Olaf Reinhartz

All Publications

Is Continuous Flow Superior to Pulsatile Flow in Single Ventricle Mechanical Support? Results from a Large Animal Pilot Study. ASAIO journal (American Society for Artificial Internal Organs : 1992) Fujii, Y., Ferro, G., Kagawa, H., Centola, L., Zhu, L., Ferrier, W. T., Talken, L., Riemer, R. K., Maeda, K., Nasirov, T., Hodges, B., Amirriazi, S., Lee, E., Sheff, D., May, J., May, R., Reinhartz, O. ; 61 (4): 443–47
Abstract

Durable mechanical support in situations of physiologic single ventricle has been met with little success so far, particularly in small children. We created an animal model to investigate whether pulsatile or continuous flow would be superior. Three 1 month old sheep (10-16 kg) were instrumented. Via sternotomy and with cardiopulmonary bypass, a large ventricular septal defect and atrial septal defect were created. The left ventricle was cannulated using a Berlin Heart inflow cannula. This was connected sequentially to a continuous flow device (Thoratec HeartMate X, Pleasanton, CA) and to a pulsatile device (Berlin Heart Excor, The Woodlands, TX). Outflow was via a Y-graft to both aorta and pulmonary artery, striving for equal flow to both. Atrial filling pressures were controlled with volume infusions over a wide range. Under comparable loading conditions, significantly higher maximum flow was obtained by HeartMate X than by Excor (4.95 ± 1.27 L/min [range, 3.84-6.34 L/min] for HeartMate X vs. 1.80 ± 0.85 L/min [range, 1.01-2.7 L/min] for Excor; p < 0.05). Judging from this limited animal study, in single ventricle scenarios, continuous flow devices may achieve higher pump flows than pulsatile devices when provided with similar filling pressures. Their clinical use should be investigated. More extensive experimental studies are needed.

View details for PubMedID 25794246
Aortic or Pulmonary Valved Homograft Right Ventricle to Pulmonary Artery Conduit in the Norwood Procedure. World journal for pediatric & congenital heart surgery Nasirov, T., Maeda, K., Reinhartz, O. 2019; 10 (4): 499–501
Abstract

BACKGROUND: Several modifications of the Norwood procedure utilizing valved right ventricle to pulmonary artery conduits have recently been reported. Our group has been using aortic or pulmonary valved homografts combined with PTFE tube grafts for now 16 years.METHODS: In this report, we review our technique in detail and describe any changes that have occurred over the years. We provide detailed illustrations of our preferred surgical technique, report outcome data, and compare it to the other conduit options available.RESULTS: Between 2006 and 2015, 130 stage I Norwood procedures were performed at our institution, 100 of them using valved conduits. Our technique is described and illustrated in detail. Early mortality was 15%. Postoperative percutaneous intervention on the conduit was required in 29% of cases.CONCLUSIONS: While a randomized trial comparing different valved conduits is lacking, we believe a composite conduit made from homograft aortic or pulmonary valves and PTFE tube grafts is an excellent choice in stage I Norwood procedure.

View details for DOI 10.1177/2150135119842865

View details for PubMedID 31307304
Bridge to Transplant with Ventricular Assist Device Support in Pediatric Patients with Single Ventricle Heart Disease. ASAIO journal (American Society for Artificial Internal Organs : 1992) Chen, S., Rosenthal, D. N., Murray, J., Dykes, J. C., Almond, C. S., Yarlagadda, V. V., Wright, G., Navaratnam, M., Reinhartz, O., Maeda, K. 2019
Abstract

Ventricular assist device (VAD) support for children with single ventricle (SV) heart disease remains challenging. We performed a single-center retrospective review of SV patients on VAD support and examined survival to transplant using the Kaplan-Meier method. Patients transplanted were compared with those who died on support. Between 2009 and 2017, there were 14 SV patients with 1,112 patient-days of VAD support. Stages of palliation included pre-Glenn (n = 5), Glenn (n = 5), and Fontan (n = 4). Eight patients (57%) were successfully bridged to transplant at a median 107 days. Deaths occurred early (n = 6, median 16 days) and in smaller patients (10.1 vs. 28.3 kg, P = 0.04). All Fontan patients survived to transplant, whereas only 20% of Glenn patients survived to transplant. Adverse events occurred in 79% (n = 11). Five patients met hospital discharge criteria, with two patients (one pre-Glenn, one Glenn) discharged and transplanted after 219 and 174 days of VAD support. All transplanted patients were discharged at a median 21 days posttransplant. SV patients in various stages of palliation can be successfully bridged to transplant with VAD support. With use of intracorporeal continuous-flow devices, longer-term support and hospital discharge are possible.

View details for PubMedID 30864969
Patient-Specific Multiscale Modeling of the Assisted Bidirectional Glenn. The Annals of thoracic surgery Shang, J. K., Esmaily, M., Verma, A., Reinhartz, O., Figliola, R. S., Hsia, T., Feinstein, J. A., Marsden, A. L. 2018
Abstract

BACKGROUND: First-stage palliation of neonates with single-ventricle physiology is associated with poor outcomes and challenging clinical management. Prior computational modeling and invitro experiments introduced the assisted bidirectional Glenn (ABG), which increased pulmonary flow and oxygenation over the bidirectional Glenn (BDG) and the systemic-to-pulmonary shunt in idealized models. In this study, we demonstrate that the ABG achieves similar performance in patient-specific models and assess the influence of varying shunt geometry.METHODS: In a small cohort of single-ventricle prestage 2 patients, we constructed three-dimensional in silico models and tuned lumped parameter networks to match clinical measurements. Each model was modified to produce virtual BDG and ABG surgeries. We simulated the hemodynamics of the stage 1 procedure, BDG, and ABG by using multiscale computational modeling, coupling a finite-element flow solver to the lumped parameter network. Two levels of pulmonary vascular resistances (PVRs) were investigated: baseline (low) PVR of the patients and doubled (high) PVR. The shunt nozzle diameter, anastomosis location, and shape were also manipulated.RESULTS: The ABG increased the pulmonary flow rate and pressure by 15% to 20%, which was accompanied by a rise in superior vena caval pressure (2 to 3 mm Hg) at both PVR values. Pulmonary flow rate and superior vena caval pressures were most sensitive to the shunt nozzle diameter.CONCLUSIONS: Patient-specific ABG performance was similar to prior idealized simulations and experiments, with good performance at lower PVR values in the range of measured clinical data. Larger shunt outlet diameters and lower PVR led to improved ABG performance.

View details for PubMedID 30471273
Effect of Inhaled Nitric Oxide on Hemodynamics in Lambs with 1 Ventricle Circulation. ASAIO journal (American Society for Artificial Internal Organs : 1992) Kanamitsu, H., Fujii, Y., Centola, L., Kinouchi, K., Zhu, L., Riemer, R. K., Reinhartz, O. 2018; 64 (6): 802–5
Abstract

Inhaled nitric oxide (NO) is widely used to treat postoperative pulmonary hypertension in congenital heart disease. It is believed that NO increases cardiac output (CO) by decreasing pulmonary vascular resistance (PVR), leading to increased left ventricular preload. However, the effect of NO on CO in patients with 1 ventricle circulation remains unclear. To evaluate this, a superior cavopulmonary (SCP) shunt was constructed in 10 juvenile sheep. A PTFE graft was inserted between the superior vena cava (SVC) and the main pulmonary artery (PA). The SVC was clamped at the right atrial junction to establish a 1 ventricle circulation. Flows, pressures, and arterial blood gases were recorded before and during inhalation of NO. Mean arterial pressure (46.6±5.4 to 44.6±5.9mm Hg; p = 0.06) and left atrial pressure (4.0±2.5 to 4.0±2.3mm Hg; p = 1.0) did not change. Mean PA pressure (13.6±2.4 to 11.7±2.9mm Hg; p = 0.006) and PVR (5.47±2.99 to 4.54±2.61 Wood Units; p = 0.037) decreased significantly. SVC flow (24.8±11.3 to 22.0±9.7ml/min/kg; p = 0.09) did not change, and CO decreased (140.2±37.2 to 132.1±39.2ml/min/kg; p = 0.033). Arterial PO2 improved (103.72±29.30 to 132.43±47.02mm Hg; p = 0.007). In this 1 ventricle model, NO surprisingly decreased cardiac output (CO) and did not increase left ventricular preload.

View details for PubMedID 29210771
Combined En-Bloc Heart Liver Transplantation in Children with Congenital Heart Disease Complicated by Cardiac Cirrhosis Conlon, S., Maeda, K., Reinhartz, O., Hollander, S., Rosenthal, D., Gallo, A., Concepcion, W., Esquivel, C., Bonham, A. LIPPINCOTT WILLIAMS & WILKINS. 2018: S295
View details for Web of Science ID 000444541200473
Characteristics of deposits and pump exchange in the Berlin Heart EXCOR ventricular assist device: Experience with 67 cases. Pediatric transplantation Maeda, K., Almond, C., Hollander, S. A., Rosenthal, D. N., Kaufman, B., Gowen, M. M., Murray, J., Shuttleworth, P., Reinhartz, O. 2018: e13181
Abstract

Pump exchanges are frequently required in the Berlin Heart EXCOR VAD. We intended to describe the characteristics of pump deposits in a larger patient series and evaluate if changes in our exchange procedure over time have led to increased complications. We reviewed all EXCOR pump exchanges in our institution from July 2004 to October 2014. We gathered data on size and location of pump deposits and exchange procedures. EXCOR devices were implanted in 38 children. Support was LVAD only in 22, BiVAD in 13, and SVAD in 3 cases. Sixty-seven pumps were exchanged. The incidence of pump exchanges per month was higher for smaller pumps and for RVADs vs LVADs. Indications were visible pump deposit in 55, stroke without visible deposit in 5, incorporation of membrane oxygenator in 3, pump size change in 2, and sepsis in 1 case, respectively. Deposits were located in the outflow valve in 73%, inflow valve in 22%, pump body in 3%, and outflow cannula in 3%. EXCOR pumps are predominantly exchanged for deposits, which are most frequently located in the outflow valves. The procedure is now carried out without sedation at the bedside. No major complications were observed during exchanges.

View details for PubMedID 29635728
Interstage evaluation of homograft-valved right ventricle to pulmonary artery conduits for palliation of hypoplastic left heart syndrome JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Sandeep, N., Punn, R., Balasubramanian, S., Smith, S. N., Reinhartz, O., Zhang, Y., Wright, G. E., Peng, L. F., Wise-Faberowski, L., Hanley, F. L., McElhinney, D. B. 2018; 155 (4): 1747-+
Abstract

Palliation of hypoplastic left heart syndrome with a standard nonvalved right ventricle to pulmonary artery conduit results in an inefficient circulation in part due to diastolic regurgitation. A composite right ventricle pulmonary artery conduit with a homograft valve has a hypothetical advantage of reducing regurgitation, but may differ in the propensity for stenosis because of valve remodeling.This retrospective cohort study included 130 patients with hypoplastic left heart syndrome who underwent a modified stage 1 procedure with a right ventricle to pulmonary artery conduit from 2002 to 2015. A composite valved conduit (cryopreserved homograft valve anastomosed to a polytetrafluoroethylene tube) was placed in 100 patients (47 aortic, 32 pulmonary, 13 femoral/saphenous vein, 8 unknown), and a nonvalved conduit was used in 30 patients. Echocardiographic functional parameters were evaluated before and after stage 1 palliation and before the bidirectional Glenn procedure, and interstage interventions were assessed.On competing risk analysis, survival over time was better in the valved conduit group (P = .040), but this difference was no longer significant after adjustment for surgical era. There was no significant difference between groups in the cumulative incidence of bidirectional Glenn completion (P = .15). Patients with a valved conduit underwent more interventions for conduit obstruction in the interstage period, but this difference did not reach significance (P = .16). There were no differences between groups in echocardiographic parameters of right ventricle function at baseline or pre-Glenn.In this cohort of patients with hypoplastic left heart syndrome, inclusion of a valved right ventricle to pulmonary artery conduit was not associated with any difference in survival on adjusted analysis and did not confer an identifiable benefit on right ventricle function.

View details for PubMedID 29223842
Ventricular Assist Devices for Neonates and Infants. Seminars in thoracic and cardiovascular surgery. Pediatric cardiac surgery annual Maeda, K., Rosenthal, D. N., Reinhartz, O. 2018; 21: 9–14
Abstract

Heart transplant waitlist survival in pediatric patients has been substantially improved since the introduction of pediatric-specific ventricular assist device. In neonates and infants, however, the waitlist mortality remains very high. The only long-term device currently approved for use in the United States is the Berlin Heart EXCOR, but this device has several important limitations because of the paracorporeal, pulsatile nature of the underlying technology. We reviewed Stanford ventricular assist experience on patients less than 1 year old since 2004. It shows overall 1-, 3-, and 5-year survival were 68%, 62%, and 49%, respectively. There are statistically significant differences in survival among cardiomyopathy group, end-stage congenital heart disease group and single ventricle group. In order to improve outcomes in this extremely high risk group, modifications were made to anticoagulation protocols, cannulation strategy in hypertrophic cardiomyopathy patients, and preferential use of continuous flow pumps in a single ventricle patients. The long-waited PumpKIN trial testing the Jarvik 2015 is about to start with the first human implant.

View details for PubMedID 29425530
Major Aortopulmonary Collateral Arteries With Anatomy Other Than Pulmonary Atresia/Ventricular Septal Defect. Annals of thoracic surgery Patrick, W. L., Mainwaring, R. D., Reinhartz, O., Punn, R., Tacy, T., Hanley, F. L. 2017
Abstract

Major aortopulmonary collateral arteries (MAPCAs) are frequently found in association with pulmonary atresia with ventricular septal defect (PA/VSD). However, some patients with MAPCAs do not have PA/VSD but have a variety of other "atypical" anatomic diagnoses.This was a retrospective review of patients with MAPCAs and atypical anatomy. The 50 patients with MAPCAs could be divided into two subgroups: (1) single ventricle anatomy (n = 33) and (2) two ventricle anatomy (n = 17).The 33 patients with MAPCAs and single ventricle included 15 with unbalanced complete atrioventricular canal (CAVC), 6 with pulmonary atresia-intact ventricular septum, and 12 with other forms of single ventricle. The initial cardiac operation included unifocalization/shunt in 24 patients and creation of aortopulmonary window or central shunt in 9 patients. There were seven operative and eight late deaths. Sixteen patients have had a bidirectional Glenn procedure and 6 had a Fontan procedure. The 17 patients with MAPCAs and two ventricles included 5 with CAVC, 4 with corrected transposition, 3 with double outlet right ventricle, 3 with scimitar syndrome, and 2 with complex D-transposition. The initial cardiac operation included single-stage complete repair in 5 patients, unifocalization/shunt in 10 patients, and aortopulmonary window in 2 patients. There were two operative and two late deaths. Thirteen patients have achieved complete repair status.The data demonstrate the wide diversity of anatomy seen in patients with MAPCAs when evaluating diagnoses other than PA/VSD. Two-thirds of the patients had single ventricle and was associated with a relatively high mortality.

View details for DOI 10.1016/j.athoracsur.2017.02.029

View details for PubMedID 28527961
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
Superior performance of continuous over pulsatile flow ventricular assist devices in the single ventricle circulation: A computational study. Journal of biomechanics Schmidt, T., Rosenthal, D., Reinhartz, O., Riemer, K., He, F., Hsia, T., Marsden, A., Kung, E. 2017; 52: 48-54
Abstract

This study compares the physiological responses of systemic-to-pulmonary shunted single ventricle patients to pulsatile and continuous flow ventricular assist devices (VADs). Performance differences between pulsatile and continuous flow VADs have been clinically observed, but the underlying mechanism remains poorly understood. Six systemic-to-pulmonary shunted single ventricle patients (mean BSA=0.30m(2)) were computationally simulated using a lumped-parameter network tuned to match patient specific clinical data. A first set of simulations compared current clinical implementation of VADs in single ventricle patients. A second set modified pulsatile flow VAD settings with the goal to optimize cardiac output (CO). For all patients, the best-case continuous flow VAD CO was at least 0.99L/min greater than the optimized pulsatile flow VAD CO (p=0.001). The 25 and 50mL pulsatile flow VADs exhibited incomplete filling at higher heart rates that reduced CO as much as 9.7% and 37.3% below expectations respectively. Optimization of pulsatile flow VAD settings did not achieve statistically significant (p<0.05) improvement to CO. Results corroborate clinical experience that continuous flow VADs produce higher CO and superior ventricular unloading in single ventricle patients. Impaired filling leads to performance degradation of pulsatile flow VADs in the single ventricle circulation.

View details for DOI 10.1016/j.jbiomech.2016.12.003

View details for PubMedID 28038771
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 PubMedID 28606584
Temporary Circulatory Support in U.S. Children Awaiting Heart Transplantation. Journal of the American College of Cardiology Yarlagadda, V. V., Maeda, K., Zhang, Y., Chen, S., Dykes, J. C., Gowen, M. A., Shuttleworth, P., Murray, J. M., Shin, A. Y., Reinhartz, O., Rosenthal, D. N., McElhinney, D. B., Almond, C. S. 2017; 70 (18): 2250–60
Abstract

Extracorporeal membrane oxygenation (ECMO) has long served as the standard of care for short-term mechanical circulatory support in pediatrics. It is unknown whether newer-generation temporary circulatory support (TCS) devices afford children a meaningful survival advantage over ECMO.This study sought to determine whether bridge-to-heart transplant survival with a TCS device is superior to ECMO after adjusting for patient differences.All children ≤21 years of age listed for heart transplant from 2011 to 2015 who received a TCS device or ECMO as a bridge to transplant were identified using Organ Procurement and Transplantation Network data. Children supported with a TCS device were compared with a propensity score (PS)-matched cohort of children supported with ECMO as a bridge to transplant. The primary endpoint was Kaplan-Meier survival to transplant.The number of TCS devices implanted in children increased from ≤3 per year before 2011 to 50 in 2015. Overall, 93 patients implanted with TCS devices were included for analysis (59% left ventricular assist devices, 23% right ventricular assist devices, 18% biventricular assist devices). The most commonly used device was the CentriMag-PediMag system (65%), followed by TandemHeart (18%), Rotaflow (6%), and Impella (5%). Among 164 PS-matched patients, support duration was longer for the TCS cohort (median 19 days vs. 6 days; p < 0.001), and was longest for the CentriMag-PediMag (24 days vs. 6 days; p < 0.001) with 27% supported for >60 days. Compared with the ECMO cohort, the PS-matched TCS cohort had longer survival to transplant (hazard ratio: 0.49; 95% confidence interval: 0.30 to 0.79) and longer overall survival (hazard ratio: 0.61; 95% confidence interval: 0.39 to 0.96), with 90-day mortality before transplant that was modestly reduced (from 45% with ECMO to 39% with TCS).The use of TCS devices in children as a bridge to transplant has risen rapidly in recent years, led by the growth of magnetically levitated centrifugal flow pumps. Compared with conventional ECMO, TCS durations are longer, and more importantly, patient survival is superior.

View details for PubMedID 29073953
Alternative Strategy for Biventricular Assist Device in an Infant With Hypertrophic Cardiomyopathy. The Annals of thoracic surgery Dykes, J. C., Reinhartz, O., Almond, C. S., Yarlagadda, V., Murray, J., Rosenthal, D. N., Maeda, K. 2017; 104 (2): e185–e186
Abstract

We report an infant with hypertrophic cardiomyopathy who underwent biventricular assist device placement with two 15-mL Berlin Heart EXCOR pediatric ventricular assist devices using an alternative atrial cannulation strategy. The systemic circulation was supported by left atrium (LA) to aorta cannulation. The LA was accessed through the right atrium by extending a 6-mm EXCOR cannula with a Gore-Tex graft connected to an atrial septal defect. The pulmonary circulation was supported with cannulation of the right atrium to pulmonary artery. This alternative cannulation strategy facilitated effective biventricular support and may be applicable to other patients with hypertrophic or restrictive physiology.

View details for PubMedID 28734448
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
Outcomes of pediatric patients supported with continuous-flow ventricular assist devices: A report from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) JOURNAL OF HEART AND LUNG TRANSPLANTATION Rossano, J. W., Lorts, A., Vanderpluym, C. J., Jeewa, A., Guleserian, K. J., Bleiweis, M. S., Reinhartz, O., Blume, E. D., Rosenthal, D. N., Naftel, D. C., Cantor, R. S., Kirklin, J. K. 2016; 35 (5): 585-590
Abstract

Continuous-flow (CF) ventricular assist devices (VADs) have largely replaced pulsatile-flow VADs in adult patients. However, there are few data on CF VADs among pediatric patients. In this study we aimed to describe the overall use, patients' characteristics and outcomes of CF VADs in this population.The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a national registry for U.S. Food and Drug Adminstration (FDA)-approved VADs in patients <19 years of age. Patients undergoing placement of durable CF VADs between September 2012 and June 2015 were included and outcomes were compared with those of adults from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS).CF VADs were implanted in 109 patients at 35 hospitals. The median age at implantation was 15 years (2.8 to 18.9 years) and median weight was 62 kg (range 16 to 141 kg). The underlying disease was cardiomyopathy in 89 (82%) patients. The INTERMACS level at time of implant was Level 1 in 20 (19%), Level 2 in 64 (61%) and Levels 3 to 7 in 21 (20%) patients. Most were implanted as LVADs (n = 102, 94%). Median duration of support was 2.3 months (range <1 day to 28 months). Serious adverse event rates were low, including neurologic dysfunction (early event rate 4.1 per 100 patient-months with 2 late events). Competing outcomes analysis at 6 months post-implant indicated 61% transplanted, 31% alive with device in place and 8% death before transplant. These outcomes compared favorably with the 3,894 adults supported with CF VADs as a bridge to transplant.CF VADs are commonly utilized in older children and adolescents, with excellent survival rates. Further study is needed to understand impact of patient and device characteristics on outcomes in pediatric patients.

View details for DOI 10.1016/j.healun.2016.01.1228

View details for Web of Science ID 000376951900008

View details for PubMedID 27056612
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
Anatomic Factors Associated With Truncal Valve Insufficiency and the Need for Truncal Valve Repair. World journal for pediatric & congenital heart surgery Patrick, W. L., Mainwaring, R. D., Carrillo, S. A., Ma, M., Reinhartz, O., Petrossian, E., Selamet Tierney, E. S., Reddy, V. M., Hanley, F. L. 2016; 7 (1): 9-15
Abstract

Truncus arteriosus is a complex and heterogeneous form of congenital heart defect. Many of the risk factors from several decades ago, including late repair and interrupted aortic arch, have been mitigated through better understanding of the entity and improved surgical techniques. However, truncal valve dysfunction remains an important cause of morbidity and mortality. The purpose of this study was to evaluate the anatomic factors associated with truncal valve dysfunction and the need for truncal valve surgery.This was a retrospective review of 72 infants who underwent repair of truncus arteriosus at our institution. The median age at surgery was nine days, and the median weight was 3.1 kg. Preoperative assessment of truncal valve insufficiency by echocardiography revealed no or trace insufficiency in 30, mild in 25, moderate in 10, and severe in 7. The need for truncal valve surgery was dictated by the severity of truncal valve insufficiency.Sixteen (22%) of the 72 patients undergoing truncus arteriosus repair had concomitant truncal valve surgery. Anatomic factors associated with the need for truncal valve surgery included an abnormal number of truncal valve cusps (P < .005), presence of valve dysplasia (P < .005), and the presence of an anomalous coronary artery pattern (P < .005). Fifteen (94%) of the sixteen patients who underwent concomitant surgery had two or all three of these anatomic factors (sensitivity = 94%, specificity = 85%).This study demonstrates that the presence of specific anatomic factors was closely associated with the presence of truncal valve insufficiency and the need for concomitant truncal valve surgery. Preoperative evaluation of these anatomic factors may provide a useful tool in determining who should undergo concomitant truncal valve surgery.

View details for DOI 10.1177/2150135115608093

View details for PubMedID 26714988
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
Elevated pretransplant pulmonary vascular resistance index does not predict mortality after isolated orthotopic heart transplantation in children: A retrospective analysis of the UNOS database PEDIATRIC TRANSPLANTATION Chiu, P., Schaffer, J. M., Sheikh, A. Y., Ha, R., Reinhartz, O., Mainwaring, R., Reitz, B. A. 2015; 19 (6): 623-633
Abstract

OHT is the definitive therapy in end-stage heart failure. Elevated PVRI is considered a relative contraindication to isolated OHT; this assumption is re-evaluated using data from the UNOS database. A retrospective review of de-identified data from the UNOS dataset was performed. There were 1943 pediatric OHT recipients between 10/87 and 12/11 with sufficient data for analysis. Cox regression was performed to examine the effect of baseline characteristics on post-transplant survival. Patients were propensity matched, and Kaplan-Meier survival analysis was performed comparing cohorts of patients using thresholds of 6 and 9 WU × m(2) . PVRI was not a significant predictor of post-transplant outcomes in either univariate or multivariate Cox regression. Kaplan-Meier analysis revealed no difference in survival between both unmatched and propensity-matched OHT recipients. In conclusion, elevated PVRI was not associated with post-transplant mortality in pediatric OHT recipients. A prospective study assessing the current use of PVRI ≥6 as a threshold to contraindicate isolated OHT should be undertaken. Removing this potentially unnecessary restriction on transplant candidacy may make this life-saving therapy available to a greater number of patients.

View details for DOI 10.1111/petr.12550

View details for Web of Science ID 000358688400018
Conserved and divergent aspects of human T-cell development and migration in humanized mice. Immunology and cell biology Halkias, J., Yen, B., Taylor, K. T., Reinhartz, O., Winoto, A., Robey, E. A., Melichar, H. J. 2015; 93 (8): 716-726
Abstract

Humanized mice represent an important model to study the development and function of the human immune system. While it is known that mouse thymic stromal cells can support human T-cell development, the extent of interspecies cross-talk and the degree to which these systems recapitulate normal human T-cell development remain unclear. To address these questions, we compared conventional and non-conventional T-cell development in a neonatal chimera humanized mouse model with that seen in human fetal and neonatal thymus samples, and also examined the impact of a human HLA-A2 transgene expressed by the mouse stroma. Given that dynamic migration and cell-cell interactions are essential for T-cell differentiation, we also studied the intrathymic migration pattern of human thymocytes developing in a murine thymic environment. We found that both conventional T-cell development and intra-thymic migration patterns in humanized mice closely resemble human thymopoiesis. Additionally, we show that developing human thymocytes engage in short, serial interactions with other human hematopoietic-derived cells. However, non-conventional T-cell differentiation in humanized mice differed from both fetal and neonatal human thymopoiesis, including a marked deficiency of Foxp3(+) T-cell development. These data suggest that although the murine thymic microenvironment can support a number of aspects of human T-cell development, important differences remain, and additional human-specific factors may be required.

View details for DOI 10.1038/icb.2015.38

View details for PubMedID 25744551

View details for PubMedCentralID PMC4575952
Changes in Risk Profile Over Time in the Population of a Pediatric Heart Transplant Program. Annals of thoracic surgery Reinhartz, O., Maeda, K., Reitz, B. A., Bernstein, D., Luikart, H., Rosenthal, D. N., Hollander, S. A. 2015; 100 (3): 989-995
Abstract

Single-center data on pediatric heart transplantation spanning long time frames is sparse. We attempted to analyze how risk profile and pediatric heart transplant survival outcomes at a large center changed over time.We divided 320 pediatric heart transplants done at Stanford University between 1974 and 2014 into three groups by era: the first 20 years (95 transplants), the subsequent 10 years (87 transplants), and the most recent 10 years (138 transplants). Differences in age at transplant, indication, mechanical support, and survival were analyzed.Follow-up was 100% complete. Average age at time of transplantation was 10.4 years, 11.9 years, and 5.6 years in eras 1, 2, and 3, respectively. The percentage of infants who received transplants by era was 21%, 7%, and 18%, respectively. The indication of end-stage congenital heart disease vs cardiomyopathy was 24%, 22%, and 49%, respectively. Only 1 patient (1%) was on mechanical support at transplant in era 1 compared with 15% in era 2 and 30% in era 3. Overall survival was 72% at 5 years and 57% at 10 years. Long-term survival increased significantly with each subsequent era. Patients with cardiomyopathy generally had a survival advantage over those with congenital heart disease.The risk profile of pediatric transplant patients in our institution has increased over time. In the last 10 years, median age has decreased and ventricular assist device support has increased dramatically. Transplantation for end-stage congenital heart disease is increasingly common. Despite this, long-term survival has significantly and consistently improved.

View details for DOI 10.1016/j.athoracsur.2015.05.111

View details for PubMedID 26228604
Changes in Risk Profile Over Time in the Population of a Pediatric Heart Transplant Program. Annals of thoracic surgery Reinhartz, O., Maeda, K., Reitz, B. A., Bernstein, D., Luikart, H., Rosenthal, D. N., Hollander, S. A. 2015; 100 (3): 989-994
Abstract

Single-center data on pediatric heart transplantation spanning long time frames is sparse. We attempted to analyze how risk profile and pediatric heart transplant survival outcomes at a large center changed over time.We divided 320 pediatric heart transplants done at Stanford University between 1974 and 2014 into three groups by era: the first 20 years (95 transplants), the subsequent 10 years (87 transplants), and the most recent 10 years (138 transplants). Differences in age at transplant, indication, mechanical support, and survival were analyzed.Follow-up was 100% complete. Average age at time of transplantation was 10.4 years, 11.9 years, and 5.6 years in eras 1, 2, and 3, respectively. The percentage of infants who received transplants by era was 21%, 7%, and 18%, respectively. The indication of end-stage congenital heart disease vs cardiomyopathy was 24%, 22%, and 49%, respectively. Only 1 patient (1%) was on mechanical support at transplant in era 1 compared with 15% in era 2 and 30% in era 3. Overall survival was 72% at 5 years and 57% at 10 years. Long-term survival increased significantly with each subsequent era. Patients with cardiomyopathy generally had a survival advantage over those with congenital heart disease.The risk profile of pediatric transplant patients in our institution has increased over time. In the last 10 years, median age has decreased and ventricular assist device support has increased dramatically. Transplantation for end-stage congenital heart disease is increasingly common. Despite this, long-term survival has significantly and consistently improved.

View details for DOI 10.1016/j.athoracsur.2015.05.111

View details for PubMedID 26228604
Is Continuous Flow Superior to Pulsatile Flow in Single Ventricle Mechanical Support? Results from a Large Animal Pilot Study ASAIO JOURNAL Fujii, Y., Ferro, G., Kagawa, H., Centola, L., Zhu, L., Ferrier, W. T., Talken, L., Riemer, R. K., Maeda, K., Nasirov, T., Hodges, B., Amirriazi, S., Lee, E., Sheff, D., May, J., May, R., Reinhartz, O. 2015; 61 (4): 443-447
Abstract

Durable mechanical support in situations of physiologic single ventricle has been met with little success so far, particularly in small children. We created an animal model to investigate whether pulsatile or continuous flow would be superior. Three 1 month old sheep (10-16 kg) were instrumented. Via sternotomy and with cardiopulmonary bypass, a large ventricular septal defect and atrial septal defect were created. The left ventricle was cannulated using a Berlin Heart inflow cannula. This was connected sequentially to a continuous flow device (Thoratec HeartMate X, Pleasanton, CA) and to a pulsatile device (Berlin Heart Excor, The Woodlands, TX). Outflow was via a Y-graft to both aorta and pulmonary artery, striving for equal flow to both. Atrial filling pressures were controlled with volume infusions over a wide range. Under comparable loading conditions, significantly higher maximum flow was obtained by HeartMate X than by Excor (4.95 ± 1.27 L/min [range, 3.84-6.34 L/min] for HeartMate X vs. 1.80 ± 0.85 L/min [range, 1.01-2.7 L/min] for Excor; p < 0.05). Judging from this limited animal study, in single ventricle scenarios, continuous flow devices may achieve higher pump flows than pulsatile devices when provided with similar filling pressures. Their clinical use should be investigated. More extensive experimental studies are needed.

View details for DOI 10.1097/MAT.0000000000000220

View details for Web of Science ID 000358285100013
High-resolution coronary MR angiography for evaluation of patients with anomalous coronary arteries: visualization of the intramural segment PEDIATRIC RADIOLOGY Biko, D. M., Chung, C., Hitt, D. M., Kurio, G., Reinhartz, O., Chung, T. 2015; 45 (8): 1146-1152
Abstract

Anomalous origin of the coronary artery from the contralateral coronary sinus is a rare coronary anomaly associated with sudden death. The inter-arterial course is most closely associated with sudden death, but it has been suggested that the presence of an intramural segment of a right anomalous coronary is associated with more symptoms and therefore may be an important criterion for intervention in these patients.To demonstrate that MR angiography can accurately determine the presence or absence of an intramural segment in an anomalous coronary artery.All studies of children who underwent MR angiography for the evaluation of an anomalous coronary artery were retrospectively reviewed by two pediatric radiologists in consensus. Criteria for an intramural anomalous coronary artery were the presence of a small or slit-like ostium and the relative smaller size of the proximal intramural portion of the coronary artery in relation to the more distal epicardial coronary artery. The anomalous coronary artery was classified as not intramural if these two findings were absent. These findings were correlated with operative reports confirming the presence or absence of an intramural segment.Twelve patients (86%) met MR angiography criteria for the presence of an intramural course. Only 2 patients (14%) met MR angiography criteria for a non-intramural course. When correlating with intraoperative findings, MR angiography was successful in distinguishing between intramural and non-intramural anomalous coronary arteries in all cases (P = 0.01).MR angiography may be able to reliably identify the intramural segment of an anomalous coronary artery in older children using the imaging criteria of a small or slit-like ostium and relative decrease in size of the proximal portion of the anomalous coronary artery compared to the distal portion of the anomalous coronary artery. Determining the presence of the intramural segment may help with surgical planning and may be an important criterion for the determination of intervention in patients with inter-arterial anomalous right coronary arteries.

View details for DOI 10.1007/s00247-015-3302-3

View details for Web of Science ID 000358328100005

View details for PubMedID 25779828
Hemodynamic Monitoring of Large Animal Chronic Studies After Median Sternotomy: Experiences With Different Telemetric Physiological Devices ASAIO JOURNAL Fujii, Y., Pitsillides, K., Ferro, G., Kagawa, H., Centola, L., Kinouchi, K., Zhu, L., Ferrier, W. T., Talken, L., Nasirov, T., Riemer, R. K., Reinhartz, O. 2015; 61 (3): 332-338
Abstract

Telemetric physiological monitoring systems (TPMS) have enabled accurate continuous measurement of animal blood pressures and flows. However, few studies describe approaches for use of TPMS in the great vessels or inside the heart. We describe our initial experiences using two types of TPMSs. Twelve lambs (20-37 kg) underwent sternotomy. Two lambs were not instrumented and were killed at 14 days to confirm normal sternal wound healing (sham group, n = 2). Ten lambs underwent placement of either standard indwelling pressure-monitoring catheter and perivascular-flow-probe (CFP group, n = 3) or TPMS implantation (TPMS group, n = 7). The TPMS used were EG1-V3S2T-M2 (EG1, n = 5; Transonic Endogear Inc.) and Physio Tel Digital L21 (PTD, n = 2; Data Sciences Inc.). Two deaths because of respiratory problems occurred in TPMS group, attributed to lung compression by the implanted device. In TPMS group, more consistent trends of blood pressures and flows were recorded, and management of animals was easier and less labor-intensive. Comparing the two TPMSs, the initiation and renewal costs for each case was $28 K vs. $20 K and $1,700 vs. $0, (PTD versus EG1, respectively). In conclusion, TPMS implantation was feasible via median sternotomy in lambs. Telemetric physiological monitoring systems significantly improve reliability of hemodynamic monitoring in chronic survival animal study. EG1 was less costly than PTD.

View details for DOI 10.1097/MAT.0000000000000202

View details for Web of Science ID 000353811800018

View details for PubMedID 25635937
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
Neurological complications and outcomes in the Berlin Heart EXCOR® pediatric investigational device exemption trial. Journal of the American Heart Association Jordan, L. C., Ichord, R. N., Reinhartz, O., Humpl, T., Pruthi, S., Tjossem, C., Rosenthal, D. N. 2015; 4 (1)
Abstract

The Berlin Heart EXCOR(®) ventricular assist device has been approved for use in the United States as a bridge to heart transplantation in children. We sought to characterize neurological events in children supported with the Berlin Heart EXCOR(®) device.The multicenter prospective cohort consisted of all 204 children implanted with the Berlin Heart EXCOR(®) device at 47 centers in North America between May 2007 and December 2010. There were 73 neurological events in 59 patients, with 29% of the cohort experiencing ≥1 neurological event. Events included 52 strokes in 43 patients (21% of the cohort). The neurological event rate was 0.51 events per 100 patient-days. Many of the neurological events occurred early in the course of support, with 30 events recorded during the first 14 days of support. The mortality rate in participants with at least 1 neurological event was 42% (25 of 59), significantly higher than the 18% mortality rate (26 of 145) for those who did not have a neurological event (P=0.0006). Risk-factor analysis did not identify significant preimplantation predictors of neurological injury.Of children treated with the Berlin Heart EXCOR(®) device as a bridge to transplant, 29% experienced at least 1 neurological event. The majority of neurological events were ischemic strokes, and many of those occurred early in the course of support. Neurological injury was the leading cause of death after implantation of the Berlin Heart EXCOR(®) device. Risk stratification for stroke or neurological injury is not possible based on baseline preimplantation characteristics.www.clinicaltrials.gov. Unique Identifier: NCT00583661.

View details for DOI 10.1161/JAHA.114.001429

View details for PubMedID 25613996
Neurological Complications and Outcomes in the Berlin Heart EXCOR® Pediatric Investigational Device Exemption Trial. Journal of the American Heart Association Jordan, L. C., Ichord, R. N., Reinhartz, O., Humpl, T., Pruthi, S., Tjossem, C., Rosenthal, D. N. 2015; 4 (1)
Abstract

The Berlin Heart EXCOR(®) ventricular assist device has been approved for use in the United States as a bridge to heart transplantation in children. We sought to characterize neurological events in children supported with the Berlin Heart EXCOR(®) device.The multicenter prospective cohort consisted of all 204 children implanted with the Berlin Heart EXCOR(®) device at 47 centers in North America between May 2007 and December 2010. There were 73 neurological events in 59 patients, with 29% of the cohort experiencing ≥1 neurological event. Events included 52 strokes in 43 patients (21% of the cohort). The neurological event rate was 0.51 events per 100 patient-days. Many of the neurological events occurred early in the course of support, with 30 events recorded during the first 14 days of support. The mortality rate in participants with at least 1 neurological event was 42% (25 of 59), significantly higher than the 18% mortality rate (26 of 145) for those who did not have a neurological event (P=0.0006). Risk-factor analysis did not identify significant preimplantation predictors of neurological injury.Of children treated with the Berlin Heart EXCOR(®) device as a bridge to transplant, 29% experienced at least 1 neurological event. The majority of neurological events were ischemic strokes, and many of those occurred early in the course of support. Neurological injury was the leading cause of death after implantation of the Berlin Heart EXCOR(®) device. Risk stratification for stroke or neurological injury is not possible based on baseline preimplantation characteristics.www.clinicaltrials.gov. Unique Identifier: NCT00583661.

View details for DOI 10.1161/JAHA.114.001429

View details for PubMedID 25613996
Tetralogy of Fallot: aorto-pulmonary collaterals and pulmonary arteries have distinctly different transcriptomes PEDIATRIC RESEARCH Ma, X., Barboza, L. A., Siyahian, A., Reinhartz, O., Maeda, K., Reddy, V. M., Hanley, F. L., Riemer, R. K. 2014; 76 (4): 341-346
View details for DOI 10.1038/pr.2014.101

View details for Web of Science ID 000342332000003
Tetralogy of Fallot: aorto-pulmonary collaterals and pulmonary arteries have distinctly different transcriptomes. Pediatric research Ma, X., Barboza, L. A., Siyahian, A., Reinhartz, O., Maeda, K., Reddy, V. M., Hanley, F. L., Riemer, R. K. 2014; 76 (4): 341-346
Abstract

Tetralogy of Fallot patients with pulmonary atresia (TOF/PA) present a pulmonary blood supply directly from aortic collateral arteries. Major aorto-pulmonary collateral arteries (MAPCAs) present substantial clinical and surgical management challenges. Surgical operations to reestablish and promote further development of a pulmonary arterial connection preferentially utilize MAPCAs for reconstruction of central pulmonary arteries. However, the propensity of some MAPCAs to develop stenosis rather than growth may impair the response to reconstructions.Probe sets prepared from MAPCAs, PA, and aorta mRNA were used to interrogate human genome microarrays. We compared expression differences between pairs of the three vessels to determine whether MAPCAs display distinct expression patterns.Functional clustering analysis identified differences in gene expression, which were further analyzed by gene ontology classification. A subset of highly regulated genes was validated using quantitative PCR. Expression differences among vessel types were observed for multiple gene classes. Of note, we observed that MAPCAs differentially express several genes at much higher levels than either PA or aorta.MAPCAs differ from PA or aorta by significantly altered levels in gene expression, suggesting a transcriptional basis for their physiology that will guide a further understanding of the pathobiology of MAPCAs and TOF.

View details for DOI 10.1038/pr.2014.101

View details for PubMedID 25000348
Surgical repair of anomalous aortic origin of a coronary artery†. European journal of cardio-thoracic surgery Mainwaring, R. D., Reddy, V. M., Reinhartz, O., Petrossian, E., Punn, R., Hanley, F. L. 2014; 46 (1): 20-26
Abstract

Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital heart defect that has been associated with myocardial ischaemia and sudden death. There is an ongoing controversy over the indications for surgical intervention and the efficacy of that treatment compared with the natural history. The purpose of this study was to evaluate the medium-term results of surgical repair of AAOCA.Seventy-six patients underwent surgical repair of AAOCA at our institution from 1999 to 2013. There were 55 males and 21 females, and the median age at surgery was 15 years. Forty-seven (62%) of the 76 patients had an anomalous right coronary artery, 27 had an anomalous left coronary and 2 had an eccentric single coronary ostia. Forty-one patients had preoperative symptoms of myocardial ischaemia.Surgical repair was accomplished by unroofing of an intramural coronary in 55, reimplantation in 7 and pulmonary artery translocation in 14. There has been no early or late mortality, with a median duration of follow-up of 6 years. One patient presented with severe myocardial ischaemia and subsequently underwent heart transplantation a year following AAOCA surgery. The remaining patients have all remained free of cardiac symptoms.The results of this study demonstrate two major principles. First, surgical repair of AAOCA is quite safe in centres that take care of a significant number of patients with this entity. Secondly, the surgery is highly effective in eliminating symptoms of myocardial ischaemia. The growing amount of data on postoperative patients suggests that surgical repair can prevent the adverse events seen in the untreated 'natural' history. Based on these observations, it is our current recommendation that all teenagers identified with AAOCA should undergo surgical repair.

View details for DOI 10.1093/ejcts/ezt614

View details for PubMedID 24431169
An inpatient rehabilitation program utilizing standardized care pathways after paracorporeal ventricular assist device placement in children. journal of heart and lung transplantation Hollander, S. A., Hollander, A. J., Rizzuto, S., Reinhartz, O., Maeda, K., Rosenthal, D. N. 2014; 33 (6): 587-592
Abstract

Structured rehabilitation programs in adults after ventricular assist device (VAD) placement result in improvements in physical function and exercise capacity, and have been shown to improve survival and accelerate post-transplant recovery. The objective of this study was to determine the safety and feasibility of an acute inpatient rehabilitation program for children utilizing standardized, age-appropriate, family-centered care pathways after paracorporeal VAD placement in both the ICU and acute-care inpatient settings.Between November 12, 2010 and March 15, 2013, 17 patients were referred to therapy after VAD implantation, 14 of whom were medically stable enough to participate. Beginning in the ICU, a structured physical and occupational therapy program was implemented utilizing novel age-appropriate, standardized care pathways for infants (age <1 year) and children (age 1 to 12 years). The infant and child pathways consisted of 8 and 10 goals, respectively. Retrospective review was conducted to ascertain the number of phases achieved per patient. Adverse events, defined as bleeding, physiologic instability, stroke, or device disruption during therapy, were also analyzed.The median age was 1.1 (range 0.5 to 14.4) years in the 14 patients considered medically stable enough to participate in rehabilitation. Nine of them were female. Eight patients participated in the infant standardized care pathway (SCP) and 6 participated in the child SCP. Seven patients were on biventricular support. Twelve patients were transplanted and survived. Two patients died while awaiting transplantation. There were 1,473 total days on the VAD (range 40 to 229 days). The median time to extubation was 2 days (range 1 to 8) and the median ICU stay was 6.5 days (range 3 to 152). Eleven patients achieved all goals of the SCP, including all of the patients in the child group. For the infant group, 5 patients achieved all goals of the SCP (range 5 to 8), and all but 1 patient achieved at least 7 goals of the SCP. There were no adverse events related to therapy.Standardized, family-centered inpatient rehabilitation care paths are safe for infants and children after paracorporeal device placement. Structured rehabilitation goals can be achieved by the majority of pediatric patients during VAD support. Early mobilization and inpatient rehabilitation in this cohort promotes normalization of function while awaiting cardiac transplantation.

View details for DOI 10.1016/j.healun.2013.12.009

View details for PubMedID 24468119
Successful bridge to transplant with a continuous flow ventricular assist device in a single ventricle patient with an aortopulmonary shunt. ASAIO journal Lal, A. K., Chen, S., Maeda, K., McCammond, A., Rosenthal, D. N., Reinhartz, O., Yeh, J. 2014; 60 (1): 119-121
Abstract

Ventricular assist devices are frequently used to bridge pediatric patients to cardiac transplantation; however, experience in single ventricle patients with aortopulmonary shunts remains limited. This case report addresses the challenge of balancing pulmonary and systemic circulation with a focus on the role of continuous versus pulsatile ventricular assist device support.

View details for DOI 10.1097/MAT.0000000000000007

View details for PubMedID 24270233
Lower socioeconomic status is associated with worse outcomes after both listing and transplanting children with heart failure PEDIATRIC TRANSPLANTATION Davies, R. R., Russo, M. J., Reinhartz, O., Maeda, K., Rosenthal, D. N., Chin, C., Bernstein, D., Mallidi, H. R. 2013; 17 (6): 573-581
Abstract

The relationship between SES and outcomes surrounding pediatric cardiac transplantation is complex and influenced by recipient race. Broad-based studies of SES have not been performed. A retrospective review of all 5125 primary pediatric heart transplants performed in the United States between 2000 and 2011. Patients were stratified by SES based on zip code of residence and U.S. census data (low SES: 1637; mid-SES: 2253; high SES: 1235). Survival following listing and transplantation was compared across strata. Risk-adjusted long-term mortality on the waitlist was higher among low SES patients (hazard 1.32, CI 1.07-1.63). The relationship between SES and outcomes varied by race. Early risk-adjusted post-transplant outcomes were worst among high SES patients (10.8% vs. low SES: 8.9%, p < 0.05). The incidence of non-compliance was higher among low SES patients (p < 0.0001). Long-term risk-adjusted patient survival was poorer among low (hazard 1.41, CI 1.10-1.80) and mid-SES (1.29, 1.04-1.59) groups. Low SES is associated with worse outcomes on both the waitlist and late following transplantation. Higher SES patients had more complex transplants with higher early mortality. Further research should be directed at identifying and addressing underlying causal factors for these disparities.

View details for DOI 10.1111/petr.12117

View details for Web of Science ID 000322317700015

View details for PubMedID 23834560
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
A Novel Scoring System for Recovery after VAD Implantation in Children: Initial Feasibility 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation Ploutz, M., Hollander, S., Reinhartz, O., Maeda, K., Yeh, J., Rosenthal, D. ELSEVIER SCIENCE INC. 2013: S289–S289
View details for Web of Science ID 000316712100800
Low Dose Factor Eight Inhibitor Bypassing Activity (FEIBA) for Incessant Bleeding in Pediatric Patients on Mechanical Circulatory Support (MCS) 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation Maeda, K., Asija, R., Hollander, S., Williams, G., Yeh, J., Rosenthal, D., Reinhartz, O. ELSEVIER SCIENCE INC. 2013: S290–S290
View details for Web of Science ID 000316712100803
Intermediate-term outcomes after combined heart-liver transplantation in children with a univentricular heart JOURNAL OF HEART AND LUNG TRANSPLANTATION Hollander, S. A., Reinhartz, O., Maeda, K., Hurwitz, M., Rosenthal, D. N., Bernstein, D. 2013; 32 (3): 368-370
Abstract

For patients with end-stage hepatic failure secondary to failing hemodynamics, combined heart-liver transplant (H-LT) remains the only option for long-term survival. We report a series of three pediatric patients who successfully underwent orthotopic H-LT for failed single-ventricle palliation. All three patients are currently living, now two, three, and five years post-transplant, and remain completely free of cardiac cellular allograft rejection despite reduced immunosuppression protocols. One patient, however, did develop acute antibody-mediated rejection in the immediate post-transplant period, suggesting that this protective effect may be less effective in attenuating humoral mechanisms of rejection.

View details for DOI 10.1016/j.healun.2012.11.023

View details for Web of Science ID 000315664600014

View details for PubMedID 23415318
Cognitive outcomes in pediatric heart transplant recipients bridged to transplantation with ventricular assist devices JOURNAL OF HEART AND LUNG TRANSPLANTATION Stein, M. L., Bruno, J. L., Konopacki, K. L., Kesler, S., Reinhartz, O., Rosenthal, D. 2013; 32 (2): 212-220
Abstract

Ventricular assist devices (VADs) have been associated with high rates of neurologic injury in pediatric patients during the period of support, but the delayed consequences of this type of injury have not been described in the literature.In this study we assess cognitive outcomes with indices of general intellectual functioning, including working memory, processing speed, perceptual reasoning and verbal comprehension, for pediatric heart transplant recipients who required VAD support as a bridge to transplant (n = 9). We present an aggregate of these VAD patients combined with heart transplant recipients who did not require mechanical circulatory support (n = 11), and compare the performance of all transplant patients (n = 20) to typically developing, healthy comparators (n = 12). We also present a post hoc analysis of those transplant recipients with significant medical morbidity in the first year of life, referred to as the "high-risk" transplant group (n = 5), and compare them with the "low-risk" transplant group (n = 15) and the typically developing comparators (n = 12).The mean performance of the VAD patients was in the average range for each of the examined indices of cognitive functioning. A total of 11% of the VAD patients performed in the impaired range and 78% performed in the average range, with 11% in the superior range on measures of general intellectual functioning. The typically developing participants performed significantly better than the aggregated transplant recipients on all indices except verbal comprehension. Lower cognitive performance in the combined transplant group appears to be associated with medical morbidity in the first year of life.Despite significant neurologic risk factors, this cohort of pediatric patients who were bridged to transplant with VAD demonstrated resiliency in terms of cognitive outcomes. In this heterogeneous population, it is likely that multiple factors contributed to the cognitive outcomes. As VAD use becomes more common in pediatric patients, a prospective evaluation of cognitive outcomes is warranted.

View details for DOI 10.1016/j.healun.2012.11.006

View details for Web of Science ID 000314445800006

View details for PubMedID 23352393
Midterm Results of the Modified Ross/Konno Procedure in Neonates and Infants ANNALS OF THORACIC SURGERY Maeda, K., Rizal, R. E., Lavrsen, M., Malhotra, S. P., Akram, S. A., Davies, R., Suleman, S., Reinhartz, O., Murphy, D. J., Hanley, F. L., Reddy, V. M. 2012; 94 (1): 156-163
Abstract

The management of congenital aortic stenosis in neonates and infants continues to be a surgical challenge. We have performed the modified Ross-Konno procedure for patients who have severe aortic insufficiency or significant residual stenosis after balloon aortic dilation. The midterm results of this procedure were evaluated in this subset of patients.Between 1994 and 2010, a total of 24 patients younger than 1 year of age underwent the modified Ross-Konno procedure. The diagnoses were aortic stenosis with or without subaortic stenosis (n = 16), Shone's complex (n = 7), and interrupted aortic arch with subaortic stenosis (n = 1). The aortic root was replaced with a pulmonary autograft, and the left ventricular outflow tract (LVOT) was enlarged with a right ventricular infundibular free wall muscular extension harvested with the autograft.Age at operation ranged from 1 to 236 days (median 28 days). The median follow-up period was 81 months (range 1-173 months). There was 1 early death and no late mortality. Overall the 1-, 2-, and 5-year survival rate was 95% ± 4.5%. Freedom from aortic stenosis was 94.7% ± 5.1% at 1, 2, and 5 years. Less than mild aortic insufficiency was 93.3% ± 6.4% at 2 years, and 74.7% ± 12.9% at 5 years. In total, 23 reoperations and reinterventions were performed; 14 were allograft conduit replacements. Two patients required aortic valve plasty. None required valve replacement. The reintervention-free rate was 64.6% ± 10.8% at 2 years and 36.9% ± 11.3% at 5 years.Pulmonary autografts demonstrated good durability with low mortality and morbidity. This study shows that the modified Ross-Konno procedure can be a practical choice in selective cases for complex LVOT stenosis in neonates and infants.

View details for DOI 10.1016/j.athoracsur.2012.03.007

View details for Web of Science ID 000305801600033

View details for PubMedID 22626750
Use of the Impella 5.0 as a bridge from ECMO to implantation of the HeartMate II left ventricular assist device in a pediatric patient PEDIATRIC TRANSPLANTATION Hollander, S. A., Reinhartz, O., Chin, C., Yeh, J., Maeda, K., Mallidi, H., Bernstein, D., Rosenthal, D. 2012; 16 (2): 205-206
View details for DOI 10.1111/j.1399-3046.2011.01578.x

View details for Web of Science ID 000300709600022

View details for PubMedID 21923883
Maintenance Dose of Warfarin in Sheep and Effect of Diet: A Preliminary Report JOURNAL OF INVESTIGATIVE SURGERY Sasaki, T., Tsuda, S., Trujillo, M., Riemer, R. K., Reinhartz, O. 2012; 25 (1): 29-32
Abstract

Sheep models are widely used to evaluate the feasibility of various cardiac assist devices. Anticoagulation therapy postoperatively, however, is seldomly reported on. Continuous heparin infusion is often used, but is cumbersome due to long-term line management with the risk of infection and dislodgement. We contemplated using warfarin instead and started a pilot dose-finding study. Three sheep were given oral warfarin between 0.1 and 0.3 mg/kg/day. Prothrombin time was monitored and INR was calculated daily. If the INR did not reach a target of 2.5-3.5, warfarin dose was doubled. We found that sheep required a dose of warfarin between 1.6 and 2.4 mg/kg/day to raise the INR to the target zone. In a subsequent study to evaluate the effect of diet on INR in sheep, three sheep were fed alfalfa hay or alfalfa pellets in a crossover design. All the animals were given warfarin at the dose of 1.6 mg/kg. The diet was switched when the INR reached the target zone of 2.5-3.5. Hay-fed animals reached the target INR on days 6 and 7. On the other hand, pellet-fed animals did not reach the target value by day 7 with the initial dose and required 2.4 mg/kg of warfarin to achieve the goal. Hay raised the INR faster and higher than pellets with the same warfarin dose. Hay may be advantageous when using oral warfarin therapy in sheep.

View details for DOI 10.3109/08941939.2011.598219

View details for Web of Science ID 000299424500006

View details for PubMedID 22272634
Challenges in Longer-Term Mechanical Support of Fontan Circulation in Sheep ASAIO JOURNAL Boni, L., Sasaki, T., Ferrier, W. T., Yeung, J. T., Reichenbach, S. H., Riemer, R. K., Reinhartz, O. 2012; 58 (1): 60-64
Abstract

Single ventricle congenital heart defects are usually palliated with the end result of a Fontan circulation. Despite improving results, this circulation is still associated with long-term failure. We previously developed an animal model of mechanical cavopulmonary circulation support that was successful in the acute and mid-term period. In the current study, we evaluated longer support durations in five Western-breed sheep. Through a right thoracotomy we instituted mechanical support from the inferior vena cava to the pulmonary artery, using a Heartmate II axial flow pump (Thoratec Corp., Pleasanton, CA). Postoperatively, the animals were anticoagulated with heparin iv. Hemodynamics, pump flow, anticoagulation, and hepatic and renal function were monitored daily. All animals survived the operation. Signs of moderate liver and kidney injury in general reversed quickly. Two animals had a fatal pump thrombosis. When anticoagulation was effective, hemodynamics and pump flow were maintained to normal values. Effective anticoagulation was difficult to achieve because of the high variability in response to heparin. Survival up to 18 days was accomplished. This study is the longest reported survival of animals with a mechanically assisted cavopulmonary circulation. The performance of the Thoratec Heartmate II has been good, but the issue of effective anticoagulation has not yet been solved.

View details for DOI 10.1097/MAT.0b013e31823c0aa4

View details for Web of Science ID 000298643200011

View details for PubMedID 22210652
Surgical Results in Patients With Pulmonary Atresia-Major Aortopulmonary Collaterals in Association With Total Anomalous Pulmonary Venous Connection ANNALS OF THORACIC SURGERY Mainwaring, R. D., Reddy, M., Reinhartz, O., Punn, R., Tacy, T., Hanley, F. L. 2011; 92 (5): 1756-1760
Abstract

Pulmonary atresia and major aortopulmonary collaterals (PA/MAPCAs) is a complex form of congenital heart disease. One to two percent of patients with PA/MAPCAs will also have total anomalous pulmonary venous connection (TAPVC). This study summarizes our surgical experience with this rare combination of life-threatening congenital heart defects.A retrospective review was performed to identify patients who had surgery for PA/MAPCAs in association with TAPVC. From November 2001 to March 2011, 9 patients presented with this combination of defects. Eight of the 9 patients had heterotaxy with an unbalanced atrioventricular canal and functional single ventricle. The ninth patient had double outlet right ventricle (two ventricles). Timing of surgical intervention was typically predicated on the degree of pulmonary venous obstruction. The median age at surgery was 14 days. All nine patients had surgical correction of TAPVC, unifocalization of MAPCA's into a central confluence, and placement of a shunt.There was one early mortality (< 30 days) and two late mortalities. For the 6 survivors, 5 have subsequently undergone a bidirectional Glenn procedure, and 3 had completion of their Fontan. Two patients are currently at the bidirectional Glenn stage; one is a good candidate for Fontan completion while the other is not suitable. The sixth patient is awaiting further assessment.The PA/MAPCAs, in association with TAPVC, is a challenging combination of defects. The data suggest that the combination of PA/MAPCAs and TAPVC can be undertaken with a reasonable midterm prognosis.

View details for DOI 10.1016/j.athoracsur.2011.06.020

View details for Web of Science ID 000296925400045

View details for PubMedID 21944736
Anomalous Aortic Origin of a Coronary Artery: Medium-Term Results After Surgical Repair in 50 Patients ANNALS OF THORACIC SURGERY Mainwaring, R. D., Reddy, V. M., Reinhartz, O., Petrossian, E., Macdonald, M., Nasirov, T., Miyake, C. Y., Hanley, F. L. 2011; 92 (2): 691-697
Abstract

Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital heart defect that has been associated with myocardial ischemia and sudden death. Controversies exist regarding the diagnosis, treatment, and long-term recommendations for patients with AAOCA. The purpose of this study is to evaluate the medium-term results of surgical repair for AAOCA.From January 1999 through August 2010, 50 patients underwent surgical repair of AAOCA. The median age at surgery was 14 years (range, 5 days to 47 years). Thirty-one patients had the right coronary originate from the left sinus of Valsalva, 17 had the left coronary originate from the right sinus, and 2 had an eccentric single coronary ostium. Twenty six of the 50 patients had symptoms of myocardial ischemia preoperatively, and 14 patients had associated congenital heart defects. Repair was accomplished by unroofing in 35, reimplantation in 6, and pulmonary artery translocation in 9.There was no operative mortality. The median time of follow-up has been 5.7 years. Two patients were lost to follow-up, and 1 patient required heart transplantation 1 year after AAOCA repair. In the remaining 47 postoperative patients, all have remained free of cardiac symptoms and no one has experienced a sudden death event.The surgical treatment of AAOCA is safe and appears to be highly effective in eliminating ischemic symptoms. These medium-term results are encouraging and suggest that many patients may be able to resume normal activities.

View details for DOI 10.1016/j.athoracsur.2011.03.127

View details for Web of Science ID 000293221000050

View details for PubMedID 21718962
Clinical usefulness of a novel C1q assay to detect immunoglobulin G antibodies capable of fixing complement in sensitized pediatric heart transplant patients JOURNAL OF HEART AND LUNG TRANSPLANTATION Chin, C., Chen, G., Sequeria, F., Berry, G., Siehr, S., Bernstein, D., Rosenthal, D., Reinhartz, O., Tyan, D. 2011; 30 (2): 158-163
Abstract

Donor-specific antibodies (DSA) against human leukocyte antigens complicate transplantation with the potential for acute antibody-mediated rejection (AMR). Complement-fixing antibodies are required to initiate the complement cascade. Not all DSAs, however, can fix complement.A novel C1q assay was developed to detect the sub-set of immunoglobulin G (IgG) antibodies capable of fixing complement. Sera from 18 pediatric heart transplant patients were analyzed for DSAs using a Luminex platform (Luminex Inc, Austin, TX) and commercially available single-antigen bead assay kits. Biopsy specimens were assessed for AMR using histopathologic criteria and immunohistochemical staining.During the study period, 5 patients had AMR; of these, 2 were C1q virtual crossmatch positive (VXM+) and had persistent C1q DSAs after transplant, and 3 were C1q VXM- but antibody developed immediately after transplant. A positive C1q assay in the immediate post-transplant period had a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%, with 100% sensitivity and 100% specificity (Fisher exact p = 0.001). Of 11 patients who were IgG VXM+, 5 had AMR; the IgG VXM had a PPV of 45% and NPV of 100%, with 100% sensitivity and 54% specificity (Fisher exact p = 0.101).The C1q assay can detect a sub-set of antibodies capable of fixing complement and predicts AMR early after transplant. Avoiding only the donor antigens that would be recognized by the C1q assay may accelerate time to transplant by expansion of the donor pool and potentially allows transplantation of previously "incompatible" organs.

View details for DOI 10.1016/j.healun.2010.08.020

View details for Web of Science ID 000286545200008

View details for PubMedID 20951058
Imaging and Surgical Repair of a Bifurcating Aortico-Left Ventricle Tunnel ANNALS OF THORACIC SURGERY Kaiser, C. A., Chung, T., Rosenfeld, H. M., Reinhartz, O. 2011; 91 (2): E23-E25
Abstract

Aortico-left ventricle tunnels are rare congenital anomalies with variable anatomy; however, by definition, they consist of an abnormal connection between the ascending aorta and the left ventricle. Diagnosis is usually by echocardiography, and treatment typically uses a two-patch surgical repair. Herein, we describe a case of an aortico-left ventricle tunnel, with the tunnel bifurcating before entering the left ventricle. Preoperative echocardiography and magnetic resonance imaging show the lesion in great detail. Two patches were required on the left-ventricular side of the tunnel for closure. A bifurcating aortico-left ventricle tunnel has not yet been described in the literature. The preoperative imaging and surgical management are discussed.

View details for DOI 10.1016/j.athoracsur.2010.10.033

View details for Web of Science ID 000286456400004

View details for PubMedID 21256259
The hemi-Mustard/bidirectional Glenn atrial switch procedure in the double-switch operation for congenitally corrected transposition of the great arteries: Rationale and midterm results 90th Annual Meeting of the American-Association-for-Thoracic-Surgery Malhotra, S. P., Reddy, V. M., Qiu, M., Pirolli, T. J., Barboza, L., Reinhartz, O., Hanley, F. L. MOSBY-ELSEVIER. 2011: 162–70
Abstract

This study was undertaken to assess the risks and benefits of the double-switch operation using a hemi-Mustard atrial switch procedure and the bidirectional Glenn operation for congenitally corrected transposition of the great arteries. To avoid complications associated with the complete Senning and Mustard procedures and to assist right-heart hemodynamics, we favor a modified atrial switch procedure, consisting of a hemi-Mustard procedure to baffle inferior vena caval return to the tricuspid valve in conjunction with a bidirectional Glenn operation.Between January 1994 and September 2009, anatomic repair was achieved in 48 patients. The Rastelli-atrial switch procedure was performed in 25 patients with pulmonary atresia and the arterial-atrial switch procedure was performed in 23 patients. A hemi-Mustard procedure was the atrial switch procedure for 70% (33/48) of anatomic repairs.There was 1 in-hospital death after anatomic repair. There were no late deaths or transplantation. At a median follow-up of 59.2 months, 43 of 47 survivors are in New York Heart Association class I. Bidirectional Glenn operation complications were uncommon (2/33), limited to the perioperative period, and seen in patients less than 4 months of age. Atrial baffle-related reoperations or sinus node dysfunction have not been observed. Tricuspid regurgitation decreased from a mean grade of 2.3 to 1.2 after repair (P = .00002). Right ventricle-pulmonary artery conduit longevity is significantly improved.We describe a 15-year experience with the double-switch operation using a modified atrial switch procedure with favorable midterm results. The risks of the hemi-mustard and bidirectional Glenn operation are minimal and are limited to a well-defined patient subset. The benefits include prolonged conduit life, reduced baffle- and sinus node-related complications, and technical simplicity.

View details for DOI 10.1016/j.jtcvs.2010.08.063

View details for Web of Science ID 000285407500029

View details for PubMedID 21055773
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
Behcet's disease and heart transplantation: A word of caution JOURNAL OF HEART AND LUNG TRANSPLANTATION Hollander, S. A., Yasnovsky, J. R., Reinhartz, O., Chan, F., Sandborg, C., Hunt, S., Bernstein, D., Chin, C. 2010; 29 (11): 1306-1308
Abstract

Behcet's disease is a rare autoimmune disease characterized by oral and genital ulcers, and by multisystem disease, including arthritis, neurologic complications and vasculitis. Large-vessel and coronary artery aneurysms are often an indication for surgery, but the return of aneurysms, thrombosis, and the tendency to exhibit an exaggerated inflammatory response at puncture sites (pathergy) complicate surgical recovery. As such, cardiac transplantation, which requires atrial and large-vessel anastomoses, has not been reported in patients with Behcet's disease. We report the first orthotopic heart transplant with >1-year survival in a patient with Behcet's disease despite major complications. The investigators remain pessimistic about cardiac transplantation in patients with Behcet's disease until advances in preventing recurrent vascular pathology ensue.

View details for DOI 10.1016/j.healun.2010.07.010

View details for PubMedID 20822920
Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)-Defined Morbidity and Mortality Associated With Pediatric Ventricular Assist Device Support at a Single US Center The Stanford Experience CIRCULATION-HEART FAILURE Stein, M. L., Robbins, R., Sabati, A. A., Reinhartz, O., Chin, C., Liu, E., Bernstein, D., Roth, S., Wright, G., Reitz, B., Rosenthal, D. 2010; 3 (6): 682-688
Abstract

The use of ventricular assist devices (VADs) to bridge pediatric patients to heart transplantation has increased dramatically over the last 15 years. In this report, we present the largest US single-center report of pediatric VAD use to date. We present detailed descriptions of morbidity and mortality associated with VAD support, using standard Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) criteria for pediatrics to facilitate the comparison of these results to other studies.We retrospectively identified 25 patients younger than 18 years with 27 episodes of mechanical circulatory support using VADs as bridge to heart transplantation from January 1998 to December 2007. Survival to transplant for the entire cohort was 74%. The most common major morbidities, as defined by INTERMACS criteria for a pediatric population, were respiratory failure, major localized infections, major bleeding events, hepatic dysfunction, and right heart failure. Major neurological events occurred in 48% of the study population. The median time to the first occurrence of an adverse event was less than 14 days for respiratory failure, right heart failure, major localized infection, and major bleeding. Patients who died before transplantation had significantly more adverse events per day of support than did those who were successfully transplanted. Episodes of major bleeding, tamponade, acute renal failure, respiratory failure, and right heart failure were all associated with increased risk of mortality.INTERMACS criteria can be successfully used to analyze pediatric VAD outcomes. These data serve as a baseline for future studies of VAD support in children and indicate good survival rates but considerable morbidity.

View details for DOI 10.1161/CIRCHEARTFAILURE.109.918672

View details for PubMedID 20807863
Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC) A Multicenter Placebo-Controlled Randomized Trial: Age Analysis 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Portman, M. A., Slee, A., Olson, A. K., Cohen, G., Karl, T., Tong, E., Hastings, L., Patel, H., Reinhartz, O., Mott, A. R., Mainwaring, R., Linam, J., Danzi, S. LIPPINCOTT WILLIAMS & WILKINS. 2010: S224–S233
Abstract

Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome.The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (P=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (P=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7-22) for placebo and 20 hours (CI, 16-45) for Triostat and (hazard ratio, 0.60; P=0.0220).T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00027417.

View details for DOI 10.1161/CIRCULATIONAHA.109.926394

View details for Web of Science ID 000282294800032

View details for PubMedID 20837917
Unusual Manifestations of Vascular Rings JOURNAL OF CARDIAC SURGERY Mainwaring, R. D., Jacobson, J. L., Reinhartz, O., Gates, R. L. 2010; 25 (1): 79-83
Abstract

Vascular rings are a relatively rare entity caused by abnormal development of the fetal aortic arches. Most patients with vascular rings present in infancy or early childhood with respiratory (inspiratory) symptoms. The treatment of patients with symptomatic vascular rings is generally straight-forward, focusing on surgical division of the ring. The majority of patients are "cured" by this simple procedure. However, a small percentage of patients do not follow this typical course. The purpose of this manuscript is to review and discuss three patients who demonstrated unusual manifestations of vascular rings. Two patients required reoperation after double aortic arch repair and one had successful treatment of an aberrant right subclavian artery.

View details for DOI 10.1111/j.1540-8191.2009.00947.x

View details for Web of Science ID 000273164700023

View details for PubMedID 19874418
Selective Right Ventricular Unloading and Novel Technical Concepts in Ebstein's Anomaly 45th Annual Meeting of the Society-of-Thoracic-Surgeons Malhotra, S. P., Petrossian, E., Reddy, V. M., Qiu, M., Maeda, K., Suleman, S., Macdonald, M., Reinhartz, O., Hanley, F. L. ELSEVIER SCIENCE INC. 2009: 1975–81
Abstract

Favorable outcomes in Ebstein's anomaly are predicated on tricuspid valve competence and right ventricular function. Successful valve repair should be aggressively pursued to avoid the morbidity of prosthetic tricuspid valve replacement. We report our experience with valve-sparing intracardiac repair, emphasizing novel concepts and techniques of valve repair supplemented by selective bidirectional Glenn (BDG).Between June 1993 and December 2008, 57 nonneonatal patients underwent Ebstein's anomaly repairs. The median age at operation was 8.1 years. All were symptomatic in New York Heart Association (NYHA) functional class II (n = 38), III (n = 17), or IV (n = 1). Preoperatively, 26 had mild or moderate cyanosis at rest. We used a number of valve reconstructive techniques that differed substantially from those currently described. BDG was performed in 31 patients (55%) who met specific criteria.No early or late deaths occurred. At the initial repair, 3 patients received a prosthetic valve. Four patients required reoperation for severe tricuspid regurgitation. Repeat repairs were successful in 2 patients. At follow-up (range, 3 months to 6 years), all patients were acyanotic and in NYHA class I. Tricuspid regurgitation was mild or less in 49 (86%) and moderate in 6 (11%). Freedom from a prosthesis was 91% (52 of 57).Following a protocol using BDG for ventricular unloading in selected patients with Ebstein's anomaly can achieve a durable valve-sparing repair using the techniques described. Excellent functional midterm outcomes can be obtained with a selective one and a half ventricle approach to Ebstein's anomaly.

View details for DOI 10.1016/j.athoracsur.2009.07.019

View details for Web of Science ID 000272029100037

View details for PubMedID 19932271
Recovery During Mid-Term Mechanical Support of Fontan Circulation in Sheep ASAIO JOURNAL Tsuda, S., Sasaki, T., Maeda, K., Riemer, R. K., Reichenbach, S. H., Reinhartz, O. 2009; 55 (4): 406-411
Abstract

Total cavopulmonary connection (CPC) has a significant incidence of late failure due to increased systemic venous pressure and low cardiac output. Mechanical support could prevent failure by correcting hemodynamics. We established a model of inferior CPC using an axial flow pump (Thoratec HeartMate II, Thoratec Corp. Pleasanton, CA) in a group of ten 47-57 kg sheep and assessed hemodynamics and metabolism as a potential chronic treatment option for failed Fontan circulation. After pilot studies (n = 7), three animals underwent pump-supported inferior CPC to assess hemodynamic and metabolic responses. Pump inflow was connected to the inferior vena cava (IVC) and outflow to the main pulmonary artery. The IVC was ligated at the right atrium. Hemodynamic and biochemical parameters were recorded over four days. The first seven animals died from pump-related causes (graft kinking, three; pump thrombosis, one) or other causes (GI bleeding, one; suspected stroke, two). The subsequent three animals were electively euthanized on postoperative day four due to IRB requirements. Over the four day postoperative period, pump flow was 3.43 +/- 0.62 L/min and IVC pressure 4.05 +/- 3.21 mm Hg (mean +/- SD). Lactate levels remained normal. Low pressure and high-volume IVC flow was sustained by mechanical support. We will next attempt chronic pump implantation.

View details for DOI 10.1097/MAT.0b013e3181a0a570

View details for Web of Science ID 000267559100016

View details for PubMedID 19471161
Use of INTERMACS Criteria To Assess Major Clinical Outcomes In Children Bridged to Heart Transplant Using Mechanical Circulatory Support 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation Stein, M. L., Robbins, R., Sabati, A., Reinhartz, O., Chin, C., Liu, E., Bernstein, D., Roth, S., Wright, G., Reitz, B. ELSEVIER SCIENCE INC. 2009: S207–S208
View details for Web of Science ID 000263539800406
Outcome Analysis for a Small, Start-up Congenital Heart Surgery Program 1st Meeting of the World-Society-for-Pediatric-and-Congenital-Heart-Surgery Mainwaring, R. D., Reddy, V. M., Reinhartz, O., Lamberti, J. J., Jacobson, J. G., Jimenez, D. L., Hanley, F. L. WILEY-BLACKWELL PUBLISHING, INC. 2008: 622–26
Abstract

There will be a continuing need to start new congenital heart surgery programs to serve communities experiencing significant population growth. However, small congenital heart programs frequently underperform their larger counterparts. This study summarizes the clinical outcome data for the first 42 months of a small, start-up congenital heart surgery program. Clinical outcomes were summarized from the start of the program in September 2003 through March 2007. Risk adjustment analysis was performed using the risk adjustment in congenital heart surgery (Rachs-1) risk adjustment model and Society of Thoracic Surgeons (STS) congenital database. Three hundred eighty-six operations have been performed during this time period, including 47 newborns, 96 infants, 217 children/adolescents, and 26 adults (greater than 18 years). There have been two operative mortalities (0.5%). Assigning these cases to the Rachs-1 categories, there were 64 level I, 188 level II, 90 level III, 12 level IV cases, with 32 "others." The predicted mortality for the 354 categorized cases calculates to be 17.4 (Rachs-1) and 10.2 (STS). The data demonstrate that a start-up program with a relatively modest surgical volume can achieve satisfactory clinical results. This model has relied upon careful case selection and direct, senior-level surgeon involvement through an affiliation with a university-based program. These results suggest that a small congenital heart surgery program can be successfully started if the circumstances are carefully controlled.

View details for DOI 10.1111/j.1540-8191.2008.00675.x

View details for Web of Science ID 000260499400007

View details for PubMedID 19016985
Dynamics of human myocardial progenitor cell Populations in the neonatal period ANNALS OF THORACIC SURGERY Amir, G., Ma, X., Reddy, V. M., Hanley, F. L., Reinhartz, O., Ramamoorthy, C., Riemer, R. K. 2008; 86 (4): 1311-1320
Abstract

Pluripotent cardiac progenitor cells resident in myocardium offer a potentially promising role in promoting recovery from injury. In pediatric congenital heart disease (CHD) patients, manipulation of resident progenitor cells may provide important new approaches to improving outcomes. Our study goals were to identify and quantitate populations of progenitor cells in human neonatal myocardium during the early postnatal period and determine the proliferative capacity of differentiated cardiac myocytes.Immunologic markers of cell lineage (stage-specific embryonic antigen 4 [SSEA-4], islet cell antigen 1 [Isl1], c-kit, Nkx2.5, sarcoplasmic reticulum calcium-regulated ATPase type 2 [SERCA2]) and proliferation (Ki67) were localized in right ventricular biopsies from 32 CHD patients aged 2 to 93 days.Neonatal myocardium contains progenitor cells and transitional cells expressing progenitor and differentiated myocyte marker proteins. Some cells expressed the pluripotent cell marker c-kit and also coexpressed the myocyte marker SERCA2. Multipotent progenitor cells, identified by the expression of Isl1, were found. Ki67 was expressed in some myocytes and in nonmyocyte cells. A few cells expressing SSEA-4 and Isl1 were observed during the early postnatal period. Cells expressing c-kit, the premyocyte marker Nkx2.5, and Ki67 were found throughout the first postnatal month. A progressive decline in cell density during the first postnatal month was observed for c-kit+ cells (p = 0.0013) and Nkx2.5+ cells (p = 0.0001). The percentage of cells expressing Ki67 declined during the first 3 postnatal months (p = 0.0030).Cells in an incomplete state of cardiomyocyte differentiation continue to reside in the infant heart. However, the relative density of progenitor cells declines during the first postnatal month.

View details for DOI 10.1016/j.athoracsur.2008.06.058

View details for Web of Science ID 000259848000036

View details for PubMedID 18805183
Surgical management of coronary artery arising from the wrong coronary sinus, using standard and novel approaches 85th Annual Meeting of the American-Association-for-Thoracic-Surgery Gulati, R., Reddy, V. M., Culbertson, C., Helton, G., Suleman, S., Reinhartz, O., Silverman, N., Hanley, F. L. MOSBY-ELSEVIER. 2007: 1171–U12
Abstract

Patients with a coronary artery arising from the wrong sinus are susceptible to ischemia and sudden death. Risk is higher when the artery courses interarterially--between the pulmonary artery and aorta--has an intramural course, or has an abnormal orifice. In single coronary ostium without intramural course, unroofing and coronary reimplantation are inappropriate, and coronary artery bypass grafting is suboptimal. For this variant, we have devised pulmonary artery translocation.A retrospective review of 18 patients undergoing repair between January 1999 and March 2005 was performed. Mean age was 8.1 years (range 6 weeks-16 years). All anomalous arteries coursed interarterially. Ten patients had a right coronary artery from the left coronary sinus; 8 had a left coronary artery from the right sinus. Eleven had an intramural course, and 4 had a single coronary ostium without an intramural course. Ten (56%) patients had symptoms: chest pain (9/10), syncope (3/10), or dyspnea (2/10). Repair was implemented by unroofing (n = 11), reimplantation (n = 3), or pulmonary artery translocation (1 lateral, 3 anterior). All patients were followed up clinically and echocardiographically.At a mean of 2.2 years (2 weeks-5 years), there was no mortality. Symptoms improved and function remained normal in all but 1 patient. He had sustained multiple infarcts in the anomalous artery's distribution and required transplantation despite repair.Repair is indicated in all patients with coronary insufficiency and in asymptomatic patients with high-risk morphologic abnormalities. We recommend unroofing when an intramural component (or slit-like orifice) is present, reimplantation for separate ostia without an intramural course, and pulmonary artery translocation for single ostium without an intramural course. Coronary artery bypass grafting is thus avoided.

View details for DOI 10.1016/j.jtcvs.2007.02.051

View details for Web of Science ID 000250576200011

View details for PubMedID 17976445
The extracardiac conduit Fontan operation using minimal approach extracorporeal circulation: Early and midterm outcomes 85th Annual Meeting of the American-Association-for-Thoracic-Surgery Petrossian, E., Reddy, V. M., Collins, K. K., Culbertson, C. B., MacDonald, M. J., Lamberti, J. J., Reinhartz, O., Mainwaring, R. D., Francis, P. D., Malhotra, S. P., Gremmels, D. B., Suleman, S., Hanley, F. L. MOSBY-ELSEVIER. 2006: 1054–63
Abstract

Our approach to the extracardiac conduit Fontan operation has evolved over time from full-pump, to partial-pump, to completely off-pump. This study is designed to report our overall experience with the extracardiac conduit Fontan operation and to evaluate the evolution in bypass technique on postoperative outcomes.From September 1992 to April 2005, 285 patients, median age 4.5 years (1.4-44 years), median weight 16 kg (9.4-94 kg), underwent a primary extracardiac conduit Fontan procedure. Early and late outcomes were analyzed for the entire cohort and for 2 patient groups depending on whether an oxygenator was used in the bypass circuit (166 patients; 58%) or not (119 patients; 42%).Early failure (including death and takedown) occurred in 7 patients (2.5%). Prevalence of new early postoperative sinus node dysfunction necessitating a permanent pacemaker was 0.4%, and that of new tachyarrhythmias necessitating discharge home on a regimen of antiarrhythmia medications was 2.5%. Ten-year actuarial freedom from Fontan failure, new sinus node dysfunction necessitating a permanent pacemaker, and reoperation for conduit thrombosis or stenosis was 90%, 96%, and 98%, respectively. Fenestration rate was lower (P = .001) in the no-oxygenator group (8%) than in the oxygenator group (25%). Patients in the no-oxygenator group had lower intraoperative Fontan pressure (12.0 +/- 2.3 vs 13.5 +/- 2.4 mm Hg, P < .001), common atrial pressure (4.6 +/- 1.8 vs 5.3 +/- 1.8 mm Hg, P = .003), and transpulmonary gradient (7.5 +/- 2.1 vs 8.3 +/- 2.2 mm Hg, P = .013) than did the oxygenator group.The extracardiac conduit Fontan operation coupled with minimal use of extracorporeal circulation is associated with favorable intraoperative hemodynamics, low fenestration rate, minimal risk of thrombosis or stenosis, and minimal early and late rhythm disturbance.

View details for DOI 10.1016/j.jtcvs.2006.05.066

View details for PubMedID 17059923
Coarctation of the aorta in the right aortic arch with left aberrant innominate artery PEDIATRIC CARDIOLOGY Bein, S., Saba, Z., Patel, H., Reinhartz, O., Hanley, F. L. 2006; 27 (5): 621-623
Abstract

Right aortic arch with an aberrant left innominate artery is a rare combination. We report a unique case of coarctation of the aorta in a patient with right aortic arch and aberrant left innominate artery. The diverticulum of Kommerell gave rise to the left innominate artery and a left ligamentum arteriosum, completing a vascular ring. This unusual case raises interesting points regarding the development of coarctation in the context of a right-sided arch and the approach to management of these patients.

View details for DOI 10.1007/s00246-006-1327-y

View details for Web of Science ID 000240913400017

View details for PubMedID 16933062
Unifocalization of major aortopulmonary collaterals in single-ventricle patients 42nd Annual Meeting of the Society-of-Thoracic-Surgeons Reinhartz, O., Reddy, V. M., Petrossian, E., Suleman, S., Mainwaring, R. D., Rosenthal, D. N., Feinstein, J. A., Gulati, R., Hanley, F. L. ELSEVIER SCIENCE INC. 2006: 934–39
Abstract

Unifocalization of major aortopulmonary collateral arteries (MAPCAs) in pulmonary atresia with ventricular septal defect and intracardiac repair has become the standard of care. However, there are no reports addressing unifocalization of MAPCAs in single-ventricle patients. It is unknown whether their pulmonary vascular bed can be reconstructed and low enough pulmonary vascular resistance achieved to allow for superior or total cavopulmonary connections.We reviewed data on all patients with functional single ventricles and unifocalization procedures of MAPCAs. From 1997 to 2005, 14 consecutive children with various single-ventricle anatomies were operated on.Patients had a median of three surgical procedures (range, 1 to 5). Two patients had absent, all others diminutive central pulmonary arteries, with an average of 3.5 +/- 1.2 MAPCAs. Seven patients (50%) had bidirectional Glenn procedures, and 3 of these had Fontan procedures. Median postoperative pulmonary artery pressures measured 12.5 mm Hg (Glenn) and 14 mm Hg (Fontan), respectively. Six patients are alive today (46%), with 1 patient lost to follow-up. Three patients died early and 3 late after initial unifocalization to shunts. One other patient survived unifocalization, but was not considered a candidate for a Glenn procedure and died after high-risk two-ventricle repair. Another patient with right-ventricle-dependent coronary circulation died of sepsis late after Glenn.In selected patients with functional single ventricles and MAPCAs, the pulmonary vascular bed can be reconstructed sufficiently to allow for cavopulmonary connections. Venous flow to the pulmonary vasculature decreases cardiac volume load and is likely to increase life expectancy and quality of life for these patients.

View details for DOI 10.1016/j.athoracsur.2006.03.063

View details for PubMedID 16928512
Homograft valved right ventricle to pulmonary artery conduit as a modification of the Norwood procedure 78th Annual Scientific Session of the American-Heart-Association Reinhartz, O., Reddy, V. M., Petrossian, E., Macdonald, M., Lamberti, J. J., Roth, S. J., Wright, G. E., Perry, S. B., Suleman, S., Hanley, F. L. LIPPINCOTT WILLIAMS & WILKINS. 2006: I594–I599
Abstract

The use of a right ventricle to pulmonary artery (RV-PA) conduit in the Norwood procedure has been proposed to increase postoperative hemodynamic stability. A valve within the conduit should further decrease RV volume load. We report our clinical experience with this modification.From February 2002 through August 2005, we performed 88 consecutive Norwood procedures using RV-PA conduits. We used composite valved conduits made from cryopreserved homograft and polytetrafluoroethylene (PTFE) in 66 cases (54 pulmonary, 12 aortic homografts), other valved conduits in 14, and unvalved PTFE in 8 cases. Hospital survival was 88.6% overall and increased to 93.1% after the initial year. Early interventions were required in 18 patients (16 for cyanosis). Prestage II cardiac catheterization was performed at a mean age of 126 days. Mean Qp/Qs was 1, with mean aortic saturation 71%, mean O2 extraction 24%, and mean right ventricular end-diastolic pressure 9 mm Hg. Patient weight, use of an aortic homograft valve in the conduit, stage I palliation within the first year of our experience, and low O2 extraction and high transpulmonary gradient prestage II were risk factors for overall death. Early interventions were more frequent in aortic valve conduits compared with all other conduits.The valved RV-PA conduit was associated with low early mortality after the Norwood procedure. The majority of these patients had normal cardiac output and well-maintained RV function. There may be a higher risk for early conduit interventions and death when aortic valve homografts are used in the RV-PA conduit.

View details for PubMedID 16820644
Clinical outcomes in pediatric patients implanted with Thoratec ventricular assist device. Seminars in thoracic and cardiovascular surgery. Pediatric cardiac surgery annual Hill, J. D., Reinhartz, O. 2006: 115-122
Abstract

Most mechanical circulatory support devices are designed for adult patients; however, some can be successfully applied to pediatric patients. The rates of complications and patient survival to transplant or native heart recovery after implantation of the Thoratec ventricular assist device (VAD) (Thoratec Corp, Pleasanton, CA) in children and adolescents were determined from the company's voluntary registry. As of January 2005, 209 patients (mean age 14.5 years; range 5 to 18 years) have been supported with the Thoratec VAD. Mean patient weight was 57 kg (range, 17 to 118 kg), and patients had a mean body surface area of 1.6 m2 (range, 0.73 to 2.3 m2). The major etiologies necessitating VAD support included cardiomyopathy (55.0%), acute myocarditis (25.4%), and end-stage congenital heart disease (5.8%). Mean duration of VAD support was 44 days (range, 0 to 434 days). Patient survival to transplantation or native heart recovery was 68.4%. Patients with cardiomyopathy and acute myocarditis had 74.1% and 86.0% survival, respectively, with only 27.3% survival in patients having congenital heart disease. The overall survival rate in smaller children (body surface area, <1.3 m2) was similar at 51.7%, although the incidence of congenital heart disease was higher.

View details for PubMedID 16638556
Effect of surgical case volume on outcome after the Norwood procedure JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MacDonald, M. J., Reinhartz, O., Hanley, F. L. 2005; 130 (6): 1731-1731
View details for DOI 10.1016/j.jtcvs.2005.06.028

View details for Web of Science ID 000233896300046

View details for PubMedID 16308032
Homograft valved right ventricle to pulmonary artery conduit as a modification of the norwood procedure 78th Annual Scientific Session of the American-Heart-Association Reinhartz, O., Reddy, V. M., MacDonald, M. J., Lamberti, J. J., Petrossian, E., Perry, S. B., Suleman, S., Hanley, F. L. LIPPINCOTT WILLIAMS & WILKINS. 2005: U577–U577
View details for Web of Science ID 000232956403391
Management of major aortopulmonary collateral arteries 78th Annual Scientific Session of the American-Heart-Association Hanley, F. L., Reinhartz, O., Suleman, S., Gremmels, D. B., Perry, S. B., Feinstein, J. A., Reddy, V. M. LIPPINCOTT WILLIAMS & WILKINS. 2005: U576–U576
View details for Web of Science ID 000232956403388
Thoratec ventricular assist devices in pediatric patients: Update on clinical results 1st International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion Reinhartz, O., Hill, J. D., Al-Khaldi, A., Pelletier, M. P., Robbins, R. C., Farrar, D. J. LIPPINCOTT WILLIAMS & WILKINS. 2005: 501–3
Abstract

Particularly in pediatric patients, mechanical circulatory support remains a clinical challenge. We analyzed the Stanford experience with use of the Thoratec ventricular assist device (VAD) in children and adolescents and data from the company's voluntary database. Through January 2005, 209 patients up to 18 years of age have been supported with the Thoratec VAD worldwide. Mean age was 14.5 years (range 5-18 years), mean weight was 57 kg (range 17-118 kg), and mean body surface area was 1.6 m2 (range 0.7-2.3 m2). The majority of patients were supported for cardiomyopathies (55%) and acute myocarditis (25%). A minority (6%) was treated for end-stage congenital heart disease. Average duration of support was 44 days (0-434 days). Overall survival to transplantation or weaning off the device was 68%. Survival rates were higher for patients with cardiomyopathies (74%) and acute myocarditis (86%) compared with patients with congenital heart disease (27%). We performed a subanalysis in small children with a body surface area of less 1.3 m2. This subgroup had a higher incidence of congenital heart disease and a slightly lower survival (52%). Aspects of the particular risks and device management in these small patients are discussed.

View details for DOI 10.1097/01.mat.0000178214.95010.c0

View details for Web of Science ID 000238586400009

View details for PubMedID 16322705
An isolated left common carotid artery from the main pulmonary artery: Possible malseptation of the truncoaortic sac PEDIATRIC CARDIOLOGY Kaushik, N., Saba, Z., Rosenfeld, H., Patel, H. T., Martin, K., Reinhartz, O., Lamberti, J. J. 2005; 26 (5): 707-709
Abstract

An isolated left common carotid artery (LCA) is an extremely rare condition with only four reported cases. In each case, the isolated carotid artery connects to the right or left pulmonary artery via the ductus arteriosus and the embryologic basis for the abnormalities is believed to reflect an error in the development of the branchial arches. We present a case of an isolated LCA connecting to the main pulmonary artery in association with a right aortic arch and an anomalous origin of the left subclavian artery from the descending aorta. The left ligamentus arteriosus was identified separately. This may represent a disturbance in the septation of the truncoaortic sac secondary to abnormal migration of neural crest cells rather than a pure developmental anomaly of the branchial arches.

View details for DOI 10.1007/s00246-004-0896-x

View details for Web of Science ID 000233663800041

View details for PubMedID 15565269
Mechanical support of total cavopulmonary connection with an axial flow pump 50th Annual Conference of the American-Society-for-Artificial-Internal-Organs Riemer, R. K., Amir, G., Reichenbach, S. H., Reinhartz, O. MOSBY-ELSEVIER. 2005: 351–54
Abstract

Even under optimal circumstances, total cavopulmonary connection is associated with a continuous late risk of death. Hemodynamics are distinctly abnormal, with increased systemic venous pressures and frequent low cardiac output. Our study uses a sheep model of total cavopulmonary connection to test the response to axial flow pump (Thoratec HeartMate II; Thoratec Corporation (Pleasanton, Calif)) support of total cavopulmonary connection, which might be suitable to treat patients with failing Fontan circulation.Eight sheep (42-48 kg) were studied. After pilot studies in 3 animals, 5 underwent both pump-supported and nonsupported total cavopulmonary connection in alternating sequence for up to 2 hours. This was achieved with a 12-mm polytetrafluoroethylene graft from the (distally ligated) superior vena cava to the main pulmonary artery and a cannula placed in the inferior vena cava with an attached 16-mm Dacron graft to the main pulmonary artery. Pressures (arterial, inferior vena cava, left atrium, and pulmonary artery) and flows (ascending aorta and inferior vena cava) were recorded over 1 hour both with unsupported total cavopulmonary connection and after placing an axial flow pump (Thoratec HeartMate II) between the inferior vena caval inflow cannula and the main pulmonary artery.Under nonsupported total cavopulmonary connection circulation, inferior vena caval and aortic blood flow decreased by nearly 50%. Inferior vena caval pressure nearly doubled, whereas arterial pressure decreased by one third. Pulmonary artery pressure became nonpulsatile; however, mean pulmonary artery pressure and left atrial pressure did not change significantly. With pump-supported Fontan circulation, cardiac output, inferior vena caval flow, and arterial pressure returned to baseline. Inferior vena caval pressure decreased to below baseline levels. Mean pulmonary artery pressure and left atrial pressure again remained unchanged.Axial flow pump support from the inferior vena cava to the pulmonary artery can prevent the substantial decrease of aortic flow and pressure associated with total cavopulmonary connection and can reverse its poor hemodynamics. This is a simple model that can be used to further evaluate the potential of mechanical support as a treatment option in failing Fontan circulation.

View details for DOI 10.1016/j.jtcvs.2004.12.037

View details for Web of Science ID 000231069700019

View details for PubMedID 16077398
Tezosentan, a combined parenteral endothelin receptor antagonist, produces pulmonary vasodilation in lambs with acute and chronic pulmonary hypertension. Pediatric critical care medicine Fitzgerald, R. K., Oishi, P., Ovadia, B., Ross, G. A., Reinhartz, O., Johengen, M. J., Fineman, J. R. 2004; 5 (6): 571-577
Abstract

To investigate the hemodynamic effects of tezosentan in the intact lamb both at rest and during acute and chronic pulmonary hypertension.Prospective, randomized experimental study.University-based research laboratory.Lambs with and without pulmonary hypertension.Six newborn lambs were instrumented to measure vascular pressures and left pulmonary blood flow. The hemodynamic effects of tezosentan (0.5, 1.0, 5.0 mg/kg, intravenously) were studied at rest and during U46619-induced pulmonary hypertension. Following in utero placement of an aortopulmonary vascular graft, nine additional lambs with increased pulmonary blood flow and chronic pulmonary hypertension (shunt) were also studied at 1 wk (n = 5) and 8 wks (n = 4) of age.At rest, tezosentan had no significant effect on any of the variables. During acute U46619-induced pulmonary hypertension, tezosentan caused a dose-dependent decrease in pulmonary arterial pressure (from 5.9% +/- 4.7 to 16.0% +/- 10.7; p < .05) and pulmonary vascular resistance (from 6.2% +/- 8.0 to 21% +/- 8.8; p < .05). Mean systemic arterial pressure was unchanged. In 1- and 8-wk-old shunt lambs with increased pulmonary blood flow, tezosentan (1 mg/kg) produced potent nonselective pulmonary vasodilation.Tezosentan, a combined endothelin receptor antagonist optimized for parenteral use, induces potent selective pulmonary vasodilation during acute U46619-induced pulmonary hypertension and potent nonselective vasodilation in chronic pulmonary hypertension secondary to increased pulmonary blood flow. In general, the hemodynamic effects of bolus doses of tezosentan occurred within 60 secs of administration and lasted approximately 5-10 mins. The hemodynamic profile of intravenous tezosentan may make it a useful adjunct therapy for acute pulmonary hypertensive disorders and warrants further study.

View details for PubMedID 15530195
Chronic endothelin A receptor blockade in lambs with increased pulmonary blood flow and pressure AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY Fratz, S., Meyrick, B., Ovadia, B., Johengen, M. J., Reinhartz, O., Azakie, A., Ross, G., Fitzgerald, R., Oishi, P., Hess, J., Black, S. M., Fineman, J. R. 2004; 287 (3): L592-L597
Abstract

Endothelin receptor blockade is an emerging therapy for pulmonary hypertension. However, hemodynamic and structural effects and potential changes in endogenous nitric oxide (NO)-cGMP and endothelin-1 signaling of chronic endothelin A receptor blockade in pulmonary hypertension secondary to congenital heart disease are unknown. Therefore, the objectives of this study were to determine hemodynamic and structural effects and potential changes in endogenous NO-cGMP and endothelin-1 signaling of chronic endothelin A receptor blockade in a lamb model of increased pulmonary blood flow following in utero placement of an aortopulmonary shunt. Immediately after spontaneous birth, shunt lambs were treated lifelong with either an endothelin A receptor antagonist (PD-156707) or placebo. At 4 wk of age, PD-156707-treated shunt lambs (n = 6) had lower pulmonary vascular resistance and right atrial pressure than placebo-treated shunt lambs (n = 8, P < 0.05). Smooth muscle thickness or arterial number per unit area was not different between the two groups. However, the number of alveolar profiles per unit area was increased in the PD-156707-treated shunt lambs (190.7 +/- 5.6 vs. 132.9 +/- 10.0, P < 0.05). Plasma endothelin-1 and cGMP levels and lung NOS activity, cGMP, eNOS, preproendothelin-1, endothelin-converting enzyme-1, endothelin A, and endothelin B receptor protein levels were similar in both groups. We conclude that chronic endothelin A receptor blockade attenuates the progression of pulmonary hypertension and augments alveolar growth in lambs with increased pulmonary blood flow.

View details for DOI 10.1152/ajplung.00093.2004

View details for Web of Science ID 000223251000021

View details for PubMedID 15155268
Pulmonary expression of the hepatocyte growth factor receptor c-Met shifts from medial to intimal layer after cavopulmonary anastomosis 83rd Annual Meeting of the American-Association-for-Thoracic-Surgery Ikai, A., Riemer, R. K., Ma, X. Y., Reinhartz, O., Hanley, F. L., Reddy, V. M. MOSBY-ELSEVIER. 2004: 1442–49
Abstract

Pulmonary arteriovenous malformations occur in up to 60% of patients after cavopulmonary anastomosis. We compared the effects of cavopulmonary anastomosis and pulmonary artery banding on lung gene expression in an ovine model to study the abnormal pulmonary vascular remodeling after the exclusion of inferior vena caval blood independent of reduced pulmonary blood flow. We previously demonstrated by contrast echocardiography that pulmonary arteriovenous malformations develop by 8 weeks after cavopulmonary anastomosis but not after pulmonary artery banding. Hepatocyte growth factor, a pleiotropic factor with morphogenic, mitogenic, and angiogenic activities, signals via its specific receptor c-Met to induce the antiapoptotic factor Bcl-2. In this study, we examined pulmonary artery expression of these factors and their potential role in pulmonary artery remodeling after cavopulmonary anastomosis and pulmonary artery banding.Eighteen lambs aged 35 to 45 days were placed into 3 groups: cavopulmonary anastomosis, pulmonary artery banding, and control (n = 6/group). In the cavopulmonary anastomosis group, the superior vena cava was anastomosed to the right pulmonary artery in an end-to-end fashion. In the pulmonary artery banding group, the left pulmonary artery was banded to reduce blood flow to 20% of control. The control group had a simple right pulmonary artery clamp for 30 minutes. Lung was harvested for Western blot, reverse transcriptase-polymerase chain reaction, and immunostaining at 2 weeks (n = 3/group) and 5 weeks (n = 3/group) after surgery.The expression of c-Met mRNA after cavopulmonary anastomosis was increased by twofold compared with the control or pulmonary artery banding group. The total lung expression of c-Met by Western blot was also up regulated at 2 weeks (P <.05). However, total lung expression of hepatocyte growth factor and Bcl-2 by Western and reverse transcriptase-polymerase chain reaction was not different from the control and pulmonary artery banding groups at both 2 and 5 weeks after surgery. Immunohistochemical analysis revealed that c-Met expression was localized to the intimal layer of the pulmonary artery in the cavopulmonary anastomosis, while its expression in the control and pulmonary artery banding lungs was localized to the medial layer. Localization of Bcl-2 on the intimal layer in lambs with cavopulmonary anastomosis followed the same pattern as c-Met.After cavopulmonary anastomosis, pulmonary artery expression of the hepatocyte growth factor receptor c-Met and one of its downstream effectors, Bcl-2, had increased in the intimal layer and decreased in the medial layer. Because the hepatocyte growth factor signaling promotes increased endothelial cell survival, it may have a role in pulmonary artery remodeling following cavopulmonary anastomosis. In addition, the change of c-Met expression in the medial layer after cavopulmonary anastomosis suggests a possible mechanism for the smooth muscle cell alteration related to abnormal angiogenesis.

View details for DOI 10.1016/j.jtcvs.2003.09.009

View details for Web of Science ID 000221134600031

View details for PubMedID 15116006
Thoratec ventricular assist devices in children with less than 1.3 m(2) of body surface area ASAIO JOURNAL Reinhartz, O., Copeland, J. G., Farrar, D. J. 2003; 49 (6): 727-730
Abstract

This report summarizes the multicenter experience with the Thoratec paracorporeal pneumatic ventricular assist device (VAD) (Thoratec Corp., Pleasanton, CA) in small children. Between October 1988 and August 2001, 19 children (11 male, 8 female) with less than 1.3 (mean 1.09, range 0.73-1.29) m2 body surface area (BSA) have been supported with univentricular (9) or biventricular (10) Thoratec VADs in 12 centers in the United States and Germany. Mean patient age was 10 (range 7-14) years, mean weight 31 (range 17-41) kg. Indications for support were end-stage cardiomyopathy in eight patients, myocarditis in three, end-stage congenital heart disease in seven, and transplant graft failure in one patient. Mean duration of support was 43 (range 0-120) days. In patients with cardiomyopathies and myocarditis, survival through discharge occurred in 8 of 11 (72%) patients; however, only 1 of 7 patients with congenital disease survived. Outcome appeared independent of patient size. Neurologic complications were significant and predominant in the congenital disease group. Our experience suggests that the Thoratec VAD can be successfully used in these difficult patients, particularly in children with cardiomyopathies and myocarditis. Congenital disease is associated with increased risk. To reduce thromboembolic risk, we recommend left ventricular as opposed to left atrial inflow cannulation and higher device rates with partial stroke volumes.

View details for DOI 10.1097/01.MAT.0000093965.33300.83

View details for Web of Science ID 000186745400022

View details for PubMedID 14655743
Emergence of smooth muscle cell endothelin B-Mediated vasoconstriction in lambs with experimental congenital heart disease and increased pulmonary blood flow CIRCULATION Black, S. M., Mata-Greenwood, E., Dettman, R. W., Ovadia, B., Fitzgerald, R. K., Reinhartz, O., Thelitz, S., Steinhorn, R. H., Gerrets, R., Hendricks-Munoz, K., Ross, G. A., Bekker, J. M., Johengen, M. J., Fineman, J. R. 2003; 108 (13): 1646-1654
Abstract

Endothelin-1 (ET-1) has been implicated in the pathophysiology of pulmonary hypertension. In 1-month-old lambs with increased pulmonary blood flow, we have demonstrated early alterations in the ET-1 cascade. The objective of this study was to investigate the role of potential later alterations of the ET cascade in the pathophysiology of pulmonary hypertension secondary to increased pulmonary blood flow.Eighteen fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt) and were studied 8 weeks after spontaneous delivery. Compared with age-matched control lambs, lung tissue ET-1 levels were increased in shunt lambs (317.2+/-113.8 versus 209.8+/-61.8 pg/g, P<0.05). In shunt lambs (n=9), exogenous ET-1 induced potent pulmonary vasoconstriction, which was blocked by the ETA receptor antagonist PD 156707 (n=3). This pulmonary vasoconstriction was mimicked by exogenous Ala1,3,11,15 ET-1 (4 Ala ET-1), the ETB receptor agonist, and was blocked by the ETB receptor antagonist BQ 788 (n=3). However, in control lambs (n=7), ET-1 and 4 Ala ET-1 did not change pulmonary vascular tone. In contrast to 4-week-old shunt lambs, immunohistochemistry revealed the emergence of ETB receptors on smooth muscle cells in the vasculature of 8-week-old shunt lambs.Over time, increased pulmonary blood flow and/or pressure results in the emergence of ETB-mediated vasoconstriction, which coincides with the emergence of ETB receptors on smooth muscle cells. These data suggest an important role for ETB receptors in the pathophysiology of pulmonary hypertension in this animal model of increased pulmonary blood flow.

View details for DOI 10.1161/01.CIR.0000087596.01416.2F

View details for Web of Science ID 000185624500033

View details for PubMedID 12963646
Alterations in ET-1, not nitric oxide, in 1-week-old lambs with increased pulmonary blood flow AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Ovadia, B., Reinhartz, O., Fitzgerald, R., Bekker, J. M., Johengen, M. J., Azakie, A., Thelitz, S., Black, S. M., Fineman, J. R. 2003; 284 (2): H480-H490
Abstract

Altered pulmonary vascular reactivity is a source of morbidity and mortality for children with congenital heart disease and increased pulmonary blood flow. Nitric oxide (NO) and endothelin (ET)-1 are important mediators of pulmonary vascular reactivity. We hypothesize that early alterations in endothelial function contribute to the altered vascular reactivity associated with congenital heart disease. The objective of this study was to characterize endothelial function in our lamb model of increased pulmonary blood flow at 1 wk of life. Eleven fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt) and were studied 7 days after delivery. The pulmonary vasodilator response to both intravenous ACh (endothelium dependent) and inhaled NO (endothelium independent) was similar in shunted and control lambs. In addition, tissue NO(x), NO synthase (NOS) activity, and endothelial NOS protein levels were similar. Conversely, the vasodilator response to both ET-1 and 4Ala-ET-1 (an ET(B) receptor agonist) were attenuated in shunted lambs, and tissue ET-1 concentrations were increased (P < 0.05). Associated with these changes were an increase in ET-converting enzyme-1 protein and a decrease in ET(B) receptor protein levels (P < 0.05). These data demonstrate that increased pulmonary blood flow induces alterations in ET-1 signaling before NO signaling and suggest an early role for ET-1 in the altered vascular reactivity associated with increased pulmonary blood flow.

View details for DOI 10.1152/ajpheart.00493.2002

View details for Web of Science ID 000180400800008

View details for PubMedID 12399254
Pulmonary vascular K+ channel expression and vasoreactivity in a model of congenital heart disease AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY Cornfield, D. N., Resnik, E. R., Herron, J. M., Reinhartz, O., Fineman, J. R. 2002; 283 (6): L1210-L1219
Abstract

K+ channels play an important role in mediating pulmonary vasodilation caused by increased oxygen tension, nitric oxide, alkalosis, and shear stress. To test the hypothesis that lung K+ channel gene expression may be altered by chronic increases in pulmonary blood flow, we measured gene and protein expression of calcium-sensitive (K Ca ) and voltage-gated (Kv2.1) K+ channels, and a pH-sensitive K+ channel (TASK), in distal lung from fetal lambs in which an aortopulmonary shunt was placed at 139 days gestation. Under baseline conditions, animals with an aortopulmonary shunt showed elevated pulmonary artery pressure and pulmonary blood flow compared with twin controls. Hypoxia caused a greater increase in pulmonary vascular tone in shunt animals compared with controls. Alkalosis caused pulmonary vasodilation in control but not shunt animals. To determine lung K+ channel mRNA levels, we performed quantitative RT-PCR. In comparison with control animals, lung K Ca channel mRNA content was increased in shunt animals, whereas TASK mRNA levels were decreased. There was no difference in Kv2.1 mRNA levels. Channel protein expression was consistent with these findings. We conclude that, in the presence of elevated pulmonary blood flow, K Ca channel expression is increased and TASK is decreased.

View details for DOI 10.1152/ajplung.00428.2001

View details for Web of Science ID 000179082700008

View details for PubMedID 12388350
Current clinical status of pulsatile pediatric circulatory support ASAIO JOURNAL Reinhartz, O., Stiller, B., Eilers, R., Farrar, D. J. 2002; 48 (5): 455-459
Abstract

Whereas circulatory support with pulsatile assist devices is an established therapy in adults today, it remains unusual and extremely challenging in children. Specifically designed smaller size pumps are, to date, only available in Europe. This review summarizes the experience with both adult size pumps in the U.S. and pediatric pumps in Europe. Thoratec ventricular assist devices (VADs) were implanted in 101 patients worldwide who were between 7 and 17 years of age. Survival in this group was 68.8%, which is comparable with that in adult patients and was independent of age or body size. Berlin Heart VADs, available in several sizes, were implanted at the Deutsches Herzzentrum Berlin in 45 patients between 2 days and 16 years old. Survival in patients with myocarditis and cardiomyopathy was 66.7% and 71.4%, respectively; overall survival was 48.9%. In a number of European centers, 64 children up to 16 years of age received Medos devices, which are also available in several sizes, with an overall survival of 36.2%, similar for all pump sizes. End-stage congenital heart defects or failure to wean off bypass carried a poorer prognosis than cardiomyopathies or myocarditis for all devices.

View details for DOI 10.1097/01.MAT.0000026978.02458.4F

View details for Web of Science ID 000178040500002

View details for PubMedID 12296561
Alterations in nitric oxide production in 8-week-old lambs with increased pulmonary blood flow PEDIATRIC RESEARCH Black, S. M., Bekker, J. M., McMullan, D. M., Parry, A. J., Ovadia, B., Reinhartz, O., Lakshminrushimha, S., Mata-Greenwood, E., Steinhorn, R. H., Fineman, J. R. 2002; 52 (2)
Abstract

Nitric oxide (NO) is an important mediator of pulmonary vascular reactivity, and decreased NO synthase expression has been demonstrated in children with advanced pulmonary hypertension secondary to congenital heart disease and increased pulmonary blood flow. Using aortopulmonary vascular graft placement in the fetal lamb, we have established a unique animal model of pulmonary hypertension with increased pulmonary blood flow. At 4 wk of age, these lambs display an early, selective impairment in agonist-induced NO responses, but an up-regulation of basal NO activity and gene expression. We hypothesized that further exposure to increased flow and/or pressure results in progressive endothelial dysfunction and a subsequent decrease in basal NO production. The objective of this study was to characterize potential later alterations in agonist-induced NO responses and basal NO activity and gene expression induced by 8 wk of increased pulmonary blood flow and pulmonary hypertension. Twenty-two fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt), and were studied 8 wk after delivery. Both in vivo and in isolated pulmonary arteries, the pulmonary vasodilating response to endothelium-dependent agents was attenuated in shunted lambs (p < 0.05), whereas the response to endothelium-independent agents was unchanged. The pulmonary vasoconstricting responses to Nomega-nitro-L-arginine, and lung tissue endothelial NO synthase mRNA, endothelial NO synthase protein, NO synthase activity, and NO(X) levels were all unchanged. These data suggest that the increase in basal NO activity demonstrated after 4 wk of increased pulmonary blood flow is lost by 8 wk of age, whereas the attenuation of agonist-induced responses persists. We speculate that the progressive decrease in basal NO activity participates in the development of pulmonary hypertension secondary to increased pulmonary blood flow.

View details for DOI 10.1023/01.PDR.0000023495.70201.55

View details for Web of Science ID 000177067600014

View details for PubMedID 12149501
Management of neonatal bronchovenous fistula after cardiopulmonary bypass ANNALS OF THORACIC SURGERY Reinhartz, O., DeSilva, A. M., Hanley, F. L. 2002; 73 (4): 1320-1322
Abstract

Bronchovenous fistula is occasionally encountered after traumatic lung injury or, in neonates, due to ventilation injuries with high ventilatory pressures. We report a case of massive air embolism associated with a bronchopulmonary venous communication in an infant post-repair of truncus arteriosus. Selective ventilation of the opposite lung for 3 days sealed the fistula.

View details for Web of Science ID 000174807400080

View details for PubMedID 11996288
Failing Fontan circulation sheep model and utilization of axial flow pump - Preliminary experiments 8th World Congress on Heart Failure - Mechanisms and Management Reinhartz, O., Reichenbach, S. H., Ikai, A., Riemer, R. K., Karl, T. R. MEDIMOND S R L. 2002: 531–535
View details for Web of Science ID 000184146900086
Multicenter experience with the Thoratec ventricular assist device in children and adolescents JOURNAL OF HEART AND LUNG TRANSPLANTATION Reinhartz, O., Keith, F. M., El-Banayosy, A., McBride, L. R., Robbins, R. C., Copeland, J. G., Farrar, D. J. 2001; 20 (4): 439-448
Abstract

Patient size is 1 determinant in selecting a mechanical circulatory support device. The current pulsatile ventricular assist devices (VADs) were designed primarily for average-sized adults. The flexibility of the Thoratec VAD, however, has encouraged physicians to use it in a significant number of intermediate-sized older children and adolescents.We conducted a retrospective study in 58 children and adolescents <18 years (41 boys, 17 girls) who had been supported with the Thoratec VAD in 27 centers worldwide as of December 1999. Mean patient age was 13.8 years (range, 7 to 17 years), and mean patient weight and body surface area were 51.6 kg (range, 17 to 93 kg) and 1.5 m(2) (range, 0.7 to 2.1 m(2)), respectively.Thirty-five patients (60%) survived to transplantation and 6 (10%) to recovery of the native heart, respectively; 38 were discharged from the hospital (66%). In the transplanted group, post-transplantation survival was 97%. Patient age and size were not associated with significantly increased risk for death or adverse events. Fifteen patients (27%) had 18 neurologic events during support, and 6 of these were fatal. Left atrial cannulation proved a risk factor for neurologic complications.The Thoratec VAD has successfully been used in a large number of children and adolescents with similar morbidity and mortality results as with adults. The risk of neurologic complications may be increased, particularly in patients cannulated in the left atria.

View details for Web of Science ID 000168040900008

View details for PubMedID 11295582
Importance of preoperative liver function as a predictor of survival in patients supported with thoratec ventricular assist devices as a bridge to transplantation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Reinhartz, O., Farrar, D. J., Hershon, J. H., Avery, G. J., Haeusslein, E. A., Hill, J. D. 1998; 116 (4): 633-640
Abstract

Patient selection is crucial for the success of ventricular assist devices as a bridge to heart transplantation.The objective of this study was to identify preoperative markers for survival and end-organ recovery in patients having a ventricular assist device.A retrospective study was performed on 32 severely ill patients with end-stage cardiac failure being mechanically bridged to heart transplantation with the Thoratec Ventricular Assist Device System (Thoratec Laboratories Corporation, Pleasanton, Calif) in a single center between 1984 and 1995. The preoperative cardiac index averaged 1.6 L/min per square meter with a pulmonary capillary wedge pressure of 29 mm Hg. Because of a high incidence of hepatic or renal dysfunction, or both (total bilirubin: 3.5 +/- 6.2 mg/dL; creatinine: 2.0 +/- 1.3 mg/dL), biventricular support was used in most patients (28/32). A total of 30 preoperative and 4 perioperative variables were evaluated for their association with survival and liver recovery.Nineteen patients (59.4%) survived to transplantation and 13 died. All 19 patients undergoing transplantation were discharged alive with a 1-year survival of 94.4%. All patients without liver recovery died of multiorgan failure. Direct and indirect bilirubin measurements were the only significant predictors for survival to discharge (P = .036, .045); all other factors failed to show significance. As direct bilirubin levels increased (normal range, 3 times normal, and >3 times normal), patient survival decreased (82 %, 56%, and 33 %, respectively). In addition, bilirubin and liver enzyme levels before insertion of the assist device were significantly associated with liver recovery during support with the device.In our patient population with ventricular assist devices, liver function is the most predictive factor of patient survival in bridging to transplantation.

View details for Web of Science ID 000076224600014

View details for PubMedID 9766593
Timing of surgery in patients with acute infective endocarditis JOURNAL OF CARDIOVASCULAR SURGERY Reinhartz, O., Herrmann, M., Redling, F., Zerkowski, H. R. 1996; 37 (4): 397-400
Abstract

Surgical intervention in patients with active infective endocarditis is generally considered as indicated in few high-risk patients who have developed severe complications such as heart failure, persistent septicemia or recurrent arterial embolism, but the question of when to intervene is still subject to discussion.Retrospective study.Cardio-Thoracic Surgery Unit, University clinic. PATIENTS, INTERVENTIONS AND RESULTS: From 1984 to 1994, 130 patients (87 male, mean age 43.2 +/- 12.7 years) underwent heart valve replacement or reconstruction for infective endocarditis of native or prosthetic valves. 89 of them had acute infection requiring urgent surgical treatment. Over-all operative mortality was 12.3%. Certain preoperative factors were investigated regarding their influence on postoperative death. Statistical analysis revealed functional class according to NYHA as well as extravalvular involvement of the infection as significant risk factors or mortality. Emergency operation was not significantly associated with increased operative mortality, neither were the causative organism, a history of arterial embolism or persistent septicemia.In active infective endocarditis the optimal time to perform surgery is before the onset of severe end-stage heart failure or spread of the infection to extravalvular tissue. If one of these complications is imminent, urgent intervention is indicated.

View details for Web of Science ID A1996UZ09600013

View details for PubMedID 8698786
BACTERIAL AND FUNGAL COLONIZATION AND INFECTIONS USING ORAL SELECTIVE BOWEL DECONTAMINATION IN ORTHOTOPIC LIVER TRANSPLANTATIONS TRANSPLANT INTERNATIONAL Steffen, R., Reinhartz, O., BLUMHARDT, G., Bechstein, W. O., Raakow, R., Langrehr, J. M., Rossaint, R., Slama, K., Neuhaus, P. 1994; 7 (2): 101-108
Abstract

Bacterial and fungal infections are a major cause of morbidity and mortality after orthotopic liver transplantation. In the immunocompromised host, infections are thought to arise from the gut, which is almost always colonized with potential pathogens. Using oral selective bowel decontamination (SBD), potential pathogens can be eradicated from the gut and infections prevented. In this catamnestic study we have reviewed gastrointestinal colonization, bacterial and fungal infections, and bacterial resistance to standard antibiotics in our first 206 liver transplant patients while under SBD. With few exceptions, gram-negatives were eradicated from the gastrointestinal tract and secondary colonization was inhibited. In spite of unsatisfactory elimination of Candida, probably because nystatin doses were too low, Candida infections were rare (n = 4) and none was fatal. One and two-year survival rates were 93% and 92%, respectively. The bacterial and fungal infection rate was 27.8% with an infection-related mortality of 1.95%. Infections with aerobic gram-positive bacteria prevailed and only 11 gram-negative and 11 fungal infections occurred; among the latter, Aspergillus and Mucor were the most serious and responsible for three of the six deaths in this series. With regard to the development of resistance, we found an increasing number of enterococci and coagulase-negative staphylococci resistant to ciprofloxacin and imipenem, respectively, but unlikely as a consequence of SBD.

View details for Web of Science ID A1994MW94900006

View details for PubMedID 8179797

Associate Professor of Cardiothoracic Surgery at the Stanford University Medical Center and the Lucile Salter Packard Children's Hospital

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