Comparison of Cardiac Refractory Periods inChildren and Adults

By IRA W. DuBRow, M. D., ELIZABETH A. FISHER, M. D., FERNANDO AMAT-Y-LEON, M.D.,

PABLO DENES, M.D., DELON WU, M. D., KENNETH ROSEN, M.D., AND

ALOIS R. HASTREITER, M.D.

SUMMARYAtrial (A) and A-V nodal (AVN) effective and functional refractory periods (ERP & FRP) were determined

by atrial extrastimulus technique in 40 children, aged 7 months to 16 years, with normal P-R intervals andQRS durations. These data were compared to adult data at longest cycle lengths (CL) assuring atrial cap-

ture. All values are listed in msee as means + standard errors of the means. CL was 566 ± 15 in children and699 ± 29 in adults (P < .001). Refractory periods (RP) in children and adults were, respectively: AERP196 ± 9 and 239 ± 13 (P < .01), AFRP 225 ± 8 and 284 ± 11 (P < .001), AVNERP 239 ± 11 and 293 ± 7(P < .001), AVNFRP 360 ± 13 and 403 ± 7 (P < .005). RP were then compared at three equivalent CLranges: CL,, 850-600; CL2, 599-460; CL3, 459-280. The following RP were significantly shorter in children(P < .05-.001): AERP, AFRP, AVNERP and AVNFRP at CL, and CL3. RP of the bundle branches were

compared and tended to be shorter in children. In conclusion, atrial and A-V nodal ERP and FRP are shorterin children than adults. This shortening is only partially related to the shorter CL in children. These data are

germane to understanding the maturation of the conduction system in man.

Additional Indexing Words:ElectrophysiologyFunctional refractory period

Extrastimulus techniqueHis bundle electrogram

Effective refractory period

ELECTROPHYSIOLOGICAL STUDIES in thecatheterization laboratory have contributed

greatly to the understanding of normal and abnormalA-V conduction in patients. The methods involvedutilize intracardiac electrogram recordings to deter-mine basic conduction intervals, to observe responsesof the conduction system to rapid atrial pacing, and tomeasure refractory periods with atrial extrastimulustechnique.1-5 Most reports of normal and abnormalconduction physiology have been in adults. There area limited number of studies concerning normalpediatric cardiac electrophysiology which deal onlywith the description of conduction intervals.6-10

In the present report, we have systematically ex-amined the cardiac refractory periods of children withnormal electrocardiograms and have compared themto a similar group of adults. With these data we wereable to draw conclusions regarding the developmentof the juvenile conduction system.

From the Sections of Pediatric and Adult Cardiology, AbrahamLincoln School of Medicine and University of Illinois College ofMedicine, Chicago, Illinois.Supported in part by the University of Illinois Foundation

Goodenberger Medical Research Grant (2-44-33-66-3-14).Address for reprints: Ira W. DuBrow, M.D., Section of Pediatric

Cardiology, University of Illinois Hospital, 840 South Wood Street,Chicago, Illinois 60612.

Received September 13, 1974; revision accepted for publicationOctober 29, 1974.

Circulation, Volume 51, March 1975

Materials and Methods

Patient Selection

Studies were performed in 40 children (ages 7 months-15years) during diagnostic cardiac catheterization. Onlychildren with evidence of normal A-V conduction on 14-leadscalar electrocardiograms were included (sinus rhythm, nor-mal P-R interval for age, normal heart rate and narrowQRS). The clinical status, ECG, and intracardiac elec-trogram intervals for these patients are summarized in table1. Patients 37, 38 and 39 were patients 6, 10 and 15previously reported by Denes et al.5

Electrophysiologic Procedure

Parents were informed of the nature of the study and asigned consent was obtained. No child was receiving cardiacdrugs. The studies were performed in the postabsorptive,lightly sedated state following the diagnostic part of the car-diac catheterization.

Electrode catheters were introduced percutaneously intothe femoral vein. In children larger than twenty-fivepounds, catheters were inserted into the same vein and inthe smaller children, one catheter was placed in eachfemoral vein. A tripolar or hexapolar catheter was positionedacross the tricuspid valve to record low atrial, His bundleand ventricular electrograms. A multipolar catheter waspositioned in the high right atrium, and the distal electrodeswere connected to a stimulus output isolator for pacing. Theproximal electrodes were utilized to record high atrial elec-trograms. Interelectrode distance between pacing and re-cording sites of the high right atrial catheter was 0.5 cm inchildren and 1 cm in adults.

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with the intracardiae electrograms on an oscilloscope. Ex-perimental procedures were similar to those describedpreviously by Wit et al. and Denes et al.4 Basic un-

stimulated intervals were first recorded at paper speeds of200 and 100 mm/sec. Controlled drive stimuli (S1) andprogrammed atrial premature stimuli (S2) were delivered tothe high right atrium.* S, was first adjusted to a rate just fastenough to assure atrial capture. S2 was then introduced in10-20 msee decrements following every eighth S, until no

intracardiac response occurred. In 31 patients, S1-S2decremental series were then recorded at 1-4 cycle lengths(CL) shorter than control (table 2). Stimuli pulses were rec-

tangular, 5 msec in duration and approximately twicediastolic threshold.

Basic intervals P-A, A-H, and H-V were measured as

previously described by Abella et al.6 A,, H,, V, were lowatrial, His bundle and ventricular electrograms induced byS,. A2, H2, V2 were corresponding electrograms following S2.Intervals S1-S2, Al-A2, A2-H2, H2-V2, H,-H2 and V1-V2 were

defined and measured as described by Denes et al.5

Definitions

Atrial effective refractory period (AERP) was the longestS,-S2 at which atrial capture failed to occur. Atrial functionalrefractory period (AFRP) was the shortest Al-A2 attainable.At times, the shortest coupling interval was too long todetermine the AERP or AFRP. When this happened, thevalues were described as being less than the shortest intervalrecorded. A-V nodal effective refractory period (AVNERP)was the longest A1-A2 at which H2 failed to be elicited. A-Vnodal functional refractory period (AVNFRP) was theshortest H1-H2 attainable. Effective refractory period of theright and left bundle branches (ERPRB & ERPLB) was thelongest H1-H2 at which the respective bundle branchpattern occurred in the surface ECG. When AFRP was

longer than AVNERP, the refractoriness of the system was

atrial limited. In this situation, the atrium becomes refrac-tory before the A-V node. Therefore, AVNERP could not bemeasured and was designated as less than AFRP. AVNFRPwas equal to or less than the shortest H1-H2.

Analysis of Data

Refractory periods at the longest cycle length assuringatrial capture were determined. Refractory periods obtainedat longest and shorter cycle lengths (table 2) were thengrouped into cycle length ranges (CL1 850-600 msec, CL2599-460 msec, CL3 459-280 msec). Means, standarddeviations and standard errors of the mean were calculatedfor each group of values.

For comparison, adult refractory period data was usedfrom the reports of Wit et al.4 and Denes et al.5 Twenty-oneof twenty-four patients, older than 16 years, were used fromthe latter to supply atrial, A-V nodal and bundle branchrefractory periods at longest cycle length, and the twentypatients from the former supplied A-V nodal refractoryperiods at cycle length just short enough to capture the rightatrium. Refractory periods from cycle length ranges (CL1,CL2, CL3) were obtained from the report of Denes et al.5Means, standard deviations and standard errors of the meanwere calculated.

Cycle length and refractory periods observed at thelongest cycle length assuring atrial capture in children were

compared to similarly obtained data in adults. Refractory

periods at the three equivalent CL ranges were then com-

pared. The significance of the difference in variables was

found by the Student's t-test for unpaired data.

Results

Basic Unstimulated Intervals. P-A, A-H and H-V ineach patient were within normal limits of previouslyreported data (table 1).

Longest Cycle Length: (table 3). The longest CLassuring atrial capture in children was significantlyshorter than in adults (P < .001). AERP, AFRP,AVNERP and AVNFRP were significantly shorter inchildren than in adults (P < .001).

Refractory Periods at CL,, 850-600 msec: (table 4).AERP, AFRP, AVNERP and AVNFRP were notsignificantly different in children than in adults.

Refractory Periods at CL2, 599-460 msec: (table 4).AERP in children was 199 ± 7 and in adults was

232 ± 10 (P < .01). AFRP in children was 234 ± 7and in adults was 271 4 9 (P < .005). AVNERP inchildren was 260 ± 9 and in adults was 328 + 10(P < .001). AVNFRP in children was 345 + 11 and inadults was 406 ± 11 (P < .005).

Refractory Periods at CL3, 459-280 msec: (table 4).AERP in children was 165 ± 5 and in adults was

199 ± 6 (P < .01). AFRP in children was 200 ± 5 andin adults was 252 7 (P < .001). AVNERP inchildren was 219 ± 6 and in adults was 280 ± 13(P < .001). AVNFRP in children was 299 ± 7 and inadults was 345 ± 8 (P < .005).

Atrial Limited Conduction. Atrial limited conduc-tion was found at all cycle lengths tested in 19 of 40children and in 6 of 21 adults (Chi square NS).

Effective Refractory Periods of the BundleBranches: (table 5). ERPRB was observed in 11children and in 5 adults. At longest CL ERPRB inchildren was 323 ± 13 and in adults was 412 + 36(P < .05). CL, was not compared as the sample sizeswere small. At CL2 and CL3, ERPRB in children was

not significantly different than in adults. ERPLB was

observed in 9 children and in 2 adults. The samplesizes were not large enough for statistical comparison,although at longest CL and CL, children tended tohave shorter values. At CL3 no adult values were

available to compare.

Discussion

There are many structural and physiologicaldifferences in the developing heart. Patten reviewedthe development of the sinoventricular conductionsystem and the electrocardiogram in chick embryoand showed that the P-R interval was present beforethe A-V node developed.11 Navaratnam reported thedevelopment of cardiac nerves in the human embryoand fetus.12 Van Mierop demonstrated that the*Stimulator built by M. Bloom, Philadelphia, Pennsylvania.

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Table 2

Cycle Lengths and Refractory Periods

Patient CIL

1 470

2 470

3 440410

4 300470

5 5106 420

3807 340

4408 470

400380

9 310

340350

10 470440380

11 440380310

12 600470390

13 420

14 420360310

15 470340300

16 380310270

17 310

380250

18 310

19 53020 610

530510470

21 530430380

22 51023 450

380340

24 350470410360

AERP AFRP

200 220

130 1350

130 140130 130180 240210 240230 280

140 160140 160160 210160 210220 230240 2.30230 240120 180120 180140 170190 200180 190130 210130 190130 210120 190280 300280 300130 240180 190100 130100 190100 190150 220130 220160 210130 200140 200130 200170 210170 180170 210

<260 <275250 290160 250180 230200 250210 220240 230260 250240 230180 190180 190170 180170 180

170 230180 240160 240140 240

AVNERP AVNFRP

<220

<140<150260

<240280

<160<160<210<210<230<230<240.180<180<170<200<190<210260220210300320290

<190220

<190<190230220220

<200<200<200<210<180<210

273<290280350330370280300300240210230260

<230<240<240<240

290

315

230230300340440260260220

330320310300300300340320310320270260400400360

270220240320300270280280260280280280330323410400420430350350350300310320470320320320310

Patient CIL

25 610310

430

380310

26 320410360300

27 310

440380300280

28 a30470

29 310470410

30 620310

43031 61032 68033 370

410360

34 310440380340

3a 620300

47036 770

620320450380

37 620310

410360

38 600443

39 763360310

480485

40 360410300

AERP

1801901901702001701802001801901701601a01602403331702001802002001,30100360170170130160

<160<210.210170160160180220180210180190190190180193190290290270260230130

<140200

AFRP

24023502502402102402402302302002101801801902702533

270220160

220200200170

<160<210<210180

17032028026026026025023 0230240210210310310290270280200200210

AVNERP AVNFRP

<240 330<250 340.230 310<240 3835.210 280.240 300.240 280<230 280<230 240<200 320<210 320<180 270<180 230<190 240300 460340 423240 380310 380290 360270 383270 340210 330210 390480 380

<220 340<200 300<200 300230 310230 330260 330260 3302350 470230 420220 430

<320 340<280 360<260 3350<260 320.260 320330 380280 330280 330300280 410

323 413<310 490

333 320330 303

370 400

200200

<210

330310300

Abbreviations: AERP Atrial effective r.efractory period;AFRP = Atrial functional refractory period: AVNERP =A-V node effective refractory period; AVNFRP = A-V nodefunctional refractory period; CL = Cycle length.

pacemaker at the initiation of the heart beat in chickembryos was in the sinus horn remnants of the rightatrium.`3 He also measured sino-atrial conduction

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Table 3

Refractory Periods at Longest Cycle Length Assuring Atrial Capture

Children AdultsMean BD SEM Mean SD SEM

CL 535 89 14 698 107 21(N = 40) (N = 26)

P <.001AERP 187 53 9 236 49 10

(N = 40) (N = 26)P < .001

AFRP 217 45 8 274 47 9(N = 35) (N = 26)

P < .001AVNERP 241 5,6 9 289 44 7

(N = 40) <N = 46)P <.001

AVNFIRP 345 71 12 406 46 7(N = 38) (N = 45)

P <.001

Abbreviations: AEIIP = Atrial effective refractory period; AFRP - Atrial functional refractory period;AVNERP = A-V node effective refractory period; AVNFRP = A-V node functional refractory period; CL-Cycle length; N = Number of patients; SD = One standard deviation; SEM = Standard error of mean.

time. Friedman et al.`4 Dawes,` Caldeyro-Barcia etal.'6 and Walsh and Lind'7 have shown that there isautonomic control of the fetal heart rate and rhythmwhich differs from adults. Lipton et al.'8 and Churchet al.'9 have shown autonomic instability with vagalpredominance in infants. James has demonstratedremodeling of the A-V junction and of His bundlebetween two weeks and two years of postnatal life,and a progressive increase in collagen in the S-A andA-V nodes until adulthood.20 Jose and Collison"showed an inverse linear relationship between age

and intrinsic heart rate in adult man by phar-macologic autonomic denervation using atropine andpropranolol. Faster heart rates in children comparedto adults is well known. Recent reports of pediatricpatients have shown that intracardiac conductiontimes in children tend to be shorter than in adults.6 10

This difference is related to age and heart rate. Thereare no published data regarding refractory periods inchildren.

Because heart rate influences refractoriness of theconduction system,22 we compared atrial and A-Vnodal refractory periods in juvenile and adult hearts atequivalent cycle length ranges. There was a signifi-cant difference at the two faster ranges. At the slowestrange the differences were not significant; however,the number of children whose cycle lengths could becontrolled at slower rates was small. Previous reportshave demonstrated a definite relationship between cy-

cle length and functional refractory periods of thecanine A-V conduction system. Mendez et al. showeda curvilinear relationship between refractory periodsand cycle length in dogs.23 Denes demonstrated a

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positive relationship between cycle length and atrialeffective and functional and A-V nodal functionalrefractory periods and an inverse relationship between

Table 4

Refractory Periods at Various Cycle Lengths

Children AdultsMean SD SEM Mean SD SEM

CL1, 850-600 msecAERP 206 -80 2.5 232 -80- 15

N =-0 NS N = 28AFRP 247 .53 22 275 49- 9

N = 6 NS N = 28AVNEI{P 303 - 81 - 29 290 - 50 - 9

N = 8 NS N = 28AVNFRP 427 - 74 - 26 401 - 48 = 9

N = 8 NS N = 26

CL2, 599-460 msecAERP 199 43- 7 232 54 10

N = 37 P <.01 N = 30AFRP 234 43- 7 271 49- 9

N = 34 P <.005 N = 30AVNERP 260 -55=5- 9 328 - 56 - 10

N = 37 P <.001 N = 30AVNFI{P 354 - 66 - 11 406 - 57 - 11

N = 37 P <.005 N = 29

CL3, 459-280 msecAERP 165 37 5 199 28=- 6

N = 57 P < .01 N = 23AFRP 200 - 35- 5 252 -34- 7

N =-4 P < .001 N = 23AVNERP 219 - 45 - 6 280 . 52 - 13

N=5 P <.001 N = 16AVNFRP 299 - 46 7 345 , 27 X 8

N =49 P <.005 N = 13

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Table 5

Effective Refractory Periods of Bundle Branches

Right bundle Left bundleChildren Adults Children Adults

CL Mean SD SEM Mean SD SEM Mean nD SEM Mean SD SaM

Longest 323 39 13 412 72 36 361 52 17 473 67 61N 11 N = 5 N = 9 N = 2

P < .0 NS

CL, 8.50-600 msec 390 443 42 21 404 31 13 434 59 30N 1 N = 4 N = 6 N 4

NS NS

CL2 599-460 msec 363 35 11 367 28 11 370 61 25) 365N = 10 N = 6 N = 6 N 1

NS NS

CL3 <459 msec 298 28 6 328 16 8 330 34 10N = 22 N = 4 N = 12

cycle length and A-V nodal effective refractory periodin adult men.5 Preston et al. showed that the A-V nodein young mammals tended to have shorter refractoryperiods and that the A-V node was a less efficient filterto progressively more premature beats.24We have shown that the juvenile state of the con-

duction system is also a determinant of refractoryperiods. Children have significantly shorter refractoryperiods than adults at equivalent cycle length ranges.Denes5 observed six of twenty-one patients in whomthe atrial functional refractory period exceeded theA-V nodal effective refractory period at all cyclelengths tested. Wit4 observed this in three of twentypatients at longest cycle lengths assuring capture. Ineight of twenty-one of Denes' patients, atrial limita-tion no longer occurred as cycle length was shortened.We found atrial limited conduction in nineteen of for-ty patients at all cycle lengths tested. Because of this,the A-V node effective refractory periods had to beless than the atrial functional refractory periods, andthe A-V nodal functional refractory periods may havebeen shorter than those observed. Ferrier and Dresel25showed atrial limited conduction in 10 of 20 caninehearts at driving intervals greater than 320 msec. Asthe driving interval decreased, atrial limitation wasless, as the atrial refractory periods became shorterthan those of the A-V node and ERP and FRP of A-Vnode could be measured. Denes was able to bring outthe refractory periods of the A-V node in eightpatients in whom AFRP exceeded AVNERP at thelongest cycle length. However, in our patients, wewere unable to bring out AVNERP. The statisticallysignificant differences between children and adults ex-ceed those which could be expected from variations inthe atrial pacing sites - both groups were paced fromthe high right atrium. This indicates that either thejuvenile AVN is a faster recovering structure relative

to the atrium or that the juvenile atrium is a slowerrecovering tissue relative to the A-V node.

Atrial echo beats were not observed in the group ofchildren.

There were not enough adult values for full com-parison of bundle branch differences, although thechildren tended to have shorter bundle branch refrac-tory periods at the various cycle length ranges. Theonly significant difference found was that the rightbundle branch was shorter in children at the longestcycle length.We conclude from the data presented that the

atrium, A-V node and His-Purkinje system proximalto the bundle branches in the juvenile heart havesignificantly shorter refractory periods than in theadult heart. There are not enough observations of thebundle branches to conclude that there is nodifference between child and adult values. Theseobservations in the juvenile heart may be related toincreased sympathetic tone, the remodeling process inthe conduction system which is known to occur withage, and only partially to the faster heart rates inchildren.

Clinical Implications

There are a number of clinical implications of thepresent data. The shorter refractory periods inchildren probably account for the faster atrial andventricular rates encountered in juvenile atrial flutterand for the faster ventricular rates in juvenile parox-ysmal supraventricular tachycardia (PSVT).26' 27 Atrialflutter, whether it be circus movement or ectopic inorigin, cannot produce an atrial cycle length shorterthan the atrial functional refractory period. Sinceatrial functional refractory period is shorter inchildren, flutter rates would be faster. Similarly, ven-tricular rates in atrial flutter and fibrillation will be

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governed by the functional refractory period of theA-V node. Children would be expected to have fasterventricular responses because of the shorter A-V nodefunctional refractory period.

Current evidence suggests that most paroxysmalsupraventricular tachycardias in adults reflect A-Vnodal re-entrance.28 It has been suggested that A-Vnodal functional refractory period is a partial determi-nant of rate during this arrhythmia - the shorter A-Vnode functional refractory period allowing a fasterventricular rate. The shorter A-V node functionalrefractory period in children could explain the morerapid rates seen in juvenile paroxysmal supraven-tricular tachycardia.Another implication of this work relates to adults

with short P-R intervals. This group is characterizedby short A-H intervals and sometimes by short A-Vnode refractory periods. Although some evidencesuggests that these adults have A-V node bypasstracts, it should be noted that electrophysiologicalfindings in this group of adults resemble normalvalues for juvenile A-V nodal conduction times andrefractory periods.29 It is possible that adults withshort P-R intervals have immature A-V nodes withoutbypass tracts.

In addition, our data should be useful in es-tablishing normal pediatric values for refractoryperiods.

Acknowledgment

The technical expertise of Mr. Frank Domanszky, Ms. AudraJarasius and Ms. Jan Littke and the secretarial assistance of Mrs.Bernice Senger, Ms. Dorothy Bradford and Mrs. Lorraine Nelsen isgratefully acknowledged.

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2. ROSEN KM: The contribution of His bundle recordings to theunderstanding of cardiac conduction in man. Circulation 43:961, 1971

3. DHINGRA RC, ROSEN KM, RAHIMTOOLA SH: Normal conductionintervals and responses in sixty-one patients using His bun-dle recording and atrial pacing. Chest 64: 55, 1973

4. WIT AL, WEISS MB, BERKOWITZ WD, ROSEN KN, STEINER C,DANIATO AN: Patterns of A-V conduction in the humanheart. Circ Res 27: 345, 1970

5. DENES P, Wu D, DHINGRA R, PIETRAS RJ, ROSEN KM: The effectof cycle length on cardiac refractory periods in man. Circula-tion 49: 32, 1974

6. ABELLA JB, TEIXIERA 0, MISRA K, HASTREITER A: Changes ofatrioventricular conduction with age in infants and children.Am J Cardiol 30: 876, 1973

7. BRODSKY SJ, MIROWvSKI M, KROVETZ J, ROWE RD: Recording ofHis bundle and other potentials in children. J Pediatr 79: 61,1971

8. ROBERTS N, OLLEY P: His bundle electrogram in children:

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Statistical correlation of the atrioventricular conductiontimes in children with their age and heart rate. Br Heart J34: 1099, 1972

9. ROBERTS N, OLLEY P: His bundle recordings in children withnormal hearts and congenital heart disease. Circulation 45:295, 1972

10. BEKHEIT S, MORTON P, MURTAGH JG, FLETCHER E: Comparisonof sino-ventricular conduction in children and adults usingbundle of His electrograms. Br Heart J 35: 507, 1973

11. PATTEN B: The development of the sinoventricular conductionsystem. Michigan Med Bull 22: 1, 1956

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W DuBrow, E A Fisher, G Amaty-Leon, P Denes, D Wu, K Rosen and A R HastreiterComparison of cardiac refractory periods in children and adults.

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