CHAPTER 82: INVASIVE DIAGNOSTIC ELECTROPHYSIOLOGY

Electrophysiology studies (EPS) are minimally invasive procedures utilized for the diagnosis and treatment of cardiac arrhythmias. They can provide insight into the mechanism underlying a variety of cardiac rhythm disorders when noninvasive testing has been unrevealing. Abnormal findings often require device therapy or catheter ablation, which is often performed concomitantly with EPS.

Indications for Electrophysiology Studies

EPS is recommended when noninvasive investigations do not establish the diagnosis or etiology of arrhythmia and the result will change the clinical management. It is indicated for the evaluation of documented or suspected bradyarrhythmias and tachyarrhythmias, syncope, and for risk stratification of individuals at risk for sudden cardiac death (SCD).^1,2 Indications are summarized in Table 82–1. EPS should not be performed in patients who have unstable angina, systemic infection, deep venous thrombosis in the region of venous access, or any other medical condition where the risks of the procedure outweigh the benefits derived from testing.

Technique

EPS involves placing catheters equipped with electrodes at the tip in the right atrium, right ventricle, coronary sinus, and the His region. Atrioventricular (AV) node activity cannot be measured directly and, therefore, His region conduction, which is situated immediately adjacent to the AV node, is used as an indirect way to measure conduction properties of the AV node.

Fluoroscopy is used for placement of catheters (Fig. 82–1), which are typically inserted into the venous system through femoral venous access, but also can be inserted through the internal jugular or subclavian veins.

The electrodes at the catheter tips are used to sense and pace cardiac tissue so that the conduction properties of the heart can be studied at baseline, with pacing, following drug infusion, and during tachycardia.

Complications

In the present era, EPS is commonly performed concomitantly with catheter ablation, particularly for supraventricular or ventricular arrhythmias. Complications associated with EPS alone, without catheter ablation, include cardiac perforation (0.2%), vascular access complications (0.4%), thromboembolic events (~0.5%), thrombophlebitis (0.6%), and death (0.1%).^3,4 Nonetheless, patients should not be exposed even to this minimal risk if there is no benefit expected from EPS.

Intracardiac Electrograms

During EPS, intracardiac electrograms from various locations in the heart, along with the 12-lead surface electrocardiogram (ECG), are recorded and displayed to the physician. The AH interval is measured between the atrial and His electrograms on the His catheter, and corresponds to conduction time from the low interatrial septum to the His, which is an indirect measure of AV node conduction (Fig. 82–2). The normal AH interval during sinus rhythm is approximately 55 to 130 ms.⁵ The AH interval varies with autonomic tone. Increased vagal tone would increase the AH interval, whereas increased sympathetic or decreased vagal tone would shorten it.^6,7 Therefore, a prolonged AH measurement out of the normal range should not be seen as pathological, but should rather increase the suspicion of AV node disease.

The HV interval is measured between the His deflection and the earliest ventricular signal, either on the surface ECG or ventricular electrogram recorded on the His catheter. The HV interval is not affected by autonomic tone and the normal range is 35 to 55 ms.⁵ Abnormal baseline intervals could suggest a pathology, for example in manifested preexcitation, Wolff-Parkinson-White syndrome (WPW), the HV interval is often noticed to be < 35 ms (Fig. 82–3).

After assessment of baseline conduction intervals, programmed electrical stimulation is performed from the atrium and ventricle with or without drug infusion. Burst pacing at a fixed or decremental cycle length is performed followed by delivery of extrastimuli. This involves pacing at fixed rate for several beats (≥ 8 beats) followed by delivery of single or multiple premature extra stimuli at progressively earlier intervals. These maneuvers can distinguish between normal and pathological conduction and refractory properties of cardiac tissue, and can also facilitate arrhythmia induction.

The pathophysiology, diagnosis, and management of bradyarrhythmias are discussed in Chapter 86. The role of EPS in the diagnosis of sinus node dysfunction, AV node, and His-Purkinje disease will be discussed next. The normal conduction system and sites of electrical block along with sites of normal or abnormal automaticity are shown in Fig. 82–4.

Sinus Node Dysfunction

Sinoatrial or sinus node dysfunction is usually observed in elderly patients. Sinus node dysfunction may accompany AV node disease in up to 12% of patients, suggesting that a degenerative process involving the conduction system is present.⁸ Sinus node dysfunction may also be present in patients with paroxysmal atrial fibrillation and prolonged conversion pauses.

Clinical examination and noninvasive testing usually are sufficient to diagnose sinus node dysfunction without the need for EPS. For example, a classical history of vasovagal syncope or carotid sinus massage in suspected patients may provide the diagnosis without the need for EPS. Ambulatory monitoring, in addition to treadmill stress testing, serve as a noninvasive means to assess for sinus node dysfunction.^9,10 In patients in whom the diagnosis of symptomatic sinus bradycardia is inconclusive despite noninvasive testing, EPS can be performed.

Sinus node recovery time (SNRT) and corrected sinus node recovery time (CSNRT) are the most common means of assessing sinus node function. The SNRT is measured after pacing the atrium at different rates up to 300 bpm for at least 30 seconds. The interval between the last atrial paced beat to the first sinus beat is the SNRT. The normal SNRT value is < 1500 ms.^11,12 As SNRT may be influenced by the baseline sinus rhythm rate, the CSNRT (which corrects for this) is an alternative method for measuring sinus node function. The normal value for CSNRT is < 525 ms.^13,14 The SNRT and CSNRT are repeated at different cycle lengths. If abnormal pauses are observed during the recovery phase after pacing, or it takes > 5 seconds to recover to the baseline cycle length (total recovery time), that would also suggest sinus node dysfunction is present.

The sinoatrial conduction time (SACT), the time required for impulse propagation from sinus node to atrium, can be measured during EPS and represents another method to ascertain sinus node function. SACT is measured by direct (recording sinus node electrograms) and indirect (pacing maneuvers) methods. Pharmacologic evaluation of sinus node function can be performed as well, although this is rarely done in the present era (see Chap. 86).

Atrioventricular Node and His-Purkinje System Dysfunction

Similar to sinus node disease, AV node dysfunction can be diagnosed on the basis of symptoms and ambulatory telemetry findings. Based on ECG findings, AV block is classified as first degree (prolonged conduction, PR > 200 ms), second degree (intermittent conduction), and third degree or complete heart block (no conduction). Second-degree AV block is further classified as type I with gradual progression of PR interval before loss of conduction, whereas type II AV block has abrupt loss of conduction. During 2:1 AV block, short PR interval, wide QRS, worsening conduction with exercise, and improvement with carotid sinus massage suggests type II second-degree AV block. Second-degree type II AV block represents underlying infra-nodal (intra- or infra-Hisian) disease. Rarely, type II AV block can occur in the AV node during periods of high vagal tone and is seen with concomitant sinus rate slowing, which confirms that the mechanism of block is caused by increased vagal tone. During atrial fibrillation, pauses > 5 seconds are suggestive of high-degree AV block.

Type I second-degree AV nodal block is very commonly seen during an electrophysiology study with atrial pacing (Fig. 82–5). This is a normal physiological phenomenon and does not warrant any intervention. Resting type I second-degree AV block can be seen with high vagal tone in young athletes and with medications such as beta-blockers, calcium channel blockers, and digoxin.¹⁵

However, intra-Hisian and infra-Hisian block are indications for permanent pacing (Fig. 82–6). EPS can provide information vital to making decisions for permanent pacing. A baseline HV interval ≥ 70 ms is considered high-risk for developing high-degree AV block in the future, whereas a HV interval ≥ 100 ms would warrant permanent pacemaker placement.¹⁶

Second-degree AV block at the intra- or infra-Hisian level, which is most commonly associated with type II block, is also pathological and also indicates a need for permanent pacing. The manifestation of infra-nodal conduction disturbance at atrial pacing rates < 150 bpm (> 400 ms cycle length) is considered abnormal, and an indication for permanent pacemaker placement.¹⁷

It is important to recognize normal versus pathological AV conduction during EPS. During programmed electrical stimulation, delivery of single premature atrial extrastimuli at progressively shorter coupling intervals will ultimately result in failure to elicit a ventricular response. However, on occasion, AV conduction will resume when extrastimuli are delivered at even shorter coupling intervals. This is a normal finding and is termed “gap phenomenon.”¹⁸ This occurs as a result of functional differences in conduction and refractory properties of at least two anatomically distinct locations in the AV conduction system. The initial site of block is distal and with progressively more premature atrial extrastimuli, proximal delay occurs allowing recovery of distal AV conduction. With progressively shorter coupled atrial extrastimuli, AV conduction is decremental and shows an exponential increase in the AH interval. However, on occasion, there may be discontinuity in the AV conduction with progressively premature atrial extrastimuli resulting in a discontinuous AH curve.¹⁸ This results from the presence of dual AV node physiology and is a normal finding even in those without AV nodal reentrant tachycardia (see Chap. 84).

Intraventricular conduction delay, defined as left bundle branch block, right bundle branch block, or bifascicular block, poses a unique challenge. Bifascicular block refers to conduction abnormality in the right bundle and either left anterior or posterior fascicle. Bifascicular block increases the risk of sudden death.¹⁹ Syncope in patients with bifascicular block could be a result of intermittent infra-Hisian block or ventricular tachycardia. EPS may be useful in elucidating the mechanism in these patients.^20,21 In patients with symptoms that are related to bifascicular block, intravenous procainamide infusion can be used to risk stratify patients at high risk for high-degree AV block. Procainamide 10 mg/kg is administered intravenously. Observation of second- or third-degree block, or increase in HV interval by 100% or ≥ 100 ms is considered abnormal and an indication for pacemaker.^22,23 As mentioned before, infra- or intra-Hisian block induced by atrial pacing would be considered abnormal. In addition to provoking infra- or intra-Hisian block, programmed ventricular stimulation (PVS) is necessary to evaluate for ventricular tachycardia susceptibility. In conclusion, EPS could identify some patients with symptomatic bifascicular block who would benefit from device therapy.

In the present era, EPS for tachyarrhythmias is generally performed with ablation or device therapy as the goal. The mechanism of all tachyarrythmias is either macro-reentry or focal. Macro-reentrant arrhythmias are most common. Focal arrhythmias may be caused by automaticity, micro-reentry, or triggered activity.²⁴ Reentry requires (1) two functionally or anatomically separate pathways, (2) unidirectional block in one pathway, and (3) recovery of excitability in blocked pathway to initiate or maintain reentry.²⁵ In the present era, EPS for tachyarrhythmia is generally performed with ablation or device therapy as the goal.

For the purposes of EPS, all tachyarrhythmias can be classified as either narrow-complex or wide-complex tachycardias. The mode of tachycardia initiation and termination as well as tachycardia characteristics can provide clues for diagnosis of the mechanism of arrhythmia. Additionally, pacing maneuvers (such as entrainment) and activation mapping together with three-dimensional (3D) electroanatomic mapping can be utilized to confirm the diagnosis and subsequently be used to guide catheter ablation (see Chap. 88).

A detailed discussion of entrainment is beyond the scope of this chapter.^26,27 However, briefly, entrainment mapping involves overdrive pacing the tachycardia from a catheter. The tachycardia is paced at slightly faster than the tachycardia cycle length (TCL). If tachycardia is accelerated, then certain findings such as progressive fusion during overdrive pacing suggests entrainment and a reentrant mechanism. If pacing were performed from within the reentry circuit, then the interval between the last paced beat and the subsequent sensed electrogram (postpacing interval, or PPI) would be equal to TCL. The farther the catheter is from the circuit, the longer the PPI (Fig. 82–7).

Activation mapping is performed in a chamber using a roving catheter and timing the local electrogram relative to a reference electrogram. A focal arrhythmia would reveal a small area of earliest activation in the chamber from which the activation spreads centrifugally (Fig. 82–8). A macro-reentrant tachycardia would not have a focal area of early activation, but would demonstrate early meets late activation, where the areas of earliest activation are adjacent to those with the latest activation times (Fig. 82–9). Electroanatomic mapping systems are utilized to record local electrical information (local activation time or voltage) in a 3D chamber reconstruction during mapping so that ablation can be targeted at the appropriate sites.

Narrow-Complex Tachycardia

Atrial fibrillation, atrial tachycardia or flutter, and supraventricular tachycardia (SVT), in the absence of aberrant ventricular conduction, are all narrow-complex tachycardias where the QRS duration is < 120 ms (see Chap. 84).

Atrial fibrillation is easily diagnosed on surface ECG. Pulmonary vein isolation continues to be the ablation strategy for both persistent and paroxysmal atrial fibrillation.²⁸ Hence, detailed EPS is generally not performed before atrial fibrillation ablation.

Atrial Tachycardia

Atrial tachycardia is a focal or micro-reentry arrhythmia, whereas atrial flutter is macro-reentrant (see Figs. 82–8 and 82–9). As described earlier, entrainment and activation mapping along with 3D electroanatomic mapping can be used to differentiate these arrhythmias. Atrial tachycardia or flutter is easily identified on intracardiac electrograms when there are more atrial than ventricular electrograms (Fig. 82–10). However, when a narrow-complex tachycardia has a 1:1 atrial to ventricular electrogram ratio, EPS can help differentiate between atrioventricular nodal reentrant tachycardia (AVNRT), atrioventricular reentrant tachycardia (AVRT), and atrial tachycardia.

Atrial flutter can be classified as cavotricuspid isthmus dependent (typical) and nonisthmus dependent (atypical). Typical atrial flutter commonly occurs in patients that have no atrial scar and is often associated with atrial fibrillation. On the other hand, atypical atrial flutter is usually seen in patients with atrial scar resulting from prior ablation, cardiac surgery, and so on. EPS can differentiate between these two types and is typically performed with catheter ablation as the goal.²⁹

Atrioventricular Nodal Reentrant Tachycardia

AVNRT is a reentry arrhythmia involving the two pathways of the AV node. In typical AVNRT, antegrade conduction is via the slow pathway and retrograde conduction via the fast pathway. In contrast, atypical AVNRT has antegrade conduction through the fast pathway and retrograde conduction through the slow pathway. In those with multiple slow pathways, atypical AVNRT may also be the result of antegrade and retrograde conduction over different slow pathways.

During EPS, atrial pacing demonstrates evidence of dual AV node pathways as described above and isoproterenol is often required to induce tachycardia. In typical AVNRT, the AV node excites the ventricle and atrium in parallel; hence the ventriculoatrial (VA) relationship is 1:1 and often simultaneous (VA time ≤ 60 ms).³⁰ As atrial activation is retrograde from the AV node, the atrial activation sequence is concentric and demonstrates earliest activation on the septum and later activity in the distal coronary sinus and high right atrium (Fig. 82–11). Rarely, AVNRT may demonstrate 2:1 AV block resulting from functional infranodal block.³¹

In atypical AVNRT, retrograde VA conduction is via the slow pathway. Therefore, the VA relationship is not simultaneous (VA time > 60 ms) although retrograde atrial activation remains concentric. A similar finding is seen with orthodromic AVRT utilizing a posteroseptal accessory pathway. Pacing maneuvers are required to differentiate between the two.³²

Atrioventricular Reentrant Tachcyardia

In AVRT or orthodromic reciprocating tachycardia, the reentry circuit is formed by antegrade conduction down the AV node and retrograde conduction over an accessory pathway that can be located anywhere along the tricuspid annulus, mitral annulus, and aortic cusps region. The accessory pathway may demonstrate antegrade conduction that is visible on the ECG as ventricular preexcitation, ie, WPW pattern, or may demonstrate only retrograde conduction properties that is not appreciated on the ECG, ie, concealed accessory pathway.

In AVRT, the approach to the tachycardia remains similar to in AVNRT. The tachycardia is induced either by burst pacing or program electrical stimulation in atrium and ventricle with or without isoproterenol. Tachycardia activation sequence is observed and entrainment maneuvers are performed. The VA relationship is 1:1 with a long VA time (VA > 70 ms). Pacing maneuvers are required to differentiate AVRT from atypical AVNRT and atrial tachycardia. For accessory pathways that are not located near the septum, retrograde atrial activation during tachycardia may be eccentric, ie, earliest atrial activation may be in the distal coronary sinus or lateral mitral annulus for a left lateral accessory pathway (Fig. 82–12). If tachycardia cannot be initiated, the finding of nondecremental or eccentric retrograde VA conduction during ventricular pacing also suggests the presence of an accessory pathway. In contrast, retrograde AV node conduction is decremental and concentric.

Rarely, a narrow QRS ventricular tachycardia originating from the upper septal fascicular region can be observed. The HV interval during tachycardia is shorter than HV interval during sinus rhythm.³³ The mechanism described for this tachycardia is reentry. The antegrade limb is part of the left posterior fascicle and retrograde limb is septal Purkinje fibers. The simultaneous activation of left anterior fascicle and right bundle branch during antegrade conduction leads to narrow QRS.^34,35

Wide-Complex Tachycardia

SVT with aberrant conduction, antidromic reciprocating tachycardia, and ventricular tachycardia all represent wide QRS complex tachycardias.

Supraventricular Tachycardia with Aberrancy

Atrial fibrillation, atrial tachycardia or flutter, AVNRT, and AVRT could all present with aberrant conduction including left bundle branch or right bundle branch block aberrancy. It can be challenging to differentiate it from ventricular tachycardia using a surface ECG alone. Various criteria have been developed to differentiate ventricular tachcardia from SVT with aberrancy.^36,37

EPS can differentiate ventricular tachycardia from SVT with aberrancy. If the intracardiac electrograms reveal VA dissociation with more ventricular electrograms than atrial electrograms, then a diagnosis of ventricular tachycardia is suggested. However, if VA association is seen, then ventricular tachycardia cannot be ruled out, as retrograde conduction from the ventricle to atrium through the AV node may occur in a 1:1 manner. Additionally, aberrancy during SVT would demonstrate antegrade conduction through the His-Purkinje system. Therefore, intracardiac electrograms would demonstrate a His electrogram prior to every ventricular electrogram (Fig. 82–13), which is not seen during ventricular tachycardia with the exception of bundle branch reentry ventricular tachycardia. Even in the presence of abberancy, the mechanism of the SVT can be further defined.^38,39

Antidromic Tachycardia

Antidromic tachycardia is characterized by reentry utilizing a bypass tract for antegrade conduction and AV node for retrograde conduction in antidromic AVRT. Antidromic tachycardia would show maximum preexcitation as complete antegrade ventricular conduction is through the bypass tract. An ECG during sinus rhythm can demonstrate a similar pattern of preexcitation as seen during tachycardia. Intracardiac electrograms would reveal retrograde ventricle to His activation followed by atrial activation. On rare occasions, bypass tracts may demonstrate decremental AV conduction properties, and may be either atriofascicular or atrioventricular connections and are referred to as Mahaim fibers.⁴⁰ These are right-sided accessory pathways, and the associated tachycardias have left bundle branch block morphology.

Ventricular Tachycardia

Sustained ventricular tachycardia is defined as a tachycardia originating from the ventricle that lasts ≥ 30 seconds or that causes hemodynamic instability. The majority of ventricular tachycardias are scar-related in patients with structural heart disease. Idiopathic ventricular tachycardia is seen in patients without structural heart disease. Reentry is the mechanism in scar-related ventricular tachycardia and idiopathic ventricular tachycardias are commonly caused by triggered activity.

EPS for induction of ventricular arrhythmias is indicated (1) for syncope in those with structural heart disease and suspected ventricular arrhythmias; (2) for risk-stratification in asymptomatic patients with coronary artery disease, depressed left ventricular function (ejection fraction ≤ 40%), and nonsustained ventricular tachycardia (41); (3) to define the mechanism of wide-complex tachycardia; (4) to guide catheter ablation (see Chap. 88); and (5) for risk-stratification in Brugada syndrome.

EPS for induction of ventricular arrhythmias consists of burst pacing and programmed electrical stimulation (PES) with delivery of up to three ventricular extrastimuli during two paced cycle lengths and from two ventricular locations. Induction of sustained monomorphic ventricular tachycardia anytime during the study or induction of ventricular fibrillation or polymorphic ventricular tachycardia with up to two premature stimuli is considered positive (Fig. 82–14). A positive study would warrant implantable cardioverter-defibrillator (ICD) implantation in those who do not have one, and potentially catheter ablation in those with an ICD.

The role of EPS in Brugada syndrome remains a controversial topic (see Chap. 80). In asymptomatic patients with Brugada syndrome, whether the induction of ventricular tachycardia/fibrillation during EPS predicts future risk of sudden death is ambiguous, with studies both supporting and refuting this.^42,43 However, a history of syncope and spontaneous type 1 Brugada ECG pattern have been shown to be predictors of future SCD.⁴⁴ As ECG findings in Brugada syndrome may be transient, in addition to recording the right precordial leads (V₁ and V₂) from higher intercostal (second or third) positions, sodium channel blockers (procainamide, flecainide, and ajmaline) can be administered to unmask a type 1 pattern in those with type 2 or 3 patterns (Fig. 82–15).^45,46,47

Syncope is a transient loss of consciousness, which is rapid onset, short duration, and with spontaneous and complete recovery because of transient global cerebral hypoperfusion.

History and physical examination are crucial in diagnosis of syncope (see Chap. 90). Diagnostic EPS are indicated when syncope is suspected to be secondary to arrhythmia and undiagnosed by noninvasive testing such as ECG, ambulatory monitoring, and tilt table testing.

Certain characteristics of the patient history, ECG, and noninvasive testing should increase the suspicion for an arrhythmic etiology of syncope and prompt EPS.² These are summarized in Table 82–2.

If the clinical suspicion is of bradyarrhythmia, then detailed EPS are performed with focus on sinus node, AV node, and infranodal conduction system. As discussed earlier, findings such as CSNRT > 525 ms, HV interval ≥ 70 ms, and second- or third-degree infranodal block would be considered abnormal findings in patients with syncope and may require the placement of a permanent pacemaker.

SVT can rarely cause syncope, and EPS with ablation can be performed when this is clinically suspected or documented. In manifest preexcitation, ie, a WPW pattern, the objective of EPS is to ascertain the conduction properties of the bypass tract and the risk of SCD. If EPS demonstrates that pathway conduction can occur faster than 240 bpm (< 250 ms), it would be considered high risk, and catheter ablation is recommended.^48,49 The concern is that during atrial fibrillation, rapid conduction to the ventricle through the accessory pathway can lead to ventricular fibrillation and SCD.

In patients with syncope and structural heart disease, such as ARVC, hypertrophic cardiomyopathy, ischemic cardiomyopathy, and nonischemic cardiomyopathy, EPS are focused at induction of sustained monomorphic ventricular tachycardia, as previously detailed.

EPS can provide crucial mechanistic information in a variety of suspected or documented cardiac arrhythmias. They are indicated when the history, clinical examination, and noninvasive testing fail to provide conclusive information and therapy is dependent upon findings. Pacemaker implantation may be necessary when EPS reveal abnormal sinus node, AV node, or His-Purkinje system function, whereas ICD implantation is indicated for those who are found to be at high risk for SCD caused by inducible ventricular tachycardia or fibrillation. Finally, EPS provide insight into the mechanism of narrow- and wide-complex tachycardia that can be used to guide curative catheter ablative therapy. Thus, diagnostic EPS have an important role in the diagnosis and management of patients with bradyarrhythmias, tachyarrhythmias, syncope, and for risk-stratification for SCD.