 Clinical Cardiac ElectrophysiologyAndrew C. Rankin ⋅ F. Russell Quinn ⋅ Alan P. Rae. Introduction .......................
  Clinical Cardiac Electrophysiology. IntroductionClinical cardiac electrophysiology (EP) techniques, involving intra...
Clinical Cardiac Electrophysiology  . Methodology.. Electrophysiological EquipmentAt its most basic, a clinical EP...
  Clinical Cardiac Electrophysiology⊡ Fig. .Radiographs of EP catheters. (a) Right Anterior Oblique (RAO) and (b) Lef...
Clinical Cardiac Electrophysiology  IaVFV1HRAHis 3-4His 1-2CS 9-10CS 7-8CS 5-6CS 3-4CS 1-2RVA1000 ms500A H V⊡ Fig. .R...
  Clinical Cardiac Electrophysiology... StimulationPacing and programmed stimulation is normally performed with rec...
Clinical Cardiac Electrophysiology  500 1,000 msV6HRAHisCS 9-10CS 7-8CS 4-5CS 3-4CS 1-2RVAH V A⊡ Fig. .Atrioventricul...
  Clinical Cardiac Electrophysiologyfirst deflection of the His bundle to the earliest indication of ventricular activa...
Clinical Cardiac Electrophysiology  aIIPCSHisA H VA H V A H VS1 S1 S2S1 S1 S2S1 S1 S2bIIPCSHisA H V A H V Ac2,000 ms1,0...
  Clinical Cardiac ElectrophysiologyThe FRP is defined as the shortest output-coupling interval produced by a tissue in...
Clinical Cardiac Electrophysiology  aaVFHRAHisCSA H VA H V A H VbaVFHRAHisCSA H VA H V A H VcaVFHRAHisCSA H V AA H V A ...
  Clinical Cardiac Electrophysiologythe pathways provides the basis of selective slow pathway ablation in the treatment...
Clinical Cardiac Electrophysiology  1,000 2,000 msS1 S1 S2IIV1HisRVAH⊡ Fig. .Bundle branch reentrant beat in response...
  Clinical Cardiac Electrophysiology2,000 4,000 6,000 8,000 msS1S1S1S1S1S1S1S1S1S1S1S1S1 S1 S1 S1 S1 S1S2S1IabV1HRARVA2...
Clinical Cardiac Electrophysiology  a1,000 2,000 3,000 4,000S1S1S1S1S1S1S1S1S1S1S1S1S1S1S1S1 S1 S2 S3 S4aVFV1HRARVAb2,0...
  Clinical Cardiac Electrophysiology.. Diagnosis of Arrhythmias... BradycardiaThe role of invasive EP studies in...
Clinical Cardiac Electrophysiology  earliest activation will be identified from the coronary sinus catheter electrogram...
  Clinical Cardiac Electrophysiology1,000 2,000 msH H H H HVPBV1HRAHisCSRVA**⊡ Fig. .His-coincident ventricular prem...
Clinical Cardiac Electrophysiology  subsequently of supraventricular [] and ventricular tachycardia [], described t...
  Clinical Cardiac Electrophysiology1,000 2,000 ms440440490490IIIIIIaVRaVLaVFV1V2V3V4V5V6MapRVAS1 S1⊡ Fig. .Conceale...
Clinical Cardiac Electrophysiology  1,000 2,000 msIIaVLaVFV1V6MapRVAS1 S1 S1⊡ Fig. .Pace mapping at a site of early ...
  Clinical Cardiac Electrophysiology1,000 2,000 msIIH 19-20H 17-18H 15-16H 13-14H 11-12H 9-10H 7-8H 5-6H 3-4H 1-2MapCS⊡...
Clinical Cardiac Electrophysiology  whose arrhythmias were non-inducible on drug therapy [], or whose tachycardia rat...
  Clinical Cardiac Electrophysiology[, ]. With the availability of the ICD, there is a need to identify high-risk...
Clinical Cardiac Electrophysiology  . Tawara, S., Das Reizleitungssystem des Säugetierherzens. EinAnatomisch-Histologi...
  Clinical Cardiac Electrophysiologyin patients with Wolff-Parkinson-White syndrome. Circulation,;: –.....
Cardiac arrhythmias and mapping techniques
Cardiac arrhythmias and mapping techniques
Cardiac arrhythmias and mapping techniques
Cardiac arrhythmias and mapping techniques
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Cardiac arrhythmias and mapping techniques

  1. 1.  Clinical Cardiac ElectrophysiologyAndrew C. Rankin ⋅ F. Russell Quinn ⋅ Alan P. Rae. Introduction ........................................................................................... . History of Clinical Electrophysiology................................................................. . Methodology ........................................................................................... .. Electrophysiological Equipment .............................................................................. .. The Electrophysiology Study................................................................................... ... His-Bundle Recording .......................................................................................... ... Intracardiac Chamber Recording ............................................................................. ... Stimulation ....................................................................................................... .. Electrophysiology Study Protocols............................................................................ ... Baseline AV Conduction Intervals ............................................................................ ... Refractory Period Assessment................................................................................. ... Induction, Definition of Mechanism, and Termination of Tachyarrhythmias.......................... .. Safety of Electrophysiological Testing ........................................................................ . Indications for Electrophysiology Studies ............................................................ .. Diagnosis of Arrhythmias...................................................................................... ... Bradycardia....................................................................................................... ... Tachycardia....................................................................................................... .. Therapeutic Role of Electrophysiology Studies.............................................................. ... Catheter Ablation ............................................................................................... ... Guidance of Therapy ............................................................................................ .. Risk Stratification................................................................................................ ... Wolff-Parkinson-White Syndrome............................................................................ ... Ventricular Arrhythmias ....................................................................................... P. W. Macfarlane et al. (eds.), Cardiac Arrhythmias and Mapping Techniques, DOI ./----_,© Springer-Verlag London Limited 
  2. 2.   Clinical Cardiac Electrophysiology. IntroductionClinical cardiac electrophysiology (EP) techniques, involving intracardiac recording and electrical stimulation, have beenof major importance in elucidating the mechanisms of cardiac arrhythmias. They not only have led to improved interpre-tation of the surface electrocardiogram (ECG) but have evolved to play a major role in the therapy of tachycardias. Thisrole has changed in recent years, with a decline in EP-guided therapy for ventricular tachyarrhythmias but an increase indiagnostic use prior to curative catheter ablation.. History of Clinical ElectrophysiologyDirect recording of intracavitary electrograms was first reported in  by Lenègre and Maurice []. Developments inrecording techniques subsequently permitted the registration of these potentials from all the cardiac chambers [–].Although the integration of the atrioventricular (AV) conducting system had been described in  by Tawara [], theHis-bundle electrogram was not recorded until  by Alanis, Gonzalez, and Lopez in the isolated canine heart []. His-bundle recordings in man were obtained using an electrode catheter in  [], but the standard endocardial cathetertechnique for recording a His-bundle potential was first described by Scherlag and coworkers in  []. Subsequently,electrode catheter recordings of electrograms from the sinus node [] and from accessory AV pathways [] have beenobtained.Initially, the major clinical application of “His-bundle electrocardiography” was as a descriptive method for the diag-nosis of AV conduction disturbances [, ]. Subsequently electrophysiological techniques were used to assess sinoatrialdisease [], and the development of programmed electrical stimulation to initiate tachycardia allowed the study of themechanisms of arrhythmias.The induction of ventricular fibrillation by electrical currents was demonstrated as early as  by Prevost andBattelli [], but the electrical induction and termination of arrhythmias essentially started in the early s. Reen-try as a mechanism for tachyarrhythmias was proposed initially by Mines [] and the presence of potential substratefor reentry was identified by Moe and coworkers [] in . Subsequently, in , the initiation and terminationof supraventricular tachycardia was demonstrated in a canine model []. A seminal study by Durrer et al. [] in demonstrated that supraventricular tachycardia could be initiated and terminated by the introduction of pre-mature beats in patients with the Wolff-Parkinson-White syndrome. Evidence for the reentrant basis for the majorityof paroxysmal supraventricular tachycardias was provided by Bigger and Goldreyer using a systematic approach withprogrammed stimulation and His-bundle recording []. These techniques were translated to patients with ventricu-lar tachycardia in  by Wellens et al. [] who suggested that the mechanism underlying this arrhythmia was alsoreentry []. A macroreentrant mechanism was described by Akhtar and colleagues in  with the demonstrationof the “V phenomenon” or bundle branch reentrant beat [], although clinically occurring tachycardias of this typeare uncommon []. The microreentrant basis for the majority of ventricular tachycardias in patients with under-lying coronary artery disease was demonstrated in a series of studies from Josephson and Horowitz and coworkers[–].The ability to reproducibly initiate ventricular arrhythmias by programmed electrical stimulation, using repeti-tive extrastimuli with varying coupling intervals, led to EP-guided drug therapy. The arrhythmia would be inducedin the drug-free state, and then the effect of drug therapy on subsequent inducibility was used to select long-termtreatment. Non-randomized studies appeared to support this practice [, ] but more recent randomized studieshave not confirmed benefit from this approach [–], leading to the virtual demise of the electrophysiology studyas the determinant of therapy for life-threatening arrhythmias. At the same time, the development of catheter abla-tion techniques has increased the use of clinical electrophysiology testing to identify the targets for this curativetherapy [].
  3. 3. Clinical Cardiac Electrophysiology  . Methodology.. Electrophysiological EquipmentAt its most basic, a clinical EP study requires equipment to allow recording of cardiac activity and delivery of electricalstimulation to the heart. A standard ECG recorder, a temporary external pacing unit, and a transvenous pacing catheterwould suffice for a simple EP study, such as the measurement of the sinus node recovery time in the evaluation of thesick sinus syndrome. However, such simple procedures are now rarely performed, and modern clinical electrophysiologyequipment is designed toundertake more complexstudies, with recordings from multiple intracardiacelectrode catheters,and programmed electrical stimulation for the induction and investigation of tachyarrhythmias.In a modern EP system, dedicated computer systems have replaced multi-channel analogue chart- and tape-recorders.Surface electrodes and intracardiac catheters are connected to the computer system via an electrically isolated patient-interface unit. Multiple ECG leads and intracardiac electrograms can be displayed on-screen, stored to hard disk, orprinted out. The simultaneous display of the signals with several surface ECGs permits the evaluation of the timing andmorphology of the surface signals relative to the intracardiac electrograms. Usually, at least three approximately orthog-onal surface leads are displayed, with additional limb and precordial ECG leads if required for tachycardia morphologyanalysis. For routine studies, bipolar intracardiac signals are amplified and band-pass filtered in the frequency range– Hz, which allows optimum definition of the intracardiac electrograms. Additional information can be obtainedfrom unipolar electrograms, using either Wilson’s central terminal or an electrode catheter placed distant from the heart,e.g., in the inferior vena cava, as the reference potential. By using different filtering of the unipolar potential, essentiallythe same as a standard ECG (.– Hz), valuable information can be obtained from the electrogram morphology, notonly the timing [].For studies involving the assessment of refractory periods and tachycardia induction, simple temporary pacing unitsare not sufficient, and a more sophisticated programmable stimulator is required. This should provide isolated outputsto prevent leakage currents that might cause arrhythmias, with the capability of delivering at least three extrastimuli atindependently variable intervals during spontaneous or paced rhythms, and with provision for a wide range of pacedcycle lengths.The studies should be performed in a dedicated EP laboratory, cardiac catheterization laboratory, or procedure roomwith fluoroscopy. In addition, it should be emphasized that the personnel should have the necessary specialist trainingand that full resuscitative equipment should be available. Recommendations have been published for training and clinicalcompetence in invasive electrophysiology studies [, ]... The Electrophysiology StudyPatients are studied in the post-absorptive state with no, or only mild, sedation (e.g., with benzodiazepines). If patientshave been on antiarrhythmic drugs, these should be withdrawn prior to study for a period of at least five half-lives, ifarrhythmia induction is planned. Other cardioactive drugs that are not used as antiarrhythmics may be continued.Electrode catheters are inserted percutaneously using standard catheterization techniques under local anesthesia, andare positioned in selected areas of the heart under fluoroscopic guidance (> Fig. .). Depending on the type of study andthe intracardiac recordings required, two to five catheters are usually inserted. The conventional EP catheter is quadripo-lar, which allows the distal pair of electrodes to deliver the stimuli for pacing and the proximal pair of electrodes to obtainbipolar electrogram recordings. Pre-shaped curves aid the placement of catheters in different positions in the heart. Thereare large varieties of specialized electrode catheters in routine use. For example, a multipolar tricuspid annulus cathetermay aid ablation of atrial flutter (> Fig. .c), and a circular multipolar catheter may be used to guide pulmonary veinisolation (> Fig. .d). Ablation catheters are deflectable to aid their placement, and have a larger electrode at their tip,usually  mm. Larger  mm tip, or irrigated tip, catheters are also used, to create larger and deeper lesions.The number of catheters, and the site of placement, varies depending on the clinical requirements. If the only clinicalquestion is whether or not a ventricular arrhythmia is inducible then a single quadripolar catheter to the right ventricular
  4. 4.   Clinical Cardiac Electrophysiology⊡ Fig. .Radiographs of EP catheters. (a) Right Anterior Oblique (RAO) and (b) Left Anterior Oblique (LAO) views of catheters placedfor a diagnostic and RF ablation procedure. Catheters have been positioned to high right atrium (HRA), tricuspid annulus torecord a His-bundle potential (His), coronary sinus (CS), right ventricular apex (RVA), and for ablation of AV nodal slow path-way (Abl). (c) Multipolar catheters placed at tricuspid valve annulus (TVA), coronary sinus (CS), and an ablation catheter (Abl)placed across the cavo-tricuspid isthmus for ablation of atrial flutter (LAO view). (d) Pulmonary vein (PV) catheter placed via atransseptal sheath at the right upper pulmonary vein to guide the ablation catheter (Abl) during a pulmonary vein isolationprocedure. Catheters also positioned at coronary sinus (CS) and His bundle (His), seen in LAO view(RV) apex may suffice, but if further assessment of cardiac electrophysiology or diagnosis is required then more cathetersare used. Many EP laboratories have routinely placed three catheters (high right atrial, His bundle, and RV apex) foran initial study, with a fourth catheter placed in the coronary sinus to provide recordings from left atrium and ventriclewhen investigating supraventricular tachycardia (> Fig. .a, b). With the expanding indications for electrophysiologicalprocedures, catheter choice and placement have become more specific, to maximize the diagnostic information requiredto proceed to ablation and to avoid unnecessary catheter use, in order to reduce complications and cost []. Much timewas previously spent on assessments of the electrophysiological properties of the heart, which now may be omitted toconcentrate on the identification and ablation of the arrhythmia substrate. For example, a single catheter approach hasbeen described for left-sided accessory pathway ablation, omitting all EP assessment prior to ablation [].... His-Bundle RecordingThe cornerstone of EP testing has been a stable, accurate His-bundle recording. To achieve this, a multipolar catheter isinserted via the femoral vein and is manipulated across the tricuspid valve into the right ventricle. While maintainingclockwise torque to hold the catheter against the tricuspid ring, the catheter is slowly withdrawn until the His-bundlesignal between the atrial and ventricular electrograms is recorded (> Fig. .). With a proximal His-bundle recording,the atrial and ventricular components of the electrogram should be of nearly equal amplitude. The normal His-bundledeflection is – ms in duration and, in the absence of a bypass pathway, the HV interval should be at least  ms.
  5. 5. Clinical Cardiac Electrophysiology  IaVFV1HRAHis 3-4His 1-2CS 9-10CS 7-8CS 5-6CS 3-4CS 1-2RVA1000 ms500A H V⊡ Fig. .Recordings in sinus rhythm. Three ECG leads (I, aVF, and V) and intracardiac bipolar electrograms from high right atrium(HRA), proximal and distal electrodes of the His-bundle catheter (His -, -), pairs of electrodes of a decapolar catheter inthe coronary sinus (CS -), and right ventricular apex (RVA) are shown. Atrial activation begins in the high right atrium,followed by septal activation at the His and then spreading across the left atriumIf this interval is less than  ms, the deflection may be a right bundle branch potential. Validation may be obtained byselective His-bundle pacing – the interval between stimulus and ventricular component should be identical to the basalHV interval [].... Intracardiac Chamber RecordingA right atrial catheter may be positioned at the superior posterolateral region near the sinus node (> Fig. .a, b). Theleft atrium can be entered directly from the right atrium through a patent foramen ovale or by means of a trans-septalprocedure, but in most cases left atrial stimulation and recording are obtained from a catheter positioned in the coronarysinus (> Figs. . and > .). This is of particular value with supraventricular tachycardia, when an accessory pathway issuspected, and a catheter with multiple electrodes, e.g., octapolar or decapolar, is placed in the coronary sinus to facilitatemapping. The coronary sinus catheter was previously most commonly inserted from above (> Fig. .a, b), via the leftantecubital, subclavian, or right internal jugular veins, but increasingly the femoral vein approach is used, deploying adeflectable multipolar catheter (> Fig. .c, d). Some laboratories use the coronary sinus catheter to pace the atria, andhence dispense with the right atrial catheter, in order to simplify procedures []. The standard catheter position in theright ventricle is with the tip in the RV apex, because it provides a stable, easily reproducible site. The RV outflow tractis also utilized, particularly for arrhythmia induction. For certain studies, such as ventricular stimulation or tachycar-dia mapping, a left ventricular (LV) electrode catheter is required []. It is inserted by the standard retrograde arterialapproach usually from the femoral artery but occasionally by means of a brachial arteriotomy. Access to the LV can alsobe achieved by crossing the mitral valve after a trans-septal puncture, and in some cases epicardial pacing of the LV canbe obtained via a branch of the CS. LV catheterization during routine EP studies is not standard.
  6. 6.   Clinical Cardiac Electrophysiology... StimulationPacing and programmed stimulation is normally performed with rectangular stimuli having a – ms pulse width and anamplitude of twice the late diastolic threshold. The electrode catheters are positioned in appropriate regions of low thresh-old for stimulation. In general, these thresholds should be less than , , and  mA for catheters positioned in the rightatrium, right ventricle, and coronary sinus, respectively. Repositioning of catheters, and interventions such as antiarrhyth-mic therapy, may alter stimulation thresholds and these should be rechecked after such maneuvers. Changing thresholdsmay influence certain electrophysiological parameters such as refractory periods. Although the use of pulse amplitude oftwice the diastolic threshold is a routine practice in many laboratories, some investigators have advocated using higherpulse amplitudes, since an increase in current strength may facilitate the induction of ventricular tachyarrhythmias bypermitting the introduction of extrastimuli at shorter coupling intervals []. However, in some patients, ventriculararrhythmias were not inducible at the higher strength although an arrhythmia was induced at twice the diastolic thresh-old []. A major concern with the use of high pulse amplitudes is the possibility of an increased induction of nonclinicalarrhythmias []... Electrophysiology Study ProtocolsAn EP study protocol must be flexible and should be selected in accordance with the particular problem to be evaluated.Unfortunately, there has been little standardization in study protocols between laboratories, particularly in relation toventricular stimulation, and this has contributed to the concerns about the evidence base for its clinical utility. However,while EP-guided therapy for ventricular arrhythmias has declined, the role of the electrophysiology study in the diag-nosis of tachycardia and the identification of a substrate for ablation has increased. The baseline diagnostic informationobtained will dependon the numberof catheters placed, and the stimulation protocols utilized, but mayinclude an assess-ment of the AV conduction system, evaluation of the refractory periods of its components and induction, definition ofmechanism, and termination of tachyarrhythmia.... Baseline AV Conduction Intervals(a) PA interval and intra-atrial conduction timesThe depolarization of the atrium usually occurs earliest in the region of the sinus node either at the high right atrium,the node itself or the mid-lateral aspect of the right atrium []. The PA interval, measured from the onset of the P wavein the surface ECG to the atrial electrogram recorded from the His-bundle electrode (AV junction) catheter is a measureof the intra-atrial conduction time []. It is not sensitive to changes in autonomic tone. The sequence of atrial activationtimes at various right and left atrial sites may be more useful than the PA interval. An example of a normal atrial activationpattern is shown in > Fig. . and an example of an abnormal pattern during atrioventricular re-entrant tachycardia(AVRT) is shown in > Fig. ..(b) AH intervalSince the depolarization of the AV node cannot be demonstrated using standard electrophysiological techniques, the AHinterval is employed for the functional evaluation of AV nodal conduction. The AH interval is measured from the firsthigh-frequency deflection in the atrial electrogram recorded from the His-bundle catheter to the first deflection of theHis-bundle electrogram (> Fig. .). The normal range of the AH interval is – ms. The AH interval is markedlyinfluenced by changes in autonomic tone. The AH interval shortens with sympathetic stimulation and lengthens withparasympathetic (vagal) stimulation. Therefore, it may vary profoundly during an EP study depending on the balance ofautonomic tone in relation to the patient’s level of sedation, anxiety, and other factors.
  7. 7. Clinical Cardiac Electrophysiology  500 1,000 msV6HRAHisCS 9-10CS 7-8CS 4-5CS 3-4CS 1-2RVAH V A⊡ Fig. .Atrioventricular (AV) tachycardia, with a left-sided accessory pathway. Electrograms from high right atrium (HRA), His-bundlecatheter (His), a decapolar coronary sinus catheter (CS -), and RV apex. Earliest atrial activation (arrowed) is recorded fromthe middle pair of electrodes of the coronary sinus catheter (CS -), indicating a left-sided pathway1,000 2,000 msIIPCSHisA A A A AH H H HS1S1S1S1S1S1⊡ Fig. .Wenckebach-type AV block with atrial pacing. The drive cycle length (S-S) is  ms, pacing from proximal coronary sinuselectrodes (PCS). The AH interval increases until block occurs (arrow) of AV nodal conductionDuring atrial pacing at increasing rates (incremental pacing), the normal physiological response is a progressivelengthening in the AH interval at successive rates until AV nodal block occurs. This block occurs usually at rates of– beats per minute (bpm) and has Wenckebach periodicity, with beat-to-beat AH prolongation prior to block(> Fig. .). With alterations in autonomic tone, however, physiological AV nodal block can occur in normal individualsoutside this range. At more rapid atrial pacing rates : or higher degrees of AV nodal block can occur (> Fig. .b).The development of AV nodal Wenckebach periods at cycle lengths of  ms or longer raises the possibility of a con-duction disturbance, especially if they persist after the administration of atropine. AV nodal block at cycle lengths of ms or shorter is suggestive of enhanced AV nodal conduction, sometimes called Lown-Ganong-Levine syndrome[]. Whether this syndrome merely constitutes one end of the spectrum of AV nodal conduction or is caused by thepresence of an atrio-His accessory pathway bypassing part or all of the AV node remains speculative [].(c) HV intervalThe HV interval, a measure of infranodal conduction, assesses conduction through the His bundle, the bundle branches,and the terminal Purkinje system. The normal His-bundle width is –ms. The total HV interval is measured from the
  8. 8.   Clinical Cardiac Electrophysiologyfirst deflection of the His bundle to the earliest indication of ventricular activation either in the surface or intracardiacleads (> Fig. .). For adults, the HV interval ranges from  to  ms. An interval less than  ms suggests that either theelectrogram is obtained from the right bundle branch, or there is an accessory AV connection bypassing at least part of theHis-Purkinje system. The HV interval is not influenced by autonomic tone and should not vary within or between studies.With atrial pacing, the HVinterval normallyremains constant, although at high-paced rates HVinterval lengthening withinfra-His block may occur in normal individuals. The development of functional bundle branch or complete infra-Hisblock can also occur because of abrupt shortening of the paced cycle length. The facilitation of AV nodal conduction,for instance by catecholamine stimulation, permitting the penetration of impulses into the His-Purkinje system can alsoincrease the likelihood of functional His-Purkinje block.(d) Intraventricular conductionTo measure intraventricular conduction, endocardial mapping of both ventricles is required, which is not usually partof a routine study. The Q-RVA conduction time may be measured, from the onset of ventricular activation to the RVapical electrogram, but is of limited clinical value, in contrast to the QRS duration from the surface ECG, which may haveprognostic value [].(e) Ventriculoatrial conductionIn the absence of an accessory pathway, ventriculoatrial (VA) conduction utilizes the normal AV conduction systemretrogradely. VA conduction may be absent in normal individuals with intact anterograde conduction and converselymay be present in patients with anterograde AV block []. In general, AV conduction is better than VA conduction.During incremental ventricular pacing, in the majority of patients, VA conduction time progressively lengthens untilthe development of VA block, although the degree of prolongation of VA conduction is relatively less than that seen withAV conduction. The site of retrograde VA block may be located in either the His-Purkinje system or the AV node, butsince retrograde His-bundle electrograms are only infrequently recorded during ventricular pacing, this localization canonly be inferred indirectly. As with AV conduction, the retrograde His-Purkinje system is sensitive to abrupt changes incycle length.... Refractory Period AssessmentThe refractory periods of the cardiac chambers and the components of the AV conduction system are evaluated bythe technique of premature stimulation. Refractoriness is influenced by several factors including the intensity of theextrastimuli and the cycle length of the spontaneous or paced rate at which the refractory period is measured. There is abasic difference in the responses of myocardium and nodal tissue to increasing rate or increasing prematurity: in atrialor ventricular muscle there is a decrease in the refractory periods, in contrast to the AV node where there is an increasein refractory intervals and conduction time (decremental conduction).By convention, the notation used is as follows: S is the basic stimulus and S is the first premature stimulus; S-Sis the paced cycle length; S-S is the coupling interval between the last complex of the paced cycle and the prematurestimulus S. The corresponding notations for the atrial, His-bundle, and ventricular electrograms are A-A and A-A,H-H and H-H, and V-V and V-V, respectively (e.g., > Fig. .).(a) Effective refractory periodThe effective refractory period (ERP) is defined as the longest premature coupling interval, S-S, which fails to produce apropagated response. For the atrium, therefore, the ERP is the longest S-S, which fails to produce an A (> Fig. .c); theAV nodal ERP is the longest A-A, which fails to produce an H (> Fig. .b); and the ERP of the His-Purkinje system isthe longest H-H, which fails to elicit a ventricular response. The ERP of the components of the AV conduction system,except for the AV node, shorten with decreasing drive cycle lengths.
  9. 9. Clinical Cardiac Electrophysiology  aIIPCSHisA H VA H V A H VS1 S1 S2S1 S1 S2S1 S1 S2bIIPCSHisA H V A H V Ac2,000 ms1,0002,000 ms1,0002,000 ms1,000IIPCSHisA H VA H V⊡ Fig. .Responses to atrial premature beats. Following an -beat drive train, S-S, cycle length  ms, from proximal coronary sinuselectrodes (PCS), a premature stimulus is delivered (S-S). With a coupling interval of  ms (a) there is prolongation of theAH interval, compared to during the drive train. With a shorter coupling interval of  ms (b) the AV nodal effective refrac-tory period (ERP) is reached and there is block of conduction, with only atrial capture - note the absence of a His potential,demonstrating that the block is at the level of the AV node. When the coupling interval is shortened further to  ms (c) theatrium is also refractory, with no atrial capture(b) Relative refractory periodThe relative refractoryperiod (RRP)is the longest premature coupling interval at which delayin conduction (prolongationof conduction time) of the extrastimulus occurs. The RRP of the atrium is, therefore, the longest S-S at which S-A isgreater than S-A, For the AV node, the RRP is the longest A-A at which A-H is greater than A-H and the RRP ofthe His-Purkinje system is the longest H-H at which H-V is greater than H-V.(c) Functional refractory periodIn contrast to the ERP and the RRP, the functional refractory period (FRP) is an indication of the conduction within tissue,not the refractoriness of the tissue. Although a misnomer, the term refractory period has remained in conventional usage.
  10. 10.   Clinical Cardiac ElectrophysiologyThe FRP is defined as the shortest output-coupling interval produced by a tissue in response to programmed extrastim-ulation. The atrial FRP is the shortest A-A produced by any S-S. The AV nodal FRP is the shortest H-H in responseto any A-A and the FRP of the His-Purkinje system is the shortest V-V in response to any H-H. Frequently, the FRPof the AV node is longer than the ERP of the His-Purkinje system preventing measurement of the His-Purkinje ERP.(d) Programmed atrial premature stimulationProgrammed atrial stimulation is performed by scanning diastole with a premature stimulus introduced initiallylate in diastole after – beats of either spontaneous rhythm or an atrial drive cycle. The coupling interval of thepremature stimulus is progressively shortened by – ms. The introduction of premature stimuli in the atriumin the region of the sinus node during sinus rhythm permits the evaluation of the sinoatrial conduction time(see > Chap. ).Decreasing the coupling interval of atrial premature stimuli produces progressive delayin AV nodal conduction man-ifested by lengthening of the A-H interval (> Fig. .). The H-H interval initially shows progressive shortening inresponse to shortening of the A-A interval until a nadir is reached, when the increase in AH interval is greater than thedecrease in A-A, followed by a slow increase in the H-H intervals. By definition, this nadir corresponds to the FRP ofthe AV node. Further shortening of A-A may produce block in the AV node (ERP of the AV node).Changes in the cycle length of the drive train tend to have a variable effect on the FRP, but with shortening of thedrive train cycle length, there is invariably a lengthening of the ERP of the AV node []. The probability, therefore, ofa b500400300200100msH1-H2A2-H2H2-V2AVNRT500400300200100ms300 400 500300 400 500A1–A2 interval (ms) A1–A2 interval (ms)H1-H2A2-H2H2-V2⊡ Fig. .Responses of the AV conduction system to atrial extrastimuli in a normal individual (a) and a patient with dual AV nodalphysiology (b). With progressive shortening of the coupling interval (A-A) there is initial associated shortening of the H-Hinterval, but as the A-A shortens further there is relatively greater increase in the AH interval, which results in prolongationof the H-H interval. In the normal individual (a) a minimum value of the H-H interval is reached ( ms), which is thefunctional refractory period (FRP) of the AV node. The presence of dual AV nodal pathways (b) is shown by a sudden increasein the AH (and correspondingly the HV) intervals. At a critical delay, this is associated with the initiation of AV nodal reentranttachycardia (AVNRT) (asterisk)
  11. 11. Clinical Cardiac Electrophysiology  aaVFHRAHisCSA H VA H V A H VbaVFHRAHisCSA H VA H V A H VcaVFHRAHisCSA H V AA H V A H VS1 S1 S2S1 S1 S2S1 S1 S22,000 ms1,0002,000 ms1,0002,000 ms1,000⊡ Fig. .Responses to atrial premature beat demonstrating dual AV nodal pathways and initiation of AVNRT. With a relatively longcoupling interval of  ms (a) there is conduction down the fast pathway, with a normal AH interval. With a short couplinginterval of  ms (b) there is marked prolongation of the AH interval, indicating conduction down the slow pathway. Withfurther shortening of the coupling interval to  ms (c) there is initiation of AVNRT. Surface lead aVF and electrograms fromhigh right atrium (HRA), His bundle, and coronary sinus (CS) are shownencountering the ERP of the AV node is increased by employing faster drive trains. In a proportion of patients, espe-cially those with AV nodal reentrant tachycardia (AVNRT), the response to atrial premature stimulation demonstratesa discontinuous curve suggesting two electrophysiologically distinct AV nodal pathways [, ]. In patients with dualpathways, the AH interval progressively grows longer until there is a sudden “jump” in the AH interval in response to asmall decrement in the premature coupling interval (> Figs. . and > .). This sudden increase in AH interval reflectsblock in the “fast” AV nodal pathway, which has a longer refractory period than the “slow” pathway. The presence of dualAV nodal pathways in itself does not imply the presence of AVNRT but only the potential substrate. In some patients,dual AV nodal pathways may not be manifest in the baseline state but can be exposed by alterations in autonomic tone orwith drug therapy []. Despite the presence of discontinuity in AV conduction, retrograde VA conduction commonlyis continuous []. However, the finding of discontinuous retrograde conduction curves in a minority of patients iden-tified differences in the site of atrial insertion, with the slow pathway retrograde activation via the area of the coronarysinus os and the fast pathway in the region of the His-bundle recording []. This anatomical differentiation between
  12. 12.   Clinical Cardiac Electrophysiologythe pathways provides the basis of selective slow pathway ablation in the treatment of AVNRT []. Further experi-ence has revealed the potential complexities of arrhythmia substrate with a diversity of AV nodal pathways described[, ].In contrast to the AV node, there is usually no change in conduction in the His-Purkinje system to atrial prematurestimulation (> Fig. .). Uncommon patterns of response include progressive delay in conduction with lengthening ofthe HV interval, an abrupt change in the HV interval, and complete block of infranodal conduction. The developmentof aberrant conduction or block within the His-Purkinje system is more likely during sinus rhythm or longer drive traincycle lengths because the refractoriness of the tissue is directly related to the preceding cycle length. At slower rates, therelative or ERPs may then be longer than the FRP of the AV node. Conduction delay or block within the His-Purkinjesystem therefore is not necessarily an abnormal response. Functional delay or block in the right bundle tends to occurmore frequently than in the left bundle.(e) Programmed ventricular premature stimulationProgrammed ventricular stimulation is performed in a similar manner to atrial stimulation. Ventricular stimuli are intro-duced after – beats of spontaneous rhythm or a ventricular drive train at progressively shorter coupling intervalsuntil ventricular refractoriness occurs. For routine studies, ventricular stimulation is performed at the RV apex. The ven-tricular ERP at the apex is usually less than  ms and, in an otherwise normal ventricle, refractoriness varies little atother sites.Retrograde refractory periods may be difficult to determine because the His-bundle electrogram is frequentlyobscured by the ventricular electrogram. With progressive shortening of the V-V (S-S) interval, the retrograde His-bundle electrogram H mayemerge from the ventricular electrogram, and with further shortening the V-H interval willprogressively lengthen until either ventricular refractoriness or retrograde His-Purkinje block occurs. Not infrequently,in the latter circumstances, with further shortening of V-V, the H will reappear because of proximal conduction delay(gap phenomenon: see > Sect. ....f). Retrograde AV nodal conduction (H-A) may show either progressive slowingof conduction with an increasing H-A interval, or an almost constant relatively short H-A interval, or discontinuouscurves analogous to the anterograde dual AV nodal pathways. Retrograde atrial activation in the absence of an accessorypathway is usually first observed in the His-bundle electrogram (> Fig. .).Ventricular premature stimulation can induce a variety of repetitive responses. AV nodal echo beats in relationto retrograde dual pathways may be initiated, although a sustained tachycardia rarely occurs. Frequently, in patientswith normal conduction, the “V phenomenon,” or bundle branch reentrant beat, (> Fig. .) may be observed [].This repetitive ventricular response is caused by the development of a macro-reentrant circuit involving the His bun-dle and bundle branches. Block in the right bundle branch is followed by retrograde conduction of the impulse bythe left bundle with retrograde conduction to the His bundle and subsequent completion of the reentrant circuit by1,000 2,000 msV1HRAHisRVAV H AS1 S1 S2⊡ Fig. .Retrogradeconduction in responseto a ventricular prematurebeat. Followingtheventricular extrastimulus, couplinginterval ms, retrograde His bundle and atrial activation are seen
  13. 13. Clinical Cardiac Electrophysiology  1,000 2,000 msS1 S1 S2IIV1HisRVAH⊡ Fig. .Bundle branch reentrant beat in response to a single ventricular extrastimulus. Following the extrastimulus (S), couplinginterval  ms, there is retrograde His-bundle activation (H) preceding the reentrant beat, which has a left bundle branchblock morphologyanterograde conduction down the now-recovered right bundle branch. Therefore, the repetitive response has a left bun-dle branch block morphology with an HV interval the same or longer than the HV interval observed during sinusrhythm.(f) Gap phenomenonDuring programmed extrastimulation, block of the impulse may occur but then be followed by the resumption of con-duction with shorter coupling intervals of the premature stimuli. This is known as the gap phenomenon. It is caused bythe development of conduction delay proximal to the site of block, allowing the distal tissue to recover and conduct [].For example, as A-A is shortened, block may occur at the level of the His bundle. With further shortening of A-A,the resulting increase in the A-H interval produces lengthening of the H-H such that it exceeds the refractory periodof the distal tissue with the resumption of conduction. Several gaps have been identified in relation to the componentsof the AV conduction system, both in the anterograde [, ] and retrograde directions []. The gap phenomenon is aphysiological response and is not of pathological significance.... Induction, Definition of Mechanism, and Termination of TachyarrhythmiasThe stimulation protocol used to induce tachycardia will depend on the specific arrhythmia. Programmed stimulationof the ventricle can induce ventricular tachycardia or fibrillation, and this has been used to guide therapy and assess risk(> Figs. . and > .). A common protocol would use up to three extrastimuli (S, S, S), at two drive cycle-lengths(S-S, e.g.,  and  ms) at two ventricular sites, such as RV apex and outflow tract. However, a variety of other proto-cols have been used, with different drive cycle lengths and number of extrastimuli []. More aggressive protocols, withfaster drive rates and increased number of extrastimuli, particularly if tightly coupled, may induce nonspecific arrhyth-mia, such as ventricular fibrillation []. The diversity of protocols, and the concerns about the specificity of inducedarrhythmia, have contributed to the decline in the clinical use of ventricular stimulation. Induced tachycardia may beterminated by further ventricular stimulation, either extrastimuli or overdrive pacing (> Fig. .b) []. There is therisk of causing acceleration of the arrhythmia, particularly if the tachycardia is fast (> Fig. .b). With respect to othertachycardias, supraventricular tachycardias may be induced by atrial or ventricular extrastimuli, and atrial arrhythmiascan be induced by atrial extrastimuli or rapid atrial pacing. Catecholamine stimulation, using isoproterenol infusion, maybe necessary for arrhythmia induction. Tachycardia induction, diagnosis, and termination, and techniques of mappingto identify targets for ablation, are discussed further below, and in > Chaps.  and > .
  14. 14.   Clinical Cardiac Electrophysiology2,000 4,000 6,000 8,000 msS1S1S1S1S1S1S1S1S1S1S1S1S1 S1 S1 S1 S1 S1S2S1IabV1HRARVA2,000 4,000 6,000 8,000 msIV1HRARVA⊡ Fig. .Initiation and termination of sustained ventricular tachycardia. Following an -beat drive train, cycle length  ms, a singlepremature ventricular beat, coupling interval  ms, initiates VT (a). There is ventricular-atrial dissociation, as seen in therecording from high right atrium (HRA). A burst of rapid ventricular pacing (b) terminates the VT and restores normal sinusrhythm.. Safety of Electrophysiological TestingClinical cardiac electrophysiological testing involves invasive techniques and therefore has a potential for complication,which is inherent in any cardiac catheterization procedure. Venous thrombosis is the most common complication, withan incidence ranging between . and .% [, ]. Factors which may influence the development of thrombosis includenot only the patient population being studied but also specific aspects of the procedure, such as the use of systemic antico-agulation and the duration the electrode catheters are in situ [, ]. Arterial injury occurs in .–.% of patients eitherbecause of local trauma during attempts at arterial cannulation or inadvertently during femoral venous catheterization[]. Cardiac perforation has been observed in .% of patients, although tamponade was less common and emergencypericardiocentesis was required only rarely []. The risk of complications has increased with the addition of ablationprocedures to the diagnostic EP study, which may include complications specific to the procedure, such as inadvertentAV block with ablation of AV nodal pathways, or thromboembolic complications with left-sided ablations, or pericardialtamponade with transseptal puncture [, ]. In a prospective study of nearly , procedures, the risk of complica-tions increased from .% for diagnostic EP procedures to .% with radiofrequency ablation []. Risk was increased witholder age patients and with the presence of systemic disease. The target of ablation also increases the risk, with highercomplications for AVNRT compared to AVRT, and for scar-related VT compared to idiopathic VT []. Pulmonary veinisolation and left atrial ablation for atrial fibrillation may also expose the patient to increased risk of up to %, includingspecific risks like pulmonary vein stenosis and atrio-esophageal fistula [, ].Complications specifically related to ventricular stimulation studies, such as the induction of heart block ornonclinical arrhythmias, are usually transient and not of clinical importance, despite the need for cardioversion in
  15. 15. Clinical Cardiac Electrophysiology  a1,000 2,000 3,000 4,000S1S1S1S1S1S1S1S1S1S1S1S1S1S1S1S1 S1 S2 S3 S4aVFV1HRARVAb2,000 4,000 6,000 8,000 msaVFV1RVA⊡ Fig. .Initiation of VT with triple extrastimuli (a), and acceleration to ventricular fibrillation with burst pacing (b)over % of these patients []. The risk of death during EP testing is low (.–.%), despite the induction of malignantventricular arrhythmias.. Indications for Electrophysiology StudiesThe indications for EP studies can be considered in three categories:. Diagnostic – to determine the mechanism of an arrhythmia, either tachycardia or bradycardia. Therapeutic – to identify the substrate of the arrhythmia prior to ablation, or to guide therapy selection. Risk stratification – to determine the risk of life-threatening arrhythmiaThe role of EP testing in each of these categories has changed, due to progress in diagnostic methodologies, the results ofclinical studies and the advances in treatment options. For example, implantable event-recorders now have an importantrole in the diagnosis of unexplained syncope [], and often replace the relatively nonspecific invasive EP study [].The exception may be patients with syncope and prior myocardial infarction (MI), where induction of monomorphicVT can indicate an arrhythmic etiology. However, there is evidence of benefit from the implantable defibrillator in manysuch patients without the need for an EP study [], further reducing the role of invasive testing. There is clearly overlapbetween the diagnostic and the therapeutic indications in that establishing the diagnosis may lead to curative catheterablation. With respect to risk stratification, the value of the EP study in predicting adverse outcome has been questioned,because of the recognition of persisting risk of sudden death despite a negative EP study in a variety of conditions, includ-ing ventricular arrhythmias occurring post-infarction [], or associated with dilated cardiomyopathy [] or Brugadasyndrome []. When considering specific arrhythmias, each of these categories (diagnosis, therapy, and risk assessment)may have a role.
  16. 16.   Clinical Cardiac Electrophysiology.. Diagnosis of Arrhythmias... BradycardiaThe role of invasive EP studies in the diagnosis of bradycardias has declined in recent years. The ACC/AHA/HRS pacing guidelines include the measurement of HV interval (  ms), the diagnosis of infranodal conduction block post-MI and the presence of major abnormalities of sinus node function as factors in the decision as to whether to implanta permanent pacemaker in selected situations []. Assessment of sinoatrial dysfunction and AV conduction disease isdescribed in > Chaps.  and >  respectively.... TachycardiaThe specific diagnostic electrophysiological procedures undertaken will depend on the clinical question and therapeu-tic aim, usually determined by the previously documented arrhythmia. Tachycardias with narrow QRS complexes aredescribed as supraventricular tachycardias, and include atrial and junctional tachycardias. The latterinclude AVRT, utiliz-ing an accessory pathway, and AVNRT, whose substrate is dual AV nodal pathways. Wide-complex tachycardias may alsobe supraventricular, with aberrant AVconduction such as bundle branch block or pre-excitation, but maybe ventricular inorigin. The surface ECG has limitations in diagnosing such broad complex tachycardias, and invasive electrophysiologicalstudies may be of particular value in this context.(a) Identification of substrateIn a patient with supraventricular tachycardia, the presence of a substrate for reentry, such as an accessory pathway, maybe manifest by an abnormal intracardiac activation sequence of either atrial or ventricular electrograms. For example, inthe presence of pre-excitation, the earliest ventricular activation during sinus rhythm will be at the site of the ventricularinsertion of the pathway (> Fig. .), or with a concealed pathway the earliest atrial activation during ventricular pacingmay be used to identify the site of the pathway. The most common pathway location is left-sided, in which case the1,000 2,000 msV1CS 9-10CS 7-8CS 4-5CS 3-4CS 1-2⊡ Fig. .Intermittent pre-excitation with a left-sided accessory pathway. The first beat is not pre-excited and left ventricular (LV) acti-vation in the coronary sinus (CS) electrograms is late. The second beat is pre-excited, with a delta wave on the surface ECG(V), and earliest ventricular activation is recorded from the distal coronary sinus electrodes (arrowed) indicating a left-lateralaccessory pathway
  17. 17. Clinical Cardiac Electrophysiology  earliest activation will be identified from the coronary sinus catheter electrograms. If the activation sequences are normalduring sinus rhythm and ventricular pacing, with earliest retrograde atrial activation recorded at the His-bundle catheter,then atrial programmed stimulation may identify the presence of dual AV nodal physiology, as the substrate for AVNRT(> Fig. .). The identification of the tachycardia substrate may allow curative catheter ablation. If there is neither anaccessory pathway nor AVNRT, then an atrial arrhythmia is likely, and it may be necessary to induce the tachycardiato allow mapping and ablation. However, if typical atrial flutter has been documented, it is not necessary to induce thearrhythmia, since it is recognized that the cavo-tricuspid isthmus is an essential component of the reentry circuit and thetarget for ablation.(b) Mechanisms of tachycardiaReentry is the most common mechanism underlying clinical sustained tachyarrhythmias. It is a characteristic of reentrantarrhythmias that they can be initiated by premature beats. Atrial reentrant and junctional tachycardias, AVNRT or AVRT,can commonly be initiated by atrial premature beats. The latter tachycardias are dependent on critical delay in the AVconduction induced by the premature beat, which allows subsequent retrograde conduction up the accessory pathwayor the fast retrograde AV nodal pathway. Ventricular premature beats may also induce AVRT, and infrequently AVNRT,or may initiate reentrant ventricular tachycardia (> Fig. .), particularly in the presence of a ventricular substrate suchas scarring from an old MI. Less commonly, arrhythmias are due to focal increased automaticity, or to triggered activity.Tachycardias that originate from an automatic focus may be less likely to be inducible by programmed stimulation butmay be initiated by catecholamine stimulation, using an infusion of isoproterenol, a β-adrenoceptor agonist. Triggeredarrhythmias, which may depend on oscillations of intracellular calcium induced by preceding beats, may also be initiatedby pacing protocols.(c) Atrial activation during tachycardiaOnce a sustained tachycardia has been induced, the mechanism may be clear from the atrial activation timing andsequence. With typical (“slow–fast”) AVNRT, atrial activation may be coincident with or precede ventricular activa-tion, and the earliest atrial activation is commonly seen from the His-bundle catheter (> Fig. .). With AVRT, theatrial activation sequence is determined by the site of the accessory pathway, and is commonly eccentric (> Fig. .),although a paraseptal pathway may have a retrograde activation sequence similar to that via the normal conducting sys-tem. Atrial tachycardia may remain a differential diagnosis of such tachycardias, and electrophysiological maneuvershave been described, which may aid the diagnosis. A ventricular premature beat timed to coincide with the His-bundleelectrogram can alter the timing of the atrial activation only in the presence of an accessory pathway, since retrogradeconduction via the normal conducting system will be refractory (> Fig. .). Differentiating between an atrial tachycar-dia and AVNRT or AVRT can be achieved by observing the responses following cessation of a short burst of ventricularpacing, faster than the tachycardia rate and with : VA conduction []. With atrial tachycardia, on termination of ven-tricular pacing the retrograde atrial signal is followed by an atrial tachycardia beat, which conducts to the ventricle – anA-A-V response – whereas AVNRT and AVRT show an A-V response (> Fig. .). There are limitations to this technique,including a “pseudo A-A-V” response in patients with AVNRT and long HV intervals, when identification of A-H or A-A-H responses is more accurate []. Differentiation between atypical AVNRT from AVRT utilizing a posterior paraseptalaccessory pathway may be aided by the appearance of V-H-A with ventricular premature beats in the former []. Thepresence of a concealed paraseptal pathway can be assessed in sinus rhythm by pacing via the His-bundle catheter andcomparing the retrograde atrial activation timing with His-bundle capture and local ventricular capture []. Atrial flutterhas a faster atrial rate and is characterized by intermittent AV conduction, commonly :. The atrial activation sequenceis typically counterclockwise around the tricuspid annulus. Ventricular tachycardia may have retrograde conduction tothe atria, with earliest activation at the His-bundle catheter, or there may be VA dissociation.(d) EntrainmentThe evidence of the reentrant basis of the majority of clinical atrial and ventricular tachycardias came from studies ofthe phenomenon of entrainment []. Waldo et al, in a series of studies initially of post-operative atrial flutter [] and
  18. 18.   Clinical Cardiac Electrophysiology1,000 2,000 msH H H H HVPBV1HRAHisCSRVA**⊡ Fig. .His-coincident ventricular premature beat (VPB) during atrio-ventricular reentrant tachycardia (AVRT). A premature stimu-lus in the right ventricle pulls ventricular activation earlier, timing with the anterograde activation of the His bundle. Thefollowing atrial activation (asterisks) occurs at an interval shorter than the tachycardia cycle length (arrows). This confirmsthe presence of an accessory pathway, since the normal conducting system would be refractory and unable to conductretrogradelya1,000 2,000 ms2,000 msS1 S1 S1A A VIIHRARVAbA V AS1 S1 S11,000IIHRARVA⊡ Fig. .A technique for the diagnosis of atrial tachycardia. During atrial tachycardia (a), following termination of ventricular pacingwith retrograde atrial activation, there is a A-A-V response. During AVNRT (b) there is a A-V-A response
  19. 19. Clinical Cardiac Electrophysiology  subsequently of supraventricular [] and ventricular tachycardia [], described three criteria for entrainment: () con-stant fusion during the transient entrainment of a tachycardia except for the last captured beat (which was entrained butnot fused), () progressive fusion at different entrainment rates, and () interruption of the tachycardia associated withlocal conduction block followed by activation from a different direction []. A fourth criterion was added based on theelectrogram equivalent of progressive fusion []. Demonstration that any of these criteria were met by pacing during asustained tachycardia was evidence of a reentrant mechanism.The demonstration of entrainment required that the reentry circuit had an excitable gap, allowing capture from pacingoutside of the circuit. Local activation sequences within the tachycardia circuit were unchanged, with the rate increasedto that of the pacing, but the surface electrogram was a fusion of the morphologies determined by the local pacing site andthe tachycardia. Since the last paced beat entered the circuit but the output did not fuse with a subsequent paced beat, thebeat following pacing had the morphology of the tachycardia but was at the pacing cycle length (> Fig. .). The degreeof fusion varied depending on the pacing rate, with the morphology more closely resembling that of the paced beatswith increased rate (progressive fusion). At a critical rate, the paced impulse may collide with the tachycardia wavefrontproducing block and termination of the tachycardia. Subsequent activation was from the direction of pacing, and had ashorter coupling interval.With the development of mapping techniques it became apparent that if the pacing site was within the reentry circuitthen none of the criteria could be met, so-called “concealed entrainment” [] or “entrainment with concealed fusion”.In this case the morphology and activation sequences of the entrained rhythm would be identical to the tachycardia, butat the pacing rate. The local return cycle would be at the tachycardia cycle length, and not the pacing rate (> Fig. .).A prolonged return cycle indicates that the pacing site was not within the reentry circuit []. The demonstration ofconcealed entrainment may be of value in confirming a site for successful catheter ablation [, ].(e) Syncope of undetermined etiologyThe role of EP studies in the diagnosis of syncope has diminished, but may still be of value in selected patients [, , ].Tilt testing to diagnose neurocardiogenic syncope and implanted loop recorders to allow correlation between symp-toms and cardiac rhythm have contributed to the decline in the use of invasive studies. The expanding indicationsfor implantable devices to treat ventricular arrhythmias have reduced the need to demonstrate inducible ventriculararrhythmias in patients in whom they are suspected. The clinical significance of an induced arrhythmia or an identi-fied conduction abnormality may be uncertain, reflecting the low sensitivity and specificity of EP testing. The diagnosticyield is particularly low in the absence of structural heart disease [, ].S1 S1 S1 S13002,000 ms1,000V1RVA300320⊡ Fig. .Entrainment of ventricular tachycardia. During pacing at cycle length  ms the ECG has a different morphology comparedto during tachycardia. The beat following the last stimulus is at the pacing cycle length, but has the morphology of thetachycardia. Pacing cycle length indicated by filled arrow, and tachycardia cycle length by interrupted arrows
  20. 20.   Clinical Cardiac Electrophysiology1,000 2,000 ms440440490490IIIIIIaVRaVLaVFV1V2V3V4V5V6MapRVAS1 S1⊡ Fig. .Concealed entrainment. Pacing using the mapping catheter (Map) at cycle length  ms produces an ECG morphologynearly identical to that during tachycardia. The return cycle of the local electrogram recorded from the mapping catheteris at almost the tachycardia cycle length (interrupted arrows). This is consistent with pacing within the reentry circuit, and thedelay between the stimulus and the ventricular activation,as indicated by the surface ECG, suggests the site is at the entranceto an area of slow conduction.. Therapeutic Role of Electrophysiology Studies... Catheter AblationA major change in the role of EP studies has followed the development of catheter ablation for the curative treatment ofcardiac arrhythmias [, , ]. Techniques and principles developed for the diagnosis of arrhythmias now are appliedin a more specific manner to identify the substrate for ablation. A more anatomical, rather than electrophysiological,approach may be applied to the ablation of some arrhythmias, including AVNRT [], atrial flutter [] or fibrillation[], and ventricular tachycardia []. Technologies have been developed to aid the mapping of complex arrhythmiasubstrates, and are described in > Chap. . However, many arrhythmias can be successfully treated by catheter ablationusing conventional electrophysiological techniques to aid the mapping and identification of the ablation target, using thefollowing methods.(a) Earliest activation. The site of successful ablation of an accessory pathway or a focal atrial or ventricular tachycardia isusually determined by the identification of the site of earliest activation (> Figs. . and > .). The use of unipolarsignals from the distal ablation catheter(filtered like a standard ECG)is ofvalue, as the presence ofan R wave identifiesa site unlikely to be successful, whereas successful sites have a QS pattern (> Fig. .) [].(b) Pace mapping. This is based on the principle that pacing at the site of origin of the tachycardia should produce theidentical ECG morphology to the clinical arrhythmia. It is of value in the ablation of focal ventricular tachycardia,such as RV outflow tachycardia (> Fig. .). One advantage is the option to continue mapping in the absence of thearrhythmia, particularly if the tachycardia is poorly tolerated by the patient.
  21. 21. Clinical Cardiac Electrophysiology  1,000 2,000 msIIaVLaVFV1V6MapRVAS1 S1 S1⊡ Fig. .Pace mapping at a site of early activation during RV outflow tachycardia. Pacing through the mapping catheter (Map) pro-duces a morphology nearly identical to that during tachycardia. The local activation at this site is early, preceding the onsetof the QRS complexes (vertical line)500 1,000 msV6CSMapUPA VA V⊡ Fig. .Site of ablation of an accessory pathway. The ventricular activation recorded from the coronary sinus (CS) catheter indicatesthatLVactivationislate.Mappingcatheter(Map)isatasiteontheRVannuluswhereventricularactivationisearlier,precedingthe onset of the delta wave (vertical line). The unipolar signal has a PQS morphology, consistent with the site of the pathway,indicating a likely successful site for ablation(c) Electrogram-guided ablation. For a number of tachycardias, the above methods may be of limited value, particularlyif the substrate is a macro-reentrant circuit, and specific characteristics of potentially successful ablation sites havebeen described. Examples include () AVNRT, where a characteristic complex signal with a slow pathway potentialhas been described [], () Mahaim tachycardia, which uses an atrio-fascicular bypass tract, and can be ablated onthe tricuspid annulus guided by a Mahaim potential [, ], and () Idiopathic LV (fascicular) tachycardia, whereablation is guided by Purkinje and pre-Purkinje potentials [, ].(d) Entrainment mapping. With reentrant arrhythmias, activation mapping may be of limited value, and the aim is toidentify a component of the circuit, which may be the site of successful ablation. The demonstration of “entrain-ment with concealed fusion” as described above, may identify an area within the circuit, or a prolonged post-pacinginterval may provide evidence that the site is outside the circuit and therefore unlikely to be a successful ablation
  22. 22.   Clinical Cardiac Electrophysiology1,000 2,000 msIIH 19-20H 17-18H 15-16H 13-14H 11-12H 9-10H 7-8H 5-6H 3-4H 1-2MapCS⊡ Fig. .Cavo-tricuspid isthmus block during radiofrequency ablation for atrial flutter. A double-decapolar “Halo”catheter (H -) isrecording activation from around the tricuspid annulus, during pacing from the coronary sinus (CS) catheter. In the first twobeats, there is activation around the annulus in both clockwise and counterclockwise directions, indicated by the arrows.During the third beat, there is only counterclockwise activation, indicating isthmus block. This is confirmed by the localelectrogram from the mapping catheter (Map) at the site of the ablation, which becomes widely split (asterisk)site. Such “entrainment mapping” may be of particular value in identifying sites for ablation in atrial and ventricularreentrant tachycardias, [, , ].(e) Assessment of ablation success. EP techniques can be used to assess whether a catheter ablation has been successful ina number of ways. In the case of an accessory pathway, the absence of abnormal ventricular or atrial activation indi-cates successful pathway block. Non-inducibility of tachycardia is the end-point for ablation of AVNRT, or reentrantVT. With AVNRT, it is not necessary to abolish slow pathway conduction since persisting dual AV nodal physiol-ogy but non-inducibility of AVNRT is an acceptable end-point, correlating with long-term benefit []. Abolition ofspontaneous or isoproterenol-induced arrhythmia, such as automatic tachycardias like RVOT tachycardia, may indi-cate success. In atrial flutter, in which the cavo-tricuspid isthmus is part of the reentrant circuit, termination of thearrhythmia during ablation by itself did not correlate with good long-term outcome [], whereas demonstration ofbi-directional isthmus block post-ablation indicated long-term benefit []. Thus, in this case, successful ablationcan be performed in the absence of the arrhythmia, using the change in atrial activation recorded from a multipolartricuspid annulus catheter (> Fig. .c) during coronary sinus pacing as the indication of isthmus block (> Fig. .).... Guidance of TherapyThe practice of EP-guided drug therapy for ventricular arrhythmias has now largely been abandoned. The ability to inducelife-threatening arrhythmias by ventricular stimulation [], led to the premise that the EP study could be used to assessthe efficacy of drug therapy [, ]. During the s, much time was spent in EP labs performing multiple ventricularstimulation studies in patients with prior ventricular arrhythmias. When sustained arrhythmia was induced at baselinein a drug-free state, re-induction was attempted following intravenous drug administration, commonly procainamide[]. Oral drug treatment was then initiated and EP studies were repeated at intervals, depending on the response [].Such serial drug testing took manydays, orweeks ifamiodarone was alsotested. Observational data indicated that patients
  23. 23. Clinical Cardiac Electrophysiology  whose arrhythmias were non-inducible on drug therapy [], or whose tachycardia rate was slowed to improve hemo-dynamic tolerability [–], had a better outcome compared to those who continued to have inducible life-threateningarrhythmia. However, randomized studies have failed to confirm the prognostic benefit from EP-guided drug therapy[, , ]. In addition, there was evidence that patients whose arrhythmias were non-inducible may remain at riskof life-threatening arrhythmia recurrence [, ]. In addition, data from the AVID registry indicated that stable VTmay not be a benign arrhythmia, with a mortality of over % at  years []. There are also concerns regarding thespecificity of induced arrhythmias in relation to the stimulation protocols [] and the day-to-day reproducibility of thetechnique [, ]. The development of the implantable cardioverter defibrillator (ICD) provided a superior therapy todug treatment for high-risk patients [].It has been suggested that an EP study may be of value in identifying those patients with VT who may respond to anti-tachycardia pacing (ATP) []. However, reproducibility of response to ATP is variable, and may not be predictive [].In particular, induced fast VT had a lower success rate of ATP, but studies have shown a high percentage success (%)with spontaneous fast VT [, ]. In addition, survivors of cardiac arrest from VF, without prior documented clinicalVT, may have recurrent monomorphic VT, which is poorly predicted by EP studies [], and which may be successfullyterminated by ATP []... Risk StratificationThe role of EP testing in risk stratification remains controversial. The ability of the EP study to induce life-threateningarrhythmia may offer a method to identify patients at high risk of sudden death, of particular value in those patients whohave not yet had an arrhythmia but have been identified as being at risk.... Wolff-Parkinson-White SyndromeIn patients with the Wolff-Parkinson-White syndrome there is a recognized risk of sudden death. A minority of patientshave an accessory pathway with a short refractory period allowing a rapid ventricular response to atrial flutter or fibrilla-tion [], which may degenerate from pre-excited atrial fibrillation to ventricular fibrillation []. Noninvasive testing,including ambulatory monitoring and exercise testing [], may reveal intermittent pre-excitation, indicating a relativelylong accessory pathway refractory period, in up to %, but in the majority of patients the properties of their pathwaycannot be determined without invasive EP assessment.A pathway ERP of less than  ms, or the shortest RR interval lessthan  ms during induced atrial fibrillation, identified increased risk []. In symptomatic patients, this is less of anissue, since catheter ablation can be curative and removes the risk from the pathway. The asymptomatic patient presentsmore of a dilemma. Conventional wisdom has been that the risk to an asymptomatic patient is low and does not meriteven the low risk associated with catheter ablation. However, recent reports have challenged this view, providing evidenceto support a more aggressive approach to ablation in the asymptomatic patient [, ].... Ventricular Arrhythmias(a) Post-myocardial infarctionSudden death due to lethal ventricular arrhythmia continues to be a major cause of mortality following MI. The peri-infarct area of myocardium provides a substrate for reentrant arrhythmias. Although ventricular fibrillation (VF) iscommonly the identified fatal arrhythmia, there is evidence that the initial arrhythmia is often fast monomorphic ventric-ular tachycardia (VT), which then degenerates into VF. Thus, ventricular stimulation may induce VT or VF in survivorsof cardiac arrest post-MI. Such potentially lethal arrhythmias may also be inducible in patients who have not yet had acardiac arrest, and therefore may identify those at risk. The initiation of VT or VF has been shown to identify a popu-lation of post-infarction patients at risk of sudden death by spontaneous development of ventricular tachyarrhythmias
  24. 24.   Clinical Cardiac Electrophysiology[, ]. With the availability of the ICD, there is a need to identify high-risk patients likely to benefit from expensivedevice therapy post-MI, so-called primary prevention. Studies utilizing combinations of risk factors, including LV dys-function, non-sustained VT, and inducibility, have shown that it is possible to identify a high-risk population which canbenefit from the ICD []. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) [] and the Mul-ticenter Unsustained Tachycardia Trial (MUSTT) [] required an EP study with inducible VT and showed mortalitybenefit with the ICD. However, MADIT II required only LV dysfunction post-MI as an entry criterion, without the needto demonstrate inducibility of arrhythmia, and showed a % reduction in the risk of death post-MI with the ICD [].In this study, % of patients who received an ICD had an EP study, and unexpectedly, ICD therapy for VF was less com-mon in inducible than in noninducible patients []. Furthermore, the induction of VF was less predictive of subsequentarrhythmia than the induction of monomorphic VT, confirming the relatively nonspecific nature of induced VF. Finally,observational data from the MUSTT registry showed that patients post-MI who did not have inducible arrhythmia atEP study had a similar mortality to those who had inducible VT/VF [], providing further evidence against the role ofinvasive EP testing following MI.(b) CardiomyopathySudden death from ventriculararrhythmia is a cause ofmortalityin both dilated and hypertrophic cardiomyopathy. WhileEP studies to induce ventricular arrhythmia have been advocated for both these conditions, there is now recognition thatventricular stimulation is of limited value, due to its unacceptably low sensitivity and specificity [, ]. However, thefinding of paced electrogram fractionation may be of prognostic value [, ]. Non-inducibility at EP study in patientswith dilated cardiomyopathy may be even less predictive of freedom from sudden death than in the post-MI patients[]. Mortality benefit from the ICD has been shown in patients with heart failure, including dilated cardiomyopathy,without the requirement of an EP study []. In hypertrophic cardiomyopathy, indications for the ICD are based onclinical risk factors, including family history, syncope, septal thickness, non-sustained VT, or hemodynamical instabilityat exercise testing [].Arrhythmogenic right ventricular dysplasia or cardiomyopathy (ARVC) is a genetically linked abnormality affectingthe RV predominantly and is characterized by monomorphic ventricular tachycardia and a risk of sudden death [].EP-guided therapyhas been shown to be of clinical value, but suffers from the same limitations as in the post-MI situation,and there is increasing use of the ICD, without a prior EP study [, ].(c) Arrhythmogenic channelopathiesA major advance in recent years has been the increased understanding of genetic disorders, which may cause life-threatening arrhythmia due to electrophysiological changes at the level of ion channels and receptors, in the absence ofstructural heart disease. These include the long QT syndrome, Brugada syndrome, and catecholaminergic polymorphicventricular tachycardia. Ventricular stimulation has little role in the management of these conditions [, ], except inthe Brugada syndrome, where it remains controversial. This is a condition characterized by baseline ECG abnormalities(RBBB with ST elevation)and can cause lethal ventricular arrhythmias [, ]. The only treatment is an ICD. Induciblearrhythmia has been shown to be of value in the identification of risk by some [], but not confirmed by others [, ].References. Lenègre, J. and P. Maurice, De quelques resultats obtenus parla dérivation directe intracavitaire des courants électriques de’oreillette et du ventricle droits. Arch. Mal. Coeur Vaiss., ;:–.. Battro, A. and H. Bidoggia, Endocardiac electrocardiogramobtained by heart catheterization in man. Am. Heart J., ;:–.. Hecht, H.H., Potential variations of the right auricular andventricular cavities in man. Am. Heart J., ;: –.. Zimmerman, H.A. and H.K., Hellerstien, Cavity potentials of thehuman ventricles. Circulation, ;: –.. LeVine, H.D. and W.T. Goodale, Studies in intracardiac elec-trography in man; IV. The potential variations in the coronaryvenous. Circulation, ;: –.
  25. 25. Clinical Cardiac Electrophysiology  . Tawara, S., Das Reizleitungssystem des Säugetierherzens. EinAnatomisch-Histologische Studie über das Atrioventrikularbun-del und die Purkinjeschen Fäden. Jena, Germany: Verslag GustavFischer, .. Alanis, J., H. Gonzalez, and E. Lopez, The electrical activity ofthe bundle of His. J. Physiol., ;: –.. Giraud, G., P. Puech, H. Latour, and J. Hertault, Variations depotentiel liées à ’activité du système de conduction auriculo-ventriculaire chez ’homme. Arch. Mal. Coeur Vaiss., ;:–.. Scherlag, B.J., S.H. Lau, R.H. Helfant, et al., Catheter techniquefor recording His bundle activity in man. Circulation, ;:–.. Reiffel, J.A., E. Gang, J. Gliklich, et al., The human sinusnode electrogram: A transvenous catheter technique and a com-parison of directly measured and indirectly estimated sinoa-trial conduction time in adults. Circulation, ;: –.. Prystowsky, E.N., K.F. Browne, and D.P. 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