electrophysiological abnormalities in the transplanted heart · electrophysiological abnormalities....

Br HeartJ 1983; 50: 555-63

Electrophysiological abnormalities in the transplantedhuman heartRODNEY S BEXTON,* ANTHONY W NATHAN,* KEVIN J HELLESTRAND, RICHARDCORY-PEARCE,t ROWORTH A J SPURRELL, TERENCE A H ENGLISH, A JOHN CAMMtFrom the Department of Cardiology, St Bartholomew's Hospital, London, and the British Heart Foundation HeartTransplant Research Unit, Papworth Hospital, Papworth Everard, Cambridge

SUMMARY Fourteen relatively long term survivors of cardiac transplantation underwent systematicelectrophysiological evaluation and ambulatory electrocardiographic monitoring. Six patients hadprolonged conduction intervals during sinus rhythm. Sinus node function could be assessed in alldonor atria and in 10 recipient atria. Sinus node recovery times were prolonged in four of the donoratria and in six recipient atria. In the donor atria abnormalities of sinus node automaticity were

invariably associated with abnormalities of sinoatrial conduction. Four patients showed functionalduality of atrioventricular nodal conduction during programmed extrastimulation, but no patientdeveloped re-entrant arrhythmia. During ambulatory electrocardiographic monitoring no pronouncedtachyarrhythmias were recorded. Three patients showed abnormalities of sinus node impulseformation. All three patients had abnormal sinus node recovery times during theirelectrophysiological study. Long term survivors of cardiac transplantation have a high incidence ofelectrophysiological abnormalities. Abnormalities of donor sinus node function are probably ofclinical significance. The clinical significance of abnormalities detected within the atrioventricularconduction system of the denervated heart remains to be elucidated.

The therapeutic and prognostic implications ofabnormalities found during invasive electro-physiological testing have been widely reported.1-5Although the sensitivity and specificity of formaltesting of sinus node function in man may belimited,67 abnormalities within the atrioventricularconduction system, particularly in certain subgroupsof patients or when associated with other cardio-vascular abnormalities, appear to carry greatertherapeutic implications.8-'0 The significance ofelectrophysiological abnormalities in asymptomatic,apparently normal subjects has obviously not beendetermined.

Although previous reports from both StanfordUniversity, California, and Papworth Hospital, Cam-bridge, have indicated a high incidence of both atrialand ventricular arrhythmias in transplant patients' ' 12together with a relatively high incidence of sinus node

*Recipient of British Heart Foundation fellowship.tBritish Heart Foundation senior research fellow.tWellcome senior lecturer.

Accepted for publication 19 July 1983

disease,3 the incidence of abnormalities found dur-ing electrophysiological testing has not been reported.The purpose of this investigation was to detail theabnormalities detected during a systematic elec-trophysiological evaluation and during the ambulat-ory electrocardiographic monitoring of a group ofrelatively long term survivors of cardiac transplanta-tion.

Patients and methods

Fourteen cardiac transplant recipients underwentroutine electrophysiological evaluation four to 28(mean 14) months after transplantation. Their agesranged from 24 to 54 (mean 38) years, and 13 patientswere men (Table). The study was performed becauseof the previous reports of a high incidence of sinusnode and conduction system disease in patients aftercardiac transplantation,"1-13 which in at least onestudy has been associated with an increased mortal-ity.'4 All patients were completely asymptomatic withno haematological, biochemical, or electrocardio-graphic evidence of rejection. All patients were

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Bexton, Nathan, Hellestrand, Cory-Pearce, Spurrell, English, CaminTable Patient details and results

Case No. Sex Diagnosis Age at time of Survival at time Abnormal Abnormal Abnormalbefore transplant study (years) of study (months) conduction sinus node refractory

intervals function tests period

1 M IHD 43 4 + - -2 M CM 41 9 - - -*3 M IHD 44 11 + - -4 M CM 37 18 - - -5 M CM 24 17 - - -6 M CM 24 14 + - -*7 M IHD 31 22 + + -*8 M IHD 54 28 + + -*9 F CM 34 8 - + -10 M IHD 28 14 - + -11 M IHD 49 18 - - -12 M IHD 35 17 - - -13 M IHD 53 15 + - -14 M IHD 42 7 - + -

IHD, ischaemic heart disease; CM, cardiomyopathy; *, functional duality of atrioventricular nodal conduction; +, present; -, absent.

taking prednisolone and azathioprine as routineimmunosuppressive treatment, and no patient wastaking cardioactive drugs. Seven patients hadimplanted epicardial ventricular demand pacemakers,which had been implanted at operation because of thepreviously reported poor prognosis associated withearly sinus node dysfunction after transplantation.14

ELECTROPHYSIOLOGICAL STUDYThe patients were studied in the non-sedated, postab-sorptive state after written informed consent had beengiven. Prior approval for the study had been obtainedfrom the ethical committee of St Bartholomew's Hos-pital. All patients were premedicated with intramus-cular flucloxacillin, which was continued orally fortwo days after the electrophysiological study, andthere was no appreciable short term or long termmorbidity associated with the study. Five pacing elec-trodes were inserted into the right femoral vein underlocal anaesthesia and positioned within the heart usingfluoroscopic guidance. During orthotopic cardiactransplantation'5 the posterior portions of the reci-pient atria are left in situ together with the recipientsinus node. A quadripolar electrode was thereforepositioned at the junction between the superior venacava and right atrium to record and stimulate therecipient atrial remnants. Two bipolar electrodes werepositioned within the appendage of the donor rightatrium for recording and stimulation. An electrodewas manipulated across the septal leaflet of the tricus-pid valve to record distinct electrograms from the lowright atrium, His potential, and the proximal portionof the right ventricular septum. A further electrodewas advanced to the apex of the right ventricle forstimulation.

Bipolar endocardial signals from the electrodeswere passed through appropriate amplification andfiltering and recorded on a Mingograf ink jet recorder

at 100 mm/s, together with four surface electrocar-diographic leads. Intracardiac stimulation wasachieved using constant voltage, current limitedsquare wave pulses of 1.5-2.5 ms duration at abouttwice diastolic threshold.

Conduction intervals were measured during sinusrhythm and during constant rate donor right atrialpacing at cycle lengths of 500 ms and 400 ms. Theintervals were measured according to previouslydescribed definitions'6 and defined as normal orabnormal based on the normal range of values fornormally innervated adult man.'7-20 Sinus noderecovery time was assessed by overdrive suppression2land was defined as the maximum sinus pause afterstopping right atrial pacing at rates of 110 (if appro-priate), 130, 150, and 170 beats/min for periods of 15,30, and 60 s at each rate. The results were correctedby subtracting sinus cycle length.22 The upper limitof normal for sinus node recovery time was acceptedas 1400 Ms23 and for corrected recovery time as 525ms.22 Both donor and recipient sinus node recoverytimes were assessed during synchronous pacing ofboth sets of atria. Sinoatrial conduction time wasassessed by introducing programmed atrial beats dur-ing sinus rhythm and calculated according to therevised method of Strauss et al.24 The upper limit ofnormal was accepted as 206 ms.25 Both donor andrecipient sinoatrial conduction times were assessed.

Anterograde and retrograde conduction charac-teristics and refractoriness of the donor heart weredetermined by introducing an extrastimulus afterregular donor atrial or ventricular pacing26 27 at cyclelengths of 500 ms and 400 ms. Standarddefinitions'62627 and normal values27-29 were usedfor estimating the effective and functional refractoryperiods of the various components of the atrioven-tricular conduction system.

Functional duality of atrioventricular nodal con-

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duction was considered to be present when, duringassessment of atrioventricular nodal refractoriness,there was a discontinuity on the anterograde conduc-tion curve with a sudden jump in the H1-H2 interval,and therefore concomitantly in the A2-H2 interval, ata critical A1-A2 coupling interval.3032 Duality ofatrioventricular nodal conduction was defined as ajump in the H1-H2 interval of 40 ms or greater for adecrease of 10 ms in the A1-A2 coupling interval.32The curve to the right of the discontinuity representsfast atrioventricular nodal pathway conduction and tothe left slow pathway conduction.

In one patient the electrophysiological study had tobe ended prematurely for technical reasons. Conduc-tion intervals and sinus node function tests from 14patients and refractory periods from 13 patients aretherefore reported below.

AMBULATORY ELECTROCARDIOGRAPHICMONITORINGEach patient underwent 24 hour ambulatory elec-trocardiographic monitoring using either four inchreel to reel two channel tape recorders or two channelcassette recorders. The recordings were subjected toautomatic and technician analysis to assess the inci-dence of arrhythmic episodes of any origin or aeti-ology or evidence of sinus node or conduction systemdisease.

Results

CONDUCTION INTERVALSDuring sinus rhythm four patients had prolonged PAintervals (55 ms, 60 ms, 60 ms, and 70 ms), twopatients had prolonged HV intervals (both 60 ms),and two patients had prolonged QRS durations (115ms and 130 ms) (Fig. 1). Both the patients with pro-longed QRS durations had complete right bundlebranch block. In one of these patients the abnormality

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Fig. 1 Conduction intervals in individual patients. The mean± I SD is also indicated. Dashed lines indicate the upper limit ofnornal for normnally innervated man.

had been present on the donor electrocardiogrambefore transplantation. Although eight patients had aprolonged QTc, no patient had a prolonged QT inter-val measured during sinus rhythm based on normalvalues.20

SINUS NODE FUNCTION (Fig. 2)In two patients no electrical activity of the recipientatrium was recorded nor could this atrium be paceddespite high pacing energies. In one patient the reci-pient atrium was fibrillating while the donor atriumremained in sinus rhythm (Fig. 3). In one patient thedonor and recipient atria remained synchronisedthroughout a variety of physiological and pacing man-oeuvres. This unique situation has been reportedelsewhere.33 The sinus node function of 14 donoratria and 10 recipient atria could therefore be asses-sed.

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Fig. 2 Results of sinus node function tests inindividual patients. The mean ± I SD is alsoindicated. Dashed lines indicate the upper limit of

* normallfor normally innervated man. SCL, sinusT * cycle length; SNRT, sinus node recovery time;

* cSNRT, corrected sinus node recovery time.a---- -4-*. SI

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RAr ,;^ * s_

RAd ) -- ~ >- ~ ~> ~ Fig. 3 Electrocardiogram illustrating the recipient atrium inatrialfibrillation while the donor atrium remains in sinus rhythm.

HBE - RAr, recipient atrial electrogram; RAd, donor atrialelectrogram; HBE, His bundle electrogram. I, aVF, VI, andV6 are surface electrocardiographic leads.

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Fig. 4 Electrocardiogram showing a considerably prolonged recovery time of the donorsinus node. The secondary pause is interrupted by a ventricular escape beat which is almostsynchronous with a sinus escape beat. The arrow indicates the last pacing stimulus (pacingboth recipient and donor atria). This pause follows pacing at a rate of 130 beatsmnin for60 s. RAr, recipient atrial electrogram; RAd, donor atrial electrogram; HBE, His bundleelectrogram. I, aVF, VI, and V6 are surface electrocardiographic leads.

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/ duality of atrioventricular nodal conduction. The curve to the100 right of the discontinuity represents fast pathway conduction and/BCL -4O

to the left of the discontinuity slow pathway conduction. In thisAl =A OOms example there is a jump in the A2-H2 interval of 70 ms for a 20

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Fig. 6 Electrocardiogram showing the jump in AH interval as the fast pathway becomesrefractory. Panel a shows a basic driven pacing cycle length (SI-SI) of500 ms with an AHinterval (Al-HI) of 65 ms foUowed by an atrial extrastimulus with a coupling interval(SI-S2) of300 ms. The extrastimulus (S2) conducts through thefast pathway with an AHinterval (A2-H2) of 160 ms. In panel b with an SI-S2 interval of 280 ms the refractoryperiod of the fast pathway has been exceeded and the extrastimulus (S2) conduc:s throughthe slow pathway with an AH interval (A2-H2) of 280 ms. All measurements are in ms.RAr, recipient right atrial ekctrogram; LA, left atrial ekectrogram; RAd, donor right atrialelectrogram; HBE, His bundle electrogram. I, aVF, VI, and V6 are surfaceelectrocardiographic leads.

The sinus cycle length was greater than 1000 msin one of the donor atria and in four of the recipientatria. Sinus node recovery times and corrected recov-ery times were prolonged in four (of the 14) donoratria and in six (of the 10) recipient atria. In twopatients (cases 8 and 9) the donor sinus node recoverytime exceeded 2500 ms (Fig. 4). One of these patients(case 9) had an implanted ventricular pacemaker, theother did not. The uncorrected sinoatrial conductiontime (measured using the method of Strauss24) of thedonor atria was prolonged in four patients (206 ms,220 ms, 240 ms, and 460 ms) and abnormally short inone patient (5 ms). Four of these five patients hadprolonged donor sinus node recovery times. In onepatient the dramatically prolonged sinoatrialconduction time (460 ms) was due to considerablesinus node suppression during the zone of reset. Evenafter correcting this value for sinus node suppression,however, the sinoatrial conduction time was stillprolonged at 275 ms. The recipient sinoatrialconduction time was prolonged in four patients (222ms, 234 ms, 235 ms, and 282 ms), but only two ofthese patients had prolonged recovery times.

REFRACTORINESSThe atrial, ventricular, and atrioventricular refractoryperiods estimated at a cycle length of 500 ms were allwithin normal limits. Four patients had evidence offunctional duality of anterograde atrioventricularnodal conduction during assessment of atrioventricu-

lar nodal refractoriness at a pacing cycle length ofeither 500 ms (three patients) or 400 ms (threepatients) (Figs. 5 and 6). Jumps in the A2-H2 intervalranged from an increase of 50 ms for a 10 msdecrease in the A1-A2 coupling interval to an increaseof 105 ms for a 5 ms decrease in A1-A2 interval.Only one patient showed functional duality of con-duction in the retrograde direction.From these previous results and the table it can be

seen that only four patients (cases 4, 5, 11, and 12)had entirely normal electrophysiology of the trans-planted donor heart.

AMBULATORY ELECTROCARDIOGRAPHICRECORDINGSA total of 447 hours of ambulatory electrocardio-graphic recordings were performed in the 14 patients.The period of monitoring ranged from 20 to 70 (mean31-9) hours. Seven patients had no abnormalities. Onepatient had flutter of the donor atrium on his first 24hour recording. He had no clinical, biochemical, orhaematological evidence of rejection and underwentDC cardioversion under a general anaesthetic fivehours before his electrophysiological study, duringwhich donor sinus node function was normal. Therewas no abnormality on his second recording. Threepatients (cases 1, 3, and 11) had infrequent unimor-phological ventricular premature beats (less than oneper hour), but in one of these patients (case 1) thepremature beats occurred in couplets. Two of these

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three patients (case 1 and 3) also had a moderatenumber of atrial premature beats, which in case 1occurred in couplets and on one occasion initiated a 3s run of atrial fibrillation. No episode of ventriculartachyarrhythmia was recorded in any patient.Three patients (cases 8, 9, and 14) showed relative

bradycardias throughout their recordings. Two ofthese patients (cases 9 and 14) had implanted ven-tricular pacemakers, the other did not (case 8). Allthree patients had abnormal donor sinus nodefunction tests during their electrophysiologicalevaluation. Patient case 8 (corrected sinus noderecovery time 1440 ms) showed sudden changes insinus rate, sometimes by as much as 33 beats/min,with the initial pause interrupted by a junctionalescape beat on occasions. The sinus rate fell to 57beats/min at times, even during waking hours. Therecordings in case 9 showed sinus rates less than 80beats/min at all times and ventricular demand pacingat 70 beats/min for a high proportion of the 24 hoursincluding waking hours. This patient had a correcteddonor sinus node recovery time of 1360 ms during herelectrophysiological study. The recording in case 14,who had a corrected donor sinus node recovery timeof 935 ms, showed several episodes of ventriculardemand pacing at 70 beats/min and donor sinus ratesnever exceeding 85 beats/min. This patient also hadsudden changes in heart rate, which usually followedan atrial premature beat. The P wave of the sloweratrial rhythm had a different morphology and vectorto that of the faster rate, suggesting different sites oforigin of the two atrial pacemakers.

Discussion

The incidence and significance of abnormalities of theatrioventricular conduction system found duringinvasive electrophysiological studies of symptomaticpatients and patients with obvious conduction systemdisease, or during routine surface electrocardio-graphic screening of asymptomatic subjects, havebeen well reported.3 4 9 1018 34-37 The incidence andsignificance of abnormalities of the conduction systemdetected during electrophysiological evaluations inasymptomatic patients with normal surface elec-trocardiograms are, naturally, unknown. Similarly, theinfluence of the denervated state of the transplantedheart on the significance of abnormalities detected isunclear. Other studies from our laboratory (unpub-lished observations) have shown that the elec-trophysiological characteristics of the atrioventricularconduction system of the transplanted heart are simi-lar to those of the innervated heart and therefore thesignificance of conduction abnormalities found in thetransplanted heart may probably be equated to thatreported for the innervated heart.

Four patients had a prolonged intra-atrial conduc-tion time. Impulse conductiorA from the sinus node tothe atrioventricular junction probably takes placeprimarily through muscular connections.38 The sur-gical technique entailed in cardiac transplantationmay result in damage to these muscular connections,and this, together with the physical distortion of thedonor atrium, may account for the high incidence ofintra-atrial conduction delay in these patients. Suchconduction delay may result in first degree heartblock,'8 but spontaneous higher degrees of block havenever been reported. Second degree Wenckebachtype block within the atrium has, however, beenreported with atrial pacing.3940The finding of a slightly prolonged HV interval in

two patients, who were asymptomatic and had normalsurface electrocardiograms, is probably of no clinicalsignificance. Although the significance of a prolongedHV interval in patients presenting with syncope iswell documented,36 in asymptomatic patients, eventhose with bundle branch block, reports of the prog-nostic implications of His-Purkinje conduction delayhave been confficting.3 4Two of the 14 patients had complete right bundle

branch block, although in one of these this had beenpresent before operation in the donor heart. Thiscompares with reported prevalences of 0.180/o in122 043 airmen,35 0 4% in an insurance population of30 000 subjects,4' 0.75% in 3983 airmen,34 and 1*15%in 8770 members of an average population.42 Thelong term follow up studies of Mathewson and Var-nam,34 Reusch and Vivas,42 and Rotman and Trieb-wasser37 of subjects with right bundle branch blockshowed that in subjects with no evidence of heart dis-ease and a normal axis the only deaths were due tonon-cardiac causes and no cases of advanced atrioven-tricular block were recorded. Similarly, in the mortal-ity study of Rodstein et al.4' the presence of rightbundle branch block did not imply a higher mortalityin the absence of other major cardiac abnormalities.The limitations of invasive electrophysiological test-

ing of sinus node function in normally innervatedman6 7 25 are well known. There is often a poor corre-lation between the results of electrophysiological test-ing and the presence or absence of symptoms.6 43 andclinical signs and symptoms may result primarilyfrom escape pacemaker malfunction and not from thesinus node malfunction itself.44 The effect of theautonomic nervous system may be important,45 andperhaps of prime importance, in terms of the prog-nosis of sinus node disease, is the coexistence ofunderlying heart disease.2446

In the absence of autonomic neural influences for-mal testing of donor sinus node function in transplantpatients may provide a more reliable indicator of trueintrinsic sinus node function than in the innervated

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heart, as has been suggested from studies using phar-macological autonomic blockade.4748 The spontane-ous abnormalities of sinus node function found duringambulatory electrocardiographic monitoring in threeof the four patients with abnormal sinus node func-tion tests during invasive testing but in none of thepatients with normal sinus node function tests addfurther credence to this theory. These three patientsalso showed relative bradycardias during their 24 hourrecordings. In the absence of the normally dominantvagal tone49 the resting heart rate of the denervatedsinus node tends to be faster than in the innervatedheart with resting heart rates of 100 beats/min or grea-ter.The clinical course of the sick sinus syndrome may

be variable but tends to be progressive,I and its prog-nosis is uncertain. The ultimate prognosis dependspartly on the characteristics and stability of the escaperhythm of lower pacemakers, which may be unreli-able in transplant patients.'4 The finding of abnor-malities of donor sinus node function during invasivetesting in transplant patients may therefore be of grea-ter clinical significance than abnormalities found inpatients with normally innervated hearts. The highincidence of recipient sinus node disease may well berelated to underlying disease before the operation andto the relative ischaemia induced by the surgery but isprobably of limited clinical importance.Four of the 13 patients in whom atrioventricular

nodal refractory periods were assessed showed func-tional duality of atrioventricular nodal conduction.Dual atrioventricular pathways predispose toatrioventricular nodal re-entrant tachycardia inman30 31 50 as originally hypothesised by Moe et al.5Iand later shown by Mendez and Moe52 in animalexperiments, and they are a common finding duringelectrophysiological testing of patients with supraven-tricular tachycardia.53 They are also a relatively com-mon finding in arrhythmia free adults54 and chil-dren.3255 Denes et al.54 showed dual pathways in 41out of 397 patients studied. Sixteen of these 41patients were arrhythmia free. Similarly Thapar andGillette32 reported an incidence of 290/o, and Casta etal.55 reported an incidence of 35% in arrhythmia freechildren with a variety of congenital cardiac defects.This high incidence of dual atrioventricular nodalpathways in children may be related to their consider-ably shorter atrial refractory periods,55 which wouldallow the unmasking and increased expression of dualpathways. The relatively high incidence of dual path-ways in transplant patients (31%) may be related tothe young age of the donor hearts, to the slightly shor-ter refractory periods of the atrioventricular conduc-tion system compared with innervated hearts, and, toan unknown extent, to the denervated state of thetransplanted heart. All four patients had retrograde

ventriculoatrial conduction, but only one patient hadretrograde functional duality of conduction and nopatient showed atrial echoes during programmedextrastimulation at either basic pacing cycle length.Hence no patient developed sustained re-entranttachycardia. Although dual pathways are the elec-trophysiological substrate for atrioventricular re-entrant tachycardia, its initiation depends on aninterplay of many factors. It is not known whether thefinding of dual pathways in an arrhythmia free patientis a benign electrophysiological phenomenon repre-senting the normal functional characteristics of thehuman atrioventricular node or whether thesepatients are at risk of developing a clinically importantarrhythmia. Long term longitudinal studies of suchpatients are not available.

Although previous studies from Stanford Univer-Sityl1 12 have reported a high incidence of both atrialand ventricular arrhythmias in asymptomatic trans-plant patients, this was not borne out by us. Infre-quent atrial and ventricular premature beats wererecorded in only four patients, and the only appreci-able arrhythmia recorded was a short run of atrialfibrillation in one of these patients. The period ofrecording was obviously relatively short and few con-clusions can be drawn about the incidence andsignificance of arrhythmias in these patients.Asymptomatic, relatively long term survivors of

cardiac transplantation thus have a high incidence ofelectrophysiological abnormalities. As already indi-cated, abnormalities of donor sinus node functionmay well be of clinical significance, although longterm follow up studies are required to clarify thispoint. Limited data from studies in normally inner-vated man suggest that the abnormalities foundwithin the atrioventricular conduction system areprobably relatively benign but obviously it is imposs-ible, and unwise, to make direct comparisons with theinnervated heart because of the unique denervatedstate of the transplanted heart.

References

1 Ferrer MI. The sick sinus syndrome. Circulation 1973;47: 635-41.

2 Levites R, Haft JI. Significance of first degree heartblock (prolonged P-R interval) in bifascicular block. AmJ Cardiol 1974; 34: 259-64.

3 Dhingra RC, Denes P, Wu D, et al. Prospective observa-tions in patients with chronic bundle branch block andmarked H-V prolongation. Circulation 1976; 53: 600-4.

4 Scheinman MM, Peters RW, Modin G, Brennan M,Mies C, O'Young J. Prognostic value of infranodal con-duction time in patients with chronic bundle branchblock. Circulation 1977; 56: 240-4.

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5 Narula OS, Narula JT. Junctional pacemakers in man.Response to overdrive suppression with and withoutparasympathetic blockade. Circulation 1978; 57: 880-9.

6 Gupta PK, Lichstein E, Chadda KD, Badui E. Appraisalof sinus nodal recovery time in patients with sick sinussyndrome. Am j Cardiol 1974; 34: 265-70.

7 Crook B, Kitson D, McComish M, Jewitt D. Indirectmeasurement of sinoatrial conduction time in patientswith sinoatrial disease and in controls. Br Heart J 1977;39: 771-7.

8 Narula OS, Samet P. Wenckebach and Mobitz type IIA-V block due to block within the His bundle andbundle branches. Circulation 1970; 41: 947-65.

9 Dhingra RC, Denes P, Wu D, Chuquimia R, RosenKM. The significance of second degree atrioventricularblock and bundle branch block. Observations regardingsite and type of block. Circulation 1974; 49: 638-46.

10 Strasberg B, Amat-y-Leon F, Dhingra RC, et al. Naturalhistory of chronic second-degree atrioventricular nodalblock. Circulation 1981; 63: 1043-9.

11 Berke DK, Graham AF, Schroeder JS, Harrison DC.Arrhythmias in the denervated transplanted humanheart. Circulation 1973; 47/48 (suppl III): III-112-5.

12 Schroeder JS, Berke DK, Graham AF, Rider AK, Harri-son DC. Arrhythmias after cardiac transplantation. AmJ7Cardiol 1974; 33: 604-7.

13 Mason JW, Harrison DC. Electrophysiology and elec-tropharmacology of the transplanted human heart. In:Narula OS, ed. Cardiac arrythmias: electrophysiology,diagnosis and management. Baltimore: Williams and Wil-kins, 1979: 66-81.

14 Mackintosh AF, Carmichael DJ, Wren C, Cory-PearceR, English TAH. Sinus node function in first threeweeks after cardiac transplantation. Br HeartJ 1982; 48:584-8.

15 Stinson EB, Dong E Jr, Iben AB, Shumway NE. Cardiactransplantation in man. III. Surgical aspects. Am J Surg1969; 118: 182-7.

16 Hellestrand KJ, Bexton RS, Nathan AW, Spurrell RAJ,Camm AJ. Acute electrophysiological effects of flecainideacetate on cardiac conduction and refractoriness in man.Br Heart J 1982; 48: 140-8.

17 Castellanos A Jr, Castillo CA, Agha AS. Contribution ofHis bundle recordings to the understanding of clinicalarrhythmias. Am J Cardiol 1971: 28: 499-508.

18 Narula OS, Scherlag BJ, Samet P, Javier RP. Atrioven-tricular block. Localization and classification by Hisbundle recordings. Am J Med 1971; 50: 146-65.

19 Castellanos A, Myerburg RJ. The resting electrocardio-gram. In: Hurst JW, ed. The heart. 2nd ed. New York:McGraw-Hill, 1982: 257-72.

20 Lipman BS, Massie E, Kleiger RE. Clinical scalar elec-trocardiography. 6th ed. Chicago: Year Book MedicalPublishers, 1972: 670.

21 Mandel W, Hayakawa H, Danzig R, Marcus HS. Evalu-ation of sino-atrial node function in man by overdrivesuppression. Circulation 1971; 44: 59-66.

22 Narula OS, Samet P, Javier RP. Significance of thesinus-node recovery time. Circulation 1972; 45: 140-58.

23 Rosen KM, Loeb HS, Sinno MZ, Rahimtoola SH, Gun-nar RM. Cardiac conduction in patients with sympto-matic sinus node disease. Circulation 1971; 43: 836-44.

24 Strauss HC, Bigger JT Jr, Saroff AL, Giardina EGV.Electrophysiologic evaluation of sinus node function inpatients with sinus node dysfunction. Circulation 1976;53: 763-76.

25 Strauss HC, Scheinman MM, LaBarre A, Browning DJ,Benditt DG, Wallace AG. Programmed atrial stimulationand rapid atrial pacing in patients with sinus pauses andsinoatrial exit block. In: Bonke FIM, ed. The sinus node.Structure, function and clinical relvance. The Hague:Martinus Nijhoff, 1978: 56-64.

26 Wit AL, Weiss MB, Berkowitz WD, Rosen KM, SteinerC, Damato AN. Patterns of atrioventricular conductionin the human heart. Circ Res 1970; 27: 345-59.

27 Akhtar M, Damato AN, Batsford WP, Ruskin JN,Ogunkelu JB. A comparative analysis of antegrade andretrograde conduction patterns in man. Circulation 1975;52: 766-78.

28 Denes P, Wu D, Dhingra R, Pietras RJ, Rosen KM. Theeffects of cycle length on cardiac refractory periods inman. Circulation 1974; 49: 32-41.

29 Schuilenburg RM, Durrer D. Conduction disturbanceslocated within the His bundle. Circulation 1972; 45:612-28.

30 Denes P, Wu D, Dhingra RC, Chuquimia R, RosenKM. Demonstration of dual A-V nodal pathways inpatients with paroxysmal supraventricular tachycardia.Circulation 1973; 48: 549-55.

31 Rosen KM, Mehta A, Miller RA. Demonstration of dualatrioventricular nodal pathways in man. Am J Cardiol1974; 33: 291-4.

32 Thapar MK, Gillette PC. Dual atrioventricular nodalpathways: a common electrophysiologic response in chil-dren. Circulation 1979; 60: 1369-74.

33 Bexton RS, Hellestrand KJ, Cory-Pearce R, SpurrellRAJ, English TAH, Canum AJ. Unusual atrial potentialsin a cardiac transplant recipient. Possible synchroniza-tion between donor and recipient atria. J7 Electrocardiol1983; 16: 313-22.

34 Mathewson FAL, Varnam GS. Abnormal electrocar-diograms in apparently healthy people. I. Long termfollow-up study. Circulation 1960; 21: 196-203.

35 Hiss RG, Lamb LE. Electrocardiographic findings in122,043 individuals. Circulation 1962; 25: 947-61.

36 Touboul P, Ibrahim M. Atrioventricular conductiondefects in patients presenting with syncope and normalPR interval. Br Heart J 1972; 34: 1005-11.

37 Rotman M, Triebwasser JH. A clinical and follow-upstudy of right and left bundle branch block. Circulation1975; 51: 477-84.

38 Merideth J, Titus JL. The anatomic atrial connectionsbetween sinus and A-V node. Circulation 1968; 37: 566-79.

39 Narula OS, Runge M, Samet P. Second-degree Wencke-bach type AV block due to block within the atrium. BrHeart J 1972; 34: 1127-36.

40 Castellanos A, Iyengar R, Agha AS, Castillo CA.Wenckebach phenomenon within the atria. Br Heart J1972; 34: 1121-6.

41 Rodstein M, Gubner R, Mills JP, Lovell JF, UngerleiderHE. A mortality study in bundle branch block. ArchIntern Med 1951; 87: 663-8.

42 Reusch CS, Vivas JR. Clinical analysis of right bundle

562



j.com/

Br H


ber 1983. Dow

nloaded from


Electrophysiological abnornalities in the transplanted human heart

branch block. Am Heart J 1959; 58: 543-6.43 Breithardt G, Seipel L, Loogen F. Sinus node recovery

time and calculated sinoatrial conduction time in normalsubjects and patients with sinus node dysfunction. Circu-lation 1977; 56: 43-50.

44 Mandel WJ, Obayashi K, Laks MM. Overview of thesick sinus syndrome. Chest 1974; 66: 223-4.

45 Jordan JL, Yamaguchi I, Mandel WJ. Studies on themechanism of sinus node dysfunction in the sick sinussyndrome. Circulation 1978; 57: 217-23.

46 Scheinman MM, Strauss HC, Abbott JA. Elec-trophysiologic testing for patients with sinus node dys-function. J Electrocardiol 1979; 12: 211-6.

47 Desai JM, Scheinman MM, Strauss HC, Massie B,O'Young J. Electrophysiologic effects of combined auto-nomic blockade in patients with sinus node disease. Cir-culation 1981; 63: 953-60.

48 Szatmary L, Medvedowsky JL, Barnay C, Coste A,Pisapia A. Electrophysiological effect of overdrive sup-pression and combined autonomic blockade with pro-pranolol and atropine in patients with sinus node dys-function. Eur Heart J 1982; 3: 47-55.

49 Jose AD, Collison D. The normal range and determi-nants of the intrinsic heart rate in man. Cardiovasc Res1970; 4: 160-7.

50 Wu D, Denes P, Dhingra R, Pietras RJ, Rosen KM.New manifestations of dual A-V nodal pathways. EurJCardiol 1975; 2: 459-6.

51 Moe GK, Preston JB, Burlington H. Physiologic evi-dence for a dual A-V transmission system. Circ Res 1956;4: 357-75.

52 Mendez C, Moe GK. Demonstration of a dual A-V nodalconduction system in the isolated rabbit heart. Circ Res1966; 19: 378-93.

53 Wu D, Denes P, Amat-y-Leon F, et al. Clinical, elec-trocardiographic and electrophysiologic observations inpatients with paroxysmal supraventricular tachycardia.Am J Cardiol 1978; 41: 1045-51.

54 Denes P, Wu D, Dhingra R, Amat-y-Leon F, WyndhamC, Rosen KM. Dual atrioventricular nodal pathways. Acommon electrophysiological response. Br HeartJ 1975;37: 1069-76.

55 Casta A, Wolff GS, Mehta AV, et al. Dual atrioventricu-lar nodal pathways: a benign finding in arrhythmia-freechildren with heart disease. Am Jf Cardiol 1980; 46:10138.

Requests for reprints to Dr R S Bexton, Departmentof Cardiology, Freeman Hospital, Freeman Road,Newcastle upon Tyne NE7 7DN.

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