飲酒與心腦血管風(fēng)險新解讀

飲酒與心腦血管風(fēng)險新解讀

大量證據(jù)表明，適量飲酒有益健康，而長期大量飲酒可增加心腦血管事件的發(fā)病率。然而生理學(xué)研究顯示，酒精對于心血管系統(tǒng)的作用具有雙面性：在急性期，中到大量飲酒后數(shù)小時可增加心率、導(dǎo)致電-機械延遲、引起纖溶亢進；而在遠(yuǎn)期，攝入酒精可降低血壓并改善凝血功能。飲酒何謂“適量”是個飽受爭議的話題，根據(jù)美國心臟病協(xié)會（AHA）的指南，適量飲酒被定義為飲酒1標(biāo)準(zhǔn)量（啤酒12液盎司約360ml，白酒5液盎司約150ml，烈酒1.5液盎司約45ml，換算為酒精量約15g），女性每天不超過1標(biāo)準(zhǔn)量，男性每天不超過2標(biāo)準(zhǔn)量。然而，最新的研究顯示，這一標(biāo)準(zhǔn)略顯苛刻了。

2016年3月1日至4日在美國亞利桑那州首府鳳凰城召開的AHA心血管流行病學(xué)與預(yù)防醫(yī)學(xué)2016年會（Epidemiology and Prevention，Lifestyle and Cardiometabolic Health 2016 Scientific Sessions，EPI-Lifestyle 2016）上，來自美國哈佛大學(xué)的流行病學(xué)專家通過薈萃分析，揭示了中等量飲酒與大量飲酒的人群，在飲酒后急性期與遠(yuǎn)期的心腦血管事件風(fēng)險。研究結(jié)果發(fā)現(xiàn)，中等量飲酒的人群，飲酒后短時間內(nèi)發(fā)生心肌梗死或卒中的風(fēng)險增高，而飲酒后1d或1周出現(xiàn)心肌梗死或卒中的風(fēng)險卻降低了。大量飲酒的人群則無論是飲酒或數(shù)小時、1d或1周，均增加心肌梗死與卒中的風(fēng)險[1]。

研究人員通過搜索各大數(shù)據(jù)庫，選取了1987年至2015年間共23項飲酒后1周內(nèi)心肌梗死與腦卒中的研究，其中有16項為病例對照研究，7項為病例交叉研究。研究中12項來自歐洲，6項來自澳大利亞與新西蘭，4項來自美國，1項為多國參與。研究共入選29 457例患者，其中包括17 966例心肌梗死患者，2599例缺血性腦卒中患者和1 262例出血性腦卒中患者。研究顯示，飲酒對于心血管的保護作用只適用于中等量飲酒的患者，而大量飲酒的患者無論在急性期還是遠(yuǎn)期均不會有任何保護作用。

例如，每天飲酒達2個標(biāo)準(zhǔn)量的人群較非飲酒者發(fā)生心肌梗死的風(fēng)險是0.67，而每天飲酒達9個標(biāo)準(zhǔn)量的人群，發(fā)生心肌梗死的風(fēng)險為非飲酒者的1.59倍。每天飲酒達2～4個標(biāo)準(zhǔn)量的人群，飲酒24h后心肌梗死和出血性卒中的風(fēng)險下降30%。習(xí)慣性飲酒每周達6個標(biāo)準(zhǔn)量的人群，1周內(nèi)發(fā)生缺血性卒中的風(fēng)險下降19%。而且，飲酒24h后這一心腦血管保護作用呈現(xiàn)劑量依賴性。

與此相比，每天飲酒達6～9個標(biāo)準(zhǔn)量的人群飲酒后1d發(fā)生心肌梗死和卒中的風(fēng)險是非飲酒者的1.3～2.3倍；每周飲酒9～30個標(biāo)準(zhǔn)量的人群發(fā)生心肌梗死和卒中的風(fēng)險是非飲酒者的2.25～6.2倍。不論飲酒24h內(nèi)還是24h后，大量飲酒均不能降低心血管事件的發(fā)生率。

研究顯示，適量飲酒后最初1h發(fā)生心肌梗死或腦卒中的風(fēng)險會短暫升高，但在適量飲酒后1d，該風(fēng)險不但下降，甚至出現(xiàn)了保護作用，適量飲酒后1d發(fā)生心肌梗死或出血性腦卒中的風(fēng)險較不飲酒的人群均有下降，而適量飲酒后1周還進一步降低了發(fā)生缺血性卒中的風(fēng)險。習(xí)慣性中等量飲酒的人群，盡管飲酒后短時間內(nèi)的心腦血管風(fēng)險升高，但在后期可起到心腦血管保護的作用。盡管本研究發(fā)現(xiàn)起到保護作用的飲酒量比既往的研究（1～2標(biāo)準(zhǔn)量/d×4d/周）要高，大量飲酒對于心腦血管的危害仍然是一致的。

本研究首次報道了飲酒與急性心腦血管事件的風(fēng)險，告訴人們習(xí)慣性適量飲酒的心腦血管保護作用只在飲酒24h后才出現(xiàn)，在飲酒24h內(nèi)仍可增加心腦血管事件，這可能為患者生活方式教育和急診醫(yī)生快速診斷提供新的證據(jù)。但遺憾的是，本研究入選的人群主要聚焦在歐美，亞洲、非洲的人群可能因基因不同、生活方式不同和酒的種類不同而有不同結(jié)果。我國的釀酒歷史悠久，酒文化深入，期待我國的流行病學(xué)專家能公布基于較大樣本的研究結(jié)果，為我們展現(xiàn)飲酒適量的“中國標(biāo)準(zhǔn)”。

[1]Mostofsky E，Chahal H S,Mukamal K J,etal.Alcohol andimmediate risk of cardiovascular events:A systematic review and dose-response meta-analysis[J].Circulation,2016,133（10）：979-987.

（陳涵編譯）

A 57-year-old man with a structurally normal heart and normal baseline ECG underwent pulmonary vein isolation for atrial fibrillation.An electrophysiology study was then undertaken with an octapolar catheter positioned at the His bundle and an ablation catheter at the mid-right atrium.

At baseline,the sinus cycle length was 890 ms,the AH interval 48 ms,the HV interval 80 ms,and the QRS duration 80 ms.During extrastimulus atrial pacing,the HV interval shortened and the QRS complex widened with a left bundle branch block morphology（Figure 1）. Atrial burst pacing at cycle length 330 ms demonstrates progressive shortening of the HV interval and widening of the QRS complex with left bundle branch block morphology（Figure 2A and 2B）.On the final 3 beats in the figure,a His bundle electrogram seems after the QRS complex.On termination of pacing,a wide QRS complex tachycardia of identical morphology is noted （Figure 3）.What is the mechanism of the tachycardia?

Discussion

Although the baseline ECG is normal,the presence of a slowly conducting accessory pathway is apparent from atrial extrastimulus pacing demonstrating HV interval shortening,QRS widening,and a long A-V interval（Figure 1）.Further inferences of the nature of the accessory pathway may also be made.The retrograde right bundle（RB）and His activation preceding the preexcited ventricular complex with left bundle branch block morphology are most consistent with an accessory pathway connection directly into the right bundle branch （atriofascicular pathway or nodofascicular pathway）.

Figure 1Atrial extrastimulus pacing.Following S2,the QRS widens,the HV interval shortens and the His and right bundle activation sequence reverses.Dotted line and arrows provide reference for the anterograde to retrograde activation change.Preexcitation with a long AV interval,left bundle branch block morphology, and right bundle activation preceding ventricular activation suggest an atriofascicular accessory pathway.His 7 to 8 through 1 to 2 His bundle catheter recordings are proximal to distal；pacing intervals in milliseconds are marked.H indicates His；RA,right atrium；S1,drive train stimulus；and S2,extrastimulus.

Similar changes are noted at the onset of atrial burst pacing（Figure 2A）.There is evidence of a slowly conducting accessory pathway with shortening of HVinterval and a long A-V interval.The His electrogram precedes the preexcited ventricular complex.Because only the distal electrode records a His electrogram, retrograde versus anterograde His activation cannot be discerned on this tracing.The H and V relationship changes further on the sixth paced beat when the His bundleelectrogramoccursaftertheventricular electrogram.Having established the presence of an atrio-fascicular（or nodo-fascicular）pathway,the only explanation for the late His is the development of retrograde block in the RB.Most likely,the His activation is still retrograde via transeptal activation of theleftbundlebranch.Thisisrepresented schematically Figure 2B.Less likely,retrograde block in the RB allows for antegrade conduction over an AV node slow pathway and anterograde His activation.

Figure 2A,Right atrial pacing at 330 ms.Note shortening of HV interval and fusion of QRS on the third-paced beat,retrograde His activation via right bundle branch on the fourth-and fifth-paced beats and sudden jump to a V-H relationship on the sixth-paced beat indicating retrograde block in the right bundle branch and conduction via left bundle branch.B,Schematic diagram of the mechanism of changes A,H,and V relationships seen in the last 3 beats in A.Atrial pacing results in anterograde block in AV node,anterograde conduction via atriofascicular pathway,and retrograde RB bock.His activation is retrograde via LB.A indicates atrial,AFP,atriofascicular pathway；AVN,AV node；H,His,LB,left bundle branch；RB,right bundle branch；and V,ventricular.

At termination of the atrial pacing,a left bundle branch block morphology wide QRS tachycardia is initiated（Figure 3）.The tachycardia morphology is identical to the pre-excited QRS complex.The His activation is not seen on the first beat of tachycardia but occurs just before the onset of the QRS for the second and third beats.The His recording is seen after the ventricular signal for the last 2 complexes.Changes in the H-H intervals precede changes in the V-V intervals as well as the subsequent A-A intervals,although the relationship is not precise（Figure 4A）.The H-A interval shortens on the last 2 beats and accounts for the inexact relationship.

Figure 3Atrial pacing initiates tachycardia with left bundle branch block morphology,variable cycle lengths and variable relationships between the A,H,and V signals.A indicates atrial；H,His；RA,right atrium；and V,ventricular.

The differential diagnosis for the wide QRS complex tachycardia includes ventricular tachycardia,supraventriculartachycardia（SVT）withaberrant conduction,SVT with bystander accessory pathway conduction and preexcited（antidromic）tachycardia. Bundle branch reentry ventricular tachycardia and SVT with aberration are excluded by the short HV interval. Myocardial ventricular tachycardia with retrograde His activation is also excluded by the variable H and V relationshipswithchangesintheH-Hinterval predicting changes in the V-V intervals.

Figure 4A,Electrogram intervals of tachycardia in Figure 4.All intervals are in milliseconds.B-D,Schematic representation of tachycardia circuit changes in A.B,First 3 beats of the tachycardia.With cessation of atrial pacing anterograde conduction continues down the atriofascicular pathway with retrograde conduction via right bundle branch completing the circuit.C,Fourth and fifth tachycardia beats where retrograde block occurs in the right bundle branch,and transseptal conduction and left bundle branch activation forms the retrograde tachycardia limb.D,Alternative possibility of dual AVN physiology1during AVNRT with atriofascicular pathway conduction as a bystander.A indicates atrial；AFP,atriofascicular pathway；AVN,atrioventricular node；AVNRT,AV node reentry tachycardia；H,His；LB,left bundle branch；RA,right atrium；RB,right bundle branch；and V,ventricular.

Two possibilities remain:antidromic tachycardia and SVT（AV node reentry tachycardia or atrial tachycardia）withbystanderaccessorypathway conduction.The most probable mechanism is antidromic atrioventricularreentrytachycardia（AVRT）. Development of retrograde block in the RB and transeptal conduction enlarges the circuit；increases the tachycardia cycle length；and-because of simultaneous conduction down the RB and up the His and AV node-shortens the RB-A interval（Figure 4B and 4C）. Thetachycardiacyclelengthprolongationduring retrograde RB block is diagnostic of antidromic AVRT as it provides evidence for participation of the ventricle in the tachycardia.However,the possibility of SVT occurring simultaneously with antidromic AVRT is not excluded.During the first 2 beats of tachycardia, antidromic AVRT with its faster cycle length could entrain SVT.In the third and fourth beat,retrograde block in the RB prolongs the AVRT cycle length beyond that of an underlying SVT,allowing it to manifest （Figure 4D）.In this scenario,the H-A interval（or RB-A interval）is longer during the first 2 AVRT beats because of the sequential retrograde conduction systemactivation and the HA interval shortens as expected for the third and fourth SVT（AV node reentry tachycardia）beats because of simultaneous conduction down the His bundle and up the AV node fast pathway.

Figure 5A premature atrial complex（S2）introduced at the time of atrial septal refractoriness during the long V-H tachycardia advances the ventricular and atrial activation.A indicates atrial；H,His；RA,right atrium；and V,ventricular.

Proofofanatriofascicularasopposedto nodofascicular accessory pathway mediated antidromic tachycardia was confirmed by delivery of a paced premature atrial complex at a time of atrial septal refractoriness during the long V-H tachycardia.This advanced ventricular and subsequent atrial activation equally（Figure 5）.A discrete accessory pathway potential was identified at the lateral tricuspid valve annulus（Figure 6）and a single 40 W radiofrequency energy application eliminated preexcitation and the tachycardia.Thiscaseillustratesthediagnostic opportunitiesandchallengeswithsimultaneous variations in multiple limbs of a reentrant rhythm.

Figure 6Atriofascicular pathway potential（M）is recorded from the ablation catheter（ABL）placed at the lateral tricuspid annulus.Ablation here eliminated preexcitation.Note the short HV intervals on H1-2 electrodes.H indicates His.

詞匯

octapolar adj.八極的

inference n.推論,推斷結(jié)果

discern v.辨明,看出,辨識,認(rèn)識,識別

schematically adv.在圖表上地，按照圖式，計劃性地

inexact adj.不精確的,不嚴(yán)格的

bystander n.旁觀者，看熱鬧的人

antidromic adj.逆向的，逆行的

participation n.參與,分享，參股

entrain v.&n.上火車,拖,產(chǎn)生,帶走；熱情

scenario n.劇本,概要,設(shè)想

proof n.&v.&adj.證明,證據(jù),校稿；檢驗,校對；不能穿透的Delivery n.投遞,分娩,交付,送貨,講話,交出

Discrete adj.&n.分離的,轉(zhuǎn)折的；獨立部件

注釋

1.dual AVN physiology指雙重的房室結(jié)生理機能，即房室結(jié)雙徑路功能

參考譯文

第70課心房、希氏束和心室關(guān)系多變的寬QRS心動過速的機制

患者男性，57歲，心臟結(jié)構(gòu)和基礎(chǔ)心電圖均正常，因心房顫動而接受肺靜脈隔離手術(shù)。電生理檢查中八極電極置于希氏束，消融電極置于中位右心房。

基礎(chǔ)狀態(tài)下，竇性心律周長890ms,A-H間期48ms，H-V間期80ms，QRS時間80ms。期外心房起搏刺激時，H-V間期縮短而QRS波群增寬呈左束支傳導(dǎo)阻滯圖形（圖1）。以周長330ms心房猝發(fā)刺激證實進行性H-V間期縮短和QRS波群增寬，并呈左束支傳導(dǎo)阻滯圖形（圖2A和2B）。圖中最后3搏顯示，希氏束電圖似乎位于QRS波群后。起搏停止后，記錄到同一形態(tài)的寬QRS波群心動過速（圖3）。心動過速的機制是什么？

討論

雖然基礎(chǔ)心電圖正常，通過期外心房起搏證實H-V間期縮短、QRS波群增寬及長A-V間期（圖1），顯然存在傳導(dǎo)緩慢的旁道，尚可對旁道性質(zhì)作進一步推論。逆?zhèn)鞯挠沂Ш拖Ｊ鲜釉缬诔首笫鲗?dǎo)阻滯圖形的預(yù)激心室波與旁道直接連接右束支（房束旁道或結(jié)束旁道）極為一致。

類似的變化見于心房猝發(fā)起搏開始時（圖2A）。存在緩慢傳導(dǎo)旁道伴隨H-V間期縮短和長A-V間期的跡象。希氏束電圖早于預(yù)激的心室波。由于只有遠(yuǎn)端電極記錄到希氏束電圖，在此圖中不能辨識逆?zhèn)骰蝽槀飨Ｊ鲜?。在?個起搏波上，希氏束電圖位于心室電圖后，H與V的關(guān)系變化愈加明顯。確定存在房-束（或結(jié)-束）旁道后，對于滯后的希氏束電位的唯一解釋是在右束支中發(fā)生逆?zhèn)髯铚?。最有可能的是希氏束激動系跨間隔后左束支激動逆?zhèn)魉隆D2B為圖示。不太可能的是右束支逆?zhèn)髯铚菰S經(jīng)房室結(jié)慢徑路順傳和前向激動希氏束。

心房起搏停止后，引發(fā)左束支傳導(dǎo)阻滯圖形的寬QRS波群心動過速（圖3）。心動過速圖形與預(yù)激的QRS波群一致。心動過速的第1個波上未見到希氏束激動，但出現(xiàn)在第2和第3個QRS波群開始前。最后兩個心室波后見到希氏束波。H-H間期變化先于V-V間期及隨后的A-A間期變化，雖然這種關(guān)系并不精確（圖4A）。最后2搏的H-A間期縮短，解釋了這種不確定關(guān)系。

寬QRS心動過速的鑒別診斷包括室性心動過速、室上性心動過速（SVT）伴差異性傳導(dǎo)，室上性心動過速伴旁觀旁道傳導(dǎo)和預(yù)激的心動過速。短H-V間期排除了束支折返性室性心動過速和室上性心動過速伴差異性傳導(dǎo)。易變的H-V關(guān)系和預(yù)示V-V間期變化的H-H間期變化也排除了室性心動過速伴逆?zhèn)飨Ｊ鲜印?/p>

剩下2種可能性：逆?zhèn)餍膭舆^速和室上性心動過速（房室結(jié)折返心動過速或房性心動過速）合并旁觀旁道傳導(dǎo)。最有可能的機制是逆?zhèn)鞣渴艺鄯敌膭舆^速（AVRT）。右束支逆?zhèn)髯铚陌l(fā)生和跨間隔傳導(dǎo)擴大了環(huán)路，增加了心動過速的周長；因同時順傳右束支和逆?zhèn)飨Ｊ鲜胺渴医Y(jié)，縮短了右束支-A間期（圖4B、C）。逆向右束支傳導(dǎo)阻滯時心動過速周長延長對于逆?zhèn)鰽VRT具有診斷意義，因為這提供了心室參與心動過速的依據(jù)。然而，不能排除SVT與逆?zhèn)鰽VRT同時發(fā)生的可能性。在心動過速的最初2個搏動中，周長較短的逆?zhèn)鰽VRT可拖帶SVT。在第3和第4個搏動中，右束支的逆?zhèn)髯铚娱L了AVRT周長并超出基礎(chǔ)SVT的周長，使得SVT得以呈現(xiàn)（圖4D）。在此情況下，因為相繼的逆?zhèn)飨到y(tǒng)激動，最初2個AVRT搏動的H-A間期（或右束支-A間期）較長，而第3個和第4個SVT（房室結(jié)折返心動過速）搏動，因為同時順傳希氏束和逆?zhèn)鞣渴医Y(jié)快徑路，H-A間期縮短，正如預(yù)期的。

長V-H心動過速發(fā)作期間，于房間隔不應(yīng)期作期前心房起搏，證實是房束而非結(jié)束旁道介導(dǎo)的逆?zhèn)餍膭舆^速。這使心室激動提前，也使隨后的心房激動提前（圖5）。在三尖瓣環(huán)側(cè)壁發(fā)現(xiàn)離散的旁道電位（圖6），40W射頻放電一次中止預(yù)激及心動過速。該病例闡述了折返節(jié)律多條徑路同時變化時的診斷機遇和挑戰(zhàn)。

圖1心房期外起搏。S2刺激后，QRS波群增寬，H-V間期縮短，希氏束和右束支激動順序逆轉(zhuǎn)。虛線和箭標(biāo)為順傳和逆?zhèn)骷幼兓峁┗鶞?zhǔn)。預(yù)激伴長A-V間期、左束支傳導(dǎo)阻滯圖形及右束支激動早于心室激動提示房束旁道。希氏束電極記錄從7-8到1-2是從近端到遠(yuǎn)端；起搏間期單位ms；H.希氏束；RA.右心房；S1.連續(xù)刺激；S2.期外刺激。

圖2A.右心房300ms起搏。注意第3個起搏波H-V間期縮短和QRS波群融合，第4和第5個起搏波經(jīng)右束支逆?zhèn)飨Ｊ鲜蛹暗?個起搏波突發(fā)跳躍至V-H關(guān)系表明右束支逆?zhèn)髯铚⒔?jīng)左束支傳導(dǎo)。B.A圖上最后3搏A、H和V關(guān)系變化機制原理圖。心房起搏引起房室結(jié)順傳阻滯，經(jīng)房束旁路順傳，右束支逆?zhèn)髯铚?。希氏束是?jīng)左束支逆?zhèn)骷印.心房；AFP.房束旁路；AVN.房室結(jié)；H.希氏束；LB.左束支；RB.右束支；V.心室。

圖3心房起搏引發(fā)左束支傳導(dǎo)阻滯圖形心動過速，周長不定，A、H和V之間關(guān)系不定。A.心房；H.希氏束；RA.右心房；V.心室。

圖4A.圖4心動過速電圖間期。所有間期單位為ms。B-D.A圖中心動過速環(huán)路變化原理圖。B.心動過速最初3個搏動。心房起搏停止后，繼續(xù)向下沿房束旁路順傳而經(jīng)右束支逆?zhèn)魍瓿森h(huán)路。C.第4和第5個心動過速搏動右束支逆?zhèn)靼l(fā)生阻滯，跨間隔傳導(dǎo)和左束支激動形成心動過速的逆?zhèn)髦?。D.房室結(jié)折返合并房束旁路傳導(dǎo)作為旁觀者時，AVN雙徑路的交替可能性。A.心房；AFP.心房束支旁路；AVN.房室結(jié)；AVNRT.房室結(jié)折返心動過速；H.希氏束；LB.左束支；RB.右束支；V.心室。

圖5長V-H心動過速時于心房間隔不應(yīng)期引入的期前心房搏動使心室和心房激動提前。A.心房；H.希氏束；RA.右心房；V.心室。

圖6置于三尖瓣環(huán)側(cè)壁上的消融導(dǎo)管記錄到房束旁路電位（M）。此處消融中止預(yù)激。注意希氏束1-2電極上的短H-V間期。H指希氏束。

參考文獻

[1]Foreman J R,Steinberg L A,Prystowsky E N,etal.Mechanism of a wide QRS complex tachycardia with variable atrial,his,and ventricular relationships[J].Circ Arrhythm Electrophysiol,2015，8 （4）：981-984.

（童鴻）

Lesson Seventy

Mechanism of a wide QRS complex tachycardia with variable atrial,his,and ventricular relationships