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A Naturalistic Study of 24-Hour Electrocardiographic Recordings and Echocardiographic Findings in Children and Adolescents Treated with Desipramine

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A Naturalistic Study of 24-Hour Electrocardiographic Recordings and Echocardiographic Findings in Children and Adolescents Treated with Desipramine
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  A NaturalisticStudy   4 HourElectrocardiographicRecordingsandEchocardiographicFindingsinChildrenandAdolescentsTreatedwithDesipramine JOSEPHBIEDERMAN,M.D.,ROSS J. BALDESSARINI,M.D.,ALLANGOLDBLATT,M.D.,KATHLEEN A. LAPEY,B.A.,ALYSADOYLE,B.A., AND PETER S.HESSLEIN,M.D. Abstract. Objective:Recentstudiesassessingcardiovasculareffects of desipramine(OMI) in pediatricpatientsconsistentlyhavefoundsmall,clinicallybenign,butstatisticallysignificant,increases in heartrateandelectrocardiographic(ECG)conductionparameters.However,single,routineECGrecordingscannotfullyassesspotentialinfrequentrhythmdisturbances.Method:Weanalyzeddatafrom24-hourECGmonitoring,two-dimensionalDopplerechocardiography,andexpertclinicalcardiacexamination of OMI-treatedpatients.Subjectswere 71 children  N = 35)andadolescents  N = 36)receivinglong-termtreatment  X ± SO = 1.5 ± 1.2years,median = 1.0year)withOMI  X ± SO = 3.5 ± 1.6mg/kg).Results:Comparedwithpreviousobservationsinuntreatedhealthychildren,OMI-treatedpatientshadsignificantlylowerrates of sinuspausesandjunctionalrhythm,butsignificantlyhigherrates of singleorpairedprematureatrialcontractionsandruns of supraventriculartachycardia.Therewas an associationbetweenOMIserumlevelsandpairedprematureatrialcontractions,butnootherassociationsweredetected.Conclusions:ThesefindingssupporttheimpressionfrompreviousECGstudiesthatDMI-associatedcardiaceffects in pediatricpatientsarequitebenign.Nevertheless,itremainstobeascertainedwhetherevenminorcardiacabnormalitiesmaypredictlater,evidentlyrare,adversecardiovasculareffectsthatmayincludesuddendeath. J Am.Acad.ChildAdolesc.Psychiatry, 1993,32,4:805-813.Key Words: cardiac,children,desipramine,druglevels,adverseeffects. Tricyclicantidepressants(TCAs),mainlyimipramineandQesipramine(DMI),havebeenusedextensivelyinpediatricpsychiatry(Biederman,199Ia).Inrecentyears,DMIinGreasinglyhasbeenusedinthetreatment of childrenandadolescentswithADHD(BiedermanetaI.,1989a;DonnellyetaI.,1986).Openreports(BiedermanetaI.,1986)andcontrolledinvestigations(Biedermanetal.,1989a;DonnellyetaI.,1986)indicatethatDMIisawell-toleratedandeffectivetreatmentforADHD,particularlyforpatientswhodo i AcceptedNovember 4, 1992.: Dr.BiedermanisChief,PediatricPsychopharmacology Unit, MassachusettsGeneralHospitalandAssociateProfessor of Psychiatry,ljarvardMedicalSchool;Dr.Baldessarini is Director,Laboratories qf PsychiatricResearch,MailmanResearchCenter,McLeanHospital, qnd Professor of PsychiatryandNeuroscience,ConsolidatedDepartment of Psychiatry,HarvardMedicalSchool;Dr.GoldblattisDirec セ PediatricCardiology,Massachusetts General Hospitaland AssociateProfessor of Pediatrics,HarvardMedicalSchool; Ms. LapeyisResearchCoordinator,PediatricPsychopharmacology,MassachusettsGeneralHospital; Ms. DoyleisResearchAssistant,PediatricPsychopharmacology,MassachusettsGeneralHospital; and Dr.8essleinisDirector,PediatricCardiology,Children'sHospital, St. Paul,Minnesota,andAssociateProfessor of PediatricCardiology,VarietyClubChildren'sHospital,University of MinnesotaMedicalSchool. : Thisworkwassupported, in part,bygrantsfromUSPHS(NIMH)grants R01 MH-41314-01A2(JB),MH-31154(RJB),andMH-47370(RJB).Theauthorsthank Dr. JamesFloodand Ms. PatriciaPuopolo Of theClinicalChemistryLaboratory,MassachusettsGeneralHospi tal, for theirhelpwithmeasurements of desipramineserumlevels.Reprintrequeststo Dr. Biederman,PediatricPsychopharmacology,ACC-725,MassachusettsGeneralHospital, 15 ParkmanStreet,Boston, MA 02114. .0890-8567/93/3204-O805$03.00/0©1993bytheAmericanAcademy of ChildandAdolescentPsychiatry. J. Am.Acad.ChildAdolesc.Psychiatry, 32:4, July1993 notrespondadequatelytostimulants or findthemintolerable.Seriousconcernsregardingpossiblecardiovasculartoxic-ity of DMI havearisenafterrecentreports of threecases of suddendeathin8- or 9-year-oldchildren during -routine-- treatmentwithDMI(Biederman,1991b; TheMedicalLetter, 1990).Thesedeathswerepresumedtohaveoccurred sec.: ondarytocardiacabnormalities,althoughthiscausewasnotestablished(Biederman,1991b; TheMedicalLetter,1990). Recentstudies of cardiovasculareffects of DMIinpediatricpatients(BartelsetaI.,1991;BiedermanetaI.,1989b,1985;Schroeder et aI.,1989)consistentlyhavefoundsmall,clinicallybenign,asymptomatic,butstatisticallysignificantincreasesinheartrate,diastolicbloodpressure,and ECG conductionparametersassociatedwithuse of DMIatdailyoraldoses ;;::5 mglkg.Thesestudieshavefailedtoidentifymeaningfulassociationsbetween DMI dose or serumlevelandcardiovascularparameters.Althoughsingle,routine, ECG assessmentsgenerallycanbequiteinformative,theyhavelittlepowertodetectinfrequenteventsandsocannotbeexpectedtoassesspotential risk of intermittentorinfrequent cardiac rhythm disturbancesduringDMItreatment. For example,ininformationmadeavailable (TheMedicalLetter, 1990)byMerrell Dow, themanufacturer of theNorpraminbrand of DMI,itwasnotedthatparoxysmalatrialtachycardiahadbeenobservedduringapreviousmusclebiopsyprocedureinone of thechildrenwhodiedsuddenlywhiletakingthisdrug.Inaddition,thestandard ECG doesnotassesscardiacfunctionalparameterssuchasventricularefficiency or cardiacoutput.AvailablenoninvasivemethodssuchasDopplerechocardiographycanmeasureventricularejectionfractionandcardiacoutput,and24-hourECGrecording(Holtermonitor) 805  BIEDERMAN ET AL. canprovideamoreextensiveassessmentofcardiovascularfunction.Wesought to determinewhethertheseextensivecardiacevaluationscouldsupportthehypothesisthatexposuretotherapeuticdoses of OMI is ariskfactorforcardiacabnormalitiesinchildren. Method Holter24-hourECGrecording,Oopplerechocardiography,andacardiacexamination by anexperiencedpediatriccardiologistwereobtainedinasample of 71 childrenandadolescentsreceivinglong-termtreatmentwithOM . Of thesepatients,66 (93%) werebeingtreatedforattentiondeficithyperactivitydisorderand5(7%)fordepression.Agesrangedfrom4to 17  X :: :: SO = 1l.5 :: :: 3.4)years.Therewere35(49%)children «12 years)and36(51%)adolescents   years).Onechildhadbeendiagnosedwithaventricularseptaldefectininfancybutwasfreeofanycardiacimpairmentatthetime of OMItreatment.Nootherchildhadknownpreviouscardiacdisease,and,withoneexception,nosubjecthaddevelopedanycardiacsymptomsduringtreatmentwithOM .Theexceptionwasa9-year-oldboywhocomplained of chestpainwhileonadailydose of 3.0mg/kgofOM .Atthetimeofcomplaint, an emergencyECGwasobtainedandread as beingwithinnormallimits,andOMIwaspromptlydiscontinuedowing to parentalconcern.Because of deterioratingclinicalcourse,however,treatmentwithOMIwasreinitiatedafewweekslaterafteranormal,drug-freeHolterwasobtainedandafterconsultationwithanexperiencedpediatriccardiologist(A.G.).Comprehensivecardiacevaluationswerecarriedoutinpatientswho(1)hadanadequateclinicalresponse to OMI,(2)toleratedtreatmentwithOMIwithoutimportantadverseeffects,and(3)werelikelytocontinuereceivinglong-termtreatmentwithOM .PatientshadaphysicalexaminationbyapediatricianwithintheyearbeforeOMItreatmentwasstarted.Allcardiacassessmentsweremadeindependently of informationregardingdoseorserumlevelsofOM .Thecomprehensivecardiacevaluationswereconductedatanaverage (:: ::SO) of 1.5 :: :: 1.2years(median = 1.0year;range = 0.1 to5.3years)afterinitiation of OMItreatment.OailyoraldosesofOMIatthetime of cardiacassessmentsrangedfrom50 to 325(1.0to8.0mg/kg)  X = 145.2 :: :: 69.0mg/d,3.5 :: :: 1.6mg/kg)intwodailydoses.Thesedailydoseswerejudgedtobenecessaryandeffectivebythetreatingclinician.Othermedicationsweretakenby24%  N = 17) of subjects as follows:aneuroleptic  N = 6),lithiumorcarbamazepine  N = 4);propranololandclonidine  N = 3);astimulant  N = 3);abenzodiazepineandbuspirone  N = 2);and6% of thesubjects  N = 4)were taking> oneagent.SerumconcentrationsofOMIatthetime of cardiac as- sessmentsrangedfrom20ng/mL to 423ng/mL  X = 148.2 :: :: 92.3ng/mL).TherewerethreecasesinwhichinformationaboutserumOMIlevelwasnotavailableatall,andtherewere 19 casesforwhichthelevelwasnotavailableonthedoseatwhichtheHolterwasobtained.Forthelattergroup,serumOMIlevelswereimputedfromOMIlevelsonpreviousdoses.Forassay of steadystateserumconcentrationsof 806 OMI,bloodwasdrawn 12 to 14 hoursafterthelastdoseafteratleast1weekonastableregimen.StandardECGswereperformedusingastandardI2-leadprocedureatrestinthesupineposition.Ventricularrate(VR,beats/minute),andtheduration(ms) of PR,QRS,andQTintervalcorrectedforheartrate(QTc)weremeasuredelectronicallyinthelimblead II configurationwithvisualconfirmation.ECGswereobtainedatthesametime as thebloodwasdrawnforserumOMIlevels. All patientsunderwentM-mode,two-dimensional,andDopplerechocardiography.Theejectionfraction(EF)alsowasindirectlycalculatedfromtheleftventricularM-modeechocardiogram.For24-hourHolterECGrecordings,patientsandfamilieswereinstructedtokeepdiaries of dailyactivities,sleeppatterns,andanypain,shortness of breath,orothersymptomssuch as dizzinessornausea.Thesecomputer-generatedobservationsweremadeforeachpatient: (I) minimum,maximum,andaverageheartrate,andtotal24-hourbeats;(2)ventricularandsupraventricularectopicbeats,includingsingle,bigeminal,andpairedbeats, as wellasruns;(3)rhythmincludingtachycardia,bradycardia,andsinusarrhythmia;(4)changesinrateandP-wavemorphologychanges.Inaddition,judgmentsweremadebythecardiologist(A.G.)aboutthepresence of (1)sinusarrhythmia;(2)sinuspauses,sinusarrest,orsinoatrialblock;(3)atrial-ventricular(A V) block(firstdegree,seconddegree,andcompleteheartblock);(4)junctionalrhythm;(5)prematurebeats(singleandpairedsupraventricularbeats,unifocalandmultifocal,pairedbigeminal,andtrigeminalventricularbeats,andR-on-Tbeats);and(6)tachycardicruns(supraventricularandventricular).Theexpertcardiacevaluationconsisted of interpretation of Holterandechocardiographicdataandaphysicalexaminationbyaseniorpediatriccardiologist(A.G.)Thisinformationwas summarized andreportedtotheclinician.Inaddition,allHoltersinitiallyinterpreted as abnormalwerereexaminedbyasecondseniorpediatriccardiologist(P.H.).Nodiscrepanciesininterpretation of Holterfindingsweredetected.Resultsreportedstemfromtheinterpretation of Holterandechocardiographicfindingsbythecardiologists.Tocomparetheresultsobtainedinthisstudywiththose of unmedicatedhealthychildren,asystematicMedlinesearchfromtheworldliteraturewasusedthatidentifiedthreearticlesdescribing24-hourECGinhealthypediatricsamples(TableI).Scottet al. (1980)reportedon 131 healthy10to 15 yearoldboys.Southallet al. (1981)reportedon92healthy7to II yearsoldchildren of bothgenders,andDickinsonandScott(1984)reportedon100healthyadolescentboysaged 14 to 16 years.ComparisonswerethenmadebetweenthesereportsandfindingsfromourOMI-treatedpatients.Additionalanalyses of OMI-treatedsubjectsincludedassociationsbetweenHolterandroutineECGbeforeandduringOMItreatment as well as thedoseandserumlevel of OMI.Categoricaldatawereanalyzedbychi-squareanalyseswithcontinuitycorrection,continuousdatabyStudent t test,andcorrelationsbyPearsonproductmomentcoefficient  r as indicated.TominimizeTypeIerrorsinthemultiplecomparisons,thelevel of statisticalsignificance J. Am.Acad.ChildAdolesc.Psychiatry, 32:4, July1993  24-HOURECGINDMI-TREATEDCHILDREN TABLE 1 Comparison of HolterMonitorResultsinNormalandMedicatedChildren and Adolescents Southallet aI., Dickinson   Scott,CurrentseriesScottetal.,(1980)(1981)(1984)(1993)HealthyHealthyHealthyDMITreated10-13years7-11years14-16years 4-17 yearsHolterParameters N = 131 N = 92 N = 100 N = 71 N   N   N   N   A.ResultsfromindividualstudiesSinusarrythmia 131 10092100100100 71 100Sinuspauses/sinusarrests/blocks 13 10606516 16 69AtrioventricularBlock i Firstdegree 11 891012 12 IISeconddegree14 II 33 1111 IIAVdissociation/completeblock00000000EctopicatrialrhythmJunctionalrhythm 17 1341 452626710PrematureContractionsAtrial(PAC)Single10 1319 21 4444 41 58PairedII00228 11 Ventricular(PVC)Single3426 4141 19 27UnifocalII 31 31 17 24 Multifocal10 10 23PairedII0033IIBi/trigeminal0000I I 00R-on-T00II i TachycardicrunsAtrial(SVT)000000710Ventricular00003300Heartraterange30-20049-164 23-20050-210 HealthyDMITreated10-16years 4-17 years (N = 323) (N = 71) DMlp<DMlp> N   N   HealthyHealthy B. Pooledhealthyvs.DMI-treatedpediatricpatients ns nsnsnsnsnsns0.00010.0001ns0.070.00010.0060.0010.030.06 II o 92724 3 I o I 1010 o 58   1006 I I o 7 1917 2 I o I 7141 8 2826109 o 23 I 24 10 I<Y II   1003228 o 763210 4 I o 84 89 73 3 Sinusarrythmia323Sinuspauses/episodes of sinusarrest/blockAtrioventricularblockFirstdegreeSeconddegreeAVdissociation/completeblockEctopicatrialrhythmJunctionalrhythmPrematurebeatsAtrial(PAC)SinglePairedVentricular(PVC)SingleUnifocalMultifocalPairedBi/trigeminalR-on-TTachycardicrunsAtrial(SVT)007Ventricular 3 I 0 Heartraterange23-200 50-210 Note: PAC = prematureatrialcontraction,PVC = prematureventricularcontraction,SVT = supraventriculartachycardia,DMI = desipramine. a Total N = 231, as thisparameternotreportedbySouthalletal.(TableIA). b Total N = 100, as thisparameternotreportedbySouthalletal. or Dickinsonetal.(TableIA). C Total N = 131, as thisparameternotreportedbySouthalletal. or Dickinson   Scott(TableIA). J Am.Acad.ChildAdolesc.Psychiatry, 32:4, July1993 807  BIEDERMAN ET AL. wasdefined as p < 0.01,withvalues of 0.05 to0.01 considered as trendsandpresentedintextandtables.Alltestsweretwotailed,anddataarepresented as frequenciesormeans ± SDunlessotherwisespecified. Results RoutineECGFindings Ventricularraterangedfrom 71 to137 BPM.Forty-threepercent  N = 30) of DMI-treatedpatientshadECGevidence of tachycardia(VR セ 100BPM)with10%havingVR セ 120BPM.TherewerenopatientswithECGevidence of firstdegreeAVblock(PRinterval>200ms).QRSrangedfrom60to129,andtherewere 16 (23%)subjectswithECGevidence of incomplete(QRS セ 100 < 120ms)and3(4%) of completerightbundlebranchblock(QRS セ 120ms,range = 120to130ms).Fourteensubjects(20%)hadQTc   440ms,andonlyonehadaQTc   460ms,withQTcrangingfrom300to476. It is importanttostressthatdifferentchildrenhadprolongation of QRSand of theQTcintervals. 24-hourHolterMonitorECGData Twenty-fourhourHoltermonitorECGdatafromhealthychildrenandadolescentsderivedfromtheliteratureandthoseobservedinDMI-treatedpatientsaresummarizedinTable 1. TofacilitatecomparisonsbetweenthehealthyhistoricalcontrolsandtheDMI-treatedpatients,datawereanalyzedforallgroupsseparatelyandthenforthepooledcontroldata(TableIB).SimilarlybenignfindingswereobservedinDMI-treatedpatientsandhealthychildren(Table 1, AandB).DMI-patientshadsignificantlylowerrates of junctionalrhythm(10%versus26%, p < 0.01)andsinuspauses(9%versus28%, p < 0.001)andsignificantlyhigherrates of single(58%versus23%, p < 0.0001),andpaired (11 %versus1 %, p < 0.0001)prematureatrialcontractions(PACs)andruns of supraventriculartachycardia(SVT)(10%versus0%, p < 0.0001)(Table 1, AandB).Although3% of healthyadolescentsstudied by Dickinsonet al. (1984)hadruns of ventriculartachycardia,none of theDMI-treatedpatientsexhibitedthisabnormality. ClinicalCharacteristics in PatientswithandwithoutPACsandSVTRuns Becauseapparentlyelevatedrates of prematureatrialcontractions(PACs)andsupraventriculartachycardia(SVT)werefoundinthe DMI-treated subjects,we examined whetherpatientswithandwithoutPACsandruns of SVTdifferedinage,doseorserumconcentration of DMI,orinotherECGparameters.AlthoughtheseanalysesfailedtoidentifydifferencesassociatedwithHolterabnormalities,thesenegativefindingscouldhavebeenowing to lowstatisticalpower(Cohen,1988).Thisissuewasparticularlynotable in thecomparisons of doseandDMIserumlevels,whichwerehigherinpatientswithPACsthaninthosewithoutthem(Table2). Of the 12 patientswithanabnormalHolterfinding(pairedPACs, N = 5;SVTruns N = 4;PACs + SVTruns, N = 3),eightunderwentfollow-upHoltermonitoringone  N = 4)ormoretimes  N = 4),threeotherpatientswithanabnormality(one of each of theabove)werelost to followups,andonewithpairedPACswasconsiderednormalforageandnofollow-uptestingwasrecommended(Table3).Evaluation of theavailablefollow-upHoltermonitoringrevealedthatnormalization of theECGfolloweddiscontinuation of DMIinonecase.YettheabnormalHolterECGfindingalsoresolvedinfivecasesandimprovedinoneonthesameorahigherdose of DMIinatleastonefollow-upmonitoring(Table4).Anotherpatient,whileonthesamedoseofDMI,showedresolution of SVTandpairedPACsuponafollow-upHolter,butdevelopedjunctionalrhythm.Onepatientwithmultiplefollow-upHolterECGmonitoringdevelopedsinusarrestwithajunctionalescapebeatandasecond-degreeatrioventricularblockonalowerdoseat 17 monthsafterstartingDMI.TwopatientsshowedresolutionofpairedPACsorSVTrunsonalowerdoseordiscontinuationofDMI.AnotherpatientwasnotedtodevelopectopicatrialrhythmafterDMIwasstopped(Table4).ToexaminewhethertherewasanassociationbetweenthedailyDMIdose(totalandweight-corrected)andserumlevelwithHolterECGdata,weexaminedHolterfindingsafterstratifyingthesample by thoseatrelativelyhigh   mglkgor セRU ng/mL)ormoderate «5 mglkgor セRU ng/mL) TABLE 2. Comparison of ChildrenandAdolescentswithandwithout Abnormal HolterFindings WithWithoutWithWithoutSingleSinglePairedPairedWithPACsPACsPACsPACsSVTRuns  N=41 N=30 N=8 N=63 N=7 X   SD X   SD X   SO X   SO X   SOAge11.4 :: :: 3.411.5 :: :: 3.4 14.2::':: 3.011.7 :: :: 3.4 11.1 :: :: 3.7OMIdose  mg/kg 3.4 :: :: 1.7 3.6 :: :: 1.4 4.3 :: :: 2.23.4 :: :: 1.4 3.3 :: :: 2.0OMIlevel(nglmL) 152.9::':: 94.9 142.1 :: :: 90.2 195.0::':: 112.6 141.9::':: 88.5153.3 :: :: 96.3Ventricularrate100.7 :: :: 12.897.0 :: :: 14.7 99.8 :: :: 13.7 99.1 :: :: 13.7103.4 :: :: 20.5PRinterval 148.2::':: 17.3 144.3::':: 20.2 148.5::'::24.1146.3::'::17.9147.4::'::14.3 QRSinterval(ms)89.5 :: :: 12.1 91.8 :: :: 16.4 93.0::':: 11.3 90.1 :: :: 14.3 90.3 :: :: 14.2QTcinterval(ms)411.6 :: :: 30.3412.7 :: :: 37.5421.0 :: :: 17.1 410.9 :: :: 34.6405.0 :: :: 21.2 Note: All ps セ 0.1.PAC = prematureatrialcontraction,OMI = desipramine,SVT = supraventriculartachycardia. a Powercalculationshowedlimitedpowertodetectmeaningfuldifferenceswithsmall Ns. WithoutSVTRuns  N = 64) X:: :: SO 12.1 :: :: 3.43.5 :: :: 1.5 147.6::':: 92.798.7 :: :: 12.8 146.5::':: 19.090.4::'::14.0412.8::'::34.3 808 J. Am.Acad.ChildAdolesc.Psychiatry, 32:4, July 1993  dailydosesandserumlevel.Thesedifferentiatingcriteriafordose(BiedermanetaI.,1989b;Hayeset aI., 1975)andserumlevels(BiedermanetaI.,1989b;PreskornetaI.,1982)havebeenrecommendedpreviously as potentiallymeaningfulvalues.Noassociationwasfoundwithdose,buttherewasanincreasedincidence of pairedPACsinpatientswithasteadystateDMIserumlevel;::250ngmL(Table5).Toadditionallyexaminethisissuewithmoreadequatestatisticalpower,findingswerealsoanalyzedafterstratifyingthesamplebythemediandose(3.4mg/kg)andDMIserumlevel(125mg/mL).TheseanalysesfailedtoidentifyanyrneaningfulassociationbetweendoseandDMIserumlevelandHolterparameters(all ps > 0.09). AssociationsbetweenRoutineECGand24-hourHolterFindings ToexaminewhetherspecificECGabnormalitieswere セ withabnormalHolterfindings,weexaminedHolterfindingsafterstratifyingtheDMI-treatedsamplebythepresenceorabsence of theseabnormalECGparameters:VR > 100BPM,prolongedQRS > 100msec,orprolongedQTc > 440 ms (Table6).Therewerenoclinicalorstatistical 24-HOURECGINDMI-TREATEDCHILDREN differencesinHolterfindingsinpatientswithandwithoutsuchabnormalparametersinroutineECGsobtainedduringDMItreatment.Resultsfromanalyses of echocardiographsalsowerebenign. Of the 71 DMI-treatedsubjectsassessed,70hadechocardiographicfindingsthatwereconsideredwithinnormallimits.Onesubjecthadevidence of pericardialeffusion,whichwasjudgedtobeofviraletiologyandnotdrugrelated.Nonehadevidence of mitralvalveprolapseorclinicallymeaningfulmitralregurgitation,ventricularseptaloratrialseptaldefects,orabnormalitiesintheaorticortricuspidvalves.Leftventricularsizeandsystolicfunctionwerenormal.Therewasnoevidenceofsignificantcardiomyopathyorleftatrialdilatation.Estimatedejectionfractions(EEFs)rangedfrom45%to86%  X = 70.44 ± 7.2).Although5%ofsubjects  N = 3) hadEEFvaluesbelow60%,allsubjectswereconsidered to haveadequate left ventricularfunction.Thesethreesubjectshadindistinguishabledose,DMIserumlevel,standardECG,orHolterfindings.Therewas no significantcorrelationbetweenechocardiographicallyderivedejectionfraction(cut-offpoint = 60%)andHolterorroutineECGdata. TABLE 3. ClinicalCharacteristics of the 12 SubjectswithPairedPACsorRuns of SVT DMISerumHolterRepeatEKGParametersAge,DoseDMIHRHoltersHRPRQRSQTcGender(mg/kg)(ng/mL)InitialFindings(BPM) (N) (BPM)(ms)(ms)(ms) 5,M 7.92872pairedPACs10601141529243722singlePACs 6,M 2.439I4-beatSVTrun1069516080377 18 singlePACs 7,M 3.5 55 2pairedPACs 108 311212084399 8,M 2.4 185 4SVTruns,longest 118 213616080422had8beats9singlePACs 9,M 3.0266 12 pairedPACs 117 512012080396I6-beatSVTrun26singlePACs2singlePVCs 2,M 1 3 126I3-beatSVTrun10l1121408038320singlePACs 2,F 3.83084pairedPACs98 88 180804367singlePACs 13, M7.6289I3-beatSVTrun 91 0 88 152100436 10 pairedPACs54singlePACs2singlePVCs 14, M 3.191 I6-beatSVTrun 91 0761561164068singlePACsIsinglePVC 16, M3.32222pairedPACs 95 284184112434938singlePACs 16, M3.5776pairedPACs86971449641513-beatSVTrun68singlePACs16,M 1.7 562pairedPACs 91 0951361004157singlePACs Note: PAC = prematureatrialcontractions,SVTsupraventriculartachycardia,PVCprematureventricularcontraction,DMIdesipramine,HR = heartrate,BPM = beats/minute. J. Am.Acad.ChildAdolesc.Psychiatry, 32:4, July1993 809
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