Donghoon Choi

A New Strategy for Discontinuation of Dual Antiplatelet Therapy The RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation)

OBJECTIVES The goal of this study was to evaluate shorter duration (3 months) dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation. BACKGROUND There have been few published reports of prospective randomized clinical studies comparing the safety and efficacy of shorter duration DAPT after DES implantation. METHODS We randomly assigned 2,117 patients with coronary artery stenosis into 2 groups according to DAPT duration and stent type: 3-month DAPT following Endeavor zotarolimus-eluting stent (E-ZES) implantation (E-ZES+3-month DAPT, n=1,059) versus 12-month DAPT following the other DES implantation (standard therapy, n=1,058). We hypothesized that the E-ZES+3-month DAPT would be noninferior to the standard therapy for the primary composite endpoint (cardiovascular death, myocardial infarction, stent thrombosis, target\vessel revascularization, or bleeding) at 1 year. RESULTS The primary endpoint occurred in 40 (4.7%) patients assigned to E-ZES+3-month DAPT compared with 41 (4.7%) patients assigned to the standard therapy (difference: 0.0%; 95% confidence interval [CI]: -2.5 to 2.5; p=0.84; p<0.001 for noninferiority). The composite rates of any death, myocardial infarction, or stent thrombosis were 0.8% and 1.3%, respectively (difference: -0.5%; 95% CI: -1.5 to 0.5; p=0.48). The rates of stent thrombosis were 0.2% and 0.3%, respectively (difference: -0.1%; 95% CI: -0.5 to 0.3; p=0.65) without its further occurrence after cessation of clopidogrel in the E-ZES+3-month DAPT group. The rates of target vessel revascularization were 3.9% and 3.7%, respectively (difference: 0.2%; 95% CI: -2.3 to 2.6; p=0.70). CONCLUSIONS E-ZES+3-month DAPT was noninferior to the standard therapy with respect to the occurrence of the primary endpoint. (REal Safety and Efficacy of a 3-month dual antiplatelet Therapy following E-ZES implantation [RESET]; NCT01145079).

Anatomic and Functional Evaluation of Bifurcation Lesions Undergoing Percutaneous Coronary Intervention

Background—We sought to investigate the mechanism of geometric changes after main branch (MB) stent implantation and to identify the predictors of functionally significant “jailed” side branch (SB) lesions. Methods and Results—Seventy-seven patients with bifurcation lesions were prospectively enrolled from 8 centers. MB intravascular ultrasound was performed before and after MB stent implantation, and fractional flow reserve was measured in the jailed SB. The vessel volume index of both the proximal and distal MB was increased after stent implantation. The plaque volume index decreased in the proximal MB (9.1±3.0 to 8.4±2.4 mm3/mm, P=0.001), implicating plaque shift, but not in the distal MB (5.4±1.8 to 5.3±1.7 mm3/mm, P=0.227), implicating carina shifting to account for the change in vessel size (N=56). The mean SB fractional flow reserve was 0.71±0.20 (N=68) and 43% of the lesions were functionally significant. Binary logistic-regression analysis revealed that preintervention % diameter stenosis of the SB (odds ratio=1.05; 95% CI, 1.01 to 1.09) and the MB minimum lumen diameter located distal to the SB ostium (odds ratio=3.86; 95% CI, 1.03 to 14.43) were independent predictors of functionally significant SB jailing. In patients with ≥75% stenosis and Thrombolysis In Myocardial Infarction grade 3 flow in the SB, no difference in poststent angiographic and intravascular ultrasound parameters was found between SB lesions with and without functional significance. Conclusions—Both plaque shift from the MB and carina shift contribute to the creation/aggravation of an SB ostial lesion after MB stent implantation. Anatomic evaluation does not reliably predict the functional significance of a jailed SB stenosis. Clinical Trial Registration:http://www.clinicaltrials.gov. Unique Identifier: NCT00553670.

Evaluation in 3 Months Duration of Neointimal Coverage After Zotarolimus-Eluting Stent Implantation by Optical Coherence Tomography: The ENDEAVOR OCT Trial

OBJECTIVES We performed this study to investigate the vascular response in early period after zotarolimus-eluting stent (ZES) (Endeavor Sprint, Medtronic CardioVascular, Minneapolis, Minnesota) implantation. BACKGROUND The ZES has different characteristics, with biocompatible polymer and rapid drug-elution, compared with the first-generation drug-eluting stents (DES). METHODS The ENDEAVOR OCT (Evaluation in 3 Months Duration of Neointimal Coverage after Zotarolimus-Eluting Stent Implantation by Optical Coherence Tomography) trial is a prospective, single-center study evaluating vascular healing patterns with optical coherence tomography (OCT) at 3 months after stent implantation. A total of 31 ZES in 30 patients underwent serial OCT at immediate post-intervention and 3 months. Neointimal growth and malapposition were analyzed at each stent strut of cross-sectional OCT images with 0.5-mm intervals. RESULTS The incidence of malapposition at post-intervention and 3 months was 6.0% and 0.2%, respectively. However, late acquired malapposition was not detected at 3 months. Of 31 stents, 27 stents (87.1%) were covered completely with neointima, but the remaining 4 stents had 2 (0.8%), 4 (0.9%), 4 (1.2%), and 6 (1.4%) uncovered struts. Overall mean percentage of covered stent struts was 99.9 +/- 0.4%. This finding was consistent among groups with acute coronary syndrome and stable angina pectoris (99.9 +/- 0.3% vs. 99.9 +/- 0.4%, p = 0.92). Intracoronary thrombus was documented in 1 stent (3.2%) among 31 stents. CONCLUSIONS Most of the stent struts were covered with neointima, and late acquired malapposition was not found at 3 months after ZES implantation. Therefore, the current study demonstrated that ZES might have a favorable in vivo vascular response at 3 months after stent implantation. (Evaluation of Zotarolimus Eluting Stent at 3 Months Using Optical Coherence Tomography [ENDEAVOR OCT]; NCT00815139).

Effect of Intravascular Ultrasound–Guided vs Angiography-Guided Everolimus-Eluting Stent Implantation: The IVUS-XPL Randomized Clinical Trial

IMPORTANCE Use of intravascular ultrasound (IVUS) promotes better clinical outcomes for coronary intervention in complex coronary lesions. However, randomized data demonstrating the clinical usefulness of IVUS are limited for lesions treated with drug-eluting stents. OBJECTIVE To determine whether the long-term clinical outcomes with IVUS-guided drug-eluting stent implantation are superior to those with angiography-guided implantation in patients with long coronary lesions. DESIGN, SETTING, AND PARTICIPANTS The Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions (IVUS-XPL) randomized, multicenter trial was conducted in 1400 patients with long coronary lesions (implanted stent ≥28 mm in length) between October 2010 and July 2014 at 20 centers in Korea. INTERVENTIONS Patients were randomly assigned to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. MAIN OUTCOMES AND MEASURES Primary outcome measure was the composite of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction, or ischemia-driven target lesion revascularization at 1 year, analyzed by intention-to-treat. RESULTS One-year follow-up was complete in 1323 patients (94.5%). Major adverse cardiac events at 1 year occurred in 19 patients (2.9%) undergoing IVUS-guided and in 39 patients (5.8%) undergoing angiography-guided stent implantation (absolute difference, -2.97% [95% CI, -5.14% to -0.79%]) (hazard ratio [HR], 0.48 [95% CI, 0.28 to 0.83], P = .007). The difference was driven by a lower risk of ischemia-driven target lesion revascularization in patients undergoing IVUS-guided (17 [2.5%]) compared with angiography-guided (33 [5.0%]) stent implantation (HR, 0.51 [95% CI, 0.28 to 0.91], P = .02). Cardiac death and target lesion-related myocardial infarction were not significantly different between the 2 groups. For cardiac death, there were 3 patients (0.4%) in the IVUS-guided group and 5 patients (0.7%) in the angiography-guided group (HR, 0.60 [95% CI, 0.14 to 2.52], P = .48). Target lesion-related myocardial infarction occurred in 1 patient (0.1%) in the angiography-guided stent implantation group (P = .32). CONCLUSIONS AND RELEVANCE Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at 1 year. These differences were primarily due to lower risk of target lesion revascularization. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01308281.

Efficacy of High-Dose Atorvastatin Loading Before Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: The STATIN STEMI Trial

OBJECTIVES This study sought to determine the efficacy of high-dose atorvastatin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND Previous randomized trials have demonstrated that statin pre-treatment reduced major adverse cardiac events (MACEs) in patients with stable angina pectoris and acute coronary syndrome. However, no randomized studies have been carried out with STEMI patients in a primary PCI setting. METHODS A total 171 patients with STEMI were randomized to 80-mg atorvastatin (n = 86) or 10-mg atorvastatin (n = 85) arms for pre-treatment before PCI. All patients were prescribed clopidogrel (600 mg) before PCI. After PCI, both groups were treated with atorvastatin (10 mg). The primary end point was 30-day incidence of MACE including death, nonfatal MI, and target vessel revascularization. Secondary end points included corrected thrombolysis in myocardial infarction frame count, myocardial blush grade, and ST-segment resolution at 90 min after PCI. RESULTS MACE occurred in 5 (5.8%) and 9 (10.6%) patients in the 80-mg and 10-mg atorvastatin pre-treatment arms, respectively (p = 0.26). Corrected thrombolysis in myocardial infarction frame count was lower in the 80-mg atorvastatin arm (26.9 +/- 12.3 vs. 34.1 +/- 19.0, p = 0.01). Myocardial blush grade and ST-segment resolution were also higher in the 80-mg atorvastatin arm (2.2 +/- 0.8 vs. 1.9 +/- 0.8, p = 0.02 and 61.8 +/- 26.2 vs. 50.6 +/- 25.8%, p = 0.01). CONCLUSIONS High-dose atorvastatin pre-treatment before PCI did not show a significant reduction of MACEs compared with low-dose atorvastatin but did show improved immediate coronary flow after primary PCI. High-dose atorvastatin may produce an optimal result for STEMI patients undergoing PCI by improving microvascular myocardial perfusion. (Efficacy of High-Dose AtorvaSTATIN Loading Before Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction [STATIN STEMI]; NCT00808717).

Clinical Benefit of Statin Pretreatment in Patients Undergoing Percutaneous Coronary Intervention A Collaborative Patient-Level Meta-Analysis of 13 Randomized Studies

Background— Previous studies suggested that statin pretreatment reduces cardiac events in patients undergoing percutaneous coronary intervention. However, most data were observational, and single randomized trials included limited numbers of patients. Methods and Results— We performed a collaborative meta-analysis using individual patient data from 13 randomized studies in which 3341 patients received either high-dose statin (n=1692) or no statin/low-dose statin (n=1649) before percutaneous coronary intervention, with all patients receiving statin therapy after intervention. Occurrence of periprocedural myocardial infarction, defined as postintervention creatine kinase–MB increase ≥3 times the upper limit of normal, and 30-day major adverse cardiac events (death, myocardial infarction, target-vessel revascularization) was evaluated. Incidence of periprocedural myocardial infarction was 7.0% in the high-dose statin versus 11.9% in the control group, which corresponds to a 44% risk reduction in the active-treatment arm (odds ratio by fixed-effects model 0.56, 95% confidence interval, 0.44 to 0.71, P <0.00001). The rate of major adverse cardiac events at 30 days was significantly lower in the high-dose statin group (7.4% versus 12.6%, a 44% risk reduction; P <0.00001), and 1-month major adverse cardiac events, excluding periprocedural events, were also reduced (0.6% versus 1.4%; P =0.05). The benefit of high-dose statins was realized irrespective of clinical presentation ( P for interaction=0.43) and was maintained across various subgroups but appeared greater in the subgroup with elevated baseline C-reactive protein levels (n=734; 68% risk reduction for periprocedural myocardial infarction versus 31% in those 1861 patients with normal CRP; P for quantitative interaction=0.025). Conclusions— High-dose statin pretreatment leads to a significant reduction in periprocedural myocardial infarction and 30-day adverse events in patients undergoing percutaneous coronary intervention. This strategy should be considered in all patients with planned percutaneous coronary intervention. # Clinical Perspective {#article-title-50}Background— Previous studies suggested that statin pretreatment reduces cardiac events in patients undergoing percutaneous coronary intervention. However, most data were observational, and single randomized trials included limited numbers of patients. Methods and Results— We performed a collaborative meta-analysis using individual patient data from 13 randomized studies in which 3341 patients received either high-dose statin (n=1692) or no statin/low-dose statin (n=1649) before percutaneous coronary intervention, with all patients receiving statin therapy after intervention. Occurrence of periprocedural myocardial infarction, defined as postintervention creatine kinase–MB increase ≥3 times the upper limit of normal, and 30-day major adverse cardiac events (death, myocardial infarction, target-vessel revascularization) was evaluated. Incidence of periprocedural myocardial infarction was 7.0% in the high-dose statin versus 11.9% in the control group, which corresponds to a 44% risk reduction in the active-treatment arm (odds ratio by fixed-effects model 0.56, 95% confidence interval, 0.44 to 0.71, P<0.00001). The rate of major adverse cardiac events at 30 days was significantly lower in the high-dose statin group (7.4% versus 12.6%, a 44% risk reduction; P<0.00001), and 1-month major adverse cardiac events, excluding periprocedural events, were also reduced (0.6% versus 1.4%; P=0.05). The benefit of high-dose statins was realized irrespective of clinical presentation (P for interaction=0.43) and was maintained across various subgroups but appeared greater in the subgroup with elevated baseline C-reactive protein levels (n=734; 68% risk reduction for periprocedural myocardial infarction versus 31% in those 1861 patients with normal CRP; P for quantitative interaction=0.025). Conclusions— High-dose statin pretreatment leads to a significant reduction in periprocedural myocardial infarction and 30-day adverse events in patients undergoing percutaneous coronary intervention. This strategy should be considered in all patients with planned percutaneous coronary intervention.

Sex Differences in Central Hemodynamics and Their Relationship to Left Ventricular Diastolic Function

OBJECTIVES This study aimed to investigate sex differences in the association between arterial stiffness and left ventricular (LV) diastolic dysfunction. BACKGROUND Heart failure with preserved ejection fraction is more common in women. Arterial stiffness has been suggested as a significant contributor to the development of heart failure. We hypothesized that the association between arterial stiffness and LV diastolic function would be stronger in women than in men. METHODS Two-dimensional, Doppler echocardiography and radial artery tonometry were performed simultaneously in 158 age-matched subjects (79 males, 79 females; mean age: 58 ± 10 years) without any structural heart disease or LV systolic dysfunction. RESULTS The peripheral blood pressure and pulse pressure (PP) were similar between sexes. However, central PP and augmentation index were significantly higher and PP amplification was significantly lower in women (1.31 vs. 1.19, p < 0.001). The associations of PP amplification with early diastolic mitral annular (Em) velocity and transmitral to mitral annular early diastolic velocity ratio (E/Em) were significant in women (r = 0.38, p = 0.001; r = -0.36, p = 0.001), whereas no significant association was found in men (r = 0.09, p = 0.428, r = -0.14, p = 0.215). Multiple regression analysis revealed that PP amplification had an independent correlation with Em velocity only in women. CONCLUSIONS Despite similar peripheral PP, the central hemodynamics reflecting arterial stiffness were different between men and women. LV diastolic function correlates significantly with the parameters representing arterial stiffness only in women. We suggest that the effects of earlier wave reflection on central pressure may contribute to greater susceptibility to heart failure with preserved LV ejection fraction in women.

Impact of contrast-induced acute kidney injury with transient or persistent renal dysfunction on long-term outcomes of patients with acute myocardial infarction undergoing percutaneous coronary intervention

Objective To investigate the long-term prognostic implications of contrast-induced acute kidney injury (CI-AKI) with transient or persistent renal dysfunction in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI). Design A retrospective observational registry study. Setting Clinical follow-up after PCI. Patients and methods A total of 1041 PCI-treated AMI patients from the Infarction Prognosis Study registry. CI-AKI was defined as an increase in serum creatinine (>25% or >0.5 mg/dl (>44.2 μmol/l)) within 2 days after PCI. Main outcome measures Two-year cumulative event rate of all-cause death or renal failure requiring dialysis. Results CI-AKI was observed in 148 patients (14.2%). Patients with CI-AKI had a higher rate of death or dialysis (25.4% vs 6.3%, p<0.001) at 2 years compared with patients without CI-AKI. CI-AKI was an important independent predictor of death or dialysis (HR 2.76, 95% CI 1.61 to 4.73, p<0.001) Persistent renal dysfunction after CI-AKI was documented in 68 patients (45.9%). Patients with transient renal dysfunction showed a lower 2-year event rate of death or dialysis compared with those with persistent renal dysfunction (17.9% vs 34.1%, p=0.013); however, they showed a higher event rate compared with those without CI-AKI (17.9% vs 6.3%, p<0.001). Conclusion Transient and persistent renal dysfunction after CI-AKI was associated with increased short and long-term mortality and morbidity in AMI patients treated by PCI. Better preventive strategies are needed to improve clinical outcomes in AMI patients at high risk of developing CI-AKI.

Incidences, Predictors, and Clinical Outcomes of Acute and Late Stent Malapposition Detected by Optical Coherence Tomography After Drug-Eluting Stent Implantation

Background—We investigated the incidences, predictors, and clinical outcomes of acute and late stent malapposition detected by optical coherence tomography (OCT) after drug-eluting stent implantation. Methods and Results—We analyzed the OCT images from 351 patients with 356 lesions who received poststent and follow-up OCT examinations. Acute stent malapposition was observed in 62% of lesions. Approximately half of the acute stent malappositions were located within the edges of the stents. Severe diameter stenosis, calcified lesions, and long stents were independent predictors of acute stent malapposition. Follow-up OCT examinations were performed 175±60 days after drug-eluting stent implantation. Thirty-one percent of lesions with acute stent malapposition remained malapposed (late-persistent stent malapposition) and were typically (72%) located within the edges of the stent. The location within the stent edges and the volume of acute stent malapposition were independent predictors of late-persistent stent malapposition. Acute stent malapposition with a volume >2.56 mm3 differentiated late-persistent stent malapposition from resolved acute stent malapposition. Late-acquired stent malapposition was detected in 15% of all lesions and was usually (61%) located within the stent body. Late-acquired stent malapposition was more frequently associated with plaque/thrombus prolapse on poststent OCT images (70% versus 42%; P<0.001). Clinical events, including cardiovascular death, nonfatal myocardial infarction, and stent thrombosis, did not occur in patients with late stent malapposition during the follow-up period of 28.6±10.3 months after drug-eluting stent implantation. Conclusions—Acute, late-persistent, and late-acquired stent malapposition had relatively high incidences but different predictors. The clinical outcome of stent malapposition was favorable.

Impact of intravascular ultrasound guidance on long-term clinical outcomes in patients treated with drug-eluting stent for bifurcation lesions: Data from a Korean multicenter bifurcation registry

BACKGROUND although intravascular ultrasound (IVUS) has been widely used for complex lesions during coronary intervention, IVUS for stenting at bifurcation lesions has not been sufficiently assessed. The aim of this study was to investigate the impact of IVUS guidance on long-term clinical outcomes during drug-eluting stent (DES) implantation for bifurcation lesions. METHODS the Korean multicenter bifurcation registry listed 1,668 patients with non-left main de novo bifurcation lesions who underwent DES implantation between January 2004 and June 2006. Using propensity score matching with clinical and angiographic characteristics, 487 patients with IVUS guidance and 487 patients with angiography guidance were selected. The long-term clinical outcomes were compared between the 2 groups. RESULTS baseline clinical and angiographic characteristics were well matched and showed no significant differences between the 2 groups. Two-stent technique and final kissing ballooning angioplasty were more frequently performed in the IVUS-guided group. Maximal stent diameters at both the main vessel and the side branch were larger in the IVUS-guided group. Periprocedural creatine kinase-MB elevation (>3 times of upper normal limits) was frequently observed in the angiography-guided group. The incidence of death or myocardial infarction was significantly lower in the IVUS-guided group compared to the angiography-guided group (3.8% vs 7.8%, log rank test P = .03, hazard ratio 0.44, 95% CI 0.12-0.96, Cox model P = .04). CONCLUSIONS intravascular ultrasound guidance during DES implantation at bifurcation lesions may be helpful to improve long-term clinical outcomes by reducing the occurrence of death or myocardial infarction.