Electrocardiography

First-degree atrioventricular (AV) block usually is caused by conduction delay within the AV node. Much less frequently, first-degree AV block is caused by intra-atrial or infra-Hisian conduction delay.⁷ Localization of the site of second-degree AV block to the AV node or His-Purkinje system can be obtained by His bundle recording during invasive electrophysiologic testing, but in most cases, careful analysis of the electrocardiogram (ECG) and the effect of various pharmacologic agents on the block will suffice.⁸ Adherence to precise definitions of second-degree AV block, particularly in cases of 2 : 1 AV block and suspected type II AV block, is critical to avoiding diagnostic errors that could result in potentially unnecessary permanent pacemaker implantation.⁹ Furthermore, type I and type II designations refer only to ECG patterns and not to the anatomic site of block.

Classic type I (Wenckebach) second-degree AV block has three characteristics: (1) progressive P-R interval prolongation before the nonconducted beat, (2) progressive decrease in the increment of P-R interval prolongation, and (3) progressive decrease in the R-R interval, parallel to the progressive decrease in the increment of change in the P-R interval.¹⁰ All patterns of type I second-degree AV block not having this pattern are called “atypical” patterns, although in actuality, they may occur more often than the classic variety¹¹ (Fig. 14-3).

Figure 14-3 Atypical or uncommon type I second-degree atrioventricular (AV) block in the AV node.

Surface leads I (1), II (2), III (3), and V1 are displayed with intracardiac electrograms recorded from the high right atrium (HRA), His bundle (HBE), and right ventricular apex (RV). There is little alteration in the A-H interval before the fourth atrial complex not conducting to the ventricle. The true nature of this arrhythmia is revealed by the first-conducted P wave (A, atrial electrogram) after the pause, which is associated with substantial shortening of the A-H interval from 230 to 240 msec to 200 msec.

(From Josephson ME: Clinical cardiac electrophysiology: techniques and interpretations, ed 3, Philadelphia, 2002, Lippincott–Williams & Wilkins, pp 92-109.)

As a general rule, type I second-degree AV block with a narrow QRS complex is almost always caused by delay within the AV node. Delay within the His bundle (intra-Hisian block), however, is a rare cause of type I second-degree AV block with a narrow QRS and requires an electrophysiologic study for definitive diagnosis. Intra-Hisian block should be suspected in a patient with a narrow QRS if type I second-degree AV block is provoked by exercise. In contrast, type I AV nodal block at rest improves with exercise. When type I second-degree AV block is associated with concomitant bundle branch block (BBB), the site of delay or block is in the His-Purkinje system (infranodal) in up to 60% to 70% of cases.¹⁰

Type II second-degree AV block is defined as a single nonconducted sinus P wave associated with fixed P-R intervals before and after the blocked beat (Fig. 14-4). The sinus rate must be stable (i.e., constant P-P intervals), and there must be at least two consecutive conducted P waves to determine the P-R interval, which can be either normal or prolonged. Type II second-degree AV block should not be diagnosed in the case of a nonconducted atrial premature beat or if there is simultaneous sinus slowing and AV nodal block (e.g., hypervagotonia). Type I block with relatively long Wenckebach sequences and small increases in AV nodal conduction time may be confused with type II AV block but should not be classified as such (even though the site of block may be either AV nodal or infranodal in such cases). Type II second-degree AV block is most often encountered when the QRS complex is prolonged (in about 70% of cases) and is localized within the His-Purkinje system; in contrast, type II AV block with a narrow QRS is within the His bundle (i.e., intra-Hisian). Sudden AV block of more than one impulse with stable sinus rhythm and 1 : 1 AV conduction with constant P-R and P-P intervals before and after the block has been labeled “advanced AV block,” “paroxysmal AV block,” and “type II AV block.” Although this rhythm does not conform to the strict definition of type II block (i.e., a single block beat), it does suggest that the anatomic site of AV block is infranodal, and that permanent pacing is indicated. On the other hand, Wenckebach periodicity before the development of high-grade AV block suggests an AV nodal site.

Figure 14-4 Type II second-degree atrioventricular (AV) block showing repeating episodes of block.

Note that the P-R interval is constant both before and after the nonconducted P wave, and that there is associated bundle branch block.

Lange et al.¹² reported on their experience with a large number of patients with transient second-degree AV block and narrow QRS complexes detected on ambulatory Holter monitoring. The researchers emphasized the many ways in which second-degree AV block can be manifested. Classic, type I AV block with progressive PR prolongation to more than 40 msec during at least three beats before the blocked P waves was seen in only 50% of patients. Another pattern observed was a subtler Wenckebach periodicity with minor PR prolongation of 20 to 40 msec before a blocked P wave in 29% of patients. A third pattern, seen in 8% of patients and termed pseudo–Mobitz type II AV block, demonstrated nearly constant P-R intervals before the blocked P wave, followed by PR shortening on the subsequent conducted beat (see Fig. 14-3). Classic Mobitz type II second-degree AV block, with constant P-R intervals for at least three beats before the blocked P wave, followed by the same P-R interval after the blocked P wave, was seen in 4% of patients (see Fig. 14-4). A mixed, type I Wenckebach and pseudo–Mobitz type II AV block was seen in 6% of all patients. Of patients showing periods of pseudo–Mobitz type II block, 44% also demonstrated classic Wenckebach conduction patterns at some time.¹² Slowing of the sinus cycle length often preceded the blocked P wave in both classic and pseudo–Mobitz type II AV blocks (Fig. 14-5).

Figure 14-5 Rhythm strip demonstrating vagally mediated second-degree atrioventricular (AV) block.

Note the progressive slowing of the heart rate before the first episode of AV block, although no change in P-R interval can be discerned. During the second episode of block, both sinus slowing and P-R interval prolongation occur, confirming the presence of type I second-degree AV block.

Diagnosis of the site of AV block may be problematic with 2 : 1 atrioventricular block, which should not be classified as type I or type II block. The anatomic site in 2 : 1 AV block can be in the AV node or His-Purkinje system (Fig. 14-6). The most likely site of AV block can often be determined by noting the company that the 2 : 1 AV block keeps. When 2 : 1 AV block is associated with a wide QRS complex, the block is in the His-Purkinje system in 80% and the AV node in 20% of cases (Fig. 14-7). A long P-R interval (>0.30 second) on conducted beats during 2 : 1 AV block with a narrow QRS complex suggests an AV nodal site, whereas a normal P-R interval favors intra-Hisian block.

Figure 14-6 Spontaneous 2 : 1 (high-grade) atrioventricular (AV) block localized to the AV node.

Surface leads I (1), II (2), III (3), and V1 are displayed with intracardiac electrograms recorded from the high right atrium (HRA), His bundle (HBE), and right ventricular apex (RV). Alternate atrial depolarizations (A) are not followed by either a His bundle or a ventricular depolarization. On the basis of a surface electrocardiogram, the finding of 2 : 1 AV block with a narrow QRS is compatible with a block at either the AV node or an infra-Hisian bundle site. The intracardiac recordings localize the site of block to the AV node.

(From Josephson ME: Clinical cardiac electrophysiology: techniques and interpretations, ed 3. Philadelphia, 2002, Lippincott–Williams & Wilkins, pp 92-109.)

Figure 14-7 Intracardiac tracing of 2 : 1 second-degree atrioventricular (AV) block located in the His-Purkinje system.

Sinus rhythm with left bundle branch block is present. Surface leads I, II, III, and V1 are displayed with intracardiac electrograms recorded from the high right atrium, His bundle (HBE), and right ventricular apex (RV). The A-H intervals are constant, but every other atrial complex fails to activate the ventricle even though each atrial depolarization is followed by a His bundle deflection. This finding shows that the site of AV block is within the His-Purkinje system.

(From Josephson ME: Clinical cardiac electrophysiology: techniques and interpretations, ed 3, Philadelphia, 2002, Lippincott–Williams & Wilkins, pp 92-109.)

In general, the response of the block, particularly 2 : 1 AV block, to pharmacologic agents may help to determine the site. Atropine generally improves AV conduction in patients with AV nodal block; however, atropine is expected to worsen conduction in patients with block localized to the His-Purkinje system, because of its effect on increasing sinus rates without improving His-Purkinje conduction (Fig. 14-8). Carotid sinus stimulation is expected to worsen block localized to the AV node, whereas it either has no effect or improves conduction in patients with His-Purkinje system disease by causing sinus node slowing. The effect of any given drug, however, may be difficult to predict because its effect on the sinus node may be greater than its effect on the AV node. For example, atropine may improve AV node conduction, but if atropine causes excessive SA node acceleration, AV conduction may improve marginally or not at all. The response to infusion of isoproterenol is less clear. Isoproterenol may improve conduction disorders localized in the AV node as well as occasionally in the His-Purkinje system.

Figure 14-8 His-Purkinje atrioventricular block after atropine-induced increase in sinus rate.

Surface leads I, II, III, and V1 are displayed with intracardiac electrograms recorded from the high right atrium (HRA), His bundle (HBE), and right ventricular apex (RV). A, Sinus rhythm at a cycle length of 1175 msec with 1 : 1 AV conduction. Left bundle branch block is present, and the H-V interval is slightly prolonged, to 70 msec. B, After injection of 1 mg of atropine, the sinus rate speeds up to 770 msec and the H-V interval increases to 80 msec, but 1 : 1 AV conduction is still present. The A-H interval shortens despite the faster sinus rate, because of the direct effect of atropine on AV nodal conduction. C, After injection of 1.5 mg of atropine, the sinus cycle length decreases further to 550 msec, and 2 : 1 AV block occurs below the His bundle. Atropine worsens AV conduction in this patient, not through a direct drug effect, but because the atropine-induced improvement in AV nodal conduction stresses the already-abnormal His-Purkinje system.

(From Miles WM, Klein LS: Sinus nodal dysfunction and atrioventricular conduction disturbances. In Naccarelli GV: Cardiac arrhythmias: a practical approach. Mt Kisco, NY, 1991, Futura, pp 243-282.)

The diagnosis of complete heart block (CHB) rests on demonstration of complete dissociation between atrial and ventricular activation. Care must be taken to distinguish transient AV dissociation caused by competing atrial and junctional or ventricular rhythms with similar rates (so-called isorhythmic AV dissociation). If sufficiently long monitoring strips are available, intermittent conduction of appropriately timed atrial events is seen. Temporary atrial pacing can be performed to accelerate the atrial rate to overdrive the competing junctional or ventricular arrhythmia, demonstrating intact AV conduction. In the presence of atrial fibrillation (AF), CHB can be inferred when the ventricular rate becomes regular rather than the typical, irregular ventricular response (Fig. 14-9). Digoxin toxicity may be the cause of heart block with AF, and this and other drug toxicity should be ruled out before one assumes that structural AV conduction disease is present. In patients with chronic AF, regular R-R intervals may occasionally be caused by “concealed” sinus rhythm (i.e., no evidence of atrial activity because of very-low-amplitude P waves) and not heart block or digitalis intoxication.¹³

Figure 14-9 Twelve-lead electrocardiogram from a patient with recent aortic valve surgery and atrial fibrillation treated with digoxin.

Surface leads I, II, III, and V1 are displayed with intracardiac electrograms recorded from the high right atrium, His bundle, and right ventricular apex. The QRS complexes are narrow and occur at a regular rate of 56 bpm, illustrating complete heart block with a junctional escape rhythm in the setting of atrial fibrillation. Despite discontinuation of digoxin, complete heart block persisted in this patient.

The escape rhythm in CHB may be generated by the AV junction, His bundle, bundle branches, or distal conduction system. Rarely, the underlying rhythm arises from the ventricular myocardium or, for all practical purposes, is absent. The site of AV block is important in that it determines to a great extent the rate and reliability of the underlying escape rhythm. The site of origin of the escape rhythm in cases of advanced AV block is more important than the escape rate itself.⁷ For example, in heart block associated with inferior AMI or congenital CHB, the escape rhythm is usually generated by the AV junction, and permanent pacing may not be required. Nevertheless, it is worth emphasizing that symptomatic AV block requires pacing regardless of the site, morphology, or rate of the escape rhythm.

Trifascicular block is present when bifascicular block is associated with HV prolongation. However, trifascicular block also is often applied loosely to the electrocardiographic patterns of bifascicular block—right bundle branch block (RBBB) plus left anterior hemiblock, RBBB plus left posterior hemiblock, or left bundle branch block (LBBB)—plus first-degree AV block. Using “trifascicular block” to describe these AV conduction disturbances on the ECG is misleading, because the site of block in such cases may be located in the AV node or His-Purkinje system.⁹ The P-R interval does not identify patients who have prolonged H-V intervals in such cases. Up to 50% of patients with bifascicular block and prolonged P-R intervals have prolongation of the A-H interval (i.e., AV nodal conduction time).¹⁴ Trifascicular block should be used only to refer to alternating RBBB and LBBB, RBBB with a prolonged H-V interval (regardless of the presence or absence of left anterior or posterior fascicular block), and LBBB with a prolonged H-V interval. In addition, the term can be used in a patient with second- or third-degree AV block in the His-Purkinje system with (a) permanent block in all three fascicles, (b) permanent block in two fascicles with intermittent conduction in the third, (c) permanent block in one fascicle with intermittent block in the other two fascicles, or (d) intermittent block in all three fascicles. Thus, according to its strict definition, when interpreting an ECG in the absence of a His bundle recording, trifascicular block should be applied only to the patterns of alternating RBBB and LBBB or RBBB with intermittent left anterior and posterior hemiblocks. These situations are class I indications for permanent pacing, even in asymptomatic individuals.

Electrophysiologic Study

Invasive electrophysiologic study (EPS; e.g., His bundle recording) is a useful means of evaluating AV conduction in patients who have symptoms and in whom the need for permanent pacing is not obvious (Fig. 14-10). Electrophysiologic studies (strictly for evaluation of the conduction system and site of block) are not required in patients with symptomatic high-grade or complete AV block recorded on surface ECGs, ambulatory Holter monitoring, or transtelephonic recordings. The need for permanent pacing has already been established in these patients (class I indication). However, EPS may be indicated in patients with high-grade AV block if another arrhythmia is suspected or is a likely cause of symptoms. For example, even if high-grade AV block is documented on spontaneous recordings, ventricular tachycardia may still be the cause of syncope in patients with extensive AMI. In patients with alternating BBB, EPS almost invariably demonstrates a high degree of His-Purkinje system disease. These patients typically have very long H-V intervals and are at very high risk of progression to CHB in a short time. Pacing in these patients is indicated on clinical grounds, and EPS may not be necessary.⁷ Electrophysiologic studies are also not indicated in patients whose symptoms are shown not to be associated with a conduction abnormality or block. In addition, patients without symptoms who have intermittent AV block associated with sinus slowing, gradual PR prolongation before a nonconducted P wave, and a narrow QRS complex should not undergo EPS, given the benign prognosis of these findings.

Figure 14-10 Surface leads I, II, III, and V1 reveal sinus rhythm with 2 : 1 AV conduction, marked P-R interval prolongation during conducted beats, and right bundle branch block.

Intracardiac electrograms from the high right atrium (HRA), proximal and distal poles of the His bundle catheter (Mp and Md, respectively), and the right ventricle (RV) are shown. The distal pole of the His bundle catheter registers a His bundle potential, which can be seen as a discrete sharp potential between the atrial and the ventricular electrograms on that channel. During nonconducted atrial complexes, spontaneous infra-Hisian block is apparent because the His bundle potential (arrow) is not followed by a ventricular electrogram.

The incidence of progression of bifascicular block to CHB is variable, ranging from 2% to 6% per year. The method of patient selection affects this incidence, with patients who have asymptomatic bifascicular block progressing to CHB at a rate of 2% per year, and patients with symptoms (e.g., syncope or presyncope) progressing at a rate closer to 6% per year.¹⁵

Many of these studies emphasize the high mortality associated with bundle branch block (BBB) and bifascicular block. It is worth emphasizing that the mortality associated with the presence of structural heart disease predominantly reflects death resulting from AMI, heart failure, or ventricular tachyarrhythmias rather than bradyarrhythmias.

Three large studies of patients with chronic BBB have been performed to assess the role of His bundle conduction (e.g., H-V interval) measurements in predicting progression to CHB. The measurement of the H-V interval represents the conduction time through the His bundle and bundle branches until ventricular activation begins. Because these studies included both asymptomatic and symptomatic patients, care must be taken to ensure that similar patient populations are compared for proper interpretation of these results. Dhingra et al.¹⁵ prospectively followed 517 patients with BBB and measured the time required for progression to second- and third-degree block. Only 13% of patients presented with syncope; the others had no symptoms. The cumulative 7-year incidence of progression to AV block was 10% in the group with a normal H-V interval and 20% in the group with H-V interval prolongation. The cumulative mortality rate at 7 years was 48% in patients with a normal H-V interval and 66% in patients with a prolonged H-V interval. This study emphasized that despite the high mortality associated with the presence of bifascicular block, there is only a low rate of progression to more advanced AV block.

McAnulty et al.¹⁶ studied 554 patients with “high-risk” BBB, defined as LBBB, RBBB and left-axis or right-axis deviation, RBBB with alternating left- and right-axis deviation, or alternating RBBB and LBBB. The cumulative incidence of AV block, either type II second-degree or CHB, was 4.9%, or 1% per year, in patients with a prolonged H-V interval and 1.9% in patients with a normal H-V interval (difference not significant). H-V interval prolongation did not predict a higher risk of development of CHB. After entry into the study, 8.5% of patients experienced syncope. The incidence of complete AV block was 17% in patients with syncope versus 2% in patients without a history of syncope.

Scheinman et al.¹⁷ studied 401 patients with chronic BBB for about 30 months. This study, in contrast to the Dhingra¹⁵ and McAnulty¹⁶ studies, primarily included patients with symptoms referred for EPS. About 40% of the patients in the Scheinman study had a history of syncope.¹⁷ In patients with an H-V interval of more than 70 msec, the incidence of progression to spontaneous second- or third-degree AV block was 12%. The incidence of complete AV block was 25% for those with an H-V interval of 100 msec or greater. The yearly incidence of spontaneous AV block was 3% in those with a normal H-V interval and 3.5% in those with a prolonged H-V interval.

These findings therefore suggest a relationship between a prolonged H-V interval and development of CHB during the ensuing years in patients with intraventricular conduction disturbances. It also seems that the risk varies directly with the extent of HV prolongation. Symptomatic patients with syncope or presyncope are at much higher risk than asymptomatic patients. The overall risk of CHB in an unselected, symptom-free group of patients with chronic BBB is low (<6%/yr). Current recommendations are not to perform EPS in patients with asymptomatic BBB.¹⁸

A number of studies evaluated the clinical usefulness of EPS in patients with BBB and syncope. Electrophysiologic studies were performed before the current era of ICD implantation in patients with syncope and advanced structural heart disease. In one study, 112 patients with chronic BBB and syncope or near-syncope underwent EPS.¹⁹ A normal result predicted a good long-term prognosis. About 25% of patients had significant conduction system disorder, underwent pacemaker implantation, and experienced recurrence of symptoms at a rate of only 6%. In the study reported by Morady et al.,²⁰ 28% of patients (7 of 32) had sustained, induced monomorphic ventricular tachycardia (VT), whereas about 20% had conduction disturbances at EPS. Six of the seven patients who received pacemakers had no recurrent symptoms.

Thus, electrophysiologic studies may be useful in patients with BBB or bifascicular block and syncope for several reasons. First, negative EPS results may identify a group of patients at low risk for cardiac events, especially in the absence of advanced structural heart disease. Induction of sustained VT during EPS identifies patients at risk for life-threatening ventricular arrhythmias who require ICDs. Programmed ventricular stimulation in patients with BBB and syncope may induce bundle branch reentrant VT, which may be readily cured with radiofrequency catheter ablation. Also, EPS identifies patients with advanced conduction system disease (e.g., prolonged H-V interval with BBB) who need pacemakers.

The clinical trials that established the role of the ICD for both primary and secondary prevention of sudden death, as well as for cardiac resynchronization therapy, have significantly affected the management of patients with BBB and syncope. Current guidelines recommend ICD implantation in patients with syncope of undetermined etiology in the setting of advanced structural heart disease, because these patients are likely to have an arrhythmic cause of syncope. Thus, if LV dysfunction is present (left ventricular ejection fraction [LVEF] ≤35%-40%) in patients with BBB and syncope, ICD implantation is indicated, and many centers may choose not to perform EPS in these patients. Electrophysiologic studies may still be considered in patients with syncope or near-syncope and BBB with no, minimal, or mild structural heart disease (LVEF >40%).

Identifying Patients at Risk for AV Block

In patients with symptomatic BBB or bifascicular block, EPS with measurement of H-V intervals has been used for several decades. A “markedly prolonged” H-V interval (≥100 msec) is predictive of development of symptomatic heart block. As noted earlier, Scheinman et al.¹⁷ demonstrated that an H-V interval of 100 msec or longer identified a group of patients who had a 25% risk of development of heart block over a mean follow-up of 22 months. According to current guidelines published by the American College of Cardiology (ACC), American Heart Association (AHA) Task Force on Practice Guidelines, and North American Society for Pacing and Electrophysiology (NASPE), an H-V interval of 100 msec or longer in an asymptomatic patient documented as an incidental finding on EPS is a class IIa indication for permanent implantation of a pacemaker.²¹ Although the finding of a markedly prolonged H-V interval is quite specific, it is very insensitive because H-V intervals of 100 msec or longer are uncommon.

Atrial pacing to stress the His-Purkinje system may provide additional information to identify patients at risk of spontaneous AV block. Healthy subjects do not experience second- or third-degree infra-Hisian block during atrial pacing when the atrial rate is gradually increased, as would occur spontaneously. Certain pacing protocols with abrupt onset of pacing at rapid rates are more likely to induce infra-Hisian block, even in healthy subjects, but even this finding is rare at pacing rates below 150 beats per minute (bpm) in healthy individuals. Because AV nodal dysfunction is frequently seen in patients with significant His-Purkinje system disease, AV nodal block may occur at lower pacing rates than those necessary to demonstrate infra-Hisian block. This “protective” effect of AV nodal dysfunction during resting states may lead to the incorrect conclusion that significant His-Purkinje disease is not present. However, a second trial of atrial pacing after administration of atropine or isoproterenol to facilitate AV nodal conduction may demonstrate infra-Hisian block. Dhingra et al.²² reported a 50% rate of progression to type II or complete AV block in patients in whom block develops distal to the His bundle at paced rates of less than 150 bpm. In a later study, Petrac et al.²³ evaluated 192 patients with chronic BBB and syncope, of whom 18 (9%) had incremental atrial pacing–induced infra-Hisian second-degree AV block at a paced rate of 150 bpm or less (mean pacing rate, 112 ±10 bpm). During a mean follow-up of 68 ±35 months, 14 of the 18 patients (78%) demonstrated spontaneous second- or third-degree AV block, confirming that this abnormal finding identifies a subgroup at a high risk for development of heart block. As with an H-V interval of 100 msec or less, however, His-Purkinje block during incremental atrial pacing at physiologic rates is uncommon in patients with BBB and syncope. According to current guidelines, if atrial pacing–induced infra-Hisian block that is “not physiologic” is demonstrated as an incidental finding on EPS, permanent pacing is recommended (class IIa indication).²¹

Provocative drug tests have been suggested as another means of evaluating the distal conduction system²⁴ (Fig. 14-11). Pharmacologic stress testing may be considered in patients with BBB and syncope who have a baseline H-V interval of 70 msec or higher (but <100 msec) and no infra-Hisian block demonstrated. Data describing the experience with intravenous type Ia (procainamide, ajmaline, disopyramide) or type Ic (flecainide) antiarrhythmic drugs are limited.^15,25–27 Only intravenous procainamide is available in the United States. Administration of these agents may result in a marked increase in the H-V interval (>15-20 msec), an H-V interval greater than 100 msec, or precipitation of spontaneous type II second- or third-degree AV block, all of which may indicate a higher risk for development of CHB. Intravenous disopyramide has the potential benefit of facilitating AV nodal conduction by its anticholinergic properties while accentuating underlying infra-Hisian disease through its membrane-stabilizing effects.²⁶ Tonkin et al.²⁷ administered procainamide at a dose of up to 10 mg/kg to 42 patients with BBB and syncope and produced intermittent second- or third-degree His-Purkinje block or H-V prolongation to more than 15 msec during sinus rhythm in 11 patients (26%).²⁸ However, only 2 of the 11 patients (18%) with a positive result had documented high-grade AV block during 38 months of follow-up, and three of five asymptomatic control patients with BBB (60%) had a positive procainamide challenge test result. Other studies of class I antiarrhythmic drug testing to stress the His-Purkinje system likewise have limited patient numbers, lack adequate control groups or follow-up, and seem to indicate that pharmacologic testing has low predictive value. Current permanent pacing guidelines do not include a recommendation regarding the need for permanent pacing on the basis of results of pharmacologic stress testing of the His-Purkinje system.

Figure 14-11 A, Electrophysiologic testing in the baseline state in a patient with syncope reveals a left bundle branch block pattern during sinus rhythm. There is 1 : 1 atrioventricular (AV) conduction with an H-V interval of 60 msec. B, After a loading dose of procainamide, 2 : 1 AV conduction develops. The first and third atrial activations are conducted to the ventricles with an H-V interval of 110 msec. The third and fourth atrial activations conduct through the AV node to generate a His bundle potential without subsequent ventricular activation. Thus, this test illustrates spontaneous infra-Hisian block induced by procainamide. HBE₁, HBE₂, and HBE₃ are proximal, middle, and distal His bundle catheter recordings, respectively; RA, right atrial recordings; RV, right ventricular recording.

Electrophysiologic testing has recognized limitations for identifying patients with significant AV nodal or His-Purkinje dysfunction. Although finding an abnormality on EPS may be helpful, its sensitivity is low and cannot be used alone to exclude a significant AV conduction disturbance. In a small study by Fujimura et al.,²⁹ 13 patients with documented symptomatic transient second- or third-degree AV block referred for implantation of a permanent pacemaker underwent AV conduction testing at pacemaker insertion. These tests included facilitation of AV nodal conduction with atropine and pharmacologic stress of His-Purkinje conduction with low doses of procainamide. Surprisingly, only 2 of the 13 patients showed significant abnormalities in the AV conduction system (inducible infra-Hisian block in both cases) during EPS, yielding a sensitivity of 15.4%. Two other patients had moderately prolonged H-V intervals, although much shorter than 100 msec. If these two patients are included in the diagnostic data, the sensitivity of EPS is increased to 46%, raising important questions about EPS sensitivity for identifying patients at risk for symptomatic AV block.

First-Degree AV Block

The prognosis and natural history in patients with primary first-degree AV block and moderate PR prolongation traditionally has been thought of as being benign. Progression to CHB over time occurred in about 4% of patients in the Mymin et al.³⁰ study, which involved only young, male U.S. Air Force pilots. Most of the patients (66%) had only mild to moderate PR prolongation, to about 0.22 to 0.23 second. In the great majority of subjects, the P-R interval remained within a narrow range, changing by less than 0.04 second. More recently, a Framingham Heart Study report challenged the long-held belief that first-degree AV block has a benign prognosis.³¹ In this large, community-based sample with long-term follow-up, patients with first-degree AV block (PR > 200 msec) at baseline were at substantially increased risk of future atrial fibrillation (about twofold) and pacemaker implantation (about threefold) and a moderately increased risk of all-cause mortality, compared with individuals without first-degree AV block.

Patients with “markedly prolonged” P-R interval may or may not be symptomatic at rest, but may demonstrate a pseudo–pacemaker syndrome caused by AV dyssynchrony, particularly during exertion. These events are more likely to become symptomatic during exercise, because the P-R interval may not shorten appropriately as the R-R interval decreases. Zornosa et al.³² described PR prolongation after radiofrequency ablation resulting from injury of the fast–AV nodal pathway in patients with AV nodal reentry. Symptoms caused by long P-R intervals resolved after DDD pacing was performed. Kim et al.³³ also described a patient with intermittent failure of fast-pathway conduction who experienced lightheadedness, weakness, and chest fullness when the P-R interval suddenly shifted from between 160 and 180 msec to 360 msec; this patient’s condition improved after pacing.

Implantation of permanent pacemakers is reasonable in patients with first-degree AV block with symptoms similar to those of pacemaker syndrome or hemodynamic compromise (class IIa indication).²¹ Previous versions of the ACC/AHA/NASPE guidelines required documentation of alleviation of symptoms with temporary AV pacing before permanent pacing. However, this requirement was removed in the 2002 revision of the guidelines, in part because a temporary AV pacing study may not demonstrate symptomatic improvement at rest and is often impractical to perform during exercise. Thus, it is reasonable to institute permanent pacing in symptomatic patients with extremely long P-R intervals (≥0.30 sec) that do not shorten during exercise. Permanent pacemaker implantation may also benefit patients with left ventricular (LV) systolic dysfunction, congestive heart failure, and marked first-degree AV block (>0.30 sec) in whom a shorter A-V interval results in hemodynamic improvement. An acute study in patients with first-degree AV block suggested that systolic performance measured using a Doppler echocardiography–derived aortic flow time-velocity integral improved after institution of DDD pacing at a rate of 70 bpm if the intrinsic AV conduction time (A-R interval) was longer than 0.27 second.³⁴ The optimal AV delay in this study was 159 ± 22 msec, which is consistent with most other studies, in that the optimal AV delay is about 150 msec at rest. However, given the need for frequent ventricular pacing support to optimize the A-V interval in these patients, atrio-biventricular pacing is likely to be the optimal long-term pacing mode in these patients with LV systolic dysfunction and heart failure.

Second-Degree AV Block

Controversy surrounds the prognosis and need for permanent pacing in patients with chronic type I second-degree AV block in the presence of a narrow QRS complex. Some consider this condition benign only in young people or athletes without organic heart disease. The natural history of 56 patients with chronic type I second-degree AV block, some of whom were younger than 35 or were well-trained athletes, was described in 1981 by Strasberg et al.³⁵ They concluded that progression to CHB is relatively uncommon in this patient population, and that this finding carries a benign prognosis in the absence of structural heart disease. In 1985, however, Shaw et al.³⁶ suggested that patients with type I second-degree AV block have a worse prognosis than age- and gender-matched individuals, unless the patients already had permanently implanted pacemakers. The 214 patients with chronic second-degree AV block (mean age, 72) were divided into three groups—type I block (77), type II block (86), and 2 : 1 or 3 : 1 block (51)—and monitored over a 14-year period. The 3-year and 5-year survival rates were similarly poor, regardless of the type of AV block. Patients with type I block without BBB fared no better than those with type II block. Patients with type I second-degree AV block who received permanent pacemakers had survival similar to that of an age- and gender-matched control population.

In 1991 the British Pacing and Electrophysiology Group (BPEG) suggested that pacing should be considered in adults in whom type I second-degree AV block occurs during much of the day or night, regardless of the presence or absence of symptoms.³⁷ In 2004, Shaw et al.³⁸ reported again on the prognosis of patients with type I second-degree AV block and once again concluded that type I second-degree AV block is not a benign condition in patients 45 years or older. The majority of their patients with type I second-degree AV block who were 45 years or older progressed to higher-degree AV block, experienced symptomatic bradycardia, or died prematurely if they did not receive pacemakers. These investigators recommended pacemaker implantation in patients with type I second-degree AV block even in the absence of symptoms or structural heart disease, except in those younger than 45. According to current ACC/AHA/NASPE guidelines, however, permanent pacemaker implantation in asymptomatic type I second-degree AV block that is at the supra-His (AV node) level or is not known to be intra-Hisian or infra-Hisian is considered insupportable by current evidence (class III indication). It seems prudent, on the basis of available data, at least to monitor closely any elderly patient with asymptomatic type I AV block or 2 : 1 AV block with narrow QRS complexes, because these electrocardiographic abnormalities may be markers for progressive conduction system disease.

The natural history of asymptomatic type II second-degree AV block initially was addressed in a University of Illinois study reported in 1974 that found most patients experienced symptoms within a relatively short period.³⁹ In 1985, Shaw et al.³⁶ reported that 86 patients (mean age, 74) monitored between 1968 and 1982 with chronic Mobitz type II second-degree heart block had a 5-year survival rate of 61%. The 5-year survival of those who underwent permanent pacemaker implantation was significantly better than those who did not. These observations form the basis for recommendations to institute permanent pacing in all patients with type II second-degree AV block, regardless of symptoms (class IIa indication with a narrow QRS; class I recommendation with a wide QRS).²¹

Complete Heart Block

The natural history of spontaneously developing asymptomatic CHB in adult life predates pacemaker therapy.^40–42 Currently, almost all adult patients with CHB eventually have symptoms and undergo pacemaker placement. Several studies in the 1960s emphasized the poor prognosis of patients with CHB. The 1-year survival rate of patients who experienced Stokes-Adams attacks caused by CHB and who did not receive pacing was only 50% to 75%, significantly less than that of a gender- and age-matched control population.⁴¹ The “best” prognosis was in patients with an idiopathic or unknown cause of CHB. At least 33% of deaths were related to CHB and Stokes-Adams attacks. These differences in survival persisted even after 15 years of follow-up and appear to be related to the considerably higher incidence of sudden death.⁴² Some debate whether the presence of syncope is associated with a worse prognosis in patients with documented CHB. The prognosis for transient CHB was poor as well, with 36% 1-year mortality reported in at least one 1970s study.⁴¹ Whether this poor prognosis applies now to patients with transient CHB who have not received pacing is unknown.

Edhag and Swahn^41,42 reported in the 1960s and 1970s on the long-term prognosis of 248 patients with high-grade AV block, most of whom had complete heart block, with a mean 6.5 years of follow-up. The mean age at pacemaker implantation was 66, and the 1-year survival of patients who received pacemakers was 86%, versus 95% for an age- and gender-matched group of Swedish patients. After the first year, survival in the patients with pacemakers was similar to that in the general population. Edhag⁴² compared survival in different age groups, found no difference in survival between elderly patients with heart block who underwent permanent pacing and the age- and gender-matched general population. In contrast, younger patients with heart block had an increased mortality even after pacing than controls. This higher mortality likely is a reflection of the underlying structural heart disease responsible for high-grade AV block.

Complete heart block can be described as acute or chronic depending on its onset. Acute AV block associated with myocardial ischemia is rare but may occur and result in transient AV block. High-grade AV block is strictly defined as 3 : 1, 4 : 1, or higher AV ratios in which AV synchrony is intermittently present. As in complete AV block, high-grade AV block may be localized anywhere in the conduction system (Fig. 14-12). In some patients, high-grade AV block may be present at multiple levels in the conduction system. Generically, “high-grade AV block” has been used to describe any form of AV block that suggests an increased risk for CHB or symptomatic bradycardia. This typically includes type II second-degree block, 2 : 1 AV block, strictly defined high-grade AV block, and CHB. The generic use of high-grade AV block is best avoided, because the multiple forms of AV block included have variable pathogeneses and prognoses that blur the clinical usefulness of the term.

Figure 14-12 Rhythm strip of high-grade atrioventricular (AV) block.

The baseline rhythm is sinus tachycardia, in which the P wave occurs simultaneously with the T wave. After the fifth QRS complex, there is an abrupt, or paroxysmal, onset of AV block with four consecutive P waves that do not conduct to the ventricles. The sixth QRS complex probably represents a junctional escape rhythm followed by three conducted complexes and then a longer episode of high-grade AV block. Before both episodes of high-grade AV block, there is no obvious P-R interval prolongation, nor is there slowing of the sinus rate to suggest hypervagotonia as a cause of this patient’s block.

Paroxysmal AV Block

Paroxysmal AV block is defined as the sudden occurrence, during a period of 1 : 1 AV conduction, of a block of sequential atrial impulses resulting in a transient total interruption of AV conduction.^43–45 It is thus the onset of a paroxysm of high-grade AV block associated with a period of ventricular asystole before conduction returns or a subsidiary pacemaker escapes. Paroxysmal AV block may occur in a variety of clinical conditions but has been described most often in association with vagal reactions, such as during vomiting, coughing, or swallowing, after urination, or with abdominal pain, carotid sinus massage, coronary angiography, or head-up tilt-table testing. Patients with neurally mediated syncopal syndromes may have transient heart block, typically with associated sinus slowing. On the other hand, paroxysmal AV block also may occur in patients with severe, distal conduction disease. This may manifest as tachycardia-dependent AV block in the His-Purkinje system (as also called phase 3 or voltage-dependent block) during or after exertion; with the abrupt onset of bradycardia or after a pause (phase 4 block); and in type II second-degree AV block. Paroxysmal AV block in these patients (not related to vagal AV block) is a marker for His-Purkinje disease, with an unpredictable escape mechanism. Permanent pacemaker implantation in these patients (with the possible exception of block mediated by acute myocardial ischemia) is almost always indicated.⁴⁵

One report described the clinical experience in 20 patients (mean age, 63 + 14 years) with paroxysmal AV block seen at a single institution over a 12-year period.⁴⁶ Paroxysmal AV block in these patients was related to a vagal reaction, AV-blocking drugs, or distal conduction disease. The AV block in these patients lasted from 2.2 to 36 seconds. Fifteen patients experienced syncope, and one patient had bradycardia-induced polymorphic VT that required electrical cardioversion. About one-half the patients had structural heart disease and a wide QRS duration.

Complete AV block can be classified as congenital or acquired. In patients with acquired complete AV block, the site of block is localized distal to the His bundle in about 70% to 90% of patients, to the His bundle in 15% to 20%, and within the AV node in 16% to 25%.⁷ In patients with congenital complete AV block, the escape rhythm is more often found in the proximal His bundle or AV node.

Bundle Branch Block

Most patients with chronic BBB or bifascicular block have underlying structural heart disease (prevalence, 50%-80%).^15–1719 Historically, it was believed that progression from chronic bifascicular block to trifascicular block was common. Retrospective studies in patients with chronic bifascicular block suggested that the risk of progression to complete AV block was 5% to 10% per year. In the early 1980s, the results of several large prospective studies questioned assumptions about the incidence and clinical implications of the progression of conduction system disease in this patient population. Prospective studies of groups of symptom-free patients with bifascicular block who were found to have prolonged H-V intervals on EPS showed that such patients are at increased risk for CHB, but that the absolute risk remains very low, about 1% to 2% per year.^15,17 McAnulty et al.¹⁶ found that the risk for development of CHB was 5% in 5 years. A prolonged H-V interval was associated with higher values for both total cardiovascular mortality and sudden death. Prolonged H-V interval is likely associated with more extensive structural heart disease. Furthermore, these studies demonstrated that in the absence of symptoms, routine His bundle recordings are of limited usefulness in patients with bifascicular block. Asymptomatic individuals with chronic BBB need no further evaluation than an occasional ECG.

On the other hand, patients with syncope and bifascicular block represent a different clinical problem. If a thorough clinical evaluation, including a history, physical examination, and ECG, do not uncover a cause of syncope, EPS may be useful.^19,20 Linzer et al.⁴⁷ found that the presence of first-degree AV block or BBB increased the odds ratio of finding abnormalities suggesting risk of bradyarrhythmia (predominantly heart block) by three- to eightfold during EPS in patients with unexplained syncope (Table 14-1). Electrophysiologic studies may uncover other causes of syncope, such as sinus node dysfunction, rapid supraventricular tachycardias, and inducible monomorphic ventricular tachycardia. In some studies, monomorphic VT was inducible in at least 30% of patients with BBB and syncope.^19,20 A minority of patients are found to have a markedly prolonged H-V interval, abnormal or fragmented His bundle electrogram, or block distal to the His bundle with atrial pacing, suggesting the need for implantation of a permanent pacemaker.

TABLE 14-1 Odds Ratio for Abnormality on Electrophysiologic Testing in Patients with Syncope

* P <.05.

† P <.001.

Modified from Linzer M, Prystowsky EN, Divine GW, et al: Predicting the outcomes of electrophysiologic studies of patients with unexplained syncope: preliminary validation of a derived model. J Gen Intern Med 6:113, 1991.

Congenital AV Block

Congenital CHB traditionally was diagnosed in the first month after birth in a child in whom a slow heart rate was detected and certain infectious etiologies rarely seen today, such as diphtheria, rheumatic fever, and congenital syphilis, were excluded.^48,49 Currently, with fetal echocardiography, many cases are diagnosed in utero and, if associated with structural heart disease, are associated with a high rate of fetal death. The incidence of congenital CHB is estimated to be 1 in 15,000 to 22,000 live births. More than one half of fetuses found to have congenital CHB have structural heart disease, including congenitally corrected transposition of the great arteries, and often have a poor prognosis in infancy. When congenital CHB is detected in utero in a child with a structurally normal heart, the condition is frequently associated with intrauterine exposure to maternal autoantibodies to Ro and La (i.e., neonatal lupus); this situation has a better prognosis than when congenital heart disease is present. The development of AV block in a child with a structurally normal heart is uncommon but should not be confused with congenital CHB. Childhood-onset heart block often is presumed to be caused by viral myocarditis. In patients with congenital CHB, the mean resting heart rate is between 40 and 60 bpm, but decreases with age.

Although controversial in the past, the indications for permanent pacemaker implantation in young patients with congenital CHB have evolved on the basis of improved understanding of the natural history of the disease. Current guidelines indicate that permanent pacemaker implantation should be performed for congenital CHB patients with a wide QRS escape, complex ventricular ectopy, ventricular dysfunction, a ventricular rate less than 55 bpm, or congenital heart disease and a ventricular rate less than 70 bpm (class I indications).²¹ Permanent pacemaker implantation may also be considered for patients after the first year of life with an average heart rate less than 50 bpm, abrupt pauses in heartbeat that are two or three times the basic cycle length, or associated with exercise intolerance caused by chronotropic incompetence (class IIa indications).

In asymptomatic children or adolescents with an acceptable rate, a narrow QRS complex, and normal ventricular function, a permanent pacemaker also may be considered (class IIb). Pacemaker implantation in asymptomatic patients with congenital CHB is associated with improved long-term survival and prevention of syncope. However, it must be recognized that ventricular dysfunction caused by right ventricular (RV) pacing–associated dyssynchrony may occur years or decades after pacemaker implantation. A 2004 study demonstrated that long-term transvenous RV apical pacing was associated with deleterious LV remodeling and reduced exercise capacity after 10 ±3 years of follow-up in patients with congenital CHB.⁵⁰ Therefore, these patients require periodic evaluation of ventricular function after pacemaker implantation. In addition, alternative ventricular pacing sites, including RV septum and left ventricle, have been proposed in patients with congenital CHB, who may require many decades of ventricular pacing but have not been definitively defined. Ventricular dysfunction in this setting may result from myocardial autoimmune disease in association with RV pacing–induced ventricular dyssynchrony. Interestingly, a recent study suggests that the natural history of patients with isolated congenital CHB who require pacing depends on their antibody status.⁵¹ Antinuclear antibody (ANA) status was a predictor for the development of heart failure and death. Long-term RV pacing was not associated with development of congestive heart failure, deterioration in ventricular function, or reduced survival in congenital AV block patients without ANAs.

Inherited Conduction System Diseases

Inherited causes of AV conduction disturbances have been increasingly recognized and better understood over the last decade. The genetics of conduction disease represents an exciting new development in our understanding of the AV conduction system.^52,53 Although at present no clear role exists for genetic testing in most forms of conduction system disease, knowledge is still limited in this area. Animal models have provided insights by elucidating molecular genetic causes of AV block. Many of the identified cases of inherited AV conduction disease previously would have been classified as idiopathic or having an unknown cause. Although inheritance makes no obvious contribution to most human conduction disease, familial clustering in cases of “idiopathic” conduction system degeneration is consistent with a hereditary basis. Some cases with familiar clustering have an autosomal dominant pattern of inheritance and associated congenital heart malformations and cardiomyopathy. However, inherited conduction system disease is not a single entity caused by a single gene mutation. Inherited conduction system disease may be associated with congenital heart diseases, neuromuscular disorders, and cardiomyopathies. Inherited conduction diseases include developmental transcription factor mutations, cardiac ion channelopathies, and mutations in genes regulating energy metabolism, gap junctions, and structural proteins.

Mutations in genes encoding cytoskeletal and nuclear membrane proteins are involved in the muscular dystrophies, including myotonic dystrophy, Emery-Dreifuss muscular dystrophy, and limb-girdle muscular dystrophy type 1B. All these neuromuscular disorders may be associated with cardiac conduction defects. Myotonic dystrophy is the most common form of muscular dystrophy. This autosomal dominant inherited disorder is caused by an expansion of cytosine-thymine-guanine repeat on chromosome 19.⁵⁴ High-degree AV block and BBB are the most common conduction system defects.⁵⁵ A mouse knockout model of the myotonic dystrophy protein kinase displays first-, second-, and third-degree AV block.⁵⁶ The mechanism of AV nodal pathology is thought to be caused by alterations in the activation kinetics or amplitude of the I_Ca,L current.

Mutations in the gene encoding for the inner nuclear membrane protein lamin A/C (LMNA) cause Emery-Dreifuss muscular dystrophy with conduction system defects.⁵⁷ Progressive conduction disease is present in virtually all cases and leads to the need for permanent pacing. LMNA also is implicated in a variety of other diseases including Hutchinson-Gilford syndrome, mandibuloacral dysplasia, Charcot-Marie-Tooth disease–type atypical Werner’s syndrome, and the Dunnigan type familial partial lipodystrophy, most of which also are associated with cardiac conduction system defects.⁵³ Lamin A/C is necessary for the structural integrity of the nucleus; in the presence of LMNA mutation, myocardial cells exposed to mechanical stress undergo cell damage. LMNA mutations also are associated with dilated cardiomyopathy, with AV conduction defects referred to as “laminopathy.”⁵⁸ Otomo et al.⁵⁹ described a large Japanese family with 21 of 224 members affected by this genetic defect, which manifests clinically as progressive AV block, dilated cardiomyopathy, heart failure, and sudden death. EPS in affected individuals demonstrated AV nodal dysfunction (marked prolongation of A-H interval) and normal HV and QRS durations. Histologic evaluation of postmortem heart specimens from affected members showed preferential degeneration, with replacement by fibrofatty tissue of the AV nodal region. Patients may die suddenly at a young age. Of note, there may be a gender difference in the severity of the cardiac phenotypes seen in lamin A/C disease. Males often have significant cardiac disease, with moderate or severe LV dysfunction developing in the first two to three decades of life, whereas females with the same mutations are more likely to have progressive conduction disease, with less severe LV dysfunction.

Mutations in the cardiac-specific sodium channel gene (SCN5A) have been associated with progressive cardiac conduction system disease.⁶⁰ Interestingly, SCN5A mutations can produce a variety of other phenotypes, including Brugada syndrome, congenital type 3 long QT syndrome (LQTS), idiopathic ventricular fibrillation, congenital sick sinus syndrome, atrial fibrillation, and dilated cardiomyopathy. An overlap syndrome involving a mutation in the cardiac sodium channel is associated with conduction system disease along with LQTS and Brugada syndrome.^61,62 Homozygous mutations in the SCN5A gene can cause a highly lethal combination of LQTS and 2 : 1 AV block in infants.⁶³ SCN5A mutations reduce cardiac sodium current, resulting in decreased action potential upstroke velocity and slowed impulse propagation, mainly in fast-conducting sodium channel–dependent conduction tissue. SCN5A mutation carriers often have long P waves and prolonged P-R and QRS intervals with normal A-H and prolonged H-V intervals, indicative of infra-Hisian delays.⁶⁴ At present, at least 11 SCN5A mutations seem to be causally related to inherited cardiac conduction system disease.^64–69 A novel SCN5A mutation involving a heterozygous single-nucleotide mutation resulted in an amino acid substitution (A1180V) in a three-generation Chinese family.⁶⁹ The mutation causes a negative shift of voltage-dependent inactivation of the cardiac sodium channels with slower recovery, leading to a rate-dependent sodium current reduction and a moderate increase in late sodium current. The A1180V mutation was associated with familial, progressive, adult-onset AV block in the third decade of life that preceded the subsequent development of dilated cardiomyopathy. Interestingly, early signs of the sodium channel defect in unaffected carriers of the pedigree were detected in the ECG manifested by QRS widening at high heart rates and QTc prolongation at rest. This suggests a possible opportunity for early diagnosis of the mutation before development of a clinically significant conduction system defect or cardiomyopathy, even in the absence of a genetic test.

Defects in potassium channel genes may be a molecular basis for some inherited AV conduction disturbances in humans. The LQT7 syndrome, or Andersen-Tawil syndrome, is caused by mutations in the KCNJ2 encoding an inward rectifier potassium channel, Kir2.1, and is another cardiac ion channelopathy associated with conduction system disorders.⁷⁰ Andersen-Tawil patients may present with conduction abnormalities, such as AV block, BBB, or intraventricular conduction delay. This syndrome is characterized by potassium-sensitive periodic paralysis, ventricular arrhythmias, and dysmorphic features. A molecular defect in KCNQ1, the pore-forming α-subunit of the I_KS potassium channel, also may be a causative mutation responsible for AV conduction disease.⁷¹ An S140G mutation in KCNQ1 has been genetically linked in a Chinese family to atrial fibrillation and to a slow ventricular response in AF as a manifestation of AV conduction disease. Thirteen of 16 AF patients in the family with the KCNQ1 S140G mutation had a slow ventricular response in AF, with mean heart rate less than 60 bpm in the absence of AV nodal–blocking medications. In addition, a transgenic mouse model with myocardium-specific expression of the human KCNQ1 S140G mutation manifested frequent episodes of first-, second-, advanced-, or third-degree AV block.

Several mutations in genes encoding proteins that regulate septation of the heart have been associated with conduction system disease. In addition to conduction disease, this phenotype includes atrial or ventricular septal defects. The Nkx2.5 homeobox gene is critically involved in development of the cardiac conduction system.^72–74 Loss-of-function mutations in the homeobox transcription factor Nkx2.5 cause a loss of DNA-binding activity of this gene. These mutations are associated with progressive AV node dysfunction and other diffuse conduction system abnormalities. Studies in Nkx2.5-deficient mice have shown that Nkx2.5 insufficiency perturbs the conduction system during development, resulting in hypoplasia of the AV node, His bundle, and Purkinje system. Mutations in the T-box transcription factor Tbx5, which similarly is an important early regulator of cardiac development, cause Holt-Oram syndrome.⁷⁵ This syndrome is manifested by congenital heart disease (usually secundum-type atrial septal defects) associated with progressive AV block and upper-limb deformities.⁷⁶ Less often, Holt-Oram patients have structurally normal hearts and clinically manifest with only AV block and subtle hand malformations. Another transcription factor associated with conduction system defects is HF-1b, an SP1-related transcription factor preferentially expressed in the cardiac conduction system and ventricular myocytes.⁷⁷ Mice deficient for HF-1b are prone to sudden death and have AV block. Downregulation of the gap-junction protein connexin 40 (Cx40) has been hypothesized as a unifying genetic mechanism responsible for the AV conduction defects in Nkx2.5, Tbx5, and HF-1b transcription factor mutations.⁵³

Mutations in the PRKAG2 gene, which encodes for a regulatory subunit of adenosine monophosphate (AMP)–activated protein kinase involved in intracellular energy metabolism, are found in association with a familial form of the Wolff-Parkinson-White (WPW) syndrome.⁷⁸ However, high-grade AV block is the dominant clinical rhythm disturbance associated with this genetic defect.⁷⁹ PRKAG2 gene mutations are characterized by pseudohypertrophy of the left and right ventricles caused by glycogen deposition in cardiac muscle. Ventricular preexcitation is thought to be caused by anulus fibrosis disruption and glycogen deposition, distinct from the muscular-appearing bypass tracts observed in typical WPW syndrome. Index of suspicion for PRKAG2 disease should be raised when massive LV wall thickening (>30 mm) is present in association with high-grade AV block. A mouse model carrying a mutation responsible for the human disease has been generated.⁸⁰

Many of the metabolic storage disorders that have a genetic basis, including Pompe disease, Anderson-Fabry disease, and Danon disease, are associated with cardiac involvement that includes prominent AV conduction disturbances.⁸¹ These diseases may also display abnormal electrical AV connections similar to the ventricular preexcitation seen in PRKAG2 disease.

Mitochondrial disorders comprise a group of diverse genetic diseases, with cardiac conduction defects reported in 10% to 40% of the patients with these disorders.⁸² Kearns-Sayre syndrome (ophthalmoplegia plus), which involves large mitochondrial DNA deletions, consists of the triad of complete AV block, chronic progressive external ophthalmoplegia, and pigmentary degeneration of the retina.⁸³ It can present with AV block and dilated cardiomyopathy, along with muscle weakness, central nervous system dysfunction, and endocrinopathies. The conduction defects typically involve the distal His bundle, bundle branches, and infranodal conduction. The accelerated and unpredictable rate of progression to complete AV block, together with an associated mortality of up to 20%, should lead to routine evaluation of patients with Kearns-Sayre syndrome for AV conduction disturbances and electrocardiographic screening of family members. Current guidelines advocate pacemaker implantation in patients with Kearns-Sayre syndrome with ECG changes indicative of conduction defects, with or without symptoms, because of the unpredictable progression of AV conduction disease in this syndrome (see Tables 14-3 and 14-4).

Acquired Causes of AV Block

Acquired AV block may be secondary to a number of causes of generalized myocardial scarring (Table 14-2). These causes include atherosclerosis, dilated cardiomyopathy, hypertension, infiltrative cardiomyopathies, inflammatory disorders, and infectious diseases. In most cases the specific etiology is clinically unknown and, with few exceptions (e.g., Lyme disease, endocarditis, sarcoidosis), is relatively unimportant from a therapeutic point of view. The most common cause of chronic acquired AV block is related to aging of the cardiac cytoskeleton. An entity known as idiopathic bilateral bundle branch fibrosis, or Lev’s disease, is characterized by slowly progressive replacement of specialized conduction tissue by fibrosis, resulting in progressive fascicular block and BBB. Lev⁸⁴ proposed that damage to the proximal LBB and adjacent main bundle or main bundle alone is the result of an aging process exaggerated by hypertension and arteriosclerosis of the blood vessels supplying the conduction system. Another variant of idiopathic conduction system disorder is Lenègre’s disease, which occurs in younger patients and is characterized by loss of conduction tissue, predominantly in the peripheral parts of the bundle branch.⁸⁵ As noted, some cases previously classified as “idiopathic” conduction disease, especially when there is familial clustering, may have a genetic cause for the conduction disease.

TABLE 14-2 Causes of Acquired Atrioventricular (AV) Block

AV Block without Bundle Branch Block

Progression of AV Block

In patients with inferior AMI, progression of AV block typically occurs in stages, whereas in those with anterior AMI, it may occur in stages, or third-degree AV block or ventricular asystole may develop suddenly¹⁷¹ (Fig. 14-15).

Figure 14-15 Lead II rhythm strip shows sudden ventricular asystole in a patient with acute myocardial infarction complicated by right bundle branch block and left-axis deviation.

(From de Guzman M, Rahimtoola SH: What is the role of pacemakers in patients with coronary artery disease and conduction abnormalities? In Rahimtoola SH, editor: Controversies in coronary artery disease. Philadelphia, 1983, Davis.)

AV Block with Bundle Branch Block

Prior to the widespread use of thrombolytic therapy, BBB was present during hospitalization in 8% to 18% of patients with AMI.^191–196 The presence of a persistent intraventricular conduction defect during the hospitalization increases the risk of high-grade AV block as well as other complications and is associated with poor survival in patients with AMI. In patients receiving thrombolytic therapy, the incidence of persistent intraventricular conduction defects appearing during the hospitalization is reduced to about 4% to 9%.^161–163197 However, the adverse risk associated with intraventricular conduction defects (except for isolated left anterior hemiblock) has persisted even in the modern era of AMI reperfusion therapy.

In an older series of 2779 patients with AMI admitted from 1966 to 1977 to the LAC-USCMC CCU, 257 (9%) had BBB¹⁸⁶ (Table 14-7). Of the 257 patients, 83 (32%) had LBBB, 80 (31%) had RBBB, 72 (28%) had RBBB plus left-axis deviation, 21 (9%) had RBBB plus right-axis deviation, and one had alternating BBB. The conduction abnormality was “new” in 60%; that is, the BBB developed during the infarction and was documented by serial ECGs or was present on admission and was not seen on previous ECGs or reverted to normal conduction later as documented by serial ECGs. When the site of infarction was not obscured by the BBB in the LAC-USCMC series, the block was associated with anterior AMI about three times as often as with inferior AMI.

TABLE 14-7 Bundle Branch Block (BBB) in Acute Myocardial Infarction (AMI)

AVB, Atrioventricular block; LAD, left anterior descending artery; RAD, right anterior descending artery.

* Data from 2779 AMI patients seen from October 1966 to March 1977 at Los Angeles County-University of Southern California Medical Center (LAC-USCMC), Los Angeles.

Modified from de Guzman M, Rahimtoola SH: What is the role of pacemakers in patients with coronary artery disease and conduction abnormalities? In Rahimtoola SH, editor: Controversies in coronary artery disease. Philadelphia, 1983, FA Davis, pp 191-207.

Progression of AV Block

In the LAC-USCMC series conducted before the thrombolytic era, progression of AV block occurred in 75 of the 257 patients (29%) with AMI and BBB (see Table 14-7).

Of the 28 patients with AV block and BBB who initially had a normal P-R interval, 13 (46%) experienced first-degree AV block. Nine of the 13 (69%) remained in first-degree block, two (15%) progressed to second-degree block type II only, one (8%) had type II second-degree block that progressed to third-degree AV block, and one had third-degree block without first having second-degree block. Six patients had type II second-degree block without initially having first-degree AV block, four of whom (67%) went on to have third-degree AV block.

Of the total 41 patients who had first-degree AV block and BBB, 13 (32%) progressed to high-grade block. Twenty-eight (68%) were admitted in first-degree AV block. Sixteen of the 28 (57%) remained in first-degree block; three (11%) progressed to type II second-degree AV block, one of whom went on to third-degree block; five (18%) progressed to type I second-degree block, two of whom went on to third-degree block; and four (14%) patients had third-degree block without initially having second-degree AV block.

Of the total 24 patients who had second-degree AV block and BBB, 11 (46%) progressed to third-degree block. Six had second-degree AV block on admission; of these, type II block occurred in four, one of whom progressed to third-degree block, and type I occurred in two, one of whom progressed to third-degree block.

There were 37 patients with third-degree AV block and BBB, 13 (35%) of whom were admitted in third-degree block. Of the 24 who progressed to third-degree block, 11 (46%) had demonstrated second-degree block; 7 of the 11 had type II second-degree block. Consistent with the LAC-USCMC series, AV block occurred in other studies in about one third of patients with AMI and BBB.^{186,198–201}

Two large studies from the 1970s and 1980s developed a data bank on patients with BBB in association with MI: a collaborative multicenter study involving five centers¹⁸⁵ and a study conducted at LAC-USCMC.¹⁸⁶ Both studies have limitations because (1) the data were obtained retrospectively and (2) at the time, no guidelines existed pertaining to pacemaker insertion, which was performed at the physician’s discretion in all cases. Thus, although these studies are unable to provide definitive answers about the natural history of BBB in association with AMI, they nevertheless do offer valuable clinical information.

In the multicenter study reported by Hindman et al.,¹⁸⁵ high-grade AV block (third- or second-degree block with a type II pattern) occurred in 55 of 432 patients (22%). To determine which patients were at considerable risk for development of high-grade AV block while hospitalized with AMI, several variables were analyzed. Combinations of the three following ECG findings identified high-risk patients: (1) first-degree AV block, (2) bilateral BBB (if both bundle branches were involved [e.g., RBBB plus left- or right-axis deviation] or alternating RBBB and LBBB), and (3) “new” BBB. The absence of all variables or the presence of only one of the three defined variables was associated with a lower risk (10%-13%) for development of high-grade AV block during hospitalization. The risk was moderate for patients with first-degree AV block with either new BBB or bilateral BBB (19%-20%), and highest (31%-38%) for new bilateral BBB regardless of the P-R interval (Fig. 14-16).

Figure 14-16 Venn diagram for 432 patients in multicenter study, depicting the risk for high-grade atrioventricular block (AVB) in patients with acute myocardial infarction and bundle branch block (BBB).

(From Hindman MC, Wagner GS, JaRo M, et al: The clinical significance of bundle branch block complicating acute myocardial infarction. 2. Indications for temporary and permanent pacemakers. Circulation 58:689, 1978. Copyright 1978 American Heart Association.)

In the LAC-USCMC study, high-grade AV block occurred in 46 of 257 patients (18%). The absence of all three variables (first-degree AV block, bilateral BBB, and new BBB) or the presence of either bilateral BBB or new BBB or new bilateral BBB was associated with the lowest risk (10%-18%) for development of high-grade AV block during hospitalization with AMI.¹⁸⁶ The risk was moderate for first-degree AV block with or without new BBB (29%-30%) and highest (50%) for bilateral BBB plus first-degree AV block, regardless of whether the BBB was old or new (Fig. 14-17).

Figure 14-17 Venn diagram for 257 patients in the Los Angeles County–University of Southern California Medical Center (LAC-USCMC) study, depicting the risk for high-grade atrioventricular block (AVB) in patients with acute myocardial infarction and bundle branch block (BBB).

(From de Guzman M, Rahimtoola SH: What is the role of pacemakers in patients with coronary artery disease and conduction abnormalities? In Rahimtoola SH, editor: Controversies in coronary artery disease. Philadelphia, 1983, Davis.)

Despite some differences in the findings between the two studies, both studies found that the following subgroups of patients were at highest risk for high-grade AV block: (1) those with new bilateral BBB plus first-degree AV block (risks, 38%¹⁸⁵ and 43%¹⁸⁶), (2) those with bilateral BBB plus first-degree AV block (risks, 20% and 50%, respectively), and (3) new BBB plus first-degree AV block (risks, 19% and 29%, respectively). Subgroups in whom the findings of the two studies show different risks can be considered to be at moderate risk for high-grade AV block. These subgroups include patients with (1) new bilateral BBB (risks, 31% and 15%, respectively) (Fig. 14-18), (2) first-degree AV block (risks, 13% and 30%, respectively), and (3) bilateral BBB (risks, 10% and 18%, respectively). The remaining subgroups of patients with AMI and BBB can be considered to be at lowest risk (≤10%) for development of high-grade AV block.

Figure 14-18 A and B, Electrocardiograms of a patient with anterior acute myocardial infarction and development of “new” bilateral bundle branch block (BBB)—left BBB and right BBB with right-axis deviation. This patient had sudden ventricular asystole.

The database assembled by the Multicenter Investigation of the Limitation of Infarct Size (MILIS) was used to develop a simplified method of predicting the occurrence of CHB. Data from 698 patients with proven MI were analyzed, and the presence or absence of ECG abnormalities of AV or intraventricular conduction was determined for each patient. Risk factors for development of CHB were as follows: first-degree AV block, Mobitz type I AV block, Mobitz type II AV block, left anterior hemiblock, left posterior hemiblock, RBBB, and LBBB. A risk score for the development of CHB was devised that consisted of the sum of each patient’s individual risk factors. Incidences of CHB of 1.2%, 7.8%, 25%, and 36% were associated with risk scores of 0, 1, 2, and 3 or more, respectively (Fig. 14-19). The risk score was subsequently tested on the published results of six studies for a combined total of 2151 patients.²⁰² The limitations of this scoring system include the lack of differentiation between newly appearing and old BBB, a factor that has been shown to be of predictive value. It is likely that consideration of such factors would further improve the accuracy of the scoring system, but it would also add to its complexity. Another criticism of the scoring system is that it would assign a risk score of only 1 to a patient with isolated Mobitz type II AV block, a disorder usually believed to be highly predictive of progression to CHB. Isolated Mobitz type II AV block is, however, relatively rare.

Figure 14-19 Comparison of the incidence of complete heart block (CHB) predicted by the CHB risk score method (purple bars), the observed incidence of CHB in the Duke University myocardial infarction database (blue bars), and the observed incidence of CHB or CHB and Mobitz II atrioventricular (AV) block in six reported studies (red bars). MILIS, Multicenter Investigation of the Limitation of Infarct Size.

(From Lamas GA, Muller JE, Turi AG, et al: A simplified method to predict occurrence of complete heart block during acute myocardial infarction. Am J Cardiol 57:1213, 1986.)

It must be recognized that the algorithms and clinical databases used to estimate the risk for occurrence of CHB in the setting of AMI were developed in the prethrombolytic era, and thus must be interpreted cautiously when applied to the modern post-AMI patient population. The availability of transcutaneous pacing and early primary percutaneous coronary interventions has had an important effect on the clinical management of these patients with AMI in the current era. The actual clinical decision whether to institute prophylactic temporary pacing should be individualized according to the patient-related risk factors and the available personnel and equipment at each institution.

Impact of Thrombolytic Therapy

Several prospective trials involving thrombolytic therapy of AMI provide data pertaining to the effect of such therapy on the development of high-grade (second- or third-degree) AV block and BBB.^168,172

Clemmensen et al.¹⁷² examined the effect of thrombolytic therapy and adjunctive angioplasty as a treatment strategy for AMI (TAMI trial) after inferior AMI. In all patients, treatment was initiated with thrombolytic agents within 6 hours of symptom onset. There were 373 patients with an inferior AMI, of whom 50 (13%) had complete AV block; 54% of these patients had complete AV block on admission. In all but two patients, the block was manifest within 72 hours of onset of symptoms. The duration of block was less than 1 hour in 25% and less than 12 hours in 15%; the median duration of block was 2.5 hours. There was no difference in the rate of infarct vessel patency between those with and those without AV block (90% and 91%, respectively). A precipitating clinical event—vessel reperfusion, performance of percutaneous transluminal coronary angioplasty (PTCA)—or vessel reocclusion was identifiable in 38% of cases of complete AV block. At the predischarge angiogram, the vessel patency rate was 11% lower in the group with AV block than in the group without block (71% vs. 82%, respectively). Those in whom AV block developed showed a decrease in LVEF between the early postthrombolytic angiogram and the predischarge angiogram. Also, those who experienced AV block had higher in-hospital mortality, 10 of 50 (20%) versus 12 of 323 (4%; P < .001). When age, LVEF in the acute phase, number of diseased vessels, and grade of blood flow through the culprit lesion were entered into a multivariate model, the development of complete AV block still contributed significantly to the risk for in-hospital death. After a median follow-up period of 22 months, mortality rates for patients with and without AV block were equivalent (2%). These data suggest that, compared with the prethrombolytic era, use of thrombolytics and angioplasty has altered neither the incidence of complete AV block nor the associated greater ventricular dysfunction or in-hospital mortality of patients with inferior AMI.

In another study of 1786 patients with inferior AMI who received recombinant tissue-type plasminogen activator (rt-PA) within 4 hours of symptom onset, high-grade (second- or third-degree) AV block developed in 214 (12%) (TIMI-II trial).¹⁶⁸ Of the group who had AV block, 113 (6.3% of total, or 52% of those who ever had AV block) had this finding on admission. The remaining 101 patients (5.7%) experienced heart block during the 24 hours after treatment with thrombolytics. Patients who already had high-grade AV block before receiving thrombolytic therapy tended to be older and had a higher prevalence of cardiogenic shock than those without heart block. Nevertheless, the presence of heart block did not carry a higher 21-day mortality rate independent of other variables, such as shock, and the 1-year mortality rate was similar to that in the group without heart block. Patients in this study were randomly assigned to coronary arteriography 18 to 48 hours after admission. Among those who had heart block after admission, the infarct-related artery was less frequently patent than in those without heart block (28 of 39 [72%] vs. 611 of 723 [84.5%]; P = .04]). The RCA was the infarct-related artery more often in patients who had heart block than in those who did not (36 of 69 [92.3%] vs. 542 of 723 [75.1%], respectively; P = .04). Among patients without heart block at hospital admission, death occurred within 48 hours in 4 of 9 patients (44%) with new heart block and in 8 of 68 (12%) without new heart block at 24 hours. The 21-day mortality rate was higher in the group with AV block than in the group without block (10 of 101 [9.9%] vs. 35 of 1572 [2.2%], respectively; P < .001), as was the 1-year mortality rate (15 of 101 [14.9%] vs. 65 of 1572 [4.2%], respectively; P = .001). A temporary pacemaker was inserted in about one third of patients who had heart block on admission and in almost 30% of patients who experienced heart block after institution of thrombolytic therapy, whereas only 6.5% of patients without heart block received temporary pacemakers. None of the patients who had heart block on admission or who experienced heart block later received permanent pacemakers, but four patients without heart block at 24 hours went on to receive permanent pacemakers. Heart block was not listed as a primary or contributing cause of death in any patient.

The data from these two studies of thrombolytic therapy suggest that aggressive treatment with thrombolytic agents or thrombolytic therapy plus angioplasty is not associated with a lower incidence of high-grade or complete AV block in patients with inferior AMI than was seen in the prethrombolytic era; the incidence remains about 10% to 13%, with about one half of cases appearing as new AV block during hospitalization. The infarct-related vessel is more often the RCA, and there is a lower vessel patency rate after thrombolysis among patients in whom AV block complicates inferior AMI. In-hospital and early posthospitalization mortality rates are higher in patients with block than in those without AV block, among patients treated with thrombolytics, with or without angioplasty. It has not been clear, however, that patients with acute AV block continue to be at greater risk of death over the long term if they survive the initial hospitalization. A study that pooled data from four large RCTs involving 70,000 patients with AMI treated with thrombolytic therapy evaluated the short- and long-term mortality rates associated with second- and third-degree AV blocks.¹⁶⁴ Compared with patients with AMI and no AV block, patients with AMI and AV block were more than three times more likely to die within 30 days and 1.5 times more likely to die during 1 year of follow-up. The higher short- and long-term mortality rates were observed in the setting of inferior as well as anterior AMI (Fig. 14-20). The presumption remains, as before the era of thrombolytic therapy, that the presence or development of AV block is associated with a higher mortality because it tends to indicate the presence of more extensive infarction or injury.

Figure 14-20 Unadjusted mortality rates in patients with and without atrioventricular block (AVB). MI, Myocardial infarction.

(From Meine TJ, Al-Khatib SM, Alexander JH, et al: Incidence, predictors, and outcomes of high-degree atrioventricular block complicating acute myocardial infarction treated with thrombolytic therapy. Am Heart J 149:670, 2005.)

In trials conducted with thrombolytic therapy in AMI, BBB is reported present on admission in up to 2% to 4% of patients.²⁰² In the first Global Utilization of Streptokinase and Tissue-Type Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial, among 26,003 North American patients, 420 (1.6%) had left (n = 131) or right (n = 289) BBB on admission ECG.²⁰⁴ Interestingly, reversion of BBB occurred in 24% of patients during hospitalization and was associated with a 50% relative risk reduction in 30-day mortality, from 20% to 10%. Prognosis for patients who recovered normal intraventricular conduction (i.e., transient BBB) was similar to that for patients who never had BBB. Another study examined the significance of RBBB in AMI in the prethrombolytic era and compared it with the incidence and prognostic significance of new RBBB in the thrombolytic era.²⁰⁵ In a multicenter prospective study of 1238 patients with 1-year follow-up, a higher rate of new and transient RBBB and lower rate of bifascicular block were found in patients receiving thrombolytic therapy. The overall prognostic implications of RBBB, however, were unchanged and included a higher rate of heart failure, greater chance of needing a permanent pacemaker, and a higher 1-year mortality rate.²⁰⁵

Bundle Branch Block after Recovery

The subset of patients with persistent BBB and transient high-grade AV block during AMI are at increased risk of late mortality.^185,206,207 It is now recognized that most of these deaths are sudden and result from ventricular tachyarrhythmias. In a previous era, however, controversy surrounded whether these patients were at high risk for sudden death from a bradyarrhythmia.^{183,201,208–210} Some investigators suggested that patients with persistent BBB plus transient AV block during the acute infarction had a higher risk of dying suddenly as a result of CHB. They attempted to identify the subset of patients at highest risk of late sudden death due to AV block in order to maximize the therapeutic benefit of permanently implanting a pacemaker.

The multicenter study by Hindman et al.¹⁸⁵ supported the previous reports by Atkins²⁰⁶ and Ritter,²⁰⁷ who found that the subset of patients with chronic BBB and transient high-grade AV block during AMI were at increased risk of late sudden death. These data showed that patients who did not receive pacing had a higher incidence of sudden death or recurrent high-grade AV block during follow-up (65%) than those who were given permanent pacing (10%), suggesting that implantation of a permanent pacemaker protected against sudden death in these patients. Waugh et al.²¹¹ likewise recommended permanent pacemaker therapy to prevent syncope or sudden death in another group of high-risk patients, those with bilateral BBB plus transient high-grade AV block (type II progression).

Other studies from the same era, however, questioned whether these patients are at high risk for sudden death from a bradyarrhythmia.^{183,203,208–210} For example, Nimetz et al.²⁰¹ reported that late sudden death occurred in 4 of 13 (31%) survivors with BBB and second- or third-degree AV block and in 14 of 41 (34%) survivors without AV block. Ginks et al.¹⁸³ found that of patients with anterior AMI complicated by CHB with return to normal sinus rhythm but with persistent BBB, 4 of 14 hospital survivors (29%) with anterior MI, persistent BBB, and transient AV block died, and 2 of 4 (50%) with permanent pacemakers died during a follow-up period averaging 49 months. In a study by Murphy et al.²⁰⁹ of patients surviving AMI complicated by BBB, none of the deaths resulted from heart block, even in patients with transient AV block during the AMI. Lie et al.²¹⁰ reported on a group of 47 patients who had survived anterior infarction complicated by BBB and who were kept for 6 weeks in the monitoring area; 17 of the 47 patients (36%) sustained late ventricular fibrillation. Likewise, the Birmingham Trial of permanent pacing in patients with persistent intraventricular defects after AMI showed no significant difference in survival between patients with and without heart block during up to 5 years of follow-up.²¹² Finally, in a prospective long-term study, Talwar et al.²¹³ monitored 18 patients with anterior AMI, intraventricular defects, and transient complete AV block for a mean of 2 years; pacemakers were permanently implanted in eight patients. There was only one death, in the unpaced group, caused by a cerebrovascular accident. Clearly, these older studies were limited by the small number of patients with AMI enrolled and monitored and may not be applicable to the current era of post-AMI management. Despite the controversy regarding whether late sudden death in patients with BBB is caused by heart block, permanent ventricular pacing is indicated for transient advanced second- or third-degree infranodal AV block and associated BBB after AMI, according to current practice guidelines (class I indication).²¹

Electrophysiologic Studies in AV Block and Bundle Branch Block

Electrophysiologic studies with recording of the His bundle electrogram (HBE) are not performed routinely at present for risk stratification of patients with AV block after AMI. HBE studies after AMI were used primarily in the 1970s and 1980s to identify the sites of AV conduction disturbances, which were shown to be either in the AV node (proximal block) or in the distal conduction system (distal block). The presence of distal block identifies patients at high risk for development of high-grade AV block. In individual cases in which the diagnosis is uncertain (e.g., type I second-degree AV block in patients with BBB) or infranodal or multilevel block is suspected, EPS is helpful in identifying the sites of AV block (Fig. 14-21).

Figure 14-21 Simultaneous surface electrocardiogram (leads I, aVF, and V1) and intracardiac recordings from the His bundle region (His_M and His_P) in a 65-year-old patient with ischemic cardiac disease and a history of syncope. Left upper panel, Sinus rhythm with normal baseline H-V interval (48 msec) and narrow QRS complex with a left anterior fascicle block pattern. Right upper panel, Prolonged H-V interval (137 msec) during atrial overdrive pacing (S1S2 = 650 msec). Lower panel, H-V Wenckebach conduction during atrial overdrive pacing (S1S1 = 600 msec). This case and figure show that serious infranodal conduction disease may be localized to within the His bundle and may be “masked” by a normal QRS as well as a normal P-R interval during sinus rhythm.

(Courtesy Drs. Yanfei Yang and Melvin Scheinman, University of California/Cardiac Electrophysiology, San Francisco.)

In patients with inferior AMI, the site of AV block is usually proximal. Harperet al.²¹⁴ showed that 30 of 32 patients (94%) with inferior AMI and third-degree AV block had AV nodal block during HBE; the remaining two patients were in normal sinus rhythm during the study and had a normal P-R interval and normal A-H and H-V intervals. Thus, in this group of patients, HBE offered no advantage over conventional ECG criteria in localizing the site of block.

In anterior AMI, the block is frequently in the distal conduction system. In the study by Harper et al.,²¹⁴ 50% of patients (9 of 18) with BBB and a normal P-R interval on ECG had a prolonged H-V interval.²¹⁴ Of the 22 patients who experienced AV block and BBB, five had proximal block, 14 had distal block, and three had both proximal and distal blocks. Thus, in both groups of patients, HBE was the only means of localizing the block in the proximal or distal portion of the conduction system. Distal block indicates disease in either the His bundle or the remaining bundle branches; clinically, this finding is a common antecedent to sudden asystole and a poorer prognosis. Despite that a prolonged H-V interval could identify a group of patients who may be at high risk for high-grade AV block, several studies have shown that it does not help in assessing the short- or long-term prognosis of patients after AMI.^214,215

Intracardiac EPS has been evaluated as a means of attempting to predict which patients with MI and BBB are most likely to die. Harper et al.²⁰⁸ reported on 72 patients with AMI complicated by AV block, BBB, or both who underwent His bundle recording or electrophysiologic (HBE) studies during their CCU stay. Thirty of 32 patients (94%) with AV block and narrow QRS had a proximal block. Hospital mortality was low (13%), and HBE provided no additional information to the surface ECG. Of 18 patients with BBB and a normal P-R interval, nine had distal block, but there were no hospital deaths in this group. Again, of 22 patients with BBB and AV block, five had proximal, 14 distal, and three proximal and distal blocks. Hospital mortality in these patients, who progressed to second- or third-degree AV block, was higher (9 of 12 patients, 75%) than in those who remained in first-degree AV block (2 of 10 patients, 20%). Lichstein²¹⁶ and Lie¹⁸⁴ also concluded that patients with BBB and AMI who had HBE evidence of a distal block had higher hospital mortality (73% and 81%, respectively) than those with normal H-V intervals (25% and 47%, respectively). On the other hand, Gould et al.²¹⁷ found that the presence or absence of a prolonged H-V interval did not affect mortality.

Indications for Pacing