2020 ESC Guidelines for themanagement of adult congenital heart disease

IntroductionPatients with a Fontan circulation are at risk for sequelae of Fontan physiology during follow-up. Fontan physiology affects all organ systems and an overview of end-organ damage is needed.MethodsWe performed a systematic review of abnormalities in multiple organ systems for patients with a longstanding Fontan circulation. We searched online databases for articles describing abnormalities in multiple organ systems. Cardio-pulmonary abnormalities, protein losing enteropathy, and Fontan associated liver disease have already extensively been described and were excluded from this systematic review.ResultsOur search returned 5,704 unique articles. After screening, we found 111 articles relating to multiple organ systems. We found abnormalities in, among others, the nervous system, pituitary, kidneys, and musculoskeletal system. Pituitary edema—relating to the unique pituitary vasculature- may affect the thyroid axis. Renal dysfunction is common. Creatinine based renal function estimates may be inappropriate due to myopenia. Both lean muscle mass and bone mineral density are decreased. These abnormalities in multiple organ systems may be related to Fontan physiology, cyanosis, iatrogenic factors, or lifestyle.ConclusionsHealth care providers should be vigilant for hypothyroidism, visual or hearing deficits, and sleep disordered breathing in Fontan patients. We recommend including cystatin C for assessment of renal function. This review may aid health care providers and guide future research.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232461, PROSPERO, identifier: CRD42021232461.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fontan Circulation Associated Organ Abnormalities Beyond the Heart, Lungs, Liver, and Gut: A Systematic Review

Ritmeester

Veger

Ven

et al. 2022

“…The development of liver fibrosis or cirrhosis in patients with congestive heart disease and heart failure is well-known ( 10 , 19 – 21 , 45 – 51 ). However, an adequate in vivo model recapitulating both, heart failure and liver fibrosis which would allow to study therapeutic interventions in the heart or lung as well as in the liver is lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, when patients with end stage heart or liver disease are evaluated for heart and/or lung transplantation, evaluation of liver fibrosis is mandatory ( 5 , 62 , 63 ), because liver cirrhosis is associated with increased mortality thereafter ( 63 , 64 ). Therefore, advanced liver fibrosis is an exclusion criterion for heart transplantation in patients with Ebstein's malformation or those with single ventricles and a Fontan circulation ( 45 , 46 ). In these patients, the underlying liver disease may require simultaneous heart-liver transplantation in expert centers ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Arterial Hypertension and Consecutive Right Heart Failure Lead to Liver Fibrosis

Hamberger

Legchenko

Chouvarine

et al. 2022

Hepatic congestion occurs in patients with right heart failure and can ultimately lead to liver fibrosis or cardiac cirrhosis. Elevated pulmonary arterial pressure is found in patients with hepatic congestion. However, whether pulmonary arterial hypertension (PAH) can be a cause of liver fibrosis is unknown. The aim of this study was to investigate whether rats in the SuHx model with severe PAH develop liver fibrosis and to explore the mechanisms of congestive hepatic fibrosis both in rats and humans. To achieve this, PAH was induced in six to eight-week old male Sprague Dawley rats by a single subcutaneous injection of the VEGFR 2 inhibitor SU5416 and subsequent hypoxia for 3 weeks, followed by a 6-week period in room air. SuHx-exposed rats developed severe PAH, right ventricular hypertrophy (RVH), and consecutive right ventricular failure. Cardiac magnetic resonance imaging (MRI) and histological analysis revealed that PAH rats developed both hepatic congestion and liver fibrosis. Gene set enrichment analysis (GSEA) of whole liver RNA sequencing data identified a hepatic stellate cell specific gene signature in PAH rats. Consistently, tissue microarray from liver of patients with histological evidence of hepatic congestion and underlying heart disease revealed similar fibrogenic gene expression patterns and signaling pathways. In conclusion, severe PAH with concomitant right heart failure leads to hepatic congestion and liver fibrosis in the SU5416/hypoxia rat PAH model. Patients with PAH should therefore be screened for unrecognized liver fibrosis.

“…It is usually felt that only the aorta is affected in Marfan syndrome with an FBN1 mutation, or that, if other arteries dilate, this is usually the consequence of aortic dissection. However, this is not true as fibrillin-1 is an ubiquitous protein, but the clinical consequences of extra-aortic alterations are rare in these patients, and not mentioned in European Society of Cardiology (ESC) Guidelines ( 2 , 3 ) or a recent review on Marfan syndrome ( 4 ). Consequently, the incidence, management, and prognostic impact of distal aortic and peripheral aneurysms (DAPA) that are not related to aortic dissection remain unknown in patients with MFS.…”

Section: Introductionmentioning

confidence: 99%

Non-Dissecting Distal Aortic and Peripheral Arterial Aneurysms in Patients With Marfan Syndrome

Pellenc

Boitet

Roussel

et al. 2022

BackgroundIn Marfan syndrome (MFS), an aortic or peripheral arterial dilatation is usually the consequence of aortic dissection. Non-dissecting distal aortic and peripheral aneurysms (DAPA) are barely described. We sought to determine the incidence and prognostic impact of non-dissecting DAPA, requiring a surgical repair in a large population of patients with MFS.MethodsThe patients referred to the French MFS reference center were included in a prospective database, and the patients treated for a non-dissecting DAPA between 2013 and 2020 were retrospectively reviewed. The first-line therapy was open surgery. The patients unfit for open repair or experiencing life-threatening complications underwent endovascular repair.ResultsAmong 1,575 patients with MFS, 19 (1.2%) were operated for 25 non-dissecting DAPA. The mean age was 42.4 ± 11.5 years. Non-dissecting DAPA involved the subclavian or axillary artery (n = 12), the descending or thoracoabdominal aorta (n = 6), the abdominal aorta andiliac arteries (n = 6), and the popliteal artery (n = 1). Open and endovascular repairs were performed in 22 and three cases, respectively. After a median follow-up of 54.2 months, no local recurrence was noticed and no secondary procedure was performed. Eight patients presented a new aortic event, including two aortic dissections and seven new aortic surgeries. Compared to the overall MFS population, the non-dissecting DAPA group presented a significantly higher risk of an aortic event (100 vs. 28%, p < 0.0001), a higher risk of aortic dissection (53 vs. 8%, p < 0.0001), and a higher rate of pejorative genetic mutations (68 vs. 40%, p = 0.011).ConclusionAmong the patients with MFS, the diagnosis of non-dissecting DAPA is infrequent but is associated with a significant adverse outcome, thus, advocating for a specific follow-up.