Optical coherence tomography characteristics of in-stent restenosis after drug-eluting stent implantation: a novel classification and its clinical significance.

This study aimed to establish a novel classification of in-stent restenosis (ISR) morphological characteristics after drug-eluting stent (DES) implantation as visualized by optical coherence tomography (OCT) and determine its clinical significance. A total of 133 lesions with intrastent restenosis after DES implantation were imaged by OCT. Neointimal tissue characteristics were categorized according to the classical classification as either homogeneous, heterogeneous, or layered. Then all tissues were also classified into six types as follows: homogeneous high-intensity tissue (type I), heterogeneous tissue with signal attenuation (type II), speckled heterogeneous tissue (type III), heterogeneous tissue containing poorly delineated region with invisible strut (type IV), heterogeneous tissue containing sharply delineated low-intensity region (type V), or bright protruding tissue with an irregular surface (type VI). The kappa value for interobserver agreement between the two observers was higher in the modified classification than in the classical classification (0.97 and 0.72, respectively). Most lesions classified as type V and VI were likely to be identified in patients on hemodialysis and located at the ostial right coronary artery. The duration from stent implantation to ISR was significantly longer in types IV and VI than in others. The incidence of stent fracture was significantly higher in types I and IV. This new modified classification enabled us to classify most ISR lesions easily with higher reproducibility. The clinical significance of neointimal restenotic tissue classification by OCT became clear while using the modified classification.

Incidence and classification of neointimal proliferation and in-stent restenosis in post-stenting patients at 1-year interval: findings from non-invasive coronary computed tomography angiography.

OBJECTIVES: To evaluate the incidence of coronary in-stent restenosis (ISR) and neointimal proliferation by coronary CT angiography (CCTA) at 1-year follow-up in asymptomatic patients. METHODS: 234 patients (mean age: 67 ± 10.2 years, range 39-88 years, 180 males and 54 females) with 379 stents were prospectively enrolled in this study. Binary ISR was classified by CCTA into 4 types using Mehran classification. Neointimal proliferation was similarly classified into focal and diffuse types. All patients with CCTA-revealed ISR or neointimal proliferation underwent further invasive coronary angiography (ICA) for validation. Fisher's exact test was used for comparison. RESULTS: ICA revealed patent stents with neointimal proliferation in 39 patients (16.7%, 39/234) and binary ISR in 23 patients (9.8%, 23/234). Lesion-based analysis showed 12 type I ISR lesions, 4 type II ISR lesions, 1 type III ISR lesion and 7 type IV ISR lesions. Among cases with neointimal proliferation, 27 lesions were classified as focal type whereas 13 lesions were classified as diffuse type. Patients with diabetes mellitus were associated with higher incidence of CCTA-revealed neointimal proliferation (21/77 vs. 18/157, p=0.002) as well as ISR (12/77 vs. 11/157, p=0.038), compared to patients without diabetes. CCTA was found to have good diagnostic performance for neointimal proliferation and ISR detection as well as classification, with an overall accuracy of 84.4% (54/64). CONCLUSIONS: Silent ISR as well as neointimal proliferation is not uncommon findings in asymptomatic post-stenting patients at 1-year interval, as revealed by CCTA. Patients with diabetes are prone to have higher incidence of neointimal proliferation.

Baseline C-reactive protein serum levels and in-stent restenosis pattern after m-TOR inhibitors drug-eluting stent implantation.

BACKGROUND: A diffuse pattern of in-stent restenosis (ISR) has been shown to have a worse prognosis when compared to a focal pattern. It is still unknown whether baseline C-reactive protein (CRP) levels predict ISR pattern. METHODS: Our database was searched retrospectively for patients presenting with ISR after m-TOR inhibitor drug-eluting stent (DES) implantation from January 2007 to December 2009. Angiographic restenosis patterns were evaluated according to the simplified Mehran classification and patients were allocated either to the diffuse or focal pattern group. Predictors of restenosis pattern were assessed among clinical, angiographic, procedural and laboratory data, including baseline high-sensitivity CRP, recorded at the time of the first percutaneous intervention. RESULTS: 72 patients (age, 65 ± 9 years; male sex, 64%) found to have ISR after DES implantation were enrolled. 34 patients presented with a focal pattern, whereas 38 patients presented with a diffuse pattern. At multivariate analysis, CRP levels were the only independent predictor of a diffuse ISR pattern [odds ratio, 2.5; 95% confidence interval, 1.4-4.3; p = 0.001)]. Rising CRP tertiles were associated with an increased rate of diffuse pattern (13% versus 26% versus 61%; p for trend = 0.0001). CONCLUSION: Baseline CRP serum levels are associated with a diffuse ISR pattern after m-TOR inhibitor DES implantation. These findings suggest that baseline inflammatory reactivity may contribute to aggressive restenosis occurring despite drug elution.

Novel paclitaxel-eluting, biodegradable polymer coated stent in the treatment of de novo coronary lesions: a prospective multicenter registry.

OBJECTIVES: The purpose of the present study was to evaluate the efficacy and safety of a biodegradable polymer coated, paclitaxel eluting stent (Luc-Chopin(2)) based on 9-months angiographic and 12-months clinical follow-up results. BACKGROUND: First-generation drug-eluting stents utilize nonbioabsorbable polymeric coatings, whose persistent presence in the arterial wall may negatively affect long-term outcomes. Bioabsorbable coatings with a degradation period matched to that of the drug elution may be a better alternative, clinically and economically. METHODS: We conducted a prospective, multicenter first-in-man registry of a novel, locally developed, bioabsorbable-coated, paclitaxel-eluting coronary stent in 116 patients with single-lesion de novo coronary disease. RESULTS: Major adverse cardiac events occurred in 7.8% patients within 12 months. There were no late thrombotic events, death, stroke, or surgical revascularization in that period. There were two myocardial infarctions, one related to recent subacute stent thrombosis and another associated with restenosis. By 12 months, target vessel revascularization was performed in 7.8%; 2.9% were ischemia-driven and the rest were mandated at 9 months in accordance with a control angiography protocol. Core-lab assessed binary in-stent restenosis (> or =50% DS) was noted in 11.9% patients and mean late loss was 0.46 +/- 0.47 mm. CONCLUSIONS: This first-in-man experience obtained in a multicenter registry of real-world de novo lesions (almost half of lesions were class B2 or C by AHA classification) showed a favorable safety profile and acceptable efficacy through 12 months. Randomized comparison with a benchmark nonbioabsorbable polymer coated paclitaxel eluting stent should be undertaken to validate this initial positive experience.

Diagnostic accuracy of coronary in-stent restenosis using 64-slice computed tomography: comparison with invasive coronary angiography.

OBJECTIVES: This study sought to evaluate the diagnostic accuracy of coronary binary in-stent restenosis (ISR) with angiography using 64-slice multislice computed tomography coronary angiography (CTCA) compared with invasive coronary angiography (ICA). BACKGROUND: A noninvasive detection of ISR would result in an easier and safer way to conduct patient follow-up. METHODS: We performed CTCA in 81 patients after stent implantation, and 125 stented lesions were scanned. Two sets of images were reconstructed with different types of convolution kernels. On CTCA, neointimal proliferation was visually evaluated according to luminal contrast attenuation inside the stent. Lesions were graded as follows: grade 1, none or slight neointimal proliferation; grade 2, neointimal proliferation with no significant stenosis (<50%); grade 3, neointimal proliferation with moderate stenosis (> or =50%); and grade 4, neointimal proliferation with severe stenosis (> or =75%). Grades 3 and 4 were considered binary ISR. The diagnostic accuracy of CTCA compared with ICA was evaluated. RESULTS: By ICA, 24 ISRs were diagnosed. Sensitivity, specificity, positive predictive value, and negative predictive value were 92%, 81%, 54%, and 98% for the overall population, whereas values were 91%, 93%, 77%, and 98% when excluding unassessable segments (15 segments, 12%). For assessable segments, CTCA correctly diagnosed 20 of the 22 ISRs detected by ICA. Six lesions without ISR were overestimated as ISR by CTCA. As the grade of neointimal proliferation by CTCA increases, the median value of percent diameter stenosis increased linearly. CONCLUSIONS: Binary ISR can be excluded with high probability by CTCA, with a moderate rate of false-positive results.

Morphology and location of restenosis following bare metal coronary stenting.

Restenosis following bare metal coronary stenting is common. The location and characteristics of restenotic lesions in patients who have undergone coronary stent implantation is not well described. The purpose of this study was to determine the location, type and temporal distribution of stent-related restenosis. We reviewed the clinical and angiographic characteristics of 203 consecutive patients with stent-related restenosis undergoing a repeat clinically-indicated coronary angiogram, 30 days to 1 year after the index procedure. All lesions within 10 mm of the proximal and distal margins of the stent were included in the analysis. An angiographic classification was developed based on lesion location. Class I lesions were those occurring within the stent, and Class II comprised those lesions occurring within 10 mm of the proximal and distal stent edge. We classified a total of 234 stent-related restenosis lesions. Class I lesions were found in 52% of patients, and Class II in 48%. Three-fifths of the patients who developed new lesions at a stent edge presented 1-3 months following the initial procedure, which was significantly earlier than other lesion types (p < 0.001). A substantial number of patients undergoing repeat angiography after stent placement have lesions proximate, but peripheral, to the stent. This may limit the effectiveness of stent-based efforts to reduce restenosis. The time interval between coronary stenting and symptom recurrence appears to vary according to lesion location.

Value of the American College of Cardiology/American Heart Association angiographic classification of coronary lesion morphology in patients with in-stent restenosis. Insights from the Restenosis Intra-stent Balloon angioplasty versus elective Stenting (RIBS) randomized trial.

BACKGROUND: The implications of the American College of Cardiology/American Heart Association (ACC/AHA) lesion classification in patients with in-stent restenosis (ISR) are unknown. METHODS: Four hundred fifty patients included in the RIBS randomized study were analyzed. A centralized core laboratory assessed ISR classifications including ACC/AHA, the classification of Mehran et al (Circulation 1999;100:1872-8), diffuse/focal, and a new quantitative ISR index (lesion length/stent length). Logistic regression models were constructed for prespecified outcome measures including (1) unsatisfactory acute results and (2) recurrent restenosis rate. RESULTS: Complex (B2/C) lesions (78%) more frequently obtained unsatisfactory acute results (20% vs 8%, P = .007), smaller minimal lumen diameter after the procedure (2.45 +/- 0.5 vs 2.73 +/- 0.5 mm, P = .001) and at follow-up (1.48 +/- 0.8 vs 1.94 +/- 0.8 mm, P = .0001), and had a higher restenosis rate (43 vs 24%, P = .001) than simple (A/B1) lesions. On logistic regression analysis, all classification schemes were useful to predict unsatisfactory initial results (area under the curve: 0.63, 0.61, 0.59, and 0.62) and recurrent restenosis (area under the curve: 0.60, 0.64, 0.61, and 0.63). The predictive ability of these schemes persisted despite adjustment for potential confounders. Although the ACC/AHA classification was a better predictor of acute results, the classification of Mehran was superior to predict restenosis. CONCLUSIONS: The ACC/AHA classification provides a useful tool to determine acute procedural results and the long-term angiographic outcome of patients with ISR.

Classification and current treatment options of in-stent restenosis. Present status and future perspectives.

Coronary stent implantation is currently performed in > 80% of percutaneous coronary interventions. Its main late complication is the development of in-stent restenosis (ISR), occurring in 10-80% of lesions treated in daily practice. The classification by Mehran et al. is most commonly used. Current therapeutic options to treat ISR include repeat balloon angioplasty, repeat stenting, cutting balloon angioplasty, directional coronary atherectomy, rotational coronary atherectomy, brachytherapy, and drug-eluting stents (DES). DES have been effective in reducing binary restenosis in de novo lesions in randomized controlled trials. The novel use of DES to treat ISR has been shown to be safe and effective in multiple studies involving sirolimus- and paclitaxel-eluting stents. As DES implantation becomes more widespread, ISR in DES is emerging as a new problem. The use of debulking techniques to treat ISR in DES is to be cautioned against. In this new era, the optimal treatment of this new problem is currently unknown. We await further data to see whether repeat DES implantation may help solve this vexing clinical problem.

Risk stratification, management and outcomes of patients with non-ST elevation acute coronary syndrome: a Canadian teaching hospital perspective.

BACKGROUND: Current guidelines for non-ST elevation acute coronary syndromes (NSTACS) recommend tailoring the intensity of therapeutic management according to the baseline risk of the patient. Although the clinical characteristics, risk stratification and therapeutic management of contemporary patients with NSTACS have been reported for other geographical regions, this information has not been documented from a Canadian perspective. OBJECTIVES: To describe the baseline clinical characteristics, therapeutic management and clinical outcomes of contemporary patients with NSTACS at a Canadian, tertiary care, teaching hospital, and to retrospectively risk stratify the patients with NSTACS according to the American College of Cardiology (ACC)/American Heart Association (AHA) and Thrombolysis in Myocardial Infarction (TIMI) risk guidelines to characterize management and outcomes according to the various risk classifications. METHODS: Baseline demographics, procedural variables and clinical outcome data were retrospectively collected in 380 patients with a diagnosis of NSTACS from July 1999 to July 2000. Patients were retrospectively categorized into high, intermediate and low risk categories using two classification schemes. RESULTS: According to the ACC/AHA guidelines, 10.3% and 89.7% of patients were intermediate and high risk, respectively. Applying the TIMI risk score, 20.0%, 52.4% and 27.6% of patients were low, intermediate and high risk, respectively. The use of antithrombotic, acetylsalicylic acid and beta-blocker therapy was very high both in hospital and at discharge. Glycoprotein IIb/IIIa inhibitors, angiotensin-converting enzyme inhibitors and lipid lowering agents were all underutilized. The use of pharmacological therapies and cardiovascular interventions did not appear to correlate with the level of risk of the patient, at least within these classification schemes. Adverse clinical events in hospital and length of hospital stay increased as the risk level of the patients increased. CONCLUSIONS: According to the ACC/AHA guidelines, patients with a discharge diagnosis of NSTACS in a nontrial setting are a high risk population, requiring prompt recognition and aggressive management. This study serves as an integral part of clinical practice to continually evaluate the quality of medical care.

Influence of residual stenosis after percutaneous coronary intervention with stent implantation on development of restenosis and stent thrombosis.

The aim of this study was to assess the effects of residual stenosis after single-stent implantation on the rate of stent thrombosis, as well as restenosis within a 6-month follow-up period. Coronary angiograms of 2,157 patients with 2,523 lesions treated with a single stent were analyzed by quantitative coronary angiography before, immediately after stent implantation, and at a planned 6-month follow-up. Lesions were classified into 4 subgroups according to the degree of residual stenosis after stent implantation: group 1, gross oversizing <-15%; group 2, slight oversizing -15% to <0%; group 3, mild residual 0% to <15%; group 4, moderate residual 15% to <30%. Stent thrombosis rates were not significantly different among the 4 subgroups (group 1: 0 of 60 [0%]; group 2: 2 of 388 [0.5%]; group 3: 8 of 1,370 [0.6%]; group 4: 8 of 705 [1.1%]; p = NS for all). An adequate dosage of ticlopidine (250 mg twice daily) and aspirin (100 mg/day) led to a lower rate of stent thrombosis (6 of 2,189 cases) than inadequate dosages or missing therapy (12 of 343 cases). In 1,882 stenoses with angiographic follow-up (77.7%), gross oversizing of stents lead to a significantly higher increase of percent stenosis (p <0.001) associated with a higher restenosis rate (group 1: 34.7% vs groups 2, 3, and 4: 32.5%, 28.2%, and 29.6%, respectively). A multiple regression analysis was performed. Optimal results with regard to stent thrombosis and restenosis were achieved with mild residual stenoses between 0% and 15% after stent implantation. Oversizing of stents is no longer necessary with an adequate dosage of ticlopidine and aspirin.