Chrysant Steven G, Chrysant George S
a Department of Cardiology , University of Oklahoma Health Sciences Center , Oklahoma City , OK , USA.
b Department of Cardiology , INTEGRIS Baptist Medical Center , Oklahoma City , OK , USA.
Hosp Pract (1995). 2019 Apr;47(2):67-72. doi: 10.1080/21548331.2019.1575662. Epub 2019 Feb 13.
Obesity has risen in the US and worldwide, and has become a major risk factor for type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease, and mostly HF with preserved ejection fraction (HFpEF). Also, the prevalence of HF is quite high in the US accounting for 6.6 million adults at present and is projected to reach 8.5 million by the year 2030 and is equally divided between HFpEF and heart failure reduced ejection fraction (HFrEF). Patients with HFpEF are resistant to treatment with drugs usually used for the treatment of HFrEF, but the reasons for this resistance are not clearly known.
In order to get a better perspective on the current status of the underlying pathophysiology and treatment of patients with HFpEF, a Medline search of the English language literature was conducted between 2015 and 2018 using the terms obesity, HFpEF, diabetes, treatment, SGLT2 inhibitors, and neprilysin inhibitors and 24 pertinent papers were selected.
The review of these papers revealed that patients with HFpEF have expanded plasma volume, restricted left ventricular distension with increased end-diastolic volume and depressed natriuretic peptide levels. In this respect, drugs that cause increased diuresis and natriuresis should a reasonable choice to treat these patients. The recently FDA approved sodium-glucose cotransporter-2 (SGLT2) inhibitors for the treatment of T2DM, are a good choice, for the treatment of HFpEF, since they cause osmotic diuresis from glucose excretion and increase salt and water excretion and decrease plasma volume. In addition, they produce loss of calories leading to weight and blood pressure reduction and have shown to prevent the new onset HFpEF and decrease hospitalizations and death from this disease.
The results of this analysis has shown that HFpEF has different pathophysiology from HFrEF and is difficult to treat. Drugs that block renal tubular glucose reabsorption and cause osmotic diuresis and natriuresis could be a good choice to treat patients with HFpEF alone or in combination with diuretics and other drugs.
肥胖在美国及全球范围内呈上升趋势，已成为2型糖尿病（T2DM）、高血压、心血管疾病以及主要是射血分数保留的心力衰竭（HFpEF）的主要危险因素。此外，美国心力衰竭的患病率相当高，目前有660万成年人患病，预计到2030年将达到850万，且HFpEF和射血分数降低的心力衰竭（HFrEF）患者人数相当。HFpEF患者对通常用于治疗HFrEF的药物治疗具有抗性，但其抗性原因尚不清楚。
为了更好地了解HFpEF患者潜在病理生理学和治疗的现状，于2015年至2018年期间使用肥胖、HFpEF、糖尿病、治疗、钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂和中性肽链内切酶抑制剂等术语对英文文献进行了Medline检索，并选择了24篇相关论文。
对这些论文的综述显示，HFpEF患者的血浆容量增加、左心室扩张受限，舒张末期容积增加，利钠肽水平降低。在这方面，导致利尿和利钠增加的药物应该是治疗这些患者的合理选择。美国食品药品监督管理局（FDA）最近批准用于治疗T2DM的钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂是治疗HFpEF的良好选择，因为它们可通过葡萄糖排泄引起渗透性利尿，增加盐和水的排泄并减少血浆容量。此外，它们会导致热量损失，从而减轻体重和降低血压，并已证明可预防新发HFpEF，并减少该疾病导致的住院和死亡。
该分析结果表明，HFpEF与HFrEF具有不同的病理生理学，且难以治疗。阻断肾小管葡萄糖重吸收并引起渗透性利尿和利钠的药物可能是单独或与利尿剂及其他药物联合治疗HFpEF患者的良好选择。
