Alexandra J. Lansky

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.

LOCALIZED INTRACORONARY GAMMA-RADIATION THERAPY TO INHIBIT THE RECURRENCE OF RESTENOSIS AFTER STENTING

BACKGROUND Although the frequency of restenosis after coronary angioplasty is reduced by stenting, when restenosis develops within a stent, the risk of subsequent restenosis is greater than 50 percent. We report on a multicenter, double-blind, randomized trial of intracoronary radiation therapy for the treatment of in-stent restenosis. METHODS Of 252 eligible patients in whom in-stent restenosis had developed, 131 were randomly assigned to receive an indwelling intracoronary ribbon containing a sealed source of iridium-192, and 121 were assigned to receive a similar-appearing nonradioactive ribbon (placebo). RESULTS The primary end point, a composite of death, myocardial infarction, and the need for repeated revascularization of the target lesion during nine months of follow-up, occurred in 53 patients assigned to placebo (43.8 percent) and 37 patients assigned to iridium-192 (28.2 percent, P=0.02). However, the reduction in the incidence of major adverse cardiac events was determined solely by a diminished need for revascularization of the target lesion, not by reductions in the incidence of death or myocardial infarction. Late thrombosis occurred in 5.3 percent of the iridium-192 group, as compared with 0.8 percent of the placebo group (P=0.07), resulting in more late myocardial infarctions in the iridium-192 group (9.9 percent vs. 4.1 percent, P=0.09). Late thrombosis occurred in irradiated patients only after the discontinuation of oral antiplatelet therapy (with ticlopidine or clopidogrel) and only in patients who had received new stents at the time of radiation treatment. CONCLUSIONS Intracoronary irradiation with iridium-192 resulted in lower rates of clinical and angiographic restenosis, although it was also associated with a higher rate of late thrombosis, resulting in an increased risk of myocardial infarction. If the problem of late thrombosis within the stent can be overcome, intracoronary irradiation with iridium-192 may become a useful approach to the treatment of in-stent restenosis.

Intracoronary β-Radiation Therapy Inhibits Recurrence of In-Stent Restenosis

Background —Intracoronary γ-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 β-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 γ-WRIST. Conclusions —β-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.

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.

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.

Late total occlusion after intracoronary brachytherapy for patients with in-stent restenosis☆

OBJECTIVES The study sought to determine the incidence and predictors of late total occlusion (LTO, >30 days) in-patients with in-stent restenosis who were treated with intracoronary radiation. BACKGROUND Intracoronary radiation both with beta and gamma emitters has been shown to reduce recurrent in-stent restenosis. METHODS We reviewed the records of 473 patients who presented with in-stent restenosis and who were enrolled in various radiation protocols, whether randomized to placebo versus radiation or entered into registries. There were 165 placebo and 308 radiated patients, including both gamma and beta emitters. Maximum dose to the vessel wall was 30 to 55 Gy. Following radiation, all patients received antiplatelet therapy with aspirin and either ticlopidine or clopidogrel for one month. All patients completed at least six months of angiographic follow-up. RESULTS The LTO was documented in 28 patients (9.1%) from the irradiated group versus 2 placebo patients (1.2%), p < 0.0001. The LTO rates were similar across studies and emitters. In the irradiated group, LTO presented as acute myocardial infarction in 12 patients (43%), unstable angina in 14 (50%), and asymptotic in 2 (7%). Mean time to LTO was 5.4 +/- 3.2 months in the irradiated group versus 4.5 +/- 2.1 in placebo patients (p = NS). The overall rate of restenting for the entire study group at the time of radiation was 48.6%. Importantly, new stents were placed in 82% of the irradiated and in 100% of the placebo patients who presented with LTO. Multivariate analysis determined that new stenting was the main predictor of LTO. CONCLUSIONS Intracoronary radiation for patients with in-stent restenosis is associated with a high rate of LTO. Restenting may contribute late thrombosis. Prolonged antiplatelet therapy (up to six months) should be considered for these patients.

Myocardial First-Pass Perfusion Magnetic Resonance Imaging A Multicenter Dose-Ranging Study

Background—MRI can identify patients with obstructive coronary artery disease by imaging the left ventricular myocardium during a first-pass contrast bolus in the presence and absence of pharmacologically induced myocardial hyperemia. The purpose of this multicenter dose-ranging study was to determine the minimally efficacious dose of gadopentetate dimeglumine injection (Magnevist Injection; Berlex Laboratories) for detecting obstructive coronary artery disease. Method and Results—A total of 99 patients scheduled for coronary artery catheterization as part of their clinical evaluation were enrolled in this study. Patients were randomized to 1 of 3 doses of gadopentate dimeglumine: 0.05, 0.10, or 0.15 mmol/kg. First-pass perfusion imaging was performed during hyperemia (induced by a 4-minute infusion of adenosine at a rate of 140 &mgr;g · kg−1 · min−1) and then again in the absence of adenosine with otherwise identical imaging parameters and the same contrast dose. Perfusion defects were evaluated subjectively by 4 blinded reviewers. Receiver-operating curve analysis showed that the areas under the receiver-operating curve were 0.90, 0.72, and 0.83 for the low-, medium-, and high-contrast doses, respectively, compared with quantitative coronary angiography (diameter stenosis ≥70%). For the low-dose group, mean sensitivity was 93±0%, mean specificity was 75±7%, and mean accuracy was 85±3%. Conclusions—First-pass perfusion MRI is a safe and accurate test for identifying patients with obstructive coronary artery disease. A low dose of 0.05 mmol/kg gadopentetate dimeglumine is at least as efficacious as higher doses.

Percutaneous Coronary Intervention and Adjunctive Pharmacotherapy in Women A Statement for Healthcare Professionals From the American Heart Association

More than 1.2 million percutaneous coronary interventions are performed annually in the United States, with only an estimated 33% performed in women, despite the established benefits of percutaneous coronary intervention and adjunctive pharmacotherapy in reducing fatal and nonfatal ischemic complications in acute myocardial infarction and high-risk acute coronary syndromes. This statement reviews sex-specific data on the safety and efficacy of contemporary interventional therapies in women.

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.

One-year follow-up after intravascular ultrasound assessment of moderate left main coronary artery disease in patients with ambiguous angiograms ☆

OBJECTIVES The purpose of this study was to correlate angiographic and intravascular ultrasound (IVUS) findings in left main coronary artery (LMCA) disease and identify the predictors of coronary events at one year in patients with LMCA stenoses. BACKGROUND Significant (> or =50% diameter stenosis [DS]) LMCA disease has a poor long-term prognosis. METHODS One hundred twenty-two patients who underwent angiographic and IVUS assessment of the severity of LMCA disease and who did not have subsequent catheter or surgical intervention were followed for one year. Standard clinical, angiographic and IVUS parameters were collected. RESULTS The quantitative coronary angiography (QCA) reference diameter (3.91 +/- 0.76 mm, mean +/- 1 SD) correlated moderately with IVUS (4.25 +/- 0.78 mm, r = 0.492, p = 0.0001). The lesion site minimum lumen diameter (MLD) (2.26 +/- 0.82 mm) by QCA correlated less well with IVUS (2.8 +/- 0.82 mm, r = 0.364, p = 0.0005). The QCA DS measured 42 +/- 16%. During the follow-up period, 4 patients died, none had a myocardial infarction, 3 underwent catheter-based LMCA intervention and 11 underwent bypass surgery. Univariate predictors of events (p < 0.05) were diabetes, presence of another lesion whether treated with catheter-based intervention or untreated with DS > 50% and IVUS reference plaque burden and lesion lumen area, maximum lumen diameter, MLD, plaque area and area stenosis. Using logistic regression analysis diabetes mellitus, an untreated vessel (with a DS > 50%) and IVUS MLD were independent predictors of cardiac events. CONCLUSIONS In selected patients assessed by IVUS, moderate LMCA disease had a one-year event rate of only 14%. Intravascular ultrasound MLD was the most important quantitative predictor of cardiac events. For any given MLD, the event rate was exaggerated in the presence of diabetes or another untreated lesion (>50% DS).