Attenuation of rebound ischemia after discontinuation of heparin therapy by glycoprotein IIb/IIIa inhibition with eptifibatide in patients with acute coronary syndromes: observations from the platelet IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial.

Background- A reactivation of ischemia after the discontinuation of intravenous heparin in acute coronary syndromes has been described. The effect of glycoprotein IIb/IIIa blockade on heparin rebound is unknown. Methods and Results- Patients with acute coronary syndromes who received heparin therapy but not initial revascularization in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial were analyzed. Rates of death or myocardial (re)infarction while on heparin therapy and in 12-hour periods in the 2 days after heparin discontinuation were compared between eptifibatide and placebo. There was no difference between study groups in event rates during heparin infusion. In the 12 hours after heparin discontinuation, there was a 2.5-fold increase in all events, an 8-fold increase in death, and a 2-fold increase in myocardial infarction. However, in the 12 hours after heparin discontinuation, there was a significantly lower rate of events (1.68% versus 2.53%, P=0.03) and death (0.77% versus 0.21%, P=0.002) in the eptifibatide group compared with the placebo group. When only considering patients who were on study drug at the time of heparin discontinuation, the reduction in the combined end point was marginally significant, but the difference in the rate of death remained significant (0.68% versus 0.06%, P=0.004). In logistic regression analyses, the multivariate predictors of rebound events were the duration of heparin therapy, age, North American site, and lack of eptifibatide treatment. Conclusions- An increase in death or myocardial infarction occurs in the 12 hours after heparin discontinuation in patients with acute coronary syndromes. This rebound is attenuated by glycoprotein IIb/IIIa inhibition with eptifibatide.

Profile and prevalence of aspirin resistance in patients with cardiovascular disease.

We determined the prevalence and clinical predictors of aspirin resistance by prospectively studying 325 patients with stable cardiovascular disease who were receiving aspirin (325 mg/day for > or =7 days) but no other antiplatelet agents. We also compared the detection of aspirin resistance with optical platelet aggregation, a widely accepted method, with a newer, more rapid method, the platelet function analyzer (PFA)-100, a whole blood test that measures platelet adhesion and aggregation ex vivo. Blood samples were analyzed in a blinded fashion for aspirin resistance by optical aggregation using adenosine diphosphate (ADP) and arachidonic acid, and by PFA-100 using collagen and/or epinephrine and collagen and/or ADP cartridges to measure aperture closure time. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microM ADP and a mean aggregation of > or =20% with 0.5 mg/ml arachidonic acid. Aspirin semiresponders were defined as meeting one, but not both of the above criteria. Aspirin resistance by PFA-100 was defined as having a normal collagen and/or epinephrine closure time (< or =193 seconds). By optical aggregation, 5.5% of the patients were aspirin resistant and 23.8% were aspirin semiresponders. By PFA-100, 9.5% of patients were aspirin resistant. Of the 18 patients who were aspirin resistant by aggregation, 4 were also aspirin resistant by PFA-100. Patients who were either aspirin resistant or aspirin semiresponders were more likely to be women (34.4% vs 17.3%, p = 0.001) and less likely to be smokers (0% vs 8.3%, p = 0.004) compared with aspirin-sensitive patients. There was a trend toward increased age in patients with aspirin resistance or aspirin semiresponders (65.7 vs 61.3 years, p = 0.06). There were no differences in aspirin sensitivity by race, diabetes, platelet count, renal disease, or liver disease.

Prognostic importance of concomitant heparin with eptifibatide in acute coronary syndromes. PURSUIT Investigators. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy.

Platelet glycoprotein IIb/IIIa inhibitors have been extensively studied in the treatment of patients with ischemic heart disease. Data regarding the use of these agents in the absence of concomitant intravenous heparin have been conflicting. We sought to determine, using propensity analysis, whether the benefit of eptifibatide, a IIb/IIIa inhibitor, in the treatment of acute coronary syndromes is affected by the concurrent administration of heparin. By trial design, patients were randomized to either eptifibatide or placebo, whereas use of intravenous heparin was left to the discretion of treating physicians. The effect of eptifibatide on the 30-day composite end point of death or myocardial infarction was studied in patients who received heparin and those who did not. Propensity analysis methods were used to control for confounding and presumed selection biases. Among 5,576 patients who were receiving heparin when the bolus dose of the study drug was administered, eptifibatide was associated with a reduced composite end point rate (13%) compared with that of placebo (14.5% vs 16.6%, p = 0.03). In contrast, among 1,441 patients who were not receiving heparin, there was no difference in 30-day event rates with eptifibatide compared with placebo (13.7% vs 13.1%, p > 0.7). After a propensity score for use of heparin was developed, however, use of heparin did not affect the reduced risk associated with eptifibatide (adjusted relative risk [RR] for heparin-eptifibatide interaction term 0.90, 95% confidence interval [CI] 0.61 to 1.32, p > 0.5), but the propensity for heparin use was a strong predictor of events (adjusted RR 1.76, 95% CI 1.42 to 2.17, p < 0.001). The use of eptifibatide independently predicted a lower risk of events (adjusted RR 0.31, 95% CI 0.10 to 0.93, p = 0.04). Thus, the apparent positive impact of heparin on the benefits of eptifibatide therapy was largely due to confounding and bias.

Evaluation of the effects of aspirin combined with angiotensin-converting enzyme inhibitors in patients with coronary artery disease.

BACKGROUND: Several studies have suggested that there may be an interaction between angiotensin-converting enzyme (ACE) inhibitors and aspirin in patients with congestive heart failure, such that their benefits are attenuated when used in combination. Whether this interaction exists in patients with coronary artery disease is not known. SUBJECTS AND METHODS: Patients enrolled in two large trials, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) and Evaluation in PTCA to Improve Long-Term Outcome with Abciximab GP IIb/IIIa Blockade (EPILOG), were stratified according to use of aspirin and ACE inhibitors on discharge from the hospital. In the EPILOG trial, left ventricular systolic function was assessed by contrast ventriculography. The primary endpoint was all-cause mortality at 1 year. EPILOG patients, all of whom were receiving aspirin, were also examined for the combined endpoint of death or nonfatal myocardial infarction. Stratified and multivariate analyses were used to adjust for baseline differences in patient characteristics. RESULTS: We studied 31,622 patients in the GUSTO-I trial and 2,619 patients in the EPILOG trial. There were 615 deaths among the GUSTO-I patients and 45 deaths among the EPILOG patients at 1 year. Unadjusted mortality was greater among patients treated with both ACE inhibitors and aspirin than among patients treated with aspirin alone (3.3% versus 1.6%, P <0.001 for GUSTO-I; and 3.7% versus 1.2%, P <0.001 for EPILOG). Similarly, the composite endpoint of death or nonfatal myocardial infarction was more frequent among EPILOG patients who were taking ACE inhibitors (6.3% versus 3.3%, P = 0. 001). After adjusting for confounders, combined use of aspirin and ACE inhibitors was associated with increased mortality in GUSTO-I patients (hazard ratio [HR] = 2.2, 95% confidence interval [CI]: 1.1 to 4.3, P = 0.03) compared with aspirin alone. In EPILOG patients, after adjusting for clinical factors and extent of left ventricular dysfunction, the combination of aspirin and ACE inhibitors was associated with an increased risk of death (HR = 2.1, 95% CI: 1.1 to 3.8, P = 0.02) and of death or nonfatal myocardial infarction (HR = 1.5, 95% CI: 1.1 to 2.5, P = 0.02) compared with aspirin alone. CONCLUSION: These observational findings suggest the possibility of an interaction between aspirin and ACE inhibitors among patients with ischemic heart disease. Further study of this issue is warranted.

Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials. Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibition in STENTing.

BACKGROUND: Abciximab during percutaneous coronary revascularization reduces ischemic complications, but concern exists regarding increased bleeding risk should emergency coronary surgical procedures be required. METHODS: Outcomes were assessed among 85 patients who required coronary artery bypass grafting operations after coronary intervention in two randomized placebo-controlled trials of abciximab. Comparisons were made between patients in the pooled placebo and abciximab groups. RESULTS: The incidence of coronary surgical procedures was 2.17% and 1.28% among patients randomized to placebo and abciximab, respectively (p = 0.021). Platelet transfusions were administered to 32% and 52% of patients in the placebo and abciximab groups, respectively (p = 0.059). Rates of major blood loss were 79% and 88% in the placebo and abciximab groups, respectively (p = 0.27); transfusions of packed red blood cells or whole blood were administered in 74% and 80% of patients, respectively (p = 0.53). Surgical reexploration for bleeding was required in 3% and 12% of patients, respectively. Death and myocardial infarction tended to occur less frequently among patients who had received abciximab. CONCLUSIONS: Urgent coronary artery bypass grafting operations can be performed without an incremental increase in major hemorrhagic risk among patients on abciximab therapy.

Risk factors and outcomes after coronary reoperation in 739 elderly patients.

BACKGROUND: As second coronary artery bypass graft (CABG) operations are becoming more common in elderly patients, we conducted a retrospective analysis of risk factors for in-hospital and late outcome in patients aged 70 and over. METHODS: We reviewed records of 739 patients who underwent second CABG at age 70 or older at our institution between 1983 and 1993. Preoperative, operative, and postoperative variables were analyzed to identify predictors of in-hospital and long-term mortality. RESULTS: The mean age (+/- standard deviation) at reoperation was 74 +/- 3 years and the mean interval after primary operation was 130 +/- 55 months. In-hospital mortality was 7.6% (n = 56). Preoperative factors associated with increased in-hospital mortality were preoperative creatinine greater than 1.6 mg/dL (p < 0.001), emergency operation (p < 0.001), female sex (p = 0.012), moderate or severe left ventricular dysfunction (p = 0.049), and left main coronary disease (p = 0.045). In-hospital, actuarial survival was 75% at 5 years and 49% at 10 years. Cardiac event-free survival was 60% at 5 years and 27% at 10 years. The factors independently associated with increased late death were hematocrit (p = 0.046), diabetes (p = 0.011), peripheral vascular disease (p < 0.001), left ventricular function (p < 0.001), history of cancer (p = 0.016), preoperative nonsinus rhythm (p = 0.003), anticoagulation or antiplatelet therapy (p = 0.018), postoperative encephalopathy (p = 0.001), and postoperative stroke (p = 0.014). CONCLUSIONS: CABG reoperation can have excellent results for many elderly patients, but mortality is markedly higher when elderly patients have certain risk factors and comorbidities, alone or in combination. This information should be helpful in educating patients before they decide whether to choose reoperation.

Predictors of death and reinfarction at 30 days after primary angioplasty: the GUSTO IIb and RAPPORT trials.

BACKGROUND: Thirty-day death among recipients of fibrinolytic therapy for acute myocardial infarction (MI) is tightly correlated with easily obtainable key demographic and clinical parameters such as age, blood pressure, heart rate, and infarct location. Similar data for primary angioplasty are not available. METHODS AND RESULTS: Data from 2 large, contemporary, primary angioplasty trials were formally combined and analyzed with respect to death and death/repeat MI at 30 days through the use of multivariate logistic regression models. The 1048 patients had a median age of 62 years, and 26% were women. Thirty-eight percent had an anterior infarction. The patients underwent angioplasty at a median delay from symptom onset of 3.8 hours. Death was independently predicted by increasing age (adjusted odds ratio [OR] per decade 2.32, 95% confidence interval [CI] 1.60 to 3.42), whereas a history of smoking (OR 0.29, CI 0.13 to 0.64), Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 after angioplasty (OR vs TIMI <3 0.21, CI 0.10 to 0.45) and higher systolic blood pressure (OR per 10 mm Hg 0.73, CI 0.62 to 0. 87) were associated with lower mortality rates. Death or repeat MI was independently associated with increasing age (OR per decade 1.40, CI 1.13 to 1.76) and anterior location of the index MI (OR 1.89, CI 1.12 to 3.20). TIMI grade 3 flow (OR vs TIMI <3 0.40, CI 0.23 to 0. 68) and higher systolic blood pressure (OR per 10 mm Hg 0.79, CI 0. 71 to 0.89) were associated with a lower incidence of death/repeat MI. Time to angioplasty, heart rate, extent of coronary artery disease, participation in 1 of the 2 trials, and all common coronary risk factors did not significantly predict outcome. CONCLUSIONS: Death and reinfarction after primary angioplasty are predominantly predicted by age, hemodynamic instability, and the attainment of TIMI 3 flow in the infarct artery.

Glycoprotein IIb/IIIa inhibitors in acute coronary syndromes.

Glycoprotein (GP) IIb/IIIa inhibitors are potent antiplatelet agents and represent an exciting breakthrough in the treatment of acute coronary syndromes. However, their safety and cost-effectiveness require further investigation, and more information on risk stratification is needed to clarify which patients benefit the most from empiric use of these agents.

Optimizing the percutaneous interventional outcomes for patients with diabetes mellitus: results of the EPISTENT (Evaluation of platelet IIb/IIIa inhibitor for stenting trial) diabetic substudy.

BACKGROUND: Stenting likely decreases the need for target-vessel revascularization procedures in diabetic patients compared with balloon angioplasty. However, the efficacy of stenting with platelet glycoprotein IIb/IIIa blockade has not yet been assessed in diabetics. METHODS AND RESULTS: We analyzed the outcomes of 491 diabetic patients within the multicenter Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial (EPISTENT). Diabetic patients were a prospectively defined subset: 173 were randomized to stent-placebo, 162 to stent-abciximab, and 156 to balloon angioplasty-abciximab. The main end point for this analysis was combined 6-month death, myocardial infarction (MI), or target-vessel revascularization (TVR). The composite end point occurred in 25.2% of stent-placebo, 23.4% of balloon-abciximab, and 13.0% of stent-abciximab patients (P=0.005). Abciximab therapy, irrespective of revascularization strategy (stent or balloon angioplasty), resulted in a significant reduction in the 6-month death or MI rate: 12.7% for stent-placebo, 7.8% for balloon angioplasty-abciximab, and 6.2% for the stent-abciximab group (P=0.029). The 6-month TVR rate was 16.6% for stent-placebo, 18.4% for balloon-abciximab, and 8.1% for stent-abciximab (P=0.021). Compared with stent-placebo, stent-abciximab therapy was associated with a significant increase in angiographic net gain (0.88 versus 0.55 mm; P=0.011) and a decrease in the late loss index (0.40 versus 0.60 mm; P=0.061). The 1-year mortality rate for diabetics was 4.1% for stent-placebo and 1. 2% for stent-abciximab patients (P=0.11). CONCLUSIONS: The combination of stenting and abciximab therapy among diabetics resulted in a significant reduction in 6-month rates of death, MI, and TVR compared with stent-placebo or balloon-abciximab therapy.

Racial differences in the management of unstable angina: results from the multicenter GUARANTEE registry.

BACKGROUND: Prior studies, usually conducted with the use of insurance databases, have shown differences in the use of cardiac procedures between black patients and white patients hospitalized with various types of coronary artery disease. However, few data are available in prospectively collected cohorts of patients with unstable angina or on the use of appropriate medications or interventions. METHODS AND RESULTS: We evaluated 2948 consecutive patients with unstable angina admitted to 35 hospitals across the United States in 1996, comparing nonwhite and white patients. Seventy-seven percent of patients were white, 14% were black, 4% were Hispanic, 1% were Asian, and 3% were other or unknown race. Differences were seen in coronary risk profile, with a higher incidence of hypertension and diabetes mellitus in nonwhites. Cardiac catheterization was performed less often in nonwhites compared with whites (36% vs 53%, P =.001). Even in patients meeting the criteria for appropriate catheterization in the Agency for Health Care Policy Research unstable angina guidelines, fewer nonwhites underwent catheterization (44% vs 61%, P =.001), but among these, fewer nonwhites had significant coronary stenosis (72% vs 90%, P =.001). However, among patients catheterized who had indications for revascularization, angioplasty and coronary artery bypass grafting were performed equally often in nonwhites and whites. CONCLUSIONS: Current guidelines would recommend more aggressive use of cardiac catheterization for nonwhite patients. However, our findings suggest that racial differences may need to be included in the diagnostic and interventional algorithms.

Differences between men and women in the management of unstable angina pectoris (The GUARANTEE Registry). The GUARANTEE Investigators.

Few data are available in prospectively collected cohorts of patients with unstable angina pectoris or on the use of appropriate medications or interventions. Accordingly, we evaluated 2,948 consecutive patients with unstable angina admitted to 35 hospitals in the United States in 1996, and comparing men and women (39% of the patients were women). Differences were seen in coronary risk profiles with a higher incidence of systemic hypertension, diabetes mellitus, and a family history of coronary disease in women. Women were less likely to receive Agency for Health Care Policy Research (AHCPR) recommended pharmacologic treatment than men. Cardiac catheterization, coronary angioplasty, and bypass was performed less often in women compared with men (44% vs. 53%, p = 0.002; 12% vs. 18%, p = 0.02; 7% vs. 10%, p = 0.001, respectively). At catheterization, women were more likely to have no significant coronary artery disease (25% vs. 14%, p = 0.001). Although fewer women than men fulfilled the AHCPR criteria for cardiac catheterization (54% vs. 64%, p = 0.001), a similar rate of men and women with positive criteria underwent catheterization and angioplasty. However, fewer women with positive criteria underwent bypass surgery (36% vs. 46%, p = 0.03). More men "ruled-in" for a myocardial infarction at admission (13% vs. 8%, p = 0.001), but there was no difference in recurrent angina, in-hospital myocardial infarction, or death. Despite different epidemiologic profiles and less evidence of coronary artery disease by noninvasive and invasive tests, women and men had similar outcomes.

Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein IIb/IIIa receptors. Evaluation of Platelet IIb/IIIa Inhibition in Stenting Investigators.

BACKGROUND: Inhibition of the platelet glycoprotein IIb/IIIa receptor with the monoclonal-antibody fragment abciximab reduces the acute ischemic complications associated with percutaneous coronary revascularization, whereas coronary-stent implantation reduces restenosis. We conducted a trial to determine the efficacy of abciximab and stent implantation in improving long-term outcome. METHODS: A total of 2399 patients were randomly assigned to stent implantation and placebo, stent implantation and abciximab, or balloon angioplasty and abciximab. The patients were followed for six months. RESULTS: At six months, the incidence of the composite end point of death or myocardial infarction was 11.4 percent in the group that received a stent and placebo, as compared with 5.6 percent in the group that received a stent and abciximab (hazard ratio, 0.47; 95 percent confidence interval, 0.33 to 0.68; P<0.001) and 7.8 percent in the group assigned to balloon angioplasty and abciximab (hazard ratio, 0.67; 95 percent confidence interval, 0.49 to 0.92; P=0.01). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.70 (95 percent confidence interval, 0.48 to 1.04; P=0.07). The rate of repeated revascularization of the target vessel was 10.6 percent in the stent-plus-placebo group, as compared with 8.7 percent in the stent-plus-abciximab group (hazard ratio, 0.82; 95 percent confidence interval, 0.59 to 1.13; P=0.22) and 15.4 percent in the angioplasty-plus-abciximab group (hazard ratio, 1.49; 95 percent confidence interval, 1.13 to 1.97; P=0.005). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.55 (95 percent confidence interval, 0.41 to 0.74; P<0.001). Among patients with diabetes, the combination of abciximab and stenting was associated with a lower rate of repeated target-vessel revascularization (8.1 percent) than was stenting and placebo (16.6 percent, P=0.02) or angioplasty and abciximab (18.4 percent, P=0.008). CONCLUSIONS: For coronary revascularization, abciximab and stent implantation confer complementary long-term clinical benefits.

Significance of mild transient release of creatine kinase-MB fraction after percutaneous coronary interventions.

BACKGROUND: The clinical significance of minor elevations in creatine kinase-myocardial band isoenzyme (CK-MB) after coronary interventions has not been systematically evaluated. METHODS AND RESULTS: We examined 4484 patients who underwent successful percutaneous transluminal coronary angioplasty or directional coronary atherectomy and whose peak CK levels did not exceed twice the upper limit of laboratory normal. Group 1 (3776 patients) had no CK or MB elevation after the procedure (ie, CK < or = 180 IU/L, with MB fraction < or = 4%). Group 2 (450 patients) had a peak CK level between 100 and 180 IU/L, with MB fraction > 4%, and group 3 (258 patients) had a peak CK level between 181 and 360 IU/L, with MB fraction > 4%. The strongest correlate of postprocedure CK-MB elevation was the performance of directional coronary atherectomy (odds ratio, 4.1; P < .0001), followed by the development of > or = 1 in-1ab minor procedural complication (odds ratio, 2.6; P < .0001). Clinical follow-up was available in 4461 patients (99.5%), with a mean duration of 36 +/- 22 months. Survival analysis, adjusted with Cox proportional hazards regression model, showed that the groups with elevated CK-MB had a significantly higher incidence of cardiac death (risk ratio, 1.3; P = .04) and myocardial infarction (risk ratio, 1.3; P = .03). Major ischemic complications (death, myocardial infarction, and coronary revascularization) occurred more frequently in the groups with increased CK-MB (groups 1 versus 2 versus 3, 37.3% versus 43.3% versus 48.9%; P = .01). CONCLUSIONS: This study shows that minor elevations of CK-MB after successful coronary interventions identify a population with a worse long-term prognosis compared with patients with no enzyme elevations and appear to have an adverse effect on long-term prognosis. Future studies of percutaneous coronary revascularization should include routine measurements of biochemical cardiac markers as important predictors of long-term prognosis.

Defining the appropriate threshold of creatine kinase elevation after percutaneous coronary interventions.

The threshold of creatine kinase elevation after coronary interventions has been set at levels ranging in different studies from 2 to > 5 times the laboratory's upper limit of normal. This high variability is caused by the absence of any systematic evaluation of the prognostic implications of cardiac-enzyme elevation in this setting. This study was undertaken to evaluate the clinical, morphologic, and procedural correlates, and the long-term follow-up of two commonly used thresholds of creatine kinase (CK) elevation after successful percutaneous coronary interventions, in an attempt to define the level of postprocedural cardiac enzymes that correlates with adverse clinical outcome. We examined 4664 consecutive patients who underwent successful coronary angioplasty or directional atherectomy at the Cleveland Clinic. Group I (4480 patients) had CK > or = 2 times control levels after the procedure (i.e., < or = 360 IU/L). Group II (123 patients) had a peak level between 361 and 900 IU/L, and group III (61 patients) had a peak level >900 IU/L with positive myocardial isoenzymes (CK-MB > 4%). Elevation of cardiac enzymes was associated with distinct clinical, morphologic, and procedural characteristics, including coronary embolism, recent infarction, transient in-laboratory closure, hemodynamic instability, vein graft procedures, and large dissections. Clinical follow-up was available in 4644 (99.6%) patients, with a mean follow-up of 36 +/- 22 months. Kaplan-Meier survival analysis adjusted with Cox proportional hazards regression model showed that cardiac-enzyme elevation was an important correlate of cardiac death (risk ratio, 2.19; p < 0.0001). The groups with elevated cardiac enzymes had a higher incidence of cardiac death compared with group I (p < 0.0001). There was also a trend toward more cardiac hospitalizations in the same groups (p = 0.15). The incidence of cardiac death and cardiac hospitalization on follow-up was not different between groups II and III, This study shows that CK elevations between 2 and 5 times control values after successful coronary interventions are associated with an adverse long-term outcome. The findings suggest that an appropriate CK threshold that has prognostic implications would be twice the upper limit of normal.

Surgical treatment of prosthetic valve endocarditis.

From 1975 through 1992, we reoperated on 146 patients for the treatment of prosthetic valve endocarditis. Prosthetic valve endocarditis was considered to be early (< 1 year after operation) in 46 cases and active in 103 cases. The extent of the infection was prosthesis only in 66 patients, anulus in 46, and cardiac invasion in 34. Surgical techniques evolved in the direction of increasingly radical débridement of infected tissue and reconstruction with biologic materials. All patients were treated with prolonged postoperative antibiotic therapy. There were 19 (13%) in-hospital deaths. Univariate analyses demonstrated trends toward increasing risk for patients with active endocarditis and extension of infection beyond the prosthesis; however, the only variables with a significant (p < 0.05) association with increased in-hospital mortality confirmed with multivariate testing were impaired left ventricular function, preoperative heart block, coronary artery disease, and culture of organisms from the surgical specimen. During the study period, mortality decreased from 20% (1975 to 1984) to 10% (1984 to 1992). For hospital survivors the mean length of stay was 25 days. Follow-up (mean interval 62 months) documented a late survival of 82% at 5 postoperative years and 60% at 10 years. Older age was the only factor associated (p = 0.006) with late death. Nineteen patients needed at least one further operation; reoperation-free survival was 75% at 5 and 50% at 10 postoperative years. Fever in the immediate preoperative period was the only factor associated with decreased late reoperation-free survival (p = 0.032). Prosthetic valve endocarditis remains a serious complication of valve replacement, but the in-hospital mortality of reoperations for prosthetic valve endocarditis has declined. With extensive débridement of infected tissue and postoperative antibiotic therapy, the extent and activity of prosthetic valve endocarditis does not appear to have a major impact on late outcome, and the majority of patients with this complication survive for 10 years after the operation.

Clinical markers, management, and long-term follow-up of early ischemia after coronary artery bypass grafting.

In summary, the occurrence of angina or myocardial infarction within 1 year after coronary bypass is associated with a high incidence of significant angiographic abnormalities. Early angiography is necessary to identify high-risk patients who could undergo revascularization. Patients with other markers of ischemia should have a noninvasive approach (stress imaging test) as initial evaluation, before coronary angiography is considered. When technically feasible, coronary angioplasty can be performed safely and with a high success rate. Repeat coronary bypass in this group of patients is associated with higher in-hospital complications. Patients with less compromised coronary anatomy can be treated medically with a good long-term outcome.

Percutaneous revascularization of ostial saphenous vein graft stenoses.

OBJECTIVES: This study sought to evaluate the short-term results and long-term outcome of percutaneous revascularization of ostial saphenous vein graft stenoses in a large patient series. BACKGROUND: Previous studies have demonstrated that the results of balloon angioplasty for native coronary ostial stenoses are significantly worse than those for nonostial lesions. However, it is controversial whether interventions in patients with ostial saphenous vein grafts carry a similar prognosis. METHODS: We identified 68 consecutive patients with ostial (group I) and 72 consecutive patients with proximal, nonostial (group II) saphenous vein graft stenoses who underwent percutaneous angioplasty or directional atherectomy for a single new stenosis at the Cleveland Clinic between 1986 and 1992. RESULTS: Success was achieved in 61 patients (89.7%) in group I and 64 (88.9%) in group II (p = 0.88). There were no differences in major procedural complications (death, Q wave infarction and bypass surgery) between the two groups. At a mean (+/- SD) follow-up of 23 +/- 17 months, 36 patients (64%) in group I had one or more adverse events (death, infarction, repeat coronary revascularization or cardiac-related hospital admission) compared with 34 patients (58%) in group II (p = 0.87). Twenty-eight patients (50%) were angina free in group I compared with 33 (56%) in group II (p = 0.65). During the follow-up period in group I, 7 patients died (13%), 10 had a myocardial infarction (18%), 11 had repeat bypass surgery (20%), 8 had repeat percutaneous interventions (14%), and 30 had one or more cardiac-related hospital admissions (54%). The incidence of these events was similar in group II except for a slightly higher incidence of myocardial infarction: 6 patients died (10%), 3 had a myocardial infarction (5%), 12 had repeat bypass surgery (20%), 12 had repeat percutaneous interventions (20%), and 26 had one or more cardiac-related hospital admissions (44%). CONCLUSIONS: Unlike ostial native coronary disease, the clinical, procedural and follow-up profile of ostial saphenous vein graft revascularization is not significantly worse than proximal nonostial disease. This finding may be related to the overall suboptimal results of percutaneous revascularization in saphenous vein grafts compared with native coronary arteries or to the unfavorable intrinsic properties of ostial native coronary arteries compared with ostial vein grafts.

Long-term outcome of transient, uncomplicated in-laboratory coronary artery closure.

BACKGROUND: Successful reversal of abrupt vessel closure without resultant major ischemic complications (death, Q-wave myocardial infarction, or coronary artery bypass graft surgery) is achieved in nearly half of all cases of abrupt vessel closure. The long-term outcome of these patients has not been previously addressed, and it is not clear whether they have a different prognosis than that of patients who have a successful procedure not associated with transient vessel closure. METHODS AND RESULTS: We examined 4863 consecutive patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA). Eighty-eight patients had an uncomplicated, successfully reversed transient in-laboratory vessel closure (group 2) and were compared with 4775 patients who had a successful procedure not associated with transient in-laboratory closure (group 1). Clinical follow-up was available in 4839 patients (99.5%), with a mean duration of 41 +/- 23 months (range, 1 to 104 months). Survival analysis showed that successfully treated, uncomplicated transient vessel closure per se does not have an adverse effect on long-term prognosis (death, myocardial infarction, or coronary interventions). However, when the procedure (PTCA or DCA) was associated with an increase in creatine kinase-MB (CK-MB), there was a significant adverse effect on long-term outcome. By multivariate logistic regression, an increase in postprocedure CK-MB was the most significant correlate for cardiac death (risk ratio, 1.25; P < .0001). An increase in CK-MB was also the most important correlate for major ischemic complications (death, infarction, or coronary interventions) on follow-up (risk ratio, 1.08; P = .0005). CONCLUSIONS: Transient, uncomplicated in-laboratory vessel closure per se does not have an adverse long-term effect. However, a concomitant elevation of postprocedure cardiac enzymes has an important and significant adverse effect on long-term outcome. This study suggests that periprocedural creatine kinase isoenzyme determination in patients experiencing in-laboratory coronary closure has important prognostic implications.

Prognosis of patients with left ventricular dysfunction, with and without viable myocardium after myocardial infarction. Relative efficacy of medical therapy and revascularization.

BACKGROUND: The uptake of F-18 deoxyglucose into dysfunction segments after myocardial infarction identifies metabolically active (FDG+) or inactive (FDG-) myocardium. Although patients with FDG+ segments have been found to be at risk for adverse events, the prognostic significance of viable myocardium in relation to other influences on postinfarction prognosis, including revascularization, remain ill defined. The purpose of this study was to investigate the relative prognostic significance of FDG+ tissue and to establish whether myocardial revascularization in patients with viable tissue attenuates the risk of adverse outcome. METHODS AND RESULTS: One hundred thirty-seven patients with left ventricular dysfunction and resting perfusion defects after myocardial infarction underwent positron emission tomography with both dipyridamole stress Rb-82 perfusion imaging and FDG imaging. After the exclusion of 4 patients proceeding to transplantation, 2 with uninterpretable scans and 2 lost to follow-up, 129 patients were followed clinically for 17 +/- 9 months. Four groups were defined: patients with FDG+ dysfunctional myocardium who were revascularized (n = 49) or treated medically (n = 21) and those with FDG- segments who were revascularized (n = 19) or treated medically (n = 40). The groups of patients with FDG+ or FDG- findings, with and without revascularization, did not differ with respect to known determinants of postinfarction prognosis: age, left ventricular ejection fraction, or the prevalence of multivessel disease. Nonfatal ischemic events occurred in 48% of medically treated FDG+ patients compared with 8% of revascularized patients with FDG+ tissue (P < .001) and 5% of patients with FDG- myocardium (P < .001). Thirteen patients died from cardiac causes; 11 (85%) had a left ventricular ejection fraction of < 30%, and these patients were evenly distributed between FDG+ and FDG- groups. Using Cox's proportional hazards model, only the presence of FDG+ myocardium (odds ratio, 12.9; P < .001) and the absence of revascularization (odds ratio, 5.8; P = .002) independently predicted ischemic events, while only age (P = .02) and ejection fraction (P < .001) but not the presence of viable myocardium were predictive of death. CONCLUSIONS: Residual viable myocardium after myocardial infarction may act as an unstable substrate for further events unless it is revascularized. Despite this association, age and left ventricular dysfunction remained the strongest predictors of cardiac death after myocardial infarction in these patients with a spectrum of left ventricular dysfunction.

Gastroepiploic and inferior epigastric arteries for coronary artery bypass. Early results and evolving applications.

BACKGROUND: Internal thoracic artery (ITA) conduits are known to provide long-term patency and increased patient survival with low morbidity after coronary artery bypass grafting (CABG). Excellent clinical results with the ITA have stimulated interest in additional arterial grafts. METHODS AND RESULTS: To review our experience and evaluate postoperative complications associated with these new conduits, from May 1985 to September 1993, we studied 290 patients who underwent CABG using additional arterial conduits. The right gastroepiploic artery (GEA) was used in 152 patients and the inferior epigastric artery (IEA) was used in 130 patients. Eight patients with both GEA and IEA grafts were excluded. Patient records were analyzed as to preoperative characteristics, angiographic findings, operative data, and postoperative complications. Statistical analysis was done using the Pearson chi 2 statistic and the t test. Ninety-eight percent of patients received one concomitant ITA graft, and the majority of patients in both groups had bilateral ITA grafts. The GEA group had a higher proportion of reoperations (GEA group, 54%; IEA group, 16%; P < .001), previous myocardial infarction (MI) (GEA group, 67%; IEA group, 50%; P = .004) and New York Heart Association class IV (GEA group, 28%; IEA group, 6%; P = .001). The IEA group was generally slightly older (IEA group, 56 years; GEA group, 52 years; P = .001). Hospital mortality (GEA group, 4%; IEA group, 0.8%) and postoperative morbidity (mediastinal bleeding, infection, stroke, MI, and low cardiac output) were not significantly different between the two groups or from our experience with routine CABG using the ITA. Three intraabdominal complications occurred in the GEA group: 2 episodes of bleeding and 1 of pancreatitis. One patient in the IEA group had abdominal wall bleeding. With overall short follow-up, angiographic patency in a small number of patients has been good: 80% for the GEA group and 85.7% for the IEA group. CONCLUSIONS: We conclude that the morbidity associated with these additional arterial conduits is low and is comparable with that associated with routine CABG using the ITA. Currently we use the ITA for primary targets and alternative arterial conduits for vessels of secondary importance or when the ITA and/or saphenous vein is not available.