Objectives The aim of this study was to evaluate the impact of the J-CTO score on long-term target lesion revascularization (TLR) after successful native chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). Background We previously reported that the J-CTO score could be used to stratify the lesion complexity and procedural success rate in CTO lesions. Methods We evaluated the prognostic significance of a high J-CTO score for long-term TLR rate in the J-CTO Registry. Results In the 425 lesions of 408 patients who underwent successful CTO-PCI during a median follow-up of 63.0 (interquartile range: 21.2-72.9) months in the J-CTO Registry, the cumulative incidence of TLR of lesions with a J-CTO score >= 2 (n = 216) was significantly higher than in those with a J-CTO score <= 1 (n = 209) (27.0 versus 19.4% at 5 years, respectively, P = 0.04). Among 323 lesions of 309 patients with a complete 5-year follow-up, the rate of TLR was 28% (n = 91). A J-CTO score >= 2 was independently associated with a higher risk of TLR (odds ratio, 1.73; 95% confidence interval, 1.01-2.99, P = 0.048) even after adjustment for clinically relevant baseline factors. Conclusions Patients with high J-CTO score lesions had a higher 5-year risk of TLR.

Background Prior stroke is regarded as risk factor for bleeding after percutaneous coronary intervention (PCI). However, there is a paucity of data on detailed bleeding risk of patients with prior hemorrhagic and ischemic strokes after PCI. Methods and Results In a pooled cohort of 19 475 patients from 3 Japanese PCI studies, we assessed the influence of prior hemorrhagic (n=285) or ischemic stroke (n=1773) relative to no‐prior stroke (n=17 417) on ischemic and bleeding outcomes after PCI. Cumulative 3‐year incidences of the co‐primary bleeding end points of intracranial hemorrhage, non‐intracranial global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (GUSTO) moderate/severe bleeding, and the primary ischemic end point of ischemic stroke/myocardial infarction were higher in the prior hemorrhagic and ischemic stroke groups than in the no‐prior stroke group (6.8%, 2.5%, and 1.3%, P<0.0001, 8.8%, 8.0%, and 6.0%, P=0.001, and 12.7%, 13.4%, and 7.5%, P<0.0001). After adjusting confounders, the excess risks of both prior hemorrhagic and ischemic strokes relative to no‐prior stroke remained significant for intracranial hemorrhage (hazard ratio (HR) 4.44, 95% CI 2.64–7.01, P<0.0001, and HR 1.52, 95% CI 1.06–2.12, P=0.02), but not for non‐intracranial bleeding (HR 1.18, 95% CI 0.76–1.73, P=0.44, and HR 0.94, 95% CI 0.78–1.13, P=0.53). The excess risks of both prior hemorrhagic and ischemic strokes relative to no‐prior stroke remained significant for ischemic events mainly driven by the higher risk for ischemic stroke (HR 1.46, 95% CI 1.02–2.01, P=0.04, and HR 1.49, 95% CI 1.29–1.72, P<0.0001). Conclusions Patients with prior hemorrhagic or ischemic stroke as compared with those with no‐prior stroke had higher risk for intracranial hemorrhage and ischemic events, but not for non‐intracranial bleeding after PCI.

We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT).

Aims: We investigated the impact of the J-CTO score, a pre-procedural risk score for successful guidewire crossing within 30 minutes through chronic total occlusion (CTO) lesions, on procedural and midterm clinical outcomes in terms of target lesion revascularisation (TLR) after CTO recanalisation.Methods and results: The primary endpoint of this substudy was midterm TLR. The net midterm success rate was calculated by multiplying the lesion success rate by the TLR-free survival rate. The initial lesion success rates according to the J-CTO score categories of 0, 1, 2, and >= 3 were 9.7.0%, 92.1%, 86.5%, and 73.6%, respectively (p<0.001). The TLR rates at one year according to the J-CTO score categories of 0, 1, 2, and >= 3 were 5.3%, 11.1%, 16.7%, and 13.4%, respectively (p=0.082). The net midterm success rates according to the J-CTO score categories of 0, 1, 2, and >= 3 were 91.9%, 81.9%, 72.1%, and 63.7%, respectively (p<0.001).Conclusions: Patients with CTO lesions with lower J-CTO scores are expected to achieve a high procedural success rate and an increased TLR-free survival rate. Patients with high J-CTO scores still remain an issue.

Here, we report a case of successful interventional revascularization of the left anterior descending artery (LAD) in two heavy calcified chronic total occlusion (CTO) lesions, which were uncrossable utilizing hybrid procedural steps of local rotational atherectomy and a retrograde approach by reverse controlled antegrade and retrograde tracking (CART) technique via an ipsilateral intraseptal collateral. A-76-year-old man that had undergone previous coronary artery bypass surgery was admitted for ischemic heart failure. Coronary angiography showed that the left internal thoracic artery graft that was anastomosed to the first diagonal branch was patent. However, his native LAD had two CTOs as if the open vessel had sandwiched them. Moreover, there were no interventional collaterals. The antegrade guidewire was successfully passed through both CTOs. However, devices were uncrossable at the entry of the distal LAD-CTO. After stent deployment at the proximal CTO, local rotational atherectomy with a 1.5 mm burr was performed as plaque modification from the protruding calcified plaque at the bifurcation of the first septal branch to the distal CTO entry for the following procedure, although the dedicated guidewire was unable to pass completely through the distal CTO segment. Staged PCI to the distal LAD-CTO was performed using a retrograde approach via an ipsilateral intraseptal collateral, which had grown due to recanalization of the proximal LAD-CTO. Due to plaque modification by rotablation at the first attempt, successful interventional revascularization to the distal LAD-CTO was accomplished using the reverse CART technique.

Relation of antiplatelet therapy (APT) discontinuation with the risk of serious cardiovascular events has not been fully addressed yet. This study is aimed to evaluate the risk of ischemic event after APT discontinuation based on long-term APT status of large cohort. In the CREDO-Kyoto Registry Cohort-2 enrolling 15939 consecutive patients undergoing first coronary revascularization, 10470 patients underwent percutaneous coronary intervention either with bare-metal stents (BMS) only (N=5392) or sirolimus-eluting stents (SES) only (N=5078). Proportions of patients taking dual-APT were 67.3% versus 33.4% at 1-year, and 48.7% versus 24.3% at 5-year in the SES and BMS strata, respectively. We evaluated daily APT status (dual-, single- and no-APT) and linked the adverse events to the APT status just 1-day before the events. No-APT as compared with dual- or single-APT was associated with significantly higher risk for stent thrombosis (ST) beyond 1-month after SES implantation (cumulative incidence rates beyond 1-month: 1.23 versus 0.15/0.29, P<0.001/P<0.001), while higher risk of no-APT for ST was evident only until 6-month after BMS implantation (incidence rates between 1- and 6-month: 8.43 versus 0.71/1.20, P<0.001/P<0.001, and cumulative incidence rates beyond 6-month: 0.31 versus 0.11/0.08, P=0.16/P=0.08). No-APT as compared with dual- or single-APT was also associated with significantly higher risk for spontaneous myocardial infarction (MI) and stroke regardless of the types of stents implanted. Single-APT as compared with dual-APT was not associated with higher risk for serious adverse events, except for the marginally higher risk for ST in the SES stratum. In conclusion, discontinuation of both aspirin and thienopyridines was associated with increased risk for serious cardiovascular events including ST, spontaneous MI and stroke beyond 1-month after coronary stenting.

Background— Female sex was reported to be associated with lower risk for midterm restenosis and repeat revascularization after bare-metal stent implantation. However, the influence of sex on very long-term outcomes after bare-metal stent implantation has not been yet reported. Methods and Results— Among the 9877 patients in the multicenter Coronary Revascularization Demonstrating Outcome study in Kyoto (CREDO-Kyoto) registry cohort-1, bare-metal stent implantation was performed in 5313 patients (men, n=3742 and women, n=1571). Follow-up was completed in 4515 patients (85.0%) at 10 years (duration, 10.3±3.1 [0.0–14.1] years). The cumulative incidence of target-lesion revascularization (TLR) was 27% at 1 year and 34% at 10 years (0.8%/y beyond 1 year). Non–target-lesion revascularization (non-TLR) was the dominant coronary revascularization beyond 1 year (13% at 1 year and 31% at 10 years [2.0%/y beyond 1 year]). Cumulative incidence of stent thrombosis was low (1.2% at 1 year and 1.9% at 10 years). Women were older and had greater prevalence of cardiovascular risk factors than men. The cumulative 10-year incidences of and adjusted risk for TLR were significantly higher in men than in women (36% versus 30%, P <0.001; adjusted hazard ratio, 1.29; 95% confidence interval, 1.15–1.46; P <0.001). The higher risk of men relative to women for TLR was consistent regardless of age (<75 years and ≥75 years). Men in comparison with women were also associated with significantly higher adjusted risks for all-cause death, myocardial infarction, stroke, coronary artery bypass grafting, TLR, and non-TLR. Conclusions— TLR and stent thrombosis continued to occur without attenuation up to 10 years after bare-metal stent implantation. Men in comparison with women were associated with higher adjusted 10-year risks for all-cause death, myocardial infarction, stroke, coronary artery bypass grafting, TLR, and non-TLR.

Curcumin is a major constituent of the spice turmeric and has various biological activities, including anticancer, antioxidant, and anti-inflammatory properties, as well as alcohol detoxification. However, because of its poor absorption efficiency, it is difficult for orally administered curcumin to reach blood levels sufficient to exert its bioactivities. To overcome this problem, several curcumin preparations with a drug-delivery system (DDS) have been developed to increase the bioavailability of curcumin after oral administration, and tested as functional foods and potential medical agents in humans. We have also produced capsules containing Theracurmin, curcumin dispersed with colloidal submicron-particles. To evaluate the absorption efficiency of three types of DDS curcumin, we performed a double-blind, 3-way crossover study. We compared plasma curcumin levels after the administration of Theracurmin and 2 other capsule types of curcumin with DDS, BCM-95 (micronized curcumin with turmeric essential oils) and Meriva (curcumin-phospholipid). Nine healthy subjects (male/female=5/4, age: 24-32 y old) were administered these 3 preparations of DDS curcumin, at commonly used dosages. Six capsules of Theracurmin, 1 capsule of BCM-95, and 2 capsules of Meriva contain 182.4 ± 1.0, 279.3 ± 10.7, and 152.5 ± 20.3 mg of curcumin, respectively. The maximal plasma curcumin concentration (0-24 h) of Theracurmin was 10.7 to 5.6 times higher than those of BCM-95 and Meriva, respectively. Moreover, the area under the blood concentration-time curve at 0-24 h was found to be 11.0- and 4.6-fold higher with Theracurmin than BCM-95 and Meriva, respectively. These data indicate that Theracurmin exhibits a much higher absorption efficiency than other curcumin DDS preparations.

The prevalence, intensity, safety, and efficacy of oral anticoagulation (OAC) in addition to dual antiplatelet therapy (DAPT) in "real-world" patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not yet been fully evaluated. In the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry cohort-2, a total of 1,057 patients with AF (8.3%) were identified among 12,716 patients undergoing first PCI. Cumulative 5-year incidence of stroke was higher in patients with AF than in no-AF patients (12.8% vs 5.8%, p <0.0001). Although most patients with AF had CHADS2 score ≥2 (75.2%), only 506 patients (47.9%) received OAC with warfarin at hospital discharge. Cumulative 5-year incidence of stroke in the OAC group was not different from that in the no-OAC group (13.8% vs 11.8%, p = 0.49). Time in therapeutic range (TTR) was only 52.6% with an international normalized ratio of 1.6 to 2.6, and only 154 of 409 patients (37.7%) with international normalized ratio data had TTR ≥65%. Cumulative 5-year incidence of stroke in patients with TTR ≥65% was markedly lower than that in patients with TTR <65% (6.9% vs 15.1%, p = 0.01). In a 4-month landmark analysis in the OAC group, there was a trend for higher cumulative incidences of stroke and major bleeding in the on-DAPT (n = 286) than in the off-DAPT (n = 173) groups (15.1% vs 6.7%, p = 0.052 and 14.7% vs 8.7%, p = 0.10, respectively). In conclusion, OAC was underused and its intensity was mostly suboptimal in real-world patients with AF undergoing PCI, which lead to inadequate stroke prevention. Long-term DAPT in patients receiving OAC did not reduce stroke incidence.

Background—Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) after first-generation sirolimus-eluting stents (SES) implantation have not been yet fully characterized at long term in comparison with those after bare-metal stent (BMS) implantation. Methods and Results—Among 13 058 consecutive patients undergoing first percutaneous coronary intervention in the Coronary REvascularization Demonstrating Outcome study-Kyoto registry Cohort-2, 5078 patients were treated with SES only, and 5392 patients were treated with BMS only. During 7-year follow-up, VLST and late TLR beyond 1 year after SES implantation occurred constantly and without attenuation at 0.24% per year and at 2.0% per year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than that in the BMS group (1.43% versus 0.68%, P<0.0001). However, there was no excess of all-cause death beyond 1 year in the SES group as compared with that in the BMS group (20.8% versus 19.6%, P=0.91). Cumulative incidences of late TLR (both overall and clinically driven) were also significantly higher in the SES group than in the BMS group (12.0% versus 4.1%, P<0.0001 and 8.5% versus 2.6%, P<0.0001, respectively), leading to late catch-up of the SES group to the BMS group regarding TLR through

Background— Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) after first-generation sirolimus-eluting stents (SES) implantation have not been yet fully characterized at long term in comparison with those after bare-metal stent (BMS) implantation. Methods and Results— Among 13 058 consecutive patients undergoing first percutaneous coronary intervention in the Coronary REvascularization Demonstrating Outcome study-Kyoto registry Cohort-2, 5078 patients were treated with SES only, and 5392 patients were treated with BMS only. During 7-year follow-up, VLST and late TLR beyond 1 year after SES implantation occurred constantly and without attenuation at 0.24% per year and at 2.0% per year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than that in the BMS group (1.43% versus 0.68%, P <0.0001). However, there was no excess of all-cause death beyond 1 year in the SES group as compared with that in the BMS group (20.8% versus 19.6%, P =0.91). Cumulative incidences of late TLR (both overall and clinically driven) were also significantly higher in the SES group than in the BMS group (12.0% versus 4.1%, P <0.0001 and 8.5% versus 2.6%, P <0.0001, respectively), leading to late catch-up of the SES group to the BMS group regarding TLR through the entire 7-year follow-up (18.8% versus 25.2%, and 10.6% versus 10.2%, respectively). Clinical presentation as acute coronary syndrome was more common at the time of late SES TLR compared with early SES TLR (21.2% and 10.0%). Conclusions— Late catch-up phenomenon regarding stent thrombosis and TLR was significantly more pronounced with SES than that with BMS. This limitation should remain the target for improvements of DES technology.

Background—Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) after first-generation sirolimus-eluting stents (SES) implantation have not been yet fully characterized at long term in comparison with those after bare-metal stent (BMS) implantation. Methods and Results—Among 13 058 consecutive patients undergoing first percutaneous coronary intervention in the Coronary REvascularization Demonstrating Outcome study-Kyoto registry Cohort-2, 5078 patients were treated with SES only, and 5392 patients were treated with BMS only. During 7-year follow-up, VLST and late TLR beyond 1 year after SES implantation occurred constantly and without attenuation at 0.24% per year and at 2.0% per year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than that in the BMS group (1.43% versus 0.68%, P<0.0001). However, there was no excess of all-cause death beyond 1 year in the SES group as compared with that in the BMS group (20.8% versus 19.6%, P=0.91). Cumulative incidences of late TLR (both overall and clinically driven) were also significantly higher in the SES group than in the BMS group (12.0% versus 4.1%, P<0.0001 and 8.5% versus 2.6%, P<0.0001, respectively), leading to late catch-up of the SES group to the BMS group regarding TLR through the entire 7-year follow-up (18.8% versus 25.2%, and 10.6% versus 10.2%, respectively). Clinical presentation as acute coronary syndrome was more common at the time of late SES TLR compared with early SES TLR (21.2% and 10.0%). Conclusions—Late catch-up phenomenon regarding stent thrombosis and TLR was significantly more pronounced with SES than that with BMS. This limitation should remain the target for improvements of DES technology.

Curcumin has various biological activities including antioxidant and antiinflammatory actions, and alcohol detoxification. However, because of its poor absorption efficiency, it is difficult for orally administered curcumin to reach blood levels sufficient to realize its bioactivities. We have generated capsules and tablets containing Theracurmin, a highly absorptive curcumin. In addition, we recently created a drinkable preparation of Theracurmin. To evaluate the absorption efficiency of this type of curcumin, we performed a single-dose, double-blind, 4-way crossover study. We compared plasma curcumin levels after the administration of Theracurmin beverage and 3 other drinkable types of curcumin sold in Japan. Twenty-four healthy subjects (male/female=13/11, age: 23-32) were administered with these 4 drinkable preparations of curcumin. The area under the blood concentration-time curve at 0-8 h was found to be 1.5 to 4.0-fold higher with Theracurmin than with the other 3 kinds of curcumin beverage. Moreover, maximal plasma curcumin concentrations (0-8 h) of Theracurmin were 1.8 to 3.8 times higher than those of the other 3 curcumin beverages. These data indicate that our newly prepared Theracurmin beverage exhibits a much better absorption efficiency than other kinds of curcumin beverage sold in Japan.

Due to serious concerns on very late stent thrombosis (VLST), extended use of dual antiplatelet therapy (DAPT) beyond 1 year after DES implantation has become a common clinical practice despite apparent lack of evidence suggesting its efficacy in reducing VLST. The study population consisted of 12812 patients in the j-Cypher registry who were treated with at least one sirolimus-eluting stent (SES). We assessed the relation between duration of thienopyridine therapy and clinical outcomes with a landmark analysis at 1 year after SES implantation. Among 11713 patients without myocardial infarction (MI), stent thrombosis and stroke at 1 year who were eligible for the landmark analysis, 7414 patients (63 %) were maintained on thienopyridine at 1-year landmark point, while 4299 patients (37 %) had discontinued thienopyridine before 1-year landmark point. Patients in the on-thienopyridine group had more complex characteristics than patients in the off-thienopyridine group. Cumulative incidence of and the risk for definite VLST in the on-thienopyridine group relative to the off-thienopyridine group favored prolonged DAPT, but were not significant [0.9 and 1.2 %, P = 0.1, and adjusted HR (95 % CI): 0.71 (0.47-1.06), P = 0.11]. Cumulative incidence of and the risk for a composite of death, MI, or stroke in the on-thienopyridine group relative to the off-thienopyridine group were also not significant [15.3 and 14.3 %, P = 0.15, and adjusted HR (95 % CI): 0.99 (0.89-1.11), P = 0.89]. Prolonged use of thienopyridine beyond 1 year after SES implantation was not associated with significant decrease in the risks for VLST or for serious cardiovascular events including death, MI or stroke.

Therapeutic strategies preventing late target lesion revascularization (TLR) after drug-eluting stent implantation have not been yet adequately investigated. In 13,087 consecutive patients undergoing first percutaneous coronary intervention in the CREDO-Kyoto Registry Cohort-2, we identified 10,221 patients who were discharged alive after implantation of sirolimus-eluting stents (SESs) only (SES stratum 5,029) or bare-metal stents (BMSs) only (BMS stratum 5,192). Impact of statin therapy at time of discharge from the index hospitalization on early (within the first year) and late (1 year to 4 years) TLR, was assessed in the SES stratum (statin group 2,735; nonstatin group 2,294) and in the BMS stratum (statin group 2,576; nonstatin group 2,616). Despite a significantly lower incidence of early TLR (7.8% vs 22.2%, p <0.0001), SES use compared to BMS use was associated with a significantly higher incidence of late TLR (7.7% vs 3.0%, p <0.0001). In the SES and BMS strata, the incidence of early TLR was similar regardless of statin use. In the SES stratum, the incidence of late TLR was significantly lower in the statin group than in the nonstatin group (6.1% vs 9.6%, p = 0.002), whereas no significant difference was found in the BMS stratum (2.6% vs 3.3%, p = 0.38). After adjusting confounders, risk for late TLR significantly favored statin use in the SES stratum (hazard ratio 0.73, 95% confidence interval 0.54 to 0.98, p = 0.04), whereas the risk decrease was not significant in the BMS stratum (hazard ratio 0.74, 95% confidence interval 0.46 to 1.20, p = 0.23). In conclusion, statin therapy at hospital discharge was associated with a significantly lower risk for late TLR after SES implantation.

Introduction The AHA/ACC guidelines recommend pre-hospital 12-lead electrocardiogram (ECG) transmission to a percutaneous coronary intervention (PCI) hospital to facilitate the care of patients with acute coronary syndrome. We created a handheld wireless 12-lead ECG transmission system called Fujiyama involving Cardiospy® Mobile, a handheld 12-lead ECG recording device. Fujiyama functions by transmitting the ECG from Cardiospy® Mobile to a smartphone through Bluetooth wireless technology, converting the ECG to MFER(Medical Waveform Format Encoding Rule)/JPEG, and sending it to a designated email address using ubiquitous and standard network. Hypothesis We predicted that our smaller device will be equally efficacious in transmitting accurate data as the current portable ECG recording device used in the healthcare industry. Methods We recorded and transmitted 12-lead ECGs using our device from a moving vehicle (simulating an ambulance), and investigated the influences of road turbulence, body movements, fast driving, as well as transmission time and accuracy by comparing ECGs recorded in a hospital setting. Furthermore, after approval from the institutional review board, the device was tested on 24 actual patients (4 emergency room, 5 clinic, 4 home hemodialysis, 11 visiting nurse care) transmitting ECGs to the attending cardiologist of a PCI hospital. Results There were no significant ECG differences found between sent and received ECGs, and vehicle speed did not affect the baseline ECG. Body movement, blood pressure measurement and cardiac compression caused the baseline to wander to some extent, but did not affect ECG interpretation. The transmission time of a 250-350 KB file was 7-95 s (median 23 s), short enough for emergency settings. Transmission rate of the 24 ECGs was 100 %, and only one had significant interference from appliances and peripheral equipment. Conclusions As far as we know, this system is the first wireless 12-lead ECG recording and transfer device in this weight (150 g, including batteries) and size category (70 × 38 × 125 mm). In conclusion, successful implementation of this system may improve the communication and care of patients with acute coronary syndrome in various settings, including emergency pre-hospital care.