射血分數降低和射血分數保留的急性心力衰竭患者遠期預后分析

謝秀峰，崔曉迎，袁海鳳，陳鳳英，牛君義

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·論著·

射血分數降低和射血分數保留的急性心力衰竭患者遠期預后分析

謝秀峰，崔曉迎，袁海鳳，陳鳳英，牛君義

背景 射血分數降低的急性心力衰竭(AHFrEF)和射血分數保留的急性心力衰竭(AHFpEF)患者短期預后差異不顯著，但遠期隨訪資料缺乏。目的 比較AHFrEF和AHFpEF患者出院后3年內再住院率和病死率，并探討影響患者再住院的危險因素。方法 選取2011—2012年于內蒙古醫科大學附屬醫院急診科和內蒙古自治區人民醫院急診科首次診斷為急性心力衰竭(AHF)的患者296例為研究對象，依據左心室射血分數(LVEF)，將患者分為AHFrEF組(LVEF<50%，n=171)和AHFpEF組(LVEF≥50%,n=125)。記錄患者性別、年齡、吸煙史、合并癥、急性冠脈綜合征(ACS)、充血性心力衰竭(CHF)、影像學檢查、B型利鈉肽(BNP)水平，以及出院醫囑用藥情況。出院后通過電話或門診隨訪3年，觀察終點為心腦血管源再住院或死亡。結果 兩組高血壓、慢性阻塞性肺疾病(COPD)、ACS、CHF、左心室擴大檢出率，以及BNP≥220 ng/L、出院醫囑口服β-受體阻滯劑(β-RB)比例比較，差異均有統計學意義(P<0.05)。兩組因ACS、腦卒中及惡性心律失常引起的再住院率比較，差異均無統計學意義(P>0.05)。AHFrEF組因心力衰竭引起的再住院率高于AHFpEF組，且總再住院率高于AHFpEF組(P<0.05)。多因素Cox比例風險回歸模型分析顯示，高血壓〔HR=1.450,95%CI(1.036,2.030)〕和BNP≥220 ng/L〔HR=1.894,95%CI(1.327,2.702)〕是AHF患者再住院的獨立危險因素(P<0.05)。AHFrEF組1、2、3年生存率分別為98%、95%、85%，AHFpEF組1、2、3年生存率分別為98%、94%、86%。兩組生存曲線比較，差異有統計學意義(χ2=6.656，P=0.010)。結論 AHFrEF患者3年內因心力衰竭引起的再住院率高于AHFpEF患者，3年生存率低于AHFpEF患者；高血壓和高水平BNP是AHF患者再住院的獨立危險因素。臨床應加強對AHFrEF患者的隨訪，改善合并高血壓患者的血壓控制水平。

心力衰竭；每搏輸出量；住院；預后；高血壓；利鈉肽，腦

謝秀峰，崔曉迎，袁海鳳，等.射血分數降低和射血分數保留的急性心力衰竭患者遠期預后分析[J].中國全科醫學，2016，19(34)：4196-4200.[www.chinagp.net]

XIE X F,CUI X Y,YUAN H F,et al.Long-term prognosis of acute heart failure patients with reduced ejection fraction and with preserved ejection fraction[J].Chinese General Practice，2016，19(34)：4196-4200.

急性心力衰竭(acute heart failure,AHF)是老年患者再住院的主要原因，依據左心室射血分數(left ventricular ejection fraction,LVEF)，AHF可分為射血分數降低的AHF(acute heart failure with reduced ejection fraction，AHFrEF)和射血分數保留的AHF(acute heart failure with preserved ejection fraction，AHFpEF)。研究表明，AHF患者發病率和病死率較高[1-3]，1/3以上的心力衰竭患者出院后90 d內再住院或死亡[4]。AHFrEF已被臨床廣泛認識，但并非所有的AHF均伴有心室的收縮功能障礙，部分AHF患者有一定的收縮功能，即AHFpEF。近期研究表明，低LVEF是AHFrEF的主要危險因素，而高B型利鈉肽(BNP)水平是AHFpEF的危險因素[5]。目前，AHFrEF和AHFpEF患者遠期預后比較研究較少。本研究旨在比較AHFrEF和AHFpEF患者出院后3年內再住院率和病死率，并探討影響患者再住院的危險因素，為改善AHF患者預后提供參考。

1 對象與方法

1.1 研究對象 選取2011—2012年于內蒙古醫科大學附屬醫院急診科和內蒙古自治區人民醫院急診科首次診斷為AHF的患者296例為研究對象，其中男154例，女142例；年齡59～80歲，平均年齡(69.7±10.3)歲。納入標準：(1)符合歐洲心臟病學會(ESC)AHF的診斷標準[6]；(2)Killip分級Ⅲ～Ⅳ級，具有肺淤血癥狀和體征；(3)經抗AHF及治療原發病好轉后出院。排除妊娠、肺動脈栓塞、心臟瓣膜病、嚴重腎功能不全等。患者均簽署知情同意書，本研究經內蒙古醫科大學附屬醫院倫理委員會倫理審查。

本文要點：

本研究旨在探討射血分數降低的急性心力衰竭(AHFrEF)與射血分數保留的急性心力衰竭(AHFpEF)患者的遠期預后。通過電話或門診隨訪3年，觀察終點為心腦血管源再住院或死亡。結果顯示，AHFrEF患者3年內的再住院率高于AHFpEF患者，3年生存率低于AHFpEF患者，高血壓和高水平的B型利鈉肽(BNP)是心力衰竭(AHF)患者再住院的獨立危險因素。

1.2 方法

1.2.1 治療 患者均接受利尿、血管擴張治療，部分患者給予嗎啡、正性肌力藥物治療。

1.2.2 LVEF的檢測 由超聲科專業人員采用多功能彩色多普勒儀(型號為Vivid 7，美國GE公司)檢測超聲心動圖，應用二維改良simipson公式計算LVEF。依據LVEF，將患者分為AHFrEF組(LVEF<50%)171例(57.8%)和AHFpEF組(LVEF≥50%)125例(42.2%)。

1.2.3 資料收集 記錄患者性別、年齡、吸煙史、合并癥〔高血壓、糖尿病、慢性腎臟病、慢性阻塞性肺疾病(COPD)、心房顫動〕、急性冠脈綜合征(ACS)、充血性心力衰竭(CHF)、影像學檢查、BNP水平，以及出院醫囑用藥〔血管緊張素轉化酶抑制劑(ACEI)、血管緊張素Ⅱ受體阻滯劑(ARB)、β-受體阻滯劑(β-RB)〕情況。

1.2.4 隨訪 出院后通過電話或門診隨訪3年，觀察終點為心腦血管源再住院或死亡，其中心腦血管源包括心力衰竭、ACS、腦卒中和惡性心律失常，惡性心律失常定義為癥狀持續的室性心動過速和心室顫動，無論血流動力學是否穩定。

2 結果

2.1 基線資料比較 兩組性別、年齡、吸煙史，糖尿病、慢性腎臟病、心房顫動、左心房擴大檢出率，Killip分級Ⅳ級、出院醫囑口服ACEI/ARB比例比較，差異均無統計學意義(P>0.05)。兩組高血壓、COPD、ACS、CHF、左心室擴大檢出率，以及BNP≥220ng/L、出院醫囑口服β-RB比例比較，差異均有統計學意義(P<0.05，見表1)。

2.2 心腦血管源再住院率比較 兩組因ACS、腦卒中及惡性心律失常引起的再住院率比較，差異均無統計學意義(P>0.05)。AHFrEF組因心力衰竭引起的再住院率高于AHFpEF組，且總再住院率高于AHFpEF組，差異均有統計學意義(P<0.05，見表2)。

2.3 再住院影響因素的多因素Cox比例風險回歸模型分析 以患者基線資料及LVEF為自變量，是否再住院為因變量，行多因素Cox比例風險回歸模型分析，變量賦值見表3。結果顯示，高血壓〔HR=1.450,95%CI(1.036,2.030)〕和BNP≥220ng/L〔HR=1.894,95%CI(1.327,2.702)〕是AHF患者再住院的危險因素(P<0.05)。

2.4 生存分析AHFrEF組1、2、3年生存率分別為98%、95%、85%，AHFpEF組1、2、3年生存率分別為98%、94%、86%。兩組生存曲線比較，差異有統計學意義(χ2=6.656，P=0.010，見圖1)。

表2 兩組患者心腦血管源再住院率比較〔n(%)〕

表3 AHF患者再住院影響因素的多因素Cox比例風險回歸模型分析變量賦值

注：LVEF=左心室射血分數

表1 兩組患者基線資料比較

注：AHFrEF=射血分數降低的急性心力衰竭，AHFpEF=射血分數保留的急性心力衰竭，COPD=慢性阻塞性肺疾病，ACS=急性冠脈綜合征，CHF=充血性心力衰竭，BNP=B型利鈉肽，ACEI=血管緊張素轉化酶抑制劑，ARB=血管緊張素Ⅱ受體阻滯劑，β-RB=β-受體阻滯劑；a為t值

注：AHFrEF=射血分數降低的急性心力衰竭，AHFpEF=射血分數保留的急性心力衰竭

3 討論

AHF常見的病因包括慢性心力衰竭加重，急性心肌梗死、急性心肌炎及藥物等導致的急性心肌壞死或損傷，瓣膜疾病、高血壓危象、急性心包填塞等導致的急性血流動力學障礙[7-8]。可見，AHF病因復雜，部分患者AHF發生前有不同程度的慢性心力衰竭史。本研究顯示，AHFrEF組患者原發病為ACS比例高于AHFpEF組，且既往有CHF病史患者比例高于AHFpEF組。

AHF可發生于既往有或無心臟病病史的患者，且心功能異常可以是收縮功能異常，也可以是舒張功能異常。既往研究表明，AHFpEF較AHFrEF更為常見[9]。然而，本組AHFrEF患者占57.8%(171/296)，與OWAN等[10]結果相近。與AHFpEF組比較，AHFrEF組有較高的左心室擴大檢出率和BNP水平。研究顯示，左心室擴大患者較左心室結構正常者心力衰竭的發生風險高[11]。BNP是心力衰竭診斷及判斷預后的重要指標，與心力衰竭的臨床表現及預后密切相關[12]。BNP受患者年齡和心臟收縮功能的影響，但變異性小，因此，入院時BNP水平可用于預測心源性及全因死亡預后。有研究表明，出院時BNP水平對心源性及全因死亡具有較好的預測價值[13]。

有研究顯示，高血壓、糖尿病及心房顫動是AHFpEF的危險因素[14]，肺部疾病、貧血及肥胖在AHFpEF患者中更常見[15-16]。本研究發現，AHFpEF組患者高血壓、COPD檢出率高于AHFrEF組,而兩組糖尿病和心房顫動檢出率無差異。

ATHER等[17]研究發現，與AHFrEF相比，AHFpEF患者與非心力衰竭住院相關的伴隨疾病負擔更重。由冠心病引起的AHFrEF患者死亡風險增加[18]。本研究發現，隨訪期間，AHFrEF組和AHFpEF組因ACS、腦卒中及惡性心律失常引起的再住院率無差異，AHFrEF組因心力衰竭引起的再住院率高于AHFpEF組，且總再住院率也高于AHFpEF組，與既往研究結果相似[19-20]。

多因素Cox比例風險回歸模型分析顯示，高血壓和BNP≥220 ng/L是AHF患者再住院的獨立危險因素。高血壓是冠心病的獨立危險因素，長期高血壓可導致全身動脈壓力升高、左心室肥厚甚至LVEF下降，進而使心力衰竭的發生率顯著上升。OPTIMIZE-HF項目登記了美國259家醫院住院的心力衰竭患者,其研究表明收縮壓是收縮功能降低或相對保存患者心力衰竭發病率和病死率的獨立預測因子[21]。TROUGHTON等[22]研究顯示，N末端B型利鈉肽前體(NT-proBNP)水平與心力衰竭癥狀的嚴重程度(基于紐約心臟病學會分類)密切相關。NT-proBNP水平與左心室收縮功能障礙的聯系已很明確,即使沒有收縮功能障礙存在,NT-proBNP水平也與舒張功能障礙相關，AHFrEF患者血漿NT-proBNP水平高于AHFpEF患者。2008年ESC心力衰竭診斷和治療指南中明確指出，對于有心力衰竭癥狀而未經治療的患者,進行BNP或NT-proBNP檢測有助于診斷[23]。因此，NT-proBNP是診斷心力衰竭及評估預后的必不可少的指標。

綜上所述，AHFrEF患者3年內再住院率高于AHFpEF患者，3年生存率低于AHFpEF患者；高血壓和高水平BNP是AHF患者再住院的獨立危險因素。本研究是患者來源于內蒙古兩家三級甲等醫院的觀察性研究，把現有結果在其他地區進行推斷時需注意。另外，本研究發現AHFrEF組和AHFpEF組患者3年生存率不同。但本研究隨訪時間短，患者病死率相對較低，兩組生存曲線未能明顯區分開。

作者貢獻：謝秀峰進行課題設計與實施、資料收集整理、成文并對文章負責；袁海鳳、陳鳳英、牛君義進行課題設計與實施、評估、資料收集整理；崔曉迎進行質量控制及審校。

本文無利益沖突。

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(本文編輯：吳立波)

Long-term Prognosis of Acute Heart Failure Patients with Reduced Ejection Fraction and with Preserved Ejection Fraction

XIEXiu-feng,CUIXiao-ying,YUANHai-feng,CHENFeng-ying,NIUJun-yi.

DepartmentofEmergency,theAffiliatedHospitalofInnerMongoliaMedicalUniversity,Hohhot010050,China

Correspondingauthor：CUIXiao-ying,DepartmentofEmergency,theAffiliatedHospitalofInnerMongoliaMedicalUniversity,Hohhot010050,China；E-mail：cuixiaoying-jiayingli@hotmail.com

Background There is no significant difference in short-term prognosis between acute heart failure(AHF)patients with reduced ejection fraction(AHFrEF)and AHF patients with preserved ejection fraction(AHFpEF),but there have been few long-term follow-up data.Objective To compare the three-year re-hospitalization rate and mortality after discharge between AHFrEF and AHFpEF,and to explore the influencing factors for re-hospitalization.Methods A total of 296 patients who were first diagnosed with AHF in Department of Emergency of the Affiliated Hospital of Inner Mongolia Medical University and Inner Mongolia People′s Hospital during 2011 to 2012,were selected as study subjects.Subjects were divided into two groups according to the left ventricular ejection fraction(LVEF)，AHFrEF group(LVEF <50%,n=171)and AHFpEF group(LVEF≥50%,n=125).The patients′ gender,age,smoking history,combined disease,acute coronary syndrome(ACS),congestive heart failure(CHF),imaging examination,BNP level,and medication status after discharge were recorded.After discharge,patients were followed up for 3 years through telephone or clinic,the end point was re-hospitalization due to cardiocerebral vascular factors or death.Results There were significant difference in detection rate of hypertension,COPD,ACS,CHF,left ventricular hypertrophy,and ratio of BNP≥220 ng/L,taking oral β receptor blockers(β-RB)between two groups(P<0.05).There were no significant difference in rate of re-hospitalization due to ACS,stroke and malignant arrhythmia between two groups(P>0.05).The rate of re-hospitalization due to heart failure and total re-hospitalization rate among AHFrEF group were significant higher than those among AHFpEF group(P<0.05).According to multiariable Cox proportional hazards regression model,hypertension 〔HR=1.450,95%CI(1.036,2.030)〕 and BNP≥220 ng/L 〔HR=1.894,95%CI(1.327,2.702)〕 were independent risk factors for re-hospitalization of AHF patients(P<0.05).One-year,two-year,and three-year survival rates among AHFrEF group were 98%，95% and 85%,respectively.One-year,two-year,and three-year survival rates among AHFpEF group were 98%，94% and 86%,respectively.There was significant difference in survival curve between two groups(χ2=6.656，P=0.010).Conclusion The rate of re-hospitalization due to heart failure in three years among AHFrEF patients is higher than that among AHFpEF patients,and survival rate in three years among AHFrEF patients is lower than that among AHFpEF patients.Hypertension and high level of BNP were independent risk factors for re-hospitalization of AHF patients.The follow-up of AHFrEF patients should be strengthened，and blood pressure in patients with hypertension should be controlled well.

Heart failure；Stroke volume；Hospitalization；Prognosis；Hypertension；Natriuretic peptide,brain

010050內蒙古呼和浩特市，內蒙古醫科大學附屬醫院急診科(謝秀峰，崔曉迎，陳鳳英，牛君義)；內蒙古自治區人民醫院急診科(袁海鳳)

崔曉迎，010050內蒙古呼和浩特市，內蒙古醫科大學附屬醫院急診科；E-mail：cuixiaoying-jiayingli@hotmail.com

R 541.6

A

10.3969/j.issn.1007-9572.2016.34.009

2016-05-05；

2016-10-18)