Tae Ho Park

A Randomized Comparison of Platinum Chromium-Based Everolimus-Eluting Stents Versus Cobalt Chromium-Based Zotarolimus-Eluting Stents in All-Comers Receiving Percutaneous Coronary Intervention : HOST–ASSURE (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis–Safety & Effectiveness of Drug-Eluting Stents & Anti-platelet Regimen), a Randomized, Controlled, Noninferiority Trial

OBJECTIVESnThis study sought to test whether the newly developed platinum chromium (PtCr)-based everolimus-eluting stent (EES) is noninferior to the cobalt chromium (CoCr)-based zotarolimus-eluting stent (ZES) in all-comers receiving percutaneous coronary intervention (PCI).nnnBACKGROUNDnPtCr provides improved radial strength, conformability, and visibility compared with the CoCr alloy, but PtCr-based stents have not been tested in a wide range of patients receiving PCI. Also, recent case series have raised the issue of longitudinal stent deformation (LSD) with newer drug-eluting stents.nnnMETHODSnWe randomly assigned 3,755 all-comers receiving PCI to PtCr-EES or CoCr-ZES. The primary outcome was target lesion failure (TLF) at 1-year post-PCI, defined as the composite of cardiac death, nonfatal target vessel-related myocardial infarction, and ischemia-driven target lesion revascularization. Post-hoc angiographic analysis was performed to qualitatively and quantitatively analyze LSD.nnnRESULTSnAt 1 year, TLF occurred in 2.9% and 2.9% of the population in the PtCr-EES and CoCr-ZES groups, respectively (superiority pxa0= 0.98, noninferiority pxa0= 0.0247). There were no significant differences in the individual components of TLF as well as the patient-oriented clinical outcome. Of 5,010 stents analyzed, LSD occurred in 0.2% and 0% in the PtCr-EES and CoCr-ZES groups, respectively (pxa0= 0.104). There was no significant difference in post-deployment stent length ratio between the 2 stents (pxa0= 0.352).nnnCONCLUSIONSnAt 1 year, PtCr-EES was noninferior to CoCr-ZES in all-comers receiving PCI. Although LSD was observed only in PtCr-EES, both the stent length ratio and the frequency of LSD were not significantly different between the 2 stent types, and PtCr-EES was not associated with adverse clinical outcomes. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-SAfety & EffectiveneSS of Drug-ElUting Stents & Anti-platelet REgimen [HOST-ASSURE]; NCT01267734).

Mesenchymal stem cells overexpressing GCP-2 improve heart function through enhanced angiogenic properties in a myocardial infarction model

AIMSnIn this study, our aim was to evaluate the angio-vasculogenic properties of human adipose tissue-derived mesenchymal stem cells overexpressing the granulocyte chemotactic protein (GCP)-2 (hASCs/GCP-2) and to determine possible therapeutic effects in an experimental ischaemic heart model.nnnMETHODS AND RESULTSnQuantitative real-time (qRT)-PCR results revealed that hASCs/GCP-2 expressed significantly higher levels of pro-angiogenic genes, including vascular endothelial growth factor (VEGF)-A, hepatocyte growth factor (HGF), and interleukin (IL)-8, when compared with control-vector transduced hASCs or human umbilical vascular endothelial cells (HUVECs). In addition, the anti-apoptotic insulin-like growth factor (IGF)-1 and Akt-1 were also highly up-regulated in the hASCs/GCP-2 cells. In vitro cell migration and proliferation assays showed that hASCs/GCP-2-derived conditioned media (CM) significantly accelerated the migration and proliferation of fibroblast cells. Examination of in vitro endothelial differentiation showed that hASCs/GCP-2 cells spontaneously formed vascular-like structures and highly expressed endothelial-specific genes and proteins. In vivo study results of our mouse myocardial infarction (MI) model revealed that hASCs/GCP-2 implantation improved the cardiac function and reduced the infarct size. Finally, transplanted hASCs/GCP-2 cells unexpectedly differentiated into endothelial cells and the engraftment rate was significantly higher than control groups.nnnCONCLUSIONnWe suggest that overexpression of GCP-2 in stem cells has the potential to enhance their angiogenic and survival properties.

Improvement of cardiac function and remodeling by transplanting adipose tissue-derived stromal cells into a mouse model of acute myocardial infarction

BACKGROUNDnWe investigated the effect of adipose tissue-derived stromal cells (ADSC) therapy on cardiac contractility and remodeling in the C57BL/6 mouse model of acute myocardial infarction (AMI).nnnMETHODSn30 adult male C57BL/6 mice were randomized into 2 groups, namely, AMI+media (control, n=15) and AMI+ADSC (n=15). AMI was produced by left anterior descending coronary artery ligation. After AMI induction, 1 x 10(6) ADSC or media were intramyocardially injected and the results compared. Echocardiographic and histological analyses of surviving mice (n=20) were conducted. Echocardiography was performed before cell implantation and 2 weeks after transplantation.nnnRESULTSnLVEF and FS improved in the ADSC group compared to the control (P<0.01). LVEDD in the ADSC group decreased slightly from 4.65+/-0.63 mm to 4.14+/-0.53 mm compared to the control, but there was no statistical difference (P=0.072). LVESD decreased significantly in the ADSC group (P<0.05). A significant difference in scar formation and infarct size was observed between the ADSC and control group 2 weeks after AMI (P<0.05). ADSC were observed to migrate into injured sites and integrate into scar areas and increased vascular density in the infarct site compared to control group (P<0.05). Additionally, some transplanted ADSC expressed the endothelial marker.nnnCONCLUSIONSnEchocardiography and histological analysis revealed that improvement in cardiac function and ventricular remodeling was better in the ADSC group than in the control. This suggests that ADSC is a good candidate for cell therapy in cardiovascular disease.

Adjunctive cilostazol versus double-dose clopidogrel after drug-eluting stent implantation: the HOST-ASSURE randomized trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Safety & Effectiveness of Drug-Eluting Stents & Anti-platelet Regimen).

OBJECTIVESnThis study sought to test the noninferiority of triple antiplatelet therapy (TAT) versus double-dose clopidogrel dual antiplatelet therapy (DDAT) in patients undergoing percutaneous coronary intervention (PCI).nnnBACKGROUNDnAntiplatelet regimen is an integral component of medical therapy after PCI. A 1-week duration of doubling the dose of clopidogrel was shown to improve outcome at 1 month compared with the conventional dose in patients with acute coronary syndrome undergoing PCI. Yet in Asia, the addition of cilostazol is used more commonly than DDAT in high-risk patients.nnnMETHODSnWe randomly assigned 3,755 all-comers undergoing PCI to either TAT or DDAT, which was continued for 1 month, to test the noninferiority of TAT versus DDAT. The primary outcome was the cumulative incidence of net clinical outcome at 1 month post-PCI defined as the composite of cardiac death, nonfatal myocardial infarction, stent thrombosis, stroke, and PLATO (Platelet Inhibition and Patient Outcomes) major bleeding.nnnRESULTSnTAT was noninferior to DDAT with respect to the primary outcome, which occurred in 1.2% and 1.4% of patients, respectively (-0.22% absolute difference, 0.34% 1-sided 97.5% confidence interval, p = 0.0007 for noninferiority; hazard ratio: 0.85; 95% confidence interval: 0.49 to 1.48; p = 0.558 for superiority). The individual risks of cardiac death, nonfatal myocardial infarction, stent thrombosis, stroke, and PLATO major bleeding did not differ significantly between the 2 groups. There were no significant between-group differences in the treatment effect with regard to the rate of the primary outcome.nnnCONCLUSIONSnThe adjunctive use of cilostazol was noninferior to doubling the dose of clopidogrel for 1 month in all-comers undergoing PCI with exclusively drug-eluting stents. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-SAfety & EffectiveneSS of Drug-ElUting Stents & Anti-platelet REgimen [HOST-ASSURE]; NCT01267734).

Subclinical Myocardial Dysfunction in Metabolic Syndrome Patients without Hypertension

Background The aim of this study was to evaluate myocardial function in patients with non-hypertensive metabolic syndrome. Methods We selected metabolic syndrome patients (n = 42) without evidence of hypertension and compared them to age-matched control individuals (n = 20). All patients were evaluated by two-dimensional and tissue Doppler echocardiography including tissue Doppler derived strain and strain rate measurements. Results There were no significant differences between the two groups in mitral E and A inflow velocities or the E/A ratio. However, systolic and early diastolic myocardial velocities, and strain rate were significantly lower in patients with metabolic syndrome than in the control group (all p < 0.05). Multiple stepwise regression analyses revealed that age, waist circumference, and systolic blood pressure were independently associated with peak systolic myocardial velocity. Conclusion These results indicate that metabolic syndrome patients without hypertension may have decrease of myocardial systolic and early diastolic velocities on tissue Doppler imaging, even if they appear to have normal systolic and diastolic function on conventional echocardiography.

Comparison of pharmacodynamics between low dose ticagrelor and clopidogrel after loading and maintenance doses in healthy Korean subjects.

Abstract The novel antiplatelet agent ticagrelor has been demonstrated to exert a faster and more powerful inhibition of platelet aggregation in comparison to clopidogrel in coronary artery disease patients. However, a ticagrelor dose of 90u2009mg twice daily might not be suitable for patients of East Asian ethnicity, and has not been fully investigated. The aim of this study was to assess the effects of low loading doses (LD, 90u2009mg) and maintenance doses (MD, 90u2009mg daily) of ticagrelor in comparison to clopidogrel (600u2009mg LD, 75u2009mg daily MD) in healthy Korean volunteers. Twelve subjects were randomized into two groups, receiving either clopidogrel (600u2009mg LD, followed by 75u2009mg MD daily for 5 days) or ticagrelor (90u2009mg LD, followed by 90u2009mg MD daily for 5 days). Following a 2-week washout period, the treatments were switched between the groups. Three platelet function assessment methods which included light transmission aggregometry (LTA), the VerifyNow assay and multiple electrode platelet aggregometry (MEA) were then used to serially measure platelet function at various time points (baseline, 0.5, 2, 6, 24, 26, 120 and 122u2009h). The mean IPA to 10u2009µM ADP in the ticagrelor group was significantly higher than that for the clopidogrel group at the 0.5, 2, 6, 26 and 122u2009h time points (pu2009≤u20090.001). However, there was no significant difference between the two groups at the 24- and 120-hour time points (pu2009>u20090.05). The assay results produced by the other two platelet function tests (VerifyNow and MEA) were similar to those obtained by LTA. The low loading and maintenance doses of ticagrelor (90u2009mg LD, 90u2009mg daily MD) cause a more rapid and potent inhibition of platelet function when compared to clopidogrel (600u2009mg LD and 75u2009mg MD). Additionally, at the lowest value of platelet inhibition strength, oral once-daily administration of ticagrelor was no less efficacious than clopidogrel at the 24- and 120-hour time points. Due to a large diurnal variation occurring with a single daily dose, a lower dose twice-daily could be a better option for patients of East Asian ethnicity.

Comparison of Antiplatelet Effect and Tolerability of Clopidogrel Resinate With Clopidogrel Bisulfate in Patients With Coronary Heart Disease (CHD) or CHD-Equivalent Risks: A Phase IV, Prospective, Double-Dummy, Parallel-Group, 4-Week Noninferiority Trial

BACKGROUNDnClopidogrel resinate is a resinate complex of (+)-clopidogrel optical isomer, wherein the (+)-clopidogrel isomer binds to a water-soluble cation exchange resin via sulfonic acid groups. It was approved by the Korean Food and Drug Administration on the basis of a Phase I study that demonstrated the bioequivalence of clopidogrel resinate and clopidogrel bisulfate. However, there are no available data regarding efficacy and tolerability in patients with vascular disease.nnnOBJECTIVEnThe goal of this study was to investigate the antiplatelet efficacy and tolerability of clopidogrel resinate in patients with coronary heart disease (CHD) or CHD-equivalent risks.nnnMETHODSnThis study was a Phase IV, randomized, double-blind, double-dummy, parallel-group, noninferiority trial. We prospectively recruited patients in 10 centers between March 2008 and July 2008. Patients who had documented CHD or CHD-equivalent risks were randomly assigned to 1 of 3 groups: group A, aspirin (100 mg) + clopidogrel bisulfate placebo + clopidogrel resinate placebo; group B, aspirin (100 mg) + clopidogrel bisulfate placebo + clopidogrel resinate (75 mg); or group C, aspirin (100 mg) + clopidogrel bisulfate (75 mg) + clopidogrel resinate placebo. The primary outcome was the percent P2Y(12) inhibition after medication, assessed by using a point-of-care assay. If the 1-sided 90% upper confidence limit for the difference was less than the prespecified delta value (-5.7), clopidogrel resinate would be considered noninferior to clopidogrel bisulfate. The secondary outcome, the prevalence of adverse events (AEs) associated with study medications, was assessed at each visit by direct interview.nnnRESULTSnA total of 314 patients (mean [SD] age, 62.2 [9.0] years; male 63.7%; weight, 67.3 [13.6] kg [range, 45-102 kg]; all Asian) were enrolled, and 287 patients finished the study (group A, n = 97; group B, n = 90; and group C, n = 100). Eight patients took no study medications and were excluded from the tolerability and efficacy analyses. Nineteen patients discontinued the study because of protocol violation (n = 15), adverse events (n = 3), or voluntary withdrawal (n = 1) and were excluded from the efficacy analysis. There were no significant differences in baseline clinical characteristics among the groups except for the frequency of a history of CHD (group A, 85.4%; group B, 73.0%; and group C, 88.3%; P = 0.01). Patients treated with either type of clopidogrel showed significant inhibition (mean [SD]) of P2Y(12) (group A, -5.9% [15.1%]; group B, 23.4% [21.9%]; and group C, 19.5% [23.8%]; P < 0.001). Differences between clopidogrel resinate and clopidogrel bisulfate in the inhibition of P2Y(12) did not exceed the predetermined value for inferiority (P for noninferiority, 0.02; 90% CI, -0.9 to 10.3). In the tolerability analysis, there was no mortality during the study period and no significant differences between groups in the frequency of AEs and serious AEs (AEs: group A, 33.0%; group B, 26.0%; and group C, 23.3% [P = 0.27]; serious AEs: group A, 1.0%; group B, 3.0%; and group C, 1.0% [P = 0.42]). One patient in group B underwent coronary stent implantation for treatment of stable angina.nnnCONCLUSIONSnIn this small, selected Asian patient population, differences in the platelet inhibition efficacies of clopidogrel resinate and clopidogrel bisulfate did not exceed the predetermined limits for noninferiority. The differences in tolerability between the 2 drugs did not reach statistical significance.

Extraskeletal Mesenchymal Chondrosarcoma of the Heart Responded to Systemic Chemotherapy: A Case Report.

Mesenchymal chondrosarcoma is a rare cartilaginous neoplasm of an extraskeletal origin, and this predominately occurs in the head and neck, and also in the lower extremities. Fewer than twenty cases of cardiac mesenchymal chondrosarcoma have so far been reported on. For the most part, the results of treatment for patients with this condition have been dismal. In this study, we describe a case of cardiac mesenchymal chondrosarcoma that responded to chemotherapy following surgical biopsy. A 46-year-old man was referred for evaluation of his pleural effusions in both lungs. Chest computed tomography revealed an ovoid-shaped mass in the posterior wall of the patients left atrium. The echocardiogram revealed a large ovoid-shaped immobile mass (11x6 cm(2)) in the pericardiac space, which was attached to the posterior wall of the left atrium. Emergency pericardiostomy with closure thoracostomy was performed. Seven days later, a thoracotomy was performed for reduction and diagnosis of the cardiac mass. The pathological diagnosis was extraskeletal mesenchymal chondrosarcoma of the heart.. Postoperative chemotherapy was performed for the huge remaining mass with a combined regimen of etoposide, ifosfamide and cisplatin. After 6 cycles, the patient showed a partial response without symptoms. Although cardiac mesenchymal chondrosarcoma has been reported to be chemotherapy-resistant with a short survival duration, chemotherapy may prove to be an effective treatment modality.

Comparison of Prasugrel and Ticagrelor Antiplatelet Effects in Korean Patients Presenting With ST-Segment Elevation Myocardial Infarction

BACKGROUNDnThere is insufficient data on the efficacy of prasugrel and ticagrelor in Korean patients with ST-segment elevation myocardial infarction (STEMI).nnnMETHODS AND RESULTSnI n the current double-blind, prospective pilot study, 39 patients with STEMI undergoing primary percutaneous coronary intervention were randomized to receive prasugrel 60 mg loading dose (LD) followed by 10 mg daily maintenance dose (n=19), or ticagrelor 180 mg LD followed by 90 mg twice daily maintenance dose (n=20). We assessed platelet reactivity with the VerifyNow and Vasodilator-Stimulated Phosphoprotein (VASP) P2Y12 assays. Compared to baseline platelet reactivity, both prasugrel and ticagrelor groups achieved similar and significantly lower P2Y12 reaction units (PRU) (259 [IQR: 230 to 281] vs. 28 [12 to 55] for prasugrel; 261 [196 to 286] vs. 43 [11 to 61] for ticagrelor), and platelet reactivity indexes (PRI) (51.2% [39.3 to 61.3] vs. 8.1% [6.1 to 14.7] for prasugrel; 47.5% [38.4 to 50.4] vs. 11.2% [7.1 to 15.5] for ticagrelor, all P values <0.001) at 48 h post-LD. Most patients had low platelet reactivity with 95% PRU values <85 and 82% with PRI <16%.nnnCONCLUSIONSnBoth prasugrel and ticagrelor were effective for platelet inhibition in Korean STEMI patients with almost no patients exhibiting high platelet reactivity at 48 h after the LD. Our finding of a high number of patients with very low platelet reactivity deserves further studies to assess the safety of the drugs (Prasugrel and Ticagrelor in ST-segment Elevation Myocardial Infarction Study, NCT02075125).

Initial experience of retrograde wire approach in coronary chronic total occlusion intervention.

Background and Objectives Retrograde wire approach has been emerged as a useful tool to enhance success rate in coronary chronic total occlusion (CTO) intervention. Therefore, we tried to report the initial experience of retrograde approach and its clinical implication on CTO intervention. Subjects and Methods From February 2007 to July 2008, retrograde approaches were performed in 28 patients with 31 CTO lesions out of 61patients. A hydrophilic coated guidewire was inserted by using microcatheter or over-the-wire (OTW) balloon through the collateral channel (septal or epicardial artery) via several strategies. Results Mean age of patients was 63.4±11.6 years. Male and female were 20 and 8 patients, respectively. The target artery with CTO lesions included the right coronary artery (45.2%), the left anterior descending artery (51.6%), and the left circumflex artery (3.2%). The mean length of CTO lesion was 18.4±16.4 mm. Overall technical success rate was 64.5%. The success rate of primary attempt was 78.9%, while the success rate of immediate and secondary attempt was 41.7%. Collateral channel dissections were observed in 3 patients and no patients among these patients developed cardiac tamponade. One patient had a silent non-Q wave myocardial infarction (MI) after the procedure. One failed patient died suddenly 3 days after the procedure. After percutaneous coronary intervention (PCI) procedure, no case was performed target vessel revascularization (TVR), urgent coronary artery bypass graft (CABG), and urgent PCI. Conclusion Retrograde approach is an evolving technique to improve the success rate of CTO intervention. After the learning curve period, this technique could be the useful tool to enhance success rate in CTO intervention.