Modifiable Risk Factor Reduction on Pediatric Ventricular Assist Device and the Impact of Persistent Modifiable Risk Factors at Transplant

Abstract

Objectives:

Ventricular assist devices-(VADs) are associated with a mortality benefit in children. Database-driven analyses have associated VADs with reduction of modifiable risk factors-(MRFs), but validation with institutional data is required. The authors studied MRF reduction on VAD and the impact of persistent MRFs on post-heart transplant survival.

Methods:

All patients at the authors’ institution on VAD at transplant (2011–2022) were retrospectively identified. MRFs included renal dysfunction-(eGFR<60mL/min/1.73 m²), hepatic dysfunction-(total bilirubin ≥1.2mg/dL), TPN-dependence, sedatives, paralytics, inotropes, mechanical ventilation.

Results:

Thirty-nine patients were identified. At time of VAD implantation, 18 patients had ≥3 MRFs, 21 had 1–2 MRFs, and 0 had zero MRFs. At time of transplant, 6 patients had ≥3 MRFs, 17 had 1–2 MRFs, and 16 had zero MRFs. Hospital mortality occurred in 50%-(3/6) patients with ≥3 MRFs at transplant vs. 0% of patients with 1–2 & zero MRFs (p=0.01 for ≥3 vs. 1–2 & zero MRFs). MRFs independently associated with hospital mortality included: paralytics-(1.76 [1.32–2.30]), ventilator-(1.59 [1.28–1.97], TPN-dependence-(1.49 [1.07–2.07]), and renal dysfunction-(1.31 [1.02–1.67]). Two late mortalities occurred (3.6 & 5.7yr), both in patients with 1–2 MRFs at transplant. Overall post-transplant survival was significantly worse for ≥3 vs. zero MRFs (p-0.006) but comparable between other cohorts (p>0.1).

Conclusions:

VADs are associated with MRF reduction in children, yet those with persistent MRFs at transplant experience a high burden of mortality. Transplanting VAD patients with ≥3 MRFs may not be prudent. Time should be given on VAD support to achieve aggressive pre-transplant optimization of MRFs.

Introduction

According to the most recent Organ Procurement and Transplant Network report (published in March 2022), the rate of pediatric heart transplantation is currently at the lowest point in more than 10 years, underscoring the need for durable and effective modalities to support children with heart failure until a suitable donor organ becomes available.¹ At present, one-third of all children are bridged to heart transplant on a ventricular assist device (VAD).^1,2 In children, as in adults, VADs carry both pre- and post-transplant mortality benefits, having been shown to improve waitlist survival by up to 50% and to yield post-transplant survival similar to that of lower-acuity (non-VAD) patients.^3–6 In addition to improved survival, database-driven analyses have associated VADs with improvement of renal and hepatic dysfunction, weaning from inotropic agents, and liberation from mechanical ventilation – all well-established modifiable risk factors (MRFs) for post-heart transplant mortality.^5,7–10 Analyses of the United Network for Organ Sharing (UNOS) and Pediatric Heart Transplant Society (PHTS) databases have also associated longer durations of VAD therapy (>1–2 months) with improvements in MRFs and superior post-transplant survival. However, modifiable risk factor reduction while on VAD is understudied in the single-institutional setting (which allows for greater clinical granularity and accuracy than administrative datasets). Additionally, the impact of persistent MRFs at the time of transplant in VAD patients is unknown.

Methods

Study approval was obtained from the Cincinnati Children’s Hospital Institutional Review Board (protocol #2022–0719, approved 10/13/2022) via waiver of informed consent for non-human subject research.

Patients and Methods

Data were compiled from the Cincinnati Children’s institutional Society for Thoracic Surgeon’s (STS) database, Advanced Cardiac Therapies Improving Outcomes Network (ACTION) database, and electronic medical record system. All first-time heart transplant recipients who were on VAD (including single-ventricle assist device [SVAD]) at time of transplant were identified. Study data were available from January 2011 through May 2022, and follow-up (performed via chart review) was complete through March 2023. Patients on total artificial heart or right ventricular assist device (RVAD) at time of transplant, those receiving retransplants, and those whose VADs were discontinued prior to transplantation were excluded from analysis.

Study cohorts were defined according to the number of MRFs present at the time of transplant, grouped by quartile: zero MRFs (1^st quartile), 1–2 MRFs (interquartile range [IQR]), and ≥3 MRFs (4^th quartile). Seven individual MRFs were studied, based upon those identified by previous reports as risk factors for post-transplant mortality:^7–9,11,12

• Renal dysfunction (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m², measured within 48 hours of transplant, or renal replacement therapy within 48 hours of transplant),

• Hepatic dysfunction (defined as total serum bilirubin ≥1.2 mg/dL within 48 hours of transplant),¹³

• Total parental nutrition (TPN)-dependence (defined as parenteral nutrition administration without enteral nutrition for >48 hours pre-transplant),

• Sedative agents (defined as administration of a sedative agent [e.g., benzodiazepine] within 24 hr of transplant)

• Paralytic agents (defined as administration of a paralytic agent within 24 hours of transplant],

• Inotrope-dependence (defined as administration of a continuous inotropic medication within 24 hours of transplant), and

• Mechanical ventilatory dependence (defined as ventilation for >24 hours pre-transplant).

In addition to MRFs, patient demographics and characteristics (i.e., non-modifiable risk factors) were studied. Non-modifiable risk factors of interest were those associated by previous studies with greater hazards of post-transplant mortality in children, including infant (<365 days) age at transplant, non-white race/ethnicity, female sex, a diagnosis of congenital heart disease (CHD), prior cardiac surgery (excluding VAD exchange, wound debridement, chest washout, or delayed sternal closure; Table S1), and non-cardiac comorbidities (Table S2).^1,11,14,15

Statistical Analyses

Statistical analyses were performed using R (R Foundation for Statistical Computing, Vienna, Austria, https://www.R-project.org/). Comparative analyses between cohorts utilized Mood’s median test for continuous variables and Fisher’s exact test for categorical variables. Post-hoc, pairwise analyses were performed when significant (p<0.05) differences existed upon group analysis, with the Benjamini and Hochberg correction for multiple comparisons employed for Mood’s median test and Fisher’s exact test. Post-transplant hospital mortality was studied as a binary variable (using Fisher’s exact test), and long-term survival was studied as a continuous variable using Kaplan-Meier with log-rank test (using the Benjamini and Hochberg adjustment method for multiple comparisons).

The independent association of each individual MRF at time of transplant on hospital mortality was assessed using multivariable binary logistic regression analyses. Potential covariates were selected on an a priori basis using previously established non-modifiable risk factors (as above) and included: age <1 year at transplant, sex, non-white race/ethnicity, diagnosis of CHD, presence of a non-cardiac comorbidity, year of transplantation, and number of days on VAD. Akaike information criterion (AIC) was used to select the most ideal covariates for the final model: CHD, age <1 year at transplant, and year of transplantation. Model diagnostics included goodness-of-fit (model chi-squared p-value >0.999) and variance inflation factor (VIF; all covariates with value <5) analyses.

Results

Baseline characteristics

A total of 39 patients received heart transplants while on VAD at the authors’ institution during the study period.

At time of VAD implantation, 18 patients (46% of cohort) had ≥3 MRFs, 21 (54%) had 1–2 MRFs, and none (0% of cohort) had zero MRFs. Patients with ≥3 MRFs at VAD implantation had greater proportions of infant age (61 vs. 15%, p=0.003), paracorporeal VAD placement (89 vs. 29%, p<0.001), and CHD (67 vs. 19%, p=0.003) than those with 1–2 MRFs, while the proportions of the other non-modifiable risk factors of female sex, non-white race/ethnicity, non-cardiac comorbidity, and prior cardiac surgery were similar (p>0.2 for all) (Table S3). Among patients with ≥3 MRFs at time of VAD implantation, 18/18 (100%) were inotrope-dependent, 16/18 (89%) were TPN-dependent, 16/18 (89%) were receiving sedative agents, 14/18 (78%) were on ventilator, 10/18 (56%) were receiving paralytic agents, 5/18 (28%) had hepatic dysfunction, and 2/18 (11%) had renal dysfunction. Among patients with 1–2 MRFs at time of VAD implantation, 19/21 (90%) were inotrope-dependent, 7/21 (35%) had renal dysfunction, and one (5%) was TPN-dependent, with a 0% prevalence of all other MRFs (Table S3).

Modifiable risk factor reduction while on VAD

Figure 1 illustrates the reduction in the number of MRFs between VAD implantation and heart transplant, and the duration of VAD therapy for each sub-group. Of the 18 patients with ≥3 MRFs at time of VAD implantation, six (33%) also had ≥3 MRFs at time of transplant (median duration of VAD therapy: 33 [IQR 24–53] days), nine (50%) had 1–2 MRFs at transplant (71 [IQR 61–137] days), and three (17%) had zero MRFs at transplant (43 [38–74] days) (p=0.065 for duration of VAD support). Of the 21 patients with 1–2 MRFs at time of VAD implantation, zero (0%) had ≥3 MRFs at time of transplant, 8 (38%) had 1–2 MRFs at transplant (56 [IQR 37–199] days), and 13 (62%) had zero MRFs at transplant (44 [IQR 38–79] days) (p=0.867 for duration of VAD support).

Figure 1.

Reduction in the number of modifiable risk factors (MRFs) between ventricular assist device (VAD) implantation and heart transplant, and post-transplant mortality.

In total, at time of transplant, six (15%) patients had ≥3 MRFs, 17 (44%) had 1–2 MRFs, and 16 (41%) had zero MRFs. The demographics and non-modifiable risk factors of each MRF-at-transplant cohort are shown in Table 1 and the type(s) of VAD implanted and at time of transplant are shown in Table S4. The proportions of the non-modifiable risk factors of infant age, female sex, non-white race/ethnicity, CHD, prior cardiac surgery, and non-cardiac comorbidities were statistically similar across all MRF-at-transplant cohorts (p>0.05 for all). The prevalence of MRF types varied between cohorts (Table 2). Among patients with ≥3 MRFs at time of transplant, all (6/6;100%) were inotrope-dependent, on ventilator, and receiving sedative agents; 3/6 (50%) were on paralytics; 3/6 (50%) had renal dysfunction; 2/6 (33%) were TPN-dependent; and 1/6 (17%) had hepatic dysfunction. Among patients with 1–2 MRFs at time of transplant, 13/17 (76%) were inotrope-dependent, 10/17 (59%) were receiving sedative agents, 4/17 (24%) had hepatic dysfunction, and 2/17 (12%) had renal dysfunction, with zero patients receiving paralytic agents, TPN-dependent, or on ventilator.

Table 1.

Demographics and characteristics of patients by modifiable risk factor (MRFs)-at- transplant cohort.

	Modifiable Risk Factors at Transplant			p-value
	(a) 0 (n = 16)	(b) 1–2 (n = 17)	(c) ≥3 (n = 6)
Age <1 year at transplant	5 (31%)	4 (24%)	5 (83%)	a-b	0.708
				a-c	0.084
				b-c	0.055
Female sex	4 (25%)	7 (41%)	2 (33%)	0.669
Non-white race/ethnicity	3 (19%)	6 (35%)	0 (0%)	0.492
Congenital heart disease	3 (19%)	9 (53%)	4 (67%)	a-b	0.106
				a-c	0.106
				b-c	0.660
Non-cardiac comorbidity	6 (38%)	9 (53%)	2 (33%)	0.619
Prior cardiac surgery*	5 (31%)	8 (47%)	4 (67%)	0.321
VAD type implanted
Intracorporeal continuous	9 (56%)	7 (41%)	0 (0%)	0.169
Paracorporeal continuous	2 (12%)	3 (18%)	2 (33%)
Paracorporeal pulsatile	5 (31%)	7 (41%)	4 (67%)

Values expressed as median (IQR) or n (%) as appropriate.

^*Excluding ventricular assist device (VAD) implantation or pump exchange.

Table 2.

Individual modifiable risk factors (MRFs) at time of ventricular assist device (VAD) implantation and transplant, by MRF-at-transplant cohort.

	Modifiable Risk Factors at Transplant
	(a) 0 (n = 16)	(b) 1–2 (n = 17)	(c) ≥3 (n = 6)
MRFs present at VAD implantation
Renal dysfunction	0 (0%)	1 (6%)	1 (17%)
Hepatic dysfunction	4 (27%)	7 (41%)	1 (17%)
TPN-dependence	3 (19%)	9 (53%)	5 (83%)
Sedatives	2 (12%)	8 (47%)	6 (100%)
Paralytics	1 (6%)	4 (24%)	5 (83%)
Inotropes	16 (100%)	15 (88%)	6 (100%)
Mechanical ventilation	2 (12%)	6 (35%)	6 (100%)
MRFs present at time of transplant
Renal dysfunction	0 (0%)	2 (12%)	3 (50%)
Hepatic dysfunction	0 (0%)	4 (25%)	1 (17%)
TPN-dependence	0 (0%)	0 (0%)	2 (33%)
Sedatives	0 (0%)	10 (59%)	6 (100%)
Paralytics	0 (0%)	0 (0%)	3 (50%)
Inotropes	0 (0%)	13 (76%)	6 (100%)
Mechanical ventilation	0 (0%)	0 (0%)	6 (100%)

Values expressed as median (IQR) or n (%) as appropriate.

^*Excluding VAD implantation or pump exchange. Renal dysfunction defined as eGFR <60 mL/min/1.73 m²; hepatic dysfunction defined as total serum bilirubin ≥1.2 mg/dL. TPN, total parenteral nutrition; VAD, ventricular assist device.

Post-transplant outcomes

Hospital mortality occurred in 50% (3/6) of patients with ≥3 MRFs at time of transplant, compared to 0% of patients with 1–2 MRFs (0/17) and zero MRFs (0/16) at time of transplant (≥3 vs. 1–2 MRFs, p=0.013; ≥3 vs. zero MRFs, p=0.011; 1–2 vs. 0 MRFs, p=0.999) (Figure 1). The characteristics of and specific MRFs present in the patients who experienced hospital mortality compared to those who survived to discharge are shown in Table 3. All three patients with hospital mortality had ≥3 MRFs both at time of VAD placement (4, 6, 6 MRFs, respectively) and at time of transplant (5, 6, 4 MRFs, respectively) and all were inotrope-dependent, on ventilator, and receiving sedative agents at both timepoints. All hospital mortality patients also had the non-modifiable risk factors of age <1 year at transplant, CHD (hypoplastic left heart syndrome in 1/3), and prior cardiac surgery. The duration of VAD therapy among the hospital non-survivors was 57-, 25-, and 144-days, respectively. Mortality occurred at 30-, 38-, and 106-days post-transplant, respectively, and all died from multisystem organ failure and were never extubated. Among patients with ≥3 MRFs at transplant, no significant differences existed between hospital survivors or mortalities in non-modifiable risk factors (infant age, female sex, non-white race/ethnicity, CHD, prior cardiac surgery, non-cardiac comorbidities), VAD type at implantation or transplant, nor the MRFs present at time of VAD implantation (p>0.4 for all) (Table S5).

Table 3.

Demographics and clinical characteristics of hospital survivors versus mortalities.

	Hospital Mortality		p-value
	No (n=36)	Yes (n=3)
Age <1 year at transplant	11 (31%)	3 (100%)	0.040
Female sex	12 (33%)	1 (33%)	0.999
Non-white race/ethnicity	9 (25%)	0 (0%)	0.999
Congenital heart disease	13 (36%)	3 (100%)	0.061
Non-cardiac comorbidity	16 (44%)	0 (0%)	0.255
Prior cardiac surgery*	14 (39%)	3 (100%)	0.074
VAD type (implanted)
Intracorporeal continuous	16 (44%)	0 (0%)	0.077
Paracorporeal continuous	5 (14%)	2 (67%)
Paracorporeal pulsatile	15 (42%)	1 (33%)
MRFs present at VAD implantation
Renal dysfunction	2 (6%)	0 (0%)	0.999
Hepatic dysfunction	12 (34%)	0 (0%)	0.538
TPN-dependence	15 (42%)	2 (67%)	0.570
Sedatives	13 (36%)	3 (100%)	0.061
Paralytics	7 (19%)	3 (100%)	0.013
Inotropes	34 (94%)	3 (100%)	0.999
Mechanical ventilation	11 (31%)	3 (100%)	0.040
VAD type (at transplant)
Intracorporeal continuous	17 (47%)	0 (0%)	0.038
Paracorporeal continuous	3 (8%)	2 (67%)
Paracorporeal pulsatile	16 (44%)	1 (33%)
MRFs present at time of transplant
Renal dysfunction	3 (8%)	2 (67%)	0.038
Hepatic dysfunction	5 (15%)	0 (0%)	0.999
TPN-dependence	1 (3%)	1 (33%)	0.150
Sedatives	13 (36%)	3 (100%)	0.061
Paralytics	1 (2%)	2 (67%)	0.012
Inotropes	16 (44%)	3 (100%)	0.106
Mechanical ventilation	3 (8%)	3 (100%)	0.002

Values expressed as median (IQR) or n (%) as appropriate.

^*Excluding VAD implantation or pump exchange. Renal dysfunction defined as eGFR <60 mL/min/1.73 m²; hepatic dysfunction defined as total serum bilirubin ≥1.2 mg/dL. TPN, total parenteral nutrition; VAD, ventricular assist device.

Upon multivariable binary logistic regression, the following MRFs at time of transplant were independently associated with hospital mortality:

• Paralytic agents: OR 1.74 (95% CI 1.32–2.30)

• Mechanical ventilation: OR 1.59 (95% CI 1.28–1.97)

• TPN-dependence: OR 1.49 (95% CI 1.07–2.07)

• Renal dysfunction: OR 1.31 (95% CI 1.02–1.67)

Hepatic dysfunction (OR 9.02 [95% CI 0.70–1.15]), sedative agents (OR 1.09 [95% CI 0.91–1.30]), and inotrope-dependence (OR 1.07 [95% CI 0.90–1.27]) were not independently associated with post-transplant hospital mortality.

Two late mortalities occurred, both in patients with 1–2 MRFs at transplant (Figure 1). The late mortalities occurred at 3.6- and 5.7-years post-transplant, and both occurred due to complications from acute rejection. The patient who expired at 3.6 years had one MRF at VAD implantation (hepatic dysfunction) and two MRFs at transplant (inotrope-dependence and sedatives). The patient who expired at 5.7 years had six MRFs at VAD implantation (all but renal dysfunction) and two MRFs at transplant (inotrope-dependence and renal dysfunction). Overall post-transplant mortality was significantly worse among patients with ≥3 MRFs at transplant compared to zero MRFs at transplant (p=0.006), with comparable overall survival between the ≥3 and 1–2 MRF-at-transplant cohorts (p=0.097) and the 1–2 versus zero MRF-at-transplant cohorts (p=0.192) (Figure 2). Overall actuarial survival among hospital survivors was 94% (34/36), with a median duration of follow-up of 4.5 (IQR 1.3–8.6) years.

Figure 2.

Long-term post-transplant survival by the number of modifiable risk factors (MRFs) present at time of transplant in ventricular assist device (VAD) patients. Survival was analyzed using Kaplan-Meier with log-rank test. Ninety-five percent confidence intervals shown. (CI 95%)

Discussion

Children on VAD, like those not on VAD, experience significantly worse post-heart transplant survival when modifiable risk factors are present. The present single-institutional analysis of nearly 40 patients bridged to transplant on VAD at a single institution confirms the findings of previous database-driven analyses showing an association between VAD and MRF reduction in children and adds to the literature by confirming what many clinicians previously believed: VAD patients with multiple persistent MRFs experience a high burden of early post-transplant mortality (Figure 3). The study findings and identification of specific MRFs that are independently associated with early mortality can assist with clinical decision-making and risk stratification when planning heart transplants for VAD patients.

Figure 3 (Graphical Abstract).

Pictorial illustration of primary study findings.

The authors, among others, have previously described the perils of “limping to heart transplantation” – that is, transplanting children with persistent modifiable risk factors.^8–11 Modifiable risk factors consistently associated with inferior post-transplant outcomes (in VAD and non-VAD children alike) include end-organ (renal and hepatic) dysfunction, requirement for mechanical ventilation, inotropes, sedatives, paralytics, and TPN. Ventricular assist devices have been shown by several studies to reduce MRFs. Using the UNOS database, Riggs et al. found that children with >2 months of VAD support prior to transplant had significantly greater functional status and less renal dysfunction, inotropes, and mechanical ventilation than those with lesser durations of VAD.⁷ Butto and colleagues in their 2021 analysis of the PHTS similarly reported lower rates of mechanical ventilation and inotrope utilization and lower serum bilirubin among patients who remained on VAD for ≥30 days than those who were on VAD for <30 days prior to transplant.¹⁶ While providing invaluable sources of information, such database-driven analyses lack the granularity afforded by institutional data: data integrity is reliant mostly upon administrative (rather than clinician-based) entry, timepoints are binary, and (for UNOS in particular) VAD duration can only be estimated by identifying patients on VAD both at time of listing and transplant and calculating the number of days between. On the other hand, single-institutional data – while plagued by smaller sample sizes – has the important benefit of chart review and access to comprehensive and accurate clinical records.

In the current analysis, VADs were clearly associated with a reduction in the number of MRFs from the time of implantation to heart transplant, confirming the associations identified previously. In the study, 66% of patients with ≥3 MRFs at time of VAD implantation had two or fewer MRFs at transplant, and 62% of patients with 1–2 MRFs at VAD implantation had no MRFs at transplant. It was interesting to note, though, that no significant differences existed in the duration of VAD therapy between MRF-reduction groups: longer VAD durations were not clearly associated with greater MRF reduction. However, the median duration of VAD therapy was <2 months in all groups (below the “threshold” for improvement in the MRFs of renal dysfunction, ventilation, and inotropes described by Riggs and colleagues using the UNOS database) and the relatively small study sample size (39 patients total) was likely underpowered to show differences in VAD durations between sub-groups.

The presence of persistent MRFs at the time of transplant significantly affected post-transplant survival in VAD patients. In-hospital mortality occurred in three patients – all of whom had more than three MRFs both at the time of VAD implantation and time of transplant. All three were inotrope-dependent, on sedatives, and on mechanical ventilation (with the latter identified as an independent risk factor for hospital mortality) both at VAD implantation and transplant. The durations of VAD therapy in these patients were 25, 57, and 144 days, so it is unclear whether additional time on VAD would have improved outcomes in these patients. Additional study – ideally using pooled multi-institutional data – is warranted to more accurately define the optimal duration of VAD therapy for MRF reduction. Clinical dogma suggests that longer durations of VAD therapy should abate more MRFs and improve functional rehabilitation in a time-dependent function, but this may not be the case. In all patients, the potential benefits of extended VAD therapy must be weighed against the risk of adverse events. Although vastly improved from prior eras, the current generation of VADs are still associated with complications, including stroke in 11% of patients and gastrointestinal bleeding complications in 7%.¹⁷ Such complications can necessitate VAD discontinuation in some cases. The current study of only those patients who successfully underwent transplants on VAD was not equipped to fully explore complication rates and the associated burdens thereof.

In the present analysis, the hazards of mortality were greatest in the early post-transplant period (with 94% of patients who survived to hospital discharge alive at last follow-up [median 4.5 years post-transplant]), but persistent MRFs at transplant also appeared to impact longer-term survival. Two patients experienced late mortality (3.6- and 5.7-years post-transplant), one of whom had six MRFs at time of VAD implantation and both of whom had two MRFs at time of transplant. On the other hand, all 16 patients with zero MRFs at the time of transplant (each of whom had MRFs present at time of VAD implantation) were alive at last follow-up. Although the clinical trends identified herein would benefit from further analyses with larger patient populations, the association with VADs and MRF reduction, as well as the overall impacts of persistent MRFs on post-transplant mortality in VAD patients are nevertheless clear. The goal of the transplant team should be to transplant patients who are fully physiologically optimized (ideally with no MRFs when possible) so that the best possible post-transplant outcome can be achieved.

Limitations and future directions

First, the study design was retrospective, and while the single-institutional nature of study allowed for complete and comprehensive chart review, the authors were reliant upon previously collected clinical data and notes. As above, the study was also likely underpowered in several regards, owing to the relatively small sample size compared to those from national databases. For example, there were no significant differences in the durations of VAD therapy between MRF-reduction sub-groups, and the small number of mortalities in the cohort (while itself a testament to the effectiveness of VAD therapy) precluded more in-depth analyses. Studies with larger sample sizes can also seek to identify a specific “cutoff” number of MRFs with which hospital and long-term mortality are more likely to occur. The current study used quartiles to define MRF cohorts, but larger patient populations could allow for cubic spline analyses. Nevertheless, the present analysis was sufficiently powered to identify specific MRFs independently associated with hospital mortality (mechanical ventilation, paralytic agents, TPN-dependence, and renal dysfunction at time of transplant) – these results can provide important risk-stratification information for clinicians. Finally, although the survival benefits of VAD have been repeatedly shown, future analyses might seek to compare the hazards of mortality associated with persistent MRFs in VAD versus no-VAD patients; such information could help inform VAD utilization and better elucidate which individual MRFs are most amenable to resolution with VAD.

Conclusions

Ventricular assist devices are associated with MRF reduction in children, yet those with persistent MRFs at the time of heart transplantation experience a high burden of mortality. The presence of specific MRFs at the time of transplant (mechanical ventilation, paralytic agents, TPN-dependence, and renal dysfunction) are independently associated with hospital mortality, and transplanting VAD patients with ≥3 MRFs (regardless of the specific MRFs present) may not be prudent. While further study can seek to identify the optimal duration of VAD therapy for MRF reduction, aggressive pre-transplant physiologic optimization of MRFs should be tenaciously sought.

Perspective Statement

In this single-institutional retrospective study, children bridged to heart transplant (HTx) on ventricular assist device (VAD) achieved a reduction in the number & severity of modifiable risk factors (MRFs). However, VAD patients with persistent MRFs at HTx experienced a high burden of mortality (50% hospital mortality with ≥3 MRFs). The current study can assist in risk-stratification & timing of HTx.

Glossary of Abbreviations

ACTION

Advanced Cardiac Therapies Improving Outcomes Network database

CHD

Congenital heart disease

eGFR

Estimated glomerular filtration rate

IQR

Interquartile range

MRF

Modifiable risk factor

PHTS

Pediatric Heart Transplant Society

RVAD

Right ventricular assist device

STS

Society for Thoracic Surgeons

TPN

Total parental nutrition

UNOS

United Network for Organ Sharing

SVAD

Single-ventricle assist device

VAD

Ventricular Assist Device