Empagliflozin, a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, has been shown to reduce mortality and hospitalization for heart failure in diabetic patients in the EMPA-REG-OUTCOME trial (Zinman et al., 2015). Surprisingly, dapagliflozin, another SGLT2 inhibitor, exerted comparable effects on clinical endpoints even in the absence of diabetes mellitus (DAPA-HF trial) (McMurray et al., 2019). There is a myriad of suggested underlying mechanisms ranging from improved glycemic control and hemodynamic effects to altered myocardial metabolism, inflammation, neurohumoral activation and intracellular ion homeostasis. Here, we review the effects of gliflozins on cardiac electro-mechanical coupling with an emphasis on novel CaMKII-mediated pathways and on cardiac glucose and ketone metabolism in the failing heart. We focus on empagliflozin as it is the gliflozin with the most abundant experimental evidence for direct effects on the heart. Where useful, we aim to compare empagliflozin to other gliflozins. To facilitate understanding of empagliflozin-induced alterations, we first give a short summary of the pathophysiological role of CaMKII in heart failure, as well as cardiac changes of glucose and ketone body metabolism in the failing heart.

中文翻译：

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CaMKII和GLUT1在心力衰竭和gliflozins中的作用。

Empagliflozin是一种选择性的钠-葡萄糖共转运蛋白2（SGLT2）抑制剂，在EMPA-REG-OUTCOME试验中已显示可降低糖尿病患者的死亡率和因心力衰竭住院（Zinman等人，2015）。令人惊讶的是，另一种SGLT2抑制剂dapagliflozin即使在没有糖尿病的情况下（DAPA-HF试验）对临床终点也具有可比的作用（McMurray等，2019）。从改善的血糖控制和血流动力学影响到改变的心肌代谢，炎症，神经体液激活和细胞内离子稳态，各种各样的潜在机制被提出。在这里，我们审查了格列净对心脏机电耦合的影响，重点是新型CaMKII介导的途径以及衰竭心脏中心脏葡萄糖和酮的代谢。我们重点研究依帕列净，因为依帕列净是对心脏有直接作用的最丰富的实验证据。在有用的地方，我们旨在将依帕列净与其他gliflozins进行比较。为了促进对依格列净诱导的改变的理解，我们首先简要介绍CaMKII在心力衰竭中的病理生理作用，以及在衰竭心脏中心脏葡萄糖和酮体代谢的心脏变化。