Division of Medicine-Cardiology, UT Health San Antonio, 7703 Floyd Curl Drive, Mail Code 7872, San Antonio, TX, 78229, USA.
Department of Internal Medicine, University of Massachusetts Medical School-Bay State, 759 Chestnut Street, Springfield, MA, 01199, USA.
Heart Fail Rev. 2022 Jan;27(1):219-234. doi: 10.1007/s10741-020-09996-y.
Recent cardiovascular outcome trials have highlighted the propensity of the antidiabetic agents, SGLT2 inhibitors (SGLT2is or -flozin drugs), to exert positive clinical outcomes in patients with cardiovascular disease at risk for major adverse cardiovascular events (MACEs). Of interest in cardiac diabetology is the physiological status of the patient with T2DM and heart failure with preserved ejection fraction (HFpEF), a well-examined association. Underlying this pathologic tandem are the effects that long-standing hyperglycemia has on the ability of the HFpEF heart to adequately deliver oxygen. It is believed that shortcomings in oxygen diffusion or utilization and the resulting hypoxia thereafter may play a role in underlying the clinical sequelae of patients with T2DM and HFpEF, with implications in the long-term decline of extra-cardiac tissue. Oxygen consumption is one of the most critical factors in indexing heart failure disease burden, warranting a probe into the role of SGLT2i on oxygen utility in HFpEF and T2DM. We investigated the role of oxygen flux in the patient with T2DM and HFpEF extending beyond the heart with focuses on cellular metabolism, perivascular fibrosis with endothelial dysfunction, hematologic changes, and renal effects with neurohormonal considerations in the patient with HFpEF and T2DM. Moreover, we give a commentary on potential therapeutic targets of these components with SGLT2i to gain insight into disease burden amelioration in patients with HFpEF and T2DM.
最近的心血管结局试验强调了抗糖尿病药物 SGLT2 抑制剂（SGLT2i 或 -flozin 药物）在有发生主要不良心血管事件（MACEs）风险的心血管疾病患者中发挥积极临床结局的倾向。在心脏糖尿病学中，人们感兴趣的是 2 型糖尿病和射血分数保留的心力衰竭（HFpEF）患者的生理状况，这是一个经过充分研究的关联。在这种病理串联的背后，是长期高血糖对 HFpEF 心脏充分输送氧气的能力的影响。人们认为，氧气扩散或利用的缺陷以及随后的缺氧可能在 2 型糖尿病和 HFpEF 患者的临床后果中发挥作用，对心脏外组织的长期衰退产生影响。氧气消耗是索引心力衰竭疾病负担的最关键因素之一，因此需要探究 SGLT2i 在 HFpEF 和 2 型糖尿病患者的氧气利用中的作用。我们研究了氧气通量在 2 型糖尿病和 HFpEF 患者中的作用，这些患者的心脏以外的组织也受到关注，包括细胞代谢、血管周围纤维化和内皮功能障碍、血液变化以及 HFpEF 和 2 型糖尿病患者的肾脏影响和神经激素考虑因素。此外，我们还对这些 SGLT2i 成分的潜在治疗靶点进行了评论，以深入了解 HFpEF 和 2 型糖尿病患者的疾病负担改善情况。
