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Jae-Bin Seo,
Si-Hyuck Kang,
Seung-Ho Hur,
Kyung Woo Park,
Tae-Jin Youn,
Jong-Seon Park, Han-Mo Yang,
Hae-Young Lee,
Hyun-Jae Kang,
Bon-Kwon Koo, [......],
Woo-Young Chung,
Soo-Joong Kim,
Doo-Il Kim,
Byung-Ok Kim,
Min-Su Hyon,
Keum-Soo Park,
Tae-Joon Cha,
Chul-Woong Yoo,
Hui-Kyung Jeon,
Hyo-Soo Kim
[show abstract]
[hide abstract]
ABSTRACT: Paclitaxel-eluting stents (PESs) have been shown to inhibit neointimal hyperplasia after percutaneous coronary intervention. Coroflex Please (B Braun, Melsungen, Germany) is a newly developed PES. We compared the clinical and angiographic efficacy of Coroflex Please with Taxus Liberte (Boston Scientific, Natick, MA) in a real-world practice.
We performed a prospective, open-label, randomized, controlled study that enrolled 945 patients undergoing percutaneous coronary interventions in 18 centers in Korea. The primary end point was clinically driven target vessel revascularization at 9 months. The baseline characteristics were mostly similar and comparable between 2 groups. At 9 months, the incidence of clinically driven target vessel revascularization was 14.6% for Coroflex and 6.4% for Taxus, which was significantly different (hazard ratio 2.43, 95% CI 1.50-3.94, noninferiority P value = 1.000). This is well corroborated by the difference of in-stent late loss between 2 stents (0.71 ± 0.64 mm vs 0.52 ± 0.50 mm, P < .001) by 9-month follow-up angiography (n = 415 vs 215). Among secondary clinical end points, stent thrombosis (definite and probable) for 1 year was 2.2% in Coroflex and 1.3% in Taxus (P = .317). Also, myocardial infarction for 9 months was higher in Coroflex group than that in Taxus (4.9% vs 1.6%, P = .012), which was partly contributed by the higher incidence of periprocedural myocardial infarction in Coroflex arm (2.2% vs 0.3%, P = .028).
Coroflex Please was inferior to Taxus Liberte with regard to clinical and angiographic efficacy.
American heart journal 05/2013; 165(5):733-43. · 4.65 Impact Factor
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Kyung Woo Park,
Jeehoon Kang,
Jin Joo Park, Han-Mo Yang,
Yoo-Wook Kwon,
Hae-Young Lee,
Hyun-Jae Kang,
Bon-Kwon Koo,
Byung-Hee Oh,
Young-Bae Park,
Hyo-Soo Kim
International journal of cardiology 03/2013; · 7.08 Impact Factor
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Jin Hur,
Jae-Il Choi,
Ji-Yeon Yun,
Chang-Hwan Yoon,
Jae Hee Jang,
Seung-Gyun Im,
Seung-Bum Ko,
Jin-A Kang,
Jonghanne Park,
Sang Eun Lee,
Ju-Young Kim, Han-Mo Yang,
Young-Bae Park,
Hyo-Soo Kim
[show abstract]
[hide abstract]
ABSTRACT: Ex vivo expansion of human circulating angiogenic cells is a major challenge in autologous cell therapy for ischemic diseases. Here, we demonstrate that hematosphere-derived CXCR4(+)CD31(+) myeloid cells using peripheral blood possess robust proangiogenic capacity such as formation of vessel-like structures and tip cell-like morphology in Matrigel. We also found that CD31 positive myeloid cells are principal cellular component of hematospheres by magnetic cell sorting. Flow cytometry analysis showed that fresh peripheral blood contained 40.3 ± 15.2% of CXCR4(+)CD31(+) myeloid cells, but at day 5 of hematosphere culture, most of myeloid cells were CXCR4(+)CD31(+) by 86.9 ± 5.4%. Hematosphere culture significantly increased the production of angiogenic niche-supporting cytokines. Moreover, CD31-homophilic interaction and VEGF-VEGF receptor loop signaling were essential for sphere formation and acquisition of angiogenic capacity in hematospheres. Matrigel plug and ischemic hindlimb model provide in vivo evidence that hematosphere-derived myeloid cells have highly vasculogenic capacities, participate in new and mature vessel formation, and exert therapeutic effects on ischemic hindlimb. In conclusion, our strategy for ex vivo expansion of human CXCR4(+)CD31(+) angiogenic cells using hematospheres provides an autologous therapeutic cell source for ischemic diseases and a new model for investigating the microenvironment of angiogenesis.
Biomaterials 03/2013; 34(8):1929-41. · 7.40 Impact Factor
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Jin Joo Park,
Kyung Woo Park,
Jeehoon Kang,
Ki-Hyun Jeon,
Si-Hyuck Kang,
Hyo Suk Ahn,
Jung-Kyu Han,
Jin-Sin Koh,
Sang Eun Lee, Han-Mo Yang,
Hae-Young Lee,
Hyun-Jae Kang,
Bon-Kwon Koo,
Byung-Hee Oh,
Young-Bae Park,
Hyo-Soo Kim
[show abstract]
[hide abstract]
ABSTRACT: Background: Calcium-channel blockers (CCBs) inhibit the CYP3A4 enzyme, which is involved in clopidogrel activation. Studies have shown conflicting results regarding the effect of concomitant CCB administration on clopidogrel response. We investigated the relationship between CYP3A4 genotype and the inhibitory effect of CCBs on clopidogrel response. Methods and Results: Clopidogrel on-treatment platelet reactivity (OPR) was measured and CYP3A4 (IVS10+12G>A) genotyped in 1,247 consecutive patients with drug-eluting stent implantation. The mean OPR was 231±83 (P2Y(12) reaction units: PRU). In total, 332 (26.6%) CCB users had higher OPR compared with 915 (73.4%) non-CCB users (245±84 vs. 227±83 PRU, P=0.001). The distribution of CYP3A4 (IVS10+12G>A) genotype was 63.6%, 32.6% and 3.8% for GG, GA and AA genotypes, respectively. After adjustment for possible confounding factors, the number of A-alleles was associated with increased vulnerability to CCB use (effect of CCB use ΔPRU: +8 PRU, P=0.210, +24 PRU, P=0.012, +50 PRU, P=0.025, for patients with 0, 1, and 2 A-alleles, respectively, +24 PRU, P=0.005 for GA/AA genotypes). Furthermore, only in the GA/AA-genotype did CCB use result in a significantly increased risk for high-OPR (odds ratio 1.84, 95% confidence interval 1.15-2.92, P=0.010). Conclusions: CCB use is associated with increased OPR. The number of CYP3A4 (IVS10+12G>A) A-alleles may be associated with an increased vulnerability to the effects of CCBs on clopidogrel response variation.
Circulation Journal 02/2013; · 3.77 Impact Factor
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Ho-Jun Jang,
Bon-Kwon Koo,
Hee-Sun Lee,
Jun-Bean Park,
Ji-Hyun Kim,
Myung-Ki Seo, Han-Mo Yang,
Kyung-Woo Park,
Chang-Wook Nam,
Joon-Hyung Doh,
Hyo-Soo Kim
[show abstract]
[hide abstract]
ABSTRACT: AimsMaximal 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 resultsWe 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 (R(2) = 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.
European Heart Journal 02/2013; · 10.48 Impact Factor
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Kyung Woo Park,
Si-Hyuck Kang,
Matthijs A Velders,
Dong-Ho Shin,
Seokyung Hahn,
Woo-Hyun Lim, Han-Mo Yang,
Hae-Young Lee,
Adrianus J Van Boven,
Sjoerd H Hofma,
Hyun-Jae Kang,
Bon-Kwon Koo,
Byung-Hee Oh,
Young-Bae Park,
David E Kandzari,
Hyo-Soo Kim
[show abstract]
[hide abstract]
ABSTRACT: While EES have proven superior to paclitaxel-eluting stents, it remains uncertain whether EES improve clinical outcomes compared to SES, which are the most efficacious among the first-generation drug-eluting stents. We performed a meta-analysis of randomized trials comparing the efficacy and safety of everolimus-eluting stents (EES) versus sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary intervention.
From online and offline search until December 2011, we identified 11 randomized trials (total 12,869 patients). The primary endpoint was major adverse cardiac events.
The risk of major adverse cardiac events did not differ significantly between the patients treated with EES versus SES [OR, 0.90 (95% CI, 0.77-1.04); P = .162]. However, we found a significant reduction in the risk of repeat revascularization in the EES arm [OR, 0.85 (95% CI, 0.71-1.00); P = .047]. There were no significant differences regarding the risk of cardiac death [OR, 0.97 (95% CI, 0.74-1.27); P = .834], or myocardial infarction [OR, 0.95 (95% CI, 0.75-1.20), P = .656]. The risk of definite or probable stent thrombosis tended to be lower [OR, 0.68 (95% CI, 0.45-1.02); P = .065], while definite ST was significantly lower [OR, 0.44 (95% CI, 0.25-0.80); P = .007] with EES.
In a large systematic overview of comparative trials involving percutaneous revascularization with drug-eluting stents, treatment with EES significantly reduced the risk of repeat revascularization and definite ST compared to SES. We found no significant differences in the risk of cardiac death or myocardial infarction.
American heart journal 02/2013; 165(2):241-250.e4. · 4.65 Impact Factor
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Kyung Woo Park,
Jin Joo Park,
Jeehoon Kang,
Ki-Hyun Jeon,
Si-Hyuck Kang,
Jung-Kyu Han,
Sang Eun Lee, Han-Mo Yang,
Hae-Young Lee,
Hyun-Jae Kang,
Bon-Kwon Koo,
Byung-Hee Oh,
Young-Bae Park,
Hyo-Soo Kim
[show abstract]
[hide abstract]
ABSTRACT: Paraoxonase (PON) is a high-density-lipoprotein (HDL) associated enzyme with antioxidative and anti-atherogenic property. Its function is associated with coronary artery disease and its activity genetically controlled. We evaluated whether genetic variation of PON-1 is associated with clinical outcome in a large cohort of Korean patients with drug-eluting stents implantation.
A total of 1676 patients with drug-eluting stent implantation were enrolled in the prospective CROSS-VERIFY cohort from June 2006 to June 2010. We genotyped the PON1-Q192R gene, measured clopidogrel on-treatment platelet reactivity (OPR), and analyzed lipid profiles. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis at 12 months.
PON-1 genotyping data were available in 1336 patients. Since the Q-allele is associated with decreased PON-activity, we analyzed the outcome between patients with QQ/QR (815 patients, 61%) and those with RR-genotype (521 patients, 39%). After adjustment for common cardiac risk factors, the QQ/QR-genotype was an independent predictor of the primary thrombotic endpoint with an 11-fold increased risk (HR 11.6, 95% CI: 1.55-87.0), but not repeat revascularization (HR 1.12, 95% CI: 0.78-1.61). The QQ/QR-genotype was not associated with OPR (QQ/QR: 231±86 PRU vs. RR 236±82 PRU, p = 0.342) but higher small-dense LDL levels (1.20±0.12 mg/dL vs. 0.76±0.15 mg/dL, p = 0.027). The increased risk of thrombotic outcomes was more profound in acute coronary syndrome (ACS) patients compared with non-ACS patients.
PON1 Q-allele is an independent predictor of worse cardiovascular outcome independent of platelet function and is associated with significantly higher levels of small dense LDL-C.
PLoS ONE 01/2013; 8(2):e52779. · 4.09 Impact Factor
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Jin Joo Park,
Kyung Woo Park,
Jeehoon Kang,
Ki-Hyun Jeon,
Si-Hyuck Kang,
Hyo Suk Ahn,
Jung-Kyu Han,
Jin-Sin Koh,
Sang Eun Lee, Han-Mo Yang,
Hae-Young Lee,
Hyun-Jae Kang,
Bon-Kwon Koo,
Byung-Hee Oh,
Young-Bae Park,
Hyo-Soo Kim
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Variations of genes encoding cytochrome enzymes, drug transporters, and paraoxonase have recently been reported to be associated with clopidogrel response variability besides the well-known CYP2C19 loss-of-function (LOF) alleles. We determined whether newly reported genetic variations are associated with clopidogrel on-treatment platelet reactivity (OPR) in Korean patients. METHODS: OPR was measured in 1264 consecutive patients who underwent percutaneous coronary intervention using the VerifyNowP2Y12 assay system and genotyping of PON-1 Q192R, ABCB1 C3435T, CYP1A2*1F, CYP2B6*6, CYP2C19*2, CYP2C19*3, CYP2C19*17, CYP3A4 (IVS10+12G>A), and CYP3A5*3 was performed. We applied two different cutoffs, i.e. 240 P2Y12 reaction units (PRU) and 253 PRU, to define high OPR. RESULTS: Mean OPR of the entire population was 231±83 PRU. Genetic variations of ABCB1 and PON-1 genes as well as that of CYP1A2, 2B6, 3A4, and 3A5 were not associated with clopidogrel response variability. As for CYP2C19, patients were classified into 4 metabolism genotypes: 0.6% ultrarapid (UM), 40.3% extensive (EM), 48.8% intermediate (IM), and 10.3% poor metabolizers (PM). After adjustment for possible confounders, CYP2C19 metabolism genotype was associated with a significant increase in OPR: effect on OPR-difference: +27 PRU, p=0.015 for EM, +53 PRU, p<0.001 for IM, and +74 PRU, p=0.006 for PM compared with UM. In multivariable analysis, the CYP2C19 genotype was the only independent predictor of high-OPR among genetic variations using two different cutoffs. CONCLUSIONS: Among genes postulated to be involved in clopidogrel metabolism, only the CYP2C19 genotype is associated with response variability and emerged as an independent predictor of high-OPR using two different cutoffs. PON-1 and ABCB1 genetic variants do not affect clopidogrel OPR in Korean patients.
International journal of cardiology 12/2012; · 7.08 Impact Factor
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Kyung Woo Park,
Joo Myung Lee,
Si-Hyuck Kang,
Hyo-Suk Ahn, Han-Mo Yang,
Hae-Young Lee,
Hyun-Jae Kang,
Bon-Kwon Koo,
Janghyun Cho,
Hyeon-Cheol Gwon,
Sung Yoon Lee,
In-Ho Chae,
Tae-Jin Youn,
Jei Keon Chae,
Kyoo-Rok Han,
Cheol Woong Yu,
Hyo-Soo Kim
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVES: This study sought to compare the safety and efficacy of the Xience V/Promus everolimus-eluting stent (EES; Abbott Vascular, Temecula, California) with the Endeavor Resolute zotarolimus-eluting stent (ZES-R; Medtronic Cardiovascular, Santa Rosa, California) in "all-comer" cohorts. BACKGROUND: Only 2 randomized controlled trials have compared these stents. METHODS: The EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with the EES and 1,998 patients treated with the ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure [TLF]) and patient-related composite outcomes were compared in crude and propensity score-matched analyses. RESULTS: Of 5,054 patients, 3,830 (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (82 [2.7%] vs. 58 [2.9%], p = 0.662) and the patient-related outcome (225 [7.4%] vs. 153 [7.7%], p = 0.702) did not differ between EES and ZES-R, respectively, at 1 year, which was corroborated by similar results from the propensity score-matched cohort. The rate of definite or probable stent thrombosis (18 [0.6%] vs. 7 [0.4%], p = 0.306) also was similar. In multivariate analysis, off-label indication was the strongest predictor of TLF (adjusted hazard ratio: 2.882; 95% confidence interval: 1.226 to 6.779; p = 0.015). CONCLUSIONS: In this robust real-world registry with unrestricted use of EES and ZES-R, both stents showed comparable safety and efficacy at 1-year follow-up. Overall incidences of TLF and definite stent thrombosis were low, even in the patients with off-label indication, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents.
Journal of the American College of Cardiology 12/2012; · 14.16 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: AimsThe association between alkaline phosphatase (ALP) and mortality was reported in several subgroups of patients. But, the role of ALP in overall coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remains unknown. The aim of this study was to examine the prognostic value of the ALP level in patients with CAD who underwent PCI with drug-eluting stent (DES).Methods and resultsWe prospectively included CAD patients who underwent PCI with DES. After exclusion of patients with liver disease and cancer, 1636 patients were selected for the analysis of clinical outcomes (median duration of follow-up; 762 days, inter-quartile range; 494-1068 days), and were classified into tertiles by baseline measurements of ALP (<63, 63-78, and >78 IU/L). After adjustment of potential confounders including angiographic data, the independent and dose-dependent association was observed between tertile of ALP and the adjusted hazard ratio (HR) of all-cause mortality (P for trend < 0.0001). Specifically, compared with the lowest ALP tertile, the adjusted HR of all-cause mortality in the highest tertile was 4.21 (95% confidence interval 2.03-8.71). In subgroup of patients with stable or unstable angina, a similar association was noted (P for trend < 0.0001). In terms of cardiovascular mortality, myocardial infarction, and stent thrombosis, the adjusted HRs in the highest ALP tertile were 3.92 (1.37-11.20), 1.98 (0.91-4.29), and 2.73 (1.33-5.61), respectively, compared with the lowest tertile. Furthermore, evaluation of both ALP and C-reactive protein provided better predictive value than either alone. Interesting result suggesting the mechanism was that ALP was significantly associated with the presence of angiographic coronary calcification (P for trend = 0.046).Conclusion
Our study demonstrated that the higher serum ALP level is an independent predictor of mortality, myocardial infarction, and stent thrombosis in CAD patients after PCI with DES.
European Heart Journal 12/2012; · 10.48 Impact Factor
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Hyun-Jai Cho,
Ho-Jae Lee,
Yeon-Ju Chung,
Ju-Young Kim,
Hyun-Ju Cho, Han-Mo Yang,
Yoo-Wook Kwon,
Hae-Young Lee,
Byung-Hee Oh,
Young-Bae Park,
Hyo-Soo Kim
[show abstract]
[hide abstract]
ABSTRACT: Cell therapy is a promising approach for repairing damaged heart. However, there are large rooms to be improved in therapeutic efficacy. We cultured a small quantity (5-10 mg) of heart biopsy tissues from 16 patients who received heart transplantation. We produced primary and secondary cardiospheres (CSs) using repeated three-dimensional culture strategy and characterized the cells. Approximately 5000 secondary CSs were acquired after 45 days. Genetic analysis confirmed that the progenitor cells in the secondary CSs originated from the innate heart, but not from extra-cardiac organs. The expressions of Oct4 and Nanog were significantly induced in secondary CSs compared with adherent cells derived from primary CSs. Those expressions in secondary CSs were higher in a cytokine-deprived medium than in a cytokine-supplemented one, suggesting that formation of the three-dimensional structure was important to enhance stemness whereas supplementation with various cytokines was not essential. Signal blocking experiments showed that the ERK and VEGF pathways are indispensable for sphere formation. To optimize cell processing, we compared four different methods of generating spheres. Method based on the hanging-drop or AggreWell™ was superior to that based on the poly-d-lysine-coated dish or Petri dish with respect to homogeneity of the product, cellular potency and overall simplicity of the process. When transplanted into the ischemic myocardium of immunocompromised mice, human secondary CSs differentiated into cardiomyocytes and endothelial cells. These results demonstrate that generation of secondary CSs from a small quantity of adult human cardiac tissue is a feasible and effective cell processing strategy to improve the therapeutic efficacy of cell therapy.
Biomaterials 10/2012; · 7.40 Impact Factor
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Hack-Lyoung Kim,
Bon-Kwon Koo,
Chang-Wook Nam,
Joon-Hyung Doh,
Ji-Hyun Kim, Han-Mo Yang,
Kyung-Woo Park,
Hae-Young Lee,
Hyun-Jae Kang,
Young-Seok Cho,
Tae-Jin Youn,
Sang-Hyun Kim,
In-Ho Chae,
Dong-Ju Choi,
Hyo-Soo Kim,
Byung-Hee Oh,
Young-Bae Park
[show abstract]
[hide abstract]
ABSTRACT: 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.
Identifying a functionally significant stenosis is difficult when several stenoses exist within 1 coronary artery.
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.
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.
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.
10/2012; 5(10):1013-8. · 1.07 Impact Factor
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Woo-Young Chung,
Jeehoon Kang,
Young-Seok Cho,
Hae-Jun Park, Han-Mo Yang,
Jae-Bin Seo,
Jung-Won Suh,
Kwang-Il Kim,
Tae-Jin Youn,
Sang-Hyun Kim,
In-Ho Chae,
Joo-Hee Zo,
Myung-A Kim,
Dong-Ju Choi
[show abstract]
[hide abstract]
ABSTRACT: The zotarolimus-eluting stent has shown larger in-stent late lumen loss compared to sirolimus-eluting stents in previous studies. However, this has not been thoroughly evaluated in ST elevation myocardial infarction.
This was a prospective, randomized, controlled trial evaluating angiographic outcomes in patients presenting with ST elevation myocardial infarction, treated with zotarolimus-eluting stents or sirolimus-eluting stents. From March 2007 to February 2009, 122 patients were randomized to zotarolimus-eluting stents or sirolimus-eluting stents in a 1:1 fashion. The primary endpoint was 9-month in-stent late lumen loss confirmed by coronary angiography, and secondary endpoints were percent diameter stenosis, binary restenosis rate, major adverse cardiac events (a composite of cardiac death, non-fatal myocardial infarction, and target vessel revascularization), and late-acquired incomplete stent apposition.
Angiographic in-stent late lumen loss was significantly higher in the zotarolimus-eluting stent group compared to the sirolimus-eluting stent group ((0.49 ± 0.65) mm vs. (0.10 ± 0.46) mm, P = 0.001). Percent diameter stenosis at 9-month follow-up was also larger in the zotarolimus-eluting stent group ((30.0 ± 17.9)% vs. (17.6 ± 14.0)%, P < 0.001). In-segment analysis showed similar findings. There were no significant differences in binary restenosis rate, major adverse cardiac events, and late-acquired incomplete stent apposition.
Compared to sirolimus-eluting stents, the zotarolimus-eluting stent is associated with significantly higher in-stent late lumen loss at 9-month angiographic follow-up in the treatment of ST elevation myocardial infarction. Although there was no significant difference in 1-year clinical outcomes, the clinical implication of increased late lumen loss should be further studied.
Chinese medical journal 10/2012; 125(19):3373-81. · 0.86 Impact Factor
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Joo Myung Lee,
Wonseok Choe,
Baek-Kyung Kim,
Won-Woo Seo,
Woo-Hyun Lim,
Chan-Koo Kang,
San Kyeong,
Khee Dong Eom,
Hyun-Ju Cho,
Young-Chan Kim,
Jin Hur, Han-Mo Yang,
Hyun-Jai Cho,
Yoon-Sik Lee,
Hyo-Soo Kim
[show abstract]
[hide abstract]
ABSTRACT: Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late endothelial progenitor cells (EPC). Therefore, VE-cadherin could be an ideal target surface molecule to capture circulating late EPC. In the present study, we evaluated whether anti-VE-cadherin antibody-coated stents (VE-cad stents) might accelerate endothelial recovery and reduce neointimal formation more than anti-CD34 antibody-coated stents (CD34 stents) through the superior ability to capture the late EPC. The stainless steel stents were coated with anti-human VE-cadherin antibodies or anti-human CD34 antibodies under the same condition. In vitro, VE-cad stents showed higher number of adhering EPC (823.6 ± 182.2 versus 379.2 ± 137.2 cells per HPF, p < 0.001). VE-cad stents also demonstrated better specific capturing of cells with endothelial lineage markers than CD34 stents did in flow cytometric analysis. VE-cad stents showed more effective re-endothelialization after 1 h, 24 h, and 3 days in vivo. At 42 days, VE-cad stents demonstrated significantly smaller neointima area (0.92 ± 0.38 versus 1.24 ± 0.41 mm(2), p = 0.002) and significantly lower PCNA positive cells in neointima (1684.8 ± 658.8/mm(2) versus 2681.7 ± 375.1/mm(2), p = 0.008), compared with CD34 stents. In conclusion, VE-cad stents captured EPC and endothelial cells more selectively in vitro, accelerated re-endothelialization over stents, and reduced neointimal formation in vivo, compared with CD34 stents.
Biomaterials 09/2012; 33(35):8917-27. · 7.40 Impact Factor
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Do-Yoon Kang, Han-Mo Yang,
Kyung Woo Park,
So-Ryoung Lee,
Min-Ho Lee,
Dong-Won Lee,
Hae-Young Lee,
Hyun-Jae Kang,
Bon-Kwon Koo,
In-Ho Chae,
Dong-Ju Choi,
Hyo-Soo Kim,
Cheol-Ho Kim
[show abstract]
[hide abstract]
ABSTRACT: Small dense low density lipoproteins (sd-LDL) are a risk factor for coronary artery disease and are known to stimulate platelet function in vitro. This study aimed to evaluate whether high proportion of sd-LDL is associated with high on-treatment platelet reactivity (HOPR).
From January 2009 to March 2010, 439 subjects (mean age: 64.3±9.7, Male : Female=306 : 133) were enrolled from the low density LIPOProtein-cholesterol Size measurement Registry with coronary artery disease, who had undergone elective percutaneous coronary intervention and measured both LDL particle size and on-treatment platelet reactivity (OPR). Mean LDL particle size was measured by gradient gel electrophoresis (Quantimetrix, Lipoprint™) and OPR by the VerifyNow™ system (aspirin and P2Y12).
Between pattern A (large, buoyant LDL dominant) and B (sd-LDL dominant) population, there were no significant difference in OPR to aspirin (441.3±71.9 vs. 434.07±63.45 aspirin reaction units, p=0.351) or clopidogrel (237.9±87.3 vs. 244.9±80.7 P2Y12 reaction units, p=0.465). There was no difference in LDL particle size between patients with HOPR compared with non-HOPR patients (aspirin: 26.8±0.5 vs. 26.7±0.6 nm, p=0.078, clopidogrel: 26.7±0.6 vs. 26.8±0.5 nm, p=0.857). Pearson's correlation coefficients between LDL particle size and platelet reactivity were not statistically significant (aspirin assay: r=0.080, p=0.098, P2Y12 assay: r=-0.027, p=0.568).
There was no significant association between LDL particle size and OPR in patients with coronary artery disease.
Korean Circulation Journal 08/2012; 42(8):551-7.
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Jin Joo Park,
In-Ho Chae,
Young-Seok Cho,
Seong-Wook Kim, Han-Mo Yang,
Jae-Bin Seo,
Song-Yi Kim,
Il-Young Oh,
Chang-Hwan Yoon,
Jung-Won Suh,
Kyung-Woo Park,
Woo-Young Chung,
Tae-Jin Youn,
Dong-Ju Choi,
Hyo-Soo Kim
[show abstract]
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ABSTRACT: This study sought to investigate the extent of and factors related to lumen and vessel area change in coronary arteries after total occlusion (TO) recanalization.
TO of a coronary artery promotes negative remodeling in distal reference segments. Recanalization can restore blood flow, potentially leading to positive vascular remodeling.
From March 2005 to June 2008, 58 consecutive patients with de novo TO lesions of at least 1-month duration were enrolled. We performed intravascular ultrasound after successful percutaneous coronary intervention and at the 6-month follow-up, and we quantified changes in the distal reference segments.
At the 6-month follow-up, there was a significant increase in the mean lumen diameter (+0.21 mm, p = 0.001), the mean external elastic membrane diameter (+0.13 mm, p = 0.010), the lumen area (+0.87 mm(2), p < 0.001), and the external elastic membrane area (+0.85 mm(2), p = 0.001) in the distal reference segments and an increase in the left ventricular ejection fraction (+2.77%, p = 0.010). Overall, 40 of 58 patients (69%) showed lumen area increase; these patients had increase in lumen diameter by 0.40 ± 0.34 mm (p < 0.001) and increase in incomplete stent apposition rate (p = 0.006). A TO duration of longer than 3 months (odds ratio [OR]: 14.8; 95% confidence interval [CI]: 1.28 to 172.8, p = 0.032), a poor collateral flow (OR: 12.0; 95% CI: 1.92 to 74.2, p = 0.008), and statin use (OR: 7.4; 95% CI: 1.03 to 53.6, p = 0.047) were independent predictors of lumen area increase.
Recanalization of TO led to lumen area increase in two-thirds of the patients. Independent predictors of lumen area increase were occlusion duration, a poor collateral flow, and statin use. These factors could be used as guides in choosing the optimal stent size during percutaneous coronary intervention to TO lesions and optimal medical therapy during follow-up.
08/2012; 5(8):827-36. · 1.07 Impact Factor
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ABSTRACT: To test the effect of a loss-of-function variation of the cytochrome P450 (CYP) 3A5 on drug-drug interaction between amlodipine and clopidogrel. Amlodipine is a well-known inhibitor of CYP 3A4, an isoenzyme of CYP3A that activates clopidogrel. However, controversy exists regarding whether amlodipine adversely affects clopidogrel response and clinical outcome after percutaneous coronary intervention (PCI). In the presence of CYP3A4 inhibitors such as amlodipine, the genetic variation of CYP3A5, the isoenzyme responsible for the backup CYP3A activity, may play an important role in clopidogrel activation.
Post hoc analysis of a prospectively enrolled cohort.
Patients enrolled in the CROSS-VERIFY cohort from June 2006 to June 2010, with successful genotyping of CYP3A5.
The pharmacodynamic analysis end point was clopidogrel on-treatment platelet reactivity (OPR) and the clinical analysis end point was the composite of cardiac death, non-fatal myocardial infarction, ischaemic stroke and stent thrombosis at 12 months post-PCI.
1258 patients had successful genotyping and were categorised as CYP3A5 non-expressers (749 patients) and expressers (509 patients) according to the CYP3A5 genotype. Amlodipine users showed higher OPR versus non-users only in CYP3A5 non-expressers (249 ± 83 vs 228 ± 84 P2Y12 reaction units, p=0.013). These findings was corroborated by clinical outcomes, in which amlodipine users had a higher incidence of events compared with non-users only in CYP3A5 non-expressers (4.6% vs 0.6%, HR 7.731, CI 2.042 to 29.264, p=0.004).
Treatment with amlodipine is associated with increased clopidogrel OPR and increased risk of thrombotic events after PCI, which is dependent on the CYP3A5 genetic status.
Heart (British Cardiac Society) 06/2012; 98(18):1366-72. · 4.22 Impact Factor
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Myung-Ki Seo,
Bon-Kwon Koo,
Ji-Hyun Kim,
Dong-Ho Shin, Han-Mo Yang,
Kyung-Woo Park,
Hae-Young Lee,
Hyun-Jae Kang,
Hyo-Soo Kim,
Byung-Hee Oh,
Young-Bae Park
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ABSTRACT: Maximal hyperemia is a prerequisite for the accurate measurement of fractional flow reserve (FFR). Although continuous infusion of adenosine via the femoral vein is considered to be the gold standard, this requires an additional invasive procedure for femoral vein access and is difficult to use during transradial coronary catheterization. We performed this prospective study to evaluate the feasibility and efficacy of peripheral intravenous infusion of adenosine for FFR measurement.
Seventy-one patients were prospectively enrolled, and FFR was measured using a 0.014-inch coronary pressure wire. Hyperemic efficacy of adenosine was compared among intracoronary bolus injection and continuous IV infusion (140 μg/min/kg) via the femoral and via the forearm vein. In 20 patients, hyperemic mean transit time and index of microcirculatory resistance were also measured. Mean FFR after bolus administration of adenosine was 0.81±0.10. As compared with femoral vein infusion (FFR: 0.80±0.10), hyperemic efficacy of forearm vein infusion of adenosine (FFR: 0.80±0.11) was not inferior (P for noninferiority=0.01). The number of functionally significant stenoses (FFR <0.75) was also not different between the 2 methods (femoral vein versus forearm vein; 17 (25.0%) versus 17 (25.0%), P=1.0). Both hyperemic mean transit time and index of microcirculatory resistance were not different between the 2 routes of adenosine infusion. Additional bolus injection of adenosine during IV infusion did not improve the hyperemic efficacy but increased the risk of atrioventricular block.
This study suggests that continuous intravenous infusion of adenosine via the forearm vein is a convenient and effective way to induce steady-state hyperemia for invasive physiological measurements.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01070420.
Circulation Cardiovascular Interventions 05/2012; 5(3):401-5. · 6.06 Impact Factor
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Howard Lee, Han-Mo Yang,
Hae-Young Lee,
Jae-Joong Kim,
Dong-Ju Choi,
Ki-Bae Seung,
Eun-Seok Jeon,
Jong-Won Ha,
Se-Joong Rim,
Jeong Bae Park,
Joon-Han Shin,
Byung-Hee Oh
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ABSTRACT: Fimasartan is a selective angiotensin II receptor blocker developed for once-daily dosing.
To meet the regulatory requirements for approval of an antihypertensive treatment in Korea, this pair of studies was conducted to evaluate the efficacy and tolerability of fimasartan, to determine its dose-response relationship and minimum effective dose, and to characterize its blood pressure (BP)-reduction profile over the dosing interval.
These 2 Phase II, randomized, double-blind, placebo-controlled, parallel-group, and dose-response studies enrolled male or nonchildbearing female Korean patients aged 18 to 65 years (study 1) or 18 to 70 years (study 2) with essential hypertension (sitting diastolic BP [DBP] 95-<115 mm Hg [study 1] or 90-<110 mm Hg [study 2]). Patients were randomly assigned to receive fimasartan 20, 60, 120, or 180 mg (study 1) or 20, 60, 120, or 240 mg (study 2) or placebo in the same ratio, once daily for 4 weeks (study 1) or 8 weeks (study 2). Clinic BP was measured at trough, and change from baseline in DBP at week 4 (study 1) or 8 (study 2) was the primary efficacy end point. In study 1, 24-hour ambulatory BP monitoring (ABPM) was conducted. Treatment-emergent adverse events (TEAEs) were assessed using a structured questionnaire, laboratory testing, physical examination, and ECG readings.
Totals of 61 and 195 patients participated in studies 1 and 2, respectively (68% male; mean age, 50.1 and 55.1 years; DBP, 98.7 and 103.6 mm Hg; systolic BP, 147.0 and 158.1 mm Hg), of whom 52 (85.2%) and 169 (86.7%) completed each study. Data from ABPM were obtained from 45 patients (73.8%), and safety profile was evaluated in 225 participants. Four-week treatment with fimasartan 180 mg once daily was associated with a significantly greater mean reduction in DBP compared with placebo in study 1 (-16.4 vs -5.5 mm Hg; P = 0.022). In study 2, fimasartan 60, 120, and 240 mg once daily were associated with significantly greater reductions in DBP after 8 weeks of treatment compared with placebo (-14.4, -14.1, and -12.7 vs -5.8 mm Hg, respectively; P < 0.0001-< 0.005). Fimasartan 60 mg once daily was the minimum effective dose, and the dose-response relationship was flat at doses >60 mg once daily. BP reduction was maintained over the full 24-hour dosing interval (trough-to-peak ratios: 0.41-0.98). The proportions of patients who experienced TEAEs were comparable among the treatment groups in both studies, with headache (9.8%) and dizziness (4.4%) being most commonly reported. No serious AEs were reported.
Once-daily oral administration of fimasartan was well tolerated and efficacious in reducing BP in these hypertensive Korean patient populations. ClinicalTrials.gov identifiers: NCT00937651 and NCT00923611.
Clinical Therapeutics 05/2012; 34(6):1273-89. · 2.32 Impact Factor
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Kyung Woo Park,
Si-Hyuck Kang,
Jeehoon Kang,
Ki-Hyun Jeon,
Jin Joo Park,
Jung-Kyu Han,
Jin-Sin Koh,
Sang Eun Lee, Han-Mo Yang,
Hae-Young Lee,
Hyun-Jae Kang,
Bon-Kwon Koo,
Byung-Hee Oh,
Young-Bae Park,
Hyo-Soo Kim
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ABSTRACT: Previous reports on smokers' paradox to clopidogrel have only been able to show an association between cigarette smoking and enhanced response to clopidogrel therapy. No study has shown reversal of enhanced clopidogrel response after smoking cessation.
To conduct a prospective observational longitudinal study in order to measure the impact of cigarette smoking on on-clopidogrel platelet reactivity (OPR).
From the prospective CROSS-VERIFY cohort, 810 subjects with repeated measurement of OPR at least 1 month apart were analysed. With smoking status ascertained at two time points, baseline and follow-up, study subjects were categorised into never smokers (n=628), smoking quitters (n=77) and persistent smokers (n=105). Dependent variables included OPR measured by the VerifyNow assay and the percentage of subjects with high OPR (HOPR).
At baseline, current smokers showed significantly lower OPR compared with never smokers, with no significant differences in OPR between future quitters and future persistent smokers within current smokers. While the OPR of never smokers and persistent smokers did not change significantly during the follow-up, the mean OPR of quitters increased significantly by 19 P2Y12 reaction units (p=0.013). The frequency of HOPR showed similar results, with an 8-10% increase in smoking quitters in contrast to no significant changes in never and persistent smokers. Both mean OPR and the frequency of HOPR showed a linear inverse relationship with the amount of smoking.
Enhanced clopidogrel response in smokers is reversed after smoking discontinuation, suggesting a causal relationship in addition to the previously reported association between smoking and enhanced clopidogrel response.
Heart (British Cardiac Society) 05/2012; 98(13):1000-6. · 4.22 Impact Factor
