Kazuaki Mitsudo

Percutaneous recanalization of chronically occluded coronary arteries: A consensus document - Part II

In Part I of this article, the definitions, prevalence, and clinical presentation of chronic total occlusions (CTOs) were reviewed, the histopathology of CTOs was examined, efforts to replicate human CTOs with experimental models were appraised, and the clinical relevance and rationale for CTO revascularization were evaluated.1 In Part II, we summarize the technical approach to and outcomes after percutaneous coronary intervention (PCI) of occluded coronary arteries, describe the novel devices and drugs approved and undergoing investigation for CTO recanalization, and conclude with practical perspectives on managing the patient with 1 or more chronic coronary occlusions. ### Patient Selection and Revascularization Strategies PCI of CTOs constitutes as many as 20% of all angioplasty procedures at selected centers,2 although a rate of &10% is more typical,3–6 suggesting that CTO angioplasty is attempted in 50 000 to 100 000 patients per year in the United States. Many more CTOs are present for which PCI is never attempted, representing one of the most common causes for referral to bypass surgery rather than PCI.6–8 Furthermore, a large proportion of patients with CTOs are managed medically, the prognosis of whom may vary depending on the extent of viable myocardium and ischemia, concomitant atherosclerosis in other coronary and noncoronary vascular territories, and other comorbid conditions. The decision to attempt PCI of a CTO (versus continued medical therapy or surgical revascularization) requires an individualized risk/benefit analysis, encompassing clinical, angiographic, and technical considerations. Clinically, the patient’s age, symptom severity, associated comorbidities (eg, diabetes mellitus and chronic renal insufficiency), and overall functional status are major determinants of treatment strategy. Angiographically, the extent and complexity of coronary artery disease (eg, single-vessel versus multivessel disease, single versus multiple total occlusions, likelihood for complete revascularization), left ventricular function, and the presence and degree of valvular heart disease should be considered. The technical probability of achieving …

Antiplatelet Therapy and Stent Thrombosis After Sirolimus-Eluting Stent Implantation

Background— The influences of antiplatelet therapy discontinuation on the risk of stent thrombosis and long-term clinical outcomes after drug-eluting stent implantation have not yet been addressed adequately. Methods and Results— In an observational study in Japan, 2-year outcomes were assessed in 10 778 patients undergoing sirolimus-eluting stent implantation. Data on status of antiplatelet therapy during follow-up were collected prospectively. Incidences of definite stent thrombosis were 0.34% at 30 days, 0.54% at 1 year, and 0.77% at 2 years. Thienopyridine use was maintained in 97%, 62%, and 50% of patients at 30 days, 1 year, and 2 years, respectively. Patients who discontinued both thienopyridine and aspirin had a significantly higher rate of stent thrombosis than those who continued both in the intervals of 31 to 180 days, 181 to 365 days, and 366 to 548 days after stent implantation (1.76% versus 0.1%, P<0.001; 0.72% versus 0.07%, P=0.02; and 2.1% versus 0.14%, P=0.004, respectively). When discontinuation of aspirin was taken into account, patients who discontinued thienopyridine only did not have an excess of stent thrombosis in any of the time intervals studied. Adjusted rates of death or myocardial infarction at 24 months were 4.1% for patients taking thienopyridine and 4.1% for patients not taking thienopyridine (P=0.99) in the 6-month landmark analysis. Conclusions— Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy only, was associated with an increased risk of stent thrombosis. Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after sirolimus-eluting stent implantation.

Predicting Successful Guidewire Crossing Through Chronic Total Occlusion of Native Coronary Lesions Within 30 Minutes : The J-CTO (Multicenter CTO Registry in Japan) Score as a Difficulty Grading and Time Assessment Tool

OBJECTIVES This study sought to establish a model for grading lesion difficulty in interventional chronic total occlusion (CTO) treatment. BACKGROUND Owing to uncertainty of success of the procedure and difficulties in selecting suitable cases for treatment, performance of interventional CTO remains infrequent. METHODS Data from 494 native CTO lesions were analyzed. To eliminate operator bias, the objective parameter of successful guidewire crossing within 30 min was set as an end point, instead of actual procedural success. All observations were randomly assigned to a derivation set and a validation set at a 2:1 ratio. The J-CTO (Multicenter CTO Registry of Japan) score was determined by assigning 1 point for each independent predictor of this end point and summing all points accrued. This value was then used to develop a model stratifying all lesions into 4 difficulty groups: easy (J-CTO score of 0), intermediate (score of 1), difficult (score of 2), and very difficult (score of ≥ 3). RESULTS The set end point was achieved in 48.2% of lesions. Independent predictors included calcification, bending, blunt stump, occlusion length >20 mm, and previously failed lesion. Easy, intermediate, difficult, and very difficult groups, stratified by J-CTO score, demonstrated stepwise, proportioned, and highly reproducible differences in probability of successful guidewire crossing within 30 min (87.7%, 67.1%, 42.4%, and 10.0% in the derivation set and 92.3%, 58.3%, 34.8%, and 22.2% in the validation set, respectively). Areas under receiver-operator characteristic curves were comparable (derivation: 0.82 vs. validation: 0.76). CONCLUSIONS This model predicted the probability of successful guidewire crossing within 30 min very well and can be applied for difficulty grading.

In-Hospital Outcomes of Contemporary Percutaneous Coronary Intervention in Patients With Chronic Total Occlusion: Insights From the J-CTO Registry (Multicenter CTO Registry in Japan)

OBJECTIVES Our aim was to investigate in-hospital outcomes of percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) using contemporary techniques. BACKGROUND Despite its increasing popularity and technical complexity, clinical outcomes of PCI for CTO using contemporary techniques have not been adequately evaluated. METHODS The J-CTO registry (multicenter CTO registry in Japan) is a large scale, multicenter registry enrolling consecutive patients undergoing PCI for CTO from 12 Japanese centers. In-hospital clinical outcomes were evaluated in 498 patients with 528 CTO lesions. RESULTS Multiple wiring strategies were frequently attempted (parallel wiring 31% and retrograde approach 25%) with relatively long guidewire manipulation time (median 30 min). Utilizing these complex strategies, high procedural success rates (88.6% in the first attempt cases and 68.5% in the retry cases) were accomplished. In-hospital adverse event rates were strikingly low (cardiac death 0.2%, Q-wave myocardial infarction 0.2%, and stroke 0%). Potential disadvantages of these procedures, including a large amount of contrast volume (median 293 ml) and long fluoroscopic time (median 45 min), were not associated with serious clinical sequelae (contrast induced nephropathy 1.2% and radiation dermatitis 0%). Although coronary perforations were documented frequently by angiography (antegrade 7.2% and retrograde 13.6%), clinically significant perforation resulting in cardiac tamponade was rare (0.4%). CONCLUSIONS Most CTO lesions can be safely and successfully treated with PCI utilizing contemporary advanced techniques. Invasiveness and potential risks of these strategies, which have been the greatest concerns of CTO treatment, may be acceptable in the majority of cases considering the actual incidences of related adverse events and the procedural success rates.

A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan

AIMS Theoretically, bioresorbable vascular scaffolds (BVSs) may provide superior long-term results compared with permanent metallic drug-eluting stents (DESs). However, whether BVSs are as safe and effective as metallic DESs prior to complete bioresorption is unknown. METHODS AND RESULTS ABSORB Japan was a single-blind, multicentre, active-controlled, randomized trial designed to support regulatory approval of the Absorb BVS in Japan. Eligible patients with one or two de novo lesions in different epicardial vessels were randomized at 38 Japanese sites in a 2:1 ratio to Absorb BVS vs. cobalt-chromium everolimus-eluting stents (CoCr-EESs). The primary endpoint was target lesion failure [TLF: a composite of cardiac death, myocardial infarction attributable to target vessel, or ischaemia-driven target lesion revascularization (ID-TLR)] at 12 months, powered for non-inferiority. The major secondary endpoint was angiographic in-segment late lumen loss (LLL) at 13 months. A total of 400 patients were randomized to BVSs (266 patients and 275 lesions) or CoCr-EESs (134 patients and 137 lesions). TLF through 12 months was 4.2% with BVSs and 3.8% with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.39% (3.95%); Pnon-inferiority < 0.0001]. Definite/probable stent/scaffold thrombosis at 12 months occurred in 1.5% of the patients with both devices (P = 1.0), and ID-TLR for restenosis was infrequent (1.1% with BVSs and 1.5% with CoCr-EESs, P = 1.0). With 96.0% angiographic follow-up, in-segment LLL at 13 months was 0.13 ± 0.30 mm with BVSs and 0.12 ± 0.32 mm with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.01 (0.07); Pnon-inferiority < 0.0001). CONCLUSION In the ABSORB Japan randomized trial, 12-month clinical and 13-month angiographic outcomes of BVSs were comparable to CoCr-EESs. CLINICAL REGISTRATION ClinicalTrials.gov, number NCT01844284.

Comparisons of Baseline Demographics, Clinical Presentation, and Long-Term Outcome Among Patients With Early, Late, and Very Late Stent Thrombosis of Sirolimus-Eluting Stents Observations From the Registry of Stent Thrombosis for Review and Reevaluation (RESTART)

Background— Stent thrombosis (ST) after sirolimus-eluting stent implantation has not yet been adequately characterized, mainly because of its low incidence. Methods and Results— The Registry of Stent Thrombosis for Review and Reevaluation (RESTART) is a Japanese nationwide registry of sirolimus-eluting stent–associated ST comprising 611 patients with definite ST (early [within 30 days; EST], 322 patients; late [between 31 and 365 days; LST], 105 patients; and very late [>1 year; VLST], 184 patients). Baseline demographics, clinical presentation, and long-term outcome of sirolimus-eluting stent–associated ST were compared among patients with EST, LST, and VLST. Baseline demographics were significantly different according to the timing of ST. Characteristic demographic factors for LST/VLST versus EST identified by multivariable model were hemodialysis, end-stage renal disease not on hemodialysis, absence of circumflex target, target of chronic total occlusion, prior percutaneous coronary intervention, and age <65 years. For LST versus VLST, they were hemodialysis, heart failure, insulin-dependent diabetes mellitus, and low body mass index. Patients with LST had a significantly higher rate of Thrombolysis in Myocardial Infarction grade 2/3 flow (36%) at the time of ST than those with EST (13%) (P<0.0001) and VLST (17%; P<0.0001). Mortality rate at 1 year after ST was significantly lower in patients with VLST (10.5%) compared with those with EST (22.4%; P=0.003) or LST (23.5%; P=0.009). Conclusion— ST timing–dependent differences in baseline demographic features, Thrombolysis in Myocardial Infarction flow grade, and mortality rate suggest possible differences in the predominant pathophysiological mechanisms of ST according to timing after sirolimus-eluting stent implantation.

Effectiveness of paclitaxel-eluting balloon catheter in patients with sirolimus-eluting stent restenosis.

OBJECTIVES The aim of this study was to investigate the efficacy of a paclitaxel-eluting balloon (PEB) for the treatment of sirolimus-eluting stent (SES) restenosis. BACKGROUND Because drug-eluting stents (DES) are being used in increasingly complicated settings, DES restenosis is no longer an uncommon phenomenon, and its optimal treatment is unknown. METHODS This study was a prospective single-blind randomized trial conducted in 50 patients with SES restenosis. Patients were randomly assigned to a PEB group (n = 25) or a conventional balloon angioplasty (BA) group (n = 25). The primary end point was late lumen loss at 6-month follow-up. Secondary end points included the rate of binary restenosis (in-segment analysis) and major adverse cardiac events (MACE) at 6-month follow-up. RESULTS At 6-month angiographic follow-up (follow-up rate: 94%), in-segment late lumen loss was lower in the PEB group than in the BA group (0.18 ± 0.45 mm vs. 0.72 ± 0.55 mm; p = 0.001). The incidence of recurrent restenosis (8.7% vs. 62.5%; p = 0.0001) and target lesion revascularization (4.3% vs. 41.7%; p = 0.003) was also lower in the PEB group than in the BA group. The cumulative MACE-free survival was significantly better in the PEB group than in the BA group (96% vs. 60%; p = 0.005). CONCLUSIONS In patients with SES restenosis, PEB provided much better clinical, angiographic outcomes than conventional BA.

Percutaneous recanalization of chronically occluded coronary arteries: Procedural techniques, devices, and results

Gregg W. Stone,* MD, Antonio Colombo, MD, Paul S. Teirstein, MD, Jeffrey W. Moses, MD, Martin B. Leon, MD, Nicolaus J. Reifart, MD, Gary S. Mintz, MD, Angela Hoye, MBchB, David A. Cox, MD, Donald S. Baim, MD, Bradley H. Strauss, MD, PhD, Matthew Selmon, MD, Issam Moussa, MD, Takahiko Suzuki, MD, Hideo Tamai, MD, Osamu Katoh, MD, Kazuaki Mitsudo, MD, Eberhard Grube, MD, Louis A. Cannon, MD, David E. Kandzari, MD, Mark Reisman, MD, Robert S. Schwartz, MD, Steven Bailey, MD, George Dangas, MD, PhD, Roxana Mehran, MD, Alexander Abizaid, MD, and Patrick W. Serruys MD, PhD

Incidence, Risk Factors, and Clinical Sequelae of Angiographic Peri-Stent Contrast Staining After Sirolimus-Eluting Stent Implantation

Background— We have noted abnormal angiographic findings—at the sites of drug-eluting stent implantation, suggesting contrast staining outside the stent struts—that do not fulfill the classic definition of coronary artery aneurysm. We propose a new term, peri-stent contrast staining (PSS), for these abnormal angiographic findings and assess their incidence, risk factors, and clinical sequelae. Methods and Results— Peri-stent contrast staining was defined as contrast staining outside the stent contour extending to ≥20% of the stent diameter. The study population consisted of 3081 lesions (1998 patients) that were treated exclusively with sirolimus-eluting stents and were evaluated by follow-up angiography within 12 months after sirolimus-eluting stent implantation in a single center. Late acquired PSS was observed in 58 lesions (1.9%) in 49 patients (2.5%). Independent risk factors of PSS included chronic total occlusion, whereas negative risk factors for PSS were left circumflex coronary artery lesion and in-stent restenosis lesion. Stent fracture was more frequently observed in lesions with PSS than in lesions without PSS (43.1% versus 5.4%, P<0.0001). Excluding 269 lesions with target-lesion revascularization within 12 months, the study population for long-term follow-up consisted of 51 lesions (42 patients) with PSS and 2761 lesions (1751 patients) without PSS. Cumulative incidence of target-lesion revascularization and definite very late stent thrombosis at 3 years in the PSS group was higher than that in the non-PSS group (15.0% versus 6.5%, and 8.2% versus 0.2%, respectively). Conclusions— Peri-stent contrast staining found within 12 months after sirolimus-eluting stent implantation appeared to be associated with subsequent target-lesion revascularization and very late stent thrombosis.

Three-Year Outcomes After Sirolimus-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Disease Insights From the j-Cypher Registry

Background— Long-term outcomes after stenting of an unprotected left main coronary artery (ULMCA) with drug-eluting stents have not been addressed adequately despite the growing popularity of this procedure. Methods and Results— j-Cypher is a multicenter prospective registry of consecutive patients undergoing sirolimus-eluting stent implantation in Japan. Among 12 824 patients enrolled in the j-Cypher registry, the unadjusted mortality rate at 3 years was significantly higher in patients with ULMCA stenting (n=582) than in patients without ULMCA stenting (n=12 242; 14.6% versus 9.2%, respectively; P<0.0001); however, there was no significant difference between the 2 groups in the adjusted risk of death (hazard ratio 1.23, 95% confidence interval 0.95 to 1.60, P=0.12). Among 476 patients whose ULMCA lesions were treated exclusively with a sirolimus-eluting stent, patients with ostial/shaft lesions (n=96) compared with those with bifurcation lesions (n=380) had a significantly lower rate of target-lesion revascularization for the ULMCA lesions (3.6% versus 17.1%, P=0.005), with similar cardiac death rates at 3 years (9.8% versus 7.6%, P=0.41). Among patients with bifurcation lesions, patients with stenting of both the main and side branches (n=119) had significantly higher rates of cardiac death (12.2% versus 5.5%; P=0.02) and target-lesion revascularization (30.9% versus 11.1%; P<0.0001) than those with main-branch stenting alone (n=261). Conclusions— The higher unadjusted mortality rate of patients undergoing ULMCA stenting with a sirolimus-eluting stent did not appear to be related to ULMCA treatment itself but rather to the patients’ high-risk profile. Although long-term outcomes in patients with ostial/shaft ULMCA lesions were favorable, outcomes in patients with bifurcation lesions treated with stenting of both the main and side branches appeared unacceptable.