Publications by authors named "Kiyuk Chang"

148 Publications

AIMP3 induces laminopathy and senescence of vascular smooth muscle cells by reducing lamin A expression and leads to vascular aging in vivo.

Exp Gerontol 2021 Jul 15:111483. Epub 2021 Jul 15.

Cardiovascular Research Institute for Intractable Disease, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

Aminoacyl-tRNA synthetase-interacting multifunctional protein 3 (AIMP3), a tumor suppressor, mediates a progeroid phenotype in mice by downregulating lamin A. We investigated whether AIMP3 induces laminopathy and senescence of human aortic smooth muscle cells (HASMCs) and is associated with vascular aging in mice and humans in line with decreased lamin A expression. Cellular senescence was evaluated after transfecting HASMCs with AIMP3. Molecular analyses of genes encoding AIMP3, lamin A, chemokine (C-C motif) ligand 2 (CCL2), and C-C chemokine receptor type 2 (CCR2) and histological comparisons of aortas were performed with mice at various ages (7 weeks, 5 months, 12 months, 24 months, and 32 months), AIMP3-transgenic mice, and human femoral arteries of cadavers. AIMP3-transfected HASMCs exhibited increased AIMP3 and senescence marker p16 protein expression and decreased lamin A protein expression in accordance with their disrupted nuclear morphology in histological analyses. AIMP3-transgenic mice displayed increased AIMP3 protein expression and decreased lamin A protein expression in aortas together with typical aging pathologies. Similar changes were observed in wild-type aging (24-month-old) mice but not in wild-type young (7-week-old) mice. In humans, AIMP3 and lamin A protein expression was higher and lower, respectively, in femoral arteries of elderly individuals than in those of their younger counterparts. This study found that AIMP3 overexpression in vitro decreased lamin A expression and induced nuclear laminopathy and cellular senescence. Similar findings were made in the vasculature of aging mice and elderly humans.
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http://dx.doi.org/10.1016/j.exger.2021.111483DOI Listing
July 2021

Nanoparticle-Mediated Blocking of Excessive Inflammation for Prevention of Heart Failure Following Myocardial Infarction.

Small 2021 Jul 3:e2101207. Epub 2021 Jul 3.

School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

Severe cardiac damage following myocardial infarction (MI) causes excessive inflammation, which sustains tissue damage and often induces adverse cardiac remodeling toward cardiac function impairment and heart failure. Timely resolution of post-MI inflammation may prevent cardiac remodeling and development of heart failure. Cell therapy approaches for MI are time-consuming and costly, and have shown marginal efficacy in clinical trials. Here, nanoparticles targeting the immune system to attenuate excessive inflammation in infarcted myocardium are presented. Liposomal nanoparticles loaded with MI antigens and rapamycin (L-Ag/R) enable effective induction of tolerogenic dendritic cells presenting the antigens and subsequent induction of antigen-specific regulatory T cells (Tregs). Impressively, intradermal injection of L-Ag/R into acute MI mice attenuates inflammation in the myocardium by inducing Tregs and an inflammatory-to-reparative macrophage polarization, inhibits adverse cardiac remodeling, and improves cardiac function. Nanoparticle-mediated blocking of excessive inflammation in infarcted myocardium may be an effective intervention to prevent the development of post-MI heart failure.
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http://dx.doi.org/10.1002/smll.202101207DOI Listing
July 2021

Activation of Aryl Hydrocarbon Receptor by ITE Improves Cardiac Function in Mice After Myocardial Infarction.

J Am Heart Assoc 2021 Jul 23;10(13):e020502. Epub 2021 Jun 23.

Division of Cardiology Seoul St. Mary's Hospital College of Medicine The Catholic University of Korea Seoul Republic of Korea.

Background The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2-[1'H-indole-3'-carbonyl]-thiazole-4-carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T-cell differentiation, modulate macrophage activity, and facilitate infarct healing. Methods and Results Acute MI was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200 µg/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE-treated mice exhibited significantly improved systolic function (<0.001) and reduced infarct size compared with control mice (<0.001). In addition, we found that ITE increased regulatory T cells in the mediastinal lymph node, spleen, and infarcted myocardium, and shifted the M1/M2 macrophage balance toward the M2 phenotype in vivo, which plays vital roles in the induction and resolution of inflammation after acute MI. In vitro, ITE expanded the Foxp3 (forkhead box protein P3-positive) regulatory T cells and tolerogenic dendritic cell populations. Conclusions Activation of AhR by a nontoxic endogenous ligand, ITE, improves cardiac function after MI. Post-MI mice treated with ITE have a significantly lower risk of developing advanced left ventricular systolic dysfunction than nontreated mice. Thus, the results imply that ITE has a potential as a stimulator of cardiac repair after MI to prevent heart failure.
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http://dx.doi.org/10.1161/JAHA.120.020502DOI Listing
July 2021

Interpretation of coronary steal syndrome and haemodynamic changes after surgical closure of coronary fistula using Doppler wire and computational fluid dynamics analysis: a case report.

Eur Heart J Case Rep 2021 Apr 24;5(4):ytab069. Epub 2021 Apr 24.

School of Mechanical Engineering, University of Ulsan, 93, Daehak-ro, Nam-gu, Ulsan 44610, Republic of Korea.

Background: Coronary arteriovenous fistulas (CAFs) are rare but can cause myocardial ischaemia and other complications. However, the haemodynamic and physiologic characteristics of significant CAFs requiring treatment are poorly described. We report a case of CAF causing coronary steal syndrome in which haemodynamic changes were assessed before and after surgical closure using a Doppler wire and computational fluid dynamics (CFD) technique.

Case Summary: A 51-year-old woman presented with exertional chest pain for 3 years. Progressive dyspnoea occurred with exertion. Treadmill and cardiopulmonary exercise tests showed suspicious myocardial ischaemia. Coronary angiography and contrast-enhanced coronary computed tomography angiography (CCTA) revealed a coronary fistula arising from the distal left main coronary artery that drained into the pulmonary artery trunk. We observed a persistent coronary steal phenomenon at baseline and during hyperaemia and a systolic dominant flow rate pattern inside the CAF by Doppler wire-based flow rate measurement. According to CFD analysis based on CCTA, low wall shear stress and a high focal oscillatory shear index were observed at the ostial sites of aneurysmal sacs in the CAF. After successful surgical closure of the CAF, the vessel sizes and flow rate distributions of the coronary arteries increased.

Discussion: Doppler wire-based flow rate distribution measurements and CFD analysis may facilitate the identification of significant coronary steal syndrome requiring closure and the evaluation of future risks of life-threatening complications such as thrombosis and rupture.
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http://dx.doi.org/10.1093/ehjcr/ytab069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188863PMC
April 2021

Five-year clinical outcomes of the first Korean-made sirolimus-eluting coronary stent with abluminal biodegradable polymer.

Medicine (Baltimore) 2021 May;100(19):e25765

Department of Cardiology, Ajou University School of Medicine, Suwon.

Abstract: This study evaluated the 5-year clinical outcomes of the Genoss DES, the first Korean-made sirolimus-eluting coronary stent with abluminal biodegradable polymer.We previously conducted the first-in-patient prospective, multicenter, randomized trial with a 1:1 ratio of patients using the Genoss DES and Promus Element stents; the angiographic and clinical outcomes of the Genoss DES stent were comparable to those of the Promus Element stent. The primary endpoint was major adverse cardiac events (MACE), which was a composite of death, myocardial infarction (MI), and target lesion revascularization (TLR) at 5 years.We enrolled 38 patients in the Genoss DES group and 39 in the Promus Element group. Thirty-eight patients (100%) from the Genoss DES group and 38 (97.4%) from the Promus Element group were followed up at 5 years. The rates of MACE (5.3% vs 12.8%, P = .431), death (5.3% vs 10.3%, P = .675), TLR (2.6% vs 2.6%, P = 1.000), and target vessel revascularization (TVR) (7.9% vs 2.6%, P = .358) at 5 years did not differ significantly between the groups. No TLR or target vessel revascularization was reported from years 1 to 5 after the index procedure, and no MI or stent thrombosis occurred in either group during 5 years.The biodegradable polymer Genoss DES and durable polymer Promus Element stents showed comparable low rates of MACE at the 5-year clinical follow-up.
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http://dx.doi.org/10.1097/MD.0000000000025765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133141PMC
May 2021

Comparison of 2-Stenting Strategies Depending on Sequence or Technique for Bifurcation Lesions in the Second-Generation Drug-Eluting Stent Era - Analysis From the COBIS (Coronary Bifurcation Stenting) III Registry.

Circ J 2021 Jun 2. Epub 2021 Jun 2.

Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital.

Background: It has not been determined which specific 2-stenting strategy is the best for bifurcation lesions. Our aim was to investigate the clinical outcomes of various 2-stenting strategies in the era of 2nd-generation drug-eluting stents (2G-DES).Methods and Results:We analyzed 454 patients who finally underwent 2-stenting for a bifurcation lesion, from among 2,648 patients enrolled in the COBIS III registry. The primary outcome was target lesion failure (TLF). Patients were analyzed according to stenting sequence (provisional [main vessel stenting first] vs. systemic [side branch stenting first]) and stenting technique (crush vs. T vs. culotte vs. kissing/V stenting). Overall, 4.4 years' TLF after 2-stenting treatment for bifurcation lesion was excellent: TLF 11.2% and stent thrombosis 1.3%. There was no difference in TLF according to 2-stenting strategy (11.1% vs. 10.5%, P=0.990 for provisional and systemic sequence; 8.6% vs. 14.4% vs. 12.9% vs. 12.2%, P=0.326 for crush, T, culotte, kissing/V technique, respectively). Only left main (LM) disease and a shorter duration of dual antiplatelet therapy (DAPT) were associated with TLF. The distribution of DAPT duration differed between patients with and without TLF, and the time-point of intersection was 2.5 years. Also, the side branch was the most common site of restenosis.

Conclusions: The stenting sequence or technique did not affect clinical outcomes, but LM disease and shorter DAPT were associated with TLF, in patients with bifurcation lesions undergoing 2-stenting with 2G-DES.
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http://dx.doi.org/10.1253/circj.CJ-20-0999DOI Listing
June 2021

Effects of Smoking on Long-Term Clinical Outcomes and Lung Cancer in Patients with Acute Myocardial Infarction.

Korean Circ J 2021 Apr;51(4):336-348

Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background And Objectives: Smoking is well-established as a risk factor for coronary artery disease. However, recent studies demonstrated favorable results, including reduced mortality, among smokers, which are referred to as the "smoker's paradox". This study examined the impact of smoking on clinical outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI).

Methods: Patients with AMI undergoing PCI between 2004 and 2014 were enrolled and classified according to smoking status. The primary endpoint was a composite of major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, stroke, and revascularization.

Results: Among the 10,683 patients, 4,352 (40.7%) were current smokers. Smokers were 10.7 years younger and less likely to have comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, stroke, and prior PCI. Smokers had less MACE (hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.594-0.698; p<0.001) and cardiac death (HR, 0.494; 95% CI, 0.443-0.551; p<0.001) compared to nonsmokers during the 5 years in an unadjusted model. However, after propensity-score matching, smokers showed higher risk of MACE (HR, 1.125; 95% CI, 1.009-1.254; p=0.034) and cardiac death (HR, 1.190; 95% CI, 1.026-1.381; p=0.022). Smoking was a strong independent predictor of lung cancer (propensity-score matched HR, 2.749; 95% CI, 1.416-5.338; p=0.003).

Conclusions: In contrast to the unadjusted model, smoking is associated with worse cardiovascular outcome and higher incidence of lung cancer after adjustment of various confounding factors. This result can be explained by the characteristics of smokers, which were young and had fewer comorbidities.
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http://dx.doi.org/10.4070/kcj.2020.0430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022024PMC
April 2021

2021 Korean Society of Myocardial Infarction Expert Consensus Document on Revascularization for Acute Myocardial Infarction.

Korean Circ J 2021 Apr;51(4):289-307

Department of Cardiovascular Medicine, Chonnam National University Hospital, Gwangju, Korea.

Acute myocardial infarction (AMI) is a fatal manifestation of ischemic heart disease and remains a major public health concern worldwide despite advances in its diagnosis and management. The characteristics of patients with AMI, as well as its disease patterns, have gradually changed over time in Korea, and the outcomes of revascularization have improved dramatically. Several characteristics associated with the revascularization of Korean patients differ from those of patients in other countries. The sophisticated state of AMI revascularization in Korea has led to the need for a Korean expert consensus. The Task Force on Expert Consensus Document of the Korean Society of Myocardial Infarction has comprehensively reviewed the outcomes of large clinical trials and current practical guidelines, as well as studies on Korean patients with AMI. Based on these comprehensive reviews, the members of the task force summarize the major guidelines and recent publications, and propose an expert consensus for revascularization in patients with AMI.
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http://dx.doi.org/10.4070/kcj.2021.0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022023PMC
April 2021

Influence of lesion and disease subsets on the diagnostic performance of the quantitative flow ratio in real-world patients.

Sci Rep 2021 Feb 4;11(1):2995. Epub 2021 Feb 4.

Department of Cardiology, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

The quantitative flow ratio (QFR) is a novel angiography-based computational method assessing functional ischemia caused by coronary stenosis. This study aimed to evaluate the diagnostic performance of quantitative flow ratio (QFR) in patients with angina and acute myocardial infarction (AMI) and to identify the conditions with low diagnostic performance. We assessed the QFR for 1077 vessels under fractional flow ratio (FFR) evaluation in 915 patients with angina and AMI. The diagnostic accuracies of the QFR for identifying an FFR ≤ 0.8 were 95.98% (95% confidence interval [CI] 94.52 to 97.14%) for the angina group and 92.42% (95% CI 86.51 to 96.31%) for the AMI group. The diagnostic accuracy of the QFR in the borderline FFR zones (> 0.75, ≤ 0.85) (91.23% [95% CI 88.25 to 93.66%]) was significantly lower than that in others (difference: 4.32; p = 0.001). The condition accompanying both AMI and the borderline FFR zone showed the lowest QFR diagnostic accuracy in our data (83.93% [95% CI 71.67 to 92.38]). The diagnostic accuracy was reduced for tandem lesions (p = 0.04, not correcting for multiple testing). Our study found that the QFR method yielded a high overall diagnostic performance in real-world patients. However, low diagnostic accuracy has been observed in borderline FFR zones with AMI, and the hybrid FFR approach needs to be considered.
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http://dx.doi.org/10.1038/s41598-021-82235-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862355PMC
February 2021

GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance.

Cells 2021 01 15;10(1). Epub 2021 Jan 15.

The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea.

Obesity, a condition characterized by excessive accumulation of body fat, is a metabolic disorder related to an increased risk of chronic inflammation. Obesity is mediated by signal transducer and activator of transcription (STAT) 3, which is regulated by genes associated with retinoid-interferon-induced mortality (GRIM) 19, a protein ubiquitously expressed in various human tissues. In this study, we investigated the role of GRIM19 in diet-induced obese C57BL/6 mice via intravenous or intramuscular administration of a plasmid encoding GRIM19. Splenocytes from wild-type and GRIM19-overexpressing mice were compared using enzyme-linked immunoassay, real-time polymerase chain reaction, Western blotting, flow cytometry, and histological analyses. GRIM19 attenuated the progression of obesity by regulating STAT3 activity and enhancing brown adipose tissue (BAT) differentiation. GRIM19 regulated the differentiation of mouse-derived 3T3-L1 preadipocytes into adipocytes, while modulating gene expression in white adipose tissue (WAT) and BAT. GRIM19 overexpression reduced diet-induced obesity and enhanced glucose and lipid metabolism in the liver. Moreover, GRIM19 overexpression reduced WAT differentiation and induced BAT differentiation in obese mice. GRIM19-transgenic mice exhibited reduced mitochondrial superoxide levels and a reciprocal balance between Th17 and Treg cells. These results suggest that GRIM19 attenuates the progression of obesity by controlling adipocyte differentiation.
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http://dx.doi.org/10.3390/cells10010162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829987PMC
January 2021

Sex differences in patients undergoing transcatheter aortic valve replacement in Asia.

Open Heart 2021 01;8(1)

Department of Cardiology, Sichuan University West China Hospital, Chengdu, China.

Objectives: Transcatheter aortic valve replacement (TAVR) is increasingly performed. Physically small Asians have smaller aortic root and peripheral vessel anatomy. The influence of gender of Asian patients undergoing TAVR is unknown and may affect outcomes. The aim of this study was to assess sex differences in Asian patients undergoing TAVR.

Methods: Patients undergoing TAVR from eight countries were enrolled. In this retrospective analysis, we examined differences in characteristics, 30-day clinical outcomes and 1-year survival between female and male Asian patients.

Results: Eight hundred and seventy-three patients (54.4% women) were included. Women were older, smaller and had less coronary artery and lung disease but tended to have higher logistic EuroSCOREs. Smaller prostheses were used more often in women. Major vascular complications occurred more frequently in women (5.5% vs 1.8%, p<0.01); however, 30-day stroke and mortality (women vs men: 1.5% vs 1.6%, p=0.95% and 4.3% vs 3.4%, p=0.48) were similar. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements (11.2% vs 9.0%, p=0.52) were also similar as was 1-year survival (women vs men: 85.6% vs 88.2%, p=0.25). The only predictors of 30-day mortality were major vascular injury in women and age in men.

Conclusions: Asian women had significantly smaller stature and anatomy with some differences in clinical profiles. Despite more frequent major vascular complications, women had similar 30-day stroke or mortality rates. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements were similar as was 1-year survival.
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http://dx.doi.org/10.1136/openhrt-2020-001541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798412PMC
January 2021

An Open-label, Single-arm, Multicenter Feasibility Study Evaluating the Safety of Catheter-based Renal Denervation with DENEX™ in Patients with Uncontrolled Hypertension on Standard Medical Therapy.

Korean Circ J 2021 Jan;51(1):43-55

Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.

Background And Objectives: DENEX™ is a novel renal sympathetic denervation (RDN) system that is equipped with 3 electrodes that deliver radiofrequency energy to the renal nerves along renal arteries. The purpose of this study was to evaluate the safety and efficacy of RDN with DENEX™ in resistant hypertension.

Methods: This was an open-label, single-arm, multicenter, first-in-man pilot study. Between November 2016 and May 2018, a total of 16 patients were enrolled at 4 centers in South Korea. The inclusion criteria were systolic blood pressure (SBP) ≥150 mmHg and use of 3 or more antihypertensive medications, including diuretics. The primary objective was the safety outcome of RDN with the DENEX™ system. The secondary objective was efficacy outcome based on changes of office, and 24-hour ambulatory SBP from baseline to 3 months. The patients underwent abdominal computed tomography (CT) or duplex ultrasonogram before and 6 months after RDN.

Results: No major adverse events occurred after RDN for 6 month of follow-up period. There was no vascular complication either by CT or duplex ultrasonogram. The office SBP was significantly reduced from 164.6±11.6 mmHg at baseline to 142.0±20.4 mmHg (-24.4±24.4 mmHg, p=0.003) at 3 months. The ambulatory SBP was reduced from 151.44±12.85 mmHg at baseline to 140.0±16.5 mmHg (-13.1±18.9 mmHg, p=0.056) at 3 months.

Conclusion: RDN with the DENEX™ system showed a favorable safety profile in resistant hypertension. A significant reduction in office SBP and a borderline reduction in ambulatory SBP were observed.

Trial Registration: ClinicalTrials.gov Identifier: NCT04248530.
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http://dx.doi.org/10.4070/kcj.2020.0391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779817PMC
January 2021

Gender differences in clinical outcomes of acute myocardial infarction undergoing percutaneous coronary intervention: insights from the KAMIR-NIH Registry.

J Geriatr Cardiol 2020 Nov;17(11):680-693

Division of Cardiology, Daejeon St. Mary's hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Background: There are numerous but conflicting data regarding gender differences in outcomes following percutaneous coronary intervention (PCI). Furthermore, gender differences in clinical outcomes with acute myocardial infarction (AMI) following PCI in Asian population remain uncertain because of the under-representation of Asian in previous trials.

Methods: A total of 13, 104 AMI patients from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) between November 2011 and December 2015 were classified into male ( = 8021, 75.9%) and female ( = 2547, 24.1%). We compared the demographic, clinical and angiographic characteristics, 30-days and 1-year major adverse cardiac and cerebrovascular events (MACCE) in women with those in men after AMI by using propensity score (PS) matching.

Results: Compared with men, women were older, had more comorbidities and more often presented with non-ST segment elevation myocardial infarction (NSTEMI) and reduced left ventricular systolic function. Over the median follow-up of 363 days, gender differences in both 30-days and 1-year MACCE as well as thrombolysis in myocardial infarction minor bleeding risk were not observed in the PS matched population (30-days MACCE: 5.3% . 4.7%, log-rank = 0.494, HR = 1.126, 95% CI: 0.800-1.585; 1-year MACCE: 9.3% . 9.0%, log-rank = 0.803, HR = 1.032, 95% CI: 0.802-1.328; TIMI minor bleeding: 4.9% . 3.9%, log-rank = 0.215, HR = 1.255, 95% CI: 0.869-1.814).

Conclusions: Among Korean AMI population undergoing contemporary PCI, women, as compared with men, had different clinical and angiographic characteristics but showed similar 30-days and 1-year clinical outcomes. The risk of bleeding after PCI was comparable between men and women during one-year follow up.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2020.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729180PMC
November 2020

Ischemic and Bleeding Events Associated with Thrombocytopenia and Thrombocytosis after Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction.

J Clin Med 2020 Oct 21;9(10). Epub 2020 Oct 21.

Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

The early and late ischemic and bleeding clinical outcomes according to baseline platelet count after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) remain unclear. Overall, 10,667 patients from the Cardiovascular Risk and identification of potential high-risk population in AMI (COREA-AMI) I and II registries were classified according to the following universal criteria on baseline platelet counts: (1) moderate to severe thrombocytopenia (platelet < 100 K/μL, = 101), (2) mild thrombocytopenia (platelet = 100~149 K/μL, = 631), (3) normal reference (platelet = 150~450 K/μL, = 9832), and (4) thrombocytosis (platelet > 450 K/μL, = 103). The primary endpoint was the occurrence of major adverse cardiovascular events (MACE). The secondary outcome was Bleeding Academic Research Consortium (BARC) 2, 3, and 5 bleeding. After adjusting for confounders, the moderate to severe thrombocytopenia (HR, 2.03; 95% CI, 1.49-2.78); 0.001), mild thrombocytopenia (HR, 1.15; 95% CI, 1.01-1.34; = 0.045), and thrombocytosis groups (HR, 1.47; 95% CI, 1.07-2.03; = 0.019) showed higher 5-year MACE rates than the normal reference. In BARC 2, 3, and 5 bleeding outcomes, the bleedings rates were higher than the normal range in the moderate to severe thrombocytopenia (HR, 2.18; 95% CI, 1.36-3.49; = 0.001) and mild thrombocytopenia (HR, 1.41; 95% CI, 1.12-1.78; = 0.004) groups. Patients with AMI had higher 5-year MACE rates after PCI if they had lower- or higher-than-normal platelet counts. Thrombocytopenia revealed higher early and late bleeding rates whereas thrombocytosis showed long-term bleeding trends, although these trends were not statistically significant.
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http://dx.doi.org/10.3390/jcm9103370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589459PMC
October 2020

Intramyocardial Transplantation of MSC-Loading Injectable Hydrogels after Myocardial Infarction in a Murine Model.

J Vis Exp 2020 09 20(163). Epub 2020 Sep 20.

Cardiovascular Research Institute for Intractable Disease, College of Medicine, The Catholic University of Korea; Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea.

One of the major issues facing current cardiac stem cell therapies for preventing postinfarct heart failure is the low retention and survival rates of transplanted cells within the injured myocardium, limiting their therapeutic efficacy. Recently, the use of scaffolding biomaterials has gained attention for improving and maximizing stem cell therapy. The objective of this protocol is to introduce a simple and straightforward technique to transplant bone marrow-derived mesenchymal stem cells (MSCs) using injectable hydroxyphenyl propionic acid (GH) hydrogels; the hydrogels are favorable as a cell delivery platform for cardiac tissue engineering applications due to their ability to be cross-linked in situ and high biocompatibility. We present a simple method to fabricate MSC-loading GH hydrogels (MSC/hydrogels) and evaluate their survival and proliferation in three-dimensional (3D) in vitro culture. In addition, we demonstrate a technique for intramyocardial transplantation of MSC/hydrogels in mice, describing a surgical procedure to induce myocardial infarction (MI) via left anterior descending (LAD) coronary artery ligation and subsequent MSC/hydrogels transplantation.
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http://dx.doi.org/10.3791/61752DOI Listing
September 2020

2020 Korean Society of Myocardial Infarction Expert Consensus Document on Pharmacotherapy for Acute Myocardial Infarction.

Korean Circ J 2020 Oct;50(10):845-866

Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.

Clinical practice guidelines published by the European Society of Cardiology and the American College of Cardiology/American Heart Association summarize the available evidence and provide recommendations for health professionals to enable appropriate clinical decisions and improve clinical outcomes for patients with acute myocardial infarction (AMI). However, most current guidelines are based on studies in non-Asian populations in the pre-percutaneous coronary intervention (PCI) era. The Korea Acute Myocardial Infarction Registry is the first nationwide registry to document many aspects of AMI from baseline characteristics to treatment strategies. There are well-organized ongoing and published randomized control trials especially for antiplatelet therapy among Korean patients with AMI. Here, members of the Task Force of the Korean Society of Myocardial Infarction review recent published studies during the current PCI era, and have summarized the expert consensus for the pharmacotherapy of AMI.
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http://dx.doi.org/10.4070/kcj.2020.0196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515755PMC
October 2020

Comparing the Procedural and Clinical Outcomes of Sapien XT and Sapien 3 Valves in Transcatheter Aortic Valve Replacement in Korean Patients.

Korean Circ J 2020 Oct 28;50(10):907-922. Epub 2020 Jul 28.

Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.

Background And Objectives: The Sapien 3 (S3) valve has not been compared to the Sapien XT (SXT) valve in Korea. We compared procedural and clinical outcomes between the 2 devices.

Methods: A total of 189 patients who underwent transcatheter aortic valve replacement (TAVR) with S3 (n=95) or SXT (n=94) valve was analyzed. The primary endpoint was cardiovascular mortality at 1 year. The median follow-up duration was 438 days.

Results: The Society of Thoracic Surgeons score was similar between the 2 groups. The device success rate (90.4% vs. 97.9%; p=0.028) was higher in the S3 than in the SXT. The S3 showed significantly fewer cases of moderate or severe paravalvular leakage (PVL) (16.7% vs. 0.0%; p=0.001) than the SXT. However, effective orifice area (EOA) (2.07±0.61 vs. 1.70±0.49 cm²; p<0.001) was smaller in the S3. Multivariable Cox regression analysis showed the S3 was associated with significantly fewer cardiovascular mortality at 1 year compared to the SXT (5.4% vs. 1.1%; hazard ratio, 0.031; 95% confidence interval, 0.001-0.951; p=0.047). Periprocedural complication rates, composite of disabling stroke or all-cause mortality, all-cause mortality, and disabling stroke at 1 year were similar between the 2 groups.

Conclusions: Cardiovascular mortality was lower in the S3 group than in the SXT group over 1 year of follow-up. The reduction in PVL was attributed to the higher device success rate of TAVR with the S3 valve. However, the benefit of S3 obtained at the expense of reduced EOA should be meticulously re-evaluated in larger studies during long-term follow-up.
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http://dx.doi.org/10.4070/kcj.2020.0061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515760PMC
October 2020

A prospective, multicentre, randomised, open-label trial to compare the efficacy and safety of clopidogrel versus ticagrelor in stabilised patients with acute myocardial infarction after percutaneous coronary intervention: rationale and design of the TALOS-AMI trial.

EuroIntervention 2021 Feb;16(14):1170-1176

Department of Cardiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Aims: In patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), the risk of ischaemic complications is highest in the early phase (during the first 30 days), while most bleeding events occur predominantly during the maintenance phase of treatment (after the first 30 days). Data on the de-escalation of dual antiplatelet therapy by switching from ticagrelor to clopidogrel in stabilised AMI patients are limited. The aim of this study is to investigate the efficacy and safety of switching from ticagrelor to clopidogrel in AMI patients with no adverse event during the first month after the index PCI with newer-generation DES.

Methods And Results: TALOS-AMI is a multicentre, randomised, open-label study enrolling 2,590 AMI patients with no adverse events during the first month after the index PCI. One month after the index PCI, eligible patients are randomly assigned either to 1) aspirin 100 mg plus clopidogrel 75 mg daily, or to 2) aspirin 100 mg plus ticagrelor 90 mg twice daily, in a 1:1 ratio. The primary endpoint is a composite of cardiovascular death, MI, stroke, and bleeding type 2, 3 or 5 according to the Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months after the index PCI.

Conclusions: The TALOS-AMI trial is the first large-scale, multicentre, randomised study exploring the efficacy and safety of the de-escalation of antiplatelet therapy by switching from ticagrelor to clopidogrel in stabilised AMI patients undergoing PCI.
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http://dx.doi.org/10.4244/EIJ-D-20-00187DOI Listing
February 2021

Practical cardiovascular risk calculator for asymptomatic patients with type 2 diabetes mellitus: PRECISE-DM risk score.

Clin Cardiol 2020 Sep 13;43(9):1040-1047. Epub 2020 Jul 13.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Obstructive coronary artery disease (OCAD) is a significant predictor of adverse clinical events in asymptomatic patients with type 2 diabetes mellitus (T2DM).

Hypothesis: We sought to develop an easy-to-use risk scoring system to predict OCAD and long-term clinical outcome in asymptomatic patients with T2DM (PRECISE-DM).

Methods: A total of 2799 asymptomatic patients with T2DM and no prior coronary disease were consecutively enrolled. OCAD was defined as ≥50% coronary artery stenosis on coronary computed tomography angiography (CCTA). A new risk scoring system was developed in 933 patients undergoing CCTA (derivation cohort) and its performance to predict OCAD and major adverse cardiac and cerebrovascular event (MACCE) was compared with other risk estimates. The scoring system was externally validated in 1899 patients not undergoing CCTA (validation cohort).

Results: The PRECISE-DM scoring system was created using seven variables that were associated with increased risk of OCAD, with scores ranging from 0 to 9. The scoring system predicted presence of OCAD with a C-statistic of 0.680 and risk of MACCE with a C-statistic of 0.708. The UKPDS risk engine and the Framingham risk score showed unreliable performance in prediction of OCAD (C-statistics 0.531 and 0.577, respectively). Calcium score was highly predictive for OCAD (C-statistic 0.825) but showed only modest accuracy in predicting MACCE (C-statistic 0.675). In the external validation cohort, the PRECISE-DM score showed acceptable discrimination for prediction of MACCE (C-statistic 0.707).

Conclusions: The PRECISE-DM scoring system accurately predicted presence of OCAD and risk of MACCE in asymptomatic patients with T2DM.
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http://dx.doi.org/10.1002/clc.23405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462187PMC
September 2020

Genomewide Association Study of Platelet Reactivity and Cardiovascular Response in Patients Treated With Clopidogrel: A Study by the International Clopidogrel Pharmacogenomics Consortium.

Clin Pharmacol Ther 2020 11 9;108(5):1067-1077. Epub 2020 Jul 9.

Department of Medicine and Program for Personalized and Genomic Medicine, University of Maryland, Baltimore, Maryland, USA.

Antiplatelet response to clopidogrel shows wide variation, and poor response is correlated with adverse clinical outcomes. CYP2C19 loss-of-function alleles play an important role in this response, but account for only a small proportion of variability in response to clopidogrel. An aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify other genetic determinants of clopidogrel pharmacodynamics and clinical response. A genomewide association study (GWAS) was performed using DNA from 2,750 European ancestry individuals, using adenosine diphosphate-induced platelet reactivity and major cardiovascular and cerebrovascular events as outcome parameters. GWAS for platelet reactivity revealed a strong signal for CYP2C19*2 (P value = 1.67e-33). After correction for CYP2C19*2 no other single-nucleotide polymorphism reached genomewide significance. GWAS for a combined clinical end point of cardiovascular death, myocardial infarction, or stroke (5.0% event rate), or a combined end point of cardiovascular death or myocardial infarction (4.7% event rate) showed no significant results, although in coronary artery disease, percutaneous coronary intervention, and acute coronary syndrome subgroups, mutations in SCOS5P1, CDC42BPA, and CTRAC1 showed genomewide significance (lowest P values: 1.07e-09, 4.53e-08, and 2.60e-10, respectively). CYP2C19*2 is the strongest genetic determinant of on-clopidogrel platelet reactivity. We identified three novel associations in clinical outcome subgroups, suggestive for each of these outcomes.
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http://dx.doi.org/10.1002/cpt.1911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689744PMC
November 2020

Cardiovascular disease burden in adult patients with cancer: An 11-year nationwide population-based cohort study.

Int J Cardiol 2020 10 29;317:167-173. Epub 2020 Apr 29.

Cardiovascular and Metabolic Disease Etiology Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Cardiovascular disease (CVD) is an important cause of morbidity and mortality in patients with cancer. However, the real-world CVD burden of adult cancer patients has not been well established. This study aimed to evaluate the prevalence and mortality of pre-existing and new-onset CVD in patients with cancers.

Methods: We analysed the prevalence and mortality of pre-existing and new-onset CVD in 41,034 adult patients with ten common solid cancers in a single payer system using data from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013.

Results: When all types of cancer were included, 11.3% (n = 4647) of patients had pre-existing CVD when they were diagnosed with cancer. After excluding patients with pre-existing CVD, 15.7% of cancer patients (n = 5703) were newly diagnosed with CVD during the follow-up period (median 68 months). Both pre-existing and new-onset CVD were associated with increased risk of overall mortality and 5-year mortality. Multivariate analysis to predict all-cause mortality indicated both pre-existing and new-onset CVD, male sex, old age, prior history of diabetes or chronic kidney disease, suburban residential area, and low-income status as significant factors.

Conclusions: Eleven percent of cancer patients had pre-existing CVD at the time of cancer diagnosis, and about 16% of cancer patients without pre-existing CVD were newly diagnosed with CVD, mostly within 5 years after the cancer diagnosis. Proper management of pre-existing CVD is necessary and pre-emptive prevention of new-onset CVD may alter treatment options and outcomes.
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http://dx.doi.org/10.1016/j.ijcard.2020.04.080DOI Listing
October 2020

Effect of Fimasartan versus Valsartan and Olmesartan on Office and Ambulatory Blood Pressure in Korean Patients with Mild-to-Moderate Essential Hypertension: A Randomized, Double-Blind, Active Control, Three-Parallel Group, Forced Titration, Multicenter, Phase IV Study (Fimasartan Achieving Systolic Blood Pressure Target (FAST) Study).

Drug Des Devel Ther 2020 23;14:347-360. Epub 2020 Jan 23.

Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.

Purpose: Head-to-head comparison of the blood pressure (BP) lowering effect of fimasartan versus valsartan, with olmesartan as a reference, on office blood pressure and ambulatory BP.

Patients And Methods: Of the 369 randomly assigned patients in this study, 365 hypertensive patients were referred as the full analysis set and divided into 3 groups with a 3:3:1 ratio (fimasartan group: 155, valsartan group: 157, olmesartan group: 53). After the 2-week single-blind placebo run-in period, initial standard doses of 60-mg fimasartan, 80-mg valsartan, and 10-mg olmesartan were administered for 2 weeks, then forcibly up-titrated higher doses (fimasartan 120 mg, valsartan 160 mg, olmesartan 20 mg) were given for 4 weeks. ABP was measured before and after the 6-week treatment. Primary endpoint was reduction of sitting office systolic BP (SiSBP) of fimasartan compared to valsartan after 6 weeks. Secondary endpoints were reduction of sitting office diastolic BP (SiDBP) and 24 hrs, day-time, and night-time mean systolic and diastolic ABP (ASBP, ADBP) after 6 weeks.

Results: Patients' mean age was 58.34±7.68 years, and 289 patients were male (79.18%). After the 6-week treatment, SiSBP reduction of fimasartan and valsartan were -16.26±15.07 and -12.81±13.87 (p=0.0298) and SiDBP were -7.63±9.67 and -5.14±8.52 (p=0.0211). Reductions in 24 hrs mean ASBP were -15.22±13.33 and -9.45±12.37 (p=0.0009), and ADBPs were -8.74±7.55 and -5.98±7.85 (p=0.0140). Reductions of night-time ASBPs were -16.80±15.81 and -10.32±14.88 (p=0.0012), and those of night-time ADBPs were -8.89±9.93 and -5.55±9.70 (p=0.0152). Reduction of BP in olmesartan group did not demonstrate significant difference with fimasartan group in all end-points.

Conclusion: Fimasartan 120-mg treatment demonstrated superior efficacy in reduction of SiSBP, SiDBP, and 24 hrs ASBP and ADBP compared to valsartan 160 mg. Reduction of night-time ASBP from baseline was largest in fimasartan group, suggesting that fimasartan may be effective for recovering dipping pattern.

Nct Number: NCT02495324 (Fimasartan Achieving SBP Target (FAST) study).
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http://dx.doi.org/10.2147/DDDT.S231293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986172PMC
January 2021

Prognostic Effects of Treatment Strategies for Left Main Versus Non-Left Main Bifurcation Percutaneous Coronary Intervention With Current-Generation Drug-Eluting Stent.

Circ Cardiovasc Interv 2020 02 7;13(2):e008543. Epub 2020 Feb 7.

Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea (D.-S.L., S.-J.H.).

Background: Although 1-stent with provisional approach is the preferred strategy for the treatment of bifurcation lesions, the optimal treatment strategy according to lesion location is still debatable. This study aimed to identify whether clinical outcomes according to treatment strategy differed between left main (LM) and non-LM bifurcation lesions in the second-generation drug-eluting stent era.

Methods: The Coronary Bifurcation Stenting registry III is a retrospective multicenter registry of 2648 patients with bifurcation lesions who underwent percutaneous coronary intervention with second-generation drug-eluting stent. Among the study population, 935 (35.3%) patients had an LM bifurcation lesion. The primary outcome was target lesion failure, a composite of cardiac death, myocardial infarction, and target lesion revascularization.

Results: Median follow-up duration was 53 months. LM bifurcation was associated with a higher risk of target lesion failure (HR, 1.846 [95% CI, 1.317-2.588]; <0.001) than non-LM bifurcation. Two-stent strategy was more frequently applied in patients with LM bifurcation than in patients with non-LM bifurcation (27.1% versus 11.7%; <0.001). In the LM bifurcation group, compared with the 1-stent strategy, the 2-stent strategy showed a significantly higher risk of target lesion failure (2-stent versus 1-stent, 17.4% versus 10.6%; HR, 1.848 [95% CI, 1.045-3.266]; =0.035), mainly driven by the higher rate of target lesion revascularization (15.3% versus 5.5%; HR, 2.698 [95% CI, 1.276-5.706]; =0.009). However, the risk of cardiac death or myocardial infarction did not differ between the 2 groups (4.4% versus 6.6%; HR, 0.694 [95% CI, 0.306-1.572]; =0.381). For patients with non-LM-bifurcation, there was no significant difference in the rate of target lesion failure between 1-stent and 2-stent strategies (5.6% versus 6.3%; HR, 0.925 [95% CI, 0.428-2.001]; =0.843).

Conclusions: Even in the second-generation drug-eluting stent era, the 1-stent strategy, if possible, should initially be considered the preferred approach for the treatment of LM bifurcation lesions. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03068494.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008543DOI Listing
February 2020

Effect of Low-Dose Nebivolol in Patients with Acute Myocardial Infarction: A Multi-Center Observational Study.

Chonnam Med J 2020 Jan 22;56(1):55-61. Epub 2020 Jan 22.

Department of Cardiology, Kyungsang National University Hospital, Jinju, Korea.

The optimal dose of beta blockers after acute myocardial infarction (MI) remains uncertain. We evaluated the effectiveness of low-dose nebivolol, a beta1 blocker and a vasodilator, in patients with acute MI. A total of 625 patients with acute MI from 14 teaching hospitals in Korea were divided into 2 groups according to the dose of nebivolol (nebistol®, Elyson Pharmaceutical Co., Ltd., Seoul, Korea): low-dose group (1.25 mg daily, n=219) and usual- to high-dose group (≥2.5 mg daily, n=406). The primary endpoints were major adverse cardiac and cerebrovascular events (MACCE, composite of death from any cause, non-fatal MI, stroke, repeat revascularization, rehospitalization for unstable angina or heart failure) at 12 months. After adjustment using inverse probability of treatment weighting, the rates of MACCE were not different between the low-dose and the usual- to high-dose groups (2.8% and 3.1%, respectively; hazard ratio: 0.92, 95% confidence interval: 0.38 to 2.24, p=0.860). The low-dose nebivolol group showed higher rates of MI than the usual- to high-dose group (1.2% and 0%, p=0.008). The 2 groups had similar rates of death from any cause (1.1% and 0.3%, p=0.273), stroke (0.4% and 1.1%, p=0.384), repeat PCI (1.2% and 0.8%, p=0.428), rehospitalization for unstable angina (1.2% and 1.0%, p=0.743) and for heart failure (0.6% and 0.7%, p=0.832). In patients with acute MI, the rates of MACCE for low-dose and usual- to high-dose nebivolol were not significantly different at 12-month follow-up.
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http://dx.doi.org/10.4068/cmj.2020.56.1.55DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976776PMC
January 2020

A randomized, double-blind clinical trial to evaluate the efficacy and safety of a fixed-dose combination of amlodipine/rosuvastatin in patients with dyslipidemia and hypertension.

J Clin Hypertens (Greenwich) 2020 02 31;22(2):261-269. Epub 2020 Jan 31.

Cardiovascular Center, Korea University Guro Hospital, Seoul, Korea.

This multicenter, randomized, double-blind, parallel-group phase III clinical trial aimed to investigate the efficacy and safety of a rosuvastatin + amlodipine combination compared with that of rosuvastatin or amlodipine monotherapy in hypertensive patients with dyslipidemia. A total of 106 patients of 15 institutions in Korea were randomly assigned to 1 of 3 treatment groups: rosuvastatin 20 mg + amlodipine 10 mg, amlodipine 10 mg, or rosuvastatin 20 mg. After 8 weeks of treatment, the mean ± SD of change in mean sitting systolic blood pressure (msSBP) was -22.82 ± 12.99 mm Hg in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. The percentage of patients whose msSBP decreased ≥20 mm Hg or msDBP decreased ≥10 mm Hg was also highest in this group (74.29%). The mean ± SD percentage change in low-density lipoprotein cholesterol (LDL-C) level from baseline after 8 weeks was -52.53% ± 11.21% in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. More patients in the rosuvastatin + amlodipine group achieved their target LDL-C goal at 8 weeks, compared with the other treatment groups (97.14%). No serious adverse events or adverse drug reactions were observed in all groups. In hypertensive patients with dyslipidemia, combination treatment with rosuvastatin 20 mg + amlodipine 10 mg effectively reduced blood pressure and LDL-C levels while maintaining safety.
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http://dx.doi.org/10.1111/jch.13774DOI Listing
February 2020

Predictors of Significant Coronary Artery Disease in Patients with Cerebral Artery Atherosclerosis.

Cerebrovasc Dis 2019 11;48(3-6):226-235. Epub 2019 Dec 11.

Department of Cardiology, Bucheon St. Mary's Hospital, The Catholic University College of Medicine, Seoul, Republic of Korea,

Objective: There are few existing data on the status of coronary artery disease (CAD) in patients with atherosclerosis of the cerebral artery detected by brain imaging studies. We aimed to analyze the predictors of asymptomatic angiographically significant CAD detected by simultaneous cerebral and coronary angiography.

Methods: This retrospective cohort study screened data obtained between August 2009 and April 2019; 11,047 patients underwent cerebral angiography for atherosclerotic change (>50% stenosis or aneurysm) seen in brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) at a single center by endovascular neurosurgeon's decision. Of these, 700 patients including 622 patients who underwent simultaneous coronary and cerebral angiography and 78 patients who underwent coronary angiography within a month were enrolled. We investigated the characteristics and predictors of angiographically significant CAD (>50% stenosis). Furthermore, we also analyzed the major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, myocardial infarction, and stroke for 5 years.

Results: The frequency of significant CAD was 59% (413/700), the mean age was 68.9 ± 10.3 years, and 60.6% were male. During mean follow-up of 50 months, the MACCE rate of our whole cohort was significantly higher in the CAD group (21.5%) than in the non-CAD group (14.6%; hazard ratio 1.65, 95% CI 1.17-2.33, p value = 0.005). Considering that the embolic stroke is less associated with atherosclerotic change, our predictive model of significant CAD was made without embolic stroke (n = 599). In our multivariate model 2 including univariate <0.1, the independent predictors of significant CAD were male (OR 1.62, 95% CI 1.11-2.35, p = 0.012), diabetes mellitus (OR 1.81, 95% CI 1.22-2.68, p = 0.003), previous stroke (OR 1.63, 95% CI 1.02-2.60, p = 0.039), low ankle-brachial index (ABI; <0.9; OR 3.25, 95% CI 1.21-8.73, p = 0.019), left ventricular ejection fraction (EF) <50% on echocardiography (OR 2.82, 95% CI 1.25-6.35, p = 0.012), troponin I or T positive (OR 2.76, 95% CI 1.69-4.53, p < 0.001), and complex features on cerebral angiography (OR 2.73, 95% CI 1.78-4.19, p < 0.001).

Conclusions: Accurate coronary evaluation by coronary angiography might be considered when patients with atherosclerotic cerebral artery detected on brain MRA or CTA planned cerebral angiography were male or have diabetes mellitus, previous stroke, low ABI (<0.9), left ventricular EF <50% on echocardiography, troponin I or T positivity, and complex features on cerebral angiography.
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http://dx.doi.org/10.1159/000504927DOI Listing
May 2020

Angiotensin Receptor Blockers as an Alternative to Angiotensin-Converting Enzyme Inhibitors in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

J Korean Med Sci 2019 Nov 25;34(45):e289. Epub 2019 Nov 25.

Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: Angiotensin-converting enzyme inhibitors (ACEIs) are the first choice for the treatment of acute myocardial infarction (AMI), and angiotensin receptor blockers (ARBs) should be considered in patients intolerant to ACEIs. Although previous studies support the use of ARBs as an alternative to ACEIs, these studies showed inconsistent results. The objective of this study was to demonstrate the clinical impact of ARBs as an alternative to ACEIs in patients with AMI undergoing percutaneous coronary intervention (PCI).

Methods: The CardiOvascular Risk and idEntificAtion of potential high-risk population in AMI (COREA-AMI) registry enrolled all consecutive patients with AMI undergoing PCI. The primary endpoint was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization due to heart failure.

Results: Of the 3,328 eligible patients, ARBs replaced ACEIs in 816 patients, while 824 patients continued to use ACEIs and 826 patients continued to use ARBs. The remaining 862 patients did not receive ACEIs/ARBs. After the adjustment with inverse probability weighting, the primary endpoints in the first groups were similar (7.5% vs. 8.0%, hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.75-1.05; = 0.164). Composite events were less frequent in the ACEI to ARB group than no ACEI/ARB group (7.5% vs. 11.8%, HR, 0.76; 95% CI, 0.64-0.90; = 0.002).

Conclusion: The alternative use of ARBs following initial treatment with ACEIs demonstrates comparable clinical outcomes to those with continued use of ACEIs and is associated with an improved rate of composite events compared to no ACEI/ARB use in patients with AMI undergoing PCI.

Trial Registration: ClinicalTrials.gov Identifier: NCT02385682.
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http://dx.doi.org/10.3346/jkms.2019.34.e289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875434PMC
November 2019

Understanding Vulnerable Plaques: Current Status and Future Directions.

Korean Circ J 2019 12;49(12):1115-1122

Cardiovascular Center and Cardiology Division, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

The main cause of acute myocardial infarction is plaque rupture accompanied by superimposed coronary thrombosis. Thin-cap fibroatheromas (TCFAs) have been suggested as a type of lesion with a vulnerability that can cause plaque rupture. However, not only the existence of a TCFA but also the fine and complex interactions of other anatomical and hemodynamic factors, such as microcalcification in the fibrous cap, cholesterol crystal-induced inflammasome activation, the apoptosis of intraplaque macrophages, and endothelial shear stress distribution should precede a clinical event caused by plaque rupture. Recent studies are being conducted to identify these mechanisms through molecular imaging and hemodynamic assessment using computational fluid dynamics, which will result in better clinical results through selective coronary interventions.
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http://dx.doi.org/10.4070/kcj.2019.0211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875591PMC
December 2019

Comparison of Two-Year Outcomes of Acute Myocardial Infarction Caused by Coronary Artery Spasm Versus that Caused by Coronary Atherosclerosis.

Am J Cardiol 2019 11 23;124(10):1493-1500. Epub 2019 Aug 23.

Chonnam National University Hospital, Gwangju, South Korea.

The study compared the 2-year outcomes of patients diagnosed with acute myocardial infarction (AMI) triggered by coronary artery atherosclerosis and AMI caused by coronary artery spasm. A total of 36,797 patients in the Korea AMI Registry were grouped into 2 categories-(1) AMI due to coronary artery spasm without stenotic lesion (CAS-AMI, n = 484); and (2) AMI induced by coronary artery atherosclerosis (CAA-AMI, n = 36,313). The major clinical outcomes of the 2 groups were compared over a 2-year clinical follow-up period. Major adverse cardiac events (MACE) were defined as the composite of total death, nonfatal myocardial infarction, and repeat revascularization. The incidence of MACE (7.1% vs 11.1%; p = 0.007) and repeat revascularization (0.4% vs 4.2%; p <0.001) in the CAS-AMI group were significantly lower than in the CAA-AMI group at 2 years. However, the incidence of total death and nonfatal myocardial infarction was similar in both the groups. Aborted cardiac arrest was strongly associated with 2-year mortality in the CAS-AMI group (hazard ratios 13.5, 95% confidence interval 5.34 to 34.15, p <0.001) The incidence of MACE in CAS-AMI patients was significantly lower than in the CAA-AMI group of patients up to 2 years due to the relatively lower rate of repeat revascularization in CAS-AMI patients. However, the incidence of total death or nonfatal myocardial infarction in CAS-AMI patients was not different from that of patients with CAA-AMI.
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http://dx.doi.org/10.1016/j.amjcard.2019.08.019DOI Listing
November 2019

Pharmacogenomic polygenic response score predicts ischaemic events and cardiovascular mortality in clopidogrel-treated patients.

Eur Heart J Cardiovasc Pharmacother 2020 07;6(4):203-210

Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, Florence 50055, Italy.

Aims: Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial.

Methods And Results: We assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10-54; CES1 G143E, P = 1.3 × 10-16; CYP2C19*17, P = 9.5 × 10-10; CYP2B6 1294 + 53 C > T, P = 3.0 × 10-4; CYP2B6 516 G > T, P = 1.0 × 10-3; CYP2C9*2, P = 1.2 × 10-3; and CYP2C9*3, P = 1.5 × 10-3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14-2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35-14.27, P = 0.01) compared to patients who carried six or fewer of these alleles.

Conclusion: Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies.
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http://dx.doi.org/10.1093/ehjcvp/pvz045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363022PMC
July 2020