Heart Transplantation Outcomes for Fontan Patients When Using Contemporary Strategies: Heart-Liver Transplantation and Ventricular Assist Device Therapy

Abstract

Background

With an increasing number of Fontan patients surviving into adulthood, the burden of end-stage heart failure is increasing. Prior studies have reported suboptimal heart transplantation (HTx) outcomes. Therefore, the authors describe their institutional experience of HTx in patients with Fontan circulation failure, including en-bloc heart-liver transplantation (HLTx) and pretransplant systemic ventricular assist device (SVAD) therapies.

Methods

All consecutive Fontan-palliated patients undergoing HTx or HLTx between 2013 and 2022 at the authors’ institution were included. Pretransplant characteristics and posttransplant outcomes were recorded.

Results

Twenty-six transplant recipients, including 5 (19%) HLTx recipients, were identified. The majority (n = 16, 62%) of patients had a cardiac diagnosis of hypoplastic left heart syndrome. Seven (26%) patients were bridged to transplant on an SVAD; the median duration of support was 104 [IQR 39-543] days. Transplantation occurred at a median of 10.6 [IQR 6.8-15.6] years post-Fontan. Fourteen (54%) patients had ≥1 in-hospital complication and 4 (15%) patients required an in-hospital reoperation. Postdischarge reinterventions included tricuspid valve repair (n = 1, 4%) and retransplantation (n = 1, 4%). Two (8%) in-hospital mortalities [22 days (post-HLTx), 2.9 months (post-HTx] and 4 (15%) postdischarge mortalities [5.4 months, 3.1 years, 5.7 years, 7.1 years (all post-HTx)] occurred. Overall survival was excellent, with in-hospital, one-year, and five-year actuarial survival being 92%, 89%, and 80%, respectively.

Conclusions

The current series demonstrates that excellent posttransplant outcomes are achievable for patients with Fontan circulation failure using a comprehensive approach including SVAD and HLTx therapies. Pretransplant optimization, sometimes including SVAD implantation, and meticulous operative planning are imperative strategies for successful patient outcomes.

Keywords

circulatory assist devices (LVAD RVAD BVAD TAH)congenital heart disease Fontan heart failure hypoplastic left heart syndrome transplantation heart

Introduction

Contemporary outcomes following Fontan palliation have vastly improved from prior eras, with approximately 90% of patients now surviving more than 10 years post-Fontan and, of those who survive to adolescence, over 90% survive to age 30.^1–4 Heart failure regularly occurs in these late survivors, necessitating heart transplantation (HTx). Prior reports have shown in-hospital posttransplant mortality rates of up to 33% and a five-year survival often below 70%.^5–7 Therefore, the authors examined their experience with HTx in patients with Fontan circulation failure, particularly with the aggressive implementation of systemic ventricular assist device (SVAD) support and selective en-bloc heart-liver transplantation (HLTx). The present study is an analysis of Fontan-palliated patients undergoing HTx or HLTx at the authors’ institution using these contemporary strategies to maximize positive posttransplant outcomes.

Patients and Methods

The Cincinnati Children's Hospital Medical Center institutional review board approved the present study with a waived requirement of individual informed consent (IRB# 2022-0050; 02/03/2022). All consecutive first-time heart transplant recipients indicated for failing Fontan circulation at the authors’ institution between 2013 and 2022 were retrospectively identified. Patients who underwent HLTx, established in 2019, were also included. Both pediatric (<18 years) and adult patients were included.

Cardiac and end-organ functions were assessed. End-organ dysfunction included protein-losing enteropathy (PLE), confirmed by fecal alpha-1 antitrypsin concentrations >0.5 mg/g; plastic bronchitis, confirmed by bronchial mucofibrinous casts visualized via expectoration or bronchoscopy; and Fontan-associated liver disease (cirrhosis), confirmed by biopsy in 4 of 5 cases and consisting of hepatocellular carcinoma in 1 of 5 patients. Acute kidney injury (AKI) was defined as a postoperative estimated glomerular filtration rate of <60 ml/min/1.73 m² and/or the initiation of continuous renal replacement therapy (CRRT). Episodes of severe acute rejection were confirmed via cardiac biopsy and defined as a 3R rejection grading on the International Society for Heart and Lung Transplantation scale and/or antibody-mediated rejection. Posttransplant outcomes, beyond survival, included freedom from cardiac reintervention, retransplant, extracorporeal cardiopulmonary resuscitation (ECPR), and/or extracorporeal membrane oxygenation (ECMO).

Descriptive statistics and actuarial survival were calculated via SPSS Statistics version 27.0 (IBM). Continuous variables were reported as median [interquartile range], and categorical variables were reported as n (% of cohort).

Results

Demographics and Prior Palliations

Twenty-six patients were identified. Twenty (77%) were male, 18 (69%) were children, and 18 (69%) were Caucasian. Sixteen (62%) patients had hypoplastic left heart syndrome (HLHS) as the dominant single ventricle morphology (Table 1). Patients were chronologically labeled from A to Z by transplant date (Table 2).

Table 1.

Cohort Demographics and Palliations up to Transplant.^a

	Variable	Value
Demographics	Male sex	20 (77%)
Demographics	Nonwhite race	8 (31%)
Cardiac diagnoses	Primary
	Hypoplastic left heart syndrome	16 (62%)
	Tricuspid atresia	4 (15%)
	Double outlet right ventricle	3 (12%)
	Double inlet left ventricle	3 (12%)
	Concomitant
	Ventricular septal defect	5 (19%)
	TAPVR	3 (12%)
	Right atrial isomerism	2 (8%)
Stage 1^b	Age (days)^b	5 [IQR 4-7]
	Norwood procedure	20 (77%)
	Modified Blalock-Taussig shunt	16 (62%)
	Sano shunt	4 (15%)
	Pulmonary artery band	6 (23%)
Stage 2^b	Age (months)	5.7 [IQR 5.1-7.8]
	Glenn procedure	24 (92%)
	Bidirectional	22 (85%)
	Unidirectional	2 (8%)
	Hemi-Fontan	2 (8%)
Fontan	Age (years)	3.6 [IQR 2.7-4.7]
	Extracardiac conduit	18 (69%)
	Lateral tunnel	8 (31%)
	Post-Fontan SVAD	7 (27%)
Heart Transplant	Age (years)	14.1 [IQR 9.7-20.8]
	HLTx	5 (19%)
	Fontan to heart transplant (years)	10.6 [IQR 6.8-15.6]
	Posttransplant follow-up (years)	2.3 [IQR 1.1-4.4]

Abbreviations: HLTx, en-bloc heart-liver transplant; SVAD, systemic ventricular assist device; TAPVR, total anomalous pulmonary venous return.

Values are expressed as median [interquartile range] or n (%) as appropriate.

Stages one and two refer to the surgical order of staged reconstruction in univentricular patients.

Table 2.

Characteristics of Individual Patients.^a

Pt.	Primary cardiac diagnosis	Fontan age (years)	Fontan comp.	SVAD duration (days)	UNOS listing status	HLTx	HTx age (years)	Vent. time (days)	Hos. LOS (days)	In-hos. mort.	Post-dis. mort.
A	HLHS	2	PB		1A		6.9	5	20
B	DORV	2.6			1A		14.2	3	26		7.1 years
C	HLHS	2	PLE		1A		14.1	1	13
D	DORV	2.7	PLE		1A		3.8	9	37		3.1 years
E	TA	3.5	PLE	127	1A		25.7	9	28		5.7 years
F	HLHS	2.5	PB		1A		9.7	8	31
G	HLHS	4.9			1A		13.3	2	35		5.4 months
H	HLHS	3.8			1A		15.4	1	13
I	DILV	3.6	PLE, PB		1A		14.1	10	29
J	DORV	3.3			1A		17.3	34	23	2.9 months
K	HLHS	5.6			1A		9.8	9	164
L	HLHS	4.5			2		23.7	3	10
M	HLHS	6.4		65	1A		15.7	2	25
N	HLHS	5			1A		13.2	3	14
O	HLHS	2.2			1A		7.6	5	24
P	HLHS	4.7			2	Y	21.2	1	42
Q	HLHS	3.6		39	2	Y	22.2	2	28
R	HLHS	-		1105	1A		26	5	14
S	TA	5.1			4	Y	20.7	4	29
T	HLHS	3.7		23	1A		12.6	5	27
U	TA	3.5	PLE		1B	Y	14.1	22	22	22 days
V	HLHS	3.5			1A		8.6	16	25
W	DILV	3.2	PB		1B		14.7	2	17
X	TA	4.7		543	2		33.9	2	15
Y	DILV	4.2	PLE		2	Y	20	2	34
Z	HLHS	2.8		104	1A		4	1	32

Abbreviations: DILV, double inlet left ventricle; DORV, double outlet right ventricle; HLHS, hypoplastic left heart syndrome; HLOS, hospital length of stay; HLTx, en-bloc heart-liver transplantation; HTx, heart transplantation; In-hos. mort., in-hospital mortality; PB, plastic bronchitis; PLE, protein-losing enteropathy; Post-dis. mort., post-discharge mortality; Pt., patient; SVAD, systemic ventricular assist device; TA, tricuspid atresia; UNOS, United Network for Organ Sharing; Vent. time, mechanical ventilation duration.

Patients are identified by a unique letter, arranged from A to Z in order of transplant date.

The first-stage univentricular repair consisted of Norwood in 20/26 (77%) patients at a median age of 5 [IQR 4-7] days: 16 with a modified Blalock-Taussig (innominate artery-to-pulmonary artery) shunt and 4 with a Sano (right ventricle-to-pulmonary artery) shunt. A hybrid approach with pulmonary artery banding was performed in the remaining 6 (23%) patients. Second-stage univentricular palliation included Glenn shunt placement for 24 (92%) patients at a median age of 5.7 [IQR 5.1-7.8] months: 22 bidirectional and 2 unidirectional. Hemi-Fontan circulation was created in the remaining 2 (8%) patients. Fontan was performed at a median age of 3.6 [IQR 2.7-4.7] years. Eighteen (69%) patients received an extracardiac conduit, and 8 (31%) patients underwent lateral tunnel creation (Table 1).

Post-Fontan Clinical Course

Post-Fontan, 9/26 (35%) patients developed associated lymphatic dysfunction: PLE in 5 of 9, plastic bronchitis in 3 of 9, and both in 1 of 9 patients. Cirrhosis occurred in 5/26 (19%) patients, all of whom underwent HLTx, with a median model for end-stage liver disease score excluding international normalized ratio of 13 [IQR 7-22] at the time of transplant (Table 2).

Two of 26 (8%) patients [E, R] required pretransplant ECPR and remained on ECMO for four and seven days, respectively; both patients underwent a subsequent SVAD placement (Table 2). Seven (26%) patients were bridged to transplant with an SVAD for a median duration of 104 [IQR 39-543] days. All bridged patients (n = 7) were on an SVAD at the time of transplant. Five of the 7 (71%) patients were supported with a HeartMate 3 (Abbott) device for 23, 65, 543, and 1105 days to HTx [T, M, X, R] and 39 days to HLTx [Q] (Table 2). All HeartMate 3 patients were discharged home pretransplant. One patient [Z] was bridged with an EXCOR Pediatric (Berlin Heart) device for 104 days (Table 2). The remaining patient [E] was supported with a CentriMag (Abbott) device and converted to a HeartWare (Medtronic) device for a cumulative support time of 127 days (Table 2). This patient [E], in addition to one non-SVAD patient [Y], had complete resolution of PLE prior to transplant (Table 2).

Transplantation Details

The median age at transplant was 14.1 [IQR 9.7-20.8] years, with a median of 10.6 [IQR 6.8-15.6] years spanning from Fontan palliation to HTx. Eighteen of 26 (69%) patients were United Network for Organ Sharing (UNOS) status 1A at listing. Five (19%) patients underwent HLTx. The median cardiopulmonary bypass (CPB), cross-clamp, and graft ischemia times were 5.2 [IQR 4.2-5.8], 3.2 [IQR 2.3-3.9], and 4.6 [IQR 4.3-5.5] hours, respectively. Concomitant procedures completed on the recipient before donor heart anastomosis included pulmonary artery angioplasty (n = 24, 92%), vena cava angioplasty (n = 4, 15%), and aortic arch reconstruction (n = 2, 8%). One SVAD patient [R] with a 10-cm ascending aorta and arch past the left subclavian, as well as an obliterated left pulmonary artery, required over 12 hours of CPB for great artery reconstruction, transplant, and chest reentry under circulatory arrest (Table 2). This patient was extubated and discharged 3- and 14-days posttransplant, respectively. At the time of transplant, one patient [E] required temporary CentriMag biventricular assist device support for five days for graft dysfunction (Table 2). This patient was discharged 28 days after transplant.

Posttransplant Outcomes: In-Hospital

The median posttransplant intensive care unit length of stay was 15 [IQR 10-23] days, and the median hospital length of stay was 26 [IQR 17-32] days. The median posttransplant ventilator days were 2.5 [IQR 2-9], including reintubation. Reintubation was required in 3 (12%) patients for respiratory insufficiency, two of whom were successfully extubated. The remaining patient [J] expired in-hospital while intubated (Table 2). Fourteen of 26 (54%) patients had one or more in-hospital complications, including severe acute graft rejection (n = 5, 19%) and AKI (n = 10, 38%), with 3 (12%) patients requiring CRRT. Four (15%) patients required an in-hospital reoperation. Three (n = 3/4) mediastinal reoperations occurred for postoperative bleeding [I], innominate vein repair for thrombosis [B], and superior vena cava repair for obstruction [A] at zero-, zero-, and six-days post-HTx, respectively (Table 2). One (n = 1/4) abdominal reoperation occurred for hematoma evacuation seven days following HLTx [Q] (Table 2). No patients required posttransplant ECMO. The overall in-hospital survival was 92% (n = 24/26). All (n = 7/7) pretransplant SVAD patients and 80% (n = 4/5) of HLTx patients survived to discharge (Table 3).

Table 3.

Patient Survival Post-Heart Transplantation.^a

Cohort	Presence	n	In-hospital survival	1-year survival	5-year survival
All		26	92% (n = 24)	89%	80%
Pre-HTx SVAD	[+]	7	100% (n = 7)	100%	100%
Pre-HTx SVAD	[−]	19	89% (n = 17)	84%	72%
HLTx	[+]	5	80% (n = 4)	80%	NA^b
HLTx	[−]	21	95% (n = 20)	90%	81%

Abbreviations: HLTx, en-bloc heart-liver transplantation; HTx, heart transplantation; SVAD, systemic ventricular assist device; [+], present; [-], not present.

All patients were followed through hospital discharge.

HLTx occurred within five years of writing for all included patients.

Two (8%) in-hospital mortalities occurred, secondary to a noncardiac [U] and a cardiac [J] complication (Table 2). Before admission, patient U was on a chronic corticosteroid regimen for PLE-induced adrenal insufficiency (Table 2). This patient's pretransplant bilirubin and lactate were severely elevated. By 48 hours posttransplant, hepatic arterial flow decreased, and transaminase levels rose precipitously, exceeding 60 times baseline values. Unamenable to Molecular Adsorbent Recirculating System therapy, patient U expired 22 days post-HLTx secondary to hepatic vascular thrombosis and abdominal bleeding (Table 2). Patient J remained inpatient for 27 days before HTx due to a severely elevated Fontan conduit pressure (33 mm Hg) and low cardiac index (2.2 L/min/m²) (Table 2). Within 48 hours of transplant, this patient necessitated CRRT for AKI. Two weeks posttransplant, severely elevated right (>30 mm Hg) and left (>40 mm Hg) ventricular end-diastolic pressures indicated graft dysfunction. Two months posttransplant, graft rejection (humoral and cellular) and myocardial ischemia were confirmed via biopsy. Multiorgan function subsequently declined until patient J's death 2.9 months posttransplant, secondary to mixed graft rejection (Table 2).

Posttransplant Outcomes: Postdischarge

The median follow-up duration was 2.3 [IQR 1.1-4.4] years posttransplant. All patients that survived through discharge achieved posttransplant resolution of Fontan-associated lymphatic dysfunction [A, C, D, F, I, W] (Table 2). One patient [K] required cardiac reintervention (tricuspid valve repair) 93 days posttransplant (Table 2). This patient was alive at the most recent follow-up, 3.8 years posttransplant. The overall cohort's actuarial one- and five-year survivals were 89% and 80%, respectively (Figure 1). For SVAD-bridged patients, both one- and five-year survivals were 100% (Figure 2). For HLTx patients, both one- and two-year survivals were 80% (Table 3). One patient [Q] received SVAD support to HLTx and was alive at the last follow-up, 1.6 years post-HLTx (Table 2).

Four l(15%) ate mortalities occurred at a median of 4.4 [IQR 1.8-6.4] years posttransplant, all in HTx recipients [B, D, E, G] (Table 2). All mortalities occurred in patients transplanted at UNOS status 1A (n = 5/6, 83%) or 1B (n = 1/6, 17%). Of the patients diagnosed with PLE, half (n = 3/6) experienced in-hospital (n = 1) [U] or post-discharge (n = 2) [D, E] mortality (Table 2). Patient G suffered a cardiac arrest two months posttransplant, necessitating ECPR, followed by withdrawal of care 5.4 months posttransplant (Table 2). Patient D expired 3.1 years posttransplant following retransplantation for rejection at 1.7 years; mortality occurred 1.4 years following retransplant (Table 2). Patient B suffered an out-of-hospital respiratory arrest and subsequent mortality 7.1 years posttransplant. Patient E suffered a cardiac arrest after emergent admission to an outside hospital for syncope; this patient expired 5.7 years posttransplant (Table 2).

Comment

Congenital heart disease remains the most significant risk factor for early mortality in pediatric HTx.⁸ Anatomical complexities requiring extensive repair elevate the risk of postoperative morbidity and mortality.⁷ Fontan-palliated patients present unique challenges due to alterations in venous flow, organ perfusion, and lymphatic drainage, as well as the high number of prior cardiac operations.^9,10 Traditional reluctance to pursue HTx in Fontan patients was largely due to multiorgan dysfunction invariably present, combined with historically poor outcomes and organ shortages. Therefore, patients with Fontan circulation failure are arguably the most challenging and resource-dependent patients to transplant effectively. Recent reports of HTx in Fontan patients have cited one- and five-year survivals of 62% to 85% and 50% to 78%, respectively (Table 4).^11–16 However, the current experience demonstrates that superior outcomes are achievable with contemporary strategies of aggressive pretransplant physiologic optimization, done in part with SVAD support, as well as multiorgan transplantation.

Table 4.

Evaluation of Institutional Reports on Heart Transplantation in Fontan-Palliated Patients.^a

First author	Year	Study time frame	n	HLTx	Pre-HTx SVAD	Age at HTx (years)	1-year survival	5-year survival
Hogue et al	2024	2013-2022	26	Yes (n = 5)	Yes (n = 7)	14.1^b	89%	80%
Cardoso et al¹⁶	2021	2007-2019	31	No	No	27.1^b	71%	67%
Sganga et al¹¹	2021	2006-2019	47	Yes (n = 9)	Yes (n = 6)	15.0^b	85%	78%
Berg et al¹³	2017	1991-2004	36	Yes (n = 2)	No	21.3^b	75%	-
Pundi et al¹⁵	2016	1988-2014	44	Yes (n = 1)	No	23.4^c	80%	72%
Backer et al⁹	2013	1990-2012	22	No	No	14.9^c	77%	66%
Murtuza et al¹⁷	2017	1990-2011	26	Yes (n = 1)	No	26.1^c	65%	-
Davies et al¹⁴	2012	1984-2007	43	No	No	14.5^b	62%	59%
Kanter et al¹²	2011	1988-2009	27	No	No	8.2^c	82%	66%
Gamba et al¹⁰	2004	1990-2002	14	No	No	17.2^c	86%	77%
Lamour et al⁷	1999	1985-1998	24	No	No	26.0^c	79%	60%

Abbreviations: HLTx, en-bloc heart-liver transplantation; HTx, heart transplantation; SVAD, systemic ventricular assist device.

Reports are shown in descending order by publication year.

Median age.

Mean age.

In the present study, the overall survival was excellent, with in-hospital, one-year, and five-year survivals of 92%, 89%, and 80%, respectively. Among SVAD-bridged patients, five-year survival was 100%. For HLTx patients, one- and two-year survivals were both 80%, with one in-hospital mortality occurring (Table 2).

Notably, 69% (n = 18/26) of the study cohort was listed as UNOS status 1A. Five-year survival for these patients alone was 80%. These results deviate considerably from previous reports of approximately 65% five-year survival among status 1A patients.^7,10,12,16 The current study also represents one of the most extensive series to date of post-Fontan HLTx. Five patients, all with Fontan-associated cirrhosis, underwent HLTx, achieving one- and two-year survivals of 80%, on par with the results of Sganga and colleagues, in which one-year survival was 89% (n = 8/9).^11,17–19 There were no deaths among patients with plastic bronchitis despite mortality rates of up to 30% cited in prior studies.^9,20,21 Finally, 16 (62%) patients had HLHS, a historically established risk factor for posttransplant morbidity and mortality.^5,22,23 Prior studies on HTx in HLHS patients have cited a 65% to 75% one-year posttransplant survival in Fontan patients.¹⁷ However, these patients’ one- and five-year survival rates were excellent in the present series, achieving 94%. In the authors’ practice, there were no anatomic variations contraindicating transplantation, yet markers of frailty (eg, chronic corticosteroids, poor handgrip strength, and subpar 2-min walk test) were considered to better understand potential recipients’ postoperative course. When high frailty was observed, SVAD support was utilized for physiologic optimization prior to transplantation.

Despite these long-term successes, the posttransplant course is often fraught with complications. Fourteen (54%) patients in the present series experienced one or more in-hospital complications, including four in-hospital reinterventions. Notably, only 1 (4%) patient was reexplored for mediastinal bleeding, which is lower than in previous reports (11% to 23%).^11,14,16 This is significant as reexploration for postoperative bleeding is associated with a 50% to 57% in-hospital mortality.^14,16 Of note, the HLTx patient explored for an abdominal hematoma did not survive to discharge. The prevalence of patients with severe acute graft rejection was 19% (n = 5/26), similar to the literature indicating 24% to 32%.^12,24,25 Although no patients required posttransplant ECMO, similar studies have reported a 6% to 29% ECMO requirement, with an in-hospital mortality of approximately 33%.^11,12 Rates of AKI posttransplant were similar to the literature, constituting >30% of our cohort, although the CRRT requirement was considerably less (12% vs up to 77%).^12,14,16,24 In the present cohort, only 1 (n = 1/7, 14%) SVAD-bridged patient developed AKI posttransplant, compared with 9 (n = 9/19, 47%) patients without SVAD bridging. No SVAD-bridged patients required CRRT. The authors hypothesize that SVAD support optimized patient hemodynamics pretransplant, improving renal perfusion and leading to superior kidney function posttransplant.

Recent literature has emphasized the importance of pretransplant physiologic optimization, as “limping” to transplant has serially shown poor outcomes.^23,26,27 Multidisciplinary and longitudinal follow-up post-Fontan and listing for transplantation only when the patient is ready (that is, when modifiable risk factors are minimized to the fullest extent possible) are paramount and underlie the current success. To achieve this, the authors emphasize early consideration for SVAD implantation; institutional candidacy details beyond current Advanced Cardiac Therapies Improving Outcomes Network (ACTION) recommendations are outlined by Villa et al.²⁶ SVAD utilization has been shown to halt, or even correct, hepatic and renal dysfunction and promote ventilator weaning in Fontan-palliated patients.^23,28,29 This, coupled with findings of excellent survival among SVAD-bridged Fontan patients, has led to increased SVAD utilization in the modern era.^27–30 The authors note that limited SVAD-implanted Fontan patients ultimately live chronically on mechanical support for varying reasons (eg, never improve to the point of transplant candidacy or elect not to pursue transplantation). Both in-hospital deaths in the present series, however, were “limped” to transplant with multiple modifiable risk factors (eg, multiorgan dysfunction, suboptimal hemodynamics, and frailty) without SVAD support.^19,28–30

The success of the current experience is also secondary to longitudinal monitoring post-Fontan to facilitate early identification and management of failure of the Fontan circulation. The functional decline for Fontan patients is gradual and often difficult to identify.³¹ However, with advanced Fontan-specific clinics and scheduled testing, recognition of functional decline and subsequent referral to advanced therapy (eg, medicine, transplantation, and SVADs) occur earlier. Fontan management conferences occur weekly and in consultation with hepatologists, supporting frequent, multiorgan surveillance; HLTx recommendations occur within these meetings. Institutional metrics triggering early referral for advanced therapy are predominately based upon current ACTION recommendations and these multidisciplinary conference discussions. The authors have noted significant improvement regarding appropriately timed transplant referrals since the opening of the institutional Fontan clinic in 2018.³² Whereas referral for advanced therapies previously constituted a “transfer of care,” this clinic has facilitated an early partnership between a patient's primary cardiologist and heart failure specialists. This comanagement in the years preceding SVAD support or transplant has improved therapeutic timing and subsequent outcomes for these patients. The authors speculate that the decreased incidence of associated lymphatic disorders since the Fontan clinic's opening may be due to its systematic and consistent monitoring as well as liberal treatment of multisystem derangements of the complex circulation.

Lastly, even with early identification, referral, and hemodynamic optimization of patients with failing Fontan circulation, advanced operative planning remains essential. Prior reports emphasize that ample expertise and time, often ≥4 hours, is necessary for proper recipient vascular dissection, reconstruction, and control of the complex anatomy before donor heart anastomosis.^33,34 Thus, the skin incision is made on the recipient during organ transport, but only after the donor heart (and liver when applicable) has been well visualized by an experienced procurement surgeon, necessitating efficient team coordination.^33,34 Further implementation of modern ex-vivo perfusion technologies may also assist in this ischemia-limiting modality. Together, promising outcomes have been demonstrated. The recent multicenter study by Shi and colleagues reports promising five-year posttransplant survival, approaching that of the present study, which is 80%.³⁴ Inversely, suboptimal outcomes, in part, have been demonstrated without implementation of these principles. In one example, >20% of reported Fontan-palliated patients experienced major intraoperative bleeding, which contributed to significant posttransplant morbidity (eg, limb amputations) and early mortality, exceeding 50%.¹⁶ Thus, the authors stress the integration of advanced operative planning into practice for heart transplant in Fontan patients, in line with prior reports, with excellent outcomes occurring in the described, complex cohort.

Limitations and Considerations for Future Investigation

Several study limitations exist. First, although large for a single-institution series, the sample size (n = 26) remains small. Thus, any inferences from the present study should be validated with larger patient populations and multicenter data. As HLTx was established only recently, future studies should include larger populations of HLTx. Finally, while this study does report modern-era outcomes from a center specialized in univentricular palliation and transplant, future studies should investigate surgical technique and timing to transplant referral relative to patient outcomes. Such granular variables, including the timing of hemodynamic normalization following Fontan HTx, are currently under investigation by the authors.

Conclusions

With an increasing number of Fontan patients surviving into adulthood, the diagnosis and management of late heart failure in this patient population are of growing importance. While previous reports cited suboptimal posttransplant outcomes, the current series, amongst the largest to date, demonstrated that excellent outcomes are achievable. The authors believe that, to achieve this, specialized programs need to offer the full range of therapies for Fontan patients, including longitudinal testing and follow-up in a Fontan-specific clinic, early referral to a heart failure care team, SVAD therapy, and heart and HLTx. Pretransplant physiologic optimization and advanced operative planning are imperative for achieving optimal survival following HTx in Fontan patients.

Footnotes

Abbreviations

Authors’ Note

IRB Approval: The Cincinnati Children's Hospital Medical Center institutional review board approved the present study with a waived requirement of individual informed consent (IRB# 2022-0050; 02/03/2022).

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Morales is a consultant for Abbott, Inc., Azyio, Inc., Berlin Heart, Inc., CorMatrix, Inc., Peca, Inc., Syncardia, Inc., and Xeltis, Inc.; Lorts is a consultant for Abbott, Inc., Abiomed, Inc., Berlin Heart, Inc., Medtronic, Inc., and Syncardia, Inc.; Chin is a consultant for Azurity Pharmaceutical, Inc. The remaining authors have no relevant conflicts of interest.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The National Institutes of Health funded the present study under the project “Novel Methods to Grow the Impact of Pediatric Thoracic Transplantation” (grant number R01HL147957). The principal investigators are Dr. Clifford Chin and Dr. David L. S. Morales.

ORCID iD

Spencer J. Hogue

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