http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Matricellular Protein CCN5 Reverses Established Cardiac Fibrosis
Jeong, Dongtak,Lee, Min-Ah,Li, Yan,Yang, Dong Kwon,Kho, Changwon,Oh, Jae Gyun,Hong, Gyeongdeok,Lee, Ahyoung,Song, Min Ho,LaRocca, Thomas J.,Chen, Jiqiu,Liang, Lifan,Mitsuyama, Shinichi,D'Escamard, Val American College of Cardiology 2016 Journal of the American College of Cardiology Vol.67 No.13
<P><B>Abstract</B></P><P><B>Background</B></P><P>Cardiac fibrosis (CF) is associated with increased ventricular stiffness and diastolic dysfunction and is an independent predictor of long-term clinical outcomes of patients with heart failure (HF). We previously showed that the matricellular CCN5 protein is cardioprotective via its ability to inhibit CF and preserve cardiac contractility.</P><P><B>Objectives</B></P><P>This study examined the role of CCN5 in human heart failure and tested whether CCN5 can reverse established CF in an experimental model of HF induced by pressure overload.</P><P><B>Methods</B></P><P>Human hearts were obtained from patients with end-stage heart failure. Extensive CF was induced by applying transverse aortic constriction for 8 weeks, which was followed by adeno-associated virus-mediated transfer of CCN5 to the heart. Eight weeks following gene transfer, cellular and molecular effects were examined.</P><P><B>Results</B></P><P>Expression of CCN5 was significantly decreased in failing hearts from patients with end-stage heart failure compared to nonfailing hearts. Trichrome staining and myofibroblast content measurements revealed that the established CF had been reversed by CCN5 gene transfer. Anti-CF effects of CCN5 were associated with inhibition of the transforming growth factor beta signaling pathway. CCN5 significantly inhibited endothelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation, which are 2 critical processes for CF progression, both in vivo and in vitro. In addition, CCN5 induced apoptosis in myofibroblasts, but not in cardiomyocytes or fibroblasts, both in vivo and in vitro. CCN5 provoked the intrinsic apoptotic pathway specifically in myofibroblasts, which may have been due the ability of CCN5 to inhibit the activity of NFκB, an antiapoptotic molecule.</P><P><B>Conclusions</B></P><P>CCN5 can reverse established CF by inhibiting the generation of and enhancing apoptosis of myofibroblasts in the myocardium. CCN5 may provide a novel platform for the development of targeted anti-CF therapies.</P>
Jeong, Han Saem,Hong, Soon Jun,Cho, Sang-A,Kim, Jong-Ho,Cho, Jae Young,Lee, Seung Hun,Joo, Hyung Joon,Park, Jae Hyoung,Yu, Cheol Woong,Lim, Do-Sun American College of Cardiology 2017 JACC. Cardiovascular interventions Vol.10 No.16
<P>CONCLUSIONS Compared with prasugrel, ticagrelor significantly decreased inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha and increased circulating EPCs, contributing to improved arterial endothelial function in diabetic non-ST-segment elevation acute coronary syndrome patients. Thus, data support that pleiotropic effects of ticagrelor beyond its potent antiplatelet effects could contribute to additional clinical benefits. (C) 2017 by the American College of Cardiology Foundation.</P>
Temporal Trends of De Novo Malignancy Development After Heart Transplantation
Youn, Jong-Chan,Stehlik, Josef,Wilk, Amber R.,Cherikh, Wida,Kim, In-Cheol,Park, Gyeong-Hun,Lund, Lars H.,Eisen, Howard J.,Kim, Do Young,Lee, Sun Ki,Choi, Suk-Won,Han, Seongwoo,Ryu, Kyu-Hyung,Kang, Seo American College of Cardiology 2018 Journal of the American College of Cardiology Vol.71 No.1
<P><B>Central Illustration</B></P><P>[Figure]</P><P><B>Abstract</B></P><P><B>Background</B></P><P>Malignancy is a concern in cardiac transplant recipients, but the temporal trends of de novo malignancy development are unknown.</P><P><B>Objectives</B></P><P>The goal of this study was to describe the temporal trends of the incidence, types, and predictors of de novo malignancy in cardiac transplant recipients.</P><P><B>Methods</B></P><P>The authors analyzed the temporal trends of post-transplant incidence, types, and predictors of malignancy using 17,587 primary adult heart-only transplant recipients from the International Society for Heart and Lung Transplantation registry. The main study outcomes included the incidence of, types of, and time to de novo malignancy.</P><P><B>Results</B></P><P>The risk of any de novo solid malignancy between years 1 and 5 after transplantation was 10.7%. The cumulative incidence by malignancy type was: skin cancer (7.0%), non-skin solid cancer (4.0%), and lymphoproliferative disorders (0.9%). There was no temporal difference in the time to development according to malignancy type. However, the cumulative incidence of de novo solid malignancy increased from 2000 to 2005 vs. 2006 to 2011 (10.0% vs. 12.4%; p < 0.0001). Survival in patients after de novo malignancy was markedly lower than in patients without malignancy (p < 0.0001). Older recipients and patients who underwent transplantation in the recent era had a higher risk of de novo malignancy.</P><P><B>Conclusions</B></P><P>More than 10% of adult heart transplant recipients developed de novo malignancy between years 1 and 5 after transplantation, and this outcome was associated with increased mortality. The incidence of post-transplant de novo solid malignancy increased temporally, with the largest increase in skin cancer. Individualized immunosuppression strategies and enhanced cancer screening should be studied to determine whether they can reduce the adverse outcomes of post-transplantation malignancy.</P>
Chang, Hyuk-Jae,Lin, Fay Y.,Gebow, Dan,An, Hae Young,Andreini, Daniele,Bathina, Ravi,Baggiano, Andrea,Beltrama, Virginia,Cerci, Rodrigo,Choi, Eui-Young,Choi, Jung-Hyun,Choi, So-Yeon,Chung, Namsik,Cole American College of Cardiology 2019 JACC. Cardiovascular imaging Vol.12 No.7
<P><B>Graphical abstract</B></P><P>[Figure]</P><P><B>Abstract</B></P><P><B>Objectives</B></P><P>This study compared the safety and diagnostic yield of a selective referral strategy using coronary computed tomographic angiography (CCTA) compared with a direct referral strategy using invasive coronary angiography (ICA) as the index procedure.</P><P><B>Background</B></P><P>Among patients presenting with signs and symptoms suggestive of coronary artery disease (CAD), a sizeable proportion who are referred to ICA do not have a significant, obstructive stenosis.</P><P><B>Methods</B></P><P>In a multinational, randomized clinical trial of patients referred to ICA for nonemergent indications, a selective referral strategy was compared with a direct referral strategy. The primary endpoint was noninferiority with a multiplicative margin of 1.33 of composite major adverse cardiovascular events (blindly adjudicated death, myocardial infarction, unstable angina, stroke, urgent and/or emergent coronary revascularization or cardiac hospitalization) at a median follow-up of 1-year.</P><P><B>Results</B></P><P>At 22 sites, 823 subjects were randomized to a selective referral and 808 to a direct referral strategy. At 1 year, selective referral met the noninferiority margin of 1.33 (p = 0.026) with a similar event rate between the randomized arms of the trial (4.6% vs. 4.6%; hazard ratio: 0.99; 95% confidence interval: 0.66 to 1.47). Following CCTA, only 23% of the selective referral arm went on to ICA, which was a rate lower than that of the direct referral strategy. Coronary revascularization occurred less often in the selective referral group compared with the direct referral to ICA (13% vs. 18%; p < 0.001). Rates of normal ICA were 24.6% in the selective referral arm compared with 61.1% in the direct referral arm of the trial (p < 0.001).</P><P><B>Conclusions</B></P><P>In stable patients with suspected CAD who are eligible for ICA, the comparable 1-year major adverse cardiovascular events rates following a selective referral and direct referral strategy suggests that both diagnostic approaches are similarly effective. In the selective referral strategy, the reduced use of ICA was associated with a greater diagnostic yield, which supported the usefulness of CCTA as an efficient and accurate method to guide decisions of ICA performance. (Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization [CONSERVE]; NCT01810198)</P>
Shin, Dong-Ho,Hong, Sung-Jin,Mintz, Gary S.,Kim, Jung-Sun,Kim, Byeong-Keuk,Ko, Young-Guk,Choi, Donghoon,Jang, Yangsoo,Hong, Myeong-Ki American College of Cardiology 2016 JACC. Cardiovascular interventions Vol.9 No.21
<P>CONCLUSIONS Compared with angiographic guidance, IVUS-guided new-generation DES implantation was associated with favorable outcomes in terms of major adverse cardiac events, the composite of cardiac death, myocardial infarction, or stent thrombosis. These findings must be interpreted only for complex lesions, because all identified patients had long lesions or chronic total occlusions.</P>
Yang, Dong Hyun,Kang, Soo-Jin,Koo, Hyun Jung,Kweon, Jihoon,Kang, Joon-Won,Lim, Tae-Hwan,Jung, Joonho,Kim, Namkug,Lee, June-Goo,Han, Seungbong,Ahn, Jung-Min,Park, Duk-Woo,Lee, Seung-Whan,Lee, Cheol Wha American College of Cardiology 2019 JACC. Cardiovascular imaging Vol.12 No.4
<P><B>Graphical abstract</B></P><P>[Figure]</P><P><B>Abstract</B></P><P><B>Objectives</B></P><P>This study examined the incremental value of subtended myocardial mass (V<SUB>sub</SUB>) as assessed by coronary computed tomography angiography (CTA) for identifying lesion-specific ischemia verified by invasive fractional flow reserve (FFR) in quantitative coronary CTA.</P><P><B>Background</B></P><P>FFR is determined not only by coronary stenosis severity, but also by V<SUB>sub</SUB>. One-step evaluation of combined V<SUB>sub</SUB> and coronary lesion morphology may improve the accuracy of coronary CTA for identifying ischemia-producing lesions.</P><P><B>Methods</B></P><P>A total of 246 intermediate coronary artery lesions (30% to 80% diameter stenosis) in 220 patients (mean age 61.7 years, 168 men) interrogated by FFR were retrospectively studied. Coronary CTA data were used to assess the V<SUB>sub</SUB> by coronary artery stenosis, minimal lumen area (MLA), percentage of aggregated plaque volume (%APV), positive remodeling, and low-attenuation plaque. The ability of V<SUB>sub</SUB>/MLA<SUP>2</SUP> to discriminate lesions with FFR ≤0.80 was examined. Diagnostic performance, odds ratios, and category-less net reclassification improvements of coronary CTA parameters for FFR-verified (≤0.80) ischemia were evaluated. On-site computed tomography (CT) derived–FFR (CT-FFR) and quantitative coronary angiography (QCA) data were also compared.</P><P><B>Results</B></P><P>Of 246 lesions, 84 (34.1%) showed an FFR ≤0.80. V<SUB>sub</SUB> was independently associated with an FFR ≤0.80 (odds ratio: 1.04/1 cm<SUP>3</SUP>; p = 0.032) and showed incremental value over MLA. V<SUB>sub</SUB>/MLA<SUP>2</SUP> >4.16 was the best single parameter for discriminating an FFR ≤0.80 with 83.3% sensitivity and 67.9% specificity. The area under the curve (AUC) of V<SUB>sub</SUB>/MLA<SUP>2</SUP> >4.16 (0.80 [95% confidence interval: 0.75 to 0.85]) was better than that of MLA (change in [Δ]AUC: 0.069; p < 0.001), %APV (ΔAUC: 0.096; p = 0.017), and diameter stenosis of QCA (ΔAUC: 0.080; p = 0.037) and was comparable to that of CT-FFR (AUC 0.77; ΔAUC: 0.035; p = 0.304).</P><P><B>Conclusions</B></P><P>V<SUB>sub</SUB> is an independent determinant of an FFR ≤0.80. The mathematical index of V<SUB>sub</SUB>/MLA<SUP>2</SUP> >4.16 assessed by coronary CTA shows better diagnostic performance for the detection of ischemia-producing lesions than CT-derived MLA alone or %APV and QCA parameters and was comparable to that of on-site CT-FFR.</P>
Yoon, Yeonyee E.,Kim, Kyoung Min,Han, Jong Soo,Kang, Si-Hyuck,Chun, Eun Ju,Ahn, Soyeon,Kim, Sun Mi,Choi, Sang Il,Yun, Bo La,Suh, Jung-Won American College of Cardiology 2019 JACC CARDIOVASCULAR IMAGING Vol.12 No.7
<P><B>Graphical abstract</B></P><P>[Figure]</P><P><B>Abstract</B></P><P><B>Objectives</B></P><P>This study sought to determine whether evaluations of breast arterial calcification (BAC) and low bone mass (LBM) could improve the ability to predict subclinical coronary artery disease (CAD) in asymptomatic women.</P><P><B>Background</B></P><P>An improved risk stratification strategy beyond the measurement of conventional risk factors is needed to identify women at high risk of CAD.</P><P><B>Methods</B></P><P>The BBC (Women Health Registry Study for Bone, Breast, and Coronary Artery Disease) enrolled 2,100 asymptomatic women who underwent dual-energy X-ray absorptiometry, digital mammography, and coronary computed tomography angiography. We assessed the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk and evaluated the presence and severity of BAC, LBM, coronary artery calcification (CAC), and coronary atherosclerotic plaque (CAP).</P><P><B>Results</B></P><P>CAC and CAP were found in 11.2% and 15.6% of participants, respectively. In women with CAC or CAP, increasing trends in the presence and severity of both BAC and LBM were observed. Both BAC and LBM were found to be associated with the presence of CAC (unadjusted odds ratios [OR]: 3.54 and 2.22, respectively) and CAP (unadjusted OR: 3.02 and 1.91, respectively). However, in multivariate analysis, only the presence of BAC and BAC score remained as independent predictors. For the prediction of CAC and CAP, addition of the BAC presence to the 10-year ASCVD risk significantly increased the areas under the curve (area under the curve: 0.71 to 0.72; p = 0.016; and area under the curve: 0.66 to 0.68; p = 0.010; respectively) and resulted in net reclassification index improvements (area under the curve: 0.304; p <0.001; and area under the curve: 0.245; p <0.001; respectively).</P><P><B>Conclusions</B></P><P>The presence and severity of BAC and LBM were significantly associated with the risk of subclinical CAD in asymptomatic women. BAC evaluation especially provides an independent and incremental value over conventional risk algorithms. (Women Health Cohort for Breast, Bone and Coronary Artery Disease [BBC]; NCT03235622)</P>