Clinical Focus


  • Pediatric Cardiology
  • Heart Failure
  • Ventricular Assist Device
  • Anticoagulation
  • Heart transplantation

Academic Appointments


Professional Education


  • Board Certification: Pediatric Cardiology, American Board of Pediatrics (2014)
  • Board Certification: Pediatrics, American Board of Pediatrics (2002)
  • Fellowship:Boston Children's Hospital (2005)
  • Fellowship:Boston Children's Hospital (2006)
  • Residency:Boston Children's Hospital (Combined Residency in Pediatrics) (2002)
  • Internship:Boston Children's Hospital (Combined Residency in Pediatrics) (2000)

2017-18 Courses


All Publications


  • The Evolution of a Pediatric Ventricular Assist Device Program: The Boston Children's Hospital Experience. Pediatric cardiology Hawkins, B., Fynn-Thompson, F., Daly, K. P., Corf, M., Blume, E., Connor, J., Porter, C., Almond, C., Vanderpluym, C. 2017; 38 (5): 1032-1041

    Abstract

    Mechanical circulatory support in the form of ventricular assist devices (VADs) in children has undergone rapid growth in the last decade. With expansion of device options available for larger children and adolescents, the field of outpatient VAD support has flourished, with many programs unprepared for the clinical, programmatic, and administrative responsibilities. From preimplantation VAD evaluation and patient education to postimplant VAD management, the VAD program, staffed with an interdisciplinary team, is essential to providing safe, effective, and sustainable care for a new technology in an exceedingly complex patient population. Herein, this paper describes the Boston Children's Hospital VAD experience over a decade and important lessons learned from developing a pediatric program focusing on a high-risk but low-volume population. We highlight the paramount role of the VAD coordinator, clinical infrastructure requirements, as well as innovation in care spanning inpatient and outpatient VAD supports at Boston Children's Hospital.

    View details for DOI 10.1007/s00246-017-1615-8

    View details for PubMedID 28456829

  • Safety and Efficacy of Warfarin Therapy in Kawasaki Disease. journal of pediatrics Baker, A. L., Vanderpluym, C., Gauvreau, K. A., Fulton, D. R., de Ferranti, S. D., Friedman, K. G., Murray, J. M., Brown, L. D., Almond, C. S., Evans-Langhorst, M., Newburger, J. W. 2017

    Abstract

    To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications.We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and <6; and INRs <1.5.In 9 patients (5 male), median age 14.4 years (range 7.1-22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 <6 in 7 patients (12 events); and INR <1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient-years (95% CI 0.9-12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients.Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin.

    View details for DOI 10.1016/j.jpeds.2017.04.051

    View details for PubMedID 28552449

  • Development and validation of a major adverse transplant event (MATE) score to predict late graft loss in pediatric heart transplantation. journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Almond, C. S., Hoen, H., Rossano, J. W., Castleberry, C., Auerbach, S. R., Yang, L., Lal, A. K., Everitt, M. D., Fenton, M., Hollander, S. A., Pahl, E., Pruitt, E., Rosenthal, D. N., McElhinney, D. B., Daly, K. P., Desai, M. 2017

    Abstract

    There is inadequate power to perform a valid clinical trial in pediatric heart transplantation (HT) using a conventional end-point, because the disease is rare and hard end-points, such as death or graft loss, are infrequent. We sought to develop and validate a surrogate end-point involving the cumulative burden of post-transplant complications to predict death/graft loss to power a randomized clinical trial of maintenance immunosuppression in pediatric HT.Pediatric Heart Transplant Study (PHTS) data were used to identify all children who underwent an isolated orthotopic HT between 2005 and 2014 who survived to 6 months post-HT. A time-varying Cox model was used to develop and evaluate a surrogate end-point comprised of 6 major adverse transplant events (MATEs) (acute cellular rejection [ACR], antibody-mediated rejection [AMR], infection, cardiac allograft vasculopathy [CAV], post-transplant lymphoproliferative disease [PTLD] and chronic kidney disease [CKD]) occurring between 6 and 36 months, where individual events were defined according to international guidelines. Two thirds of the study cohort was used for score development, and one third of the cohort was used to test the score.Among 2,118 children, 6.4% underwent graft loss between 6 and 36 months post-HT, whereas 39% developed CKD, 34% ACR, 34% infection, 9% AMR, 4% CAV and 2% PTLD. The best predictive score involved a simple MATE score sum, yielding a concordance probability estimate (CPE) statistic of 0.74. Whereas the power to detect non-inferiority (NI), assuming the NI hazard ratio of 1.45 in graft survival was 10% (assuming 200 subjects and 6% graft loss rate), the power to detect NI assuming a 2-point non-inferiority margin was >85% using the MATE score.The MATE score reflects the cumulative burden of MATEs and has acceptable prediction characteristics for death/graft loss post-HT. The MATE score may be useful as a surrogate end-point to power a clinical trial in pediatric HT.

    View details for DOI 10.1016/j.healun.2017.03.013

    View details for PubMedID 28465118

  • A multicenter study of the impella device for mechanical support of the systemic circulation in pediatric and adolescent patients. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Dimas, V. V., Morray, B. H., Kim, D. W., Almond, C. S., Shahanavaz, S., Tume, S. C., Peng, L. F., McElhinney, D. B., Justino, H. 2017

    Abstract

    The objective was to review the use of Impella devices (Abiomed Inc, Danvers, MA) for temporary circulatory support in pediatric and adolescent patients (age ≤ 21 yrs).Options for minimally invasive circulatory support in children are limited, and published data are confined to case reports and small case series.This was a retrospective, multicenter review of Impella implants in pediatric and adolescent patients from 2009-15, using standardized data collection and INTERMACS definitions.A total of 39 implants were performed in 38 patients from 16 centers. Median age and weight were 16 yrs (4-21 yrs) and 62 kg (15-134 kg). The primary indication for implant was cardiogenic shock in 28 patients (72%). Cardiac allograft rejection, myocarditis, or cardiomyopathy were the underlying diagnosis in 23 patients (59%); 11 patients had congenital heart disease. The median duration of support was 45 hr (1-1224 hr). Indications for explant included ventricular recovery in 16 patients, transition to another device in 12, death in 5, and transplant in 1. Survival was 85% at 7 days and 68% at 30 days. Major adverse events occurred in 8 patients: hemolysis in 3, bleeding in 2, stroke in 1 (unclear if related to Impella), sepsis in 1, and critical leg ischemia in 1. An increase in aortic regurgitation was noted in three patients, with no evidence of valve injury.Temporary circulatory support with Impella devices is feasible in pediatric and adolescent patients, with acceptable risk profiles. More experience and follow up is needed to improve technical performance and patient selection. © 2017 Wiley Periodicals, Inc.

    View details for DOI 10.1002/ccd.26973

    View details for PubMedID 28295963

  • Impact of Heart Transplantation on the Functional Status of US Children With End-Stage Heart Failure. Circulation Peng, D. M., Zhang, Y., Rosenthal, D. N., Palmon, M., Chen, S., Kaufman, B. D., Maeda, K., Hollander, S. A., McDonald, N., Smoot, L. B., Bernstein, D., Almond, C. S. 2017; 135 (10): 939-950

    Abstract

    There are limited data describing the functional status (FS) of children after heart transplant (HT). We sought to describe the FS of children surviving at least 1 year after HT, to evaluate the impact of HT on FS, and to identify factors associated with abnormal FS post-HT.Organ Procurement and Transplantation Network data were used to identify all US children <21 years of age surviving ≥1 year post-HT from 2005 to 2014 with a functional status score (FSS) available at 3 time points (listing, transplant, ≥1 year post-HT). Logistic regression and generalized estimating equations were used to identify factors associated with abnormal FS (FSS≤8) post-HT.A total of 1633 children met study criteria. At the 1-year assessment, 64% were "fully active/no limitations" (FSS=10), 21% had "minor limitations with strenuous activity" (FSS=9); and 15% scored ≤8. In comparison with listing FS, FS at 1 year post-HT increased in 91% and declined/remained unchanged in 9%. A stepwise regression procedure selected the following variables for association with abnormal FS at 1 year post-HT: ≥18 years of age (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.7), black race (OR, 1.5; 95% CI, 1.1-2.0), support with ≥inotropes at HT (OR, 1.7; 95% CI, 1.2-2.5), hospitalization status at HT (OR, 1.5; 95% CI, 1.0-2.19), chronic steroid use at HT (OR, 1.5; 95% CI, 1.0-2.2), and treatment for early rejection (OR, 2.0; 95% CI, 1.5-2.7).Among US children who survive at least 1 year after HT, FS is excellent for the majority of patients. HT is associated with substantial improvement in FS for most children. Early rejection, older age, black race, chronic steroid use, hemodynamic support at HT, and being hospitalized at HT are associated with abnormal FS post-HT.

    View details for DOI 10.1161/CIRCULATIONAHA.115.016520

    View details for PubMedID 28119383

  • Pediatric Heart Donor Assessment Tool (PH-DAT): A novel donor risk scoring system to predict 1-year mortality in pediatric heart transplantation. journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Zafar, F., Jaquiss, R. D., Almond, C. S., Lorts, A., Chin, C., Rizwan, R., Bryant, R., Tweddell, J. S., Morales, D. L. 2017

    Abstract

    In this study we sought to quantify hazards associated with various donor factors into a cumulative risk scoring system (the Pediatric Heart Donor Assessment Tool, or PH-DAT) to predict 1-year mortality after pediatric heart transplantation (PHT).PHT data with complete donor information (5,732) were randomly divided into a derivation cohort and a validation cohort (3:1). From the derivation cohort, donor-specific variables associated with 1-year mortality (exploratory p-value < 0.2) were incorporated into a multivariate logistic regression model. Scores were assigned to independent predictors (p < 0.05) based on relative odds ratios (ORs).The final model had an acceptable predictive value (c-statistic = 0.62). The significant 5 variables (ischemic time, stroke as the cause of death, donor-to-recipient height ratio, donor left ventricular ejection fraction, glomerular filtration rate) were used for the scoring system. The validation cohort demonstrated a strong correlation between the observed and expected rates of 1-year mortality (r = 0.87). The risk of 1-year mortality increases by 11% (OR 1.11 [1.08 to 1.14]; p < 0.001) in the derivation cohort and 9% (OR 1.09 [1.04 to 1.14]; p = 0.001) in the validation cohort with an increase of 1-point in score. Mortality risk increased 5 times from the lowest to the highest donor score in this cohort. Based on this model, a donor score range of 10 to 28 predicted 1-year recipient mortality of 11% to 31%.This novel pediatric-specific, donor risk scoring system appears capable of predicting post-transplant mortality. Although the PH-DAT may benefit organ allocation and assessment of recipient risk while controlling for donor risk, prospective validation of this model is warranted.

    View details for DOI 10.1016/j.healun.2017.03.002

    View details for PubMedID 28365178

  • Functional status of United States children supported with a left ventricular assist device at heart transplantation. journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Bulic, A., Maeda, K., Zhang, Y., Chen, S., McElhinney, D. B., Dykes, J. C., Hollander, A. M., Hollander, S. A., Murray, J., Reinhartz, O., Gowan, M. A., Rosenthal, D. N., Almond, C. S. 2017

    Abstract

    As survival with pediatric left ventricular assist devices (LVADs) has improved, decisions regarding the optimal support strategy may depend more on quality of life and functional status (FS) rather than mortality alone. Limited data are available regarding the FS of children supported with LVADs. We sought to compare the FS of children supported with LVADs vs vasoactive infusions to inform decision making around support strategies.Organ Procurement and Transplant Network data were used to identify all United States children aged between 1 and 21 years at heart transplant (HT) between 2006 and 2015 for dilated cardiomyopathy and supported with an LVAD or vasoactive infusions alone at HT. FS was measured using the 10-point Karnofsky and Lansky scale.Of 701 children who met the inclusion criteria, 430 (61%) were supported with vasoactive infusions, and 271 (39%) were supported with an LVAD at HT. Children in the LVAD group had higher median FS scores at HT than children in the vasoactive infusion group (6 vs 5, p < 0.001) but lower FS scores at listing (4 vs 6, p < 0.001). The effect persisted regardless of patient location at HT (home, hospital, intensive care) or device type. Discharge by HT occurred in 46% of children in the LVAD group compared with 26% of children in the vasoactive infusion cohort (p = 0.001). Stroke was reported at HT in 3% of children in the LVAD cohort and in 1% in the vasoactive infusion cohort (p = 0.04).Among children with dilated cardiomyopathy undergoing HT, children supported with LVADs at HT have higher FS than children supported with vasoactive infusions at HT, regardless of device type or hospitalization status. Children supported with LVADs at HT were more likely to be discharged from the hospital but had a higher prevalence of stroke at HT.

    View details for DOI 10.1016/j.healun.2017.02.024

    View details for PubMedID 28363739

  • Long-term pediatric ventricular assist device therapy: a case report of 2100+ days of support. ASAIO journal Purkey, N. J., Lin, A., Murray, J. M., Gowen, M., Shuttleworth, P., Maeda, K., Almond, C. S., Rosenthal, D. N., Chen, S. 2017

    Abstract

    Ventricular assist devices (VADs) have been placed as destination therapy in adults for over twenty years but have only recently been considered an option in a subset of pediatric patients. A 2016 report from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) revealed only eight pediatric patients implanted as destination therapy. We report the case of an adolescent male with Becker Muscular Dystrophy (BMD) who underwent VAD placement in 2011 as bridge to candidacy. He subsequently decided to remain as destination therapy and so far has accrued over 2100 days on VAD support, the longest duration of pediatric VAD support reported in the literature to date.

    View details for DOI 10.1097/MAT.0000000000000546

    View details for PubMedID 28195883

  • Berlin Heart EXCOR use in patients with congenital heart disease. journal of heart and lung transplantation Morales, D. L., Zafar, F., Almond, C. S., Canter, C., Fynn-Thompson, F., Conway, J., Adachi, I., Lorts, A. 2017

    Abstract

    Management of mechanical circulatory support in children with congenital heart disease (CHD) is challenging due to physiologic variations and anatomic limitations to device placement. In this study we examine the use of Berlin Heart EXCOR in CHD patients.CHD patients were identified from the EXCOR Pediatric Study data set (2007 to 2010). Mortality and serious adverse events were compared between CHD and non-CHD cohorts, and predictors of poor outcomes in the CHD cohort were identified.CHD was present in 29% (n = 59, 18 with 1-ventricle physiology) of all EXCOR patients (N = 204). Successful bridge (transplant or wean) was less likely in CHD patients compared with non-CHD patients (48% vs 80%; p < 0.01). Among CHD patients, no neonates, 25% of infants (30 days to 1 year) and 65% of children (>1 year) were successfully bridged. Pre-implant congenital heart surgery (CHS) and extracorporeal membrane oxygenation (ECMO) on the same admission occurred in 60% of children ≤1 year of age (83% of neonates, 50% of infants), with 8% survival. Regardless of age, patients who did not have CHS and ECMO had 61% survival. Smaller pump, pre-implant bilirubin >1.2 mg/dl and renal dysfunction were independently associated with mortality.End-organ function at implant reliably predicts adverse outcomes and should be considered when making implant decisions. EXCOR use in neonates and infants with CHD should be approached cautiously. If patients have undergone pre-implant CHS and ECMO, EXCOR support may not provide any survival benefit. EXCOR support in non-infants with CHD is challenging but can be consistently successful with appropriate patient selection.

    View details for DOI 10.1016/j.healun.2017.02.003

    View details for PubMedID 28259596

  • Rehospitalization after pediatric heart transplantation: Incidence, indications, and outcomes. Pediatric transplantation Hollander, S. A., McElhinney, D. B., Almond, C. S., McDonald, N., Chen, S., Kaufman, B. D., Bernstein, D., Rosenthal, D. N. 2017; 21 (1)

    Abstract

    We report the patterns of rehospitalization after pediatric heart transplant (Htx) at a single center. Retrospective review of 107 consecutive pediatric Htx recipients between January 22, 2007, and August 28, 2014, who survived their initial transplant hospitalization. The frequency, duration, and indications for all hospitalizations between transplant hospitalization discharge and September 30, 2015, were analyzed. A total of 444 hospitalization episodes occurred in 90 of 107 (84%) patients. The median time to first rehospitalization was 59.5 (range 1-1526) days, and the median length of stay was 2.5 (range 0-81) days. There were an average of two hospitalizations per patient in the first year following transplant hospitalization, declining to about 0.8 per patient per year starting at 3 years post-transplant. Admissions for viral infections were most common, occurring in 93 of 386 (24%), followed by rule out sepsis in 61 of 386 (16%). Admissions for suspected or confirmed rejection were less frequent, accounting for 41 of 386 (11%) and 31 of 386 (8%) of all admissions, respectively. Survival to discharge after rehospitalization was 97%. Hospitalization is common after pediatric Htx, particularly in the first post-transplant year, with the most frequent indications for hospitalization being viral illness and rule out sepsis. After the first post-transplant year, the risk for readmission falls significantly but remains constant for several years.

    View details for DOI 10.1111/petr.12857

    View details for PubMedID 27891727

  • Impact of a modified anti-thrombotic guideline on stroke in children supported with a pediatric ventricular assist device. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Rosenthal, D. N., Lancaster, C. A., McElhinney, D. B., Chen, S., Stein, M., Lin, A., Doan, L., Murray, J. M., Gowan, M. A., Maeda, K., Reinhartz, O., Almond, C. S. 2017

    Abstract

    Stroke is the most feared complication associated with the Berlin Heart EXCOR pediatric ventricular assist device (VAD), the most commonly used VAD in children, and affects 1 in 3 children. We sought to determine whether a modified anti-thrombotic guideline, involving more intense platelet inhibition and less reliance on platelet function testing, is associated with a lower incidence of stroke.All children supported with the EXCOR at Stanford from 2009 to 2014 were divided into 2 cohorts based on the primary anti-thrombotic guideline used to prevent pump thrombosis: (1) the Edmonton Anti-thrombotic Guideline (EG) cohort, which included children implanted before September 2012 when dual anti-platelet therapy was used with doses titrated to Thromboelastrography/PlateletMapping (TEG/PM); and (2) the Stanford Modified Anti-thrombotic Guideline (SG) cohort, which included children implanted on or after September 2012 when triple anti-platelet therapy was used routinely and where doses were uptitrated to high, weight-based dosing targets, with low-dose steroids administered as needed for inflammation.At baseline, the EG (N = 16) and SG (N = 11) cohorts were similar. The incidence rate of stroke in the SG cohort was 84% lower than in the EG cohort (0.8 vs 4.9 events per 1,000 days of support, p = 0.031), and 86% lower than in the previous Investigational Device Exemption trial (p = 0.006). The bleeding rate was also lower in the SG cohort (p = 0.015). Target doses of aspirin, clopidogrel and dipyridamole were higher (all p < 0.003), with less dosing variability in the SG cohort than in the EG cohort. There was no difference in adenosine diphosphate inhibition by TEG/PM, but arachidonic acid inhibition was higher in the SG cohort (median 75% vs 39%, p = 0.008).Stroke was significantly less common in pediatric patients supported with the Berlin Heart EXCOR VAD using a triple anti-platelet regimen uptitrated to high, weight-based dosing targets as compared with the dual anti-platelet regimen titrated to PM, and without a higher risk of bleeding. Larger studies are needed to confirm these findings.

    View details for DOI 10.1016/j.healun.2017.05.020

    View details for PubMedID 28606584

  • Closing in on the PumpKIN Trial of the Jarvik 2015 Ventricular Assist Device. Seminars in thoracic and cardiovascular surgery. Pediatric cardiac surgery annual Baldwin, J. T., Adachi, I., Teal, J., Almond, C. A., Jaquiss, R. D., Massicotte, M. P., Dasse, K., Siami, F. S., Zak, V., Kaltman, J. R., Mahle, W. T., Jarvik, R. 2017; 20: 9-15

    Abstract

    The Infant Jarvik ventricular assist device (VAD; Jarvik Heart, Inc., New York, NY) has been developed to support the circulation of infants and children with advanced heart failure. The first version of the device was determined to have elevated hemolysis under certain conditions. The objective of this work was to determine appropriate modifications to the Infant Jarvik VAD that would result in acceptably low hemolysis levels. In vitro hemolysis testing revealed that hemolysis was related to the shape of the pump blade tips and a critical speed over which hemolysis would occur. Various design modifications were tested and a final design was selected that met the hemolysis performance goal. The new version was named the Jarvik 2015 VAD. Chronic in vivo tests, virtual fit studies, and a series of other performance tests were carried out to assess the device's performance characteristics. In vivo test results revealed acceptable hemolysis levels in a series of animals and virtual fit studies showed that the device would fit into children 8 kg and above, but could fit in smaller children as well. Additional FDA-required testing has been completed and all of the data are being submitted to the FDA so that a clinical trial of the Jarvik 2015 VAD can begin. Development of a Jarvik VAD for use in young children has been challenging for various reasons. However, with the hemolysis issue addressed in the Jarvik 2015 VAD, the device is well-poised for the start of the PumpKIN clinical trial in the near future.

    View details for DOI 10.1053/j.pcsu.2016.09.003

    View details for PubMedID 28007073

  • Clinical practice patterns are relatively uniform between pediatric heart transplant centers: A survey-based assessment. Pediatric transplantation Castleberry, C., Ziniel, S., Almond, C., Auerbach, S., Hollander, S. A., Lal, A. K., Fenton, M., Pahl, E., Rossano, J. W., Everitt, M. D., Daly, K. P. 2017

    Abstract

    Clinical practice variations are a barrier to the study of pediatric heart transplants and coordination of multicenter RCTs in this patient population. We surveyed centers to describe practice patterns, understand areas of variation, and willingness to modify protocol. Pediatric heart transplant centers were identified, and one survey was completed per center. Simple descriptive statistics were used. The response rate was 77% (40 responses from 52 contacted centers, 37 with complete responses). Median center volume of respondents was eight transplants/year (IQR 3-19). Most centers reported tacrolimus (36/38, 95%) and mycophenolate mofetil (36/38, 95%) as maintenance immunosuppression. Other immunosuppression agents reported were cyclosporine (7/38, 18%), everolimus or sirolimus (3/38, 8%), and azathioprine (2/38, 5%). Overall, respondents answered similarly for questions regarding clinical practices including induction therapy, maintenance immunosuppression, and rejection treatment threshold (>85% agreement for all). Additionally, willingness to change clinical practices was over 70% for all practices surveyed (35 total respondents), and 97% of centers (36/37) were willing to participate in a RCT of maintenance immunosuppression. In conclusion, we found many similar clinical practice protocols. Most centers are willing to collaborate on a common protocol in order to participate in a RCT and support a trial investigating maintenance immunosuppression.

    View details for DOI 10.1111/petr.13013

    View details for PubMedID 28670871

  • HeartWare HVAD for Biventricular Support in Children and Adolescents: The Stanford Experience. ASAIO journal Stein, M. L., Yeh, J., Reinhartz, O., Rosenthal, D. N., Kaufman, B. D., Almond, C. S., Hollander, S. A., Maeda, K. 2016; 62 (5): e46-51

    Abstract

    Despite increasing use of mechanical circulatory support in children, experience with biventricular device implantation remains limited. We describe our experience using the HeartWare HVAD to provide biventricular support to 3 patients and compare these patients with 5 patients supported with HeartWare LVAD. At the end of the study period, all three BiVAD patients had been transplanted and were alive. LVAD patients were out of bed and ambulating a median of 10.5 days post implantation. The BiVAD patients were out of bed a median of 31 days post implantation. Pediatric patients with both left ventricular and biventricular heart failure can be successfully bridged to transplantation with the HeartWare HVAD. Rapid improvement in functional status following HVAD implantation for isolated left ventricular support is seen. Patients supported with BiVAD also demonstrate functional recovery, albeit more modestly. In the absence of infection, systemic inflammatory response raises concern for inadequate support.

    View details for DOI 10.1097/MAT.0000000000000356

    View details for PubMedID 26919182

  • Electrocardiographic repolarization abnormalities and increased risk of life-threatening arrhythmias in children with dilated cardiomyopathy HEART RHYTHM Chen, S., Motonaga, K. S., Hollander, S. A., Almond, C. S., Rosenthal, D. N., Kaufman, B. D., May, L. J., Avasarala, K., Dao, D. T., Dubin, A. M., Ceresnak, S. R. 2016; 13 (6): 1289-1296

    Abstract

    Life-threatening arrhythmia events (LTEs) occur in ~5% of children with dilated cardiomyopathy (DCM). While prolonged QRS duration has been shown to be associated with LTEs, electrocardiographic (ECG) repolarization findings have not been examined.We sought to determine the associations between ECG repolarization abnormalities and LTEs in children with DCM.A single-center retrospective review of children with DCM was performed. LTEs were defined as documented ventricular tachycardia or fibrillation requiring medical intervention. Three pediatric cardiologists, blinded to clinical events, evaluated ECGs obtained at the time of initial referral. Kaplan-Meier survival and Cox proportional hazards analyses were used to evaluate time to LTEs.A total of 137 patients (mean age 7.8 ± 6.7 years; 75(55%) male patients) with DCM (mean ejection fraction 35% ± 16%) were included; 67 patients (49%) had a corrected JT (JTc) interval of ≥340 ms, 72 (53%) had a corrected QT (QTc) interval of ≥450 ms, and 41 (30%) had abnormal T waves. LTEs occurred in 15 patients at a median of 12 months (interquartile range 3-36 months) after the initial ECG. Patients with LTEs had a longer JTc interval (371 ± 77 ms vs 342 ± 41 ms; P = .02) and a longer QTc interval (488 ± 96 ms vs 453 ± 44 ms; P = .01). In survival analysis, a JTc interval of ≥390 ms (hazard ratio [HR] 4.07; 95% confidence interval [CI] 1.12-14.83; P = .03), a QTc interval of ≥510 ms (HR 6.95; 95% CI 1.53-31.49; P = .01), abnormal T-wave inversion (HR 11.62; 95% CI 2.75-49.00; P = .001), and ST-segment depression (HR 6.91; 95% CI 1.25-38.27; P = .03) were associated with an increased risk of LTEs, even after adjusting for QRS duration and amiodarone use.Repolarization abnormalities are common in children with DCM. Certain ECG repolarization abnormalities, such as significantly prolonged JTc and QTc intervals, may be useful in identifying patients at risk of LTEs.

    View details for DOI 10.1016/j.hrthm.2016.02.014

    View details for Web of Science ID 000376334800016

    View details for PubMedID 26945851

  • Adverse events in children implanted with ventricular assist devices in the United States: Data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) JOURNAL OF HEART AND LUNG TRANSPLANTATION Rosenthal, D. N., Almond, C. S., Jaquiss, R. D., Peyton, C. E., Auerbach, S. R., Morales, D. R., Epstein, D. J., Cantor, R. S., Kormos, R. L., Naftel, D. C., Butts, R. J., Ghanayem, N. S., Kirklin, J. K., Blume, E. D. 2016; 35 (5): 569-577

    Abstract

    Ventricular assist devices (VADs) have been used in children on an increasing basis in recent years. One-year survival rates are now >80% in multiple reports. In this report we describe adverse events experienced by children with durable ventricular assist devices, using a national-level registry (PediMACS, a component of INTERMACS) METHODS: PediMACS is a national registry that contains clinical data on patients who are <19 years of age at the time of VAD implantation. Data collection concludes at the time of VAD explantation. All FDA-approved devices are included. PediMACS was launched on September 1, 2012, and this report includes all data from launch until August 2014. Adverse events were coded with a uniform, pre-specified set of definitions.This report comprises data from 200 patients with a median age of 11 years (range 11 days to 18 years), and total follow-up of 783 patient-months. The diagnoses were cardiomyopathy (n = 146, 73%), myocarditis (n = 17, 9%), congenital heart disease (n = 35, 18%) and other (n = 2, 1%). Pulsatile-flow devices were used in 91 patients (45%) and continuous-flow devices in 109 patients (55%). Actuarial survival was 86% at 6 months. There were 418 adverse events reported. The most frequent events were device malfunction (n = 79), infection (n = 78), neurologic dysfunction (n = 52) and bleeding (n = 68). Together, these accounted for 277 events, 66% of the total. Although 38% of patients had no reported adverse event and 16% of patients had ≥5 adverse events. Adverse events occurred at all time-points after implantation, but were most likely to occur in the first 30 days. For continuous-flow devices, there were broad similarities in adverse event rates between this cohort and historic rates from the INTERMACS population.In this study cohort, the overall rate of early adverse events (within 90 days of implantation) was 86.3 events per 100 patient-months, and of late adverse events it was 20.4 events per 100 patient-months. The most common adverse events in recipients of pulsatile VADs were device malfunction, neurologic dysfunction, bleeding and infection. For continuous-flow VADs, the most common adverse events were infection, bleeding, cardiac arrhythmia, neurologic dysfunction and respiratory failure. Compared with an adult INTERMACS cohort, the overall rate and distribution of adverse events appears similar.

    View details for DOI 10.1016/j.healun.2016.03.005

    View details for Web of Science ID 000376951900006

    View details for PubMedID 27197775

  • Outcomes of children implanted with ventricular assist devices in the United States: First analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) JOURNAL OF HEART AND LUNG TRANSPLANTATION Blume, E. D., Rosenthal, D. N., Rossano, J. W., Baldwin, J. T., Eghtesady, P., Morales, D. L., Cantor, R. S., Conway, J., Lorts, A., Almond, C. S., Naftel, D. C., Kirklin, J. K. 2016; 35 (5): 578-584

    Abstract

    Use of mechanical circulatory support in children has increased as more options have become available. A national account of the use of mechanical support in children and adolescents is essential to understanding outcomes, refining patient selection and improving quality of care.The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a National Heart, Lung, and Blood Institute-supported nationwide registry for temporary and durable ventricular assist device (VAD) use in patients <19 years of age. Between the launch in September 2012 and June 2015, 37 hospitals in the USA have enrolled patients. This first report of data from PediMACS analyzed pre-implant patient characteristics, survival using competing outcomes, and adverse events.Two hundred pediatric patients underwent 222 durable VAD implants. Patients' characteristics and outcomes of children supported with a temporary device (n = 41) were not analyzed in this report. The etiology of heart disease included 146 (73%) patients with cardiomyopathy and 35 (18%) with congenital heart disease. Thirty patients (15%) transitioned from extracorporeal membrane oxygenation (ECMO) and 76 (38%) had previous cardiac surgery. Most patients were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Level 1 (27%) or Level 2 (56%) at implant, with 13% at Level 3. Of the 200 patients supported with a durable device, 91 (46%) were supported with a pulsatile-flow device and 109 (55%) with a continuous-flow (CF) device. Patient age at first implant included 30 patients (15%) <1 year of age, 37 (19%) 1 to 5 years, 32 (16%) 6 to 10 years and 101 (51%) 10 to 18 years. Patients were supported with left ventricular assist device alone in 161 (81%), biventricular ventricular assist device in 29 (15%), right ventricular assist device in 4 (2.0%) and total artificial heart in 6 (3%), together comprising 783 months of follow-up. The 200 patients receiving primary durable devices had an actuarial survival of 81% at 6 months. Competing risk analysis at 6 months revealed that 58% of patients had been transplanted, 28% were alive on support, 14% had died and 0.6% recovered. In the overall cohort, there were 28 deaths. Reported serious adverse events included infection (n = 78), bleeding (n = 68), device malfunction (n = 79) and neurologic dysfunction (n = 52).PediMACS constitutes the largest single data repository with detailed information of pediatric patients implanted with VADs. The first PediMACS report reveals favorable outcomes despite the varying patient characteristics and pump types. However, the rate of adverse events remains high. With further data collection, analysis of patient risk factors critical to improving outcomes will be possible.

    View details for DOI 10.1016/j.healun.2016.01.1227

    View details for Web of Science ID 000376951900007

    View details for PubMedID 27009673

  • Impact of ventricular assist device placement on longitudinal renal function in children with end-stage heart failure. journal of heart and lung transplantation May, L. J., Montez-Rath, M. E., Yeh, J., Axelrod, D. M., Chen, S., Maeda, K., Almond, C. S., Rosenthal, D. N., Hollander, S. A., Sutherland, S. M. 2016; 35 (4): 449-456

    Abstract

    Although ventricular assist devices (VADs) restore hemodynamics in those with heart failure, reversibility of end-organ dysfunction with VAD support is not well characterized. Renal function often improves in adults after VAD placement, but this has not been comprehensively explored in children.Sixty-three children on VAD support were studied. Acute kidney injury (AKI) was defined by Kidney Disease: Improving Global Outcomes criteria. Estimated glomerular filtration rate (eGFR) was determined by the Schwartz method. Generalized linear mixed-effects models compared the pre-VAD and post-VAD eGFR for the cohort and sub-groups with and without pre-VAD renal dysfunction (pre-VAD eGFR < 90 ml/min/1.73 m(2)).The pre-VAD eGFR across the cohort was 84.0 ml/min/1.73 m(2) (interquartile range [IQR] 62.3-122.7), and 55.6% (34 of 63) had pre-VAD renal dysfunction. AKI affected 60.3% (38 of 63), with similar rates in those with and without pre-existing renal dysfunction. Within the cohort, the nadir eGFR occurred 1 day post-operatively (62.9 ml/min/1.73 m(2); IQR, 51.2-88.9 ml/min/1.73 m(2); p < 0.001). By Day 5, however, the eGFR exceeded the baseline (99.0 ml/min/1.73 m(2); IQR, 59.3-146.7 ml/min/1.73 m(2); p = 0.03) and remained significantly higher through the first post-operative week. After adjusting for age, gender, and AKI, the eGFR continued to increase throughout the entire 180-day study period (β = 0.0025; 95% confidence interval, 0.0015-0.0036; p < 0.001). Patients with pre-VAD renal dysfunction experienced the greatest improvement in the eGFR (β = 0.0051 vs β = 0.0013, p < 0.001).Renal dysfunction is prevalent in children with heart failure undergoing VAD placement. Although peri-operative AKI is common, renal function improves substantially in the first post-operative week and for months thereafter. This is particularly pronounced in those with pre-VAD renal impairment, suggesting that VADs may facilitate recovery and maintenance of kidney function in children with advanced heart failure.

    View details for DOI 10.1016/j.healun.2015.10.039

    View details for PubMedID 26653933

  • Outpatient Outcomes of Pediatric Patients with Left Ventricular Assist Devices. ASAIO journal Chen, S., Lin, A., Liu, E., Gowan, M., May, L. J., Doan, L. N., Almond, C. S., Maeda, K., Reinhartz, O., Hollander, S. A., Rosenthal, D. N. 2016; 62 (2): 163-168

    Abstract

    Outpatient experience of children supported with continuous flow ventricular assist devices (CFVAD) is limited. We reviewed our experience with children discharged with CF-VAD support.All pediatric patients <18 years old with CF-VADs implanted at our institution were included. Discharge criteria included a stable medication regimen, completion of a VAD education program and standardized rehabilitation plan, and presence of a caregiver. Hospital re-admissions (excluding scheduled admissions) were reviewed. Adverse events were defined by INTERMACS criteria.Of 17 patients with CF-VADs, 8(47%) were discharged from the hospital (1 Heartware HVAD, 7 Heartmate II). Median age was 15.3(range 9.6-17.1) years and weight was 50.6(33.6-141) kg. Device strategies were destination therapy (n=4) and bridge to transplant (n=4). Patients spent a median 49(26-107) days hospitalized post-implant and had 2(1-5) hospital re-admissions. Total support duration was 3154 patient-days, with 2413 as outpatient. Most frequent adverse events were device malfunction and arrhythmias. There was one death due to pump thrombosis, and no bleeding or stroke events. Overall adverse event rate was 15.22 per 100-patient-months.Early experience suggests that children with CF-VADs can be safely discharged. Device malfunction and arrhythmia were the most common adverse events but were recognized quickly with structured outpatient surveillance.

    View details for DOI 10.1097/MAT.0000000000000324

    View details for PubMedID 26720740

  • Ventricular assist devices in a contemporary pediatric cohort: Morbidity, functional recovery, and survival. journal of heart and lung transplantation Stein, M. L., Dao, D. T., Doan, L. N., Reinhartz, O., Maeda, K., Hollander, S. A., Yeh, J., Kaufman, B. D., Almond, C. S., Rosenthal, D. N. 2016; 35 (1): 92-98

    Abstract

    Limited availability of donor organs has led to the use of ventricular assist devices (VADs) to treat heart failure in pediatric patients, primarily as bridge to transplantation. How effective VAD therapy is in promoting functional recovery in children is currently not known.We report morbidity and mortality as defined by the Interagency Registry for Mechanically Assisted Circulatory Support Modified for Pediatrics (PediMACS) and the use of the Treatment Intensity Score to assess functional status for 50 VAD patients supported at a single pediatric program from 2004 to 2013.In this cohort, 30-day survival on VAD was 98%, and 180-day survival was 83%. Stroke occurred in 11 patients (22%), with 8 (16%) resulting in persistent neurologic deficit or death. The adverse event rate was 2-fold to 3-fold higher in the first 7 days of support compared with the subsequent support period. Functional status, as measured by the Treatment Intensity Score, improved with duration of support. Successful bridge to transplantation was associated with fewer adverse events during support and greater improvement in the Treatment Intensity Score during the period of support.Overall survival in this cohort is excellent. The risk of serious adverse events decreases over the first month of support. However, a clinically significant risk of morbidity and mortality persists for the duration of pediatric VAD support. Measures of functional status improve with duration of support and are associated with survival to transplantation.

    View details for DOI 10.1016/j.healun.2015.06.006

    View details for PubMedID 26210751

  • Obesity and Premature Loss of Mobility in Two Adolescents with Becker Muscular Dystrophy After HeartMate II Implantation ASAIO JOURNAL Holander, S. A., Rizzuto, S., Holander, A. M., Lin, A., Liu, E., Murray, J. M., Almond, C. S., Rosenthal, D. N. 2016; 62 (1): E5-E7
  • Obesity and Premature Loss of Mobility in Two Adolescents with Becker Muscular Dystrophy After HeartMate II Implantation. ASAIO journal Hollander, S. A., Rizzuto, S., Hollander, A. M., Lin, A., Liu, E., Murray, J. M., Almond, C. S., Rosenthal, D. N. 2016; 62 (1): e5-7

    Abstract

    Weight gain is common following implantation of continuous flow ventricular assist devices (VADS). Obesity can have a significant negative impact on mobility. For adolescents with Becker Muscular Dystrophy (BMD) for whom the ability to ambulate often persists into the mid-third decade, preservation of functional ability is critical. We report two cases of Thoratec HeartMate II left ventricular assist device (LVAD) implantation in adolescents with Becker Muscular Dystrophy for whom post-operative weight gain contributed significantly to accelerated loss of ambulation and, in one case, drive line fracture in the context of repeated falls. As LVADS become an increasingly common therapy for end-stage heart failure in adolescents with BMD, care must focus not only on maintaining device functionality, but aggressive weight management and preservation of ambulation and skeletal muscle strength.

    View details for DOI 10.1097/MAT.0000000000000292

    View details for PubMedID 26461240

  • Extracorporeal Membrane Oxygenation as a Bridge to Pediatric Heart Transplantation Effect on Post-Listing and Post-Transplantation Outcomes CIRCULATION-HEART FAILURE Dipchand, A. I., Mahle, W. T., Tresler, M., Naftel, D. C., Almond, C., Kirklin, J. K., Pruitt, E., Webber, S. A. 2015; 8 (5): 960-969

    Abstract

    -Current organ allocation algorithms direct hearts to the sickest recipients to mitigate death while waiting. This may result in lower post-transplant (Tx) survival for high risk candidates mandating close examination to determine the appropriateness of different technologies as a bridge to Tx.-We analyzed all patients (<18 years old) from the Pediatric Heart Transplant Study database listed for heart Tx (1993 - 2013) to determine the impact of ECMO support at the time of listing and the time of Tx on waitlist mortality and post-Tx outcomes. 8% of patients were listed on ECMO and, within 12 months, 49% had undergone Tx, 35% were deceased and 16% were alive waiting. Survival at 12 months after listing (censored at Tx) was worse in patients on ECMO at listing (50%) compared to VAD at listing (76%) or not on ECMO/VAD at listing (76%, p<0.0001). 203 (5%) patients underwent Tx from ECMO; 135 (67%) had been on ECMO since listing and 67 (33%) had deteriorated to ECMO support while waiting. Survival after Tx was worse in patients Tx from ECMO (3y: 64%) vs on VAD at Tx (3y: 84%) or not on ECMO/VAD at Tx (3y: 85%, p<0.0001). Patients transplanted from ECMO at age <1year had the worst survival.-Pediatric patients requiring ECMO support prior to heart Tx have poor outcomes. Prioritization of donor hearts to children waitlisted on ECMO on warrants careful consideration due to ECMO's high pre- and post-Tx mortality.

    View details for DOI 10.1161/CIRCHEARTFAILURE.114.001553

    View details for Web of Science ID 000361186000017

    View details for PubMedID 26206854

  • Antithrombotic therapy for ventricular assist devices in children: do we really know what to do? JOURNAL OF THROMBOSIS AND HAEMOSTASIS Massicotte, M. P., BAUMAN, M. E., Murray, J., Almond, C. S. 2015; 13: S343-S350

    View details for DOI 10.1111/jth.12928

    View details for Web of Science ID 000356677500046

    View details for PubMedID 26149046

  • Antithrombotic therapy for ventricular assist devices in children: do we really know what to do? Journal of thrombosis and haemostasis Massicotte, M. P., BAUMAN, M. E., Murray, J., Almond, C. S. 2015; 13: S343-50

    Abstract

    The use of ventricular assist devices (VADs) in children is increasing. Stroke and device-related thromboembolism remain the most feared complications associated with VAD therapy in children. The presence of a VAD causes dysregulation of hemostasis due to the presence of foreign materials and sheer forces intrinsic to the device resulting in hypercoagulability and potentially life-threatening thrombosis. The use of antithrombotic therapy in adults with VADs modulates this disruption in hemostasis, decreasing the risk of thrombosis. Yet, differences in hemostasis in children (developmental hemostasis) may result in variances in dysregulation by these devices and preclude the use of adult guidelines. Consequently, pediatric device studies must include safety and efficacy estimates of device-specific antithrombotic therapy guidelines. This review will discuss mechanisms of hemostatic dysregulation as it pertains to VADs, goals of VAD antithrombotic therapy for children and adults, and emerging antithrombotic strategies for VAD use in children.

    View details for DOI 10.1111/jth.12928

    View details for PubMedID 26149046

  • Utility of a Dedicated Pediatric Cardiac Anticoagulation Program: The Boston Children's Hospital Experience PEDIATRIC CARDIOLOGY Murray, J. M., Hellinger, A., Dionne, R., Brown, L., Galvin, R., Griggs, S., Mittler, K., Harney, K., Manzi, S., Vanderpluym, C., Baker, A., O'Brien, P., O'Connell, C., Almond, C. S. 2015; 36 (4): 842-850

    Abstract

    Congenital heart disease is the leading cause of stroke in children. Warfarin therapy can be difficult to manage safely in this population because of its narrow therapeutic index, multiple drug and dietary interactions, small patient size, high-risk cardiac indications, and lack of data to support anticoagulation recommendations. We sought to describe our institution's effort to develop a dedicated cardiac anticoagulation service to address the special needs of this population and to review the literature. In 2009, in response to Joint Commission National Patient Safety Goals for Anticoagulation, Boston Children's Hospital created a dedicated pediatric Cardiac Anticoagulation Monitoring Program (CAMP). The primary purpose was to provide centralized management of outpatient anticoagulation to cardiac patients, to serve as a disease-specific resource to families and providers, and to devise strategies to evolve clinical care with rapidly emerging trends in anticoagulation care. Over 5 years the CAMP Service, staffed by a primary pediatric cardiology attending, a full-time nurse practitioner, and administrative assistant with dedicated support from pharmacy and nutrition, has enrolled over 240 patients ranging in age from 5 months to 55 years. The most common indications include a prosthetic valve (34 %), Fontan prophylaxis (20 %), atrial arrhythmias (11 %), cardiomyopathy (10 %), Kawasaki disease (7 %), and a ventricular assist device (2 %). A patient-centered multi-disciplinary cardiac anticoagulation clinic was created in 2012. Overall program international normalized ratio (INR) time in therapeutic range (TTR) is favorable at 67 % (81 % with a 0.2 margin) and has improved steadily over 5 years. Pediatric-specific guidelines for VKOR1 and CYP2C9 pharmacogenomics testing, procedural bridging with enoxaparin, novel anticoagulant use, and quality metrics have been developed. Program satisfaction is rated highly among families and providers. A dedicated pediatric cardiac anticoagulation program offers a safe and effective strategy to standardize anticoagulation care for pediatric cardiology patients, is associated with high patient and provider satisfaction, and is capable of evolving care strategies with emerging trends in anticoagulation.

    View details for DOI 10.1007/s00246-014-1089-x

    View details for Web of Science ID 000351553700020

    View details for PubMedID 25573076

  • 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

  • Predicting Graft Loss by 1 Year in Pediatric Heart Transplantation Candidates An Analysis of the Pediatric Heart Transplant Study Database CIRCULATION Schumacher, K. R., Almond, C., Singh, T. P., Kirk, R., Spicer, R., Hoffman, T. M., Hsu, D., Naftel, D. C., Pruitt, E., Zamberlan, M., Canter, C. E., Gajarski, R. J. 2015; 131 (10): 890-?

    Abstract

    Pediatric data on the impact of pre-heart transplantation (HTx) risk factors on early post-HTx outcomes remain inconclusive. Thus, among patients with previous congenital heart disease or cardiomyopathy, disease-specific risk models for graft loss were developed with the use pre-HTx recipient and donor characteristics.Patients enrolled in the Pediatric Heart Transplant Study (PHTS) from 1996 to 2006 were stratified by pre-HTx diagnosis into cardiomyopathy and congenital heart disease cohorts. Logistic regression identified independent, pre-HTx risk factors. Risk models were constructed for 1-year post-HTx graft loss. Donor factors were added for model refinement. The models were validated with the use of patients transplanted from 2007 to 2009. Risk factors for graft loss were identified in patients with cardiomyopathy (n=896) and congenital heart disease (n=965). For cardiomyopathy, independent risk factors were earlier year of transplantation, nonwhite race, female sex, diagnosis other than dilated cardiomyopathy, higher blood urea nitrogen, and panel reactive antibody >10%. The recipient characteristic risk model had good accuracy in the validation cohort, with predicted versus actual survival of 97.5% versus 95.3% (C statistic, 0.73). For patients with congenital heart disease, independent risk factors were nonwhite race, history of Fontan, ventilator dependence, higher blood urea nitrogen, panel reactive antibody >10%, and lower body surface area. The risk model was less accurate, with 86.6% predicted versus 92.4% actual survival, in the validation cohort (C statistic, 0.63). Donor characteristics did not enhance model precision.Risk factors for 1-year post-HTx graft loss differ on the basis of pre-HTx cardiac diagnosis. Modeling effectively stratifies the risk of graft loss in patients with cardiomyopathy and may be an adjunctive tool in allocation policies and center performance metrics.

    View details for DOI 10.1161/CIRCULATIONAHA.114.009120

    View details for Web of Science ID 000350771700012

    View details for PubMedID 25587099

  • Stroke in children with cardiac disease: report from the International Pediatric Stroke Study Group Symposium. Pediatric neurology Sinclair, A. J., Fox, C. K., Ichord, R. N., Almond, C. S., Bernard, T. J., Beslow, L. A., Chan, A. K., Cheung, M., DeVeber, G., Dowling, M. M., Friedman, N., Giglia, T. M., Guilliams, K. P., Humpl, T., Licht, D. J., Mackay, M. T., Jordan, L. C. 2015; 52 (1): 5-15

    Abstract

    Cardiac disease is a leading cause of stroke in children, yet limited data support the current stroke prevention and treatment recommendations. A multidisciplinary panel of clinicians was convened in February 2014 by the International Pediatric Stroke Study group to identify knowledge gaps and prioritize clinical research efforts for children with cardiac disease and stroke.Significant knowledge gaps exist, including a lack of data on stroke incidence, predictors, primary and secondary stroke prevention, hyperacute treatment, and outcome in children with cardiac disease. Commonly used diagnostic techniques including brain computed tomography and ultrasound have low rates of stroke detection, and diagnosis is frequently delayed. The challenges of research studies in this population include epidemiologic barriers to research such as small patient numbers, heterogeneity of cardiac disease, and coexistence of multiple risk factors. Based on stroke burden and study feasibility, studies involving mechanical circulatory support, single ventricle patients, early stroke detection strategies, and understanding secondary stroke risk factors and prevention are the highest research priorities over the next 5-10 years. The development of large-scale multicenter and multispecialty collaborative research is a critical next step. The designation of centers of expertise will assist in clinical care and research.There is an urgent need for additional research to improve the quality of evidence in guideline recommendations for cardiogenic stroke in children. Although significant barriers to clinical research exist, multicenter and multispecialty collaboration is an important step toward advancing clinical care and research for children with cardiac disease and stroke.

    View details for DOI 10.1016/j.pediatrneurol.2014.09.016

    View details for PubMedID 25532775

  • Challenges and Priorities for Research A Report From the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH) Working Group on Thrombosis in Pediatric Cardiology and Congenital Heart Disease CIRCULATION McCrindle, B. W., Li, J. S., Manlhiot, C., Tweddell, J. S., Giglia, T. M., Massicotte, M. P., Monagle, P., Krishnamurthy, R., Mahaffey, K. W., Michelson, A. D., Verdun, N., Almond, C. S., Newburger, J. W., Brandao, L. R., Esmon, C. T., Manco-Johnson, M. J., Ichord, R., Ortel, T. L., Chan, A. K., Portman, R., Rose, M., Strony, J., Kaltman, J. R. 2014; 130 (14): 1192-1203
  • Survival Benefit From Transplantation in Patients Listed for Heart Transplantation in the United States JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Singh, T. P., Milliren, C. E., Almond, C. S., Graham, D. 2014; 63 (12): 1169-1178

    Abstract

    The aim of this study was to assess the survival benefit from heart transplantation (HT), defined as reduction in the risks for 90-day and 1-year mortality on undergoing HT close to listing, in candidates stratified by their risk for waiting list mortality.Among patients listed for HT, those at higher risk for death without transplantation are also at higher risk for early post-transplantation mortality.All patients age ≥18 years listed for HT in the United States from 2007 to 2010 were analyzed. A model was developed to predict the risk for waiting list mortality within 90 days, and listed patients were stratified into 10 risk groups (deciles). All groups were followed for 1 year to assess cumulative 1-year mortality while on the waiting list. Models of 90-day and 1-year post-transplantation mortality were developed using recipient data, and these risks were estimated at listing in all listed candidates.Of 10,159 patients listed for HT, 596 (5.9%) died within 90 days and 1,054 (10.4%) within 1 year without undergoing transplantation. Of 5,720 recipients of transplants with 1-year follow-up, 576 (10.1%) died within 1 year. The risk for death while on the waiting list within 90 days increased from 1.6% to 19% across the 10 risk groups. The survival benefit from HT increased progressively with higher risk for death without transplantation (p < 0.001 for trend), but there was no benefit in the first 6 risk groups.The risk for waiting list mortality varies considerably among HT candidates. Although the survival benefit of HT generally increases with increasing risk for waiting list mortality, there is no measurable benefit in many candidates at the lower end of the risk spectrum.

    View details for DOI 10.1016/j.jacc.2013.11.045

    View details for Web of Science ID 000333256100009

    View details for PubMedID 24462511

  • Survival in patients removed from the heart transplant waiting List before receiving a transplant JOURNAL OF HEART AND LUNG TRANSPLANTATION Vanderpluym, C., Graham, D. A., Almond, C. S., Blume, E. D., Milliren, C. E., Singh, T. P. 2014; 33 (3): 261-269

    Abstract

    Little is known about the outcomes in patients who are removed from the heart transplant (HT) waiting list before receiving a transplant. We sought to analyze outcomes in such patients in the United States (U.S.) in the current era.All patients aged ≥ 18 years old listed for a primary HT in the U.S. between July 2004 and September 2010 were identified. Outcomes in those removed from the list by March 2011 (survival, relisting, HT) were examined using time-to-event analyses.Of 15,061 patients listed for primary HT, 10,168 (68%) received a HT, 1,393 (9%) died on the waiting list, and 1,871(12%) were removed before receiving HT. Of patients removed from the list, 560 (30%) were removed due to clinical improvement, 692 (37%) due to deterioration, and 619 (33%) due to other reasons. After removal, 30-day and 1-year survival were 99.6% and 94%, respectively, in patients removed due to improvement and 44% and 26%, respectively, in patients removed due to deterioration. Multivariable predictors of death after removal were removal due to clinical deterioration, hypertrophic or restrictive cardiomyopathy, United Network of Organ Sharing status 1A/1B at listing, and renal dysfunction. Only 27 patients (4.8%) among those removed due to improvement, 21 (3.0%) removed due to deterioration, and 46 (7.4%) removed due to other reasons were relisted.One in 8 patients listed for HT in the U.S. are removed from the waiting list before receiving HT. The indication for removal (clinical deterioration vs improvement) is the strongest independent predictor of survival after removal from the list.

    View details for DOI 10.1016/j.healun.2013.12.010

    View details for Web of Science ID 000332444000008

    View details for PubMedID 24559944

  • Antibody depletion for the treatment of crossmatch-positive pediatric heart transplant recipients PEDIATRIC TRANSPLANTATION Daly, K. P., Chandler, S. F., Almond, C. S., Singh, T. P., Mah, H., Milford, E., Matte, G. S., Bastardi, H. J., Mayer, J. E., Fynn-Thompson, F., Blume, E. D. 2013; 17 (7): 661-669

    Abstract

    Sensitization to HLA is a risk factor for adverse outcomes after heart transplantation. Requiring a negative prospective CM results in longer waiting times and increased waitlist mortality. We report outcomes in a cohort of sensitized children who underwent transplant despite a positive CDC CM+ using a protocol of antibody depletion at time of transplant, followed by serial IVIG administration. All patients <21 yrs old who underwent heart transplantation at Boston Children's Hospital from 1/1998 to 1/2011 were included. We compared freedom from allograft loss, allograft rejection, and serious infection between CM+ and CM- recipients. Of 134 patients in the cohort, 33 (25%) were sensitized prior to transplantation and 12 (9%) received a CM+ heart transplant. Serious infection in the first post-transplant year was more prevalent in the CM+ patients compared with CM- patients (50% vs. 16%; p = 0.005), as was HD-AMR (50% vs. 2%; p < 0.001). There was no difference in freedom from allograft loss or any rejection. At our center, children transplanted despite a positive CM had acceptable allograft survival and risk of any rejection, but a higher risk of HD-AMR and serious infection.

    View details for DOI 10.1111/petr.12131

    View details for Web of Science ID 000325369400019

    View details for PubMedID 23919762

  • Post-transplant Outcomes of Children Bridged to Transplant With the Berlin Heart EXCOR Pediatric Ventricular Assist Device Scientific Sessions of the American-Heart-Association (AHA) Eghtesady, P., Almond, C. S., Tjossem, C., Epstein, D., Imamura, M., Turrentine, M., Tweddell, J., Jaquiss, R. D., Canter, C. LIPPINCOTT WILLIAMS & WILKINS. 2013: S24–S31

    Abstract

    Recent data suggest that Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device improves waiting list survival for pediatric heart transplant candidates. Little is known about their post-transplant outcomes. The aim of this analysis was to determine whether there was a difference in early survival for children bridged to transplant with EXCOR versus status 1A pediatric heart transplant patients not transplanted with ventricular assist device support.Pediatric heart transplant patients (n=106) bridged to transplantation with EXCOR were compared with a similarly aged cohort (n=1021) within the Organ Procurement and Transplant Network (OPTN) database (both cohorts from May 2007 to December 2010). In the EXCOR group, 12-month post-transplant survival (88.7%) was similar to OPTN patients listed status 1A who were not on ventricular assist device support at transplant (89.3%; P=0.85) and significantly better than 12-month survival in OPTN patients on extracorporeal membrane oxygenation at transplant (60.3%; P<0.001). Rejection (50%) was a significantly (P=0.005) higher cause of 12-month post-transplant mortality in the EXCOR compared with the OPTN group. Death after transplant was also higher in EXCOR patients with congenital heart disease compared with those with cardiomyopathy (26.1% versus 7.2%; P=0.02). Post-transplant survival was similar in EXCOR patients with ≥1 serious adverse event during ventricular assist device support as those without an event during support.The 12-month post-transplant survival with EXCOR is comparable with overall pediatric heart transplant survival and superior to survival after extracorporeal membrane oxygenation. Neither adverse events during support nor factors associated with mortality during support influence post-transplant survival. Rejection was a significantly greater cause of post-transplant mortality in EXCOR than in OPTN patients.

    View details for DOI 10.1161/CIRCULATIONAHA.112.000446

    View details for Web of Science ID 000330535500003

    View details for PubMedID 24030413

  • Impact of medication non-adherence on survival after pediatric heart transplantation in the USA JOURNAL OF HEART AND LUNG TRANSPLANTATION Oliva, M., Singh, T. P., Gauvreau, K., Vanderpluym, C. J., Bastardi, H. J., Almond, C. S. 2013; 32 (9): 881-888

    Abstract

    Medication non-adherence (NA) can result in life-threatening illness in children after solid-organ transplantation. Little is known about the incidence, risk factors and outcomes of NA in large numbers of pediatric heart transplant (HT) recipients.Organ Procurement Transplant Network (OPTN) data were used to identify all children <18 years of age in the U.S.A. who underwent HT from October 1999 to January 2007. Cox proportional hazards analysis was used to identify risk factors for NA and the effect on graft survival.Of 2,070 pediatric heart transplants performed the median age at transplant was 6 years (interquartile range [IQR] 0 to 13 years); 40% had congenital heart disease (CHD), 7% were re-transplants, 42% were non-white and 43% had Medicaid insurance. Overall, 186 (9%) children had a report of NA at a median age of 15 years with more than two-thirds of NA episodes occurring after 12 years of age. Factors independently associated with NA were: adolescent age at transplant (hazard ratio [HR] 7.0, 95% confidence interval [CI] 4.1 to 12, compared with infants); black race (HR 2.3, 95% CI 1.7 to 3.3, compared with white); Medicaid insurance (HR 2.0, 95% CI 1.5 to 2.7, compared with non-Medicaid insurance); and ventilator or ventricular assist device (VAD) support at transplant. The risk of mortality conditional upon report of NA was 26% at 1 year and 33% at 2 years.Medication NA is an important problem in pediatric HT recipients and is associated with high mortality. Adolescent age, black race, Medicaid insurance and invasive hemodynamic support at transplant were associated with NA, whereas time on the wait list and gender were not. Targeted interventions among at-risk populations may be warranted.

    View details for DOI 10.1016/j.healun.2013.03.008

    View details for Web of Science ID 000324445100006

    View details for PubMedID 23755899

  • Risk Stratification and Transplant Benefit in Children Listed for Heart Transplant in the United States CIRCULATION-HEART FAILURE Singh, T. P., Almond, C. S., Piercey, G., Gauvreau, K. 2013; 6 (4): 800-808

    Abstract

    The sickest children among those listed for heart transplant (HT) are also at higher risk of post-transplant mortality. We hypothesized that transplant benefit, defined as percentage reduction in risk of 1-year mortality on receiving HT, increases with higher risk of wait-list mortality.We analyzed all children aged <18 years listed for first HT in the United States between July 2004 and December 2010. We developed a model for 90-day wait-list mortality (or removal because of deterioration) and stratified listed children into deciles based on their risk of wait-list mortality. Listed children were followed up for 1 year to assess cumulative 1-year wait-list mortality among the 10 risk groups. We developed a model for 1-year post-transplant mortality to estimate the risk of post-transplant mortality for children in each risk group. Of 2979 listed children, 15% reached the wait-list end point within 90 days and 18% within 1 year. Of 2034 HT recipients, 6.8% died within 90 days and 10.8% within 1 year. The risk of 90-day wait-list mortality increased progressively from 2.4% to 51.6% from the first to the tenth risk decile. Transplant benefit increased progressively across the wait-list risk groups (P<0.001 for trend). However, transplant benefit for children in the top 5% of risk (7.4%) was lower than that for children in the 91st to 95th percentile of risk (10.3%).Sicker children on the wait-list benefit more from HT unless the post-transplant mortality is predicted to be very high. Whether consideration of transplant benefit in allocation policy can improve overall survival among listed children requires further analysis.

    View details for DOI 10.1161/CIRCHEARTFAILURE.112.000280

    View details for Web of Science ID 000335157800030

    View details for PubMedID 23704137

  • Berlin Heart EXCOR Pediatric Ventricular Assist Device for Bridge to Heart Transplantation in US Children CIRCULATION Almond, C. S., Morales, D. L., Blackstone, E. H., Turrentine, M. W., Imamura, M., Massicotte, M. P., Jordan, L. C., Devaney, E. J., Ravishankar, C., Kanter, K. R., Holman, W., Kroslowitz, R., Tjossem, C., Thuita, L., Cohen, G. A., Buchholz, H., St Louis, J. D., Khanh Nguyen, K., Niebler, R. A., Walters, H. L., Reemtsen, B., Wearden, P. D., Reinhartz, O., Guleserian, K. J., Mitchell, M. B., Bleiweis, M. S., Canter, C. E., Humpl, T. 2013; 127 (16): 1702-?

    Abstract

    Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection.This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device at 47 centers from May 2007 through December 2010. Multiphase nonproportional hazards modeling was used to identify risk factors for early (<2 months) and late mortality. Of 204 children supported with the EXCOR, the median duration of support was 40 days (range, 1-435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death.Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.

    View details for DOI 10.1161/CIRCULATIONAHA.112.000685

    View details for Web of Science ID 000318031800012

    View details for PubMedID 23538380

  • Outcomes of Cardiac Transplantation in Single-Ventricle Patients With Plastic Bronchitis: A Multicenter Study JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Gossett, J. G., Almond, C. S., Kirk, R., Zangwill, S., Richmond, M. E., Kantor, P. F., Tresler, M. A., Lenderman, S. M., Naftel, D. C., Matthews, K. L., Pahl, E. 2013; 61 (9): 985-986

    View details for DOI 10.1016/j.jacc.2012.10.042

    View details for Web of Science ID 000315294100016

    View details for PubMedID 23290545

  • Pediatric ECMO Outcomes: Comparison of Centrifugal Versus Roller Blood Pumps Using Propensity Score Matching ASAIO JOURNAL Barrett, C. S., Jaggers, J. J., Cook, E. F., Graham, D. A., Yarlagadda, V. V., Teele, S. A., Almond, C. S., Bratton, S. L., Seeger, J. D., Dalton, H. J., Rycus, P. T., Laussen, P. C., Thiagarajan, R. R. 2013; 59 (2): 145-151

    Abstract

    Centrifugal blood pumps are being increasingly utilized in children supported with extracorporeal membrane oxygenation (ECMO). Our aim was to determine if survival and ECMO-related morbidities in children supported with venoarterial (VA) ECMO differed by blood pump type.Children aged less than 18 years who underwent VA ECMO support from 2007 to 2009 and reported to the Extracorporeal Life Support Organization registry were propensity score matched (Greedy 1:1 matching) using pre-ECMO characteristics.A total of 2,656 (centrifugal = 2,231, roller = 425) patients were identified and 548 patients (274 per pump type) were included in the propensity score-matched cohort. Children supported with centrifugal pumps had increased odds of hemolysis (odds ratio [OR], 4.03 95% confidence interval [CI], 2.37-6.87), hyperbilirubinemia (OR, 5.48; 95% CI, 2.62-11.49), need for inotropic support during ECMO (OR, 1.54; 95% CI, 1.09-2.17), metabolic alkalosis (blood pH > 7.6) during ECMO (OR, 3.13; 95% CI, 1.49-6.54), and acute renal failure (OR, 1.61; 95% CI, 1.10-2.39). Survival to hospital discharge did not differ by pump type.In a propensity score-matched cohort of pediatric ECMO patients, children supported with centrifugal pumps had increased odds of ECMO-related complications. There was no difference in survival between groups.

    View details for DOI 10.1097/MAT.0b013e31828387cd

    View details for Web of Science ID 000315599400009

    View details for PubMedID 23438777

  • Outcomes of Neonates Undergoing Extracorporeal Membrane Oxygenation Support Using Centrifugal Versus Roller Blood Pumps ANNALS OF THORACIC SURGERY Barrett, C. S., Jaggers, J. J., Cook, E. F., Graham, D. A., Rajagopal, S. K., Almond, C. S., Seeger, J. D., Rycus, P. T., Thiagarajan, R. R. 2012; 94 (5): 1635-1642

    Abstract

    Advances in centrifugal blood pump technology have led to increased use of centrifugal pumps in extracorporeal membrane oxygenation (ECMO) circuits. Their efficacy and safety in critically ill neonates remains unknown. Blood cell trauma leading to hemolysis may result in end-organ injury in critically ill neonates receiving centrifugal pump ECMO. We hypothesized that neonates undergoing ECMO support using centrifugal pumps were at increased odds of hemolysis and subsequent end-organ injury.Children 30 days of age or younger who received support with venoarterial ECMO and were reported to the Extracorporeal Life Support Registry during 2007 to 2009 underwent propensity score matching (Greedy matching 1:1) using pre-ECMO support characteristics.A total of 1,592 neonates receiving ECMO (centrifugal pump = 163 and roller pump = 1,492) were identified. Significant differences in demographic, presupport, and cannulation variables were present before matching. One hundred seventy-six neonates who were supported using either centrifugal (n = 88) or roller pumps (n = 88) were matched using propensity scoring. No significant differences in demographic, presupport, or cannulation variables were present after matching. Neonates undergoing support using centrifugal pumps had increased odds of hemolysis (odds ratio [OR], 7.7 [2.8-21.2]), hyperbilirubinemia (OR, 20.8 [2.7-160.4]), hypertension (OR, 3.2 [1.3-8.0]), and acute renal failure (OR, 2.4 [1.1-5.6]). Survival to discharge was not different between pump types.Use of ECMO using centrifugal pumps is associated with increased odds of hemolysis that likely contributes to other end-organ injury. Research into the optimal use of centrifugal pumps and strategies to prevent support-related complications need to be investigated.

    View details for DOI 10.1016/j.athoracsur.2012.06.061

    View details for Web of Science ID 000310439700045

    View details for PubMedID 22921236

  • Pediatric cardiovascular safety: Challenges in drug and device development and clinical application AMERICAN HEART JOURNAL Bates, K. E., Vetter, V. L., Li, J. S., Cummins, S., Aguel, F., Almond, C., Dubin, A. M., Elia, J., Finkle, J., Hausner, E. A., Joseph, F., Karkowsky, A. M., Killeen, M., Lemacks, J., Mathis, L., McMahon, A. W., Pinnow, E., Rodriguez, I., Stockbridge, N. L., Stockwell, M., Tassinari, M., Krucoff, M. W. 2012; 164 (4): 481-492

    Abstract

    Development of pediatric medications and devices is complicated by differences in pediatric physiology and pathophysiology (both compared with adults and within the pediatric age range), small patient populations, and practical and ethical challenges to designing clinical trials. This article summarizes the discussions that occurred at a Cardiac Safety Research Consortium-sponsored Think Tank convened on December 10, 2010, where members from academia, industry, and regulatory agencies discussed important issues regarding pediatric cardiovascular safety of medications and cardiovascular devices. Pediatric drug and device development may use adult data but often requires additional preclinical and clinical testing to characterize effects on cardiac function and development. Challenges in preclinical trials include identifying appropriate animal models, clinically relevant efficacy end points, and methods to monitor cardiovascular safety. Pediatric clinical trials have different ethical concerns from adult trials, including consideration of the subjects' families. Clinical trial design in pediatrics should assess risks and benefits as well as incorporate input from families. Postmarketing surveillance, mandated by federal law, plays an important role in both drug and device safety assessment and becomes crucial in the pediatric population because of the limitations of premarketing pediatric studies. Solutions for this wide array of issues will require collaboration between academia, industry, and government as well as creativity in pediatric study design. Formation of various epidemiologic tools including registries to describe outcomes of pediatric cardiac disease and its treatment as well as cardiac effects of noncardiovascular medications, should inform preclinical and clinical development and improve benefit-risk assessments for the patients. The discussions in this article summarize areas of emerging consensus and other areas in which consensus remains elusive and provide suggestions for additional research to further our knowledge and understanding of this topic.

    View details for DOI 10.1016/j.ahj.2012.07.019

    View details for Web of Science ID 000310506000010

    View details for PubMedID 23067905

  • Current Outcomes in US Children With Cardiomyopathy Listed for Heart Transplantation CIRCULATION-HEART FAILURE Singh, T. P., Almond, C. S., Piercey, G., Gauvreau, K. 2012; 5 (5): 594-601

    Abstract

    Previous studies have reported worse outcomes in children with nondilated cardiomyopathy (CMP) listed for heart transplant compared with children with dilated CMP. We sought to compare wait-list and posttransplant outcomes in these groups in the current era.We analyzed all children <18 years of age with a diagnosis of CMP listed for heart transplant in the United States between July 2004 and December 2010. Multivariable risk factors for death on the wait-list (or becoming too sick to transplant) and posttransplant graft loss (median follow-up 2 years) were assessed using Cox models. Of the 1436 children analyzed, 1197 (83%) had dilated CMP and 239 (17%) had nondilated CMP (167 restrictive CMP, 72 hypertrophic CMP). In adjusted analysis, children with nondilated CMP were at higher risk of wait-list mortality only if they were on a ventilator support at listing (hazard ratio, 2.3; CI, 1.2-4.5). The risk was similar among children not on a ventilator support (hazard ratio, 0.6; CI, 0.3-1.1). Posttransplant 30-day and 1-year survival was 98% and 94%, respectively, in children with dilated CMP versus 95% and 89%, respectively, in children with nondilated CMP (P=0.17, log-rank test). In adjusted analysis, the risk of posttransplant graft loss was higher in nondilated CMP (hazard ratio, 1.8; CI, 1.2-2.7) versus dilated CMP.The increased risk of wait-list mortality in children with nondilated CMP is limited to those on ventilator support at listing. Although the risk of graft loss is modestly higher in children with nondilated forms of CMP, their short-term transplant outcomes are good.

    View details for DOI 10.1161/CIRCHEARTFAILURE.112.969980

    View details for Web of Science ID 000313579500011

    View details for PubMedID 22899768

  • Prospective Trial of a Pediatric Ventricular Assist Device NEW ENGLAND JOURNAL OF MEDICINE Fraser, C. D., Jaquiss, R. D., Rosenthal, D. N., Humpl, T., Canter, C. E., Blackstone, E. H., Naftel, D. C., Ichord, R. N., Bomgaars, L., Tweddell, J. S., Massicotte, M. P., Turrentine, M. W., Cohen, G. A., Devaney, E. J., Pearce, F. B., Carberry, K. E., Kroslowitz, R., Almond, C. S. 2012; 367 (6): 532-541

    Abstract

    Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited.We conducted a prospective, single-group trial of a ventricular assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO).For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%).Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).

    View details for DOI 10.1056/NEJMoa1014164

    View details for Web of Science ID 000307310800007

    View details for PubMedID 22873533

  • Racial and Ethnic Differences in Wait-List Outcomes in Patients Listed for Heart Transplantation in the United States CIRCULATION Singh, T. P., Almond, C. S., Taylor, D. O., Milliren, C. E., Graham, D. A. 2012; 125 (24): 3022-?

    Abstract

    Racial differences in long-term survival after heart transplant (HT) are well known. We sought to assess racial/ethnic differences in wait-list outcomes among patients listed for HT in the United States in the current era.We compared wait-list and posttransplant in-hospital mortality among white, black, and Hispanic patients ≥ 18 years of age listed for their primary HT in the United States between July 2006 and September 2010. Of 10 377 patients analyzed, 71% were white, 21% were black, and 8% were Hispanic. Black and Hispanic patients were more likely to be listed with higher urgency (listing status 1A/1B) in comparison with white patients (P<0.001). Overall, 10.5% of white, 11.6% of black, and 13.4% of Hispanic candidates died on the wait-list or became too sick for a transplant within 1 year of listing. After adjusting for baseline risk factors, Hispanic patients were at higher risk of wait-list mortality (hazard ratio 1.51, 95% CI 1.23, 1.85) in comparison with white patients, but not black patients (hazard ratio 1.13, 95% CI 0.97, 1.31). In comparison with white HT recipients, posttransplant in-hospital mortality was higher in black recipients (odds ratio 1.53, 95% CI 1.15, 2.03) but was not different in Hispanic recipients (odds ratio 0.78, 95% CI 0.48, 1.29).Hispanic patients listed for HT in the United States appear to be at higher risk of dying on the wait-list or becoming too sick for a transplant in comparison with white patients. Black patients are not at higher risk of wait-list mortality, but they have higher early posttransplant mortality.

    View details for DOI 10.1161/CIRCULATIONAHA.112.092643

    View details for Web of Science ID 000306975700015

    View details for PubMedID 22589383

  • A Risk-Prediction Model for In-hospital Mortality After Heart Transplantation in US Children AMERICAN JOURNAL OF TRANSPLANTATION Almond, C. S., Gauvreau, K., Canter, C. E., Rajagopal, S. K., Piercey, G. E., Singh, T. P. 2012; 12 (5): 1240-1248

    Abstract

    We sought to develop and validate a quantitative risk-prediction model for predicting the risk of posttransplant in-hospital mortality in pediatric heart transplantation (HT). Children <18 years of age who underwent primary HT in the United States during 1999-2008 (n = 2707) were identified using Organ Procurement and Transplant Network data. A risk-prediction model was developed using two-thirds of the cohort (random sample), internally validated in the remaining one-third, and independently validated in a cohort of 338 children transplanted during 2009-2010. The best predictive model had four categorical variables: hemodynamic support (ECMO, ventilator support, VAD support vs. medical therapy), cardiac diagnosis (repaired congenital heart disease [CHD], unrepaired CHD vs. cardiomyopathy), renal dysfunction (severe, mild-moderate vs. normal) and total bilirubin (≥ 2.0, 0.6 to <2.0 vs. <0.6 mg/dL). The C-statistic (0.78) and the Hosmer-Lemeshow goodness-of-fit (p = 0.89) in the model-development cohort were replicated in the internal validation and independent validation cohorts (C-statistic 0.75, 0.81 and the Hosmer-Lemeshow goodness-of-fit p = 0.49, 0.53, respectively) suggesting acceptable prediction for posttransplant in-hospital mortality. We conclude that this risk-prediction model using four factors at the time of transplant has good prediction characteristics for posttransplant in-hospital mortality in children and may be useful to guide decision-making around patient listing for transplant and timing of mechanical support.

    View details for DOI 10.1111/j.1600-6143.2011.03932.x

    View details for Web of Science ID 000303235100022

    View details for PubMedID 22300640

  • Decline in Heart Transplant Wait List Mortality in the United States Following Broader Regional Sharing of Donor Hearts CIRCULATION-HEART FAILURE Singh, T. P., Almond, C. S., Taylor, D. O., Graham, D. A. 2012; 5 (2): 249-U225

    Abstract

    A change in allocation algorithm in July 2006 allowed broader regional sharing of donor hearts in the United States (US). We assessed if the allocation change has been associated with a decline in wait list mortality in the US.We compared baseline characteristics and outcomes in patients ≥18 years old listed for a primary heart transplant in the US before (July 1, 2004-July 11, 2006, Era1) and after (July 12, 2006-June 30, 2009, Era 2) the change in allocation algorithm. Of 11 864 patients in the study, 4503 were listed during Era 1 and 7361 during Era 2. Patients listed during Era 2 were more likely to be listed status 1A, have an implantable cardioverter-defibrillator, and supported on a continuous flow assist device (P<0.001 for distribution. Patients listed in Era 2 were at a 17% lower risk of dying on the wait list or becoming too sick to transplant (adjusted hazard ratio, 0.83, 95% CI 0.75, 0.93). Transplant recipients in Era 2 were more likely to be transplanted as status 1A (37% versus 48%, respectively, P<0.001). Post-transplant in-hospital mortality (6.3% versus 5.4%; adjusted odds ratio, 0.86 for Era 2, 95% CI 0.79, 1.06) and 1-year survival were similar.The risk of death on the wait list or becoming too sick to transplant has decreased by 17% in the US since the allocation algorithm allowing broader regional sharing was implemented in 2006. The shift in hearts to sicker candidates has not resulted in higher in-hospital or first year post-transplant mortality.

    View details for DOI 10.1161/CIRCHEARTFAILURE.111.964247

    View details for Web of Science ID 000302120800026

    View details for PubMedID 22247484

  • Pediatric heart failure and worsening renal function: Association with outcomes after heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Rajagopal, S. K., Yarlagadda, V. V., Thiagarajan, R. R., Singh, T. P., Givertz, M. M., Almond, C. S. 2012; 31 (3): 252-258

    Abstract

    Renal function deteriorates in some children awaiting heart transplantation. This study was initiated to assess the effects of worsening renal function (WRF) on post-heart transplantation outcomes and to determine the effect of waiting-list associated WRF on survival after heart transplantation.All children aged <18 years who underwent their first heart transplantation between 1999 and 2009, had reported plasma creatinine concentrations at listing and at transplantation, and were free of renal replacement therapy at listing were identified using the Organ Procurement and Transplant Network database. The independent effects of WRF on in-hospital mortality and post-discharge survival were assessed using logistic regression and log-rank analyses, respectively.Of the 2,216 children included in the analysis, WRF occurred in 334 (15%) awaiting heart transplantation: WRF was mild (stage 1) in 210 (63%), moderate (stage 2) in 40 (12%), and severe (stage 3) in 84 (25%). All WRF stages were independently associated with in-hospital, post-transplant mortality: mild WRF with adjusted odds ratio (AOR) of 2.1 (95% confidence interval [CI], 1.2-3.5); moderate WRF, 2.7 (95% CI, 1.1-6.7); and severe WRF, 3.6 (95% CI, 2.0-6.5). WRF was not associated with death after discharge (hazard ratio, 1.2; 95% CI, 0.9-1.7) at a median follow-up of 2.7 years.WRF occurs in 15% of children awaiting heart transplantation and is associated with early but not late post-transplant mortality.

    View details for DOI 10.1016/j.healun.2011.08.018

    View details for Web of Science ID 000300806500005

    View details for PubMedID 22014450

  • Risk Prediction for Early In-Hospital Mortality Following Heart Transplantation in the United States CIRCULATION-HEART FAILURE Singh, T. P., Almond, C. S., Semigran, M. J., Piercey, G., Gauvreau, K. 2012; 5 (2): 259-U239

    Abstract

    Risk factors for early mortality after heart transplant (HT) have not been used for quantitative risk prediction. We sought to develop and validate a risk prediction model for posttransplant in-hospital mortality in HT recipients.We derived the model in subjects aged ≥18 years who underwent primary HT in the United States from January 2007 to June 2009 (n=4248) and validated it internally using a bootstrapping technique (200 random samples, n=4248). We then assessed the model's performance in patients receiving an HT from July 2009 to October 2010 (external validation cohort, n=2346). Posttransplant in-hospital mortality was 4.7% in the model derivation cohort. The best-fitting model based on recipient characteristics at transplant had 6 variables: age, diagnosis, type of mechanical support, ventilator support, estimated glomerular filtration rate, and total serum bilirubin. Model discrimination for survivors versus nonsurvivors was acceptable during derivation and internal validation (C statistic, 0.722 and 0.731, respectively) as was model calibration during derivation (Hosmer Lemeshow [HL] P=0.47). Model performance was reasonable in the external validation cohort (predicted mortality, 4.9%; actual mortality, 4.3%; R(2)=0.95; C statistic, 0.68; HL P=0.48). Adding the donor-related variables of age and ischemic time to the model improved its performance in both the model derivation (C statistic, 0.742; HL P=0.70) and the external validation (C statistic, 0.695; HL P=0.42) cohorts.The proposed model allows risk stratification of HT candidates for early posttransplant mortality and may be useful in counseling patients with regard to their posttransplant prognosis. The model with additional donor-related variables may be useful during donor selection.

    View details for DOI 10.1161/CIRCHEARTFAILURE.111.965996

    View details for Web of Science ID 000302120800027

    View details for PubMedID 22308287

  • Ventricular assist devices for mechanical circulatory support in children. World journal for pediatric & congenital heart surgery Thiagarajan, R. R., Almond, C. S., Cooper, D. S., Morales, D. L. 2012; 3 (1): 104-109

    Abstract

    Ventricular assist devices (VADs) are increasingly used in children to provide mechanical circulatory support as a bridge to cardiac transplantation. In this article, we review information on the current status, outcomes, and future directions for the use of VADs in children.

    View details for DOI 10.1177/2150135111425393

    View details for PubMedID 23804692

  • The FDA Review Process for Cardiac Medical Devices in Children: A Review for the Clinician. Progress in pediatric cardiology 2012; 33 (2): 105–9

    Abstract

    Pediatric medical devices play a vital role in the treatment of children with cardiovascular disease. Most cardiac medical devices used in children today are used off-label where the risk-benefit of devices has not been well characterized. Pediatric medical devices face a variety of challenges to FDA approval related in large part to the small target population, heterogeneity of the patient population and ethical considerations of device testing in children. While relatively few cardiac devices have received FDA approval in children, the number of devices navigating the approval process successfully is growing. Most pediatric device approvals are being granted through the humanitarian device exemption (HDE) pathway, which is designed for rare diseases making it suitable for devices treating congenital heart disease. This review summarizes the FDA review process for pediatric medical devices as it continues to evolve in response to the unique challenges of understanding device performance in the pediatric population.

    View details for DOI 10.1016/j.ppedcard.2012.02.002

    View details for PubMedID 22661882

  • Trends in Wait-List Mortality in Children Listed for Heart Transplantation in the United States: Era Effect Across Racial/Ethnic Groups AMERICAN JOURNAL OF TRANSPLANTATION Singh, T. P., Almond, C. S., Piercey, G., Gauvreau, K. 2011; 11 (12): 2692-2699

    Abstract

    We sought to evaluate trends in overall and race-specific pediatric heart transplant (HT) wait-list mortality in the United States (US) during the last 20 years. We identified all children <18 years old listed for primary HT in the US during 1989-2009 (N = 8096, 62% White, 19% Black, 13% Hispanic and 6% Other) using the Organ Procurement and Transplant Network database. Wait-list mortality was assessed in four successive eras (1989-1994, 1995-1999, 2000-2004 and 2005-2009). Overall wait-list mortality declined in successive eras (26%, 23%, 18% and 13%, respectively). The decline across eras remained significant in adjusted analysis (hazard ratio [HR] 0.70 in successive eras, 95% confidence interval [CI], 0.67-0.74) and was 67% lower for children listed during 2005-2009 versus those listed during 1989-1994 (HR 0.33; CI, 0.28-0.39). In models stratified by race, wait-list mortality decreased in all racial groups in successive eras. In models stratified by era, minority children were not at higher risk of wait-list mortality in the most recent era. We conclude that the risk of wait-list mortality among US children listed for HT has decreased by two-thirds during the last 20 years. Racial gaps in wait-list mortality present variably in the past are not present in the current era.

    View details for DOI 10.1111/j.1600-6143.2011.03723.x

    View details for Web of Science ID 000297411800021

    View details for PubMedID 21883920

  • Sudden death after pediatric heart transplantation: Analysis of data from the Pediatric Heart Transplant Study Group JOURNAL OF HEART AND LUNG TRANSPLANTATION Daly, K. P., Chakravarti, S. B., Tresler, M., Naftel, D. C., Blume, E. D., Dipchand, A. I., Almond, C. S. 2011; 30 (12): 1395-1402

    Abstract

    Sudden death is a well-recognized complication of heart transplantation. Little is known about the incidence and risk factors for sudden death after transplant in children. The purpose of this study was to determine the incidence of and risk factors for sudden death.This retrospective multicenter cohort study used the Pediatric Heart Transplant Study Group (PHTS) database, an event-driven registry of children aged <18 at listing undergoing heart transplantation between 1993 and 2007. Standard Kaplan-Meier and parametric analyses were used for survival analysis. Multivariate analysis in the hazard-function domain was used to identify risk factors for sudden death after transplant.Of 604 deaths in 2,491 children who underwent heart transplantation, 94 (16%) were classified as sudden. Freedom from sudden death was 97% at 5 years, and the hazard for sudden death remained constant over time at 0.01 deaths/year. Multivariate risk factors associated with sudden death included black race (hazard ratio [HR], 2.6; p < 0.0001), United Network of Organ Sharing (UNOS) status 2 at transplant (HR, 1.8; p = 0.008), older age (HR, 1.4/10 years of age; p = 0.03), and an increased number of rejection episodes in the first post-transplant year (HR, 1.6/episode; p = 0.03).Sudden death accounts for 1 in 6 deaths after heart transplant in children. Older recipient age, recurrent rejection within the first year, black race, and UNOS status 2 at listing were associated with sudden death. Patients with 1 or more of these risk factors may benefit from primary prevention efforts.

    View details for DOI 10.1016/j.healun.2011.08.015

    View details for Web of Science ID 000297385400014

    View details for PubMedID 21996348

  • Association of graft ischemic time with survival after heart transplant among children in the United States JOURNAL OF HEART AND LUNG TRANSPLANTATION Ford, M. A., Almond, C. S., Gauvreau, K., Piercey, G., Blume, E. D., Smoot, L. B., Fynn-Thompson, F., Singh, T. P. 2011; 30 (11): 1244-1249

    Abstract

    Previous studies have found no association between graft ischemic time (IT) and survival in pediatric heart transplant (HTx) recipients. However, previous studies were small or analyzed risk only at the extremes of IT, where observations are few. We sought to determine whether graft IT is independently associated with graft survival in a large cohort of children with no a priori assumptions about where the risk threshold may lie.All children aged <18 years in the U.S. undergoing primary HTx (1987 to 2008) were included. The primary end point was graft loss (death or retransplant) within 6 months. Multivariate analysis was performed to analyze the association between graft IT and graft loss within 6 months after transplant. A secondary end point of longer-term graft loss was assessed among recipients who survived the first 6 months after transplant.Of 4,716 pediatric HTxs performed, the median IT was 3.5 hours (interquartile range, 2.7-4.3 hours). Adjusted analysis showed that children with an IT > 3.5 hours were at increased risk of graft loss within 6 months after transplant (hazard ratio, 1.3; 95% confidence interval, 1.1-1.5; p = 0.002). Among 6-month survivors, IT was not associated with longer-term graft loss.IT beyond 3.5 hours is associated with a 30% increase in risk of graft loss within 6 months in pediatric HT recipients. Although the magnitude of risk associated with IT is small compared with the risk associated with recipient factors, these findings may be important during donor assessment for high-risk transplant candidates.

    View details for DOI 10.1016/j.healun.2011.05.001

    View details for Web of Science ID 000296399600006

    View details for PubMedID 21676628

  • Berlin Heart EXCOR Pediatric ventricular assist device Investigational Device Exemption study: Study design and rationale AMERICAN HEART JOURNAL Almond, C. S., Buchholz, H., Massicotte, P., Ichord, R., Rosenthal, D. N., Uzark, K., Jaquiss, R. D., Kroslowitz, R., Kepler, M. B., Lobbestael, A., Bellinger, D., Blume, E. D., Fraser, C. D., Bartlett, R. H., Thiagarajan, R., Jenkins, K. 2011; 162 (3): 425-U41

    Abstract

    Currently, there are no Food and Drug Administration-approved devices available that can provide long-term mechanical circulatory support to smaller children with severe heart failure as a bridge to heart transplant (HT). In recent years, the Berlin Heart EXCOR Pediatric ventricular assist device (VAD) has emerged as a potential treatment option. Systematic data on the safety and efficacy of the EXCOR are limited.The Investigational Device Exemption (IDE) clinical study is designed to evaluate the safety and probable benefit of the EXCOR to support regulatory review of the device under the Humanitarian Device Exemption regulation. The study design and rationale are reviewed in light of the well-described challenges inherent in small population studies.The Berlin Heart EXCOR IDE clinical study is a prospective, multicenter, single-arm, clinical cohort study. Children aged 0 to 16 years with severe heart failure (Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2) due to 2-ventricle heart disease and actively listed for HT comprise the primary study cohort. The control population is a propensity-matched retrospective cohort of children supported with extracorporeal membrane oxygenation, the only bridge device available to smaller children before the EXCOR. The primary efficacy end point is survival to heart transplantation or recovery. The primary safety end point is the incidence of serious adverse events as defined by pediatric Interagency Registry for Mechanically Assisted Circulatory Support criteria. The study will enroll a total of 48 subjects in 2 cohorts based on body surface area (cohort 1 <0.7 m(2), cohort 2 0.7-1.5 m(2)) and is powered to show safety superiority to a prespecified performance goal of 0.25 serious adverse events per day of support. Children ineligible for the primary cohort will still have access to the device in a third compassionate-use cohort where adverse event data will be collected for additional safety characterization of the device.The Berlin Heart IDE clinical study will be the first bridge-to-HT VAD study designed exclusively for children. It is anticipated that the study will provide important information on the safety and efficacy of the Berlin Heart EXCOR Pediatric in children while providing valuable lessons into the design and conduct of future VAD studies in children.

    View details for DOI 10.1016/j.ahj.2011.05.026

    View details for Web of Science ID 000294447400003

    View details for PubMedID 21884857

  • Extracorporeal Membrane Oxygenation for Bridge to Heart Transplantation Among Children in the United States Analysis of Data From the Organ Procurement and Transplant Network and Extracorporeal Life Support Organization Registry CIRCULATION Almond, C. S., Singh, T. P., Gauvreau, K., Piercey, G. E., Fynn-Thompson, F., Rycus, P. T., Bartlett, R. H., Thiagarajan, R. R. 2011; 123 (25): 2975-2984

    Abstract

    Extracorporeal membrane oxygenation (ECMO) has served for >2 decades as the standard of care for US children requiring mechanical support as a bridge to heart transplantation. Objective data on the safety and efficacy of ECMO for this indication are limited. We describe the outcomes of ECMO as a bridge to heart transplantation to serve as performance benchmarks for emerging miniaturized assist devices intended to replace ECMO.Data from the Extracorporeal Life Support Organization Registry and the Organ Procurement Transplant Network database were merged to identify children supported with ECMO and listed for heart transplantation from 1994 to 2009. Independent predictors of wait-list and posttransplantation in-hospital mortality were identified. Objective performance goals for ECMO were developed. Of 773 children, the median age was 6 months (interquartile range, 1 to 44 months); 28% had cardiomyopathy; and in 38%, a bridge to transplantation was intended at ECMO initiation. Overall, 45% of subjects reached transplantation, although one third of those transplanted died before discharge; overall survival to hospital discharge was 47%. Wait-list mortality was independently associated with congenital heart disease, cardiopulmonary resuscitation before ECMO, and renal dysfunction. Posttransplantation mortality was associated with congenital heart disease, renal dysfunction, ECMO duration of >14 days, and initial ECMO indication as a bridge to recovery. In the objective performance goal cohort (n=485), patients with cardiomyopathy had the highest survival to hospital discharge (63%), followed by patients with myocarditis (59%), 2-ventricle congenital heart disease (44%) and 1-ventricle congenital heart disease (33%).Although ECMO is effective for short-term circulatory support, it is not reliable for the long-term circulatory support necessary for children awaiting heart transplantation. Fewer than half of patients bridged with ECMO survive to hospital discharge. More effective modalities for chronic circulatory support in children are urgently needed.

    View details for DOI 10.1161/CIRCULATIONAHA.110.991505

    View details for Web of Science ID 000292092200016

    View details for PubMedID 21670232

  • Improved Survival in Heart Transplant Recipients in the United States Racial Differences in Era Effect CIRCULATION-HEART FAILURE Singh, T. P., Almond, C., Givertz, M. M., Piercey, G., Gauvreau, K. 2011; 4 (2): 153-U75

    Abstract

    Posttransplant survival in heart transplant recipients has progressively improved during the past 2 decades. It is unknown, however, whether the major racial groups in the United States have benefited equally.We analyzed all primary heart transplant recipients aged ≥18 years in the United States from 1987 to 2008. We compared posttransplant survival in white, black, and Hispanic recipients in 5 successive eras (1987 to 1992, 1993 to 1996, 1997 to 2000, 2001 to 2004, 2005 to 2008). Early survival was defined as freedom from death or retransplantation during the first 6 months posttransplant. Longer-term, conditional survival was assessed in patients who survived the first 6 months. There were 29 986 (81.6%) white, 4745 (12.9%) black, and 2017 (5.5%) Hispanic patients in the study cohort. Black patients were at increased risk of early death or retransplant (hazard ratio [HR], 1.15; 95% CI, 1.05 to 1.26) in adjusted analysis. Early posttransplant survival improved (HR, 0.83; 95% CI, 0.80 to 0.87 for successive eras) equally in all 3 groups (black-era interaction, P=0.94; Hispanic-era interaction, P=0.40). Longer-term survival improved in white (HR, 0.95; 95% CI, 0.92 to 0.97 for successive eras) but not in black (HR, 1.04; 95% CI, 0.99 to 1.09) or Hispanic (HR, 1.02; 95% CI, 0.95 to 1.09) recipients, resulting in increased disparities in longer-term survival with time.Early posttransplant survival has improved equally in white, black, and Hispanic heart transplant recipients. Longer-term survival has improved in white but not in black or Hispanic recipients, resulting in a more marked disparity in outcomes in the current era. These disparities warrant further investigation and targeted interventions.

    View details for DOI 10.1161/CIRCHEARTFAILURE.110.957829

    View details for Web of Science ID 000288445300009

    View details for PubMedID 21228316

  • Factors associated with in-hospital mortality in infants undergoing heart transplantation in the United States JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Gandhi, R., Almond, C., Singh, T. P., Gauvreau, K., Piercey, G., Thiagarajan, R. R. 2011; 141 (2): 531-U1267

    Abstract

    Infants undergoing heart transplantation have the highest early posttransplant mortality of any age group. We sought to determine the pretransplantation factors associated with in-hospital mortality in transplanted infants in the current era.All infants under 12 months of age who underwent primary heart transplantation during a recent 10-year period (1999-2009) in the United States were identified using the Organ Procurement and Transplant Network database. Multivariable logistic regression was used to identify independent pretransplantation factors associated with in-hospital mortality.Of 730 infants in the study (median age 3.8 months), 462 (63%) had congenital heart disease, 282 (39%) were supported by a ventilator, 94 (13%) with extracorporeal membrane oxygenation, and 22 (3%) with a ventricular assist device at the time of transplantation. Overall, 82 (11.2%) infants died before their initial hospital discharge. In adjusted analysis, in-hospital mortality was associated with repaired congenital heart disease (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.8, 7.2), unrepaired congenital heart disease not on prostaglandin E (OR, 2.8; CI, 1.3, 6.1), extracorporeal membrane oxygenator support (OR, 6.1; CI, 2.8, 13.4), ventilator support (OR, 4.4; CI, 2.3, 8.3), creatinine clearance less than 40 mL·min(-1)·1.73 m(-2) (OR, 3.1; CI, 1.7, 5.3), and dialysis (OR, 6.2; CI, 2.1, 18.3) at transplantation.One in 9 infants undergoing heart transplantation dies before hospital discharge. Pretranplantation factors associated with early mortality include congenital heart disease, extracorporeal membrane oxygenator support, mechanical ventilation, and renal failure. Risk stratification for early posttransplant mortality among infants listed for heart transplantation may improve decision-making for transplant eligibility, organ allocation, and posttransplant interventions to reduce mortality.

    View details for DOI 10.1016/j.jtcvs.2010.10.025

    View details for Web of Science ID 000286222800038

    View details for PubMedID 21241863

  • Bridging children of all sizes to cardiac transplantation: The initial multicenter North American experience with the Berlin Heart EXCOR ventricular assist device JOURNAL OF HEART AND LUNG TRANSPLANTATION Morales, D. L., Almond, C. S., Jaquiss, R. D., Rosenthal, D. N., Naftel, D. C., Massicotte, M. P., Humpl, T., Turrentine, M. W., Tweddell, J. S., Cohen, G. A., Kroslowitz, R., Devaney, E. J., Canter, C. E., Fynn-Thompson, F., Reinhartz, O., Imamura, M., Ghanayem, N. S., Buchholz, H., Furness, S., Mazor, R., Gandhi, S. K., Fraser, C. D. 2011; 30 (1): 1-8

    Abstract

    Beginning in 2000 and accelerating in 2004, the Berlin Heart EXCOR (Berlin Heart Inc Woodlands, TX) became the first pediatric-specific ventricular assist device (VAD) applied throughout North America for children of all sizes. This retrospective study analyzed the initial Berlin Heart EXCOR pediatric experience as a bridge to transplantation.Between June 2000 and May 2007, 97 EXCOR VADs were implanted in North America at 29 different institutions. The analysis is limited to 73 patients (75%) from 17 institutions, for which retrospective data were available.Median age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR.This limited but large preliminary North American experience with the Berlin Heart EXCOR VAD as a bridge to cardiac transplantation for children of all ages and sizes points to the feasibility of this approach. The prospective investigational device evaluation trial presently underway will further characterize the safety and efficacy of the EXCOR as a bridge to pediatric cardiac transplantation.

    View details for DOI 10.1016/j.healun.2010.08.033

    View details for Web of Science ID 000286287000001

    View details for PubMedID 21145473

  • Improved Survival in Pediatric Heart Transplant Recipients: Have White, Black and Hispanic Children Benefited Equally? AMERICAN JOURNAL OF TRANSPLANTATION Singh, T. P., Almond, C. S., Gauvreau, K. 2011; 11 (1): 120-128

    Abstract

    We assessed whether the improvement in posttransplant survival in pediatric heart transplant (HT) recipients during the last two decades has benefited the major racial groups in the United States equally. We analyzed all children <18 years of age who underwent their first HT in the US during 1987-2008. We compared trends in graft loss (death or retransplant) in white, black and Hispanic children in five successive cohorts (1987-1992, 1993-1996, 1997-2000, 2001-2004, 2005-2008). The primary endpoint was early graft loss within 6 months posttransplant. Longer-term survival was assessed in recipients who survived the first 6 months. The improvement in early posttransplant survival was similar (hazard ratio [HR] for successive eras 0.80, 95% confidence interval [CI] 0.7, 0.9, p = 0.24 for black-era interaction, p = 0.22 for Hispanic-era interaction) in adjusted analysis. Longer-term survival was worse in black children (HR 2.2, CI 1.9, 2.5) and did not improve in any group with time (HR 1.0 for successive eras, CI 0.9, 1.1, p = 0.57; p = 0.19 for black-era interaction, p = 0.21 for Hispanic-era interaction). Thus, the improvement in early post-HT survival during the last two decades has benefited white, black and Hispanic children equally. Disparities in longer-term survival have not narrowed with time; the survival remains worse in black recipients.

    View details for DOI 10.1111/j.1600-6143.2010.03357.x

    View details for Web of Science ID 000285783500018

    View details for PubMedID 21199352

  • Outcomes of heart transplantation using donor hearts from infants with sudden infant death syndrome JOURNAL OF HEART AND LUNG TRANSPLANTATION Silva, J. N., Canter, C. E., Singh, T. P., Gauvreau, K., Piercey, G. E., Berul, C. I., Smoot, L. B., Blume, E. D., Fynn-Thompson, F., Almond, C. S. 2010; 29 (11): 1226-1230

    Abstract

    Uncertainty exists whether hearts from infants who have died of sudden infant death syndrome (SIDS) are acceptable for transplantation because the mechanism of death in SIDS remains unclear. We analyzed post-transplant outcomes in infants who received a heart from a donor where SIDS was the primary cause of brain death.This retrospective multicenter cohort study used data from the Organ Procurement and Transplant Network (OPTN). All infants aged < 12 months undergoing heart transplant between 1994 and 2008 were included. A Cox proportional hazards model was used to determine whether donor SIDS was independently associated with post-transplant graft loss (death or retransplant).During the study period, 66 of 1033 infants (6.4%) who underwent heart transplant received an allograft from a SIDS donor. These infants were similar to the remaining infants with respect to age, diagnosis, blood type, and invasive support. In multivariable analysis, graft loss was associated with congenital heart disease (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.2-2.1), ventilator (HR, 1.4; 95% CI, 1.1-1.9), and extracorporeal membrane oxygenation support (HR, 3.0; 95% CI, 2.2-4.3), but not donor SIDS (HR, 1.0; 95% CI, 0.6-1.5), suggesting graft survival in SIDS-donor heart recipients was similar to the remaining infants. Primary causes of post-transplant death in infants receiving SIDS-donor hearts and the remaining infants were similar.Graft survival was similar in infants who received SIDS-donor hearts compared with those who received hearts from donors who died of other causes. There was no increase in incidence of non-rejection-related cardiac deaths after transplant in these children.

    View details for DOI 10.1016/j.healun.2010.06.004

    View details for Web of Science ID 000284030700004

    View details for PubMedID 20691612

  • Are Angiotensin-Converting Enzyme Inhibitors and Beta-Blockers Ineffective in Children With Dilated Cardiomyopathy and Heart Failure? JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Singh, T. P., Almond, C. 2010; 56 (10): 823-823

    View details for DOI 10.1016/j.jacc.2010.04.037

    View details for Web of Science ID 000281207700015

    View details for PubMedID 20797500

  • Impact of ABO-Incompatible Listing on Wait-List Outcomes Among Infants Listed for Heart Transplantation in the United States A Propensity Analysis CIRCULATION Almond, C. S., Gauvreau, K., Thiagarajan, R. R., Piercey, G. E., Blume, E. D., Smoot, L. B., Fynn-Thompson, F., Singh, T. P. 2010; 121 (17): 1926-1933

    Abstract

    The purported advantage of ABO-incompatible (ABO-I) listing is to reduce wait times and wait-list mortality among infants awaiting heart transplantation. We sought to describe recent trends in ABO-I listing for US infants and to determine the impact of ABO-I listing on wait times and wait-list mortality.In this multicenter retrospective cohort study using Organ Procurement and Transplant Network data, infants<12 months of age listed for heart transplantation between 1999 and 2008 (n=1331) were analyzed. Infants listed for an ABO-I transplant were compared with a propensity score-matched cohort listed for an ABO-compatible transplant through the use of a Cox shared-frailty model. The primary end point was time to heart transplantation. The percentage of eligible infants listed for an ABO-I heart increased from 0% before 2002 to 53% in 2007 (P<0.001 for trend). Compared with infants listed exclusively for an ABO-compatible heart, infants with a primary ABO-I listing strategy (n=235) were more likely to be listed 1A, to have congenital heart disease and renal failure, and to require extracorporeal membrane oxygenation. For the propensity score-matched groups (n=197 matched pairs), there was no difference in wait-list mortality; however, infants with blood type O assigned an ABO-I listing strategy were more likely to undergo heart transplantation by 30 days (31% versus 16%; P=0.007) with a less pronounced effect for infants with other blood types.The proportion of US infants listed for an ABO-I heart transplantation has risen dramatically in recent years but still appears to be preferentially used for sicker infant candidates. The ABO-I listing strategy is associated with a higher likelihood of transplantation within 30 days for infants with blood group O and may benefit a broader range of transplantation candidates.

    View details for DOI 10.1161/CIRCULATIONAHA.109.885756

    View details for Web of Science ID 000277262300007

    View details for PubMedID 20404257

  • Safety and early outcomes using a corticosteroid-avoidance immunosuppression protocol in pediatric heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Singh, T. P., Faber, C., Blume, E. D., Worley, S., Almond, C. S., Smoot, L. B., Dillis, S., Nasman, C., Boyle, G. J. 2010; 29 (5): 517-522

    Abstract

    Long-term oral corticosteroids have been a mainstay of maintenance immunosuppression in pediatric heart transplantation. In this study, we report early clinical outcomes in a cohort of pediatric heart transplant recipients managed using a steroid-avoidance protocol.Of the 70 patients who underwent heart transplantation during the study period, 55 eligible recipients, including 49 non-sensitized and 6 sensitized (all 55 with negative crossmatch) patients, entered a steroid-avoidance immunosuppression protocol consisting of thymoglobin induction followed by a 2-drug, tacrolimus-based, corticosteroid-free regimen. The primary outcome variable was freedom from moderate rejection (International Society for Heart and Lung Transplantation [ISHLT] Grade 2R/3A or antibody-mediated rejection).The median age at transplant was 7.1 years (range 2 weeks to 22 years) and median follow-up was 19 months (range 2 to 46 months). Fifty patients survived to discharge after transplantation. Of these patients, 2 (4%) were discharged on steroids and 8 (16%) started on maintenance steroids at follow-up. Rejection was diagnosed in 8 patients (Grade 2R cellular rejection in 3 and antibody-mediated rejection in 5). Freedom from rejection was 92% at 6 months (95% confidence interval [CI] 80% to 97%) and 87% at 1 year (CI 73% to 94%). Post-transplant survival was 91% at 6 months (CI 79% to 96%) and 88% at 12 and 24 months (CI 75% to 95%). There was 1 death due to rejection (antibody-mediated) 8 months after transplantation.An immunosuppression protocol consisting of induction followed by corticosteroid avoidance appears to achieve acceptable rejection rates during the first year post-transplant in pediatric heart transplant recipients.

    View details for DOI 10.1016/j.healun.2009.11.601

    View details for Web of Science ID 000277169900005

    View details for PubMedID 20061164

  • Extracorporeal membrane oxygenation for the support of infants, children, and young adults with acute myocarditis: A review of the Extracorporeal Life Support Organization registry CRITICAL CARE MEDICINE Rajagopal, S. K., Almond, C. S., Laussen, P. C., Rycus, P. T., Wypij, D., Thiagarajan, R. R. 2010; 38 (2): 382-387

    Abstract

    To describe survival outcomes for pediatric patients supported with extracorporeal membrane oxygenation for severe myocarditis and identify risk factors for in-hospital mortality.Retrospective review of Extracorporeal Life Support Organization registry database.Data reported to Extracorporeal Life Support Organization from 116 extracorporeal membrane oxygenation centers.Patients < or = 18 yrs of age supported with extracorporeal membrane oxygenation for myocarditis during 1995 to 2006.None.Of 19,348 reported pediatric extracorporeal membrane oxygenation uses from 1995 to 2006, 260 runs were for 255 patients with a diagnosis of myocarditis (1.3%). Survival to hospital discharge was 61%. Seven patients (3%) underwent heart transplantation and six patients survived to discharge. Of 100 patients not surviving to hospital discharge, extracorporeal membrane oxygenation support was withdrawn in 70 (70%) with multiple organ failure as the indication in 58 (83%) patients. In a multivariable model, female gender (adjusted odds ratio, 2.3, 95% confidence interval, 1.3-4.2), arrhythmia on extracorporeal membrane oxygenation (adjusted odds ratio, 2.7, 95% confidence interval, 1.5-5.1), and renal failure requiring dialysis (adjusted odds ratio, 5.1, 95% confidence interval, 2.3-11.4) were associated with increased odds of in-hospital mortality.Extracorporeal membrane oxygenation is a valuable tool to rescue children with severe cardiorespiratory compromise related to myocarditis. Female gender, arrhythmia on extracorporeal membrane oxygenation, and need for dialysis during extracorporeal membrane oxygenation were associated with increased mortality.

    View details for DOI 10.1097/CCM.0b013e3181bc8293

    View details for Web of Science ID 000273927700003

    View details for PubMedID 19789437

  • Outcome of Pediatric Patients With Dilated Cardiomyopathy Listed for Transplant: A Multi-institutional Study JOURNAL OF HEART AND LUNG TRANSPLANTATION Kirk, R., Naftel, D., Hoffman, T. M., Almond, C., Boyle, G., Caldwell, R. L., Kirklin, J. K., White, K., Dipchand, A. I. 2009; 28 (12): 1322-1328

    Abstract

    The course of dilated cardiomyopathy (DCM) leading to heart failure in children varies; survival with conventional treatment is 64% at 5 years. Heart transplantation (HTx) enables improved survival; however, outcomes from listing for transplant are not well described. This study reports survival of patients with DCM from listing with the availability of mechanical bridge to transplant.Patients with a primary diagnosis of DCM (n = 1,098) were identified from a multi-institutional, prospective, registry of patients aged < 18 years listed for HTx from January 1, 1993, to December 31, 2006.Characteristics of DCM patients at listing included a mean age of 7.3 years; 51% male, 64% white ethnicity, 77% United Network for Organ Sharing status I, 66% on inotropic support, 28% mechanically ventilated, and 15% on mechanical support. Waitlist mortality was 11%, and 75% underwent HTx at 2 years after listing. Overall 10-year survival after listing was 72%, with higher risk of death associated with arrhythmias, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO) support, but not ventricular assist device (VAD) support. Survival at 10 years post-HTx was 72%, with a higher risk of death associated with black race, older age, mechanical ventilation, longer ischemic time, and earlier era of transplant.Transplantation for DCM in the pediatric population offers enhanced survival compared with the natural history. Overall waitlist mortality for DCM is low, with the exception of patients on ECMO, mechanically ventilated, or with arrhythmias. DCM patients fared well after transplant, making HTx a key therapeutic intervention.

    View details for DOI 10.1016/j.healun.2009.05.027

    View details for Web of Science ID 000272943500015

    View details for PubMedID 19782601

  • Incidence and Risk Factors for Mortality in Infants Awaiting Heart Transplantation in the USA JOURNAL OF HEART AND LUNG TRANSPLANTATION Mah, D., Singh, T. P., Thiagarajan, R. R., Gauvreau, K., Piercey, G. E., Blume, E. D., Fynn-Thompson, F., Almond, C. S. 2009; 28 (12): 1292-1298

    Abstract

    Infants awaiting heart transplantation (HT) face the highest wait-list mortality among all children and adults listed for HT in the USA. We sought to determine the risk of death for infants <12 months old while awaiting HT in the current era, and to identify the principle risk factors associated with wait-list mortality.We analyzed outcomes for all infants listed for HT in the USA from January 1999 to July 2006, using data reported to the U.S. Scientific Registry of Transplant Recipients.Of the 1,133 listed infants, 61% were <3 months of age, 80% were listed as Status 1A, 64% had a congenital heart disease (CHD) and 31% had cardiomyopathy. Of 724 infants with CHD, 25% were on prostaglandin (PG) and 27% had a history of prior surgery. By 6 months after listing, 23% died on the wait-list and 54% were transplanted. Multivariate factors associated with wait-list mortality were weight <3 kg (hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), extracorporeal membrane oxygenation (ECMO) support (HR 5.6, CI 4.0 to 7.9), ventilator support (HR 2.1, 95% CI 1.6 to 2.8), CHD with PG support (HR 2.8, 95% CI 1.8 to 4.3), CHD without prior surgery (HR 2.8, 95% CI 1.9 to 3.9) and non-white race/ethnicity (HR 1.8, 95% CI 1.4 to 2.3).One in four infants listed for HT in the USA die before a donor heart can be identified. Wait-list mortality is associated with weight <3 kg, level of invasive support and CHD, but not listing status, which captures medical urgency poorly. Measures to expand infant organ donation, especially among neonates, are urgently needed.

    View details for DOI 10.1016/j.healun.2009.06.013

    View details for Web of Science ID 000272943500011

    View details for PubMedID 19782580

  • Racial and Ethnic Differences in Mortality in Children Awaiting Heart Transplant in the United States AMERICAN JOURNAL OF TRANSPLANTATION Singh, T. P., Gauvreau, K., Thiagarajan, R., Blume, E. D., Piercey, G., Almond, C. S. 2009; 9 (12): 2808-2815

    Abstract

    Racial differences in outcomes are well known in children after heart transplant (HT) but not in children awaiting HT. We assessed racial and ethnic differences in wait-list mortality in children <18 years old listed for primary HT in the United States during 1999-2006 using multivariable Cox models. Of 3299 listed children, 58% were listed as white, 20% as black, 16% as Hispanic, 3% as Asian and 3% were defined as 'Other'. Mortality on the wait-list was 14%, 19%, 21%, 17% and 27% for white, black, Hispanic, Asian and Other children, respectively. Black (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.3, 1.9), Hispanic (HR 1.5, CI 1.2, 1.9), Asian (HR, 2.0, CI 1.3, 3.3) and Other children (HR 2.3, CI 1.5, 3.4) were all at higher risk of wait-list death compared to white children after controlling for age, listing status, cardiac diagnosis, hemodyamic support, renal function and blood group. After adjusting additionally for medical insurance and area household income, the risk remained higher for all minorities. We conclude that minority children listed for HT have significantly higher wait-list mortality compared to white children. Socioeconomic variables appear to explain a small fraction of this increased risk.

    View details for DOI 10.1111/j.1600-6143.2009.02852.x

    View details for Web of Science ID 000272127600022

    View details for PubMedID 19845580

  • Waiting List Mortality Among Children Listed for Heart Transplantation in the United States CIRCULATION Almond, C. S., Thiagarajan, R. R., Piercey, G. E., Gauvreau, K., Blume, E. D., Bastardi, H. J., Fynn-Thompson, F., Singh, T. P. 2009; 119 (5): 717-727

    Abstract

    Children listed for heart transplantation face the highest waiting list mortality in solid-organ transplantation medicine. We examined waiting list mortality since the pediatric heart allocation system was revised in 1999 to determine whether the revised allocation system is prioritizing patients optimally and to identify specific high-risk populations that may benefit from emerging pediatric cardiac assist devices.We conducted a multicenter cohort study using the US Scientific Registry of Transplant Recipients. All children <18 years of age who were listed for a heart transplant between 1999 and 2006 were included. Among 3098 children, the median age was 2 years (interquartile range 0.3 to 12 years), and median weight was 12.3 kg (interquartile range 5 to 38 kg); 1294 (42%) were nonwhite; and 1874 (60%) were listed as status 1A (of whom 30% were ventilated and 18% were on extracorporeal membrane oxygenation). Overall, 533 (17%) died, 1943 (63%) received transplants, and 252 (8%) recovered; 370 (12%) remained listed. Multivariate predictors of waiting list mortality include extracorporeal membrane oxygenation support (hazard ratio [HR] 3.1, 95% confidence interval [CI] 2.4 to 3.9), ventilator support (HR 1.9, 95% CI 1.6 to 2.4), listing status 1A (HR 2.2, 95% CI 1.7 to 2.7), congenital heart disease (HR 2.2, 95% CI 1.8 to 2.6), dialysis support (HR 1.9, 95% CI 1.2 to 3.0), and nonwhite race/ethnicity (HR 1.7, 95% CI 1.4 to 2.0).US waiting list mortality for pediatric heart transplantation remains unacceptably high in the current era. Specific high-risk subgroups can be identified that may benefit from emerging pediatric cardiac assist technologies. The current pediatric heart-allocation system captures medical urgency poorly. Further research is needed to define the optimal organ-allocation system for pediatric heart transplantation.

    View details for DOI 10.1161/CIRCULATIONAHA.108.815712

    View details for Web of Science ID 000263186500011

    View details for PubMedID 19171850

  • Pediatric Circulatory Support Contractors' Meeting Report of the Clinical Trials Working Group ASAIO JOURNAL Webber, S. 2009; 55 (1): 10-12

    View details for Web of Science ID 000262425400004

    View details for PubMedID 19139653

  • Outcome after Fontan failure and takedown to an intermediate palliative circulation ANNALS OF THORACIC SURGERY Almond, C. S., Mayer, J. E., Thiagarajan, R. R., Blume, E. D., del Nido, P. J., McElhinney, D. B. 2007; 84 (3): 880-887

    Abstract

    Fontan takedown to an intermediate palliative circulation is an important treatment option for patients with acute or subacute failure of a Fontan circulation from a variety of causes. Little is known about the subsequent outcome of these patients or their potential candidacy for a second attempt at Fontan completion.Patients followed up at Children's Hospital Boston who underwent takedown of a Fontan circulation to an intermediate palliative circulation within 1 year of Fontan completion were reviewed.Between 1979 and 2006, 53 patients underwent Fontan takedown at a median age of 2.3 years (range, 0.3 to 36.5 years). Takedown was performed during the Fontan procedure itself in 12 patients (22%), within the first postoperative month in 31(58%), and between 1 month and 1 year in 10 (18%). Overall, 29 patients (55%) survived the early period after takedown, and 19 ultimately underwent successful Fontan completion a median of 4.6 years after takedown; all but one was alive a median of 6.4 years later. Thirteen (68%) of the 19 had treatable abnormalities contributing to Fontan failure.Fontan takedown can provide effective stabilization of the acutely or subacutely failing Fontan circulation, although a substantial number of patients die early despite Fontan takedown. Subjects surviving the perioperative period can often undergo uneventful redo Fontan. A thorough evaluation for treatable abnormalities should be performed in all patients with a failing Fontan circulation and in patients who undergo Fontan takedown.

    View details for DOI 10.1016/j.athoracsur.2007.02.092

    View details for Web of Science ID 000248982400025

    View details for PubMedID 17720394

  • Pediatric ventricular assist devices PEDIATRIC CARDIOLOGY Fynn-Thompson, F., Almond, C. 2007; 28 (2): 149-155

    Abstract

    Ventricular assist device therapy is continuing to evolve in the practice of pediatric cardiac surgery. Although ECMO is still the most often applied mechanical support for infants and young children, a broader range of pulsatile, paracorporeal, as well as implantable ventricular assist devices are now available for pediatric application. A number of these innovative devices have been developed specifically for pediatric use with miniaturized pumps and optimized cannulas suitable for the entire age range of pediatric patients including neonates. Unlike ECMO, these devices can offer medium- to long-term support and have been successfully utilized as a bridge to transplant as well as a bridge to recovery. This review examines the different types of devices currently available, their clinical indications for use, future devices, and the current results of pediatric ventricular assist device therapy in the treatment of heart failure in the pediatric population.

    View details for DOI 10.1007/s00246-006-1453-6

    View details for Web of Science ID 000246359400011

    View details for PubMedID 17265106

  • Cardiac troponin increases among runners in the Boston Marathon ANNALS OF EMERGENCY MEDICINE Fortescue, E. B., Shin, A. Y., Greenes, D. S., Mannix, R. C., Agarwal, S., Feldman, B. J., Shah, M. I., Rifai, N., Landzberg, M. J., Newburger, J. W., Almond, C. S. 2007; 49 (2): 137-143

    Abstract

    Studies indicate that running a marathon can be associated with increases in serum cardiac troponin levels. The clinical significance of such increases remains unclear. We seek to determine the prevalence of troponin increases and epidemiologic factors associated with these increases in a large and heterogeneous cohort of marathon finishers.Entrants in the 2002 Boston Marathon were recruited 1 to 2 days before the race. Data collected included demographic and training history, symptoms experienced during the run, and postrace troponin T and I levels. Simple descriptive statistics were performed to describe the prevalence of troponin increases and runner characteristics.Of 766 runners enrolled, 482 had blood analyzed at the finish line. In all, 34% were women, 20% were younger than 30 years, and 92% had run at least 1 previous marathon. Most runners (68%) had some degree of postrace troponin increase (troponin T > or = 0.01 ng/mL or troponin I > or = 0.1 ng/mL), and 55 (11%) had significant increases (troponin T > or = 0.075 ng/mL or troponin I > or = 0.5 ng/mL). Running inexperience (< 5 previous marathons) and young age (< 30 years) were associated with elevated troponins. These correlates were robust throughout a wide range of troponin thresholds considered. Health factors, family history, training, race performance, and symptoms were not associated with increases.Troponin increases were relatively common among marathon finishers and can reach levels typically diagnostic for acute myocardial infarction. Less marathon experience and younger age appeared to be associated with troponin increases, whereas race duration and the presence of traditional cardiovascular risk factors were not. Further work is needed to determine the clinical significance of these findings.

    View details for DOI 10.1016/j.annemergmed.2006.09.024

    View details for Web of Science ID 000243957800002

    View details for PubMedID 17145114

  • High-risk medical devices, children and the FDA: Regulatory challenges facing pediatric mechanical circulatory support devices 2nd International Conference on Pediatric Mechanical Circulatory Support Systems/Pediatric Cardiopulmonary Perfusion Almond, C. S., Chen, E. A., Berman, M. R., Less, J. R., Baldwin, J. T., Linde-Feucht, S. R., Hoke, T. R., Pearson, G. D., Jenkins, K., Duncan, B. W., Zuckerman, B. D. LIPPINCOTT WILLIAMS & WILKINS. 2007: 4–7

    Abstract

    Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

    View details for DOI 10.1097/01.mat.0000247958.84788.3a

    View details for Web of Science ID 000243692200002

    View details for PubMedID 17237642

  • Successful use of bivalirudin for cardiac transplantation in a child with heparin-induced thrombocytopenia JOURNAL OF HEART AND LUNG TRANSPLANTATION Almond, C. S., Harrington, J., Thiagarajan, R., Duncan, C. N., LaPierre, R., Halwick, D., Blume, E. D., del Nido, P. J., Neufeld, E. J., McGowan, F. X. 2006; 25 (11): 1376-1379

    Abstract

    Bivalirudin, a direct thrombin inhibitor, has recently emerged as a promising option for anti-coagulation during cardiopulmonary bypass in patients who cannot receive heparin. There is limited experience with the use of bivalirudin in children. We present the case of a child with heparin-induced thrombocytopenia with thrombosis (HIT Type II) who underwent successful orthotopic cardiac transplantation using bivalirudin as the primary anti-coagulant for cardiopulmonary bypass.

    View details for DOI 10.1016/j.healun.2006.08.005

    View details for Web of Science ID 000242222100017

    View details for PubMedID 17097505

  • Successful implantation of a Berlin heart biventricular assist device in a failing single ventricle JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Nathan, M., Baird, C., Fynn-Thompson, F., Almond, C., Thiagarajan, R., Laussen, P., Blume, E., Pigula, F. 2006; 131 (6): 1407-1408

    View details for DOI 10.1016/j.jtcvs.2006.02.015

    View details for Web of Science ID 000238023300041

    View details for PubMedID 16733184

  • The Boston Marathon study: A novel approach to research during residency PEDIATRICS Shin, A. Y., Almond, C. S., Mannix, R. C., Duncan, C. N., Son, M. B., McLauchlan, H. M., Kanaan, U. B., Litzow, J. M., Riney, P. S., Trenor, C. C., Fortescue, E. B., Vinci, R. J., Greenes, D. S. 2006; 117 (5): 1818-1822

    Abstract

    Resident physicians from a pediatric academic training program developed a hospital-wide research project in an effort to enhance their residency research experience. In this model, residents themselves assumed primary responsibility for each stage of a large prospective clinical research study. The project, which was integrated successfully into the residency program, enabled a large group of residents, with mentorship from a dedicated faculty member, to benefit from a structured clinical research experience while providing the flexibility necessary to meet the demands of a busy residency curriculum. Careful topic selection with a well-defined end point, faculty involvement, resident collegiality, and institutional support were factors identified by study leaders as central to the success of this model.

    View details for DOI 10.1542/peds.2005-1249

    View details for Web of Science ID 000237207300076

    View details for PubMedID 16651344

  • Three independent biological mechanisms cause exercise-associated hyponatremia: Evidence from 2,135 weighed competitive athletic performances PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Noakes, T. D., Sharwood, K., Speedy, D., Hew, T., Reid, S., Dugas, J., Almond, C., Wharam, P., Weschler, L. 2005; 102 (51): 18550-18555

    Abstract

    To evaluate the role of fluid and Na+ balance in the development of exercise-associated hyponatremia (EAH), changes in serum Na+ concentrations ([Na+]) and in body weight were analyzed in 2,135 athletes in endurance events. Eighty-nine percent of athletes completed these events either euhydrated (39%) or with weight loss (50%) and with normal (80%) or elevated (13%) serum [Na+]. Of 231 (11%) athletes who gained weight during exercise, 70% were normonatremic or hypernatremic, 19% had a serum [Na+] between 129-135 mmol/liter, and 11% a serum [Na+] of <129 mmol/liter. Serum [Na+] after racing was a linear function with a negative slope of the body weight change during exercise. The final serum [Na+] in a subset of 18 subjects was predicted from the amount of Na+ that remained osmotically inactive at the completion of the trial. Weight gain consequent to excessive fluid consumption was the principal cause of a reduced serum [Na+] after exercise, yet most (70%) subjects who gained weight maintained or increased serum [Na+], requiring the addition of significant amounts of Na+ (>500 mmol) into an expanded volume of total body water. This Na+ likely originated from osmotically inactive, exchangeable stores. Thus, EAH occurs in athletes who (i) drink to excess during exercise, (ii) retain excess fluid because of inadequate suppression of antidiuretic hormone secretion, and (iii) osmotically inactivate circulating Na+ or fail to mobilize osmotically inactive sodium from internal stores. EAH can be prevented by insuring that athletes do not drink to excess during exercise, which has been known since 1985.

    View details for DOI 10.1073/pnas.0509096102

    View details for Web of Science ID 000234174300055

    View details for PubMedID 16344476

  • Current management of severe congenital mitral stenosis - Outcomes of transcatheter and surgical therapy in 108 infants and children CIRCULATION McElhinney, D. B., Sherwood, M. C., Keane, J. F., Del Nido, P. J., Almond, C. S., Lock, J. E. 2005; 112 (5): 707-714

    Abstract

    Severe congenital mitral stenosis (MS) is a rare anomaly that is frequently associated with additional left heart obstructions. Anatomic treatments for congenital MS include balloon mitral valvuloplasty (BMVP), surgical mitral valvuloplasty (SMVP), and mitral valve replacement (MVR), although the optimal therapeutic strategy is unclear.Between 1985 and 2003, 108 patients with severe congenital MS underwent BMVP or surgical intervention at a median age of 18 months (range 1 month to 17.9 years). Anatomic subtypes of MS were "typical" congenital MS in 78 patients, supravalvar mitral ring in 46, parachute mitral valve in 28, and double-orifice mitral valve in 11, with multiple types in approximately 50% of patients. Additional left heart anomalies were present in 82 patients (76%). The first MS intervention was BMVP in 64 patients, SMVP in 33, and MVR in 11. BMVP decreased peak and mean MS gradients by a median of 33% and 38%, respectively (P<0.001), but was complicated by significant mitral regurgitation in 28%. Cross-sectional follow-up was obtained at 4.8+/-4.2 years. Overall, Kaplan-Meier survival was 92% at 1 month, 84% at 1 year, and 77% at 5 years, with 69% 5-year survival during the first decade of our experience and 87% since (P=0.09). Initial MVR and younger age were associated with worse survival. Survival free from failure of biventricular repair or mitral valve reintervention was 55% at 1 year among patients who underwent BMVP and 69% among patients who underwent supravalvar mitral ring resection initially. Among patients who underwent BMVP, survival free from failure of biventricular repair or MVR was 79% at 1 month and 55% at 5 years, with worse outcome in younger patients and those who developed significant postdilation mitral regurgitation.BMVP effectively relieves left ventricular inflow obstruction in most infants and children with severe congenital MS who require intervention. However, surgical resection is preferable in patients with MS due to a supravalvar mitral ring. Five-year survival is relatively poor in patients with severe congenital MS, with worse outcomes in infants and patients undergoing MVR, but has improved in our more recent experience. Many patients have undergone second procedures for either recurrent/residual MS or mitral regurgitation resulting from dilation-related disruption of the mitral valve apparatus.

    View details for DOI 10.1161/CIRCULATIONAHA.104.500207

    View details for Web of Science ID 000230895200013

    View details for PubMedID 16043648

  • Consensus statement of the 1st International Exercise-Associated Hyponatremia Consensus Development Conference, Cape Town, South Africa 2005. Clinical journal of sport medicine Hew-Butler, T., Almond, C., Ayus, J. C., Dugas, J., Meeuwisse, W., Noakes, T., Reid, S., Siegel, A., Speedy, D., Stuempfle, K., Verbalis, J., Weschler, L. 2005; 15 (4): 208-213

    View details for PubMedID 16003032

  • Consensus statement of the 1st International Exercise-Associated Hyponatremia Consensus Development Conference, Cape Town, South Africa 2005 CLINICAL JOURNAL OF SPORT MEDICINE Hew-Butler, T., Almond, C., Ayus, J. C., Dugas, J., Meeuwisse, W., Noakes, T., Reid, S., Siegel, A., Speedy, D., Stuempfle, K., Verbalis, J., Weschler, L. 2005; 15 (4): 206-211
  • Hyponatremia among runners in the Boston Marathon NEW ENGLAND JOURNAL OF MEDICINE Almond, C. S., Shin, A. Y., Fortescue, E. B., Mannix, R. C., Wypij, D., Binstadt, B. A., Duncan, C. N., Olson, D. P., Salerno, A. E., Newburger, J. W., Greenes, D. S. 2005; 352 (15): 1550-1556

    Abstract

    Hyponatremia has emerged as an important cause of race-related death and life-threatening illness among marathon runners. We studied a cohort of marathon runners to estimate the incidence of hyponatremia and to identify the principal risk factors.Participants in the 2002 Boston Marathon were recruited one or two days before the race. Subjects completed a survey describing demographic information and training history. After the race, runners provided a blood sample and completed a questionnaire detailing their fluid consumption and urine output during the race. Prerace and postrace weights were recorded. Multivariate regression analyses were performed to identify risk factors associated with hyponatremia.Of 766 runners enrolled, 488 runners (64 percent) provided a usable blood sample at the finish line. Thirteen percent had hyponatremia (a serum sodium concentration of 135 mmol per liter or less); 0.6 percent had critical hyponatremia (120 mmol per liter or less). On univariate analyses, hyponatremia was associated with substantial weight gain, consumption of more than 3 liters of fluids during the race, consumption of fluids every mile, a racing time of >4:00 hours, female sex, and low body-mass index. On multivariate analysis, hyponatremia was associated with weight gain (odds ratio, 4.2; 95 percent confidence interval, 2.2 to 8.2), a racing time of >4:00 hours (odds ratio for the comparison with a time of <3:30 hours, 7.4; 95 percent confidence interval, 2.9 to 23.1), and body-mass-index extremes.Hyponatremia occurs in a substantial fraction of nonelite marathon runners and can be severe. Considerable weight gain while running, a long racing time, and body-mass-index extremes were associated with hyponatremia, whereas female sex, composition of fluids ingested, and use of nonsteroidal antiinflammatory drugs were not.

    View details for Web of Science ID 000228324200007

    View details for PubMedID 15829535