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Sjogren Syndrome and Outcomes of Acute Myocardial Infarction: A Propensity Score-Matched Analysis of the Nationwide Inpatient Sample 2005-2018. Sjogren综合征与急性心肌梗死的预后:2005-2018年全国住院患者样本倾向得分匹配分析》。
IF 2.6 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001603
Bu-Yuan Hsiao

Abstract: The aim of this study was to evaluate the potential associations between Sjogren syndrome and outcomes of acute myocardial infarction (AMI) hospitalization. This population-based, retrospective observational study extracted data from the US Nationwide Inpatient Sample between 2005 and 2018. Adults aged 20 years or older hospitalized for AMI were eligible for inclusion. Propensity score matching was applied to balance the characteristics between the comparison groups (ie, with and without Sjogren syndrome). Associations between Sjogren syndrome and in-hospital outcomes were determined using univariate and multivariable logistic regression analyses. A total of 1,735,142 patients were included. After propensity score matching, 4740 patients remained for subsequent analyses (948 had Sjogren syndrome and 3792 did not). After adjustment, patients with Sjogren syndrome had significantly lower in-hospital mortality (adjusted OR: 0.52, 95% CI, 0.36-0.73, P < 0.001), prolonged length of stay (aOR: 0.83, 95% CI, 0.69-0.995, P = 0.044), cardiogenic shock (aOR: 0.58, 95% CI, 0.40-0.83, P = 0.004), cardiac dysrhythmias (aOR: 0.77, 95% CI, 0.66-0.90, P < 0.001), acute kidney injury (aOR: 0.56, 95% CI, 0.45-0.70, P < 0.001), or respiratory failure (aOR: 0.63, 95% CI, 0.48-0.81, P < 0.001) than those without Sjogren syndrome. The stratified analysis revealed that Sjogren syndrome was associated with decreased odds of in-hospital mortality in patients with non-ST elevation myocardial infarction or ST-elevation myocardial infarction. In conclusion, among patients admitted to US hospitals for AMI, the patients with Sjogren syndrome have a lowered probability of in-hospital mortality, certain morbidities, and prolonged length of stay. Further investigations should be conducted to establish a robust understanding of the associations observed.

本研究旨在评估Sjogren综合征与急性心肌梗死(AMI)住院治疗结果之间的潜在关联。这项基于人群的回顾性观察研究从美国全国住院患者样本(NIS)中提取了2005年至2018年期间的数据。因急性心肌梗死住院的年龄≥20岁的成年人符合纳入条件。研究采用倾向得分匹配法(PSM)来平衡对比组(即有Sjogren综合征和无Sjogren综合征)之间的特征。通过单变量和多变量逻辑回归分析确定了 Sjogren 综合征与院内预后之间的关系。共纳入 1,735,142 名患者。经过 PSM 分析后,4740 名患者被纳入后续分析(948 名患者患有 Sjogren 综合征,3792 名患者未患有 Sjogren 综合征)。经调整后,Sjogren 综合征患者的院内死亡率明显降低(调整后 OR [aOR]:0.52,95% CI:0.36- 0.73,p
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引用次数: 0
From Risk to Resilience: Improved Outcomes After Myocardial Infarction in Patients With Sjogren's Syndrome. 从风险到恢复力:改善斯约格伦综合征患者心肌梗死后的预后。
IF 2.6 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001615
Catherine X Wright, Attila Feher
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引用次数: 0
The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension. 室旁核中的硫化氢对高盐诱发高血压的 MAPK 通路的影响
IF 2.6 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001622
Yan-Feng Liang, Qing-Xin You, Shu-Yue Chen, Lei Ni, Xiang-Lian Meng, Jian-Xiang Gao, Yong-Bo Ren, Han-Jun Song, Jia-Lu Su, Yang Teng, Qing-Yun Gu, Chao Lv, Bo-Yang Yuan, Xuan Wang, Yong-Tai Zheng, Dong-Dong Zhang

Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.

下丘脑室旁核(PVN)在调节心血管活动和血压(BP)方面起着核心作用。我们将胱硫醚-β-合成酶(CBS)抑制剂盐酸羟胺(HA)注入下丘脑室旁核,以抑制内源性硫化氢(H2S),并研究其对高盐诱导的高血压中丝裂原活化蛋白激酶(MAPK)通路的影响。我们将 40 只雄性 Dahl 盐敏感大鼠随机分为 4 组:NS+PVN 车辆组、NS+PVN HA 组、HS+PVN 车辆组和 HS+PVN HA 组,每组 10 只。NS(正常盐)组大鼠食用含 0.3% NaCl 的正常盐饮食,而 HS(高盐)组大鼠食用含 8% NaCl 的高盐饮食。每周一次使用自动血压计闭合尾部袖带进行无创测量,然后计算平均动脉压(MAP)。高血压模型成功建立后,使用 Alzet 渗透压微型泵将 HA 或药物注入双侧 PVN,持续 6 周。我们用酶联免疫吸附法测定了PVN中的H2S水平和血浆去甲肾上腺素(NE)水平。此外,我们还通过 Western 印迹、免疫组化分析或实时 PCR 评估了 MAPK 通路、炎症和氧化应激的参数。在目前的研究中,我们发现PVN中内源性硫化氢水平的降低是高盐诱导的高血压发病的原因之一。这与 MAPK 信号通路的激活、促炎细胞因子和 PVN 中的氧化应激以及交感神经系统的激活有关。
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引用次数: 0
Finerenone Proves Beneficial for Heart Failure with Preserved Ejection Fraction. 非格列酮能有效治疗射血分数保留型心力衰竭。
IF 2.6 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-26 DOI: 10.1097/FJC.0000000000001636
Giuseppe Biondi-Zoccai, Mattia Galli, George W Booz
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引用次数: 0
Effect of an Enteral Formula Enriched with ω-3 Fatty Acids, Carnitine, and Vitamin D on Body Weight, Heart Weight, and Blood Biochemical Parameters in a Dahl Rat Heart Failure Model. 富含ω-3脂肪酸、肉碱和维生素D的肠内配方对达尔大鼠心衰模型的体重、心脏重量和血液生化指标的影响
IF 2.6 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-26 DOI: 10.1097/FJC.0000000000001637
Yoshikazu Ryuno, Jun-Ichi Kobayashi, Yudai Fujimoto, Taishi Dotare, Yuya Matsue, Yoshihito Iwanami

Malnutrition is known to worsen the prognosis of chronic heart failure. To gain information that may be helpful in establishing appropriate nutritional interventions for chronic heart failure, the present study was performed to investigate the efficacy of nutritional management with two enteral formulas, EH, with a standard nutritional composition, and ER, fortified with omega-3 fatty acids, vitamin D, and carnitine. Experiments were performed in a Dahl rat heart failure model. After being fed a standard rodent feed (MF) containing 8% NaCl (high salt-MF [HS-MF]) from 6 to 11 weeks of age, rats were assigned to freeze-dried EH or ER diets with an NaCl concentration of 8% (HS-ER or HS-EH) until 18 weeks of age. Serum albumin was significantly higher at 14 and 17 weeks of age in rats fed the HS-ER and HS-EH diets compared with those remaining on the HS-MF diet. Body weight was also significantly higher at 14 and 17 weeks of age in animals fed the HS-ER diet, showing that nutritional deterioration was prevented. Additionally, heart weight was significantly lower at 18 weeks of age in the HS-ER group than that in the HS-MF group, suggesting that cardiac hypertrophy was prevented. This study demonstrated improved nutritional status in a heart failure model in Dahl rats presumably owing to differences in nutritional composition in the diets. Future studies are needed to explore optimal nutritional management with enteral formulas in patients with chronic heart failure.

众所周知,营养不良会使慢性心力衰竭的预后恶化。为了获得有助于为慢性心力衰竭制定适当营养干预措施的信息,本研究调查了两种肠内配方营养管理的疗效,一种是具有标准营养成分的 EH,另一种是强化了欧米伽-3 脂肪酸、维生素 D 和肉碱的 ER。实验在达尔大鼠心力衰竭模型中进行。大鼠在6至11周龄期间喂食含8% NaCl的标准啮齿动物饲料(MF)(高盐-MF [HS-MF])后,在18周龄之前被分配到NaCl浓度为8%的冻干EH或ER饮食(HS-ER或HS-EH)中。与继续食用 HS-MF 日粮的大鼠相比,食用 HS-ER 和 HS-EH 日粮的大鼠在 14 周龄和 17 周龄时的血清白蛋白明显更高。喂食 HS-ER 的大鼠在 14 周龄和 17 周龄时体重也明显增加,这表明营养恶化得到了预防。此外,在 18 周龄时,HS-ER 组的心脏重量明显低于 HS-MF 组,这表明心脏肥大得到了预防。这项研究表明,Dahl 大鼠心力衰竭模型的营养状况有所改善,这可能是由于饮食中营养成分的差异。未来的研究需要探索慢性心力衰竭患者肠内配方的最佳营养管理。
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引用次数: 0
PDE8 Inhibition and Its Impact on ICa,L in Persistent Atrial Fibrillation: Evaluation of PDE8 as a Potential Drug Target. PDE8 抑制及其对持续性心房颤动 ICa,L 的影响:评估作为潜在药物靶点的 PDE8。
IF 3 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-13 DOI: 10.1097/fjc.0000000000001630
Djemail Ismaili,Johannes Petersen,Carl Schulz,Thomas Eschenhagen,Jussi T Koivumäki,Torsten Christ
Atrial fibrillation (AF) poses a significant therapeutic challenge with drug interventions showing only limited success. Phosphodiesterases (PDE) regulate cardiac electrical stability and may represent an interesting target. Recently, PDE8 inhibition was proposed as an antiarrhythmic intervention by increasing L-type Ca2+ current (ICa,L) and action potential duration (APD). However, the effect size of PDE8 inhibition on ICa,L and APD seems discrepant and effects on force are unknown. We investigated the impact of PDE8 inhibition on force using PF-04957325 in right atrial appendages, obtained from patients in sinus rhythm (SR) and with persistent AF (peAF) undergoing cardiac surgery. A computational model was employed to predict the effects of PDE8 inhibition on APD in SR and peAF. Results showed no increase in force after exposure to increasing concentrations of the PDE8 inhibitor PF-04957325 in either SR or peAF tissues. Furthermore, PDE8 inhibition did not affect the potency or efficacy of norepinephrine-induced inotropic effects in either group. Arrhythmic events triggered by norepinephrine were observed in both SR and peAF, but their frequency remained unaffected by PF-04957325 treatment. Computational modeling predicted that the reported increase in ICa,L induced by PDE8 inhibition would lead to substantial APD prolongation at all repolarization states, particularly in peAF. Our findings indicate that PDE8 inhibition does not significantly impact force or arrhythmogenicity in human atrial tissue.
心房颤动(房颤)给治疗带来了巨大挑战,药物干预的效果有限。磷酸二酯酶(PDE)调节心电稳定性,可能是一个有趣的靶点。最近,有人提出通过增加 L 型 Ca2+ 电流(ICa,L)和动作电位持续时间(APD)来抑制 PDE8,从而达到抗心律失常的目的。然而,PDE8 抑制对 ICa,L 和 APD 的影响大小似乎并不一致,对力量的影响也不清楚。我们在接受心脏手术的窦性心律(SR)和持续性房颤(peAF)患者的右心房阑尾中使用 PF-04957325 研究了 PDE8 抑制对力量的影响。采用计算模型预测了 PDE8 抑制对 SR 和 peAF 的 APD 的影响。结果显示,在SR和peAF组织中暴露于浓度不断增加的PDE8抑制剂PF-04957325后,肌力没有增加。此外,PDE8 抑制剂对去甲肾上腺素诱导的肌力作用的效力和效果均无影响。在 SR 和 peAF 中都观察到了由去甲肾上腺素引发的心律失常事件,但其频率不受 PF-04957325 治疗的影响。计算模型预测,PDE8 抑制引起的 ICa,L 增加将导致所有复极化状态下 APD 的大幅延长,尤其是在 peAF 中。我们的研究结果表明,PDE8 抑制不会对人体心房组织的力量或心律失常发生率产生重大影响。
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引用次数: 0
Peroxisome Proliferator-Activated Receptor Gamma Regulates Interleukin-6-Induced Lipoprotein (a) Gene Expression in Human HepG2 Cells. 过氧化物酶体增殖激活受体γ调节白细胞介素-6 诱导的人 HepG2 细胞中脂蛋白(a)基因表达。
IF 3 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-13 DOI: 10.1097/fjc.0000000000001634
Tarek Harb,Efthymios Ziogos,Núria Amat-Alarcon,Shenghan Lai,Gary Gerstenblith,Marios Arvanitis,Thorsten M Leucker
Lipoprotein(a) [Lp(a)] is a risk factor for coronary disease. Although levels are primarily genetically determined, data from patients with inflammatory diseases indicate that the inflammatory milieu is associated with increased Lp(a) levels. Lp(a) is synthesized in the liver and the LPA gene promoter contains an interleukin-6 (IL-6) responsive binding site, but the regulatory steps linking inflammation with hepatic Lp(a) synthesis are not well clarified. We explored the interplay between IL-6, peroxisome proliferator-activated receptor gamma (PPARγ), and Lp(a) synthesis in HepG2 cells. Through genetic mapping, a regulatory variant within the LPA promoter overlapping with a PPARγ binding site was identified. In in vitro experiments, IL-6-mediated LPA gene transcription was heightened with PPARγ knock-down and suppressed with pioglitazone, a PPARγ agonist. These results demonstrate an important role of PPARγ as a negative regulator of IL-6 induced hepatic Lp(a) production and may represent a new therapeutic target for patients with inflammatory conditions characterized by elevated Lp(a).
脂蛋白(a)[Lp(a)]是冠心病的一个危险因素。虽然脂蛋白(a)水平主要由基因决定,但来自炎症性疾病患者的数据表明,炎症环境与脂蛋白(a)水平升高有关。脂蛋白(a)在肝脏中合成,LPA 基因启动子包含一个白细胞介素-6(IL-6)反应结合位点,但炎症与肝脏脂蛋白(a)合成之间的调控步骤尚未明确。我们探索了 IL-6、过氧化物酶体增殖激活受体γ(PPARγ)和肝脏脂蛋白(a)合成在 HepG2 细胞中的相互作用。通过基因图谱绘制,确定了 LPA 启动子中与 PPARγ 结合位点重叠的调控变体。在体外实验中,PPARγ 基因敲除会增强 IL-6 介导的 LPA 基因转录,而 PPARγ 激动剂吡格列酮会抑制 LPA 基因转录。这些结果表明 PPARγ 在 IL-6 诱导的肝脏脂蛋白(a)生成中起着重要的负调控作用,可能成为以脂蛋白(a)升高为特征的炎症患者的一个新的治疗靶点。
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引用次数: 0
Atrial hiPSC-CM as a pharmacological model to evaluate anti-AF drugs: Some lessons from IKur. 将心房 hiPSC-CM 作为评估抗心房颤动药物的药理学模型:IKur 的一些经验
IF 3 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-13 DOI: 10.1097/fjc.0000000000001631
Carl Schulz,Thomas Eschenhagen,Torsten Christ
Human induced pluripotent stem cells (hiPSC) and atrial hiPSC-derived cardiomyocytes (hiPSC-CM) have entered the arena of preclinical AF research. A central question is whether they reproduce the physiological contribution of atrial selective potassium currents (such as the ultrarapid potassium current, IKur) to repolarization. Of note, two studies in single atrial hiPSC-CM reported prolongation of action potential duration by IKur block indicating that IKur might in fact represent a valuable target for the treatment of human AF. However, the results and interpretation are at odds with the literature on IKur block in human atria and the results of clinical studies. We believe that the discrepancies indicate that experiments in single atrial CM (both adult atrial CM and atrial hiPSC-CM) might be misleading. Under particular experimental conditions, atrial hiPSC-CMs may not closely resemble the electrophysiology of the human atrium. Therefore, we recapitulate here methodological issues evaluating potential value of the IKur as an antiarrhythmic target when investigated in animal models, in human atrial tissues and finally in atrial hiPSC-CM.
人类诱导多能干细胞(hiPSC)和心房 hiPSC 衍生心肌细胞(hiPSC-CM)已进入临床前房颤研究领域。一个核心问题是它们是否能再现心房选择性钾电流(如超快速钾电流IKur)对复极化的生理贡献。值得注意的是,有两项针对单心房 hiPSC-CM 的研究报告称,IKur 阻断可延长动作电位持续时间,这表明 IKur 实际上可能是治疗人类房颤的一个有价值的靶点。然而,这些结果和解释与有关人类心房 IKur 阻滞的文献和临床研究结果不一致。我们认为,这些差异表明,在单个心房 CM(包括成人心房 CM 和心房 hiPSC-CM)中进行的实验可能会产生误导。在特定的实验条件下,心房 hiPSC-CM 可能与人类心房的电生理学并不十分相似。因此,我们在此概述了评估 IKur 作为抗心律失常靶点在动物模型、人类心房组织和心房 hiPSC-CM 中的潜在价值的方法学问题。
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引用次数: 0
Rethinking beta-blockers after ST-elevation myocardial infarction: essential for some, questionable for others. 重新思考 ST 段抬高型心肌梗死后的β-受体阻滞剂:对某些人是必要的,对另一些人则值得商榷。
IF 3 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-06 DOI: 10.1097/fjc.0000000000001632
Federico Russo,Angela Palma,Stefano Cacciatore,Elisa Tomarelli,Luigi Spadafora
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引用次数: 0
Bivalirudin in Extracorporeal Membrane Oxygenation. 体外膜氧合中的比伐卢定
IF 2.6 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-06 DOI: 10.1097/FJC.0000000000001633
Sabrina Dunham, Patrick M Wieruszewski, James E Gerrald

Abstract: Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality utilized in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most utilized anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on co-factors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of co-factors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. Additionally, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification.

摘要:体外膜肺氧合(ECMO)是一种用于难治性心脏和/或肺衰竭患者的机械支持治疗模式。与 ECMO 相关的出血和血栓并发症是需要谨慎处理的固有问题。抗凝优化可提供更充分的治疗性抗凝,降低出血风险,从而帮助减轻这些风险。肝素是最常用的抗凝剂,但由于其药理作用依赖于辅助因子和循环蛋白,因此存在肝素诱导的血小板减少症和可能的抗药性问题。相比之下,比伐卢定是一种直接凝血酶抑制剂,它的作用不受辅助因子或血浆蛋白的影响,并具有凝血酶结合和新陈代谢的特点,在 ECMO 管理中可能具有优势。本文对双醋芦定在 ECMO 中应用的证据进行了综述,结果表明,双醋芦定在与回路相关的血栓形成、出血和用药可靠性方面具有良好的效果。此外,血液制品利用率、回路干预、ECMO 拔管成功率和存活率也是与双醋芦定相关的积极发现,值得考虑。本综述还讨论了与比伐卢定的使用有关的常见问题和顾虑,包括实验室监测、低流量状态下的使用、肾脏替代疗法中的剂量考虑、可逆性和成本。此外,本综述还指出,使用比伐卢定为简化 ECMO 管理提供了机会。
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引用次数: 0
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Journal of Cardiovascular Pharmacology
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