After decades of design innovations and the expanded use of pulsatile ventricular assist devices (VADs) for end-stage heart failure in adults, rapid advances in continuous flow technologies have produced highly durable and much smaller VADs with improved patient survival.1 After the report of the Pediatric Heart Transplant Study by Blume et al.2 in 2006 showing a significant survival discrepancy between older children and infants awaiting heart transplantation, there has been a tremendous focus on the expanded use of mechanical circulatory support in smaller children.
This discrepancy was, at least in part, due to the fact that the initial option for mechanical circulatory support for young children was limited to extracorporeal membrane oxygenation (ECMO), a lifesaving technology with limited utility as bridge to transplantation (BTT) due to cumulative morbidity and mortality with duration of use. The most recent Extracorporeal Life Support Organization (ELSO) registry report demonstrates that the majority of supported patients have respiratory failure or congenital heart disease and survival to discharge for cardiac indications ranged from 45% to 57% over the past 8 years.3 Additionally, Merrill et al.4 reported a very poor outcome of patients supported with prolonged ECMO greater than 28 days with survival to discharge of only 25% for noncongenital indications, 7% for congenital indications, and a very low transplant rate.
In the early 1990s, the Berlin Heart EXCOR, a paracorporeal pulsatile flow device (PFD), filled a long-awaited need as a mechanical bridge to transplant for children with the goal of lower morbidity and mortality compared with ECMO. After years of increasing implantation internationally and use under humanitarian device exemption in the United States, a multicenter trial comparing EXCOR safety and efficacy to ECMO provided favorable results and led to United States Food and Drug Administration (FDA) approval as the only currently approved mechanical support device for small children and neonates.5 Over time, VAD use in children as BTT has increased and has resulted in significantly improved wait-list survival.6 Recently, Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS), the pediatric arm of INTERMACS, published its first report in 2016 with 37 participating hospitals and 200 patients, demonstrated favorable outcomes despite the varying patient demographics, diagnoses, and pump technology.7
However, as pediatric VAD experience has grown, two major issues that continue to limit expanded EXCOR use in the United States are the frequency of acute neurologic adverse events (29%) and the inability to discharge patients on a paracorporeal device while awaiting heart transplantation compared with implantable continuous flow devices (CFDs).8 This has resulted in a continued evolution and expanded use of adult CFD in children, including implantable centrifugal CFD; primarily the HeartWare HVAD (HeartWare Inc., MA) and axial CFD such as the Thoratec HeartMate II (Thoratec Corp., CA). In this edition of the ASAIO Journal, three papers highlight some of the progress regarding trends and challenges of implantable CFD in children requiring mechanical circulatory support for end-stage heart failure.
Authors from Cincinnati Children’s Hospital9 and from Washington University in Saint Louis10 report analyses from the United Network of Organ Sharing (UNOS) database regarding differences in pediatric VAD utilization and selection as a BTT in the United States. The St. Louis group focused their analysis on a subpopulation of patients large enough to receive either CFD or PFD which they defined as those with a BSA greater than 1 m2. Both studies report increased utilization of CFD technology for patients at or above 25 kg; particularly marked in those with BSA greater than 1 m2 which increased from 11% to 88% over the past 7 years. Both studies found no difference in device technology-specific survival despite a higher prevalence of known risk factors associated with PFD use and longer wait time to transplantation for those supported by CFD.
The increasing use of implantable CFDs is not surprising because of its durability, survival and morbidity profile, and the option for patient discharge. Data from the PediMACS Registry demonstrate similar outcomes to adult patients with CFD with 1, 3, and 6 month survivals of 96%, 92%, and 89%, respectively.11 Compared with PFD, more patients supported with CFD were transplanted (61.2% vs. 54.7% at 6 months), mortality was lower (7.5% vs. 20.8% at 6 months),7 and adverse events were less common.12 As noted by the authors, the differences in neurologic events, in particular, should be interpreted with caution because of varied group characteristics, specifically related to age, congenital heart disease diagnosis, prior ECMO, and INTERMACS profile. These morbidity events will continue to be important outcome indicators as CFD use increases; however, because of continued evolution of patient and device selection, innovation in device technology, and population heterogeneity, a direct comparison between PFD and CFD in children may continue to be challenging.
The Cincinnati group also noted a transition from axial to centrifugal CFD use. It remains unclear as to whether this was due to clinician preference or specific pump mechanics. It could be assumed that for many patients, the HVAD was chosen because of its size and ability to support smaller patients. The recently published ENDURANCE trial evaluating the use of centrifugal CFD when compared with axial CFD for permanent use that demonstrated no difference in overall survival but that device malfunction was more common in axial CFD although stroke was more common in centrifugal CFD.13 A multicenter morbidity comparison of the two technologies, specifically with regards to stroke, hemolysis, and survival, remains to be completed. Small cohort comparison of the HVAD versus the HMII demonstrated an increased incidence of gastrointestinal (GI) bleeding and stroke in the HVAD group with no difference in survival or rate of transplant.14 Additional studies have demonstrated no difference in transplant outcomes when comparing HVAD with HMII; however, when stratified by duration of support, those supported with HVAD did better when supported for more than 6 months compared with HMII.15,16
Now that children have implantable devices with morbidity profiles amenable to discharge from the hospital, outpatient VAD programs have become a new frontier for pediatric centers. This provides improved quality of life for children and the potential for better rehabilitation in preparation for heart transplantation. As reviewed by Conway et al.,17 discharge from the hospital requires extensive evaluation of both medical and social circumstances that can affect success of home integration including the potential for returning to school. Recently, a review of the evolution of the pediatric VAD program at Boston Children’s Hospital discusses the development of a comprehensive communication strategy for patients outside of the hospital to reach the VAD team.18 Both of these papers demonstrate that outpatient management can be done successfully through adequate preparation, thoughtfulness, and communication.
The group from Stanford report the rehospitalization patterns for children after CFD implantation.19 Though the goal is continued outpatient care, readmission after pediatric VAD implantation is not uncommon and are similar to readmission rates noted in adults.11 The Stanford group demonstrated that 84% of patients required rehospitalization with more than half experiencing an admission within 2 weeks from discharge most often due to infection (28%) or concern for pump thrombosis (17%) which is consistent to the late events reported by PediMACS.7 Regardless, these patients spent 89% of the time after initial discharge out of the hospital which, compared with the PFD alternative, is a substantial improvement in quality of life and reduction in cumulative medical cost.
The progress in pediatric heart failure management and outcomes continues to be encouraging, particularly in the area of pediatric VAD support. As experience continues to mature, continued innovation and critical analysis are likely to further improve outcomes.
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3. Barbaro RP, Paden ML, Guner YS, et al. Pediatric Extracorporeal Life Support Organization Registry International Report 2016. ASAIO J 2017.63: 456–463.
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5. Fraser CD Jr, Jaquiss RD, Rosenthal DN, et al; Berlin Heart Study Investigators: Prospective trial of a pediatric ventricular assist device. N Engl J Med 2012.367: 532–541.
6. Zafar F, Castleberry C, Khan MS, et al. Pediatric heart transplant waiting list mortality in the era of ventricular assist devices. J Heart Lung Transplant 2015.34: 82–88.
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16. Magruder JT, Grimm JC, Crawford TC, et al. Survival after orthotopic heart transplantation in patients undergoing bridge to transplantation with the HeartWare HVAD versus the Heartmate II. Ann Thorac Surg 2017.103: 1505–1511.
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18. Hawkins B, Fynn-Thompson F, Daly KP, et al. The evolution of a pediatric ventricular assist device program: The Boston Children’s Hospital experience. Pediatr Cardiol 2017.38: 1032–1041.
19. Hollander S, Chen S, Murray J, McBreaty E, Almond C, Rosenthal D. Rehospitalization patterns in pediatric outpatients with continuous flow VADs. ASAIO J 2017.63: 476–481.