Korean Circulation Journal最新文献

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Real-World Experience of Mavacamten for Patients With Obstructive Hypertrophic Cardiomyopathy in South Korea: A Prospective Multi-Center Observational Study.
IF 3 3区 医学
Korean Circulation Journal Pub Date : 2025-03-19 DOI: 10.4070/kcj.2024.0443
Jaehyun Lim, Jae Yeong Cho, Soongu Kwak, Chan-Soon Park, Jiesuck Park, Hong-Mi Choi, Goo-Yeong Cho, Ga Hui Choi, Jihoon Kim, Jin-Oh Na, Sun Hwa Lee, Mi-Hyang Jung, Kye Hun Kim, Hae Ok Jung, Sang-Chol Lee, Hyung-Kwan Kim
{"title":"Real-World Experience of Mavacamten for Patients With Obstructive Hypertrophic Cardiomyopathy in South Korea: A Prospective Multi-Center Observational Study.","authors":"Jaehyun Lim, Jae Yeong Cho, Soongu Kwak, Chan-Soon Park, Jiesuck Park, Hong-Mi Choi, Goo-Yeong Cho, Ga Hui Choi, Jihoon Kim, Jin-Oh Na, Sun Hwa Lee, Mi-Hyang Jung, Kye Hun Kim, Hae Ok Jung, Sang-Chol Lee, Hyung-Kwan Kim","doi":"10.4070/kcj.2024.0443","DOIUrl":"https://doi.org/10.4070/kcj.2024.0443","url":null,"abstract":"<p><strong>Background and objectives: </strong>Mavacamten has shown promise in obstructive hypertrophic cardiomyopathy (oHCM); however, real-world evidence is limited in Asians. We aimed to provide the first multicenter, real-world analysis of mavacamten use in Korea.</p><p><strong>Methods: </strong>This prospective observational study included symptomatic oHCM patients treated at 7 tertiary hospitals in Korea. Changes in key parameters, including left ventricular outflow tract (LVOT) gradients, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and New York Heart Association functional class (NYHA Fc), were serially assessed. Adverse events, including death, arrhythmia, and heart failure hospitalizations were documented.</p><p><strong>Results: </strong>Forty-six patients were followed for a median of 147 days (interquartile range 56-205). There was one sudden cardiac death and one non-cardiac death. Resting and Valsalva LVOT gradients significantly decreased from 58.4±46.4 mmHg and 92.6±46.8 mmHg to 17.5±21.3 mmHg and 25.7±27.1 mmHg, respectively (both p<0.001). NT-proBNP levels also decreased significantly, strongly correlating with LVOT gradient reductions. Among the 44 survivors, 25 (58.1%) had at least one NYHA Fc improvement. Moreover, left atrial volume and maximal left ventricular (LV) wall thickness significantly decreased. However, mean reduction in LV ejection fraction (LVEF) was -3.4% with one patient experiencing LVEF <50%. We observed 2 newly-detected atrial fibrillations and 2 ischemic strokes.</p><p><strong>Conclusions: </strong>This first real-world experience of mavacamten in Korean patients with oHCM demonstrates its efficacy and safety, aligning with previous pivotal trials. With the implementation of national insurance coverage, mavacamten will be more accessible to broader oHCM population, offering a non-invasive and effective therapeutic option aside from invasive septal reduction therapies.</p>","PeriodicalId":17850,"journal":{"name":"Korean Circulation Journal","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Increasing Very Low-Dose Edoxaban Prescription: Effectiveness and Safety Data of Korean AF Patients. 增加极低剂量埃多沙班处方:韩国房颤患者的有效性和安全性数据。
IF 3 3区 医学
Korean Circulation Journal Pub Date : 2025-03-01 Epub Date: 2024-11-04 DOI: 10.4070/kcj.2024.0222
JungMin Choi, So-Young Yang, So-Ryoung Lee, Min Soo Cho, Kyung-Yeon Lee, Hyo-Jeong Ahn, Soonil Kwon, Myung-Jin Cha, Jun Kim, Gi-Byoung Nam, Kee-Joon Choi, Eue-Keun Choi, Seil Oh, Gregory Y H Lip
{"title":"Increasing Very Low-Dose Edoxaban Prescription: Effectiveness and Safety Data of Korean AF Patients.","authors":"JungMin Choi, So-Young Yang, So-Ryoung Lee, Min Soo Cho, Kyung-Yeon Lee, Hyo-Jeong Ahn, Soonil Kwon, Myung-Jin Cha, Jun Kim, Gi-Byoung Nam, Kee-Joon Choi, Eue-Keun Choi, Seil Oh, Gregory Y H Lip","doi":"10.4070/kcj.2024.0222","DOIUrl":"10.4070/kcj.2024.0222","url":null,"abstract":"<p><strong>Background and objectives: </strong>Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily).</p><p><strong>Methods: </strong>Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events.</p><p><strong>Results: </strong>A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA<sub>2</sub>DS<sub>2</sub>-VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very low-dose edoxaban prescriptions increased. The main reasons for the prescription of very low-dose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3-16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding.</p><p><strong>Conclusions: </strong>The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.</p>","PeriodicalId":17850,"journal":{"name":"Korean Circulation Journal","volume":" ","pages":"215-227"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Erratum: Correction of Text in the Article "The Long-term Outcomes and Risk Factors of Complications After Fontan Surgery: From the Korean Fontan Registry (KFR)".
IF 3 3区 医学
Korean Circulation Journal Pub Date : 2025-03-01 DOI: 10.4070/kcj.2025.0999
Sang-Yun Lee, Soo-Jin Kim, Chang-Ha Lee, Chun Soo Park, Eun Seok Choi, Hoon Ko, Hyo Soon An, I Seok Kang, Ja Kyoung Yoon, Jae Suk Baek, Jae Young Lee, Jinyoung Song, Joowon Lee, June Huh, Kyung-Jin Ahn, Se Yong Jung, Seul Gi Cha, Yeo Hyang Kim, Youngseok Lee, Sanghoon Cho
{"title":"Erratum: Correction of Text in the Article \"The Long-term Outcomes and Risk Factors of Complications After Fontan Surgery: From the Korean Fontan Registry (KFR)\".","authors":"Sang-Yun Lee, Soo-Jin Kim, Chang-Ha Lee, Chun Soo Park, Eun Seok Choi, Hoon Ko, Hyo Soon An, I Seok Kang, Ja Kyoung Yoon, Jae Suk Baek, Jae Young Lee, Jinyoung Song, Joowon Lee, June Huh, Kyung-Jin Ahn, Se Yong Jung, Seul Gi Cha, Yeo Hyang Kim, Youngseok Lee, Sanghoon Cho","doi":"10.4070/kcj.2025.0999","DOIUrl":"10.4070/kcj.2025.0999","url":null,"abstract":"<p><p>This corrects the article on p. 653 in vol. 54, PMID: 39175341.</p>","PeriodicalId":17850,"journal":{"name":"Korean Circulation Journal","volume":"55 3","pages":"256-257"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epigenetic Modulation in Heart Failure: HDAC Inhibitors as Emerging Therapeutic Allies.
IF 3 3区 医学
Korean Circulation Journal Pub Date : 2025-03-01 DOI: 10.4070/kcj.2024.0424
Jin-Oh Choi
{"title":"Epigenetic Modulation in Heart Failure: HDAC Inhibitors as Emerging Therapeutic Allies.","authors":"Jin-Oh Choi","doi":"10.4070/kcj.2024.0424","DOIUrl":"10.4070/kcj.2024.0424","url":null,"abstract":"","PeriodicalId":17850,"journal":{"name":"Korean Circulation Journal","volume":"55 3","pages":"248-250"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Successful Customized Fenestrated Endovascular Aortic Aneurysm Repair in a Patient With Complex Abdominal Aortic Aneurysm.
IF 3 3区 医学
Korean Circulation Journal Pub Date : 2025-03-01 DOI: 10.4070/kcj.2024.0297
Markz Rmp Sinurat, Sungkwon Kang, Soohyung Park, Seung-Woon Rha
{"title":"Successful Customized Fenestrated Endovascular Aortic Aneurysm Repair in a Patient With Complex Abdominal Aortic Aneurysm.","authors":"Markz Rmp Sinurat, Sungkwon Kang, Soohyung Park, Seung-Woon Rha","doi":"10.4070/kcj.2024.0297","DOIUrl":"10.4070/kcj.2024.0297","url":null,"abstract":"","PeriodicalId":17850,"journal":{"name":"Korean Circulation Journal","volume":"55 3","pages":"251-255"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Outcomes of Deferring Percutaneous Coronary Intervention Without Physiologic Assessment for Intermediate Coronary Lesions.
IF 3 3区 医学
Korean Circulation Journal Pub Date : 2025-03-01 Epub Date: 2024-12-02 DOI: 10.4070/kcj.2023.0223
Jihoon Kim, Seong-Hoon Lim, Joo-Yong Hahn, Jin-Ok Jeong, Yong Hwan Park, Woo Jung Chun, Ju Hyeon Oh, Dae Kyoung Cho, Yu Jeong Choi, Eul-Soon Im, Kyung-Heon Won, Sung Yun Lee, Sang-Wook Kim, Ki Hong Choi, Joo Myung Lee, Taek Kyu Park, Jeong Hoon Yang, Young Bin Song, Seung-Hyuk Choi, Hyeon-Cheol Gwon
{"title":"Outcomes of Deferring Percutaneous Coronary Intervention Without Physiologic Assessment for Intermediate Coronary Lesions.","authors":"Jihoon Kim, Seong-Hoon Lim, Joo-Yong Hahn, Jin-Ok Jeong, Yong Hwan Park, Woo Jung Chun, Ju Hyeon Oh, Dae Kyoung Cho, Yu Jeong Choi, Eul-Soon Im, Kyung-Heon Won, Sung Yun Lee, Sang-Wook Kim, Ki Hong Choi, Joo Myung Lee, Taek Kyu Park, Jeong Hoon Yang, Young Bin Song, Seung-Hyuk Choi, Hyeon-Cheol Gwon","doi":"10.4070/kcj.2023.0223","DOIUrl":"10.4070/kcj.2023.0223","url":null,"abstract":"<p><strong>Background and objectives: </strong>Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain. We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment.</p><p><strong>Methods: </strong>A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years.</p><p><strong>Results: </strong>The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00-2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20-14.73; p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs. 0.7%; HR, 4.34; 95% CI, 1.24-15.22; p=0.022) and ischemia-driven any revascularization.</p><p><strong>Conclusions: </strong>For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT00743899.</p>","PeriodicalId":17850,"journal":{"name":"Korean Circulation Journal","volume":" ","pages":"185-195"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Coronary Artery Fistula Transcatheter Closure Driven by Device Development.
IF 3 3区 医学
Korean Circulation Journal Pub Date : 2025-03-01 DOI: 10.4070/kcj.2024.0389
Jinyoung Song
{"title":"Coronary Artery Fistula Transcatheter Closure Driven by Device Development.","authors":"Jinyoung Song","doi":"10.4070/kcj.2024.0389","DOIUrl":"10.4070/kcj.2024.0389","url":null,"abstract":"","PeriodicalId":17850,"journal":{"name":"Korean Circulation Journal","volume":"55 3","pages":"213-214"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is Lower-Dose Edoxaban Sufficiently Effective and Safe for the Treatment of Korean Patients With Atrial Fibrillation?
IF 3 3区 医学
Korean Circulation Journal Pub Date : 2025-03-01 DOI: 10.4070/kcj.2024.0402
Sung Il Im
{"title":"Is Lower-Dose Edoxaban Sufficiently Effective and Safe for the Treatment of Korean Patients With Atrial Fibrillation?","authors":"Sung Il Im","doi":"10.4070/kcj.2024.0402","DOIUrl":"10.4070/kcj.2024.0402","url":null,"abstract":"","PeriodicalId":17850,"journal":{"name":"Korean Circulation Journal","volume":"55 3","pages":"228-230"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of Embolization Coils and Patent Ductus Arteriosus Occluders for Coronary Artery Fistula Transcatheter Closure: A Single Centre Experience. 栓塞线圈与动脉导管未闭闭塞器在冠状动脉瘘经导管封堵中的比较:单中心经验。
IF 3 3区 医学
Korean Circulation Journal Pub Date : 2025-03-01 Epub Date: 2024-11-25 DOI: 10.4070/kcj.2024.0202
Peijian Wei, Yihang Li, Liang Xu, Junyi Wan, Fengwen Zhang, Gary Tse, Jeffrey Shi Kai Chan, Shouzheng Wang, Wenbin Ouyang, Gejun Zhang, Fang Fang, Xiangbin Pan
{"title":"Comparison of Embolization Coils and Patent Ductus Arteriosus Occluders for Coronary Artery Fistula Transcatheter Closure: A Single Centre Experience.","authors":"Peijian Wei, Yihang Li, Liang Xu, Junyi Wan, Fengwen Zhang, Gary Tse, Jeffrey Shi Kai Chan, Shouzheng Wang, Wenbin Ouyang, Gejun Zhang, Fang Fang, Xiangbin Pan","doi":"10.4070/kcj.2024.0202","DOIUrl":"10.4070/kcj.2024.0202","url":null,"abstract":"<p><strong>Background and objectives: </strong>There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce.</p><p><strong>Methods: </strong>Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66).</p><p><strong>Results: </strong>No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs. 62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59-32.64; p=0.01). In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342).</p><p><strong>Conclusions: </strong>Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.</p>","PeriodicalId":17850,"journal":{"name":"Korean Circulation Journal","volume":" ","pages":"199-212"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12. YAK577通过下调MMP12减轻异丙肾上腺素灌注心衰小鼠的心脏重塑和纤维化
IF 3 3区 医学
Korean Circulation Journal Pub Date : 2025-03-01 Epub Date: 2024-10-11 DOI: 10.4070/kcj.2024.0093
Hongyan Zhou, Hae Jin Kee, Le Wan, Yodita Asfaha, Fabian Fischer, Matthias U Kassack, Thomas Kurz, Seong Hoon Kim, Seung-Jung Kee, Young Joon Hong, Myung Ho Jeong
{"title":"YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12.","authors":"Hongyan Zhou, Hae Jin Kee, Le Wan, Yodita Asfaha, Fabian Fischer, Matthias U Kassack, Thomas Kurz, Seong Hoon Kim, Seung-Jung Kee, Young Joon Hong, Myung Ho Jeong","doi":"10.4070/kcj.2024.0093","DOIUrl":"10.4070/kcj.2024.0093","url":null,"abstract":"<p><strong>Background and objectives: </strong>Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism.</p><p><strong>Methods: </strong>New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area. The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12).</p><p><strong>Results: </strong>YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9-11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, <i>NPPB</i>, and myosin heavy chain 7, <i>MYH7</i>) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes. HDAC8 overexpression stimulated <i>MMP12</i> and <i>NPPB</i> mRNA levels, while HDAC8 knockdown downregulated these genes.</p><p><strong>Conclusions: </strong>YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.</p>","PeriodicalId":17850,"journal":{"name":"Korean Circulation Journal","volume":" ","pages":"231-247"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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