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Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

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The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
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Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
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严格的监测可以降低免疫检查点抑制剂诱导的心脏毒性的死亡率.

Ying Wang1, Carolin Ertl1,2, Christina Schmitt1

  • 1Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany.

Frontiers in cardiovascular medicine
|June 25, 2024
PubMed
概括

免疫检查点抑制剂 (ICI) 诱导的心肌炎是一种严重的不良事件. 在最近的一项研究中,加强患者管理和监测显著降低了死亡率.

关键词:
心血管毒性心血管毒性检查点抑制剂检查点抑制剂免疫疗法 免疫疗法黑色素瘤是一种黑色素瘤.肌性心肌炎是一种心肌炎.

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科学领域:

  • 免疫学 免疫学 免疫学
  • 心脏病学 心脏病学
  • 在瘤学瘤学.

背景情况:

  • 免疫检查点抑制剂 (ICI) 可以导致心肌炎,一种罕见但可能致命的免疫相关不良事件 (irAE).
  • 目前ICI诱导心肌炎的死亡率在40%-46%之间,病例往往无症状,需要改进监测和治疗策略.
  • 这项研究旨在阐明ICI诱导心肌炎的致病性,并评估癌症中心使用强化患者管理协议的结果.

研究的目的:

  • 为了研究免疫检查点抑制剂 (ICI) 诱导的心肌炎的发病性.
  • 评估心脏IRAE患者在癌症中心强化管理下的结果.
  • 为了确定ICI诱导心肌炎的潜在预测生物标志物.

主要方法:

  • 分析来自SERIO注册表的患者数据,包括人口统计,ICI细节,irAE治疗和结果.
  • 从irMyocarditis患者的心脏活检使用纳米链进行了分析,与健康对照者相比.
  • 用流细胞计进行了周围血液单核细胞 (PBMC) 的长度免疫类型定型.

主要成果:

  • 总共分析了51名患有53例心脏激发性意外事件的患者;11.3%是致命的.
  • 已建立托罗邦监测和及时治疗的中心显示死亡率明显较低.
  • 在心肌活检中观察到细胞因子介导信号通路的差异调节;在PBMC中观察到CD4+Treg细胞和效应记忆T细胞的ICI驱动的变化.
  • LAG3和PD-L1表达显示出作为irMyocarditis的预测指标的潜力.

结论:

  • 加强患者管理,包括监测和及时治疗,大大降低了ICI诱导心肌炎的死亡率.
  • 已经确定了与ICI诱导心脏毒性相关的新型局部和全身免疫学模式.
  • 对LAG3和PD-L1表达等预测性生物标志物的进一步研究是有必要的.