Outcomes and complications of combined heart-liver transplantation in patients with failing Fontan physiology: A systematic review

Table 1 Baseline demographic and clinical characteristics of studies and combined heart-liver transplantation patients included in the systematic review, median (range)/mean ± SD

Ref.	Year	Country	Study design	Population (n)	Age (years)	Male (n/N)	Female (n/N)	Albumin levels (g/dL)	Gastroesophageal Varices on EGD/CT scan (n/N)	Ascites (n/N)	Wedge Hepatic Venous Pressure (mmHg)	MELD score	Pre- biopsy
													Stage 1 Perivascular fibrosis	Stage 2 Bridging fibrosis	Stage 3 Nodules	Stage 4 Cirrhosis
Vaikunth et al[19]	2024	United States	Retrospective Cohort	40	30.85 (14.2–49.5)	19/40	21/40	4.05 (1.8–5)	5/40	11/40	14 (6–22)	11 (7–26)	N/A	29/33	N/A	N/A
Vaikunth et al[20]	2019	United States	Retrospective cohort	9	20.7 (14.2–41.3)	3/9	6/9	3.4 (2.2–4.5)	N/A	N/A	N/A	10 (7–26)	0	9/9	0	0
Wu et al[18]	2024	United States	Retrospective cohort	11	37.0 (30.0–48.0)	7/11	4/11	3.6 (2.9–4.1)	6/11	9/11	16.0 (14.0–20.0)	13.0 (9.4–15.4)	1/11	3/11	1/11	2/11
Sganga et al[21]	2021	United States	Retrospective cohort	9	19 (16, 21)	3/9	6/9	4 (3.5–4.2)	6/9	8/9	17 (14, 18)	10 (9, 11)	1/9	2/9	3/9	N/A
D’Souza et al[10]	2016	United States	Retrospective cohort	7	36.8 (27.3–41.7)	4/7	3/7	3.0 (1.6–4.4)	3/7	5/7	16.0 (12.0–28.0)	6.8 (0.6–18.5)	N/A	N/A	4/7	2/7
Reardon et al[22]	2018	United States	Retrospective cohort	5	29.5 (5.37–53.63)	N/A	N/A	4 (2.5–5)	N/A	N/A	18 (15–23)	13.5 (9.4–22.9)	N/A	N/A	N/A	N/A
Lewis et al[34]	2023	United States and Canada	Retrospective cohort	40	33 ± 7.7	N/A	N/A	3.7 ± 0.9	14/40	29/40	N/A	10.1 ± 6.3	N/A	N/A	N/A	34/40

MELD: Model for end-stage liver disease; EGD: Esophagogastroduodenoscopy; N/A: Not applicable.

Table 2 Study characteristics, cardiac anatomy, and time variables, median (range)

Ref.	Time from Fontan to listing (years)	Tricuspid Atresia	DORV	DILV	CAVC	D-TGA/VSD/HRV	Time Elapsed from Fontan (years)	NYHA class III/IV (n/N)
Vaikunth et al[19] (2019)	22.6 (8.4–34.9)	8/40	3/40	8/40	6/40	23/40	22.6 (8.4–34.9)	6/40
Vaikunth et al[20] (2024)	16.6 (8.4–25.9)	2/9	2/9	1/9	3/9	1/9	16.6 (8.4–25.9)	6/9
Wu et al[18] (2024)	80.0 (16.0–117.0)	2/11	3/11	3/11	1/11	2/11	16.0 (14.0–20.0)	N/A
Sganga et al[21] (2021)	N/A	1/9	0	0	2/9	6/9	N/A	N/A
D’Souza et al[10] (2016)	0.7 (0.1–3.5)	1/7	2/7	2/7	1/7	1/7	22.9 (18.7–28.5)	5/7
Reardon et al[22] (2018)	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Lewis et al[34] (2023)	2.4 ± 2.6	N/A	N/A	N/A	N/A	N/A	N/A	N/A

DORV: Double-outlet right ventricle; DILV: Double-inlet left ventricle; CAVC: Complete atrioventricular canal; D-TGA/VSD/HRV: Dextro-Transposition of the great arteries/ventricular septal defect/hypoplastic right ventricle; NYHA: New York Heart Association; N/A: Not applicable.

Table 3 Type of Fontan procedure by study

Ref.	Atriopulmonary	RA-PA	RA-RV	Lateral tunnel	Extra-cardiac
Vaikunth et al[19] (2019)	4/40	0	0	16/40	20/40
Vaikunth et al[20] (2024)	0	0	0	3/9	6/9
Wu et al[18] (2024)	2/11	0	0	1/11	6/11
Sganga et al[21] (2021)	N/A	N/A	N/A	N/A	N/A
D’Souza et al[10] (2016)	1/7	1/7	1/7	1/7	2/7
Reardon et al[22] (2018)	0	N/A	N/A	N/A	N/A
Lewis et al[34] (2023)	N/A	N/A	N/A	N/A	N/A

RA-PA: Right atrium to pulmonary artery; RA-RV: Right atrium to right ventricle; N/A: Not applicable.

Table 4 Newcastle-Ottawa Scale quality assessment of included non-randomized studies

Ref.	Type of study	Representativeness of the exposed cohort	Ascertainment of exposure	Selection of the non-exposed cohort	Outcome not present at start	Comparability of cohorts	Assessment of outcome	Sufficient follow-Up Time	Adequacy of follow-up of cohorts	Total score
Sganga et al[21] (2021)	Retrospective cohort study	1	1	1	1	1	1	1	1	8
Lewis et al[34] (2023)	Retrospective cohort study	1	1	1	1	1	1	1	1	8
Wu et al[18] (2024)	Retrospective cohort study	1	1	1	1	1	1	0	1	7
D’Souza et al[10] (2016)	Retrospective cohort study	1	1	1	1	1	1	1	1	8
Reardon et al[22] (2018)	Retrospective cohort study	1	1	1	1	1	1	1	1	8
Vaikunth et al[19] (2019)	Retrospective cohort study	1	1	1	1	1	1	1	1	8
Vaikunth et al[20] (2024)	Dual-center retrospective study	1	1	1	1	1	1	1	1	8

Table 5 Perioperative metrics and survival outcomes, median (range)/mean ± SD

Ref.	Population	ICU stay (days)	Hospital stay (days)	CPB time (minute)	RBC units	Ischemic time (minute)	30-day survival	1-year	5-year	10-year
Vaikunth et al[19] (2019)	40	23 (1–272)	38.5 (1–339)	316 (171–837)	21 (3–46)	231.5 (122–410)	36/40	32/40	30/40	30/40
Vaikunth et al[20] (2024)	9	19	36	260 (178–307)	22 (5–42)	280 (227–396)	9/9	9/9	N/A	N/A
Wu et al[18] (2024)	11	7.5 (5–11)	27.5 (17–33.5)	199 (158–261)	18 (6–26)	N/A	N/A	7/11	N/A	N/A
Sganga et al[21] (2021)	9	8 (6–19)	29 (16–42)	264 (243–327)	N/A	293 (255–336)	N/A	8/9	N/A	N/A
D’Souza et al[10] (2016)	7	N/A	29 (25–112)	218 (197–341)	N/A	211 (146–247)	N/A	7/7	N/A	N/A
Reardon et al[22] (2018)	5	N/A	51 (26–77)	260 (161–495)	N/A	181 (159–396)	5/5	5/5	5/5	5/5
Lewis et al[34] (2023)	40	30 ± 95.91	66 ± 124.58	310 ± 704.96	N/A	237 ± 1799.74	N/A	37/40	34/40	N/A
Aggregate	—	8.46 (4.66–12.25)	28.16 (19.56–36.76)	260.27 (227–293)	19.38 (8–30)	267.29 (227–307)	92.6%	86.8%	81.2%	77.8%

ICU: Intensive care unit; LOS: Length of stay; CPB: Cardiopulmonary bypass; N/A: Not applicable.

Table 6 Postoperative complications and study conclusions

Ref.	MCS (n/N)	RRT (n/N)	Tracheostomy (n/N)	Rejection (n/N)	Infection (n/N)	Reoperation (n/N)	Conclusions
Vaikunth et al[19] (2019)	9/40	17/40	8/40	0	N/A	N/A	Further study needed to reduce early mortality and complications (MCS, RRT, bleeding, vasoplegia) in CHLT patients with failing Fontan physiology
Vaikunth et al[20] (2024)	2/9	3/9	0	7/9	N/A	N/A	CHLT is a viable option in Fontan patients with liver cirrhosis
Wu et al[18] (2024)	4/11	5/11	N/A	3/11	1/11	5/11	CHLT in Fontan patients is associated with higher morbidity; early intervention may improve outcomes
Sganga et al[21] (2021)	0	1/9	0	0	5/9	3/9	Despite higher liver disease burden, Fontan patients had comparable outcomes to HT
D’Souza et al[10] (2016)	N/A	2/7	N/A	0	N/A	N/A	CHLT is acceptable in failing Fontan + fibrosis; long-term data needed
Reardon et al[22] (2018)	N/A	N/A	N/A	2/5	N/A	0/5	CHLT is reasonable despite peri/postoperative risks
Lewis et al[34] (2023)	N/A	N/A	N/A	N/A	N/A	N/A	Fontan patients had worse outcomes with higher FALD scores; survival possibly better at experienced centers
Aggregate (%)	22%	36.84%	13.79%	12.34%	30%	32%	—

CHLT: Combined heart-liver transplantation; FALD: Fontan-associated liver disease; MCS: Mechanical circulatory support; RRT: Renal replacement therapy; N/A: Not applicable.