Second-Generation vs. First-Generation Drug-Eluting Stents in Patients With Calcified Coronary Lesions　- Pooled Analysis From the RESET and NEXT Trials.

BACKGROUND: The comparative efficacy of second-generation (G2) vs. first-generation (G1) drug-eluting stents (DES) for calcified coronary lesions is unknown.Methods and Results:We compared the 3-year clinical outcomes of patients with G1- or G2-DES according to the presence or absence of calcified coronary lesions as assessed in an angiographic core laboratory using data from 2 large-scale prospective multicenter randomized trials, RESET and NEXT. G1-DES and G2-DES were implanted in 299 and 1,033 patients, respectively, in the Calc stratum (≥1 lesion with moderate/severe calcification), and 1,208 and 3,550 patients, respectively, in the Non-calc stratum (no/mild calcification). The patients in the Calc stratum had a significantly higher adjusted risk for the primary outcome measure (any target-lesion revascularization (TLR)) than those in the Non-calc stratum (HR: 1.38, 95% CI: 1.11-1.71, P=0.004). The cumulative 3-year incidence of any TLR was not significantly different between the G1-DES and G2-DES groups in both the Calc and Non-calc strata (12.1% vs. 9.7%, P=0.22, and 6.8% vs. 6.1%, P=0.44, respectively). After adjusting for confounders, the effect of G2DES relative to G1-DES for any TLR remained insignificant in both the Calc and Non-calc strata (HR: 0.78, 95% CI: 0.48-1.25, P=0.3, and HR: 0.84, 95% CI: 0.61-1.17, P=0.31, respectively, P interaction=0.55). CONCLUSIONS: The effect of G2-DES relative to G1-DES for TLR was not significantly different regardless of the presence or absence of lesion calcification.

Vascular response to drug-eluting stent with biodegradable vs. durable polymer. Optical coherence tomography substudy of the NEXT.

BACKGROUND: The aim of the present study was to compare vascular healing response between everolimus-eluting stent (EES) and biolimus-eluting stent (BES) using optical coherence tomography (OCT). METHODS AND RESULTS: In the NOBORI Biolimus-Eluting Versus XIENCE V/PROMUS Everolimus-Eluting Stent Trial (NEXT), a formal OCT substudy investigated 91 patients (55 EES-treated lesions in 48 patients and 51 BES-treated lesions in 43 patients) with 8-12 months follow-up imaging at 18 centers. A total of 980 frames with 8,996 struts in EES and 907 frames with 8,745 struts in BES were analyzed. Mean neointima thickness in EES and BES was 105±82µm and 91±80µm, respectively (P<0.001). With regard to stent-treated lesions, the percentage of struts not covered by neointima (3±7% vs. 9±10%, P<0.001) and the frequency of stent-treated lesions with any uncovered struts (n=28, 51% vs. n=42, 82%; P<0.001) were significantly lower in EES compared with BES. In addition, the percentage of malapposed struts (0.2±0.8% vs. 1.3±2.8%, P=0.006) and the frequency of stent-treated lesions with any malapposed struts (n=6, 11% vs. n=14, 27%; P=0.028) were significantly lower in EES compared with BES. CONCLUSIONS: Incomplete vascular healing characterized by the presence of struts not covered by neointima and malapposed struts was less common in EES compared with BES.

Comparison of everolimus-eluting and sirolimus-eluting coronary stents: 1-year outcomes from the Randomized Evaluation of Sirolimus-eluting Versus Everolimus-eluting stent Trial (RESET).

BACKGROUND: Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization. METHODS AND RESULTS: Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES (P(noninferiority)<0.0001, and P(superiority)=0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%, P=0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm, P(noninferiority)<0.0001, and P(superiority)=0.24) at 278±63 days after index stent implantation. CONCLUSIONS: One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035450.

Clopidogrel trial in patients with elective percutaneous coronary intervention for stable angina and old myocardial infarction (CLEAN).

Clopidogrel in combination with aspirin has been widely used in patients who have undergone coronary stent implantation. However, the benefit to Japanese patients with stable angina (SA) or old myocardial infarction (OMI) undergoing percutaneous coronary intervention (PCI) still remains unclear.The aim of this multicenter, randomized, double-blind, clinical study was to evaluate the safety of a clopidogrel 300 mg loading dose followed by a 75 mg maintenance dose compared to ticlopidine 100 mg twice daily in patients with SA or OMI undergoing PCI who were on aspirin (81 to 100 mg once daily). The primary endpoint was the composite of safety events comprising clinically significant bleeding, blood disorders, elevated liver function values, and study drug discontinuation up to week 12. The key secondary endpoints were major adverse cardiac events (MACE), major adverse cardiac and cerebrovascular events (MACCE), and bleeding events. A total of 1003 patients were randomly allocated to receive either clopidogrel or ticlopidine and 931 patients underwent PCI. The cumulative incidence of the composite safety endpoint in the clopidogrel group was statistically lower than that of ticlopidine (P < 0.0001, hazard ratio; 0.259; 95%CI; 0.187 to 0.359). There were no statistically significant differences between treatments with respect to MACE at week 12 (P = 0.7899) nor to the bleeding events (P = 0.5292, stratified log-rank test).Clopidogrel was found to have a better benefit/risk profile than ticlopidine in Japanese patients with SA or OMI undergoing PCI.

[Examination of the effectiveness of heart rate control using intravenous ß-blocker in 64-slice coronary computed tomography angiography].

The purpose of this study is to clarify the effectiveness of the use of ß-blocker in coronary computed tomography angiography (CCTA). In 1783 patients, heart rate was controlled by propranolol injection to patients with heart rates of 61 bpm or more. As a result, the scan heart rate (58.8±6.5 bpm) decreased significantly compared with the initial heart rate (72.7±9.4 bpm). Prospective gating method was used by 61.9% including 64.3% of the intravenous ß-blocker injection group. Moreover, daily use of oral ß-blocker had influence on reduction of the scan heart rate (daily use group: 60.1±6.5 bpm vs. unuse group: 58.5±6.3 bpm p<0.01). When we evaluated the image quality of CCTA by the score, the improvement of the score was obviously admitted by 65 bpm or less of the scan heart rate. The ratio of scan heart rate that was controlled by 65 bpm or less was decreased in the initial heart rate groups that were 81 bpm or more. The incidence of adverse reactions by the propranolol injection was few, and these instances only involved slight symptoms. Therefore, heart rate control with the use of ß-blocker is useful for the image quality improvement of CCTA. This form of treatment can be safely enforced.

[Percutaneous coronary intervention and stent thrombosis].

Despite improved stent implantation technologies and effective antiplatelet regimens, stent thrombosis has been one of the most important problem in percutaneous coronary intervention. Stent thrombosis is a rare but usually catastrophic event, frequently associated with large MI or death. Stent thrombosis is generally categorized according to the timing of the event as early (0 to 30 days), late (31 days to 1 year), very late (> 1 year). Late and very late stent thrombosis after stent implantation has not yet been adequately characterized, mainly because of its low incidence. And the optimal duration of dual antiplatelet therapy remains uncertain for patients receiving drug-eluting stents.

Second-generation versus first-generation drug-eluting stents in patients with and without diabetes mellitus: pooled analysis from the RESET and NEXT trials.

The impact of second-generation drug-eluting stent (G2-DES) implantations compared with first-generation drug-eluting stents (G1-DES) implantations on long-term clinical outcomes after percutaneous coronary intervention in patients with and without diabetes mellitus (DM) has not yet been adequately assessed. This pooled analysis compared 3-year clinical outcomes between G1- and G2-DES according to the presence or absence of DM, using individual patient-level data from the RESET and NEXT trials. Among 6431 patients, G1-DES and G2-DES were used in 713 and 2211 patients, respectively, in the DM stratum, and 887 and 2620 patients, respectively, in the non-DM stratum. Cumulative incidence of and adjusted hazard ratio (HR) for target-lesion revascularization (TLR) were not significantly different between G2- and G1-DES in both strata [DM, 8.7 versus 10.1%, adjusted HR: 0.80, 95% confidence interval (CI) 0.59-1.10, P = 0.17; non-DM, 5.7 versus 6.2%, adjusted HR: 0.86, 95% CI 0.62-1.22, P = 0.38]. In the insulin-treated DM (ITDM), G2-DES had a significantly lower adjusted HR for TLR compared with G1-DES, although there was no significant difference in the non-ITDM (ITDM, adjusted HR: 0.54, 95% CI 0.32-0.96, P = 0.04; non-ITDM, adjusted HR: 0.95, 95% CI 0.66-1.42, P = 0.81). G2-DES provided similar risk for TLR in non-ITDM and non-DM patients compared with G1-DES. However, G2-DES compared with G1-DES had a lower risk for TLR among ITDM patients.

Impact of Angiographic Residual Stenosis on Clinical Outcomes After New-Generation Drug-Eluting Stents Implantation: Insights From a Pooled Analysis of the RESET and NEXT Trials.

BACKGROUND: Previous intravascular ultrasound studies suggested the association of stent underexpansion with increased risk of stent thrombosis and restenosis. However, no previous study has addressed the association of the suboptimal angiographic result with target-lesion revascularization (TLR) in patients receiving new-generation drug-eluting stents (DES). METHODS AND RESULTS: RESET (Randomized evaluation of sirolimus-eluting versus everolimus-eluting stent trial) and NEXT (NOBORI biolimus-eluting versus XIENCE/PROMUS everolimus-eluting stent trial) are prospective, multicenter, randomized "DES versus DES" trials; 3196 patients and 3235 patients were enrolled in the RESET and NEXT, respectively. Using the pooled individual patient-level data, the current study population consisted of 3679 patients who received single-lesion treatment using new-generation DES such as everolimus-eluting stent and biolimus-eluting stent. The study population was divided into 3 groups according to the residual in-stent % diameter stenosis (%DS) after stent implantation by offline quantitative coronary angiography assessed in a core angiographic laboratory (optimal group: %DS <10%, intermediate group: %DS=10% to 20%, suboptimal group: %DS ≧20%). The cumulative 3-year incidence of TLR was significantly higher in the suboptimal group than in the intermediate and optimal groups (9.8% versus 5.8% versus 5.7%, log-rank P=0.004). Even after adjusting for the clinical, angiographic, and procedural characteristics, the excess TLR risk of the suboptimal group relative to the optimal group remained significant (hazard ratio: 1.65, 95% confidence interval, 1.14-2.41, P=0.009). The excess TLR risk of the suboptimal group relative to the optimal group was consistently seen across all the subgroups including heavy calcification. CONCLUSIONS: The residual angiographic in-stent %DS ≥20% was associated with increased risk for TLR in patients treated with the new-generation DES.

A New Contrast Enhancement Protocol for Subtraction Coronary Computed Tomography Requiring a Short Breath-Holding Time.

RATIONALE AND OBJECTIVES: We have developed a new contrast enhancement protocol for subtraction coronary computed tomography (SCCTA) requiring a short breath-holding time. In the protocol, test and main boluses were sequentially and automatically injected, and correct timings for pre-contrast and contrast-enhanced scans for main bolus were automatically determined only by the test bolus tracking. Combined with a fixed short main bolus injection for 7 seconds, the breath-holding time was shortened as possible. The purpose of this study was to evaluate whether use of this new protocol produced adequate quality images, taking into account calcified lesions and in-stent lumens. MATERIALS AND METHODS: Patients (n = 127) with calcium scores of >400 Agatston units or a history of stent placement were enrolled. Breath-holding times were recorded, and image quality was visually evaluated by two observers. RESULTS: The mean ± standard deviation breath-holding time was 13.2 ± 0.6 seconds. The mean ± SD computed tomography (CT) number of coronary arteries for the pre-contrast scan was sufficiently low [99.2 ± 32.2 Hounsfield units (HU)] and, simultaneously, that for SCCTA was 367.0 ± 77.2 HU. The rate of segments evaluated as unreadable was sufficiently low (3.8%). CONCLUSIONS: Use of the SCCTA protocol was efficient and allowed for a shorter breath-holding time and adequate diagnostic accuracy of SCCTA images, including images of calcified and stent implantation segments.

Two-year vascular responses to drug-eluting stents with biodegradable polymer versus durable polymer: An optical coherence tomography sub-study of the NEXT.

BACKGROUND: This study aimed to compare very late vascular response after stent implantation between everolimus-eluting stent (EES) with a thin, non-adhesive, durable, biocompatible fluorinated polymer and biolimus-eluting stent (BES) with a biodegradable polymer by optical coherence tomography (OCT). METHODS AND RESULTS: In the NOBORI-BES Versus XIENCE V/PROMUS-EES Trial (NEXT), a formal OCT substudy investigated 48 patients (27 EES-treated lesions in 23 patients and 28 BES-treated lesions in 25 patients) with 2-year (18-30 months) follow-up imaging at 18 centers. The percentage of uncovered strut by neointima was significantly lower in EES compared with BES (2.1±4.7% vs. 7.9±10.8%, p=0.013). The percentage of malapposed strut was not different between EES and BES (0.1±0.3% vs. 0.5±1.3%, p=0.138). The frequency of stent with evagination, which is identified as outward bulges in the luminal contour between struts, was significantly lower in EES compared with BES (22% vs. 86%, p<0.001). The frequency of neoatherosclerosis was not different between EES and BES (11% vs. 11%, p=1.000). CONCLUSIONS: At 2 years after stent implantation, uncovered stent strut by neointima and evagination were less frequently observed in EES compared with BES. This OCT study suggests that the very late vascular response is different between EES and BES.

Visualization of collateral channels with coronary computed tomography angiography for the retrograde approach in percutaneous coronary intervention for chronic total occlusion.

BACKGROUND: There have been no reports about the diagnostic ability of coronary computed tomography angiography (CTA) in evaluating collateral channels used for retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI). OBJECTIVE: We investigated the ability and diagnostic accuracy of coronary CTA compared with invasive coronary angiography to detect collaterals used in retrograde CTO PCI and to compared the success rates for wire crossing between collaterals that are detectable and not detectable in coronary CTA. METHODS: We retrospectively reviewed data from 43 patients (55 collaterals) who underwent coronary CTA and PCI for CTO with the retrograde approach. We compared the ability of coronary CTA to visualize collaterals to invasive coronary angiography and evaluated the rates of successful wire crossing between CTA-visible and invisible collaterals. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of coronary CTA for detecting collaterals which were used for the retrograde approach was 100.0%, 50.0%, 65.9%, 100.0%, and 74.5%, respectively. Guidewire collateral crossing was more successful in CT-visible collaterals than those not detectable in CT (74.1% vs. 46.4%, p = 0.034). There were fewer collateral vessel injuries in CTA-visible collaterals (11.1% vs. 32.1%, p = 0.041). CONCLUSION: Coronary CTA provides good visualization of collaterals used in retrograde CTO PCI. For retrograde guidewire crossing, a higher success rate with fewer complications was observed in CTA-visible collaterals than in those not detectable in coronary CTA.

One-year outcome of a prospective trial stopping dual antiplatelet therapy at 3 months after everolimus-eluting cobalt-chromium stent implantation: ShortT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent (STOPDAPT) trial.

There has been no previous prospective study evaluating dual antiplatelet therapy (DAPT) duration shorter than 6 months after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation. STOPDAPT trial is a prospective multi-center single-arm study evaluating 3-month DAPT duration after CoCr-EES implantation. The primary endpoint was a composite of cardiovascular death, myocardial infarction (MI), stroke, definite stent thrombosis (ST) and TIMI major/minor bleeding at 1 year. Between September 2012 and October 2013, a total of 1525 patients were enrolled from 58 Japanese centers, with complete 1-year follow-up in 1519 patients (99.6 %). Thienopyridine was discontinued within 4 months in 1444 patients (94.7 %). The event rates beyond 3 months were very low (cardiovascular death: 0.5 %, MI: 0.1 %, ST: 0 %, stroke: 0.7 %, and TIMI major/minor bleeding: 0.8 %). Cumulative 1-year incidence of the primary endpoint was 2.8 % [upper 97.5 % confidence interval (CI) 3.6 %], which was lower than the pre-defined performance goal of 6.6 % (P < 0.0001). Using the CoCr-EES group in the RESET trial as a historical comparison group, where nearly 90 % of patients had continued DAPT at 1 year, cumulative incidence of the primary endpoint tended to be lower in the STOPDAPT than in the RESET (2.8 versus 4.0 %, P = 0.06) and adjusted hazard ratio was 0.64 (95 % CI 0.42-0.95, P = 0.03). The cumulative incidence of definite/probable ST was lower in the STOPDAPT than in the RESET [0 patient (0 %) versus 5 patients (0.3 %), P = 0.03]. In conclusion, stopping DAPT at 3 months in selected patients after CoCr-EES implantation was at least as safe as the prolonged DAPT regimen adopted in the historical control group.

Two-year clinical, angiographic, and serial optical coherence tomographic follow-up after implantation of an everolimus-eluting bioresorbable scaffold and an everolimus-eluting metallic stent: insights from the randomised ABSORB Japan trial.

AIMS: We sought to investigate two-year clinical and serial optical coherence tomography (OCT) outcomes after implantation of a fully bioresorbable vascular scaffold (BVS) or a cobalt-chromium everolimus-eluting stent (CoCr-EES). METHODS AND RESULTS: In the ABSORB Japan trial, 400 patients were randomised in a 2:1 ratio to BVS (N=266) or CoCr-EES (N=134). A pre-specified OCT subgroup (N=125, OCT-1 group) underwent angio-graphy and OCT post procedure and at two years. Overall, the two-year TLF rates were 7.3% and 3.8% in the BVS and CoCr-EES arms (p=0.18), respectively. Very late scaffold thrombosis (VLST) beyond one year was observed in 1.6% (four cases: all in non-OCT-1 subgroups) of the BVS arm, while there was no VLST in the CoCr-EES arm. In three cases, OCT at the time of or shortly after VLST demonstrated strut discontinuities, malapposition and/or uncovered struts. However, the vessel healing by two-year OCT was nearly complete in both BVS and CoCr-EES arms with almost fully covered struts, and minimal malapposition. The flow area by two-year OCT was smaller in the BVS arm than in the CoCr-EES arm, mainly due to tissue growth inside the device. However, there were no differences between the BVS and CoCr-EES with regard to the quality of homogenous tissues growing inside the devices. CONCLUSIONS: The rate of TLF was numerically higher in the BVS arm than in the CoCr-EES arm, although this difference was not statistically significant. VLST was observed only in the BVS arm at a rate of 1.6% between one and two years. Further studies are mandatory to investigate the risk of BVS relative to metallic stents for VLST, and the underlying mechanisms of BVS VLST.

Independent predictors of the severity of angiographic coronary atherosclerosis: the lack of association between impaired glucose tolerance and stenosis severity.

Independent predictors of the severity of coronary atherosclerosis are ill defined. We sought to determine the predictors and examine the association of impaired glucose tolerance with stenosis severity. Four hundred thirty-seven patients were studied who underwent coronary angiography for suspected coronary artery disease. Serum concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLc), lipoprotein(a) [Lp(a)] and apolipoproteins (Apo A-I and Apo B) were measured and low-density lipoprotein cholesterol (LDLc) concentration was calculated. Except the patients treated for diabetes mellitus (DM), patients were classified into three groups such as normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and DM by glucose tolerance test. Coronary atherosclerosis index (CAI) representing the severity of coronary atherosclerosis was determined by summation of the stenosis score of all lesions on coronary angiograms. Results indicated that age, total amount of cigarettes smoked, Apo B/Apo A-I, and LDLc/HDLc correlated with CAI, whereas HDLc and Apo A-I concentrations inversely correlated with CAI. TC, TG, Lp(a), LDLc, Apo B concentrations and body mass index did not correlate with CAI. One- and two-hour plasma glucose concentrations and the area of plasma glucose concentration under the curve at the glucose tolerance test did not correlate with CAI, revealing that post-challenge glycemia is not associated with stenosis severity. CAI in IGT patients was significantly lower than that in DM patients but did not differ from that in NGT patients, indicating that IGT does not affect the stenosis severity. Multivariate analysis showed that age, male gender, Apo B/Apo A-I, DM, systemic hypertension, and total amount of cigarettes smoked were independent predictors of CAI.

Final 3-Year Outcome of a Randomized Trial Comparing Second-Generation Drug-Eluting Stents Using Either Biodegradable Polymer or Durable Polymer: NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial.

BACKGROUND: There is a paucity of data reporting the clinical outcomes of biodegradable polymer biolimus-eluting stent (BP-BES) compared with durable polymer everolimus-eluting stent (DP-EES) beyond 1 year after stent implantation when the polymer is fully degraded. METHODS AND RESULTS: The NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) is a prospective, multicenter, randomized, open-label, noninferiority trial comparing BP-BES with DP-EES in patients scheduled for percutaneous coronary intervention using drug-eluting stent (DES) without any exclusion criteria among 98 participating centers in Japan. The trial was designed to evaluate noninferiority of BP-BES relative to DP-EES in terms of any target-lesion revascularization at 1 year and death or myocardial infarction at 3 years. Between May and October 2011, 3235 patients were randomly assigned to receive either BP-BES (1617 patients) or DP-EES (1618 patients). Complete 3-year follow-up was achieved in 97.6% of patients. At 3 years, the primary safety end point of death or myocardial infarction occurred in 159 patients (9.9%) in the BP-BES group and in 166 patients (10.3%) in the DP-EES group, demonstrating noninferiority of BP-BES relative to DP-EES (P noninferiority<0.0001 and P superiority=0.7). Cumulative incidence of target-lesion revascularization was not significantly different between the 2 groups (7.4% versus 7.1%; P=0.8). By a landmark analysis at 1 year, the cumulative incidences of death or myocardial infarction and target-lesion revascularization were also not significantly different between the 2 groups (4.6% versus 5.2%; P=0.46 and 3.3% versus 2.7%; P=0.39, respectively). CONCLUSIONS: Safety and efficacy outcomes of BP-BES were non inferior to those of DP-EES 3 years after stent implantation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01303640.

Outcomes of everolimus-eluting stent incomplete stent apposition: a serial optical coherence tomography analysis.

AIM: The aim of the present study was to evaluate the natural course of acute incomplete stent apposition (ISA) after second-generation everolimus-eluting stent (EES) when compared with first-generation sirolimus-eluting stent (SES) by using optical coherence tomography (OCT). METHODS AND RESULTS: From the OCT substudy of the RESET trial, we identified 77 patients (EES = 38 and SES = 39) who successfully underwent serial OCT examination at post-stenting and 8-12-month follow-up. The presence of ISA was assessed in the OCT images, and ISA distance was measured from the centre of the strut blooming to the adjacent lumen border. Incomplete stent apposition was observed in all EES and SES at post-stenting, and it was persistent in 26% of EES and 38% of SES at 8-12-month follow-up. Maximum ISA distance was significantly decreased during the follow-up period in both EES (315 ± 94-110 ± 165 µm, P < 0.001) and SES (308 ± 119-143 ± 195 µm, P < 0.001). Receiver-operating curve analysis identified that the best cut-off value of OCT-estimated ISA distance at post-stenting for predicting late-persistent ISA at 8-12-month follow-up in EES and SES was >355 and >285 µm, respectively. CONCLUSIONS: The second-generation EES showed better healing of acute ISA in comparison with the first-generation SES. Optical coherence tomography can predict late-persistent ISA after DES implantation and provide useful information to optimize PCI.

Defect of delta-sarcoglycan gene is responsible for development of dilated cardiomyopathy of a novel hamster strain, J2N-k: calcineurin/PP2B activity in the heart of J2N-k hamster.

It has been shown that calcineurin (CN), a serine/threonine protein phosphatase type 2B (PP2B), plays an important role in the development and diseases of cardiac muscles. However, reports on CN activity in dilated cardiomyopathy (DCM) are inconsistent, since there are few good disease models and the measurement of the amount of CN is difficult. Previously, we developed a novel line of DCM hamster, J2N-k, and its healthy control counterpart, J2N-n, by crossbreeding cardiomyopathy (CM) hamsters, Bio 14.6, and Golden hamsters followed by consecutive sib mating. In this study, we identified the DCM-causative gene in J2N-k by analysis of F2 of these two lines, and then we analyzed the change in CN gene expression in the course of the disease, and the change in CN activity using a newly developed method. We show that: (i) the DCM gene of J2N-k hamster is the delta- sarcoglycan (SG) gene, (ii) CN expression and potential CN activities (CN activity fully activated with Ca(2+) and calmodulin) in the hearts of J2N-k and J2N-n hamsters are the same levels, (iii) transcription levels of natriuretic peptides, which are augmented by activation of Ca(2+)/calmodulin-dependent enzyme including CN, are significantly increased in the DCM stage in J2N-k hamster. J2N-k and J2N-n hamsters will be a useful tool for studying the pathogenesis, therapy, and prevention of human DCM. Although the total amount and potential activity of CN did not change in the cell extracts, targets of CN in vivo were activated in cardiomyocytes of DCM, suggesting that CN activity in the cells is activated by the raising of Ca(2+) concentration in cardiomyocytes of DCM, which is caused by the defect in the delta-SG gene. Our results reveal the complexity of CN regulation in the heart and indicate the need for additional experimentation.

Microvascular angina accompanied by epicardial coronary artery spasm.

A case of microvascular angina accompanied by coronary artery spasm is described. A 54-year-old woman had anginal pain at rest and during exercise. Both exercise testing and rapid atrial pacing caused significant ST depression in the inferior and all precordial leads. Exercise thallium myocardial scintigraphy was negative despite similar ST depressions. Coronary angiography revealed insignificant stenoses of the left anterior descending coronary artery after the injection of nitrate. Intracoronary acetylcholine provoked diffuse spasm of the artery with concurrent myocardial lactate production. Coronary flow reserve assessed with papaverine was 2.75. The combined use of amlodipine and high-dose nicorandil was effective for the treatment of angina.

Japanese and non-Japanese patient outcomes in the PLATINUM randomized trial comparing the PROMUS Element and XIENCE V everolimus-eluting stents.

BACKGROUND: The PLATINUM randomized trial enrolled 1530 patients treated with either the platinum chromium PROMUS Element everolimus-eluting stent (PtCr-EES; Boston Scientific, Natick, MA, USA) or the predicate cobalt chromium PROMUS/XIENCE V EES (CoCr-EES; manufactured as XIENCE V by Abbott Vascular, Santa Clara, CA, USA also distributed as PROMUS by Boston Scientific), including 124 patients from Japanese sites. This substudy examines 2-year outcomes in the Japanese and non-Japanese cohorts. METHODS: Patients with 1 or 2 de novo native coronary artery lesions (baseline vessel diameter ≥2.50mm to ≤4.25mm and length ≤24mm) were randomized 1:1 to PtCr-EES (N=63 patients in Japan) versus CoCr-EES (N=61 patients in Japan). RESULTS: Several significant differences were noted in baseline demographics, lesion characteristics, and procedural technique between Japanese and non-Japanese patients, including longer fluoroscopy time, less use of contrast, and greater post-dilatation usage and maximum pressure in Japan. Dual antiplatelet usage at 2 years was also higher in Japan. Despite these differences, the 2-year rates of target lesion failure were comparable in patients treated with PtCr-EES and CoCr-EES both in Japan (3.2% vs 5.0% respectively, p=0.68) and outside Japan (4.7% vs 5.9% respectively, p=0.33; p for interaction=0.82). CONCLUSIONS: This PLATINUM study subanalysis suggests that the PtCr-EES and CoCr-EES provide comparable safety and efficacy in both Japanese and non-Japanese patients.

Long-term clinical outcomes after everolimus- and sirolimus-eluting coronary stent implantation: final 3-year follow-up of the Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial.

BACKGROUND: Long-term clinical outcomes of everolimus-eluting stent (EES) compared with sirolimus-eluting stent (SES) have not been evaluated fully yet, especially whether EES implantation could positively affect late adverse events reported after SES implantation occurring >1 year. METHODS AND RESULTS: In this all-comer prospective multicenter randomized open-label trial, 3196 patients were assigned randomly to implant either EES (n=1596) or SES (n=1600). At 3 years, EES was noninferior to SES on the primary safety end point (all-cause death or myocardial infarction; 10.1% versus 11.5%; noninferiority P <0.001; and superiority P=0.19). Cumulative incidence of definite stent thrombosis was low and was not significantly different between the 2 groups (0.5% versus 0.6%; P=0.81). There was no significant difference in the efficacy end point of target-lesion revascularization between the EES and SES groups (6.6% versus 7.9%; P=0.16). However, the cumulative incidence of target-lesion failure (cardiac death/target-vessel myocardial infarction/ischemia-driven target-lesion revascularization) was significantly lower in the EES group than in the SES group (8.8% versus 11.4%; P=0.01). By a landmark analysis at 1 year, the cumulative incidence of very late stent thrombosis and late target-lesion revascularization was not significantly different between the 2 groups (0.2% versus 0.2%; P=0.99 and 2.2% versus 2.9%; P=0.21, respectively). CONCLUSIONS: The efficacy and safety outcomes for this trial after EES implantation remained comparable with those after SES implantation through 3-year follow-up. However, improvement of clinical outcome after EES implantation compared with SES implantation was suggested by the significantly lower cumulative incidences of target-lesion failure, which has been the most widely used primary end point in the stent-versus-stent trials. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035450.