Heart transplant remains the only long-term treatment option for end-stage heart failure patients. The number of children listed for heart transplant continues to increase every year; however, the number of donors has stayed relatively stable. Children awaiting a heart transplant have the highest wait-list mortality, roughly 17%, compared with all age groups and all other solid organ recipients.1 Unfortunately, these patients are usually critically ill and require escalation of medical therapies including mechanical circulatory support. Ventricular assist devices (VADs) were first used in pediatrics in the 1980s and in the current era 86% children supported on a VAD are successfully bridged to transplant.2,3 Biventricular heart failure presents a unique challenge and can be supported by paracorporeal biventricular assist devices (BiVADs), implantable BiVADs, or the SynCardia total artificial heart (TAH).2,4 In recent years, there has been an increase in the use of the SynCardia for biventricular support in pediatric patients.5 The SynCardia is a pneumatic device comprised of polyurethane prosthetic ventricles controlled by an external driver.4 It eliminates or reduces several VAD complications such as left ventricular clot formation, arrhythmias, and need for inotropic support.2 It also allows for the discontinuation of immunosuppression in patients awaiting repeat heart transplant. Currently, the 70 cc TAH is approved by the FDA for patients with a body surface area (BSA) > 1.7 m2 and an anteroposterior dimension of > 10 cm.2,6,7 The smaller 50 cc device is currently being studied but is recommended for patients with a BSA of 1.2–1.7 m2.6,7
To our knowledge, we present the first care of successful pediatric bridge to transplant utilizing the 50 cc SynCardia device.
Eleven year old male with a past medical history of hypoplastic left heart syndrome status post Glenn and partial anomalous pulmonary venous return bridged to initial orthotropic heart transplant with a TandemHeart in October 2012. He had an uneventful post-transplant course other than grade 2 R cellular rejection 9 months post-transplant. Four years post-transplant, at his annual cardiac catheterization, he was noted to have grade 1 cardiac allograft vasculopathy (CAV) and grade 0 R cellular rejection but clinical concerns for antibody-mediated rejection (AMR), with negative C4d staining. His donor-specific antibodies returned moderately positive for DQ4 1:256 and DQ9 1:128, which had previously been 1:1. His admission echocardiogram showed normal left ventricular size and function but mildly reduced right ventricular function which quickly progressed to severely reduced biventricular function and severe bradycardia with a junctional rhythm. Because of rapid decompensated heart failure, he required intubation and initiation of milrinone, vasopressin, and epinephrine. He underwent treatment with plasmapheresis, intravenous immunoglobulin (IVIG), rituximab, antithymocyte globulin, and steroids for AMR. In less than 1 month a repeat catheterization demonstrated worsening hemodynamics with pulmonary capillary wedge pressure of 30 mm Hg, right ventricular end-diastolic pressure of 32 mm Hg, and rapid progression to grade 3 CAV Table 1. Multisystem organ dysfunction (MSOD) ensued necessitating ongoing ventilation and renal replacement therapy. After virtual fit via computed tomography (performed by Cincinnati Children’s Hospital Medical Center and previously described8), the 50 cc SynCardia TAH was implanted as bridge to HT, and his immunosuppression was stopped. The patient had a relatively short sternum which facilitated implantation, and the only modification to the usual implantation was using a longer outflow graft from the prosthetic right ventricle to the pulmonary artery. His explant showed severe CAV and myocardial fibrosis. At implant, his BSA was 1.1 m2 (0.9 m2 after postoperative diuresis). Implantation of the TAH allowed for excellent cardiac output (cardiac index, 4.2–5 L/min) while significantly lowering his central venous pressure (12–14 mm Hg in the early postoperative period and predominantly 8–10 mm Hg approximately 2 weeks after implantation). These factors, combined with a goal mean arterial pressure of 60–75 resulted in excellent organ perfusion and recovery in our critically ill patient. His MSOD resolved, he was extubated on postoperative day 10, his renal function improved and continuous renal replacement therapy was stopped on postoperative day 24, and he was listed for heart transplant 20 days post-TAH. Early bleeding necessitated chest exploration on postoperative day 6 and again on postoperative day 7 for evacuation of mediastinal thrombus that was impacting device function. During the second chest washout, an aortic leak was identified at the site of the aortic graft and was sutured closed. Despite discontinuation of all immunosuppressive medications, he did experience a Methicillin-sensitive Staphylococcus aureus driveline infection approximately 4 months after implantation that was successfully treated with a 3 week course of cefazolin and rifampin. Because of his CAV and moderate titers, DQ4 and DQ9 human leukocyte antigen (HLA) expressing donors were excluded. On presentation, he had Calculated Panel Reactive Antibodies (cPRA)s of 40% to class I and 76% to class II. After desensitization therapy, his cPRA decreased to 17% and 68% for class I and class II, respectively. However, after prolonged artificial circulatory support, he developed 100% sensitization to both HLA class I and class II. Desensitization therapy including monthly IVIG for 6 months and weekly rituximab for 4 weeks was attempted with little success. He remained admitted to the cardiac intensive care service throughout his hospitalization. Once stabilized he was transitioned to the freedom driver without complication. He was supported on the TAH for a total of 278 days before successful transplant. Other than the formation of additional scar tissue secondary to reoperation, the implantation of the TAH did not complicate the repeat transplant more than other VADs that are used for bridge to transplant. Postoperatively, he received multiple therapies for AMR. He was discharged home 2 months post-transplant and continues to do well, although he has required readmissions that were unrelated to his support with the TAH. He remains an active 13 year old boy, now 15 months post-transplant.
In 2000, fewer than 5% of pediatric patients were supported with ventricular assist devices, which rose to over 20% by 20137, and over 40% in 2017.9 It has also been shown that waitlist mortality decreases by 50% for centers with a pediatric VAD program.7 The SynCardia TAH is an option for pediatric patients with biventricular failure awaiting transplant. Patients with transplant rejection accounted for 19% of the worldwide pediatric use of the TAH.10 This number is likely to increase with the addition of the 50 cc TAH.5 The SynCardia TAH represents one of the next innovations in pediatric mechanical support and in adults has been shown to reduce the incidence of stroke.2 Several VAD complications, such as left ventricular clot formation, arrhythmias, and need for inotropic support, are mitigated with the TAH.2 In our case, the ability to discontinue immunosuppression and reduce the risk of infection weighed heavily into our decision to use the TAH. We demonstrated that the 50 cc TAH can be successfully implanted in patients smaller than 1.2 m2 but virtual fit is recommended and technical modifications may be necessary. For our patient, the TAH allowed for discontinuation of immunosuppression to minimize infection risk, and despite allosensitization, he was successfully bridged to repeat heart transplant.
The authors thank the staff of the cardiac care unit and team at Cincinnati Children’s Hospital Medical Center for assisting with the virtual fit and implantation.
1. Almond CSD, Thiagarajan RR, Piercey GE, et al. Waiting list mortality among children listed for heart transplantation in the United States. Circulation 2009.119: 717–727.
2. Park SS, Sanders DB, Smith BP, et al. Total artificial heart
in the pediatric patient with biventricular heart failure. Perfusion 2014.29: 82–88.
3. Blume ED, Naftel DC, Bastardi HJ, et al. Outcomes of children bridged to heart transplantation with ventricular assist devices: A multi-institutional study. Circulation 2006.113: 2313–2319.
4. Kirsch ME, Nguyen A, Mastroianni C, et al. SynCardia temporary total artificial heart
as bridge to transplantation: Current results at la pitié hospital. Ann Thorac Surg 2013.95: 1640–1646.
5. Lorts A, Rizwan R, Zafar F, et al. Worldwide use of SynCardia total artificial heart
in pediatric population: A 30 year experience. J Heart Lung Transplant 2016.35: S352–S353.
6. Devaney EJ. The total artificial heart
in pediatrics: Expanding the repertoire. J Thorac Cardiovasc Surg 2016.151: e73–e734.
7. Kirklin JK. Advances in mechanical assist devices and artificial hearts for children. Curr Opin Pediatr 2015.27: 597–603.
8. Moore RA, Madueme PC, Lorts A, Morales DL, Taylor MD. Virtual implantation evaluation of the total artificial heart
and compatibility: Beyond standard fit criteria. J Heart Lung Transplant 2014.33: 1180–1183.
9. Blume ED, VanderPluym C, Lorts A, et al. Second annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) report: Pre-implant characteristics and outcomes. J Heart Lung Transplant 2018.37: 38–45.
10. Morales DLS, Lorts A, Rizwan R, Zafar F, Arabia FA, Villa CR. Worldwide experience with the Syncardia total artificial heart
in the pediatric population. ASAIO J 2017.63: 518–519.