In vitro versus in vivo correlations of chemosensitivity of human medulloblastoma.

An in vitro clonogenic assay was used to test the chemosensitivity of the human medulloblastoma cell line TE-671. Dose-response relationships for reduction in colony formation were generated for cyclophosphamide, vincristine, Adriamycin, 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC 409962), and 1,4-cyclohexadiene-1,4-dicarbamic acid, 2,5-bis(1-aziridinyl)-3,6-dioxo-diethylester (NSC 182986); and the in vitro drug dose at which there is a 75% reduction in the number of colonies in comparison to controls (ID75S) were derived from these data. Methotrexate produced no colony reduction at any dose tested up to 1000 micrograms/ml. The in vitro results were compared to growth delays in s.c. TE-671 xenografts in athymic mice treated with the same agents. Agents with an ID75 less than assumed in vivo plasma drug concentrations were all active in vivo, whereas two of the three agents with an ID75 greater than assumed in vivo plasma drug concentrations demonstrated no in vivo activity. These results suggest that for these agents, the relationship between the ID75 of the drug and its in vivo concentration allows in vitro clonogenic assay results to agree with in vivo growth delay responses.

Comparison of monoclonal antibody delivery to intracranial glioma xenografts by intravenous and intracarotid administration.

Monoclonal antibody 81C6, which is directed against a human gliomamesenchymal extracellular matrix antigen, was used to evaluate the potential advantage of intracarotid (i.c.) administration versus i.v. delivery to D-54 MG human glioma intracranial xenografts in immunosuppressed rats. Two approaches were taken. In paired-label analysis, 125I-labeled 81C6 and 131I-labeled isotype control antibody were given to separate groups of animals by either the i.v. or i.c. route. Biodistribution measurements as a function of time were analyzed in terms of the percentage of injected dose/g of tissue and localization indices. No significant difference (P greater than 0.19 to P greater than 0.56) was demonstrated between the i.v. and i.c. routes. To control for the large localization variation inherent in the animal model used, an alternative experimental design, paired-injection analysis, was performed in which 125I- and 131I-labeled 81C6 were simultaneously administered by the i.c. and i.v. routes to the same animal. Significantly higher levels of percentage of dose/g of tissue and localization ratios (P less than 0.05 to P less than 0.005) were shown from Day 1 to Day 3 for 81C6 given i.c. Approximately 20% more antibody was delivered to the D-54 MG intracranial tumor by the i.c. route during the experimental period of 5 days. No difference in the levels of normal tissue exposure between the two routes of administration was seen. These data suggest an advantage exists for whole monoclonal antibody given i.c. and that, theoretically, a greater advantage may be present for smaller molecules such as Fab and F(ab')2 fragments.

Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents.

A series of bifunctional alkylators were tested against the genotypically and phenotypically heterogeneous continuous human medulloblastoma cell lines, TE-671, Daoy, and D283 Med in vitro and against TE-671 and Daoy growing as s.c. and intracranial xenografts in athymic mice. Drugs tested included melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, thiotepa, 1,3-bis(2-chloroethyl)-1-nitrosourea (in vivo), and busulfan (in vivo). Melphalan and phenylketocyclophosphamide were the most active agents in vitro with drug doses at which there is a 90% reduction in the number of colonies in comparison to controls of 2.13, 5.29, and 4.72 microM for melphalan and 4.60, 5.01, and 4.34 microM for phenylketocyclophosphamide against TE-671, D283 Med, and Daoy, respectively. Melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, and thiotepa produced significant growth delays against s.c. TE-671 and Daoy xenografts, while no activity could be demonstrated for 1,3-bis(2-chloroethyl)-1-nitrosourea or busulfan. Melphalan, cyclophosphamide, iphosphamide, and thiotepa also produced significant increases in median survival in mice bearing intracranial TE-671 and Daoy xenografts. These results extend our previous studies demonstrating the antitumor activity of nitrogen and phosphoramide mustard-based bifunctional alkylating agents in the treatment of human medulloblastoma continuous cell lines and transplantable xenografts, and support the continued use of these agents in clinical trials.

Specific chromosomal abnormalities in malignant human gliomas.

Karyotypic analysis of 54 malignant human gliomas (5 anaplastic astrocytomas, 43 glioblastoma multiformes, 3 gliosarcomas, 2 giant cell glioblastomas, 1 anaplastic mixed glioma) has demonstrated that 12 tumors contained normal stemlines or only lacked one sex chromosome. The 42 tumors with abnormal karyotypes included 38 tumors which could be completely analyzed. Six of these 38 cases had near-triploid or near-tetraploid stemlines and 32 had near-diploid stemlines. Statistically significant numerical deviations in the near-diploid group were gains of chromosome 7 (26 of 32; P less than 0.001), and losses of chromosome 10 (19 of 32; P less than 0.001). Double minutes occurred in 18 of 32 near diploid tumors. The distribution of structural abnormalities was analyzed statistically by comparing the incidence of breakpoint in each chromosomal arm to the expected value based on chromosomal arm length. This analysis demonstrated that structural abnormalities of 9p and 19q were significant statistically (P less than 0.005 and P = 0.02, respectively). Although chromosome 1, 6p, the centromeric region of chromosome 11, 13q, and 15q were also frequently involved in structural abnormalities, the incidence of these breaks did not reach statistical significance. This demonstration of specific chromosomal abnormalities in near-diploid gliomas provides the basis for the investigation of genes which may be quantitatively or qualitatively altered in these neoplasms.

Activity of intrathecal 4-hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis.

Neoplastic meningitis can result from leptomeningeal dissemination of a variety of cancers. We now report the development of animal models of human neoplastic meningitis and activity of intrathecal 4-hydroperoxycyclophosphamide (4-HC) against the human rhabdomyosarcoma cell line TE-671 and the human glioma cell line D-54 MG grown in the subarachnoid space of athymic rats. The injection of 5 x 10(5) TE-671 or D-54 MG cells resulted in leptomeningeal tumor growth from the base of the brain to the cauda equina. Daily weights and neurological examinations revealed progressive neurological deficits and weight loss, with death occurring between Days 21 and 27 for TE-671 and Days 14 and 26 for D-54 MG. 4-HC toxicity in non-tumor-bearing rats was assessed at dose levels of 2.0, 10.0, 15.0, and 20.0 mM, with clinical and histological evidence of neurotoxicity observed at the 2 highest dose levels. Intrathecal treatment with 4-HC on Day 8 following injection of TE-671 resulted in an increase in median survival of 20% (P = 0.04) at 1.0 mM 4-HC and 41% (P less than 0.001) at 2.5 mM 4-HC. Intrathecal treatment with 4-HC (2.5 mM) on Day 5 following injection of D-54 MG resulted in an increase in median survival of 23% (P = 0.009). These studies show the usefulness of the athymic rat model of human neoplastic meningitis and demonstrate the efficacy in vivo of intrathecally administered 4-HC against a human glioma and a human rhabdomyosarcoma cell line and the lack of toxicity at therapeutic levels of 4-HC in normal athymic rats.

Data for cardiovascular modeling.

Data are required for a meaningful approach to quality and cost-conscious cardiovascular care. How to identify the types of data available and their sources, advantages and limitations to their use, issues involved in combining data from different sources for decision modeling and some possible solutions are discussed in this summary of the Working Group on Data for Cardiovascular Modeling.

The effects of New York's bypass surgery provider profiling on access to care and patient outcomes in the elderly.

OBJECTIVE: The aim of this study was to examine the effects of provider profiling on bypass surgery access and outcomes in elderly patients in New York. BACKGROUND: Since 1989, New York (NY) has compiled provider-specific bypass surgery mortality reports. While some have proposed that "provider profiling" has led to lower surgical mortality rates, critics have suggested that such programs lower in-state procedural access (increasing out-of-state transfers) without improving patient outcomes. METHODS: Using national Medicare data, we examined trends in the percentages of NY residents aged 65 years or older receiving out-of-state bypass surgery between 1987 and 1992 (before and after program initiation). We also examined in-state procedure use among elderly myocardial infarction patients during this period. Finally, we compared trends in surgical outcomes in NY Medicare patients with those for the rest of the nation. RESULTS: Between 1987 and 1992, the percentage of NY residents receiving bypass out-of-state actually declined (from 12.5% to 11.3%, p < 0.01 for trend). An elderly patient's likelihood for bypass following myocardial infarction in NY increased significantly since the program's initiation. Between 1987 and 1992, unadjusted 30-day mortality rates following bypass declined by 33% in NY Medicare patients compared with a 19% decline nationwide (p < 0.001). As a result of this improvement, NY had the lowest risk-adjusted bypass mortality rate of any state in 1992. CONCLUSIONS: We found no evidence that NY's provider profiling limited procedure access in NY's elderly or increased out-of-state transfers. Despite an increasing preoperative risk profile, procedural outcomes in NY improved significantly faster than the national average.

Contemporary outcome trends in the elderly undergoing percutaneous coronary interventions: results in 7,472 octogenarians. National Cardiovascular Network Collaboration.

OBJECTIVES: We sought to define the risks facing octogenarians undergoing contemporary percutaneous coronary interventions (PCIs). BACKGROUND: The procedural risks of PCI for octogenarians have not been well established. METHODS: We compared the clinical characteristics and in-hospital outcomes of 7,472 octogenarians (mean age 83 years) with those of 102,236 younger patients (mean age 62 years) who underwent PCI at 22 National Cardiovascular Network (NCN) hospitals from 1994 through 1997. RESULTS: Octogenarians had more comorbidities, more extensive coronary disease and a two- to fourfold increased risk of complications, including death (3.8% vs. 1.1%), Qwave myocardial infarction (1.9% vs. 1.3%), stroke (0.58% vs. 0.23%), renal failure (3.2% vs. 1.0%) and vascular complications (6.7% vs. 3.3%) (p < 0.001 for all comparisons). Independent predictors of procedural mortality in octogenarians included shock (odds ratio [OR] 5.4, 95% confidence interval [CI] 3.3 to 8.8), acute myocardial infarction (OR 3.2, 95% CI 2.3 to 4.4), left ventricular ejection fraction (LVEF) <35% (OR 2.9, 95% CI 2.1 to 3.9), renal insufficiency (OR 2.8, 95% CI 2.0 to 3.8), first PCI (OR 2.3, 95% CI 1.7 to 3.3), age >85 years (OR 2.1, 95% CI 1.5 to 2.7) and diabetes mellitus (OR 1.5, 95% CI 1.1 to 2.0). For elective procedures, octogenarian mortality varied nearly 10-fold, and was strongly influenced by comorbidities (0.79% mortality with no risk factors vs. 7.2% with renal insufficiency or LVEF <35%). Despite similar case-mix, PCI outcomes in octogenarians improved significantly over the four years of observation (OR of 0.61 for death/myocardial infarction/stroke in 1997 vs. 1994; 95% CI 0.45 to 0.85). CONCLUSIONS: Risks to octogenarians undergoing PCI are two- to fourfold higher than those of younger patients, strongly influenced by comorbidities, and have decreased in the stent era.

Challenges in comparing risk-adjusted bypass surgery mortality results: results from the Cooperative Cardiovascular Project.

OBJECTIVES: We sought to evaluate the predictive accuracy of four bypass surgery mortality clinical risk models and to examine the extent to which hospitals' risk-adjusted surgical outcomes vary depending on which risk-adjustment method is applied. BACKGROUND: Cardiovascular "report cards" often compare risk-adjusted surgical outcomes; however, it is unclear to what extent the risk-adjustment process itself may affect these metrics. METHODS: As part of the Cooperative Cardiovascular Project's Pilot Revascularization Study, we compared the predictive accuracy of four bypass clinical risk models among 3,654 Medicare patients undergoing surgery at 28 hospitals in Alabama and Iowa. We also compared the agreement in hospital-level risk-adjusted bypass outcome performance ratings depending on which of the four risk models was applied. RESULTS: Although the four risk models had similar discriminatory abilities (C-index, 0.71 to 0.74), certain models tended to overpredict mortality in higher-risk patients. There was high correlation between a hospital's risk-adjusted mortality rates regardless of which of the four models was used (correlation between risk-adjusted rating, 0.93 to 0.97). In contrast, there was limited agreement in which hospitals were identified as "performance outliers" depending on which risk-adjustment model was used and how outlier status was defined. CONCLUSIONS: A hospital's risk-adjusted bypass surgery mortality rating, relative to its peers, was consistent regardless of the risk-adjustment model applied, supporting their use as a means of provider performance feedback. Designation of performance outliers, however, can vary significantly depending on the benchmark and methods used for this determination.

Outcomes of cardiac surgery in patients > or = 80 years: results from the National Cardiovascular Network.

OBJECTIVES: The purpose of this study was to evaluate characteristics and outcomes of patients age > or =80 undergoing cardiac surgery. BACKGROUND: Prior single-institution series have found high mortality rates in octogenarians after cardiac surgery. However, the major preoperative risk factors in this age group have not been identified. In addition, the additive risks in the elderly of valve replacement surgery at the time of bypass are unknown. METHODS: We report in-hospital morbidity and mortality in 67,764 patients (4,743 octogenarians) undergoing cardiac surgery at 22 centers in the National Cardiovascular Network. We examine the predictors of in-hospital mortality in octogenarians compared with those predictors in younger patients. RESULTS: Octogenarians undergoing cardiac surgery had fewer comorbid illnesses but higher disease severity and surgical urgency than younger patients. Octogenarians had significantly higher in-hospital mortality after cardiac surgery than younger patients: coronary artery bypass grafting (CABG) only (8.1% vs. 3.0%), CABG/aortic valve (10.1% vs. 7.9%), CABG/mitral valve (19.6% vs. 12.2%). In addition, they had twice the incidence of postoperative stroke and renal failure. The preoperative clinical factors predicting CABG mortality in the very elderly were quite similar to those for younger patients with age, emergency surgery and prior CABG being the powerful predictors of outcome in both age categories. Of note, elderly patients without significant comorbidity had in-hospital mortality rates of 4.2% after CABG, 7% after CABG with aortic valve replacement (CABG/AVR), and 18.2% after CABG with mitral valve replacement (CABG/MVR). CONCLUSIONS: Risks for octogenarians undergoing cardiac surgery are less than previously reported, especially for CABG only or CABG/AVR. In selected octogenarians without significant comorbidity, mortality approaches that seen in younger patients.

Impact of early discharge after coronary artery bypass graft surgery on rates of hospital readmission and death. The Ischemic Heart Disease (IHD) Patient Outcomes Research Team (PORT) Investigators.

OBJECTIVES: This study examined the impact of early hospital discharge on short-term clinical outcomes of elderly patients treated with coronary artery bypass graft surgery (CABG) in the United States in 1992. BACKGROUND: Protocols that encourage earlier discharge of patients who have had CABG have been implemented across the country. Although delivery of efficient care benefits both patients and providers, premature discharge can adversely affect clinical outcomes, resulting in increased hospital readmissions and higher long-term costs. METHODS: We examined the prevalence of early discharge (postoperative length of stay < or = 5 days) among 83,347 non-health maintenance organization (HMO) Medicare patients who underwent CABG in the United States in 1992. Using logistic regression models, we identified patient characteristics associated with early discharge and obtained risk-adjusted rates of death and readmission or death for postoperative lengths of stay between 4 and 14 days. RESULTS: In 1992, 6% of Medicare patients undergoing CABG were discharged within 5 days of the operation. The prevalence of early discharge varied considerably among states, ranging from 1% to 21%. Patients discharged early tended to be younger and male and have fewer comorbid illnesses. Risk-adjusted rates of death and death or cardiovascular readmission were lowest among patients discharged early. CONCLUSIONS: As of 1992, early discharge of elderly patients treated with CABG in non-HMO settings was not associated with higher 60-day rates of death or readmission. This suggests that physicians were able to identify low risk candidates for early discharge. Variation across the nation in early discharge rates, along with the percentage of patients without major risk factors for adverse outcomes, suggests that higher rates of early discharge might be safely achieved.

Clinical judgment and therapeutic decision making.

Clinical decision making is under increased scrutiny due to concerns about the cost and quality of medical care. Variability in physician decision making is common, in part because of deficiencies in the knowledge base, but also due to the difference in physicians' approaches to clinical problem solving. Evaluation of patient prognosis is a critical factor in the selection of therapy, and careful attention to methodology is essential to provide reliable information. Randomized controlled clinical trials provide the most solid basis for the establishment of broad therapeutic principles. Because randomized studies cannot be performed to address every question, observational studies will continue to play a complementary role in the evaluation of therapy. Randomized studies in progress, meta analyses of existing data, and increased use of administrative and collaborative clinical data bases will improve the knowledge base for decision making in the future.

The impact of statistical adjustment on economic profiles of interventional cardiologists.

OBJECTIVES: The objective of this study was to identify preprocedure patient factors associated with percutaneous intervention costs and to examine the impact of these patient factors on economic profiles of interventional cardiologists. BACKGROUND: There is increasing demand for information about comparative resource use patterns of interventional cardiologists. Economic provider profiles, however, often fail to account for patient characteristics. METHODS: Data were obtained from Duke Medical Center cost and clinical information systems for 1,949 procedures performed by 13 providers between July 1, 1997, and December 31, 1998. Patient factors that influenced cost were identified using multiple regression analysis. After assessing interprovider variation in unadjusted cost, mixed linear models were used to examine how much cost variability was associated with the provider when patient characteristics were taken into account. RESULTS: Total hospital costs averaged $15,643 (median, $13,809), $6,515 of which represented catheterization laboratory costs. Disease severity, acuity, comorbid illness and lesion type influenced total costs (R(2) = 38%), whereas catheterization costs were affected by lesion type and acuity (R(2) = 32%). Patient characteristics varied significantly among providers. Unadjusted total costs were weakly associated with provider, and this association disappeared after accounting for patient factors. The provider influence on catheterization costs persisted after adjusting for patient characteristics. Furthermore, the pattern of variation changed: the adjusted analysis identified three new outliers, and two providers lost their outlier status. Only one provider was consistently identified as an outlier in the unadjusted and adjusted analyses. CONCLUSIONS: Economic profiles of interventional cardiologists may be misleading if they do not adequately adjust for patient characteristics before procedure.

Gene amplification in malignant human gliomas: clinical and histopathologic aspects.

Gene amplification occurs in 45-50% of malignant human gliomas (MHG). In the present study, 64 genetically characterized gliomas were evaluated to determine if tumors with amplification of the epidermal growth factor receptor (EGFR), N-myc, c-myc, or gli genes had distinctive histopathologic features. There was no significant difference in age (p = 0.10) or gender (p = 0.78) between patients whose tumors contained amplified genes and those whose tumors did not exhibit this characteristic. Although the patients with amplified genes in their tumors survived slightly longer than patients whose tumors had no detectable gene amplification, these differences were not statistically significant (p = 0.21). The 28 tumors with amplification included 24/48 (50%) glioblastoma multiforme, 2/6 (33%) anaplastic astrocytomas and 2/5 (40%) gliosarcomas. No amplification was seen in one oligodendroglioma, three anaplastic mixed gliomas or one giant cell glioblastoma multiforme. Necrosis and endothelial proliferation were equally prevalent among tumors with and without amplification. Comparison of tumors with gene amplification and tumors without this characteristic revealed similar distributions of most morphologic cells types. Although prominent perivascular lymphocytic infiltrates were more frequent in tumors without amplification, this association was of borderline significance statistically. In situ hybridization of tumors with amplification using an EGFR mRNA probe showed intense labeling of different neoplastic cell types including fibrillary and protoplasmic astrocytes, gemistocytes, anaplastic cells, and multinucleated giant cells. Non-neoplastic cells such as hyperplastic endothelium within the tumors did not express detectable EGFR mRNA. These studies demonstrate that (a) cells with quite different morphology within the same tumor can contain the same genetic alteration; (b) tumors of identical histological appearance may have arisen and evolved by different molecular mechanisms; and (c) molecular analyses are necessary to evaluate gene amplification in MHG since this characteristic cannot be accurately predicted by the morphologic or clinical criteria used in this study.

Estimating the likelihood of severe coronary artery disease.

PURPOSE: To determine which clinical characteristics obtained by a physician during an initial clinical examination are important for estimating the likelihood of severe coronary artery disease, and to determine whether estimates based on these characteristics remain valid when applied prospectively and in different patient groups. PATIENTS AND METHODS: We examined clinical characteristics predictive of severe disease in 6,435 consecutive symptomatic patients referred for suspected coronary artery disease between 1969 and 1983. RESULTS: Eleven of 23 characteristics were important for estimating the likelihood of severe coronary artery disease. A model using these characteristics accurately estimated the likelihood of severe disease in an independent sample of 2,342 patients referred since 1983. The model also accurately estimated the prevalence of severe disease in large series of patients reported in the literature. CONCLUSIONS: These findings suggest that the clinician's initial evaluation can identify patients at high or low risk of anatomically severe coronary artery disease. Cost-conscious quality care is encouraged by identifying patients at higher risk for severe coronary artery disease who are most likely to benefit from further evaluation.

Outcomes following interventions in small coronary arteries with the use of hand-crimped Palmaz-Schatz stents.

Although coronary stenting has been shown to be effective, retrospective studies have suggested that stents do not provide better results than angioplasty in small coronary arteries. We sought to examine procedural, in-hospital, and long-term outcomes of patients undergoing small-vessel stenting with Palmaz-Schatz stents hand-crimped on a balloon catheter <3 mm in diameter. We retrospectively analyzed the outcomes of 117 patients who underwent this type of coronary stent implantation at Duke University Medical Center between January 1, 1997 and May 30, 1998. The clinical indications for percutaneous revascularization included unstable angina in 67.5% of patients, acute myocardial infarction in 4.3%, postinfarct angina in 3.4%, silent ischemia in 3.4%, and stable angina in 1% of patients. Quantitative angiographic analysis was performed immediately before angioplasty and after stent implantation. Stents were used for elective indications in 24%, for suboptimal angiographic result in 61.5%, and for abrupt and/or threatened closure in 14.5% of patients. Reference vessel diameter was similar before and after the procedure. Minimum luminal diameter increased from 0.63 to 2.35 mm, an acute gain of 1.72+/-0.43 mm. Percent stenosis decreased from 74.2% to 4.7%. The clinical composite of death (n = 1, 1%), nonfatal myocardial infarction (n = 6, 5.1%), and revascularization (n = 1, 1%) occurred in-hospital in only 8 patients (6.8%), resulting in clinical procedure success in 109 patients (93%). Our data suggest that stents designed for vessels >3.0 mm can be deployed in small vessels, with a low in-hospital event rate. However, target lesion revascularization in small vessels remains high. Development of antiproliferative strategies could improve long-term outcomes for small-vessel interventions.

Statistical methods in SUPPORT.

The analysis and interpretation of the data collected in SUPPORT provide great potential for understanding the relationships among treatment choices, patient and physician values and preferences, perceptions about the risks and benefits of treatments, institutional characteristics, and outcomes (as measured by quality of life, survival, and satisfaction). The complicated analyses required to elucidate these relationships will pose many technical challenges in dealing with longitudinal observational data collected from seriously ill patients at multiple sites. Major challenges include the handling of incomplete data, proper parameterization of treatment effects, strategies to avoid various potential biases, validating predictive models, and constructing endpoints that combine survival with quality of life. Within the structure of the SUPPORT study, mechanisms have been established to guide the analyses and to ensure their quality and validity.

Associations among family support, family stress, and personal functional health status.

The self-reported family support and stress of 249 ambulatory adult patients, aged 18-49 years, were studied relative to their self-reported functional health. Support from family members was found to be related positively with emotional function. Stress from family members was associated negatively with symptom status, physical function, and emotional function. Patients' severity of illness was related negatively to their symptom status, physical function, and social function, but not to their emotional function. During the study a new self-report instrument, the Duke Social Support and Stress Scale (DUSOCS), was developed to measure family and non-family support and stress. Also, a new chart audit methodology, the Duke Severity of Illness Scale (DUSOI), was designed to assess severity in the ambulatory setting. Reliability and validity of the DUSOCS and the DUSOI were supported. The importance of the patient's perception of health and its family determinants is emphasized.

Immediate versus delayed coronary grafting after streptokinase treatment. Postoperative blood loss and clinical results.

Of all patients with acute evolving myocardial infarction treated surgically at Duke University Medical Center between 1984 and 1986, 27 patients given high doses (greater than 1.5 million units) of streptokinase preoperatively were studied. Eleven patients who received streptokinase had coronary bypass grafting 12 hours after thrombolytic therapy (early hours), eight patients between 12 and 72 hours (delayed), and eight patients beyond 72 hours (late hours). Seventeen patients who underwent coronary bypass grafting within 6 hours of the onset of symptoms, without preoperative streptokinase, were included as control patients. Only the patients having early operation had significantly greater postoperative blood loss; postoperative use of red blood cells; fresh-frozen plasma; cryoprecipitate; prolonged postoperative prothrombin time; and prolonged partial thromboplastin time. Patients having delayed or late operations did not differ significantly from patients not receiving streptokinase. Only the interval between time of streptokinase administration and operation could account for the coagulopathy and the postoperative bleeding complications in the early group. Patients in the early group had a higher in-hospital mortality (27% versus 6% for the non-streptokinase group) and major noncardiac morbidity (36% versus 12% for the non-streptokinase group). Patients in the delayed and late groups had minimal postoperative complications and no mortality. Observations were not explained by differences in total ischemic time, number of angioplasty failures, or number of patients with cardiogenic shock between the early group and the non-streptokinase group. Postoperative bleeding and massive use of blood products seemed to be contributory factors: Two of three deaths in the patients having early operations were associated with clinical suspicion of tamponade. Patients undergoing coronary bypass grafting within 12 hours of streptokinase therapy appear to be a high-risk group in a more emergent, uncontrolled clinical setting and require aggressive monitoring and correction of coagulopathy.

Coronary bypass grafting after failed elective and failed emergent percutaneous angioplasty. Relative risks of emergent surgical intervention.

Emergency coronary artery bypass grafting after failed elective percutaneous transluminal coronary angioplasty can be performed with acceptable complication rates. Recently, however, a new class of patients with unsuccessful angioplasty has evolved with the use of thrombolytic therapy and emergent angioplasty as treatment for developing acute myocardial infarction. The efficacy of surgical intervention after failure of angioplasty in this setting has not been demonstrated. This report compares the results of coronary bypass done emergently after either failed elective or failed emergent angioplasty. Between March 1984 and September 1986; 1350 angioplasty procedures were performed at our institution, 393 for acute myocardial infarction. Of the 111 patients who came to operation, 42 had had unsuccessful elective angioplasty and 69 unsuccessful angioplasty done in the clinical setting of an evolving acute myocardial infarction detected by electrocardiographic criteria. Twenty-one of the 42 patients having unsuccessful elective angioplasty (group I) and 32 of the 69 with unsuccessful emergent angioplasty (group II) underwent emergency coronary artery bypass grafting. A retrospective nonparametric statistical comparison of the two groups was performed. Age, preoperative ejection fraction, distribution of vessels undergoing angioplasty, and number of vessels bypassed were not statistically different. All group II patients received thrombolytic therapy, and a reperfusion catheter was used in over half the patients in each group. Three group I and six group II patients required a preoperative balloon pump, and half the patients in each group required postoperative inotropic support. One patient in group I (4.7%) and two patients in group II (6.2%) died (no significant difference). Only five patients in group I (23.8%) and 11 in group II (34.3%) had enzymatic and electrocardiographic evidence of an acute myocardial infarction at discharge. Six patients in group II (15.6%) required reexploration for bleeding, versus none in group I (p = 0.04). Nonhemorrhagic complication rates, mean in-patient and acute care days, total hospital charges, and blood product utilization rates were not statistically different. These data indicate that emergency coronary artery bypass grafting can be performed when necessary in the setting of failed emergent percutaneous transluminal coronary angioplasty with results comparable to coronary bypass after failed elective angioplasty.