The field of pediatric mechanical circulatory support as practiced in the United States faces challenges similar to those encountered worldwide. Although several device options are available for adults who require mechanical support of the failing myocardium, historically, many of these same options have been unavailable for children. The main cause for limited device availability for pediatric applications in the United States and elsewhere is clear—small numbers of affected children make it difficult for manufacturers to justify the expense and other resources required for the limited pediatric market. Although device availability is a worldwide issue, practice in the United States is further limited in that the pulsatile paracorporeal systems available in Europe and elsewhere have not been approved for use.
Despite these recognized limitations, the field of pediatric mechanical circulatory support has witnessed a number of significant developments in the last few years (Table 1).1 These developments reflect clinical and research advances and informational events that have already improved practice and suggest that further progress is likely in the future. The following review examines the current state-of-the-art for pediatric mechanical circulatory support in the United States in the context of patterns of device utilization in the past, the present, and likely developments for the future.
The Past: ECMO, Centrifugal Pump VAD, and Adult VAD Systems
Extracorporeal Membrane Oxygenation and the Bio-Pump
Extracorporeal membrane oxygenation (ECMO) remains the most commonly used form of pediatric mechanical circulatory support in the United States.2–4 As demonstrated in Figure 1, more than 3,500 cases of pediatric cardiac ECMO have been recorded in the registry of the Extracorporeal Life Support Organization.5 ECMO is a versatile and effective method of support in the acute setting and has been particularly effective in providing support for newborn infants and infants due to lack of other support options in these smallest patients. However, ECMO is limited to short-term use and precludes effective physical rehabilitation during support. These factors contribute to the high mortality rate of approximately 60% that has been consistently observed in pediatric cardiac patients who require ECMO support (Figure 1).
The Bio-Pump (Medtronic Corp., Minneapolis, MN), a centrifugal pump–based system, has been the most commonly used ventricular assist device (VAD) for pediatric support in the United States. The Bio-Pump provides nonpulsatile flow by a constrained vortex design that is both preload and afterload sensitive. The VAD circuit based on this pump uses short tubing lengths to connect the pump to the venous and aortic cannulas, which reduces priming volumes compared with ECMO and makes the system easy to maintain.4,6,7 The Bio-Pump is also a versatile system and can be applied to patients of all ages. In fact, the ability to provide circulatory support even for newborn patients undoubtedly accounts for the widespread use of this system, because until recently, there were few other options for VAD support for these smallest patients. Heparin requirements as well as trauma to blood elements are reduced compared with ECMO, owing to the absence of an oxygenator or venous reservoirs. Despite its simplicity and proven track record, the chief limitation for the Bio-Pump VAD, similar to ECMO, is its unsuitability for prolonged support.
Throughout the 1980s and 1990s, ECMO and the Bio-Pump were the two most common circulatory support modalities used for children in the United States; at many centers, these have been the only pediatric mechanical circulatory support devices available. A typical single-center experience in the United States that compared these two systems was reported in 1999.4 In this series, ECMO-supported patients tended to be younger, with a higher incidence of complex cyanotic congenital heart disease. VAD-supported patients more often had relatively isolated left ventricular failure caused by anomalous left coronary artery from the pulmonary artery or cardiomyopathy. This experience is consistent with other centers; because of the presence of an oxygenator in the circuit, ECMO is particularly useful in complex cyanotic heart disease in which respiratory failure and pulmonary hypertension may contribute to the underlying pathophysiology. In addition, ECMO can provide biventricular support with only two cannulation sites compared with four cannulation sites required for biventricular assist device (BVAD) support, which is especially important in the youngest patients, in whom size constraints may make cannulation for BVAD difficult. Conversely, the Bio-Pump VAD is useful in cases of relatively “pure” left ventricular failure in which the absence of an oxygenator simplifies the circuit and minimizes the impact of support on blood elements and the inflammatory cascade. VAD also provides excellent unloading of the left ventricle and in many of these cases helps with ventricular decompression. Both modalities are limited to similar short-term periods of support, which is largely responsible for the nearly identical hospital outcomes observed in this single-center report; approximately two thirds of patients supported with either modality were successfully weaned, whereas 40% in each group survived to hospital discharge.
The long-term follow-up of the same cohort of children after ECMO or Bio-Pump VAD support was also performed.8 There were 37 hospital survivors (26 ECMO; 11 VAD patients), with only a single death in either group (overall long-term survival of 95%) during a median follow-up of more than 4 years. In both groups, 80% of the patients were described as exhibiting good to excellent general health. Ninety percent of the patients were in New York Heart Association class I or II, whereas echocardiographic evaluation of ventricular function was normal in all of the ECMO-supported patients and 90% of the VAD supported patients. These results are reassuring in that children with heart disease who survive to hospital discharge after requiring ECMO or VAD support demonstrate favorable long-term survival, overall general health, and cardiac outcomes.
Poor neurologic outcomes were more common in ECMO- than in VAD-supported patients. More than 60% of the ECMO-supported patients demonstrated moderate to severe neurologic impairment, whereas 20% of the VAD survivors demonstrated this degree of neurologic impairment. Relatively higher rates of neurologic complications in the ECMO-supported group are of concern and appear to suggest an advantage for VAD support, possibly as the result of decreased requirements for anticoagulation with less attendant risk of neurologic complications such as intracranial hemorrhage; however, these results must also be interpreted with the understanding that the ECMO-supported group in this study had a higher proportion of critically ill neonates with more complex underlying cardiac conditions. Nevertheless, the potential for greater neurologic risk in ECMO-supported patients should be appreciated, and appropriate management such as carefully avoiding excess anticoagulation should be routine.
Adult Systems Used for Pediatric Support
Recently, Blume and colleagues9 summarized data from the Pediatric Heart Transplant Study (PHTS) regarding VADs used as a bridge to transplantation in children. The PHTS maintains a multicenter database for pediatric heart transplant recipients throughout North America. This study summarized a 10-year experience ending in 2003, during which the PHTS accumulated data for nearly 2400 patients <18 years of age listed for heart transplantation; 99 (4%) of these children required VAD support. Most of these patients were older than 10 years of age, which is reflective of VAD utilization patterns in North America at that time, where the majority of the pediatric bridge-to-transplant experience was limited to older children supported with devices designed for adults. This is reflected in Figure 2, which depicts the breakdown of the devices used in these patients, demonstrating that pulsatile devices designed for adults such as the Thoratec and Heartmate VADs (Thoratec Corp., Pleasanton, CA) and the BVS 5000 (ABIOMED, Danvers, MA) accounted for nearly 75% of the devices used.
A typical single-center report from the United States, using the Thoratec VAD, was recently published by Arabia et al.10 This device was used in five children (ages 8 to 14 years with body surface area [BSA] 0.8 to 1.4 m2) as a bridge to transplantation, with 105 days being the longest period of support. Eighty percent survived to hospital discharge, although significant thromboembolic events occurred in two of the five patients. Hill and Reinhartz11 reported the worldwide pediatric experience from the Thoratec registry. Through January 2005, 209 pediatric patients with a mean age of 14.5 years (range, 5 to 18 years) and a mean BSA of 1.6 m2 (range, 0.73 to 2.3 m2) had been supported. Support modes used were the BVAD, 53%; LVAD, 42%; and RVAD, 3%, with the remainder unknown. The mean duration of support was 44 days, with the longest period of support >430 days. More than 68% of the patients survived to heart transplantation or native heart recovery; the overall survival for smaller children in the series (BSA <1.3 m2) was 52%.
Helman et al.12 described the use of the Heartmate VAD in 12 adolescent patients, the majority of whom had idiopathic dilated cardiomyopathy. The relatively older age for these patients (range, 11 to 20 years) and size (BSA, 1.4 to 2.2 m2) allowed the use of this device. As in the adult experience, the majority of children supported by the vented electric model were discharged home with resumption of normal activities. Ashton and coworkers13 used the ABIOMED BVS 5000 in four older children. The ABIOMED device was used to provide temporary circulatory support for patients with a BSA >1.2 m2 with flows >2 l/min. A particular limitation to more widespread pediatric application of these devices designed primarily for adults can be attributed to low pump rates during support for all but the largest children, limiting pump washout leading to increased thromboembolic risk.13,14
The Present: The Berlin Heart VAD and the Micromed Debakey VAD Child
The Berlin Heart VAD
The Berlin Heart VAD (Berlin Heart AG, Berlin, Germany) is a pulsatile, paracorporeal VAD that is suitable for the entire age range of pediatric patients, including neonates.15 The Berlin Heart VAD uses pneumatically driven, thin-membrane pumps to provide pulsatile flow and is available in a variety of pump sizes (10 to 80 ml), with the smallest pump sizes suitable for infant support. The Berlin Heart VAD has been used successfully in pediatric patients for more than a decade in Europe, and a number of reports exist detailing these results.15–17 The Berlin Heart VAD appears to have fewer bleeding complications compared with ECMO, with decreased blood product utilization during support.16 A recent report noted improving results for infant support in the latest cohort of patients with survival rates now approaching those achieved in adults.17 The worldwide experience with the Berlin Heart VAD in pediatric patients now exceeds 100 patients. Throughout North America, more than 50 cases have been performed, with an overall survival of >80% (Dr. Peter Goettel, Berlin Heart AG, Berlin, Germany, personal communication). The Berlin Heart VAD is superior to ECMO or the Bio-Pump VAD in providing moderate to long-term support while preserving the options of bridging to transplantation or recovery for children. Of particular importance, this pulsatile paracorporeal system allows extubation and ambulation during support with the same salutary effects provided by similar systems designed for adults. The chief impediment to more widespread use of the Berlin Heart VAD in the United States is its limited availability. This system is available at US centers only on an emergency, compassionate-use basis; however, because of the successful use of this device in providing support for even the smallest children, use is increasing. In 2005 and 2006, the Berlin Heart was used in more than 40 cases, accounting for >80% of all cases performed to date with this device.
The Micromed Debakey VAD Child
The DeBakey VAD Child (MicroMed Technology, Inc., Houston, TX) was granted Humanitarian Device Exemption (HDE) status by the Food and Drug Administration and became available for use in 2004 (Table 2).18 This pediatric device uses the same axial-flow pump used in the adult version, with design modifications aimed at reducing the lateral space requirements for device implantation. These design modifications include a shortened inflow cannula with a more acute angle for the inflow tubing, a shortened plastic outflow graft protector, and reduced size of the flow probe on the outflow graft. Under the current HDE, the VAD Child is to be used as a bridge to cardiac transplantation for children from 5 to 16 years of age with a BSA >0.7 m2 and <1.5 m2 and is designed to be fully implantable in this size range. Because of its implantability, this device allows ambulation and rehabilitation during support. Fraser et al.19 recently summarized the experience with the VAD Child, which consisted of six patients at the time of this report. The average age of the patients was 11 years (range, 6 to 15 years) with a BSA of 0.8 to 1.7 m2. The average duration of support was 39 days, with 84 days being the longest duration of support. Three of these patients were successfully transplanted, whereas three died during support, before transplantation.
The Future: The NHLBI's Pediatric Circulatory Support Program
Clearly, lack of suitable devices designed to address the unique anatomic and physiologic needs of children remains the single largest issue in pediatric mechanical circulatory support worldwide. In recognition of this fact, the US federal government made funds available under the Pediatric Circulatory Support Program of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.20 As stated in its proposal, the program was established to support research programs that “will perform basic and applied research to develop novel circulatory assist devices or other bioengineered systems for infants and children with congenital and acquired cardiovascular disease who experience cardiopulmonary failure and circulatory collapse.”20
In the spring of 2004, five contracts were awarded by the NHLBI to support preclinical development of a variety of pediatric VADs and similar circulatory support systems (Table 3). The five projects awarded include an implantable, magnetically suspended, mixed-flow turbodynamic VAD (The PediaFlow VAD),21 an implantable, mixed-flow VAD with a magnetically suspended impeller (The PediPump),22,23 a compact integrated pediatric cardiopulmonary assist system (The pCAS),20 an axial-flow, apically implanted pediatric VAD (The Pediatric Jarvik 2000 Flowmaker),20 and a pulsatile-flow pediatric VAD (PVAD).24 The goals and progress of the NHLBI's Pediatric Circulatory Support Program was summarized in a recent report by Baldwin and coauthors.20 The program is now beginning the third year of funding; most of the devices have either begun or are scheduled to begin animal testing in the near future. The goal of the program is to have these devices ready to begin human trials at the completion of the funding period in 2009. The support of early technology development provided by this program will hopefully yield several devices that are clinically useful in the future.
Pediatric mechanical circulatory support in the United States faces similar challenges as those faced worldwide: lack of device availability remains the chief limitation, especially for support of the smallest patients. Although ECMO utilizes technology that was first developed decades ago, it retains its status as the mainstay of mechanical circulatory support in children, largely because of the lack of other suitable devices for these smallest patients. In the past as well as currently, devices designed for adults, such as the Thoratec VAD, can be used effectively in larger children and adolescents. Growing experience with newly available devices such as the MicroMed DeBakey VAD Child and the Berlin Heart will make these devices increasingly important treatment options. It is particularly important for the United States market to have access to devices with a proven track record abroad such as the Berlin Heart VAD. Finally, practitioners in this field have been encouraged by the efforts of the NHLBI to support the development of a new generation of circulatory support devices designed specifically for children through the Pediatric Circulatory Support Program.
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