Gregg W. Stone

Angiographic Patterns of In-Stent Restenosis Classification and Implications for Long-Term Outcome

BACKGROUNDnThe angiographic presentation of in-stent restenosis (ISR) may convey prognostic information on subsequent target vessel revascularizations (TLR).nnnMETHODS AND RESULTSnWe developed an angiographic classification of ISR according to the geographic distribution of intimal hyperplasia in reference to the implanted stent. Pattern I includes focal (< or =10 mm in length) lesions, pattern II is ISR>10 mm within the stent, pattern III includes ISR>10 mm extending outside the stent, and pattern IV is totally occluded ISR. We classified a total of 288 ISR lesions in 245 patients and verified the angiographic accuracy of the classification by intravascular ultrasound. Pattern I was found in 42% of patients, pattern II in 21%, pattern III in 30%, and pattern IV in 7%. Previously recurrent ISR was more frequent with increasing grades of classification (9%, 20%, 34%, and 50% for classes I to IV, respectively; P=0.0001), as was diabetes (28%, 32%, 39%, and 48% in classes I to IV, respectively; P<0.01). Angioplasty and stenting were used predominantly in classes I and II, whereas classes III and IV were treated with atheroablation. Final diameter stenosis ranged between 21% and 28% (P=NS among ISR patterns). TLR increased with increasing ISR class; it was 19%, 35%, 50%, and 83% in classes I to IV, respectively (P<0.001). Multivariate analysis showed that diabetes (odds ratio, 2.8), previously recurrent ISR (odds ratio, 2. 7), and ISR class (odds ratio, 1.7) were independent predictors of TLR.nnnCONCLUSIONSnThe introduced angiographic classification is prognostically important, and it may be used for appropriate and early patient triage for clinical and investigational purposes.

Atherosclerotic plaque burden and CK-MB enzyme elevation after coronary interventions : Intravascular ultrasound study of 2256 patients

BACKGROUNDnElevation of serum creatine kinase MB fraction (CK-MB) after percutaneous coronary interventions has been associated with early and late mortality; however, the pathogenesis of CK-MB elevation is still unknown. We hypothesized that CK-MB elevation was related to atherosclerotic plaque burden as assessed by preintervention intravascular ultrasound (IVUS).nnnMETHODS AND RESULTSnWe studied 2256 consecutive patients who underwent intervention of 2780 native coronary lesions and had complete high-quality preintervention IVUS imaging in the era before routine use of platelet glycoprotein IIb/IIIa inhibitors. Patients were divided into 3 groups: CK-MB within normal range (1675 patients; 2061 lesions); CK-MB elevation 1 to 5 times upper limit of normal (292 patients; 355 lesions); and CK-MB elevation > or = 5 times upper limit of normal (289 patients; 364 lesions). Qualitative angiographic lesion morphology and quantitative analysis were similar among the 3 groups. On preintervention IVUS, progressively more reference segment and lesion site plaque burden and lesion site calcium occurred in the groups with CK-MB elevation. Positive remodeling was more common in lesions with CK-MB elevation. As levels of CK-MB increased, cross-sectional narrowing (percentage plaque burden) increased, both at the reference site (mean cross-sectional narrowing values were 45.1%, <49.3%, and <52.2% for normal CK-MB, 1 to 5 times upper limit of normal, and > or =5 times upper limit of normal groups, respectively; P=0.03) and at the lesion site (81.9%, <85.4%, and <87.1%, respectively; P=0.04). Multivariate analysis indicated that de novo lesions, atheroablative technique, plaque burden at the lesion and reference segments, and final minimal lumen diameter were independent predictors of CK-MB elevation.nnnCONCLUSIONSnCK-MB elevation correlates with a greater atherosclerotic plaque burden. CK-MB elevation after intervention may be a marker of diffuse atherosclerotic disease or a consequence of catheter-based intervention in more diseased arteries or both.

Creatine kinase-MB enzyme elevation following successful saphenous vein graft intervention is associated with late mortality

BACKGROUNDnAlthough the risk for development of creatine kinase (CK-MB) elevation after saphenous vein graft (SVG) intervention is high, its prognostic significance remains unknown. This study evaluated the impact of periprocedural CK-MB elevation on late clinical events following successful SVG angioplasty.nnnMETHODS AND RESULTSnWe studied 1056 consecutive patients with successful (defined by angiographic success and absence of major complications) intervention of 1693 SVG lesions. These patients were grouped as normal CK-MB (n=556), minor CK-MB rise (CK-MB 1 to 5 times normal, n=339), and major CK-MB rise (CK-MB >5 times normal, n=161). There were no differences in major clinical events at 30-day follow-up among the 3 groups. However, 1-year mortality was 4.8%, 6.5%, and 11. 7%, respectively, P<0.05 (ANOVA). Even within a population without any intraprocedure or in-hospital complications (n=727, 69% of the overall cohort), 1-year mortality remained significantly higher with CK-MB elevation: 2.4%, 5.5%, and 10.7%, respectively, P<0.05 (ANOVA). Multivariate analysis revealed major CK-MB elevation as the strongest independent predictor of late mortality (odds ratio 3.3, with 95% CI 1.7 to 6.2), followed by diabetes mellitus (odds ratio 2. 6, with 95% CI 1.5 to 4.5).nnnCONCLUSIONSnMajor CK-MB elevation occurs after 15% of otherwise successful SVG interventions and is associated with increased late mortality.

Long-term clinical events following creatine kinase-myocardial band isoenzyme elevation after successful coronary stenting

OBJECTIVEnWe sought to evaluate the impact of intermediate creatine kinase-myocardial band isoenzyme (CK-MB) elevation on late clinical outcomes in patients undergoing successful stent implantation in native coronary arteries.nnnBACKGROUNDnElevations of CK-MB after percutaneous coronary interventions are frequent. An association between high level of CK-MB elevation (>5 times normal) and late mortality after balloon and new device angioplasty has been reported previously. However, significant controversy remains on the long-term clinical importance of lower CK-MB elevations (one to five times normal) after percutaneous coronary revascularization. Moreover, the incidence and prognostic importance of cardiac enzyme elevation after coronary stenting have not been well established.nnnMETHODSnProspectively collected data from 900 consecutive patients (1,213 lesions) undergoing successful stenting in native vessels were analyzed. Based on the CK-MB levels after coronary stenting, patients were classified into three groups: normal group 1 (n = 585), elevation of >1 to 5 times normal group 2 (n = 238) and elevation of >5 times normal group 3 (n = 77).nnnRESULTSnPatients in group 3 had more in-hospital recurrent ischemia (p = 0.001) and pulmonary edema (p = 0.01) than patients in groups 1 and 2. Long-term clinical end points were similar between groups 1 and 2. However, patients in group 3 had an increased incidence of late mortality compared with patients in groups 2 and 1 (6.9%, 1.2% and 1.7%, respectively, p = 0.01). Multivariate analysis showed that patients with CK-MB >5 times normal after coronary stenting had an increased risk of major adverse clinical events (relative risk: 1.70, p < 0.05) and death (relative risk: 3.25, p < 0.05) that was not observed in patients with lower CK-MB rise.nnnCONCLUSIONSnPatients with CK-MB elevation >5 times normal had higher late mortality and more unfavorable event-free survival than those patients with normal or lower CK-MB rise after coronary stenting. While intermediate CK-MB elevation (>1 to 5 times normal) is frequent after coronary stenting (26%), this was not associated with an increased risk of late mortality or major adverse clinical events.

Treatment of In-Stent Restenosis With Excimer Laser Coronary Angioplasty Versus Rotational Atherectomy Comparative Mechanisms and Results

BACKGROUNDnAtheroablation yields improved clinical results for balloon angioplasty (percutaneous transluminal coronary angioplasty, PTCA) in the treatment of diffuse in-stent restenosis (ISR).nnnMETHODS AND RESULTSnWe compared the mechanisms and clinical results of excimer laser coronary angioplasty (ELCA) versus rotational atherectomy (RA), both followed by adjunct PTCA; 119 patients (158 ISR lesions) were treated with ELCA+PTCA and 130 patients (161 ISR lesions) were treated with RA+PTCA. Quantitative coronary angiographic and planar intravascular ultrasound (IVUS) measurements were performed routinely. In addition, volumetric IVUS analysis to compare the mechanisms of lumen enlargement was performed in 28 patients with 30 lesions (16 ELCA+PTCA, 14 RA+PTCA). There were no significant between-group differences in preintervention or final postintervention quantitative coronary angiographic or planar IVUS measurements of luminal dimensions. Angiographic success and major in-hospital complications with the 2 techniques were also similar. Volumetric IVUS analysis showed significantly greater reduction in intimal hyperplasia volume after RA than after ELCA (43+/-14 versus 19+/-10 mm(3), P<0.001) because of a significantly higher ablation efficiency (90+/-10% versus 76+/-12%, P = 0.004). However, both interventional strategies had similar long-term clinical outcome; 1-year target lesion revascularization rate was 26% with ELCA+PTCA versus 28% with RA+PTCA (P = NS).nnnCONCLUSIONSnDespite certain differences in the mechanisms of lumen enlargement, both ELCA+PTCA and RA+PTCA can be used to treat diffuse ISR with similar clinical results.

Prognostic value of cardiac troponin-I levels following catheter-based coronary interventions

This study has examined the prognostic significance of troponin-I (Tn-I) levels after catheter-based coronary interventions in coronary arteries and saphenous vein grafts lesions. Tn-I and creatine kinase-MB (CK-MB) fraction levels were measured at 6 and 18 to 24 hours after catheter-based coronary intervention in 1,129 consecutive patients with normal preintervention plasma levels of Tn-I, and CK-MB levels below the cutoff for myocardial infarction. Patients were stratified according to maximal postangioplasty Tn-I levels. Group I (n = 784) had no elevated Tn-I (<0.15 ng/ml), group II (n = 170) had Tn-I at 0.15 to 0.45 ng/ml, and group III (n = 175) had Tn-I elevation >0.45 ng/ml. Major in-hospital complications (death, 0-wave infarction, and emergent coronary bypass grafting) and out-of-hospital intermediate-term (8 months) outcomes were compared between the 3 groups. Tn-I elevation >0.45 ng/ml was associated with increased risk of mortality (group III, 1.6%; group II, 0.6%; and group I, 0.1%; p = 0.019) and major in-hospital complications (3.2%, 1.7%, and 0.5%; p = 0.004). There was no difference in death (1.8%, 3.2%, and 2.4%; p = 0.74), Q-wave infarction (0.6%, 0%, and 0.3%; p = 0.66), or target lesion revascularization (10.1%, 9.0%, and 9.3%; p = 0.86) between the 3 groups at follow-up. Cardiac event-free survival was similar between groups (p = 0.3). By multivariate analysis, Tn-I >0.45 ng/ml was an independent predictor for major in-hospital complications (odds ratio 2.1, 95% confidence interval 1.2 to 3.9, p = 0.01). The degree of risk was also associated with the conjoint elevation of Tn-I and CK-MB levels (odds ratio 1.1, 95% confidence interval 1.02 to 1.2, p = 0.01). We conclude that Tn-I levels >3 times the normal limit and conjoint elevation of Tn-I and CK-MB levels after coronary angioplasty are associated with increased risk of major in-hospital complications, but have no incremental risk of adverse intermediate-term (8 months) clinical outcomes.

Preintervention Arterial Remodeling as an Independent Predictor of Target-Lesion Revascularization After Nonstent Coronary Intervention An Analysis of 777 Lesions With Intravascular Ultrasound Imaging

BACKGROUNDnPathological and intravascular ultrasound (IVUS) studies have documented arterial remodeling during atherogenesis. However, the impact of this remodeling process on the long-term outcome after percutaneous intervention is unknown.nnnMETHODS AND RESULTSnWe used preintervention IVUS to define positive and negative/intermediate remodeling in a total of 777 lesions in 715 patients treated with nonstent techniques. Positive remodeling (lesion external elastic membrane area greater than average reference) was present in 313 lesions; intermediate/negative remodeling (lesion external elastic membrane area less than or equal to reference) was present in the other 464. Baseline clinical and angiographic characteristics were similar, except for a slightly higher percentage of insulin-dependent diabetic patients (10.2% versus 6.1%; P=0.054) in the negative/intermediate-remodeling group. Angiographic success and in-hospital and short-term complications were comparable in the 2 groups. There was no significant correlation between remodeling (as a continuous variable) and final lumen area (r=0.06) or final lesion plaque burden (r=0.17). At 18+/-13 months of clinical follow-up, both groups had similar rates of death and Q-wave myocardial infarction: 3.4% and 2.5% for the negative/intermediate-remodeling group versus 2.7% and 2.7% for the positive-remodeling group. However, the target-lesion revascularization (TLR) rate was 20.2% for the negative/intermediate-remodeling group versus 31.2% for the positive-remodeling group (P=0.007), and remodeling, as a continuous variable, was strongly correlated with probability of TLR (P=0.0001). By multivariable logistic regression analysis, diabetes (OR=2.3), left anterior descending artery location (OR=1.8), and remodeling (OR=5.9) were independent predictors of TLR.nnnCONCLUSIONSnPositive lesion-site remodeling is associated with a higher long-term TLR after a nonstent interventional procedure. Thus, long-term clinical outcome appears to be determined in part by preintervention lesion characteristics.

Clinical and angiographic outcomes in patients with previous coronary artery bypass graft surgery treated with primary balloon angioplasty for acute myocardial infarction

OBJECTIVES We sought to characterize the presenting characteristics of patients with previous coronary artery bypass graft surgery (CABG) and acute myocardial infarction (AMI) and to determine the angiographic success rate and clinical outcomes of a primary percutaneous transluminal coronary angioplasty (PTCA) strategy. BACKGROUND Patients who have had previous CABG and AMI comprise a high risk group with decreased reperfusion success and increased mortality after thrombolytic therapy. Little is known about the efficacy of primary PTCA in AMI. METHODS Early cardiac catheterization was performed in 1,100 patients within 12 h of onset of AMI at 34 centers in the prospective, controlled Second Primary Angioplasty in Myocardial Infarction trial (PAMI-2), followed by primary PTCA when appropriate. Data were collected by independent study monitors, end points were adjudicated and films were read at an independent core laboratory. RESULTS Of 1,100 patients with AMI, 58 (5.3%) had undergone previous CABG. The infarct-related vessel in these patients was a bypass graft in 32 patients (55%) and a native coronary artery in 26 patients. Compared with patients without previous CABG, patients with previous CABG were older and more frequently had a previous myocardial infarction and triple-vessel disease. Coronary angioplasty was less likely to be performed when the infarct-related vessel was a bypass graft rather than a native coronary artery (71.9% vs. 89.8%, p = 0.001); Thrombolysis in Myocardial Infarction trial (TIMI) flow grade 3 was less frequently achieved (70.2% vs. 94.3%, p < 0.0001); and in-hospital mortality was increased (9.4% vs. 2.6%, p = 0.02). As a result, mortality at six months was 14.3% versus 4.1% in patients with versus without previous CABG (p = 0.001). By multivariate analysis, independent determinants of late mortality in the entire study group were advanced age, triple-vessel disease, Killip class and post-PTCA TIMI flow grade <3. CONCLUSIONS Reperfusion success of a primary PTCA strategy in patients with previous CABG, although favorable with respect to historic control studies, is reduced as compared with that in patients without previous CABG. New approaches are required to treat patients with previous CABG and AMI, especially when the infarct-related vessel is a diseased saphenous vein graft.

Role of cardiac surgery in the hospital phase management of patients treated with primary angioplasty for acute myocardial infarction.

Although cardiac surgery is performed in approximately 10% of acute myocardial infarction (AMI) patients undergoing a primary percutaneous transluminal coronary angioplasty (PTCA) reperfusion strategy before discharge, the indications for and timing of operative revascularization, and the short- and long-term outcomes after surgery have not been characterized. In the prospective, controlled Primary Angioplasty in Myocardial Infarction-2 trial, cardiac catheterization was performed in 1,100 patients within 12 hours of onset of AMI at 34 centers, followed by primary PTCA when appropriate. Cardiac surgery was performed before hospital discharge in 120 patients (10.9%), electively in 42.6%, and on an urgent or emergent basis in 57.4%. Surgery was performed in 6.1% of 982 patients after primary PTCA (although emergently for failed PTCA in only 4 cases [0.4%]), and in 53 of 118 patients (44.9%) not undergoing primary PTCA. Patients requiring surgery were older, and more frequently had diabetes and 3-vessel disease than those managed nonoperatively. Internal mammary artery grafts were placed in only 31% of patients. In-hospital mortality was 6.4% in patients undergoing urgent/emergent surgery, 2.0% after elective surgery, and 2.6% in patients not undergoing surgery (p = NS). After multivariate correction for baseline risk factors, early and late survival free of reinfarction were similar in patients undergoing versus not undergoing in-hospital cardiac surgery. Thus, the appropriate use of coronary artery bypass graft surgery in the peri-infarction period is an integral component of the primary PTCA approach, and is frequently used to optimize the prognosis of a high-risk AMI cohort with unfavorable baseline features. The implications for the performance of primary PTCA in AMI at centers without on-site surgical facilities are discussed.

Safety and efficacy of switching from either unfractionated Heparin or Enoxaparin to Bivalirudin in patients with Non-ST-Segment elevation acute coronary syndromes managed with an invasive strategy. Results from the ACUITY trial

OBJECTIVESnThe aim of this study was to compare outcomes in patients receiving consistent unfractionated heparin (UFH)/enoxaparin (ENOX) therapy and in those switched at randomization to bivalirudin monotherapy.nnnBACKGROUNDnCrossover between UFH and ENOX has been associated with increased adverse outcomes in patients with acute coronary syndromes. The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial demonstrated superior net clinical outcomes with similar rates of ischemia and significantly less major bleeding with bivalirudin monotherapy compared with UFH/ENOX plus a glycoprotein (GP) IIb/IIIa inhibitor. It is unknown if these results would be preserved in patients switched from UFH/ENOX to bivalirudin monotherapy.nnnMETHODSnWe compared composite ischemia, major bleeding, and net clinical outcomes at 30 days in patients receiving consistent UFH/ENOX therapy and in those switched at randomization from pre-treatment with UFH/ENOX to bivalirudin monotherapy. We also compared outcomes in patients naive to antithrombin therapy who were randomized to UFH/ENOX or bivalirudin monotherapy.nnnRESULTSnTwo thousand one hundred thirty-seven patients received consistent UFH/ENOX (UFH n = 1,294, ENOX n = 843), and 2,078 patients pre-treated with UFH/ENOX were switched to bivalirudin. Patients switching to bivalirudin had similar rates of ischemia (6.9% vs. 7.4%, p = 0.52), less major bleeding (2.8% vs. 5.8%, p < 0.01), and improved net clinical outcomes (9.2% vs. 11.9%, p < 0.01) than those on consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy who were administered bivalirudin (n = 1,427) had similar rates of ischemia (6.2% vs. 5.5%, p = 0.47), less major bleeding (2.5% vs. 4.9%, p < 0.001), and similar net clinical outcomes (8.0% vs. 9.4%, p = 0.17) compared with naive patients administered UFH/ENOX plus a GP IIb/IIIa inhibitor (n = 1,462).nnnCONCLUSIONSnSwitching from UFH/ENOX to bivalirudin monotherapy results in comparable ischemic outcomes and an approximately 50% reduction in major bleeding compared with consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy administered bivalirudin monotherapy had a significant reduction in bleeding and similar rates of ischemia compared with naive patients initiated with UFH or ENOX plus a GP IIb/IIIa inhibitor.