Ticlopidine pretreatment before coronary stenting is associated with sustained decrease in adverse cardiac events: data from the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) Trial.

BACKGROUND: Platelet inhibition at the time of a percutaneous coronary intervention has consistently been shown to decrease the risk of thrombotic adverse events but not restenosis. The role of enhanced antiplatelet protection through pretreatment with the platelet ADP-receptor antagonist ticlopidine in preventing both the early and late complications of coronary stenting has not previously been explored. METHODS AND RESULTS: In the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial, approximately 1600 patients were randomized to stenting with either placebo or abciximab in addition to aspirin and heparin. All stented patients also received ticlopidine after the procedure, but 58% of these patients were given ticlopidine before stenting at the discretion of the investigating physician. Among patients randomized to placebo, ticlopidine pretreatment was associated with a significant decrease in the incidence of the composite end point of death, myocardial infarction, or target vessel revascularization (TVR) at 1 year (adjusted hazard ratio, 0.73; 95% CI, 0.54 to 0.98; P:=0.036). Ticlopidine pretreatment did not significantly influence the risk of death or myocardial infarction in patients randomized to abciximab. Controlling for patient characteristics and for the propensity of being on ticlopidine, Cox proportional hazards regression identified ticlopidine pretreatment as an independent predictor of the need for TVR at 1 year (hazard ratio, 0.62; 95% CI, 0.43 to 0.89; P:=0.010) in both placebo-treated and abciximab-treated patients. CONCLUSIONS: In the EPISTENT trial, among patients randomized to stenting, starting ticlopidine before the percutaneous coronary intervention was associated with a significant decrease in the incidence of the 12-month composite end point for patients not receiving abciximab and the need for TVR among all patients.

Relation between lesion characteristics and risk with percutaneous intervention in the stent and glycoprotein IIb/IIIa era: An analysis of results from 10,907 lesions and proposal for new classification scheme.

BACKGROUND: The currently used American College of Cardiology/American Heart Association lesion classification scheme dates from an era when balloon angioplasty was the only percutaneous treatment available and major complications occurred in approximately 7% of patients. Major advances in treatment options would suggest that this scheme may be outmoded, but the schemes that have been suggested to update lesion classification have not been widely accepted. METHODS AND RESULTS: Four thousand one hundred eighty-one consecutive patients (6,676 lesions) formed a training set and 2,146 patients (4,231 lesions) formed a validation set treated from 1995 to 1997 at a single center used by 3 hospital groups. Twenty-seven pretreatment candidate variables were analyzed with the use of stepwise proportional logistic regression, and 9 (nonchronic total occlusion with TIMI flow 0, degenerated vein graft, vein graft age >10 years, lesion length >/= 10 mm, severe calcium, lesion irregularity, large filling defect, angulated >/= 45 degrees plus calcium, and eccentricity) were independently correlated (P<0.05) with ranked adverse outcome (death, Q-wave or creatine kinase >/= 3x normal myocardial infarction, or emergency coronary artery bypass grafting>>creatine kinase 2 to 3x myocardial infarction>>possibly related to non-Q-wave myocardial infarction>>no complication). A scheme based on these findings and the old American College of Cardiology/American Heart Association scheme were found to have c-statistics in the validation set of 0.672 and 0.620 (P = 0.010 vs old scheme), respectively. CONCLUSIONS: Appreciation of these contemporary risk factors for complications of coronary intervention may assist in patient selection and in risk adjustment for comparison of outcomes between providers.

Incremental prognostic value of elevated baseline C-reactive protein among established markers of risk in percutaneous coronary intervention.

BACKGROUND: Established methods of risk assessment in percutaneous coronary intervention have focused on clinical and anatomical lesion characteristics. Emerging evidence indicates the substantial contribution of inflammatory processes to short-term and long-term outcomes in coronary artery disease. METHODS AND RESULTS: Within a single-center registry of contemporary percutaneous coronary revascularization strategies with postprocedural creatine kinase and clinical events routinely recorded, we assessed the association of baseline C-reactive protein with death or myocardial infarction within the first 30 days. Predictive usefulness of baseline C-reactive protein within the context of established clinical and angiographic predictors of risk was also examined. Among 727 consecutive patients, elevated baseline C-reactive protein before percutaneous coronary intervention was associated with progressive increase in death or myocardial infarction at 30 days (lowest quartile, 3.9%, versus highest quartile, 14.2%; P=0.002). Among clinical and procedural characteristics, baseline C-reactive protein remained independently predictive of adverse events, with the highest quartile of C-reactive protein associated with an odds ratio for excess 30-day death or myocardial infarction of 3.68 (95% CI, 1.51 to 8.99; P=0.004). A predictive model that included baseline C-reactive protein quartiles, American College of Cardiology/American Heart Association lesion score, acute coronary syndrome presentation, and coronary stenting appears strongly predictive of 30-day death or myocardial infarction within this population (C-statistic, 0.735) and among individual patients (Brier score, 0.006). CONCLUSIONS: Elevated baseline C-reactive protein portends heightened risk of 30-day death or myocardial infarction after coronary intervention. Coupled anatomic, clinical, and inflammatory risk stratification demonstrates strong predictive utility among patients undergoing percutaneous coronary intervention and may be useful for guiding future strategies.

beta-blockers before percutaneous coronary intervention do not attenuate postprocedural creatine kinase isoenzyme rise.

BACKGROUND: beta-blocker (BB) use reduces infarct size in spontaneously occurring nonreperfused infarcts but probably does not change infarct size in patients treated with reperfusion therapy. A recent observational study suggested that BB use concurrent with percutaneous coronary intervention (PCI) decreased the risk of creatine kinase (CK)-MB elevation. The cogency of such a conclusion is dependent on the ability to risk-adjust for the multiple differences in patients treated with and without BBs. METHODS AND RESULTS: Using propensity score and multivariate regression analyses, 6200 consecutive patients were analyzed to assess the relationship between BB use before PCI and per protocol-measured CK and CK-MB rise. There were several highly significant (P<0.001) differences between patients with and without BB treatment (eg, age, prior infarction, unstable angina). Maximum CK and CK-MB levels were higher in patients taking BBs (CK median, 95 U [interquartile range: 61, 175]; CK-MB, 3 U [2, 5]) than in patients not taking BBs (CK, 91 U [60, 157]; CK-MB, 3 U [2, 4]) (P=0.011 and P=0.021 for CK and CK-MB, respectively). After adjustment for significant differences in baseline characteristics there was no difference in either maximum CK rise (P=0.21) or maximum CK-MB rise (P=0.99). CONCLUSIONS: The results of this large observation study do not support the contention that BB use before PCI decreases myocardial injury.

Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction: results from the global use of strategies to open occluded arteries in Acute Coronary Syndromes (GUSTO-IIb) trial.

BACKGROUND: Time to treatment with thrombolytic therapy is a critical determinant of mortality in acute myocardial infarction. Little is known about the relationship between the time to treatment with direct coronary angioplasty and clinical outcome. The objectives of this study were to determine both the time required to perform direct coronary angioplasty in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) trial and its relationship to clinical outcome. METHODS AND RESULTS: Patients randomized to direct coronary angioplasty (n=565) were divided into groups based on the time between study enrollment and first balloon inflation. Patients randomized to angioplasty who did not undergo the procedure were also analyzed. The median time from study enrollment to first balloon inflation was 76 minutes; 19% of patients assigned to angioplasty did not undergo an angioplasty procedure. The 30-day mortality rate of patients who underwent balloon inflation /=91 minutes after enrollment, 6.4%. The mortality rate of patients assigned to angioplasty who never underwent the procedure was 14.1% (P=0.001). Logistic regression analysis revealed that the time from enrollment to first balloon inflation was a significant predictor of mortality within 30 days; after adjustment for differences in baseline characteristics, the odds of death increased 1.6 times (P=0.008) for a movement from each time interval to the next. CONCLUSIONS: The time to treatment with direct PTCA, as with thrombolytic therapy, is a critical determinant of mortality.

Long-term clinical outcomes after unprotected left main trunk percutaneous revascularization in 279 patients.

BACKGROUND: Percutaneous coronary revascularization (PCI) has been increasingly applied to unprotected left main trunk (LMT) lesions, with varied long-term success. This study attempts to define the predictors of outcome in this population. METHODS AND RESULTS: Two hundred seventy-nine consecutive patients who had LMT PCI at 1 of 25 sites between 1993 and 1998 were studied. Forty-six percent of these patients were deemed inoperable or at high surgical risk. Thirty-eight patients (13.7%) died in hospital, and the rest were followed up for a mean of 19 months. The 1-year incidence was 24.2% for all-cause mortality, 20.2% for cardiac mortality, 9.8% for myocardial infarction, and 9.4% for CABG. Independent correlates of all-cause mortality were left ventricular ejection fraction /=2.0 mg/dL, and severe lesion calcification. For the 32% of patients <65 years old with left ventricular ejection fraction >30% and without shock, the prevalence of these adverse risk factors was low. No periprocedural deaths were observed in this low-risk subset, and the 1-year mortality was only 3.4%. CONCLUSIONS: Patients undergoing unprotected LMT PCI have frequent serious comorbidities and consequently have high event rates. PCI may be an alternative to CABG for a select proportion of elective patients and may also be appropriate for highly symptomatic inoperable patients. Meticulous follow-up of hospital survivors is required because of the rather high mortality during the first few months after treatment.

Pronounced benefit of coronary stenting and adjunctive platelet glycoprotein IIb/IIIa inhibition in complex atherosclerotic lesions.

BACKGROUND: Previous trials testing stents compared with balloon angioplasty excluded patients with complex lesions and did not assess the effect of adjunctive platelet IIb/IIIa inhibition. This analysis sought to assess the effect of stenting and abciximab specifically for patients with complex lesions. METHODS AND RESULTS: Patients with complex lesions (long, tandem, severely calcified, restenotic, thrombotic, or ostial; total occlusions; bifurcations; saphenous vein grafts; and multivessel interventions) from the Evaluation of PTCA to Improve Long-Term Outcome by c7E3 GP IIb/IIIa Receptor Blockade (EPILOG) and the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials were included in the analysis. The 1-year combined death or myocardial infarction rates in the 4 treatment groups were as follows: balloon angioplasty/placebo, 14.2%; stent/placebo, 15.8%; balloon angioplasty/abciximab, 7.6%; and stent/abciximab, 8.0% (P<0.001). Death rates were 3.2%, 3.1%, 2.1%, and 0.5%, respectively (P=0.03). The incidence of target vessel revascularization at 1 year was 30.5%, 18.0%, 24.4%, and 19.7% in the 4 groups, respectively (P<0.001). After adjustment for baseline differences, multivariate analysis demonstrated that the rate of death or myocardial infarction was independently reduced by balloon angioplasty/abciximab (hazard ratio, 0.51; P<0.001) and stent/abciximab (hazard ratio, 0.60; P=0.02) but was not affected by the use of stents alone. Conversely, target vessel revascularization was reduced by stent/placebo (hazard ratio, 0.53; P<0.001), stent/abciximab (hazard ratio, 0.58; P<0.001), and balloon angioplasty/abciximab (hazard ratio, 0.74; P=0.006) compared with balloon angioplasty/placebo, respectively. CONCLUSIONS: The combination of stenting and abciximab during percutaneous coronary interventions for patients with angiographically complex lesions confers additive long-term benefit with respect to death, myocardial infarction, and target vessel revascularization.

Effect of intracoronary gamma-radiation therapy on in-stent restenosis: An intravascular ultrasound analysis from the gamma-1 study.

BACKGROUND: The aim of this study was to use serial volumetric intravascular ultrasound to evaluate the effect of gamma-radiation on recurrent in-stent restenosis. METHODS AND RESULTS: After successful reintervention, patients were randomized to receive either (192)Ir or placebo. Intravascular ultrasound studies with motorized pullback (0.5 mm/s) were performed immediately after irradiation and at 8-month follow-up in 70 patients. Paired volumetric analysis of the stented segment and of 5-mm proximal and distal reference segments was performed; this included measurements of the external elastic membrane, lumen, plaque and media (external elastic membrane minus lumen), stent, and intimal hyperplasia (stent minus lumen). Baseline proximal reference, stent, and distal reference measurements were similar in both groups. The changes in proximal and distal reference measurements of the external elastic membrane, plaque and media, and lumen areas were similar in both groups. However, the decrease in stented segment lumen volume was less in the (192)Ir patients than the placebo patients (-25+/-34 mm(3) versus -48+/-42 mm(3); P:=0.0225), and the increase in the volume of intimal hyperplasia in the stented segment was less in the (192)Ir patients than in the placebo patients (28+/-37 mm(3) versus 50+/-40 mm(3); P:=0.0352). When averaged over the length of the stented segment (32+/-13 mm versus 33+/-14 mm; P:=0.9), the increase in mean area of intimal hyperplasia was 0.8+/-1.0 mm(2) in the (192)Ir group and 1.6+/-1.2 mm(2) in the control group (P:=0.0065). Late stent-vessel wall malapposition was noted in one placebo patient and no (192)Ir patients. CONCLUSIONS: gamma-Radiation therapy can effectively prevent recurrent in-stent restenosis by inhibiting neointimal formation within the stent. At the stent edge, there were no significant differences between (192)Ir and placebo patients.

Intracoronary stents: will they fulfill their promise as an adjunct to angioplasty?

Coronary angioplasty as it is now performed has several limitations, including abrupt early arterial closure and delayed restenosis. To obviate these problems and to enhance the safety of the technique, several intracoronary stenting devices have been developed and are under investigation. This report reviews the scientific rationale behind stenting, the results of stenting in animal models and the early results in humans. In early clinical investigation, restenosis appears uncommon but abrupt, presumably thrombotic, occlusion has been reported despite aggressive anticoagulation. As long as the potential for this problem remains and the long-term consequences of placing these devices into arteries of great functional importance remain unknown, stent placement must be undertaken with great caution and should be performed under carefully monitored circumstances with meticulous patient follow-up.

Detection of endocarditis-associated perivalvular abscesses by two-dimensional echocardiography.

The development of a perivalvular abscess as a complication of infective endocarditis adds appreciably to the expected morbidity and mortality of patients, but such abscesses are seldom recognized by available noninvasive techniques. Therefore, two-dimensional echocardiographic findings in 22 patients with perivalvular abscess found at surgery or necropsy were compared with those in 24 patients without abscess in a retrospective but blinded study. Forty-six valves were examined (31 aortic and 15 mitral, 35 prosthetic and 11 native); 4.0 +/- 2.4 days (range 0 to 7) elapsed between echocardiography and surgery or necropsy. Patients with perivalvular abscess had a somewhat higher incidence of serious complications (emergency repeat valve replacement or death) than did patients with endocarditis alone (63 versus 35%, respectively, p less than 0.05). No single echocardiographic finding was frequently seen with a perivalvular abscess. A "typical" echo-free abscess was noted in only one patient; however, the presence of one or more of the following had a positive predictive value of 86% and a negative predictive value of 87% for the presence of perivalvular abscess: prosthetic valve rocking; sinus of Valsalva aneurysm, anterior aortic root thickness of 10 mm or greater, posterior aortic root thickness of 10 mm or greater or perivalvular density in a septum of 14 mm or greater. These predictive values, of course, apply only to patients with infective endocarditis going to surgery, and may assist the surgeon in knowing whether or not to expect an abscess.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental models of coronary artery restenosis.

The study of potentially effective drug therapies and mechanical devices for the prevention of restenosis after percutaneous coronary revascularization has relied heavily on the use of experimental animal models. To date, greater than 50 experimental studies have been reported and have suggested that at least nine different classes of pharmacologic agents inhibit the intimal proliferative response to arterial injury. However, no pharmacologic intervention has yet been shown to reproducibly reduce the incidence of restenosis after coronary balloon angioplasty in humans. To identify the reasons for the apparent nonspecificity of the animal models and to determine which model should most reliably predict the efficacy of individual therapies in humans, the distinguishing characteristics of the experimental models were compared. Particular attention was paid to the size and morphologic structure of the treated artery, the susceptibility of the species to spontaneous and diet-induced arterial disease, the nature of the stimulus to intimal proliferation and several practical and logistic considerations. Finally, the reported efficacies of specific drug therapies in the respective animal models and in humans were compared. This review suggests that significant interspecies and occasionally intraspecies differences do exist among the respective animal models, particularly in the extent and composition of the neointimal thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of recurrent ischemia after thrombolysis and successful reperfusion for acute myocardial infarction: effect on in-hospital mortality and left ventricular function.

To determine the effect of treatment of recurrent ischemia after reperfusion for acute myocardial infarction on in-hospital mortality and left ventricular function recovery and to identify patients at highest risk of serious consequences in the event of recurrent ischemia in this setting, 405 consecutively treated patients were studied retrospectively. All patients received intravenous thrombolytic therapy within 6 h of ST segment elevation-documented infarction and had angiographic confirmation of their reperfusion status performed within 120 min of treatment. Three hundred three patients had successful reperfusion with or without rescue angioplasty and had no recurrent ischemia (group 1), 74 patients had initially successful reperfusion but subsequent recurrent ischemia (group 2) and 28 patients had failed reperfusion (group 3). The in-hospital mortality in groups 1 to 3 was 2.0%, 14.9% and 32.1%, respectively (p less than 0.001) and the change from baseline to prehospital discharge left ventricular ejection fraction was 1.2 +/- 9.3%, -0.8 +/- 8.7% and -4.3 +/- 5.3%, respectively (p = NS). Within the recurrent ischemia group (group 2), multiple regression analysis found absence of cardiogenic shock at presentation (p = 0.002) and successful treatment initiated within 90 min of recurrent ischemia (p = 0.045) to be the only variables independently correlated with in-hospital survival. Later successful reperfusion was not associated with improved hospital survival. The timing and success of treatment did not affect recovery of global or regional left ventricular function in the patients with paired angiographic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Colchicine and antineoplastic therapy for the prevention of restenosis after percutaneous coronary interventions.

The complexity of the events that culminate in intimal proliferation after arterial injury and similarities between this response and benign neoplasia suggest that conventional medical therapies will continue to be unsuccessful in preventing recurrent stenosis after percutaneous coronary revascularization. By preventing cell division after smooth muscle cell activation, antimitogenic therapy may inhibit the final common pathway in this complex chain of events and offset the apparent loss of local growth control. Colchicine, which causes metaphase arrest of cell division, has been shown in experimental studies to decrease the extent of atheromatous plaque formation and reduce the severity of arterial restenosis after balloon angioplasty. However, preliminary results from a randomized placebo-controlled clinical trial suggest that low dose colchicine (0.6 mg twice a day orally) does not prevent restenosis. The use of more potent antineoplastic agents is limited by the potential for life-threatening side effects. It is possible that these adverse effects can be averted by using novel drug delivery systems to administer antimitogenic therapy locally at the site of arterial injury or by using low dose synergistic combinations of antiproliferative agents. This review examines the potential role of antimitogenic therapy in the prevention of restenosis after coronary interventions and considers the possibility of an overlap of the therapeutic realms of interventional cardiology and medical oncology.

Subacute stent thrombosis: evolving issues and current concepts.

During percutaneous coronary revascularization, intracoronary stents are effective in the treatment of abrupt vessel closure and improvement of suboptimal angioplasty results, and compared to balloon angioplasty, they reduce stenosis recurrence. Opposing these benefits, subacute thrombosis of stents is associated with a substantial increase in periprocedural morbidity and mortality. To review factors associated with stent thrombosis and to study the impact of evolving procedural techniques on the incidence of stent thrombosis, we reviewed all English articles from MEDLINE (1988 to 1995) with key words "stent" and "thrombosis." Stent registry data and recent abstracts from scientific meetings were also reviewed. Factors related to the clinical setting, the lesion, the stent and the procedural technique that affect the risk of stent thrombosis were identified. Sixty clinical studies were reviewed and include 7,914 patients receiving intracoronary stents. Studies were separated into those reporting stents placed emergently or electively without adjunct high-pressure balloon inflations, stents placed in saphenous vein graft conduits, and stents placed with high-pressure balloon inflations but without subsequent oral anticoagulants. Overall, subacute thrombosis was substantially higher in stents placed emergently (10.1%) compared to those placed electively (4.3%). Among contemporary trials employing high-pressure balloon inflations, the rate of stent thrombosis appears markedly lower (1.3%) despite reduced postprocedural anticoagulation. Taken together, these studies suggest factors associated with a heightened risk of stent thrombosis, many of which can be avoided with proper case selection and contemporary techniques.

Directional coronary atherectomy in unstable angina.

OBJECTIVES: To determine whether excision of complex, ulcerated plaque improves the risk of patients with unstable angina to the level of those with stable angina, the results of directional coronary atherectomy were compared in patients with these two syndromes. BACKGROUND: The procedural results of angioplasty in the setting of unstable angina are not as favorable as those observed for chronic stable angina, presumably because thrombus-associated plaque augments the risk of abrupt closure. METHODS: Two hundred eighty-seven consecutive patients who had undergone directional atherectomy for a single new stenosis were studied. Seventy-seven patients had stable angina (Group I); 110 patients had progressively worsening angina in the absence of rest or postinfarction angina (Group II); and 100 patients had rest or postinfarction angina, or both (Group III). RESULTS: Major ischemic complications (death, Q wave infarction, emergency bypass surgery) occurred more frequently in Group III (1.3% [Group I] vs. 0.9% [Group II] vs. 7% [Group III], p = 0.036). This difference was largely due to a higher incidence of emergency surgery in Group III (1.3% [Group I] vs. 0% [Group II] vs. 5% [Group III], p = 0.05). Clinical follow-up was obtained in 97% of successful procedures for a mean follow-up period of 22 months (range 9 to 52) and revealed a higher incidence of hospital admission for angina (p = 0.05) and a trend toward more bypass surgery (p = 0.09) and myocardial infarction (p = 0.16) in Group III. There was no difference in repeat percutaneous interventions among the three groups (range 19% to 24%, p = 0.75). CONCLUSIONS: These results show that the definition of unstable angina is important in determining the immediate outcome of directional atherectomy. In the absence of rest or postinfarction angina, the immediate results are not significantly different from those obtained in stable angina. Our results also suggest that both the immediate and short-term outcome in unstable angina are not greatly influenced by atherectomy but more so by the pathophysiology of unstable angina, which increases the complications of percutaneous interventions.

Present status of rescue coronary angioplasty: current polarization of opinion and randomized trials.

Whereas coronary angioplasty has been demonstrated to be unnecessary and perhaps harmful for most patients after successful thrombolytic treatment of acute myocardial infarction, the clinical benefit of rescue angioplasty after failed thrombolysis remains untested in a randomized clinical trial. However, in the clinical judgment of many physicians it is unethical to withhold such treatment, whereas a nearly equal number of physicians believe that such treatment cannot be justified. A review of reported nonrandomized data from a limited number of patients suggests that 1) coronary angioplasty is successful in only 80% of patients after failed thrombolysis, 2) later reocclusion rates may depend on the thrombolytic agent used, 3) left ventricular ejection fraction is seldom improved, and 4) mortality rates after successful angioplasty approximate those after successful thrombolysis alone but mortality rates after failed angioplasty are remarkably high. The arguments for and against rescue angioplasty are reviewed, and it is concluded that results of randomized trials are needed to replace disparate clinical opinion on whether this potentially costly form of therapy should be widely implemented.

Abrupt vessel closure complicating coronary angioplasty: clinical, angiographic and therapeutic profile.

To assess the clinical, angiographic and procedural correlates of outcome after abrupt vessel closure during coronary angioplasty, results were analyzed of 109 patients (8.3%) who had abrupt vessel closure during 1,319 consecutive coronary angioplasty procedures performed between July 1, 1988 and June 30, 1990. These 109 patients had a mean age of 59 +/- 11 years; 63% were male, 57% had had a prior myocardial infarction and 61% had multivessel disease. Coronary angioplasty was performed in the settings of acute myocardial infarction (14%), recent myocardial infarction (36%), unstable angina (34%) and stable ischemia (29%). Abrupt vessel closure occurred at a median of 27 min (range 0 min to 5 days) from the first balloon inflation. By angiographic criteria, thrombus or coronary dissection was identified in 20% and 28% of cases, respectively; both thrombus and dissection were present in 7% of closures, and 45% were due to indeterminate mechanisms. Successful reversal of abrupt vessel closure, defined as restoration of normal Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow without resultant Q wave myocardial infarction, emergency bypass surgery or death, was achieved in 47 patients (43%). By hierarchal analysis, the incidence of death, emergency coronary bypass surgery, Q wave and non-Q wave myocardial infarction was 8%, 20%, 9% and 11%, respectively. Univariate analysis using 23 clinical, morphologic and procedural variables demonstrated that successful outcome after abrupt closure was associated with prolonged balloon inflations (greater than 120 s) (odds ratio = 6.87, p less than 0.001), unstable angina (odds ratio = 2.37, p = 0.034) and placement of an intracoronary stent (odds ratio = 5.33, p = 0.062). By multivariate analysis, independent correlates of successful outcome were prolonged balloon inflations (odds ratio = 5.11, p = 0.001) and intracoronary stenting (odds ratio = 4.37, p = 0.049). Thus, although prolonged balloon inflations and intracoronary stents may improve outcome after abrupt vessel closure, the cumulative risk of morbidity or mortality remains significant and mandates investigation into improved strategies for its prevention and treatment.

Intramural methotrexate therapy for the prevention of neointimal thickening after balloon angioplasty.

OBJECTIVES: The study was performed to test the hypothesis that high local, intramural concentrations of antineoplastic agents at the site of balloon injury inhibit vascular smooth muscle cell proliferation without systemic toxicity. BACKGROUND: The predominant mechanism for recurrent stenosis after coronary balloon angioplasty is neointimal thickening due to medial smooth muscle cell proliferation. The clinical use of potent antiproliferative agents to prevent restenosis has been limited by the potential for severe systemic side effects. Local therapy with these agents may be effective and free of systemic complications. METHODS: After bilateral balloon angioplasty of the carotid arteries of 14 juvenile farm pigs, the dilated arterial segments were treated locally with methotrexate (6.25 mg/ml, total dose 25 mg) or 0.9% saline solution through a perforated balloon catheter. The animals were then killed 30 days after balloon injury to determine the effects of this therapy on neointimal thickness. In an additional six animals, tritium-labeled methotrexate was used to determine the concentration and duration of detectability of methotrexate in the wall of the treated arteries and in the systemic circulation. RESULTS: Two hours after drug instillation the concentration of labeled drug was greater than 1,000-fold greater in the wall of the treated artery than in circulating blood, and this ratio remained between 50 and 100 for at least 7 days. Despite this difference, the mean intimal thickness 30 days after the procedure was similar in the 10 methotrexate-treated arteries and the 18 saline-treated arteries (59 +/- 30 vs. 56 +/- 25 microns, p = 0.6). The morphologic appearance of the neointima was similar in each group and suggested an important role for mural thrombus in the genesis of the intimal thickening. CONCLUSIONS: Treatment with intramural methotrexate, delivered through a perforated balloon catheter at the selected concentration and total dose, failed to prevent intimal thickening after balloon injury. Nonetheless, the perforated balloon catheter appears to be a promising means of delivering a high local concentration of drugs with potentially life-threatening systemic side effects. The optimal concentrations and combinations of candidate drug therapies warrant further evaluation.

Percutaneous support devices for high risk or complicated coronary angioplasty.

Indications for coronary angioplasty have expanded to include patients with unstable acute ischemic syndromes, severe multivessel coronary artery disease and impaired left ventricular function. Several mechanical approaches have been developed as adjuncts to high risk coronary angioplasty to improve patient tolerance of coronary balloon occlusion and maintain hemodynamic stability in the event of complications. These percutaneous techniques include intraaortic balloon counterpulsation, anterograde transcatheter coronary perfusion, coronary sinus retroperfusion, cardiopulmonary bypass, Hemopump left ventricular assistance and partial left heart bypass. The intraaortic balloon pump provides hemodynamic support and ameliorates ischemia by decreasing myocardial work; it may be inserted for periprocedural complications or before angioplasty in patients with ischemia or hypotension. Anterograde distal coronary artery perfusion may be accomplished passively through an autoperfusion catheter or by active pumping of oxygenated blood or fluorocarbons through the central lumen of an angioplasty catheter. Synchronized coronary sinus retroperfusion produces pulsatile blood flow via the cardiac veins to the coronary bed distal to a stenosis. Both perfusion techniques limit development of ischemic chest pain and myocardial dysfunction in patients undergoing prolonged balloon inflations. Percutaneous cardiopulmonary bypass provides complete systemic hemodynamic support which is independent of intrinsic cardiac function or rhythm and has been employed prophylactically in very high risk patients before coronary angioplasty or emergently for abrupt closure. These and newer support devices, while associated with significant complications, may ultimately improve the safety of coronary angioplasty and allow its application to those who would otherwise not be candidates for revascularization.

Prospects for the use of antagonists to the platelet glycoprotein IIb/IIIa receptor to prevent post-angioplasty restenosis and thrombosis.

Despite many advances since its inception in humans in 1977, coronary angioplasty continues to be limited by the problems of abrupt arterial closure and late restenosis. Excessive platelet deposition at the site of angioplasty undoubtedly plays an important role in the pathophysiology of both of these problems. Monoclonal antibodies and snake venom-derived or synthetic peptides directed against a common protein recognition sequence on the platelet glycoprotein IIb/IIIa receptor are currently in the early stages of preclinical and clinical testing and hold promise of preventing abrupt closure and restenosis by inhibiting platelet function. Whether any of these agents will eventually be commonly used in clinical practice will depend on their effects on the complex pathophysiology of these problems and on their safety profile when administered to patients who are likely to receive other antithrombotic medications and who are instrumented for coronary angioplasty.