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冠状动脉粥样硬化性心脏病猝死的危险分层

2012-01-01 刘金秋 大连医科大学附属第一医院

    冠状动脉粥样硬化性心脏病(冠心病)是心源性猝死的高危人群,欧美国家心源性猝死的发病率50-60/10万,美国每年大概18万-25万例猝死,心源性猝死占猝死患者的80%,在心源性猝死当中,80%死于冠心病,10-15%心肌病,5-10%死于少见心脏病[1]。二级预防的有效实施降低了冠心病的死亡率,使冠心病患者数量的持续增长,心源性猝死的发病率也在逐年升高,中国发

    冠状动脉粥样硬化性心脏病(冠心病)是心源性猝死的高危人群,欧美国家心源性猝死的发病率50-60/10万,美国每年大概18-25万例猝死,心源性猝死占猝死患者的80%,在心源性猝死当中,80%死于冠心病,10-15%心肌病,5-10%死于少见心脏病[1]。二级预防的有效实施降低了冠心病的死亡率,使冠心病患者数量的持续增长,心源性猝死的发病率也在逐年升高,中国发病率略低,但是人口基数很大,问题更加严重。心脏内转律除颤器(ICD)虽然可以有效预防猝死,但是还有很多未植入的患者发生了猝死,部分植入的患者没有派上用场而且发生了误放电等不良反应[2],究其原因,就是对冠心病猝死缺少强有效的评估策略,如何对冠心病猝死进行危险分层,更加有针对性植入ICD,是猝死预防和治疗领域的关键问题也是困扰心内科医生的难题。

心源性猝死的危险因子包括[3]:急性心肌梗死、室性心动过速病史或电生理检查阳性、左室射血分数降低、糖尿病、社会地位低和受教育程度低等。其中射血分数低无论对于冠心病和非冠心病猝死都是强有力的预测指标,而且久经考验,1983年发现其预测价值以来,不断有研究进一步证实,射血分数每降低5%,猝死的风险增加21%。但是遗憾的是只有30%的猝死可以用射血分数低来解释,射血分数正常的冠心病患者猝死的风险依然很高,Stecker[4]研究显示65%猝死不具有现有的ICD植入标准,显然,现有的单一标准已经不能满足临床实际工作的要求,冠心病急性心肌缺血期和非急性缺血期的有创和无创指标的评估,包括电生理检查、左心功能、临床特征、心电图、信号平均心电图、动态心电图、心率变异性、心率震荡、T波电交替、心脏核磁共振等,多因素综合评估有一定的实践意义。

急性心肌梗死后猝死的危险分层

急性心肌梗死的药物治疗和介入治疗取得了重大成效,存活的患者越来越多,急性心肌梗死因后死亡率增加[5]与以下因素相关(表1),患者的因素包括年龄、合并糖尿病高血压等,心脏参数包括梗死部位、范围、房颤、束支阻滞等。急性心梗幸存的患者是以后猝死的高危人群,评估这些患者猝死风险主要需要从以下几个方面进行:室性心动过速、左心功能、残存心肌的缺血、自主神经功能紊乱、心律失常的心肌基质等。心肌梗死48小时后,因发生室颤致心脏骤停的患者,心脏骤停的复发率很高,除了最佳的改善缺血治疗之外,需要评价是否需要ICD,如果有直接和明确的证据证实室颤继发于急性心肌缺血,既往患者没有心肌梗死的病史,应首选心肌血管重建术。如果患者不能接受心肌血管重建术,而且心功能显著降低时,植入ICD是首选的治疗方法。

1:独立预测急性心肌梗死后死亡风险增加的参数

患者因素

年龄

女性

吸烟

糖尿病

高血压

脑血管病史

抑郁症

心脏参数

左室射血分数

存在充血性心衰

存在二尖瓣返流

梗死面积

梗死部位(前壁、右室梗死差)

冠脉病变(左主干、多支病变更差)

房颤

存在束支阻滞

高度方式阻滞

 

有创性心内电生理检查(EPS

早期的研究结果意见不一,可能由于患者选择、心梗后多长时间开始检查、程序刺激方案有关,但是基于MADITMUSTT研究结果,指南仍然强调用EPS作为指导ICD植入的标准之一。将来联合应用微服极T波电交替(MTWA)、心率变异性(HRV)等无创指标可能更有前景。

左心功能评价

射血分数(LVEF)低无论对于冠心病和非冠心病猝死都是强有力的预测指标,但是急性心梗早期LVEF下降不是ICD植入的适应症,40天以后如果LVEF<35%,心功能II-III级,是ICD植入IA类适应症;心功能I级,LVEF<30%,IA类适应症。(原为IIa类,现I类适应症)。LVEF与死亡率和再梗的发生率呈负相关。但是遗憾的是只有30%的猝死可以用射血分数低来解释,其他的评价指标要综合考虑。其他超声指标:左室收缩末容积、左室舒张末容积、左室壁运动指数、左室舒张功能指标以及应用组织多普勒测定心肌收缩功能等对猝死也有一定预测价值。

12导心电图评价

心电图改变包括存在束支阻滞、QRS间期、左室肥厚、QT离散度等,这些心电图改变提示心肌功能受损,死亡率增加,但是不一定都与猝死相关。MUSTT研究发现左束支阻滞和室内阻滞患者死亡率增加,但是与可诱发的室速之间没有相关性,PainFreeRX II研究发现有无室性心律失常与QT离散度之间没有相关性,因此根据心电图改变指导ICD植入没有还没有相关证据。近来研究发现QRS波的碎裂与心室异常除极相关,与猝死相关,但是不管是存在于宽QRS波基础上还是窄QRS波基础上的QRS波碎裂,都需要进一步研究才能指导ICD植入。

信号平均心电图(SAECG

25-50%急性心梗患者SAECG阳性,可见碎裂除级的晚电位,晚电位代表病变心肌的缓慢传导现象。Kuchar等和Steinberg等各随访近200例急性心梗患者11-14个月,SAECG有预测猝死的意义,阴性预测价值更大>95%,但是阳性预测价值低,限制了它的单独预测应用。CABG Patch试验包括了900例急性心梗患者,LVEF<36%,随访32+-16个月,没有发现SAECG的预测价值,可能是介入治疗降低了SAECG的预测意义,如果联合应用LVEF等也许有希望。                                                             

动态心电图(Holter

早期的研究发现Holter记录到的非持续性室速和室早与远期猝死相关,最近有研究(2130例急性心梗)表明经过对年龄、左室射血分数和糖尿病等多因素校正分析后,对于LVEF>35%的患者,非持续性室速对猝死有预测意义,但是单纯用它敏感性特异性都太低,可能与心律变异性、心率震荡联合应用更有价值。其他Holter复极化参数:T波变异性、QT动态变化也许有前景。

心率变异性(HRV

心率变异性是反应迷走神经功能的指标,心梗早期HRV降低,6-12周恢复正常。一项包括808例急性心梗患者的研究发现,急性心梗患者出院前SDNN<50ms,与SDNN50-100msSDNN>100ms患者相比,1年后死亡率增加。影响HRV因素很多:性别、年龄、溶栓药物、倍他阻滞剂、ACEI、抗心律失常药物等,房颤和心律不齐的患者不能进行HRV的分析。新近研究发现新的软件测定的HRV新指标:心率减速能力,对猝死的预测价值可能更大,甚至可以与LVEF相比。

心率震荡(HRT

REFINE研究包括884例急性心梗患者,心梗后10-14周,HRT可以预测猝死,而在急性期2-4周内HRT没有预测意义。新近的一项包括2343例急性心梗患者的研究发现,HRT与心率减速能力一起预测猝死的价值与LVEF<30%的预测价值相当。MADIT II研究发现HRT对猝死没有预测意义,但是研究中只记录了10minECG

T波电交替(TWA

TWA是复极化离散的指标,与室性心律失常相关。比SAECGLVEFEPS联合应用的预测价值大,Rosenbaum等首先证实微伏级TWA与心肌缺血后室性心律失常相关,以后陆续有研究证实。ABCD试验发现TWA有助于预测ICD受益,1年阳性预测价值95%,阴性预测价值9%。但CHOU等研究发现对于LVEF<30%的缺血性心脏病患者,虽然TWA阳性组死亡率高于阴性组,对猝死没有预测价值。

心脏核磁共振

近几年兴起核磁共振评价心脏瘢痕负荷与心律失常和死亡的关系。Yan等首先应用对比增强核磁共振定量分析了梗塞周围瘢痕增加与激发比死亡相关,以后研究相继发表,证实其与室速和猝死相关。但需要大规模临床研究证实。

冠心病非急性心肌梗死猝死的风险评估

冠心病发生单形性室速或室颤,伴心肌酶轻度升高的患者应与心肌酶正常的冠心病室速患者一样考虑ICD治疗。冠心病患者发生持续时间很长的单形性室速的患者,心肌酶可以继发升高,如果没有其他临床资料证实有新发生的心肌梗死(原发心肌酶升高),建议ICD植入。陈旧性心梗,LVEF<40%,合并非持续性室速,EPS可诱发室颤或者持续性室速的患者,也需要植入ICD(IB类适应症)

Hsia[6]研究了8290LVEF正常的冠心病患者,所有患者接受二级预防治疗包括血管重建术,分为对照组和群多普利治疗组,平均随访4.8年。结果发现猝死的阳性预测因子包括:年龄、目前有无心绞痛事件、射血分数40%-50%、应用利尿剂和洋地黄制剂;猝死的阴性预测因子包括:既往曾经进行血管重建术、女性和种族。群多普利不增加也不减少猝死的发生。

Piccini[7]2010年在JACC上发表了一项包括4865LVEF>35%的冠心病患者行核素心肌灌注显像(SPECT-MPI)检查,随访6.5年,猝死风险增加与负荷心肌灌注缺损的程度有关。大规模前瞻性研究有待进一步识别射血分数正常的冠心病猝死高危患者,指导ICD植入。

Duke大学研究中心的一项大规模冠心病与猝死研究[8],包括了37258例冠脉造影证实至少有1支血管狭窄超过75%的冠心病患者,平均随访6.2年,遴选和优化出7个变量进行临床评分(表2Duke 心源性猝死评分):左室射血分数、冠脉病变的血管数量、高血压、糖尿病、心力衰竭、脑血管疾病和吸烟。Duke 心源性猝死评分对135710年猝死的风险预测见表3Duke 评分系统紧密联系临床,避免了单纯依靠射血分数带来的偏倚,提炼出了临床的与猝死相关其他风险因子,便于临床参考,但是它也有局限性,没有包括心电图等其他无创评价指标。具体临床实施还需要实践检验。

2  Duke 心源性猝死评分标准

危险因子

评分

左室射血分数%

1-5

56

6-10

51

11-15

46

16-20

42

21-25

37

26-30

32

31-35

28

36-40

23

41-45

19

46-50

14

51-55%

9

56-60%

5

61

0

病变血管数

1

0

2

6

3

13

脑血管病

8

心衰

7

糖尿病

7

高血压

6

吸烟

4

  3. Duke 心源性猝死评分对135710年猝死的风险预测

Duke猝死评分

1年猝死风险%

3年猝死风险%

5年猝死风险%

7年猝死风险%

10年猝死风险%

0–10   

0.2–0.3

0.3–0.6

0.5–0.9

0.8–1.3

1.2–1.9

11–20 

0.3–0.4

0.7–0.9

1.1–1.4

1.6–2.1

  2.5–3.2

21–30  

0.6–0.7

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  2. [GetPortalCommentsPageByObjectIdResponse(id=1944321, encodeId=96021944321fc, content=<a href='/topic/show?id=411de6300ad' target=_blank style='color:#2F92EE;'>#粥样硬化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76300, encryptionId=411de6300ad, topicName=粥样硬化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b30d401, createdName=huangshifeng, createdTime=Sat Aug 11 20:06:00 CST 2012, time=2012-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1720497, encodeId=a3fb1e2049717, content=<a href='/topic/show?id=09bf36e741d' target=_blank style='color:#2F92EE;'>#危险分层#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36774, encryptionId=09bf36e741d, topicName=危险分层)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1d5032846700, createdName=tidiq, createdTime=Mon Nov 05 04:06:00 CST 2012, time=2012-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1994982, encodeId=9bfc19949825e, content=<a href='/topic/show?id=f1f230899f4' target=_blank style='color:#2F92EE;'>#冠状动脉粥样硬化性心脏病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30899, encryptionId=f1f230899f4, topicName=冠状动脉粥样硬化性心脏病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2ba9118, createdName=makuansheng, createdTime=Fri May 11 23:06:00 CST 2012, time=2012-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1804071, encodeId=036018040e19a, content=<a href='/topic/show?id=d1b2e630123' target=_blank style='color:#2F92EE;'>#粥样硬化性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76301, encryptionId=d1b2e630123, topicName=粥样硬化性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=976a57, createdName=liubm555, createdTime=Tue Jan 17 17:06:00 CST 2012, time=2012-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496262, encodeId=b435149626230, content=<a href='/topic/show?id=43b6e358710' target=_blank style='color:#2F92EE;'>#硬化性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=120, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73587, encryptionId=43b6e358710, topicName=硬化性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d8119265602, createdName=Smile2683, createdTime=Tue Jan 03 02:06:00 CST 2012, time=2012-01-03, status=1, ipAttribution=)]
  3. [GetPortalCommentsPageByObjectIdResponse(id=1944321, encodeId=96021944321fc, content=<a href='/topic/show?id=411de6300ad' target=_blank style='color:#2F92EE;'>#粥样硬化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76300, encryptionId=411de6300ad, topicName=粥样硬化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b30d401, createdName=huangshifeng, createdTime=Sat Aug 11 20:06:00 CST 2012, time=2012-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1720497, encodeId=a3fb1e2049717, content=<a href='/topic/show?id=09bf36e741d' target=_blank style='color:#2F92EE;'>#危险分层#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36774, encryptionId=09bf36e741d, topicName=危险分层)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1d5032846700, createdName=tidiq, createdTime=Mon Nov 05 04:06:00 CST 2012, time=2012-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1994982, encodeId=9bfc19949825e, content=<a href='/topic/show?id=f1f230899f4' target=_blank style='color:#2F92EE;'>#冠状动脉粥样硬化性心脏病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30899, encryptionId=f1f230899f4, topicName=冠状动脉粥样硬化性心脏病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2ba9118, createdName=makuansheng, createdTime=Fri May 11 23:06:00 CST 2012, time=2012-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1804071, encodeId=036018040e19a, content=<a href='/topic/show?id=d1b2e630123' target=_blank style='color:#2F92EE;'>#粥样硬化性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76301, encryptionId=d1b2e630123, topicName=粥样硬化性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=976a57, createdName=liubm555, createdTime=Tue Jan 17 17:06:00 CST 2012, time=2012-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496262, encodeId=b435149626230, content=<a href='/topic/show?id=43b6e358710' target=_blank style='color:#2F92EE;'>#硬化性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=120, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73587, encryptionId=43b6e358710, topicName=硬化性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d8119265602, createdName=Smile2683, createdTime=Tue Jan 03 02:06:00 CST 2012, time=2012-01-03, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1944321, encodeId=96021944321fc, content=<a href='/topic/show?id=411de6300ad' target=_blank style='color:#2F92EE;'>#粥样硬化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76300, encryptionId=411de6300ad, topicName=粥样硬化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b30d401, createdName=huangshifeng, createdTime=Sat Aug 11 20:06:00 CST 2012, time=2012-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1720497, encodeId=a3fb1e2049717, content=<a href='/topic/show?id=09bf36e741d' target=_blank style='color:#2F92EE;'>#危险分层#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36774, encryptionId=09bf36e741d, topicName=危险分层)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1d5032846700, createdName=tidiq, createdTime=Mon Nov 05 04:06:00 CST 2012, time=2012-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1994982, encodeId=9bfc19949825e, content=<a href='/topic/show?id=f1f230899f4' target=_blank style='color:#2F92EE;'>#冠状动脉粥样硬化性心脏病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30899, encryptionId=f1f230899f4, topicName=冠状动脉粥样硬化性心脏病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2ba9118, createdName=makuansheng, createdTime=Fri May 11 23:06:00 CST 2012, time=2012-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1804071, encodeId=036018040e19a, content=<a href='/topic/show?id=d1b2e630123' target=_blank style='color:#2F92EE;'>#粥样硬化性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76301, encryptionId=d1b2e630123, topicName=粥样硬化性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=976a57, createdName=liubm555, createdTime=Tue Jan 17 17:06:00 CST 2012, time=2012-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496262, encodeId=b435149626230, content=<a href='/topic/show?id=43b6e358710' target=_blank style='color:#2F92EE;'>#硬化性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=120, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73587, encryptionId=43b6e358710, topicName=硬化性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d8119265602, createdName=Smile2683, createdTime=Tue Jan 03 02:06:00 CST 2012, time=2012-01-03, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1944321, encodeId=96021944321fc, content=<a href='/topic/show?id=411de6300ad' target=_blank style='color:#2F92EE;'>#粥样硬化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76300, encryptionId=411de6300ad, topicName=粥样硬化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b30d401, createdName=huangshifeng, createdTime=Sat Aug 11 20:06:00 CST 2012, time=2012-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1720497, encodeId=a3fb1e2049717, content=<a href='/topic/show?id=09bf36e741d' target=_blank style='color:#2F92EE;'>#危险分层#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36774, encryptionId=09bf36e741d, topicName=危险分层)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1d5032846700, createdName=tidiq, createdTime=Mon Nov 05 04:06:00 CST 2012, time=2012-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1994982, encodeId=9bfc19949825e, content=<a href='/topic/show?id=f1f230899f4' target=_blank style='color:#2F92EE;'>#冠状动脉粥样硬化性心脏病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30899, encryptionId=f1f230899f4, topicName=冠状动脉粥样硬化性心脏病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2ba9118, createdName=makuansheng, createdTime=Fri May 11 23:06:00 CST 2012, time=2012-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1804071, encodeId=036018040e19a, content=<a href='/topic/show?id=d1b2e630123' target=_blank style='color:#2F92EE;'>#粥样硬化性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76301, encryptionId=d1b2e630123, topicName=粥样硬化性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=976a57, createdName=liubm555, createdTime=Tue Jan 17 17:06:00 CST 2012, time=2012-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496262, encodeId=b435149626230, content=<a href='/topic/show?id=43b6e358710' target=_blank style='color:#2F92EE;'>#硬化性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=120, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73587, encryptionId=43b6e358710, topicName=硬化性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d8119265602, createdName=Smile2683, createdTime=Tue Jan 03 02:06:00 CST 2012, time=2012-01-03, status=1, ipAttribution=)]
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