Impact of diabetes on long-term outcomes of bifurcation percutaneous coronary intervention. An analysis from the BIFURCAT registry.

BACKGROUND: It is still unclear the impact of diabetes mellitus (DM) in complex coronary lesions treated with percutaneous coronary intervention (PCI) which themselves are at increased incidence of adverse events. METHODS: BIFURCAT registry encompassed patients treated with PCI for coronary bifurcation lesion from the COBIS III and the RAIN registry. The primary endpoint was the occurrence of major cardiovascular adverse event (MACE), a composite and mutual exclusive of all-cause death or myocardial infarction (MI) or target-lesion revascularization (TLR). A total of 5537 patients were included in the analysis and 1834 (33%) suffered from DM. RESULTS: After a median follow-up of 21 months, diabetic patients had a higher incidence of MACE (17% vs. 9%, p < 0.001), all-cause mortality (9% vs. 4%, p < 0.001), TLR (5% vs. 3%, p = 0.001), MI (4% vs. 2%, p < 0.001), and stent thrombosis (ST) (2% vs. 1%, p = 0.007). After multivariate analysis, diabetes remained significantly associated with MACE (hazard ratio [HR]: 1.37; confidence interval [CI]: 1.13-1.65; p = 0.001), all-cause death (HR: 1.65; 95% CI: 1.24-2.19, p = 0.001), TLR (HR: 1.45; CI: 1.03-2.04; p = 0.031) and ST (HR: 1.73, CI: 1.04-2.88; p = 0.036), but not with MI (HR: 1.34; CI: 0.93-1.92; p = 0.11). Among diabetics, chronic kidney disease (HR: 2.99; CI: 2.21-4.04), baseline left ventricular ejection fraction (HR: 0.98; CI: 0.97-0.99), femoral access (HR: 1.62; CI: 1.23-2.15), left main coronary artery (HR: 1.44; CI: 1.06-1.94), main branch diameter (HR: 0.79; CI: 0.66-0.94) and final kissing balloon (HR: 0.70; CI: 0.52-0.93) were independent predictors of MACE at follow-up. CONCLUSIONS: Patients with DM treated with PCI for coronary bifurcations have a worse prognosis due to higher incidence of MACE, all-cause mortality, TLR and ST compared to the non-diabetics.

A New Digital Analysis Technique for the Mechanical Aperture and Contact Area of Rock Fractures.

In this study, a new digital technique for the analysis of the mechanical aperture and contact area of rock fractures under various normal stresses is proposed. The technique requires point cloud data of the upper and lower fracture surfaces, pressure film image data of the fracture, and normal deformation data of the fracture as input data. Three steps of algorithms were constructed using these input data: (1) a primary matching algorithm that considers the shape of the fracture surfaces; (2) a secondary matching algorithm that uses pressure film images; and (3) a translation algorithm that considers the normal deformation of a fracture. The applicability of the proposed technique was investigated using natural fracture specimens sampled at an underground research facility in Korea. In this process, the technique was validated through a comparison with the empirical equation suggested in a previous study. The proposed technique has the advantage of being able to analyze changes in the mechanical aperture and contact area under various normal stresses without multiple experiments. In addition, the change in the contact area on the fracture surface according to the normal stress can be analyzed in detail.

Reduced Mortality With Antiplatelet Therapy Deescalation After Percutaneous Coronary Intervention in Acute Coronary Syndromes: A Meta-Analysis.

BACKGROUND: Antiplatelet therapy deescalation has been suggested as an alternative to standard treatment with potent dual antiplatelet therapy (DAPT) for 1 year in low bleeding risk patients with acute coronary syndromes undergoing percutaneous coronary intervention to mitigate the increased risk of bleeding. Whether this strategy preserves the ischemic and survival benefits of potent DAPT is uncertain. METHODS: We performed a pairwise meta-analysis in patients with acute coronary syndrome undergoing percutaneous coronary intervention treated with either 1-year standard potent DAPT versus deescalation therapy (potent DAPT for 1-3 months followed by either reduced potency DAPT or ticagrelor monotherapy for up to 1 year). Randomized trials comparing standard DAPT versus deescalation therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. The primary end point was 1-year all-cause mortality. RESULTS: The meta-analysis included 6 trials in which 20 837 patients were randomized to potent DAPT for 1 to 3 months followed by deescalation therapy for up to 1 year (n=10 392) or standard potent DAPT for 1 year (n=10 445). Deescalation therapy was associated with lower 1-year rates of all-cause mortality compared with standard therapy (odds ratio, 0.75 [95% CI, 0.59-0.95]; P=0.02). Deescalation therapy was also associated with lower rates of major bleeding (odds ratio, 0.59 [95% CI, 0.48-0.72]; P<0.0001), with no significant difference in major adverse cardiac events (major adverse cardiovascular events; odds ratio, 0.89 [95% CI, 0.77-1.04]; P=0.14). CONCLUSIONS: In low bleeding risk patients with acute coronary syndrome undergoing percutaneous coronary intervention, compared with 1-year of potent DAPT, antiplatelet therapy deescalation therapy after 1 to 3 months was associated with decreased mortality and major bleeding with similar rates of major adverse cardiovascular events.

Impact of Left Ventricular Ejection Fraction on Procedural and Long-Term Outcomes of Bifurcation Percutaneous Coronary Intervention.

The association of left ventricular ejection fraction (LVEF) with procedural and long-term outcomes after state-of-the-art percutaneous coronary intervention (PCI) of bifurcation lesions remains unsettled. A total of 5,333 patients who underwent contemporary coronary bifurcation PCI were included in the intercontinental retrospective combined insights from the unified RAIN (veRy thin stents for patients with left mAIn or bifurcatioN in real life) and COBIS (COronary BIfurcation Stenting) III bifurcation registries. Of 5,003 patients (93.8%) with known baseline LVEF, 244 (4.9%) had LVEF <40% (bifurcation with reduced ejection fraction [BIFrEF] group), 430 (8.6%) had LVEF 40% to 49% (bifurcation with mildly reduced ejection fraction [BIFmEF] group) and 4,329 (86.5%) had ejection fraction (EF) ≥50% (bifurcation with preserved ejection fraction [BIFpEF] group). The primary end point was the Kaplan-Meier estimate of major adverse cardiac events (MACEs) (a composite of all-cause death, myocardial infarction, and target vessel revascularization). Patients with BIFrEF had a more complex clinical profile and coronary anatomy. No difference in procedural (30 days) MACE was observed across EF categories, also after adjustment for in-study outcome predictors (BIFrEF vs BIFmEF: adjusted hazard ratio [adj-HR] 1.39, 95% confidence interval [CI] 0.37 to 5.21, p = 0.626; BIFrEF vs BIFpEF: adj-HR 1.11, 95% CI 0.25 to 2.87, p = 0.883; BIFmEF vs BIFpEF: adj-HR 0.81, 95% CI 0.29 to 2.27, p = 0.683). BIFrEF was independently associated with long-term MACE (median follow-up 21 months, interquartile range 10 to 21 months) than both BIFmEF (adj-HR 2.20, 95% CI 1.41 to 3.41, p <0.001) and BIFpEF (adj-HR 1.91, 95% CI 1.41 to 2.60, p <0.001) groups, although no difference was observed between BIFmEF and BIFpEF groups (adj-HR 0.87, 95% CI 0.61 to 1.24, p = 0.449). In conclusion, in patients who underwent PCI of a coronary bifurcation lesion according to contemporary clinical practice, reduced LVEF (<40%), although a strong predictor of long-term MACEs, does not affect procedural outcomes.

Benefit of Extended Dual Antiplatelet Therapy Duration in Acute Coronary Syndrome Patients Treated with Drug Eluting Stents for Coronary Bifurcation Lesions (from the BIFURCAT Registry).

Optimal dual antiplatelet therapy (DAPT) duration for patients undergoing percutaneous coronary intervention (PCI) for coronary bifurcations is an unmet issue. The BIFURCAT registry was obtained by merging two registries on coronary bifurcations. Three groups were compared in a two-by-two fashion: short-term DAPT (≤ 6 months), intermediate-term DAPT (6-12 months) and extended DAPT (>12 months). Major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction (MI), target-lesion revascularization and stent thrombosis) were the primary endpoint. Single components of MACE were the secondary endpoints. Events were appraised according to the clinical presentation: chronic coronary syndrome (CCS) versus acute coronary syndrome (ACS). 5537 patients (3231 ACS, 2306 CCS) were included. After a median follow-up of 2.1 years (IQR 0.9-2.2), extended DAPT was associated with a lower incidence of MACE compared with intermediate-term DAPT (2.8% versus 3.4%, adjusted HR 0.23 [0.1-0.54], p <0.001), driven by a reduction of all-cause death in the ACS cohort. In the CCS cohort, an extended DAPT strategy was not associated with a reduced risk of MACE. In conclusion, among real-world patients receiving PCI for coronary bifurcation, an extended DAPT strategy was associated with a reduction of MACE in ACS but not in CCS patients.

Longitudinal Patterns in Antithrombotic Therapy in Patients with Atrial Fibrillation after Percutaneous Coronary Intervention in the Non-Vitamin K Oral Anticoagulant Era: A Nationwide Population-Based Study.

We investigated whether longitudinal patterns in antithrombotic therapy have changed after the introduction of non-vitamin K oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI). Using a claims database of the Korean AF population who underwent PCI between 2012 and 2016 (n = 18,691), we analyzed prescription records of oral anticoagulants (OACs) and antiplatelets at 3-month intervals over 2 years after PCI. The study population was stratified (pre-NOAC, transition, and NOAC era) using time-periods of NOAC introduction in Korea and an expansion of reimbursement for NOAC in AF as indicators. The overall rates of OAC were low at baseline (24.9%, 26.9%, and 35.2% in pre-NOAC, transition, and NOAC era, respectively), contrary to high rates of dual antiplatelet therapy (DAPT) (73.3%, 71.4%, and 63.6%). However, OAC prescription rates were increased at 1-year (18.5%, 22.5%, and 31.6%), and 2-year follow-up (17.8%, 24.2%, and 31.8%) from pre-NOAC to NOAC era. In NOAC era, 63.5% of baseline OAC prescriptions comprised NOAC, of which 96.4% included triple therapy with DAPT. Over 2 years, we observed increasing rates of double therapy with a single antiplatelet (18.3% and 20.0% at 1- and 2-year follow-up) and OAC monotherapy (2.7% and 8.9% at 1- and 2-year follow-up).

Long-term efficacy of vasodilating ß-blocker in patients with acute myocardial infarction: nationwide multicenter prospective registry.

BACKGROUND/AIMS: Long-term benefit of vasodilating ß-blockers is unknown. This study aimed to investigate the long-term benefit of vasodilating ß-blockers over conventional ß-blockers in patients with acute myocardial infarction (AMI). METHODS: Using nationwide prospective multicenter Korean Acute Myocardial Infarction Registry data, we analyzed 3-year clinical outcomes of 7,269 patients with AMI who received percutaneous coronary intervention (PCI) and ß-blocker therapy. Patients were classified according to treatment strategy (vasodilating ß-blockers vs. conventional ß-blockers). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), and hospitalization for heart failure (HF) at 3 years. Secondary outcomes were each component of the primary outcome. Propensity score matching was performed to adjust for differences of baseline characteristics. RESULTS: In 3,079 pairs (6,158 patients) of propensity score-matched patients, the primary outcome occurred significantly less in the vasodilating ß-blockers group compared with the conventional ß-blockers group (7.6% vs. 9.8%, p = 0.003). Among the secondary outcomes, cardiac death occurred significantly less in the vasodilating ß-blockers group than in the conventional group (3.5% vs. 4.8%, p = 0.015). The incidence rates of MI (2.4% vs. 3.0%, p = 0.160) or hospitalization for HF (2.6% vs. 3.2%, p = 0.192) were not significantly different between the two groups. CONCLUSION: Vasodilating ß-blocker therapy was associated with better clinical outcomes compared with conventional ß-blocker therapy in AMI patients undergoing PCI during 3 years follow-up. Vasodilating ß-blockers could be recommended preferentially for these patients.

The Effect of Cilostazol on the Angiographic Outcome of Drug-Eluting Coronary Stents Angiographic Analysis of the CILON-T (Influence of CILostazol-Based Triple Antiplatelet Therapy ON Ischemi Complication after Drug-Eluting StenT Implantation) Trial.

It is not clear if anti-restonotic effect of cilostazol is consistent for different types of drug-eluting stents (DES).The purpose of this study was to compare the anti-proliferative effect of cilostazol between DAT and TAT with consideration of confounding influences of DES type.Nine hundred and fifteen patients were randomized to either dual antiplatelet therapy (DAT; aspirin and clopidogrel) or triple antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol) in the previous CILON-T trial. After excluding 70 patients who received both or neither stents, we analyzed 845 patients who received exclusively PES or ZES, and compared in-stent late loss at 6 months between both antiplatelet regimens (DAT versus TAT).Baseline angiographic and clinical characteristics were similar between the DAT (656 lesions in 425 patients) and the TAT group (600 lesions in 420 patients). The 6-month follow-up angiography was completed in 745 patients (88.2%). Quantitative coronary angiography showed that TAT significantly reduced in-stent late loss (DAT 0.62 ± 0.62 mm versus TAT 0.54 ± 0.49 mm, P = 0.015). Stent type, diabetes or lesion length did not interact with difference of late loss. However, reduction of late loss by cilostazol did not lead to a significant reduction in the rate of target lesion revascularization (TLR) (DAT 7.8% versus TAT 6.9%, P = 0.69) due to a nonlinear relationship found between late loss and TLR.The TAT group showed less in-stent late loss as compared to the DAT group. This was consistently observed regardless of DES type, lesion length, or diabetic status. However, reduction of late loss by cilostazol did not lead to a significant reduction in TLR.

Benefit of Vasodilating ß-Blockers in Patients With Acute Myocardial Infarction After Percutaneous Coronary Intervention: Nationwide Multicenter Cohort Study.

BACKGROUND: Although current guidelines recommend ß-blocker after acute myocardial infarction (MI), the role of ß-blocker has not been well investigated in the modern reperfusion era. In particular, the benefit of vasodilating ß-blocker over conventional ß-blocker is still unexplored. METHODS AND RESULTS: Using nation-wide multicenter Korean Acute Myocardial Infarction Registry data, we analyzed clinical outcomes of 7127 patients with acute MI who underwent successful percutaneous coronary intervention with stents and took ß-blockers: vasodilating ß-blocker (n=3482), and conventional ß-blocker (n=3645). In the whole population, incidence of cardiac death at 1 year was significantly lower in the vasodilating ß-blocker group (vasodilating ß-blockers versus conventional ß-blockers, 1.0% versus 1.9%; P=0.003). In 2882 pairs of propensity score-matched population, the incidence of cardiac death was significantly lower in the vasodilating ß-blocker group (1.1% versus 1.8%; P=0.028). Although incidences of MI (1.1% versus 1.5%; P=0.277), any revascularization (2.8% versus 3.0%; P=0.791), and hospitalization for heart failure (1.4% versus 1.9%; P=0.210) were not different between the 2 groups, incidences of cardiac death or MI (2.0% versus 3.1%; P=0.010), cardiac death, MI, or hospitalization for heart failure (3.0% versus 4.5%; P=0.003), cardiac death, MI, or any revascularization (3.9% versus 5.3%; P=0.026), and cardiac death, MI, any revascularization, or hospitalization for heart failure (4.8% versus 6.5%; P=0.011) were significantly lower in the vasodilating ß-blocker group. CONCLUSIONS: Vasodilating ß-blocker therapy resulted in better clinical outcomes than conventional ß-blocker therapy did in patients with acute MI in the modern reperfusion era. Vasodilating ß-blockers could be recommended preferentially to conventional ones for acute MI patients.

Activation of Protein Kinase G (PKG) Reduces Neointimal Hyperplasia, Inhibits Platelet Aggregation, and Facilitates Re-endothelialization.

In spite of its great success in reducing restenosis, drug-eluting stent (DES) has unfavorable aspects such as stent thrombosis and delayed re-endothelialization. We examined the effects of PKG activation by Exisulind on neointimal formation, platelet aggregation, and re-endothelialization. Exisulind significantly reduced VSMCs viability, cell cycle progression, migration, and neointimal hyperplasia after vascular injury in rat carotid arteries. Interestingly, in contrast to the effect on VSMC viability, Exisulind did not reduce the viability of endothelial cells. Increased PKG activity by Exisulind inhibited PDGF-stimulated phenotype change of VSMCs from a contractile to a synthetic form. Conversely, the use of PKG inhibitor or gene transfer of dominant-negative PKG reversed the effects of Exisulind, resulting in the increased viability of VSMCs and neointimal formation. In addition, Exisulind facilitated the differentiation of peripheral blood mononuclear cells to endothelial lineage via PKG pathway, while inhibiting to VSMCs lineage, which was correlated with the enhanced re-endothelialization in vivo. Finally, Exisulind reduced platelet aggregation, which was mediated via PKG activation. This study demonstrated that Exisulind inhibits neointimal formation and platelet aggregation while increasing re-endothelialization via PKG pathway. These findings suggest that Exisulind could be a promising candidate drug of DES for the prevention of restenosis without other complications.

Different prognostic factors according to left ventricular systolic function in patients with acute myocardial infarction.

BACKGROUND: Initial left ventricular (LV) systolic function is a main determinant of clinical outcomes in patients with acute myocardial infarction (AMI). This study was performed to investigate whether AMI patients have different prognostic factors according to their baseline LV systolic function. METHODS: A total of 12,988 patients with AMI from a nationwide database were analyzed. Major adverse cardiovascular events (MACEs) within 12months of AMI, including death, nonfatal myocardial infarction (MI), and revascularization, were assessed. RESULTS: Patients were stratified into two groups according to LV ejection fraction (LVEF): those with LVEF<40% and those with LVEF≥40%. Patients with LVEF<40% (n=1962, 15.1%) were older and had more unfavorable cardiovascular risk factors than those with LVEF≥40% (n=11,026, 84.9%). The rate of MACE was higher in patients with LVEF<40% than in those with LVEF≥40% (26.8% vs 11.4%, p<0.001). Independent predictors of 12-month MACEs in patients with LVEF≥40% were history of MI, high Killip stage, three-vessel disease, and lower renal function, which are already known as risk factors. However, diabetes mellitus (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.17-2.40; p=0.008), and the use of rennin-angiotensin system (RAS) blockers (HR, 0.63; 95% CI, 0.41-0.95; p=0.029) were independent factors for 12-month MACE in patients with LVEF <40%. CONCLUSIONS: Prognostic factors determining 12-month MACE after AMI are different according to LVEF. Management following AMI should be tailored according to their LV systolic function.

Influence of second- and third-degree heart block on 30-day outcome following acute myocardial infarction in the drug-eluting stent era.

This study was conducted to investigate the prognostic value of heart block among patients with acute myocardial infarction (AMI) treated with drug-eluting stents. A total of 13,862 patients with AMI, registered in the nation-wide AMI database from January 2005 to June 2013, were analyzed. Second- (Mobitz type I or II) and third-degree atrioventricular block were considered as heart block in this study. Thirty-day major adverse cardiac events (MACE) including all causes of death, recurrent myocardial infarction, and revascularization were evaluated. Percutaneous coronary intervention with implantation of drug-eluting stent was performed in 89.8% of the patients. Heart block occurred in 378 patients (2.7%). Thirty-day MACE occurred in 1,144 patients (8.2%). Patients with heart block showed worse clinical parameters at initial admission, and the presence of heart block was associated with 30-day MACE in univariate analyses. However, the prognostic impact of heart block was not significant after adjustment of potential confounders (p = 0.489). Among patients with heart block, patients with a culprit in the left anterior descending (LAD) coronary artery had worse clinical outcomes than those of patients with a culprit in the left circumflex or right coronary artery. LAD culprit was a significant risk factor for 30-day MACE even after controlling for confounders (odds ratio 5.28, 95% confidence interval 1.22 to 22.81, p = 0.026). In conclusion, despite differences in clinical parameters at the initial admission, heart block was not an independent risk factor for 30-day MACE in adjusted analyses. However, a LAD culprit was an independent risk factor for 30-day MACE among patients with heart block.

Optimal intravascular ultrasound criteria for defining the functional significance of intermediate coronary stenosis: an international multicenter study.

OBJECTIVE: We aimed to assess the ideal cut-off value of minimal lumen area (MLA) by intravascular ultrasound (IVUS) and its diagnostic performance to predict ischemia, using a large-scale, pooled analysis. METHODS: Eleven centers worldwide were invited to provide their clinical, IVUS and fractional flow reserve (FFR) data. A total of 881 lesions were enrolled. RESULTS: Angiographic % diameter stenosis (r = -0.373, p < 0.0001) and IVUS MLA (r = 0.289, p < 0.0001) correlated with FFR. Best cut-off value (BCV) of IVUS MLA to define the functional significance (FFR <0.8) was 2.75 mm(2) (AUC 0.646, 95% CI 0.609-0.684). When the diagnostic performance of IVUS MLA was tested according to the lesion location, BCV could be found only in lesions in the proximal artery and the mid-left anterior descending artery. Interestingly, Asians (n = 623) and Westerners (n = 258) showed different demographic and lesion characteristics as well as different BCVs to define ischemia. The BCV for the proximal/mid-left anterior descending artery lesions was 2.75 mm(2) (AUC 0.688, 95% CI 0.635-0.742) in Asians and 3.0 mm(2) (AUC 0.695, 95% CI 0.605-0.786) in Westerners. CONCLUSION: In this pooled analysis, an IVUS MLA of 2.75 mm(2) was the BCV to define the functional significance of intermediate coronary stenosis. However, when IVUS MLA is used to determine the functional significance, both the lesion and patient characteristics should be considered.

A novel noninvasive technology for treatment planning using virtual coronary stenting and computed tomography-derived computed fractional flow reserve.

OBJECTIVES: This study sought to determine whether computational modeling can be used to predict the functional outcome of coronary stenting by virtual stenting of ischemia-causing stenoses identified on the pre-treatment model. BACKGROUND: Computed tomography (CT)-derived fractional flow reserve (FFR) is a novel noninvasive technology that can provide computed (FFRct) using standard coronary CT angiography protocols. METHODS: We prospectively enrolled 44 patients (48 lesions) who had coronary CT angiography before angiography and stenting, and invasively measured FFR before and after stenting. FFRct was computed in blinded fashion using coronary CT angiography and computational fluid dynamics before and after virtual coronary stenting. Virtual stenting was performed by modification of the computational model to restore the area of the target lesion according to the proximal and distal reference areas. RESULTS: Before intervention, invasive FFR was 0.70 ± 0.14 and noninvasive FFRct was 0.70 ± 0.15. FFR after stenting and FFRct after virtual stenting were 0.90 ± 0.05 and 0.88 ± 0.05, respectively (R = 0.55, p < 0.001). The mean difference between FFRct and FFR was 0.006 for pre-intervention (95% limit of agreement: -0.27 to 0.28) and 0.024 for post-intervention (95% limit of agreement: -0.08 to 0.13). Diagnostic accuracy of FFRct to predict ischemia (FFR ≤ 0.8) prior to stenting was 77% (sensitivity: 85.3%, specificity: 57.1%, positive predictive value: 83%, and negative predictive value: 62%) and after stenting was 96% (sensitivity: 100%, specificity: 96% positive predictive value: 50%, and negative predictive value: 100%). CONCLUSIONS: Virtual coronary stenting of CT-derived computational models is feasible, and this novel noninvasive technology may be useful in predicting functional outcome after coronary stenting. (Virtual Coronary Intervention and Noninvasive Fractional Flow Reserve [FFR]; NCT01478100).

Mechanism of edge restenosis after drug-eluting stent implantation. Angulation at the edge and mechanical properties of the stent.

BACKGROUND: Edge restenosis is not an unusual finding after implantation of drug-eluting stents (DES). We hypothesized that mechanical stress imposed on the stent edge would cause vessel wall injury and inflammation, which may consequently lead to edge restenosis. METHODS AND RESULTS: In total, 1,496 patients were implanted with a sirolimus-eluting stent (SES), paclitaxel-eluting stent (PES) or zotarolimus-eluting stent (ZES) in Seoul National University Hospital between 2007 and 2009. Binary restenosis occurred in 161 lesions in 119 patients. We retrospectively compared the 3 DES with regard to the percentage of edge stent restenosis among all cases of restenosis. We also evaluated the maximal, minimal, and Δ (maximal angle-minimal angle) angles. The percentage of edge restenosis was higher for SES than for ZES (37.5% vs. 16.7%, P=0.017). Maximal angle at the proximal edge was 64.82°±33.46° for 26 stents with proximal edge restenosis compared with 31.84°±31.51° for 89 stents without proximal edge restenosis (P=0.001). The Δ angle was also significantly different between the 2 groups (14.81°±15.98° vs. 7.60°±8.86°, P=0.035). Similar findings were observed for distal edge restenosis. Both the maximal angle (39.09°±21.04° vs. 22.71°±22.83°, P=0.010) and Δ angle (20.23°±15.39° vs. 9.18°±9.66°, P=0.016) at the distal edge were significantly different between the 2 groups. CONCLUSIONS: Physical stress determined by angulation at the stent edge segment and biomechanical properties of the DES can be considered as one of the plausible mechanisms for edge stent restenosis.

Comparison of antiplatelet effect and safety of clopidogrel napadisilate with clopidogrel bisulfate in coronary artery disease patients: multi-center, randomized, double-blind, phase IV, non-inferiority clinical trial.

BACKGROUND: Clopidogrel napadisilate has better clopidogrel stability than clopidogrel bisulfate. There are no data, however, on the antiplatelet efficacy and tolerability of clopidogrel napadisilate in coronary artery disease (CAD) patients. OBJECTIVE: The aim of this study is to demonstrate that the combination therapy of aspirin and clopidogrel napadisilate is not inferior to that of aspirin and clopidogrel bisulfate with respect to its effectiveness in inhibiting platelet aggregation, if it is given for 4 weeks to CAD patients who had been treated with a drug-eluting stent more than 12 months prior and had remained in a stable condition with a single antiplatelet agent, aspirin. METHODS: This study was a prospective, randomized, double-blind, double-dummy, parallel-group, phase IV clinical trial. A total of 162 patients were prospectively recruited from three centers. The subjects were randomized to either the test group that was treated with 75 mg of clopidogrel napadisilate once daily or to the control group that was treated with 75 mg of clopidogrel bisulfate once daily. The primary outcome was the percent inhibition of the platelet aggregation change after the medication, as assessed by a VerifyNow™ P2Y12 assay. The secondary outcome was the change in P2Y12 reaction units (PRUs) from the baseline to the end of 4 weeks of treatment. The prevalence of adverse events was assessed at each visit through a direct interview. RESULTS: The mean increase in the percent inhibition after 4 weeks of treatment was 19.4 % in the clopidogrel napadisilate group and 19.5 % in the clopidogrel bisulfate group. The lower bound of the 95 % two-sided confidence interval for the difference in the change between the two groups (-5.46) was greater than the pre-defined non-inferiority margin of (-10.5). Therefore, clopidogrel napadisilate was deemed non-inferior to clopidogrel bisulfate with respect to its effectiveness in inhibiting platelet aggregation. The PRU decreased by 73.1 ± 30.7 in the clopidogrel napadisilate group, which decreased by -7.8 more than in the clopidogrel bisulfate group (65.3 ± 62.1); but the difference between the two groups was statistically insignificant (p = 0.435). There was no significant difference in the drug-related adverse events between the two groups (12.3 vs. 10.1 %; p = 0.804). CONCLUSION: The platelet inhibitory efficacy of clopidogrel napadisilate is not inferior to that of clopidogrel bisulfate. There were also no statistically significant differences between the two treatment groups in the safety analyses. Therefore, clopidogrel napadisilate can be a suitable alternative to clopidogrel bisulfate in stable CAD patients who have undergone a drug-eluting stent placement. CLINICAL TRIAL REGISTRATION: Registered at ClinicalTrials.gov as NCT01830491.

Safety and efficacy of a novel hyperaemic agent, intracoronary nicorandil, for invasive physiological assessments in the cardiac catheterization laboratory.

AIMS: Maximal hyperaemia is a key element of invasive physiological studies and adenosine is the most commonly used agent. However, infusion of adenosine requires additional venous access and can cause chest discomfort, bronchial hyper-reactivity, and atrioventricular conduction block. The aim of this study was to evaluate the feasibility and efficacy of intracoronary (IC) nicorandil as a novel hyperaemic agent for invasive physiological studies. METHODS AND RESULTS: We enrolled 210 patients who underwent fractional flow reserve (FFR) measurement. Hyperaemic efficacy of the following methods was compared: IC bolus injection of adenosine; intravenous (i.v.) infusion of adenosine (140 µg/kg/min); and IC bolus of nicorandil (1 and 2 mg). In 70 patients, the index of microcirculatory resistance was also measured. Hyperaemic efficacy of IC nicorandil 2 mg was non-inferior to that of i.v. adenosine infusion (FFR: 0.82 ± 0.10 vs. 0.82 ± 0.10; P for non-inferiority < 0.001). There was a strong correlation between FFRs measured by i.v. adenosine and IC nicorandil (R² = 0.934). Nicorandil produced fewer changes in blood pressure, heart rate and PR interval, and less chest pain than adenosine (all P-values < 0.05). Atrioventricular block occurred in 12 patients with IC adenosine, 4 patients with i.v. adenosine and none with IC nicorandil. The index of microcirculatory resistance was 18.3 ± 8.7 with i.v. adenosine and 17.2 ± 7.6 with IC nicorandil (P = 0.126). CONCLUSION: This study suggests that IC bolus injection of nicorandil is a simple, safe, and effective way to induce steady-state hyperaemia for invasive physiological evaluations. Clinicaltrials.gov number: NCT01331902.

Noninvasive diagnosis of ischemia-causing coronary stenosis using CT angiography: diagnostic value of transluminal attenuation gradient and fractional flow reserve computed from coronary CT angiography compared to invasively measured fractional flow reserve.

OBJECTIVES: The aim of this study was to compare the diagnostic performance of coronary computed tomography angiography (CCTA)-derived computed fractional flow reserve (FFR(CT)) and transluminal attenuation gradient (TAG) for the diagnosis of lesion-specific ischemia. BACKGROUND: Although CCTA is commonly used to detect coronary artery disease (CAD), it cannot reliably assess the functional significance of CAD. Novel technologies based on CCTA were developed to integrate anatomical and functional assessment of CAD; however, the diagnostic performance of these methods has never been compared. METHODS: Fifty-three consecutive patients who underwent CCTA and coronary angiography with FFR measurement were included. Independent core laboratories determined CAD severity by CCTA, TAG, and FFR(CT). The TAG was defined as the linear regression coefficient between intraluminal radiological attenuation and length from the ostium; FFR(CT) was computed from CCTA data using computational fluid dynamics technology. RESULTS: Among 82 vessels, 32 lesions (39%) had ischemia by invasive FFR (FFR ≤0.80). Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratio of TAG (≤ -0.654 HU/mm) for detection of ischemia were 38%, 88%, 67%, 69%, 3.13, and 0.71, respectively; and those of FFR(CT) were 81%, 94%, 90%, 89%, 13.54, and 0.20, respectively. Receiver-operating characteristic curve analysis showed a significantly larger area under the curve (AUC) for FFR(CT) (0.94) compared to that for TAG (0.63, p < 0.001) and CCTA stenosis (0.73, p < 0.001). In vessels with noncalcified plaque or partially calcified plaque, FFR(CT) showed a larger AUC (0.94) compared to that of TAG (0.63, p < 0.001) or CCTA stenosis (0.70, p < 0.001). In vessels with calcified plaque, AUC of FFR(CT) (0.92) was not statistically larger than that of TAG (0.75, p = 0.168) or CCTA stenosis (0.80, p = 0.195). CONCLUSIONS: Noninvasive FFR computed from CCTA provides better diagnostic performance for the diagnosis of lesion-specific ischemia compared to CCTA stenosis and TAG.

Assessment of clinical, electrocardiographic, and physiological relevance of diagonal branch in left anterior descending coronary artery bifurcation lesions.

OBJECTIVES: This study sought to investigate the clinical, electrocardiographic, and physiological relevance of main and side branches in coronary bifurcation lesions. BACKGROUND: Discrepancy exists between stenosis severity and clinical outcomes in bifurcation lesions. However, its mechanism has not been fully evaluated yet. METHODS: Sixty-five patients with left anterior descending coronary artery (LAD) bifurcation lesions were prospectively enrolled. Chest pain and 12-lead electrocardiogram were assessed after 1-min occlusion of coronary flow and coronary wedge pressure (Pw) was measured using a pressure wire. RESULTS: ST-segment elevation was more frequent during LAD occlusion (92%) than during diagonal branch occlusion (37%) (p < 0.001). Pain score was also higher with the occlusion of LAD than with the diagonal branch (p < 0.001). However, both Pw and Pw/aortic pressure (Pa) were lower in the LAD than in diagonal branches (Pw: 21.0 ± 6.5 vs. 26.7 ± 9.4, p < 0.0001; Pw/Pa: 0.22 ± 0.07 vs. 0.27 ± 0.08, p = 0.001). The corrected QT interval was prolonged with LAD occlusion (435.0 ± 39.6 ms to 454.0 ± 45.4 ms, p < 0.0001) but not with diagonal branch occlusion. There was no difference in vessel size between the diagonal branches with and without ST-segment elevation during occlusion. Positive and negative predictive values of vessel size (≥2.5 mm) to determine the presence of ST-segment elevation were 48% and 72%, respectively. CONCLUSIONS: Diagonal branch occlusion caused fewer anginas, less electrocardiogram change, less arrhythmogenic potential, and higher Pw than did a LAD occlusion. These differences seem to be the main mechanism explaining why aggressive treatment for side branches has not translated into clinical benefit in coronary bifurcation lesions. (Comparison Between Main Branch and Side Branch Vessels; NCT01046409).

Clinical and physiological outcomes of fractional flow reserve-guided percutaneous coronary intervention in patients with serial stenoses within one coronary artery.

OBJECTIVES: This study was performed to evaluate the physiological and clinical outcomes of fractional flow reserve (FFR)-guided revascularization strategy with drug-eluting stents in serial stenoses within the same coronary artery. BACKGROUND: Identifying a functionally significant stenosis is difficult when several stenoses exist within 1 coronary artery. METHODS: A total of 131 patients (141 vessels and 298 lesions) with multiple intermediate stenoses within the same coronary artery were assessed by FFR with pullback pressure tracings. In vessels with an FFR <0.8, the stenosis that caused the largest pressure step-up was stented first. Major adverse cardiac events were assessed during follow-up. RESULTS: FFR was measured 239 times and there were no procedure-related complications. There was a weak negative correlation between FFR and angiographic percent diameter stenosis (r = -0.282, p < 0.001). In total, 116 stents were implanted and revascularization was deferred in 61.1% (182 of 298) of lesions. When the vessels with an initial FFR <0.8 were divided into 2 groups according to FFR after first stenting (FFR ≥0.8 vs. FFR <0.8), there were no differences in baseline angiographic and physiological parameters between the 2 groups. During the mean follow-up of 501 ± 311 days, there was only 1 target vessel revascularization due to in-stent restenosis. There were no events related to deferred lesions. CONCLUSIONS: FFR-guided revascularization strategy using pullback pressure tracing in serial stenoses was safe and effective. This strategy can reduce unnecessary intervention and maximize the benefit of percutaneous coronary intervention with drug-eluting stents in patients with multiple stenoses within 1 coronary artery.