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.

Clinical Characteristics and Outcome of Immediate-Release Versus SLOW-Release Carvedilol in Heart Failure Patient (SLOW-HF): a Prospective Randomized, Open-Label, Multicenter Study.

PURPOSE: Carvedilol demonstrated therapeutic benefits in patients with heart failure and reduced ejection fraction (HFrEF). However, it had a short half-life time mandating twice a day administration. We investigated whether slow-release carvedilol (carvedilol-SR) is non-inferior to standard immediate-release carvedilol (carvedilol-IR) in terms of clinical efficacy in patients with HFrEF. METHODS: We randomly assigned patients with HFrEF to receive carvedilol-SR once a day or carvedilol-IR twice a day. The primary endpoint was the change in N-terminal pro B-natriuretic peptide (NT-proBNP) level from baseline to 6 months after randomization. The secondary outcomes were proportion of patients with NT-proBNP increment > 10% from baseline, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance. RESULTS: A total of 272 patients were randomized and treated (median follow-up time, 173 days). In each group of patients taking carvedilol-SR and those taking carvedilol-IR, clinical characteristics were well balanced. No patient died during follow-up, and there was no significant difference in the change of NT-proBNP level between two groups (-107.4 [-440.2-70.3] pg/mL vs. -91.2 [-504.1-37.4] pg/mL, p = 0.101). Change of systolic and diastolic blood pressure, control rate and response rate of blood pressure, readmission rate, and drug compliance rate were also similar. For safety outcomes, the occurrence of adverse reactions did not differ between carvedilol-SR group and carvedilol-IR group. CONCLUSION: Carvedilol-SR once a day was non-inferior to carvedilol-IR twice a day in patients with HFrEF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03209180 (registration date: July 6, 2017).

Impact of stent designs of second-generation drug-eluting stents on long-term outcomes in coronary bifurcation lesions.

OBJECTIVES: We compared the long-term clinical outcomes of four different types of second-generation drug-eluting stents (DESs) in coronary bifurcation lesions. BACKGROUND: Clinical outcomes of different designs of second-generation DESs are not well known in bifurcation lesions. METHODS: Patients who underwent percutaneous coronary intervention with second-generation DESs for coronary bifurcation lesion were enrolled from 21 centers in South Korea. A total of 2,526 patients was evaluated and divided into four treatment groups according to DES type: bioabsorbable polymer biolimus-eluting stent (BP-BES group, n = 514), platinum chromium everolimus-eluting stent (PtCr-EES group, n = 473), cobalt nickel zotarolimus-eluting stent (CoNi-ZES group, n = 736), or cobalt chromium everolimus-eluting stent (CoCr-EES group, n = 803). Primary outcome was target lesion failure (TLF, defined as a composite of cardiac death, target vessel myocardial infarction, or target lesion revascularization). Inverse probability of treatment weighting (IPTW) was performed to reduce selection bias and potential confounding factors. RESULTS: For 5 years of follow-up, the rates of TLF among the four DES groups were not significantly different (6.2% for BP-BES group, 8.2% for PtCr-EES group, 6.5% for CoNi-ZES group, and 8.6% for CoCr-EES group, p = .434). The results were consistent after IPTW adjustment (6.8, 8.4, 6.0, and 7.5%, respectively, p = .554). In subgroup analysis, the similarity of long-term outcomes among the four different types of second-generation DES was consistent across subgroups regardless of side branch treatment (p for interaction = .691). CONCLUSION: There seems to be no significant difference in long-term clinical outcomes among patients who received different types of second-generation DES for coronary bifurcation lesion.

Comparison of 2-Stenting Strategies Depending on Sequence or Technique for Bifurcation Lesions in the Second-Generation Drug-Eluting Stent Era　- Analysis From the COBIS (Coronary Bifurcation Stenting) III Registry.

BACKGROUND: It has not been determined which specific 2-stenting strategy is the best for bifurcation lesions. Our aim was to investigate the clinical outcomes of various 2-stenting strategies in the era of 2nd-generation drug-eluting stents (2G-DES).Methods and Results:We analyzed 454 patients who finally underwent 2-stenting for a bifurcation lesion, from among 2,648 patients enrolled in the COBIS III registry. The primary outcome was target lesion failure (TLF). Patients were analyzed according to stenting sequence (provisional [main vessel stenting first] vs. systemic [side branch stenting first]) and stenting technique (crush vs. T vs. culotte vs. kissing/V stenting). Overall, 4.4 years' TLF after 2-stenting treatment for bifurcation lesion was excellent: TLF 11.2% and stent thrombosis 1.3%. There was no difference in TLF according to 2-stenting strategy (11.1% vs. 10.5%, P=0.990 for provisional and systemic sequence; 8.6% vs. 14.4% vs. 12.9% vs. 12.2%, P=0.326 for crush, T, culotte, kissing/V technique, respectively). Only left main (LM) disease and a shorter duration of dual antiplatelet therapy (DAPT) were associated with TLF. The distribution of DAPT duration differed between patients with and without TLF, and the time-point of intersection was 2.5 years. Also, the side branch was the most common site of restenosis. CONCLUSIONS: The stenting sequence or technique did not affect clinical outcomes, but LM disease and shorter DAPT were associated with TLF, in patients with bifurcation lesions undergoing 2-stenting with 2G-DES.

Mixl1 and Flk1 Are Key Players of Wnt/TGF-ß Signaling During DMSO-Induced Mesodermal Specification in P19 cells.

Dimethyl sulfoxide (DMSO) is widely used to induce multilineage differentiation of embryonic and adult progenitor cells. To date, little is known about the mechanisms underlying DMSO-induced mesodermal specification. In this study, we investigated the signaling pathways and lineage-determining genes involved in DMSO-induced mesodermal specification in P19 cells. Wnt/ß-catenin and TGF-ß superfamily signaling pathways such as BMP, TGF-ß and GDF1 signaling were significantly activated during DMSO-induced mesodermal specification. In contrast, Nodal/Cripto signaling pathway molecules, required for endoderm specification, were severely downregulated. DMSO significantly upregulated the expression of cardiac mesoderm markers but inhibited the expression of endodermal and hematopoietic lineage markers. Among the DMSO-activated cell lineage markers, the expression of Mixl1 and Flk1 was dramatically upregulated at both the transcript and protein levels, and the populations of Mixl1+, Flk1+ and Mixl1+/Flk1+ cells also increased significantly. DMSO modulated cell cycle molecules and induced cell apoptosis, resulting in significant cell death during EB formation of P19 cells. An inhibitor of Flk1, SU5416 significantly blocked expressions of TGF-ß superfamily members, mesodermal cell lineage markers and cell cycle molecules but it did not affect Wnt molecules. These results demonstrate that Mixl1 and Flk1 play roles as key downstream or interacting effectors of Wnt/TGF-ß signaling pathway during DMSO-induced mesodermal specification in P19 cells.

Acute changes of left ventricular hemodynamics and function during percutaneous coronary intervention in patients with unprotected left main coronary artery disease.

Percutaneous coronary interventions (PCIs) are increasingly being used to treat unprotected left main coronary artery (ULMCA) lesions. However, research is sparse on the acute changes of left ventricular (LV) hemodynamics and function during PCI in patients with ULMCA stenosis. We aimed to assess the acute changes of LV function using speckle-tracking imaging during PCI in these patients. Fifteen consecutive patients who underwent elective PCI for ULMCA stenosis were enrolled. Echocardiographic studies and pressure measurement were performed at baseline, during PCI and after PCI. LMCA occlusion with a first balloon inflation induced a marked reduction in the peak positive derivative of LV pressure (dP/dt max), LV global longitudinal strain (GLS), and systolic and diastolic strain rates, and a marked increase in LV end-diastolic pressure (EDP) (all P < 0.01). During the second inflation, the degrees of LV hemodynamic and functional changes were similar to those of the first inflation, even with a higher inflation pressure. During the third inflation, the values of GLS and dP/dt max were higher than those of the second inflation (P = 0.03 and P = 0.05, respectively). After optimal PCI, dP/dt max, LVEDP, and strain parameters were improved to baseline values. LV hemodynamics and function were considerably impaired with the first ballooning during PCI for ULMCA stenosis. However, the degrees of LV hemodynamic and functional changes decreased with each successive balloon inflation, which can be explained by ischemic preconditioning. After all procedures were safely completed, LV systolic function was improved without LV diastolic stunning.

A Randomized, Multicenter, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Quadruple Combination of Amlodipine, Losartan, Rosuvastatin, and Ezetimibe in Patients with Concomitant Essential Hypertension and Dyslipidemia.

BACKGROUND: Few data are available regarding the efficacy and safety of a single-pill combination (SPC) consisting of four medications in patients with concomitant hypertension and dyslipidemia. OBJECTIVE: We aimed to determine the efficacy and tolerability of a fixed-dose SPC consisting of 5 mg amlodipine, 100 mg losartan, 20 mg rosuvastatin, and 10 mg ezetimibe (A/L/R/E) in patients with concomitant hypertension and dyslipidemia. METHODS: This was a 14-week, randomized, multicenter, double-blind, placebo-controlled, phase III clinical trial. In total, 145 patients were randomized to receive A/L/R/E, A/L, or L/R/E. The primary endpoints were the average change in the low-density lipoprotein cholesterol (LDL-C) level in the A/L/R/E and A/L groups and the sitting systolic blood pressure (sitSBP) in the A/L/R/E and L/R/E groups. The numbers of patients with adverse drug reactions (ADRs) were compared as safety variables. RESULTS: The average percentage change in the LDL-C level as the least squares mean (LSM) from the baseline LDL-C level at the end of the 8-week treatment was - 59.0% in the A/L/R/E group and 0.2% in the A/L group (LSM difference - 59.2, 95% confidence interval [CI] - 68.1 to - 50.4; p < 0.0001). The average change in the sitSBP as the LSM was - 15.8 mmHg in the A/L/R/E group and -4.7 mmHg in the L/R/E group (LSM difference - 11.1, 95% CI - 16.8 to - 5.4; p = 0.0002). No ADRs occurred in the A/L/R/E group. CONCLUSIONS: A/L/R/E as an SPC could be an effective treatment for patients with hypertension and dyslipidemia without significant safety issues. CLINICAL TRIALS REGISTRATION: NCT04074551 (registered 30 August 2019).

Nanog regulates molecules involved in stemness and cell cycle-signaling pathway for maintenance of pluripotency of P19 embryonal carcinoma stem cells.

To identify potential downstream targets of Nanog, a key transcription factor in the maintenance of pluripotency of embryonic stem (ES) and embryonal carcinoma (EC) cells, global gene expression profiles in Nanog small interfering RNA (siRNA)-transfected P19 EC stem cells were performed using cDNA, 60-mer, and 30-mer microarray platforms. The putative Nanog target genes identified by Nanog silencing were verified using reverse transcription-polymerase chain reaction after Nanog overexpression. Downregulation of Nanog in P19 cells resulted in reduction of pluripotency markers, such as Fgf4, Klf2, Mtf2, Oct-4, Rex1, Sox1, Yes, and Zfp143, whereas overexpression of Nanog in P19 cells reversely upregulated their expression. However, expressions of pluripotency markers Cripto, germ cell nuclear factor, Sox2, and Zfp57 as well as leukemia inhibitory factor (LIF)/Stat3 pathway molecules LIF, IL6st, and Stat3 were not affected after 48 h transfection with Nanog siRNA or construct. Nanog silencing also downregulated expression of molecules involved in the p53- and cell cycle-signaling pathway (Atf3, Jdp2, Cul3, Hist1hic, and Bcl6), whereas expression of E2f1, Tob1, Lyn, and Smarcc1 was upregulated by Nanog silencing. Expressions of cyclins D1, D2, D3, and E1 as well as cyclin-dependent kinase (Cdk) 1 and Cdk6 were downregulated by Nanog silencing in P19 cells, whereas Nanog overexpression reversely increased their expressions. Taken together, examination of global transcriptional changes after Nanog silencing followed by verification by Nanog overexpression has revealed new molecules involved in the maintenance of self-renewal and in the regulation of the p53- and cell cycle-pathway of P19 cells.

Osstem Cardiotec Centum Stent Versus Xience Alpine Stent for De Novo Coronary Artery Lesion: A Multicenter, Randomized, Parallel-Designed, Single Blind Test.

BACKGROUND AND OBJECTIVES: To compare the safety and efficacy of a new everolimus-eluting stent with an abluminal-coated biodegradable polymer (Osstem Cardiotec Centum) with those of the Xience Alpine stent (Xience). METHODS: This randomized, prospective, multicenter, parallel-designed, single-blind trial was conducted among patients with myocardial ischemia undergoing percutaneous coronary intervention (PCI) from 21st September 2018 until 3rd July 2020. The primary efficacy endpoint was in-segment late lumen loss (LLL) at 270 days after the procedure and the primary safety endpoints were major adverse cardiac events (MACE), composite of cardiac death, myocardial infarction, and target lesion revascularization. RESULTS: We enrolled 121 patients and analyzed 113 patients who finished 270 days of follow-up for the primary efficacy endpoint. The mean age of the participants was 66.8 years. As for the primary efficacy endpoint, LLL of the Osstem Cardiotec Centum group was 0.09±0.13 mm and that of the Xience group was 0.12±0.14 mm (upper limit of 1-sided 95% confidence interval, 0.02; p for non-inferiority, 0.0084). This result demonstrates the non-inferiority of the Osstem Cardiotec Centum. As for the primary safety endpoint, MACE occurred in one patient (1.59% of the Xience group). Meanwhile, no MACE occurred in the Osstem Cardiotec Centum group. CONCLUSIONS: The Osstem Cardiotec Centum is non-inferior to the Xience Alpine® stent and is confirmed to be safe. It could be safely and effectively applied to patients with coronary artery disease undergoing PCI.

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.

Impact of Clinical and Lesion Features on Outcomes After Percutaneous Coronary Intervention in Bifurcation Lesions.

Background: Bifurcation percutaneous coronary intervention (PCI) is associated with higher risk of clinical events. Objectives: This study aimed to determine clinical and lesion features that predict adverse outcomes, and to evaluate the differential prognostic impact of these features in patients undergoing PCI for bifurcation lesions. Methods: We analyzed 5,537 patients from the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry. The primary outcome was major adverse cardiac events (MACE) at 2-year follow-up; secondary outcomes included hard endpoints (all-cause death, myocardial infarction) and lesion-oriented clinical outcomes (LOCO) (target-vessel myocardial infarction, target lesion revascularization). The least absolute shrinkage and selection operator (LASSO) model was used for feature selection. Results: During the 2-year follow-up period, MACE occurred in 492 patients (8.9%). The LASSO model identified 5 clinical features (old age, chronic renal disease, diabetes mellitus, current smoking, and left ventricular dysfunction) and 4 lesion features (left main disease, proximal main branch disease, side branch disease, and a small main branch diameter) as significant features that predict MACE. A combination of all 9 features improved the predictive value for MACE compared with clinical and lesion features (area under the receiver-operating characteristics curve: 0.657 vs 0.636 vs 0.581; P < 0.001). For secondary endpoints, the clinical features had a higher impact than lesion features on hard endpoints, whereas lesion features had a higher impact than clinical features on LOCO. Conclusions: In bifurcation PCI, 9 features were associated with MACE. Clinical features were predominant predictors for hard endpoints, and lesion features were predominant for predicting LOCO. Clinical and lesion features have distinct values, and both should be considered in bifurcation PCI.

Effect of Wire Jailing at Side Branch in 1-Stent Strategy for Coronary Bifurcation Lesions.

OBJECTIVES: This study aimed to determine whether side branch (SB) wire jailing before main vessel (MV) stenting could prevent SB occlusion after the 1-stent strategy for bifurcation percutaneous coronary intervention. BACKGROUND: The benefits of SB wire jailing in the 1-stent strategy remain unclear. METHODS: From the COBIS (Coronary Bifurcation Stenting) III registry, 1,890 patients with bifurcation lesions who underwent the 1-stent strategy using second-generation drug-eluting stents were identified and classified into 2 groups according to the use of SB wire jailing: wire jailing (n = 819) and non-wire jailing (n = 1,071). The incidence of SB occlusion (Thrombolysis In Myocardial Infarction flow grade <3) and target lesion failure (cardiac death, myocardial infarction, or target lesion revascularization) was compared. RESULTS: The incidence of final SB occlusion was not significantly different between wire jailing (1.8%) vs non-wire jailing (2.9%; P = 0.182). However, wire jailing at the SB was a significant protective factor for SB occlusion after MV stenting on multivariate analysis and was significantly associated with a lower incidence of SB occlusion in patients with significant stenoses (≥60%) at the SB (5.1% vs 11.3%; odds ratio: 0.42; 95% CI: 0.19-0.89; P = 0.028) or MV (3.1% vs 6.2%; odds ratio: 0.49; 95% CI: 0.24-0.95; P = 0.039). During follow-up (median 52 months), the incidence of target lesion failure was not significantly different between wire jailing and non-wire jailing (7.6% vs 6.3%; P = 0.343). CONCLUSIONS: During bifurcation percutaneous coronary intervention with the 1-stent strategy, wire jailing at the SB was associated with a lower rate of final SB occlusion following MV stenting in patients with severe stenoses at the SB or MV but not with overall bifurcation lesions. Long-term clinical outcomes were comparable between the 2 groups.

Relationship between ultrasonic tissue characterization and myocardial deformation for prediction of left ventricular reverse remodelling in non-ischaemic dilated cardiomyopathy.

AIMS: This study was to evaluate the relationship between ultrasonic tissue characterization by integrated backscatter (IBS) and myocardial deformation assessed by two-dimensional speckled tracking (2DS) imaging for prediction of left ventricular (LV) reverse remodelling in patients with non-ischaemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Forty-five consecutive patients with non-ischaemic DCM were enrolled prospectively. The mean cyclic variation of integrated backscatter (CVIBS) was calculated as the mean of the septal and posterior wall CVIBS. LV global longitudinal, radial, and circumferential peak strain (GLS, GRS, and GCS, respectively) and twist were obtained. LV reverse remodelling was decided with follow-up echocardiography 12 months. The GLS, GRS, and GCS were correlated with the mean CVIBS. The mean CVIBS and GCS were significantly larger in the 24 patients who had LV reverse remodelling than the 21 patients who had no LV reverse remodelling and the GRS tended to be larger; the GLS and twist did not differ between the two groups. The mean CVIBS and GCS were independent predictors of LV reverse remodelling. CONCLUSION: Myocardial deformation assessed by 2DS was related to myocardial fibrosis assessed by IBS. LV reverse remodelling was predicted by mean CVIBS and GCS in patients with non-ischaemic DCM and GCS assessed by 2DS imaging is a simple method and therefore it can be readily used in clinical practice.

Differentiation of the left- from right-side ventricular septum in acute anterior myocardial infarction by tissue Doppler imaging.

OBJECTIVES: This study was to evaluate the longitudinal and radial function of the left- and right-side ventricular septum (Ls and Rs) in patients with acute anterior myocardial infarction (AMI) by tissue Doppler imaging. METHODS: Thirty patients with anterior ST-elevation AMI and revascularization and 20 age-matched normal subjects were enrolled as controls. The longitudinal and radial systolic tissue velocity (TV), strain rate (SR) and strain (ɛ) of both Ls and Rs were assessed. RESULTS: In normal, there were no significant differences of longitudinal TV, SR and ɛ between the Ls and Rs. The radial TV was same directed, but larger in Ls than Rs (P < 0.001). The radial SR and ɛ were positive values of Ls and negative values of Rs, but the degrees were similar in both sides. In AMI, longitudinal and radial TV were significantly decreased in both sides. However, longitudinal and radial SR and ɛ were significantly decreased in Ls only (P < 0.001 in all). Fourteen patients with AMI who showed no functional recovery had more reduced radial ɛ of Ls (3.9 ± 1.5% vs. 5.5 ± 2.1%, P = 0.02), but not longitudinal ɛ of Ls than the other 16 patients with recovery. CONCLUSION: This study showed the ventricular septum can be functionally differentiated the Ls from the Rs, which can be well demonstrated by SR imaging. The impairment of radial rather than longitudinal function of the Ls was related to no functional recovery.

A First-in-Man Clinical Evaluation of Sirolimus and Ascorbic Acid-Eluting Stent Systems: a Multicenter, Subject-Blinded, Randomized Study.

BACKGROUND AND OBJECTIVES: This clinical trial was conducted to evaluate the safety and efficacy of D+Storm™ drug-eluting stent (DES) and BioMatrix Flex™ DES. METHODS: This study was a multicenter, subject-single-blind, randomized, and confirmed comparative clinical trial. According to the inclusion criteria, those diagnosed with stable angina, unstable angina, silent ischemia, or non-ST-segment myocardial infarction were selected among patients with coronary artery stenosis as subjects. Among the subjects with 50% stenosis on coronary angiography, the experiment was performed on those who had a lesion with reference vessel 2.5-4.0 mm in diameter and ≤40 mm in length. The primary endpoint was an in-segment late loss and the secondary endpoints were in-stent late lumen loss, stent malapposition, the incidence of mortality, myocardial infarction, reoperation, and stent thrombosis at 36 weeks. RESULTS: 57 patients in the D+Storm™ DES group and 55 patients in the BioMatrix Flex™ DES group were enrolled in the study. Fifty-seven patients in the D+Storm™ DES group and Fifty-five patients in the BioMatrix Flex™ DES group were enrolled in the study. An average of in-segment late lumen loss was 0.08±0.13 mm in the D+Storm™ DES group and 0.14±0.32 mm in the BioMatrix Flex™ DES group with no significant difference between the 2 groups (p=0.879). In addition, there was no significant difference in adverse events between D+Storm™ DES and BioMatrix Flex™ DES. CONCLUSIONS: This study demonstrated the clinical effectiveness and safety of D+Storm™ DES implantation in patients with coronary artery disease over a 36-week follow-up period.

Incidence and Predictors of Stent Thrombosis in Patients Treated with Stents for Coronary Bifurcation Narrowing (From the BIFURCAT Registry).

Percutaneous coronary interventions performed at coronary bifurcations yield high rates of stent thrombosis (ST). The aim of the present study was to investigate the predictors of ST in contemporary coronary bifurcation percutaneous coronary interventions. We retrospectively investigated the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry on coronary bifurcations to assess the incidence and predictors of definite ST, which were the study primary endpoints. Predictors of ST among patients on dual antiplatelet therapy (DAPT) were also examined. A total of 5330 patients were included. After a mean 2-years follow-up, 64 (1.2%) patients experienced ST. 42 (65.6%) ST patients were on DAPT. At multivariable analysis, age (HR 1.02, CI 1.01 to 1.05, p = 0,027), smoking status (HR 2.57, CI 1.49 to 4.44, p = 0.001), chronic kidney disease (HR 2.26, CI 1.24 to 4.12, p = 0.007) and a 2-stent strategy (HR 2.38, CI 1.37 to 4.14, p = 0.002) were independent predictors of ST, whereas intracoronary imaging (HR 0.42, CI 0.23 to 0.78, p = 0.006) and final kissing balloon (FKB) (HR 0.48, CI 0.29 to 0.82, p = 0.007) were protective against ST. Among patients on DAPT, smoking status and a 2-stent strategy significantly increased the risk of ST, while intracoronary imaging and FKB reduced the risk. In conclusion, age, smoking status, chronic kidney disease and a 2-stent strategy were significant predictors of ST, whereas intracoronary imaging use and FKB had a protective effect. Only smoking status and a 2-stent strategy significantly predicted ST in DAPT subgroup, while intracoronary imaging and FKB had a protective role.

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.

Ten-Year Trends in Coronary Bifurcation Percutaneous Coronary Intervention: Prognostic Effects of Patient and Lesion Characteristics, Devices, and Techniques.

Background Despite advances in devices and techniques, coronary bifurcation lesion remains a challenging lesion subset in the field of percutaneous coronary intervention (PCI). We evaluate 10-year trends in bifurcation PCI and their effects on patient outcomes. Methods and Results We analyzed 10-year trends in patient/lesion characteristics, devices, PCI strategy, stent optimization techniques, and clinical outcomes using data from 5498 patients who underwent bifurcation PCI from 2004 to 2015. Clinical outcomes 2 years after the index procedure were evaluated in terms of target vessel failure (a composite of cardiac death, myocardial infarction, and target vessel revascularization) and a patient-oriented composite outcome (a composite of all-cause death, myocardial infarction, and any revascularization). During the 10-year study period, patient and lesion complexity, such as multivessel disease, diabetes mellitus, chronic kidney disease, and left main bifurcation, increased continuously (all P<0.001). The risk of target vessel failure or patient-oriented composite outcome decreased continuously from 2004 to 2015 (target vessel failure: from 12.3% to 6.9%, log-rank P<0.001; patient-oriented composite outcome: from 13.6% to 9.3%, log-rank P<0.001). The use of a second-generation drug-eluting stent and decreased target vessel failure risk in true bifurcation lesions were the major contributors to improved patient prognosis (interaction P values were <0.001 and 0.013, respectively). Conclusions During the past decade of bifurcation PCI, patient and lesion characteristics, devices, PCI techniques, and patient prognosis have all significantly changed. Despite increased patient and lesion complexity, clinical outcomes after bifurcation PCI have improved, mainly because of better devices and more widespread adoption of procedural optimization techniques and appropriate treatment strategies. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01642992 and NCT03068494.

Differential Long-Term Effects of First- and Second-Generation DES in Patients With Bifurcation Lesions Undergoing PCI.

Background: There is a paucity of data regarding the long-term clinical outcomes of first- versus second-generation drug-eluting stent (DES), especially when used to treat complex lesions such as bifurcation lesions. Objectives: The current study compares the efficacy and safety of first- versus second-generation DES at the 5-year follow-up in patients who underwent bifurcation percutaneous coronary intervention (PCI). Methods: A total of 5,498 patients with a bifurcation lesion who underwent PCI were pooled at a single patient level from COBIS (Coronary Bifurcation Stenting) registries II and III. Five-year target lesion failure (TLF) (the composite of cardiac death, myocardial infarction [MI], and target lesion revascularization [TLR]) and cardiac death or MI were compared between the use of first-generation DES (n = 2,436) and second-generation DES (n = 3,062) during PCI. Propensity score matching was performed to reduce selection bias. Results: After a 1:1 propensity score matching procedure was conducted, the cohort consisted of 1,702 matched pairs. Patients treated with second-generation DES had a significantly lower risk of TLF at 5 years than those treated with first-generation DES in both overall and propensity-matched populations (matched hazard ratio [HRmatched]: 0.576; 95% confidence interval [CI]: 0.456 to 0.727; p <0.001). There were no significant differences in risk of a composite of cardiac death or MI between the 2 groups (HRmatched: 0.782; 95% CI: 0.539 to 1.133, P = 0.193). However, among patients who required a 2-stent technique, use of the second-generation DES reduced cardiac death or MI (HRmatched:0.422; 95% CI: 0.209 to 0.851, P = 0.016). On the other hand, among patients who required a one-stent technique, the risk of a composite of cardiac death or MI was similar between the 2 groups (HRmatched: 1.046; 95% CI: 0.664 to 1.650, P = 0.845). There was a significant interaction between stent generation and treatment strategy for cardiac death or MI (interaction P = 0.029). Conclusions: In patients treated with PCI for a bifurcation lesion, the use of second-generation DES was associated with a significantly reduced risk of 5-year TLF than the use of first-generation DES. (Korean Coronary Bifurcation Stenting Registry II [NCT01642992]; COBIS II) (Korean Coronary Bifurcation Stenting Registry III [NCT03068494] COBIS III).

5-Year Outcome of Simple Crossover Stenting in Coronary Bifurcation Lesions Compared With Side Branch Opening.

Background: The optimal side branch (SB) treatment strategy after simple crossover stenting in bifurcation lesions is still controversial. Objectives: The purpose of this study was to compare the long-term outcomes of a 1-stent strategy with simple crossover alone versus with an additional SB-opening procedure in patients with left main (LM) and non-LM coronary bifurcation lesions. Methods: Patients who underwent percutaneous coronary intervention with a 1-stent strategy for bifurcation lesions including LM were selected from the COBIS (Coronary Bifurcation Stenting) III registry and divided into the simple crossover-alone group and SB-opening group. Clinical outcomes were assessed by the 5-year rate of target lesion failure (a composite of cardiac death, target vessel myocardial infarction, and target lesion repeat revascularization). Results: Among 2,194 patients who underwent the 1-stent strategy, 1,685 (76.8%) patients were treated with simple crossover alone, and 509 (23.2%) patients were treated with an additional SB-opening procedure. Although the baseline SB angiographic disease was more severe in the SB-opening group, the final lumen diameter of the SB was larger. The 5-year observed target lesion failure rate was similar between the 2 groups (7.0% in the simple crossover vs. 6.7% in SB-opening group; hazard ratio: 0.99; 95% confidence interval: 0.66 to 1.48; p = 0.947), even in the subgroup analyses including LM (9.5% vs. 11.3%; p = 0.442) and true bifurcation (5.3% vs. 7.8%; p = 0.362). The results were not changed after an inverse probability of treatment weighting adjustment. There was no difference in the overall and SB-related target lesion revascularization rate in both groups. Conclusions: The long-term clinical outcome of the 1-stent strategy with simple crossover alone for coronary bifurcation lesions was acceptable compared to those of additional SB-opening procedures. (Korean Coronary Bifurcation Stenting [COBIS] Registry III [COBIS III]; NCT03068494).