Publications by authors named "Wang Soo Lee"

55 Publications

IGF-1 protects against angiotensin II-induced cardiac fibrosis by targeting αSMA.

Cell Death Dis 2021 Jul 9;12(7):688. Epub 2021 Jul 9.

Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.

The insulin-like growth factor 1 receptor (IGF-1R) signaling in cardiomyocytes is implicated in physiological hypertrophy and myocardial aging. Although fibroblasts account for a small amount of the heart, they are activated when the heart is damaged to promote cardiac remodeling. However, the role of IGF-1R signaling in cardiac fibroblasts is still unknown. In this study, we investigated the roles of IGF-1 signaling during agonist-induced cardiac fibrosis and evaluated the molecular mechanisms in cultured cardiac fibroblasts. Using an experimental model of cardiac fibrosis with angiotensin II/phenylephrine (AngII/PE) infusion, we found severe interstitial fibrosis in the AngII/PE infused myofibroblast-specific IGF-1R knockout mice compared to the wild-type mice. In contrast, low-dose IGF-1 infusion markedly attenuated AngII-induced cardiac fibrosis by inhibiting fibroblast proliferation and differentiation. Mechanistically, we demonstrated that IGF-1-attenuated AngII-induced cardiac fibrosis through the Akt pathway and through suppression of rho-associated coiled-coil containing kinases (ROCK)2-mediated α-smooth muscle actin (αSMA) expression. Our study highlights a novel function of the IGF-1/IGF-1R signaling in agonist-induced cardiac fibrosis. We propose that low-dose IGF-1 may be an efficacious therapeutic avenue against cardiac fibrosis.
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http://dx.doi.org/10.1038/s41419-021-03965-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270920PMC
July 2021

Comparison of in-hospital outcomes of patients with vs. without ischaemic cardiomyopathy undergoing veno-arterial-extracorporeal membrane oxygenation.

ESC Heart Fail 2021 Jun 18. Epub 2021 Jun 18.

Division of Cardiology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Republic of Korea.

Aims: This study aimed to investigate differences in baseline and treatment characteristics, and in-hospital mortality according to the aetiologies of cardiogenic shock in patients undergoing veno-arterial-extracorporeal membrane oxygenation (VA-ECMO).

Methods And Results: The RESCUE registry is a multicentre, observational cohort that includes 1247 patients with cardiogenic shock from 12 centres. A total of 496 patients requiring VA-ECMO were finally selected, and the study population was stratified by cardiogenic shock aetiology [ischaemic cardiomyopathy (ICM, n = 342) and non-ICM (NICM, n = 154)]. The primary outcome of interest was in-hospital mortality. Sensitivity analyses including propensity-score matching adjustments were performed. Mean age of the entire population was 61.8 ± 14.2, and 30.8% were women. There were significant differences in baseline characteristics; notable differences included the older age of patients with ICM (65.1 ± 13.7 vs. 58.2 ± 13.8, P < 0.001), preponderance of males [258 (75.4%) vs. 85 (55.2%), P < 0.001], and higher prevalence of diabetes mellitus [140 (40.9%) vs. 39 (25.3%), P = 0.001] compared with patients in the NICM aetiology group. Patients with ischaemic cardiogenic shock were more likely to have longer shock duration before VA-ECMO implantation (518.7 ± 941.4 min vs. 292.4 ± 707.8 min, P = 0.003) and were less likely to undergo distal limb perfusion than those with NICM [108 (31.6%) vs. 79 (51.3%), P < 0.001]. In-hospital mortality in the overall cohort was 52.2%; patients with ICM had a higher unadjusted risk of in-hospital mortality [203 (59.4%) vs. 56 (36.4%); unadjusted hazard ratio, 2.295; 95% confidence interval, 1.698-3.100; P < 0.001]. There were no significant differences in the primary outcome between the two aetiologies following propensity-score matching multiple adjustments (adjusted hazard ratio, 1.265; 95% confidence interval, 0.840-1.906; P = 0.260).

Conclusions: Results of the current study indicated among patients with cardiogenic shock undergoing VA-ECMO, ischaemic aetiology does not seem to impact in-hospital mortality. These findings underline that early initiation and appropriate treatment strategies of VA-ECMO for patients with ICM shock are required.
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http://dx.doi.org/10.1002/ehf2.13481DOI Listing
June 2021

Clinical Characteristics and Predictors of In-Hospital Mortality in Patients With Cardiogenic Shock: Results From the RESCUE Registry.

Circ Heart Fail 2021 Jun 15;14(6):e008141. Epub 2021 Jun 15.

Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center (J.H.Y., K.H.C., T.K.P., J.M.L., Y.B.S., J.-Y.H., S.-H.C., H.-C.G.), Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: In the current era of mechanical circulatory support, limited data are available on prognosis of cardiogenic shock (CS) caused by various diseases. We investigated the characteristics and predictors of in-hospital mortality in Korean patients with CS.

Methods: The RESCUE study (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With CS) is a multicenter, retrospective, and prospective registry of patients that presented with CS. Between January 2014 and December 2018, 1247 patients with CS were enrolled from 12 major centers in Korea. The primary outcome was in-hospital mortality.

Results: In-hospital mortality rate was 33.6%. The main causes of shock were ischemic heart disease (80.7%), dilated cardiomyopathy (6.1%), myocarditis (3.2%), and nonischemic ventricular arrhythmia (2.5%). Vasopressors were used in 1081 patients (86.7%). The most frequently used vasopressor was dopamine (63.4%) followed by norepinephrine (57.3%). An intraaortic balloon pump was used in 314 patients (25.2%) and extracorporeal membrane oxygenator in 496 patients (39.8%). In multivariable analysis, age ≥70years (odds ratio [OR], 2.73 [95% CI, 1.89-3.94], <0.001), body mass index <25 kg/m (OR, 1.52 [95% CI, 1.08-2.16], =0.017), cardiac arrest at presentation (OR, 2.16 [95% CI, 1.44-3.23], <0.001), vasoactive-inotrope score >80 (OR, 3.55 [95% CI, 2.54-4.95], <0.001), requiring continuous renal replacement therapy (OR, 4.14 [95% CI, 2.88-5.95], <0.001), mechanical ventilator (OR, 3.17 [95% CI, 2.16-4.63], <0.001), intraaortic balloon pump (OR, 1.55 [95% CI, 1.07-2.24], =0.020), and extracorporeal membrane oxygenator (OR, 1.85 [95% CI, 1.25-2.76], =0.002) were independent predictors for in-hospital mortality.

Conclusions: The in-hospital mortality of patients with CS remains high despite the high utilization of mechanical circulatory support. Age, low body mass index, cardiac arrest at presentation, amount of vasopressor, and advanced organ failure requiring various support devices were poor prognostic factors for in-hospital mortality. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008141DOI Listing
June 2021

Rapid Progression of Coronary Atherosclerosis in Patients Taking an Oral Antitumor, Multikinase Receptor Inhibitor.

Circ Cardiovasc Interv 2021 Jun 7;14(6):e010705. Epub 2021 Jun 7.

Division of Hemato-Oncology, Department of Internal Medicine, Chung-Ang University College of Medicine (I.G.H.), Chung-Ang University Hospital, Seoul, Korea.

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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.121.010705DOI Listing
June 2021

Application of Animal Models in Diabetic Cardiomyopathy.

Diabetes Metab J 2021 Mar 25;45(2):129-145. Epub 2021 Mar 25.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.
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http://dx.doi.org/10.4093/dmj.2020.0285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024147PMC
March 2021

P2Y12 inhibitor monotherapy after coronary stenting according to type of P2Y12 inhibitor.

Heart 2021 Mar 23. Epub 2021 Mar 23.

Department of Cardiology, Korea University Guro Hospital, Seoul, Korea (the Republic of).

Objective: To compare P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) with 12-month DAPT according to the type of P2Y12 inhibitor in patients undergoing percutaneous coronary intervention (PCI).

Methods: The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) randomised trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT. In this trial, 2993 patients undergoing successful PCI with drug-eluting stent were enrolled in Korea. As a prespecified analysis, P2Y12 inhibitor monotherapy after 3-month DAPT versus 12-month DAPT were compared among patients receiving clopidogrel and those receiving potent P2Y12 inhibitor (ticagrelor or prasugrel), respectively. The primary endpoint was a composite of all-cause death, myocardial infarction or stroke at 12 months after the index procedure.

Results: Among 2993 patients (mean age 64 years), 58.2% presented with acute coronary syndrome. Clopidogrel was prescribed in 2312 patients (77.2%) and a potent P2Y12 inhibitor in 681 (22.8%). There were no significant differences in the primary endpoint between the P2Y12 inhibitor monotherapy group and the DAPT group among patients receiving clopidogrel (3.0% vs 3.0%; HR: 1.02; 95% CI 0.64 to 1.65; p=0.93) as well as among patients receiving potent P2Y12 inhibitors (2.4% vs 0.7%; HR: 3.37; 95% CI 0.77 to 14.78; p=0.11; interaction p=0.1). Among patients receiving clopidogrel, P2Y12 inhibitor monotherapy compared with DAPT showed consistent treatment effects across various subgroups for the primary endpoint. Among patients receiving potent P2Y12 inhibitors, the rate of bleeding (Bleeding Academic Research Consortium types 2- 5) was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (1.5% vs 5.0%; HR: 0.33; 95% CI 0.12 to 0.87; p=0.03).

Conclusions: Compared with 12-month DAPT, clopidogrel monotherapy after 3-month DAPT showed comparable cardiovascular outcomes in patients undergoing PCI.

Trial Registration Number: NCT02079194.
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http://dx.doi.org/10.1136/heartjnl-2020-318821DOI Listing
March 2021

Differential Prognostic Implications of Vasoactive Inotropic Score for Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock According to Use of Mechanical Circulatory Support.

Crit Care Med 2021 May;49(5):770-780

Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Objectives: To identify whether the prognostic implications of Vasoactive Inotropic Score according to use of mechanical circulatory support differ in the treatment of acute myocardial infarction complicated by cardiogenic shock.

Design: A multicenter retrospective and prospective observational cohort study.

Setting/patient: The REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy registry includes 1,247 patients with cardiogenic shock from 12 centers in Korea. A total of 836 patients with acute myocardial infarction complicated by cardiogenic shock were finally selected, and the study population was stratified by quartiles of Vasoactive Inotropic Score (< 10, 10-30, 30-90, and > 90) for the present study.

Interventions: None.

Measurements And Main Results: Primary endpoint was in-hospital mortality and secondary endpoint was follow-up mortality. Among the study population, 326 patients (39.0%) received medical treatment alone, 218 (26.1%) received intra-aortic balloon pump, and 292 (34.9%) received extracorporeal membrane oxygenation. In-hospital mortality occurred in 305 patients (36.5%) and was significantly higher in patients with higher Vasoactive Inotropic Score (15.6%, 20.8%, 40.2%, and 67.3%, for < 10, 10-30, 30-90, and > 90; p < 0.001). Vasoactive Inotropic Score showed better ability to predict in-hospital mortality in acute myocardial infarction patients with cardiogenic shock who received medical treatment alone (area under the curve: 0.797; 95% CI, 0.728-0.865) than in those who received intra-aortic balloon pump (area under the curve, 0.704; 95% CI, 0.625-0.783) or extracorporeal membrane oxygenation (area under the curve, 0.644; 95% CI, 0.580-0.709). The best cutoff value of Vasoactive Inotropic Score for the prediction of in-hospital mortality also differed according to the use of mechanical circulatory support (16.5, 40.1, and 84.0 for medical treatment alone, intra-aortic balloon pump, and extracorporeal membrane oxygenation, respectively). There was a significant interaction between Vasoactive Inotropic Score as a continuous value and the use of mechanical circulatory support including intra-aortic balloon pump (interaction-p = 0.006) and extracorporeal membrane oxygenation (interaction-p < 0.001) for all-cause mortality during follow-up.

Conclusions: High Vasoactive Inotropic Score was associated with significantly higher in-hospital and follow-up mortality in patients with acute myocardial infarction complicated by cardiogenic shock. The predictive value of Vasoactive Inotropic Score for mortality was significantly higher in acute myocardial infarction patients with cardiogenic shock treated by medical treatment alone than in those treated by mechanical circulatory support such as intra-aortic balloon pump or extracorporeal membrane oxygenation.
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http://dx.doi.org/10.1097/CCM.0000000000004815DOI Listing
May 2021

Adherence to triple-component antihypertensive regimens is higher with single-pill than equivalent two-pill regimens: A randomized controlled trial.

Clin Transl Sci 2021 05 13;14(3):1185-1192. Epub 2021 Feb 13.

Chung-Ang University Hospital, Seoul, Korea.

Using a single-pill combination (SPC) for hypertension (HTN) treatment resulted in better adherence and persistence than a free-equivalent combination in previous observational studies. The aim of this study is to confirm superior adherence with a triple-component SPC compared with an equivalent two-pill regimen in a randomized controlled trial (RCT) using a medication event monitoring system (MEMS). This is a multicenter, open-label, RCT. Subjects were persons with HTN whose clinic blood pressure was not adequately controlled (systolic >140 mmHg or diastolic >90 mmHg) with a dual combination. Eligible patients were randomized to either the triple-component SPC (olmesartan/amlodipine/hydrochlorothiazide 20/5/12.5 mg) group or the equivalent two-pill (olmesartan/hydrochlorothiazide 20/12.5 mg + amlodipine 5 mg) group and maintained for 12 weeks. Primary outcomes were the difference in percentage of doses taken (PDT) and percentage of days with the prescribed dose taken correctly (PDTc) between the single- and two-pill therapy groups, calculated from MEMS data. From 8 hospitals, 145 patients with HTN were randomized. The single-pill group had significantly higher PDT and PDTc than the two-pill group: median (25-75 percentile) PDT 95.1 (86.7-100.0) versus 92.1 (73.0-97.3); and PDTc 91.0 (79.4-96.5) versus 88.6 (69.2-96.3%), P = 0.04 for both by the Wilcoxon rank sum test. The single-pill combination of the triple-component antihypertensive regimen showed better adherence than the equivalent two-pill therapy. Reducing pill burden by means of a single-pill combination is an effective strategy for enhancing adherence to multiple-agent antihypertensive therapy. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Previous studies suggested that the use of a single-pill combination (SPC) in hypertension (HTN) treatment produced better adherence and persistence than a free-equivalent combination. However, supportive data are confined to dual-component SPC and came from observational studies using medication possession ratio as an outcome. WHAT QUESTION DID THIS STUDY ADDRESS? The objective of this study is to investigate whether a triple-component SPC improved medication adherence over an equivalent two-pill combination therapy in a randomized controlled trial using medication event monitoring systems. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Medication adherence in the SPC group was superior to that of two-pill group, confirming previous findings from observational studies. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This finding strongly supports the current HTN treatment guideline to prefer SPC with a higher level of evidence.
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http://dx.doi.org/10.1111/cts.12979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212718PMC
May 2021

Clinical outcomes between calcium channel blockers and angiotensin receptor blockers in hypertensive patients without established cardiovascular diseases during a 3-year follow-up.

Sci Rep 2021 Jan 19;11(1):1783. Epub 2021 Jan 19.

Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 126-1, 5ka, Anam-dong, Sungbuk-ku, Seoul, 136-705, Republic of Korea.

Although both angiotensin receptor blockers (ARBs) and dihydropyridine calcium channel blockers (CCBs) are all suitable for the initiation of antihypertensive treatment, studies investigating efficacy and safety between ARBs and CCBs are limited, and there is no previous study comparing their clinical outcomes during long-term follow-up periods in real world setting. We compared cardiovascular (CV) events between ARBs and CCBs in 464,948 hypertensive adults using the Korean National Health Insurance Service database during a 3-year follow-up. The patients with hypertension without heart failure, ischemic heart disease, cerebrovascular disease, or peripheral artery disease were enrolled. The CV events between only single prescription of CCBs and ARBs were finally compared. The primary endpoint for this study was the first occurrence of a major adverse CV events, defined as the composite of all-cause death, cardiac death, nonfatal myocardial infarction, or nonfatal stroke. ARB was significantly more administered in male and patients with higher income, diabetes mellitus, chronic kidney diseases, and higher Charlson comorbidity index. The primary endpoints occurred in 10,526 patients (5.2%) in the ARB group and in 19,363 patients (7.3%) in the CCB group (p < 0.001) during a 3-year follow-up (HR 0.96, 95% CI 0.93-0.98). All the components of CV events including all-cause death, cardiac death, nonfatal myocardial infarction, and nonfatal stroke occurred more frequently in the CCB group. With multivariable models adjusting age, sex, income, diabetes, chronic kidney disease, and Charlson comorbidity index, the primary endpoints less frequently developed in the ARB group than in the CCB group (HR 0.957, 95% CI 0.933-0.983, p < 0.001). After the propensity-score matching, baseline characteristics were similar and still showed significantly better primary endpoints in ARB group than CCB group (5.3% vs. 5.8%, p < 0.001). In this nationwide population-based simple hypertension study, administration of ARBs showed superior protection against CV events than CCBs during a 3-year follow-up. Our results suggest that ARBs could be preferred over CCBs as the initial choice of antihypertensive treatment regardless of age in real-world practice.
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http://dx.doi.org/10.1038/s41598-021-81373-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815918PMC
January 2021

Effects of Prolonged Dual Antiplatelet Therapy in ST-Segment Elevation vs. Non-ST-Segment Elevation Myocardial Infarction.

Circ J 2021 May 9;85(6):817-825. Epub 2021 Jan 9.

Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine.

Background: The benefits and risks of prolonged dual antiplatelet therapy (DAPT) have not been studied extensively across a broad spectrum of acute coronary syndromes. In this study we investigated whether treatment effects of prolonged DAPT were consistent in patients presenting with ST-segment elevation myocardial infarction (STEMI) vs. non-STEMI (NSTEMI).Methods and Results:As a post hoc analysis of the SMART-DATE trial, effects of ≥12 vs. 6 months DAPT were compared among 1,023 patients presenting with STEMI and 853 NSTEMI patients. The primary outcome was a composite of recurrent myocardial infarction (MI) or stent thrombosis at 18 months after the index procedure. Compared with the 6-month DAPT group, the rate of the composite endpoint was significantly lower in the ≥12-month DAPT group (1.2% vs. 3.8%; hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.12-0.77; P=0.012). The treatment effect of ≥12- vs. 6-month DAPT on the composite endpoint was consistent among NSTEMI patients (0.2% vs. 1.2%, respectively; HR 0.20, 95% CI 0.02-1.70; P=0.140; P=0.718). In addition, ≥12-month DAPT increased Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding among both STEMI (4.4% vs. 2.0%; HR 2.18, 95% CI 1.03-4.60; P=0.041) and NSTEMI (5.1% vs. 2.2%; HR 2.37, 95% CI 1.08-5.17; P=0.031; P=0.885) patients.

Conclusions: Compared with 6-month DAPT, ≥12-month DAPT reduced recurrent MI or stent thrombosis regardless of the type of MI at presentation.
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http://dx.doi.org/10.1253/circj.CJ-20-0704DOI Listing
May 2021

Safety of 3-Month Dual Antiplatelet Therapy After Implantation of Ultrathin Sirolimus-Eluting Stents With Biodegradable Polymer (Orsiro): Results From the SMART-CHOICE Trial.

J Am Heart Assoc 2021 01 21;10(1):e018366. Epub 2020 Dec 21.

Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea.

Background This study sought to investigate the safety of 3-month dual antiplatelet therapy (DAPT) in patients receiving ultrathin sirolimus-eluting stents with biodegradable polymer (Orsiro). Methods and Results The SMART-CHOICE (Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Anti- platelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents) randomized trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT in 2993 patients undergoing percutaneous coronary intervention. The present analysis was a prespecified subgroup analysis for patients receiving Orsiro stents. As a post hoc analysis, comparisons between Orsiro and everolimus-eluting stents were also done among patients receiving 3-month DAPT. Of 972 patients receiving Orsiro stents, 481 patients were randomly assigned to 3-month DAPT and 491 to 12-month DAPT. At 12 months, the target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization, occurred in 8 patients (1.7%) in the 3-month DAPT group and in 14 patients (2.9%) in the 12-month DAPT group (hazard ratio [HR], 0.58; 95% CI, 0.24-1.39; =0.22). In whole population who were randomly assigned to receive 3-month DAPT (n=1495), there was no significant difference in the target vessel failure between the Orsiro group and the everolimus-eluting stent group (n=1014) (1.7% versus 1.8%; HR, 0.96; 95% CI, 0.41-2.22; =0.92). Conclusions In patients receiving Orsiro stents, clinical outcomes at 1 year were similar between the 3-month DAPT followed by P2Y12 inhibitor monotherapy and 12-month DAPT strategies. With 3-month DAPT, there was no significant difference in target vessel failure between Orsiro and everolimus-eluting stents. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02079194.
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http://dx.doi.org/10.1161/JAHA.120.018366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955499PMC
January 2021

Inter-ethnic differences in normal coronary anatomy between Caucasian (Polish) and Asian (Korean) populations.

Eur J Radiol 2020 Sep 18;130:109185. Epub 2020 Jul 18.

Department of Interventional Cardiology and Angiology, Institute of Cardiology, Alpejska 42, 04-628, Warsaw, Poland. Electronic address:

Purpose: Little is known about ethnic differences in the size of coronary arteries in disease-free individuals. Our aim was to compare coronary artery dimensions between Asian and Caucasian population without atherosclerosis.

Methods: One hundred and twelve Caucasian patients without any discernible atherosclerosis detected on coronary computed tomography angiography were matched with 112 Asian patients using sex, age, coronary dominance pattern and body surface area (BSA). Maximal and minimal lumen areas (LA) and diameters (LD) of proximal and middle coronary segments were measured, and the mean values were used for analyses.

Results: Caucasians had larger LA and LD than Asian patients in all proximal coronary segments. Overall, the mean difference in LA and LD was 11.4 % and 5.2 %, respectively. Significant differences were observed for all proximal segments (left anterior descending: 13 % and 6%, left circumflex 14 % and 8% and right coronary artery 8% and 4% for LA and LD), but not for mid segments. The greatest difference between Caucasians and Asians was found in left main coronary artery (LMCA) LA (21.2 ± 6.5 vs.16.8 ± 5.4 mm, p < 0.01 respectively). The independent predictors of larger LA and LD of LMCA and proximal coronary segments were male sex (p < 0.05), Caucasian ethnicity (p < 0.05), and left dominance pattern (p < 0.05).

Conclusion: In subjects without atherosclerosis, Asians have smaller dimensions of all proximal coronary arteries, most prominently displayed in LMCA, than the Caucasians regardless of age, sex, or body size.
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http://dx.doi.org/10.1016/j.ejrad.2020.109185DOI Listing
September 2020

Clinical Usefulness of PRECISE-DAPT Score for Predicting Bleeding Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: An Analysis From the SMART-DATE Randomized Trial.

Circ Cardiovasc Interv 2020 05 1;13(5):e008530. Epub 2020 May 1.

Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (K.H.C., Y.B.S., J.M.L., T.K.P., J.H.Y., J.-H.C., S.-H.C., H.-C.G., J.-Y.H.).

Background: Although the current guidelines endorse the PRECISE-DAPT score (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) to inform clinical decisions regarding duration of DAPT in patients undergoing percutaneous coronary intervention, use of the PRECISE-DAPT score to guide duration of DAPT has not been properly validated by randomized trials focused on the population with acute coronary syndrome. This study aimed to evaluate the usefulness of the PRECISE-DAPT score for predicting future bleeding and ischemic events and to compare clinical outcomes of short-term and long-term DAPT duration according to the PRECISE-DAPT score in patients with acute coronary syndrome.

Methods: This was a substudy of the SMART-DATE trial (6- Versus 12-Month or Longer Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome), in which patients with acute coronary syndrome undergoing percutaneous coronary intervention were randomly assigned to either 6- (n=1357) or 12-month or longer DAPT (n=1355). Major bleeding (Bleeding Academic Research Consortium type 3-5) and ischemic (myocardial infarction, stent thrombosis, or ischemic stroke) events at 18 months after the index procedure were compared between the 6- and 12-month or longer DAPT groups, according to PRECISE-DAPT score.

Results: The PRECISE-DAPT score was moderately effective at predicting bleeding events (area under the curve, 0.754 [95% CI, 0.655-0.854]; <0.001). In patients with nonhigh PRECISE-DAPT score (<25, n=1967 [72.5%]), 6-month DAPT was associated with higher ischemic risk (2.7% versus 1.3%; HR, 2.01 [95% CI, 1.03-3.91]; =0.040; absolute risk difference, +1.3%; =0.035) with similar bleeding risk (0.4% versus 0.3%; HR, 2.00 [95% CI, 0.37-10.94]; =0.422; absolute risk difference, +0.2%; =0.498), compared with 12-month or longer DAPT. Among patients with high PRECISE-DAPT score (≥25, n=745 [27.5%]), 6-month DAPT presented a similar ischemic risk (4.8% versus 3.4%; HR, 1.43 [95% CI, 0.68-2.98], =0.348; absolute risk difference, +1.5%; =0.327) but significantly reduced major bleeding risk (0.6% versus 2.3%; HR, 0.25 [95% CI, 0.05-1.17]; =0.079; absolute risk difference, -1.7%; =0.045).

Conclusions: Consistent with current guidelines, determination of the duration of DAPT according to PRECISE-DAPT score could improve the clinical outcomes in patients with acute coronary syndrome after percutaneous coronary intervention with current-generation drug-eluting stents. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01701453.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008530DOI Listing
May 2020

Usefulness of P Wave Duration in Embolic Stroke of Undetermined Source.

J Clin Med 2020 Apr 15;9(4). Epub 2020 Apr 15.

Cardiovascular & Arrhythmia Center, Chung-Ang University Hospital, Chung-Ang University, Seoul 06973, Korea.

The investigation of the potential association between ischemic stroke and subclinical atrial fibrillation (SCAF) is important for secondary prevention. We aimed to determine whether SCAF can be predicted by atrial substrate measurement with P wave signal-averaged electrocardiography (SAECG). We recruited 125 consecutive patients with embolic stroke of undetermined source (ESUS) and 125 patients with paroxysmal atrial fibrillation as controls. All participants underwent P wave SAECG at baseline, and patients with ESUS were followed up with Holter monitoring and electrocardiography at baseline, 3, 6, and 12 months after discharge and every 6 months thereafter. In the ESUS group, 32 (25.6%) patients were diagnosed with SCAF during follow-up. There were no significant differences between the groups regarding atrial substrate. P wave duration (PWD) was a significant predictor of SCAF. Stroke recurrence occurred in 22 patients (17.6%), and prolonged PWD (≥ 135 ms) predicted stroke recurrence more robustly than SCAF detection. In ESUS patients, PWD can be a useful biomarker to predict SCAF and to identify patients who are more likely to have a recurrent embolic stroke associated with an atrial cardiopathy. Further research is needed for supporting the utility and applicability of PWD.
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http://dx.doi.org/10.3390/jcm9041134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230630PMC
April 2020

Therapeutic strategy for atherosclerosis based on bone-vascular axis hypothesis.

Pharmacol Ther 2020 02 9;206:107436. Epub 2019 Nov 9.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea. Electronic address:

As the world's older population grows, the disease burden of atherosclerosis is rapidly increasing, causing significant morbidity and mortality worldwide. Despite recent improvements in the control of vascular risk factors, a significant number of patients still suffer from vascular events and the progression of atherosclerosis. Aging also results in decreased bone mineral density. Since bones are a home for hematopoietic stem cells as well as reservoirs of the minerals required for vascular integrity, it is conceivable that a novel therapeutic strategy for atherosclerosis treatment can be developed by focusing on the complex interplay between bones and blood vessels. The correction of mineral dyshomeostasis, disrupted bone marrow microenvironments, and triggered inflammatory cell production provide potential therapeutic options against the atherosclerotic process. This review highlights recent advances in our understanding of the bone-vascular link and discusses new insights into treatment targets for atherosclerosis.
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http://dx.doi.org/10.1016/j.pharmthera.2019.107436DOI Listing
February 2020

Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention: The SMART-CHOICE Randomized Clinical Trial.

JAMA 2019 06;321(24):2428-2437

Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Importance: Data on P2Y12 inhibitor monotherapy after short-duration dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention are limited.

Objective: To determine whether P2Y12 inhibitor monotherapy after 3 months of DAPT is noninferior to 12 months of DAPT in patients undergoing PCI.

Design, Setting, And Participants: The SMART-CHOICE trial was an open-label, noninferiority, randomized study that was conducted in 33 hospitals in Korea and included 2993 patients undergoing PCI with drug-eluting stents. Enrollment began March 18, 2014, and follow-up was completed July 19, 2018.

Interventions: Patients were randomly assigned to receive aspirin plus a P2Y12 inhibitor for 3 months and thereafter P2Y12 inhibitor alone (n = 1495) or DAPT for 12 months (n = 1498).

Main Outcomes And Measures: The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 12 months after the index procedure. Secondary end points included the components of the primary end point and bleeding defined as Bleeding Academic Research Consortium type 2 to 5. The noninferiority margin was 1.8%.

Results: Among 2993 patients who were randomized (mean age, 64 years; 795 women [26.6%]), 2912 (97.3%) completed the trial. Adherence to the study protocol was 79.3% of the P2Y12 inhibitor monotherapy group and 95.2% of the DAPT group. At 12 months, major adverse cardiac and cerebrovascular events occurred in 42 patients in the P2Y12 inhibitor monotherapy group and in 36 patients in the DAPT group (2.9% vs 2.5%; difference, 0.4% [1-sided 95% CI, -∞% to 1.3%]; P = .007 for noninferiority). There were no significant differences in all-cause death (21 [1.4%] vs 18 [1.2%]; hazard ratio [HR], 1.18; 95% CI, 0.63-2.21; P = .61), myocardial infarction (11 [0.8%] vs 17 [1.2%]; HR, 0.66; 95% CI, 0.31-1.40; P = .28), or stroke (11 [0.8%] vs 5 [0.3%]; HR, 2.23; 95% CI, 0.78-6.43; P = .14) between the 2 groups. The rate of bleeding was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (2.0% vs 3.4%; HR, 0.58; 95% CI, 0.36-0.92; P = .02).

Conclusions And Relevance: Among patients undergoing percutaneous coronary intervention, P2Y12 inhibitor monotherapy after 3 months of DAPT compared with prolonged DAPT resulted in noninferior rates of major adverse cardiac and cerebrovascular events. Because of limitations in the study population and adherence, further research is needed in other populations.

Trial Registration: ClinicalTrials.gov Identifier: NCT02079194.
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http://dx.doi.org/10.1001/jama.2019.8146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593635PMC
June 2019

Imaging Characteristics of Mismatch Lesions: An Angiographic and Intravascular Ultrasound Analysis of 1369 Coronary Lesions.

Angiology 2019 Sep 21;70(8):756-764. Epub 2019 Jan 21.

2 Heart Research Institute, ChungAng University Hospital, Seoul, Korea.

Objectives: To evaluate the angiographic and intravascular ultrasound (IVUS) characteristics of coronary mismatch lesions.

Background: Better understanding about the characteristics of mismatch lesions may help to achieve more accurate lesion assessment and, thereby, to improve the outcomes of percutaneous coronary intervention (PCI).

Methods: Angiographic and IVUS data from 1369 lesions were analyzed. Mismatch lesion was defined as the difference between proximal and distal reference lumen diameters of ≥1.0 mm or ≥30% of the distal reference lumen diameter.

Results: The incidence of mismatch lesions was 20.1% (275/1369). Compared to nonmismatch group, mismatch group had longer lesions (21.3 [6.4] mm vs 18.4 [6.4] mm, < .001) with smaller minimum lumen diameter (0.87 [0.29] mm vs 1.10 [0.31] mm, < .001) and more severe diameter stenosis (78.8% [9.2%] vs 66.3% [10.3%], < .001). On IVUS, mismatch group had larger lumen area (18.7 [5.0] vs 15.8 [5.1] mm, < .001) but lower plaque burden at the proximal reference segment (41.0% [9.2%] vs 45.7% [9.9%], < .001) and smaller lumen area (4.83 [1.89] vs 7.36 [2.89] mm, < .001) but higher plaque burden at the distal reference segment (42.9% [10.4%] vs 41.4% [10.1%], = .023). Multivariable logistic regression analysis showed that mismatch lesions were frequently accompanied by diffuse lesions (odds ratio [OR] = 2.50; 95% confidence interval [CI]: 1.83-3.40; < .001), bifurcation lesions (OR = 5.83; 95% CI: 4.40-7.74; < .001), and lesions with a low TIMI flow grade (OR = 1.70; 95% CI: 1.08-2.67; = .022) or severe diameter stenosis (OR = 3.05; 95% CI: 2.10-4.43; < .001).

Conclusions: Mismatch lesions are quite common and characterized by greater lesion complexity compared with nonmismatch lesions. Further studies may be necessary to address the impact of this lesion type on the outcome of PCI.
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http://dx.doi.org/10.1177/0003319718822348DOI Listing
September 2019

Percutaneous closure of perimembranous ventricular septal defect using patent ductus arteriosus occluders.

PLoS One 2018 15;13(11):e0206535. Epub 2018 Nov 15.

Intervention Center, Chung-Ang University Hospital, Seoul, South Korea.

Objectives: To assess the safety and efficacy of percutaneous closure of perimembranous ventricular septal defect (PmVSD) using patent ductus arteriosus (PDA) occluders.

Background: Widespread use of conventional PmVSD closure devices has been limited by unacceptable high rate of complete heart block (CHB). The elegant design of PDA occluders is supposed to ease implantation, increase closure rate and minimize damage to adjacent structures. Thus, PDA occluders may reduce complications, especially the CHB, and offer a good alternative for PmVSD closure.

Method: From September 2008 to October 2015, patients who underwent attempted percutaneous VSD closure using PDA occluders were included in the study. Patient demographics, echocardiography measurements, procedure details and follow-up data until October 2017 were collected.

Results: In total, 321 patients with a mean age of 15.5±12.6 years and mean a weight of 33.3±20.5 kg were included in this study. The mean defect size was 4.8±2.1 mm. Implantation was successful in 307 (95.6%) patients. The median follow-up time was 63 months (24 to 108 months). The closure rates were 89.5%, 91.5%, and 99.3% after the procedure 24 hours, 6 months and 2 years, respectively. Major complications occurred in 5 (1.7%) patients during the procedure and follow-up, including persistent CHB in 2 (0.7%) patients and device embolization in 3 (1.0%) patients. No death, disability, or other major complication was detected.

Conclusion: Percutaneous closure of PmVSD using PDA occluders is feasible, safe and efficacious in selected patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206535PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237304PMC
April 2019

Morphological characteristics of optical coherence tomography defined plaque fissure in patients with acute coronary syndrome.

Heart Vessels 2019 Mar 4;34(3):427-434. Epub 2018 Oct 4.

Heart Research Institute, Cardiovascular-Arrhythmia Center, College of Medicine, Chung-Ang University Hospital, 102, Heukseok-ro, Dongjak-gu, Seoul, 06973, Korea.

We assessed the plaque disruption in 245 consecutive patients with acute coronary syndrome undergoing percutaneous coronary intervention. The plaque fissure was diagnosed with optical coherence tomography, and intravascular ultrasound was used to determine arterial remodeling. Of them, 26 fissures were found in this study. The definite fissure was seen in 17 (65.4%) and probable fissure was seen in 9 (34.6%) patients. In 18 (69.2%), plaque fissure component was lipidic or thin-capped fibroatheroma. Eighteen (69.2%) of fissured plaque were seen within 30 mm of coronary ostium. Combined plaque fissure with plaque rupture/erosion was seen in 21 (80.8%) cases. The isolated fissure was seen in 5 (19.2%). Compared to the maximal necrotic core site of the ruptured plaque, the fissure site showed a smaller %necrotic core (p = 0.012), however, greater in fissure site than minimal lumen area site (24.93 ± 11.50% vs 15.34 ± 10.40%, p < 0.0001). The remodeling index was higher at fissure site as compared to minimal lumen area site (1.02 ± 0.22 vs 0.94 ± 0.27; p = 0.047), but similar to the rupture plaque (p = 0.31). The frequency of positive remodeling was 34.6% (9/26) at the plaque fissure. Although the plaque fissure can be interchangeable with the rupture in acute coronary syndrome, the limited extension to the small lipid core might and less positive remodeling provoke a fissuring of the plaque. Further study is necessary to assess the plaque fissure.
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http://dx.doi.org/10.1007/s00380-018-1271-9DOI Listing
March 2019

Impact of left atrial appendage closure on cardiac functional and structural remodeling: A difference-in-difference analysis of propensity score matched samples.

Cardiol J 2019 2;26(5):519-528. Epub 2018 May 2.

Cardiovascular Center, Chung-Ang University Hospital, Seoul, South Korea.

Background: Although the safety and efficacy of left atrial (LA) appendage (LAA) closure (LAAC) in nonvalvular atrial fibrillation (NVAF) patients have been well documented in randomized controlled trials and real-world experience, there are limited data in the literature about the impact of LAAC on cardiac remodeling. The aim of the study was to examine the impact of LAAC on cardiac functional and structural remodeling in NVAF patients.

Methods: Between March 2014 and November 2016, 47 NVAF patients who underwent LAAC were included in this study (LAAC group). A control group (non-LAAC group) was formed from 141 NVAF patients without LAAC using propensity score matching. The difference-in-difference analysis was used to evaluate the difference in cardiac remodeling between the two groups at baseline and follow-up evaluations.

Results: The LAAC group had a larger increase in LA dimension, volume and volume index than the non-LAAC group (+3.9 mm, p = 0.001; +9.7 mL, p = 0.006 and +5.9 mL/m2, p = 0.011, respectively). Besides, a significant increase in E and E/e' ratio was also observed in the LAAC group (+14.6 cm/s, p = 0.002 and +2.3, p = 0.028, respectively). Compared with the non-LAAC group, left ventricular (LV) ejection fraction and fractional shortening decreased in LAAC patients, but were statistically insignificant (-3.5%, p = 0.109 and -2.0%, p = 0.167, respectively).

Conclusions: There were significant increases in LA size and LV filling pressure among NVAF patients after LAAC. These impacts of LAAC on cardiac functional and structural remodeling may have some clinical implications that need to be addressed in future studies.
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http://dx.doi.org/10.5603/CJ.a2018.0047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084400PMC
July 2020

6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial.

Lancet 2018 03 12;391(10127):1274-1284. Epub 2018 Mar 12.

Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address:

Background: Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population.

Methods: We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2-5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453.

Findings: Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; p=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2·6%] patients vs 39 [2·9%]; hazard ratio [HR] 0·90 [95% CI 0·57-1·42]; p=0·90) and neither did stroke (11 [0·8%] patients vs 12 [0·9%]; 0·92 [0·41-2·08]; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8%] patients vs ten [0·8%]; 2·41 [1·15-5·05]; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 [95% CI 0·68-3·35]; p=0·32). The rate of BARC type 2-5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 [95% CI 0·45-1·05]; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis.

Interpretation: The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care.

Funding: Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.
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http://dx.doi.org/10.1016/S0140-6736(18)30493-8DOI Listing
March 2018

Connexin43 and zonula occludens-1 are targets of Akt in cardiomyocytes that correlate with cardiac contractile dysfunction in Akt deficient hearts.

Biochim Biophys Acta Mol Basis Dis 2018 Apr 31;1864(4 Pt A):1183-1191. Epub 2018 Jan 31.

Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. Electronic address:

While deletion of Akt1 results in a smaller heart size and Akt2 mice are mildly insulin resistant, Akt1/Akt2 mice exhibit perinatal lethality, indicating a large degree of functional overlap between the isoforms of the serine/threonine kinase Akt. The present study aimed to determine the cooperative contribution of Akt1 and Akt2 on the structure and contractile function of adult hearts. To generate an inducible, cardiomyocyte-restricted Akt2 knockout (KO) model, Akt2 mice were crossed with tamoxifen-inducible MerCreMer transgenic (MCM) mice and germline Akt1 mice to generate the following genotypes:Akt1; Akt2 (WT), Akt2; α-MHC-MCM (iAkt2 KO), Akt1, and Akt1; Akt2; α-MHC-MCM mice (Akt1/iAkt2 KO). At 28 days after the first tamoxifen injection, Akt1/iAkt2 KO mice developed contractile dysfunction paralleling increased atrial and brain natriuretic peptide (ANP and BNP) levels, and repressed mitochondrial gene expression. Neither cardiac fibrosis nor apoptosis were detected in Akt1/iAkt2 KO hearts. To explore potential molecular mechanisms for contractile dysfunction, we investigated myocardial microstructure before the onset of heart failure. At 3 days after the first tamoxifen injection, Akt1/iAkt2 KO hearts showed decreased expression of connexin43 (Cx43) and connexin-interacting protein zonula occludens-1 (ZO-1). Furthermore, Akt1/2 silencing significantly decreased both Cx43 and ZO-1 expression in cultured neonatal rat cardiomyocytes in concert with reduced beating frequency. Akt1 and Akt2 are required to maintain cardiac contraction. Loss of Akt signaling disrupts gap junction protein, which might precipitate early contractile dysfunction prior to heart failure in the absence of myocardial remodeling, such as hypertrophy, fibrosis, or cell death.
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http://dx.doi.org/10.1016/j.bbadis.2018.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342503PMC
April 2018

Insulin-like growth factor-1 signaling in cardiac aging.

Biochim Biophys Acta Mol Basis Dis 2018 May 25;1864(5 Pt B):1931-1938. Epub 2017 Aug 25.

Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. Electronic address:

Cardiovascular disease (CVD) is the leading cause of death in most developed countries. Aging is associated with enhanced risk of CVD. Insulin-like growth factor-1 (IGF-1) binds to its cognate receptor, IGF-1 receptor (IGF-1R), and exerts pleiotropic effects on cell growth, differentiation, development, and tissue repair. Importantly, IGF-1/IGF-1R signaling is implicated in cardiac aging and longevity. Cardiac aging is an intrinsic process that results in cardiac dysfunction, accompanied by molecular and cellular changes. In this review, we summarize the current state of knowledge regarding the link between the IGF-1/IGF-1R system and cardiac aging. The biological effects of IGF-1R and insulin receptor will be discussed and compared. Furthermore, we describe data regarding how deletion of IGF-1R in cardiomyocytes of aged knockout mice may delay the development of senescence-associated myocardial pathologies. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.
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http://dx.doi.org/10.1016/j.bbadis.2017.08.029DOI Listing
May 2018

Safety and efficacy of transradial coronary angiography and intervention in patients older than 80 years: from the Korean Transradial Intervention Prospective Registry.

J Geriatr Cardiol 2017 Feb;14(2):81-86

Department of Cardiology, Korea University Guro Hospital, Seoul, South Korea.

Background: Radial artery access for coronary procedures is a safe and beneficial technique. However, elderly patients have been considered as a higher risk group of access site related complications compared to younger patients. This study was conducted to investigate the feasibility and safety of transradial coronary angiography or intervention in the elderly.

Methods: A total of 6132 patients from Korean Transradial Intervention Prospective Registry at 20 centers were analyzed. Patients were divided into the non-elderly group ( = 5667) and the elderly (≥ 80 years) group ( = 465). Using propensity score matching, the elderly group ( = 465) was compared with one-to-one matched the non-elderly group ( = 465).

Results: After propensity score matching, mean age was 64.3 ± 10.3 years in the non-elderly group and 83.5 ± 3.3 years in the elderly group. There was no difference of procedural characteristics, procedural and fluoroscopic times. Access site cross-over rate was not different between the non-elderly group and elderly group (7.5% 6.2%, = 0.074). Bleeding complications occurred similarly in two groups (2.6% of the non-elderly group 1.9% of the elderly group, = 0.660). Access site complications were 1.9% of the non-elderly group and 0.9% of the elderly group ( = 0.263). Both of in hospital death and cardiovascular death for one year were also similar between two groups.

Conclusions: Transradial angiography or intervention was safe and feasible in elderly patients. Complication rates and clinical outcomes in elderly patients were comparable with those in non-elderly patients.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2017.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409348PMC
February 2017

Diabetic cardiomyopathy: where we are and where we are going.

Korean J Intern Med 2017 May 18;32(3):404-421. Epub 2017 Apr 18.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

The global burden of diabetes mellitus and its related complications are currently increasing. Diabetes mellitus affects the heart through various mechanisms including microvascular impairment, metabolic disturbance, subcellular component abnormalities, cardiac autonomic dysfunction, and a maladaptive immune response. Eventually, diabetes mellitus can cause functional and structural changes in the myocardium without coronary artery disease, a disorder known as diabetic cardiomyopathy (DCM). There are many diagnostic tools and management options for DCM, although it is difficult to detect its development and effectively prevent its progression. In this review, we summarize the current research regarding the pathophysiology and pathogenesis of DCM. Moreover, we discuss emerging diagnostic evaluation methods and treatment strategies for DCM, which may help our understanding of its underlying mechanisms and facilitate the identification of possible new therapeutic targets.
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http://dx.doi.org/10.3904/kjim.2016.208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432803PMC
May 2017

Plaque Vulnerability as Assessed by Radiofrequency Intravascular Ultrasound in Patients with Valvular Calcification.

PLoS One 2016 2;11(11):e0165885. Epub 2016 Nov 2.

Heart Research Institute, Chung-Ang University Hospital, Seoul, 06973, Korea.

Background: Cardiac valvular calcification is associated with the overall coronary plaque burden and considered an independent cardiovascular risk and prognostic factor. The purpose of this study was to evaluate the relationship between the presence of valvular calcification and plaque morphology and/or vulnerability.

Methods: Transthoracic echocardiography was used to assess valvular calcification in 280 patients with coronary artery disease who underwent radiofrequency intravascular ultrasound (Virtual Histology IVUS, VH-IVUS). A propensity score-matched cohort of 192 patients (n = 96 in each group) was analyzed. Thin-capped fibroatheroma (TCFA) was defined as a necrotic core (NC) >10% of the plaque area with a plaque burden >40% and NC in contact with the lumen for ≥3 image slices. A remodeling index (lesion/reference vessel area) >1.05 was considered to be positive.

Results: Patients were divided into two groups: any calcification in at least one valve (152 patients) vs. no detectable valvular calcification (128 patients). Groups were similar in terms of age, risk factors, clinical diagnosis, and angiographic analysis after propensity score-matched analysis. Gray-scale IVUS analysis showed that the vessel size, plaque burden, minimal lumen area, and remodeling index were similar. By VH-IVUS, % NC and % dense calcium (DC) were greater in patients with valvular calcification (p = 0.024, and p = 0.016, respectively). However, only % DC was higher at the maximal NC site by propensity score-matched analysis (p = 0.029). The frequency of VH-TCFA occurrence was higher depending on the complexity (p = 0.0064) and severity (p = 0.013) of valvular calcification.

Conclusions: There is a significant relationship between valvular calcifications and VH-IVUS assessment of TCFAs. Valvular calcification indicates a greater atherosclerosis disease complexity (increased calcification of the coronary plaque) and vulnerable coronary plaques (higher incidence of VH-TCFA).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165885PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091909PMC
June 2017

Gender differences in plaque characteristics of culprit lesions in patients with ST elevation myocardial infarction.

Heart Vessels 2016 Nov 13;31(11):1767-1775. Epub 2016 Feb 13.

Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan-doro, Dong-gu, Ulsan, 682-714, South Korea.

There is limited research on plaque characteristics of ST elevation myocardial infarction (STEMI) patients according to the gender and age. 280 Consecutive STEMI patients who underwent VH-IVUS imaging on culprit before percutaneous coronary intervention (PCI) were enrolled in this study. Women were significantly older than men (69.8 ± 10 vs. 55.9 ± 11.3, p < 0.001). After propensity matching, men had higher plaque burden (79.7 ± 7.8 vs. 73.7 ± 13.0 %, p = 0.010), more fibro-fatty tissue (12.8 ± 9.9 vs. 9.5 ± 6.8 %, p = 0.04) and less dense calcium than women (8.4 ± 5.8 vs. 12.3 ± 8.7 %, p = 0.007). Subgroups dividing by 50, 65, 75 years old, plaque burden was higher in elderly men aged 66-75 years compared to the young men aged less than 50 (75.5 ± 9.2 vs. 68.4 ± 10.1 %, p = 0.012). And middle aged men ranged 51-65 years showed significantly more plaque burden at minimal lumen area site than matched aged women (77.5 ± 8.0 vs. 69.0 ± 17.6 %, p = 0.012). Elderly women aged 66-75 years showed significantly more necrotic core (28.6 ± 7.3 %) and dense calcium (14.9 ± 7.5 %) compared to all the younger or matched subgroups of men. These differences in plaque composition are blunted in the very elderly of men and women aged over 75 years. The findings may explain the gender differences in clinical prognosis in STEMI patients.
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http://dx.doi.org/10.1007/s00380-016-0806-1DOI Listing
November 2016

Is Stopping Heparin Safe in Patients on Extracorporeal Membrane Oxygenation Treatment?

ASAIO J 2017 Jan/Feb;63(1):32-36

From the *Departments of Thoracic and Cardiovascular Surgery, †Cardiology, ‡Emergency Medicine, and §Anesthesiology and Pain Medicine, Chung-Ang University Hospital, Seoul, Korea.

Anticoagulation treatment during extracorporeal membrane oxygenation (ECMO) treatment is unavoidable. However, discontinuation of heparin infusion is necessary when challenges associated with the use of heparin, such as bleeding and thrombocytopenia, are encountered. The medical records of 94 adult (age ≥ 18 years) patients treated with ECMO from January 2011 to March 2015, at Chung-Ang University Hospital, Seoul, Korea, were reviewed. Among the 94 patients, 55 patients underwent ECMO treatment for three or more days. In 52.7% of these patients (n = 29, group A), heparin was stopped for three or more days because of thrombocytopenic events (< 50,000 cells/mm), higher than target range (> 230 seconds) activated clotting time (ACT), bleeding complications, or the need for other surgical procedures. In 43.6% of patients (n = 24, group B), heparin was continuously infused during the entire ECMO process. The mean length of ECMO support after the initiation of heparin discontinuation in patients in group A was 10.2 ± 14.7 days. There were no intracardiac, intravascular, or intracircuit thrombotic complications in group A. There was no difference in the ECMO weaning success rate between the two groups (41.4% in group A vs. 54.2% in group B, p = 0.353). Heparin discontinuation can be considered in a select group of patients with coagulation abnormalities or bleeding.
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http://dx.doi.org/10.1097/MAT.0000000000000442DOI Listing
October 2017

Multimodality Intravascular Imaging Assessment of Plaque Erosion versus Plaque Rupture in Patients with Acute Coronary Syndrome.

Korean Circ J 2016 Jul 21;46(4):499-506. Epub 2016 Jul 21.

Heart Research Institute, Cardiovascular-Arrhythmia Center, College of Medicine, Chung-Ang University Hospital, Seoul, Korea.

Background And Objectives: We assessed plaque erosion of culprit lesions in patients with acute coronary syndrome in real world practice.

Subjects And Methods: Culprit lesion plaque rupture or plaque erosion was diagnosed with optical coherence tomography (OCT). Intravascular ultrasound (IVUS) was used to determine arterial remodeling. Positive remodeling was defined as a remodeling index (lesion/reference EEM [external elastic membrane area) >1.05.

Results: A total of 90 patients who had plaque rupture showing fibrous-cap discontinuity and ruptured cavity were enrolled. 36 patients showed definite OCT-plaque erosion, while 7 patients had probable OCT-plaque erosion. Overall, 26% (11/43) of definite/probable plaque erosion had non-ST elevation myocardial infarction (NSTEMI) while 35% (15/43) had ST elevation myocardial infarction (STEMI). Conversely, 14.5% (13/90) of plaque rupture had NSTEMI while 71% (64/90) had STEMI (p<0.0001). Among plaque erosion, white thrombus was seen in 55.8% (24/43) of patients and red thrombus in 27.9% (12/43) of patients. Compared to plaque erosion, plaque rupture more often showed positive remodeling (p=0.003) with a larger necrotic core area examined by virtual histology (VH)-IVUS, while negative remodeling was prominent in plaque erosion. Overall, 65% 28/43 of plaque erosions were located in the proximal 30 mm of a culprit vessel-similar to plaque ruptures (72%, 65/90, p=0.29).

Conclusion: Although most of plaque erosions show nearly normal coronary angiogram, modest plaque burden with negative remodeling and an uncommon fibroatheroma might be the nature of plaque erosion. Multimodality intravascular imaging with OCT and VH-IVUS showed fundamentally different pathoanatomic substrates underlying plaque rupture and erosion.
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http://dx.doi.org/10.4070/kcj.2016.46.4.499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965428PMC
July 2016
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