Bum-Kee Hong

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.

Lipoprotein(a) and LDL Particle Size Are Related to the Severity of Coronary Artery Disease

Background: The pathophysiological role and metabolic pathway of Lp(a) have not been clearly defined. An association between Lp(a) and oxidative low-density lipoprotein (LDL) were recently reported. And small dense LDL (sd-LDL) were associated with circulating malondialdehyde-modified LDL. We investigated the relationships between serum Lp(a) level and LDL particle size in coronary artery disease (CAD) patients. Further, we investigated the relationships of sd-LDL and Lp(a) with the extent and severity of CAD. Methods: A total of 490 patients (mean: 60.5 ± 11.5 years old) who underwent coronary angiography to evaluate chest pain were investigated. Patients were classified into two groups, a CAD group (n = 256), who had significant stenosis observed by coronary angiogram, and a control group (n = 234), who had normal, or minimal coronary arteries. CAD severity was measured by Gensini scores. The distribution of the LDL subfraction was analyzed using a Quantimetrix Lipoprint LDL System. Results: The serum Lp(a) concentration was correlated with the fraction of sd-LDL (r = 0.193, p < 0.001) and mean LDL size (r = 0.160, p = 0.003). The Lp(a) level and mean LDL particle size were significantly correlated with a high Gensini score. LDL particle size in the CAD group was smaller than in the control group (26.74 ± 0.64 vs. 26.43 ± 0.93 nm, p < 0.001). The Gensini score was significantly higher in small LDL with high Lp(a) level groups. Conclusion: The positive correlation of the level of Lp(a) and sd-LDL fraction were demonstrated. The mechanism of this association is not clearly defined; we can suggest that it may stem from the individual atherogenic condition that linked to increased oxidative stress. Both increased Lp(a) and sd-LDL fraction were correlated with the severity of CAD.

Impact of Metabolic Syndrome and Its Individual Components on the Presence and Severity of Angiographic Coronary Artery Disease

Purpose Metabolic syndrome (MS) has been reported as a potential risk factor of coronary artery disease (CAD). The aims of this study were to assess whether there was a relationship between MS score and CAD angiographic severity, and to assess the predictive value of individual components of MS for CAD. Materials and Methods We retrospectively enrolled 632 patients who underwent coronary angiography for suspected CAD (394 men, 61.0 ± 10.6 years of age). MS was defined by the National Cholesterol Education Program criteria with the waist criterion modified into a body mass index (BMI) of more than 25 kg/m2. The MS score defined as the number of MS components. CAD was defined as > 50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD angiographic severity was evaluated with a Gensini scoring system. Results Of the patients, 497 (78.6%) had CAD and 283 (44.8%) were diagnosed with MS. The MS score was significantly related to the Gensini score. High fasting blood glucose (FBG) was the only predictive factor for CAD. A cluster including high FBG, high blood pressure (BP), and low high-density lipoprotein cholesterol (HDL-C) showed the highest CAD risk. Conclusion The MS score correlates with the angiographic severity of CAD. The predictive ability of MS for CAD was carried almost completely by high FBG, and individual traits with high BP and low HDL-C may act synergistically as risk factors for CAD.

Local increase in microparticles from the aspirate of culprit coronary arteries in patients with ST-segment elevation myocardial infarction.

OBJECTIVE It has been reported that the levels of procoagulant microparticles (MPs) are increased in patients with acute coronary syndromes and this may contribute to the formation of intracoronary thrombi. In the current study, we investigated the presence of locally elevated MPs within the culprit coronary arteries of patients with ST-segment elevation myocardial infarction (STEMI). METHODS The study population consisted of 45 patients with STEMI who underwent primary percutaneous coronary intervention (PCI), and 16 control patients. Before and after PCI, blood samples were collected from the femoral artery and from the culprit coronary arteries. In controls, only peripheral blood was obtained. MPs were measured by a solid-phase capture assay using a commercial kit. The cell origins of MPs were determined by antigenic capture with specific antibodies. RESULTS Baseline levels of MPs in patients with STEMI were higher than in controls. Before PCI, the levels of MPs were significantly higher in culprit coronary arteries than in peripheral arteries in STEMI patients (20.7 ± 15.5 vs. 14.6 ± 15.4 nM phosphatidylserine (PS) equivalent, p = 0.027). MPs from the culprit coronary artery were significantly reduced after PCI (20.7 ± 15.5 vs. 14.3 ± 14.9 nM PS equivalent, p = 0.010). Similarly, the locally increased levels of endothelial- and platelet-derived MPs within the culprit coronary arteries were significantly decreased after PCI. CONCLUSION Locally increased levels of MPs in culprit coronary arteries and their significant reduction after successful PCI suggest a potential role in coronary atherothrombosis in the early period of STEMI.

Incidence and natural history of coronary artery aneurysm developing after drug-eluting stent implantation.

AIMS There is a growing concern about the occurrence of coronary artery aneurysms (CAAs) after drug-eluting stent (DES) implantation and their long-term course. We assessed the occurrence and the factors affecting the long-term outcome of DES-associated CAA. METHODS AND RESULTS We analyzed 3,612 consecutive patients (4,419 lesions) who underwent follow-up angiography after DES implantation. All 34 CAAs (0.76% per lesion) in 29 patients (0.8% per patient) were detected at follow-up, and the mean elapsed time from DES implantation to CAA diagnosis was 414 ± 213 days. Angiographically, CAAs developed almost exclusively in complex (type B2/C) de novo lesions (30 [88.2%] of 34 lesions), and lesion length was significantly greater in patients with CAA than without CAA (26.9 ± 9.03 vs 23.1 ± 7.14 mm; P = .004). Myocardial infarction with stent thrombosis occurred in 5 patients with CAA (17.2%), 4 of whom were on aspirin only without clopidogrel. CONCLUSION Although CAAs rarely develop after DES implantation and show mostly favorable clinical courses, long-term maintenance of clopidogrel therapy might be required to minimize occurrence of adverse clinical events resulting from stent thrombosis.

Pathobiological role of advanced glycation endproducts via mitogen-activated protein kinase dependent pathway in the diabetic vasculopathy

Advanced glycation endproducts (AGEs) have been reported to play a role in neointimal formation and increase the rate of in-stent restenosis (ISR) in the diabetic coronary artery disease patients treated with stents, but the potential pathogenic mechanisms of AGEs in vascular smooth muscle cell proliferation remain unclear. We sought to determine the AGEs related pathobiological mechanism of diabetic vasculopathy. Rat aortic smooth muscle cell (RAoSMC) culture was done with different concentrations of AGEs and proliferation was assessed. Immunohistochemistry for receptor of AGEs (RAGE) was performed with human carotid atheroma. Western blotting was performed to assess the activation of MAP kinase system in the cultured RAoSMC. AGEs increased RAoSMC proliferation and were associated with increased phosphorylation of ERK and p38 kinase by time and dose dependent manner. The MAP kinase activity was decreased by RNA interference for RAGE. AGEs stimulation increased reactive oxygen species (ROS) generation in cultured RAoSMC. From this study it is concluded that AGEs played a key role in RAoSMC proliferation via MAP kinase dependent pathways. Activation of vascular smooth muscle cell (VSMC) proliferation by MAP kinase system and increased formation of ROS may be the possible mechanisms of AGEs induced diabetic vasculopathy.

Left Atrial Strain Assessed by Speckle Tracking Imaging Is Related to New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting

BACKGROUND Left atrial (LA) dysfunction was recently proposed as an important factor in the development of postoperative atrial fibrillation (POAF). LA strain analysis by 2-dimensional (2D) speckle tracking imaging is emerging as a new tool to evaluate LA function. We aimed to evaluate the correlation of LA dysfunction assessed by 2D speckle tracking imaging with the occurrence of POAF after coronary artery bypass grafting (CABG). METHODS In this study, 53 patients (mean age 66 ± 9 years) undergoing elective isolated CABG were enrolled. Conventional transthoracic echocardiography and 2D speckle tracking strain analysis were performed before surgery. POAF was detected with continuous electrocardiography monitoring throughout hospitalization (mean duration 17 ± 10 days). RESULTS POAF occurred in 13 of 53 patients (24%). Patients with POAF were significantly older than patients with normal sinus rhythm after surgery (71 ± 5 vs 64 ± 10 years, P = 0.026). Compared with patients with normal sinus rhythm, patients with POAF had a significantly larger LA volume index (32.6 ± 5.1 vs 27.3 ± 7.2 mL/m(2), P = 0.018), lower value of LA global strain (25.4 ± 10.4 vs 36.8 ± 7.6%, P = 0.001), and strain rate (1.2 ± 0.6 vs 1.6 ± 0.8 seconds, P = 0.024). By multivariate logistic regression analysis, only LA global strain (odds ratio, 1.12; 95% confidence interval, 1.00-1.24; P = 0.040) was an independent predictor of POAF after CABG. CONCLUSIONS Preoperative LA global strain measured by 2D speckle tracking strain analysis is associated with the development of POAF after CABG.

Long-Term Clinical Outcomes and Stent Thrombosis of Sirolimus-Eluting Versus Bare Metal Stents in Patients with End-Stage Renal Disease: Results of Korean Multicenter Angioplasty Team (KOMATE) Registry

BACKGROUND There are still controversies about long-term clinical outcomes of sirolimus-eluting stents (SES) versus bare metal stents (BMS) implantation in patients with end-stage renal diseases (ESRD). OBJECTIVE To compare long-term outcomes in patients with (ESRD) following SES versus BMS implantation. METHODS Between March 2003 and July 2005, a total of 54 patients (80 lesions) with ESRD undergoing SES implantation [SES-ESRD] were enrolled and compared with 51 patients (54 lesions) with ESRD receiving BMS during the same periods [BMS-ESRD] in the Korean Multicenter Angioplasty Team Registry. The primary outcome was the composite of death, myocardial infarction (MI), or any stent thrombosis (ST) according to the Academic Research Consortium definition during a 3-year follow-up. RESULTS The cumulative 3-year rate of composite of death, MI, or ST of the SES-ESRD group (24%) was nearly similar with that of the BMS-ESRD group (24%, P = 1.000). The 3-year rates of death (26% vs. 24%, P = 0.824) or MACE (37% vs. 43%, P = 0.331) in the SES-ESRD did not differ significantly from those in the BMS-ESRD. However, the SES-ESRD showed a sustained lower 3-year TVR rate (9%), compared with BMS-ESRD (24%, P = 0.042). The rate of any ST in SES-ESRD was not significantly higher than that in the BMS-ESRD (17% vs. 14%, P = 0.788). There was no significant difference in the rate of late or very late ST between SES-ESRD (15%) versus BMS-ESRD group (10%, P = 0.557). CONCLUSIONS SES did not increase the risks for death, MI, or any ST in patients with ESRD during the long-term follow-up, compared with BMS.

SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World (SUGAR): A Multi-Center, Retrospective, Observational Study

Background Clinical practice guidelines have been slowly and inconsistently applied in clinical practice, and certain evidence-based, guideline-driven therapies for heart failure (HF) have been significantly underused. The purpose of this study was to survey guideline compliance and its effect on clinical outcomes in the treatment of systolic HF in Korea. Method and Results The SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World (SUGAR) trial was a multi-center, retrospective, observational study on subjects with systolic HF (ejection fraction <45%) admitted to 23 university hospitals. The guideline adherence indicator (GAI) was defined as a performance measure on the basis of 3 pharmacological classes: angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), beta-blocker (BB), and aldosterone antagonist (AA). Based on the overall adherence percentage, subjects were divided into 2 groups: those with good guideline adherence (GAI ≥50%) and poor guideline adherence (GAI <50%). We included 1319 regional participants as representatives of the standard population from the Korean national census in 2008. Adherence to drugs at discharge was as follows: ACEI or ARB, 89.7%; BB, 69.2%; and AA, 65.9%. Overall, 82.7% of the patients had good guideline adherence. Overall mortality and re-hospitalization rates at 1 year were 6.2% and 37.4%, respectively. Survival analysis by log-rank test showed a significant difference in event-free survival rate of mortality (94.7% vs. 89.8%, p = 0.003) and re-hospitalization (62.3% vs. 56.4%, p = 0.041) between the good and poor guideline-adherence groups. Conclusions Among patients with systolic HF in Korea, adherence to pharmacologic treatment guidelines as determined by performance measures, including prescription of ACEI/ARB and BB at discharge, was associated with improved clinical outcomes.

Left atrial function assessed by Doppler echocardiography rather than left atrial volume predicts recurrence in patients with paroxysmal atrial fibrillation.

Paroxysmal atrial fibrillation (PaAF) may present as a single self‐terminating episode of atrial fibrillation (AF) or a more persistent form after sinus conversion. We investigated predictors of recurrence in patients with PaAF.