Bio

Clinical Focus


  • Pediatric Cardiology
  • Pediatric Cardiomyopathy, Heart Failure, and Heart Transplantation

Academic Appointments


Administrative Appointments


  • Director, Cardiomyopathy Program, Stanford University, School of Medicine (2013 - Present)

Boards, Advisory Committees, Professional Organizations


  • Review Board Member, United Network for Organ Sharing (2007 - 2011)
  • Vice Chair, Pediatric Council, International Society of Heart and Lung Transplantation (2010 - 2010)
  • Chair, Pediatric Council, International Society of Heart and Lung Transplantation (2011 - 2012)

Professional Education


  • Fellowship:Columbia University/New York Presbyterian Hospital (1996) NY
  • Residency:John Hopkins University School of Medicine (1996) MD
  • Medical Education:Weill Medical College Cornell University (1996) NY
  • Board Certification: Pediatric Cardiology, American Board of Pediatrics (2004)
  • Board Certification: Pediatrics, American Board of Pediatrics (1999)

Publications

Journal Articles


  • A novel pediatric treatment intensity score: development and feasibility in heart failure patients with ventricular assist devices. journal of heart and lung transplantation May, L. J., Ploutz, M., Hollander, S. A., Reinhartz, O., Almond, C. S., Chen, S., Maeda, K., Kaufman, B. D., Yeh, J., Rosenthal, D. N. 2015; 34 (4): 509-515

    Abstract

    The evolution of pharmacologic therapies and mechanical support including ventricular assist devices (VADs) has broadened the scope of care available to children with advanced heart failure. At the present time, there are only limited means of quantifying disease severity or the concomitant morbidity for this population. This study describes the development of a novel pediatric treatment intensity score (TIS), designed to quantify the burden of illness and clinical trajectory in children on VAD support.There were 5 clinical domains assessed: nutrition, respiratory support, activity level, cardiovascular medications, and care environment. A scale was developed through expert consensus. Higher scores indicate greater morbidity as reflected by intensity of medical management. To evaluate feasibility and face validity, the TIS was applied retrospectively to a subset of pediatric inpatients with VADs. The Bland-Altman method was used to assess limits of agreement.The study comprised 39 patients with 42 implantations. Bland-Altman interobserver and intraobserver comparisons showed good agreement (mean differences in scores of 0.02, limits of agreement ±0.12). Trends in TIS were concordant with the overall clinical impression of improvement. Scores remained ≥0.6 preceding VAD implantation and peaked at 0.71 3 days after VAD implantation.We describe a pediatric VAD scoring tool, to assess global patient morbidity and clinical recovery. We demonstrate feasibility of using this TIS in a test population of inpatients on VAD support.

    View details for DOI 10.1016/j.healun.2014.10.007

    View details for PubMedID 25538014

  • Adrenergic receptor genotype influences heart failure severity and ß-blocker response in children with dilated cardiomyopathy. Pediatric research Reddy, S., Fung, A., Manlhiot, C., Selamet Tierney, E. S., Chung, W. K., Blume, E., Kaufman, B. D., Goldmuntz, E., Colan, S., Mital, S. 2015; 77 (2): 363-369

    Abstract

    Adrenergic receptor (ADR) genotypes are associated with heart failure (HF) and β-blocker response in adults. We assessed the influence of ADR genotypes in children with dilated cardiomyopathy (DCM).Ninety-one children with advanced DCM and 44 with stable DCM were genotyped for three ADR genotypes associated with HF risk in adults: α2cdel322-325, β1Arg389, and β2Arg16. Data were analyzed by genotype and β-blocker use. Mean age at enrollment was 8.5 y.One-year event-free survival was 51% in advanced and 80% in stable DCM. High-risk genotypes were associated with higher left ventricular (LV) filling pressures, higher systemic and pulmonary vascular resistance, greater decline in LV ejection fraction (P < 0.05), and a higher frequency of mechanical circulatory support while awaiting transplant (P = 0.05). While β-blockers did not reduce HF severity in the overall cohort, in the subset with multiple high-risk genotypes, those receiving β-blockers showed better preservation of cardiac function and hemodynamics compared with those not receiving β-blockers (interaction P < 0.05).Our study identifies genetic risk markers that may help in the identification of patients at risk for developing decompensated HF and who may benefit from early institution of β-blocker therapy before progression to decompensated HF.

    View details for DOI 10.1038/pr.2014.183

    View details for PubMedID 25406899

  • Procollagen type III amino-terminal propeptide: a serum biomarker of left ventricular remodelling in paediatric dilated cardiomyopathy CARDIOLOGY IN THE YOUNG Kaufman, B. D., Videon, N., Zhang, X., Harris, M. A., Shaddy, R. E., Goldmuntz, E. 2015; 25 (2): 228-236

    Abstract

    Procollagen type III amino-terminal propeptide is a collagen III cleavage product released in blood. The serum levels of this propeptide in adults with dilated cardiomyopathy are associated with cardiac remodelling and prognosis. The utility of procollagen type III amino-terminal propeptide as a biomarker in paediatric dilated cardiomyopathy is unknown.This was a prospective, longitudinal study of children with dilated cardiomyopathy and changes in procollagen type III amino-terminal propeptide. The serum level of propeptide was measured serially, compared with paediatric normal values, and correlated with clinical status and left ventricular size and function on echocardiograms and cardiac magnetic resonance imaging.Procollagen type III amino-terminal propeptide was measured serially in 149 samples from 39 patients, age 9.0±6.4 years, followed up for 16.8±16.3 months. Procollagen type III amino-terminal propeptide in dilated cardiomyopathy was higher than in normal children. On multivariate analyses, procollagen type III amino-terminal propeptide had a positive correlation with left ventricular dilation, left ventricular end-diastolic diameter index (p<0.0001), and left ventricular end-diastolic diameter Z-score (p=0.0003), and a negative correlation with shortening fraction changes over time (p=0.001). Patients with myocarditis (n=12) had higher procollagen type III amino-terminal propeptide values than those with idiopathic dilated cardiomyopathy (n=20).Procollagen type III amino-terminal propeptide increases with left ventricular dilation and decreases with improvement in systolic function in paediatric dilated cardiomyopathy, indicating a role as a biomarker of cardiac remodelling in children. The diagnostic utility of procollagen type III amino-terminal propeptide to differentiate myocarditis from idiopathic dilated cardiomyopathy warrants further investigation.

    View details for DOI 10.1017/S1047951113001820

    View details for Web of Science ID 000349387000005

    View details for PubMedID 24192074

  • Reliability of echocardiographic measurements of left ventricular systolic function in potential pediatric heart transplant donors. journal of heart and lung transplantation Chen, S., Selamet Tierney, E. S., Khush, K. K., Nguyen, J., Goldstein, B. A., May, L. J., Hollander, S. A., Kaufman, B. D., Rosenthal, D. N. 2015; 34 (1): 100-106

    Abstract

    Echocardiogram reports, but not images, are usually available for the evaluation of potential donor hearts. To assess the reliability of local reports of potential pediatric heart donors, we compared echocardiographic measurements of left ventricular (LV) systolic function between local hospitals and a central echocardiography laboratory.We identified all potential donors aged <18 years managed by the California Transplant Donor Network from 2009 to 2013. Echocardiograms and reports were obtained from local hospitals. All studies were reviewed in a central laboratory by an experienced pediatric cardiologist blinded to local reports. Local and central measurements of fractional shortening (FS) were compared using the Bland-Altman method (mean difference ± 2 standard deviations). LV function was categorized based on FS as normal or mild, moderately, or severely depressed.There were 70 studies from 59 donors with local and central measurements of FS. The mean difference between local and central FS was 3.9 ± 9.0. The limits of agreement ranged from -14.2 to 22. Twenty-five studies had discordant measurements of LV function, with 17 discordant by 1 category and 8 by 2 or more categories. Of 55 studies categorized as normal by local measurement, 6 were moderately to severely depressed by central review. Of 15 studies categorized as depressed by local measurement, 3 were normal by central review.Local and central measurements of LV systolic function were discordant in 36% of studies. Given such discordance, efforts to obtain and view actual echocardiographic images should be part of the standard evaluation of potential pediatric heart donors.

    View details for DOI 10.1016/j.healun.2014.08.019

    View details for PubMedID 25307622

  • Maintenance steroid use at 30 days post-transplant and outcomes of pediatric heart transplantation: A propensity matched analysis of the Pediatric Heart Transplant Study database. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Auerbach, S. R., Kukreja, M., Gilbert, D., Bastardi, H., Feingold, B., Knecht, K., Kaufman, B. D., Brown, R. N., Miyamoto, S. D. 2015; 34 (8): 1066-72

    Abstract

    Maintenance steroid (MS) use in pediatric heart transplantation is variable. The purpose of this study was to evaluate the impact of MS use on graft outcomes.All patients <18 years old in the Pediatric Heart Transplant Study database at the time of first heart transplant between 1993 and 2011 who survived ≥30 days post-transplant and were from centers with a protocolized approach to MS use were included (N = 2,178). Patients were grouped by MS use at 30 days post-transplant as MS+ or MS- (no MS use). Propensity score analysis was used to generate matched groups of MS+ and MS- patients based on pre-transplant and peri-transplant factors. Kaplan-Meier survival analysis was used to compare freedom from graft loss, graft loss secondary to rejection, rejection, rejection with severe hemodynamic compromise (RSHC), malignancy, and infection between groups.Of patients, 1,393 (64%) were MS+ and 785 (36%) were MS-. There were 315 MS- patients who had propensity matched MS+ controls. Kaplan-Meier estimates showed no difference in graft loss (p = 0.9) or graft loss secondary to rejection (p = 0.09). At 1 year post-transplant, there was no difference in freedom from rejection (p = 0.15) or malignancy (p = 0.07), but there was lower freedom from RSHC and infection in the MS- group (p = 0.05 and p = 0.02, respectively).MS use at 30 days post-transplant was not associated with enhanced graft survival after pediatric heart transplant. MS- patients had a higher incidence of RSHC and infection. These risks should be taken into consideration when determining MS use for pediatric recipients of heart transplants.

    View details for DOI 10.1016/j.healun.2015.03.003

    View details for PubMedID 25980572

  • The Use of Pediatric Ventricular Assist Devices in Children's Hospitals From 2000 to 2010: Morbidity, Mortality, and Hospital Charges. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Mansfield, R. T., Lin, K. Y., Zaoutis, T., Mott, A. R., Mohamad, Z., Luan, X., Kaufman, B. D., Ravishankar, C., Gaynor, J. W., Shaddy, R. E., Rossano, J. W. 2015; 16 (6): 522-8

    Abstract

    The use of ventricular assist devices has increased dramatically in adult heart failure patients. However, the overall use, outcome, comorbidities, and resource utilization of ventricular assist devices in pediatric patients have not been well described. We sought to demonstrate that the use of ventricular assist devices in pediatric patients has increased over time and that mortality has decreased.A retrospective study of the Pediatric Health Information System database was performed for patients 20 years old or younger undergoing ventricular assist device placement from 2000 to 2010.None.Four hundred seventy-five pediatric patients were implanted with ventricular assist devices during the study period: 69 in 2000-2003 (era 1), 135 in 2004-2006 (era 2), and 271 in 2007-2010 (era 3). Median age at ventricular assist device implantation was 6.0 years (interquartile range, 0.5-13.8), and the proportion of children who were 1-12 years old increased from 29% in era 1 to 47% in era 3 (p = 0.002). The majority of patients had a diagnosis of cardiomyopathy; this increased from 52% in era 1 to 72% in era 3 (p = 0.003). Comorbidities included arrhythmias (48%), pulmonary hypertension (16%), acute renal failure (34%), cerebrovascular disease (28%), and sepsis/systemic inflammatory response syndrome (34%). Two hundred forty-seven patients (52%) underwent heart transplantation and 327 (69%) survived to hospital discharge. Hospital mortality decreased from 42% in era 1 to 25% in era 3 (p = 0.004). Median hospital length of stay increased (37 d [interquartile range, 12-64 d] in era 1 vs 69 d [interquartile range, 35-130] in era 3; p < 0.001) and median adjusted hospital charges increased ($630,630 [interquartile range, $227,052-$853,318] in era 1 vs $1,577,983 [interquartile range, $874,463-$2,280,435] in era 3; p < 0.001). Factors associated with increased mortality include age less than 1 year (odds ratio, 2.04; 95% CI, 1.01-3.83), acute renal failure (odds ratio, 2.1; 95% CI, 1.26-3.65), cerebrovascular disease (odds ratio, 2.1; 95% CI, 1.25-3.62), and extracorporeal membrane oxygenation (odds ratio, 3.16; 95% CI, 1.79-5.60). Ventricular assist device placement in era 3 (odds ratio, 0.3; 95% CI, 0.15-0.57) and a diagnosis of cardiomyopathy (odds ratio, 0.5; 95% CI, 0.32-0.84), were associated with decreased mortality. Large-volume centers had lower mortality (odds ratio, 0.55; 95% CI, 0.34-0.88), lower use of extracorporeal membrane oxygenation, and higher charges.The use of ventricular assist devices and survival after ventricular assist device placement in pediatric patients have increased over time, with a concomitant increase in resource utilization. Age under 1 year, certain noncardiac morbidities, and the use of extracorporeal membrane oxygenation are associated with worse outcomes. Lower mortality was seen at larger volume ventricular assist device centers.

    View details for DOI 10.1097/PCC.0000000000000401

    View details for PubMedID 25850863

  • HLA desensitization with bortezomib in a highly sensitized pediatric patient PEDIATRIC TRANSPLANTATION May, L. J., Yeh, J., Maeda, K., Tyan, D. B., Chen, S., Kaufman, B. D., Bernstein, D., Rosenthal, D. N., Hollander, S. A. 2014; 18 (8): E280-E282

    View details for DOI 10.1111/petr.12347

    View details for Web of Science ID 000344360500006

  • Thrombotic events in critically ill children with myocarditis CARDIOLOGY IN THE YOUNG Lin, K. Y., Kerur, B., Witmer, C. M., Beslow, L. A., Licht, D. J., Ichord, R. N., Kaufman, B. D. 2014; 24 (5): 840-847

    Abstract

    Children with myocarditis have multiple risk factors for thrombotic events, yet the role of antithrombotic therapy is unclear in this population. We hypothesised that thrombotic events in critically ill children with myocarditis are common and that children with myocarditis are at higher risk for thrombotic events than children with non-inflammatory dilated cardiomyopathy.This is a retrospective chart review of all children presenting to a single centre cardiac intensive care unit with myocarditis from 1995 to 2008. A comparison group of children with dilated cardiomyopathy was also examined. Antithrombotic regimens were recorded. The primary outcome of thrombotic events included intracardiac clots and any thromboembolic events.Out of 45 cases with myocarditis, 40% were biopsy-proven, 24% viral polymerase chain reaction-supported, and 36% diagnosed based on high clinical suspicion. There were two (4.4%) thrombotic events in the myocarditis group and three (6.7%) in the dilated cardiomyopathy group (p = 1.0). Neither the use of any antiplatelet or anticoagulation therapy, use of intravenous immune globulin, presence of any arrhythmia, nor need for mechanical circulatory support were predictive of thrombotic events in the myocarditis, dilated cardiomyopathy, or combined groups.Thrombotic events in critically ill children with myocarditis and dilated cardiomyopathy occurred in 6% of the combined cohort. There was no difference in thrombotic events between inflammatory and non-inflammatory cardiomyopathy groups, suggesting that the decision to use antithrombotic prophylaxis should be based on factors other than the underlying aetiology of a child's acute decompensated heart failure.

    View details for DOI 10.1017/S1047951113001145

    View details for Web of Science ID 000346331200009

    View details for PubMedID 24016733

  • Hypoalbuminemia and poor growth predict worse outcomes in pediatric heart transplant recipients PEDIATRIC TRANSPLANTATION Castleberry, C., White-Williams, C., Naftel, D., Tresler, M. A., Pruitt, E., Miyamoto, S. D., Murphy, D., Spicer, R., Bannister, L., Schowengerdt, K., Gilmore, L., Kaufman, B., Zangwill, S. 2014; 18 (3): 280-287

    Abstract

    Children with end-stage cardiac failure are at risk of HA and PG. The effects of these factors on post-transplant outcome are not well defined. Using the PHTS database, albumin and growth data from pediatric heart transplant patients from 12/1999 to 12/2009 were analyzed for effect on mortality. Covariables were examined to determine whether HA and PG were risk factors for mortality at listing and transplant. HA patients had higher waitlist mortality (15.81% vs. 10.59%, p = 0.015) with an OR of 1.59 (95% CI 1.09-2.30). Survival was worse for patients with HA at listing and transplant (p ≤ 0.01 and p = 0.026). Infants and patients with congenital heart disease did worse if they were HA at time of transplant (p = 0.020 and p = 0.028). Growth was poor while waiting with PG as risk factor for mortality in multivariate analysis (p = 0.008). HA and PG are risk factors for mortality. Survival was worse in infants and patients with congenital heart disease. PG was a risk factor for mortality in multivariate analysis. These results suggest that an opportunity may exist to improve outcomes for these patients by employing strategies to mitigate these risk factors.

    View details for DOI 10.1111/petr.12239

    View details for Web of Science ID 000333807400015

    View details for PubMedID 24646199

  • Impact of congenital heart disease on outcomes of pediatric heart-lung transplantation PEDIATRIC TRANSPLANTATION Keeshan, B. C., Goldfarb, S. B., Lin, K. Y., Kreindler, J. L., Kaufman, B. D., Gaynor, J. W., Shaddy, R. E., Rossano, J. W. 2014; 18 (2): 204-210

    Abstract

    HLT is reserved for children with cardiopulmonary disease not amendable to alternative therapies. Children with CHD with or without ES may be considered for HLT. Outcomes of HLT in this population are not well described. To test the hypothesis that CHD without ES is associated with worse graft survival and identify factors associated with poor outcome, a retrospective analysis of the UNOS database was performed. One hundred and seventy-eight pediatric HLTs were performed between 1987 and 2011. CHD was the diagnosis in 65 patients, of which 34 had CHD without ES. Patients with CHD without ES had decreased patient survival (median 1.31 yr) compared with CHD with ES (4.80 yr, p = 0.05). On multivariable analysis, the following were associated with graft failure: CHD without ES (adjusted HR 1.69, 95% CI 1.09-2.62), younger age (1.04, 1.01-1.08), pretransplant mechanical ventilation (1.75, 1.01-3.06), pretransplant ECMO (3.07, 1.32-7.12), pretransplant PRAs (1.53, 1.06-2.20), and transplant era (1.85, 1.16-2.94). In children with CHD who require HLT, underlying physiology influences outcomes. Those without ES have a worse prognosis. The diagnosis of CHD without ES and preoperative factors may inform decisions in a complex patient population.

    View details for DOI 10.1111/petr.12208

    View details for Web of Science ID 000330740100019

    View details for PubMedID 24373099

  • Hot Topics in Tetralogy of Fallot JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Villafane, J., Feinstein, J. A., Jenkins, K. J., Vincent, R. N., Walsh, E. P., Dubin, A. M., Geva, T., Towbin, J. A., Cohen, M. S., Fraser, C., Dearani, J., Rosenthal, D., Kaufman, B., Graham, T. P. 2013; 62 (23): 2155-2166

    Abstract

    Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. We explore "hot topics" to highlight areas of emerging science for clinicians and scientists in moving toward a better understanding of the long-term management of patients with repaired TOF. From a genetic perspective, the etiology of TOF is multifactorial, with a familial recurrence risk of 3%. Cardiac magnetic resonance is the gold standard assessment tool based on its superior imaging of the right ventricular (RV) outflow tract, pulmonary arteries, aorta, and aortopulmonary collaterals, and on its ability to quantify biventricular size and function, pulmonary regurgitation (PR), and myocardial viability. Atrial re-entrant tachycardia will develop in more than 30% of patients, and high-grade ventricular arrhythmias will be seen in about 10% of patients. The overall incidence of sudden cardiac death is estimated at 0.2%/yr. Risk stratification, even with electrophysiologic testing and cardiac magnetic resonance, remains imperfect. Drug therapy has largely been abandoned, and defibrillator placement, despite its high risks for complications and inappropriate discharges, is often recommended for patients at higher risk. Definitive information about optimal surgical strategies for primary repair to preserve RV function, reduce arrhythmia, and optimize functional status is lacking. Post-operative lesions are often amenable to transcatheter intervention. In selected cases, PR may be treated with transcatheter valve insertion. Ongoing surveillance of RV function is a crucial component of clinical assessment. Except for resynchronization with biventricular pacing, no medical therapies have been shown to be effective after RV dysfunction occurs. In patients with significant PR with RV dilation, optimal timing of pulmonary valve replacement remains uncertain, although accepted criteria are emerging.

    View details for DOI 10.1016/j.jacc.2013.07.100

    View details for Web of Science ID 000328073000002

  • Pediatric heart transplantation from donors with depressed ventricular function: an analysis of the United Network of Organ Sharing Database. Circulation. Heart failure Rossano, J. W., Lin, K. Y., Paridon, S. M., Zhang, X., Gaynor, J. W., Kaufman, B. D., Shaddy, R. E. 2013; 6 (6): 1223-1229

    Abstract

    Wait-list mortality for children awaiting heart transplantation remains high. Potential donor hearts with depressed ventricular function are often declined. We aimed to test the hypothesis that pediatric heart transplant recipients of grafts with depressed ventricular function would have comparable survival with those with normal function.A retrospective study was performed for pediatric heart transplants from the United Network of Organ Sharing Database from October 26, 1999, to June 30, 2011. Patients were grouped based on accepted donor left ventricular ejection fraction (LVEF): normal function (LVEF ≥55%), mildly depressed function (LVEF 45%-54%), or moderately-to-severely depressed function (LVEF <45%). During the study period, there were 3672 pediatric heart transplants; 3306 (90%) had a LVEF reported. Ventricular function was mildly depressed in 245 (7%) and moderately-to-severely depressed in 172 (5%). Patients receiving grafts with moderately-to-severely depressed function were more likely to be younger and weigh less (P<0.001 for both) than those receiving grafts with normal function. Median graft survival from accepted donors with normal ventricular function (10.6 years) was similar to survival from accepted donors with mildly depressed ventricular function (9.7 years; P=0.24) and from accepted donors with moderately-to-severely depressed ventricular function (9.1 years; P=0.13). On propensity-matched analysis, donor ventricular function was not associated with graft survival.The use of donors with depressed ventricular function is uncommon in pediatric heart transplantation (<15% of all transplants), yet graft survival does not differ significantly from accepted donors with normal ventricular function. Hearts from donors with depressed ventricular function may be considered in selected patients.

    View details for DOI 10.1161/CIRCHEARTFAILURE.112.000029

    View details for PubMedID 23985431

  • Adult and pediatric perspectives on heart retransplant. World journal for pediatric & congenital heart surgery Kaufman, B. D., Jessup, M. 2013; 4 (1): 75-79

    Abstract

    At the Ethics of the Heart II: Ethical and Policy Challenges in Congenital Heart Disease Conference, March 16-17, 2012 in Philadelphia, Pennsylvania, one of the sessions focused on the issues related to end-stage heart failure in patients with congenital heart disease including utilizing the therapy of heart transplantation. This article will summarize the session related to repeat heart transplant that was based on discussion of actual patient cases, two adults and one pediatric, presented, respectively, by an adult and a pediatric heart transplant specialist. Outcome data related to retransplant for both adult and pediatric heart transplant populations are reviewed. The complicated ethical issues related to considerations of beneficence versus nonmalfeasance by a medical care team for an individual patient, patient autonomy related to adherence, and obligations to society to fairly allocate the scarce precious resource of donor organs are discussed.

    View details for DOI 10.1177/2150135112469972

    View details for PubMedID 23799759

  • Ethical considerations related to the use of mechanical support in congenital heart disease. World journal for pediatric & congenital heart surgery Rossano, J. W., Kaufman, B. D., Rame, J. E. 2013; 4 (1): 70-74

    Abstract

    Heart failure frequently complicates congenital heart disease (CHD) in children and adults. In patients with end-stage disease, mechanical circulatory support may improve survival, quality of life, and serve as bridge to cardiac transplantation. There are many ethical issues surrounding the use of mechanical circulatory support in patients with CHD including the use of prospective and randomized trials, proper oversight of new therapies, and transparency in reporting. Additionally, there are ethical considerations relevant to the greater society as these therapies are highly resource intensive in a resource-limited society. This article will review the burden of disease of heart failure in patients with CHD, the challenges of mechanical circulatory support and heart transplantation, and the ethical considerations and problems that arise for this population.

    View details for DOI 10.1177/2150135112469040

    View details for PubMedID 23799758

  • Why should we care about ethical and policy challenges in congenital heart disease? World journal for pediatric & congenital heart surgery Kirkpatrick, J. N., Kaufman, B. 2013; 4 (1): 7-9

    Abstract

    Congenital heart disease (CHD) affects 1% of infants worldwide, and approximately 90% of children with serious CHD who have access to surgery survive to adulthood. Particularly as this population ages, there are unique ethical and policy challenges pertaining to this diverse population of children and adults, which also serve as a paradigm for other chronic diseases. A unique forum to discuss these issues occurred at the University of Pennsylvania in Philadelphia on March 16 to 17, 2012, and was entitled "Ethics of the Heart: Ethical and Policy Challenges in Adult and Pediatric Congenital Heart Disease." The conference convened a multidisciplinary panel of nationally known experts in the fields of Pediatric Congenital Heart Disease, Adult Congenital Heart Disease, and Bioethics to identify and discuss the most important ethical issues in CHD through talks, panel discussions, and one-on-one interviews in six topic areas: genetic testing, transitions of care from pediatric to adult CHD, transplantation and mechanical circulatory support, research and development in CHD, the social and personal costs of success in treating CHD, and end-of-life considerations. This article is an introduction to the topics discussed.

    View details for DOI 10.1177/2150135112454666

    View details for PubMedID 23799747

  • Ethics Priorities in Adult Congenital Heart Disease PROGRESS IN CARDIOVASCULAR DISEASES Kirkpatrick, J. N., Kim, Y. Y., Kaufman, B. D. 2012; 55 (3): 266-273

    Abstract

    The success of modern therapies in congenital heart disease has produced a large and growing population of adults with congenital heart disease as a chronic condition. Such success increasingly raises a host of ethical issues, from resource utilization to end of life decision-making. The importance of a multidisciplinary approach to the care of adult congenital heart disease (ACHD) patients has been emphasized for some time, but addressing the challenges in this population requires a broad range of ethical expertise as well. This paper is based on a conference entitled "Ethical and Policy Challenges in Pediatric and Adult Congenital Heart Disease" held in March of 2012. Herein, we present a compilation of the ethics priorities in ACHD discussed at the conference, including ethical aspects of clinical care, ethics research and policy development in the areas of providing clinical care for challenging ACHD patients, improving transitions from pediatric to adult healthcare systems, advance care planning, and addressing costs.

    View details for DOI 10.1016/j.pcad.2012.10.004

    View details for Web of Science ID 000312433100005

    View details for PubMedID 23217430

  • Incidence of and Risk Factors for Sudden Cardiac Death in Children With Dilated Cardiomyopathy A Report From the Pediatric Cardiomyopathy Registry JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Pahl, E., Sleeper, L. A., Canter, C. E., Hsu, D. T., Lu, M., Webber, S. A., Colan, S. D., Kantor, P. F., Everitt, M. D., Towbin, J. A., Jefferies, J. L., Kaufman, B. D., Wilkinson, J. D., Lipshultz, S. E. 2012; 59 (6): 607-615

    Abstract

    The purpose of this study was to establish the incidence of and risk factors for sudden cardiac death (SCD) in pediatric dilated cardiomyopathy (DCM).The incidence of SCD in children with DCM is unknown. The ability to predict patients at high risk of SCD will help to define who may benefit most from implantable cardioverter-defibrillators.The cohort was 1,803 children in the PCMR (Pediatric Cardiomyopathy Registry) with a diagnosis of DCM from 1990 to 2009. Cumulative incidence competing-risks event rates were estimated. We achieved risk stratification using Classification and Regression Tree methodology.The 5-year incidence rates were 29% for heart transplantation, 12.1% non-SCD, 4.0% death from unknown cause, and 2.4% for SCD. Of 280 deaths, 35 were SCD, and the cause was unknown for 56. The 5-year incidence rate for SCD incorporating a subset of the unknown deaths is 3%. Patients receiving antiarrhythmic medication were at higher risk of SCD (hazard ratio: 3.0, 95% confidence interval: 1.1 to 8.3, p = 0.025). A risk stratification model based on most recent echocardiographic values had 86% sensitivity and 57% specificity. Thirty of 35 SCDs occurred in patients who met all these criteria: left ventricular (LV) end-systolic dimension z-score >2.6, age at diagnosis younger than 14.3 years, and the LV posterior wall thickness to end-diastolic dimension ratio <0.14. Sex, ethnicity, cause of DCM, and family history were not associated with SCD.The 5-year incidence rate of SCD in children with DCM is 3%. A risk stratification rule (86% sensitivity) included age at diagnosis younger than 14.3 years, LV dilation, and LV posterior wall thinning. Patients who consistently meet these criteria should be considered for implantable cardioverter-defibrillator placement.

    View details for DOI 10.1016/j.jacc.2011.10.878

    View details for Web of Science ID 000300196500009

    View details for PubMedID 22300696

  • Unusual cardiac "masses" in a newborn with infantile pompe disease. JIMD reports Swarr, D. T., Kaufman, B., Fogel, M. A., Finkel, R., Ganesh, J. 2012; 5: 17-20

    Abstract

    Glycogen storage disease type II (OMIM #232300), or Pompe disease, may present in the newborn period with moderate-to-severe biventricular hypertrophy with or without left ventricular outflow tract obstruction that typically leads to death from cardiorespiratory failure in the first year of life. Glycogen deposition tends to be uniform, and is only occasionally accompanied by patchy areas of fibrosis. Here, we present an infant identified with biventricular hypertrophy and cardiac masses by prenatal ultrasound. Postnatal molecular studies did not support the diagnosis of tuberous sclerosis in this case. Additional evaluation for infantile hypertrophic cardiomyopathy confirmed the diagnosis of Pompe disease. We discuss whether the "cardiac masses," which brought this infant to medical attention and facilitated an early diagnosis of Pompe disease, may represent an unusual manifestation of GSD type II or the coincidental occurrence of an unrelated disease process.

    View details for DOI 10.1007/8904_2011_85

    View details for PubMedID 23430912

  • Troponin I levels from donors accepted for pediatric heart transplantation do not predict recipient graft survival JOURNAL OF HEART AND LUNG TRANSPLANTATION Lin, K. Y., Sullivan, P., Salam, A., Kaufman, B., Paridon, S., Hanna, B. D., Spray, T. L., Weber, J., Shaddy, R. 2011; 30 (8): 920-927

    Abstract

    Troponin I is often obtained during the evaluation of a potential transplant donor heart. It is not clear whether elevations in donor troponin I levels predict adverse outcomes and should thus preclude acceptance of a donor heart. This study examined whether troponin I levels from donors accepted for pediatric heart transplantation predicted graft failure.Deidentified data on heart transplants performed in recipients aged < 21 years between April 2007 and April 2009 was provided by the Organ Procurement and Transplantation Network. Donor troponin I level and recipient outcomes, including survival without retransplantation (graft survival), were examined for statistical correlation.Overall graft survival in 839 heart transplants was 81% at 2 years. At least 1 troponin I level was recorded in 657 donors before transplant, with a median value of 0.1 ng/ml (range, 0-50 ng/ml). Troponin I level and graft status were not correlated (p = 0.74). A receiver operating characteristic curve showed no association between troponin I and graft status (area under the curve, 0.51; p = 0.98). Graft survival did not differ significantly (p = 0.60) among quartiles of troponin I levels (<0.04, 0.04-<0.1, 0.1-<0.35, ≥ 0.35 ng/ml). A troponin I level ≥ 1 ng/ml was found in 74 transplanted donor hearts; graft survival was not associated with troponin I ≥ 1 (80%) vs < 1 (80%) at 2 years (p = 0.93). Troponin I values were not associated with post-transplant hospital length of stay (r = -0.06; p = 0.10).In donor hearts accepted for pediatric heart transplantation, troponin I elevation before procurement is not associated with increased graft failure. The significance of elevated troponin I levels, which occurs in many heart donors, remains unclear and should therefore be considered in the context of other clinical information.

    View details for DOI 10.1016/j.healun.2011.02.011

    View details for Web of Science ID 000293038800010

    View details for PubMedID 21489812

  • Invasive fungal infections in pediatric heart transplant recipients: Incidence, risk factors, and outcomes PEDIATRIC TRANSPLANTATION Zaoutis, T. E., Webber, S., Naftel, D. C., Chrisant, M. A., Kaufman, B., Pearce, F. B., Spicer, R., Dipchand, A. I. 2011; 15 (5): 465-469

    Abstract

    There are limited data on the incidence or risk factors for IFI in pediatric heart transplant recipients. The purpose of this study was to describe the incidence and types of IFI, to determine risk factors for outcomes of IFI, and to assist in decision-making concerning the need for prophylactic strategies in pediatric heart transplant recipients. Data from a multi-institutional registry of 1854 patients transplanted between 01/93 and 12/04 were analyzed to determine risk factors and outcomes of children with IFI post-heart transplantation. One hundred and thirty-nine episodes of IFI occurred in 123 patients and made up 6.8% of the total number of post-transplant infections. IFI was most commonly attributed to yeast (66.2%), followed by mold (15.8%) and Pneumocystis jiroveci (13%). Ninety percent of the yeast infections were caused by Candida spp., and Aspergillus spp. was causative in 82% of the mold infections. There was a significantly increased risk of fungal infection associated with pretransplant invasive procedures (e.g., ECMO, prior surgery, VAD, mechanical ventilation) with an incremental risk with increasing numbers of invasive procedures (early phase 0 vs. 1, RR 1.3; 0 vs. 3, RR 2.3; p<0.001). In multivariate analysis, previous surgery (p=0.05) and mechanical support at transplantation (p=0.01) remained significant. Forty-nine percent of recipients with IFI died, all within six months post-transplant. Invasive fungal infections are uncommon in pediatric heart transplant recipients. Risk and mortality are highest in the first six months post-transplant especially in patients with previous surgery and those requiring mechanical support. Prophylactic strategies for high-risk patients should be considered and warrants further study.

    View details for DOI 10.1111/j.1399-3046.2010.01415.x

    View details for Web of Science ID 000292908600010

    View details for PubMedID 21108712

  • Immunologic considerations in heart transplantation for congenital heart disease. Current cardiology reviews Kaufman, B. D., Shaddy, R. E. 2011; 7 (2): 67-71

    Abstract

    Children and adults with congenital heart disease (CHD) can require interventions that result in immunologic alterations that are different than those seen in patients with cardiomyopathies. Patients with CHD can be exposed to heart surgeries, blood products, valved and non-valved allograft tissue, and mechanical circulatory support, all of which can alter the immunologic status of these patients. This change in immunologic status is most commonly manifested as the development of anti-human leukocyte antigen (HLA) antibodies. This review will delineate a) the causes of anti-HLA anti-body production (often referred to as allosensitization); b) preventive strategies for anti-HLA antibody production before transplantation; c) treatment strategies for those patients who develop anti-HLA antibodies before transplantation; d) consequences of HLA allosensitization after transplantation; and e) treatment of HLA allosensitization and antibody-mediated rejection after transplantation.

    View details for DOI 10.2174/157340311797484204

    View details for PubMedID 22548029

  • Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA) AMERICAN HEART JOURNAL Lagedrost, S. J., Sutton, M. S., Cohen, M. S., Satou, G. M., Kaufman, B. D., Perlman, S. L., Rummey, C., Meier, T., Lynch, D. R. 2011; 161 (3): 639-?

    Abstract

    Friedreich ataxia (FRDA) is commonly associated with hypertrophic cardiomyopathy, but little is known about its frequency, severity, or treatment. In this 6-month randomized, double-blind, controlled study, we sought to determine whether idebenone improves cardiac measures in FRDA.Seventy pediatric subjects were treated either with idebenone (450/900 mg/d or 1,350/2,250 mg/d) or with placebo. Electrocardiograms (ECGs) were assessed at each visit, and echocardiograms, at baseline and week 24.We found ECG abnormalities in 90% of the subjects. On echocardiogram, 81.4% of the total cohort had left ventricular (LV) hypertrophy, as measured by increased LV mass index-Dubois, and the mean ejection fraction (EF) was 56.9%. In linear regression models, longer PR intervals at baseline were marginally associated with longer GAA repeat length (P = .011). Similarly, GAA repeat length did not clearly predict baseline EF (P = .086) and LV mass by M-mode (P = .045). Left ventricular mass index, posterior wall thickness, EF, and ECG parameters were not significantly improved by treatment with idebenone. Some changes in echocardiographic parameters during the treatment phase correlated with baseline status but not with treatment group.Idebenone did not decrease LV hypertrophy or improve cardiac function in subjects with FRDA. The present study does not provide evidence of benefit in this cohort over a 6-month treatment period.

    View details for DOI 10.1016/j.ahj.2010.10.038

    View details for Web of Science ID 000288156400032

    View details for PubMedID 21392622

  • Brain-type natriuretic peptide correlates with right heart pressures in a cross section of pediatric heart transplant patients PEDIATRIC TRANSPLANTATION Hall, E. K., Glatz, A. C., Quartermain, M. D., Ravishankar, C., Kaufman, B., Cohen, M. S., Hanna, B. D., Goldberg, D. J. 2011; 15 (1): 70-74

    Abstract

    Serum brain-type natriuretic peptide level (BNP) correlates with hemodynamic parameters measured during cardiac catheterization in adult patients with heart failure. We sought to describe the relationship of BNP with invasive hemodynamic measurements and cellular rejection in children following OHT. Children undergoing catheterization for OHT surveillance had simultaneous measurement of BNP. A total of 62 subjects were studied. The median BNP was 171 pg/mL (range 19-1130). There were significant positive correlations between BNP and mean PAP (R=0.33, p=0.009), RVSP (R=0.25, p=0.05), RVEDP (R=0.29, p=0.02), and mean RAP (R=0.39, p=0.002). Rejection grade varied from 0 to 3A (58 patients < ISHLT 3A and four patients ≥ ISHLT 3A). There was no significant difference in BNP based on cellular rejection grade. In a cohort of pediatric patients after heart transplantation, BNP correlates with direct measurements of right-sided pressures, but not with other hemodynamic measurements, time from transplant or rejection grade. This suggests that BNP may have a complimentary role in the monitoring of children following heart transplantation.

    View details for DOI 10.1111/j.1399-3046.2010.01421.x

    View details for Web of Science ID 000286329400018

    View details for PubMedID 21199206

  • Ventricular assist device-associated anti-human leukocyte antigen antibody sensitization in pediatric patients bridged to heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION O'Connor, M. J., Menteer, J., Chrisant, M. R., Monos, D., Lind, C., Levine, S., Gaynor, J. W., Hanna, B. D., Paridon, S. M., Ravishankar, C., Kaufman, B. D. 2010; 29 (1): 109-116

    Abstract

    Ventricular assist devices (VAD) are associated with the formation of antibodies to anti-human leukocyte antigens (HLA) or sensitization. The incidence and effects of VAD-associated anti-HLA sensitization have not been well studied in the pediatric population.A retrospective review of all patients undergoing VAD implant at our institution from 1998 to 2008 was performed. Panel reactive antibody (PRA) results before VAD implant, after VAD implant, and after orthotopic heart transplantation (OHT) were recorded. Patients who became sensitized (PRA for class I and/or II immunoglobulin G antibodies >or= 10%) on VAD support were compared with non-sensitized patients with regard to demographics, diagnosis, device type, and blood product exposure on VAD support. Outcomes after OHT were also compared between groups.VAD support was initiated in 20 patients (median age, 14.4 years), with 75% survival to OHT or recovery. PRA data before and after VAD implant were available for 17 patients. VAD-associated sensitization developed in 35% of recipients. There were no differences between those sensitized in association with VAD support and non-sensitized patients with regard to age, gender, diagnosis, device type, extracorporeal membrane oxygenation use, or blood product exposure on VAD support. Black race predicted sensitization on VAD (p = 0.02). There were no differences in survival or rejection between groups.VAD therapy was associated with the development of anti-HLA sensitization in 35% of recipients. Black race predicted sensitization, but there were no differences in overall survival or outcomes after OHT.

    View details for DOI 10.1016/j.healun.2009.08.028

    View details for Web of Science ID 000273795500019

    View details for PubMedID 20123248

  • Outcomes of Children With Cardiomyopathy Listed for Transplant: A Multi-institutional Study JOURNAL OF HEART AND LUNG TRANSPLANTATION Dipchand, A. I., Naftel, D. C., Feingold, B., Spicer, R., Yung, D., Kaufman, B., Kirklin, J. K., Atlain-Rooney, T., Hsu, D. 2009; 28 (12): 1312-1321

    Abstract

    Dilated (DCM), restrictive (RCM), and hypertrophic (HCM) cardiomyopathies (CM) in children have varying clinical courses and therapeutic options. Heart transplantation (HTx) offers a chance for long-term survival; but outcomes after listing have not been well defined.A multi-institutional registry of 3,147 patients listed for HTx (January 1993-December 2006) was used to compare outcomes of 1,320 children with CM (42%) and 1,827 with non-CM (58%) etiologies. Comparisons were made between sub-groups: 1,098 DCM (83%), 145 RCM (11%), and 77 HCM (6%).CM patients had a waitlist mortality of 17% vs 32% for non-CM patients (p < 0.0001), with no difference between the CM sub-groups. Risk factors were younger age, black race (relative risk [RR], 1.65; p = 0.009), mechanical ventilation (RR, 3.17; p < 0.001), and extracorporeal membrane oxygenation (RR, 2.16; p < 0.001). Ten-year survival after listing was 66% for CM vs 53% for non-CM (p < 0.0001). HCM and RCM patients aged < 1 year at the time of listing had the highest waitlist mortality and the lowest overall survival. CM patients had a better 10-year survival after HTx (68% vs 61%, p < 0.0001). Risk factors for death early after HTx included mechanical ventilation at HTx (RR, 3.07; p < 0.001), longer ischemic time (RR, 1.27; p = 0.01), and earlier era (RR, 1.77; p = 0.002). Late risk factors included black race (RR, 3.01; p < 0.001), HCM or RCM (RR, 1.93; p = 0.007), and older age (RR, 1.9; p < 0.001).Children with CM have a lower waitlist mortality and better survival post-HTx than children with a non-CM diagnosis. DCM patients have the best and HCM or RCM patients aged younger than 1 year have the worst overall outcomes.

    View details for DOI 10.1016/j.healun.2009.05.019

    View details for Web of Science ID 000272943500014

    View details for PubMedID 19782592

  • Wasting or Obesity at Time of Transplant Does Not Predict Pediatric Heart Transplant Outcomes: Analysis of ISHLT Pediatric Heart Transplant Registry JOURNAL OF HEART AND LUNG TRANSPLANTATION Kaufman, B. D., Chuai, S., Dobbels, F., Shaddy, R. E. 2009; 28 (12): 1273-1278

    Abstract

    Body mass index (BMI) both before and after heart transplant (HT) is used to risk stratify in adult HT. Single-center studies identify BMI as a potential predictor of outcome after HT in children; large-scale analyses in pediatric HT have not been performed.The ISHLT pediatric heart transplant registry was queried for HT recipients >2 years old between 1996 and 2006 with data for BMI percentile (BMI%ile) at HT. Survival and morbidity rates post-HT were compared between BMI%ile cohorts defined as: wasted, <5th BMI%ile; normal, 5th to 95th BMI%ile; and obese, >95th BMI%ile at HT.Data from 2,333 pediatric HT patients were available for analysis. Incidence of abnormal BMI%ile at HT was: wasted = 23% and obese = 8%. Wasting and obesity were similar in patients with congenital or cardiomyopathic diagnoses. Wasted or obese patients at HT did not differ from patients with normal BMI in survival on Kaplan-Meier or multivariate analyses. There were no significant differences in pre-, peri- or post-operative adverse events between patients with wasting or obesity and those with normal BMI%ile at HT.In contrast to adults, abnormal body mass at time of transplant was not associated with decreased survival in pediatric HT recipients. Potential pediatric transplant candidates should not be excluded based on the perception that wasting or obesity will increase the risk of adverse outcomes.

    View details for DOI 10.1016/j.healun.2009.07.020

    View details for Web of Science ID 000272943500008

    View details for PubMedID 19783177

  • Assessment and management of the failing heart in children CARDIOLOGY IN THE YOUNG Kaufman, B. D., Shaddy, R. E., Shirali, G. S., Tanel, R., Towbin, J. A. 2008; 18: 63-71

    View details for Web of Science ID 000266381000008

    View details for PubMedID 19094380

  • Genomic Profiling of Left and Right Ventricular Hypertrophy in Congenital Heart Disease JOURNAL OF CARDIAC FAILURE Kaufman, B. D., Desai, M., Reddy, S., Osorio, J. C., Chen, J. M., Mosca, R. S., Ferrante, A. W., Mital, S. 2008; 14 (9): 760-767

    Abstract

    The right ventricle (RV) has a lower ability than the left ventricle (LV) to adapt to systemic load. The molecular basis of these differences is not known. We compared hypertrophy-signaling pathways between the RV and the LV in patients with congenital heart disease (CHD).Gene expression was measured using DNA microarrays in myocardium from children with CHD with LV or RV obstructive lesions undergoing surgery. The expression of 175 hypertrophy-signaling genes was compared between the LV (n=7) and the RV (n=11). Hierarchic clustering was performed.Seventeen genes (10%) were differentially expressed between the LV and the RV. Expression of genes for angiotensin, adrenergic, G-proteins, cytoskeletal, and contractile components was lower (P < .05) and expression of maladaptive factors (fibroblast growth factors, transforming growth factor-beta, caspases, ubiquitin) was higher in the RV compared with the LV (P < .05). Five of 7 LV samples clustered together. Only 4 of 11 RV samples clustered with the LV. Genes critical to adaptive remodeling correlated with the degree of LV hypertrophy but not RV hypertrophy.The transcription of pathways of adaptive remodeling was lower in the RV compared with the LV. This may explain the lower ability of the RV to adapt to hemodynamic load in CHD.

    View details for DOI 10.1016/j.cardfail.2008.06.002

    View details for Web of Science ID 000261269800008

    View details for PubMedID 18995181

  • Too fat or too thin? Body habitus assessment in children listed for heart transplant and impact on outcome JOURNAL OF HEART AND LUNG TRANSPLANTATION Kaufman, B. D., Nagle, M. L., Levine, S. R., Vijaynathan, N., Hanna, B. D., Paridon, S., Ravishankar, C., Chrisant, M. K. 2008; 27 (5): 508-513

    Abstract

    Body habitus assessment (BHA), be it wasted or obese, is a useful marker of nutritional status and overall medical condition. Wasting and obesity pre-heart transplant adversely affects outcomes in adults. The utility of BHA as a prognostic factor in children post-transplant is unknown.Weight and height at listing and standard growth charts were used to determine the ideal body weight (%IBW) and percentiles for body mass index for age (BMI%) and weight-for-length (W:L%). Wasting was defined as <90%IBW and/or 120%IBW and/or >or=95th percentile BMI% or W:L%. Outcomes of cohorts based on these criteria were compared.From June 1990 to December 2006, 180 children, aged 5.81 +/- 6 years, were listed for transplant. Wasting occurred in 66 (37%) and obesity in 22 (12%) children, without differences between diagnoses of cardiomyopathy or congenital heart disease. %IBW was a prognostic factor for survival post-transplant on multivariate analysis: obese patients had a hazard ratio (HR) of 3.82 (95% confidence interval [CI] 1.81 to 8.06) compared with normal BHA (p < 0.001). Wasting had a survival advantage compared with normal BHA (HR 0.51, 95% CI 0.27 to 0.94, p = 0.032). There were no significant differences between cohorts in incidence of infections, first-year rejections or graft vasculopathy.Abnormal BHA at listing was a prognostic factor for survival post-transplant. Obese children had increased mortality, but wasting did not adversely affect post-transplant survival in our population. Body habitus assessment may risk-stratify children at listing, potentially providing a complex target for intervention.

    View details for DOI 10.1016/j.healun.2008.01.026

    View details for Web of Science ID 000255556900007

    View details for PubMedID 18442716

  • RAAS gene polymorphisms influence progression of pediatric hypertrophic cardiomyopathy HUMAN GENETICS Kaufman, B. D., Auerbach, S., Reddy, S., Manlhiot, C., Deng, L., Prakash, A., Printz, B. F., Gruber, D., Papavassiliou, D. P., Hsu, D. T., Sehnert, A. J., Chung, W. K., Mital, S. 2007; 122 (5): 515-523

    Abstract

    Hypertrophic Cardiomyopathy (HCM) is a disease with variable rate of progression. Young age is an independent risk factor for poor outcome in HCM. The influence of renin-angiotensin-aldosterone (RAAS) genotype on the progression of HCM in children is unknown. Children with HCM (n = 65) were enrolled prospectively across two centers (2001-2005). All subjects were genotyped for five RAAS gene polymorphisms previously associated with LV hypertrophy (pro-LVH): AGT M235T, ACE DD, CMA-1903 A/G, AGTR1 1666 A/C and CYP11B2-344 C/T. Linear regression models, based on maximum likelihood estimates, were created to assess the independent effect of RAAS genotype on LV hypertrophy (LVH). Forty-six subjects were homozygous for <2 and 19 were homozygous for > or =2 pro-LVH RAAS polymorphisms. Mean age at presentation was 9.6 +/- 6 years. Forty children had follow-up echocardiograms after a median of 1.5 years. Indexed LV mass (LVMI) and LV mass z-scores were higher at presentation and follow-up in subjects with > or =2 pro-LVH genotypes compared to those with <2 (P < 0.05). Subjects with > or =2 pro-LVH genotypes also demonstrated a greater increase in septal thickness (IVST) and in LV outflow tract (LVOT) obstruction on follow-up (P < 0.05). On multivariate analysis, a higher number of pro-LVH genotypes was associated with a larger effect size (P < 0.05). Pro-LVH RAAS gene polymorphisms are associated with progressive septal hypertrophy and LVOT obstruction in children with HCM. Identification of RAAS modifier genes may help to risk-stratify patients with HCM.

    View details for DOI 10.1007/s00439-007-0429-9

    View details for Web of Science ID 000251143900011

    View details for PubMedID 17851694

  • Failure of right ventricular adaptation in children with tetralogy of Fallot CIRCULATION Reddy, S., Osorio, J. C., Duque, A. M., Kaufman, B. D., Phillips, A. B., Chen, J. M., Quaegebeur, J., Mosca, R. S., Mital, S. 2006; 114: I37-I42

    Abstract

    The left ventricle (LV) adapts to chronic hypoxia by expressing protective angiogenic, metabolic, and antioxidant genes to improve O2 delivery and energy production, and to minimize reoxygenation injury. The ability of the right ventricle (RV) to adapt to hypoxia in children with tetralogy of Fallot (TOF) is unknown.Gene expression using real-time polymerase chain reaction was measured in RV myocardium obtained during surgical repair of TOF from 23 patients: 13 cyanotic and 10 acyanotic. Results were compared between the 2 groups and correlated with age at surgery, severity of cyanosis, and early postoperative course. The cyanotic patients were younger at surgery compared with acyanotic (5+/-3 versus 9+/-4 months; P=0.01), had higher hematocrit (43+/-4 versus 38+/-3 grams/dL; P=0.004), and lower O2 saturations (84+/-4% versus 98+/-2%; (P<0.001). Cyanotic patients had a significantly lower expression of vascular endothelial growth factor (VEGF), glycolytic enzymes, and glutathione peroxidase (GPX) (P<0.05), and a higher expression of collagen (P<0.01) compared with acyanotic patients. Gene expression correlated inversely with severity of cyanosis ie, preoperative hematocrit (P<0.01) and positively with preoperative saturation (P<0.05). The relationship between gene expression and cyanosis was independent of age at surgery. Ca2+ handling genes did not correlate with the severity of hypoxia. Lower angiogenic, glycolytic, and antioxidant gene expression correlated with increasing postoperative lactate (P<0.05).The RV fails to up regulate adaptive pathways in response to increasing hypoxia in children with TOF. The implications of an early maladaptive response of the RV on long-term RV function require further investigation.

    View details for DOI 10.1161/CIRCULATIONAHA.105.001248

    View details for Web of Science ID 000238688200008

    View details for PubMedID 16820602

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