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马爱群教授谈DHF诊疗进展(下篇)丨ESC2020
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   马爱群教授谈DHF诊疗进展(下篇)丨ESC2020

 
  西安交通大学第一医院心内科 冯云飞 马爱群
 
  编者按:在ESC2020大会上,舒张性心力衰竭(diastolic heart failure,DHF)的诊治作为临床热点,被列入Late-Breaking Science环节讨论,西安交通大学第一医院马爱群教授团队对DHF相关研究及诊疗进展进行了总结。现整理如下,以飨读者。
 
  四、  DHF的临床表现与诊断
 
  01、临床表现
 
  DHF临床症状不典型,老龄多见,可出现气短、疲乏、咳嗽、劳力性呼吸困难、水肿等心力衰竭症状;严重时出现端坐呼吸、咳粉红色泡沫痰。
 
  DHF缺乏特异性体征,心界不大,心音一般不低,偶可闻及第四心音,心率快,常伴心房颤动。双侧肺底可闻及细湿性啰音,严重者满肺可以闻及大、中、细湿性啰音。
 
  02、DHF的诊断
 
  目前DHF的诊断主要是结合心衰的症状及体征,心电图、X线片、超声心动图、氨基末端脑钠肽前体(NT-proBNP)进行综合分析,但仍缺乏严格、统一的诊断标准,这也是DHF相关大型临床面临的严峻挑战。现临床用于评估心室舒张功能的心动超声图参数主要包括:
 
  ① E峰、A峰值:是测量心脏舒张期二尖瓣口前向血流速度的两个峰值,E峰是左心室舒张早期最大血流,A峰是二尖瓣心房收缩期最大血流。而E/A比值可以进一步评估舒张功能,并进行舒张功能分级。
 
  ② e’速度(e’ velocity):是指左室间隔侧和侧壁侧的二尖瓣环运动频谱,经组织多普勒(TDI)测量,若间隔侧e’<7cm/s或侧壁侧e’<10 cm/s提示舒张功能异常。
 
  ③ E/e’比值:与左室僵硬度及纤维化相关,可以用来评估左室充盈压,当E/e’≥15时提示异常。
 
  ④ 三尖瓣反流峰值速度(TRPV):TRPV>2.8 m/s时提示异常。
 
  ⑤ 左心房容积指数(LAVI):LAVI=左心房容积/体表面积,当LAVI>34 ml/m2时提示异常。
 
  另外还包括左心室质量指数(LVMI)、左室整体长轴应变(GLS)、左室相对室壁厚度(relative wall thickness,RWT)等反映左心功能及形态的指标。
 
  DHF患者尽管存在舒张功能障碍,但某些测量值可能仍在正常范围内,因此诊断时不应单独使用任何指标来评估舒张功能。欧洲心脏病学会(ESC)心力衰竭协会(HFA)颁布的共识建议应用HFA-PEFF诊断流程进行DHF的诊断,具体分为以下4个步骤。
 
  (1) 初始评估(Pre-test assessment,P)
 
  对于任何出现心衰相关症状和/或体征的患者,应进行初始评估。通常在门诊进行,评估内容包括心衰症状和体征、典型的临床和人口统计学情况(肥胖、高血压、糖尿病、老年人、心房颤动)、诊断性实验室检测(包括血常规、肝肾功、电解质等)、心电图以、标准超声心动图及运动试验。排除其他导致呼吸困难的心源性及非心源性原因,同时LVEF正常,利钠肽(natriuretic peptide,NP)升高或正常,至少有一个DHF的危险因素,则疑诊DHF,进行下一评估。
 
  (2) 超声心动图及利钠肽评分(Echocardiographic and natriuretic peptide score,E)
 
  对于DHF疑似患者,应结合超声心动图测量的心脏结构和功能的综合情况以及NP水平来判断,如图1所示。若得分≥5分提示明确的HFpEF,≤1分诊断为HFpEF的可能性小;2~4分表明诊断存在不确定性,建议进一步评估。评分详见表1。
 
  如果超声心动图不能测量LAVI、LVMI或室壁厚度,建议进行心脏核磁(CMR)检查。
 
表1. 基于心动超声图及利钠肽的评分
 
  (3) 功能测试(Functional testing,F1)
 
  包括运动负荷超声心动图和静息、运动时的侵入性血流动力学监测。
 
  经运动负荷超声图检查,若平均E/e’≥15,则在第二步的评分系统中加2分,若平均E/e’≥15且TRPV>3.4m/s,则加3分。重新评分,若得分≥5分则可诊断DHF。若得分仍<5分,或者不能完成运动负荷超声图,建议进行侵入性血流动力学监测。
 
  侵入性血流动力学监测包括左心及右心导管检查。经监测,静息状态下,若左室舒张时间常数τ>48 ms或左心室舒张末压(LVEDP)≥16 mm Hg或肺毛细血管楔压(PCWP)≥15 mm Hg,则可诊断DHF;运动负荷状态下,PCWP ≥25 mm Hg可诊断DHF。而静息状态下的高PCWP和运动状态下病理性升高的PCWP是DHF预后不良的预测指标。
 
  来自澳大利亚国家超声数据库(NEDA)最新研究数据表明,无论是LVEF保留还是LVEF受损的患者,与舒张功能正常者相比,舒张功能障碍增加了死亡风险。在单独分析各项舒张功能指标时,E、e’、E/e’及LAVI是增加心血管相关死亡风险的关键点。当E≥90cm/s、e’≤9cm/s、E/e’≥9及LAVI≥32 ml/m2时,死亡率明显增加(图1)。而LVEF受损和年龄增加均可明显影响舒张功能。
 
 
  (4) 病因学诊断(Final aetiology,F2)
 
  确定HFpEF病因或具有类DHF样表现的相似疾病。共识中推荐可以进一步进行心脏核磁、核素显像、PET/CT、病理学检查(如心脏或非心脏的活检)、免疫炎性因子及代谢因子检测、基因检测等。其中心脏核磁在缺血性心肌病、肥厚型心肌病、心肌致密化不全、心肌浸润性疾病、微血管病变等方面具有很高的诊断及鉴别诊断价值。尤其对于年轻、有心肌病/心衰家族史、没有或仅有轻微的危险因素/合并症、左室肥厚、局部心室运动异常、室性心律失常、严重的右心扩张、存在心肌瘢痕组织的人群,更进一步的检测是必要的。而病因或其他相关疾病的诊断,对于DHF的精准治疗意义重大。
 
  五、 DHF的治疗
 
  目前,尚无可降低DHF患病率和死亡率的确切治疗。特别是,用于HF的传统药物并不能使HFpEF的发病率和死亡率降低,一些DHF治疗相关的大型临床研究也均未得到满意结果。较早的CHARM试验未能证明坎地沙坦对DHF有益,随后一些针对肾素-血管紧张素系统的治疗亦不能降低DHF的死亡率。在PARAGON-HF试验中,与缬沙坦相比,沙库巴曲缬沙坦也不能改善HFpEF患者的DHF再住院率和心源性死亡率,但也有研究表明沙库巴曲缬沙坦具有的抗纤维化特性可能对DHF患者有益。TOPCAT试验研究结果显示,螺内酯仅可降低部分地区DHF患者的心血管死亡和心衰住院率,对于EF≥50%的患者,使用β受体阻滞剂与甚至与心衰住院的风险增加相关。因此目前治疗DHF患者的主要是是病因治疗和对症治疗。
 
  01、病因治疗
 
  积极治疗常见且对DHF临床进程有明显促进作用的危险因素和合并症,如肥胖、高血压、冠心病、心房颤动、糖尿病、慢性阻塞性肺病、贫血、慢性肾脏病和睡眠呼吸障碍等。这也是DHF患者治疗中最为重要的部分。其中,心动过速时舒张期充盈时间缩短,进一步影响心搏量,因此合并心房颤动的DHF患者,转复并维持窦性心律是首选,慢性心房颤动应控制心室率、积极抗凝]。
 
  02、对症治疗
 
  可以应用最低有效剂量的利尿剂进行对症治疗。
 
  总之,DHF是一种组复杂的系统性临床综合征,常伴有多脏器多系统病变,以功能受限、预后差为特点。DHF是老年人中一种快速增长的疾病,NEDA最新研究也表明年龄可以显著影响舒张功能,因此DHF可以认为是衰老并影响所有器官系统的老年综合症,包括多种表型,这可能是诸多针对任何具体、单一治疗方法的临床试验不能获得阳性结果的原因之一。因此,对DHF病理生理、发病机制的进一步认知,并采用表型特异性治疗方法可能是成功管理DHF的关键。
 
 
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专家简介
 
 
  马爱群,医学博士,博士生导师,二级教授/一级主任医师,教育部骨干教师,陕西省“35”人才,陕西省卫生厅“215”人才。现任陕西省分子心脏病学重点实验室主任,陕西省心血管疾病质量控制中心主任,陕西省全科医学会主任委员,中华医学会全科医学分会常务委员,《中国分子心脏病学杂志》副主编,《中华心力衰竭和心肌病杂志》副总编辑。主要研究方向为心力衰竭、心血管离子通道病及心血管疾病精准医学的应用研究。先后主持科技部科技惠民计划1项、科技部国际科技合作项目1项、国家自然科学基金4项(重点项目1项,面上项目3项)、卫生部科研基金4项、教育部项目3项及陕西省自然科学基金4项;共发表论文300余篇,其中SCI收录130多篇(H因子为24),主编专著9部,主编国家临床(助理)医师执业资格考试系列丛书6部,主译专著1部,参编专著5部;获得国家实用新型专利1项,软件著作权2项。先后获陕西省科学技术奖一等奖2项、二等奖1项,中华医学科技奖三等奖1项及其他厅级科技成果奖4项;先后指导毕业博士研究生65名,硕士研究生70名。
 
  冯云飞,2008.09-2015.06 就读于吉林大学临床医学七年制;2015.08-2019.03就职于空军军医大学附属西京医院急诊科;2019.09加入西安交通大学第一附属医院心内科马爱群老师课题组,进行博士学习,目前主要研究方向为心力衰竭的诊治及心脏离子通道病的基础研究。
 
 
 
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