Secondary Logo

Journal Logo

Pediatric Circulatory Support

Intracorporeal Biventricular Assist Devices Using the Heartware Ventricular Assist Device in Children

Schweiger, Martin*; E. Mascio, Christoph; Kanter, Kirk R.; Marasco, Silvana§; Eghtesady, Pirooz; Miera, Oliver; Hübler, Michael*; Kavarana, Minoo N.#

Author Information
doi: 10.1097/MAT.0000000000001149
  • Free

Abstract

Continuous flow (cf) devices have opened the doors to the discharge of pediatric patients on left ventricular assist devices (LVADs). Whereas some years ago only a few centers reported discharging pediatric patients on cf-devices,1 nowadays the reported numbers are between 55%2 and 72%.3 Most reports suggest that children with a cf-VAD can be safely discharged home with device malfunction and arrhythmia being the most common adverse events.4

The majority of implants in children are only for isolated left ventricular support. However, there are a certain percentage of patients who require biventricular support.

The two largest databases of children needing VADs (EUROMACS and PEDIMACS) suggested 15%2 to 16%5 suffering from biventricular failure generally needed durable long-term biventricular VAD (BiVAD) support. Unlike adults who have access to a wide variety of reliable Food and Drug Administration-approved long-term VADs, children have only limited options. The Berlin Heart (BH) EXCOR represents the gold standard for children with a body surface area (BsA) < 1 m2 suffering from biventricular heart failure when durable VAD support is anticipated. While the BH EXCOR is vastly superior to extracorporeal membrane oxygenation in terms of survival as bridge to transplantation,6 its use for pump chambers of 50 ml or less generally precludes discharge from hospital.7 Neurologic event(s) from thromboembolic complications (>20%8,9) complicates the use of BH EXCOR for these patients.2,9 The PEDIMACS registry also indicated a higher stroke rate for extra (para)-corporeal devices such as the Berlin heart compared with cf-devices,2,9 but with a clear hint that age and health status of the child at implantation (more ill) may be a factor in adverse event rates. There is a predominance of infants and younger children implanted with paracorporeal devices when compared with older children and adolescent with implantable cf-VADs.

Some centers have published case reports where two cf-VADs were used in pediatrics with successful bridge to transplantation and BsA as low as 0.6 m2.10–13 Conway et al. performed a global survey on children using HeartWare VAD (HVAD). The authors revealed that 2% (n: 4) of the population had a BiVAD implantation14 without giving details of complication rates on these four patients. We sought to describe outcomes for children (age ≤18 years) supported with the HVAD used as BiVAD.

Methods

As of May 2017, using the HVAD database, 11 centers were identified as having used HVAD in BiVAD configuration. These centers were contacted and a positive response was obtained from eight of them (five US, one Australian, and two European) encompassing 11 patients. A questionnaire was sent out to these centers using closed questions, multiple-choice elements, numerical data, and free text elements. The primary variable was survival due to either transplant or recovery. The secondary variables included re-operations due to bleeding and pump thrombosis needing either pump replacement or conservative treatment and discharge of patient home.

Each institution obtained institutional review board approval for submission of de-identified data for analysis and inclusion in the study. Data completion was done in seven centers (four US, one Australian, and two European) for 10 patients (Table 1). Simple measures of distribution were used for descriptive statistical analysis. Data are presented as median or frequency with percentage.

Table 1. - Participating Center Submitting Data of Children on BiVAD Support (Alphabetic Order)
Cardiothoracic Surgical Unit The Alfred, Australia
Children’s Hospital of Philadelphia, USA
Children’s Hospital Zurich, Switzerland
Emory University School of Medicine Atlanta, USA
Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Germany
Division of Pediatric Cardiothoracic Surgery Charleston, USA
Washington University in St. Louis and St. Louis Children’s Hospital, USA

Results

The median age of the study population (n = 10, 4♀, 6♂) at the time of implantation was 12.7 ± 4.6 years (5.3–16.9), median BsA was 1.56 (0.6–1.9). Patient diagnoses were myocarditis (n = 1), cardiomyopathy (n = 8; three dilative, two restrictive, one HCM, one postpartum, one toxic), and one post-transplant heart failure (Table 2). Three patients had prior sternotomy. All patients were on inotropic support before implantation.

Table 2. - Children on Intracorporeal BiVAD Support
Pat. No. Age at Implantation (years) Weight at Implantation (kg) Diagnosis Congenital Heart Disease Previous Sternotomy INTERMACS Profile
1 14.5 58.6 DCMP No No 1
2 16.0 72 Post Partum CMP No Yes 2
3 6.0 13.5 RCMP No No On ECLS
4 8.8 21.4 RCMP No No 3
5 16.7 81.2 DCMP No No 2
6 10.9 26 Toxic CMP No Yes 2
7 5.4 19.5 DCMP No Yes 1
8 16.8 49.5 HCMP No No 2
9 16.9 54.0 Myocarditis No No 2
10 8.1 18.4 DCMP No No 2
CMP, cardiomyopathy; DCMP, dilated cardiomyopathy; ECLS, extra corporeal life support; HCMP, hypertrophic cardiomyopathy; RCMP, restrictive cardiomyopathy.
Highlighted patients died on support.

Six patients had a primary BiVAD implantation. Three of them had a body weight >50 kg. In four patients, a primary LVAD placement was done followed by the implantation of an intra-corporeal RVAD/HVAD 4–26 days later (4, 9, 11, 26 days). All these four patients showed RV failure either with maximal conservative treatment (inotropic support, iNO, and LVAD adjustments) or they could not be weaned off a temporary RVAD. Only one patient with secondary RVAD implantation died (odds ratio 0.66).

Technical details included excision of the left AV valve in three patients, presumably due to restrictive physiology, to create enough space and achieve unobstructed flow into the pump. RVAD revolutions per minute (RPM) ranged between 1,800 and 2,400, resulting in a calculated flow of 1.7–4.5 L per minute. One center narrowed the RVAD outflow graft to avoid uncontrolled flow through the pulmonary vascular bed. In all patients RPMs for the RVAD were lower than for LVAD, with also slightly lower calculated flow rates. On the left side RPMs ranged from 1,800 to 3,000 resulting in a calculated flow of 1.5–4.1 L per minute.

Outcomes for the patients are shown in Table 3. No patient was weaned from support. Median support time was 52 days, with the longest support time of 235 days. Two patients (20%) were discharged from hospital before transplant; one remained in the hospital due to concerns about family’s ability to care for the patient, waiting on the floor unit and attending rehabilitation and hospital school until transplant on day 117 postoperation.

Table 3. - Outcome of Children on Intracorporeal BiVAD Support
Pat. No. Primary BiVAD Support time (days) Heart Transplantation Died on Support Discharged Home*
1 Yes 51 Yes No No
2 No 117 Yes No No
3 No 17 Yes No No
4 Yes 16 No Yes No
5 Yes 53 No Yes No
6 Yes 19 Yes No No
7 Yes 21 No Yes No
8 No 84 No Yes No
9 Yes 75 Yes No Yes
10 No 235 No No Yes
Highlighted patients died on support.
*Discharge home refers to discharge on BiVAD support.

Of the patients, 60% survived transplant (n = 5) or are still on support (n = 1). For those who underwent the transplant, median support time was 51 days. Of those five patients operated on, one died within 30 days of the transplant. All others survived with a follow-up period of 1–4 years.

Four patients died. Reasons for death included bleeding (n = 2), intracerebral hemorrhage (n = 1), and multi system organ failure (n = 1) (Table 4).

Table 4. - Reasons of Death and Severe Complications
Pat. No. Support Time (days) Reason for Death Other Severe Complications*
1 51 N.a. Reoperation for postoperative bleeding
2 117 N.a. No
3 17 N.a. No
4 16 Cerebral hemorrhage No
5 53 Postoperative bleeding Reoperation for postoperative bleeding
6 19 N.a. Reoperation for postoperative bleeding
7 21 Postoperative bleeding Reoperation for postoperative bleeding
8 84 Multi-organ failure Reoperation for postoperative bleeding
9 75 N.a. Reoperation for postoperative bleeding
10 235 N.a. Lysis therapy for RVAD thrombus
*Complications include requirement for reoperations, cerebral stroke, or major infections.

Eight out of 10 patients had at least one major complication. Complication included major bleeding requiring re-operation (n = 6), one severe neurologic injury leading to the death of the patient, and thrombus formation in one of the pumps (n: 2). In one case, pump thrombosis occurred in an LVAD pump within the first 30 days of initial VAD placement. The pump had to be replaced. In another case, the RVAD was affected 213 days after RVAD implantation and was treated successful with lysis therapy. In one patient gastrointestinal bleeding was diagnosed.

Concerning anticoagulation all except one center used at least heparin intravenously and switched to oral anticoagulation with a vitamin-K antagonist. Some centers added acetylsalicylic acid when there was no bleeding. Unfortunately specific measurements (aPTT, INR, anti-Xa) as well as long-term information on anticoagulation were not available.

Discussion

In this report, the authors investigate the frequency of HVAD implantations as BiVAD around the world and the report reveals some interesting findings. The sample size itself is small and the experience of each center ranges from 1 to 2 patients. Almost 50% of the cohort was supported for >60 days with the intra-corporeal BiVAD, making this approach feasible. Still results were disappointing with a high mortality rate of 40% as well as a high complication rate and a low discharge rate (20%). Because of this the authors think it is crucial to share these experiences with the pediatric MCS community.

Device selection in children remains crucial and factors such as weight, BsA, chest dimensions, or the underlying diagnosis, especially the presence of residua or sequelae of CHD have to be considered. In this observational study, it was found that intra-corporeal BiVAD implantation was done in different underlying diagnoses but without any CHD. Underlying diagnosis did not impact the likelihood of success. There were, clearly, patients with restrictive cardiomyopathy who benefited from this approach while those with DCM did not.

Concerning weight and BsA the authors cannot draw any conclusion for cutoff values. They had both very young patients who survived with BiVAD support and those who did not as they were of adolescent age or older/bigger.

It is well known that BiVAD placement is associated with a higher mortality and complication rates in relation to LVAD.8,15–17 Yet, there are no clear guidelines for selection of either primary LVAD implantation or BiVAD implantation in the case of children and protocols vary from center to center. In our cohort almost half of the patients (40%) had a primary LVAD implantation. The advantages of going home after discharge and school integration for children >25 kg supported with cf-LVADs are now widely accepted.1–3,5,18 Still some patients will need a secondary RVAD placement. In our cohort subsequent RVAD implantation was done within a few days after LVAD implantation and was not associated with any worse outcome (odds ratio 0.66).

For patient needing primary biventricular support the “golden standard” remains the BH Excor. Still, occasionally implantations of two cf-VADs in children10–13 and even in an adult patient with single ventricle with subsequent discharge home have been reported.19 Out of those six patients in our cohort planned for a primary intra-corporeal BiVAD implantation, three had a weight >50 kg. In these patients, the advantage of discharge was prioritized and was the reason why a BH Excor was not implanted. In the other three patients with a body weight <30 kg, a cf-BiVAD was chosen over a BH Excor due to the risks of thrombus formation or bad ventricle decompression. In a recent systematic review, the authors describe mortality rates in the BH Excor BiVAD group ranging from 35.5% to 83.3% with an overall mortality rate of 45.9%.17 The latest published data from Pedimacs reports a much lower mortality rate of paracorporeal pulsatile devices of 19% at 6 months without a distinction between BiVADs and LVADs.9 Still it should be emphasized that the cited group is not comparable to our cohort in terms of underlying disease (CHD patients included) as well as age, weight, and BsA.

At this weight range, the potential advantage of this strategy over a BiVAD BH Excor would be improved mobility, independence, rehabilitation potential, and the ability to discharge the child home. Surprisingly, a finding of our study is that the use of HVAD in BiVAD configuration often does not necessarily translate into hospital discharge for pediatric patients. Since only 20% of the patients ever left the hospital and 55% survived the transplantation, it would, therefore, be premature to conclude that the configuration approach results in hospital discharge. Some children, however, were kept in hospital due to security reasons and the lack of discharge experience. However, given the appropriate clinical outcome and social environment, the discharge home option would exist.

The stroke rate was 4.6 per 100 patient months. According to the latest PEDIMACS report, stroke rates with paracorporeal VADs have declined. Morales et al. reported an early neurologic dysfunction rate of 27% which translates into a rate of 2.3 per patient years.9

The most frequent complication in this patient collective was postoperative bleeding, with two deaths (20%) due to uncontrollable loss of blood, which required re-exploration (60% of all patients). The possible explanations are that first, two cf-VADs may translate into twice as much of blood trauma with hemolysis and coagulopathy and, second, it may be an expression of the severity of end-organ failure especially liver dysfunction.8,15,16 Finally, not surprisingly, there is no uniform anticoagulation protocol.

Finally, new options are becoming available combining biventricular support and the possibility of discharge home. Recently, the new 50 cc total artificial heart was introduced and has gained attention in the pediatric heart failure community.20 This might be a valuable option for these patients as well; however, these results remain to be seen.

Limitations

The authors acknowledge that the use of two HeartWare HVAD in children as BiVAD is off-label. This experience is very limited and it is possible that it stems from underreporting of poor outcomes of BiVAD HVAD support in children. The period being reported could also present a learning curve to the pediatric community with regard to HVAD use in children, especially with regard to RVAD placement.

Conclusion

The worldwide experience of using two cf-VADs as BiVADs in children is a rare procedure, with high mortality and low discharge rates. Bleeding requiring re-operation is the predominant postoperative challenge. Although discharge home can be achieved, the current experience to support that is very limited. The risk and benefit ratio of such an approach should be carefully reviewed and still compared with the current standard strategy using the Berlin EXCOR.

References

1. Schweiger M, Vanderpluym C, Jeewa A, et al. Outpatient management of intra-corporeal left ventricular assist device system in children: A multi-center experience. Am J Transplant 2015.15: 453–460.
2. Blume ED, VanderPluym C, Lorts A, et al.; Pedimacs Investigators: Second annual pediatric interagency registry for mechanical circulatory support (Pedimacs) report: Pre-implant characteristics and outcomes. J Heart Lung Transplant 2018.37: 38–45.
3. Schweiger M, Miera O, de By TMMH, et al. Cerebral strokes in children on intracorporeal ventricular assist devices: Analysis of the EUROMACS Registry. Eur J Cardiothorac Surg 2017.53: 416–421.
4. Chen S, Lin A, Liu E, et al. Outpatient outcomes of pediatric patients with left ventricular assist devices. ASAIO J 2016.62: 163–168.
5. de By TMMH, Schweiger M, Waheed H, et al. The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): First EUROMACS Paediatric (Paedi-EUROMACS) report. Eur J Cardiothorac Surg 2018.54: 800–808.
6. Fraser CD Jr, Jaquiss RD, Rosenthal DN, et al.; Berlin Heart Study Investigators: Prospective trial of a pediatric ventricular assist device. N Engl J Med 2012.367: 532–541.
7. Jeewa A, Manlhiot C, McCrindle BW, Van Arsdell G, Humpl T, Dipchand AI. Outcomes with ventricular assist device versus extracorporeal membrane oxygenation as a bridge to pediatric heart transplantation. Artif Organs 2010.34: 1087–1091.
8. Almond CS, Morales DL, Blackstone EH, et al. Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children. Circulation 2013.127: 1702–1711.
9. Morales DLS, Rossano JW, VanderPluym C, et al.; Pedimacs Investigators: Third annual pediatric interagency registry for mechanical circulatory support (Pedimacs) report: Preimplant characteristics and outcomes. Ann Thorac Surg 2019.107: 993–1004.
10. Glass L, Savage A, Haddad O, Kavarana MN. Continuous-flow, implantable biventricular assist device as bridge to cardiac transplantation in a small child with restrictive cardiomyopathy. J Heart Lung Transplant 2018.37: 173–174.
11. Stein ML, Yeh J, Reinhartz O, et al. HeartWare HVAD for biventricular support in children and adolescents: The stanford experience. ASAIO J 2016.62: e46–e51.
12. Schweiger M, Krüger B, Cavigelli-Brunner A, Dave H, Schmiady M, Hübler M. Biventricular intracorporeal ventricular assist device in a 10-year-old child. Int J Artif Organs 2016.39: 48–50.
13. Peng E, Kirk R, Wrightson N, et al. An extended role of continuous flow device in pediatric mechanical circulatory support. Ann Thorac Surg 2016.102: 620–627.
14. Conway J, Miera O, Adachi I, et al. World-wide experience of a durable centrifugal flow pump in pediatric patients. Semin Thorac Cardiovasc Surg 2018.30: 327–335.
15. Fan Y, Zhang AM, Weng YG, et al. Factors associated with the need of biventricular mechanical circulatory support in children with advanced heart failure. Eur J Cardiothorac Surg 2013.43: 1028–1035.
16. Morales DL, Almond CS, Jaquiss RD, et al. Bridging children of all sizes to cardiac transplantation: The initial multicenter North American experience with the Berlin Heart EXCOR ventricular assist device. J Heart Lung Transplant 2011.30: 1–8.
17. Rohde S, Antonides CFJ, Dalinghaus M, Muslem R, Bogers AJJC. Clinical outcomes of paediatric patients supported by the Berlin Heart EXCOR: A systematic review. Eur J Cardiothorac Surg 2019.56: 830–839.
18. Villa CR, Khan MS, Zafar F, Morales DLS, Lorts A. United States trends in pediatric ventricular assist implantation as bridge to transplantation. ASAIO J 2017.63: 470–475.
19. Ovroutski S, Miera O, Krabatsch T, Berger F, Photiadis J, Potapov E. Two pumps for single ventricle: Mechanical support for establishment of biventricular circulation. Ann Thorac Surg 2017.104: e143–e145.
20. Wells D, Villa CR, Simón Morales DL. The 50/50 cc total artificial heart trial: Extending the benefits of the total artificial heart to underserved populations. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 201720: 16–19.
Keywords:

biventiricular assist device; children; HVAD; MCS

Copyright © 2020 by the ASAIO