Holger Buchholz

Berlin Heart EXCOR Pediatric Ventricular Assist Device for Bridge to Heart Transplantation in US Children

Background— 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. Methods and Results— 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. Conclusions— 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.

Bridging children of all sizes to cardiac transplantation: The initial multicenter North American experience with the Berlin Heart EXCOR ventricular assist device

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Presentation, Diagnosis, and Medical Management of Heart Failure in Children: Canadian Cardiovascular Society Guidelines

Pediatric heart failure (HF) is an important cause of morbidity and mortality in childhood. This article presents guidelines for the recognition, diagnosis, and early medical management of HF in infancy, childhood, and adolescence. The guidelines are intended to assist practitioners in office-based or emergency room practice, who encounter children with undiagnosed heart disease and symptoms of possible HF, rather than those who have already received surgical palliation. The guidelines have been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and are accompanied by practical Recommendations for their application in the clinical setting, supplemented by online material. This work does not include Recommendations for advanced management involving ventricular assist devices, or other device therapies.

The use of ventricular assist devices in pediatric patients with univentricular hearts

Improved survival outcomes for pediatric patients with ventricular assist devices (VADs) has expanded their application to complex univentricular cardiac lesions, including patients with systemic-to-pulmonary shunts, bidirectional cavopulmonary anastomoses (BCPAs), and total cavopulmonary Fontan circulations. Although it is generally recognized that complex cardiac anatomy is likely a significant risk factor affecting VAD survival, there remains a paucity of data examining the pediatric VAD experience with univentricular hearts.

Berlin Heart EXCOR Pediatric ventricular assist device Investigational Device Exemption study: Study design and rationale

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

A multicenter study of the HeartWare ventricular assist device in small children

A multicenter study of the HeartWare ventricular assist device in small children Oliver Miera, MD, Richard Kirk, MD, Holger Buchholz, MD, Katharina R.L. Schmitt, MD, Christina VanderPluym, MD, Ivan M. Rebeyka, MD, Neil Wrightson, MD, Felix Berger, MD, Massimo Griselli, MD, and Jennifer Conway, MD From the Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany; Department of Pediatric Cardiology, Freeman Hospital, Newcastle Upon Tyne, UK; Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada; and the Department of Cardiology, Boston Children’s Hospital, Boston, Massachusetts, USA

Advanced Therapies for Congenital Heart Disease: Ventricular Assist Devices and Heart Transplantation

Improvement in pre-, peri-, and postoperative management of congenital heart disease (CHD) has significantly increased long-term survival in children with CHD. However, there is a subset of patients with CHD who are either poor candidates for surgical palliation or in whom surgical intervention has failed and require advanced cardiac support. Heart transplant (HT) as a therapy for CHD has undergone tremendous evolution. Though transplantation remains the standard of care to improve survival and quality of life when conventional medical and surgical therapies have failed, it remains limited by the scarcity and unpredictability of donor organ availability. As such, the use of ventricular assist devices (VADs) as a bridge to transplant is gaining increasing popularity. Because of improvement in device technology, and reduced rate of VAD-related complications, the use of these devices is expanding to smaller children and more complex congenital anatomy. Challenges with VAD support and HT in the congenital heart population will be addressed in this review with focus on: (1) reasons for VAD implantation; (2) VAD support in Fontan circulation; (3) challenges with human leukocyte antigen (HLA) sensitization in HT; and (4) effect of VAD support on HT in CHD.

Antithrombotic strategies in children receiving long-term Berlin Heart EXCOR ventricular assist device therapy

BACKGROUND Thromboembolic events while receiving ventricular assist device (VAD) support remain a significant cause of morbidity and mortality despite standard anti-coagulation and anti-platelet therapies. The use of bivalirudin and epoprostenol infusions as an alternate anti-thrombotic (AT) regimen in pediatric VAD patients was reviewed. METHODS This was a retrospective record review of 6 pediatric patients (aged ≤17 years) at 2 institutions treated with bivalirudin and epoprostenol infusions while being supported with the Berlin Heart EXCOR (Berlin Heart GmbH, Berlin, Germany) VAD. RESULTS Six patients (age, 0.8-14 years; weight, 6.7-29.7 kg) were treated. Diagnoses included cardiomyopathy in 2 and congenital heart disease in 4. VAD support was left VAD in 2 and bi-VAD in 4, with duration of support of 21 to 155 days. Three patients required extracorporeal membrane oxygenation before VAD support. Bivalirudin/epoprostenol was used after recurrent thromboses on conventional medication in 3 patients, heparin-induced thrombocytopenia in 2, and in 1 patient considered high risk with a prosthetic mitral valve. The bivalirudin dose was titrated to partial thromboplastin time (PTT) of 1.5- to 2-times baseline (0.1-0.8 mg/kg/hour); the epoprostenol dose was 2 to 10 ng/kg/min. Additional anti-platelet agents included acetylsalicylic acid, dipyridamole, and clopidogrel in 5 patients each. No bleeding complications occurred. One patient sustained a cerebrovascular infarct on therapy, with subsequent complete recovery. No other complications occurred. Five patients underwent successful transplantation, and 1 patient died of multisystem organ failure. CONCLUSIONS This report provides data on estimated safety and efficacy of bivalirudin and epoprostenol as an AT strategy in pediatric patients on extended VAD support. The short drug half-life and predictable AT response facilitated conversion to standard AT regimens at the time of transplantation (heparin-induced thrombocytopenia-negative patients). These agents should be considered for management of pediatric VAD patients when standard regimens fail.

Mechanical Circulatory Support in Univentricular Hearts: Current Management

Failing single-ventricle patients have now come into focus as the next cohort where improvement in outcomes for mechanical circulatory support can be realized. There is a paucity of published patient reports or management protocols in this patient population. Increased interest exists in finding answers of how to bridge these patients to transplant. We review the current literature and describe our approach to the patient with univentricular heart needing mechanical circulatory support.

Anesthesia for noncardiac procedures for children with a Berlin Heart EXCOR® Pediatric Ventricular Assist Device: a case series

Objectives:  To report our experience of providing anesthesia for noncardiac procedures in children with in situ Berlin Heart EXCOR Pediatric® ventricular assist devices and to suggest principles of anesthetic management.