Fontan-palliated patients are at risk for the development of Fontan-associated liver disease (FALD). In this study, we performed a detailed hemodynamic and hepatic assessment to analyze the incidence and spectrum of FALD and its association with patients' hemodynamics. From 2017 to 2019, 145 patients underwent a detailed, age-adjusted hepatic examination including laboratory analysis (FibroTest ® , n = 101), liver ultrasound (n = 117) and transient elastography (FibroScan ® , n = 61). The median patient age was 16.0 years [IQR 14.2], and the median duration of the Fontan circulation was 10.3 years [IQR 14.7]. Hemodynamic assessment was performed using echocardiography, cardiopulmonary exercise capacity testing and cardiac catheterization. Liver ultrasound revealed hepatic parenchymal changes in 83 patients (70.9%). Severe liver cirrhosis was detectable in 20 patients (17.1%). Median liver stiffness measured by FibroScan ® was 27.7 kPa [IQR 14.5], and the median Fibrotest ® score was 0.5 [IQR 0.3], corresponding to fibrosis stage ≥ 2. Liver stiffness values and Fibrotest ® scores correlated significantly with Fontan duration (P 1 = 0.013, P 2 = 0.012). Exercise performance was significantly impaired in patients with severe liver cirrhosis (P = 0.003). Pulmonary artery pressure and end-diastolic pressure were highly elevated in cirrhotic patients (P 1 = 0.008, P 2 = 0.003). Multivariable risk factor analysis revealed Fontan duration to be a major risk factor for the development of FALD (P < 0.001, OR 0.77, CI 0.68-0.87). In the majority of patients, hepatic abnormalities suggestive of FALD were detectable by liver ultrasound, transient elastography and laboratory analysis. The severity of FALD correlated significantly with Fontan duration and impaired Fontan hemodynamics. A detailed hepatic assessment is indispensable for long-term surveillance of Fontan patients.

The mouse is a quickly reproducing, inexpensive animal and often used for transgenic approaches. Due to its small size, only the aorta is frequently taken to assess vascular function. However, atherosclerosis is a generalized disease and becomes symptomatic when the perfusion of specific organs is impaired. We have therefore compared the thoracic and abdominal aorta with carotid, femoral, mesenteric, renal and coronary arteries to see whether aortic vasomotion can indeed serve as a surrogate for other, organ-specific vascular territories. Arterial segments of male C57BL/6J mice were dissected and mounted on a myograph for isometric force measurement. Vasoconstriction was determined in response to depolarization by potassium chloride (KCl), which was not different with or without an α-adrenoceptor antagonist. Vascular responses were determined in response to receptor activation by the neurotransmitter norepinephrine (± inhibition of nitric oxide synthase; ± α- and β-adrenoceptor antagonists) and the platelet-derived mediator serotonin (± inhibition of nitric oxide synthesis; ± 5-hydroxytryptamine receptor antagonist). Endothelium-dependent and -independent vasodilation was determined in response to carbachol and nitroprusside after norepinephrine-induced pre-constriction (± β-adrenoceptor antagonist). Vasoconstriction in response to KCl, norepinephrine and serotonin differed in magnitude between thoracic and abdominal aorta and between aorta and the other arterial segments. Endothelium-dependent and -independent vasodilation differed also in magnitude between the arterial segments. Thus, the murine aorta is not a general surrogate to assess vascular function of organ-specific vascular territories.

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