Effect of QRS Morphology and Duration on Clinical Outcomes After Cardiac Resynchronization Therapy　- Analysis of Japanese Multicenter Registry.

BACKGROUND: QRS duration (QRSd) and morphology are established response predictors of cardiac resynchronization therapy (CRT). However, evidence in Japanese populations is lacking.Methods and Results:We retrospectively analyzed the Japanese multicenter CRT database. We divided patients according to their intrinsic QRSd and morphology, and assessed echocardiographic responses and clinical outcomes. The primary endpoint was a composite of all-cause death or hospitalization because of heart failure. A total of 510 patients were enrolled: 200 (39%) had left bundle branch block (LBBB) and QRSd ≥150 ms; 80 (16%) had LBBB (QRSd: 120-149 ms); 61 (12%) had non-LBBB (NLBBB) (QRSd: ≥150 ms); 54 (11%) had NLBBB (QRSd: 120-149 ms); 115 (23%), narrow (<120 ms). The proportion of echocardiographic responders was higher in LBBB (QRSd ≥150 ms) [74% vs. 51% vs. 38% vs. 52% vs. 50%, LBBB (QRSd ≥150 ms) vs. LBBB (QRSd 120-149 ms) vs. NLBBB (QRSd ≥150 ms) vs. NLBBB (QRSd 120-149 ms) vs. narrow, respectively, P<0.001]. During follow-up (3.2±1.5 years), the incidence of the primary endpoint was lowest in the LBBB group (QRSd ≥150) (28.6% vs. 42.3% vs. 45.9% vs. 55.6% vs. 55.3%, respectively, P<0.001). This difference was still significant after adjusting for other baseline characteristics. CONCLUSIONS: In this Japanese patient population, LBBB intrinsic QRS morphology and prolonged QRSd (≥150 ms) exhibited the best response to CRT.

Duration of reverse remodeling response to cardiac resynchronization therapy: Rates, predictors, and clinical outcomes.

BACKGROUND: A subset of patients undergoing cardiac resynchronization therapy (CRT) for heart failure (HF) with severe left ventricular (LV) dysfunction experience only short-lived LV reverse remodeling. Little is known about the incidence and prognosis of this finding. We sought to identify predictors of a brief response and investigated the prognosis in a retrospective study. METHODS: A total of 528 patients from a Japanese multicenter database with full echocardiography datasets were enrolled. Follow-up was 3.4±1.3years. Based on relative reduction in LV end-systolic volume (LVESV) at 6months, we categorized patients as responders (reduction in LVESV ≥15%) and non-responders (NRs; reduction in LVESV <15%). Based on reduction in LVESV at 1-2years, responders were subdivided into long-lasting responders (reduction in LVESV ≥15%) and brief responders (reduction in LVESV <15%). RESULTS: Of 328 responders, 50 (15%) were brief responders. Predictors of brief response were prior ventricular tachyarrhythmia, a non-left bundle-branch block (LBBB) intrinsic QRS pattern, and prior hospitalization for HF. The risk of all-cause death in brief responders was significantly lower than that in NRs (P=0.034) and tended to be higher than that in long-lasting responders (P=0.080). CONCLUSIONS: Approximately 15% of responders were brief responders. Prior ventricular tachyarrhythmia, a non-LBBB pattern, and HF hospitalization were independent predictors of a brief response. Brief response was significantly associated with decreased risk of all-cause death compared with NRs and had a tendency toward increased risk of all-cause death compared with long-lasting responders.

Drug-eluting stents or balloon angioplasty for drug-eluting stent-associated restenosis: An observational follow-up study of first-time versus repeated restenosis.

BACKGROUND: The treatment of patients with repeated drug-eluting stent-in stent restenosis (DES-ISR) remains a challenge and a burdensome clinical problem. METHODS: Over a 3-year period, 130 lesions in 123 patients who underwent target lesion revascularization (TLR) for DES restenosis were included in the study. They were classified into two main groups: the first group having first-time DES-ISR (n = 84), and the second group having rerestenosis of DES-treated DES-ISR (n = 39). Further classification according to the treatment strategy yielded four subgroups: balloon angioplasty (BA) in first-time DES-ISR (n = 66), re-DES in the same group (n = 22), BA in rerestenosis of DES-treated DES-ISR (n = 30), and re-DES in the same group (n = 10). Angiographic follow-up was planned at 1 year, and clinical follow-up for re-TLR up to 2 years later. RESULTS: The mean duration of clinical follow-up was 24.8 ± 9.7 months. The angiographic follow-up data were obtained for 108 patients (87.8%) at 1 year. Among patients treated for first-time DES-ISR, late lumen loss (0.65 ± 0.83 mm and 1.02 ± 0.52 mm, p = 0.02) and binary restenosis rates (25% and 49.1%, p = 0.05) were significantly less in those undergoing re-DES compared with BA. This benefit was not evident in patients having rerestenosis of DES-treated DES-ISR. Re-TLR at 2 years was significantly less in the re-DES group compared with BA (log rank p = 0.038) in first-time DES-ISR patients, while no significant difference (log rank p = 0.58) was observed in those having rerestenosis of DES-treated DES-ISR. CONCLUSION: While a strategy of re-DES would be better than BA in first-time DES-ISR, this could not be extrapolated to rerestenosis cases.

Mortality and predictors of appropriate implantable cardioverter defibrillator therapy in Japanese patients with Multicenter Automatic Defibrillator Implantation Trial II criteria.

BACKGROUND: Data regarding long-term mortality and factors influencing appropriate therapies in Japanese patients with implantable cardioverter defibrillators (ICD), who satisfy the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) criteria for primary prevention, remain scarce. METHODS: A total of 118 consecutive patients who underwent ICD implantation without any prior ventricular arrhythmic event, from January 2000 to December 2012, were enrolled based on the MADIT II criteria: left ventricular ejection fraction (LVEF) of ≤30% with ischemic heart disease and at least 4 weeks after a myocardial infarction. We investigated the mortality and factors influencing appropriate ICD therapies in this population. RESULTS: The mean age was 69±10 years, and the mean LVEF was 25.1±4.5%. During the median follow up of 1406 days, the mortality rate was 20%, and the incidence of appropriate ICD therapy was 37% at 3 years. Multivariate analysis by using Cox regression model showed that left ventricular diastolic diameter ≥60 mm (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.07-5.38; P=0.033) and the presence of non-sustained ventricular tachycardia (NSVT) before implantation (HR, 2.26; 95% CI, 1.17-4.39; P=0.015) were independent predictors of appropriate ICD therapy. CONCLUSIONS: The mortality and incidence of appropriate ICD therapy were 20% and 37%, respectively, at 3 years in Japanese patients who met the MADIT II criteria during ICD implantation for primary prevention of sudden cardiac death. The presence of NSVT and dilated left ventricle independently predicted the incidence of appropriate ICD therapy after implantation.

Antiplatelet therapy discontinuation and stent thrombosis after sirolimus-eluting stent implantation: five-year outcome of the j-Cypher Registry.

BACKGROUND: The influence of antiplatelet therapy discontinuation on the incidence of stent thrombosis, especially very late stent thrombosis, after drug-eluting stent implantation has not been yet fully addressed. METHODS: Relationship between antiplatelet therapy discontinuation and stent thrombosis up to 5years was evaluated in 12,812 consecutive patients undergoing sirolimus-eluting stents (SES) implantation in the j-Cypher registry. Data on status of antiplatelet therapy during follow-up were collected prospectively. RESULTS: Median follow-up interval was 1699days (interquartile range, 1184-1928days). Incidences of definite stent thrombosis were 0.34% at 30days, 0.55% at 1year, and 1.6% at 5years. Dual antiplatelet therapy was maintained in 97.4%, 63%, and 43.9% of patients at 30days, 1year, and 5years, respectively. The rates of stent thrombosis in patients who discontinued both thienopyridine and aspirin were significantly higher in the time intervals of 31-365days, 2-3years and 3-4years, and tended to be higher in the time intervals of 1-2years and 4-5years than those in patients who continued both (31-365days: 1.26% versus 0.2%, P<0.001; 1-2years: 0.59% versus 0.15%, P=0.06; 2-3years: 1.35% versus 0.2%, P=0.004; 3-4years: 1.09% versus 0.25%, P=0.0496; 4-5years: 1.35% versus 0.43%, P=0.17). Patients who discontinued either thienopyridine or aspirin only did not have an excess of stent thrombosis in any time intervals. CONCLUSIONS: In conclusion, discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine or aspirin only, was associated with an increased incidence of late and very late stent thrombosis up to 5years after SES implantation.

Clinical efficacy of thrombus aspiration on 5-year clinical outcomes in patients with ST-segment elevation acute myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: Adjunctive thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) was reported to promote better coronary and myocardial reperfusion. However, long-term mortality benefit of TA remains controversial. The objective of this study is to investigate the clinical impact of TA on long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. METHODS AND RESULTS: The CREDO-Kyoto AMI Registry is a large-scale cohort study of acute myocardial infarction patients undergoing coronary revascularization in 2005-2007 at 26 hospitals in Japan. Among 5429 patients enrolled in the registry, the current study population consisted of 3536 patients who arrived at the hospital within 12 hours after the symptom onset and underwent primary PCI. Clinical outcomes were compared between the 2 patient groups with or without TA. During primary PCI procedures, 2239 out of 3536 (63%) patients underwent TA (TA group). The cumulative 5-year incidence of all-cause death was significantly lower in the TA group than in the non-TA group (18.5% versus 23.9%, log-rank P<0.001). After adjusting for confounders, however, the risk for all-cause death in the TA group was not significantly lower than that in the non-TA group (hazard ratio: 0.90, 95% CI: 0.76 to 1.06, P=0.21). The adjusted risks for cardiac death, myocardial infarction, stroke, and target-lesion revascularization were also not significantly different between the 2 groups. CONCLUSIONS: Adjunctive TA during primary PCI was not associated with better 5-year mortality in STEMI patients.

Antiplatelet therapy discontinuation and the risk of serious cardiovascular events after coronary stenting: observations from the CREDO-Kyoto Registry Cohort-2.

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.

Vascular response after Zilver PTX stent implantation for superficial femoral artery lesions: serial optical coherence tomography findings at 6 and 12 months.

PURPOSE: To compare the vascular response after paclitaxel-coated nitinol drug-eluting stent (Zilver PTX) implantation for superficial femoral artery lesions after 6 and 12 months using optical coherence tomography (OCT). METHODS: Serial OCT examinations were performed in 5 patients (4 men; mean age 78.4 ± 6.8 years) with 9 Zilver PTX stents at 6- and 12-month follow-up. Variables evaluated included neointimal thickness and apposition on each strut, the incidence of extrastent lumen (ESL), peristrut low-intensity area (PLIA), and neovascularization at 1-mm intervals. RESULTS: A total of 249 matched cross-section images were evaluated and included 4788 and 4826 struts at 6 and 12 months, respectively. Mean neointimal thickness significantly increased from 480 to 540 µm between 6 and 12 months (p < 0.001). The percentage of uncovered struts tended to decrease at 12 months (3% vs. 2.3%, p = 0.054), whereas the percentage of malapposed struts were similar at both examinations (0.2% vs. 0.2%, p > 0.99). Although the incidence of ESL in cross sections was not different (35% vs. 31%, p = 0.29), median ESL area significantly increased from 6 to 12 months [0.12 (0.04-0.36) vs. 0.31 (0.14-0.59) mm(2), p = 0.003)]. The presence of PLIA (29% vs. 44%, p < 0.001) and neovascularization (14% vs. 27%, p < 0.001) increased from 6 to 12 months. CONCLUSION: These findings suggest that delayed vascular healing and persistent peristent inflammation may be present even at 12 months after Zilver PTX implantation.

Association of localized hypersensitivity and in-stent neoatherosclerosis with the very late drug-eluting stent thrombosis.

BACKGROUND: Localized hypersensitivity reaction, delayed arterial healing, and neoatherosclerosis inside the stent have been suggested as the underlying pathologic mechanisms of very late stent thrombosis (VLST) of drug-eluting stent (DES). The present study sought to explore the prevalence of inflammatory cell infiltrates and evidence for fragments of atherosclerotic plaques in the aspirated thrombi in patients with DES VLST. METHODS AND RESULTS: From April 2004 to September 2012, 48 patients with stent thrombosis (ST) of DES underwent thrombus aspiration with retrieved material sufficient for the histopathologic analysis; early ST (EST, within 30 days): N = 17, late ST (LST, between 31 and 365 days): N = 7, and very late ST (VLST, >1 year): N = 24. Eosinophil fraction in the aspirated thrombi was significantly higher in patients with VLST (8.2±5.7%) as compared with those with EST (4.3±3.0%) and LST (5.5±3.8%) (P = 0.03). Eosinophil fraction in the aspirated thrombi was significantly higher in 12 VLST patients with angiographic peri-stent contrast staining (PSS) and/or incomplete stent apposition (ISA) by intravascular ultrasound than in 12 VLST patients without PSS or ISA (10.6±6.1% versus 5.8±4.1%, P = 0.03). Evidences for fragments of atherosclerotic plaques in the aspirated thrombi were observed only in 3 (13%) out of 24 patients with DES VLST. CONCLUSIONS: Eosinophil fraction in the aspirated thrombi was significantly higher in patients with DES VLST as compared with those with EST and LST. Evidences for fragments of atherosclerotic plaques were relatively uncommon in patients with DES VLST.

Long-term coronary arterial response to biodegradable polymer biolimus-eluting stents in comparison with durable polymer sirolimus-eluting stents and bare-metal stents: five-year follow-up optical coherence tomography study.

OBJECTIVE: The long-term coronary arterial response of biodegradable polymer biolimus-eluting stents (BES) remains unclear. We sought to evaluate the coronary arterial response of biodegradable polymer BES at 5 years after stent implantation using optical coherence tomography (OCT) as compared with that of durable polymer sirolimus-eluting stents (SES) and bare-metal stents (BMS). METHODS: Five-year follow-up OCT was performed in 30 patients with 33 stents (10 with 12 BES; 10 with 11 SES; 10 with 10 BMS). Quantitative parameters and qualitative characteristics of the neointima were evaluated. A total of 5178 struts (BES, n = 2056; SES, n = 1410; BMS, n = 1712) were analyzed. RESULTS: Uncovered struts were found in 15 out of 2055 struts in the BES (weighted estimate 0.01%, 95% confidence intervals [CI]: 0.00-0.33%) and 54 out of 1410 struts in the SES (0.11%, 95% CI: 0.00-3.33%) (odds ratio [OR] 0.12, 95% CI: 0.01-1.95, p = 0.13). None of 1712 struts were uncovered in the BMS. Cross-sectional qualitative analysis of neointimal tissue showed that the frequency of lipid-laden neointima tended to be lower in the BES (2.26%, 95% CI: 0.38-12.3%) compared with the SES (9.90%, 95% CI: 4.37-20.9%; OR 0.21, 95% CI 0.03-1.16, p = 0.07), and was similar to the BMS (2.23%, 95% CI: 0.54-8.74%; OR 0.98, 95% CI 0.13-7.14, p = 0.98). CONCLUSIONS: Biodegradable polymer BES shows a favorable coronary arterial response compared with SES, but different response with BMS at 5 years follow-up. The observed frequency of in-stent neoatherosclerosis within BES was similar to BMS and tended to be lower than SES.

Impact of clinical and echocardiographic characteristics on occurrence of cardiac events in cardiac amyloidosis as proven by endomyocardial biopsy.

BACKGROUND: Although patients with immunoglobulin light chain (AL) cardiac amyloidosis exhibit worse outcomes than those with transthyretin (TTR) cardiac amyloidosis, few data exist regarding the occurrence of cardiac events and the echocardiographic indices in endomyocardial biopsy (EMBx) proven amyloidosis. METHODS: From November 2007 to October 2012, we identified 33 patients with EMBx-proven amyloidosis. There were 12 patients (8 men; mean age: 66 years) with AL and 21 patients (20 men; mean age: 78 years) with TTR. We performed serial echocardiography and observed the patients during follow-up; defining all-cause mortality as the primary endpoint and hospitalization for heart failure as the secondary endpoint. RESULTS: The survival rates at 12 months were 20.8% and 85.7% in AL and TTR, respectively (p<0.001). The cumulative incidences of the composite of death or readmission for heart failure at 12 months were 91.7% and 51.3% in AL and TTR, respectively (p<0.001). A multivariate analysis showed that the AL type amyloid was the powerful predictor of mortality (hazard ratio: 8.50, 95% confidence interval: 1.79 to 40.57, p<0.05). Under these conditions, the E/e' in AL tended to increase from 23±13 to 28±11 (p=0.06) with marked increases in B-type natriuretic peptide (779±456 pg/ml to 1576±895 pg/ml, p<0.05), although these remained unchanged in TTR, which exhibited significantly increased left ventricular end-diastolic dimensions from 40±4 mm to 42±4 mm (p<0.05). CONCLUSIONS: The survival rate was generally worse in AL cardiac amyloidosis, although the readmission for heart failure remains high in TTR cardiac amyloidosis with the occurrence of left ventricular dilatation.

Incidence and outcome of surgical procedures after coronary artery bypass grafting compared with those after percutaneous coronary intervention: a report from the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry Cohort-2.

BACKGROUND: Noncardiac surgery after percutaneous coronary intervention (PCI) has been reported to be carrying high risk for both ischemic and bleeding complications. However, there has been no report comparing the incidence and outcomes of surgical procedures after coronary artery bypass grafting (CABG) with those after PCI. METHODS AND RESULTS: Among 14 383 patients undergoing first coronary revascularization (PCI, n=12 207; CABG, n=2176) enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) PCI/CABG Registry Cohort-2, surgical procedures were performed more frequently after CABG (n=560) than after PCI (n=2398; cumulative 3-year incidence: 27% versus 22%; unadjusted P<0.0001), particularly <6 months of coronary revascularization. The risk for the primary ischemic outcome measure (death/myocardial infarction) at 30-day postsurgical procedures was not significantly different between the CABG and PCI groups (cumulative incidence: 3.1% versus 3.2%; unadjusted P=0.9; adjusted hazard ratio, 0.97; 95% confidence interval, 0.47-1.89; P=0.9). The risk for the primary bleeding outcome measure (moderate or severe bleeding by Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries classification) was lower in the CABG groups than in the PCI group (cumulative incidence: 1.3% versus 2.6%; unadjusted P=0.07; adjusted hazard ratio, 0.36; 95% confidence interval, 0.12-0.87; P=0.02). There were no interactions between the timing of surgery and the types of coronary revascularization (CABG/PCI) for both ischemic and bleeding outcomes. CONCLUSIONS: Surgical procedures were performed significantly more frequently after CABG than after PCI, particularly <6 months after coronary revascularization. Surgical procedures after CABG as compared with those after PCI were associated with similar risk for ischemic events and lower risk for bleeding events, regardless of the timing after coronary revascularization.

Anticoagulant and antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

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.

Incidence and clinical impact of stent fracture after the Nobori biolimus-eluting stent implantation.

BACKGROUND: Stent fracture (SF) after drug-eluting stent implantation has become an important concern. The aim of this study was to assess the incidence, predictors, and clinical impact of SF after biolimus-eluting stent. METHODS AND RESULTS: A total of 1026 patients with 1407 lesions undergoing the Nobori biolimus-eluting stent implantation and follow-up angiography within 9 months after index procedure were analyzed. SF was defined as complete or partial separation of the stent, as assessed by using plain fluoroscopy, intravascular ultrasound, or optical coherence tomography during the follow-up. We assessed the rate of SF and the cumulative incidence of clinically driven target lesion revascularization and definite stent thrombosis within 9 months. SF was observed in 58 (4.1%) of 1407 lesions and 57 (5.5%) of 1026 patients. Lesions with hinge motion (OR 8.90, 95% CI 3.84 to 20.6, P<0.001), tortuosity (OR 4.16, 95% CI 1.75 to 9.88, P=0.001), and overlapping stents (OR 2.41, 95% CI 0.95 to 6.10, P=0.06) were predictors of SF. Cumulative incidence of clinically driven target lesion revascularization within 9 months was numerically higher in the SF group than that in the non-SF group (12.0% versus 1.0%). Cumulative incidence of definite stent thrombosis within 9 months tended to be higher in the SF group than that in the non-SF group (1.7% versus 0.5%). CONCLUSIONS: SF after biolimus-eluting stent occurs in 4.1% of lesions and appears to be associated with clinically driven target lesion revascularization.

A comparison of bolus injection of landiolol versus oral administration of propranolol before cardiac computed tomography.

Heart rate (HR) reduction is essential to achieve good image quality for cardiac computed tomography (CCT). We evaluated the efficacy of a bolus injection of landiolol, an ultra-short acting ß-blocker, without the administration of oral ß-blocker to reduce HR prior to CCT. We enrolled 678 consecutive patients who underwent CCT from December 2011 to March 2012 and divided them into three groups, which were a propranolol group (n = 277), a low-dose landiolol group (n = 188), and a high-dose landiolol group (n = 213). Patients in the propranolol group received oral propranolol (10-20 mg) prior to CCT. Patients in the low-dose and high-dose landiolol groups were administered a bolus injection of landiolol (0.125 mg/kg), while the high-dose group received an additional 3.75 mg of landiolol if the baseline HR was ≥75/min. Although the average HR was significantly lower in the propranolol group (61.6 ± 8.0/min) than in the low-dose landiolol group (64.1 ± 7.4/min, P < 0.001), there was no significant difference in the image quality (P = 0.91). Among patients with baseline HR ≥75/min, the average HR tended to be lower in the high-dose landiolol group (67.2 ± 6.9/min) compared with the low-dose landiolol group (69.0 ± 6.9/min, P = 0.10), and there was a corresponding difference in image quality between these two groups (P = 0.02). In conclusion, Although the decrease of HR was significantly larger in the propranolol group than in the landiolol groups, the image quality was similar. Among the patients who received landiolol, a higher dose was associated with a lower HR and better image quality. Further investigation to assess higher-dose bolus injection of landiolol or bolus injection following oral administration of a ß-blocker would be needed.

Late adverse events after implantation of sirolimus-eluting stent and bare-metal stent: long-term (5-7 years) follow-up of the Coronary Revascularization Demonstrating Outcome study-Kyoto registry Cohort-2.

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.

Impact of the bifurcation angle on major cardiac events after cross-over single stent strategy in unprotected left main bifurcation lesions: 3-dimensional quantitative coronary angiographic analysis.

The impact of the bifurcation angle (BA) between the left main (LM) and the main branch on clinical outcomes after single stenting has never been documented. Therefore, the aim of this study was to investigate the impact of the BA on clinical outcomes after single cross-over LM to left anterior descending artery (LAD) stenting. A total of 170 patients who underwent percutaneous coronary intervention (PCI) in unprotected LM bifurcation with successful single cross-over stenting from the LM into the LAD were enrolled. The main vessel angle between the LM and the LAD was computed in end-diastole before PCI with three-dimensional (3D) quantitative coronary angiography (QCA) software. The patients were classified into three groups according to tertiles of the main vessel angle. The cumulative incidence of major adverse cardiac event (MACE: cardiac death, myocardial infarction, any revascularization including target lesion revascularization) rates throughout a 12-month period were compared between the three groups. Baseline patient characteristics were not a significant difference between the three groups. Compared to the high angle group, the low angle group had a significantly higher incidence of MACE (p = 0.041). In conclusion, this study revealed that low BA between the LM and the LAD had an adverse clinical impact after single cross-over LM to LAD stenting.

Percutaneous coronary intervention in patients with previous coronary artery bypass grafting (from the j-Cypher Registry).

A paucity of data is available from large-scale studies evaluating the long-term outcomes of percutaneous coronary intervention in patients who had previously undergone coronary artery bypass grafting (CABG) in the drug-eluting stent era. Of 12,812 patients who had undergone sirolimus-eluting stent implantation in the j-Cypher registry, 919 (7.2%) had a history of CABG and had significantly higher crude 5-year mortality (19.9% vs 14.0%, p <0.001). After adjusting for confounders, the excess risk of death was no longer significant (hazard ratio 0.99, 95% confidence interval 0.83 to 1.18, p = 0.90), and the adjusted risk of target lesion revascularization was significantly higher in patients with previous CABG than in those without (hazard ratio 1.25, 95% confidence interval 1.06 to 1.47, p = 0.01). Of the patients with previous CABG, those who had undergone ≥1 saphenous vein graft intervention had significantly higher adjusted risks of cardiac death (hazard ratio 2.21, 95% confidence interval 1.26 to 3.76, p = 0.01), myocardial infarction (hazard ratio 2.56, 95% confidence interval 1.10 to 5.60, p = 0.03), target lesion revascularization (hazard ratio 2.65, 95% confidence interval 1.82 to 3.81, p <0.001), and definite stent thrombosis (hazard ratio 7.70, 95% confidence interval 1.99 to 29.1, p = 0.004) compared with those who underwent percutaneous coronary intervention only for the native coronary artery. In conclusion, the adjusted mortality was similar between patients with and without previous CABG, despite a significantly different risk of target lesion revascularization. Among the patients with previous CABG, those with saphenous vein graft intervention using a first-generation drug-eluting stent had worse clinical outcomes than those with a native coronary artery target only.

Efficacy of statin treatment after endovascular therapy for isolated below-the-knee disease in patients with critical limb ischemia.

To investigate the efficacy of statin treatment after endovascular therapy (EVT) for isolated below-the-knee (BTK) lesions in patients with critical limb ischemia (CLI). From March 2004 to June 2011, 812 patients (984 limbs, 69.0 % male, 71.6 ± 10.0 years old) with CLI underwent successful EVT for de novo isolated BTK lesions at 11 cardiovascular centers in Japan. Of these patients, 169 patients were treated with statins. Successful EVT was defined as direct-line flow to the pedal arch with <30 % residual stenosis. The multicenter data were analyzed retrospectively for outcomes of overall survival, amputation-free survival (AFS), cardiovascular death, limb salvage, freedom from repeat revascularization, and major adverse limb events [MALE: repeat revascularization for the limb or major amputation (defined as above-the-ankle amputation)]. The mean follow-up period was 19.4 ± 17.6 months. Overall survival, AFS and freedom from repeat revascularization at 4 years were significantly higher in patients treated with statins (64.5 vs. 45.9 %, P = 0.004; 64.1 vs. 43.0 %, P = 0.003; and 56.4 vs. 45.4 %, P = 0.03, respectively). However, rates of cardiovascular death, limb salvage, and MALE at 4 years did not differ significantly between the two groups (86.0 vs. 75.2 %, P = 0.11; 87.2 vs. 87.7 %, P = 0.39; and 84.4 vs. 82.9 %, P = 0.64, respectively). After adjusting all outcomes against differences in prespecified baseline variables, there was no significant difference in overall survival, AFS, cardiovascular death, limb salvage, repeat revascularization, and MALE between the groups. In a subgroup of 513 patients who were ambulatory at baseline, statin treatment significantly improved overall survival [hazard ratio (HR) 0.54, 95 % confidential interval (CI) 0.29-0.97, adjusted P = 0.04] and numerically improved AFS (HR 0.63, 95 % CI 0.35-1.07, adjusted P = 0.086). In this subgroup analysis, there was no significant difference in the rates of repeat revascularization, cardiovascular death, limb salvage, and MALE between patients treated with and without statins. In this retrospective study, the statin treatment after successful EVT establishing one straight line for isolated BTK lesions with CLI do not influence overall survival, AFS, and the rates of cardiovascular death, limb salvage, and MALE. However, in ambulatory patients, the statins may improve overall survival and AFS after successful EVT establishing one straight line for isolated BTK lesions.

Long-term outcomes after percutaneous coronary intervention for chronic total occlusion (from the CREDO-Kyoto registry cohort-2).

Despite improving success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions, the clinical benefit of recanalization of CTO is still a matter of debate. Of 13,087 patients who underwent PCI in the CREDO-Kyoto registry cohort-2, 1,524 patients received PCI for CTO (CTO-PCI). Clinical outcomes were compared between 1,192 patients with successful CTO-PCI and 332 patients with failed CTO-PCI. In-hospital death tended to occur less frequently in the successful CTO-PCI group than in the failed CTO-PCI group (1.4% vs 3.0%, p = 0.053). Through 3-year follow-up, the cumulative incidence of all-cause death was not significantly different between the successful and failed CTO-PCI groups (9.0% vs 13.1%, p = 0.18), whereas the cumulative incidence of cardiac death was significantly less in the successful CTO-PCI group than in the failed CTO-PCI group (4.5% vs 8.4%, p = 0.03). However, after adjusting confounders, successful CTO-PCI was associated with lesser risk for neither all-cause death (hazard ratio 0.93, 95% confidence interval 0.64 to 1.37, p = 0.69) nor cardiac death (hazard ratio 0.71, 95% confidence interval 0.44 to 1.16, p = 0.16). The cumulative incidence of coronary artery bypass grafting (CABG) was remarkably less in patients with successful PCI compared with those with failed PCI (1.8% vs 19.6%, p <0.0001). In conclusion, successful CTO-PCI compared with failed PCI was not associated with lesser risk for 3-year mortality. However, successful CTO-PCI was associated with significantly less subsequent CABG.