Rate dependent blocks - Dan-Dominic Ionescu

Content Preface by Hein J. Wellens ............................................................................................................................... 7

1. INTRODUCTION.................................................................................................................................. 9 2. CLINICAL ELECTROPHYSIOLOGY OF RATE-DEPENDENT BLOCKS ..............................17 2.1. A simplified presentation of cardiac electrophysiology for the clinician .............................................17 2.2. General mechanisms of rate-dependent blocks ..................................................................................20 2.3. Disclosure of rate-dependent blocks by heart rate modulations .........................................................24

3. RATE-DEPENDENT INTRAVENTRICULAR BLOCKS...............................................................33 3.1. A short presentation of bundle branch blocks ....................................................................................33 3.1.1. Right bundle branch block (RBBB) ..........................................................................................33 3.1.2. Left bundle branch block (LBBB) ............................................................................................33 3.1.3. Left divisional fascicular blocks .................................................................................................35 3.1.4. Bifascicular and trifascicular blocks ...........................................................................................36 3.2. General data on RD intraventricular blocks .......................................................................................36 3.3. RD bundle branch blocks in practice..................................................................................................38 Appendix A: Supplemental ECG tracings for Chapter 3 .........................................................................59

4. RATE-DEPENDENT ATRIOVENTRICULAR BLOCKS ..............................................................79 4.1. A brief general presentation of atrioventricular blocks .......................................................................79 4.2. Rate-dependent 2:1 atrioventricular blocks ........................................................................................82 4.3. Other rate-dependent 2° atrioventricular blocks ..............................................................................100 4.4. A drug for rate-dependent 2:1 atrioventricular blocks? ....................................................................105 Appendix B: Supplemental ECG tracings for Chapter 4 ........................................................................111 5

List of abbreviations AAVB = advanced atrioventricular block AF = atrial fibrillation AFL = atrial flutter AMI = acute myocardial infarction AT = atrial tachycardia AP = action potential ARP = absolute refractory period AV = atrioventricular AVB = atrioventricular block AVN = atrioventricular node AIWP = alternating inferior Wenckebach periods ASWP = alternating superior Wenckebach periods AWP = alternating Wenckebach periods

BB = bundle branch BBB = bundle branch block bpm = beats per minute CEBiG = capture-escape bigeminy CR = conduction ratio CSM = carotid sinus massage ECG = electrocardiogram ERP = effective refractory period FRP = functional refractory period HB = His bundle LAFB = left anterior fascicular block LSFB = left septal fascicular block LPFB = left posterior fascicular block LBB = left bundle branch LBBB = left bundle branch block

M-I = Mobitz type I M-II = Mobitz type II RBB = right bundle branch RBBB = right bundle branch block RD = rate-dependent SR = sinus rhythm SRC = sinus rhythm cycle STEMI = ST elevation myocardial infarction SV = supraventricular SVC = supraventricular cycle TIA = transient ischemic attack VC = ventricular cycle WP = Wenckebach period WPW = Wolff-Parkinson-White

Preface Unfortunately, knowledge how to interpret the electrocardiogram (ECG) correctly is decreasing.

More value is currently given to much more expensive imaging methods such as echocardiography, the CT scan and MRI. However, the ECG is still an unique method to give us immediate information about acute and chronic cardiac ischemia, rhythm and conduction disturbances, structural changes in the cardiac chambers, ECG changes caused by medication, the evaluation and programming of implantable devices, electrolyte and metabolic disorders, monogenic ECG changes, and cardiovascular risk prediction.

The ECG is everywhere available, easy and rapid to make, non-invasive, reproducible, patient friendly and inexpensive.

It is surprising therefore that in the core curriculum of every cardiologist, not only during the training phase, but also during postgraduate education, insufficient attention is given to old and new knowledge of the ECG. One of the (many!) unique features of the ECG is our ability to obtain information about the effect of rate changes on intracardiac conduction and QRS configuration.

Heart rate is an important determinant of sino-atrial conduction and conduction over the AV node, the bundle of His and the bundle branches. Based upon the ECG characteristics during conduction disturbances the need for pacemaker implantation is established.

In this monograph Dr. Ionescu gives a detailed description of disturbances at the different levels of the intracardiac conduction system starting with a survey of its history, fol-

lowed by basic electrophysiologic information helpful in understanding the clinical electrocardiographic manifestations.

He is doing this, on purpose, without the help of a registration of the His bundle electrogram, to educate the physician to make a correct diagnosis using only the 12 lead ECG. He indicates how worsening or improvement of conduction during spontaneous rate changes or simple non-invasive maneuvres such as exercise, atropine or carotid massage can be used to determine the level of conduction block or the mechanism of changes in QRS configuration.

In the discussion on rate-dependent intraventricular blocks four mechanisms are mentioned. Two are easy to understand: one is phase-3 block in the bundle branch when the refractory period of the bundle branch is reached at a critical high rate. Also the mechanism of bundle branch block by retrograde invasion into the bundle branch has been well demonstrated.

Both mechanisms are physiologic, occuring in the healthy heart.

However for the two remaining ones, acceleration dependent block and phase-4 block we lack information about the exact mechanism because of our inability to study this at the cellular level in the intact human heart. The appearance of bundle branch block at a rate of 80 beats per minute can not be explained by the length of the refractory period of the bundle branch. Post repolarization refractoriness of the bundle branch has been suggested. Acceleration dependent block is a typical forerunner of a constant bundle branch block independent of the heart rate.

7

8

RATE-DEPENDENT BLOCKS

Also the role of phase-4 block in creating bundle branch block or complete (paroxysmal) AV block, is still hypothetical in the absence of basic electrophysiologic evidence in the intact human heart. Both acceleration-dependent block and paroxysmal AV block point to a pathologic mechanism with consequenses for clinical management.

In this book the different ECG patterns and clinical significance of rate-dependent blocks are well explained. It helps to better understand and interpret the electrocardiogram and is thereby of great benefit for our patients.

Hein J. Wellens

CHAPTER

1

Introduction The history of rate-dependent (RD) blocks begins with an intraventricular block that was published as a transient one in the right bundle branch (but on that three-lead ECG of the time we can see now that it was in the left bundle branch) by T. Lewis in 1913 in a febrile patient aged 32 with clinical signs of heart failure [1]. No comments were made about any relationships to heart rate in the two ECGs recorded one day apart so the dependence to rate of that block is uncertain although the heart rate on the tracing with normal QRS complexes was slower. The first real RD intraventricular blocks in sinus rhythm (SR) were published in 1921 [2] and were followed by an increasing number of case reports, patient series of various sizes and electrophysiological studies that have established the clinical and ECG features of this particular diagnosis [3-12]. In a striking contrast, the RD atrioventricular blocks were very rarely observed and much less studied.

It is common knowledge that conduction of electric impulses in the heart is governed by the functional properties and morphologic integrity of both specific tissues and the myocardium [13, 14]. In the hearts beating in SR, each impulse originated in the sinus node travels through a variety of structures (non-specific in the atria and specific below the atria) before reaching the working myocardium tissues.

These structures have a large diversity of electrophysiological characteristics that are modulated by the heart rate among many other factors. At the same time, the cardiac electrical activity is under a tight autonomic control that is stronger at supraventricular levels. In very simple terms, the heart rate (as the equivalent of clinical pulse rate) is expressed as a ratio between the number of cardiac impulses appearing over one minute meaning that cardiac cycles have a duration expressed in milliseconds (ms). From ECG tracings encountered in clinical practice we know that in some arrhythmias the supraventricular cycles (SVCs) are different from ventricular cycles (VCs) which give the heart rate. On the other hand, the conduction of impulses through specific structures depends on the duration of their functional refractory period (FRP) also expressed in ms. The various possible relationships between SVCs (or VCs) and FRPs may define both normal and abnormal conduction of impulses everywhere in the heart. It must be added that, at many levels of the specific conduction system, the normal FRPs shorten with shorter SVCs (much less in the His bundle) and lengthen with longer SVCs, a rate-adaptation that is both a beat-to-beat process and a slowly progressive long-term phenomenon [15]. With any normal SVC in terms of its rate ranges and regularity, as is the case of the physiologic SR cycle (SRC), the normal conduction results when the rate-adapted FRP in the specific system is always much shorter than the SRCs as expressed by the formula normal SRCs >> normal FRPs (fig. 1.1A). By definition, a 9

10

RATE-DEPENDENT BLOCKS

FIGURE 1.1. All the possible comparative relationships between sinus rhythm cycles (SRCs) with their physiological ranges and the functional refractory periods (FRPs) of a conduction structure below the atria (detailed in text)

block obviously means no conduction of at least one impulse at any level but the repetitive nature of heart beats may lead to different relationships between rate and conduction. The first consequence is that the above formula is clearly applicable mainly to intraventricular conduction where a longer than normal FRP may lead to three types of relationships in terms of rate-dependent (RD) blocks. When FRPs are slightly shorter than the average SRC then the block may be absent at rest but can be disclosed by accelerations of SR (fig. 1.1B).

If FRPs are approximately equal to the average SRC then the surface ECGs show both normally conducted P waves and P waves followed by a block (fig. 1.1C). When FRPs are close to the longest SRC values then the block seems stable (fig.

1.1D) but may disappear after slowing of SR rates as sometimes happens during sleep or, for instance, after a mild carotid sinus massage (CSM). Finally, if FRPs are very much longer than the longest SRC then the block can be considered as stable or permanent (fig. 1.1E). The variants B, C and D (from fig. 1.1) correspond to three simple formulae: normal SRCs > longer FRPs, normal SRCs = longer FRPs and normal SRCs < longer FRPs which define the RD blocks

that appear during phase 3 of the action potential (AP) of the intraventricular structures involved in conduction of all atrial impulses. This oversimplified approach does not take into account all the possible electrophysiological explanations for RD blocks in SR (presented in section 2.2 of Chapter 2).

A closely similar situation is encountered in the WolffParkinson-White syndrome where a relationship between the conduction over an accessory pathway and the heart rate is possible. In order to evaluate the risks of very fast ventricular rates during an incidental episode of atrial fibrillation (AF) the refractory period of the accessory pathway must be known because it is well correlated with the ventricular fibrillation risk. If ventricular preexcitation is absent or variable at rest, this refractory period of the Kent bundle is safely long and has a value close to that of SRCs. The same conclusion applies when preexcitation is known from previously documented ECG tracings but it is absent on actual examination. In such cases the typical pattern of the WPW syndrome can be disclosed by CSM and the result of PR shortening and QRS widening because of  wave appearance, without a change in PJ interval, is known as “the concertina effect” [16, 17]. When the preexcitation pattern seems to be permanent, in order to assess the conduction capacity of the accessory pathway, especially in individuals with certain professions or occupations, it is needed to increase the atrial rate with either a stress test or an atrial pacing with fast rates [17, 18]. The critically short atrial cycles when and if preexcitation disappears approximate the anterograde refractory period of the accessory fascicle. If  wave is still present with the highest atrial rates, only the induction of AF by very fast atrial pacing during an electrophysiologic study (sometimes with addition of isoproterenol infusion) may really ascertain the risk of ventricular fibrillation. On ECG tracings recorded for at least one minute in AF, the refractoriness duration of the Kent bundle is given by the shortest preexcited RR interval [19-22]. All of the above evaluations prove that the conduction over the accessory pathway depends on heart rate and can be both phase 3 and phase 4 blocks [23-25], but none of the variants with disap-

Chapter 1. INTRODUCTION

pearance or appearance of  wave was ever included between RD blocks.

During the early years of electrophysiologic studies development it was observed that at a critically high value of induced atrial rate, the global AV conduction shows Wenckebach periods generated in the AVN [26, 27]. This atrial paced rate value is known as the Wenckebach point and has the usual normal value of 150-160 beats/minute (bpm), lower with advancing age. At these heart rates, the equivalent FRP of AVN has a value of 375-400 ms which is longer than any of the other conduction structures in the heart as a good protection of ventricles against risky fast rhythms. As a routine procedure during this invasive type of investigation, the atrial pacing rate is increased up to 200-220 bpm when a 2:1 conduction appears. The corresponding rate-adapted FRP of the AVN node is ~270-300 ms, a value that is still longer than the shortest physiologically possible normal value of intraventricular bundle branches rate-adapted FRP meaning that a bundle branch block does not occur. None of these AVN conduction patterns appearing under fast atrial pacing is considered a RD block and there is no Wenckebach point in healthy people undergoing standard stress tests even at the most rapid atrial rates.

An impaired conduction at any level in the heart may be called differently according to the various possible relationships between SVCs (or VCs in AF) and FRPs. For instance, when rate-adapted FRPs in SR are longer than normal, a block becomes possible either rarely in the AVN or, most frequently, in the His-Purkinje system. This block may be a RD one depending on how much longer are the FRPs compared to the ranges of SRC variability. A second simple variety of RD block appears during phase 4 of the AP and has a complicated mechanism in which long FRPs are present but not directly causative (see Chapter 2, section 2.2 for a detailed presentation).

Many descriptive terms are used in the medical literature for RD blocks which may be transient, unstable, temporary or intermittent [4, 5, 28] in contrast with the permanent forms but not always with remarks regarding the concomittant

heart rate or about its presence together with normal conduction on the same ECG tracings. In a few cases of intermittent blocks it was specifically mentioned a non-RD feature ignoring the fact that any critical changes smaller than 10 ms of SRCs leading to block are very difficult if not impossible to measure on ECG recordings at their standard speed of 25 mm/s. More logical terms used for a RD block are tachycardia (or acceleration) induced block (or aberrancy), bradycardia (or acceleration) induced block (or aberrancy) and rate related block [29-32]. The tachycardia and bradycardia terms are not always appropriate because a RD block appears in SR during its rate variability (as stated above) while acceleration or deceleration are acceptable. Acceleration dependent block denominates a specific form of RD block which appears in diseased hearts with a different mechanism while the term deceleration dependent blocks, instead of phase-4 RD blocks, is much less used [32]. A RD block is not equal to “aberrancy” (to avoid confusion with the Ashman phenomenon), a term which may alternatively be used in supraventricular arrhythmias when a specific relationship between the shorter cardiac cycles and the refractoriness of the intraventricular conduction system is not defined and it cannot be demonstrated at the time of observation. Contrary to the name block, the word “aberrancy” is not applicable in AVBs. The designation as “dependent” for the block is a feature that seems less aggressive than “induced” but it is really stronger than “related” in terms of causality.

A heart block may also be present at supraventricular levels starting at the connection of the sinoatrial (SA) node with the atrial tissue (SA exit block), within the atrial tissue (intraatrial block), between the two atria (inter-atrial block), and then further on between the atria and the AVN [33-35]. The SA exit block can be seen on surface ECG only if it is of grade II or higher, based on a classification similar to that of AV blocks. Its possible rate dependence was documented in some electrophysiological studies as Wenckebach or 2:1 SA block [36, 37] and was suggested in a clinical report where episodes of Wenckebach SA block were observed more frequently during daytime when heart rates are higher than

11

12

RATE-DEPENDENT BLOCKS

overnight in patients with structural heart disease [38]. Additionally, it was proved that, in a case with 2:1 SA block, a vagal stimulation (carotid sinus massage) may lead to a temporary normalization of SR [39]. A temporary RD complete SA exit block is also possible in rare clinical cases and it was observed after high right atrium overdriving stimulation in electrophysiologic studies of sinus node function. The rate of this overdrive pacing was only slightly higher than that of the basic SR. The atrial tissues lack specialized fibers and impulses are conducted via preferential pathways called tracts which have unclear individual specific contribution to P wave morphol-

FIGURE 1.2. A laddergram of various conduction ratios with alternate inferior Wenckebach periods

FIGURE 1.3. A laddergram of various conduction ratios with alternate superior Wenckebach periods

ogy. Therefore, intra-atrial blocks do not have accepted definitive criteria for diagnosis and there is no proof for their possible rate dependence. An inter-atrial block called Bachmannâ&#x20AC;&#x2122;s bundle block (baptised as Bayes de Luna syndrome by some authors) has clearly established ECG morphologic criteria and is considered a risk factor for supraventricular tachyarrhythmias [40-42]. This type of block may be a RD one because, in a few cases, it was intermittent (but not on the same ECG tracing) with only one case showing a normal P wave after a post-extrasystolic pause [43], a so-called Chung phenomenon. An altered atrio-AVN conduction, seen only on rare invasive ECG recordings, was not proved to depend on heart rate. Generally, with the exception of the well documented RD SA blocks, none of the altered conduction varieties above the AVN was specifically studied in relation to heart rate.

The formulae and conditions presented above for all phase 3 RD blocks are certainly applicable for at least one beat in any case of a grade II atrioventricular block (AVB) but with a limitation: AVBs are preferably defined as such only when the atrial rhythm is SR or another rate equivalent regular rhythm.

In regular supraventricular arrhythmias as atrial flutter (AFL) and fast atrial tachycardias (AT) the conduction of atrial impulses to ventricles is frequently non 1:1 which is not an AVB but a conduction ratio (CR). With normal intraventricular conduction and a rate-adapted FRP in the AVN, a common CR is 2:1 at atrial rates higher than about 220/min because the SVCs are too short to allow the conduction of every atrial impulse expressed by the formula: short SVCs < normal rate-adapted FRPs. The atrial beats followed by QRS complexes have usually normal F-QRS intervals (or A-QRS in AT) proving that a normal AV conduction is possible.

Sometimes, in relatively rare cases of AFL and fast AT, the CR is not 2:1 but it remains systematic and complicated by the presence of alternating Wenckebach periods (evidenced as group beatings). These alternating Wenckebach periods can be inferior (AIWP - fig. 1.2) or superior (ASWP - fig.

Chapter 1. INTRODUCTION

1.3) resulting from associations of different types of conduction along three functional levels of the AVN [44-46]. Atrial impulses are conducted via the atrio-nodal (AN) level with CRs of 1:1 or 2:1, they enter in the medio-nodal (N) level where the conduction is 1:1 or with Wenckebach periods and finally they reach the nodo-hisian (NH) level where the conduction is again either 1:1 or 2:1. The resulting global CRs in the AVN are expressed by two formulae: (2k +2):k in AIWP (fig. 1.2) and (2k +1):k for ASWP (fig. 1.3) where k is the number of QRS complexes in a group beating and the left part is the number of atrial beats. Exactly as in the 2:1 CR, the first F-QRS intervals (or A-QRS in AT) in each group beating is most frequently normal. As can easily be seen, the two types of complex CRs can be identified by the number of atrial beats which is even in AIWP and odd in ASWP. Both of them are always stable in any given case and do not switch from one to the other. The various CRs seen in such cases appear more frequently after negative chronotropic drugs given for ventricular rate control. If there are no group beatings and the ventricular rates are not fast, the name used for this situation is that of the supraventricular arrhythmia to which the rate designation is added as low or average, but with no mention of a block. In extremely rare cases of AFL, without bundle branch blocks, the association of three levels of different conduction types in the AVN (AN + N + NH) may lead to very low CRs with more complicated formulae for the group beatings.

In all the supraventricular arrhythmias, whether regular or irregular, the surface ECG may show a bundle branch block (BBB) which receives no additional designation if it was previously documented in SR or if it is stably present after the conversion of the arrhythmia. At the moment of its discovery, when it is permanent during the arrhythmia or the data in SR are missing, the BBB is called aberrancy or aberration, as described for the first time by Sir Thomas Lewis in 1910. The same name also applies if this BBB is intermittent in relation to SVC variations, if it disappears after slowing of heart rate with a CSM or after restoration of SR. The last variety is fre-

quently a real RD-BBB to be disclosed by active interventions to increase the SR rate as closely as possible to the heart rate during the arrhythmia. The causes of a BBB during any regular supraventricular tachycardia may include, apart from a phase-3 block, a different mechanism consisting of the transseptal concealed retrograde activation of a bundle branch from the contralateral one. Sometimes, an intraventricular conduction defect may appear in SR after an occasional atrial premature beat that is conducted with a BBB (most often a right BBB) which is known as the Ashman (or Gouaux-Ashman) phenomenon [47], typically appearing due to a longshort cycle relationship. It is clear that such an event cannot be called RD block because this is seen after only one short atrial cycle (rarely more [32]) and no heart rate is involved. In exceptionally rare ECG cases, such as the syndrome of variable intraventricular conduction, a few atrial premature beats appear with relatively fixed coupling intervals and they are either blocked in the AVN, or conducted normally or with almost all possible single or double intraventricular BBBs. Such cases may have variable intraventricular FRPs which are not fully explained and they may be caused by an unstable ventricular repolarization due to autonomic tone lability common in young healthy people.

During atrial fibrillation (AF), only a part of the very fast and irregular atrial impulses are conducted to ventricles, but this is never considered a real AV block and it does not depend on atrial cycles. The ventricular rate in AF is always irregularly irregular with largely variable cycles depending on how strong is the protective action of the AVN. As a result, the intraventricular conduction in the bundle branches depends only on the VCs which modulate the FRPs in complex ways (both beat-to-beat and long-term). When an occasional wide QRS beat comes after a sequence of long-short VCs it is an Ashman phenomenon. Many patients with AF may have associated background pathology with abnormal FRPs of the bundle branches so that the formula of the mismatch leading to a BBB is short VCs < long FRPs. Such situations are also considered RD blocks because they share many simi-

13

14

RATE-DEPENDENT BLOCKS

larities with what happens in SR (as in fig. 1.1). Depending on the comparative values of each side of this formula, a BBB seems permanent when all the VCs are very short and the RD can be disclosed only after slowing of heart rates by a CSM or after negative chronotropic therapies. If the average VCs values are equal to or longer than the long FRPs, the ECG shows QRS complexes that are either normal or conducted with a BBB. The reverse is also true when a phase 4 BBB occurrence is related to long VCs [28]. Occasionally on the same tracing, the same BBB can be either phase 3 dependent (i.e. with short VCs) or phase 4 dependent (i.e. with long VCs). Most frequently, the great majority of QRS complexes are normal and only a few are wide after very short VCs and this calls for a differential diagnosis with ventricular premature beats. When a RD-BBB is present during AF, it may persist after conversion to SR of the arrhythmia due to very long FRPs. In cases with a normal physiology of the conduction system, the global FRP of the AVN is usually longer than any FRP of the bundle branches and a seemingly stable intraventricular block only during AF is very rare.

In summary, an altered conduction anywhere in the heart that appears or disappears during cardiac cycle variations, both at rest or after exercise, during SR or atrial arrhythmias, is a RD block. This name is not used when a variable conduction over an accessory pathway is related to heart rate in patients with Wolff-Parkinson-White syndrome. In cases with fast atrial rhythms, when the ECG shows a persistent intraventricular conduction defect, this is temporarily called aberrancy (instead of block) which may later be proved to be either a permanent block or a RD one - once SR is restored.

The term aberrancy is a definitive name used only for the Ashman phenomenon. A non 1:1 AV conduction in regular supraventricular arrhythmias is a conduction ratio and not an AVB when the relationships between the atrial waves and QRS complexes are either 2:1 or other more complex ratios resulting from group beatings. If ventricular rhythms are bradycardic in any instance of fast supraventricular arrhythmias, no AVB is ever mentioned and the heart rate is simply defined as slow by comparison with normal SR.

References 1.

2.

3.

4.

5.

Lewis T: An address on certain physical signs of myocardial involvement. Br Med J 1913; 1 (2723): 484-489 Danielopolu D, Danulescu V.: Lesions latentes des branches du faisceau auriculo-ventriculaire: Moyens de les deceler. Arch Mal Coeur 1921; 14: 529-540 Baker BM Jr: The effect of cardiac rate and the inhalation of oxygen on transient bundle branch block. Arch Intern Med 1930; 45: 814-822 Herrman G, Ashman R: Partial bundle-branch block: Theoretical consideration of transient normal intraventricular conduction in the presence of apparently complete bundle-branch block. Am Heart J 1941; 6: 375-403 Sandberg AA, Wener J, Master AM, Scherlis L: Intermittent and transient bundle branch block: a clinical and electrocardiographic study. Ann Intern Med 1951; 35: 1085-1109

6.

Shern MA, Rytand DA: Intermittent bundlebranch block. Observations with special reference to the critical heart rate. Arch Intern Med 1953; 91: 448-463 7. Singer DH, Lazzara R, Hoffman BF: Interrelationships between automaticity and conduction in Purkinje fibers. Circ Res 1967; 21: 537-558 8. Rosenbaum MB, Elizari MV, Lazzari JO, Halpern S, Nau GJ, Levi RJ: The mechanism of intermittent bundle branch block: Relationship to prolonged recovery, hypopolarization and spontaneous diastolic depolarization. Chest 1973; 63: 666-677.

9. Denes P, Wu D, Dhingra RC, Amat-y-Leon F, Wyndham C, Rosen KM: Electrophysiological observations in patients with rate dependent bundle branch block. Circulation 1975; 51:244-250.

10. Kinoshita S: Variations in the critical cycle length inducing rate dependent bundle branch block.

Am Heart J 1978; 96: 54-61.

11. Chiale PA, Pastori JD, Sanchez RA, Elizari MV, Rosenbaum MB: Contrasting effects of verapamil and procainamide on rate-dependent bundle branch block: pharmacologic evidence for the role of depressed sodium channel responses. J Am Coll Cardiol 1990; 15: 633-639 12. Fisher JD, Aronson RS: Rate-dependent bundle branch block: Occurrence, causes and clinical correlations. J Am Coll Cardiol 1990; 16: 240-243.

13. Issa ZF, Miller JM, Zipes DP: Clinical Arrhythmology and Electrophysiology. A Companion to Braunwald’s Heart Disease. 2nd Ed., Elsevier Saunders, Philadelphia, 2012; pp. 1-9 14. Mirvis DM, Goldberger AL: Electrocardiography.

In Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. DL Mann, DP Zipes, P Libby, RO Bonow eds. 10th Ed., Elsevier Saunders, Philadelphia, 2014; pp. 121-122

Chapter 1. INTRODUCTION

15. Denes P, Wu D, Dhingra R, Pietras RJ, Rosen KM: The effects of cycle length on cardiac refractory periods in man. Circulation 1974; 49: 32-41 16. Grant RP, Tomlinson FB, van Buren JK: Ventricular activation in the pre-excitation syndrome (Wolff-Parkinson-White). Circulation 1958; 18: 355-366 17. Surawicz B, Knilans K: Chou’s Electrocardiography in Clinical Practice. 6th Ed., Saunders Elsevier, Philadelphia, 2008; pp. 481-508 18. Wellens HJ, Durrer D: Wolff-Parkinson-White syndrome and atrial fibrillation. Relation between refractory period of accessory pathway and ventricular rate during atrial fibrillation. Am J Cardiol 1974; 34: 777-782 19. Pappone C, Santinelli V, Rosanio S, Vicedomini G, Nardi S, Pappone A, Tortoriello V, Manguso F, Mazzone P, Gulletta S, Oreto G, Alfieri O: Usefulness of invasive electrophysiological testing to stratify the risk of arrhythmic events in asymptomatic patients with Wolff-ParkinsonWhite pattern: results from a large prospective long-term follow-up study. J Am Coll Cardiol 2003; 41: 239-244 20. Klein GJ, Yee R, Sharma AD: Longitudinal electrophysiologic assessment of asymptomatic patients with the WPW electrocardiographic pattern. N Engl J Med 1989; 320: 1229-1233 21. Sharma AD, Yee R, Guiraudon G, Klein GJ: Sensitivity and specificity of invasive and noninvasive testing for risk of sudden death in Wolff-Parkinson-White syndrome. J Am Coll Cardiol 1987; 10: 373-381 22. Beckman KJ, Gallastegui JL, Bauman JL, Hariman RJ: The predictive value of electrophysiologic studies in untreated patients with WolffParkinson-White syndrome. J Am Coll Cardiol 1990; 15: 640-647 23. Ortega-Canicer J, Benezet-Penaranda J: Bradycardia-dependent block in the accessory pathway in a patient with alternans Wolff-Parkinson-White syndrome. J Electrocardiol 2006; 39: 419-420.

24. Fujiki A, Tani M, Mizumaki K, Yoshida S, Sasayama S: Rate-dependent accessory pathway conduction due to phase 3 and phase 4 block. J Electrocardiol 1992; 25: 25-31

25. Kinoshita S, Katoh T: Apparent bradycardiadependent block in the accessory pathway in intermittent Wolff-Parkinson-White syndrome. J Electrocardiol 1998; 31: 151-153 26. Bissett JK, Kane JJ, De Soyza N, Murphy ML: Electrophysiological significance of rapid atrial pacing as a test of atrioventricular conduction.

Cardiovasc Res 1975; 9: 593-599 27. Levy S: Invasive electrophysiologic studies.

Technical aspects and definition of common electrophysiologic variables and their use in the study of antiarrhythmic agents. In: Cardiac Arrhythmias. From diagnosis to therapy. Levy S, Scheinman M, eds. Futura Publishing Co., Mount Kisco, New York, 1984, pp. 57-72 28. Vesell H: Critical rates in ventricular conduction: Unstable branch block. Am J Med Sci 1941; 202: 198-206 29. Fisch C, Zipes DP, McHenry PL: Rate dependent aberrancy. Circulation 1973; 48: 714-724 30. Cannom DS, Goodman DJ, Harrison DC: Electrophysiologicalal studies in patients with rate related intermittent left bundle-branch block. Br Heart J 1974; 36: 653-659 31. Chugh SN: Textbook of Clinical Electrocardiography. 3rd Ed.; Jaypee Brothers Medical Publishers (P) Ltd., New Delhi, 2012; pp.

467-471 32. Issa ZF, Miller JM, Ziper DP: Clinical Arrhythmology and Electrophysiology. A Companion to Braunwald’s Heart Disease. 2nd Ed., Elsevier Saunders, Philadelphia, 2012; pp. 194-198 33. Bradley SM, Marriott HJL: Intra-atrial block.

Circulation 1956; 14: 1073-1078 34. Cohen J, Scherf D: Complete interatrial and intra-atrial block (atrial dissociation). Am Heart J 1965; 70: 23-24 35. Gomes JAC, Kang PS, El-Sherif N: The sinus node electrogram in patients with and without sick sinus syndrome: Techniques and correlation between directly measured and indirectly estimated sinoatrial conduction time. Circulation 1982; 66: 864-873 36. Reiffel JA, Bigger T Jr, Konstam MA: The relationship between sinoatrial conduction time and sinus cycle length during spontaneous sinus arrhythmia in adults. Circulation 1974; 50: 924-934

15

37. Gomes JAC, Hariman RI, Chowdry IA: New applications of direct sinus node recordings in man: assessment of sinus node recovery time.

Circulation 1984; 70: 663-671 38. Kramarz E & Makowski K: Clinical significance of second degree Wenckebach type sinoatrial block identified during Holter monitoring in patients with symptoms suggestive of arrhythmia. Europace 2015; 17: 123-130 39. Littman L, Tenczer J, Svenson RH: Two-to-one sinoatrial block. Normalization by carotid massage. Chest 1988; 94: 650-652 40. Bayés de Luna A, Platonov P, Cosio FG, Cygankiewicz I, Pastore C, Baranowski R, Bayés-Genis A, Guindo J, Viñolas X, Garcia-Niebla J, Barbosa R, Stern S, Spodick D: Interatrial blocks. A separate entity from left atrial enlargement: a consensus report. J Electrocardiol 2012; 45: 445-451 41. Bayes de Luna A: The long journey to interatrial block discovery. Proceedings of the 41st International Congress of Electrocardiology.

June 4-7, 2014, Bratislava, Slovakia; pp. 31-42 42. Conde D, Baranchuk A, Bayes de Luna A: Advanced interatrial block as a substrate of supraventricular tachyarrhythmias: a well recognized syndrome. J Electrocardiol 2015; 48: 135-140 43. Bayes de Luna A, Fort de Ribot R, Trilla E, Julia J, Garcia J, Sadurni J, Riba J, Sagues F: Electrocardiographic and vectorcardiographic study of interatrial conduction disturbances with left atrial retrograde activation. J Electrocardiol 1985; 18: 1-14 44. Kosowsky BD, Latif P, Radoff AM: Multilevel atrioventricular block. Circulation 1976; 54: 914-921 45. Slama R, Leclercq JF, Rosengarten M, Coumel Ph, Bouvrain Y: Multilevel block in the atrioventricular node during atrial tachycardia and flutter alternating with Wenckebach phenomenon. Br Heart J 1979; 42: 463-470 46. Meijler FL, Janse MJ: Morphology and electrophysiology of the mammalian atrioventricular node. Physiol Rev 1988; 68: 608-647 47. Gouaux JL, Ashman R: Auricular fibrillation with aberration stimulating ventricular paroxysmal tachycardia. Am Heart J 1947; 34: 366-373

CHAPTER

2

Clinical electrophysiology of rate-dependent blocks 2.1. A simplified presentation of cardiac electrophysiology for the clinician The first relationship between heart rate and various cardiac phenomena revealed by ECG appeared during the first decades of the 20th century. The QT interval as a measure of ventricular repolarization was correlated with heart rate, translated into RR intervals, in the famous formulae of Bazett (still largely used in our days) and Fredericia, both published in 1920. An advanced approach came later with detailed analyses of electrical characteristics of the specialized conduction system which are not visible or expressed on surface ECGs [1, 2]. Each structure belonging to this specific system has a different waveform of the action potential (AP) which results from complex, nonlinear and rate-dependent (RD) interactions between diverse modulating factors (inward and outward Na+, K+ and Ca++ ion currents, membrane potential levels and ionic environment of the cells)[3]. A nonspecific general AP representation (fig. 2.1), close to that of the Purkinje cells fast type, underlines the periods when an impulse is blocked or conducted depending on the moment of its arrival in time [4, 5]. The phase of supernormal conduction, when a stimulus of a weaker than normal strength may result in a response, was experimentally observed in Purkinje fibers but not in the His bundle or in ventricular muscle fibers and it is not

FIGURE 2.1. The general nonspecific representation of an action potential. ARP = absolute refractory period; ERP = effective refractory period (ends at about – 25 mV); FRP = functional refractory period; RRP = relative refractory period (ends at about – 70 mV, close to the threshold potential). For the purpose of clarity, the slope of phase 3 is less steeper than in reality 17

18

RATE-DEPENDENT BLOCKS

represented because it is not involved in any RD block. The influence of heart rate on impulse conduction begins with the relationship between phase 0 of the AP and the maximum diastolic potential (MDP) reached after the end of each cardiac cycle. More negative MDP values lead to higher speeds of voltage rise (V/s, fig. 2.2), steeper slopes of depolarization expressed as high (dV/dt)max, and greater upstroke amplitudes expressed as Vmax of phase 0 followed by a greater speed of conduction [6-8]. The reverse influence is also true: less negative MDP values lead to slower conduction due to reduced (dV/dt)max and smaller Vmax. After phase 0 and related to the magnitude of positive values of transmembrane potential reached with Vmax, a great number of ion channels, currents and pumps start the complicated process of repolarization.

The factors involved in this process are voltage-gated or voltage-dependent (i.e. start or open and stop or close at relatively fixed voltage levels), time-dependent (i.e. act in sequences for a limited time at different moments of the AP) or

FIGURE 2.2. Relationships between phase 0 potential rise (V/s) and maximum diastolic potential (MDP). The fastest potential rise is produced by MDP values of â&#x20AC;&#x201C;80 mV to â&#x20AC;&#x201C;90 mV (normal for healthy Purkinje cells). Drawn and simplified from [6-8].

both and act in concert to decrease the transmembrane potential down to the resting MDP [9, 10]. It means that, with increasing negativity of voltage, at a given moment, the types and the number of modulating factors change. It is logical to assume that, because of interdependency of all these phenomena, their duration varies according to heart rate. All the components of the specialized conduction system also have a pacemaking potential (automaticity), stronger in the AVN and weaker in the His-Purkinje cells. This property results from the slope of spontaneous diastolic depolarization during phase 4 of the AP which is steeper in the AVN than that in Purkinje fibers (also depicted in fig. 2.1). As a result, without an overdrive suppression induced by the activity of the sinus node, the intrinsic automatic rate of impulse discharge is about 45-50 beats/min (bpm) in the AVN, 40-45 bpm in the His bundle (HB) and the bundle branches (BB), and 30-40 bpm in the Purkinje cells. At the final ventricular myocardial levels the APs have different shapes and durations across the myocardium, with almost no slow diastolic depolarization but with the same refractory periods which are seen by summation as the repolarization phase on surface ECG tracings (fig.

2.3). It is worth mentioning that in the AVN both the pacemaking activity and impulse conduction are strongly influenced by the autonomic system [11].

The refractory period is grossly divided into 2 parts (fig.

2.1): the absolute refractory period (ARP) and the relative refractory period (RRP). The ARP in fig. 2.1 and fig. 2.3 is defined as the total time of phases 1 and 2 when all the Na+ channels are closed and therefore no impulse of any strength can elicit a response. A more detailed functional division depends on how the membrane responds to the impulses that come after phase 0 at various moments in time. The effective refractory period (ERP) which is measured together with ARP during invasive electrophysiologic studies is a time when an induced depolarization can be observed but the strength of electric stimuli introduced after 8-10 fixed pacing cycles is the double of a threshold value for an impulse to elicit any response â&#x20AC;&#x201C; a non-physiologic intensity [12-14]. The duration of ERP is not always exactly defined in milliseconds

Chapter 2. CLINICAL ELECTROPHYSIOLOGY OF RATE-DEPENDENT BLOCKS

During the RRP, when progressively more Na+ channels become open, all the normal impulse can be conducted but with lower speeds to generate an AP. Normally the RRP is very short and the slope of phase 3 is very steep but in diseased hearts it may be longer due to slower repolarization.

Any impulse coming during this period, when the transmembrane potential is insufficiently low, would generate an AP with smaller (dV/dt)max and lower Vmax (fig. 2.4) which means slower conduction [15, 16]. With discrete variability of consecutive SRCs, the conduction of impulses over a diseased BB may lead to variable width of the ventricular complexes. This type of variable intraventricular conduction is rarely seen if a RD bundle branch block (BBB) is absent when SRCs are longer than the FRP of that BB. With discretely shorter and shorter SRCs, when impulses are conducted earlier and earlier during the RRP, the QRS morphology is slowly and beatto-beat gradually changing from normal to that of a BBB [17].

FIGURE 2.3. A general aspect of the left ventricular myocardium action potential corresponding to a single beat ECG morphology in a peripheral lead. This aspect results from sumation of diďŹ&#x20AC;erent shapes of the conventional transversal levels of the myocardium (epicardial, mid-ventricular and endocardial)

(ms) and may be related to the fact that during ERP progressively more Na+ channels start to open and an impulse strong enough may lead to some local activity as an electrotonic potential or a non-propagated AP. The third term used is the functional refractory period (FRP), a physiologic time period that is longer than ERP; it is defined as the shortest cardiac cycle that allows propagation or conduction of stimuli of normal physiological strength, i.e. atrial impulses. For clinical practice, the best option is to use FRP which is much easier to understand and it is the most appropriate for surface ECG interpretation and/or analysis in order to avoid any confusion between the three terms.

FIGURE 2.4. Variable phase 0 slopes with smaller (dV/dt)tmax and lower Vmax for depolarizations (a, b and c) induced by impulses coming variously earlier during a longer RRP (open circles) of an action potential with longer duration and less steeper phase 3. A very early impulse (black circle) is blocked and does not generate any changes of membrane potential but an impulse coming discretely later (dark pink circle) produces a small local depolarization that further delays the repolarization (derived from [17])

19

20

RATE-DEPENDENT BLOCKS

2.2. General mechanisms of rate-dependent blocks The conduction of electric impulses from the atrial level to ventricles in normal hearts is governed by complex electrophysiologic relationships with heart rate. In both normal and diseased hearts the most easily understandable mechanisms of RD blocks are based on abnormal phase 3 and phase 4 of the AP. The phase 3 block is the most common one, the simplest and the first observed variety of RD blocks reported as a latent, temporary, transient, intermittent or unstable block in contrast with the permanent or stable forms of intraventricular blocks [18-26]. It appears when SRCs become shorter than the FRPs at a certain site of the specialized conduction system, most frequently at the level of BBs (fig. 2.5). After a modest but critical shortening of SRCs, atrial impulses arrive below the HB when one of the BBs is refractory (incompletely repolarized) and they are blocked. That still functional BB is depolarized from the contralateral BB with a small delay and the block is perpetuated as long as the SRCs remain shorter. It must be stressed that the critical difference between the SRCs of normally conducted atrial impulses and those which initiate the block may be very small, often smaller than

10 ms (an increase in heart rate of 1 bpm). On surface ECG this event is seen as P waves followed by BB blocks with unchanged PR intervals (see section 3.3. in Chapter 3).

The FRPs of BBs change after the immediately preceding cardiac cycle and gradually shorten when the heart rates increase [27-29] but there is a difference between the slope of this rate adaptation of the two BBs which is steeper for the RBB than for the main trunk of LBB (fig. 2.6) [29]. At rest, the magnitude order of FRP values is RBB > LBB ≥ AVN >> HP system. As a result, at normal average SRCs, the prevalence of RBBB is higher than that of LBBB in the general population, in apparently healthy individuals and in the young [30-32]. In diseased hearts and with increasing age, the quasilinear relationship between the FRP of LBB with SRCs is shifted upwards because of left ventricular ischemia, hypertrophy or dilatation which leads to a higher incidence of LBBB (and especially of RD-LBBB) [17, 33, 34]. In spontaneous intermittent RD-BBBs the critical cycles at the onset of blocks on long ECG recordings are constantly shorter than the first cycles when normal intraventricular conduction returns [28, 35, 36]. This phenomenon is called “hysteresis” and has values of 50 ms or greater depending on the background pathology. It results from a delayed concealed transseptal

FIGURE 2.5. The general mechanism of phase 3 RD blocks characteristic for BBBs. The block is favored by a mismatch between an abnormally long FRP and normal but shorter SRCs and leads to a delayed action potential of the involved BB (pink circles). This initially blocked BB is still depolarized from contralateral transmission of impulses but a little later and, with the already long FRP, perpetuates the RD-BBB

Chapter 2. CLINICAL ELECTROPHYSIOLOGY OF RATE-DEPENDENT BLOCKS

FIGURE 2.6. DiďŹ&#x20AC;erences between the slopes of FRP adaptation to SRCs of LBB and RBB (modified from [29])

cretely before the end of FRP then a possible local subthreshold depolarization may further delay repolarization resulting in an even longer FRP that increases the value of hysteresis (x depolarization in fig. 2.4).

When the site of the long FRP is in the AVN then some P waves are blocked, most often with a 2:1 or with other types of atrioventricular block (AVB â&#x20AC;&#x201C; see sections 4.2 and 4.3 in Chapter 4). In rare cases, since the intraventricular conduction is accepted of having three fascicles, if more than one fascicle has a longer FRP then a variety of RD blocks may appear with different shorter SRCs or PP intervals on ECG tracings (fig. 2.8). The spontaneous RD-AVBs have been much less studied and the hysteresis phenomenon is practically impossible but may theoretically result from a lower excitability of the AVN even after its longer but complete repolarization [27].

FIGURE 2.7. Schematic representation of delayed concealed transseptal activation of the left bundle branch (LBB) below the site of RD block (in pink) from the right bundle branch (RBB) leading to further prolongation of FRP in the LBB which explains the hysteresis phenomenon

right-to-left activation in the case of LBBB (fig. 2.7) or from normal left-to-right activation during RBBB [37]. If the interventricular septum is not electrically functional, this delayed activation of BB area from the opposite ventricle may come even later because the impulses are transmitted over a longer way through the myocardial tissue. Both hysteresis mechanisms lead to a longer FRP of the RD site of BB block and explain why the recovery of normal conduction needs a much longer SRC. When the blocked impulse arrives dis-

FIGURE 2.8. Mechanisms of various phase 3 single or associated intraventricular blocks depending on SRCs based on the conventional concept of trifascicular conduction. The FRP of each fascicle must be much longer than normal

21

22

RATE-DEPENDENT BLOCKS

A very simple example of RD-AVB is the Wenckebach periodicity (or Mobitz type I grade II AVB) which appears because either the SRCs are too short or the FRP of the AVN is too long. The characteristic progressive lengthening of PR intervals further delays the nodal recovery of excitability until a single atrial impulse is blocked [38]. The same phenomenon is observed during atrial pacing with decreasing cycle lengths leading to the Wenckebach point with normal FRP of the AVN. In cases with atypical Wenckebach periods usually longer than 6:5 the duration of PR intervals increase and decrease in correlation with variations of SRCs. The normal shortening of FRP from rate adaptation is much weaker in the AVN than in the BBBs and, with increasing atrial rates, the intraventricular conduction remains unaltered.

A phase 4 block, also called bradycardia-dependent or deceleration-dependent block, is defined as no conduction of impulses that come after long preceding cycles at a time when the FRP of a BB has ended much earlier, with recovery of normal conduction after critically shorter cycles [39, 40]. This type of RD block is less often observed in clinical practice as a spontaneous phenomenon compared to phase 3 blocks and it appears to have been suggested first in 1915 as a vagal effect

by F.N. Wilson [41]. It was well documented later both in AF

by H. Vesell in 1941 [22] and in SR by W. Dressler in 1959 [42]. The established criteria for a phase 4 RD BBB (table 2.I)[43] must be present whatever the moment of ECG recordings (better and more convincing on the same tracing).

TABLE 2.I. Criteria identifying a phase 4 BBB (updated from [43]) 1. The beats displaying wide QRS complexes must result from atrial

impulses conducted to the ventricles along the normal pathways.

The P waves must precede the QRS complexes at reasonable (and stable) PR intervals.

2. Atrial fibrillation or atrial flutter must not be present for in such cases a ventricular escape beat after long cycles can be eliminated only if the same wide QRS morphology also appears after shorter cycles (as a phase 3 block).

3. The phenomenon must appear in at least two successive beats.

4. Incomplete bilateral BBB with intraventricular conduction varying from normal to LBBB or RBBB must be excluded.

5. The concept of supernormal conduction must not apply to the normally conducted beats.

Its mechanisms are still a matter of some debate but the main electrophysiological alteration seem to be an increased slope of the spontaneous diastolic depolarization in phase 4 of the AP. This phenomenon induced by the slow heart rates is not at all sufficient to explain the block and it generates other factors: lower (dV/dt)max and long FRPs (fig. 2.9)[4447]. The associated hypopolarization of the cell membrane and the shifted Vthreshold as contributors to phase 4 block appear only in diseased hearts and are expressed most frequently as a LBBB because of the properties of the left ventricular conduction system which has a steeper phase 4 slope and an increased susceptibility to damages induced by ischemia or hypertrophy. The higher left ventricular volume/dilatation

FIGURE 2.9. The more complicated mechanism of phase 4 block. All the altered features of action potentials are depicted and described in pink (details in text)

Chapter 2. CLINICAL ELECTROPHYSIOLOGY OF RATE-DEPENDENT BLOCKS

during longer diastoles with greater stretching of the LBB may also play a certain role. A phase 4 block disappears with the first critically shorter SRC when the level of membrane potential is more negative and the diastolic depolarization is very small leading to a greater (dV/dt)max, and the hypopolarization and the shifted Vthreshold no longer count but the FRP remains longer than normal. At the level of BBs, this longer FRP frequently if not always determines the associated presence of a phase 3 block with a window of normal intraventricular conduction between the slower and faster heart rates accompanied by BBBs [40, 43, 48-50].

The appearance of a phase 4 RD block seems impossible in grade II AVBs and was speculatively involved in rare cases of paroxismal AVB [51, 52]. When such a block is seen at rest with slow heart rates but disappears with exercise then most probably its explanation is an increased vagal tone that impairs AVN conduction and not a phase 4 block.

Together with phase 3 and phase 4 blocks, other mechanisms are important in generation of RD blocks especially in diseased hearts. These subtle mechanisms are not visible on standard surface ECG tracings but were convincingly demonstrated in experimental and clinical electrophysiologic studies [46].

The acceleration dependent block (or aberration) is electrophysiologically different from phase 3 block and results from a specific phenomenon: post repolarization refractoriness (PRR). This PRR was first described for the AVN by T. Lewis and A.M. Masters in 1925 (it was named “fatigue”), then it was later demonstrated in animal experiments [47, 53] and suspected in patients with BBBs [17, 54, 55]. Clinical electrophysiologic studies in cases with documented RD BBBs have proved that the acceleration of heart rate with atrial pacing was not followed by the expected reduction of refractoriness of the diseased bundle branches as an adaptation to rate [28, 56]. The result of persistently shorter atrial cycle lengths was in fact an increase in refractoriness of the intraventricular conduction system. This behaviour, that is named PRR, was observed in the majority of patients with RD BBBs in direct relationships with the magnitude and du-

ration of heart rate acceleration [56]. In this last study it was also noticed a good correlation of PRR dimension with a more advanced disease of the bundle branches. Typically, PRR appears after several accelerated regular beats or after a gradual and slowly shortening of SRCs [47], the reason why PRR may be called “fatigue”. The SRC at the onset of BBB is only discretely shorter than the preceding one with a normal QRS, often by less than 5 ms. In some of the cases, after a variably great number of accelerated beats, the BBB may disappear because of a delayed adaptation of refractoriness to rate, a phenomenon called “restitution” [47]. For common cardiology practice it is useful to add that the PRR is induced or augmented by some antiarrhythmic drugs (sodium channel blocking agents)[56-58].

From a clinical point of view, all these data suggest with a high probability that the mechanism of RD BBBs appearing after progressively accelerated heart rates (but not to the level of tachycardia) in many of the cases with diseased hearts is PRR and not a phase 3 block; at the same time, the presence of PRR can be considered a good predictor of a definitive and stable BBB. The concealed transseptal conduction (CTC) of impulses arriving at intraventricular main bundle branches is a mechanism that explains the perpetuation of aberant conduction mainly during regular supraventricular tachycardias but also during AF [47]. This phenomenon may also be the underlying cause of BBB persistence after acceleration dependent block (or aberration). A similar mechanisms of CTC in SR may result from small differences between the refractoriness of LBB and that of RBB. When sinus cycles decrease for a couple of beats (not a persistent acceleration – see above), these differences may increase and one of the BBs becomes refractory for one beat because of its invasion by an impulse coming via CTC from the contralateral BB. After this first beat with a BBB, the following QRS complexes remain wide from the same CTC until the sinus cycle becomes much longer than the critical value at the onset of the conduction defect [59, 60](discussed above with the “hysteresis” effect and depicted in fig. 2.7 for LBBB). Thus, only the first wide ven-

23

24

RATE-DEPENDENT BLOCKS

tricular beat may be explained by a discrete difference in refractoriness of the BBs while the rest of QRS complexes with BBB result from CTC. The same phenomenon of CTC is also present in some cases of alternation of aberation [47, 61].

In Chapters 3 and 4, these two last mechanisms are neither mentioned nor correlated with changes of ECG tracings which present RD blocks in relation to heart rate. The reason is that, whatever the mechanism of RD blocks, active heart rate modulations may convincingly reveal that any given block may not be permanent.

2.3. Disclosure of rate-dependent blocks by heart rate modulations Current practice of clinical electrocardiography routinely involves technicians and nurses who are much less trained than physicians to interpret or understand ECG recordings.

This leads to what can be called passive electrocardiography which does not reveal the whole picture of abnormal electric cardiac phenomena. The need for an active electrocardiography, which includes a few simple clinical manoeuvres that, for instance, modulate the heart rate during ECG recordings, is supported by the fact that a conduction block may be a RD one. Pharmacological interventions that increase the heart rate (atropine or isoproterenol and other -adrenergic agonists) were frequently used in historical studies of RD blocks but they are not commonly indicated today for this purpose in clinical practice. The bradycardic agents previously used to decrease the heart rate (veratrum alkaloids and a few others) in suspected phase 3 RD blocks were withdrawn from the market a long time ago while the newer ones (non-DHP calcium channel blockers, central 2-adrenergic receptor agonists, I1-imidazolin receptor agonists and -adrenergic receptor blockers) are not selective for SR slowing, have some undesired effects (not limited to lengthening of AVN conduction) and only a few are injectable. By far, the most logical choice for this purpose would be ivabradine, a drug which has

a specific and highly selective bradycardic effect on sino-atrial node [62, 63], but with no indication for the clinical study of RD blocks. All these pharmacological limitations leave the practitioner with two simple tools for noninvasive heart rate manipulation for the evaluation of suspected RD blocks, one to accelerate the SR with physical efforts and the other one to slow the heart rate by carotid sinus massage (CSM). Both of these clinical interventions that can be included in the concept of active electrocardiography have the significant advantages of physiological actions only and of very short duration of effects.

Although a phase 3 RD block appears with acceleration of heart rate during a physical effort, the standard stress test performed on a treadmill or on a cycle ergometer is never used to disclose a RD-BBB. This variety of block is a rare incidental discovery (see section 3.3 of Chapter 3) and repeated stress tests may be indicated only for the follow up of patients who undergo a cardiac rehabilitation exercise training to treat their angina with a secondary aim to reduce the critical heart rate which leads to a LBBB [64]. A similar attitude might be useful in cases with “painful” RD-LBBBs who systematically do not have coronary heart disease [65]. The presence of critical heart rates lower than 125 bpm at the LBBB onset during a stress test in all the patients with documented ischemic heart disease [66] was not studied in cases with BBBs during fast supraventricular arrhythmias (aberrancy) having normal QRS complexes after the conversion to SR. As a consequence, a stress test milder than standard with the only aim to prove the existence of a RD block, although scientifically provocative, is not indicated in such cases.

The only situation when a mild physical exercise may disclose a RD block is that of a BBB present on the background of slow heart rates. Whatever the atrial rhythm, SR or AF, a certain acceleration of heart rate up to a critical value may result in normalization of the QRS complexes, a fact that proves the phase 4 type of RD-BBB [39, 43, 67]. The exercise intensity that leads to disappearance the BBB is neither standardized, nor specifically defined but it is certainly light and can be done at bed side. A low grade physical exercise can

Chapter 2. CLINICAL ELECTROPHYSIOLOGY OF RATE-DEPENDENT BLOCKS

easily be done in a recumbent position by cycling with the legs in the air or by keeping the legs raised from the bed, unsupported, for a few tens of seconds. Current class III recommendations [68] or contraindications [69] for stress tests are not applicable for lighter physical efforts if some medical common sense limitations are considered (as acute myocardial infarction or unstable angina, severe aortic stenosis, class IV uncontrolled heart failure, acute pulmonary edema, aortic dissection, and acute pulmonary embolism).

It is well documented that in very rare cases an AVB may occur during exercises of normal daily or during a stress test with both baseline normal QRS complexes and mono- or bifascicular BBBs [70-75]. These observations do not suggest that any physical effort may be indicated to disclose a RD. In patients with apparently stable grade II AVBs the behaviour of conduction after exercise is indicative for the block site: if they disappear then the block is most likely located in the AVN while if they worsen the the block is below the AVN [70, 75-77]. This general approach does not involve only a dependence of block on heart rate in the AVN but implies supplimentary autonomic factors. A typical phase 4 RD-AVB located in the AVN, which would be a good indication for a light exercise to disclose it (exactly like in vagally induced cases), is most probably impossible or, at best, exceptionally rare.

From the clinical vagal stimulation manoeuvres still currently in use, the old Valsalva manoeuvre is less preferable because it needs a very good cooperation with the patient which is rarely satisfactory but mostly because its intensity of effect is impossible to control. The best method is the carotid sinus massage (CSM) which depends entirely on the knowledge and practical training of the operator.

The CSM should always be performed in a setting having all the facilities of intensive care under continuous 12 lead ECG surveillance (or preferable recording) and blood pressure monitoring. A thorough clinical examination of the patient before the procedure is crucial in establishing if the CSM can be done or not according to the common contraindications (table 2.II)[78]. This evaluation must mainly prove

that both carotid arteries are pulsatile without any murmur and, on ultrasound examination, plaques are absent or minimal and there is no significant carotid stenosis. Before the manoeuvre the patient must give a witnessed (or better written in some countries) informed consent after receiving a good set of data about the procedure and its possible effects.

The CSM is done with the patient in supine position with the head in hyperextension and slightly turned away from the side to be used for the manoeuvre. The carotid sinus location is largely variable [79] and the classical site for CSM application at a level between the angle of the mandible and the superior border of the thyroid cartilage should probably be replaced by the point of maximum carotid artery pulsatility that can be found by gentle palpation. It is possible that even the side for the manoeuvre can be chosen to that carotid artery which has a mildly stronger pulsatility than the other. Because of the unpredictable and variable effect of CSM it is prudent and wise to try first a very light and brief vagal manoeuvre; its heart rate slowing effect decides what pressure strength (at choice, not always standard) and what massage duration (never more than 5 seconds) will be used afterwards at about 1-2 minutes intervals. The standard pressure intensity is generally defined as the amount of pressure needed to indent a tennis ball which may be too strong for the study of possible RD blocks. At least for this purpose, the CSM must only slow significantly the SR with no or as little as possible lengthening of AVN conduction. Although not definitively proved, such an effect can result from a gentler pressure and by choosing the right side for the manoeuvre because the right carotid sinus seems to have a stronger effect on heart rate than the left which has a discretely predominant inhibitory effect on AVN [80-82]. At least for the study of RD blocks it is not logical to perform the manoeuvre in the upright position as sometimes recommended in patients with syncope of unclear origin; moreover, the posture seems to have a controversial influence on the expected vagal effect [83]. If the CSM done on the right side are repeatedly followed by unsatisfactory reductions of heart rate, the common practice is to repeat the procedure on the left side using the

25

26

RATE-DEPENDENT BLOCKS

same technique. It is important to mention that the massage should be done longitudinally on a limited area with a pressure controlled by the finger sensibility of the operator to permit a good repoductibility of later manoeuvres.

TABLE 2.II. Contraindications to CSM [78] 1. Acute myocardial infarction 2. History of stroke or TIA in the last 3 months 3. Carotid artery occlusion or significant (> 50%) stenosis 4. History of malignant arrhythmias (VT or VF) 5. Previous adverse reactions to CSM

With all the precautions taken and the best technique, the bradycardic effect of CSM for the study of RD blocks is not accompanied by vasodepression or other undesired effects. At the same time, whatever the intensity of CSM manoeuvre, its heart rate slowing effect in common practice may be absent or insignificant in some patient series, more often in women and young subjects [84-86]. Many clinical observations suggest that, because of an inherent psychological stress of the manoeuvre, a few patients may have a strong adrenergic reaction which diminishes after repeated CSMs resulting in a better vagal response.

Under the same circumstances the CSM is well tolerated with relatively rare and mild undesired effects (transient cough, dizziness, visual disturbance, and light pain at the massage site)[87, 88] while the extremely severe side effect of ventricular fibrillation is exceptionally rare [89, 90]. Severe asystole is avoided even in patients with a hypersensitive carotid sinus syndrome if the protocol with the preliminary test CSM is respected. The incidence of all neurological complications was reported to be very low (0.17-0.9%) in a large meta-analysis of 5 studies with 10,711 cases [91].

CSM induced reduction of heart rate is a very good tool to disclose intraventricular phase 3 RD blocks [78, 92-94] presented as selected cases in Chapter 3. The question of how many patients with BBBs have RD blocks is not definitively answered; in a very simple study of 105 consecutive patients with LBBB, it was proved by CSM that 28 (26.7%) had a RD

block [95]. The same effect of temporary disappearance of BBBs induced by CSM can also be obtained in some patients with regular supraventricular arrhythmias or with AF [96, 97]. In cases with previously documented BBBs at relatively long SRCs, when the current ECG tracings show narrow QRS complexes, a CSM can reveal exactly the same BBB which certainly is a phase 4 block [92, 97]. Because this mechanism is practically always associated with a phase 3 block, a light bed-side exercise with a mild acceleration of heart rate may also reveal the same BBB. The CSM effect of disclosing a phase 4 BBB might be added to the Massumi criteria presented above (table 2.I). The presence of a LBBB hides the current ECG criteria for the diagnosis of myocardial necrosis whatever its age and a prudent CSM may confirm or exclude an acute myocardial infarction in tachycardic patients with chest pain when troponin tests are not readily available [98, 99].

In patients with RD-LBBB revealed by CSM, when QRS complexes return to normal morphology, the T waves may frequently show deep symmetrical inversions in right and mid-precordial leads raising the question of what is the cause of the abnormal repolarization. The negative T waves with normal QRS complexes are a sign of “cardiac memory” or “Twave memory” that was described in 1969 in patients with right ventricular pacing [100] and later in patients with RDLBBB [101]. A few examples of this phenomenon which does not appear in RD-RBBB are presented in section 3.3 of Chapter 3. The ischemic origin of this T wave pattern was excluded in most of the patients who were studied with coronary angiography [101]. The “T-wave memory” is more prominent immediately after longer times of LBBB persistence at normal heart rates or after a few days of right ventricular pacing and vanishes slowly afterwards when normal intraventricular conduction is restored [102-104]. Sometimes this phenomenon is also seen after the conversion to SR of sustained ventricular tachycardias originated in the right ventricle (mainly idiopathic forms in the young) or after persistent ventricular preexcitation from right sided accessory pathways (most often after antidromic supraventricular

Chapter 2. CLINICAL ELECTROPHYSIOLOGY OF RATE-DEPENDENT BLOCKS

tachycardias). The T wave pattern of “cardiac memory” in contrast to the T waves of coronary artery disease was defined by three criteria: positive T-waves in lead aVL, positive (or isoelectric) T-waves in lead I and maximum T-waves negativity in precordial leads greater than that in lead III [104]; together these criteria yield a 92% sensitivity and a 100% specificity. Another clue for excluding the ischemic origin of the negative T waves of “cardiac memory” comes from their comparative polarity analysis with the QRS complexes showing LBBB in every ECG lead: if there is concordance between the two (i.e. negative T waves correspond to negative QRS complexes with LBBB) then the T waves are “pseudo-primary” or non ischemic; if there is no concordance, then the T waves may be ischemic or primary [105]. The “T-wave memory” in all of the settings mentioned above results from an electro-mechanical remodeling of left ventricular electrical activity after persistent reversal (i.e. from the right side to the left) of normal repolarization direction which is also involved in the long term persistence of RD-LBBB [104-106].

Phase 3 RD-AVBs are rarely seen on standard ECGs [107] or Holter ECG recordings and the temporary recovery of 1:1 AV conduction after CSM were published only as isolated cases [108, 109]. The frequent statement that CSM worsens an incomplete AVB located in the AVN [109] is not always true because, when looking for a RD block, a mild vagal manoeuvre should only reduce SR rate without the slightest inhibition of AV conduction. A relatively large personal series of patients with RD grade II AVBs which transiently disappeared after CSM (18 cases with 2:1 AVB) is presented in Chapter 4.

In current clinical practice the most important justification of any investigation, apart from its academic interest, is the impact of the significant positive results on therapy. At least in patients with LBBB there is a convincing negative effect of this conduction defect on left ventricular ejection fraction due to intraventricular dyssynchrony of contraction

[110-112]. Moreover, in patients with heart failure under optimal medical therapy from the SHIFT trial, the presence of LBBB significantly increased all-cause mortality by 49%, cardiovascular mortality by 49% and heart failure hospitalization by 86% (all P < 0.001)[113]. The authors of this SHIFT trial sub-study on LBBB stated that “the strategy of heart rate lowering with ivabradine is not contraindicated and may be helpful in patients with LBBB” [113]. When a LBBB is proved to be a RD block induced by high heart rates the only specific useful intervention seems to be a cardiac rehabilitation program with exercise training [64] which was not evaluated in a large scale study. If a RD-LBBB is disclosed by CSM a few reports have proved that a -blocker has a nonspecific (it may lengthen AV conduction) good effect at rest even at relatively low doses. Otherwise there is no medication recommended to slow the heart rate maintaining the normal intraventricular conduction although one modern drug, ivabradine, has exactly the desired effect of specific and highly selective inhibition of sino-atrial node without any effect on conduction anywhere in the heart [62, 63]. The effect of this drug was not yet studied in selected patients with RD-LBBB. The presence of a RBBB is not as benign as sometimes considered; in a recent large meta-analysis of 19 cohort studies with 201,437 participants it was shown that the mortality risks were significantly higher in patients with RBBB whatever the direct cause of death. [114]. Similarly with the case of RD-LBBB, no study has been done to evaluate the effect of ivabradine on RD-RBBB. In summary, RD blocks depend on dynamic normal or abnormal electrophysiologic phenomena. This type of altered conduction can result from various mechanisms: phase 3 block, phase 4 block, acceleration dependent block (or aberration) or from concealed transseptal conduction. A RD block, whatever its mechanism, may be disclosed on surface ECG tracings by an active modulation of heart rate.

27

28

RATE-DEPENDENT BLOCKS

References 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

Hoffman BF, Cranefield PF: Electrophysiology of the Heart. McGraw-Hill Book Company, New York. 1960, pp. 1-15 Antzelevitch C, Dumaine R: Electrical heterogeneity in the heart: physiological, pharmacological and clinical implications. In: Handbook of Physiology. The Cardiovascular System. The Heart., Bethesda, MD: Am. Physiol. Soc., 2002, vol. I, sect. 2, pp. 654-692 Rudy Y: Molecular basis of cardiac action potential repolarization. Ann NY Acad Sci 2008; 1123: 113-118 Weidmann S: The electrical constants of Purkinje fibres. J Physiol 1952; 118: 348-360 Surawicz B: Role of potassium channels in cycle length dependent regulation of action potential duration in mammalian cardiac Purkinje and ventricular fibres. Cardiovasc Res 1992; 26: 1021-1029 Weidman S: Effect of the cardiac membrane potential on the rapid availability of the carrying system. J Physiol 1955; 127: 213-224 Hoffman BF, Cranefield PF, Stuckey JH, Amer NS, Cappelletti R, Domingo RT: Direct measurement of conduction velocity on the in situ specialized conduction system of the mammalian heart.

Proc Soc Exp Biol Med 1959; 102: 55-57 Jalife J, Delmar B, Anumonwo J, Berenfeld O, Kalifa J: Basic Cardiac Electrophysiology for the Clinician. 2nd Ed., Wiley-Blackwell, Chichester, West Sussex, UK; 2011, pp. 22-25 Nerbonne JM, Kass RS: Molecular physiology of cardiac repolarization. Physiol Rev 2005; 85: 1205-1253 Grant AO: Cardiac ion channels. Circ Arrhythmia Electrophysiol 2009; 2: 185-194 Malfatto G, Rocchetti M, Zaza A: The role of the autonomic system in rate-dependent repolarization changes. Heart Rhythm 2010; 7: 1700-1703 Issa ZF, Miller JM, Zipes DP: Clinical Arrhythmology and Electrophysiology. A Companion to Braunwald’s Heart Disease. 2nd Ed., Elsevier Saunders, Philadelphia, 2012; pp. 62-91 Wagner GS, Strauss DG: Marriott’s Practical Electrocardiography. 12th Ed. Lippincot Williams & Wilkins, Philadelphia, 2014; pp. 455-476

14. Issa ZF, Miller JM, Zipes DP: Clinical Arrhythmology and Electrophysiology. A Companion to Braunwald’s Heart Disease. 2nd Ed., Elsevier Saunders, Philadelphia, 2012; pp. 36-40 15. Weidmann S: Cardiac cellular electrophysiology: past and present. Experientia 1987; 43: 133-146 16. Singer DH, Ten Eick RE: Pharmacology of cardiac arrhythmias. Prog Cardiovasc Dis 1969; 11: 488-514 17. Fisch C, Zipes DP, McHenry PL: Rate dependent aberrancy. Circulation 1973; 48: 714-724 18. Danielopolu D, Danulescu V.: Lesions latentes des branches du faisceau auriculo-ventriculaire: Moyens de les deceler. Arch Mal Coeur 1921; 14: 529-540 19. Baker BM Jr: The effect of cardiac rate and the inhalation of oxygen on transient bundle branch block. Arch Intern Med 1930; 45: 814-822 20. Herrman G, Ashman R: Partial bundle-branch block: Theoretical consideration of transient normal intraventricular conduction in the presence of apparently complete bundle-branch block. Am Heart J 1931; 6: 375-403 21. Comeau WJ, Hamilton JGM, White PD: Paroxysmal bundle branch block associated with heart disease. Am Heart J 1938; 15: 276-316 22. Vesell H: Critical rates in ventricular conduction.

Unstable bundle branch block. Am J Med Sci 1941; 202: 198-206 23. Eichert H: Transient bundle branch block associated with tachycardia. Am Heart J 1946; 31: 511-518 24. Sandberg AA, Wener J, Master AM, Scherlis L: Intermittent and transient bundle branch block.

Ann Intern Med 1951; 35: 1085-1109 25. Shearn MA, Rytand DA: Intermittent bundle branch block. Observation with special reference to the critical heart rate. Arch Intern Med 1953; 91: 448-463 26. Bauer GE: Transient bundle-branch block.

Circulation 1964; 29: 730-738 27. Denes P, Wu D, Dhingra R Pietras RJ, Rosen KM: The effect of cycle length on cardiac refractory periods in man. Circulation 1974; 49: 32-41 28. Denes P, Wu D, Dhingra RC, Amat-y-Leon F, Wyndham C, Rosen KM: Electrophysiological

29.

30.

31.

32.

33.

34.

35.

36.

37.

38.

39.

observations in patients with rate dependent bundle branch block. Circulation 1975; 51: 244-250 Chilson DA, Zipes DP, Heger JJ, Browne KF, Prystowsky EN: Functional bundle branch block: Discordant response of right and left bundle branches to changes in heart rate. Am J Cardiol 1984; 54: 313-316 Hiss RG, Lamb LE: Electrocardiographic findings in 122,043 individuals. Circulation 1962; 25: 947-961 Rotman M, Triebwasser JH: A clinical and follow-up study of right and left bundle branch block. Circulation 1975; 51: 477-484 Eriksson P, Hansson PO, Eriksson H, Dellborg M: Bundle-branch block in a general male population: the study of men born 1913.

Circulation 1998; 98: 2494-2500 Ostrander LD Jr: Bundle-branch block: an epidemiologic study. Circulation 1964; 30: 872-888 Imanishi R, Seto S, Ichimaru S, Nakashima E, Yano K, Akahoshi M: Prognostic significance of incident complete left bundle branch block observed over a 40-year period. Am J Cardiol 2006; 98: 644-648 Kinoshita S: Variations in the critical cycle length inducing rate dependent bundle branch block.

Am Heart J 1978; 96: 54-61 Fisher JD, Aronson RS: Rate-dependent bundle branch block: Occurrence, causes and clinical correlations. J Am Coll Cardiol 1990; 16: 240-243.

Maury P, Duparc A, Hébrard A, Mondoly P, Rollin A, Delay M: Reverse left septal activation during intermittent left bundle-branch block. Indirect proof for concealed retrograde left bundlebranch activation. J Electrocardiol 2009; 42: 671-673 Jalife J, Delmar B, Anumonwo J, Berenfeld O, Kalifa J: Basic Cardiac Electrophysiology for the Clinician. 2nd Ed., Wiley-Blackwell, Chichester, West Sussex, UK; 2009, pp. 121-151 Vesell H, Lowen G: Bundle branch block on cardiac slowing at a critical slow heart rate. Am Heart J 1963; 66: 329-337

Chapter 2. CLINICAL ELECTROPHYSIOLOGY OF RATE-DEPENDENT BLOCKS

40. Singer DH, Lazzara R, Hoffman BF: Interrelationships between automaticity and conduction in Purkinje fibers. Circ Res 1967; 21: 537-558 41. Wilson FN: A case in which the vagus influenced the form of the ventricular complex of the electrocardiogram. Arch Intern Med 1915; XVI: 1008-1027 42. Dressler W: Transient bundle-branch block occurring during slowing of the heart beat and following gagging. Am Heart J 1959; 58: 760-764 43. Massumi RA: Bradycardia-dependent bundle branch block. A critique and proposed criteria.

Circulation 1968; 38: 1066-1073 44. Gambetta M, Childers RW: Reverse rate related bundle branch block. J Electrocardiol 1973; 6: 153-157 45. Rosenbaum MB, Elizari MV, Chiale P, Levi RJ, Nau GJ, Halpern S, Lazzari JO, Novakoski A: Relationship between increased automaticity and depressed conduction in the main intraventricular conducting fascicles of the human and canine hearts. Circulation 1974; 49: 818-828 46. Issa ZF, Miller JM, Ziper DP: Clinical Arrhythmology and Electrophysiology. A Companion to Braunwald’s Heart Disease. 2nd Ed., Elsevier Saunders, Philadelphia, 2012; pp. 194-198 47. Jalife J, Antzelevitch C, Lamanna V, Moe GK: Rate-dependent changes in excitability of depressed cardiac purkinje fibers as a mechanism of intermittent bundle branch block.

Circulation 1983; 67: 912-922 48. Rosenbaum MB, Elizari MV, Lazzari JO, Halpern MS, Nau GJ, Levi RJ: Mechanism of intermittent bundle branch block: Relationship to prolonged recovery, hypopolarization and spontaneous diastolic depolarization. Chest 1973; 63: 666-677 49. Al Hashimi HMM, van Es AJJ, Szili-Torok T, Gardien M, Molhoek GP, Verhorst PMJ: Coexistence of a bradycardia- and tachycardiadependent bundle branch block. Neth Heart J 2004; 12: 226-229 50. Jurado-Roman A, Jimenez-Jaimes J, GonzalezMansilla A, de Dios-Perezi S, Martin-Asenjo R, Arribas-Ynsaurriaga F: Rate-dependent bundle branch block: Not only phase 3 exists.

Rev Argent Cardiol 2013; 81: 245-247

51. Shohat-Zxabarski R, Lakobishvilli Z, Kusniec J, Mazur A, Strasberg B: Paroxysmal atrioventricular block: clinical experience with 20 patients.

Int J Cardiol 2004; 97: 399-405.

52. Lee S, Wellens HJ, Josephson ME: Paroxysmal atrioventricular block. Heart Rhythm 2009; 6: 1229-1234 53. Davidenko JM, Antzelevitch C: Electrophysiological mechanisms underlying rate-dependent changes of refractoriness in normal and segmentally depressed canine Purkinje fibers.

The characteristics of post-repolarization refractoriness. Circ Res 1986; 58: 257-268 54. Wald RW, Waxman MB: Case report: depression of distal AV conduction following ventricular pacing. PACE 1981; 4: 84-88 55. Fisch C: Bundle branch block after ventricular tachycardia: a manifestation of “fatigue” or “overdrive suppression”. J Am Coll Cardiol 1984; 3: 1562-1564 56. Chiale PA, Sanchez RA, Franco DA, Elizari MV, Rosenbaum MB: Overdrive prolongation of refractoriness and fatigue in the early stages of human bundle branch disease. J Am Coll Cardiol 1994; 23: 724-733 57. Kirchhof PF, Fabritz CL, Franz MR: Postrepolarization refractoriness versus conduction slowing caused by class I antiarrhythmic drugs.

Antiarrhythmic and proarrhythmic effects.

Circulation 1998; 97: 2567-2574 58. Franz MR, Gray RA, Karasik P, Moore HJ, Singh SN: Drug-induced post-repolarization refractoriness as an antiarrhythmic principle and its underlying mechanism. Europace 2014; 16: iv39-iv45 59. Jazayeri MR, Deshpande SS, Sra JS, Akhtar M: Retrograde (transseptal) activation of right bundle branch during sinus rhythm. J Cardiovasc Electrophysiol 1993; 4: 280-287 60. Qi WH, Fisch C: Concealed transseptal conduction. Chin Med J 1985; 98: 271-285 61. Barold HS, Newman M, Flanagan M, Barold SS: Two-to-one bundle branch block during atrioventricular nodal reentrant tachycardia: What is the mechanism? Heart Rhythm 2007; 4: 371-373 62. DiFrancesco D, Camm JA: Heart rate lowering by specific and selective I(f) current inhibition with

63.

64.

65.

66.

67.

68.

69.

70.

71.

72.

29

ivabradine: a new therapeutic perspective in cardiovascular disease. Drugs 2004; 64: 1757-1765 Tardif JC: Ivabradine in clinical practice: benefits of If inhibition. Eur Heart J 2005; 26 Suppl H: H29-H32 Anderson NS, Ramirez A, Slim A, Malik J: Exercise induced left bundle branch block treated with cardiac rehabilitation: A case report and a review of the literature.

Case Rep Vasc Med 2014; article ID 204805 Perin E, Petersen F, Massumi A: Rate-related left bundle branch block as a cause of non-ischemic chest pain. Cathet Cardiovasc Diagn 1991; 22: 45-46 Vasey C, O’Donnell J, Morris S, McHenry P: Exercise-induced left bundle branch block and its relation to coronary artery disease.

Am J Cardiol 1985; 56: 892-895 Constantini M: Blocco di branca intermittente: un modello clinico per lo studio de fenomeni elettrofisiologici. G Ital Cardiol 2014; 15: 25-36 Gibbons RJ, Balady GJ, Beasley JW, Bricker JT, Duvernoy WFC, Froelicher VF, Mark DB, Marwick TH, McCallister BD, Thompson PD, Winters WL Jr, Yanowitz FG: ACC/AHA Guidelines for Exercise Testing: Executive Summary. A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). Circulation 1997; 96: 345-354 Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, Froelicher VF, Leon AS, Pina IL, Rodney R, Simons-Morton DA, Williams MA, Bazzarre T: Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation 2001; 104: 1694-1740 Woelfel AK, Simpson RJ, Gettes LS, Foster JR: Exercise-induced distal atrioventricular block.

J Am Coll Cardiol 1983; 2: 578-581 Wellens HJJ, Conover M: The ECG in Emergency Decision Making. 2nd ed, Saunders Elsevier, St. Louis, Missouri, 2006. pp. 72-75 Park M-Y, Shin W-S, Shim B-J, Lee S-J, Park J-H, Koh Y-S, Lee J-M: Exercise-induced intranodal atrioventricular block. Korean Circ J 2012; 42: 698-701

30

RATE-DEPENDENT BLOCKS

73. Moulopoulos SD, Darsinos J, Sideris DA: Atrioventricular block response to exercise and intraventricular conduction at rest. Br Heart J 1972; 34: 998-1004 74. Freeman G, Hwang MH, Danoviz J, Moran JF, Gunnar RM: Exercise induced “Mobitz type II” second degree AV block in a patient with chronic bifascicular block (right bundle branch block and left anterior hemiblock).

J Electrocardiol 1984; 17: 409-412 75. Wellens HJJ: Atrioventricular nodal and subnodal conduction disturbances. In Cardiovascular Medicine. JT Willerson, JN Cohn, HJJ Wellens, DR Holmes Jr (eds). 3rd Ed. SpringerVerlag, London, 2007; pp. 1991-1999 76. Gilchrist MR: Clinical aspects of high grade heart block. Scott Med J 1958; 3: 53-75 77. Zepelli P, Fenici R, Sassava M, Pirrami MM. Caselli G: Wenckebach second-degree A-V block in top-ranking athletes: an old problem revisited. Am Heart J 1980; 100: 281-294 78. Schweitzer P, Teichholtz LE: Carotid sinus massage. Its diagnostic and therapeutic value in arrhythmias. Am J Med 1985; 78: 645-654 79. Furukawa S, Wingenfeld L, Takaya A, Nakagawa T, Sakaguchi I, Nishi K: Morphological variation of the carotid sinus location.

J Clin Exp Cardiol 2012; 3: 207. doi:10.4172/ 2155-9880.1000207 80. Sigler LH: Electrocardiographic observations on the carotid sinus reflex. Am Heart J 1934; 9: 782-791 81. Kendrick Purks W: Electrocardiographic findings following carotid sinus stimulation. Ann Intern Med 1939; 13: 270-279 82. Morley CA, Sutton R: Carotid sinus syncope.

Int J Cardiol 1984; 6: 287-293 83. Mickley H, Hansen KN, Oxhøj H, Møller M: The effect of carotid sinus massage is independent of posture in patients with heart disease.

Eur Heart J 1989; 10: 459-463 84. Linenthal AJ: Effect of carotid sinus reflex on cardiac impulse formation and conduction.

Circulation 1959; 20: 595-601 85. Mankikar GD, Clark AN: Cardiac effects of carotid sinus massage in old age.

Age Ageing 1975; 4: 86-94

86. Tan MP, Newton JL, Reeve P, Murray A, Chadwick TJ, Parry SW: Results of carotid sinus massage in a tertiary referral unit - is carotid sinus syndrome still relevant ? Age Ageing 2009; 38: 680-686 87. Richardson D, Bexton R, Shaw F, Steen N, Bond J, Kenny R: Complications of carotid sinus massage – a prospective series of older patients.

Age Ageing 2000; 29: 413-417 88. Lacerda GC, Pedrosa RC, de Lacerda RC, dos Santos MC, Teixeira Brasil A, de Siqueira-Filho AG: Complications related to carotid sinus massage in 502 ambulatory patients. Arq Bras Cardiol 2009; 92: 78-83 89. Greenwood RJ, Dupler DA: Death following carotid sinus pressure. JAMA 1962; 181: 605-609 90. Porus RL, Marcus FI: Ventricular fibrillation during carotid-sinus stimulation. N Engl J Med 1963; 268: 1338-1342 91. Walsh T, Clinch D, Costelloe A, Moore A, Sheehy T, Watts M, Bryant CA, Close J, Gonzalez J, Ouldred E, Pathansali R, Swift CG, Lyons D, Jackson SHD: Carotid sinus massage – How safe is it? Age Aging 2006; 35: 518-535 92. Lown B, Levine S: Carotid sinus: Clinical value of its stimulation. Circulation 1961; 23: 766-789 93. Harrington JF: Reversion of left-bundle-branch block to normal conduction by carotid-sinus pressure. N Engl J Med 1967; 277: 37-38 94. Chiale PA, Pastori JD, Sanchez RA, Elizari MV, Rosenbaum MB: Contrasting effects of verapamil and procainamide on rate-dependent bundle branch block: Pharmacologic evidence for the role of depressed sodium channel responses. J Am Coll Cardiol 1990; 15: 633-639 95. Voicu F: [The rate-dependent left bundle branch block. Clinical significance, ECG and vectorcardiographic correlations]. In Romanian: Blocul complet de ramură stângă dependent de frecvenţa cardiacă. Semnificaţii clinice, corelaţii ECG și vectocardiografice. University Graduation Paper. Administrative coordinator: M. Albulescu; Scientific and clinical advisor: D.-D. Ionescu.

UMF “Carol Davila”, Bucharest, Romania, 1982 96. Waxman MB, Wald RW, Bonet JF, Finley JP: Carotid sinus massage induced elimination of rate related bundle branch block during

paroxysmal atrial tachycardia: a simple method of proving bypass tract participation in the tachycardia. J Electrocardiol 1979; 12: 371-376 97. Watanabe Y, Nishimura M: Terminology and electrophysiologic concepts in cardiac arrhythmias. VI. Phase 3 block and phase 4 block. Part 2. PACE 1979; 2: 624-633 98. Almog C, Gabizon D, Bezetshli I: Carotid massage as a means of ECG diagnosis of acute myocardial infarction in the presence of left bundle branch block. Chest 1975; 67: 249-250 99. Weiss T, Elitzur Y, Rott D, Leibowitz D: Carotid sinus massage in patients with suspected acute myocardial infarction, tachycardia, and left bundle branch block. Am J Med 2009; 122: e1-e2 100. Chaterjee K, Harris A, Davies G, Leathman A: Electrocardiographic changes subsequent to artificial ventricular depolarization. Br Heart J 1969; 31: 770-779 101. Denes P, Pick A, Miller RH, Pietras RJ, Rosen KM: A characteristic precordial repolarization abnormality with intermittent left bundlebranch block. Ann Intern Med 1978; 89: 55-57 102. Rosenbaum MB, Blanco HH, Elizari MV, Lázzari JO, Davidenko JM. Electrotonic modulation of the T wave and cardiac memory. | Am J Cardiol 1982; 50: 213-222 103. Geller JC, Rosen MR: Persistent T-wave changes after alteration of the ventricular activation sequence. New insights into cellular mechanisms of “cardiac memory”. Circulation 1993; 88 [part 1]: 1811-1819 104. Patberg KW, Shvilkin A, Plotnikov AN, Chandra P, Josephson ME, Rosen MR: Cardiac memory: mechanisms and clinical implications.

Heart Rhythm 2005; 2:1376-1382 105. Shvilkin A, Ho K, Rosen M, Josephson M: T-vector direction differentiates postpacing from ischemic T-wave inversion in precordial leads.

Circulation 2005; 111: 969-974 106. Chiale PA, Etcheverry D, Pastori JD, Fernández PA, Garro HA, González MD, Elizari MV: The multiple electrocardiographic manifestations of ventricular repolarization memory. Curr Cardiol Rev 2014; 10: 190-201 107. Ogura Y, Kato J, Ogawa Y, Shiokoshi T, Kitaoka T, Suzuki T, Kawamura Y, Tanabe Y, Sato N, Hasebe N, Kikuchi K: A case of alternating

Chapter 2. CLINICAL ELECTROPHYSIOLOGY OF RATE-DEPENDENT BLOCKS

bundle branch block in combination with intra-Hisian block. Int Heart J 2005; 46: 737-744 108. Wellens HJJ, Conover M: The ECG in Emergency Decision Making. 2nd ed, Saunders Elsevier, St. Louis, Missouri, 2006. pp. 72-75 109. Josephson ME: Clinical Cardiac Electrophysiology. Techniques and Interpretations. 4th ed., Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, 2008. pp. 104-106 110. Xiao HB, Lee CH, Gibson DG: Effect of left bundle branch block on diastolic function in dilated cardiomyopathy. Br Heart J 1991; 66: 443-447

111. Bader H, Garrigue S, Lafitte S, Reuter S, Jais P, Haissaguerre M, Bonnet J, Clementy J, Roudaut R: Intra-left ventricular electromechanical asynchrony. A new independent predictor of severe cardiac events in heart failure patients.

J Am Coll Cardiol 2004; 43: 248-256 112. Barretto RB, Piegas LS, Assef JE, Melo Neto JF, Resende TU, Moreira DA, Lebihan DC, França FF, Meneghelo RS, Sousa AG: Mechanical dyssynchrony is similar in different patterns of left bundle-branch block. Arq Bras Cardiol 2013; 101: 449-456

31

113. Reil J-C, Robertson M, Ford I, Borer J, Komajda M, Swedberg K, Tavazzi L, Böhm M: Impact of left bundle branch block on heart rate and its relationship to treatment with ivabradine in chronic heart failure. Eur Heart Fail 2013; 15: 1044-1052 114. Xiong Y, Wang L, Liu W, Hankey GJ, Xu B, Wang S: The prognostic significance of right bundle branch block: A meta-analysis of prospective cohort studies. Clin Cardiol 2015; 38: 604-613

CHAPTER

3

Rate-dependent intraventricular blocks 3.1. A short presentation of bundle branch blocks 3.1.1. Right bundle branch block (RBBB) The RBBB in its complete form (wrongly called “major”) does not alter the initial part of QRS complexes and allows an easy diagnosis of common left ventricular diseases. It also has various degrees from complete, advanced or third-degree (defined in table 3.I)[1, 2] to lesser second, and first degrees with QRS duration < 120 ms [3]. This classification has an undefined practical importance and only the complete form has a significant long-term impact on mortality whatever the direct cardiac cause of death [4].

TABLE 3.I. ECG criteria for complete right bundle branch block [1,2]  QRS duration ≥ 120 ms in adults  Broad, notched secondary R waves (rsr’, rsR’, or rSR’ patterns) in right precordial leads (V1 and V2); R’ or r’ deflection usually wider than the initial R wave; in a minority of patients, a wide and often notched R wave pattern may be seen in lead V1 and/or V2  Wide, deep S waves (qRS pattern) of greater duration than R wave or greater than 40 msec in leads I and V6  Normal R wave peak time in leads V5 and V6 but > 50 ms in lead V1  Of the foregoing criteria, the first three should be present to make the diagnosis; when a pure dominant R wave with or without a notch is present in V1, criterion 4 should be satisfied

3.1.2. Left bundle branch block (LBBB) A LBBB is easily recognised on standard surface ECG based on universally accepted criteria (table 3.II)[1, 2]. These criteria refer only to the complete (or sometimes wrongly called major) form called by some authors as an advanced or third-degree block (corresponding to the Mexican school type III). In this last classification there are two other variants of LBBBs: partial (first-degree or Mexican school types I and II) with QRS complex duration < 120 ms also named incomplete and second degree which is considered a form of aberrant conduction [3]. For important practical reasons we consider only the complete form of LBBB which is the one most frequently demonstrated to be rate-dependent (RD).

33

34

RATE-DEPENDENT BLOCKS

TABLE 3.II. ECG criteria for complete left bundle branch block [1,2]  QRS duration ≥ 120 msc in adults  Broad, notched or slurred R waves in I, aVL, V5 and V6 and an occasional RS pattern in V5 and V6 attributed to a displaced transition of QRS complex  Absent q waves in I, V5 and V6, but in the lead aVL a narrow q wave may be present in the absence of myocardial disease  R wave peak time > 60 msec in leads V5 and V6 but normal in leads V1, V2 and V3 when small initial r waves can be discerned in the above leads  ST and T waves usually opposite in direction to QRS  Positive T waves in leads with upright QRS may be normal (positive concordance)  Depressed ST segment and/or negative T wave in leads with negative QRS (negative concordance) are abnormal  Appearance of LBBB may change the mean QRS axis in the frontal plane to the right, to the left, or superiorly, in some cases in a rate-dependent manner

The presence of a LBBB (exactly as with QRS complexes during right ventricular paced rhythms) makes the ECG detection of an acute myocardial infarction (AMI) very difficult.

In the original Sgarbossa criteria with three quantitative ST segment changes, each weighted with 2-5 points, a global score ≥ 3 had a high specificity but a relatively low sensitivity for the diagnosis of ST-elevation AMI (STEMI)[5]. A number of other studies that followed observed different individual specificity and sensitivity of these criteria, the less convenient being the third one (discordant ST elevation of ≥ 5 mm, weighted 2 points)[6, 7]. This Sgarbossa criterion was later modified [8] and the newest set of criteria (table 3.II) was recently validated with the same high specificity and a sensitivity of 80%, both weighted and unweighted [9].

TABLE 3.III. Modified Sgarbossa criteria [8,9] 1. Concordant ST elevation ≥ 1 mm in leads with a positive QRS complex (originally weighted 5 points) 2. Concordant ST depression ≥ 1 mm in V1-V3 (originally weighted 3 points) 3. Discordant ST elevation (STE) ≥ 5 mm in a precordial lead replaced with: A proportion (at least 1 mm STE) of STE/S wave ≤ −0.25

LBBB cases may be very complicated depending on QRS frontal axis and/or on the site of block in the main trunk or below [3], a subject that is beyond the purpose of this chapter.

Some discrete morphological features of QRS complexes with LBBB in various clinical settings that suggest the presence of an acute or old myocardial necrosis may be of some help if they are found. The Cabrera’s sign is a notching of ≥ 50 ms duration on the ascending limb of the S wave (after its nadir) in leads V3, V4 or V5 and has a sensitivity of 27% (higher for an anterior infarction and also higher together with left axis deviation)[10, 11]. The Chapman’s sign – a similar notch as above – on the ascending limb of the R wave in leads I, aVL and/or V5, V6 which appears approximately 30 ms after the beginning of QRS complexes (a “delayed Q wave”) – has a specificity of 90% but also a low sensitivity [12]. Both the Cabrera’s sign and the Chapman’s sign were analyzed in the paper that generated the original Sgarbossa criteria but no results were provided [5]. Other QRS features with a possible role in the identification of an old myocardial infarction (Q waves > 30 ms in leads I, aVL, or V6; notching of the first 40 ms of the QRS complex in leads II, III, and aVF; Q waves > 30 ms in leads II, III, and aVF; presence of a qR in leads I,

Chapter 3. RATE-DEPENDENT INTRAVENTRICULAR BLOCKS

aVL, or V6; presence of a qR in leads II, III, or aVF) were studied either alone or in various associations in patients with right ventricular pacing and yielded the best results in terms of specificity and sensitivity only for the combination of Cabrera’s and Chapman’s signs [13, 14]. In cases of LBBB with very large QRS complexes, the presence of q waves in I, aVL, V5 and V6 usually suggests an old anterior myocardial infarction and a q wave present only in lead V6 may mean that, with blocks in the anterior and posterior fascicles explaining the LBBB, the left septal fascicle remained functional with normal left-to-right septal activation (Medrano GA et al., 1970 quoted by [3]).

Another ECG approach to identify the presence of a myocardial scar under a LBBB is the updated Selvester score which gives points for amplitudes, durations and notching of QRS waves in many leads (without III, aVR and V3). This complicated score includes a modified Chapman’s sign and it did not achieve a widespread use in clinical practice. A recent study in patients with various intraventricular conduction blocks evaluated by cardiac magnetic resonance imaging was not able to convincingly validate this score in the presence of LBBB [15].

3.1.3. Left divisional fascicular blocks The most frequently observed fascicular block in practice is the left anterior fascicular block (LAFB) also known under the old name of left anterior hemiblock. Its ECG diagnosis is simple (table 3.IV) but sometimes, in the presence of massive left ventricular hypertrophy, it is ignored. In almost all the populations studied (apparently healthy individuals, hospital subjects, settings of cardiological services) the reported prevalence of LAFB is 1.03-6.2% surprisingly higher in the young without heart disease [16]. Its presence seems to be related more frequently to ischemic heart disease, hypertension, cardiomyopathies and sclerodegenerative diseases of the conduction system. The independent impact of LAFB on long-term clinical prognosis and even on the evolution of

acute coronary syndromes is controversial but most probably minor [16, 17].

TABLE 3.IV. ECG criteria for left anterior fascicular block [1,2]  Frontal plane axis between –45 and –90 degrees  qR pattern in lead aVL  R wave peak time in lead aVL ≥ 45 ms  QRS duration < 120 ms

The left posterior fascicular block (LPFB), or left posterior hemiblock as originally named, is much less prevalent than the LAFB probably because this division of LBB is thicker, with a fan-shaped structure located in the less turbulent inflow tract of the left ventricle and has a triple blood supply (AVN artery, branches from the left posterior descending artery and directly from circumflex artery)[18]. This diverse and rich source of blood explains why a LPFB is extremely rare as a single conduction defect (prevalence lower than 0.1% in large populational studies)[19,20]. It appears frequently together with a RBBB on the background of a significant ischemic heart disease and this association implies a high risk of complete AVB [16]. LPFB has diagnostic criteria (table 3.V) that are applicable only if other reasons of right axis deviation can be excluded (chronic obstructive pulmonary disease, right ventricular hypertrophy and a few others).

Sometimes, a typical LPFB may mask the presence of an inferior myocardial infarction by reducing the q wave duration in leads III and aVF [21].

TABLE 3.V. ECG criteria for left posterior fascicular block [1,2]  Frontal plane axis between 90 and 180 degrees in adults  rS pattern in leads I and aVL  qR pattern in leads III and aVF  QRS duration < 120 ms

The left septal (or middle) fascicular block (LSFB) has rather controversial diagnostic ECG criteria [22], probably

35

36

RATE-DEPENDENT BLOCKS

explained by morphologic variants of fascicle origin from the left bundle, and it is very rare or frequently overlooked in clinical cardiology. It may appear as a single conduction defect or it can appear associated with other stable intraventricular blocks in patients with severe ischemic heart disease [23, 24]. The possible additional presence of the LSFB made Fernando de Padua et al., state many years ago that “if hemiblocks do exist, they are only two – if a third fascicular block is postulated, hemiblocks do not exist!” [25]. Apart from some patient-to-patient variability of the criteria for LSFB diagnosis, it is worth mentioning that the left septal fascicle is present in 55% of normal hearts and it originates directly from the main LBB in only 25% of all cases [26].

3.1.4. Bifascicular and trifascicular blocks A trifascicular block is considered when a RBBB appears with alternating LAFB and LPFB which, as Bayes de Luna notes, “…merits the name of Rosenbaum-Elizari’s syndrome” to honor the authors who gave its detailed description [3]. In very rare cases, a trifascicular block is also present when a bifascicular block is associated with a RD block in the third fascicle and its common ECG expression is that of a grade II AVB (most often as a 2:1 AVB – see section 4.2 in Chapter 4). An association of a bifascicular block with blocks above the His bundle bifurcation should not be considered a trifascicular block but a triple (or multiple) site block.

The alternating LBBB and RBBB on the same ECG recording is very rare in practice, it may also be considered a trifascicular block and it has an extremely high risk of an impending complete AVB, especially when it is associated with variable PR intervals [2, 27]; at least one of the intraventricular blocks in such an association seems to be rate-dependent [27, 28]. A closely similar variant is the discovery of a new bifascicular block in a patient already known to have a documented different bifascicular block on a recently recorded ECG (a case is presented at the end of section 3.3).

3.2. General data on RD intraventricular blocks Rate-dependent (RD) intraventricular blocks are defined by conduction defects that occur in direct relationships with spontaneous (or induced) variations of atrial impulse rates that are within physiological ranges and arrive to the ventricles from the His bundle (HB) bifurcation. This definition includes regular atrial impulses coming from the atria at normal rates, as in the case of physiological sinus rhythm (SR) or from irregular atrial impulses of atrial fibrillation that cross the atrioventricular node (AVN). The supraventricular impulses originated from regular supraventricular (SV) arrhythmias do not qualify here because they generally do not show cycle variations and are not susceptible to clinically induced significant rate changes (drugs excluded). All the intraventricular bundle branches and fascicles can show RD blocks due to their fast type of action potential (AP). The most frequently observed and studied RD intraventricular blocks are the LBBB and the RBBB. RD blocks in one of the three fascicular divisions of the left bundle branch – anterior, posterior and middle (or septal) – are extremely rarely seen as a single conduction defect. Other intraventricular blocks that are not known to be rate-dependent are the incomplete LBBB (diagnosed with QRS duration < 120 ms and no q waves in I, aVL, V5 and V6) and the non-specific intraventricular conduction defects. The last form results from a diffuse slowing of impulse conduction in the entire specific system which significantly increases QRS duration over 120 ms without any resemblence with the two complete intraventricular blocks. According to its mechanism (possibly similar to the effects of some class IC antiarrhythmic drugs), this form is generated by severe alterations of phase 0 of the ventricular AP which are not independently influenced by heart rate fluctuations.

The first case of a possible RD intraventricular block was published as a transient block in the right bundle branch (but on that three-lead ECG of the time we can see now that it

Chapter 3. RATE-DEPENDENT INTRAVENTRICULAR BLOCKS

was in the left bundle branch) by T. Lewis in 1913 in a febrile patient aged 32 with clinical signs of heart failure [29]. No comments were made about any relationships to heart rate although there was a difference in cardiac cycles between the two ECGs recorded one day apart. The first real RD intraventricular blocks were published in 1921 [30] and were followed by a plethora of case reports, patient series of various sizes and electrophysiological studies that have established the clinical and ECG characteristics of this peculiar diagnosis [31-38].

All the intraventricular blocks can be phase 3 or phase 4 blocks as presented in section 2.2 of Chapter 2. It is generally considered that a phase 4 block is very frequently if not always a phase 3 block meaning that the normal intraventricular conduction is possible only in a window of heart rates which is worth knowing. None of the phase 3 RD blocks needs an investigation to identify whether it is also a phase 4 block because this possibility is not important for practice as it may be disclosed only with very slow, non-clinical, heart rates.

The prevalence of RD intraventricular blocks among patients with LBBB or RBBB is not known because the usual evaluation in most cases includes only the standard short term passive ECG recordings made by technicians or less informed physicians. Identification of either a RD-LBBB or a RD-RBBB must include longer ECG observations done by bed-side monitoring, 12 lead tracings recorded for a few minutes or Holter ECG recordings and medical interventions to modulate heart rate like a light exercise or carotid sinus massage (CSM) in the concept of active electrocardiography. In a very simple study of 105 consecutive patients with LBBB done by a student for graduation it was proved by CSM that 28 (26.7%) had a RD block [39]. Knowing that a LBBB dramatically alters the initial phase of ventricular depolarization, we think that a gentle CSM should regularly be done in such patients in order to reveal the QRS morphology for the sake of a more complete diagnosis. In patients who present normal QRS complexes on standard ECGs and have a documented

history of a bundle branch block (BBB) or clues suggesting a possible RD block (altered QRS morphology only with the first P wave after premature beats, transient QRS widenings in SR on Holter ECG recordings for one or more beats), the addition of manoeuvres that modulate heart rate may be certainly useful.

In clinical practice, the discovery of a RD-BBB is incidental and is related to spontaneous variations of SRCs at rest on standard ECG tracings, on Holter ECG recordings or during some investigations done for diverse other purposes. Only occasionally, in patients with an apparently stable BBB who have previously documented normal ECGs, a CSM is done in order to reveal if the wide QRS complexes hide a background pathology that is not evident because of faster but still normal heart rates. The reverse is also true: in cases with normal QRS complexes at the time of investigation, if a patient has an old ECG tracing showing a BBB at a different heart rate, an active exploration with either a CSM or a mild exercise is supposed to be useful for therapeutic decisions and/or for further investigation.

A standard stress test performed on a treadmill or on a cycle ergometer is not usually indicated to study a possible abnormal intraventricular conduction but occasionally it leads to an unexpected appearance of a phase 3 RD block with a global incidence of 0.24-1.1% [40-43]. Statistically, the distribution of BBBs was in favor of LBBB (as an example: 74% for LBBB vs. 26% for RBBB)[40] which explains the greater number of studies addressed to this variant [44-47]. From the total of 199 patients from published series (without the isolated case reports) who developed a RD-LBBB during the stress test and were explored by coronary angiography, a number of 117 (58.8%) had coronary artery disease [46, 48, 49].

Interestingly, at the onset of LBBB in these patients the heart rate was less than 125 bpm while all the patients without coronary artery disease had heart rates above this value [44, 49]. A very special clinical form of angina pectoris with typical chest pain appearing exactly at the onset of RD-LBBB was reported in 1976 [50] and confirmed by many later re-

37

38

RATE-DEPENDENT BLOCKS

ports [48, 49, 51-53]. In this so-called “painful” LBBB, because the coronary arteriography was normal or with nonsignificant lesions in all cases, the origin of chest pain was attributed to the contraction dysynchrony of the left ventricle with mechanoreceptor stimulation [53, 54].

Very little studied with active electrocardiography are the blocks in the divisions of the LBB. An isolated RD-LAFB is exceptionally rare whether spontaneous at rest as a phase 3 block (only one of five cases with various severe pathologies and an intermittent LAFB communicated by Rosenbaum et al. [55] was certainly a RD block) or appearing during a stress test [56-58]. In the largest series of patients undergoing a stress test, LAFB with increasing heart rates had an incidence of only 0.13% [59]. The appearance of LAFB is followed by an increase of QRS duration by ≤ 20 msec never reaching values > 120 msec but in some cases the smaller widening of QRS complexes was that of an “incomplete” LAFB [16, 56].

The compliance with QRS duration criterion for LAFB is important in some post-infarction patients when ventricular complexes become wider than 120 msec after shorter SR cycles most probably due to a RD peri-infarction or peripheral block [60]. Most of the RD-LAFB cases coexist with other stable or RD intraventricular blocks and carry a considerable high risk of advanced or complete AVB [16, 61]. A phase 4 RD-LAFB is extremely rare [62]. When an association of a RBBB with LPFB leads to a transient RD-AVB then the best explanation may be either a phase 4 RD-LAFB [61] or a phase 3 RD-LAFB (see Chapter 4).

Isolated RD-LPFBs are also exceptionally rare in practice and may be observed during a stress test [63, 64]. In the aforementioned large study of patients undergoing such a test, the incidence of RD-LPFB was 0,15% [59]. Exactly as with RD-LAFB, most of RD-LPFBs appear in associations with other stable or RD intraventricular blocks and always confer an extremely high risk of later developing advanced grades of AVB [16, 65].

ECG tracings with RD-LSFB were also communicated in a few case reports as disclosed by exercise stress tests or by

CSM [66, 67]. RD-LSFB was present both as a single block and in association with other stable or RD intraventricular blocks in patients with severe coronary artery disease.

The causes of RD intraventricular blocks are probably the same as for permanent forms and include coronary heart disease, hypertension with left ventricular hypertrophy, aortic valve stenosis, dilated cardiomyopathy, sclerodegenerative diseases of the conduction system (Lenegre and Lev) and a few others [16]. All of these pathological backgrounds may be in an early stage of conduction alteration without definitive morphological interruption of BBs. In practice, the exact knowledge of RD-BBB causes is frequently difficult or impossible to identify and it is of little importance as therapy is decided based on other criteria.

3.3. RD bundle branch blocks in practice (with supplemental ECG tracings in Appendix A) The clinical cardiology practice offers a large variety of ECG presentations of RD blocks which, although rare, needs an active attitude and knowledge according to the rule “you see only what you look for and recognize only what you know” – attributed to Dr. Merrill C. Sosman (1890-1959), a distinguished radiologist at Peter Bent Brigham Hospital, Boston, MA, USA. In order to disclose the presence of a RDBBB, apart from incidental findings on passively recorded surface ECG tracings (including Holter ECG recordings), an active attitude with simple bed-side clinical interventions modulating the heart rate is very useful for a better understanding of the abnormal intraventricular conduction. This active approach provides more scientific knowledge in any case of RD-BBB, but for practice it is much more important in cases with LBBB. The type of block (phase 3 or phase 4) can be identified by both passive or active ECG recordings (table 3.VI).

Chapter 3. RATE-DEPENDENT INTRAVENTRICULAR BLOCKS

39

A

B

FIGURE 3.1. Leads V1-V2 in case 1: spontaneous disappearance of RBBB for a couple of beats (A) or after a premature ventricular beat (B)

TABLE 3.VI. Identification of RD-BBB types 1. Spontaneous RD-BBBs at rest: 1.1. Small normal variations of heart rate: both phase 3 and phase 4 blocks 1.2. Post-extrasystolic pauses: 1.2.1. Phase 3 block if baseline QRS complexes are with BBB 1.2.2. Phase 4 block if baseline QRS complexes are normal 1.3. Post-intercalated premature ventricular beats: phase 3 block 2. RD-BBBs induced by various interventions that modulate heart rate: 2.1. Physical exercise (or atrial pacing): 2.1.1. Phase 3 block if baseline QRS complexes are normal 2.1.2. Phase 4 block if baseline QRS complexes are with BBB 2.2. Carotid sinus massage (CSM): 2.2.1. Phase 3 block if baseline QRS complexes are with BBB 2.2.2. Phase 4 block if baseline QRS complexes are normal

The discovery that an uncomplicated RBBB is a RD one is of an academic interest at the time of diagnosis. It spontaneously appears as a phase 3 block with very discrete variations of SRCs at rest that sometimes are extremely difficult to measure on standard ECG recording speed of 25 mm/s. As an example (case 1, fig. 3.1A), the SRCs with RBBB are of approximately 760-780 ms while, with the few normal QRS complexes, they are seemingly longer, of 790-800 ms. In the same case, a premature ventricular beat (PVB), most probably originated in the right ventricle, is followed by three normal QRS complexes that come after the postextrasystolic pause with PP intervals which do not appear to be obviously longer in comparison with those before the PVB (fig. 3.1B). The re-