Ventricular Assist Device in Children with Cardiac Graft Failure

Abstract

We sought to determine whether ventricular assist device (VAD) support is an effective therapy in children with cardiac graft dysfunction. We conducted a retrospective review of VAD usage in this scenario at our institution. Although short-term VAD support was highly successful (89% [eight out of nine] were bridged to recovery), only 29% (2 out of 7) with long-term VAD survived to retransplant. Of note, three out of five mortalities with long-term VAD were related to sepsis (two fungal and one Gram-negative bacterial). Infectious risk imposed by ongoing immunosuppressive therapy limits the role of long-term VAD in this population.

We sought to determine whether ventricular assist device (VAD) support is an effective therapy in children with cardiac graft dysfunction. We conducted a retrospective review of VAD usage in this scenario at our institution. Although short-term VAD support was highly successful (89% [eight out of nine] were bridged to recovery), only 29% (2 out of 7) with long-term VAD survived to retransplant. Of note, three out of five mortalities with long-term VAD were related to sepsis (two fungal and one Gram-negative bacterial). Infectious risk imposed by ongoing immunosuppressive therapy limits the role of long-term VAD in this population.

The number of pediatric heart transplantations has been gradually increasing, exceeding 500 annual cases worldwide in recent years.¹ Along with an improvement in perioperative survival, the number of children who suffer from cardiac graft dysfunction has risen in a parallel fashion.² Although VAD support has become an integral part of contemporary heart failure management, its efficacy in pediatric heart transplant recipients remains unclear. Circulatory support in this vulnerable population is more problematic given the elevated risk for infection associated with ongoing immunosuppression.³

This is a single-center, retrospective study approved by the Baylor Institutional Review Board. All pediatric (≤18 years old) heart transplant recipients who required VAD support from 2001 to 2013 were included. Patients were categorized into two groups defined by the type of support provided: short-term or long-term VAD. The type of VAD was primarily determined based on the etiology of graft failure and anticipated duration of support. A short-term VAD is favored for patients presenting in acute cardiogenic shock with a working diagnosis of acute rejection where the possibility of cardiac recovery is foreseeable. Conversely, a long-term VAD is implemented in patients with chronic etiologies of graft dysfunction (e.g., transplant coronary vasculopathy).

In total, 15 patients underwent 16 VAD runs; 9 with short-term extracorporeal centrifugal VAD and 7 with long-term devices. Patient demographics and VAD outcomes are summarized in Table 1. One patient who had been bridged from short-term to long-term VAD was counted separately in each group. Left ventricular assist device (LVAD) support was used in 10 (63%), whereas biventricular assist device (BiVAD) support and right ventricular assist device (RVAD) were used in 3 (19%) each. Short-term VAD support was successfully weaned following cardiac recovery in eight (89%) after a median support duration of 4 (2–6) days. The remaining patients did not show signs of cardiac recovery and were bridged to long-term VAD. Although the chest was electively left open during short-term VAD support in all patients, there were no infectious complications in this group. Four (44%) patients underwent hemodialysis or had plasmapheresis incorporated in the short-term VAD circuit as part of their antirejection management.

Table 1: Patient Demographic Characteristics and Outcomes

By contrast, outcomes with long-term VAD were dismal. Only two (29%) patients with long-term VAD support were bridged to retransplant after 28 and 83 days of support. Five patients (71%) expired on long-term VAD after a median support of 20 (4–143) days. Three of the five mortalities were caused by fungal (n = 2) and Gram-negative (n = 1) sepsis, representing 3.0 events per patient-year. Both patients with fungal sepsis had significant comorbidities: one had acute renal and hepatic dysfunction, and the other suffered from posttransplant lymphoproliferative disease of the heart and renal failure. The patient with Gram-negative sepsis was a 12 year-old girl with history of end-stage congenital heart disease who presented with severe humoral rejection. Despite aggressive antirejection therapy while on short-term VAD support for 6 days, there were no signs of cardiac recovery. Subsequent conversion to long-term BiVAD support was unable to restore graft function, and the patient subsequently died of enterococcal sepsis after 20 days of support. The remaining two patients had transplant coronary vasculopathy: one patient suffered a cardiac arrest because of a right ventricular infarction that required extracorporeal membrane oxygenation (ECMO) resuscitation. She was placed on long-term RVAD but expired because of multisystem organ failure. The other patient developed an extremely severe prothrombogenic state that resulted in complete thrombosis of the HeartMate II (Thoratec Corp., Pleasanton, CA). Despite heavy anticoagulation and two subsequent pump exchanges, the patient developed a fatal thromboembolic stroke. Although blood culture did not identify any causative organisms, systemic infection was suspected because of persistently elevated inflammatory markers.

This study supports the use of short-term VAD as an effective mode of mechanical support in children with acute cardiac graft failure. Although central cannulation with an open chest while ongoing short-term VAD support may represent a period of peak vulnerability to infection, the brief support duration as well as strict antimicrobial prophylaxis may have played a role in keeping all patients infection free. Conversely, the outcome of long-term VAD support in this series was sobering. Only two (29%) patients survived to retransplantation. The increasing wait list duration for pediatric heart transplant in the current era⁴ along with a heightened risk for infection while undergoing VAD support after a failing graft³ justifies concerns when considering this practice. In this regard, a recent report from Columbia University⁵ warrants discussion. By using a reduced immunosuppression regimen (steroids only), 73% (11 out of 15) of mechanically supported patients were successfully bridged to retransplantation, and all remained free from infection. Although nearly half of these patients had histological evidence of rejection at the time of cardiac explantation, this report highlights that modulation of immunosuppression may influence the feasibility long-term VAD support for graft failure. The use of a total artificial heart may also represent an alternative because it alleviates the need of immunosuppressive therapy. Although size constraints limit the applicability of this option in the pediatric population, the smaller system (50 mL pumps, SynCardia, Tucson, AZ) is on the horizon. Certainly, more studies are necessary to establish effective treatment strategies for children with chronic graft failure.