TECHNOLOGY

Comparison of the normal sinus node with seven

types of rate responsive pacemaker duringeveryday activity

A N Sulke, A Pipilis, R A Henderson, C A Bucknall, E Sowton

AbstractThe heart rate response of 59 patientsaged 17-79 years implanted with sevendifferent types of rate responsivepacemakers was evaluated duringgraded exercise treadmill testing andduring standardised daily activities. Theheart rate response in patients withpacemakers was compared with thechronotropic response in 20 healthy con-trols of similar age and sex distributionwho performed identical protocols. Allpacemaker types adequately simulatedthe control heart rate response duringthe graded exercise treadmill test exceptduring the early stages of exercise.However, during everyday activities, theresponse of ventricular rate responsive(VVIR) pacemakers was varied. Activitysensing systems rapidly overrespondedto staircase descent, to changes in walk-ing speed, and to suitcase lifting withthe pacemaker arm, and these systemsdid not respond to mental stress."Physiological" sensors (QT and minuteventilation units) responded slowly torapid changes in physiological demand.The QT pacemaker patients did respondto mental stress but showed a paradox-ical increase in rate during the recoveryphases of burst exercise protocols suchas staircase ascent/descent and walkingdeceleration. Dual chamber pacemakersin VDD, DDD, and DDDR modes mostclosely simulated the normal chrono-tropic response during everydayactivities.Graded exercise treadmill testing, in

isolation, may not be the best way toassess or program the heart rate res-ponse in patients with rate adaptivepacemakers because changes in heartrate during everyday activities maydeviate considerably from the normalsinus response despite satisfactorysimulation of the normal chronotropicresponse during treadmill testing.

Pacemaker implantation, as well as increasinglife expectancy by preventing Adams-Stokesseizures and life threatening bradycardias,'can also improve the patient's quality of lifeby increasing physical capability.2 Rate res-

ponsive pacing systems are now increasinglyused to achieve this end.The advantages of single chamber rate res-

ponsive pacing over VVI pacing are now wellestablished.7 Several different types of rateresponsive pacemakers are currently available(both single and dual chamber) with varioussensors including those that detect activity,8minute ventilation,9 QT interval,'0 centralvenous temperature," venous oxygensaturation,12 pH value,13 and, more recently,dP/dt'4 and the integral of the evoked res-ponse."5Most previous studies to assess sensor

driven rate responsive pacemakers used tread-mill testing or bicycle ergometry.'l'8 Wecompared heart rate changes in patients withsingle and dual chamber rate responsivepacemakers with the chronotropic response ina group of healthy controls during variousstandardised everyday activities and duringgraded exercise treadmill tests.

Patients and methodsPATIENTSFifty nine patients aged 17-79 years (mean57-9, 35 (590o) men) had seven types of rateresponsive pacemaker implanted. Ventricularrate responsive pacemakers (VVIR) wereimplanted in 33 patients. They were theactivity sensing Siemens Sensolog I (10),minute ventilation sensing Telectronics Meta(8), activity sensing Medtronic Activitrax (8),and QT sensing Vitatron Tx II (7). None ofthese patients had the signs or symptoms ofthe pacemaker syndrome."'Dual chamber rate responsive systems were

implanted in 26 patients. Six had MedicoPhymos VDD systems, which require a singlelead with free floating atrial bipolar sensingand unipolar ventricular sensing and pacing;10 had DDD systems; and 10 had activitysensing DDDR systems. The table shows theindications for implantation.

All patients were followed up at 6 weeksand 3 months after pacemaker implantationand were optimally programmed to the rateresponse mode according to the manufac-turers' instructions.We studied heart rate responses in a group

of 20 apparently healthy people aged 23-76years (mean 55 0, 12 (60%) men) duringstandardised daily activities and treadmilltesting.

Department ofCardiology, Guy'sHospital, LondonA N SulkeA PipilisR A HendersonC A BucknallE SowtonCorrespondence toDr A N Sulke,Department of Cardiology,Guy's Hospital, St ThomasStreet, London SEI 9RT.Accepted for publication12 February 1990

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Patient details and indication for pacemaker implantation

Pacemaker type Mode No No male (%) Age range (mean) Indication for implant

Telectronic Meta WIR 8 2(25) 38-79 (633) PHA(2),B(2),AVII +AVIII(4)Medtronic Activitrax WIR 8 1(12-5) 22-77 (58-9) PHA(3),AF+ B(1),SSS(2),AVII +AVIII(2)Siemens Sensolog WIR 10 8 (80) 43-73 (55-8) PHA(5),AF+B(1),SSS(1),B(1),AVII +AVIII(2)Vitatron Tx II WIR 7 5(71) 52-69 (57-9) PHA(2),AF+ B(2),SSS(2),AVII +AVIII(1)Medico Phymos VDD 6 5(83) 52-78 (62-1) AVII(2),AVIII(4)Various DDD 10 8 (80) 22-77 (59-6) B(1),SSS+AVII(1),AVII(2),AVII+AVIII(6)Siemens Multilog (3) Pacesetter Synchrony (7) DDDR 10 6 (60) 17-68 (50-6) SSS +AVII + AVIII(8),AVII + AVIII(2)Total 59 35 (59) 17-79 (57-9)

PHA, post His bundle ablation; B, symptomatic bradycardia; AF, slow atrial fibrillation; SSS, sick sinus syndrome; AVII, 2nd degree atrioventricular block (Mobitztype II); AVIII, complete atrioventricular block.

HEART RATE MONITORINGDuring the study continuous six lead electro-cardiograms were recorded with a SiemensMingolog 7 at a paper speed of 25 mm/s. Theheart rate was calculated from the mean RRinterval of the five consecutive beats recordedimmediately after each stage was completed.Before each activity protocol the resting heartrate was measured after the individual had satat rest for 2 minutes.

STUDY PROTOCOLS: GRADED TREADMILL TESTPatients performed graded exercise treadmilltesting according to the Chronotropic Assess-ment Exercise Protocol (CAEP).20 Allindividuals were exercised to peak efforttolerance.

POSTURE CHANGEThe effects of changes in posture on heart ratewere determined by measuring mean RRinterval over five beats when the individualwas lying, seated, and standing. Heart ratewas measured after individuals had restedsupine on a standard examination couch for 2minutes. The heart rate was measuredimmediately after the subjects sAt upright andimmediately they stood up.

MENTAL STRESSThe effect of mental stress on heart rate wasdetermined over a 2 minute period duringwhich the individual was asked to subtract 7from 100 serially aloud. The supervisi-ngclinician vigorously encouraged the subjectthroughout the study period. Heart rate wasmeasured at rest before mental stress, after 60seconds of stress, and after 120 seconds ofstress (that is, immediately after it stopped.

SUITCASE LIFTINGThe subjects were asked to lift a standardsuitcase (45 cm x 35 cm x 12 cm weighing10 kg) with both hands from the floor on tothe examination couch (a height of 82 cm) andthen immediately back on to the floor. Heartrate was measured before and immediatelyafter they lifted the suitcase.

Subjects were then randomly assigned tosuitcase lifting with either the right or left armand instructed to raise the case from the floorto above hip height four times without stop-ping and heart rate was assessed at rest andafter the procedure. The subject was resteduntil the basal heart rate was achieved andthey repeated the suitcase lifts with theopposite arm.

CHANGES IN WALKING SPEEDWe assessed the response of heart rate to rapidacceleration and deceleration and talkingwhile walking.

Subjects were rested until basal heart ratewas attained (stage 0). They were then in-structed to walk with normal arm movementon a treadmill at 1 mph (16 km/h) and O°gradient for 30 seconds (stage 1). They werethen engaged in active conversation (discuss-ing their travel plans to and from the studycentre) while walking normally at this tread-mill rate for 30 seconds (stage 2). Treadmillspeed was gradually accelerated over the next30 seconds to reach 4 mph (6 4 km/h) (stage3). This rate was maintained for a further 30seconds (stage 4). The treadmill rate was thengradually decelerated to 1 mph (1 6 km/h)during the next 30 seconds (stage 5). Thetreadmill was maintained at 1 mph (1 6 km/h)for the final 30 seconds of the procedure(stage 6). Throughout, individuals wereencouraged to walk without using the supportbars, if possible.

STAIRCASE ASCENT AND DESCENTWe measured the response of heart rate tostaircase ascent and descent from telemeteredelectrocardiographic recordings from aHewlett Packard 78571B recorder.

Subjects were asked to climb two flights ofstairs (30 steps, each 15 cm tall, pitch 27 cm)as rapidly as possible and to rest in the erectposture at the top of the second flight. Heartrate was measured at rest and every 15seconds from the start of the ascent.Once heart rate had returned to resting

values individuals were asked to descend thestairs as fast as possible and to rest at the baseof the second flight. Heart rate during stair-case descent was calculated every 15 secondsfrom start of the descent.

STATISTICAL ANALYSISHeart rate and percentage change in heart ratewere calculated for each individual at everystage of the protocol in the study, wherepercentage change in heart rate = observedheart rate - resting heart rate . resting heartrate x 100Mean heart rate and mean percentage

change in heart rate were calculated for eachpacemaker type and for the control populationfor every stage of each protocol.We used unpaired Student's t tests to

measure statistical differences between per-centage change in heart rates in the pacemaker

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70-Figure 1 A comparisonby the graded exercisetreadmill test of sevendifferent types of rateresponsive pacemaker. 60-

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groups and the controls. A p value of < 0 05was regarded as statistically significant.

ResultsGRADED EXERCISE TREADMILL TESTS (FIG 1)During the first 4 minutes of exercise theobserved increase in heart rate varied in allsingle chamber systems. Sensolog, Activitrax,and Meta significantly overresponded whileVitatron Tx patients were significantly(p < 0-001) underresponsive compared withthe value in the controls.During the latter stages of the exercise test

and the recovery phase all pacemakers closelysimulated heart rate changes in the controls.During recovery, heart rate fell appropriatelyin all groups except for Vitatron Tx patientsin whom high rates decayed more slowly(p < 0 05) than in the controls. The VDDpatients showed a significant (p < 001)underresponse after 5 minutes of exercisebecause the essential rate limiting program-ming required a pacemaker Wenckebach 2:3

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Figure 2 The effect of mental stress on change in heart rate in controls and patientswith pacemakers.

block to start at comparatively low heart ratesunless a very short (< 100 ms) atrioventriculardelay was programmed. This trend occurredin both the other dual chamber modes athigh workloads but did not reach statisticalsignificance.

POSTURE CHANGEIn the controls the heart rate increased whenthey sat up from the lying position, andincreased further when they stood up from thesitting position. The heart rate response withdual chamber and Sensolog pacemakers wassimilar to that of the controls.The heart rate response to posture change in

patients with Activitrax, Meta, and VitatronTx pacemakers was significantly less than thatin the controls (p < 0 05, p < 0 001, andp < 0-001 respectively).

MENTAL STRESS (FIG 2)The increase in heart rate seen during mentalstress was similar in patients with DDDpacemakers and controls. Initially the heartrate response in patients with VDD andDDDR pacemakers was significantly less thanthat in the controls (p < 0 05), though at theend of the mental stress test the heart rateresponse was similar to that of the controls.The Vitatron Tx group showed a delayed heartrate response to mental stress but the meanpercentage increase at the end of the stressprotocol was similar to that of the controls.Patients with all other pacemakers showedlittle or no response to mental stress and thechanges in heart rate in these patients weresignificantly less than those in the controls(p < 0o0O1).SUITCASE LIFTING (FIG 3)The increase in heart rate in the controls wassimilar with four lifts ofthe right or left arm or asingle lift with both arms. All pacemakersperformed well except the Vitatron Tx whichsignificantly underresponded (p < 0 01) to allforms of suitcase lifting. Patients with Sensolog

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.........0...... Sensolog

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Figure 3 The effect of suitcase lifting on heart rate in controls and patients withpacenmakers. Both before, before lifting with both arms; both after, after lifting with botharms; PM before, before lifting with pacemaker arm; PM after, after lifting withpacemaker arm; non-PM before, before lifting with non-pacemaker arm; non-PM after,after lifting with non-pacemaker arm.

pacemakers significantly overresponded tosuitcase lifting with the pacemaker arm

(p < 0 001), and patients with Activitraxpacemakers showed a similar trend (p < 0 08).

CHANGE IN WALKING SPEED (FIG 4)The controls showed a gradual increase in heartrate with a greater increase after stage 4 and a

gradual decrease in heart rate after stage 5.Dual chamber systems closely mimicked thenormal sinus response at all stages of thisprotocol.

Vitatron Tx patients responded slowly to the

Figure 4 Effect ofwalking acceleration anddeceleration on change inheart rate. Protocol stagesare described in text.

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acceleration phase (stage 3) and fast walking(stage 4) with a paradoxical rate increase duringthe deceleration phase (stage 5) and final slowwalking (stage 6).The activity sensing VVIR systems

produced greater increases in heart rate thanwere seen in controls (p < 0-001) at all stages.Meta patients overresponded to the accel-

eration, fast walking, deceleration, and finalslow walk (stages 3-6) but the increase in heartrate was appropriate during slow walking andtalking.

STAIRCASE ASCENT (FIG 5)All individuals completed the ascent within 15seconds and therefore the remaining 60seconds of the protocol represents the recoveryperiod. Controls showed a rapid increase inheart rate to a peak after 15 seconds of theprotocol, with a plateau at 30 seconds and agradual decay to resting rate by 75 seconds.Both Meta patients (p < 0 01) and Vitatron Txpatients (p < 0 001) underresponded to theinitial effort of rapid staircase ascent. VitatronTx patients also showed a paradoxical rateincrease up to 45 seconds after the initialexertion.During ascent and recovery, patients with

the Activitrax, VDD, DDD, and DDDR sys-tems and controls had similar changes in heartrate.

STAIRCASE DESCENTControls showed half the change in heart rateseen in staircase ascent with a gradual decreasein heart rate from 15 seconds to resting rateby 60 seconds. Activity sensing pacemakers(Sensolog, Activitrax, and DDDR) initiallyoverresponded to rapid staircase descent(p < 0-001, p < 0-01, and p < 0 05 respec-tively). Sensolog patients were slow to return toresting heart rate after the initial exertion.

Vitatron Tx patients underresponded to the

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initial effort phase (p < 000 1) and showed aparadoxical rate increase in the recovery phase.Patients with Meta and DDD systems showedno significant difference in changes in heartrate compared with the controls.

DiscussionPrevious studies comparing adaptive ratepacing and fixed rate pacing"23 and thosecomparing different types of rate responsivepacemakers""'8 used either treadmill testing or

bicycle ergometry to assess haemodynamicfunction, oxygen consumption', and the heartrate response. In addition, the graded exercisetreadmill test is widely used to assess theprogramming of rate responsive systems.24However, burst exercise is far more common

in everyday out of hospital activity thangradually increasing or prolonged physicalexertion. Treadmill exercise is also "synthetic"in that the normal movement of the upper bodyis largely inhibited by both bicycle ergometryand exercise treadmill testing because patientsgrip either cycle handlebars or treadmill sup-port bars.We compared the heart rate response of

patients with seven different types of rateresponsive pacemakers, both dual and singlechamber, with the natural chronotropic res-

ponse of the normal sinus node during variousstandardised daily activities and during a

graded exercise treadmill test. The study was

designed to reproduce commonly encountereddaily activities that involve burst exercise andalso mental stress at rest.

In our patients the paced heart rate responseduring the graded exercise treadmill testsclosely simulated the heart rate response inapparently healthy controls. This is not sur-

prising because rate adaptive pacemakers are

developed and evaluated by such tests. Thesefindings confirm those of previous comparative

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60 75

studies,'1'8 and also suggest that by conven-tional criteria programming of the pacemakersunder study was appropriate.25During the early exercise phase (up to stage

2, or 4 minutes of exercise) the single chamberunits that sensed activity and minute ventila-tion overresponded while the QT sensingpacemakers underresponded. Dual chamberpacemakers most closely simulated the naturalchronotropic response. During the laterexercise stages, however, the single chamberunits more accurately simulated the normalresponse. In the dual chamber systems ratelimiting programming, which avoids a pace-maker mediated "endless loop" tachycardia byinducing Wenckebach or 2:1 block, causedunderresponse at high metabolic demand.These data confirm previous studies of theperformance of the single chamber units dur-ing treadmill testing.8-0Assessment by the treadmill test indicates

that the pacemakers under study are adequatesimulators of the normal chronotropic res-

ponse. The performance of the single chamberunits assessed by the daily activity protocolswas, however, less satisfactory. During posturechange, control heart rates increased moreduring the change from lying to sitting thanfrom sitting to standing. This was probablybecause the height of the examination couchmeant that subjects required less effort to"stand down" from the seated posture than torise from the supine to the seated position. Thedual chamber systems and the activity sensingSensolog VVIR pacemakers respondedappropriately to this protocol.The activity sensing units (Sensolog and

Activitrax) tended to rapidly overrespond tomost of the burst exercise protocols. Thesewere specifically designed to evaluatepacemaker response while subjects were un-

inhibited by support bars and therefore showedthe same movement of the upper body that

Figure S The effect ofascending stairs on changein heart rate.

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would be encountered during everyday living.The almost universal overresponse suggeststhat algorithms were designed on the basis ofresponse during "synthetic" exercise such astreadmill exercise or bicycle ergometry. Whenthe patient has uninhibited physical mobilitythe manufacturers' suggestions for the settingsof slope and threshold produce a relativeoverresponse of paced heart rate for agiven physiological demand. There was nosignificant response to mental, resting stress aswould be expected from the sensitivity andspecificity of this type of sensor that isdescribed as "non-physiological" by Rossi.26Similarly, lack of heart rate response to theValsalva manoeuvre and hand grip was shownwith activity sensors.27 Both Activitrax andSensolog overresponded to suitcase liftingwith the pacemaker arm, but respondedappropriately to lifting with both arms and toarm lifting on the non-pacemaker side, againsuggesting oversensitivity to movement of theupper torso. The piezo sensor is shaken morewhen the pectoral muscle on the side of theimplant is active than when there is counter-balancing by symmetrical activity of the uppertorso as when both arms are lifted or whenlifting with the opposite arm.The variation in the response of the two

types of activity sensing pacemaker, as well asbeing the result of differing programmingrecommendations by the manufacturers, mayalso be the result of different processing of thesensor signal. The piezo crystal, which isbonded to the can in the Sensolog unit, and theactivity sensors in both DDDR units that westudied, respond more to pressure than vibra-tion because processing takes account ofamplitude, frequency, and total variation insignal length. In the Activitrax pacemaker thesensor is also can-bonded but responds more tocan vibration, with the piezo crystal actingpartly as a vibration counter, and less topressure over the pacemaker itself.28 This maymake the Activitrax less specific than theSensolog but the programming algorithmsseem to allow better simulation of the naturalchronotropic response to a wider variety ofdaily activities with the Activitrax than with theSensolog.The Meta unit, which senses minute ventila-

tion, and Vitatron Tx, which senses thestimulus-QT interval, proved slow to react toburst exercise and tended to underrespond tomost protocols. Similar findings were recentlyreported with these pacemakers during theperformance of daily activities.29 The Tx unitsoften responded so slowly to stress-for exam-ple staircase ascent and descent and walkingdeceleration-that rates increased paradox-ically in the recovery phases. This slowness torespond is the result of the changes in thestimulus-QT interval at the start of exercise.Baig et al showed an acute prolongation of thestimulus-QT interval at the start of treadmillexercise before the widely accepted shorteningafter more prolonged stress.30 Despiteimprovements in detection algorithms and rateresponse slopes this finding will make it dif-ficult for this type of sensor to respond rapidly

and accurately to everyday burst activity.Patients with Vitatron Tx units, however,responded best of all the VVIR systems to themental stress protocol, closely simulating thenatural chronotropic response. This confirmsthat functioning of this sensor was more"physiological", with the response based on aprobable increase in adrenergic drive duringthe protocol; this ultimately shortened thestimulus-QT interval giving a good simulationof the normal chronotropic response to restingstress.The Meta patients underresponded to men-

tal stress and change in posture. They wereslow to respond when they walked up a stair-case and remained in high rate response wellinto the recovery period, though their responseto walking down stairs was appropriate. Thissensor lacks specificity because an increase inheart rate does not always correlate with anincrease in either respiratory rate or minuteventilation.26 Thus though there was signifi-cantly more response to resting stress than thatfound with the activity sensors it was signifi-cantly less than in the controls. The persistenceof high heart rates during recovery phasesparalleled the increased respiratory rate whichdecays more slowly than heart rate in controls.Other workers found a paradoxical change in

pacing rate in patients implanted with Metaunits when they performed the Valsalva man-oeuvre while supine.3' An increase in rate witharm swinging was also reported with VVIRunits sensing minute ventilation and unitssensing respiratory rate such as the BiotecBiorate32; we did not find that this was animportant effect in our studies.The dual chamber pacemakers all tended to

simulate the natural chronotopic responseduring standardised daily activities. In ourstudy the Medico Phymos VDD units under-responded to mental stress. This was becausein two patients heart rate increased sufficientlyto activate the rate limiting function that wasprogrammed to avoid pacemaker mediatedtachycardia by inducing a 2:3 heart block atrates over 150 beats per minute. This may havebiased the group result and it is thereforedifficult to draw firm conclusions from thesedata.Most patients implanted with DDDR

pacemakers in this study had both sinus nodedysfunction and high grade atrioventricularblock. This system, therefore, is the only onewe have assessed where a "combination" sen-sor is operating by tracking the sinus responseand using an activity sensor to augment the rateresponse and thus "support" the sinus nodewhen its response is inadequate. During mentalstress when the activity sensor is not contribut-ing to the rate adaptation, the tracking responseincreases heart rate although significantly lessthan in controls. The activity sensor, however,seems to predominate during the staircasedescent protocol, causing an initial over-response to this stress. Overall, however, theseunits performed better than any of the singlesensor, single chamber rate adaptive pace-makers we studied.

In all but one patient with a DDD pacemaker

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in our study group, the response of the sinusnode to exercise was normal. Overall simula-tion of the normal chronotropic response dur-ing the everyday activity protocols was best inpatients with DDD pacemakers.

CONCLUSIONAll the pacemakers under investigation showedappropriate heart rate response to exercisetreadmill testing when compared with healthycontrols. Our data show that the simulation ofnatural chronotropic response during dailyactivities is generally poor in patients implan-ted with VVIR pacemakers. The advantagesand disadvantages of different sensors dependon their specificity and sensitivity to increasedphysiological demand.A combination sensor may improve the rate

adaptation of single chamber rate responsivepacemakers during everyday activity. Earlyrate adaptation to physical stress by sensorsthat rapidly respond to activity followed bylater input by "physiological" sensors (that isthose that respond to minute ventilation,stimulus to QT interval, pH, temperature, oroxygen saturation) would improve pacemakersensitivity and specificity to a wide variety ofstresses and facilitate better simulation of thenormal sinus node response to everydayactivities and circadian variations in heartrate.33 Recent work with multiple sensors seemspromising.34At present, dual chamber pacemakers still

give the best form of rate responsive pacing interms of heart rate changes during everydayactivities.

1 Alt E, Volker R, Wirtzfeld A, Ulm K. Survival and follow-up after pacemaker implantation: a comparison ofpatientswith sick sinus syndrome, complete heart block and atrialfibrillation. PACE 1985;8:849-55.

2 Rickards AF, Donaldson RM. Rate responsive pacing. ClinProg Pacing Electrophysiol 1983;1:12-9.

3 Karlof I. Haemodynamic effect of atrial triggered versusfixed rate pacing at rest and during exercise in completeheart block. Acta Med Scand 1975;197:195-203.

4 Rossi P, Rognoni G, Occhetta E, et al. Respiration depen-dent ventricular pacing compared with fixed ventricularand A-V synchronous pacing: aerobic and haemodynamicvariables. J Am Coll Cardiol 1985;6:646-52.

5 Beyersdorf F, Kreuzer J, Happ J, Zegelman M, Satter P.Increase in cardiac output with rate responsive pace-makers. Ann Thorac Surg 1986;42:201-5.

6 Humen DP, Kostuk WS, Klein GJ. Activity sensing, rateresponsive pacing: improvement in myocardial perfor-mance with exercise. PACE 1985;8:52-9.

7 Lau CP, Camm AJ. Role of left ventricular function andDoppler derived variables in predicting haemodynamicbenefits of rate responsive pacing. Am J Cardiol1988;62:906-1 1.

8 Humen DP, Anderson K, Brumwell D, et al. A pacemakerwhich automatically increases its rate with physicalactivity. In: World symposium of cardiac pacing: proceed-ings. Dormstadt, Federal Republic of Germany:Steinkopff Verlag, 1983:259-64.

9 Rossi P, Plicchi G, Canducci GC, Rognoni G, Aina F.Respiratory rate as a determinant of optimal pacing rate.PACE 1983;6:502-10.

10 Rickards AF, Donaldson RM, Thalen HJ. The use of QTinterval to determine pacing rate: early clinical experience.PACE 1983;6:346-54.

11 Alt E, Hirgstetter C, Heinze M, Blomer H. Rate control ofphysiologic pacemakers by central venous blood tem-perature. Circulation 1986;73:1206-12.

12 Wirtzfeld A, Goedel-Meinen L, Bock T, Heinze R, LissHD, Munteanu J. Central venous oxygen saturation forthe control of automatic rate responsive pacing. PACE1982;5:829-35.

13 Cammilli L, Alcidi L, Papeschi G, et al. Preliminaryexperience with pH-triggered pacemaker. PACE 1978;1:448-57.

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17 Alt E, Volker R, Hogl B, MacCarter D. Comparison ofActivitrax and Nova MR pacemakers with VVI/AAIpacing. Circulation 1988;78 (suppl III):1 16-24.

18 Maisch B, Langenfeld H. Rate adaptive pacing-clinicalexperience with 3 different pacing systems. PACE1986;9:997-1004.

19 Ausubel K, Furman S. The pacemaker syndrome. AnnIntern Med 1985;103:420-9.

20 Wilkoff BL, Corey J, Blackburn C. Analytic techniques inthe assessment of chronotropic response to exercise[Abstract]. PACE 1988;11:530.

21 Lipkin DP, Buller N, Frenneaux M, et al. Randomisedcrossover trial of rate responsive Activitrax and conven-tional fixed rate ventricular pacing. Br Heart J 1987;58:613-6.

22 Faerestrand S, Breivik K, Ohm 0. Assessment of the workcapacity and relationship between rate response andexercise tolerance associated with activity sensing rateresponsive ventricular pacing. PACE 1987;10: 1277-90.

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