SECTION
ON CARDIOLOGY
FRIDAY, OCTOBER 8,1999 8:15 am-5:15 pm
Room 30, Washington Convention Center
8:15 Welcome
Larry T.Mahoney,MD, FAAP
Abstract Presentations
Moderators: LarryT.Mahoney, MD, FAAP and Derek Fyfe, MD,FAAP
1) 8:30 am Evaluation of an Analog Electronic Stetho-scopefor Pediatric Telecardiology. Leone Mattioli, MD, FAAP, John Belmont, PhD,KenGoertz, MD,FAAP andMari Hag-gart, RN, BSN, Department of Pediatrics, Universityof Kansas Medical Center, Kan-sasCity KS.
2) 8:45 am Inhaled Nitric Oxide is Associated with IncreasedEndothelin-1 Levels:APotential Causeof the Rebound Pulmonary Hyper-tensionPhenomenon.
JeffreyM. Pearl, MD, David P. Nelson, MD, PhD, Jenni L. Raake, RRT, Peter B. Manning, MD, StevenM.Schwartz,MD, ThomasP. Shan-ley,MDandHector R. Wong,MD.Divisionof Pediatric Cardiothoracic Surgery, Children's HospitalMedical Center, Cincinnati OH. 3) 9:00 am Natural History ofCongenital Aortic
Ste-nosis as Determined by Serial Doppler Echocardiography.
JenniferH.Lindsey,MDandHowardP. Gutge-sell, MD,FAAP.DepartmentofPediatrics, Di-visionof Pediatric Cardiology, University of VirginiaMedical Center,CharlottesvilleVA. RestrictiveCardiomyopathyinChildhood: Presentation and Timing for Cardiac Transplantation
M.T. Kimberling, MD, D.T. Balzer, MD, R.
Hirsh,MB Ch.B andC.E.Canter,MD. Depart-mentofPediatrics,Division ofCardiology, Washington University,St LouisMO. PerioperativeCare of Adults with Congen-ital Heart Disease inaPediatricFacility
AntonioMott, MD, FAAP,CharlesFraser,Jr, MD, George Reul, MD, Louis Bezold, MD, FAAP, Dean Andropoulos, MD and Timothy Feltes, MD,FAAP.PediatricCardiology, An-esthesiologyandCongenitalHeartSurgery, Baylor CollegeofMedicine,Texas Heart In-stitute and Texas Children's Hospital, Houston TX.
6) 9:45am Assessment ofSystolicandDiastolic Ven-tricular Function in Children Receiving Anthracyclines-A Quantitative Approach Benjamin W. Eidem, MD, FAAP,BrianSapp,
MD and Frank Cetta, MD, FAAP. Depart-mentofPediatrics, LoyolaUniversity Med-icalCenter, MaywoodIL.
7) 10:00am When Innocent Murmur SeemsLikelybut Doubts Linger. How Frequently Does Echocardiography Reveal HeartDisease?
David A. Danford, MD, FAAP, Ameeta B.
Martin, MD, FAAP, Scott E. Fletcher, MD,
FAAP and Carl H. Gumbiner, MD, FAAP.
Joint Section of Pediatric Cardiology, Uni-versity of Nebraska Medical Center and Creighton University School of Medicine, Childrens Hospital (Omaha NE) and St. Elizabeth Hospital(Lincoln NE).
8) 10:15 am Somatic Growth in Children with Single Ventricle
MitchellI.Cohen,MD,DavidBush,MD,PhD, Gil Wernovsky, MD and Victoria L. Vetter, MD. Divisions of Cardiology, Endocrinol-ogy,andCardiothoracic Surgery, The Chil-dren's Hospital of Philadelphia and The UniversityofPennsylvania School of Med-icine,PhiladelphiaPA.
10:30 am Break
Abstract presentations
Moderators: David Danford, MD, FAAPand Thomas S. Klitzner, MD, PhD,FAAP 9) 11:00 am Cardiac Conduction in Mutant
Microph-thalmia Mice
ColinT.Maguire, BS, DavidE.Fisher,MDand CharlesI.Berul, MD,FAAP.Children's Hos-pital-Boston, Dana-Farber Cancer Institute, HarvardMedicalSchool,Boston MA. 10) 11:15 am
11) 11:30 am
12) 11:45am
Progressive Atrioventricular Conduction Block in a Mouse Myotonic Dystrophy Model
Charles I.Berul, MD, FAAP, ColinT.Maguire, BS,Josef Gehrmann,MDandSitaReddy, PhD. Children'sHospital-Boston, Harvard Med-ical School, Boston MAand University of SouthernCalifornia,LosAngelesCA. Endothelin-1 Blockade withBosentan De-creases Post-Reoxygenation Ventricular Dysfunction and Leukocyte-Mediated In-jury.
JeffreyM.Pearl, MD, DonaldW.Thomas, CCP, JerriL.McNamara,CCP, JenniL. Taake,RRT and David P. Nelson,MD, PhD. Children's Hospital Medical Center, Cincinnati OH. Mitochondrial Cardiomyopathy: Specific Enzymatic andDNADefects
JoseMarin-Garcia, MD, FAAP, Radha Anan-thakrishnan, PhD, Michael J. Goldenthal, PhD andMary EllaPierpont, MD, PhD. The Mo-lecularCardiology Institute, Highland Park NJ and Department ofPediatrics, University ofMinnesota,MinneapolisMN.
12:00pm Lunch
1:30pm Symposium-Hyperlipidemia inYouth Noninvasive Assessment of the Atheroscle-roticProcess
LarryT.Mahoney, MD,FAAP(Moderator) Diet andthe DISCStudy
PeterKwiterovich,MD
Practical Consideration for Diet Modifica-tion
Linda VanHorn, PhD,RD DrugTherapy
BrianMcCrindle,MD
Panel Discussion
3:30pm Break 4) 9:15 am
AbstractPresentations
Moderators: Christopher L. Case, MD, FAAP andWilliamB.Moskowitz,MD,FAAP 13) 3:45 pm What is the Yield of Echocardiographyin
the Evaluation ofSyncope?
Saskia Ritter,MD,LuAnnMinich,MD,FAAP, Richard Williams, MD, FAAP, Susan Ether-idge, MD, FAAP, Janet Craig,PNPand Lloyd Tani, MD,FAAP. Department ofPediatrics, University of Utah, Salt LakeCity UT. 14) 4:00pm Cardiac EventMonitoringinPediatric
Pa-tients.
Marguerite M.Crawford,MD,Howard P. Gut-gesell, MD, FAAP and Nancy L. McDaniel, MD, FAAP. Division of Pediatric Cardiol-ogy,Universityof Virginia Health Sciences Center, Charlottesville VA.
15) 4:15pm Is Amiodarone More Hepatotoxic in Pa-tients withFontanOperation?
Mayte I. Figueroa, MD and Seshadri Balaji, MRCP. Division of Pediatric Cardiology, Medical University of South Carolina, Charleston SC.
16) 4:30 pm Amiodarone is Safe and Highly Effective asPrimaryTherapy for Tachycardia in In-fancy
Susan P. Etheridge, MD, FAAP, Janet Craig, PNP.Universityof Utah and Primary Chil-dren's Medical Center, Salt Lake CityUT. 17) 4:45pm DiagnosticAccuracyof the Screening
Elec-trocardiogram in Genotyped Long QT Syndrome
MishaD. Miller, BA, Co-burn J. Porter, MD and Michael J. Ackerman, MD, PhD, FAAP. Mayo MedicalSchool, Department of Pedi-atric and Adolescent Medicine, Section of Pediatric Cardiology, Mayo Foundation/ Mayo ClinicRochester, RochesterMN. 18) 5:00pm Pediatric Syncope: Comparison of
Emer-gencyDepartment and Cardiology Clinic Evaluation Practices
VenkatRamesh, MD, Tammy S. Wieand,MS, Ronn E. Tanel, MD, Mitchell I. Cohen, MD, Victoria L. Vetter, MDand LarryA. Rhodes, MD. The Children's Hospital of Philadel-phia,PhiladelphiaPA.
5:15 pm
5:30pm
20) 8:45am AProspectiveAnalysisof the Immunoge-nicityofCryopreservedNon-Valved Allo-graftsUsed inPediatric CardiacSurgery John P. Breinholt, BS,JohnA. Hawkins, MD, Linda M.Lambert, BS,Thomas C.Fuller, PhD, Tracie Profaizer and Robert E. Shaddy, MD. DepartmentsofPediatrics, Surgeryand Pa-thology, Primary Children's MedicalCenter and theUniversity ofUtah,Salt Lake City UT.
21) 9:00am InVivo Electrophysiology Studiesin En-dothelial Nitric Oxide Synthase (eNOS) Deficient Mice
AmitRakhit, MD, ColinT.Maguire,BS,Josef Gehrmann, MD, Ralph A. Kelly, MD,Thomas Michel,MD, PhD and Charles I. Berul, MD, FAAP.Children's Hospital,Boston MA. 22) 9:15am The
Emergency
Center vs the ComputerWhich istheBetterElectrocardiographer? ChristopherS. Snyder, MD,Richard A. Fried-man, MD, FAAP, Arnold L. Fenrich, MD, FAAP, Kelly O'Reilly,MS, Scott Reeves,MD and Naomi J. Kertesz, MD, FAAP. Texas Chil-dren's Hospital/Baylor College of Medi-cine,Houston TX.
23) 9:30am
24) 9:45am
25) 10:00am
Adjoum
SectiononCardiology, Executive Commit-teeMeeting
26) 10:15 am SATURDAY,OCTOBER9
8:30 am-5:30pm
Room30,Washington Convention Center YoungInvestigator Presentations
19) 8:30 am
Moderators: Thomas S. Klitzner, MD, PhD, FAAP and Reginald L. Washington, MD, FAAP
The Early Profile of Myocardial Dysfunc-tion in Chicken Embryos After Neural CrestAblation
HongJin, MD, MargaretKirby,PhD andLinda Leatherbury, MD,FAAP. Department of Pe-diatrics, IMMAG Developmental Biology, MedicalCollege of Georgia, Augusta GA.
DopplerCharacterization of Dorsal Aortic Blood Flow intheMouseEmbryo:Insights Into theEarly DevelopingCirculation Colin K.Phoon, MD, FAAP, Orlando Aristizabal, PhD and Daniel H. Turnbull, PhD. Pediatric Cardiology Program and Skirbail Instituteof BiomolecularMedicine, New York University School ofMedicine,NewYork NY.
ComparisonofHolter Results Orderedby Pediatric Cardiologists Versus Pediatri-cians in Patients Without Known Heart Disease
Elise M. Riddle, MD, Naomi J. Kertesz, MD, FAAP, Arnold L. Fenrich, MD, FAAP and Richard Friedman, MD, FAAP. Baylor Col-lege ofMedicine, Texas Children's Hospital, Houston TX.
Lack of Electrophysiologic Phenotype in Immature Familial Hypertrophic Cardio-myopathyMice
Laura M.Bevilacqua, MD, Colin T. Maguire, BS, JosefGehrnann, MD, Christine E. Seidman, MD, JonathanG.Seidman, PhD and Charles L Berul, MD, FAAP. Children's Hospital, Boston, Howard Hughes Medical Institutions, Har-vard MedicalSchool,BostonMA.
Coarctation Index: A Novel Approach to Identify Aortic Arch Obstruction in In-fants with Hypoplastic Left Heart Syn-drome After the Norwood Procedure Matthew S. Lemler, MD, FAAP, Thomas M. Zellers, MD, FAAP, Katherine A. Harris, RDCSand ClaudioRamaciotti,MD. Depart-ment of Pediatrics, University of Texas Southwestem MedicalSchool, Dallas TX. 10:30am Break
Abstract Presentations
Moderators: Roger Mee, MB, ChB, FRACS, FAAPandJohn W.M.Moore, MD, FAAP 27) 10:45am Conversation ofAtriopulmonaryorLateral
Anastomo-sis to Extracardiac Conduit Cavopulmo-naryAnastomosis
J.A.M. van Son, MD, F. W. Mohr, MD, J. Hambsch, MD, P. Schneider, MD and G.S. Haas, MD. University of Leipzig, Leipzig, Germany.
28) 11:00 am Impact of Initial Palliation on Outcome in Patients with Pulmonary Atresia and In-tactVentricularSeptum: A Two Institution Study
Cathryn S. Finch, MD, Zahid Amin, MD, James M Berry, RDMS, William B. Strong, MD,JohnL. Bass, MD,HollandV. Moore,MD andJohnF.Foker,MD.Departmentof Pedi-atrics,Medical College of Georgia,Augusta and University of Minnesota, Minneapolis. 29) 11:15 am Pediatric Cardiac Surgery in a Low
Vol-umeInstitution: QualityAssessment Rodolfo Neirotti, MD, FETCS, Donald Mal-colm, MD, Dominic Sanfilippo, MD, Donald Jones, DO, Gwendolyn Fosse, RN, BSN and Thomas Steffens, CCP. DeVos Children's Hospital, Grand RapidsMI.
30) 11:30 am LateResults After Repair ofCompleteA-V Canal:25-YearFollow-up
J.A. Dearani, F.J. Puga, H.V. Schaff, P.W. O'Leary, D.J. Driscoll and G.K. Danielson. Mayo Clinic, Department of Cardiac Sur-gery,RochesterMN.
31) 11:45 am Randomized, Controlled Trial of Inhaled Nitric Oxide Following Surgery for Con-genitalHeartDisease
Ronald W. Day, MD, FAAP. University of Utah andPrimary Children's Medical Cen-ter,Salt Lake CityUT.
32) 12:00pm Intra-aortic Balloon Pumping in Infants and Children:ATen-year Experience JohnA.Hawkins, MD,L.LuAnnMinich,MD, FAAP,LloydY. Tani, MD, FAAP, GeorgeM. Pantalos, PhD, GregoryB.DiRusso, MDand Edwin C.McGough,MD.Departmentsof Pe-diatrics and Surgery, Primary Children's Medical Center andUniversityof Utah, Salt LakeCityUT.
33) 12:15pm DifferencesinIncidence of Infant Congen-ital Heart Procedures from a Multicenter Consortium
Lee A.Pyles,FAAP,Stanley Einzig, WilliamA. Neal,FAAPandJamesH.Moller,FAAP. Uni-versityof MinnesotaMNand West Virginia University, MorgantownWV.
12:30 pm Lunch
2:00pm Symposium-The ICUManagementof the Child with CongenitalHeartDisease SponsoredbySectionsonCardiology, Con-genitalHeartSurgery, andCriticalCare Moderator: Roger Mee, MB, ChB, FRACS, FAAP andNiranjan Kissoon, MD,FAAP Postoperative Management of Pulmonary Hypertension.
JonMeliones,MD
Pre/Postoperative managementofHLHS/ Norwood
Edward Bove,MD
Postoperative Management of Cavopulmo-naryAnastomosis
DesBohn,MD,
Myocardial and Central Nervous System Dysfunction afterCardiopulmonaryBypass GilWernovsky,MD
Panel Discussion
4:15 pm Break
4:30 pm Section Business Meeting Chair:J.Timothy Bricker,MD,FAAP 5:30pm Adjourn
7:00 pm Section on Cardiology Banquet(Advance registrationrequired for tickets)
SUNDAY, OCTOBER10 8:30am-4:45 pm
Room 30,WashingtonConventionCenter
8:30 am Presentation of AAP Section on Cardiol-ogy 1999Young InvestigatorAwardsin Ba-sic and ClinicalScience
J. TimothyBricker,MD,FAAP
8:45 am Presentation of AAP Section on Cardiol-ogy 1999 Research Fellowship Award to Benjamin L.Siu,MDand Presentationof Results ofAAPSectiononCardiology1998 Research Fellowship Award by Andrew Robinson,MD
The 1999-2000Research Fellowship Award is supported byaneducationalgrantfrom Wilton W. Webster, Jr. The 1998-99 Award is sup-portedbyaneducationalgrantfrom the Friends of Children Corp. Fund.
9:15 am Presentation of the 1999Founders Award toSamuelKaplan, MD,FAAP.
9:30 am Founder's Address Richard Meyer,MD 10:30 am Break
Abstract Presentations
Moderators: Christopher L. Case, MD, FAAP andDerek A. Fyfe, MD, PhD,FAAP 34) 10:45 am Incidence and Predictors of
Supradia-phragmatic Systemic Venous Collateral Formation Following the Fontan Opera-tion
Howard S. Weber, MD, FAAP, Steven Zang-will,MD,FAAPandStephen E. Cyran,MD, FAAP. Departmentof Pediatrics (Cardiolo-gy), Pennsylvania State University Chil-dren'sHospital, HersheyPA.
35) 11:00 am ExtracardiacRepairof Complex Unroofed Coronary Sinus
J.A.M.vanSon,MD, G.S. Haas, MD, J. Hamb-sch,MDandF.W.Mohr,MD.Herzzentrum, University ofLeipzig, Leipzig,Germany. 36) 11:15am Closure of Single and Multiple Atrial
Communications Using the Amplatzer Septal Occluder
WolfgangA.K. Radtke, MD, B. Rush Waller, MD,GirishShirali, MD,FAAPandHenryB. Wiles, MD, FAAP. Medical University of SouthCarolina, Charleston SC.
37) 11:30 am Five-YearExperience with Coil Occlusion of Patent Ductus Arteriosus Using Long GianturcoCoils with4-6Loops
38) 11:45 am The Use of Telemedicine in Patientswith Possible Congenital Heart Disease to Op-timizeCare and Facilitate Transport Kenneth M. Shaffer, MD, Howard Heiman, MD,FAAP,JohnBrownlee,MD,FAAP,Herb Witley, MD, FAAP. SanAntonio Military Pe-diatricCenter (SAMPC), Lackland AFBTX. 39) 12:00 pm Cardiac Troponin I Levels inPediatric
Pa-tientswithAcquired Heart Disease RichardV.Williams,MD,FAAP,TimothyM. Olson,MD,FAAP,PaulC. Young, MD, FAAP and Robert E. Shaddy, MD, FAAP. Primary Children's Medical Center, University of Utah, Salt Lake City UT.
12:15pm Lunch
1:30pm Symposium-Acquired Cardiac DiseaseIn Children
Moderator: Reginald L. Washington, MD, FAAP
Cardiac Aspects ofHIV StevenE.Lipshultz,MD Myocarditis
Jeffrey Towban,MD Kawasaki Disease Update MasatoTakahashi,MD Anthracycline Toxicity RobertE. Shaddy,MD, FAAP PanelDiscussion
3:30pm Break Abstract Presentations
Moderators: LarryT.Mahoney, MD,FAAPand DavidA. Danford, MD,FAAP
40) 3:45pm Hemodynamic Disturbancesin Human Fe-tuses with Obstructive Congenital Heart Disease
MichaelR. Brumund,MDand WilliamA. Lu-tin, MD,PhD,FAAP.Departmentof Pediat-rics, Sectionof Pediatric Cardiology, Medi-calCollege of Georgia, Augusta GA. 41) 4:00pm Course of Left Ventricular Function and
DimensionsBefore and After Aortic Valve Replacement for Chronic Aortic Regurgi-tation
Anne G.Farrell,MD, Roger A. Hurwitz, MD, FAAPand Timothy M. Cordes, MD. Depart-ment of Pediatrics, Indiana University SchoolofMedicine,IndianapolisIN. 42) 4:15pm ContrastEchoDuring Cardiac
Catheteriza-tion for the Diagnosis of Pulmonary AVMs in Patientswith Fontan/Hemi-Fon-tanConnection
Marcus S.Schamberger, MD,Anne G.Farrell, MD, Eric S. Ebenroth, MD, Timothy M. Cordes, MD, RobertK.Darragh,MDand San-jayR.Parikh,MD.Departmentof Pediatrics, Indiana UniversitySchool of Medicine, In-dianapolisIN.
43) 4:30pm Echocardiographic Predictors of Restric-tiveInteratrial Communication Requiring BalloonAtrial SeptostomyinInfants with Hypoplastic LeftHeartSyndrome NedaMulla, MD, FAAP, Anne Osher, DVM, Lawrence Beeson, DrPH and Renae Larsen, MD,FAAP. LomaLinda Children's Hospi-tal,LomaLinda CA.
4:45pm Adjourn
CARDIOLOGY SESSION
1
EVALUATION OFANANALOG ELECTRONIC STETHOSCOPEFORPEDIATRIC TELECARDIOLOGY. Leone Mattioli, MD, FAAP, John Belmont, PhD, Ken Goertz, MD,FAAPand Mari Haggart, RN, BSN. Deptof Peds, Univ of Kansas Medical Center, Kansas City, KS 66160-7330.
Objective: To test the reliability and diagnostic validity of a narrow-bandwidth electronic stethoscope used for pediatric tele-cardiology between the hospital andpublic schools.
Materials and Methods:Twopediatric cardiologistsparticipated. One used hisown acousticstethoscope(AS)aspartof theroutine outpatientexamination.The other usedaremoteanalog electronic stethoscope (ES) connected by ordinary telephone line to the examination room. Thestudynursemanipulatedthestethoscope chestpiece asdirectedby the remoteexaminer via intercom. For this conservativetrialtheremote examiner wasnotbriefed about patient's history and neithersawnorspoke with the patient. For 46consecutivepediatric cardiology outpatients (age: mean 10.8, median 10.3, SD 7.1) the examiners made independent judgments regarding heart sounds and murmurs, heart disease, necessityof echocardiography, and provisional diagnosis. The Kappastatistic (K) indexed inter-examiner agreement (reliability) for dichoto-mous variables. Validity was measured by assessing the ES's heart-disease detection accuracy using echocardiography as the gold standard (N=36).
Results:There was satisfactoryES/AS agreement on presence of heartdisease (K=0.63) and need for follow-upechocardiography (K=0.64). There was also satisfactory agreement on presence of murmur(K=0.85), organicmurmur(K=0.82), functionalmurmur (K=0.75), diastolic murmur (K=0.75), systolic murmur (K=0.78), and somespecific murmurs and heart sounds: Vibratory (K=0.76), diastolic aortic (K=0.81), diastolic pulmonic(K=0.73) andaortic click (K=0.64). For other specific murmurs and heart sounds inter-examineragreementwaslow(K<0.60) or couldnotbe com-putedfor lack ofprevalence. Taking the latest echo-cardiogramas gold standard for presence of disease, ES had overall accura-cy=83%, sensitivity=88%, specificity=75%. Heart-disease detec-tion errors were found primarily in the youngest patients (P<0.03). Forthose age
.5
yr,accuracy=92%, sensitivity= 94%, specificity=88%.Conclusions: The analog ES used with ordinary telephone linesprovided reliable, valid screening forpediatric heart dis-ease, especially for patients age
>-5
yr. However, for some specific sounds and murmurs, agreement with AS was unsat-isfactory. Asingle adult-size diaphragm was used for all pa-tients,which maypartlyaccountfor therelatively poor perfor-mance among the youngest. Interchangeable diaphragms, conversationwith the parent/patient, and use of video to vi-sualize the precordium would probably improve overall per-formance. We regard the analog ES as a highly satisfactory, inexpensive toolforpediatric telecardiology.2
INHALEDNITRIC OXIDE ISASSOCIATEDWITH INCREASEDENDOTHELIN-1 LEVELS: A POTENTIAL CAUSE OF THE REBOUND PULMONARY HYPERTENSION PHENOMENON.
Jeffrey M. Pearl, M.D., David P. Nelson, M.D.,Ph.D., JenniL. Raake, R.R.T., Peter B. Manning, M.D., Steven M. Schwartz, M.D., Thomas P. Shanley, M.D.,Hector R. Wong, M.D. Chil-dren's Hospital Medical Center, Cincinnati, OH
following repair of congenital heart disease. Proposed advantages of iNO include its lack of significant systemic hemodynamic ef-fects, and its relative 'safety'. However, 'rebound' PHTN has been described when inhaled NO is weaned, suggesting either im-pairedendogenous NO production or elevated levels of vasocon-stricting agents such as ET-1. ET-1 and NO are known to cross-talk, and itis possible that iNO may affect levels ofET-1. This clinicalstudy was undertakeninorder to determine theeffects of inhaled NO on levels of ET-1.
Methods: Group1-Fifteen infants and children with congenital heartdisease (age 3 d-23 mos) requiring iNO for post-CPB PHTN. Arterial blood was obtained prior to iNO, at several time points during, and24hoursfollowing cessation of inNO. Group2 con-sisted of ten adult medical patients placed on iNO therapy, and Group3includedsixinfants post-CPB who wereatriskforPHTN butwho did not require iNO.
Results:InGroup 1,the average increase in ET-1 levels was 48% by12hrs of iNO therapy (mean average values= 3.94 pg/ml vs. 2.83 pg/ml), and levels remained elevated at 48 hours. With cessationof iNO ET-1levels decreasedanaverage of.59pg/ml, from 107% of baselineto86%of baseline.InGroup 2,ET-1levels increasedabovebaseline byanaverage of 44%, 61%, 51%, and 50% at2,12, 24, and 48hours(mean averagevalues= 3.25, 3.3, 3.1, and 3.0 pg/ml compared with baseline of2.33pg/ml). Priorto cessa-tion of iNO, ET-1 levels were 124% of baseline (2.89 pg/ml) and felldramaticallyto54%of baseline (1.26pg/ml) within24hours of discontinuing iNO. InGroup 3, ET-1 levels decreased by an average of 24% and 35%at 12and 24 hours post-op. (2.29, 1.68, 1.21pg/mlatbaseline, 12, and 24 hours).
Conclusion: ET-1levelsincreasebyasmuchas61%following institutionof inhaledNOtherapy. The increaseinET-1doesnot appear to be a result of CPB as levels did not increase in non-treated patients post-CPB, but did occur in non-surgical adult patients. These data suggest that iNO results in an in-crease in systemic ET-1 levels. Levels decrease back towards baseline after 48 hours, and decrease abruptly when iNO is stopped. Thisincrease inET-1mayexplain part of the rebound phenomenon seen when attempting to wean iNO, and suggests thatonceiNO therapyisbegun, it should be continued forat least 48hours until ET-1 levels begin to decrease back towards baseline.
3
NATURALHISTORYOF CONGENITALAORTIC STENOSISASDETERMINED BYSERIALDOPPLER ECHOCARDIOGRAPHY.
JenniferH.Lindsey, MD, and HowardP.Gutgesell, MD,FAAP. DepartmentofPediatrics, Division ofPediatric Cardiology, Uni-versityof Virginia Medical Center,Charlottesville, Virginia.
Background:Ourcurrentunderstandingof the naturalhistory of congenital aortic stenosis isderived from catheter-based studies whichhave shown progression of disease severity overtime. To date, therearefew studies basedonnon-invasivemethods illus-tratingthe naturalhistory of congenitalaortic stenosis.Thisstudy evaluates the progression ofcongenital aortic stenosisbased on serial Doppler echocardiography. Methods: Doppler echocardio-gramsof102pediatric patients with valvular ASwerereviewed. All patients hadatleasttwo Dopplerechocardiograms prior to anyinterventionfor AS. Agesranged from1 dayto19yearsold, and the average intervaloffollowupwas5.7years(range1month to 14.2years).
Results: Transvalvar Doppler gradients at initial evaluation ranged from5 to 80mmHg. Gradientsatfollow up evaluation ranged from 7to 96 mmHg. Over the courseof follow up, 64 patientshadanincrease intheir transvalvargradient, andin18 of these patients, theincreasewas > 20mmHg (maximal gra-dientincrease 49mmHg).In32patients,thegradient decreased during follow up. The likelihood ofprogressionof congenital
AS was related totheageatinitial evaluation. Among the33 patients who were 2 years old or younger at the time of initial evaluation, 12(36%)hadanincreaseofmorethan20mmHgin their aorticgradient. However,inthe69 patients over2 years oldattimeof initialevaluation, only5(8%) patients had greater than 20 mmHgincrease in aortic gradient over the period of follow up. The likelihood of progression of AS and need for intervention was likewise related to theseverity of aortic valve gradient at initial evaluation. Of the 95 patients with gradients less than 50 mmHg at initial evaluation, only 14 (14%) pro-gressed to gradients of greater than 60 mmHg over theperiod offollowup. Of the 8 patients who ultimately required inter-vention, 6 patients had initial gradients of > 40 mmHg, and 4 patients had initial gradients 2 60 mmHg.
Conclusion:Contrary to earlier studies based on serial cardiac catheterizations, congential aortic stenosis is not always pro-gressive; early age at diagnosis and higher initial gradient appear to be risk factors for ultimate need for intervention.
4
RESTRICTIVE CARDIOMYOPATHY INCHILDHOOD: PRESENTATIONANDTIMING FOR CARDIAC TRANSPLANTATION.
M.T.Kimberling M.D., D.T. Balzer M.D., R. HirschM.B.Ch.B., C.E.CanterM.D.,Washington University, St. Louis, MO.
Background: Restrictivecardiomyopathy (RCM)israrely seen in children. Limited experience hassuggested that elevation of pul-monary vascular resistance (Rp) is so commonly observed that children with RCMshould belisted for transplantation at the time ofdiagnosis.
Methods: In the past 10 years,9children with RCM havebeen refered for evaluation at Washington University. RCM was de-fined by 1) marked biatrial dilitation, 2) normalLVchamber size and ejectionfraction (>50%), and 3)LVend-diastolic pressure> 15mmHg. Presenting symptoms included palpitations (2), chest pain(2),exertional shortness of breath(3), abdominal pain(1), and cardiacarrest (1). All patients underwent cardiac catheterization as part oftheir evaluation.
Results:4/9 had a normal pulmonary vascularresistance(Rp) index (<3 WU/m2) at the time ofdiagnosis. Median interval from diagnosis to evaluation for transplant was 68 months (range 2-100 months). Atthe time of evaluation fortransplant, 6/9 had elevated Rp index (median=10.6WU/m2,range 3.8-24 WU/m2). Median transpulmonary gradient (TPG) for these 6 was 25 mmHg (range 17-30 mmHg). All 6 demonstrated re-versible Rp index and 5/6 had reversable TPG with Nitric Oxide(NO) administration. In2/6NOwastheonlymediatorto demonstrate Rp reversibility. The median best Rp index and TPG was 3.17 WU/m2 and 15 mmHg respectively. Only one patientdidnotachieve aRp index <5WU/m2.The4patients with normal Rp indexattimeofdiagnosiswerefollowedfora mean of80months (range 60-100 months) and only 1/4 had mild Rpelevation(4.8WU/m2)at timeoftransplant evaluation. 7/9 have been successfully transplanted to date and all have been documentedtohave normal Rp index and TPG<15mmHg within the first yearafter transplantation.
5
PERIOPERATIVECAREOF ADULTSWITH CONGENITAL HEART DISEASEIN APEDIATRIC FACILITY.
Antonio Mott, MD, FAAP, Charles Fraser, Jr., MD, George Reul, MD, LouisBezold, MD, FAAP, Dean Andropoulos, MD, Timothy Feltes, MD, FAAP. Pediatric Cardiology, Anesthesi-ology and CongenitalHeartSurgery, Baylor College of Medi-cine, Texas Heart Institute and Texas Children's Hospital, Houston,TX.
Background: Anincreasing numberof patients (pts) with con-genital heart disease (CHD) present for cardiothoracic surgery during adulthood. These pts are often cared for in a pediatric facility. The purpose of this project is to describe the operative outcomeand perioperative courseof a large cohort of adult pts who have undergonecardiothoracic surgery at a tertiary pediatric hospital.
Methods: Our clinical database was used to identify all adult CHD pts (>18 yr) who had undergone cardiothoracic surgery between 1/95 and1/99atour institution. Dataretrievedincluded ptdemographics, cardiac dx, previous & current surgical proce-dures, perioperative complications, hospital length of stay (HLOS), postoperativelength of stay (POLOS), and outcome. Pro-ceduresweredividedinto 3 treatmentgroups. Group 1:pts un-derwent initial insertion or replacement ofapacemaker system; Group 2: pts underwentpalliativeordefinitive cardiac operations; Group 3: pts underwent other types of thoracicprocedures. CPR events = need for CPR +/or emergent cardioversion. Early death= <30dafter surgery.
Results: 83 procedures were performed in 74 ptsduring the study period. Early mortality was 7.2%. There were 2 late deaths. Group1 (n=19):meanage was26.6 yr (20-56yr). The median HLOSwas 7.5d(2-25 d) & median postoperative LOS was 3 d (2-33 d). Complications included: pulmonary artery thrombus &transfertoadulthospital (1) and CPRevents (1). There was 1 early death (5%). Group 2 (n=57): mean age was 26.6 yr (18-72 yr). Each pt averaged 1.4 previous operative procedures. Current operativeprocedures included: AV valve revision/replacement (n= 10), semilunar valve revision/re-placement (11),Fontanprocedure (9),RV-PAconduit (8), ASD closure(6), and other(12). The median HLOSwas9d (3-39d) and the median POLOS was 7d (2-36 d). Complications in-cluded re-operationfor bleeding(3) and ECMO (1). 5 pts had new onsetpostoperativearrhythmias (9%) that required treat-ment: atrial fib/flutter (2), ventricular tachycardia (2), CAVB (1), 20AVB (1). Transient peripheral neurologic deficits were observed (4). 1 ptsustained hypoxic-ischemic encephalopathy progressingtoEEGsilence.5ptsweretreated for depression.1 pt required transfer to an adult hospital for extended care. There were 13 CPRevents(4 pts)or 23events/100procedures. Therewere5earlydeaths (9%) and2late deaths. Group 3 (n= 7): meanagewas 23.5 yr(18-34 yr). The median HLOSwas24d (3-40 d) and median POLOS was 8 d (2-28 d). Procedures included sternalwireremoval (2), open lung biopsy (1), peri-cardial window (1), right lung lobectomy (1), AV fistula cre-ation (1), and sternotomy debridement (1). 1 pthad postoper-ative recurrentpneumothoraces. Therewere nodeathsorCPR events.
Conclusions:1)Cardiothoracicprocedures performedonadult CHD pts at apediatricfacilitycanbeperformedwith accept-able mortality; 2) New onset arrhythmias necessitating treat-ment arerelativelycommonamongadultsundergoing cardiac surgery; 3)Postoperative depression should be anticipated in this group of pts,4)Despiteacceptable outcomes, the number of CPReventsinthe CHD adultundergoingcardiac surgeryis significant.
6
ASSESSMENT OFSYSTOLIC & DIASTOLIC
VENTRICULAR FUNCTIONIN CHILDREN RECEIVING ANTHRACYCLINES-A QUANTITATIVE APPROACH. Benjamin W.Eidem M.D., FAAP,BrianSapp M.D.,Frank Cetta M.D., FAAP, Departmentof Pediatrics, Loyola University Medical Center, Maywood,IL
Background: Use of anthracycline antibiotics are common in chemotherapeutic regimens fortreatmentof childhood malignan-cies.Studies havedocumented thelong-term cardiotoxic effects of these agentsoncardiacperformanceincumulative dosesinexcess of450mg/m2. Routine noninvasiveassessmentof cardiac function currently relies on serialechocardiographic measurementof left ventricular systolicfunction (fxn), namely ejection fraction. Quan-titative assessmentof left ventricular diastolic fxn andright ven-tricular fxnarenotroutinely performedinthese pts.Amyocardial performance index (MPI) has been reportedinpediatric and adult studieswhich isasimple, Doppler-derived, non-geometric mea-surementof global (ie systolic anddiastolic) ventricular fxn. The MPI = [(Isovolumic contraction time) + (isovolumic relaxation time)] / (ejection time). The purpose of this studywas toserially assessthe impactofanthracyclines onglobal ventricular fxn (as assessedby the MPI) for both theLVandRVandtocomparethis with standard echocardiographic measurements of ventricular fxn.
Methods:LVand RV MPIwereserially measuredin26 patients receiving adriamycin. In addition, standard echocardiographic measurementsof fxnwereperformed, including M-mode and2-D ejectionfraction,shorteningfraction,and mitralinflowDoppler. These data were compared toeach patient'sbaseline functional assessmentpriortoinitiationofanthracyclines andto agroupof normalpediatric controls.Statistical comparisonsweremade be-tweengroupsusingunpairedt-tests.
Results:Serial results for26study ptsareshown below.Mean duration offollow-upwas 24 months. Meantotalanthracycline dose=285mg/M2.Table: CumulativeAdriamycindose(mg/M2)
Baseline 0-50 51-100
LV MPI 0.37(.07) 0.39(.09) 0.40(.09)
LVEF(%) 62(7) 64(11) 57(7)
LVICT(ms) 42(17) 43(14) 48(23) LV IRT(ms) 55(16) 65(18) 59(16) MitralE/A 2.0(1.0) 1.8(0.4) 2.0(0.6) RVMPI 0.30(.06) 0.30(.06) 0.32(.05)
101-200 201-300 301-400
0.41(.12) 0.42(.08) 0.50(.15)
58(9) 57(10) 57(9)
50(22) 46(14) 59(15)
56(17) 58(12) 59(20)
1.7(0.4) 1.6(0.3) 1.7(0.7)
0.31(.07) 0.33(.08) 0.27(.07)
Nostatistical differencewaspresent between154normal pedi-atriccontrols (ages 3-18 yrs,meanage 9.3yrs) and the baseline examsinstudypatients(age6 mos-17yrs,meanage9.3yrs)for either theLV MPI(0.37vs0.35incontrols,p=NS)orRV MPI(0.30 vs0.33in controls, p=NS). With cumulativeanthracycline dos-age>300mg/M2,theLVMPI wassignificantlyelevateddespite normal ejection fraction and other standard measurements of ventricular fxn (LV MPI = 0.50vs 0.37baseline, p<0.001). No significant changeinRV MPI was seenwithincreasing anthracy-clinedosage.In 4studyptswhodevelopedLV EF<45%,theLV MPI wassignificantlyelevated priortoother standard
miss early signs of ventricular dysfunction at cumulative anthra-cyclinedosages significantly lessthan450mg/M2. The MPI, be-cause itis a simple and reproducible Doppler measure of both systolic and diastolic ventricularperformance, isapromising se-rial tool toquantitatively assess ventricular function. Further long-term serial follow-up in these patients with the MPI deserves ongoinginvestigation.
7
WHENINNOCENT MURMUR SEEMS LIKELY BUT DOUBTS LINGER. HOW FREQUENTLY DOES ECHOCARDIOGRAPHY REVEAL HEART DISEASE?
David A. Danford, MD, FAAP, Ameeta B. Martin, MD, FAAP, Scott E.Fletcher,MD, FAAP,and CarlH.Gumbiner,MD,FAAP. Joint Section of Pediatric Cardiology, University of Nebraska Medical Center and Creighton University School of Medicine, Childrens Hospital (Omaha, NE) and St. Elizabeth Hospital (Lin-coln, NE).
Objectives. Discovery of the incidenceandnatureof heart dis-easeidentified among children with murmurs clinically ambiguous to the expert examiner, and elucidation ofclinically recognizable features which correlate with the discovery of actual heart disease in this group. Design. Prospective, blinded study of diagnostic accuracyof the expert examination was made using echocardiog-raphy (echo) as the diagnostic standard. Setting. Pediatric cardiol-ogy outpatient department. Patients. 804 outpatients with heart murmurunder21 years old, without prior echo or pediatric car-diology consultation.Intervention. Echoasclinically indicatedfor evaluation of heart murmur of uncertain cause. Measurements. Expert examiners' clinical diagnoses and echo results in patients (pts) grouped by theexaminer'slevelof suspicion of heart disease, by age of pt, and by indication for echo. OutcomeMeasures.Clinical diagnoseswerecomparedwithechoresults across groups using chi square testingfor dichotomous variables, and Wilcoxon 2-sam-pleranktestfor continuous or multi-level variables.
Results. Expert's level of suspicion of heart disease was strongly andpositively associated with presence of disease (P<0.0001).
Clinical IM not on IMondiffl dx, but less Impression diff'l dx likelythan otherdx IMlikelihood 26/389, 6.7% 44/176, 40.5%
IM mostlikely, IMtheonly
butother dx consideration also listed
116/144, 80.6% 143/155, 92.3% Abbreviations: diff'l dx=differential
murmur.
diagnosis; IM=innocent
Ageof ptatpresentationtocardiology clinic has strong negative associationwithlikelihood of heart disease (p<0.0001).
Patientage <0.10years 0.10-1.00years IMlikelihood 39/185,21.1% 87/243,35.8%
Patientage 1.00-4.00years >4.00years IMlikelihood 73/154, 47.4% 133/222,59.9%
Amongthe 155cases inwhich the experts'diff'l dx containedIMas the sole consideration therewere 12 in which heart disease was discoveredbyecho.Fourof these12have had catheterorsurgical intervention (atrioventricular septal defect repair-1, cor triatriatum repair-1, secundum atrialseptal defect repair-1, and patent ductus arteriosuscoil-1).WhenIM wasthe soleconsideration (n=155) and
the only stated reason forecho was pt, family, orreferring physician anxiety (n=43) there was only 1 case of heart disease discovered (2.3%). When symptoms, anabnormal electrocardiogram, or chest X-ray were among theconsiderationscompelling the echo (n=112) 11cases of heart diseasewere discovered (9.8%);p<0.05.
Conclusions. Recognizing thatinmany casesIM isdiagnosed clin-ically, conclusions drawn from this study are limited to those mur-murs in which diagnostic ambiguity remainsafter the expert clinical examination. In this context, the examiner's clinical impression of likelihood of heart disease correlates well with presence of actual disease.However,important disease is occasionally discovered even when the expertformulates no plausible diagnosis except IM, espe-cially whenreasonsbeyond family and referring physician anxiety compel thecardiologist toobtain an echo. Evenwhena murmur soundsinnocent tothe expert examiner, clinical andlaboratory clues suggestiveof heart disease should not besuppressedasindications forechoinanefforttocontain costs.
8
SOMATIC GROWTH IN CHILDREN WITH SINGLE VENTRICLE.
MitchellI. Cohen,MD1, David Bush,MD PhD',RobertJ. Ferry MD2, Thomas L. Spray, MD3, Thomas Moshang Jr., MD2, Gil Wernovsky,MD',Victoria L.Vetter,MD'.FromtheDivisionsof Cardiology', Endocrinology2, andCardiothoracicSurgery3atThe Children'sHospital ofPhiladelphia&The Universityof Pennsyl-vaniaSchoolofMedicine, Philadelphia,PA.
Background: Growth failureoccurscommonly with congenital heart disease and may be related to congestive heartfailure and hypoxia. Surgical repair of simple congenital heart lesions appears to reverse the growth retardation. Surgical repair of complex single ventricle anatomy and/or physiology includes a staged Fontan operationtoreducetheadverse effects ofprolonged ven-tricular volume overload andhypoxemia. The impact of this ap-proachon somaticgrowthisunknown. Theaimof thisstudywas designedtocharacterize the mid-termgrowthpatternsinchildren managed initially with a hemi-Fontan followed by a modified Fontanoperationinearly childhood.
Methods: Retrospectively, we reviewed the growth measure-mentsof all childrenwith single ventricle followedprimarily at ourinstitutionwhocompletedastagedFontanoperation between 1/90-12/95. Growthmeasurements wereavailableonallchildren priortosurgery and thenannually for three yearsfollowing the Fontan operation. Growth data were obtained on siblings and parentsfor comparative purposes.
Results: During thestudy period65patientsmeteligibility cri-teria. The mean weight Z score was -1.49+1.12 at the hemi-Fontan operation. Weight gain improved by the Fontan
(-0.91±0.99)
and for the first two years following the Fontan operation, butnevernormalized. ThemeanheightZscore atthe hemi-Fontan and Fontan operations were-0.67±1.14 and -0.89±1.18respectively.Lineargrowth velocitycontinuedto de-cline after theFontanoperation.At mostrecentfollow-up(mean age 6.1±1.3 years; mean time from Fontan operation 4.4+1.4 years), themeanheightZ score was -1.15±1.2 and was signifi-cantlyless thanheightZscoresfor their parents andsiblings.The Qp/Qs(pulmonary: systemic flow ratio) after theFontan opera-tion was0.95±0.2 and themost recent meanpulseoximetry re-cordingwas94%(range88-98%).0.5-
0--0.5
--1
--1.5 --2
-U-,
*
Height*
Weight El
Weight/
m Birth Hemi- Fontan YearsPostFontan HeightFontan 1 3 5
9
CARDIAC CONDUCTION IN MUTANT MICROPHTHALMIA MICE.
Colin T. Maguire, BS, David E. Fisher, MD, Charles I. Berul, MD, FAAP. Children's Hospital * Boston, Dana-Farber Cancer Institute,Harvard MedicalSchool, Boston, MA
Background: The microphthalmia (Mi) gene encodes a helix-loop-helixtranscriptionfactorimportantinneuralcrest develop-ment. TheMi genebinds Ebox promoter/enhance elementin target genes and is subject toregulation via cytokine signaling pathways. AlthoughMitissueexpressionis strikinglytissue re-stricted, itis foundto bemost abundantly expressedin cardiac myocytes.However,asthereis noobvious cardiacphenotype, the purposeof this studyis todeterminewhetherMiorrelatedfamily members may modulate subtlefeatures of cardiac development, suchasregulation of electrical conduction.
Methods:Surface 12-lead ECG's were obtainedon 19 homozy-gousmutantMi-deficientmiceand matched littermate controls. Heartrate,rhythm, axis, and ECG intervalswere compared be-tweenthe2groups.
Results: The mutant mice were significantly smaller (weight 12±4gramsvs.20± 5grams, p<0.05). The mean heart ratein mutant mice was 484 ± 31 BPM, compared with 488 ± 48 in age-matchedwild-type littermates. Therewere nosignificant dif-ferences in heart rate, rhythm, axis, or ECG intervals between homozygousmutantandwild-typemice.
ECG
Findings:
PR QRS QT SCL
MutantMi 35 + 3ms 17 ±3ms 62 + 7ms 124 + 32ms Wild-type 36± 3 ms 18 + 3 ms 60 + 12ms 123± 48 ms
Conclusion: The lack of measurable conduction defectsinthese micesuggestsseveralpossibilities.TheMifactor maynotregulate cardiacconduction, ormightbe compensatedforbyotherHLH family membersorother transcriptionfactors. There may bemore subtle defects incardiacconduction, notappreciable on surface ECG. Conductiondelay may becomemoremanifest with provo-cationusingprogrammed electricalstimulation,ionchannel mod-ulatingdrugs,experimentalischemia,orelectrolyte disturbances. Mi and associated factors may altematively regulate different aspects of cardiac physiology or development, possibilities cur-rently under investigation.
10
PROGRESSIVE ATRIOVENTRICULAR CONDUCTION BLOCKIN AMOUSEMYOTONICDYSTROPHY MODEL. CharlesI.Berul, MD, FAAP, ColinT.Maguire, BS,Josef Gehr-mann, MD, SitaReddy, PhD. Children'sHospital * Boston, Har-vard Medical School, Boston, MA and University of Southem California,LosAngeles,CA.
Background: Myotonic dystrophy (DM)iscausedby expansion of a CTG trinucleotide repeat on human chromosome 19, and leads to progressive atrioventricular conduction disturbances.
Haploinsufficiency of DMPK, DMAHP and/or titration of RNA binding proteinsby expanded CUG sequences likely underlie the cardiac defects observed in DM. The purposeof this study was to determine whether developmental progression ofA-Vblock oc-curs in a mousemodelof DMPK-deficiency.
Methods:Surface ECGs and intracardiac electrophysiology (EP) studies were performed in immature and adult DMPK-/-, DMPK'/- mice and wild-type (WT) DMPK+/+ controls. The RR, PR, QRS, and QT intervals were measured on ECG. Sinusnode recovery time, AV refractory periods, paced AV Wenckebach and 2:1 block cycle lengths, atrial and ventricular effective refractory periods werecompared between genotypes and age groups.
Results: There were no differences in ECG intervals orEP find-ingsinthe young mutant mice, butprogressivePRprolongation inolder mice.
so 5o 40 30 210 la
1-2 mo 46mo 12-15 mo 18-21 mo
TheA-Vconduction defects are also sensitive to DMPKgene dosage. Adult DMPK-'- micedevelop 10,2°and 3°A-Vblock, whereasDMPK+'-micedeveloponly10heart block. Conclusion: These datademonstrate that developmental age aswellasDMPK doseare critical factorsmodulating cardiac conduction and link DMPKhaploinsufficiency with cardiac diseaseinmyotonic dys-trophy.
11
ENDOTHELIN-1BLOCKADE WITH BOSENTAN DECREASESPOST-REOXYGENATIONVENTRICULAR DYSFUNCTIONANDLEUKOCYTE-MEDIATED INJURY JeffreyM.Pearl, M.D., Donald W.Thomas, C.CP., JerriL. Mc-Namara, C.C.P., JenniL.Raake, R.R.T., David P.Nelson, MD, PhD.Children's Hospital Medical Center, Cincinnati, Ohio
Background: Reoxygenation of hypoxic myocardium during re-pairofcongenital heart defects resultsinleukocyte-mediated in-jury and poorventricular function. Endothelin-1 (ET-1) whichis increased under conditionsof hypoxiais apotent vasoconstrictor, directly depresses myocardial function,and stimulatesleukocyte adhesion and activation. Inorderto determine ifET-1 blockade improves post-reoxygenationventricularfunction and decreases leukocyte-mediated injury neonatalpigletswerestudied.
Methods: Following instrumentation and baseline measure-ments,14open-chest piglets underwent 90minutesof ventilator hypoxia(FI02=.12),onehour of reoxygenationon cardiopulmo-narybypass, andtwohours of recovery(Group 1).Anadditional 9animalsundergoinganidenticalprotocolreceivedaninfusion of Bosentan(5mg/kg/hr) during hypoxia and reoxygenation (Group 2). Systolic ventricular function (+dp/dt) was determined. LV myocardiumwasanalyzedatend-recoveryformyeloperoxidase (MPO) activity and lipid peroxidase activity (LPO).
Results:InGroup 1,RVdp/dtincreasedto148%ofbaseline(533 vs. 369) during hypoxia, but fell to 78% of baseline following reoxygenation(281vs.360,p<.05).LVdp/dt decreasedto80%of baseline by end-hypoxia (994 vs. 1242, p<.05) and following reoxygenationdecreasedto52%of baseline(646vs.1242,p<.005). Incontrast, Group 2 animals had complete preservation of RV dp/dt(102% ofbaseline)atend-recovery.InGroup 2,LVdp/dt wassignificantly less depressedatend-recovery thaninGroup1 (74% of baseline). LV dp/dt at end-recovery was significantly greater(p<.05)inGroup2thaninGroup1 (903vs.646). Group2 had significantly lower (p<.05) myocardial tissue MPO than 1RDMPK+/+
Group 1;LVMPO inmU/50mgtissue was 80.9ingroup 1,21.7 in Group 2,and 13.1 in control hearts. LV LPOinnM/100 mg wet tissue was also significantly lower in Group2 (p<.05) than in Group1 atend-recovery; 4.6inGroup 1,3.5 inGroup 2,and 3.0in control hearts. Conclusions: Reoxygenation of hypoxic myocar-diumresults in leukocyte-mediated injury and decreased ventric-ularfunction. Increased levels of ET-1 during hypoxia may con-tribute to reoxygenation injury. ET-1 blockade with Bosentan decreases myocardial leukocyte activity as evidenced by lower MPO and LPOvalues. This decrease in leukocyte mediated reoxy-genation injury may accountfor theimprovedfunctional recovery seenwithBosentan.
12
MITOCHONDRIAL CARDIOMYOPATHY: SPECIFIC ENZYMATIC AND DNA DEFECTS.
JoseMarin-Garcia*, MD, FAAP, RadhaAnanthakrishnan* PhD., Michael J. Goldenthal*, PhD, Mary Ella Pierpontt, MD, PhD. The Molecular Cardiology Institute*, Highland Park, NJ, Depart-mentof Pediatricst,U.Minnesota,Minneapolis, MN
Background: In a group of 30 children (ranging in age from 2 weeks to 18 years) presenting with end-stage cardiomyopathy, 25 (19 with DCM, 6 with HCM) manifested cardiac mitochondrial enzymaticdefects.Inthisstudy we sought toestablish the molec-ularbasis for the enzymaticabnormalities using combined molec-ular andbiochemical analyses.
Methods: Biopsied endomyocardial tissues were analyzed to determinespecificcardiac respiratory enzyme activity levels, mi-tochondrialDNA(mtDNA)levels, large-scale deletions and point mutationsinmtDNAbyDNAsequenceanalysis.
Results: In this patient group, specific activity levels of car-diac mitochondrial respiratory enzymes were significantly re-duced compared to age-matched controls. Decreased activity levels werefoundincomplexI(n=9),III(n= 13),IV(n=11) and V (n=9) but not in complex II, the only entirely nuclear-en-coded respiratory complex. Sequence analysis of cardiac mtDNAshowed that 4of the patientsharbored novel hetero-plasmic mtDNA mutations in cytb (15508), tRNAARG(10424), tRNAALA(5655), ND4L (10554) and ND5 (14969); mutations in mtDNA-encoded structural proteins (cytb, ND4L, ND5) resided inhighly conserved amino acid residues while thetRNA mu-tations werepresent in highly conserved nucleotides. A fifth patient exhibited a heteroplasmic mutation in cytb (15236) which has been previously reported in association with mito-chondrial cardiomyopathy (MCM). Noneof these potentially pathogenic mutations were present in controls (n=6) or in cardiomyopathic patients with noenzymatic defect (n=5). In addition, 2 patients exhibited marked reduction in cardiac mtDNAlevels. Whilespecific mtDNA deletionsweredetected in 7patients,they werefoundinlow proportioncomparedto wild-type mtDNA levels (< 0.1%) andnorelationship could be established between the levels ofspecificmtDNAdeletions and enzymeactivities.
Conclusions: In summary, specific mitochondrial enzymatic abnormalitiesarefrequently present and heterogenousin chil-dren with both DCM and HCM. The basis for the respiratory enzyme abnormalities can be explained in a subset of our patients as a result of eitherpathogenic mtDNA mutation or mtDNA depletion. These patients harboring both DNA and enzymaticdefects fulfillarigorouscriteriadefining mitochon-drialcardiomyopathy. Further studyisunderwaytodefine the molecular basis for the observed respiratory enzyme defectsin the remaining patientsasinvolving defective nuclearDNAloci.
13
WHATIS THEYIELDOFECHOCARDIOGRAPHYIN THE EVALUATION OF SYNCOPE?
Saskia Ritter MD, LuAnn Minich, MD, FAAP, Richard Wil-liams, MD, FAAP, Susan Etheridge, MD, FAAP, Janet Craig, PNP,Lloyd Tani, MD,FAAPDepartmentof Pediatrics, Univer-sityofUtah, Salt Lake City, Utah
Background: Syncope is common in children and most causes arebenign. Studies published in1995 suggestthat routine echo-cardiographyisnotusefulinthe evaluation of adults with syn-cope.Similarstudies havenotbeenreportedfor children and the role of echointhe evaluationof childhood syncope remains con-troversial.
Purpose:The purposes of this study were todetermine the yield ofechocardiography and to define any changesinitsusefor the evaluation of children with syncopeover a 6yearperiod.
Methods: Thecardiology data basewassearched for all patients (pts) presenting with syncope between1/93 and 1/99. Ptswith previously diagnosed cardiac disease who subsequently devel-oped syncopewereexcluded. The medical recordswerereviewed for patient demographics, year of presentation, physical exam, cardiactestsordered and their results, and finaldiagnosis. Echo abnormalitieswereobtainedby reviewing reports and videotapes. Results:The 480 pts (266females) rangedinagefrom 1.5-18.0 yr (12.3 ± 3.7, mean ± SD) and weight from 10.3-113.6 kg (47.4 ± 17.9). Final diagnoses included vasovagal syncopein341,long QT syndrome in 14, arrhythmias in 6, cardiomyopathy in 2, and noncardiac causes in the remaining 117 pts. Echoes were per-formedin 322 pts (67%). Echocardiographic abnormalities were detectedin 11of 230 pts (4.8%) withanormalexamandECG, and in 26of 92 pts (28.3%) with anabnormal exam or ECG. The37 abnormalities demonstrated by echo included 26 minor valve abnormalities, 7hemodynamically insignificant shunt lesions, 2 mildly decreased shortening fractions (25%,27%),and 2 cardio-myopathies.
Only
the2cardiomyopathies (hypertrophic obstruc-tivecardiomyopathy, right ventricular dysplasia)wereconsidered tobepotential causes of syncope, andinbothcasesthe ECGwas markedly abnormal. There was no significant difference in the percentageof echoes ordered beforevsafter the1995published studies(60%vs70%, p=0.27).Conclusions: In the absence of anabnormal physical exam or ECG,echo adds littletothe evaluationof syncopeinchildren.We speculate thatpediatricians andpediatric cardiologistscontinue its routineusebecauseof the paucity of data regarding the value of echo in evaluating pediatric syncope. This pediatric study showsalowyield of echo and shoulddiscourageits routine use for the evaluation of syncope.
14
CARDIACEVENTMONITORINGINPEDIATRIC PATIENTS
Marguerite M. Crawford, M.D., Howard P. Gutgesell, M.D., F.A.A.P, NancyL.McDaniel, M.D.,F.A.A.P. Divisionof Pediatric Cardiology,University ofVirginia Health SciencesCenter, Char-lottesville, Virginia.
Background: Cardiacevent monitors arefrequentlyprescribed for the evaluation of patients with complaints referable to the cardiovascular system. Studies on the use of thesemonitors in adults have found them to be efficacious for the evaluation of palpitations. The purpose of this studywas todetermine theuse andresults of cardiaceventmonitoringinchildren.
Methods:Retrospective chartreviewof 109consecutivepatients seen in a tertiarycare center pediatric cardiology clinic and issued acardiaceventmonitorbetween 1995 and 1998.
normal cardiovascular systems. Forty-one patients had underly-ing cardiac diagnoses including; suspected supraventricular tachycardia (SVT), Wolff Parkinson White syndrome, and 17 had previously undergone cardiac surgery for structural heart abnor-malities. Indications for monitoring included complaints of: fast heart rate (78%), chest pain (54%) and syncope or presyncope (43%). Some patients had multiple complaints. Standard non-looping cardiac event monitors were issued to 107 patients for 30 days. Two patients under 3 yearsof age were issued continuous loop event recorders. Six patients weregiven a monitor for more than one month.The number of events recorded by each patient ranged from 0 to 28,withthe majority(58%) recording between 1 and 3 events. Recordings in 100 patients (92%) demonstrated negativefindings with normal sinus rhythm (35%), sinus arrhyth-mia (31%) or sinus tachycardia (26%). Nine patients (8%) had positivefindings. Seven of these patients had at least1episode of SVT.Of these7patients,only 1had newly diagnosed SVT. Two had undergone prior electrophysiologic ablationof reentrant path-ways, and4had previously suspected SVT. The 2 other patients with positivefindings were found to haveprofound bradycardia. Ten additional patientswerehighly suspected to have arrhyth-miasdespite negative findingson eventrecordings. Twoof these patients werefound to have non-sustained ventricular tachycardia on 24 hour Holter monitor. One patient with pre-excitation on electrocardiogram and symptoms highly suspicious for SVT hada positiveelectrophysiologic study. The remaining 7patients sus-pected of having SVTwereeducated ontechniques to terminate tachycardia and when to seek medicalattention. Cardiacevent monitorsdetected only 9 positive diagnoses out of 109 patients (8%),at a costof$70,800 (118 monthsat$600).
Conclusion: Cardiac event monitoring of pediatric patients is unlikely to revealapathologic diagnosis exceptinchildren witha known orpreviously treated arrhythmia. The majority of children withpalpitations, chest pain, or syncope will haveasinusrhythm atthetimeof their symptoms. However, the use ofeventmonitors maybehelpful to provide reassurance to children and their fam-ilies.
15
IS AMIODARONE MORE HEPATOTOXIC IN PATIENTS WITHFONTANOPERATION?
MayteI.Figueroa, MD, and Seshadri Balaji,MRCP.Divisionof Pediatric Cardiology, Medical University of South Carolina, Charleston,SC.
Background: Amiodarone (Amio) is often used for atrial flutter after the Fontan operation(FO). FO patients have elevatedvenous pressure andhepatic congestion. We sought to determinewhether Amio'shepatotoxicityis morepronouncedinFO patients.
Methods:Between 1984and 1997,12FOpatients(age8-26yrs, median 16.9) and 18 non-Fontan (NF) patients (age 2-33 yrs, median 14) received Amio. In the NF group, 13 patients had congenital heart disease. Their arrhythmia diagnosiswas ventric-ular tachycardia in 10, atrial flutter in 6, and supraventricular tachycardiain2.Liverfunctiontests(LFT) (ALT, GGT,bilirubin) wereperformed before starting Amio, and6monthlythereafter. Meanfollow-upintheFO group was 37mos(range4mos-8yrs) andintheNFgroup54 mos(range 7mos-10yrs).
Results:
ALTpre ALTpost GGT pre GGT post
NF 28 +22 29 +10 32+25 39 + 30
FO 26 + 15 43 + 23 102±85 161 + 141
p ns <0.05 <0.05 <0.05
Amio, 8 FO patientsand 3 NF patients(all with repaired tetralogy of Fallot and right ventricular dilatation) had elevated LFT.
Conclusion: 1) Amio causes significant hepatotoxicity in FO patients; 2) LFT abnormalities are uncommon in NF patients, exceptafter TOF repair with rightventricular dilatation; 3) Amio should be used with cautioninthese two groupsof patients with regular monitoringofLFT.
16
AMIODARONE ISSAFE AND HIGHLY EFFECTIVEAS PRIMARYTHERAPYFOR TACHYCARDIAININFANCY SusanP.Etheridge, MD, FAAP, Janet Craig, PNP, University of Utah and PrimaryChildren's MedicalCenter, Salt Lake City, UT Background: Amiodarone is effective for life-threatening ar-rhythmias. Frequent side effect have limited its use as initial therapy, yetitmaysucceed where otherantiarrhythmics fail. We found amiodarone aloneorwithpropranololtosafe and effective fortreatmentof tachycardiaininfancy.
Methods: Between 6/94-present, 44 infants (age 1 ± 1 mo, mean ± SD) with tachycardiaweretreated withamiodarone (19 pts)oramiodarone andpropranolol(25 pts). Diagnoseswere: AV reentry tachycardia (AVRT)-26, AV node reentrytachycardia-4, atrial ectopic tachycardia (AET)-6, multifocal atrial tachycardia (MAT)-1, permanent form ofjunctional reciprocatingtachycardia (PJRT)-4,and incisional atrial reentrytachycardia (IART)-3. Diag-nosiswasmadeby ECGand/or esophagealEPstudy.At presen-tation, 14 pts had mild CHF and 5 were in shock. On initial echocardiogram,8(18%) pts had congenital heart disease14(32%) had decreased ventricular function. All patients underwent oral amiodaroneload.Propranolol (1-2 mg/kg) wasadded if tachy-cardia continued after4-5days. Baseline andfollow-upECG, T4, TSH, andALTwereperformed.
Results:Amiodaroneloading andmaintenancedoseswere 14± 5mg/kg and7 ±2mg/kg, respectively. Ptswere ontelemetryfor 8 ± 2days during loading andnoproarrhythmiasnoted. All pts had tachycardia control with amiodarone +/- propranolol. At discharge, all pts were asymptomatic with normal ventricular function. Forty pts(91%)were in sinusrhythm without tachycar-dia, and4pts(PJRT-1, AET-2,MAT-1)hadoccasionalepisodesof asymptomatic tachycardia. Based on history, ECG and Holter monitoring, all pts werefree oftachycardia within2mo. of dis-charge.Pts werefollowed for16 ± 14mo.Thebaseline QTcwas 430 ±30 msandthe maximalQTconamiodaronewas466± 30 ms. This increasewasnotstatisticallysignificant, but 27/44 (61%) hadaQTc>450atsometime during therapy. Typically the QTc increasedduringloading and retumedtonormalduring mainte-nancetherapy. Torsades de pointes didnot occur.Therewas no increase in ALT or T4.TheaverageTSH increasedduring therapy (3.8±2.8 vs 4.8±2.2) but remained within the normal rangeinall pts. Nosideeffects necessitateddrug withdrawal.Propranololhas been discontinuedin14/25 (56%) pts after6± 4 mo. and amio-darone discontinued in31/44 (70%) pts after9 ± 7 mo.without tachycardia recurrence.Thirty pts (68%)thathave beenfollowed for > 9 mo. Medication is still needed in 8/30 (27%) (AET-2, PJRT-1, MAT-1,AVRT-4)inwhom discontinuation of medication resultedintachycardia recurrence.
Conclusions: Amiodarone +/- propranolol is safe andhighly effective fortachycardia control evenininfants with difficultto control arrhythmias such as PJRT, IART, and AET. Although frequent side effects have been reported, none occurred in our pts. Althoughaninitialhospitalization may be necessary, pts may be safely dischargedoncetachycardiaiscontrolled. Medicationscan often be discontinued after9mo.oftherapy.
Post-17
DIAGNOSTIC ACCURACY OF THE SCREENING ELECTROCARDIOGRAMINGENOTYPED LONG QT SYNDROME.
Misha D.Miller,BA,Co-burn J. Porter, MD*, Michael J. Acker-man, MD,PhD., FAAP* Mayo Medical School; *Department of Pediatric and Adolescent Medicine, Section of Pediatric Cardiol-ogy, MayoFoundation/Mayo Clinic Rochester, Rochester,MN.
Background: Inherited long QT syndrome (LQTS) may present withsyncope, seizures, and/or sudden death due to ventricular tachyarrhythmias. Identification of at-risk family members who have the geneticsubstrate for LQTSiscritical.
Methods: Molecular testing of the 23 family members for the KVLQT1 mutationand symptomatic status facilitated the classifi-cationof eachfamily member into the following patient groups; 13 noncarriers,5asymptomatic carriers, and 5symptomatic carriers. Each individual had a standard 12-lead electrocardiogram from which the computerand manual (lead II) QTc, the maximum QTc, and the QT dispersion (QTd = maximum QT-minimum QT, irrespective of lead) were determined. Additionally, we deter-mined the accuracyof the computer ECG diagnostic interpretation for each patient group.
Results: The computer generated QTc, when using a diagnostic cut-off of QTc 2 460 ms, demonstrated a positive and negative predictive value of 100% for identifying those with LQTS. Despite thiscomplete separation of noncarriers from carriers, the auto-mated ECG diagnostic interpretation erroneouslyclassified 6 of 23 family members. Moreover, the interpretive statement, "normal ECG",wasascribed for 50%of the family members proven to have the ion channel defect. Although themaximumQTc was signifi-cantly longer forcarriersthanfor noncarriers, therewas consid-erable overlap between patient subsets. QT dispersion failed to distinguish LQTS individuals from noncarriers.
Conclusion: Relianceonthe ECG interpretation will failto iden-tify many at-risk family members. Careful consideration of the QTc with adherence to the QTccut-off value of 460 ms must be givenindependentof the ECG interpretive statements. Itis sug-gestedthat allfirst-degreerelatives ofanidentified LQTSproband havea12-lead ECG thatisindependently reviewed bya cardiol-ogist familiar withLQTSin anefforttoimprove screeningfor this potentiallylethalsyndrome.
18
PEDIATRICSYNCOPE:COMPARISON OF EMERGENCY DEPARTMENT AND CARDIOLOGYCLINIC EVALUATION PRACTICES.
Venkat Ramesh, MD, Tammy S. Wieand, MS,RonnE.Tanel, MD, Mitchell I. Cohen, MD, Victoria L Vetter, MD, Larry A. Rhodes, MD, The Children'sHospital of Philadelphia, Philadel-phia,PA
Syncopecanbeanalarming symptom that often resultsin exten-sivediagnostic testing and hospitalization in pediatric patients. The purposeof this studyis tocompare the evaluation of patients whoareself-referred to anemergencydepartment (ED)vsthose who are seen by appointmentin acardiology clinic (CC).
Methods:Aretrospective search wasperformed on apediatric electrocardiogram (ECG) database (1991-1998) for thetest indica-tion of syncope. Patients with known congenital heart disease wereexcluded (n=19). All ECGs, echocardiograms (ECHO),24hr Holter monitors, head up tilttests(HUTT) and follow-up CCvisits for eachpatientwerereviewed.
Results: Therewere620patients(agelm to18y) identified with a similar evaluation site distribution (ED, n=286; CC, n=315). Therewasnosignificantdifferenceinageorgender betweensites. Despite theequal proportion of abnormal ECGs, additionaltests wereperformed morefrequentlyinCC(p<0.05)(Table). Holters
were ordered more frequently than ECHO or HUTT, but abnor-mal results for all tests occurred with similar incidence at both sites. There were more frequent abnormalities in Holters and HUTT. Pre-excitation was diagnosed in3patients (all CC). Pro-longed QT interval incidence was similar (ED, 5.2%; CC, 5.1%). Fourhemodynamically insignificant structural lesions were iden-tified (ED, 2; CC, 2).Follow up was less likely when seen in ED (19% vs 44%)(p<0.05).
Abn EKG Echo
Total Abn
ED(n = 286) 118 (41%) 27 (9%) 2(7%) CC(n = 315) 123(39%) 77*(24%) 7(9%)
Holter HUTT
Total Abn Total Abn
49 (17%) 30(61%) 12 (4%) 7(58%)
164* (52%) 123(75%) 85*(27%) 53(62%)
*p<0.05 betweenEDand CC.
Conclusions: Non-invasive tests were performed less often for patients presenting with syncopeto ED. Since abnormaltest re-sults were of similar incidence in the 2 groups, some patients evaluatedin ED mayhaveunrecognized abnormalities. Patients seen in EDfor syncopemayneedmoreaggressivefollow-up.
19
THE EARLYPROFILEOF MYOCARDIALDYSFUNCTION INCHICKENEMBRYOS AFTER NEURALCREST ABLATION.
Hong Jin, MD, Margaret Kirby, PhD., and LindaLeatherbury, MD, FAAP. Department of Pediatrics, IMMAG Developmental Biology, Medical Collegeof Georgia, Augusta, GA.
Background: Ablation of premigratory cardiac neural crest causes notonlyhighincidence ofpersistenttruncusarteriosusand aorticarchanomalies (interrupted aorta) but alsomyocardial dys-function in early cardiovascular development prior to thetime that neuralcrestcells would normally migrateintothe heart and far before the time when cardiovascular defects are seen. We hypothesized that complete ablation of the cardiac neural crest would induce moreseverelydepressed contractility thanpartial ablation; furthermore,wedesiredtoidentifythe earliest develop-ment stage with myocardial dysfunction. Knowing this stage would helpus focusonhow the migrating cardiac neural crest cells are important formyocardial function before reaching the heart.
Methods: Complete ablation of the premigratory neural crest from theoticplacodetosomite3,orpartial ablationtosomite2,at stage 9 producedthe experimentalchickembryo groups.Using normal-control chick embryos with theeggshellopenedjust prior to
filming
and sham-operated control embryos that were pro-cessedinparallelwithexperimental embryos,depressed contrac-tility and abnormalconfigurationof the heart tubewereratedat stage 14. Using high-speed microcinephotography, end-systolic and end-diastolic dimensions of the outflow segment ventricle weremeasuredatstages16and18 to assesscardiacperformance. Pathological evaluationwasperformedatmaturestage28.Partial neural crest ablation caused less severely depressed con-tractilityat stage 16,but similar cardiacdysfunction as complete ablationby stage 18.
Conclusion: After complete cardiac neural crest cell ablation, myocardial dysfunction occurs earlier andismoresevere. Inter-estingly, partial neuralcrestablation onlycauses adifference in the timing,not inthe extentof the observed cardiac dysfunction, whencompared with complete ablation. This study showsthatthe cardiac neuralcrestcellsareessential for normalmyocardial func-tionbefore they reach the heartat astagewhen they should be migratingthrough the pharyngeal arches around the aortic arch arteries. There may be some specific modulating factors of the cardiac neural crest cells responsible for myocardial function, which is not necessarily associatedwithsubsequent development ofspecific cardiac structural defects.
20
APROSPECTIVE ANALYSIS OF THE IMMUNOGENICITY OF CRYOPRESERVED NON-VALVED ALLOGRAFTS USED INPEDIATRICCARDIAC SURGERY.
JohnP.Breinholt BS,JohnA.HawkinsMD, Linda M.Lambert BS,ThomasC.FullerPh.D.,TracieProfaizer, RobertE.Shaddy MD.Depts ofPediatrics, Surgery, and Pathology, Primary Chil-dren'sMedical Center and the University ofUtah, Salt Lake City, UT.
Background: We have previously reported that cryopreserved valvedallografts usedtorepaircongenital heart defects inducea significant human leukocyte antigen (HLA) humoral antibody response thatbroadensinreactivitywithin 3months of surgery and persists beyond 1 year. The purpose of this study was to prospectively determine the immunogenicity of non-valved allo-grafttissueusedinthe repair of congenital heart disease.
Methods: Weprospectively analyzed theimmuneresponseof6 children, age2 months to 10years, whorequired anon-valved allograftpatchtoalleviatestenosis during repair ofacongenital cardiacdefect. Thediagnosesinthese patientswere:Transposition in2patients,aorticarchobstructionin3patients, andpulmonary atresia in 1 patient. Non-valved allografts were required in 2 patients to repair or reconstruct the pulmonary artery, in 3 to relieve the obstructed aorticarch, andin 1 patientto reconstruct theright ventricular outflowtract. In6cases,pulmonary arterial grafts were used; in 1 patient, a sectionof glutaraldehyde-pre-servedallograft pericardiumwasused. Allpatients received leu-kocyte filtered and irradiated blood products perioperatively to preventsensitizationagainst blooddonorproducts.We prospec-tively measured the level ofHLApanel-reactive antibody (PRA) priortosurgery,1 weekafter,1 monthafter, and 3 months after allograft placement. PRA wasdetermined in 2 ways: using the antiglobulincytotoxicitytechniqueagainstanHLA-select frozen T-lymphocyte panel and by flow cytometry usingapool ofHLA Class I and II purified antigen coupled to latex beads. PRA is expressedasthe percentage oflymphocyte panel members (anti-globulin technique)orfluorescentpositivebeads(flow cytometry) againstwhich the patient'ssera react.
Results:Inthe 5patients who receivedpulmonary allografttissue, PRA measurements were 3.2±5.6%preoperativelyand 0.0 % at one weekafter surgery. However, withinonemonth,allpatientsshowed avigorousimmuneresponse. The measuredPRAincreasedto52.4±
19% at 37.8±8days after surgery, and further increasedto78.4±
26%at3.2±0.4months after surgery. Flow cytometry demonstrated bothHLAClassIandClassIIantibodies.Atonemonth, ClassI PRA increased to67 + 38%andClassII was 52 ± 43%.By3months, Class Iand Class II PRAincreased to85 ± 31% and 58 ± 31%, respectively. In thepatient who received thepericardial allograft, therewas noincrease in PRA inthe firstmonth,andonlyaminimal increase inthePRAlevelto 5 %by3months.
Conclusions: Similartovalvedallografts,cryopreserved non-valved allograftsinduceastrongHLAantibody response that broadensin
reactivitywithin 3 months. This response represents antibody to both HLAClassI and ClassII antigens. This suggests that evensmall piecesof cryopreserved non-valvedallograft tissue exhibit sufficient immunogenicity toinduceastrongantibody responsethat could be damaging to the tissue. The fact that the one patientinthis study who received glutaraldehyde-preserved allograft pericardium demon-stratedno immuneresponsewarrantsfurther investigation.
21
INVIVO ELECTROPHYSIOLOGY STUDIES IN ENDOTHELIAL NITRIC OXIDE SYNTHASE (eNOS) DEFICIENTMICE.
Amit Rakhit, MD, Colin T. Maguire, BS, JosefGehrmann, MD, RalphA.Kelly, MD, Thomas Michel, MD, PhD,CharlesI.Bedl, MD,FAAP. Children's Hospital - Boston, Brigham &Women's
Hospital, Harvard Medical School, Boston,MA.
Background: Nitric oxide has been implicated inthe control of autonomicfunction of the heart. There are three known isoforms of nitric oxide synthase expressed in varying cell types with cardiac myocytes expressing the endothelial isoform of the en-zyme.Endothelial nitric oxidesynthase (eNOS) has been shownto mediate theattenuationof the L-type calcium channel and myo-cytecontractility by cholinergicandbeta-adrenergic stimulation. Arrhythmogenic aftercontractions have been found in ouabain-treatedisolated myocytesfrom eNOS-deficient mice though there have been no similar in vivo studies on the role of eNOS in arrhythmogenesis.
Methods: In vivo cardiac electrophysiology studies (EPS) were performed in 10 mice completely lacking the eNOS gene (eNOS-/-)andwild-type(eNOS'++)littermate controlmice. Base-line conduction intervals (RR, PR, QRS, and QTc)weremeasured from surface ECG recordings and then intracardiac EPS testing was performed. Cycle length (SCL), sinus node recovery time (SNRT, cSNRT),AV and ventricularrefractory periods (AVERP, VERP) and paced AV and VA Wenckebach cycle lengths (AVWCL, VAWCL) were measured. Subsequently, VERP and VAWCLwereremeasuredafter intracardiac isoproterenol admin-istration.
Results:Dataanalysis by Pearsont-testrevealed nosignificant differencesinECGintervals, cardiac conduction times,refractory periods, orsusceptibilityto induciblearrhythmia in eNOS-defi-cient mice versuswild-type controls.
EPdata SCL cSNRT AVERP AVWCL VERP VAWCL (msec)
eNOS-/- 152+3 70 +58 61±12 77±13 51 ±3 105 + 10 (n= 10)
eNOS+/+ 124±7 88+ 83 60 + 4 75 +4 50 +5 110 + 2 (n = 5)
t-test .07 .85 .89 .69 .50 .54
(p-value)
Conclusion: Despite the modulation ofionchannelphysiologyin the heart,a transgenic eNOS deficiencymouse model does not predisposetocardiacconduction disordersorarrhythmia vulner-ability. Potential abnormalities might be inducibleinprovocative experimental conditions.
22
THEEMERGENCY CENTER VS THE COMPUTER: WHICH IS THE BETTER ELECTROCARDIOGRAPHER?
