A Single-Institutional Experience with 36 Children Smaller Than 5 Kilograms Supported with the Berlin Heart Ventricular Assist Device (VAD) over 12 Years: Comparison of Patients with Biventricular versus Functionally Univentricular Circulation

Abstract

Objectives

We reviewed outcomes in all 36 consecutive children <5 kg supported with the Berlin Heart pulsatile ventricular assist device (VAD) at the University of Florida, comparing those with univentricular circulation (n = 23) to those with biventricular circulation (n = 13).

Methods

The primary outcome was mortality. Kaplan-Meier methods and log-rank tests were used to assess group differences in long-term survival after VAD insertion. T-tests using estimated survival proportions and standard errors were used to compare groups at specific time points.

Results

Of all 82 patients ever supported with Berlin Heart at our institution, 49 (49/82 = 59.76%) weighed <10 kg and 36 (36/82 = 43.90%) weighed <5 kg. Of these 36 patients who weighed <5 kg, 26 (26/36 = 72.22%) were successfully bridged to transplantation. Of these 36 patients who weighed <5 kg, 13 (13/36 = 36.1%) had biventricular circulation and were supported with 12 biventricular assist devices (BiVADs) and 1 left ventricular assist device (LVAD) (Age [days]: median = 67, range = 17–212; Weight [kilograms]: median = 4.1, range = 3.1–4.9), while 23 (23/36 = 63.9%) had univentricular circulation and were supported with 23 single ventricle-ventricular assist devices (sVADs) (Age [days]: median = 25, range = 4–215; Weight [kilograms]: median = 3.4, range = 2.4–4.9). Of 13 biventricular patients who weighed <5 kg, 12 (12/23 = 92.3%) were successfully bridged to cardiac transplantation. Of 23 functionally univentricular patients who weighed <5 kg, 14 (14/23 = 60.87%) were successfully bridged to cardiac transplantation. For all 36 patients who weighed <5 kg: 1-year survival estimate after VAD insertion = 62.7% (95% confidence interval [CI] = 48.5%-81.2%) and 5-year survival estimate after VAD insertion = 58.5% (95% CI = 43.8%-78.3%). One-year survival after VAD insertion: 84.6% (95% CI = 67.1%-99.9%) in biventricular patients and 49.7% (95% CI = 32.3%-76.4%) in univentricular patients, P = 0.018. Three-year survival after VAD insertion: 84.6% (95% CI = 67.1%-99.9%) in biventricular patients and 41.4% (95% CI = 23.6%-72.5%) in univentricular patients, P = 0.005.

Conclusion

Keywords

ventricular assist device VAD single ventricle functionally univentricular heart

Introduction

Providing mechanical circulatory support with a ventricular assist device (VAD) for patients weighing <5 kg presents multiple challenges, and and supporting patients weighing <5 kg with functionally univentricular circulation is especially complex.^1–6 Survival of patients weighing <5 kg with functionally univentricular physiology supported with a VAD is novel.^1–6

Over the past four years, our program has published a series of manuscripts describing our evolving approach to providing support with a “Single Ventricle-Ventricular Assist Device” (sVAD) to patients with functionally univentricular circulation.^7–13 These seven previous publications describe the evolving details of our techniques for preemptive sVAD utilization in functionally univentricular neonates with unfavorable cardiac anatomy and extreme risk of cardiac compromise before or during staged palliation, who have either ductal-dependent pulmonary circulation or ductal-dependent systemic circulation. Neonates with functionally univentricular ductal-dependent pulmonary circulation undergo combined palliation + sVAD insertion, while neonates with functionally univentricular ductal-dependent systemic circulation undergo combined hybrid + sVAD insertion. Palliation + sVAD for patients with ductal-dependent pulmonary circulation includes sVAD insertion plus stent placement in the arterial duct or systemic-to-pulmonary artery shunt with pulmonary arterioplasty, if needed. Hybrid + sVAD for patients with ductal-dependent systemic circulation includes sVAD insertion plus application of bilateral pulmonary artery bands, stent placement in the arterial duct, and atrial septectomy, if needed.

Despite the challenges associated with sVAD support in functionally univentricular neonates and infants, it is reasonable to strive to achieve outcomes in these functionally univentricular patients supported with sVAD equivalent to the outcomes achieved after support with left VAD (LVAD) or biventricular assist device (BiVAD) in patients with biventricular circulation. The purpose of this study is to review our clinical experience in all 36 consecutive children <5 kg at the University of Florida who were supported with a pulsatile paracorporeal VAD (Berlin EXCOR [Berlin Heart, Inc.]) (n = 36) and to compare characteristics and outcomes of those patients with functionally univentricular circulation (n = 23) to the characteristics and outcomes of those patients with biventricular circulation (n = 13).

Materials and Methods

Patients

This analysis includes all 36 consecutive patients who weighed <5 kg at the time of VAD insertion who were supported with the Berlin Heart pulsatile VAD at the University of Florida, with the first patient cannulated on October 19, 2009, and the most recent patient in this consecutive series cannulated on November 1, 2021. Of these 36 consecutive patients, 13 consecutive patients with biventricular circulation were supported with VAD, and 23 consecutive patients with functionally univentricular circulation were supported with VAD.

Of 23 patients with functionally univentricular circulation, 12 (52.2%) high-risk patients had hypoplastic left heart syndrome (HLHS) or HLHS-related malformations with ductal-dependent systemic circulation, and 11 (47.8%) high-risk functionally univentricular patients had hypoplastic right heart syndrome (HRHS) or HRHS-related malformations with ductal-dependent pulmonary circulation. Of 12 patients with HLHS or HLHS-related malformations with ductal-dependent systemic circulation, nine high-risk patients underwent primary hybrid + sVAD insertion without prior cardiac surgery; detailed analyses of these nine patients have been published.⁹ During the same era that these nine high-risk patients with HLHS or HLHS-related malformations underwent hybrid + sVAD, 62 standard-risk patients underwent Norwood (Stage 1) at the University of Florida with an operative mortality of 3.2% (2/62).¹² The remaining three patients in this current manuscript with HLHS or HLHS-related malformations underwent VAD insertion after having undergone:

Norwood (Stage 1) (n = 2), or

Hybrid (Stage 1) (n = 1).

Of 11 patients with HRHS or HRHS-related malformations with ductal-dependent pulmonary circulation, seven high-risk patients with pulmonary atresia and intact ventricular septum (PA-IVS) underwent primary palliation + sVAD insertion without prior cardiac surgery; detailed analyses of the first six of these patients have been published,¹¹ and one additional patient with PA-IVS has been managed with this approach since that time. The remaining four patients with HRHS or HRHS-related malformations with ductal-dependent pulmonary circulation underwent VAD insertion after having undergone:

Central shunt (n = 2), or

No interventions prior to VAD implantation (n = 2).

Of 13 patients with biventricular circulation, 62% (n = 8) had acquired heart disease, and 38% (n = 5) had congenital heart disease. The following fundamental diagnoses were present in the eight patients with biventricular circulation and acquired heart disease:

Cardiomyopathy (n = 7), or

Myocarditis (n = 1 [This single patient with myocarditis and biventricular circulation actually underwent two separate episodes of support with the Berlin Heart, only the first of which is included in this current analysis of 36 children smaller than 5 kg supported with the Berlin Heart over 12 years. This infant was initially cannulated with Berlin Heart BiVAD at 46 days of age and 4.1 kg; after 39 days of VAD support, the child underwent successful cardiac transplantation. Then, 615 days after the initial heart transplant, this child was again cannulated with Berlin Heart BiVAD at 700 days of age and 11.1 kg {secondary to chronic allograft rejection}; after 13 days of VAD support, the child underwent successful cardiac retransplantation and is currently alive at the time of submission of this manuscript at nine years of age.]).

The following fundamental diagnoses were present in the five patients with biventricular circulation and congenital heart disease:

Coronary artery stenosis (n = 1),

Status post repair of tetralogy of Fallot with left ventricular failure (n = 1),

Status post repair of truncus arteriosus with interrupted aortic arch (n = 1),

Hypoplastic aortic isthmus, supravalvar aortic stenosis, reduced left ventricular function (n = 1), or

Status post resection of cardiac rhabdomyoma (n = 1).

Surgical Technique, VAD Management, and Anticoagulation Protocol

Our surgical techniques for VAD insertion, and our detailed protocols for anticoagulation, have been published.¹⁰ Patients with functionally univentricular anatomy and physiology are supported with sVAD, which includes an inflow cannula in the common atrium or systemic ventricle and an outflow cannula in a systemic artery (either the ascending aorta or the main pulmonary artery in patients with ductal-dependent systemic circulation and hypoplastic ascending aorta), in the setting of parallel pulmonary flow. Patients with biventricular anatomy and physiology are supported with a BiVAD or LVAD. BiVAD support uses inflow cannulas in the right atrium and left ventricle with outflow cannulas in the pulmonary artery and aorta, respectively, while LVAD support uses an isolated inflow cannula in the left ventricle and an isolated outflow cannula in the aorta.

The VAD rate is gradually increased as needed to assure adequate cardiac output and systemic tissue perfusion. The patient is extubated as soon as possible. Appropriate weight gain and end-organ function are maintained on VAD support until transplantation.

During the first 24 hours after VAD insertion, no anticoagulation is given (with the exception of patients with a systemic-to-pulmonary artery shunt who receive aspirin on the initial night of sVAD insertion, as described below). The following anticoagulation protocol is then initiated:

Bivalirudin: Bivalirudin is initiated on postoperative day 1. During hours 24 to 72, bivalirudin is titrated to a partial thromboplastin time (PTT) of 50 to 70. After 72 hours, bivalirudin is titrated to a PTT of 70 to 100.

Aspirin: For patients with a systemic-to-pulmonary artery shunt, aspirin is started on the initial night of VAD insertion at a dose of 5 mg/kg/d (divided into two daily doses), and aspirin is increased each week until a dose of 30 mg/kg/d is reached by week 4. For patients without a systemic-to-pulmonary artery shunt, aspirin is started on day 5 after VAD implantation at a dose of 5 mg/kg/d (divided into two daily doses), and aspirin is increased each week until a dose of 30 mg/kg/d is reached by week 4.

Dipyridamole: Dipyridamole is started on week 5 after VAD implantation at a dose of 2.5 mg/kg/d, and dipyridamole is increased twice each week until a dose of 15 mg/kg/d is reached by week 6.

Omega-3 fatty acid: Omega-3 fatty acid is typically started at 3 to 4 months after VAD implantation.

Statistics and Institutional Review Board Approval

Descriptive summaries of the data were tabulated using mean with standard deviation (SD) and median with range. The primary outcome of interest was mortality. Kaplan-Meier methods and log-rank tests were used to assess group differences in long-term survival after VAD insertion. “Time zero” for this analysis was the time of VAD insertion, so all survival estimates are estimates of survival after VAD insertion. To compare groups at specific time points, Z-tests were performed using the Kaplan-Meier estimated survival rates and standard errors at each time point. All analyses were performed using the R statistical software package (V.4.1.1, the R Foundation for Statistical Computing). A P value of 0.05 was considered statistically significant.

Data were sourced from a registry and database that uses software certified by the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS CHSD) and has been prospectively maintained on all patients undergoing pediatric and congenital cardiac surgery at our institution (a component of the CardioAccess International Clinical Outcomes Database: Comprehensive Cardiovascular and Thoracic Module, CardioAccess Incorporated, Saint Petersburg, Florida, and Fort Lauderdale, Florida: http://www.cardioaccess.com). In this manuscript, a stroke was defined using the definition of stroke used by STS CHSD: “A stroke is any confirmed neurological deficit of abrupt onset caused by a disturbance in blood flow to the brain, when the neurologic deficit does not resolve within 24 h.” In this manuscript, the complication of bleeding includes all patients with surgical bleeding requiring reoperation, as well as all patients with any significant form of bleeding requiring transfusion, including gastrointestinal bleeding. This study was approved by the University of Florida Institutional Review Board with waiver of the need for consent: IRB202102055, approved 9/15/2021 and IRB202102664, approved 3/18/2022.

Results

At the University of Florida, of 82 patients who were supported with the Berlin Heart, 49 (49/82 = 59.76%) weighed <10 kg at the time of VAD insertion, and 36 (36/82 = 43.90%) weighed <5 kg at the time of VAD insertion. This analysis will report the patient characteristics and outcomes of these 36 consecutive children <5 kg who were supported with the Berlin Heart VAD (age [days]: mean ± SD = 55.9 ± 51.4, median = 35, range = 4-215; weight [kg]: mean ± SD = 3.7 ± 0.69, median = 3.6, range = 2.4-4.9), with the first patient cannulated on October 19, 2009, and the most recent patient cannulated on November 1, 2021. Thirteen patients with biventricular circulation were supported (12 BiVAD, 1 LVAD only), and 23 patients with functionally univentricular circulation were supported with sVAD. Table 1 documents demographic and outcome data for all 36 patients, as well as these same data stratified by ventricular status.

Table 1.

Demographic and Outcome Data for All 36 Patients Weighing Less than 5 kg at the Time of VAD Insertion, as well as These Same Data Stratified by Ventricular Status.

	All patients	Biventricular circulation	Functionally univentricular circulation
Number of patients	36	13	23
BiVAD	12	12	0
LVAD	1	1	0
sVAD	23	0	23
Stroke on VAD	15	5	10
Bleeding on VAD	9	3	6
Underwent Heart Transplant	26	12	14
Death while on VAD	10	1	9
Death after heart transplant	4	1	3
Death prior to hospital discharge from hospitalization for VAD insertion	11	1	10
Death after hospital discharge from hospitalization for VAD insertion	3	1	2
Alive at time of manuscript submission	22	11	11
Dead at time of manuscript submission	14	2	12

Abbreviations: BiVAD, biventricular assist device; LVAD, left ventricular assist device; sVAD, single ventricle-ventricular assist device; VAD, ventricular assist device. Data related to all 36 patients weighing less than 5 kg at the time of VAD insertion are shown in bold.

For the overall population of 36 patients, 72.2% (n = 26) underwent heart transplantation (1 of whom required subsequent BiVAD support 615 days after initial transplantation, followed by a second cardiac transplant 13 days later [as discussed in detail in the Materials and Methods section of this paper]) and 27.8% (n = 10) died on VAD. Duration of VAD support [days]: mean ± SD = 119 ± 81.0, median = 109, range = 4-305. Cumulative days on VAD in 36 patients was 4296 days (11.76 years). Figure 1 documents longitudinal Kaplan-Meier survival after VAD insertion with 95% confidence intervals (CIs) for all 36 patients with a one-year survival estimate after VAD insertion of 62.7% (95% CI = 48.5%-81.2%) and a five-year survival estimate after VAD insertion of 58.5% (95% CI = 43.8%-78.3%).

Thirteen patients with biventricular circulation were supported (age [days]: mean ± SD = 71.8 ± 48.8, median = 67, range = 17-212; weight [kg]: mean ± SD = 4.1 ± 0.67, median = 4.1, range = 3.1-4.9), including 12 BiVAD and 1 LVAD only. Of 13 biventricular patients, 92.3% (n = 12) underwent heart transplantation, and 7.7% (n = 1) died on VAD. In 13 biventricular patients, duration of VAD support was [days]: mean ± SD = 96.4 ± 73.2, median = 63, range = 9-234. Cumulative days on VAD in 13 biventricular patients separated from VAD was 1253 days (3.43 years).

Twenty-three patients with functionally univentricular circulation were supported with sVAD (age [days]: mean ± SD = 46.9 ± 51.8, median = 25, range = 4-215; weight [kg]: mean ± SD = 3.5 ± 0.63, median = 3.4, range = 2.4-4.9). Of 23 univentricular patients, 60.9% (n = 14) underwent transplantation, and 39.1% (n = 9) died on VAD. Duration of VAD support was [days]: mean ± SD = 132 ± 83.8, median = 134, range = 4-305. Cumulative days on VAD in 23 univentricular patients separated from VAD was 3043 days (8.33 years).

Figure 2 documents longitudinal Kaplan-Meier survival after VAD insertion with 95% CIs for all 36 patients, stratified by ventricular status (log-rank P = .02). One-year survival after VAD insertion was 84.6% (95% CI = 67.1%-99.9%) in biventricular patients and 49.7% (95% CI = 32.3%-76.4%) in univentricular patients, P = .018. Three-year survival after VAD insertion was 84.6% (95% CI = 67.1%-99.9%) in biventricular patients and 41.4% (95% CI = 23.6%-72.5%) in univentricular patients, P = .005.

Stroke occurred while on VAD support in 15/36 patients. Of 5/13 biventricular patients who had a stroke while on VAD: all five underwent subsequent cardiac transplantation. Of 10/23 univentricular patients who had a stroke while on VAD: six underwent subsequent cardiac transplantation, and four died on VAD.

Bleeding complications while on VAD occurred in 9/36 patients. Of 3/13 biventricular patients who had bleeding complications while on VAD: two underwent subsequent cardiac transplantation, and one died while on VAD. Of 6/23 univentricular patients who had bleeding complications while on VAD: one underwent subsequent cardiac transplantation, and five died on VAD.

Discussion

In our single-institutional analysis of 36 neonates and infants <5 kg supported with pulsatile VAD, overall longitudinal Kaplan-Meier estimates for survival after VAD insertion were 62.7% (95% CI = 48.5%-81.2%) at one year and 58.5% (95% CI = 43.8%-78.3%) at five years. One-year survival after VAD insertion was 84.6% (95% CI = 67.1%-99.9%) in biventricular patients and 49.7% (95% CI = 32.3%-76.4%) in univentricular patients, P = .018. Three-year survival after VAD insertion was 84.6% (95% CI = 67.1%-99.9%) in biventricular patients and 41.4% (95% CI = 23.6%-72.5%) in univentricular patients, P = .005.

Clearly, pulsatile VAD facilitates bridge to transplantation in neonates and infants <5 kg; however, survival after VAD insertion is less in patients with functionally univentricular circulation than in patients with biventricular circulation. Nevertheless, our analysis demonstrates that high-risk patients <5 kg with functionally univentricular hearts who are suboptimal candidates for conventional palliation or who have failed conventional palliation can be successfully stabilized with pulsatile VAD insertion while awaiting transplantation. These patients may be extubated, enterally nourished, and optimized for transplantation while on VAD. In our analysis, univentricular patients supported with VAD have an average duration of VAD support that is 36 days longer than that of biventricular patients, a finding likely related to their smaller size, younger age, and longer period of time waiting for a suitable donor heart.

In children, and especially in neonates and infants with biventricular hearts, our institutional preference is to use BiVAD rather than LVAD, especially if any evidence of biventricular dysfunction exists. Because of the challenges associated with predicting the development of right ventricular failure in patients supported with LVAD,¹⁴ as well as our low rate of complications with BiVAD combined with the length of time that we often need to wait for a suitable donor heart, our institutional preference is for BiVAD, especially in smaller children, unless right ventricular function is clearly normal.

In patients with functionally univentricular hearts, we prefer pulsatile VAD rather than continuous-flow VAD^7–13 because we believe that:

Pulsatile VAD is more physiologic,

The management of patients on pulsatile VAD is more intuitive to the healthcare team,

Pulsatile VAD is associated with decreased risk of pulmonary overcirculation, and

Pulsatile VAD is associated with improved renal function.

Not enough donor hearts exist to offer transplantation to all patients with functionally univentricular circulation. However, it is reasonable to offer transplantation to patients at high risk for conventional staged palliation, as well as to those who have failed staged palliation. Unfortunately, because of the shortage of donor organs, time on the waiting list for a heart can be long, leading to increasing concern about the potential for waitlist mortality. Because of these potentially long waiting times, it is also reasonable to stabilize these high-risk patients with functionally univentricular hearts with VAD while awaiting transplantation.^7–13 This approach facilitates early extubation and optimization for transplantation while on VAD in this high-risk population.^7–13

In very high-risk patients with functionally univentricular circulation, primary transplantation can be considered rather than surgical palliation^7–13 because rescue transplantation after failed surgical palliation is associated with worse outcomes.^15–20 Survival after transplantation for HLHS or HLHS-related malformations is better with primary transplantation in comparison to transplantation after previous cardiac surgery.^16–20 As published in an analysis of the Congenital Heart Surgeons’ Society Database, “Notwithstanding the limited availability of neonatal and infant donor hearts, primary transplantation may be considered for those neonates with risk factors predictive of exceptionally poor survival after surgical palliation.”¹⁶

Survival of patients weighing <5 kg with functionally univentricular physiology supported with VAD is novel.^1–6 In 2008, Pearce and colleagues reported successful cardiac transplantation after Berlin Heart insertion and bridging in a functionally univentricular 15-month-old.¹ In 2014, a retrospective review of the EXCOR Investigational Device Exemption study database reported that only 26 of 281 patients supported with a VAD had univentricular physiology, including 15 with HLHS. Eight of nine patients supported with VAD after neonatal palliation died, all within 17 days of implantation.² Also in 2014, Conway and colleagues reported an analysis of all children weighing <10 kg who were enrolled in the sponsor's U.S. regulatory database and supported with the Berlin Heart EXCOR Pediatric VAD as a bridge to transplant.³ Only 27.3% (9 of 33) of children weighing <5 kg experienced a successful outcome, while 71.9% of patients weighing between 5 and 10 kg achieved a successful outcome (P < .001). In 2019, Adachi and colleagues reported their single-center experience with centrifugal-flow VAD support in children: 40 implantations in 39 patients (28 with cardiomyopathy, 11 with congenital heart disease, including only 3 with univentricular physiology).⁴ A 2021 publication from Puri and Adachi documented that, “The outcomes of Stage I and Stage II SV-CHD [single ventricle-congenital heart disease] patients on VAD support from the Pedimacs database are poor, with less than 50% survival on VAD by the 3-month mark in both.”⁵

The major challenge of prolonged VAD support in neonates and infants is the prevention of thromboembolic complications and stroke. In our series of patients reported in this manuscript, out of 15 patients who had strokes, four died while supported with VAD, while out of nine patients who had bleeding, six died while supported with VAD. Clearly, further research is needed to prevent both bleeding and stroke while on VAD. Our program is considering augmentation of our current protocol of anticoagulation while on VAD, including the possible addition of clopidogrel after 120 days of VAD support. Additional studies are needed to develop even safer strategies for anticoagulation and to develop VADs for neonates, infants, and children that have enhanced biocompatibility, allowing either a decreased need for anticoagulation or possibly no need for anticoagulation. Thrombotic and bleeding complications are major causes of morbidity and mortality in pediatric VAD support.²¹ Standard anticoagulation with unfractionated heparin is challenging secondary to the heterogeneous biochemical composition and unpredictable pharmacokinetics of heparin.²¹ Direct thrombin inhibitors (DTIs) (eg, bivalirudin [Angiomax], argatroban, and hirudin [lepirudin]) are an alternative to heparin. Many centers, including ours, now use bivalirudin as their anticoagulant of choice for patients supported with extracorporeal membrane oxygenation and for patients supported with VAD. In 2020, VanderPluym and colleagues published an analysis designed “to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with DTIs antithrombosis therapy.”²¹ This retrospective multicenter review is “the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support.”²¹ The authors conclude that “Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in the literature using other anticoagulation agents in pediatric VAD support.”²¹ Meanwhile, most adults supported with intracorporeal VAD are maintained on a vitamin K antagonist (VKA) such as warfarin, with goal international normalized ratio (INR) that varies mostly between 2 and 3.²² However, direct oral anticoagulants (DOACs) are increasingly used in place of VKAs.²² DOACs include factor Xa inhibitors (apixaban and rivaroxaban) and DTIs (dabigatran). Potential advantages of DOACs include (1) ease of administration with oral formulations, (2) lack of dependency on antithrombin, (3) lack of dietary interaction, and (4) the requirement of less monitoring.²²

The Value of This Analysis

Our study adds to the body of knowledge and the literature because the utilization of VAD support for bridge to transplantation in neonates and infants with failing univentricular circulation is novel, as evidenced by the paucity of published literature on this topic.^1–6 This current manuscript provides an analysis of all 36 patients <5 kg who were supported with the Berlin Heart pulsatile VAD at the University of Florida; the overall detailed outcomes of this entire cohort have not been published until this current manuscript. Our rationale for this approach is that this manuscript allows for a complete assessment and analysis of our comprehensive approach to the management of these challenging patients <5 kg, as well as a comparison of the characteristics and outcomes of those patients <5 kg with functionally univentricular circulation to the characteristics and outcomes of those patients <5 kg with biventricular circulation.

Limitations

This analysis is based on our single-institutional experience and the available data in our database. Potential limitations include patient selection bias, institutional bias, confounding bias, and potentially under-powering of the analysis due to the small sample size. Additional follow-up is required on all surviving patients. Further patient accrual will enhance the continued analysis of outcomes. We plan to continue gathering data to provide additional insight as to guideposts for patient selection and predictors of outcomes. It is our hope that by sharing our experience, other hospitals and patients may benefit.

Conclusions

Pulsatile VAD facilitates bridge to transplantation in neonates and infants weighing <5 kg; however, survival after VAD insertion in these small patients is less in those with univentricular circulation compared to those with biventricular circulation. One-year survival after VAD insertion was 84.6% (95% CI = 67.1%-99.9%) in biventricular patients and 49.7% (95% CI = 32.3%-76.4%) in univentricular patients, P = .018. Three-year survival after VAD insertion was 84.6% (95% CI = 67.1%-99.9%) in biventricular patients and 41.4% (95% CI = 23.6%-72.5%) in univentricular patients, P = .005. Nevertheless, high-risk patients with functionally univentricular hearts who are suboptimal candidates for conventional palliation or who have failed conventional palliation can be successfully stabilized with pulsatile VAD insertion while awaiting transplantation; these patients may be extubated, enterally nourished, and optimized for transplantation while on VAD.

Footnotes

Abbreviations

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Yuriy Stukov

Jeffrey P. Jacobs

References

Pearce

Kirklin

Holman

Barrett

Romp

Lau

. Successful cardiac transplant after Berlin Heart bridge in a single ventricle heart: Use of aortopulmonary shunt as a supplementary source of pulmonary blood flow. J Thorac Cardiovasc Surg. 2009;137(1):e40-e42. doi:10.1016/j.jtcvs.2008.02.044. Epub 2008 Jun 2.

Weinstein

Bello

Pizarro

, et al. The use of the Berlin Heart EXCOR in patients with functional single ventricle. J Thorac Cardiovasc Surg. 2014;147(2):697-704.

Conway

St Louis

Morales

DLS

Law

Tjossem

Humpl

. Delineating survival outcomes in children <10 kg bridged to transplant or recovery with the Berlin Heart EXCOR ventricular assist device. JACC Heart Fail. 2015;3(1):70-77. doi:10.1016/j.jchf.2014.07.011. Epub 2014 Nov 11.

Adachi

Zea-Vera

Tunuguntla

, et al. Centrifugal-flow ventricular assist device support in children: a single-center experience. J Thorac Cardiovasc Surg. 2019;157(4):1609-1617. e2. doi:10.1016/j.jtcvs.2018.12.045. Epub 2018 Dec 27.

Puri

Adachi

. Mechanical support for the failing single ventricle at pre-Fontan stage: current state of the field and future directions. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2021;24:10-18. doi:10.1053/j.pcsu.2021.04.004.

Lorts

Conway

Schweiger

, et al. ISHLT consensus statement for the selection and management of pediatric and congenital heart disease patients on ventricular assist devices endorsed by the American Heart Association. J Heart Lung Transplant. 2021;40(8):709-732. doi:10.1016/j.healun.2021.04.015. Epub 2021 May 20.

Philip

Reyes

Ebraheem

Gupta

Fudge

Bleiweis

. Hybrid procedure with pulsatile ventricular assist device for hypoplastic left heart syndrome awaiting transplantation. J Thorac Cardiovasc Surg. 2019;158(2):e59-e61. doi:10.1016/j.jtcvs.2018.12.025. Epub 2018 Dec 21.

Philip

Powers

Machado

, et al. Pulsatile ventricular assist device as a bridge to transplant for the early high-risk single-ventricle physiology. J Thorac Cardiovasc Surg. 2021;162(2):405-413. e4. doi:10.1016/j.jtcvs.2020.09.071. Epub 2020 Oct 6.

Bleiweis

Philip

Peek

, et al. Combined hybrid procedure and VAD insertion in 9 high-risk neonates and infants with HLHS. Ann Thorac Surg. 2022;114(3):809-816. doi:10.1016/j.athoracsur.2021.05.073. Epub 2021 Jun 27.

10.

Bleiweis

Fudge

Peek

, et al. Ventricular assist device support in neonates and infants with a failing functionally univentricular circulation. JTCVS Tech. 2021;13:194-204. doi:10.1016/j.xjtc.2021.09.056.

11.

Bleiweis

Philip

Peek

, et al. Palliation plus ventricular assist device insertion in 15 neonates and infants with functionally univentricular circulation. Ann Thorac Surg. 2022:S0003–4975(22)00336–8. doi:10.1016/j.athoracsur.2022.02.051. Epub ahead of print.

12.

Bleiweis

Peek

Philip

, et al. A comprehensive approach to the management of patients with HLHS and related malformations: An analysis of 83 patients (2015–2021). World J Pediatr Congenit Heart Surg. 2022;13(5):664-675. doi:10.1177/21501351221088030. Epub 2022 May 5.

13.

Bleiweis

Stukov

Philip

, et al. Analysis of 82 children supported with pulsatile paracorporeal ventricular assist device: Comparison of patients with biventricular versus univentricular circulation. Semin Thorac Cardiovasc Surg. 2022:S1043–0679(22)00120–4. doi:10.1053/j.semtcvs.2022.05.002. Epub ahead of print.

14.

Frankfurter

Molinero

Vishram-Nielsen

JKK

, et al. Predicting the risk of right ventricular failure in patients undergoing left ventricular assist device implantation: a systematic review. Circ Heart Fail. 2020;13(10):e006994. doi:10.1161/CIRCHEARTFAILURE.120.006994. Epub 2020 Sep 28.

15.

Michielon

Carotti

Pongiglione

Cogo

Parisi

. Orthotopic heart transplantation in patients with univentricular physiology. Curr Cardiol Rev. 2011;7(2):85-91.

16.

Stackhouse

McCrindle

Blackstone

, et al. Surgical palliation or primary transplantation for aortic valve atresia. J Thorac Cardiovasc Surg. 2020;159(4):1451-1461.e7.

17.

Quintessenza

Morell

Jacobs

. Achieving a balance in the current approach to the surgical treatment of hypoplastic left heart syndrome. Cardiol Young. 2004;14(suppl 1):127-130.

18.

Jacobs

O’Brien

Chai

Morell

Lindberg

Quintessenza

. Management of 239 patients with hypoplastic left heart syndrome and related malformations from 1993 to 2007. Ann Thorac Surg. 2008;85(5):1691-1696.

19.

Jacobs

Quintessenza

Chai

, et al. Rescue cardiac transplantation for failing staged palliation in patients with hypoplastic left heart syndrome. Cardiol Young. 2006;16(6):556-562.

20.

Shah

Asante-Korang

Ghazarian

, et al. Risk factors for survival after heart transplantation in children and young adults: a 22-year study of 179 transplants. World J Pediatr Congenit Heart Surg. 2018;9(5):557-564.

21.

VanderPluym

Cantor

Machado

, et al. Utilization and outcomes of children treated with direct thrombin inhibitors on paracorporeal ventricular assist device support. ASAIO J. 2020;66(8):939-945. doi:10.1097/MAT.0000000000001093.

22.

Ghbeis

Vander Pluym

Thiagarajan

. Hemostatic challenges in pediatric critical care medicine-hemostatic balance in VAD. Front Pediatr. 2021;9:625632. doi:10.3389/fped.2021.625632.