Quantification of Human Atrioventricular Nodal Concealed Conduction Utilizing S^Sg Stimulation

Transcription

1 659 Quantification of Human Atrioventricular Nodal Concealed Conduction Utilizing S^Sg Stimulation DELON WU, M.D., PABLO DENES, M.D., RAMESH C. DHINGRA, M.D., CHRISTOPHER R. WYNDHAM, M.D., AND KENNETH M. ROSEN, M.D. SUMMARY We studied antegrade concealed conduction of alrial extrastimuli (A 2 ) that blocked in the atrioventricular (AV) node in eight subjects, using a third extrastimulus (A 3 ), coupled at decreasing coupling intervals to A 2. Three A,-A 2 intervals were tested in each subject: late (just shorter than AV nodal effective refractory period), intermediate, and early (just longer than atrial functional refractory period). The curves relating the following variables were constructed for each A 2 : A,-A 3, H,-H 3 and A 2 -A 3, A 3 -H 3. The former was compared to the control A,-A 2, H,-H 2 curve. Concealment of A 2 was demonstrated in all eight subjects at the three tested values of A,-A,. The A,-A 3, Aj-H, curve allowed analysis of AV nodal conduction time (A3-H3) and AV nodal recovery time (defined as the shortest A 2 -A 3 at which the impulse conducted to the His bundle) at identical values of A 2 -A 3. In all subjects the timing of blocked A 2 nad minimal effect on both AV nodal conduction time and recovery time. In five of the eight subjects a late A 2 sporadically conducted to the His bundle. Conduction of A, to the His bundle resulted in marked lengthening of both AV nodal conduction and recovery times. Concealed conduction of A 2 was always demonstrated, but the degree of concealment was relatively fixed, whether A 2 was an early, intermediate, or late blocked premature beat. Slow conduction of A 2 had a much greater effect than concealment of A 2 on subsequent impulse conduction. CONCEALED conduction is defined as the effect of a partially penetrating impulse on conduction of a subsequent impulse. 1 Common examples of concealed conduction include the P-R prolongation that follows blocked interpolated premature atrial or ventricular contractions. 2 " 4 In both cases, concealed conduction usually is in the atrioventricular (AV) node. 58 It has been suggested that the depth of penetration is related to the timing of the blocked premature impulse. 3 - " '" For example, with antegrade concealed conduction of blocked atrial premature impulses, one might expect deep penetration of a late impulse with a marked effect on subsequent impulse conduction and superficial penetration of a very early impulse with minimal or no effect on subsequent conduction. In the present study we have attempted to quantify concealed conduction of antegrade blocked premature atrial contractions, using His bundle recording and extrastimulus techniques. We were specifically interested in how the timing of blocked atrial impulses affected the conduction of subsequent impulses. Methods Eight subjects were studied during diagnostic electrophysiological study for suspected sinus node or intraventricular From the Cardiology Section, Department of Medicine, Abraham Lincoln School of Medicine, and the Department of Physiology, School of Basic Medical Sciences, University of Illinois College of Medicine, Chicago, Illinois; and the West Side Veterans Administration Hospital, Chicago, Illinois. Supported in part by National Institutes of Health Grant HL-I8794-0I, U.S. Public Health Service Training Grant HL , and Basic Institutional Support of West Side Veterans Administration, Chicago, Illinois. Address for reprints: Dr. Delon Wu, Section of Cardiology, University of Illinois Hospital, P.O. Box 6998, Chicago, Illinois Received April 2, 1976; accepted for publication July 9, conduction disease. To be included in this study, subjects had to show AV conduction limited to the AV node and a zone of coupling intervals of at least 50 msec separating the AV nodal effective refractory period and the atrial functional refractory period. In addition, the AV nodal conduction curves during the control state had to be continuous (not discontinuous, as in the case of dual AV nodal pathways) and stable."- 12 The study group consisted of six males and two females, between 48 and 75 years in age. Five had suspected sinus node dysfunction, and three had intraventricular conduction defects. All eight showed intact AV conduction during sinus rhythm, two (cases 1 and 2) had prolonged A-H interval (normal = msec) and five (cases 1, 3, 5, 7, and 8) had a prolonged AV nodal effective refractory period (normal = msec) during sinus rhythm. Electrophysiological studies were performed in the postabsorptive, nonsedated state. Cardiac medications were discontinued at least 72 hours prior to the study. Informed written consent was obtained from each subject. A tripolar electrode catheter was placed across the tricuspid valve percutaneously via the femoral vein for His bundle recording; 13 a second, quadripolar, electrode catheter was positioned at the high lateral right atrium percutaneously via the other femoral vein. The distal two electrodes were used for atrial stimulation, and the proximal two electrodes were used to record high right atrial electrograms. Multiple electrocardiographic leads and high right atrial and His bundle electrograms were simultaneously recorded on a multichannel oscilloscopic recorder (Electronics for Medicine DR-16) at paper speeds of 100 and 200 mm/sec. Recordings also were stored on an eight-channel tape system for further analysis. Stimuli were rectangular waves, approximately twice diastolic threshold and 2 msec in duration, and were provided by a programmable digital stimula-

2 660 CIRCULATION RESEARCH VOL. 39, No. 5, NOVEMBER 1976 tor (M. Bloom, Philadelphia). For each subject, the properties of the AV conducting system were evaluated by the incremental pacing and extrastimulus techniques. The atrial functional refractory period was defined as the shortest attainable A,-A, interval. The AV nodal effective refractory period was defined as the longest A,-Ai interval at which Ai was not conducted to the His bundle. 14 AVN H ~ X ELECTROPHYSIOLOGICAL PROTOCOL For each subject (at an atrial driven cycle length slightly shorter than sinus cycle length) the zone encompassing the AV nodal effective refractory period (outer limit) and atrial functional refractory period (inner limit) were defined (Fig. 1A). By definition, within this zone all A, were concealed within the AV node, except for sporadic conduction of A 2 at intervals close to the AV nodal effective refractory period. Three A,-Ai coupling intervals then were tested with a third extrastimulus (Aj) which was moved closer to A 2 in 5- to 10-msec decrements. The three A,-A, intervals tested included a long A,-A 2, which was just shorter than the AV nodal effective refractory period (Fig. IB), an intermediate A,-Aj (Fig. 1C), and a shortest A,-A,, which was just longer than the atrial functional refractory period (Fig. ID). The maximal difference between the longest and the shortest A-FRP AVN-ERP FIGURE 2 Diagrammatic representation of A,-A,, H r H, curves. Long-dashed line represents the control A t -A t, Hi-H,. With entrance block of At, the A x -A,, Hi-H, curve would be identical to this control curve. Dotted line represents the hypothetical curve with the presence of a blocked A,. A, A VN, and H as in Figure I. A,-A 2 interval in the eight subjects ranged from 50 to 180 msec with a mean ± SD of 107 ± 42 msec. D AVN AVN A, A A 2 H, H, H, FIGURE 1 Ladder diagrams demonstrating the study protocol. A, A VN, and H, respectively, represent atrium, atrioventricular (A V) node, and His bundle. A, and H t are atrial and His bundle responses to the driven stimuli: A t is the blocked premature atrial impulse; A, and //, are the atrial and His bundle responses to the atrial extrastimulus following A,. Shaded area represents the interval between A V nodal effective refractory period (A VN-ERP) and atrial functional refractory period (A-FRP). (See text for discussion.) DATA ANALYSIS AND RATIONALE OF STUDY H^H, responses were plotted as a function of A,-A 3 coupling intervals for each of the three concealed A, tested. A control A,-A,, H,-H, curve also was plotted (without A,) (Fig. 2). Plotting of A,-A,, H,-H 3 curves with the control curve allowed determination of the presence or absence of concealed conduction. If A, failed to penetrate the node because of AV nodal entry block, then the A,-A a, H,-H, curve would be identical to the control curve. However, if A 2 penetrated the node, the resultant curve could be expected to be shifted upward and rightward, demonstrating the presence of concealed conduction (Fig. 2). In addition, A,-H s responses were plotted as a function of A,-A, coupling intervals for the three concealed beats in each subject. This allowed examination of AV nodal conduction time (A,-Hj) following the concealed A, at identical A 2 -A, coupling intervals (Fig. 3, left). AV nodal recovery time, defined as the shortest A,-A, coupling interval at which A, was conducted to the His bundle, also was measured for the 3 concealed beats (Fig. 3, right). The plotting of A,-A,, A^Hj curves allowed us to isolate A, and its effects on subsequent conduction. If A, penetrated only superficially, minimal effects on A,-H, and on AV nodal recovery time would be expected (Fig. 3, top panels). If penetration was intermediate, more effect on A,-H a and AV nodal recovery time would be expected (Fig. 3, middle panels). With deep penetration, the most marked effects on conduction and recovery time would be expected (Fig. 3, bottom panels). We recognize that with the above method of data analysis, superficial penetration with slow conduction might mimic the expected effects of deep penetration. The same limitation would hold true for deep penetration with rapid conduction, which would mimic superficial penetration.

3 AV NODAL CONCEALED CONDUCTION/ Wu el al. 661 Results A, A, A? H s H, FIGURE 3 Ladder diagrams demonstrating data analysis with hypothetical considerations. Panels A and D are early concealed A, with superficial penetration, panels B and E are intermediate concealed A t with intermediate penetration, and panels C and Fare late concealed A, with deep penetration. Panels A-C depict hypothetical atrioveniricular (A V) nodal conduction times al identical A,-A, coupling intervals. The longest A r H, occurs in panel C. Panels D-F depict A V nodal recovery limes. The longest A V nodal recovery time occurs in panel F. Shaded area represents A V nodal effective refractory period following A,. {See text for discussion.) Tabulated results for the eight subjects are presented in Table 1. Analysis of A,-A,, H r H, curves in all eight subjects revealed that the presence of A, shifted the curves rightward and upward (compared to the control curve), suggesting concealment of A, to the AV node. An example is shown in Figure 4. The degree of rightward and upward shift was related proportionally to the timing of the blocked A,. An early concealed A, produced the least shift, intermediate concealed A,, an intermediate shift and a late concealed A,, the most rightward and upward shift. AV nodal entry block of A 2 was not observed in any of the eight subjects. Analysis of A,-A,, A,-H, curves for the three concealed A, in each subject revealed that AV nodal conduction times (A,-H,) were minimally affected by a change in the timing of the concealed A,. Typical examples are shown in Figures 5 and 6. AV nodal recovery times also were minimally affected by a change in the timing of the concealed A,. This was demonstrated by plotting for each of the eight subjects the recovery times against the concealed A r A, tested (Fig. 7). The maximum change in recovery time, comparing longest and shortest concealed A,, ranged from 0 to 80 msec with a mean ± SD of 29 ± 25 msec. These were small changes when compared to the range of concealed A,-A, tested in each of the subjects, which ranged from 50 to 180 TABLE I Atrioveniricular {A V) Nodal Recovery Time and Conduction Time following a Nonpropagated Impulse (A^) Subject no Basic driven cycle length (msec) A,-A, A,-H, A A (msec) * * * * * AV nodal r^f-n rv time (msec) > 355 ' (-)t 305 \ 295 > 325 J 250 \ 250 > 260' > \ 255 \ 2407 > \ 290> 330/ > \ 250 > I5 \ 315 f 320/ 265 j 265 > 275/ >430 A U oi yhrntirai A raj intervals MnYimiim A H achieved (msec) Conducted. t Dan not generated from experiment.

4 662 CIRCULATION RESEARCH VOL. 39, No. 5, NOVEMBER 1976 msec 1400i- Case OO b Ii i.. V I A,-A msec FIGURE 4 A,-A,, H^H, curves demonstrating alriovenlricular (A V) nodal concealment in case 8. The basic driven cycle length was 600 msec. Curve A (D) was the control curve. Curve a ( ), curve b (A), and curve c (x) were curves with A r A, of, 350, and 405 msec, respectively. Note the progressive rightward and upward shift of curves from a to c. msec with a mean ± SD of 107 ± 42 msec. The AV nodal recovery time was longest for the longest Ai-A 2 in two subjects (cases I and 2), longest for the intermediate A,-A 2 in one subject (case 6), longest for the shortest A,-A 2 in two subjects (cases 4 and 5), and showed no significant change (a change of 10 msec or less) in three subjects (cases 3, 7, and 8) (Fig. 7). In five of eight subjects, A 2 conducted sporadically to the His bundle at the longest tested A,-A, interval (cases 1, 3,4, 5, and 8). In all five subjects there was a marked increase in AV nodal conduction times (A 3 -H,) when sporadic conduction of A s occurred (Figs. 8 and 9). In four of the five subjects (cases 3, 4, 5, and 8), AV nodal effective refractory period could be measured using the sporadically conducted A, and the extrastimulus A 3. These values for effective refractory periods were consideraly longer than AV nodal recovery times with late concealed A, (Figs. 8 and 9). Discussion In 1948 LangendorP introduced the term "concealed conduction" to describe the effect of an incompletely penetrating impulse on subsequent impulse conduction or formation. Subsequent studies on animals and humans have demonstrated that concealment of a nonpropagated impulse or incompletely penetrating impulse can depress conduction of a subsequent impulse. 2 " 9 Concealed conduction can occur at a number of sites in the AV conducting system.' 1B The most common site of concealment appears to be in the AV node. The concept of concealed conduction is essential to an understanding of complex arrhythmias. Quantification of concealed conduction relating the timing of a blocked impulse to subsequent conduction has been infrequently reported. Moe et al.' noted the effect of the timing of a blocked impulse (A,) on conduction of a subsequent impulse A, in dog hearts. They demonstrated the presence of concealed conduction of A, by demonstrating a rightward and upward shift of A,-Ai, V,-V 3 curves when compared to control curves without A,. The degree of rightward and upward shift of A,-A,, V,-V, curve was related proportionally to the timing of A,, with late A, producing maximal shifts. The results of our present study are consistent with those of Moe's previous study, in that concealment of A, was demonstrated in all subjects at all values of A,-A, tested, and in that the rightward and upward shift of A,-Aj, H,-H, curve was proportionally related to the timing of the concealed A 2. In contrast, Varghese et al. 1 * recently reported that AV nodal entry block occurred frequently in man. In 5 of 15 subjects they found a narrow msec. 200 r A 3 -H b Case 1 J_ I0O msec FIGURE 5 A t -A a, A,-H, curves showing atrioventricular (A V) nodal conduction limes and recovery limes in case I. Curves a ( ), b (A), and c (x) were curves at A,-A, of 410, 445, and 520 msec, respectively. The basic driven cycle length was 870 msec. Note the small differences in A,-H, al identical A,-A, intervals on the three curves. The A V nodal recovery times of curvs a, b, and c were 305, 355, and 355 msec, respectively.

5 AV NODAL CONCEALED CONDUCTION/ Wu et al. 663 msec. 200 r A 3 -H Case A 2 -A 3 j msec. FIGURE 6 A,-A± A,-H, curves showing airioventricular (A V) nodal conduction times and recovery times in case 5. Curves a ( ), b (A), and c (x) were curves al A^-A r of 280, 360, and 460 msec, respectively. The basic driven cycle length was 760 msec. Note the minimal differences of A,-H, at identical A r A t intervals. The AV nodal recovery times of curves a, b, and c were 370, 290, and 330 msec, respectively. RT msec L I msec A,-A 2 FIGURE 7 Effects of timing of blocked A, on the atrioventriculai (A V) nodal recovery times in the eight subjects. Each subject is represented as a line with three points representing the three concealed A x. A ra t intervals are plotted on the abscissa and the AV nodal recovery times (RT) on the ordinate. There was no significant change of AV nodal recovery lime relating to the changes in A t -A, intervals (mean slope = +0.03; SE - /.//; r ). zone (28-33% of basic cycle length) during which the AV nodal conduction time (A,-H,) of the subsequent impulse (A 3 ) was not affected by the presence of a blocked A,. However, they did not systematically describe AV nodal conduction and recovery time for A, with AV nodal entry block. Although AV nodal entry block probably is a real electrophysiological phenomenon, the electrophysiological diagnosis of AV nodal entry block would necessitate plotting of both AV nodal conduction times and recovery times. It has been suggested that the depth of penetration into the AV node is related to the timing of a blocked A3-H3 impulse.'- 10 A late blocked impulse should penetrate deeper than an earlier blocked impulse, and thus produce more marked effects on the conduction of subsequent impulses. However, studies on the isolated rat heart by Van Capelle et al." demonstrated that after a blocked impulse (A,) AV nodal recovery time changed only minimally in relation to the timing of A,, and that a sudden increase of AV nodal recovery time (refractory period) occurred when A, was conducted. In our present study we demonstrated that both AV nodal conduction time and recovery time after a blocked impulse changed only slightly with changes in the timing of blocked A 2, and that a drastic prolongation of both AV nodal conduction time and recovery time occurred when A, was conducted to the His bundle. These results could not be explained by the hypothesis that late blocked impulses have greater effects on subsequent impulse conduction because of deeper penetration. Our present results may be explained in several ways. Hoffman and Cranefield" have suggested that the weakest link in AV nodal conduction tissue occurs at the atrionodal junction (A-N region). If this were the case in man, then both AV nodal conduction and recovery time might not change significantly, despite change in the timing of A 2, because A 2 would be blocked in the proximal AV node. of AV nodal conduction and recovery time could be expected if A, were conducted to the His bundle with depolarization of the whole AV node. Merideth et al." have suggested that the weakest link in AV nodal transmission is at the junction of the node" and His bundle (N-H region). Mendez and Moe" also demonstrated that when a blocked impulse penetrated the AV node, the action potential duration and refractory period of the cells proximsec 3OO r A Case 3 *-*i«.4 I 1 0. l_ msec FIGURE 8 A,-A,, A,-H, curves showing alrioventricular (A V) nodal conduction limes and recovery limes in case 3. Curves a ( ), b (L), and c (x) were curves al which A, were blocked proximal to the His bundle with A,-A t intervals of 280, 320, 430, respectively. Curved (*) was the curve al an A i-a t identical to curve c (430 msec), with A, conducted to the His bundle. The basic driven cycle length was 800 msec. Note that conduction of A, to the His bundle results in a marked upward and rightward shift of curve d, indicating marked lengthening of AV nodal conduction and recovery lime (refractory period).

6 664 CIRCULATION RESEARCH VOL. 39, No. 5, NOVEMBER 1976 A V.- BCL'600 A-A,-405 ll A f -A^430 vl iy FIGURE 9 Recordings from case 8, showing effects of both late concealed A, (panels A and B) and sporadically conducted A, (panels C and D). Shown are electrocardiographs lead V,, high right atrial electrogram (HRA), and His bundle electrogram (HBE). S,, A,, and Hi are the stimulus, atrial electrogram, and His bundle eleclrograms of the first of a series of driven beats. Si and A, are the stimulus artifact and atrial response to the first extrastimulus which is blocked (concealed) in paneb A and B and conducted in panels C and D (and therefore has a response //,). 5,, A,, and H, are the stimulus and responses to the third extrastimulus. The basic driving cycle length (BCL) is 600 msec and all panels show an A,-A, interval of 405 msec (longest A X-A,). Paneb A and B show A ra, coupling intervab oj'275 and 460 msec with A,-//, inlervab of 225 and 145 msec, respectively (these are listed on the illustration). Paneb C and D show A r A, coupling intervab of 430 and 490 msec with a blocked A, in panel C, and A,-H, of 250 msec in panel D. Note that when A,b blocked, recovery lime b 275 msec (panel A), the shortest A,-A, conducted to the Hb bundle. With conduction of A,, atrioventricular (A V) nodal effective refractory period (A,-/t,) b greater than 430 msec (panel C). At approximately equivalent A r A, coupling intervab, A,-//, conduction time b much longer when A,b conducted (panel B vs. panel D). Time lines are at I second and paper speed is 100 nm/sec. mal to the site of block shortened considerably and allowed conduction of a second impulse which otherwise would have been blocked. If such were the case in man, AV nodal conduction and recovery times might not change significantly in relation to the timing of the blocked A,, even with different levels of penetration, and both would be lengthened markedly if A, was conducted to the His bundle. Our present study was performed at a cycle length just shorter than sinus cycle length. Similar studies at shorter cycle lengths would be of interest. One could expect an

7 AV NODAL CONCEALED CONDUCTION/ Wu el al. 665 increase in AV nodal effective refractory period and widening of the zone of concealment; this would allow a wider range of A,-A, intervals to be tested. Whether or not a more pronounced effect on AV nodal conduction times and recovery times would occur with these studies is not known. However, studies by Van Capelle et al." on the isolated rat heart demonstrated that changes in basic driven cycle lengths did not have much influence on the AV nodal recovery times after a blocked atrial impulse; only at the shortest driven cycle length was a minimal displacement of curves seen. In summary, the present study has several interesting electrophysiological implications relevant to surface electrocardiography in man. First, blocked atrial premature beats usually should affect subsequent impulse conduction because of concealed conduction to the AV node. Lack of effect of such beats on subsequent conduction, because of AV nodal entry block, should be unusual. Second, conduction time (P-R interval) after a blocked atrial premature beat should be dependent on the coupling interval of the subsequent impulse to the blocked impulse, and not on the timing of the blocked atrial premature beat. This should be true, since we have demonstrated that time required for antegrade concealed conduction of a blocked atrial premature beat is relatively fixed, and independent of the timing of the blocked premature beat. Third, the slow conduction of an impulse has a much greater effect than concealment of an impulse on subsequent impulse conduction. Acknowledgments We express our appreciation for the secretarial assistance of Valeric Woods and Thercse Molyneux. References 1. Langendorf R: Concealed A-V conduction, the effect of blocked impulse on the formation and conduction of jubsequent impulse. Am Heart J 35: , Langendorf R, Pick A: Concealed conduction; further evaluation of a fundamental aspect of propagation of the cardiac impulse. Circulation 13: , Langendorf R, Pick A, Edclist A, Katz LN- Experimental demonstration of concealed A-V conduction in the human heart. Circulation 32: , Langendorf R, Pick A: Concealed conduction in the A-V junction. In Mechanisms and Therapy of Cardiac Arrhythmias, edited by LS Dreifus, V Likoff. New York, Grune & Stratton, Hoffman BF, Craneficld PF, Stuckey JH: Concealed conduction. Circ Res 9: , Moore NE: Microclcctrode studies on concealment of multiple premature atrial responses. Circ Res 18: , Moore NE; Microelcctrode studies on retrograde concealment of multiple premature ventricular responses. Circ Res 20: 88-98, Damato AN, Lau SH: Concealed and supernormal atnovcntncular conduction. Circulation 43: , Moe GK, Abikbkov JA, Mcndez C: An experimental study of concealed conduction. Am Heart J 67: , Jansc, MJ, Van Capelle FJL, Anderson RH, Touboul P, Billette J: Electrophysiology and structure of the atrioventricular node of the isolated rabbit heart. In The Conduction System of the Heart, edited by HJ Wcllens, Kl Lie, MJ Janse. Leiden, Stenfert Kroese, Denes P, Wu D, Dhingra R, Amat-y-Leon F, Wyndham C, Rosen KM: Dual atnoventricular nodal pathways; a common electrophysiological response. Br Heart J 37: , Reddy CP, Damato AN, Akhtar M, Ogunkelu JB, Caracta AR, Ruskin JN, Lau SH: Time dependent changes in the functional properties of the atnoventricular conduction system in man. Circulation 52: , Scherlag BJ, Lau SH, Helfant RH, Berkowitz WD, Stem E, Damato AN Catheter technique for recording His bundle activity in man. Circulation 39: 13-18, Denes P, Wu D, Dhingra R, Pietras RJ, Rosen KM: The effects of cycle length on cardiac refractory periods in man. Circulation 49: 32^41, Watanabe Y, Dreifus LS Levels of concealment in second degree and advanced second degree A-V block. Am Heart J 84: , Varghese PJ, Damato AN, Paulay KL, Gallagher JJ, Lau SH: Demonstration of entrance block into the atnoventricular node of man. Circulation 46: , Van Capelle HJL, Du Perron JC, Durrer D: Atriovcntncular conduction in isolated rat heart Am J Physiol 221: , Hoffman BF, CranefieW PF: Electrophysiology of the Heart. New York, McGraw-Hill, I Merideth J, Mendez C, Mueller WJ, Moe GK: Electncal excitability of atrioventricular nodal cells. Circ Res 23: 69-85, Mendez C, Moe GK: Some characteristics of transmembrane potentials of A-V nodal cells during propagation of premature beats. Circ Res 19: , 1966