HeartWare HVAD Market Withdrawal and Impact on the Pediatric Field

Abstract

On June 3, 2021, Medtronic announced the withdrawal of the HeartWare Ventricular Assist Device (HVAD) from the global market.1 Within North America, it was one of only two commonly used, Federal Drug Administration (FDA)-approved ventricular assist device (VAD) devices at that time.2 Current estimates suggest that there are 4,000–5,000 patients on HVAD support in the community, either as bridge for transplantation or destination therapy. Although this withdrawal affects a wide range of heart failure patients, one of the most important repercussions of this decision will be felt in the world of pediatric mechanical circulatory support. In this commentary, we discuss the impact such a change in device armamentarium availability will have on the pediatric community, and review potential next steps in the light of the same. The Landscape Currently, there are more than 200 durable devices implanted annually in children in North America.3 Additional 40–50 devices are implanted annually in Europe, based on the current Paedi-EUROMACS report.4 Estimates of device implantation around the world are difficult to ascertain. However, it is clear that the need and utilization of both short-term and long-term pediatric devices is rapidly growing.3 Given the positive impact of VAD support on rehabilitation, nutrition, and organ improvement in failing patients awaiting heart transplantation, it has been reported that 30–40% of these patients are now supported by VADs.5 At the time of that report, the most commonly used durable devices in North America and Europe are the Berlin Heart Excor and HeartWare HVAD. The positive impact of VAD support has resulted in less extracorporeal membrane oxygenation (ECMO) utilization in children awaiting heart transplantation over time.5 Compared to ECMO, VAD use in children awaiting heart transplantation has been shown to be associated with decreased waitlist mortality and improved posttransplant survival.5 The role of VAD support has expanded to infants and older children with congenital heart disease who need transplantation for failed surgical repair or multi-stage palliation strategy of single ventricle anomalies. Improved experience with VAD support in this population, along with innovative implantation techniques and utilization strategies to adjust for anatomic variations have all led to improved VAD outcomes in children with congenital heart disease.6 The Potential Impact In this landscape of increasing need, utilization and expansion of application to other patient groups, having device options is extremely important. Berlin Heart Excor continues to be the mainstay for children <15 kg in weight (in addition to short-term support with para-corporeal devices such as PediMag or CentriMag [Abbott, Abbott Park, IL]).3 HVAD use in pediatric patients has increased over the past decade. PEDIMACS registry analysis showed that between 2012 and 2017, the HVAD was implanted in 192 children. The smallest child in this series weighed 13.1 kg and had a body surface area of 0.6 m2. In that cohort, There were 12 children who weighed less than 20 kg.7 Since 2017, the utilization of HVAD in small patients (15–30 kg in weight) increased with the use of inventive implantation techniques. The increased interest in HVAD use in this age group stems from the fact that the HAVD allowed better mobilization compared to paracorporeal devices and the possibility of patient discharge whereas awaiting heart transplantation. Additionally, several reports demonstrated provision of biventricular support with the HVAD, including children. More recently, Heartmate 3 (HM3) was introduced by Abbott (Abbott Park, IL) and approved by the FDA for adult heart failure.8 Since the rapid adoption in the adult population, it has also become an option for pediatric patients. In December 2020, the FDA approved a pediatric device label for the device. This was primarily based on data from the centers participating in the ACTION Learning Network for 35 pediatric patients implanted with HM3. The median age for these patients was 16 years, with the majority having dilated cardiomyopathy. There are important differences in the device size, profile, weight between the HVAD and HM3 that have influenced the use in pediatric patients. Although there is no minimum weight recommendation in the FDA labeling for HM3, the general consensus is that this is an appropriate device for children above 30 kg of weight. The withdrawal of the HVAD therefore leaves a clear gap for children under 30 kg of weight now, with the Berlin Excor remaining as the only durable device option. Although HM3 is relatively larger than the HVAD, the expectation with the lack of an HAVD option is that surgeons would adapt to this size difference with some surgical modification that would allow similar utilization of HM3 in small childen, those requiring biventricular support, and those with congenital heart disease and challenging anatomy. In the interim, the Berlin Excor may be the likely used device in children 15–30 kg in weight. In North America, the Berlin Excor does not as yet have a discharge option. Therefore, this will result in all of these patients remaining as inpatients, with limitations to mobility, and consequently, they will not be able to attend regular school. Currently, about 50% of children supported with implantable devices are discharged home whereas awaiting transplantation or as a bridge-to-decision. Given the increasing transplant waitlist duration, the increased use of the Berlin Excor would likely impact some of these practical and important determinants of outcome. One of the important reasons why the outcomes in children supported by VADs have been improving is because of the cumulative experience as well as competency acquired within teams. At this time, a change in the device necessitates reinventing the wheel. It requires establishing competency for HM3 for centers that were otherwise facile with the HVAD. This is a significant stress especially for small and medium size centers where devices are use occurs at low frequency and where it takes longer to mature the care delivery system. This could potentially impact adverse events and outcomes in the transition period. Lastly, given the pandemic, a large number of Children’s hospitals have experienced economic stress. An unexpected change such as this necessitates capitol expenses that can add additional pressure on these institutions. Looking Forward Pediatric hospitalizations for decompensated heart failure are rapidly increasing.9 The largest increase is because of the growth of the population of children with congenital heart disease with prior surgical repair or palliation who fail to progress after their surgery and reach the point of requiring heart transplantation. Additional etiologies include postmyocarditis chronic heart failure and postchemotherapy cardiomyopathy. Therefore, the demand for treatment options of severe heart failure in children will continue to increase. The number of available pediatric donors has been static for North America.5 That is the current bottleneck in the system. Increasing the utilization of potential donors is important and was highlighted in the ISHLT statement on donor selection.10 Nonetheless, because of increase in demand and limitation on supply, patients needing VAD support as bridge to transplant will continue to grow. It is anticipated that by the end of the decade, the overall VAD market would be approach 5 billion USD. We need all hands on the deck – innovators, device companies and academic institutions to foster innovation and embrace the development more devices. More importantly, governmental agencies that play a role in medical device research, development and certification will need to join in facilitating this effort. The FDA and National Institute of Health should look at this as an opportunity to push for innovation and support startups that can be game-changers similar to as occurred during the coronavirus disease pandemic with development of RNA-based diagnostic tests sponsored via Rapid Acceleration of Diagnostics.11 That program provided the exact pipeline, initial funds and oversight that allowed many a startup to develop break through products. Although a push was attempted more than a decade ago with the PUMPKIN trial, it is time to strongly consider a PUMPKIN-II, with stronger emphasis on supporting smaller companies and startups along with more mature industry partners to promote development of appropriate devices. Further, device development does not have to be limited to the pediatric age group. As we witnessed with the HVAD, a suitable device can serve both the adult and pediatric populations. A device platform could be created that supports a range of recipient sizes with minor component changes. Thus, the focus of PUMPKIN-II could be on “cross over” devices, making them economically sustainable. In summary, withdrawal of the HeartWare HVAD will have a significant impact on the pediatric field, especially in smaller children with complex implantation needs. Given the limited current options, surgeons and clinicians will need to adapt to HM3 to fill in the gaps. It will become clear in the near future how this strategy will work out. Lastly, as clinician and patient advocates, collectively we should put out a call to all disciplines to come together, to advance better technologies for the overall support of the health and wellbeing of our patients.

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