Generalized pairwise comparison methods to analyze (non)prioritized composite endpoints.

In the analysis of composite endpoints in a clinical trial, time to first event analysis techniques such as the logrank test and Cox proportional hazard test do not take into account the multiplicity, importance, and the severity of events in the composite endpoint. Several generalized pairwise comparison analysis methods have been described recently that do allow to take these aspects into account. These methods have the additional benefit that all types of outcomes can be included, such as longitudinal quantitative outcomes, to evaluate the full treatment effect. Four of the generalized pairwise comparison methods, ie, the Finkelstein-Schoenfeld, the Buyse, unmatched Pocock, and adapted O'Brien test, are summarized. They are compared to each other and to the logrank test by means of simulations while specifically evaluating the effect of correlation between components of the composite endpoint on the power to detect a treatment difference. These simulations show that prioritized generalized pairwise comparison methods perform very similarly, are sensitive to the priority rank of the components in the composite endpoint, and do not measure the true treatment effect from the second priority-ranked component onward. The nonprioritized pairwise comparison test does not suffer from these limitations and correlation affects only its variance.

Predictors of marital longevity after new spinal cord injury.

STUDY DESIGN: Prospective cohort design of married persons with new spinal cord injury (SCI). OBJECTIVES: To examine the relationship of demographic and injury characteristics, self-rated health, physical functioning, and life satisfaction to the duration of marriage 1 to 15 years after SCI among individuals who were married at the time of injury. SETTING: United States. METHODS: Survival analysis was chosen to determine the predictors related to marital longevity, which is defined as non-occurrence of divorce after injury. In all, 2327 subjects were included in the analyses. Predictors were demographics and injury characteristics, level of handicap, self-perceived health, and functional independence. RESULTS: Age at injury, being Caucasian vs African American, having a college education vs high school, having 'other' employment status vs being unemployed, having higher social integration and improved or stable self-rated health vs poor health were all significant factors that delayed the time of divorce after injury. Contrary to expectations, level of injury, function, mobility and independence were not significant predictors of marriage longevity. CONCLUSION: Social integration and health perception, the most powerful indicators of marriage longevity, can be addressed and facilitated by health care providers and rehabilitation programs.

Echocardiographic assessment of pressure volume relations in heart failure and valvular heart disease: using imaging to understand physiology.

Pressure volume (PV) based analysis, using classic hemodynamic principles, has served as a basis for our understanding of cardiac physiology and disease states for decades. However, PV analysis has been restricted to primarily the basic research setting and for preclinical testing and has not be widely applied in part because of the invasive nature of the procedure and the expertise required to obtain adequate data using the conductance catheter. Development of single beat methodologies that rely on echocardiographic measurements of ventricular volume and Doppler and peripheral estimates of ventricular pressure and timing of the cardiac cycle has enabled broader application of PV analysis. This review explores the physiologic background, basic methodology, and recent and potential future applications of noninvasive PV analysis.

Potential role of human cytomegalovirus and p53 interaction in coronary restenosis.

A subset of patients who have undergone coronary angioplasty develop restenosis, a vessel renarrowing characterized by excessive proliferation of smooth muscle cells (SMCs). Of 60 human restenosis lesions examined, 23 (38 percent) were found to have accumulated high amounts of the tumor suppressor protein p53, and this correlated with the presence of human cytomegalovirus (HCMV) in the lesions. SMCs grown from the lesions expressed HCMV protein IE84 and high amounts of p53. HCMV infection of cultured SMCs enhanced p53 accumulation, which correlated temporally with IE84 expression. IE84 also bound to p53 and abolished its ability to transcriptionally activate a reporter gene. Thus, HCMV, and IE84-mediated inhibition of p53 function, may contribute to the development of restenosis.

Delivery strategies to achieve therapeutic myocardial angiogenesis.

The use of recombinant genes or growth factors to enhance myocardial collateral blood vessel function may represent a new approach to the treatment of cardiovascular disease. Proof of concept has been demonstrated in animal models of myocardial ischemia, and clinical trials are underway. Currently, it is unknown which is the safest and most effective delivery strategy to induce clinically important therapeutic angiogenic responses in ischemic myocardium. Most strategies for transcatheter delivery of angiogenic factors have used an intracoronary route, which may have limitations because of imprecise localization of genes or proteins and systemic delivery to noncardiac tissue. The effect of direct intraoperative intramyocardial injection of angiogenic factors on collateral function has been reported in experimental models, and angiogenesis is being studied after direct intramyocardial injection of angiogenic peptides or plasmid vectors during open heart surgery in patients. Catheter-based transendocardial injection of angiogenic factors may provide equivalent benefit without the need for surgery. Intrapericardial delivery of angiogenic factors may offer a theoretical advantage of prolonged exposure of either coronary or myocardial tissue to the administered drug as result of a reservoir function of the pericardium. In this article, we review the different modes of administration for therapeutic myocardial angiogenesis therapy.

Effect of the distal-balloon protection system on microembolization during carotid stenting.

BACKGROUND: The distal-balloon protection system is being evaluated for its efficacy in preventing embolic neurological events during carotid stenting (CAS). We sought to determine the effect of this system on the frequency of Doppler-detected microembolic signals (MES) during CAS. METHODS AND RESULTS: Using transcranial Doppler, we compared the frequency of MES during CAS in 2 groups: 39 patients without distal protection and 37 who used the distal-balloon protection system (GuardWire). There were no significant differences in the clinical or angiographic characteristics between the 2 groups. Three phases with increased MES counts were identified during unprotected CAS; these were stent deployment, predilation, and postdilation (75+/-57, 32+/-36, and 27+/-25 METS, respectively). The distal-balloon protection significantly reduced the frequency of MES during CAS (MES counts: 164+/-108 in the control versus 68+/-83 in the protection group; P=0.002), particularly during these 3 phases. MES in the protection group were detected predominantly during sheath placement, guidewire manipulation, and distal-balloon deflation. CONCLUSION: Three phases with increased MES counts were identified during unprotected CAS (eg, stent deployment, predilation, and postdilation). The distal-balloon protection system significantly reduced the frequency of MES during CAS, particularly during these 3 phases.

Differential impact on survival of electrocardiographic Q-wave versus enzymatic myocardial infarction after percutaneous intervention: a device-specific analysis of 7147 patients.

BACKGROUND: The relative prognostic importance of ECG myocardial infarction (MI) after intervention compared with varying degrees of enzymatic elevation has not been characterized, and the device-specific implications of periprocedural MI are also unknown. METHODS AND RESULTS: Serial creatine phosphokinase (CPK)-MB levels were determined after elective percutaneous intervention of 12 098 lesions in 7147 consecutive patients at a tertiary referral center. Procedural, in-hospital, and follow-up data were collected by independent research nurses, and clinical and ECG events were adjudicated by a separate committee. Stents were implanted in 50.6% of lesions, atheroablation was performed in 54.8%, and PTCA alone was performed in 9.8%. The peak periprocedural CPK-MB level was >3x the upper limit of normal (ULN) in 17.9% of patients, and Q-wave MI developed in 0.6%. By multivariate analysis, the periprocedural development of new Q waves was the most powerful independent determinant of death (2-year mortality rate, 38.3%; hazard ratio, 9.9; P<0.0001). Non-Q-wave MI with CPK-MB >8x ULN was also a strong predictor of death (2-year mortality rate, 16.3%; hazard ratio, 2.2; P<0.0001); survival was unaffected by lesser degrees of CPK-MB elevation. Though CPK-MB elevation was more common after atheroablation and stenting than PTCA, the rates of Q-wave MI and survival were device-independent. CONCLUSIONS: Myonecrosis after percutaneous intervention is common in a high-risk referral population dominated by atheroablation and stent use. Large periprocedural infarctions (signified by new Q waves and CPK-MB >8xULN) are powerful determinants of death, whereas lesser degrees of CPK-MB release and specific device use do not adversely affect survival.

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

BACKGROUND: Elevation 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). METHODS AND RESULTS: We 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. CONCLUSIONS: CK-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.

Safety of intracoronary gamma-radiation on uninjured reference segments during the first 6 months after treatment of in-stent restenosis: a serial intravascular ultrasound study.

BACKGROUND: The effects of endovascular irradiation on uninjured reference segments during the treatment of in-stent restenosis are unknown. METHODS AND RESULTS: In the Washington Radiation for In-Stent restenosis Trial (WRIST), patients with in-stent restenosis were first treated with conventional catheter-based techniques and then randomized (blinded) to receive either gamma-irradiation ((192)Ir) or a placebo (dummy seeds). We identified all patients in whom the active (n=19) or dummy seeds (n=19) extended >10 mm proximal and distal to the in-stent restenosis lesion. Serial (postirradiation and follow-up) external elastic membrane (EEM), lumen, and plaque and media (EEM-lumen) areas were measured (using intravascular ultrasound) every 1 mm over 5-mm-long reference segments that were 6 to 10 mm proximal and distal to the in-stent restenosis lesion. During follow-up, a similar small increase occurred in the plaque and media area in the proximal and distal reference segments in both (192)Ir and placebo patients. However, in the (192)Ir patients, an increase in both proximal and distal EEM area occurred; as a result, no change in lumen area occurred. Conversely, in the placebo patients, the proximal reference EEM area decreased, and no change occurred in the distal reference EEM area; this contributed to a decrease in lumen area. CONCLUSIONS: There was no evidence of a deleterious effect of gamma-irradiation on angiographically normal uninjured reference segments in the first 6 months after the treatment of in-stent restenosis.

One-year clinical outcome after minimally invasive direct coronary artery bypass.

BACKGROUND: Minimally invasive coronary artery bypass (MIDCAB) is a new surgical technique by which the left internal mammary artery is anastomosed under direct visualization to the left anterior descending artery without cardiopulmonary bypass. METHODS AND RESULTS: We followed all 274 patients who underwent MIDCAB from the time it was introduced at a single center. In-hospital and 1-year clinical events were source-documented and adjudicated. The in-hospital major acute cardiac event rate was 2.2%; this included a 1.1% mortality rate. At 1 year, the respective rates were 7.8% and 2. 5%. When compared with the initial 100 procedures, the subsequent 174 procedures had shorter vessel occlusion times (10+/-5 versus 14+/-6 minutes; P:=0.009), times to extubation (6+/-3 versus 14+/-10 hours; P:<0.001), and lengths of hospital stay (2.1+/-1.9 versus 3. 2+/-3.1 days; P:=0.04). Cumulative 1-year adverse cardiac events were 11% in the initial 100 cases and 6% in the subsequent 174 cases (P:=0.17). CONCLUSIONS: Excellent clinical results can be achieved with the MIDCAB technique. The clinical adverse event rate may decrease with accumulated experience.

Preintervention arterial remodeling as an independent predictor of target-lesion revascularization after nonstent coronary intervention: an analysis of 777 lesions with intravascular ultrasound imaging.

BACKGROUND: Pathological 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. METHODS AND RESULTS: We 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. CONCLUSIONS: Positive 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.

Three-year clinical and angiographic follow-up after intracoronary radiation : results of a randomized clinical trial.

BACKGROUND: Although several early trials indicate treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The objective of this report is to document angiographic and clinical outcome 3 years after treatment of restenotic stented coronary arteries with catheter-based (192)Ir. METHODS AND RESULTS: A double-blind, randomized trial compared (192)Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to (192)Ir and 29 to placebo. At 3-year follow-up, target-lesion revascularization was significantly lower in the (192)Ir group (15. 4% versus 48.3%; P<0.01). The dichotomous restenosis rate at 3-year follow-up was also significantly lower in (192)Ir patients (33% versus 64%; P<0.05). In a subgroup of patients with 3-year angiographic follow-up not subjected to target-lesion revascularization by the 6-month angiogram, the mean minimal luminal diameter between 6 months and 3 years decreased from 2.49+/-0.81 to 2.12+/-0.73 mm in (192)Ir patients but was unchanged in placebo patients. CONCLUSIONS: The early clinical benefits observed after treatment of coronary restenosis with (192)Ir appear durable at late follow-up. Angiographic restenosis continues to be significantly reduced in (192)Ir-treated patients, but a small amount of late loss was observed between the 6-month and 3-year follow-up time points. No events occurred in the (192)Ir group to suggest major untoward effects of vascular radiotherapy. At 3-year follow-up, vascular radiotherapy continues to be a promising new treatment for restenosis.

Intracoronary beta-radiation therapy inhibits recurrence of in-stent restenosis.

BACKGROUND: Intracoronary gamma-radiation therapy reduces recurrent in-stent restenosis (ISR). This study, BETA WRIST (Washington Radiation for In-Stent restenosis Trial) was designed to examine the efficacy and safety of the beta-emitter 90-yttrium for the prevention of recurrent ISR. METHODS AND RESULTS: A total of 50 consecutive patients with ISR in native coronaries underwent percutaneous transluminal coronary angioplasty, laser angioplasty, rotational atherectomy, and/or stent implantation. Afterward, a segmented balloon catheter was positioned and automatically loaded with a 90-yttrium, 0.014-inch source wire that was 29 mm in length to deliver a dose of 20.6 Gy at 1.0 mm from the balloon surface. In 17 patients, manual stepping of the radiation catheter was necessary for lesions >25 mm in length. The radiation was delivered successfully to all patients, with a mean dwell time of 3.0+/-0.4 minutes. Fractionation of the dose due to ischemia was required in 11 patients. At 6 months, the binary angiographic restenosis rate was 22%, the target lesion revascularization rate was 26%, and the target vessel revascularization rate was 34%; all rates were significantly lower than those of the placebo group of gamma-WRIST. CONCLUSIONS: beta-Radiation with a 90-yttrium source used as adjunct therapy for patients with ISR results in a lower-than-expected rate of angiographic and clinical restenosis.

Short- and intermediate-term clinical outcomes from direct myocardial laser revascularization guided by biosense left ventricular electromechanical mapping.

BACKGROUND: Direct myocardial revascularization (DMR) has been examined as an alternative treatment for patients with chronic refractory myocardial ischemic syndromes who are not candidates for conventional coronary revascularization. Methods and Results-We used left ventricular electromagnetic guidance in 77 patients with chronic refractory angina (56 men, mean age 61+/-11 years, ejection fraction 0.48+/-0.11) to perform percutaneous DMR with an Ho:YAG laser at 2 J/pulse. Procedural success (laser channels placed in prespecified target zones) was achieved in 76 of 77 patients with an average of 26+/-10 channels (range 11 to 50 channels). The rate of major in-hospital cardiac adverse events was 2.6%, with no deaths or emergency operations, 1 patient with postprocedural pericardiocentesis, and 1 patient with minor embolic stroke. The rate of out-of-hospital adverse cardiac events (up to 6 months) was 2.6%, with 1 patient with myocardial infarction and 1 patient with stroke. Exercise duration after DMR increased from 387+/-179 to 454+/-166 seconds at 1 month and to 479+/-161 seconds at 6 months (P=0.0001). The time to onset of angina increased from 293+/-167 to 377+/-176 seconds at 1 month and to 414+/-169 seconds at 6 months (P=0.0001). Importantly, the time to ST-segment depression (>/=1 mm) also increased from 327+/-178 to 400+/-172 seconds at 1 month and to 436+/-175 seconds at 6 months (P=0.001). Angina (Canadian Cardiovascular Society classification) improved from 3.3+/-0.5 to 2.0+/-1.2 at 6 months (P<0.001). Nuclear perfusion imaging studies with a dual-isotope technique, however, showed no significant improvements at 1 or 6 months. CONCLUSIONS: Percutaneous DMR guided by left ventricular mapping is feasible and safe and reveals improved angina and prolonged exercise duration for up to a 6-month follow-up.

Treatment of in-stent restenosis with excimer laser coronary angioplasty versus rotational atherectomy: comparative mechanisms and results.

BACKGROUND: Atheroablation yields improved clinical results for balloon angioplasty (percutaneous transluminal coronary angioplasty, PTCA) in the treatment of diffuse in-stent restenosis (ISR). METHODS AND RESULTS: We 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). CONCLUSIONS: Despite 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.

Effect of short pulsed nonablative infrared laser irradiation on vascular cells in vitro and neointimal hyperplasia in a rabbit balloon injury model.

BACKGROUND: Neointimal hyperplasia after PTCA is an important component of restenosis. METHODS AND RESULTS: Cultures of rabbit endothelial cells and smooth muscle cells (SMCs) were irradiated with different doses of nonablative infrared (1064-nm) radiation. Normalized viability index detected with nondestructive Alamar Blue assay and direct cell count were studied. Our experiments demonstrated dose-dependent cytostatic or cytotoxic effects of laser irradiation. We also evaluated the long-term effect of endoluminal nonablative infrared laser irradiation on neointimal hyperplasia in a rabbit balloon injury model. PTCA of both iliac arteries of 23 New Zealand White rabbits was performed. One iliac artery was subjected to intra-arterial subablative infrared irradiation via a diffuse tip fiber. The contralateral vessel served as control. The diet was supplemented with 0.25% cholesterol and 2% peanut oil for 10 days before and 60 days after PTCA. Morphometry after 60 days showed that intimal areas were 0.76+/-0.18 and 1.85+/-0.30 mm(2) in the laser and control arteries, respectively (P=2.2x10(-11)). CONCLUSIONS: We conclude that nonablative infrared laser inhibited neointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to 60 days.

Long-term follow-up after percutaneous transluminal coronary angioplasty was not performed based on intravascular ultrasound findings: importance of lumen dimensions.

BACKGROUND: Angiography is limited in determining the anatomic severity of coronary artery stenoses. Clinical decision-making in patients with symptoms and intermediate lesions remains challenging. METHODS AND RESULTS: The current analysis included 300 patients (357 intermediate native artery lesions) in whom intervention was deferred based on intravascular ultrasound (IVUS) findings. Standard clinical, angiographic, and IVUS parameters were collected. Patients were followed for >1 year. Events occurred in 24 patients (8%). They included 2 cardiac deaths, 4 myocardial infarctions, and 18 target-lesion revascularizations (TLR; 12 percutaneous transluminal coronary angiographies and 6 coronary artery bypass grafts; only 3 TLRs occurred within 6 months after the IVUS study). All significant univariate clinical, angiographic, and IVUS parameters (P<0.05) were tested in multivariate models. These included diabetes mellitus, IVUS lesion lumen area, maximum lumen diameter, minimum lumen diameter, plaque area, plaque burden, and area stenosis (AS). No angiographic measurement was significant at P<0.05. The only independent predictors of an event (death, myocardial infarction, or TLR) were IVUS minimum lumen area and AS. The only independent predictors of TLR were diabetes mellitus, IVUS minimum lumen area, and AS. In 248 lesions with a minimum lumen area >/=4.0 mm(2), the event rate was only 4.4% and the TLR rate 2.8%. CONCLUSIONS: Long-term follow-up after IVUS-guided deferred interventions in patients with de novo intermediate native artery lesions showed a low event rate. In patients with a minimum lumen area >/=4.0 mm(2), the event rate was especially low. IVUS imaging is an acceptable alternative to physiological assessment in these patients.

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

BACKGROUND: Although 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. METHODS AND RESULTS: We 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). CONCLUSIONS: Major CK-MB elevation occurs after 15% of otherwise successful SVG interventions and is associated with increased late mortality.

Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome.

BACKGROUND: The angiographic presentation of in-stent restenosis (ISR) may convey prognostic information on subsequent target vessel revascularizations (TLR). METHODS AND RESULTS: We 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. CONCLUSIONS: The introduced angiographic classification is prognostically important, and it may be used for appropriate and early patient triage for clinical and investigational purposes.

Randomized comparison of GR-II stent and Palmaz-Schatz stent for elective treatment of coronary stenoses.

BACKGROUND: This prospective multicenter randomized clinical trial was designed to evaluate the long-term angiographic and clinical outcomes of elective treatment with the GR-II stent compared with the Palmaz-Schatz (PS) stent in patients with coronary stenoses. METHODS AND RESULTS: Seven hundred fifty-five patients with myocardial ischemia and de novo native coronary stenoses in 3- to 4-mm vessels were randomly assigned to the PS (375 patients) or the GR-II stent (380 patients). The primary end point was 12-month target lesion revascularization (TLR)-free survival. Angiography was performed at baseline and at follow-up in the first 300 consecutive patients to assess the frequency of angiographic restenosis. Procedure success was 98.5% for the GR-II stent and 99.4% for the PS stent (P:=0.19). At 30 days, patients assigned to the GR-II stent had a higher stent thrombosis rate (3.9% versus 0.3% for PS stent, P:<0.001) and TLR rate (3.9% versus 0.5% for PS stent, P:<0.001). The GR-II group had a higher follow-up restenosis frequency (47.3% versus 20.6% for the PS group, P:<0.001) and a lower 12-month TLR-free survival rate (71.7% versus 83.9% for the PS group, P:<0. 001). Multivariate logistic regression analysis identified a smaller final stent minimal lumen diameter (odds ratio [OR] 2.49, 95% CI 1. 56 to 3.98; P:<0.001), diabetes mellitus (OR 2.14, 95% CI 1.42 to 3. 22; P:<0.001), and use of the GR-II stent (OR 1.78, 95% CI 1.20 to 2. 64; P:<0.01) as independent determinants of 12-month TLR. CONCLUSIONS: On the basis of these long-term follow-up data, we conclude that use of the GR-II stent should be limited to the acute treatment of abrupt or threatened closure after failed conventional balloon angioplasty procedures.