricular function of equal to or less than 30% is appropriate and applicable. Analysis of CCAB and OPCAB variables was nonsignificant except for operative and postoperative blood loss and peak cardiac enzyme leak. Attention to intraoperative detail and hemodynamic management could be credited for the success with OPCAB.

Does multivessel, off-pump coronary artery bypass reduce postoperative morbidity?

BACKGROUND: Off-pump coronary artery bypass (OPCAB) is an emerging procedure. It is assumed that elimination of cardiopulmonary bypass for coronary artery bypass grafting has the potential for reducing postoperative morbidity. This review evaluates the safety and impact of multivessel OPCABG as compared to CABG. METHODS: A retrospective review of 744 patients undergoing multivessel coronary artery bypass between January 1, 1997, and March 31, 1999, was done. The total population was divided into two groups: group A (n = 609 cardiopulmonary bypass) and group B (n = 135 OPCAB). This consecutive study cohort was elective status, full sternotomy with three or more distal anastomoses performed at a single institution. RESULTS: The mean risk adjusted predicted mortality was 2.3% in group A and 2.7% in group B (p = NS), with the mean number of distal anastomosis being greater in group A (3.8 vs 3.5/patient, p < 0.001). Major postoperative complications were similar but were not statistically significant between groups. Postoperative blood loss and use of blood transfusions were the only significant variables (p < 0.001). CONCLUSIONS: Multivessel OPCABG can be safely performed in selected patients. Elimination of cardiopulmonary bypass did not significantly reduce postoperative morbidity. Prospective randomized trials and long-term follow-up are needed to better define patient selection and the role of OPCABG.

Safety and efficacy of off-pump coronary artery bypass grafting.

BACKGROUND: We evaluated the application of the off-pump coronary artery bypass (OPCAB) procedure relative to safety and efficiency as measured by operative mortality postoperative complications and longitudinal outcome. METHODS: Three hundred and fifty OPCAB patients were compared to 3,171 on-pump or conventional coronary artery bypass (CCAB) patients between January 1, 1997 and December 31, 1998. The groups were divided into three preoperative predicted risk categories: low-risk (0 to 2.59%), medium-risk (2.6 to 9.9%), and high-risk (> or =10%). Society of Thoracic Surgeons National Cardiac Surgery Database definitions and predicted risk group models were utilized to compare all preoperative, intraoperative, and postoperative variables using univariate analysis. RESULTS: Overall comparison of the immediate outcome of CCAB and OPCAB shows little statistical significance in the variables analyzed. The operative mortality was 3.4% in both groups. When the immediate outcome was compared between groups (CCAB vs OPCAB), as well as individual risk groups (low, medium, and high), similar patterns of operative variables and postoperative complications were observed. The operative mortality in the low-risk group was 1.1% for CCAB and 1.4% for OPCAB; 7% for CCAB and 6% for OPCAB in the medium-risk group; and in the high-risk group 28.5% for CCAB compared to 7.7% for OPCAB group (p = 0.008). Short-term follow-up shows a trend of increased recurring angina and reinterventional procedures in the OPCAB patients. CONCLUSIONS: Safety for OPCAB is assessed through retrospective data review. Longitudinal follow-up for survival, reintervention, and quality of postoperative document efficacy and patency rates, compared to on-pump procedures, is mandatory. This study documented the immediate safety of the OPCAB procedure. Preliminary findings at 1-year follow-up is an important finding in this study, but it is not conclusive at this time. Long-term longitudinal follow-up is required to assess the future effectiveness of OPCAB.

A case for minimally invasive coronary surgery as primary treatment for left anterior descending coronary artery disease.

OBJECTIVE: The introduction of minimally invasive coronary bypass surgery has allowed the application of multiple approaches to coronary artery disease. METHODS: Technologic developments have resolved patency and myocardial ischemic issues and increased surgical experience and training have combined to make more coronary bypass surgeons facile in minimally invasive surgical techniques. RESULTS: These advances, along with the decreased invasiveness, shortened recovery and lower cost, suggest the application of these techniques to the primary treatment of disease of the anterior descending artery. CONCLUSION: In selected circumstances such as these in which patient co-morbid risk factors would suggest high recurrence rates in complex lesions or total occlusion of the anterior descending coronary artery and present in cases of in-stent restenosis, primary application of minimally invasive bypass techniques may create long-term benefits for patients.

Cost-effectiveness of minimally invasive coronary artery bypass surgery.

BACKGROUND: Coronary artery bypass grafting without cardiopulmonary bypass is gaining popularity as an alternative to conventional on-pump technique for myocardial revascularization. This includes minimally invasive direct coronary artery bypass (MIDCAB) and full sternotomy off-pump (OPCAB) methods. These two approaches should be evaluated for financial and clinical appropriateness. METHODS: Records of patients who had single or double bypass (internal mammary artery and/or saphenous vein) grafts between January 1997 and June 1998 were reviewed. These included 44 MIDCAB, 62 OPCAB, and 243 conventional coronary artery bypass (CCAB) patients. Univariate analysis was applied to pre, intra, and postoperative variables, comparing MIDCAB and OPCAB to the CCAB group. Procedural cost information was obtained from participating institutions. RESULTS: MIDCAB patients compared to CCAB patients had a higher predicted risk (5.4+/-11 versus 2.3+/-2.8, p = 0.012) and OPCAB patients had a predicted risk of 5.3+/-7.8. MIDCAB and OPCAB procedures required less operating room time and blood utilization. Observed operative mortality rates were MIDCAB 4.5%, OPCAB 1.6%, and CCAB 2.8% (not significant). Mean hospital costs were CCAB at $19,000, OPCAB at $15,000, and $17,000 for MIDCAB. CONCLUSIONS: Off pump procedures currently reflect acute episode-of-care cost savings over CCAB.

Prolongation of cardiac graft survival with anti-CD4Ig plus hCTLA4Ig in primates.

BACKGROUND: The aim of this study was to determine whether the use of combined immunotherapy with a brief course of humanized anti-CD4Ig and hCTLA4Ig would prolong heterotopic cardiac allograft survival in primates (rhesus monkeys). This model was based on work in "high responder" rats where a brief course of depletive anti-CD4mAb plus hCTLA4Ig was successful in inducing transplantation tolerance. METHODS: Heterotopic cardiac transplants were performed in rhesus recipients. Donor/recipient pairs between groups were confirmed to be reactive prior to transplantation by MLR matching. Humanized anti-CD4Ig, a recently developed anti-CD4mAb, was given at a dose of 20 mg/kg i.v. on days -3, -2, -1, and 0. hCTLA4Ig was administered at 6 mg/kg/dose i.v. on days 0 and 2 for the first recipient and days 0, 2, 4, and 6 for the second recipient. No further immunosuppression was administered. The treated (n = 2) or untreated (n = 5) recipients were followed for graft function by daily palpitation. RESULTS: Treatment with anti-CD4Ig plus hCTLA4Ig resulted in a significant prolongation of heart graft survival (42 days for the first recipient and 52 days for the second recipient) compared to untreated recipients (7 days x 4, 11 days x 1). FACS analysis demonstrated CD4 depletion of anti-CD4 treated animals to <2% on posttransplant day 1. The CD4+ T cells gradually repopulated to 50-70% pretransplant levels just prior to rejection. No adverse responses (fever, tachypnea, tachycardia, infections) were observed. CONCLUSIONS: These are the first results demonstrating that a brief course of combined specific induction immunotherapy with humanized anti-CD4Ig plus hCTLA4Ig, in the absence of adjuvant posttransplant immunosuppression, was well tolerated and resulted in marked prolongation of cardiac allograft survival in primates.

Minimally invasive direct coronary artery bypass grafting: experimental and clinical experiences.

BACKGROUND: This communication briefly details the goals, indications, surgical approaches, and limitations of minimally invasive direct coronary artery bypass grafting (MIDCABG). The experimental experiences from various institutions are summarized. METHODS: The clinical experiences of 72 consecutive MIDCABG procedures performed at our institutions between June 5, 1995, and August 13, 1996, were analyzed. We have divided patients into two groups. Group A consists of healthy low-risk patients with single lesions of the left anterior descending coronary artery or the right coronary artery, or with both lesions of both arteries. Group B consists of high-risk patients who had major contraindications to conventional cardiopulmonary bypass procedures. There were 55 patients in group A and 17 patients in group B. Using The Society of Thoracic Surgeons preoperative predicted risk module, group A had a 1% predicted mortality versus 4% in group B. RESULTS: The 30-day mortality was 2% in group A and 6% in group B. The mean postoperative length of stay was 4 days for group A and 5 1/2 days for group B. Short-term follow-up of the survivors appears promising, and 81% of patients were angina free at the time of last follow-up. CONCLUSIONS: The MIDCABG techniques are still developing. The short-term results during the learning period appear to be quite good, but long-term results remain yet to be seen. The addition of new equipment to facilitate construction of the anastomosis will enhance application and results. The lessons learned from these approaches are already being applied to other areas of cardiac surgery including valve replacement and the repair of congenital heart defects.

Revascularization using angioplasty and minimally invasive techniques documented by thermal imaging.

Minimally invasive direct coronary artery bypass grafting offers mortality and morbidity advantages to selected patients. To broaden indications for such, an appropriate and combined disciplinary approach using angioplasty and minimally invasive direct coronary artery bypass grafting is described in a patient requiring reoperative grafting. Documentation of patency of new left internal mammary artery-to-left anterior descending artery anastomoses performed without the use of cardiopulmonary bypass was obtained intraoperatively using a Thermal Imaging Camera.

Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers.

The anti-HIV agent (+/-)-calanolide A (1) has been synthesized in a five-step approach starting with phloroglucinol [-->5-->6-->11-->18-->(+/-)-1], which includes Pechmann reaction, Friedel-Crafts acylation, chromenylation with 4,4-dimethoxy-2-methylbutan-2-ol, cyclization, and Luche reduction. Cyclization of chromene 11 to chromanone 18 was achieved by employing either acetaldehyde diethyl acetal or paraldehyde in the presence of trifluoroacetic acid and pyridine or PPTS. Luche reduction of chromanone 18 at lower temperature preferably yielded (+/-)-1. Reduction of chromone 12, synthesized by Kostanecki-Robinson reaction from chromene 11, failed to afford (+/-)-1. The synthetic (+/-)-1 has been chromatographically resolved into its optically active forms, (+)- and (-)-1. The anti-HIV activities for synthetic (+/-)-1, as well as resultant (+)- and (-)-1, have been determined. Only (+)-1 accounted for anti-HIV activity, which was similar to the data reported for the natural product, and (-)-1 was inactive.

Pulmonary capillary pressure measurement from pulmonary artery occlusion pressure decay profile analysis in sheep.

Pulmonary capillary pressure (Ppc), the major factor responsible for pulmonary edema, cannot be directly measured in intact subjects but may be estimated by analysis of the pressure decay profile after pulmonary artery catheter balloon inflation. We compared three different methods of pulmonary artery occlusion pressure (Ppao) decay profile analysis to estimates of Ppc derived from lymph flow measurements in halothane-anesthesized sheep. The relationship between Ppc and lymph flow was first determined by increasing Ppc by left atrial balloon inflation, and was then used to determine Ppc during pulmonary hypertension produced by infusion of a thromboxane analog. All three methods of Ppao decay profile analysis demonstrated a correlation with Ppc estimated from lymph flow. However, the method using a single exponential analysis significantly overestimated Ppc, and none of the methods reliably estimated changes in the longitudinal distribution of pulmonary vascular resistance during pulmonary hypertension. These results suggest that Ppao decay profile analysis as currently performed has limited application.

The use of granzyme A as a marker of heart transplant rejection in cyclosporine or anti-CD4 monoclonal antibody-treated rats.

Granzyme A is a serine protease expressed by populations of human and mouse natural killer cells and activated CD4+ and CD8+ cytotoxic lymphocytes; its expression marks a subset of inflammatory cells in allografts, autoimmune diabetes, and a number of other inflammatory lesions. In order to describe more completely the correlation between granzyme A expression and the presence of in vivo cytolytic effects, we grafted allogeneic rat hearts with vascular anastomoses in a heterotopic location, and treated the hosts with either cyclosporine, anti-CD4 monoclonal antibody (MRC OX38), or no therapy. The grafts were evaluated by palpation for cardiac functions, by immunohistochemistry for CD4/CD8 expression, by hematoxylin-and-eosin staining for inflammatory infiltration, and by in situ hybridization for granzyme A expression. The appearance of granzyme A+ cells in untreated allografts preceded both functional and standard histopathological and immunohistochemical evidence of graft rejection by two days. In donor-recipient combinations where cyclosporine and anti-CD4 treatments allowed indefinite allograft survival, the allografts showed minimal numbers of granzyme A+ cells, whether cellular infiltrates developed or not. The number of granzyme A+ cells present in the cardiac allografts in treated and untreated animals correlated with either current or impending episodes of rejection. The early time course of granzyme A expression suggests that it can be used as an early and reliable marker of graft rejection.

Selective T-cell depletion with Ox-38 anti-CD4 monoclonal antibody prevents cardiac allograft rejection in rats.

New monoclonal antibodies directed to membrane molecules unique to lymphocyte subsets have provided the means to alter the immune response to alloantigens in a more selective fashion. This investigation demonstrates that monoclonal antibody-induced depletion of CD4 helper/inducer T lymphocytes before transplantation of a fully mismatched heart allograft allows permanent engraftment in rats without further immunosuppression. Five adult male ACI (RT1a) rats received cell-depleting doses of the mouse anti-rat CD4 monoclonal antibody, MRC Ox-38, for 1 month before undergoing heterotopic abdominal heart transplantation. No other immunosuppression was administered, and immunotherapy was discontinued the day of transplantation. After all five Lewis rat (RT1(1)) hearts were maintained free of rejection for more than 3 months, a second heterotopic transplant was performed, this time to the femoral vessels, using either fresh Lewis heart allografts (n = 3) or third-party, Brown-Norway (RT1n) hearts (n = 2). Histologic evaluation was performed 3 weeks later and revealed severe rejection of the femoral Brown-Norway grafts with no evidence of rejection in any of the femoral or original abdominal Lewis grafts. These results suggested that limited, pretransplant anti-CD4 immunotherapy allowed permanent engraftment of fully mismatched cardiac allografts in rats and conferred donor-specific unresponsiveness.

Induction of donor-specific unresponsiveness to cardiac allografts in rats by pretransplant anti-CD4 monoclonal antibody therapy.

In the present report a monoclonal antibody designated OX-38 directed against the rat CD4 molecule was tested for its ability to prolong the survival of heterotopic vascularized rat heart allografts transplanted across major histocompatibility barriers. Fluorescence-activated cell-sorter analysis showed that administration of OX-38 selectively depleted 80-95% of CD4+ cells from peripheral blood of treated rats. The immunosuppressive effects of OX-38 in vivo were verified by suppression of an antibody response against OX-38 itself as a heterologous protein immunogen. Recipient rats received OX-38 antibody as a single agent given in pretransplant regimens. Nine of 12 treated rats have maintained heterotopic abdominal heart allografts for greater than 175 days. Control rats that did not receive antibody therapy rejected their grafts within 14 days. Rats that maintained heart allografts for greater than 100 days accepted second donor strain hearts but rejected third-party heart grafts transplanted into the femoral space. Anti-CD4-induced allograft unresponsiveness persisted for at least 90 days following surgical removal of donor tissue and retransplantation of a second donor-matched heart. These results indicated that transient, pretransplant therapy with monoclonal antibodies directed against the CD4+ lymphocyte induced specific, long-lasting unresponsiveness to fully MHC-mismatched cardiac allografts in rats without additional immunosuppression.