Cognitive function

Since there is a close connection of an abnormal cognitive function with overall quality of life, employment opportunities as well as educational attainments, it is important to follow this in patients with CHD into adulthood. ^{Reference Cohen and Earing13} Neonates and infants are most often reported with neurodevelopmental delays, especially in patients with complex CHD. ^{Reference Ellert and Kurth22–Reference Reich, Heye and Tuura25} Hypoxaemia during pregnancy, perioperative as well as postoperative, haemodynamic changes, and early surgeries are related to adverse effects on brain development and neurodevelopment. ^{Reference Klaver, Knirsch, Wurmitzer and von Allmen26} For example, because of the enormous advantages in medicine and surgical procedures, surgeries with cardiopulmonary bypass have become a widespread, low-risk standard procedure; in Germany alone, around 3852 children (newborns up to the age <18 years) underwent heart surgery with cardiopulmonary bypass in 2019. ^{Reference Wray27} In addition to the benefits, however, there are also side effects that can affect the lungs, kidneys, liver, or brain. Studies from the early 2000s reported neurological deficits in up to 80% of adults after heart surgery with cardiopulmonary bypass. ^{28–Reference Nathan, Wells, Munson and Wozny31} This does not seem to apply to children with CHD, Gunn et al. investigated the neurodevelopmental status after early heart surgery of 130 children at the age of 2 years in a direct comparison of CHD surgery with cardiopulmonary bypass and surgery without cardiopulmonary bypass. They found no significant differences in terms of the cardiopulmonary bypass use or aortic clamp on its own but reported repeated surgeries as a high-risk factor for neurodevelopment impairments. ^{Reference Fearn, Pole, Wesnes, Faragher, Hooper and McCollum32} In our study, number of surgeries or interventions did not show a relation with cognitive function in adulthood. Our study population of adult CHD patients showed no impairment in cognitive function compared with the german norms. Interestingly, Fontan patients had partly significant higher scores than patients with acyanotic CHD, although the control group had the first intervention or surgery at a significantly later time, that is, after the critical developmental age. Our results are not in line with other studies, but since most of them focus on younger CHD patients it is hardly comparable. Based on advances, different technics came to use to get an improved knowledge of the developing brain and its relations to CHD. More recent studies focus on neurodevelopmental outcomes combined with brain imaging using MRI to identify differences that can explain the neurodevelopmental delay in neonates and young CHD patients. They reported a high incidence of white matter lesions. ^{Reference Guo, Chau and Peyvandi9,Reference Gunn, Beca and Hunt33–Reference Desai, Hamrick, Strickland, Matthews, McMaster and Mahle36} Additionally, Claessens et al. reported impaired cortical volume and brain gyrification in patients with univentricular heart circulation and white matter development resembling premature birth ^{Reference Claessens, Moeskops and Buchmann10,Reference Bertholdt, Latal and Liamlahi37} changes that can predict developmental problems. Most of the studies in adolescents with CHD reported on executive function problems with reduced working memory and additionally, Fontes et al. on volume changes of the hippocampus with a structure–function relation of hippocampal subfields in this context in adolescents with complex CHD. ^{Reference Claessens, Kelly, Counsell and Benders38} In another study, functional MRI was used which brought out a reduced prefrontal inhibition in patients with CHD compared to a healthy control group and a correlation with executive functioning. ^{Reference Fontes, Rohlicek and Saint-Martin39} However, besides all these advanced findings resulting from technical possibilities, it remains unclear what this means for our growing group of adult CHD. It remains unclear what impact the differences/abnormalities found will ultimately have on the function of the mature brain in adult CHD, due to the enormous neuroplasticity of the developing child’s brain. ^{Reference King, Smith and Burns40}

In our study cohort, there was no impairment in cognitive function, and one reason might be that none of the patients in this study had been diagnosed with neuro events like ischaemic stroke. Of course, that does not mean they do not exist but it seems the brain found adaption mechanisms to enable normal cognitive function. It would be most interesting to do MRI with our Fontan cohort to find out whether there are still existing changes or undiagnosed lesions. On the one hand, it can be discussed whether MRI findings in neonates and young children with CHD present some kind of pathophysiology due to less oxygen or changes in the blood flow. For example, reported in the literature is liquor space enlargements associated with neurodevelopmental delay, ^{Reference Heye, Knirsch and Latal7,Reference Knirsch, Mayer and Scheer8} which may be due to a higher rate of ultrafiltration in the brain to prevent oxygen deficiency in the growing brain. On the other hand, a recently published work by Ehlert et al. reported reduced fractional anisotropy of the brain in both patients with cyanotic CHD and with acyanotic CHD as well in comparison with healthy controls in adolescents, especially in the frontal lobe which is associated with working memory. ^{Reference Kolb and Gibb41} It would be interesting if these changes of the brain still exist in older ages of our adult survivors or what kind of adaption mechanism leads the brain to normal function. MRI studies on adult CHD survivors may promise an improvement in understanding brain adaptions due to the underlying CHD.

Health-related quality of life

The adult CHD patients of both groups showed normal to good self-reported health-related quality of life measured with the SF-36 in this study without significant differences between both groups. This is in line with a recent study reporting on a large cohort of about 4000 patients with all kinds of adult CHD. ^{Reference Ehrler, Latal, Kretschmar, von Rhein and O'Gorman42} They also pointed out that health-related quality of life is not dependent on the complexity of the underlying CHD. With a closer look at the descriptive data (Fig 3), there were differences, without statistical significance but of interest, in the dimensions of physical role functioning, physical function, and bodily pain with worse results in patients with simple to moderate CHD, especially in comparison with normal data. Since patients with complex CHD usually have to be treated surgically postnatally and are now more often diagnosed during pregnancy than in previous decades, families have time to cope with the diagnosis. Furthermore, the need for repeated surgeries in the case of Fotan patients leads to those patients having to live with CHD from the beginning. They had to find coping strategies within their family as well as for their own, which leads to a higher sense of coherence with more mindfulness. ^{Reference Andonian, Freilinger and Achenbach43} In a recently published study, Moons et al. reported on the positive association of sense of coherence with QoL in a large study with 15 enrolled countries and concluded strategies to improve SOC may improve QoL. ^{Reference Muller, Hess and Hager44} However, the enhanced sense of coherence develops during childhood through the successful application of generalised resistance resources. ^{Reference Moons, Apers and Kovacs45} This implies that when patients experience new, life-altering situations due to CHD later in life, we need to accompany them to help them develop their coping strategies and improve their health-related quality of life. Further studies on adult CHD patients, especially those underinvestigated with a simple CHD, should be invited to get more knowledge about their needs and worries since they do not have regular appointments like patients with moderate or complex CHD. Once this has been done, the next step is to develop programmes that support and strengthen patients in dealing with their CHD.