Guest Editorial: The changing paradigms of VAD use in neonates, infants, and children

The use of ventricular assist devices (VAD) in pediatrics has evolved over the past two decades. Initially, the development of the adult-sized Berlin EXCOR VAD allowed for a viable option in older children, with the subsequent development of techniques to successfully support children with dilated cardiomyopathy. Several continuous flow devices emerged, with Heart Mate II (axial) and HeartWare HVAD (centrifugal) becoming the more commonly used in older children and adults.[1,2]

However, comprehensive analyses of multi-institutional data revealed several poor prognostic factors, such as the era of implantation and congenital heart disease (CHD).[3] Additionally, in 2012, Fraser et al noted that despite significantly increased survival to transplant with the Berlin EXCOR, VAD implant was associated with significant neurologic comorbidities and risk of infection.[4] Hence, the limitations in the care of patients with CHD and infants became apparent.[5] Conway et al had shown that pulsatile pumps were most inefficient in patients below 10 kg with CHD.[6] However, in the latter half of the last decade, there was a breakthrough that changed the face of VAD use in the smaller pediatric population.

This breakthrough was the use of bivalirudin, which dramatically changed the safety profile, leading to a reduced rate of thrombotic complications across all ages, especially in infants.[7,8] Additionally, there were changes in the antiplatelet therapy protocols, which had their origins in the Edmonton protocol. It was noted the basic thromboelastography (TEG) and anticoagulation studies were better understood and applied at the bedside in comparison to TEG platelet mapping. The latter studies often prevented clinicians from maximizing antiplatelet therapy, leading to its limited use. This observation led to the development of standard protocols that incorporate scheduled increases in antiplatelet therapy.[9]

Optimized anticoagulation and antiplatelet therapy allowed increasing success in the use of VAD support of neonates, infants, and toddlers with dilated cardiomyopathy, as well as younger children with CHD. This advance then opened the final challenge that remained i.e., the support of patients below 5 kg with CHD, with a focus on functionally univentricular physiology. Over the past five years, an increasing number of centers in the country have successfully implanted the Berlin EXCOR VAD and “short-term” devices like PediMAG to support neonates and infants with functionally univentricular physiology and heart failure.[10] Some of these implants were a bridge to transplant and some were a bridge to decision making. The experience at these centers showed an improvement in survival to 40-50% in neonates and infants with functionally univentricular physiology, when previously it was less than 10-20%.  These VAD implants can be combined with traditional modes of palliation (e.g., Hybrid palliation, PDA stenting, or creation of surgical aortopulmonary shunt) in order to ensure balanced systemic and pulmonary circulations.[11]

The key factor postulated for success in this population is the timing of VAD implantation. Patients with marginal anatomy for successful palliation, who did poorly after initial palliative surgery, often incurred significant end-organ injury and were likely to fail VAD implantation. This challenge promoted the use of elective VAD implantation for patients who were likely to progress to heart failure while awaiting cardiac transplantation.[12, 13] In addition, this strategy of elective VAD implantation while awaiting cardiac transplantation facilitated optimization of nutrition and physical rehabilitation for babies as small as 3 kg, as they often waited for 4-6 months or longer for transplantation. With the use of bivalirudin and the previously described protocols of anticoagulation, thrombotic complications were decreased, although not completely eliminated. Interest in this area continues to grow, and morbidities associated with longer durations of support in this complex population are becoming more apparent.

As we complete this discussion of VAD use, we cannot do so without the mention of the use of VADs as a bridge to recovery. Data continues to emerge that myocardial rest, which was previously defined as a 1-2 week period on ECMO, could now be extended in the context of durable VADs.[14] This strategy utilizes VAD support combined with medical therapy designed to facilitate remodeling of the resting heart and myocardial recovery. Although this approach applies mainly to the younger patient population with myocarditis or dilated cardiomyopathy, it has also been utilized in a few older patients with CHD. This finding would indicate that VAD centers need to have a protocol for both surveillance of remodeling and myocardial recovery.

As the outcomes of VADs in neonates, infants, and children continue to improve, we are faced with new challenges like the loss of the HVAD, which creates a gap in the mid-size pediatric patient population who cannot be supported with devices like Heart Mate III. In addition, the quest for a continuous flow pump that is suitable for an infant continues in the PUMPKIN trial. Cardiac intensivists across the country continue to learn about the art and science of caring for these challenging patients, as we combine nuances of antithrombotic therapy, hemodynamic management post VAD implant, infection control, and many others. We must continue to collaborate through networks like Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) and Advanced Cardiac Therapies Improving Outcomes Network (ACTION), as such organizations allow communication across disciplines, as well as real-time sharing of new innovations in the context of evolving guidelines authored by member teams.

Acknowledgment: Special thanks to Dr. Jeff Jacobs for his guidance in structuring the paper and reading over it.

References

1. Mera, O.  et al. First experiences with the HeartWare ventricular assist system in children. Ann Thorac Surg, v. 91, n. 4, p. 1256-60, Apr 2011. ISSN 1552-6259.
2. Owens, W. R.  et al. Initial clinical experience with the HeartMate II ventricular assist system in a pediatric institution. Artif Organs, v. 34, n. 7, p. 600-3, Jul 2010. ISSN 1525-1594.
3. Blume, E. D.  et al. Outcomes of children bridged to heart transplantation with ventricular assist devices: a multi-institutional study. Circulation, v. 113, n. 19, p. 2313-9, May 2006. ISSN 1524-4539.
4. Fraser, C. D., JR.  et al. Prospective trial of a pediatric ventricular assist device. N Engl J Med, v. 367, n. 6, p. 532-41, Aug 9 2012. ISSN 1533-4406 0028-4793.
5. Weinstein, S.  et al. The use of the Berlin Heart EXCOR in patients with functional single ventricle. J Thorac Cardiovasc Surg, v. 147, n. 2, p. 697-704; discussion 704-5, Feb 2014. ISSN 1097-685X.
6. Conway, J.  et al. Delineating survival outcomes in children <10 kg bridged to transplant or recovery with the Berlin Heart EXCOR Ventricular Assist Device. JACC Heart Fail, v. 3, n. 1, p. 70-7, Jan 2015. ISSN 2213-1787.
7. Rutledge, J. M.  et al. Antithrombotic strategies in children receiving long-term Berlin Heart EXCOR ventricular assist device therapy. J Heart Lung Transplant, v. 32, n. 5, p. 569-73, May 2013. ISSN 1557-3117.
8. Vanderpluym, C. J.  et al. Utilization and Outcomes of Children Treated with Direct Thrombin Inhibitors on Paracorporeal Ventricular Assist Device Support. ASAIO J, v. 66, n. 8, p. 939-945, 08 2020. ISSN 1538-943X.
9. Rosenthal, D. N.  et al. Impact of a modified anti-thrombotic guideline on stroke in children supported with a pediatric ventricular assist device. J Heart Lung Transplant, v. 36, n. 11, p. 1250-1257, Nov 2017. ISSN 1557-3117.
10. Gazit, A. Z.  et al. A Novel Surgical Approach to Mechanical Circulatory Support in Univentricular Infants. Ann Thorac Surg, v. 104, n. 5, p. 1630-1636, Nov 2017. ISSN 1552-6259.
11. Philip, J.  et al. Hybrid procedure with pulsatile ventricular assist device for hypoplastic left heart syndrome awaiting transplantation. J Thorac Cardiovasc Surg, Dec 2018. ISSN 1097-685X.
12. Philip J. et al. Pulsatile ventricular assist device as a bridge to transplant for the early high-risk single-ventricle physiology. J Thorac Cardiovasc Surg, Oct 2020. ISSN 1097-685X.
13. Bleiweis M. S. et al.  Combined Hybrid Procedure and VAD insertion in 9 High-Risk Neonates and Infants with HLHS.  Ann Thorac Surg. 2021 Jun 26:S0003-4975(21)01051-1.  doi: 10.1016/j.athoracsur.2021.05.073.  Online ahead of print.  PMID:  34186096.
14. Hetzer R., et al. Paediatric mechanical circulatory support with Berlin Heart EXCOR: development and outcome of a 23-year experience. Eur J Cardiothorac Surg, v. 50, n. 2, p. 203-10, Aug 2016. ISSN 1873-734X.