Initial experience with a physiological, rate responsive pacemaker

Transcription

1 BRITISH MEDICAL JOURNAL VOLUME FEBRUARY CLINICAL RESEARCH Initil experience with physiologicl, rte responsive pcemker R M DONALDSON, K FOX, A F RICKARDS Abstrct A new pcemker tht cn dpt the hert rte in response to the ptient's metbolic requirements hs been developed. This pcemker uses the QT intervl s the indictor of physiologicl demnd. Experience in five ptients showed the rte response to exercise to be smooth nd progressive nd to return grdully to the bsic pced rte fter ctivity stopped. Physiologicl rte responsive pcing resulted in 45% increse in crdic output when compred with fixed rte pcing. Similrly, 57%o increse in mximl exercise cpcity ws noted when rte responsive pcing ws compred with conventionl pcing t 7 bets, min. This study showed tht physiologicl rte responsive pcing using the QT intervl provides simple mens of incresing the hert rte in ccordnce with the body's requirements. Introduction One of the min problems of long term crdic pcing is tht pcemkers re electronic devices tht mintin ventriculr ctivtion t fixed, rbitrry rte. They re therefore insensitive to the usul vribility of physiologicl demnds. This is prticulrly evident during exercise, when the inbility to increse the pcing rte results in limited crdic response often insufficient to meet the incresed metbolic demnds. The idel physiologicl form of pcing is thus one tht responds to the body's needs by vrying the crdic output. We recently described rte responsive pcemker tht uses the QT intervl s n indictor of physiologicl demnd1 2 nd report here our erly experience with this pcing system. Ntionl Hert Hospitl, London WlM 8BA, nd Crdiothorcic Institute R M DONALDSON, MD, MRCP, senior medicl registrr K FOX, MD, MRCP, consultnt crdiologist A F RICKARDS, MB, MRCP, consultnt crdiologist Ptients A QT sensing pcemker ws implnted in five ptients (men ge 54 yers) with complete, estblished hert block (tble). Three ptients were undergoing routine chnge of pulse genertor nd hd ventriculr inhibited, fixed rte pcemkers nd long term electrodes. The two other ptients were undergoing routine implnttion of pcemker nd hd short term electrodes. The three ptients with fixed rte pcemkers hd restricted exercise tolernce. One hd chronic rheumtic crditis nd hd undergone ortic vlve replcement, mitrl vlvotomy, nd permnent pcing seven yers previously. A second hd ischemic hert disese, proxysml tril rrhythmis, nd hert block. The etiology of the hert block in the third ptient ws unknown. All three ptients hd dequte increses in the tril rte in response to exercise nd infusion of isoprenline. The two ptients undergoing implnttion of their first pcemker hd been leding n ctive life before the onset of hert block nd were thought likely to benefit hemodynmiclly from rte responsive pcing. One hd tril fibrilltion in ddition to complete trioventriculr block; the etiology of the hert block in the other ws relted to n underlying congestive crdiomyopthy. The pcemker We recently reported the design of this rte responsive pcemker, which uses the QT principle, s well s our initil evlution of the pced evoked response.1 2 The system uses conventionl unipolr pcing electrode with pcemker cpble of sensing the timing of the evoked T wve tht follows ventriculr depolristion. This intervl between stimulus nd T wve depends not only on the pced rte but lso on circulting ctecholmine concentrtions, which provide independent physiologicl informtion.2 The pcemker (TX1, Vittron medicl dignostic pulse genertor; Vittron Medicl BV, The Netherlnds) is lithium powered nd microprocessor bsed (RCA 182) with bit seril I/O tht permits full trnscutneous progrmmbility through rdiofrequency coupling vi progrmmer hed to n externl microcomputer (Hewlett-Pckrd HP85) contining the monitor progrm in its opertionl memory. This permits nlysis nd progrmming of ll conventionl nd T wve trcking, pcing, nd sensing vribles. Anlysis of the mplitude of the evoked T wve (in mv) nd the durtion of the intervl between the pcing stimulus nd the pek of the T wve (in ms) my be obtined; the ltter mesurement permits non-invsive ssessment of phrmco-

2 668 logicl nd physiologicl events in the durtion (ltency) of the pced evoked response.2 Algorithms simulting norml physiologicl response lter the pced rte in response to reltive chnges in the intervl between the stimulus nd the T wve; decrese in this intervl cuses n increse in the rte nd vice vers. The sensitivity or slope of the system to the chnges in the intervl (from 5 to 5 bets/min/ms) nd the slow exponentil drift bck to the bsic rte (nulling) (from 35 to 125 bets/min/h) were progrmmed non-invsively soon fter implnttion nd tilored individully to produce stedy increses in rte (with mximl rte of chnge set t 3 bets/min2) to rech the preset upper rte (up to 18 bets/min) over six to 12 minutes, nd then grdully decrese to the bsic pcing rte (6 to 7 bets/min). In cse of mlfunction of the T wve trcking mode the pcemker cn revert to stndrd ventriculr inhibited (progrmmble) fixed rte mode. BRITISH MEDICAL JOURNAL VOLUME FEBRUARY 1983 Edwrds Lb model No 93A 1317F) positioned in the pulmonry rtery. Holter monitoring-the ptients underwent Holter monitoring over periods of 24 hours using the Oxford Medilog system. From these dt trend nlysis (rte v time) ws computed. Sttisticl nlysis-student's t test ws pplied to evlute chnges in crdic output with both forms of pcing. Results The results were obtined over three month follow up period. In one ptient with crdiomyopthy nd low mplitude (1 mv) T wves trnsient loss of T wve sensing occurred on dys 2-5 fter the implnttion of short term electrodes. There were no other sensing or pcing problems t this erly follow up stge. Mxi,nl work lod nd crdic output with fixed rte nd rte responsive pcing Crdic output (1/min) Mximl work lod (ml oxygen uptke/min/ kg 3 5) Fixed rte pcing (7 bets'min) Rte responsive pcing Age Sex Aetiology of hert block (yers) Fixed rte Rte responsive Rest Exercise pcing pcing (mximl Rest Exercise (men rte (mximl (7 bets,'min) 125 bets/min) 66 bets min) 125 bets/min) 43 M Rheumtic hert disese M Ischemic F Unknown F Atril fibrilltion + complete hert block M Crdiomyopthy Men SD 5-3 j i i 1 87 FIG 1-Chnges in length of pced ventriculr cycle (ms) in response to isoprenline 2,ug intrvenously, mesured by continuous electrocrdiogrphy in led II t stndrd speed (25 mm/s) nd sensitivity 5 cm/mv. Assessment study Phrmcologiclly induced chnges in rte were obtined soon fter implnttion of the pcemker with dministrtion of isoprenline in boluses of 2,ug intrvenously. Chnges in the computer ssessed intervl between the stimulus nd the T wve were lso documented, s ws the timing of the rte increse from continuous recordings obtined on n HP47A electrocrdiogrph. Exercise testing-in ech ptient the effects of ventriculr inhibited, fixed rte pcing t 7 bets/min nd of rte responsive pcing (with mximl rte set t 125 bets/min) were comprtively ssessed on two seprte occsions by mesurements of tolernce to tredmill exercise following the Bruce protocol.4 Studies were performed on verge two weeks fter implnttion of the pcemker, nd the ptients were unwre of which pcing mode ws being evluted. Exercise tolernce ws reported in terms of metbolic equivlents (METS) nd expressed s ml oxygen uptke/min/kg/3-5. Crdic output ws mesured in triplicte both t rest nd t pek exercise with both modes of pcing by the thermodilution technique (CVI model 6, Edwrds Lb Model 951A) fter insertion of Swn Gnz flow directed triple lumen ctheter (CVI model 6-17, Phrmcologiclly induced chnges in rte-figure 1 shows chnges in the pced ventriculr rte in response to isoprenline infusion, the slope being set t 5 bet/min/ms. The mximl rte of 125 bets/min (cycle length 48 ms) ws chieved round three nd hlf minutes fter the infusion nd then fell grdully over the next six minutes. The intervl between the stimulus nd the T wve ssessed noninvsively t two minutes fter the infusion hd decresed from 34 to 32 ms. Exercise stress testing-figure 2 shows the smooth nd progressive dpttion of ventriculr rte during tredmill exercise testing with the slope progrmmed t 1 bet/min/ms. Increses in rte occurred within one minute of the strt of the exercise; fter four minutes the ptient hd chieved rte of 12 bets/min nd t six minutes lmost 12 bets/min (pced cycle length 48 ms). Figure 3 shows this progressive decrese in the pced cycle length in the continuous electrocrdiogrphic recordings during exercise. A grdul decline in the pced rte ensued from the eight minute period of exercise, coinciding with pek exercise work lod nd enbling the ptient to mintin fst rtes for the durtion of the exercise. The ventriculr rte then decresed further to resting levels (cycle length 76 ms). The exponentil negtive drift in the cse illustrted ws set t 65 bets/

3 BRITISH MEDICAL JOURNAL VOLUME FEBRUARY 1983 min/h (fig 2). Exercise tolernce t fixed rte (7 bets/min) nd t the mximl rte response to the shortening of the intervl between the stimulus nd the T wve (125 bets/min) ws plotted (fig 4, tble). Mximl exercise cpcity t the rte 7 bets/min ws 5-3 ± SD 1-2 ml oxygen uptke/min/kg/3 5 while t the pced rte 125 bets/min it ws 8-4± 96 ml oxygen uptke/min/kg/3-5 (p<1). An lmost liner reltion between mximl exercise tolernce nd pced hert rte ws chieved. Crdic output-the chnges in crdic output on exercise prlleled the incresed exercise tolernce (tble). Men resting crdic output ws /min t fixed pced rtes of 7 bets/min; on pek exercise this incresed to /min (p < 1). With rte responsive pcing resting crdic output ws similr ( /min) t men pced rtes of 66 bets/min nd incresed with mximl exercise to /min. The difference between resting nd exercise crdic outputs with rte responsive pcing ws highly significnt (p < -1); the difference between mximl crdic output with fixed rte pcing nd with rte responsive pcing ws lso significnt (p < -1). Holter monitoring-the fluctutions in the ventriculr pced rte 669 during vrious dily ctivities were documented by mbultory monitoring (fig 5); comprison with the ptient's diry permitted confirmtion of pproprite rte responses to exercise. The predominntly bsl rte of round 8 bets/min during overnight rest is lso shown / 75- >5 ul D_E -, u } L- o Exercise work lod z7 77/177, * D 1- ~~~~~~~ 9- * l Minutes FIG 2-Rte responsive pcing during tredmill exercise testing, showing smooth nd progressive increse nd decrese in ventriculr pced rte in womn ged 53. FIG 3-Continuous electrocrdiogrphic recording in led II during tredmill exercise test, showing grdul decrese in pced cycle length from 76 to 48C1 ms s work lod incresed. 25 Discussion Exercise tolernce (rl oxygen uptke/min/kg/3 5) FIG 4-Exercise work lod during ventriculr inhibited, fixed rte pcing t 7 bets/min (A) nd during rte responsive pcing with pek rte of 125 bets/min (*). Men exercise cpcity incresed from 5-24_62 to 8-5±-82 ml oxygen uptke/min/kg/3-5. Most stndrd ventriculr inhibited pcemkers re set t rtes fixed between 6 nd 9 bets/min. The optiml rte in ny person t rest, however, is not the optiml rte for exercise. The two vribles tht determine crdic output re hert rte nd stroke volume. Becuse the hert dpts to pcing by long term increse in the ventriculr end distolic volume nd chmber size the compenstion by chnges in stroke volume chievble on exertion is limited. This together with the fixed pced rte ultimtely benefits the crdic output on exercise in mny of these ptients. The idel physiologicl form of pcing is one tht responds to the body's needs for vrying crdic output. The reltion between trioventriculr synchrony, crdic contrctility, hert rte, nd exercise plys n importnt prt in this. An pproprite tril nd ventriculr ctivtion sequence in ptients with hert block my be chieved with trioventriculr sequentil pcemkers. Although this trioventriculr synchrony my increse crdic output by s much s 2-3/o in ptients with norml ventriculr function,5 this increse by tril systole becomes inconsequentil when 2-3% increses re required by the demnds of exercise. Intrinsic ventriculr function,6 venous return, nd the metbolic demnds modified by exercise7 re lso importnt determinnts of exercise cpcity in ptients with pcemkers. The most importnt determinnt of crdic output, however, is the intrinsic pced rte even in the bsence of tril synchrony.8 Approprite chnges in the ventriculr pced rte my double or triple the crdic output without chnges in filling pressures, even in the bsence of the tril contribution. Furthermore, Krloff9 showed tht t mtched fst pcing rtes (12 bets/min) lmost identicl work nd crdic output re chieved by trioventriculr sequentil (tril synchronous) nd rte djusted, non-trioventriculr sequentil ventriculr pcing. Knudson et l'l lso showed tht considerble increses in exercise cpcity nd crdic output my be chieved by ppropritely incresing the synchronous pced ventriculr rte in response to the physicl ctivity. The new genertion of pcing devices currently under evlution include rte responsive devices, which sense the trium nd pce the ventricle, nd dul chmber utomtic pcers, which pce nd sense both trium nd ventricle. These

4 67 BRITISH MEDICAL JOURNAL VOLUME FEBRUARY 1983 tril synchronous pcemkers re superior to the ventriculr inhibited, fixed rte pcing mode.'1 Some of the initil problems with these pcing devices were relted to the inbility of the pcemker to differentite between physiologicl nd pthologicl tchycrdis, the loss of tril synchrony in tchycrdi, the preset upper rte limits, nd the incidence of pcemker induced re-entrnt trioventriculr rrhythmis"2in ptients with intct retrogrde conduction. With single chmber ventriculr pcing or when sinotril function is bnorml lterntive methods of sensing the physiologicl demnds need to be used, tht produce physiologicl rte response to exercise. Two rte responsive pproches hve been explored. The first uses n tril electrogrphic detector, nd the vritions in the QT intervl in response to ntirrhythmic drugs such s miodrone nd bet-blockers. As in the study reported by Knudson et l,' we found n lmost liner reltion between exercise tolernce nd the pek hert rtes chieved on exercise (fig 5). The men exercise tolernce incresed from 53 ±1-2 ml oxygen uptke/min/kg/3-5 (with fixed rte pcing t 7 bets/min) to 8-4 ±96 (t rte responsive pced rtes reching 125 bets/min). Striking symptomtic improvement ws noted in the three ptients who were originlly restricted to low exercise levels t low fixed pced rtes of 7 bets/min. These three ptients ll hd ner norml exercise tolernce t rnges tht were not pprecibly different from the rnge reported in group of seven subjects with norml Time mrker (hours) 'Betsihour ; 117P 1i l 4 U -7 i 2: 1A E ' 475: ; OS 4W5 ~~~~~~~ 4.~~~~~~~~~~~~~~ O<i -4782,P M Me. SDs 8 S161 I W ZL 439 "'S 8 FIG 5-Trend nlysis of continuous ventriculr rte s recorded by Holter monitor in ptient with complete hert block nd pced rte responsive rhythm, showing fluctutions in rte during vrious dily ctivities. (Note incresed rte during 7-8, corresponding to ptient's erly morning exercises, nd predominntly bsl rte of 8 bets/min throughout night.) which senses verge tril rte nd the chnge in tril rte s indicting metbolic demnds. This informtion is then used to control the ventriculr rte. There is no trioventriculr synchrony with this system (RS4/SRT pcemker, Crdic Pcemkers Inc). The second pproch to rte responsiveness hs been to use indictors of physiologicl demnd tht re independent of the tril electrogrph. Pcing systems responsive to chnges in ph, oxygen tension, nd respirtory rte hve been designed but hve not undergone successful clinicl trils. We recently described the system bsed on QT sensing.1 2 Its dvntges include the use of conventionl electrodes for pcing nd sensing, the independence of the system from tril ctivity nd tril sensing problems, nd the bsence of pcemker induced re-entrnt rrhythmis. Becuse the pced rte is not ffected by fst tril rtes the mximl pced rtes tht cn be chieved during exercise with this pcemker re considerbly higher (18 bets/min) thn those chieved with tril synchronous systems (round 13 bets/min) or synchronous tril sensing, rte responsive pcemkers (round 11 bets/min). Disdvntges of this T wve trcking pcemker include those of unipolr pcing (interference), the lck of tril synchrony, trioventriculr conduction."' Furthermore, the improved exercise tolernce ws mimicked by 45% increse in the men exercise crdic output from 9-32±2 19 1/min (t 7 bets/min) to (t rtes of 125 bets/min) (p < 1). This is lmost within the norml reltion seen between metbolic rte nd crdic output incresing on exercise in norml subjects." This initil experience confirms the possibility of obtining physiologicl response to exercise by using pcing system dependent only on conventionl unipolr endocrdil electrode nd thus independent of problems of tril ctivity nd sensing. Physiologicl rte responsive pcing my result in considerble improvement in the qulity of life, prticulrly in young people who re likely to indulge in physicl ctivities, s evidenced by the differences in exercise tolernce nd crdic output between fixed rte nd rte responsive pcing. References Rickrds AF, Normn J. Reltion between QT intervl nd hert rte. New design of physiologiclly dptive crdic pcemker. Br Hert J 1981 ;45:56-61.

5 BRITISH MEDICAL JOURNAL VOLUME FEBRUARY Donldson RM, Rickrds AF. Evlution of drug induced chnges in myocrdil repolriztion using the pced evoked response. Br Hert-J 1982 ;48 : Vughn-Willims EM, Hssn MO, Flors JS, Sleight P, Jones JW. Adpttion of hypertensives to tretment with crdioselective nd nonselective 5-blockers. Absence of correltion between brdycrdi nd blood pressure control, nd reduction in slope of QT/RR reltion. Br HertJ 198;44: Bruce RA. Exercise testing of ptients with coronry hert disese: principles nd norml stndrds for evlution. Ann Clin Res 1971;3: Smet P, Cstillo C, Bernstein WH. Hemodynmic sequele of tril ventriculr nd sequentil trioventriculr pcing in crdic ptients. Am Hertr7 1966;72: Greenberg B, Chtterjee K, Prmley WW, Werner JA, Holly AN. The influence of left ventriculr filling pressure on tril contribution to crdic output. Am Hertr 1979;98: Koym T, Nkjim S, Horimoto M. Initil djustment of crdic ouput in response to onset of exercise in ptients with chronic pcemking s studied by the mesurement of pulmonry blood flow. Am Hert J 1976;91 : Goldreyer BN. Physiologic pcing: the role of AV synchrony. (Editoril.) PACE 1982;5: Krloff I. Hemodynmic effect of tril triggered versus fixed rte pcing t rest nd during exercise in complete hert block. Act Med Scnd 1975 ;197: Knudson MB, Amundson DC, Moshrrf M. Hemodynmic demnd pcing. In: Brold SS, Mugic J, eds. The third decde of crdic pcing. New York: Futur Publishing, 1982: Kruse I, Arnmn K, Conrdson TB, Ryden L. A comprison of the cute nd long term hemodynmic effects of ventriculr inhibited nd tril synchronous ventriculr inhibited pcing. Circultion 1981;65: Furmn S. Arrhythmis of dul chmber pcemkers. (Editoril.) PACE 1982 ;5 : Hermnsen L, Ekblom B, Sltin B. Crdic output during submximl nd mximl tredmill nd bicycle exercise. J Appl Physiol 197;29:82-6. (Accepted 23 November 1982) Consequences of hypontremi nd hyperntremi in children with cute dirrhoe in Bngldesh AZIZ R SAMADI, MOHAMMAD A WAHED, MOHAMMAD R ISLAM, SYED M AHMED Abstrct A totl of 133 children under 3 yers of ge who during 1979 hd been dmitted to the generl wrd of ICDDR,B Helth Complex for dirrhoe with complictions were studied retrospectively for the reltion between types of dehydrtion, ge, nd nutritionl stte. Of the 133 children, 276 (2 8%) were hypontremic, 969 (72-8%) isontremic, nd 85 (6-4%) hyperntremic. The incidence of hypontremi incresed with ge, while the incidence of hyperntremi decresed with ge. There ws strong reltion between types of dehydrtion nd nutritionl stte. The incidence of hypontremi ws directly relted to the degree of mlnutrition. The cse ftlity rtes for types of dehydrtion were 1 1% in hypontremi, 3 8% in isontremi, nd 1-2% in hyperntremi. These observtions suggest tht hypontremi is serious compliction of dirrhoe in Bngldesh. Introduction Dehydrtion s result of dirrhoe continues to be leding cuse of deth in children, especilly in developing countries.' In res where infnt mlnutrition is prevlent cute gstroenteritis is common nd there is tendency towrds serious complictions.2 Although in Western countries the vrious types of dehydrtion hve been studied in smll numbers, hyperntremi is frequently recorded in dirrhoe with higher mortlity rte.3-6 The incidence of specific types of dehydrtion in developing countries where mlnutrition is prevlent hs not been well documented. Nevertheless, few reports indicte higher incidence of hypontremi, which is ssocited with Interntionl Centre for Dirrhoel Disese Reserch, Bngldesh (ICDDR,B), GPO Box 128, Dhk-2, Bngldesh AZIZ R SAMADI, MD, DPH, scientific progrmme hed, disese trnsmission MOHAMMAD A WAHED, BSC, senior reserch officer MOHAMMAD R ISLAM, MB, DTM&H, ssocite scientist SYED M AHMED, MB, BS, reserch trinee (clinicl reserch) mlnutrition.7-' Hyperntremi is reportedly rre in developing countries, possibly becuse of the high prevlence of mlnutrition.78 We present the results of retrospective nlysis of the types of dehydrtion in reltion to ge nd nutritionl stte of children dmitted to the generl wrd of this hospitl for dirrhoe with complictions. The ICDDR,B, formerly the Choler Reserch Lbortory, is specilised centre for reserch in dirrhoel diseses in the region. The ICDDR,B Helth Complex, Dcc, comprises tretment centre, generl wrd, nd study wrd. All cses of dirrhoe with complictions re dmitted to the generl wrd for intensive medicl cre, while uncomplicted cses re treted in n mbultory tretment centre. Ptients for reserch re dmitted to the study wrd. The helth complex trets bout 1 cses of dirrhoe yer"1 in ptients from the Dcc metropolitn re nd beyond. Mterils nd methods During 1979 totl of 3716 ptients with dirrhoe nd complictions were dmitted to the generl wrd, of whom 1382 were children ged less thn 3 yers. Of these, 133 children met our criteri nd were ccepted into the study. On dmission complete medicl history ws obtined from the prents of ech child nd physicl exmintion performed. Mesurement of serum electrolytes, stool microscopy, nd stool culture were done long with other routine lbortory exmintions. Blood for electrolyte estimtions ws tken on dmission nd serum electrolytes mesured on n I-L flme photometer.'2 Our biochemistry lbortory uses qulity control system of smples from the World Helth Orgnistion." The height nd weight of the children were recorded fter complete rehydrtion. All the children hd mild to severe dehydrtion nd were treted intrvenously with cette solution13 for initil rehydrtion followed by either physiologicl sline or hlf strength sline plus 5 ',' dextrose, depending on the serum sodium concentrtion received from the lbortory within six to eight hours. The types of dehydrtion were defined s hypontremic (serum sodium concentrtion < 13 mmol (meq),ll), hyperntremic (serum sodium concentrtion > 15 mmol/l), nd isontremic (serum sodium concentrtion mmol/1).141" Nutritionl stte of the children ws ssessed by the Gomez clssifiction using weight for ge.'6 Birgil7 confirmed tht weight for ge is better screening test for mlnutrition thn weight for height. Using weight over ge (expressed s percentge) nd the stndrds of the