Je Sang Kim

Cellular and Molecular Changes Associated With Inhibitory Effect of Pioglitazone on Neointimal Growth in Patients With Type 2 Diabetes After Zotarolimus-Eluting Stent Implantation

Objective—To investigate the mechanistic basis underlying antirestenosis and the antiatherogenic effect of pioglitazone in patients with type 2 diabetes mellitus who were undergoing zotarolimus-eluting stent implantation. Methods and Results—Recent studies highlight the beneficial effect of pioglitazone in attenuating neointimal growth after stent implantation. Patients with coronary artery diseases were randomly assigned to pioglitazone (n=47) or placebo (n=47) after stent implantation. Pioglitazone significantly reduced neointimal hyperplasia within the stented lesion and attenuated total plaque burden in the in-segment regions of the stent, as assessed by intravascular ultrasonography at the 8-month follow-up. These changes were preceded by reduced circulating natural killer (NK) cells, diminished interleukin 6 and monocyte chemoattractant protein-1 levels, and downregulation of chemokine receptor 2 at 2 days after stent implantation; and an elevated interleukin 10 level at 10 days after implantation. Furthermore, the proliferation and migration of vascular smooth muscle cells were inhibited in the presence of pioglitazone-treated patient serum, demonstrating that the antiproliferative effects of pioglitazone occurred concurrently with its antiinflammatory action. Conclusion—Our data present early cellular and immunologic changes by pioglitazone that might have been associated with antirestenotic and antiatherogenic effects in diabetic patients. Inhibiting proinflammatory responses while promoting antiinflammatory circuits, together with an antiproliferative action, may, in part, account for the antirestenotic effect of pioglitazone by altering vascular remodeling processes in the early phase.

Prospective randomized comparison of clinical and angiographic outcomes between everolimus-eluting vs. zotarolimus-eluting stents for treatment of coronary restenosis in drug-eluting stents: intravascular ultrasound volumetric analysis (RESTENT-ISR trial).

AIMS At present no proven standard treatment for drug-eluting stent (DES) restenosis is available, and the efficacy and safety of everolimus-eluting stent (EES) and zotarolimus-eluting stent (ZES) for DES restenosis are limited. The purpose of this prospective, randomized 9-month intracoronary ultrasound (IVUS) and 3-year clinical follow-up study was to compare the effects of EESs and ZESs on neointima volume and major adverse cardiovascular events (MACEs) such as death, myocardial infarction (MI), target lesion revascularization (TLR) and stent thrombosis in DES restenosis patients. METHODS AND RESULTS Patients were eligible for this study if they were between 40 and 75 years old with in-stent restenosis >50% by quantitative coronary angiographic analysis in DES or within 5 mm of the stent edges with signs of ischaemia. Eligible patients (n = 304, 146 women and 158 men) were randomly assigned to receive either EES (158 patients) or ZES (146 patients). The primary endpoint of the study was to compare neointima volume between the EES and ZES groups at the 9-month follow-up IVUS. MACEs, including death, non-fatal MI, stent thrombosis and the need for repeated TLR within 3 years, were noted. The 9-month angiographic and IVUS follow-up showed no significant differences in late lumen loss (0.40 ± 0.56 vs. 0.45 ± 0.61 mm, P = 0.57, respectively) and neointima volume (0.51 ± 0.48 vs. 0.56 ± 0.54 mm3/1 mm, P = 0.47, respectively) in the EES and the ZES groups. Composite MACEs such as death, MI, stent thrombosis and TLR during 3-year follow-up were comparable between the two groups [15.8% (n = 25) in the EES group and 22.6% (n = 33) in the ZES group, P = 0.276], independent of de novo DES type, sex, age, body mass index, presence of diabetes, hypertension and dyslipidaemia. CONCLUSIONS Patients with first- and second-generation DES restenosis, both EES and ZES implantation were effective and safe in reducing neointima volume and late loss with a comparable rate of MACEs independent of cardiovascular risk factors.

Different impacts of acute myocardial infarction on left ventricular apical and basal rotation

AIMS The impacts of acute myocardial infarction (AMI) with different regional wall motion abnormalities on left ventricular (LV) rotation have not been well investigated. We assessed the impacts of AMI on LV rotational mechanics and to compare the alterations in basal and apical rotation between patients with anterior and inferior AMI. METHODS AND RESULTS Thirty-five patients with anterior AMI and 31 patients with inferior AMI who had a single culprit lesion were analysed. Thirty age-matched subjects were included for controls. The apical and basal rotations were obtained and LV twist and torsion were measured by two-dimensional speckle tracking imaging. Compared with normal, LV twist was reduced in all AMI patients. The basal rotation was larger in anterior AMI than in inferior AMI and normal (-9.0 ± 2.6 vs. -3.4 ± 2.1° and -6.0 ± 1.9°, P < 0.001), although the apical rotation was lower in anterior AMI. As a result, LV twist and torsion were not different between anterior AMI and inferior AMI (17.0 ± 4.6 vs. 16.7 ± 3.3° and 2.08 ± 0.59 vs. 2.07 ± 0.44°/cm, P = NS, respectively), although LV ejection fraction was lower in anterior AMI. By multivariate analysis, LV torsion [odds ratio (OR) =0.13, 95% confidential interval (CI) = 0.02-0.75, P = 0.02] and basal rotation (OR = 0.67, 95% CI = 0.45-1.00, P = 0.05) were independently related to LV recovery in patients with anterior AMI and in patients with inferior AMI, respectively. CONCLUSION Although LV twist and torsion were decreased either by reduced apical and basal rotation in AMI patients; the basal rotation was rather increased in anterior AMI. LV functional recovery can be predicted by LV torsion in anterior AMI and by basal rotation in inferior AMI. The basal rotation has often been ignored; however, our findings suggest that the basal rotation has an important role in LV function.

Triple antithrombotic therapy versus dual antiplatelet therapy in patients with atrial fibrillation undergoing drug-eluting stent implantation

BackgroundThe optimal antithrombotic regimen in patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation for complex coronary artery disease is unclear. We compared the net clinical outcomes of triple antithrombotic therapy (TAT; aspirin, thienopyridine, and warfarin) and dual antiplatelet therapy (DAPT; aspirin and thienopyridine) in AF patients who had undergone DES implantation. MethodsA total of 367 patients were enrolled and analyzed retrospectively; 131 patients (35.7%) received TAT and 236 patients (64.3%) received DAPT. DAPT and warfarin were maintained for a minimum of 12 and 24 months, respectively. The primary endpoint was the 2-year net clinical outcomes, a composite of major bleeding and major adverse cardiac and cerebral events (MACCE). Propensity score-matching analysis was carried out in 99 patient pairs. ResultsThe 2-year net clinical outcomes of the TAT group were worse than those of the DAPT group (34.3 vs. 21.1%, P=0.006), which was mainly due to the higher incidence of major bleeding (16.7 vs. 4.6%, P<0.001), without any significant increase in MACCE (22.1 vs. 17.7%, P=0.313). In the multivariate analysis, TAT was an independent predictor of worse net clinical outcomes (odds ratio 1.63, 95% confidence interval 1.06–2.50) and major bleeding (odds ratio 3.54, 95% confidence interval 1.65–7.58). After propensity score matching, the TAT group still had worse net clinical outcomes and a higher incidence of major bleeding compared with the DAPT group. ConclusionIn AF patients undergoing DES implantation, prolonged administration of TAT may be harmful due to the substantial increase in the risk for major bleeding without any reduction in MACCE.

Comparison of inflammatory markers between diabetic and nondiabetic ST segment elevation myocardial infarction

BACKGROUND Inflammation plays a significant role in acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM). There may be similar inflammatory changes in non-DM patients with ST elevation myocardial infarction (STEMI) and DM patients with stable angina (SA), and DM patients with STEMI may have more severe changes than the former two groups. The objectives of this study were to investigate whether the level of inflammation was similar in patients with non-DM STEMI and DM SA, and to evaluate whether the changes in the level of inflammation were more severe in patients with DM STEMI compared to the other two groups. METHODS AND RESULTS A variety of inflammatory markers including: highly sensitive C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), IL-18, vascular cell adhesion molecule-1 (VCAM-1), and matrix metallopeptidase-9 (MMP-9) as well as insulin resistance were compared among the three groups: DM STEMI (90 patients), DM SA (91 patients), and non-DM STEMI (76 patients). Inflammatory marker levels were not significantly different between the DM SA and non-DM STEMI groups. However, hsCRP and IL-6 were increased in the DM STEMI compared to the DM SA patients (p=0.005 and p=0.004, respectively). In addition, hsCRP, ESR, and IL-18 were increased in the DM STEMI compared to the non-DM STEMI patients (p=0.017, p=0.020, and p=0.033, respectively). Furthermore, the fasting insulin and the homeostasis model assessment were significantly increased in the DM STEMI compared to the DM SA patients (p=0.04 and p=0.004, respectively). CONCLUSIONS DM SA and non-DM STEMI may have similar inflammatory changes. DM STEMI may be a more severe inflammatory condition compared to patients with DM SA or non-DM STEMI.

How Well Does the Target INR Level Maintain in Warfarin- Treated Patients with Non-ValvularAtrial Fibrillation?

Purpose Although warfarin is an effective oral anticoagulation (OAC) drug to reduce the risk of thromboembolism in patients with non-valvular atrial fibrillation (NVAF), long term follow-up data are scarce to be certain whether the target INR level is maintained in warfarin-treated patients in Korea. The aim of this study was to evaluate how well INRs are maintained within the target range using a new index, INR stability (= 100 × number of INRs within target range/total number of INR measurements) which we made, and to find out any correlation between thromboembolic events and INR stability. Materials and Methods This study was an observational analysis of retrospectively collected data of 129 patients with NVAF from April 2000 to December 2005 at a single tertiary hospital. All patients were registered at the anticoagulation service. Results The median duration of follow up was 2.03 years (interquartile range 1.35 - 2.96). During the follow-up period, 60.9 ± 14.9% of the INR were within the target INR range. INR stability was not significantly different between patients without and with stroke (61.2 ± 15.0% vs 53.3 ± 4.9%). Among the known factors affecting fluctuations of the INR value, the most frequent factor was noncompliance (41.8%). Conclusion The present study showed that it was not enough to maintain INR values within the target range in warfarin-treated patients with NVAF even at a tertiary hospital. Noncompliance is an important problem which interferes with maintaining target INR range.

INNOVATION Study (Impact of Immediate Stent Implantation Versus Deferred Stent Implantation on Infarct Size and Microvascular Perfusion in Patients With ST-Segment–Elevation Myocardial Infarction)

Background—The aim of this study was to assess whether deferred stenting (DS) reduces infarct size and microvascular obstruction (MVO) compared with immediate stenting (IS) in primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction. Methods and Results—From February 2013 to August 2015, 114 patients (mean age: 69 years) were randomized into the following 2 groups: DS with an intention to stent 3 to 7 days later or IS after primary reperfusion in 2 centers. The primary and secondary end points were infarct size and the incidence of MVO, respectively, assessed by cardiac magnetic resonance imaging at 30 days after primary reperfusion. The median time to the second procedure in the DS was 72.8 hours. Six patients in the DS group were crossed over to the IS group because of progression of dissection or safety concerns after randomization. In the intention-to-treat analysis, DS did not significantly reduce infarct size (15.0% versus 19.4%; P=0.112) and the incidence of MVO (42.6% versus 57.4%; P=0.196), compared with IS. However, in anterior wall myocardial infarction, infarct size (16.1% versus 22.7%; P=0.017) and the incidence of MVO (43.8% versus 70.3%; P=0.047) were significantly reduced in the DS group. There was no urgent revascularization event during deferral period. Conclusions—A routine DS did not significantly reduce infarct size and MVO compared with IS, although it was safe. The beneficial effect of DS in patients with anterior myocardial infarction should be confirmed by larger randomized studies. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02324348.

Impact of final kissing balloon inflation after simple stent implantation for the treatment of non-left main true coronary bifurcation lesions in patients with acute coronary syndrome

OBJECTIVES We sought to evaluate the impact of final kissing balloon inflation (FKBI) after simple stent implantation for the treatment of non-left main true coronary bifurcation lesions in patients with acute coronary syndrome (ACS). BACKGROUND Whether FKBI should be mandatory after simple stent implantation for the treatment of coronary bifurcation lesion is controversial. Besides, ACS patients who have undergone bifurcation percutaneous coronary intervention with simple stent implantation may experience worse prognosis compared to stable angina pectoris patients. METHODS Two hundred and fifty one eligible patients (67.7% male, mean age 61.7 ± 10.4 years) were enrolled. The study population was divided into two groups according to the performance of FKBI. The primary end points were major adverse cardiac event (MACE); target lesion revascularization (TLR), non-fatal myocardial infarction (MI) and cardiac death during the follow-up period. RESULTS Over a mean follow-up period of 3.0 ± 1.9 years, there were 29 MACEs (10 TLR, 6 non-fatal MI, and 13 cardiac deaths), representing an event rate of 11.6%. Kaplan-Meier survival analysis revealed that FBKI group had favorable outcome compared to non-FKBI group with regard to hard events (p = 0.010) as well as composite MACEs (p = 0.008). In multivariable analysis, FKBI was a significant predictor of composite MACEs [hazard ratio 0.398 (95% confidence interval 0.190-0.836, p = 0.015)] and hard events [hazard ratio 0.325 (95% confidence interval 0.130-0.811, p = 0.016)]. CONCLUSIONS In terms of prognosis, performing FKBI after simple stent implantation for the treatment of non-left main true coronary bifurcation lesions may be mandatory in ACS patients.

Numbness after Transradial Cardiac Catheterization: the Results from a Nerve Conduction Study of the Superficial Radial Nerve

Background and Objectives Numbness on the hand occurs infrequently after a transradial cardiac catheterization (TRC). The symptom resembles that of neuropathy. We, therefore, investigated the prevalence, the predicting factors and the presence of neurological abnormalities of numbness, using a nerve conduction study (NCS). Subjects and Methods From April to December 2013, all patients who underwent a TRC were prospectively enrolled. From among these, the patients who experienced numbness on the ipsilateral hand were instructed to describe their symptoms using a visual analogue scale; subsequently, NCSs were performed on these patients. Results Of the total 479 patients in the study sample, numbness occurred in nine (1.8%) following the procedure. The NCS was performed for eight out of the nine patients, four (50%) of which had an abnormal NCS result at the superficial radial nerve. A larger sheath and history of myocardial infarction (p=0.14 and 0.08 respectively) tended towards the occurrence of numbness; however, only the use of size 7 French sheaths was an independent predictor for the occurrence of numbness (odds ratio: 5.50, 95% confidence interval: 1.06-28.58, p=0.042). The symptoms disappeared for all patients but one, within four months. Conclusion A transient injury of the superficial radial nerve could be one reason for numbness after a TRC. A large sheath size was an independent predictor of numbness; therefore, large sized sheaths should be used with caution when performing a TRC.

First-Generation Versus Second-Generation Drug-Eluting Stents in Coronary Chronic Total Occlusions: Two-Year Results of a Multicenter Registry

Background Limited data are available regarding the long-term clinical outcomes of second-generation drug-eluting stents (DES) versus first-generation DES in patients with coronary chronic total occlusion (CTO) who undergo percutaneous coronary intervention (PCI). The aim of this study was to compare the clinical outcomes of second-generation DES with those of first-generation DES for the treatment of CTO. Methods and Results Between March 2003 and February 2012, 1,006 consecutive patients with CTO who underwent successful PCI using either first-generation DES (n = 557) or second-generation DES (n = 449) were enrolled in a multicenter, observational registry. Propensity-score matching was also performed. The primary outcome was cardiac death over a 2-year follow-up period. No significant differences were observed between the two groups regarding the incidence of cardiac death (first-generation DES versus second-generation DES; 2.5% vs 2.0%; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.37 to 1.98; p = 0.72) or major adverse cardiac events (MACE, 11.8% vs 11.4%; HR: 1.00; 95% CI: 0.67 to 1.50; p = 0.99). After propensity score matching, the incidences of cardiac death (HR: 0.86; 95% CI: 0.35 to 2.06; p = 0.86) and MACE (HR: 0.93; 95% CI: 0.63 to 1.37; p = 0.71) were still similar in both groups. Furthermore, no significant differences were observed between sirolimus-eluting, paclitaxel-eluting, zotarolimus-eluting, and everolimus-eluting stents regarding the incidence of cardiac death or MACE. Conclusion This study shows that the efficacy of second-generation DES is comparable to that of first-generation DES for treatment of CTO over 2 years of follow-up.