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  • 1. DIVISION OF CARDIOLOGY DIVISION PROFILE Number of Faculty -17 Number of Fellows - 10 Clinical- 6 Research - 4 Number of Support Personnel - 101 Annual Total Grant Support (direct costs) - $2,220,136 Annual Total Industry Contracts (direct costs) - $2,223,114 Number of Peer Reviewed Publications – 48 Patient Encounters Inpatient – 5,627 Outpatient – 9,358 FACULTY LISTING Robert H. Beekman, III, M.D., Division Director, Professor D. Woodrow Benson, M.D., Ph.D., Professor; Director, Cardiovascular Genetics Randal P. Claytor, Adjunct Associate Professor Linda Cripe, M.D., Assistant Professor Stephen Daniels, M.D., Ph.D., Professor; Director, Preventive Cardiology, Associate Chair, Department of Pediatrics Catherine Dent, M.D., Assistant Professor Michael Epstein, M.D., Assistant Professor Russel Hirsch, M.D., Assistant Professor; Director, Cardiac Cath Lab Jeanne James, M.D., Research Professor Thomas Kimball, M.D., Professor; Director, Echocardiography Timothy Knilans, M.D., Associate Professor; Director, Electrophysiology Richard Meyer, M.D., Professor Erik Michelfelder, M.D., Assistant Professor John Morrison, Ph.D., Research Associate Professor David Nelson, M.D., Ph.D., Associate Professor; Co-director, Cardiac ICU Steven Schwartz, M.D., Associate Professor; Co-director, Cardiac ICU Robert Spicer, M.D., Professor; Medical Director of Heart Transplant Program Karen Uzark, R.N., Ph.D., Associate Professor; Director, Cardiac Process Improvement and Clinical Effectiveness Kathy Wright, D.V.M., Adjunct Research Assistant Professor 23
  • 2. OVERVIEW The three fundamental missions of the Division of Cardiology are: 1) to advance pediatric cardiovascular medicine through clinical and basic research; 2) to train future leaders in academic pediatric cardiology; and 3) to provide outstanding care to pediatric and young adult patients with congenital or acquired cardiovascular disease. Left to right: (1st row) D. Nelson, J. James, J. Morrison, T. Knilans, (2nd row) R. Hirsch, L. Cripe, V. Tuzcu, W. Gottliebson, E. Michelfelder, R. Meyer, S. Schwartz, C. Dent, R. Beekman, R. Spicer, K. Uzark, T. Kimball The division provides comprehensive diagnostic and therapeutic clinical services for patients ranging in age from the fetus to the young adult. A large number of outpatient clinics are held weekly, including general cardiology and subspecialty cardiology clinics. Active inpatient services include the cardiac intensive care unit and the cardiology ward service located in the new hospital tower. Outstanding clinical services are also provided in all clinical subspecialties including echocardiography, electrophysiology, cardiac catheterization and intervention, genetic cardiology, heart failure and cardiac transplantation, and preventive cardiology. The division is actively involved in teaching activities which include medical students, residents and fellows. The Pediatric Cardiology Fellowship is a 3-4 year program that accepts three fellows a year. This program is very strong clinically and academically, and has gained recognition nationally as one of the top training programs in our specialty. The core three-year fellowship includes 20 months of intense clinical rotations, and approximately 12-14 months of academic time for each fellow to pursue clinical or basic research interests. 24
  • 3. The division is actively involved in clinical and laboratory research. Excellent clinical research is ongoing in numerous areas, including preventive cardiology, echocardiography, interventional cardiology, genetic cardiology, heart failure and cardiac intensive care. Particularly strong basic research exists in the area of molecular and genetic cardiology. A unique academic strength lies in the close research relationship that exists between the division’s Cardiovascular Genetics Research Program and the Division of Molecular Cardiovascular Biology. HIGHLIGHTS Some highlights during the past academic year include new developments in cardiovascular research, and new and enhanced clinical cardiac programs. Russel Hirsch, M.D. joined our faculty from Washington University in St. Louis, and is the new Director of the Cardiac Catheterization and Interventional Cardiology Program. The Cardiovascular Genetics Research Program directed by D. Woodrow Benson, M.D., Ph.D. continues to make important inroads into the genetic origin of congenital heart disease. One such example is a pioneering study of the genetics of bicuspid aortic valve which was performed by Drs. Benson and Cripe. Echocardiographic evaluation of family members of 50 bicuspid aortic valve (BAV) probands was performed. Three generations of family history were obtained for each proband, and a complete medical history was obtained for all 378 participating family members. Bicuspid aortic valve was identified echocardiographically in 75 individuals, for a prevalence of 20%. The prevalence of all congenital heart disease was 24%, which in addition to BAV included coarctation, atrial septal defect, ventricular septal defect and mitral valve abnormalities. Morphologic characteristics of the bicuspid aortic valves suggested that BAV morphology is not random but rather is under genetic control. The prevalence of BAV and other congenital heart disease was found to be much higher than in the general population indicating that these families are “enriched” for affected individuals and suggesting a strong genetic component to BAV development. Expanding importantly on these preliminary genetic studies of congenital heart disease, Dr. Benson and the Division of Molecular Cardiovascular Biology have submitted an exciting NIH SCCOR application. A new Fetal Cardiac Research Program was also initiated this year, by Dr. Michelfelder and Dr. Eghtesady of the Division of Cardiothoracic Surgery. This program has begun pioneering research into the morphogenesis of univentricular heart in a fetal lamb model. In the near future this program intends to initiate an investigational human fetal cardiac therapeutics program. New clinical programs this year include the opening of our new all digital cardiac catheterization and electrophysiology laboratories. These two labs represent state-of-the- art technology, as all images are networked throughout the heart center and are available instantaneously in multiple locations. The Cardiac Cath and Intervention Program has been relocated to the new patient care tower and is integrated onto the cardiac ward. This has enabled the division to provide much enhanced patient and family care by unifocalizing all patient precath, intracath, and postcath management. The quality of 25
  • 4. patient care, communication and family comfort has been greatly enhanced by this new programmatic development. The division also initiated a new outpatient program this year, the Neuromuscular Cardiology Clinic. This multidisciplinary program provides diagnostic and therapeutic cardiac care to children with neuromuscular diseases. It is staffed jointly by Drs. Cripe and Spicer from Cardiology, and the divisions of Neurology and Pulmonology. This new clinical program is a model of multidisciplinary care for complex cardiovascular issues, and has resulted in greatly improved clinical services to these complex patients. TRAINING Brooke Hanaway, M.D. PL IV University of Colorado Robert Hinton, M.D. PL IV Memorial Health Univ. Med. Ctr. Suzanne Mone, M.D. PL IV University of Rochester Larry Markham, M.D. PL V University of Arkansas Holly Ippisch, M.D. PL V Loma Linda University Children’s Angela Lorts, M.D. PL V University of Colorado Terrence Chun, M.D. PL VI Cedars-Sinai Medical Center Gerald Johnson, M.D. PL VI Vanderbilt University Medical Ctr. Mark Zilberman, M.D. PL VI Indiana University Medical Center Gregory Andelfinger, M.D. PL VII University Children’s Hospital Hamburg Germany GRANTS, CONTRACTS AND INDUSTRY AGREEMENTS Grant and Contract Awards Annual Direct/Project Period Direct Andelfinger, G. Genetic Study of Canine Tricuspid Valve Malformation American Heart Associate – Ohio Valley Affiliate 07/01/02 – 06/30/04 $37,000/$76,000 Benson, W. Genetic Mechanisms of Cardiac Disease in the Young National Institutes of Health K24 HL69712 06/15/01 - 05/31/06 $122,526/$612,630 Benson, W. Genetic Origin of Structural and Functional Defects of Atrioventricular Conduction in Humans National Institutes of Health (Medical University of South Carolina subcontract) P01 HD39946 06/28/01 – 04/30/06 $88,055/$440,658 26
  • 5. Benson, W. Molecular Determinants of Pediatric Heart Disease National Institutes of Health (Washington University subcontract) P50 HL61006 03/01/01 - 12/31/03 $157,645/$439,487 Benson, W. Ebstein Anomaly: Molecular Genetic Studies of a Canine Equivalent The Children’s Heart Foundation 01/01/03 – 12/31/04 $51,123/$102,246 Chun, T. Neurohormones Pulmonary Regurgitation and Aerobic Capacity in Repaired Tetralogy of Fallot American Heart Associate – Ohio Valley Affiliate 07/01/02 – 06/30/04 $37,000/$76,000 Daniels, S. Visceral Adiposity and CVD Risk in Women National Institutes of Health R01 HL66430-02 03/05/01 – 02/28/06 $496,402/$1,967,619 Daniels, S. Fibromyalgia and TMD in Young Women-Multiracial Study National Institutes of Health (University of California San Francisco subcontract) R01 DE13487 09/25/99 – 08/31/03 $3,079/$106,701 Daniels, S. The Epidemiology of Body Mass Index Rebound National Institutes of Health R01 HL64022 08/17/01 – 07/31/05 $475,835/$2,317,851 Daniels, S. Genetic Epidemiology of Energy Metabolism in Black Girls National Institutes of Health (University of Pittsburgh subcontract) R01 HL66070 05/01/01 – 04/30/05 $177,329/$676,944 27
  • 6. Daniels, S. Effects of Pregnancy on Adolescent Growth and Health National Institutes of Health (University of California, Berkley subcontract) R01 HD039304 05/01/02 – 04/30/05 $73,365/$227,862 Michelfelder, E. Echocardiographic Evaluation of Cardiac Anatomy and Function in an Ovine Model of Fetal Left Heart Hypoplasia American Heart Associate – Ohio Valley Affiliate 05/01/03 – 08/31/03 $2,500 Morrison, J. Longitudinal LDL-C Studies in Black and White Families National Institutes of Health R01 HL62394 07/01/00 – 06/30/04 $462,726/$1,674,525 Wright, K. Assessment and Treatment of Canine Accessory Pathways Morris Animal Foundation 12/01/02 – 11/30/05 $15,551/$40,416 Current Year Direct $ 2,220,136 Industry Contracts Daniels, S. Knoll Pharmaceuticals $2,292 Nelson, D. Baxter Healthcare Corporation $3,716 Shim, D. General Electric $3,812 Spicer, R. SmithKlineBeecham $5,756 Wright, K. Procter and Gamble $7,402 Current Year Direct Receipts $ 22,978 TOTAL $2,223,114 28
  • 7. Funded Collaborative Efforts Daniels, S Landmarks in the Progression to Type II Diabetes National Institutes of Health PI: Dolan, L 09/30/00 – 09/20/05 5% Childhood Diabetes: Prevalence, Incidence and Characteristics Centers for Disease Control PI: Dolan, L 09/30/00 – 09/29/05 5% Mechanisms Mediating Cardiac and Vascular Disease in Children with OSA National Institutes of Health PI: Amin, R 04/01/03 – 03/31/08 5% Bone Density and Forearm Fractures in Injured Children National Institutes of Health PI: Kalkwarf, H 07/01/00 – 06/30/03 5% Kimball, T Mechanisms Mediating Cardiac and Vascular Disease in Children with OSA National Institutes of Health PI: Amin, R 04/01/03 – 03/31/08 5% Morrison, J Landmarks in the Progression to Type II Diabetes National Institutes of Health PI: Dolan, L 09/30/00 – 09/20/05 5% Spicer, R Pursuing Perfection: Raising The Bar For Health Care Performance Robert Wood Johnson Foundation PI: Kotagal, U 04/01/02 – 03/31/04 5% Uzark, K Pursuing Perfection: Raising The Bar For Health Care Performance Robert Wood Johnson Foundation PI: Kotagal, U 04/01/02 – 03/31/04 15% PUBLICATIONS 1. Raake JL, Cooper DS, Beekman RH, III, Nelson DP, Schwartz SM. ECMO as a bridge to interventional catheterization. RT: the Journal for Respiratory Care Practitioners 2002/2003;15(6):10,12,14. 29
  • 8. 2. Beekman RH, Lloyd TR. Balloon valvuloplasty and stenting for congenital heart disease. In: Topol EJ, editor. Textbook of interventional cardiology. 4th ed. Philadelphia: Saunders Co.; 2003. p. 955-76. 3. Watanabe Y, Benson DW, Yano S, Akagi T, Yoshino M, Murray JC. Two novel frameshift mutations in NKX2.5 result in novel features including visceral inversus and sinus venosus type ASD. J Med Genet 2002;39(11):807-11. 4. Andelfinger G, Tapper AR, Welch RC, Vanoye CG, George AL, Jr., Benson DW. KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. Am J Hum Genet 2002;71(3):663-8. 5. Benson DW. The genetics of congenital heart disease: a point in the revolution. Cardiol Clin 2002;20(3):385-94, vi. 6. Robbins J, Benson DW. Structure-function relationships in myosin binding protein-C: taking off the blinders and collaring hypertrophic cardiomyopathy. Circ Res 2002;91(8):656-8. 7. Viswanathan PC, Benson DW, Balser JR. A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation. J Clin Invest 2003;111(3):341-6. 8. Johnson WH, Jr., Yang P, Yang T, Lau YR, Mostella BA, Wolff DJ, Roden DM, Benson DW. Clinical, genetic, and biophysical characterization of a homozygous HERG mutation causing severe neonatal long QT syndrome. Pediatr Res 2003;53(5):744-8. 9. Benson DW. The genetic origin of atrioventricular conduction disturbance in humans. In: Chadwick D, Goode J, Watanabe M, Rothenberg F, Rosenbaum DS, Novartis Foundation., et al., editors. Development of the cardiac conduction system. Chichester, UK ; Hoboken, NJ: Wiley; 2003. p. ix, 289 p. 10. Pearl JM, Cripe LW, Manning PB. Biventricular repair after Norwood palliation. Ann Thorac Surg 2003;75(1):132-6; discussion 136-7. 11. Williams CL, Hayman LL, Daniels SR, Robinson TN, Steinberger J, Paridon S, Bazzarre T. Cardiovascular health in childhood: A statement for health professionals from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 2002;106(1):143-60. 12. Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Greenland P, Grundy SM, Hong Y, Miller NH, Lauer RM, Ockene IS, Sacco RL, Sallis JF, Jr., Smith SC, Jr., Stone NJ, Taubert KA. AHA 30
  • 9. Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation 2002;106(3):388-91. 13. Daniels SR, Witt SA, Glascock B, Khoury PR, Kimball TR. Left atrial size in children with hypertension: the influence of obesity, blood pressure, and left ventricular mass. J Pediatr 2002;141(2):186-90. 14. Kimm SY, Glynn NW, Kriska AM, Barton BA, Kronsberg SS, Daniels SR, Crawford PB, Sabry ZI, Liu K. Decline in physical activity in black girls and white girls during adolescence. N Engl J Med 2002;347(10):709-15. 15. Sorof J, Daniels S. Obesity hypertension in children: a problem of epidemic proportions. Hypertension 2002;40(4):441-7. 16. Affenito SG, Dohm FA, Crawford PB, Daniels SR, Striegel-Moore RH. Macronutrient intake in anorexia nervosa: The National Heart, Lung, and Blood Institute Growth and Health Study. J Pediatr 2002;141(5):701-5. 17. Pearson TA, Bazzarre TL, Daniels SR, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Hong Y, Mensah GA, Sallis JF, Jr., Smith S, Jr., Stone NJ, Taubert KA. American Heart Association guide for improving cardiovascular health at the community level: a statement for public health practitioners, healthcare providers, and health policy makers from the American Heart Association Expert Panel on Population and Prevention Science. Circulation 2003;107(4):645-51. 18. Blumer JL, Daniels SR, Dreyer WJ, Batisky D, Walson PD, Roman D, Ouellet D. Pharmacokinetics of quinapril in children: assessment during substitution for chronic angiotensin-converting enzyme inhibitor treatment. J Clin Pharmacol 2003;43(2):128-32. 19. Donnelly LF, O'Brien KJ, Dardzinski BJ, Poe SA, Bean JA, Holland SK, Daniels SR. Using a phantom to compare MR techniques for determining the ratio of intraabdominal to subcutaneous adipose tissue. AJR Am J Roentgenol 2003;180(4):993-8. 20. Kavey RE, Daniels SR, Lauer RM, Atkins DL, Hayman LL, Taubert K. American Heart Association guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood. Circulation 2003;107(11):1562-6. 21. Brehm BJ, Seeley RJ, Daniels SR, D'Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003;88(4):1617-23. 31
  • 10. 22. Steinberger J, Daniels S R . Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Circulation 2003;107(10):1448-53. 23. Biro FM, Lucky AW, Simbartl LA, Barton BA, Daniels SR, Striegel-Moore R, Kronsberg SS, Morrison JA. Pubertal maturation in girls and the relationship to anthropometric changes: pathways through puberty. J Pediatr 2003;142(6):643-6. 24. Stephenson EA, Collins KK, Dubin AM, Epstein MR, Hamilton RM, Kertesz NJ, Alexander ME, Cecchin F, Triedman JK, Walsh EP, Berul CI. Circadian and seasonal variation of malignant arrhythmias in a pediatric and congenital heart disease population. J Cardiovasc Electrophysiol 2002;13(10):1009-14. 25. Yi MS, Kimball TR, Tsevat J, Mrus JM, Kotagal UR. Evaluation of heart murmurs in children: cost-effectiveness and practical implications. J Pediatr 2002;141(4):504-11. 26. Wilkins BJ, De Windt LJ, Bueno OF, Braz JC, Glascock BJ, Kimball TF, Molkentin JD. Targeted disruption of NFATc3, but not NFATc4, reveals an intrinsic defect in calcineurin-mediated cardiac hypertrophic growth. Mol Cell Biol 2002;22(21):7603-13. 27. Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR. Left ventricular mass and systolic performance in pediatric patients with chronic renal failure. Circulation 2003;107(6):864-8. 28. Mitsnefes MM, Kimball TR, Daniels SR. Office and ambulatory blood pressure elevation in children with chronic renal failure. Pediatr Nephrol 2003;18(2):145- 9. 29. Zilberman MV, Goya G, Witt SA, Glascock B, Kimball TR. Dobutamine stress echocardiography in the evaluation of young patients with Kawasaki disease. Pediatr Cardiol 2003;24(4):338-43. 30. Cnota JF, Ross JE, Knilans TK, Epstein MR. Does intermittent accessory pathway block during slow sinus rhythm always imply a low risk for rapid AV conduction of preexcited atrial fibrillation? Cardiology 2002;98(1-2):106-8. 31. Mathewson JW, Dyar D, Jones FD, Sklansky MS, Perry JC, Michelfelder EC, Cripe L, Kimball TR. Conversion to digital technology improves efficiency in the pediatric echocardiography laboratory. J Am Soc Echocardiogr 2002;15(12):1515-22. 32
  • 11. 32. Syed AU, Border WL, Michelfelder EC, Manning PB, Pearl JM. Pancreatitis in Fontan patients is related to impaired ventricular relaxation. Ann Thorac Surg 2003;75(1):153-7; discussion 157. 33. Michelfelder EC, Witt SA, Khoury P, Kimball TR. Moderate-dose dobutamine maximizes left ventricular contractile response during dobutamine stress echocardiography in children. J Am Soc Echocardiogr 2003;16(2):140-6. 34. Michelfelder EC, Ochsner JE, Khoury P, Kimball TR. Does assessment of pretest probability of disease improve the utility of echocardiography in suspected endocarditis in children? J Pediatr 2003;142(3):263-7. 35. Kimm SY, Barton BA, Obarzanek E, McMahon RP, Kronsberg SS, Waclawiw MA, Morrison JA, Schreiber GB, Sabry ZI, Daniels SR. Obesity development during adolescence in a biracial cohort: the NHLBI Growth and Health Study. Pediatrics 2002;110(5):e54. 36. Miles MV, Horn PS, Morrison JA, Tang PH, DeGrauw T, Pesce AJ. Plasma coenzyme Q(10) reference intervals, but not redox status, are affected by gender and race in self-reported healthy adults. Clin Chim Acta 2003;332(1-2):123-32. 37. Morrison JA, Barton BA, Biro FM, Sprecher DL. Sex hormones and the changes in adolescent male lipids: longitudinal studies in a biracial cohort. J Pediatr 2003;142(6):637-42. 38. Pearl JM, Nelson DP, Schwartz SM, Wagner CJ, Bauer SM, Setser EA, Duffy JY. Glucocorticoids reduce ischemia-reperfusion-induced myocardial apoptosis in immature hearts. Ann Thorac Surg 2002;74(3):830-6; discussion 836-7. 39. Hoffman TM, Wernovsky G, Atz AM, Kulik TJ, Nelson DP, Chang AC, Bailey JM, Akbary A, Kocsis JF, Kaczmarek R, Spray TL, Wessel DL. Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation 2003;107(7):996-1002. 40. Yang J, Jones SP, Suhara T, Greer JJ, Ware PD, Nguyen NP, Perlman H, Nelson DP, Lefer DJ, Walsh K. Endothelial cell overexpression of fas ligand attenuates ischemia-reperfusion injury in the heart. J Biol Chem 2003;278(17):15185-91. 41. Schroeder VA, Pearl JM, Schwartz SM, Shanley TP, Manning PB, Nelson DP. Combined steroid treatment for congenital heart surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression. Circulation 2003;107(22):2823-8. 33
  • 12. 42. Schwartz SM, Nelson DP, Taeed R. Intensive care of infants and children with hypoplastic left heart syndrome. In: Hennein HA, Bove EL, editors. Hypoplastic left heart syndrome. Armonk, NY: Futura Pub. Co.; 2002. p. 199-240. 43. Andelfinger G, Wright KN, Lee HS, Siemens LM, Benson DW. Canine tricuspid valve malformation, a model of human Ebstein anomaly, maps to dog chromosome 9. J Med Genet 2003;40(5):320-4. 34