Lesson Eighty-nine Noninvasive clues for diagnosing ventricular tachycardia mechanism

The electrophysiologic mechanisms responsible for ventricular tachycardia（VT）fall in one of 3 categories：abnormal automaticity;triggered activity;and reentry.

Abnormal automaticity

Automaticity is the property of cardiac cells to generate spontaneous action potentials and is the result of diastolic depolarization caused by a net inward current during phase 4 of the action potential.Normal automaticity isa property ofthe sinoatrialand atrioventricularnodesand dependsmainly on 2 phenomena：diastolic activation of If（funny current），a mixed Na-K inward current，which unlike most voltagesensitive currents，is activated by hyperpolarization rather than depolarization;and release of calcium from the sarcoplasmic reticulum into the cytosol.The calcium，in turn，activates the Na+-Ca2+exchanger，resulting in a net influx of sodium ions.

Ventricularmyocardialcells do notdisplay spontaneous diastolic depolarization or automaticity under normal conditions，but abnormal automaticity may occur under pathological conditions when the resting membrane potential becomes less negative.This may be consequence of a decrease in IK1 or an enhanced calcium release from the sarcoplasmic reticulum.Similar to normal automaticity，abnormal automaticity is enhanced by β-adrenergic agonists and by reduction of external potassium.

Examples ofabnormalautomaticity include accelerated idioventricular rhythm in the setting of acute ischemia，myocarditis or cocaine intoxication

Triggered activity

It refers to action potential formation resulting from oscillations in membrane potential that are dependent on the preceding action potential.When the amplitude of one ofthese afterdepolarizations reaches certain threshold，voltage-gated ion channels are activated，generating an action potential.Triggered activity can occur in the form of early or delayed afterdepolarizations.Early afterdepolarizations（EADs）occur during phase 2 or 3 of the cardiac action potential and are more manifest at slower heart rates，whereas delayed afterdepolarizations（DADs）occur during phase 4 of the action potential，after full repolarization，and are more dependent on faster heart rates.

Examples of EADs include drug and electrolyte-induced Torsades de Pointes1and some forms of polymorphic VT due to congenital long QT syndrome.DADs are responsible for the majority of outflow tractVTs，catecholaminergic polymorphic ventricular tachycardia （CPVT） and ventricular arrhythmias associated with digitalis toxicity.

Reentry

It is the most common mechanism of VT.It involves continuous repetitive propagation of an impulse around an area of anatomical or functional conduction block.The following 3 criteria were originally proposed by Mines for identification of reentry：1）unidirectional block must occur;2）a region of slow conduction with return of the excitatory wave to its point of origin;and 3）interruption of the reentrant circuit at any points should terminate the tachycardia.The substrate for reentry requires the presence of 2 pathways with different electrophysiologic properties separated by a central area of block （anatomical or functional）.When an impulse encounters the central obstacle，unidirectional block occurs in one of the pathways and slow conduction occurs through the other pathway，creating a circus movement.For reentry to occur，the conduction within the unblocked pathway must be slow enough so the previously blocked pathway can recover its excitability by the time the reentrant wavefront returns.In other words，the anatomical length of the circuit should equal or exceed the reentrant wavelength.

Reentrantarrhythmias can be reproducibly initiated and terminated by programmed stimulation.They can also interact with pacing and demonstrate the hallmark features of resetting and entrainment with fusion.

Examples of reentry include：1）scar-related VT in patients with structurally abnormal hearts due to ischemic or nonischemic cardiomyopathies;2）bundle branch reentry，which is typically seen in patients with infrahisian conduction disease and involves antegrade conduction overtherightbundleand retrograde conduction over the left bundle （or vice versa）;3）idiopathic left ventricular tachycardia（also known as fascicular VT，Belhassen VT or verapamil-sensitive VT），in which the macro-reentrant circuit involves the left posterior fascicle（or less commonly the left anterior fascicle）and abnormal slowly conducting Purkinje fibers;and 4）Phase 2 reentry associated with VAs in Brugada syndrome.

Sinus rhythm ECG

Baseline sinus rhythm 12-lead ECG may be helpful by indicating disease processes known to be associated with specific VT mechanisms.The presence of Q waves consistent with prior myocardial infarction indicates the substrate for scar-related reentry，especially if the VT morphology is consistent with an exit from the region of the infarct.Epsilon waves in the right precordial leads，especially in the setting of a left bundle-branch block VT，is a marker of arrhythmogenic right ventricular cardiomyopathy/dysplasia（ARVC/D）and suggestsreentryinvolvingnon-ischemicscar localized to the right ventricle.Any evidence for His-Purkinje system disease as indexed by QRS widening，especially in the setting ofa dilated cardiomyopathy，can predispose to bundle branch reentrant VT.A Brugada pattern is associated with phase 2 reentry，a special type of reentry proposed to be caused by heterogeneity in action potential distribution between the epicardium and endocardium.

Twelve-lead morphology of the ventricular tachycardia

Outflow tract VT and premature ventricular contractions（PVCs）characterized by large monophasic R waves in the inferior leads，especially in patients with structurally normal heart，can confidently be attributed to DAD-induced triggered activity.However，reentrant VTs associated with nonischemic cardiomyopathies can frequently originate near the perivalvular region.As such，these tachycardias will mimic morphology of outflow tract VT due to a triggered mechanism.The presence ofmultiple VT morphologies and the identification ofa region oflow bipolarvoltage surrounding these valvularstructuressupportthe diagnosis ofnonischemic cardiomyopathy and a probable reentrant VT mechanism.

A QRS morphology during VT typical for LBBB is suggestive of bundle branch reentrant VT.This typically occurs in the context of dilated cardiomyopathy with underlying His-Purkinje system disease.The VT is typically rapid and often presents with presyncope，syncope or cardiac arrest.

A situation commonly encountered in patients with structural heart disease is the presence of more than one VT morphology.Paired VTs with similar cycle length but opposite axis，especially in the context of an ischemic etiology，points to macro-reentry involving a large circuit（Fig.1）.For example，2 different VTs with LBBB pattern and left axis，one of them with a basal exit and another with apical axis，suggests macro-reentry involving a septal substrate.The presence of multiple LBBB VT morphologies with late precordial transition should suggest the possibility of ARVC.

A particular and rare ECG pattern is bidirectional VT，defined as a tachycardia showing beat-to-beat alternation in the QRS axis.The most common causes of bidirectional VT are digitalis toxicity and CPVT，and the proposed mechanismis DAD-mediated triggered activity in anatomically separate parts of the conduction system.

Figure 1 Paired VT morphologies in a patient with ischemic cardiomyopathy.The superior panel shows a right bundle left superior（RBLS）axis VTwith a CL of 518ms and the inferior panel shows a right bundle right inferior （RBRI） axis VT with a CL of 510ms. This is manifestation of a large macro-reentrant circuit with exit sites mapped to the septal and lateral aspects of the ischemic scar.

Tachycardia onset and termination

Two different patterns of VT initiation have been described：VT preceded by ventricular ectopy（single or multiple）of different morphology than that of the tachycardia;and VT not preceded by ventricular ectopy（sudden onset）.As previously mentioned，a hallmark of reentrant VTs is reproducible initiation with ventricular programmed stimulation.This type of initiation can also be seen in triggered VTs，but not in automatic VTs.Spontaneous PVCs are a noninvasive correlate of ventricular extrastimuli and，thus，initiation with a PVC of different morphology than that of the tachycardia suggests a reentrant mechanism（fig.2）.This in contrast with automatic and triggered VTs，which typically start with a beat similar to the ensuing beats of tachycardia.However，it must be said that sudden onset does not exclude reentry.In summary，consistent initiation with a PVC morphologically distinct to the VT typically will indicate reentry.On the other side，sudden initiation can be seen with any VT mechanism.

Figure 2 Examples of VT initiation with a PVC of different morphology than the ensuing beats of tachycardia（arrow）.

The prototype of automatic VT is accelerated idioventricular tachycardia（AIVT），which is most often observed in the setting of acute myocardial infarction and reperfusion，but it can also be seen in acute myocarditis， hypertensive heart disease， digitalis intoxication and cocaine intoxication.It often begins as a late-coupled ventricular beat at a rate just faster than the preceding sinus rate.

A progressive increase in rate with tachycardia onset（warm-up）and/or progressive deceleration before tachycardia termination（cool-down）are also suggestive of an automatic mechanism.

Response to pharmacologic agents

Probably the most useful and specific response to pharmacological intervention is the effect of adenosine on VT due to triggered activity.The cellular basis for triggered activity due to DAD is intracellular calcium overload，which induces a Ca2+-dependent depolarizing current （transient inward current or Iti），mainly given by activation of the Na+-Ca2+exchanger.The transient inward sodium current gives rise to DADs，which，if of sufficient amplitude，triggers a new action potential that may result in tachycardia.Catecholamines，through stimulation ofthe β-adrenergicreceptor，causes activation of adenylyl cyclase （AC），increase of cAMP，activation of protein kinase A and phosphorylation of the L-type Ca channel， ryanodine receptor2， and phospholamban3.This results in increased intracellular calcium levels and enhanced activity of the Na+-Ca2+exchanger.Adenosine exerts an inhibitory effect on AC and cAMP，reversing intracellular calcium overload.Given that adenosine has no antiarrhythmic effect in reentrant VT and only transiently suppresses（but does not terminate） automatic VT，termination of VT in response to adenosine is considered diagnostic of cAMP-mediated triggered activity.

詞 匯

sarcoplasmic adj.肌質(zhì)的

cytosol n.細(xì)胞溶質(zhì)

afterdepolarization n.后除極

catecholaminergic adj.兒茶酚胺活性的，兒茶酚胺能的

excitatory adj.顯示激動(dòng)的，有刺激性的，興奮的

infrahisian adv.在希氏束下

hallmark n.&vt.標(biāo)記，標(biāo)志;給 打上烙印，給 標(biāo)識(shí)

correlate n.&vt.相關(guān)物，相關(guān)聯(lián)的人；與 相關(guān)，相互聯(lián)系，

注 釋

1.Torsades de Pointes指尖端扭轉(zhuǎn)型室性心動(dòng)過速，是一種特殊的室性快速心律失常，多見于QT間期延長及低血鉀患者，常呈慢心率依賴。

2.ryanodine receptor可音譯為雷諾丁受體，是一種大流量鈣離子釋放通道，介導(dǎo)細(xì)胞內(nèi)內(nèi)質(zhì)網(wǎng)和肌漿網(wǎng)的鈣離子釋放，在眾多生物學(xué)功能中起關(guān)鍵作用。

3.phospholamban是一種受磷蛋白，是心肌收縮的關(guān)鍵性調(diào)節(jié)蛋白，能可逆性抑制肌漿網(wǎng)上的鈣離子泵功能，導(dǎo)致心肌收縮力下降，并可引起擴(kuò)張型心肌病。

參考譯文

第89課 室性心動(dòng)過速機(jī)制的無創(chuàng)診斷線束

室性心動(dòng)過速的電生理機(jī)制不外乎以下3種:自律性異常、觸發(fā)活動(dòng)和折返。

自律性異常

自律性是心肌細(xì)胞產(chǎn)生自發(fā)動(dòng)作電位的特性，是動(dòng)作電位四相期間內(nèi)向凈電流導(dǎo)致舒張期除極的結(jié)果。正常自律性是竇房結(jié)和房室結(jié)的特性，主要基于兩種現(xiàn)象:If（funny電流）的舒張期激動(dòng)，一種混合型鈉-鉀內(nèi)向電流，這不同于多數(shù)電壓敏感的電流，是由超極化而非除極激動(dòng)激活，和從內(nèi)質(zhì)網(wǎng)釋放的鈣進(jìn)入胞內(nèi)，隨后鈣激活鈉-鈣交換器，導(dǎo)致鈉離子凈內(nèi)流。

正常情況下心室肌細(xì)胞并不發(fā)生舒張期除極或無自律性。但在病理情況下，當(dāng)靜息膜電位負(fù)值減小時(shí)可發(fā)生異常自律性。這可能是IK1減少或從肌質(zhì)網(wǎng)釋放的鈣增加的結(jié)果。與正常自律性相似，beta激動(dòng)劑和胞外鉀減少可促進(jìn)異常自律性。

自律性異常包括急性心肌缺血、心肌炎或可卡因中毒情況下的加速性室性自主節(jié)律。

觸發(fā)活動(dòng)

動(dòng)作電位形成來自膜電位振蕩，依賴于前面的動(dòng)作電位。當(dāng)這些后除極中有振幅達(dá)到一定閾值時(shí)，電壓門控離子通道激活，產(chǎn)生動(dòng)作電位。觸發(fā)活動(dòng)可發(fā)生于早后除極或延遲后除極。早后除極發(fā)生于心臟動(dòng)作電位的2相或3相，多見于心率較慢時(shí)，而延遲后除極發(fā)生于動(dòng)作電位4相，即完全復(fù)極后，多呈較快心率依賴。

早后除極的例子有藥物和電解質(zhì)誘發(fā)的尖端扭轉(zhuǎn)型室性心動(dòng)過速和某些與先天性長QT間期綜合征相關(guān)的多形性室性心動(dòng)過速。延遲后除極是多數(shù)流出道室性心動(dòng)過速、兒茶酚胺類多形性室性心動(dòng)過速和地高辛中毒相關(guān)室性心動(dòng)過速的發(fā)病機(jī)制。

折返

這是室性心動(dòng)過速最常見的機(jī)制。涉及沖動(dòng)圍繞解剖區(qū)域或功能傳導(dǎo)阻滯區(qū)連續(xù)重復(fù)傳導(dǎo)。Mines最初提出鑒別折返的下述3條標(biāo)準(zhǔn):（1）必須存在單向阻滯；（2）經(jīng)緩慢傳導(dǎo)區(qū)激動(dòng)波回到其起點(diǎn):（3）折返環(huán)的任一點(diǎn)中斷將終止心動(dòng)過速。折返基質(zhì)需存在兩條電生理特性不同的通路，并由（解剖或功能）阻滯中心區(qū)分隔開。當(dāng)脈沖遇到中心屏障時(shí)，一條通路發(fā)生單向阻滯，而另一條通路呈緩慢傳導(dǎo)，產(chǎn)生循環(huán)運(yùn)動(dòng)。要發(fā)生折返，單向阻滯通路上的傳導(dǎo)必須足夠慢，以保證折返波回來時(shí)其前阻滯的通路已恢復(fù)興奮性。換言之，環(huán)路的解剖長度應(yīng)等于或大于折返波長。

折返型心律失常可通過程控刺激反復(fù)誘發(fā)和中止。他們可以與起搏相互影響，證實(shí)重置和融合拖帶的標(biāo)志性特性。

折返的例子有:（1）因缺血性或非缺血性心肌病導(dǎo)致心臟結(jié)構(gòu)異常患者的疤痕相關(guān)室性心動(dòng)過速；（2）束支折返，典型的見于希氏束以下傳導(dǎo)病變的患者，涉及經(jīng)右束支前傳和經(jīng)左束支逆?zhèn)鳎ɑ蚍粗唬?）特發(fā)性左室心動(dòng)過速（也稱分支型室性心動(dòng)過速、Belhassen室性心動(dòng)過速、異博定敏感型室性心動(dòng)過速），其大折返環(huán)涉及左后分支（左前分支不常見）；（4）與Brugada綜合征室性心律失常相關(guān)的2相折返。

竇性節(jié)律心電圖

基礎(chǔ)竇性節(jié)律12導(dǎo)聯(lián)心電圖有助于提示與特殊室性心動(dòng)過速機(jī)制相關(guān)的疾病過程。與以往心肌梗死相一致的Q波提示瘢痕相關(guān)的折返，特別當(dāng)室性心動(dòng)過速的形態(tài)與梗死區(qū)出口相一致時(shí)。右胸導(dǎo)聯(lián)Epsilon波，特別在左束支阻滯圖形室性心動(dòng)過速時(shí)，是致心律失常右室心肌病/心肌發(fā)育不良的標(biāo)志，提示折返涉及位于右心室的非缺血疤痕。希浦系統(tǒng)病變跡象如QRS波群增寬，特別在擴(kuò)張型心肌病，傾向于束支折返室性心動(dòng)過速。Brugada圖形與2相折返有關(guān)，是一種特殊的折返，認(rèn)為由心外膜與心內(nèi)膜之間動(dòng)作電位不均質(zhì)引起。

室性心動(dòng)過速的12導(dǎo)聯(lián)形態(tài)

流出道室性心動(dòng)過速和期前收縮特征表現(xiàn)為下壁導(dǎo)聯(lián)大的單向R波，特別是心臟結(jié)構(gòu)正常的患者，可以確信為延遲后除極誘發(fā)的觸發(fā)活動(dòng)所致。然而，與非缺血心肌病相關(guān)的折返型室性心動(dòng)過速常起源于瓣周附近。因?yàn)槿绱耍@些心動(dòng)過速形態(tài)類似于由觸發(fā)機(jī)制引起的流出道室性心動(dòng)過速。室性心動(dòng)過速呈多種形態(tài)和瓣膜結(jié)構(gòu)周邊的低雙極電壓區(qū)支持非缺血性心肌病的診斷和可能的折返機(jī)制。

室性心動(dòng)過速Q(mào)RS波群呈典型的LBBB形態(tài)提示束支型折返室性心動(dòng)過速。這通常發(fā)生于擴(kuò)張型心肌病合并希氏束系統(tǒng)疾病者。這種室性心動(dòng)過速典型的是速率快，常以先兆暈厥、暈厥和心跳驟停而就診。 .

結(jié)構(gòu)性心臟病患者常見的情況是出現(xiàn)一種以上的室性心動(dòng)過速形態(tài)。成對(duì)室性心動(dòng)過速周長相似而極性相反，尤其存在缺血病因時(shí)，提示涉及大環(huán)的巨折返（圖1）。例如，2種不同的LBBB形態(tài)且電軸左偏的室性心動(dòng)過速，一種呈基底部出口電軸，而另一種呈心尖出口電軸，提示涉及間隔基質(zhì)的巨折返。表現(xiàn)為多種LBBB室性心動(dòng)過速形態(tài)且胸導(dǎo)聯(lián)移行晚提示致心律失常心肌病/心肌發(fā)育不良可能。

雙向性室性心動(dòng)過速是一種特殊而罕見的心電圖類型。心動(dòng)過速顯示QRS波群電軸每搏交替。雙向性室性心動(dòng)過速的最常見原因是地高辛中毒和兒茶酚胺類心動(dòng)過速，其可能的機(jī)制為解剖上隔離的傳導(dǎo)系統(tǒng)部分延遲后除極介導(dǎo)的觸發(fā)活動(dòng)。

心動(dòng)過速的發(fā)生與中止

已描述過兩種室性心動(dòng)過速發(fā)作類型:一種為室性心動(dòng)過速前有與其形態(tài)不同（一種或多種）的室性期前收縮；另一種室性心動(dòng)過速前無心室異位波動(dòng)（突發(fā)）。如以前所述，折返型室性心動(dòng)過速可由心室程序刺激反復(fù)誘發(fā)。這種類型發(fā)作也見于觸發(fā)型室性心動(dòng)過速，但不見于自律性室性心動(dòng)過速。自發(fā)性室性期前搏動(dòng)相當(dāng)于一種非侵入性的室性期外刺激，因此，由與室性心動(dòng)過速形態(tài)不同的室性期前搏動(dòng)誘發(fā)的提示屬折返機(jī)制（圖2）。這與自律性和觸發(fā)的室性心動(dòng)過速不同，這兩種室性心動(dòng)過速的起始搏動(dòng)與其后心動(dòng)過速的搏動(dòng)相似。然而，有必要說的是突發(fā)并不能排除折返。總之，始終由不同于室性心動(dòng)過速的室性期前搏動(dòng)誘發(fā)的室性心動(dòng)過速通常是折返。相反，突發(fā)的可見于任何室性心動(dòng)過速機(jī)制。

自律性室性心動(dòng)過速的原型是加速的室性自主心動(dòng)過速，這最常見于急性心肌梗死和再灌注過程，但也可見于心肌炎、高血壓性心臟病、地高辛中毒和可卡因中毒。這常始于一速率略快于其前竇性節(jié)律的長聯(lián)律間期室性搏動(dòng)。

心動(dòng)過速開始時(shí)速率逐漸增加（溫?zé)幔┖椭兄骨八俾手饾u下降（冷卻）也支持自律性機(jī)制。

對(duì)藥物的反應(yīng)

腺苷對(duì)觸發(fā)活動(dòng)引起的室性心動(dòng)過速的影響可能是對(duì)藥物干預(yù)最有用和特異的反應(yīng)。與延遲后除極相關(guān)的觸發(fā)活動(dòng)的細(xì)胞基礎(chǔ)是胞內(nèi)鈣過負(fù)荷，這誘發(fā)鈣離子依賴除極電流（短暫內(nèi)向電流或Iti），主要通過激活鈉-鈣（Na+-Ca2+）交換器。短暫的內(nèi)向鈉電流引發(fā)延遲后除極，這在振幅足夠高時(shí)觸發(fā)一新的動(dòng)作電位而導(dǎo)致心動(dòng)過速。兒茶酚胺通過刺激β腎上腺素能受體，激活腺苷環(huán)化酶（AC），增加cAMP，激活蛋白激酶A和使L型鈣通道、ryanodine受體和phospholamban磷酸化。這可引起胞內(nèi)鈣水平提高并促進(jìn)Na+-Ca2+交換器的活化。腺苷抑制AC和cAMP，逆轉(zhuǎn)胞內(nèi)鈣過負(fù)荷。鑒于腺苷對(duì)折返型室性心動(dòng)過速無抗心律失常作用，對(duì)自律性室性心動(dòng)過速只是短暫抑制（不能中止），因此，腺苷中止的室性心動(dòng)過速應(yīng)考慮為cAMP介導(dǎo)的觸發(fā)活動(dòng)。

圖1缺血性心肌病患者成對(duì)室性心動(dòng)過速形態(tài)。上圖顯示右束支左上電軸室性心動(dòng)過速，周長518ms，下圖顯示右束支右下電軸室性心動(dòng)過速，周長510ms。這是一種大的巨折返環(huán)表現(xiàn)，標(biāo)測(cè)到出口部位位于缺血性疤痕的間隔面和外側(cè)面。

圖2不同于室性心動(dòng)過速形態(tài)的室性期前搏動(dòng)誘發(fā)室性心動(dòng)過速圖例（箭頭所示）。