更新于：2024-05-01

Cardiomyopathy, Alcoholic

酒精性心肌病

更新于：2024-05-01

基本信息

别名

Alcohol induced heart muscle disease、Alcohol-induced heart muscle disease、Alcoholic Cardiomyopathy

+ [25]

简介

Disease of CARDIAC MUSCLE resulting from chronic excessive alcohol consumption. Myocardial damage can be caused by: (1) a toxic effect of alcohol; (2) malnutrition in alcoholics such as THIAMINE DEFICIENCY; or (3) toxic effect of additives in alcoholic beverages such as COBALT. This disease is usually manifested by DYSPNEA and palpitations with CARDIOMEGALY and congestive heart failure (HEART FAILURE).

关联

项与酒精性心肌病相关的临床试验

ACTRN12616000256471 / CompletedN/A

Exploring the link between alcohol and atrial fibrillation recurrence: a multicentre randomised controlled trial (ETOH-AF)

开始日期2016-03-07

申办/合作机构-

NCT00226109 / Suspended临床4期IIT

Effect of Spironolactone Treatment on Heart- and Skeletal Muscle in Chronic Alcoholics

Chronic alcoholics suffer from weak skeletal and cardiac muscle. The investigators have discovered a beneficial effect of spironolactone-treatment in that regard. Therefore, a double blind placebo controlled study is conducted, to examine the effects of spironolactone on cardiac and skeletal muscle-function in chronic alcoholics.

开始日期2004-04-30

申办/合作机构

University of Aarhus

100 项与酒精性心肌病相关的临床结果

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100 项与酒精性心肌病相关的转化医学

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0 项与酒精性心肌病相关的专利（医药）

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857

项与酒精性心肌病相关的文献（医药）

2024-02-19·Life sciences

Elevated levels of alcohol dehydrogenase aggravate ethanol-evoked cardiac remodeling and contractile anomalies through FKBP5-yap-mediated regulation of ferroptosis and ER stress.

Article

作者: Qi Lu ; Xing Qin ; Chu Chen ; Wei Yu ; Jie Lin ; Xiaoyu Liu ; Rui Guo ; Russel J Reiter ; Milad Ashrafizadeh ; Ming Yuan ; Jun Ren

Alcohol intake provokes severe organ injuries including alcoholic cardiomyopathy with hallmarks of cardiac remodeling and contractile defects. This study examined the toxicity of facilitated ethanol metabolism in alcoholism-evoked changes in myocardial morphology and contractile function, insulin signaling and various cell death domains using cardiac-selective overexpression of alcohol dehydrogenase (ADH). WT and ADH mice were offered an alcohol liquid diet for 12 weeks prior to assessment of cardiac geometry, function, ER stress, apoptosis and ferroptosis. Alcohol intake provoked pronounced glucose intolerance, cardiac remodeling and contractile anomalies with apoptosis, ER stress, and ferroptosis, the effects were accentuated by ADH with the exception of global glucose intolerance. Hearts from alcohol ingesting mice displayed dampened insulin-stimulated phosphorylation of insulin receptor (tyr1146) and IRS-1 (tyrosine) along with elevated IRS-1 serine phosphorylation, the effect was augmented by ADH. Alcohol challenge dampened phosphorylation of Akt and GSK-3β, and increased phosphorylation of c-Jun and JNK, the effects were accentuated by ADH. Alcohol challenge promoted ER stress, FK506 binding protein 5 (FKBP5), YAP, apoptosis and ferroptosis, the effects were exaggerated by ADH. Using a short-term ethanol challenge model (3 g/kg, i.p., twice in three days), we found that inhibition of FKBP5-YAP signaling or facilitated ethanol detoxification by Alda-1 alleviated ethanol cardiotoxicity. In vitro study revealed that the ethanol metabolite acetaldehyde evoked cardiac contractile anomalies, lipid peroxidation, and apoptosis, the effects of which were mitigated by Alda-1, inhibition of ER stress, FKBP5 and YAP. These data suggest that facilitated ethanol metabolism via ADH exacerbates alcohol-evoked myocardial remodeling, functional defects, and insulin insensitivity possibly through a FKBP5-YAP-associated regulation of ER stress and ferroptosis.

2024-02-08·Heart, lung & circulation

Clinical Trajectories and Long-Term Outcomes of Alcoholic Versus Other Forms of Dilated Cardiomyopathy.

Article

作者: Amanda Fernandes ; Alan Manivannan ; Morten Schou ; Emil Fosbøl ; Lars Køber ; Finn Gustafsson ; Gunnar H Gislason ; Christian Torp-Pedersen ; Charlotte Andersson

BACKGROUND:

Alcoholic cardiomyopathy (ACM) is a form of dilated cardiomyopathy (DCM) occurring secondary to long-standing heavy alcohol use and is associated with poor outcomes, but the cause-specific risks are insufficiently understood.

METHOD:

Between 1997 and 2018, we identified all patients with a first diagnosis of ACM or DCM. The cumulative incidence of different causes of hospitalisation and mortality in the two groups was calculated using the Fine-Gray and Kaplan-Meier methods.

RESULTS:

A Total of 1,237 patients with ACM (mean age 56.3±10.1 years, 89% men) and 17,211 individuals with DCM (mean age 63.6±13.8 years, 71% men) were identified. Diabetes (10% vs 15%), hypertension (22% vs 31%), and stroke (8% vs 10%) were less common in ACM than DCM, whereas obstructive lung disease (15% vs 12%) and liver disease (17% vs 2%) were more prevalent (p<0.05). Cumulative 5-year mortality was 49% in ACM vs 33% in DCM, p<0.0001, multivariable adjusted hazards ratio 2.11 (95% confidence interval 1.97-2.26). The distribution of causes of death was similar in ACM and DCM, with the predominance of cardiovascular causes in both groups (42% in ACM vs 44% in DCM). 5-year cumulative incidence of heart failure hospitalisations (48% vs 54%) and any somatic cause (59% vs 65%) were also similar in ACM vs DCM. At 1 year, the use of beta blockers (55% vs 80%) and implantable cardioverter defibrillators (3% vs 14%) were significantly less often used in ACM vs DCM.

CONCLUSIONS:

Patients with ACM had similar cardiovascular risks and hospitalisation patterns as other forms of DCM, but lower use of guideline-directed cardiovascular therapies and greater mortality.

2023-12-07·Cells

Abstinence Restores Cardiac Function in Mice with Established Alcohol-Induced Cardiomyopathy.

Article

作者: Joshua M Edavettal ; Nicholas R Harris ; Sarah E Cohen ; Janos Paloczi ; Bysani Chandrasekar ; Jason D Gardner

Alcohol-induced cardiomyopathy (ACM) has a poor prognosis with up to a 50% chance of death within four years of diagnosis. There are limited studies investigating the potential of abstinence for promoting repair after alcohol-induced cardiac damage, particularly in a controlled preclinical study design. Here, we developed an exposure protocol that led to significant decreases in cardiac function in C57BL6/J mice within 30 days; dP/dt max decreased in the mice fed alcohol for 30 days (8054 ± 664.5 mmHg/s compared to control mice: 11,188 ± 724.2 mmHg/s, p < 0.01), and the dP/dt min decreased, as well (-7711 ± 561 mmHg/s compared to control mice: -10,147 ± 448.2 mmHg/s, p < 0.01). Quantitative PCR was used to investigate inflammatory and fibrotic biomarkers, while histology was used to depict overt changes in cardiac fibrosis. We observed a complete recovery of function after abstinence (dP/dt max increased from 8054 ± 664 mmHg/s at 30 days to 11,967 ± 449 mmHg/s after abstinence, p < 0.01); further, both inflammatory and fibrotic biomarkers decreased after abstinence. These results lay the groundwork for future investigation of the molecular mechanisms underlying recovery from alcohol-induced damage in the heart.

项与酒精性心肌病相关的新闻（医药）

2024-03-20

·Science Daily

Low social status increases risk of health problems from alcohol problems

Men and women with lower income or education levels are more likely to develop medical conditions related to alcohol abuse compared to similar individuals with a higher socioeconomic status, according to a new study. Men and women with lower income or education levels are more likely to develop medical conditions related to alcohol abuse compared to similar individuals with a higher socioeconomic status. Alexis Edwards of Virginia Commonwealth University, US, and colleagues report these findings in a new study published March 19 in the open access journal PLOS Medicine. The World Health Organization estimates that harmful alcohol use accounts for 5.1% of the global burden of disease and injury worldwide, and results in three million deaths each year. Excessive alcohol consumption can also take an economic toll. Previous studies have identified links between a person's socioeconomic status and alcohol use, but currently it is unclear how an individual's social class impacts their future risk of acquiring alcohol-related medical conditions, like alcoholic liver disease. In the new study, researchers used a model that follows people over time to estimate their risk of developing medical conditions from alcohol abuse using two indicators for socioeconomic status: income and education level. The researchers analyzed data from more than 2.3 million individuals in a Swedish database to show that both men and women with a lower income or education level were more likely to develop these conditions. The associations held true, even when researchers controlled for other relevant factors, such as marital status, history of psychiatric illness and having a genetic predisposition to abuse alcohol. The new findings are important for understanding which populations are most likely to suffer from medical conditions resulting from alcohol abuse, and contribute to a growing body of literature on health disparities that stem from socioeconomic factors. The researchers recommend that individuals with lower income or education levels might warrant additional screening by clinicians to evaluate their alcohol consumption and identify related conditions. The authors add, "Among individuals with an alcohol use disorder, those with lower levels of education or lower incomes are at higher risk for developing an alcohol-related medical condition, such as cirrhosis or alcoholic cardiomyopathy. Additional screening and prevention efforts may be warranted to reduce health disparities."

2024-02-04

·生物探索

Circ Res | 华中科技大学汪道文/陈琛发现扩张型心肌病的致病新机制

引言先前对扩张型心肌病(DCM)患者的人类心脏长链非编码RNA (lncRNA)谱进行了分析，发现长链非编码RNA CHKB(胆碱激酶β)发散转录物(CHKB-DT)水平在心脏中大部分下调。2024年2月1日，华中科技大学汪道文及陈琛共同通讯在Circulation Research（IF 20）在线发表题为“LncRNA CHKB-DT Downregulation Enhances Dilated Cardiomyopathy Through ALDH2”的研究论文，该研究证明，LncRNA CHKB-DT下调通过ALDH2加剧了扩张型心肌病。CHKB-DT水平在DCM患者和横主动脉缩窄性心力衰竭小鼠中显著降低。心肌细胞中CHKB-DT的杂合敲除引起心脏扩张和功能障碍，降低原代心肌细胞的收缩力。此外，CHKB-DT杂合敲除会损害线粒体功能，降低ATP的产生和心脏能量代谢。从机制上讲，ALDH2(醛脱氢酶2)是CHKB-DT的直接靶点。CHKB-DT通过GGUG基序与ALDH2和FUS (rna结合蛋白FUS)的mRNA相互作用。CHKB-DT敲低会加剧ALDH2 mRNA的降解和4-羟基-2-壬烯醛的产生，而CHKB-DT过表达则会逆转这些分子变化。此外，恢复CHKB-DT+/−小鼠的ALDH2表达可减轻心脏扩张和功能障碍。CHKB-DT在DCM中显著下调。CHKB-DT作为一种与能量代谢相关的长链非编码RNA，代表了一种有希望的治疗DCM的靶点。心力衰竭仍然是最常见、最昂贵、最致命的疾病之一。扩张型心肌病(DCM)是一种导致收缩期心力衰竭的原因，通常影响生存率低的年轻患者。欧洲心脏病学会将DCM定义为在没有异常负荷条件(高血压或瓣膜疾病)或冠状动脉疾病的情况下，心肌表现下降和心室增大。DCM的病因各不相同，从基因突变和感染性原因到心脏毒素和代谢紊乱。新的证据表明，线粒体功能缺陷和能量消耗可能导致心力衰竭和扩张型心肌病线粒体异常包括电子传递链活性受损、离子稳态改变、代谢底物利用受损和活性氧(ROS)形成增加。线粒体ALDH2(醛脱氢酶2)以其在乙醛代谢和酒精性心肌病中的作用而闻名。越来越多的证据表明，ALDH2在氧化应激和线粒体功能障碍的调节中发挥了更大的作用，ALDH2缺乏显著增加ROS的形成和整体心脏氧化应激，并有助于心脏损伤。然而，ALDH2在DCM中的功能和上游调控在很大程度上是不明确的。更好地了解这种酶可能有助于确定DCM的新治疗靶点。人类基因组产生数千个长度超过200个核苷酸的长链非编码RNA (lncRNA)转录本，它们不编码任何蛋白质lncRNA是一类具有多种生物学功能的转录本。高通量RNA测序能够鉴定出在各种疾病发病机制中具有潜在作用的lncRNA。lncRNA通过其致癌和肿瘤抑制作用在癌症的发生和发展中发挥复杂的调节作用。一些lncRNA，如Chast, Chaer, CPR和Caren，在心血管疾病中起重要作用。lncRNA已经在动物心血管疾病模型中得到了很好的研究，但它们在人类心脏病，特别是DCM中的功能尚不清楚。模式图（Credit: Circulation Research）该研究发现了一个以前未定义的与糖尿病相关的lncRNA CHKB-DT。CHKB-DT在患病人心脏组织中的抑制作用突出了其功能潜力。研究发现CHKB-DT与FUS相互作用，通过GGUG基序调节ALDH2 mRNA的稳定性。内源性CHKB-DT敲低可降低ALDH2的表达，引起线粒体功能障碍，进而导致心脏扩张和功能障碍。该研究为DCM发病机制中lncRNA对ALDH2表达的调控提供了新的见解。原文链接https://www.ahajournals.org/doi/abs/10.1161/CIRCRESAHA.123.323428责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Science最新发布：全世界最前沿的125个科学问题热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文Nature | 颠覆性发现：我们肠道微生物中隐藏的“奇异RNA碎片”

信使RNA临床结果核酸药物

2022-06-06

·药明康德

还以为少喝点就没事？酒精对心脏的危害有多大，这项研究告诉你

▎药明康德内容团队编辑俗话说，“小酌怡情，大饮伤身”。很多人虽然知道酒精损害健康，但往往以为“适量”喝一点没什么问题。然而越来越多的科学研究告诉我们，喝酒并没有一个“安全”的界限，即使是喝得不多也会造成健康损害。近期，根据欧洲心脏病学会（European Society of Cardiology）“心力衰竭”主题年会上新发表的一项研究，酒精对心脏的风险可能比过去以为的更大。尽管世界各地对饮酒量的限制并不一致，然而低于某些地区所谓的“推荐量”或“安全量”水平，仍然可以发现饮酒与心力衰竭的发展密切相关。图片来源：123RF 研究人员重点关注了一种被称为“ 酒精性心肌病 ”的心力衰竭。这种疾病的罪魁祸首就是酒精，由于酒精以及酒精在人体内的代谢产物——乙醛对心肌有直接毒害，日结月累，心肌会变得像被牵扯过度的橡皮筋，弹性变差，无法有效地泵送血液。酒精性心肌病通常被认为是长期大量饮酒导致的结果。所谓的“大量”，以爱尔兰为例，定义为每周纯酒精摄入量女性超过110克、男性超过170克。但在这项研究中，爱尔兰都柏林圣文森特大学医院的研究人员发现，实际上低于这个饮酒量仍然有危险。图片来源：123RF 研究人员分析了有心力衰竭高危风险（例如高血压、糖尿病、肥胖等）或是处于心力衰竭前期（有前述危险因素且心脏出现异常，但还未发展出症状）的700多名受试者，通过超声心动图测量了他们的心脏功能，并进行了平均5.4年时间的随访，调查了这些受试者心脏健康与酒精摄入之间的关系。根据每周纯酒精摄入量，研究人员将受试者分为4组，分别是：不饮酒；少量饮酒（少于70克，相当于最多一瓶750毫升12.5%葡萄酒，或三罐半、每罐500毫升的4.5%啤酒）；中度饮酒（70克~140克，相当于最多两瓶12.5%葡萄酒，或七罐4.5%啤酒）；大量饮酒（140克以上，相当于两瓶以上12.5%葡萄酒或七罐以上4.5%啤酒）。分析结果显示，心力衰竭前期的受试者中，与不饮酒相比，中度饮酒和大量饮酒组的心脏健康恶化风险增加4.5倍，更有可能进展为有症状的心力衰竭。“我们的研究表明，欧洲人每周饮酒超过 70 克与心力衰竭前期的恶化或进展为症状性心力衰竭有关。研究人员强调。“这一结果意味着，我们发现的安全量只有爱尔兰建议的每周酒精摄入量的一半不到。” 在高危风险受试者中，中度饮酒或大量饮酒与是否进展为心力衰竭前期或有症状的心力衰竭之间没有关系。此外，研究结果没有发现少量饮酒有任何保护作用。图片来源：123RF 值得一提的是，这项研究主要调查了饮酒量较大的欧洲人，而一些来自亚洲人群的证据表明，相比欧洲人群，更低的酒精摄入量就可能对亚洲人造成心肌损伤。由于遗传基因的差别，很多亚洲人无法顺利代谢酒精，导致酒精及其代谢产物在体内造成的损伤更多，换句话说，亚洲人在酒精面前的抵抗力更弱。也许有的人是为了开心而喝酒，然而种种研究证据告诉我们，酒精却会造成真正的“伤心” 。“这项研究增加了大量证据表明应当更谨慎地看待喝酒，”研究作者Bethany Wong博士说。“为了尽量减少酒精对心脏造成伤害的风险，能不喝酒就不要开始喝酒，喝酒的人最好把每周饮酒量限制在一瓶葡萄酒或者三罐半啤酒以下。参考资料： [1] Alcohol may be more risky to the heart than previously thought. Retrieved May 31, 2022 from https://www.eurekalert.org/news-releases/953314 [2] Bethany Wong (2022) Moderate alcohol consumption is associated with progression of left ventricular dysfunction in a European stage B heart failure population. 本文来自药明康德内容微信团队，欢迎转发到朋友圈，谢绝转载到其他平台。如有开设白名单需求，请在“学术经纬”公众号主页回复“转载”获取转载须知。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。