The effect of insulin cardioplegia on atrial fibrillation after high-risk coronary bypass surgery: a double-blinded, randomized, controlled trial.

UNLABELLED: Atrial fibrillation after coronary bypass (CABG) surgery is an important cause of morbidity and increased resource utilization. Insulin-enhanced cardioplegia may reduce postoperative arrhythmias by improving aerobic myocardial metabolism and mitigating the deleterious effects of ischemia. We performed a double-blinded, randomized, controlled clinical trial to determine if insulin-enhanced cardioplegia decreases the risk of post-CABG atrial fibrillation in a high-risk patient population. We randomized 501 patients undergoing urgent CABG to receive insulin-enhanced (Humulin R 10 IU/L, Insulin group, n = 243) or standard (Control group, n = 258) blood cardioplegia during cardiopulmonary bypass. Patients were monitored by using continuous electrocardiography for a minimum of 3 days postoperatively. All standard cardiac medications, including beta-adrenergic blockers, were continued postoperatively. Insulin-enhanced cardioplegia did not result in a significant reduction in postoperative atrial fibrillation. Furthermore, we failed to detect a difference in the incidence of conduction defects, ventricular tachycardia, or pacemaker requirements between insulin and placebo patients. Atrial fibrillation was the most common arrhythmia, occurring in 31% of all patients. Independent predictors of atrial fibrillation were elderly age, preoperative atrial fibrillation, and renal insufficiency. Right bundle branch block was the most common conduction abnormality. Predictors of right bundle branch block were elderly age, female sex, and circumflex coronary artery disease. The incidence of postoperative ventricular tachycardia, left bundle branch block, and permanent pacemaker requirement was small. We conclude that insulin-enhanced cardioplegia does not reduce the incidence of postoperative atrial fibrillation in high-risk CABG patients. IMPLICATIONS: We conducted a double-blinded, randomized, placebo-controlled trial of insulin-enhanced cardioplegia in 501 patients undergoing urgent coronary bypass surgery. Insulin did not decrease the incidence of postoperative atrial fibrillation when compared with placebo. We also failed to demonstrate a difference in the incidence of other postoperative arrhythmias between the two groups of patients.

The radial artery versus the saphenous vein graft in contemporary CABG: a case-matched study.

BACKGROUND: Although use of the internal thoracic artery has been shown to improve outcomes after coronary artery bypass grafting, the same cannot be said of alternative arterial conduits. To determine the benefit of radial artery (RA) grafting, a case-matched review was undertaken. METHODS: Between March 1994 and March 1999, 2,847 patients underwent isolated coronary artery bypass grafting with a left internal thoracic artery graft, plus saphenous vein grafts (SVGs). Of these patients, 478 also received an RA graft (RA group). The RA patients were matched at a ratio of 1:2 with patients receiving only SVGs and a left internal thoracic artery graft (SVG group; n = 956) using six prognostic risk factors: age, sex, Canadian Cardiovascular Society class, left ventricular grade, number of diseased vessels, and timing of operation. Target vessels were graded according to quality and graftability and were similar between groups. Outcomes were evaluated by univariate and multivariate analyses. RESULTS: There was a significantly higher prevalence of diabetes, hypertension, and peripheral vascular disease in the RA group (p < 0.05). Although stay in the intensive care unit was shorter in the RA group (RA, 30 +/- 2 hours, and SVG, 37 +/- 2 hours; p = 0.0002), total hospital stay was similar between groups. The incidence of perioperative myocardial infarction was higher in the SVG group (SVG, 31 of 956 or 3.2%, and RA, 6 of 478 or 1.3%; p = 0.02). Multivariate analysis revealed RA grafting to be protective against early mortality and morbidity (odds ratio = 0.58; 95% confidence interval, 0.37 to 0.90; p = 0.015) and late mortality and morbidity including late reintervention (risk ratio = 0.60; 95% confidence interval, 0.37 to 0.93; p = 0.02). Actuarial freedom from events at 36 months postoperatively was greater in the RA group (RA, 95% +/- 2%, and SVG, 86% +/- 4%; p = 0.01). CONCLUSIONS: Despite a higher prevalence of preoperative comorbidity, patients in the RA group demonstrated improved outcomes after coronary artery bypass grafting. The RA is a viable and beneficial conduit for this operation.

Late results of the Warm Heart Trial: the influence of nonfatal cardiac events on late survival.

BACKGROUND: The Warm Heart Trial randomized 1732 CABG patients to receive warm or cold blood cardioplegia. In the warm cardioplegia patients, nonfatal perioperative cardiac events were significantly decreased and the mortality rate was nonsignificantly decreased (1. 4% versus 2.5%, P:=0.12). The purpose of the present study was to evaluate the late results of these trial patients. METHODS AND RESULTS: Randomization was stratified according to surgeon and urgency of the operation. Seven hundred sixty-two patients recruited from 1 of the centers were followed through the hospital clinic for late events. Late survival (including perioperative deaths) at 72 months was nonsignificantly greater in the warm cardioplegia patients (94.5+/-1.7%, mean+/-SEM) than in the cold cardioplegia patients (90.9+/-2.6%). Independent predictors of mortality by Cox proportional hazards model were redo CABG, diabetes mellitus, renal insufficiency, and increasing age. The influence of nonfatal perioperative events (perioperative myocardial infarction according to computerized ECG readings or low output syndrome as determined by an outcome committee) on late survival was also analyzed. Late survival at 84 months was significantly reduced in the group who experienced nonfatal perioperative outcomes (94.5+/-1.7% versus 84. 9+/-4.5%, P:<0.001) and remained a significant predictor after adjustment for other important variables (risk ratio 6.4, 95% CI 1. 87 to 8.73, P:<0.0001). CONCLUSIONS: Effective myocardial protection through either cold or warm blood cardioplegia is essential, because late survival is significantly reduced in patients with nonfatal perioperative cardiac outcomes.

The influence of gender on the outcome of coronary artery bypass surgery.

BACKGROUND: To assess the impact of gender as an independent risk factor for early and late morbidity and mortality following coronary artery bypass surgery. METHODS: Perioperative and long-term data on all 4,823 patients undergoing isolated coronary bypass operations from November 1989 to July 1998 were analyzed. Of these patients, 932 (19.3%) were females. RESULTS: During the years 1989 to 1998 there was a progressive increase in the percentage of women undergoing coronary artery bypass surgery. The following preoperative risk factors were more prevalent among women than men: age above 70, angina class 3 or 4, urgent operation, preoperative intraaortic balloon pump usage, congestive heart failure, previous percutaneous transluminal coronary angioplasty, diabetes, hypertension, and peripheral vascular disease (all p < 0.05). Men were more likely to have an ejection fraction less than 35%, three-vessel disease, repeat operations, and a recent history of smoking. Women had a statistically significant smaller mean body surface area than men (1.72+/-0.18 versus 1.96%+/-0.26% m2). On average, women had fewer bypass grafts constructed than men (2.9%+/-0.8% versus 3.2%+/-0.9%) and were less likely to have internal mammary artery grafting (76.2% versus 86.1%), multiple arterial conduits (10.1% versus 19.8%), or coronary endarterectomy performed (4.9% versus 8.6%). The early mortality rate in women was 2.7% versus 1.8% in men (p = 0.09). Women were more prone to perioperative myocardial infarction (4.5% versus 3.1% p < 0.05). After adjustment for other risk variables, female gender was not an independent predictor of early mortality but was a weak independent predictor for the prespecified composite endpoint of death, perioperative myocardial infarction, intraaortic balloon counterpulsation pump insertion, or stroke (8.55 versus 5.9%; odds ratio, 1.30; 95% confidence interval, 0.99 to 1.68; p = 0.05) Recurrent angina class 3 or 4 was more frequent in female patients (15.2%+/-4.0% versus 8.5%+/-2.0% at 60 months, p = 0.001) but not repeat revascularization procedures (percutaneous transluminal coronary angioplasty, redo) (0.6%+/-0.3% versus 4.1%+/-0.8% at 60 months). Actuarial survival at 60 months was greater in women then men (93.1%+/-1.7% versus 90.0%+/-1.0%), and after adjustment for other risk variables, female gender was protective for late survival (risk ratio, 0.40; 95% confidence interval, 0.16-0.74; p < 0.005). CONCLUSIONS: Perioperative complications were increased and recurrent angina more frequent in women. Despite this, late survival was increased in women compared with men after adjustment for other risk variables

Trends in coronary artery bypass surgery results: a recent, 9-year study.

BACKGROUND: The demographics of patients undergoing coronary artery bypass grafting (CABG) have changed over time and may contribute to differing operative mortality and the combination of mortality and morbidity (M + M). In this study, the trends in results are analyzed and causes are suggested. METHODS: Prospectively collected data concerning 4,839 CABG operations was divided into three time cohorts (1990 to 1992, 1993 to 1995, 1996 to 1998) and analyzed by univariate and multivariate techniques. RESULTS: Mean age and female gender frequency increased in the later time cohorts (60.7 +/- 9.0 to 63.4 +/- 9.9 years and 16.5% to 21.4%, respectively). The following comorbidities were more prevalent in the later time cohorts: diabetes (26.7% versus 18.6%), renal failure (8.5% versus 2.2%), peripheral vascular disease (20.7% versus 11.0%), previous cerebrovascular accident (6.7% versus 5.0%), urgent procedures (41.5% versus 26.9%), unstable angina (47.8% versus 31.7%), urgent CABG following myocardial infarction (17.1% versus 7.3%), previous percutaneous transluminal coronary angioplasty (8.0% versus 4.5%), ejection fraction less than 35% (20.5% versus 10.4%), (all p < 0.05). Procedurally, increased utilization of the left internal mammary artery, multiple arterial conduits, and warm blood cardioplegia occurred in the later cohorts (91.2%, 22.2%, and 80.4% versus 78.7%, 3.4%, and 38.0%, respectively). The mortality rate was 2.0% and the M + M rate was 15.6% in all 4,839 patients. The mortality and M + M for the three cohorts were 1.6%, 2.0%, and 2.3% and 18.4%, 17.2% and 12.5%, respectively. The risk-adjusted mortality and M + M decreased from 2.4% and 15.9%, respectively, in 1990 to 1992 to 1.8% and 8.4% in 1996 to 1998 (p < 0.001). The difference in adjusted event rates was minimized when the surgical factors were entered into the model. CONCLUSIONS: Over time, there has been a trend toward operating on older patients with more comorbidities. Though hospital mortality has been stable, risk-adjusted M + M has been in a constant decline. This decline was associated with an increased use of left internal mammary artery grafts, multiple arterial conduits, and warm blood cardioplegia during the later years of the study.

Insulin cardioplegia for elective coronary bypass surgery.

BACKGROUND: Improved methods of myocardial preservation are required to reduce the morbidity and mortality of coronary bypass surgery for high-risk subgroups. Metabolic stimulation with insulin, glucose solutions, or both has been proposed as a method to preserve the ischemic myocardium. We performed a prospective, double-blind, randomized trial to evaluate the effects of insulin and glucose as cardioplegic additives when used as part of a tepid continuous blood cardioplegic strategy. METHODS: We randomized 56 male patients undergoing elective isolated coronary bypass surgery to 1 of 4 cardioplegic groups containing either 42 or 84 mmol/L glucose with or without 10 IU/L of insulin. Perioperative assessments of myocardial metabolism and left ventricular function were performed. RESULTS: Insulin-enhanced cardioplegia was associated with beneficial effects on both myocardial metabolic and functional recovery after cardioplegic arrest. Insulin's effect was independent of the ambient glucose concentration. CONCLUSIONS: Cardioplegic formulations containing a 42 mmol/L concentration of glucose and a 10 IU/L concentration of insulin provide significant benefit to patients undergoing isolated coronary bypass surgery. The clinical effect of these formulations will need to be assessed in high-risk subgroups of patients, such as those with unstable angina, recent myocardial infarction, or poor left ventricular function.

Aprotinin and tranexamic acid for high transfusion risk cardiac surgery.

BACKGROUND: Studies have shown that aprotinin and tranexamic acid can reduce postoperative blood loss after cardiac operation. However, which drug is more efficacious in a higher risk surgical group of patients, has yet to be defined in a randomized study. METHODS: With informed consent, 80 patients undergoing elective high transfusion risk cardiac procedures (repeat sternotomy, multiple valve, combined procedures, or aortic arch operation) were randomized in a double-blind fashion, to receive either high dose aprotinin or tranexamic acid. Patient and operative characteristics, chest tube drainage and transfusion requirements were recorded. RESULTS: There was no significant difference between the 2 treatment groups with respect to age, cardiopulmonary bypass time, complications (myocardial infarction, stroke, death), chest tube drainage (6, 12, or 24 hours), blood transfusions up to 24 hours postoperatively, total allogeneic blood transfusions for entire hospital stay, or induction/postoperative hemoglobin levels. However, multiple regression analysis revealed a positive relationship between cardiopulmonary bypass time and 24 hour blood loss in the tranexamic acid group (p = 0.001), unlike the aprotinin group where 24 hour blood loss is independent of cardiopulmonary bypass time (p = 0.423). CONCLUSIONS: Overall, there was no significant difference in blood loss, or transfusion requirements, when patients received either aprotinin or tranexamic acid for high transfusion risk cardiac operation. Aprotinin, when given as an infusion in a high-dose regimen, was able to negate the usual positive effect of cardiopulmonary bypass time on chest tube blood loss.

A novel comparison of stentless versus stented valves in the small aortic root.

BACKGROUND: Previous studies have compared prosthetic valves on the basis of industry-labeled valve sizes. Unfortunately, the relationship between the labeled size and the true measured external or internal diameter differs between valve manufacturers. Therefore hemodynamic comparisons between prosthetic valves are inaccurate if based solely on industry-labeled valve sizes. METHODS: We have previously demonstrated that the internal diameter of a 21-mm Carpentier-Edwards pericardial stented valve is similar to that of a 25-mm Toronto stentless porcine valve. Therefore we chose to compare postoperative hemodynamics in patients who received 19-, 21-, or 23-mm Carpentier-Edwards pericardial stented valves (inner diameter 18-22 mm, n = 69) with those in patients who received 23- or 25-mm stentless porcine valves (internal diameter 19-21 mm, n = 41). RESULTS: Patients in the Carpentier-Edwards group were more likely to be elderly and more likely to require concomitant revascularization. Operative mortality was lower in the stentless porcine valve group (0% vs 9%, P =.06). Hospital stay and ventilation requirements were shorter in the stentless porcine valve group. Postoperative hemodynamics were similar in the two groups. CONCLUSIONS: These data provide evidence that stentless and stented valves have similar hemodynamic profiles in the small aortic root when matched on true measured internal diameters. The clinical benefit of the stentless porcine valve may be due to patient selection or the lack of a rigid stent in the small aortic root, but it is not due to hemodynamic superiority over stented aortic valves of similar sizes.

Multiple arterial grafts. Radial versus right internal thoracic arteries.

BACKGROUND: Left internal thoracic artery (LITA) grafts to the left anterior descending coronary artery (LAD) during coronary bypass surgery (CABG) have greater patency rates than saphenous vein grafts and reduce long-term cardiac morbidity and mortality rates. The benefits of multiple versus single arterial grafts and the role of different arterial conduits with respect to short- and medium-term outcome remains controversial. The purpose of this study was to compare the perioperative and intermediate-term results of: (1) patients receiving 2 arterial grafts versus 1 arterial graft and (2) patients receiving a right internal thoracic artery (RITA) versus a radial artery (RA) as the second arterial graft. METHODS AND RESULTS: Retrospective analysis of prospectively gathered data on consecutive patients undergoing isolated CABG at our institution between 1989 and 1996 was conducted. The first section of the study compared outcomes for 1 arterial graft (LITA to LAD, n = 2333) versus 2 arterial grafts (LITA + RA or LITA + RITA, n = 378). The second section of the study compared outcomes for the RITA (n = 132) versus the RA (n = 171) as second arterial grafts since 1992, when the radial series was initiated. Part I: By multivariable stepwise logistic regression, the use of 1 arterial graft was associated with an increased incidence of perioperative cardiac morbidity and mortality (odds ratio 2.2, 95% confidence interval 1.4 to 3.3), with the use of our current patient selection criteria. Double-arterial graft patients had a nonsignificant trend toward increased intermediate-term actuarial survival (P = 0.12) and cardiac event-free survival (P = 0.09). Part II: Comparison of preoperative demographics revealed a higher incidence of diabetes (27% vs 11%, P < 0.001), peripheral vascular disease (16% vs 8%, P = 0.03), and elderly age (13% vs 2%, P = 0.001) in patients receiving an RA versus those receiving a RITA as the second arterial graft. Perioperative outcome analysis revealed a decreased intensive care unit stay in the RA versus RITA group (median 30.4 vs 36.2 hours, respectively, P = 0.005) but no significant difference in hospital length of stay. There was no significant difference in perioperative mortality or cardiac morbidity rates. RITA patients had a higher incidence of sternal wound infection (5.3% vs 0.6%, P = 0.01), however, and tended to have increased blood product transfusion rates (51% vs 40%, P = 0.06). CONCLUSIONS: The use of 2 arterial grafts is safe, with a reduction in perioperative cardiac morbidity or mortality rates compared with 1 arterial graft after adjustment for other risk variables. When comparing RITA to RA as second arterial grafts, patients receiving an RA have a lower incidence of sternal wound infection and decreased transfusion requirements, with no difference in perioperative or intermediate-term cardiac morbidity or mortality rates.

Elevated insulin-like growth factor-I and transforming growth factor-beta 1 and their receptors in patients with idiopathic hypertrophic obstructive cardiomyopathy. A possible mechanism.

BACKGROUND: Idiopathic hypertrophic obstructive cardiomyopathy (HOCM) is characterized by regional myocardial hypertrophy. In our previous study, we demonstrated that mRNA levels for insulin-like growth factor-I (IGF-I) and transforming growth factor-beta 1 (TGF-beta 1) were elevated in HOCM tissue. In this study, we investigated IGF-I and TGF-beta 1 protein levels and their respective receptor levels and localization. METHODS AND RESULTS: Myocardial growth factor protein levels were quantified with the use of chemiluminescent slot blot analysis with monoclonal antibodies against IGF-I and TGF-beta. The growth factor receptor binding sites were evaluated with 125I-labeled IGF-I and TGF-beta 1. The receptors were localized with immunohistochemistry. Data were expressed as mean +/- SEM. IGF-I and TGF-beta protein levels in HOCM myocardium (351.8 +/- 46.5 and 17.4 +/- 2.0 ng/g tissue, respectively; n = 6) were significantly higher (P < 0.01 for all groups) than in non-HOCM myocardium obtained from patients with aortic stenosis (AS, 182.1 +/- 22.7 and 8.0 +/- 1.2 ng/g tissue, respectively; n = 5), stable angina (SA, 117.4 +/- 20.9 and 7.5 +/- 2.7 ng/g tissue, respectively; n = 5), and transplanted hearts (TM, 166.3 +/- 30.1 and 6.4 +/- 1.2 ng/g tissue, respectively; n = 5). Maximal and high-affinity binding sites for IGF-I receptor in the HOCM were greater (P < 0.01 and P < 0.05) than the levels in AS, SA, and TM. The maximal receptor binding sites for TGF-beta 1 in HOCM were greater (P < 0.05) than those for SA and TM. Immunohistochemistry demonstrated that IGF-I and TGF-beta 1 receptors were located on the cardiomyocytes and TGF-beta 1 receptors were located on the fibroblasts. CONCLUSIONS: Increased IGF-I and TGF-beta 1 gene expression previously observed in HOCM myocardium results in elevated protein levels. IGF-I and TGF-beta 1 signals may be further amplified by increased receptor numbers on cardiomyocytes and fibroblasts. The data suggest a possible autocrine mechanism of IGF-I-stimulated cardiomyocyte hypertrophy and a paracrine mechanism of TGF-beta 1-stimulated extracellular matrix overproduction in HOCM.

Phase 2 studies of adenosine cardioplegia.

BACKGROUND: Laboratory evidence supports the use of adenosine-supplemented cardioplegia. An initial phase 1 dose-ranging clinical evaluation demonstrated that an adenosine concentration of 15 mumol/L could be safely administered with warm blood cardioplegia and suggested that phase 2 studies were warranted. METHODS AND RESULTS: Two separate double-blind, randomized, placebo-controlled trials were performed in patients undergoing primary, isolated, nonemergent coronary artery bypass graft surgery. Patients were randomized to receive adenosine 15 mumol/L versus placebo in the first study (n = 200) and adenosine 50 or 100 mumol/L versus placebo in the second study (n = 128). Adenosine was infused with both initial and final doses of warm antegrade blood cardioplegia. The data from the 2 trials were combined using the methods of Mantel and Haenszel, and the results of the meta-analysis are presented as the relative risk with their associated 95% confidence intervals (CI). The different study groups were comparable with respect to all preoperative clinical characteristics, angiographic findings, and intraoperative variables. In both trials 1 and 2, no differences were found between groups in the incidence of the individual primary or secondary outcomes. Similarly, when both studies were combined, there was no significant evidence of any consistent treatment benefit (primary: death: relative risk [RR] = 1.02, 95% CI = 0.06, 16.6; myocardial infarction by CK-MB: RR = 0.84, CI = 0.54, 1.31; low output syndrome: RR = 1.38, CI = 0.29, 6.42; any of the above: RR = 0.98, CI = 0.78, 1.25; secondary: Q-wave myocardial infarction: RR = 1.30, CI = 0.41, 4.13; myocardial infarction by troponin T: RR = 0.7, CI = 0.40, 1.21; inotrope requirement: RR = 0.9, CI = 0.46, 1.79; intra-aortic balloon pump requirement: RR = 0.6, CI = 0.07, 4.81; P > 0.20). CONCLUSIONS: Despite promising experimental data, adenosine supplementation of warm blood cardioplegia did not demonstrate any statistically significant benefit in patients undergoing elective coronary artery bypass graft surgery. Although sample sizes were relatively small, based on our interim analyses, it is unlikely that increased patient enrollment would reveal any substantive clinical differences between groups.

Inaccurate and misleading valve sizing: a proposed standard for valve size nomenclature.

BACKGROUND: The sizes with which manufacturers label valves are nonuniform and haphazard. This has led to confusion and inappropriate comparisons of hemodynamics between valves with the same labeled size. Hemodynamic performance of valves is primarily determined by the internal diameter (ID) of their orifice. METHODS: The purpose of this study was to determine the ID and external diameter of aortic valves used at our institution and compare the measurements to manufacturers' labeled sizes. We also evaluated valve size (ID, manufacturers' labeled size) in 527 patients undergoing isolated aortic valve replacement between 1990 and 1996. RESULTS: We demonstrated that no two manufacturers' tissue or mechanical valves have the same ID or external diameter for a given labeled size. The labeled size of tissue valves was 1 to 4 mm larger than the measured ID. The labeled size of mechanical valves was 3 to 5 mm larger than the measured ID. The St. Jude HP mechanical valve has a greater ID than all other mechanical valves for each labeled size. Among 403 patients operated on for predominant aortic stenosis, those patients receiving the Toronto Stented Porcine Valve (n = 98) had a larger mean ID (22.3+/-1.9 mm) than 204 patients receiving stented tissue valves (ID = 20.9+/-1.9 mm) and the 101 patients receiving mechanical valves (ID = 19.3+/-1.9 mm, p < 0.0001). However, when the manufacturers' labeled size was used as a measure of the size, the results were greatly exaggerated in favor of the Toronto Stented Porcine Valve (ID = 26.3+/-1.9 mm) compared with stented tissue valves (ID = 23.1+/-2.1) or mechanical valves (ID = 23.6+/-1.9) (p < 0.0001). CONCLUSIONS: Manufacturers' labeling of valves is nonuniform and may lead to erroneous comparisons and conclusions of hemodynamic differences between valves. We therefore recommend a standardized nomenclature for the size of all valves based on the ID measurement.

Coronary bypass with arterial conduits.

To assess the efficacy of arterial revascularization 368 patients were studied who underwent myocardial revascularization with two or more arterial conduits (group M) and compared with 2092 patients in whom a single internal mammary artery +/- veins (group S), and to a third group in which only saphenous vein conduits (group V, n = 602) were used. Group M patients were younger (aged 54.0(9.5) years; 4.1% aged > 70 years) than either group V (67.6(8.9) years, 40.7% > 70 years, P < 0.0001) or group S patients (62.0(8.5) years, 15.7% > 70 years, P < 0.0001). Furthermore, this cohort group had the lowest percentage of females (8.4%), of urgent cases (21.7%), of preoperative myocardial infarction (6.0%), and of redo surgery (0.8%). In contrast, patients who received only saphenous vein conduits had the highest proportion of female patients (29.2%), of urgent cases (47.4%), of preoperative myocardial infarction (16.5%), and of redo surgery (5.5%). By multivariate logistic regression analysis (odds ratio in parentheses), redo surgery (6.06, P = 0.0001), preoperative intra-aortic balloon pump assist (6.11, P = 0.0001), diabetes (1.97, P = 0.03), urgent surgery (1.80, P = 0.05), and advanced age (2.14, P = 0.01) were all predictors of operative mortality. In contrast, while choice of conduit appeared to influence outcome by univariate analysis (4.2% mortality in group V, P < 0.001), it was not found to be a predictor of either mortality or morbidity by regression analysis. The present results indicate that, in carefully selected patients, despite increased technical demands with longer periods of aortic occlusion and longer pump times, multi-arterial grafting (compared with conventional revascularization) is a safe and efficacious procedure. Whether or not this approach to revascularization will increase long-term survival and freedom from reoperation will require further study.

Early results using an ePTFE membrane for pericardial closure following coronary bypass grafting.

A prospective randomized trial was conducted to evaluate the early efficacy and safety of the Gortex surgical membrane. Three hundred two patients (265 males, 37 females) undergoing isolated coronary bypass surgery were randomized to receive a Gortex membrane (GM = 138) or have the pericardium left open (complication [C] = 164). The groups did not differ in age, gender, urgency of procedure, length of procedure, or use of arterial grafts. Two deaths occurred in each group giving an overall mortality of 1.3%. Fifty-three (17%) patients experienced some complication (C = 34, 21%), GM = 19 (14%). Although the combined complication rate was higher in the control group, this was not statistically significant (chi2 = 2.51, p = 0.11). Postoperative ischemic events (C = 8, GM = 4) observed between the groups were not significant (chi2 = 0.05, p = 0.8), and no statistically significant difference was observed between the incidences of infections (C = 7, GM = 5) or mediastinal complications (C = 3, GM = 3). The Gortex surgical membrane can be used safely without increasing the risk of infection or mediastinal complications. The incidence of recurrent myocardial ischemia, a possible indicator of graft compression, was not higher following membrane implantation. Efficacy at injury prevention will need to be determined by a longitudinal follow-up study presently underway.

Preferred method for insertion of the Toronto Stentless Porcine Valve.

The Toronto Stentless Porcine Valve has been extensively used for aortic valve replacement. A standardized, detailed description of a preferred operative technique has been absent from the literature. A method is described that stresses (a) proper position and orientation of the aortotomy, (b) debridement of the diseased native valve, (C) proper sizing of the aortic root and choice of prosthesis and (d) implantation of the valve. Using this technique, the prosthesis can be reproducibly implanted with relative ease, without valvular insufficiency or coronary obstruction.

Coronary artery bypass grafting in patients with non-dialysis-dependent renal insufficiency.

BACKGROUND: Preoperative renal failure increases the morbidity and mortality of coronary artery bypass graft (CABG) surgery. The results of CABG in patients with non-dialysis-dependent, mild renal insufficiency are unknown. METHODS: From a population of 2978 consecutive patients undergoing isolated CABG from 1990 to 1996, 38 patients with preoperative renal insufficiency (Renal group; serum creatinine >150 micromol/L) were identified and matched on six prognostic variables to a cohort of 152 control patients (Control group). Two patients with preoperative dialysis-dependent renal failure were excluded from analysis. RESULTS: Compared to the overall population, the Renal group were more likely to be over age 70, diabetic, hypertensive, and suffer from peripheral vascular disease and left ventricular dysfunction. Compared to the Control group, the Renal group were more likely to require perioperative blood transfusions (P<.001) and had a greater requirement for postoperative dialysis (P<.01). The Renal group had longer ventilation times, intensive care unit stay, and postoperative hospital stay. Mild renal insufficiency was found to be an independent predictor of postoperative low output syndrome (odds ratio=3.6). CONCLUSIONS: Mild renal insufficiency, even in the absence of dialysis, increases the risk of blood transfusion, low output syndrome and prolonged the length of intensive care unit and postoperative stay for patients undergoing CABG.

Early experience with stentless versus stented valves.

BACKGROUND: The Toronto stentless porcine valve (SPV) was designed to improve hemodynamics after aortic valve replacement by maximizing available flow area in comparison to stented valves (STD). METHODS: To assess possible hemodynamic differences between STD and SPV, 59 patients undergoing isolated aortic valve replacement (+/-coronary artery bypass graft) were prospectively evaluated by preoperative and 3- to 6-month postoperative echocardiography. Among these, 23 patients received a STD, whereas 36 received the Toronto SPV. RESULTS: The mean size (mm) of SPV implanted was larger (SPV, 26.6+/-2.1; STD, 24.0+/-2.9; P=0.0002). Patients receiving STD valves were older and had a higher prevalence of coronary artery disease and congestive heart failure. There were no preoperative differences in left ventricular mass index (g/mo2), peak or mean pressure gradients (mmHg), effective orifice area (cm2), extent of fractional shortening (%), or velocity of circumferential shortening (cf/sec). ANOVA demonstrated a significant reduction in left ventricular mass index at 3 to 6 months (P=.0001) but no differences in left ventricular mass index regression between groups (STD, -28.8+/-37.5; SPV, -31.2+/-32.4; P=.36). Effective orafice area was increased postoperatively (P=.0001), particularly among SPV cases (STD, 1.5+/-0.4; SPV, 1.9+/-0.7; P=.01). Postoperative left ventricular mass index and mean pressure gradient were reduced (P=.0001) but did not differ between groups. Fractional shortening and velocity of circumferential shortening were greater in the SPV patients at 3 to 6 months after aortic valve replacement (P=.0004 and .0001, respectively), and an interactive effect was seen between time and prosthetic group (P=.0028 and .032, respectively). CONCLUSIONS: In a consecutive series of patients, we identified no hemodynamic differences between STD and SPV, although ventricular function improved after SPV. Because of the nonrandomized nature of the study, selection bias may have accounted for some of the observed results. A prospective, randomized trial is necessary to determine the hemodynamic advantages, if any, of the SPV valve.

Overexpression of transforming growth factor-beta1 and insulin-like growth factor-I in patients with idiopathic hypertrophic cardiomyopathy.

BACKGROUND: Idiopathic hypertrophic cardiomyopathy (HCM) is characterized by regional myocardial hypertrophy. To investigate involvement of growth factors on myocardial hypertrophy in HCM patients, we evaluated gene expression and cellular localization of transforming growth factor-beta1 (TGF-beta1), insulin-like growth factors (IGF-I and IGF-II), and platelet-derived growth factor-B (PDGF-B) in ventricular biopsies obtained from patients with HCM (n=8), aortic stenosis (AS) (n=8), or stable angina (SA) (n=8) and from explanted hearts with ischemic cardiomyopathy (TM) (n=7). METHODS AND RESULTS: Levels of TGF-beta1, IGF-I, IGF-II, and PDGF-B transcripts were quantified with the use of multiplex RT-PCR. Glyceraldehyde 3-phosphate dehydrogenase was used as an internal standard. Antibodies against TGF-beta and IGF-I were used to localize their peptides within the myocardium. Antisense and sense (control) cRNA probes of TGF-beta1 and IGF-I, labeled with digoxigenin, were used to localize the growth factor transcripts by in situ hybridization. mRNA levels (densitometric ratio of growth factor/glyceraldehyde-3-phosphate dehydrogenase) of TGF-beta1 and IGF-I in HCM (0.75+/-0.05 and 0.85+/-0.15, respectively; mean+/-1 SEM) were significantly (P<.01 for all groups) elevated in comparison with non-HCM myocardium (AS: 0.38+/-0.07, 0.29+/-0.06; SA: 0.32+/-0.04, 0.18+/-0.05; TM: 0.25+/-0.03, 0.15+/-0.03). mRNA levels of TGF-beta1 and IGF-I in the hypertrophic AS myocardium were greater (P=.02, P=.05) than those in the explanted myocardium (TM). Immunohistochemical and in situ hybridization studies showed increased expression of TGF-beta1 and IGF-I in the HCM cardiomyocytes. CONCLUSIONS: Gene expression of TGF-beta1 and IGF-I was enhanced in idiopathic hypertrophic cardiomyopathy and may be associated with its development.

The influence of risk on the results of warm heart surgery: a substudy of a randomized trial.

OBJECTIVE: The Warm Heart Investigators Trial randomized isolated coronary bypass patients to cold or warm cardioplegia, and demonstrated that warm cardioplegia significantly reduced the prevalence of low output syndrome and myocardial infarction (as defined by CKMB enzyme release). This study was designed prospectively as a subanalysis of the original trial, to determine the effect of warm heart surgery on high risk patients, who were anticipated to derive the major benefit from warm cardioplegia. METHODS: The prespecified endpoint for this study was a composite outcome of morbidity and mortality (death and/or low output syndrome and/or enzymatic myocardial infarction). Only patients with complete data for all outcomes were included, totalling 1374 patients (692 warm cardioplegia, 682 cold cardioplegia) who were randomized in the Warm Heart Investigators Trial. High medium and low risk patients were identified by a multivariate model of predicted risk for the study outcome. RESULTS: Analysis of the independent and interactive influence of cardioplegia technique and predicted risk demonstrated that warm cardioplegia significantly reduced the overall prevalence of morbidity and mortality (warm: 15.9 versus cold: 25.2%, P < 0.01). However, no significant differences in warm-cold effects were detected among risk terciles. Cardioplegia technique had a similar differential influence on mortality and morbidity in low risk patients (warm: 7.3, cold: 17.4%) as it did in high risk patients (warm: 31.1, cold: 39.9%). CONCLUSIONS: Although our analysis confirms the overall benefits of warm cardioplegia, our unanticipated finding in high risk subjects may be explained by the fact that morbidity and mortality in that patient subgroup is caused not only by poor myocardial protection, but by other clinical and technical factors. Further studies are necessary to identify those patients who might benefit most from improved myocardial protection techniques.