Abstract: Background　Ejection fraction-preserving heart failure（HFpEF）is a highly heterogeneous disease involving multiple systems with mild symptoms，but its morbidity and mortality are high and traditional drugs are not effective.Spironolactone is a diuretic commonly used in the treatment of chronic heart failure and has a potassium-sparing effect.Recently，it has been found to play an important role in antiventricular remodeling，which may be related to the patient's left ventricular ejection fraction（LVEF）．Objective　To investigate the relationship between ejection fraction and the efficacy and prognosis of low-dose spironolactone in the treatment of HFpEF and to provide evidence for clinical treatment of HFpEF.Methods　A total of 187 patients with HFpEF diagnosed in the DepartmentⅡ of Cardiology，Xinyang Central Hospital，Henan Province were enrolled from January 2014 to January 2016.Baseline data of patients were collected and they were divided into LVEF 45%-49% group（36 cases），LVEF 50%-54% group（42 cases），LVEF 55%-59% group（49 cases），LVEF≥60% group（60 cases）according to LVEF.All patients were treated with 25 mg of spironolactone for one week on the basis of the original treatment plan at the start of the study.If hyperkalemia were not found in patients，then they would continue to be administered at a dose of 25 mg once daily for 180 days.The efficacy was tested at 3 months after drug withdrawal.The patients were followed up for 30 months and the main endpoint events including death from heart failure，heart failure rehospitalization，and all-cause death in each group were counted.Results　In December 2016，one patient in LVEF 50%-54% group was lost to follow-up due to work reasons.In June 2017，one patient in LVEF≥60% group was lost to follow up due to invalid contact.The incidence of myocardial infarction in LVEF 50%-54% group was lower than that in LVEF 45%-49% group，while the incidence of hypertension，diabetes，and the utilization ratio of diuretics were higher than those in LVEF 45%-49% group（P<0.05）；the proportion of women，age and the incidence of hypertension，diabetes，and the utilization ratio of diuretics in LVEF 55%-59% group were higher than those in LVEF 45%-49% group，but the diastolic blood pressure，myocardial infarction，and the utilization ratio of angiotensin-converting enzyme inhibition（ACEI）/angiotensinⅡ receptor antagonist（ARB）were lower than those in LVEF 45%-49% group（P<0.05）；the proportion of women and the incidence of hypertension，diabetes in LVEF 55%-59% group were higher than those in LVEF 50%-54% group，while the diastolic blood pressure，the incidence of myocardial infarction，the utilization ratio of ACEI/ARB and diuretics were lower than those in LVEF 50%-54% group（P<0.05）；the proportion of women，age，Body Mass Index（BMI）and the incidence of hypertension，diabetes in LVEF≥60% group were higher than those in LVEF 45%-49% and 50%-54% group，but the diastolic blood pressure，heart rate，estimated glomerular filtration rate（eGFR），hospitalization due to heart failure within one year，incidence of myocardial infarction and the utilization ratio of ACEI/ARB were lower than those in LVEF 45%-49% and 50%-54% group（P<0.05）；the utilization ratio of diuretics in LVEF≥60% group was higher than that of LVEF 45%-49% group（P<0.05）and the proportion of women，age，incidence of diabetes were higher than those in LVEF 55%-59% group，and the heart rate，hospitalization due to heart failure within one year and the utilization ratio of ACEI/ARB were lower than those in LVEF 55%-59% group（P<0.05）．The efficacy of LVEF 45%-49% group was better than that in LVEF 55%-59% group and LVEF ≥60% group（P<0.05）．The efficacy decreased with increasing LVEF（χ2trend=9.049，P=0.003）．LVEF was negatively correlated with efficacy（rs=-0.222，P=0.002）．The incidence of primary end point events in LVEF 55%-59% group was higher than that in LVEF 45%-49% and 50%-54% group（P<0.05）；the incidence of primary end point events in LVEF≥60% group was higher than that in LVEF 45%-49%，50%-54% and 55%-59% groups（P<0.05）．The incidence of re-hospitalization due to heart failure in LVEF 55%-59% group was higher than that in LVEF 45%-49% and 50%-54% group（P<0.05）．The incidence of re-hospitalization of heart failure in LVEF≥60% group was higher than that in LVEF 45%-49%，50%-54% and 55%-59% groups（P<0.05）．Multivariate Cox regression analysis showed that LVEF，gender，age，history of hypertension，and New York Heart Association（NYHA）classification were the influencing factors of the main endpoints of HFpEF patients（P<0.05），and the LVEF，age，eGFR，and history of myocardial infarction，hypertension and diabetes were the influencing factors of heart failure rehospitalization in patients with HFpEF（P<0.05）．Conclusion　Patients with HFpEF who have lower LVEF（≤54%）had better efficacy with Spironolactone and lower incidence of major endpoint events and re-hospitalization.

Key words: Heart failure, Stroke volume, Spironolactone, Treatment outcome, Prognosis, Left ventricular ejection fraction, Ejection fraction-preserving heart failure

摘要： 背景　射血分数保留型心力衰竭（HFpEF）是一类多系统参与的高度异质性疾病，其症状较轻，但其发病率与病死率较高且传统药物效果不佳，目前仍缺少有效的治疗方法。螺内酯常用于治疗慢性心力衰竭，具有保钾利尿的作用，近年来发现其在抗心室重构方面发挥着重要作用，其可能与患者左心室射血分数（LVEF）相关。目的　探究射血分数与低剂量螺内酯治疗HFpEF疗效和患者预后的关系，为临床治疗HFpEF提供依据。方法　选取2014年1月—2016年1月在河南省信阳市中心医院心血管二科住院的HFpEF患者187例。收集患者基线资料。根据患者LVEF将其分为LVEF 45%~49%组（36例）、LVEF 50%~54%组（42例）、LVEF 55%~59%组（49例）、LVEF≥60%组（60例）。研究开始后，患者在原有治疗方案基础上服用25 mg螺内酯治疗1周，如果患者未发生高钾血症，继续以25 mg、1次/d的剂量给药，维持180 d。停药后3个月检测患者疗效。对患者进行为期30个月的随访，统计各组患者主要终点事件、心力衰竭死亡、心力衰竭再住院、全因死亡发生情况。结果　2016年12月时LVEF 50%~54%组有1例患者因工作原因失访，2017年6月时LVEF≥60%组有1例患者因无效联系失访。LVEF 50%~54%组心肌梗死发生率小于LVEF 45%~49%组，高血压发生率、糖尿病发生率、利尿剂使用率大于LVEF 45%~49%组（P<0.05）；LVEF 55%~59%组女性所占比例、年龄、高血压发生率、糖尿病发生率、利尿剂使用率大于LVEF 45%~49%组，舒张压、心肌梗死发生率、血管紧张素转换酶抑制剂（ACEI）/血管紧张素Ⅱ受体拮抗剂（ARB）使用率小于LVEF 45%~49%组（P<0.05）；LVEF 55%~59%组女性所占比例、高血压发生率、糖尿病发生率大于LVEF 50%~54%组，舒张压、心肌梗死发生率、ACEI/ARB使用率、利尿剂使用率小于LVEF 50%~54%组（P<0.05）；LVEF≥60%组女性所占比例、年龄、BMI、高血压发生率、糖尿病发生率大于LVEF 45%~49%组、LVEF 50%~54%组，舒张压、心率、估算肾小球滤过率（eGFR）、1年内心力衰竭住院发生率、心肌梗死发生率、ACEI/ARB使用率小于LVEF 45%~49%组、LVEF 50%~54%组（P<0.05）；LVEF≥60%组利尿剂使用率大于LVEF 45%~49%组（P<0.05）；LVEF≥60%组女性所占比例、年龄、糖尿病发生率大于LVEF 55%~59%组，心率、1年内心力衰竭住院发生率、ACEI/ARB使用率小于LVEF 55%~59%组（P<0.05）。LVEF 45%~49%组疗效优于LVEF 55%~59%组、LVEF≥60%组（P<0.05）。疗效随着LVEF的增大而变差（χ2趋势=9.049，P=0.003）。LVEF与疗效呈负相关（rs=-0.222，P=0.002）。LVEF 55%~59%组主要终点事件发生率大于LVEF 45%~49%组、LVEF 50%~54%组（P<0.05）；LVEF≥60%组主要终点事件发生率大于LVEF 45%~49%组、LVEF 50%~54%组、LVEF 55%~59%组（P<0.05）。LVEF 55%~59%组心力衰竭再住院发生率大于LVEF 45%~49%组、LVEF 50%~54%组（P<0.05）；LVEF≥60%组心力衰竭再住院发生率大于LVEF 45%~49%组、LVEF 50%~54%组、LVEF 55%~59%组（P<0.05）。多因素Cox回归模型分析结果显示，LVEF、性别、年龄、高血压病史、美国纽约心脏病学会（NYHA）分级是HFpEF患者发生主要终点事件的影响因素（P<0.05）；LVEF、年龄、eGFR、心肌梗死病史、高血压病史、糖尿病病史是HFpEF患者发生心力衰竭再住院的影响因素（P<0.05）。结论　LVEF较低（≤54%）的HFpEF患者服用低剂量螺内酯的疗效更佳，其主要终点事件发生率和再住院治疗率更低。

关键词: 心力衰竭, 每搏输出量, 螺内酯, 治疗结果, 预后, 左心室射血分数, 射血分数保留型心力衰竭