Predictors of length of stay after coronary stenting.

BACKGROUND: Postprocedure length of stay (LOS) remains an important determinant of medical costs after coronary stenting. Variables that predict LOS in this setting have not been well characterized. METHODS: We evaluated 359 consecutive patients who underwent coronary stenting with antiplatelet therapy. Sequential multiple linear regression (MLR) models were constructed with use of 4 types of variables to predict log-transformed LOS: preprocedure, intraprocedure, and postprocedure factors and adverse outcomes. RESULTS: Preprocedure factors alone explained more than one third of the variability in postprocedure LOS (adjusted R(2) = 0.37). The addition of procedural variables added little to the model (adjusted R(2) = 0.39). Entering nonoutcome postprocedure variables significantly enhanced the predictive capacity of the model, explaining more than half the variability in postprocedure LOS (adjusted R(2) = 0.54). In the final model, addition of outcome variables increased its predictive capacity only slightly (adjusted R(2) = 0.61). In this model, significant preprocedure factors included: myocardial infarction (MI) within 24 hours, MI within 1 to 30 days, women with peripheral vascular disease, intravenous heparin, and chronic atrial fibrillation. High-risk intervention was the only significant intraprocedure variable. Significant postprocedure factors included periprocedure ischemia; cerebrovascular accident or transient ischemic attack; treatment with intravenous heparin or nitroglycerin or intra-aortic balloon pump; and need for blood transfusion. Significant adverse outcomes included contrast nephropathy, gastrointestinal bleeding, arrhythmia, vascular complication, and repeat angiography. CONCLUSION: This prediction model identifies a number of potentially reversible factors responsible for prolonging LOS and may enable the development of more accurate risk-adjusted methods with which to improve or compare care.

Effects of adenosine on thrombosis and thrombolysis in a canine experimental preparation.

Intracoronary infusion of adenosine is reported to inhibit cyclic flow variations after coronary artery injury and stenosis. This study was performed in the anesthetized dog to determine if adenosine prevents arterial thrombosis and/or reocclusion after thrombolysis. Carotid and coronary arteries were instrumented with Doppler(TM) flow probes, a critical stenosis, infusion line and an anodal electrode. Two protocols were employed. In the thrombosis protocol, intracarotid infusion of adenosine (20 microg/kg/min for 3 h) did not alter cyclic flow variations or patency during induction of vessel wall injury. In the second protocol, occlusive arterial thrombi were induced by anodal current injury and lysed with local application of tissue plasminogen activator. Whereas adenosine prolonged the time to arterial occlusion, it did not affect cyclic flow variations or time to reocclusion after thrombolysis.

Thrombostatin inhibits cyclic flow variations in stenosed canine coronary arteries.

Thrombostatins are a group of compounds based upon a breakdown product of bradykinin, RPPGF. They inhibit alpha-thrombin-induced platelet activation by binding to protease activated receptor 1 and, at a lower affinity, by interacting with thrombin's active site. After a single intravenous infusion of MAP4-RPPGF (11.58 mg/kg), its t1/2alpha was 4.5 min with a clearance of 2.0 ml/min. MAP4-RPPGF administration had a sustained antiplatelet effect, preventing gamma-thrombin-induced (12.5 nM) platelet activation for 4 h. Its antiplatelet effect summated with that of aspirin and/or clopidogrel. MAP4-RPPGF was compared with aspirin and clopidogrel in the Folts model of coronary artery thrombosis. Dogs were randomized to 3 treatment groups: aspirin 1.14 mg/kg i.v., clopidogrel 0.5 mg/kg i.v., or MAP4-RPPGF 0.77 mg/kg i.v. Cyclic flow variations (CFV) were recorded in 5 untreated dogs hourly for 3 successive hours and for 1 h before (all groups >11 CFV/h), and for 2 h after drug infusion in each of the 3 treatment groups. After 1 h drug treatment, all groups of animals had <6 CFV/h; after 2 h treatment, all had <1 CFV/h. All agents significantly reduced CFV from control at each hour, but none was significantly better than any other. Thrombostatin was as effective as aspirin or clopidogrel in inhibiting coronary artery thrombosis in this canine model.

Comparison of artificial neural networks with logistic regression in prediction of in-hospital death after percutaneous transluminal coronary angioplasty.

OBJECTIVES: Our objective was to compare artificial neural networks (ANNs) with logistic regression for prediction of in-hospital death after percutaneous transluminal coronary angioplasty and to assess the impact of guiding initial ANN variable selection with univariate analysis. BACKGROUND: ANNs can detect complex patterns within data. Criticisms include the unpredictability of variable selection. They have not previously been applied to outcomes modeling for percutaneous coronary interventions. METHODS: A database of consecutive (n = 3019) percutaneous transluminal coronary angioplasty procedures from an academic tertiary referral center between July 1994 and July 1997 was used. An ANN was developed for 38 variables (unguided model) (n = 1554). A second model was developed with predictors from an univariate analysis (guided model). Both were compared with a logistic regression model developed from the same database. Model validation was performed on independent data (n = 1465). Model predictive accuracy was assessed by the area under receiver operating characteristic curves. Goodness of fit was assessed with the Hosmer-Lemeshow statistic. RESULTS: Sixty unguided and guided ANNs were developed. Predictive accuracy and model calibration for all models were similar for training data but were significantly better for logistic regression for independent validation data. Overestimation of event rate in higher risk patients accounted for the majority of discrepancy in model calibration for the ANNs. This difference was partially amended by guiding variable selection. CONCLUSION: ANNs were able to model in-hospital death after percutaneous transluminal coronary angioplasty when guiding variable selection. However, performance was not better than traditional modeling techniques. Further investigations are needed to understand the impact of this methodology on outcomes analysis.

Validation of risk adjustment models for in-hospital percutaneous transluminal coronary angioplasty mortality on an independent data set.

OBJECTIVES: We sought to validate recently proposed risk adjustment models for in-hospital percutaneous transluminal coronary angioplasty (PTCA) mortality on an independent data set of high risk patients undergoing PTCA. BACKGROUND: Risk adjustment models for PTCA mortality have recently been reported, but external validation on independent data sets and on high risk patient groups is lacking. METHODS: Between July 1, 1994 and June 1, 1996, 1,476 consecutive procedures were performed on a high risk patient group characterized by a high incidence of cardiogenic shock (3.3%) and acute myocardial infarction (14.3%). Predictors of in-hospital mortality were identified using multivariate logistic regression analysis. Two external models of in-hospital mortality, one developed by the Northern New England Cardiovascular Disease Study Group (model NNE) and the other by the Cleveland Clinic (model CC), were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: In this patient group, an overall in-hospital mortality rate of 3.4% was observed. Multivariate regression analysis identified risk factors for death in the hospital that were similar to the risk factors identified by the two external models. When fitted to the data set, both external models had an area under the ROC curve >0.85, indicating overall excellent model discrimination, and both models were accurate in predicting mortality in different patient subgroups. There was a trend toward a greater ability to predict mortality for model NNE as compared with model CC, but the difference was not significant. CONCLUSIONS: Predictive models for PTCA mortality yield comparable results when applied to patient groups other than the one on which the original model was developed. The accuracy of the two models tested in adjusting for the relatively high mortality rate observed in this patient group supports their application in quality assessment or quality improvement efforts.

Comparison of slow oscillating versus fast balloon inflation strategies for coronary angioplasty.

Previous studies suggest that slow and/or oscillating balloon inflation during coronary angioplasty may decrease the incidence of coronary dissection and improve clinical outcomes. To compare the effect of slow oscillating versus conventional fast inflation techniques on the incidence of severe coronary dissection during angioplasty, 622 patients were randomized to slow oscillating inflation versus fast inflation. Angiographic outcomes of the procedures and in-hospital clinical events were recorded. The primary end point of severe (type C, D, E, F) dissection occurred in 7.7% of patients undergoing slow oscillation and 6.6% of patients undergoing fast inflation (p = 0.87). Major complications (death, urgent coronary artery bypass graft surgery, stroke, abrupt closure, or Q-wave myocardial infarction) occurred in 4.7% of patients undergoing slow oscillation and 3.5% of patients undergoing fast inflation (p = 0.45). The 2 inflation strategies did not differ in the pressure at which the balloon achieved full expansion, angiographic success rate, residual stenosis, and incidence of all minor and/or major complications. We conclude that there is no benefit of slow oscillating inflation over routine fast inflation in angioplasty. Slow oscillating inflation did not dilate lesions at lower pressures, decrease the incidence of dissection or severe dissection, or reduce the incidence of adverse clinical outcomes.

Acute myocardial infarction in two adolescent males.

Acute myocardial infarction in previously healthy children is rare in the absence of congenital anomalies. We describe two cases of acute anterior myocardial infarction in adolescent males with no congenital heart disease, without prior history of or risk factors for coronary heart disease, and with no history of drug abuse. These cases illustrate that myocardial infarction in the absence of systemic illness or coronary anomalies can occur in an adolescent population.

Frequency, predictors, and appropriateness of blood transfusion after percutaneous coronary interventions.

Increased awareness of the risks of blood-borne infections has recently led to profound changes in the practice of transfusion medicine. These changes include, among others, the development of guidelines by the American College of Physicians (ACP) for transfusion. Although the incidence and predictors of vascular complications of percutaneous interventions have been well defined, there are currently no data on frequency, risk factors, and appropriateness of blood transfusions. We performed a retrospective analysis of 628 consecutive percutaneous coronary revascularization procedures. Predictors of blood transfusion were identified using multivariate logistic regression analysis. Appropriateness of transfusions was determined using modified ACP guidelines. Transfusions were administered after 8.9% of interventions (56 of 628). Multivariate analysis identified age >70 years, female gender, procedure duration, coronary stenting, acute myocardial infarction, postprocedural use of heparin and intra-aortic balloon pump placement as independent predictors of blood transfusions (all p <0.05). According to the ACP guidelines, 36 of 56 patients (64%) received transfusions inappropriately. Transfusion reactions (fever) occurred in 10% of patients who received tranfusions appropriately and in 5% of patients who received tranfusions inappropriately. The estimated additional costs per procedure related to transfusions were $551 and $419, respectively. In conclusion, unnecessary transfusions were performed frequently after percutaneous coronary interventions. Application of available guidelines could reduce the number of unnecessary transfusions, thus avoiding exposure of patients to additional risks and reducing procedural costs.

Usefulness of dobutamine stress echocardiography in detecting coronary artery disease in end-stage renal disease.

The cardiovascular evaluation of patients with end-stage renal disease (ESRD) has been hampered by the suboptimal sensitivity and specificity of currently employed diagnostic tests. Dobutamine stress echocardiography (DSE) is a recently developed technique which is accurate for the diagnosis of coronary artery disease (CAD) in general populations. The purpose of this study was to assess its diagnostic accuracy and prognostic implications in patients with ESRD. Patients with ESRD (n = 97) underwent DSE as part of a preoperative evaluation before being listed for renal transplantation. Patients were followed for 12 +/- 6 months (range 1 to 24) after the study. Rest and dobutamine stress echocardiograms were analyzed for regional and global function. Coronary angiography was performed in 30 patients, and 25 underwent renal transplantation in the follow-up period. DSE had a sensitivity of 95% (92% for 1-vessel, 100% for > or = 2-vessel disease), specificity of 86%, and accuracy of 90% for the detection of CAD. During the follow-up period, 6 patients died; DSE revealed inducible ischemia in 4, and catheterization before death revealed multivessel CAD in 2. Conversely, a normal DSE identified a very low risk population, with a 97% probability of being free of cardiac complications or death during the follow-up period. We conclude that DSE accurately identifies CAD in patients with ESRD and identifies a cohort of patients at low risk for cardiac complications.

Coronary artery dissection caused by exit of the guidewire through the distal perfusion sidehole of an auto-perfusion angioplasty balloon catheter.

A previously unrecognized cause of coronary artery dissection is reported. A 67-year-old woman underwent angioplasty of the right coronary artery using an autoperfusion balloon catheter. Dissection occurred because the balloon catheter was advanced while the guidewire exited from one of the distal perfusion sideholes.

Nitroglycerin inhibits experimental thrombosis and reocclusion after thrombolysis.

Nitroglycerin inhibits platelet aggregation in vitro, but its effect on thrombosis and platelet function in vivo is controversial. This study assessed the effect of nitroglycerin on primary thrombus formation in response to vessel wall injury and secondary thrombus formation, or rethrombosis, after lysis of an existing thrombus. In the first protocol the right carotid artery was instrumented with a flow probe, stenosis, an anodal electrode, and a proximal infusion line. A 300 microA anodal current was used to induce endothelial injury and subsequent thrombotic occlusion of the vessel. Anisoylated plasminogen streptokinase activator complex (APSAC; 0.05 U/kg intraarterially) was injected proximal to the thrombus 30 minutes after occlusion. After APSAC, nitroglycerin (1 microgram/kg/min intraarterially, n = 7) or vehicle (n = 6) was infused proximal to the thrombus for 3 hours. Reocclusion occurred in two of seven nitroglycerin-treated dogs and six of six vehicle-treated dogs (p < 0.05). In the second protocol both carotid arteries were instrumented as described previously. Anodal current (300 microA, 180 minutes) was applied to the right carotid (n = 12) artery to determine control times to occlusion. The left carotid artery served as the test vessel, receiving either nitroglycerin (1 microgram/kg/min intraarterially, n = 6) or trimethaphan (0.05 mg/kg/hr intraarterially, n = 6). Trimethaphan was used to produce controlled hypotension to match the approximately 10% decrease in mean arterial blood pressure that was observed during nitroglycerin infusion. Control arteries and those treated with trimethaphan formed occlusive thrombi in all instances. Nitroglycerin infusion resulted in a lower incidence of occlusion (1 of 6; p < 0.05 vs control value) and inhibited ex vivo platelet aggregation to adenosine diphosphate and arachidonic acid (p < 0.05). Local infusion of nitroglycerin reduced the formation of primary thrombi, independent of the hypotensive effect of the drug, and exerted systemic effects on platelet aggregation. Furthermore, platelet inhibition with nitroglycerin reduced the incidence of secondary thrombus formation (rethrombosis) after thrombolysis. The results suggest that a potential benefit of nitroglycerin therapy may be derived from its ability to inhibit thrombotic events in patients with unstable angina or myocardial infarction.

Platelet GPIIb/IIIa receptor inhibition by SC-49992 prevents thrombosis and rethrombosis in the canine carotid artery.

OBJECTIVE: Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptors represent the final common pathway for aggregation. GPIIb/IIIa inhibition with antibodies or RGD peptides prevents arterial thrombosis. The present study examined the ability of SC-49992 (SC), a GPIIb/IIIa receptor antagonist, to prevent thrombosis in a canine model of carotid artery thrombosis. METHODS: Both carotid arteries of anaesthetised dogs were instrumented with Doppler probes. A 300 microA current was applied to the intimal surface of the right carotid artery via an intraluminal electrode; time to occlusive thrombus formation was noted. SC (30 and 60 micrograms/.kg-1 x min-1, intravenously) or saline was infused for 240 min. The procedure for thrombus formation was repeated after 60 min of drug infusion for the left carotid artery. RESULTS: SC did not alter heart rate or blood pressure. Frequency of occlusive thrombus formation was reduced or prevented in a dose dependent manner (control = 100%, n = 12; SC 30 micrograms = 50%, n = 6; SC 60 micrograms = 0%, n = 6; p < 0.05). SC resulted in a reduction in thrombus weight (p < 0.05) v control. Ex vivo platelet aggregation to ADP and arachidonic acid was inhibited. Platelet reactivity remained inhibited 60 min after cessation of SC infusion. In a second group of animals, a carotid artery thrombus was formed and lysed with administration of anisoylated plasminogen streptokinase activator complex (0.05 U.kg-1). SC (60 micrograms.kg-1 x min-1, intravenously, n = 6) or saline (n = 6) was infused for 240 min. In dogs receiving saline there was an 83% rate of rethrombosis; none of the SC treated animals had reocclusion after recanalisation (p < 0.05). CONCLUSIONS: SC-49992 inhibits ex vivo platelet aggregation, prevents occlusive thrombus formation in a canine model of arterial thrombosis, and prevents rethrombosis after thrombolysis. The data are consistent with results obtained with murine monoclonal antibodies directed against the platelet GPIIb/IIIa receptor.

Myocardial glutathione depletion impairs recovery of isolated blood-perfused hearts after global ischaemia.

This study was performed to determine whether depletion of myocardial glutathione would impair recovery of left ventricular function of blood-perfused, isolated hearts after reversible ischaemic injury. Cats were treated with either vehicle or buthionine sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in the synthesis of glutathione. The feline isolated hearts were perfused with the blood of normal donor cats before and after 40 min of global myocardial ischaemia. The myocardial concentration of glutathione of the BSO group, 178 +/- 38 ng/mg tissue, was significantly less than that of the control group, 292 +/- 38 ng/mg tissue (P < 0.05). The peak left ventricular developed pressure (LVDP) 1 h after reperfusion, expressed as a fraction of the peak LVDP before ischaemia, was 0.87 +/- 0.10 for the control group and 0.64 +/- 0.08 for the BSO group (P = 0.05 vs. control). The peak left ventricular dP/dt after reperfusion, expressed as a fraction of the peak dP/dt before ischaemia, was 1.08 +/- 0.14 for the control group and 0.78 +/- 0.09 for the BSO group (P = 0.05 vs. control). The myocardial creatine kinase activity of the BSO group, 1046 +/- 46 U/g tissue, was not significantly different from that of the control group, 1038 +/- 17 U/g tissue (P = 0.87). Thus, depletion of myocardial glutathione resulted in impaired post-ischaemic contractile function that cannot be attributed to a greater extent of irreversible cell injury.

Xanthine oxidase inhibition does not limit canine infarct size.

BACKGROUND: Evidence supporting the role of xanthine oxidase in myocardial reperfusion injury is based on studies with pharmacological interventions used to inhibit enzyme function. Controversy exists, however, regarding the true role of xanthine oxidase in reperfusion injury. This study was performed to determine whether xanthine oxidase inhibition limits myocardial injury due to coronary artery occlusion and reperfusion. METHODS AND RESULTS: Anesthetized dogs underwent coronary artery occlusion (90 minutes) and reperfusion (6 hours). Oxypurinol (28 mg/kg) or amflutizole (30 mg/kg), chemically unrelated inhibitors of xanthine oxidase, or vehicle was infused intravenously 15 minutes before and 3 hours after reperfusion. Regional myocardial blood flow was determined with radiolabeled microspheres. Infarct size was determined with the tetrazolium method. Myocardial infarct size (percent of risk region) was less in oxypurinol-treated dogs, 32 +/- 16%, compared with that of the control group, 46 +/- 15%. Infarct size for the amflutizole-treated dogs, 40 +/- 21%, was not significantly different from that of the control group. There were no differences in rate-pressure product or collateral blood flow to account for differences in infarct size. Uric acid concentration in the coronary venous plasma increased after reperfusion in the dogs treated with vehicle but not in the drug-treated dogs. Xanthine oxidase inhibition was demonstrated in each of the drug treatment groups, but only oxypurinol limited the extent of myocardial injury. CONCLUSIONS: Previously reported cardioprotective effects of allopurinol, noted to occur only when the drug was administered chronically, may be related to a property of oxypurinol, a major metabolite of allopurinol. The beneficial effect of oxypurinol is unrelated to inhibition of superoxide formation during xanthine oxidase-catalyzed oxidation of xanthine and hypoxanthine.

A randomized placebo-controlled trial of combined early intravenous captopril and recombinant tissue-type plasminogen activator therapy in acute myocardial infarction.

The adjunctive use of intravenous captopril with tissue plasminogen activator early during acute myocardial infarction offers theoretic advantages of diminishing left ventricular volume, preventing ventricular dilation and improving patient survival. To test the safety and efficacy of combined early administration of intravenous captopril and recombinant tissue-type plasminogen activator (rt-PA), 38 patients treated with rt-PA 3 +/- 0.3 h (mean +/- SE) after the onset of myocardial infarction were randomized to intravenous followed by oral captopril or placebo therapy. They underwent cardiac catheterization with measurement of hemodynamic variables and left ventricular function and determination of serum renin, angiotensin and aldosterone levels on days 1 and 7. Oral administration of the selected agent was continued for 3 months along with other antianginal medications, including nonangiotensin-converting enzyme inhibitor vasodilators. Repeat measurements of left ventricular function were obtained before hospital discharge and at 3 months. There were no significant differences in baseline clinical characteristics between groups. One patient in the captopril-treated group became hypotensive during intravenous therapy, requiring discontinuation of treatment. Compared with the placebo-treated group, the captopril-treated group had significant reductions at day 7 in left ventricular end-diastolic pressure (22.5 +/- 1.5 versus 16.3 +/- 1.6 mm Hg, p less than 0.01) and mean systemic arterial pressure (93.6 +/- 3.3 versus 86.2 +/- 2.7 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Free radicals and ischemic tissue injury.

There is growing evidence that reperfusion of ischemic organs is associated with the formation of free radicals that exacerbate the ischemic injury. Free radicals may damage viable tissue via the peroxidation of lipids and oxidation of protein sulfhydryl groups, leading to perturbations of membrane permeability and enzyme function. Steven Werns and Benedict Lucchesi discuss evidence that activated neutrophils are an important source of free radicals after cardiac and intestinal ischemia, and assess the strategies that have been investigated as ways of alleviating damage caused by free radicals during ischemia-reperfusion.

Implications for patient triage from survival and left ventricular functional recovery analyses in 500 patients treated with coronary angioplasty for acute myocardial infarction.

The in-hospital course of 500 consecutive patients treated with coronary angioplasty for acute myocardial infarction was reviewed in relation to their clinical and angiographic presentation and angioplasty outcome to determine which patients benefit most from successful angioplasty in this setting. Patient age was 56 +/- 11 years (mean +/- SD) and 78% were men; 46% had anterior myocardial infarction, 49% received concomitant intravenous thrombolytic therapy, left ventricular ejection fraction was 47 +/- 11% and median time to angioplasty was 4.7 h (range 1 to 24). Angioplasty was successful in 78% of patients and partially successful in 7% of patients; the overall in-hospital mortality rate was 10.2%. Multivariate analysis found six independent correlates (p less than 0.05) of in-hospital mortality: left ventricular ejection fraction less than or equal to 30%, lack of postangioplasty infarct artery patency, age greater than 65 years, recurrent ischemia after successful angioplasty, emergency bypass surgery and arterial pressure on admission to the catheterization laboratory less than 100 mm Hg. After consideration of these predictors of survival in multivariate analyses, angioplasty success still was independently correlated with improved in-hospital survival for patients with cardiogenic shock (p = 0.002) and anterior myocardial infarction (p = 0.007). A trend toward an independent beneficial effect of successful angioplasty on survival was also noted in patients with inferior wall infarction and precordial ST segment depression (p = 0.063) and for all patients who were hypotensive on admission to the catheterization laboratory, regardless of the infarct site (p = 0.057).(ABSTRACT TRUNCATED AT 250 WORDS)