Vibeke Elisabeth Hjortdal

Positive pressure ventilation increases the intrathoracic pressure and the central venous pressure, impeding venous return to the heart. Likewise, both central and peripheral lymphatic function is haltered during positive pressure ventilation, presenting as a possible explanation for fluid retention and edema in post‐operative and intensive care unit patients. We aimed to examine the effects of biphasic cuirass ventilation on the peripheral lymphatic system. Peripheral lymphatic function was examined in twenty healthy, young adults during spontaneous breathing and during biphasic cuirass ventilation. The peripheral lymphatic function was assessed with near‐infrared fluorescence imaging, and the microvascular circulation was assessed with strain gauge plethysmography. Mean peripheral lymphatic contraction frequency (mean ± SD) was 1.46 0.73/min at baseline and 1.43 0.76/min during biphasic cuirass ventilation. There was no significant difference (mean difference = 0.03, 95% CI: −0.23–0.29, p = 0.81, n = 19). Capillary filtration rates did not differ between baseline and biphasic cuirass ventilation across all pressure levels ( F (1,18) = 1.13, p = 0.30). Likewise, there were no significant differences in isovolumetric pressures (mean difference = −2.61, 95% CI: −8.92–3.71, p = 0.39, n = 15), or capillary filtration coefficients (mean difference = 1.21 × 10 ⁻⁴ , 95% CI: −4,87 × 10 ⁻⁴ – 7.29 × 10 ⁻⁴ , p = 0.68, n = 19). We observed no changes in peripheral lymphatic activity in awake, healthy, young adults during BCV.

Objective: Infertility affects up to 20% of couples in high‐income countries, which has led to an increased use of assisted reproductive technology (ART). While previous studies have linked ART to a higher risk of major congenital heart defects (CHD), less is known about the associated risk of minor CHD. As minor CHD are associated with premature early‐onset cardiac morbidity and mortality, this study aimed to evaluate the risk of minor CHD in singleton infants conceived via ART compared with in those conceived spontaneously. Methods: The Copenhagen Baby Heart Study (CBHS) is a Danish, prospective, multicenter study of neonates delivered between 1 April 2016 and 31 October 2018. Included in this cohort study based on CBHS data were singleton infants who met the inclusion criteria and had undergone neonatal transthoracic echocardiography (TTE) within 60 days after birth. Infants conceived via ART, defined as either in‐vitro fertilization or intracytoplasmic sperm injection, were matched randomly, based on sex and maternal age, in a 1:4 ratio with spontaneously conceived singleton infants, who formed the control group. The primary outcome was the diagnosis of minor CHD, defined as a ventricular septal defect (VSD), bicuspid aortic valve (BAV) and/or atrial septal defect (ASD), detected on neonatal TTE. For analysis of ASD, we assessed a subgroup of the matched infants included within the overall cohort who were evaluated using TTE from 15 May 2017 onwards using an algorithm for the TTE classification of interatrial communications implemented in the CBHS. Using multiple logistic regression analysis, we compared the risk of minor CHD in infants conceived via ART vs those conceived spontaneously, adjusting for maternal age, parental CHD, pregestational diabetes mellitus and maternal body mass index. Results: Of 23 493 infants who met the inclusion criteria, 1630 singletons were conceived by ART. These were matched with 6520 controls who were conceived spontaneously. The subgroup of infants evaluated using the algorithm for TTE classification of interatrial communications comprised 862 infants conceived by ART and 3448 matched infants who were conceived spontaneously. The risk of minor CHD overall (VSD, BAV and/or ASD) in the subcohort evaluated using this algorithm was not significantly different between singleton infants conceived via ART and those conceived spontaneously (adjusted odds ratio, 1.07 (95% CI, 0.83–1.38)). Furthermore, we observed no significant differences in the risk of specific minor CHD subtypes (VSD, BAV and/or ASD) between singleton infants conceived via ART and those conceived spontaneously. Similarly, no significant differences in the risk of minor CHD were observed between ART subtypes, including conception via fresh in‐vitro fertilization, fresh intracytoplasmic sperm injection and fresh‐ and frozen‐embryo transfer, or between each ART subtype and infants conceived spontaneously. Conclusion: There was no increased risk of minor CHD in singleton infants conceived via ART compared with singleton infants conceived spontaneously. These findings provide reassuring evidence that ART is unlikely to impose an increased long‐term cardiovascular risk attributable to subclinical minor CHD that would otherwise remain undiagnosed in the absence of screening. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The lymphatic system plays a fundamental role in cardiovascular physiology by maintaining whole-body fluid balance, facilitating immune trafficking, and enabling lipid transport. Through these functions, lymphatic performance is tightly coupled to cardiovascular health, and disturbances in lymphatic flow, pumping, or lympho-venous return can directly influence the development and progression of heart disease. This review examines the relationship between the lymphatic and cardiovascular systems with an emphasis on systemic lymphatic function and its relevance to cardiovascular pathology. We describe the structure and physiology of the human lymphatic vasculature, including mechanisms governing lymph formation, transport, and return to the venous circulation, and discuss how these processes are challenged in conditions such as heart failure, venous congestion, and altered hemodynamics. Clinical and experimental evidence linking lymphatic dysfunction to edema, inflammation, and impaired organ function across multiple cardiovascular disease states – including heart failure, atherosclerosis, congenital heart disease, and heart transplantation – is considered. In addition, comparative and translational perspectives are presented illustrating how diverse vertebrate lymphatic strategies inform fundamental principles of lymphatic regulation and translational cardiovascular research. Finally, emerging imaging modalities and therapeutic approaches targeting lymphatic structure and function are discussed as potential avenues for improving the diagnosis and treatment of cardiovascular disease. Together, this review positions the lymphatic system as an integral, system-level contributor to cardiovascular physiology and disease, underscoring the need to consider lymphatic function alongside the blood circulation in both research and clinical practice.

Lymphatic disease represents a well‐described manifestation of Noonan syndrome (NS), yet the full phenotypic spectrum remains incompletely characterized, especially in asymptomatic individuals. We conducted a cross‐sectional study including 10 individuals with NS (four with peripheral lymphedema and six without) and 10 age‐ and sex‐matched cardiovascularly healthy controls. Central lymphatic anatomy was visualized using non‐contrast T2‐weighted MR‐lymphangiography, and peripheral lymphatic morphology and function were assessed with near‐infrared fluorescence (NIRF) imaging and strain gauge plethysmography (SGP). Variations in thoracic duct morphology were observed in 89% (8/9) of NS individuals compared to 20% (2/10) of controls. Thoracic lymphatic classifications (Biko/Dori scale) differed significantly in NS individuals, both with and without lymphedema, compared with healthy controls ( p < 0.05). Central lymphatic abnormalities were observed in five of nine NS individuals, including three without clinical signs of lymphatic disease. Abnormal peripheral conduction in collective vessels, characterized by retrograde or absent flow, was detected in all four NS individuals with lymphedema ( p < 0.05), while normal conduction was observed in asymptomatic NS individuals and controls. Findings from this study indicate that central lymphatic abnormalities may be present in NS regardless of symptom status, with abnormal peripheral conduction developing later in association with clinically manifest lymphedema. Central lymphatic abnormalities extend beyond clinically apparent disease and broaden the recognized phenotype, highlighting the value of lymphatic imaging for diagnosis and monitoring.

While much is known about the risks associated with complex congenital heart defects (CHDs), research on the emotional and behavioural outcomes in children with ventricular septal defects (VSDs), the most common form of CHDs, remains limited. Evidence of increased psychiatric morbidity and social challenges in adults with VSDs underscores the importance of addressing emotional and behavioural difficulties earlier in life. We conducted a cross-sectional national survey of Danish children aged 5-17 years (born between 2007 and 2019) with VSDs (n = 704, 248 surgically treated), using the Strengths and Difficulties Questionnaire (SDQ) to compare parent-reported emotional and behavioural difficulties with normative data stratified by age and sex. We examined whether children with probable psychiatric disorders (per SDQ algorithms) had received mental health support and whether parents reported unmet support needs. Parent-reported difficulties were higher across all SDQ scales compared to normative data. When stratified by sex, girls especially exhibited more hyperactivity/inattention, conduct, peer, and prosocial difficulties, while boys showed more emotional challenges. Only approximately half of children with a probable psychiatric disorder had received mental health support, and 65.3% of their parents reported unmet needs. Children with VSDs exhibited significantly more emotional and behavioural difficulties compared to the general population, highlighting critical gaps in mental health support and the need for greater awareness and targeted interventions.

Background: Despite multiple surgeries and extensive follow‐up, individuals with a univentricular heart have significant residual morbidity and mortality throughout life. By applying a state‐of‐the‐art characterization of the plasma proteome, this study aimed at providing a comprehensive insight into the proteomic impact of living with a Fontan circulation. Methods and Results: This study enrolled individuals with a Fontan circulation and compared them 2:1 with healthy controls. Relative quantification of the levels of 2943 plasma proteins was performed using Olink Explorer 3072 panels. The unprecedented number of plasma proteins constitutes the most detailed characterization of the Fontan proteome to date. A total of 87 individuals, 58 with a Fontan circulation age 26 (23–38) and 29 healthy controls age 24 years (20–27) were included. Following quality control 2605 proteins were quantifiable. Of these, 513 were changed in the group with Fontan (424 increased and 89 decreased) after covariate adjustment for age, sex, and body mass index . Looking at the related biological function(s), a pathway enrichment analysis found that proteins involved in angiogenesis, bone and calcium homeostasis, metabolism, and inflammation and fibrosis increased, whereas proteins involved in cholesterol synthesis and muscle structure and function were decreased. Conclusions: This study represents a small step in understanding the pathophysiological consequences of the Fontan circulation. Based on biological pathways and proteins displaying changes, we speculate local hypoxia to be a potential driver for multiple of the reported changes. This study provides the foundation and direction for future studies wanting to examine changes in detail or explore possible therapeutic targets.

Background: Identifying modifiable risk factors for congenital heart disease (CHD) is important for prevention. Previous studies have reported associations between 25‐hydroxyvitamin D (25(OH)D) in pregnancy and CHD in the offspring. However, these studies contain important methodological limitations. We aimed to investigate 25(OH)D levels during pregnancy in relation to offspring risk of CHD using both multivariable regression (MVR) analysis and Mendelian randomization (MR) analysis. Methods: Data from the ALSPAC (Avon Longitudinal Study of Parents and Children), BiB (Born in Bradford), and MoBa (Norwegian Mother, Father and Child Cohort) studies (N=8722 (77 cases) for MVR analysis, N=74 953 (646 cases) for MR) were used. MVR analysis was adjusted for offspring sex, maternal age, education, body mass index, smoking, alcohol consumption, and parity. One sample MR was performed with weighted genetic risk score for 25(OH)D based on published genome‐wide significant genetic variants. Sensitivity analyses explored the relevance and validity of the genetic risk score. Results were pooled across the 3 cohorts in a meta‐analysis with random effects and consistency between results from the MVR and MR was examined. Results: Pooled results from the adjusted MVR suggested higher maternal pregnancy 25(OH)D associated with lower CHD risk, though the CIs were wide and included the null (odds ratio [OR], 0.79 [95% CI, 0.53, 1.06] per 1 SD higher 25(OH)D). By contrast precise MR results did not support a causal relationship (OR, 0.99 [95% CI, 0.91, 1.07] per 1 SD higher 25(OH)D genetic risk score). Conclusions: We did not find robust evidence supporting an effect of maternal pregnancy 25(OH)D levels on offspring CHD.

Background: Low Apgar scores have been associated with an increased risk of brain injury and neurodevelopmental disorders in newborns with congenital heart defects (CHDs). However, the relation between CHD subtypes and low Apgar scores remains unknown. This study aimed to assess the association between major subtypes of CHD and low (<7) Apgar scores at 5 minutes. Methods and Results: This population‐based study included 1 040 474 liveborn singletons in Denmark from 1997 to 2013. The association between CHD and low Apgar scores was estimated by confounder‐adjusted, multivariable logistic regression. In mediation analyses, the underlying mechanisms were examined. Low Apgar scores were present in 3.0% of newborns with CHD and in 0.7% of newborns without CHD. Overall, CHD was associated with an increased risk of a low Apgar score (adjusted odds ratio, 2.5 [95% CI, 2.1–3.0]). CHD subtypes associated with the highest risks were anomalous pulmonary venous return (adjusted odds ratio, 5.7 [95% CI, 2.2–14.9]), hypoplastic left heart syndrome (adjusted odds ratio, 5.1 [95% CI, 2.2–11.8]), and transposition of the great arteries (adjusted odds ratio, 3.5 [95% CI, 1.7–7.4]). In mediation analyses, preterm birth explained 25.2% (95% CI, 11.8–38.6) of the association between CHD and low Apgar scores. Conclusions: Nearly all CHD subtypes were associated with an increased risk of a low Apgar score. The association was most pronounced in severe and potentially cyanotic types of CHD. These findings suggest that CHD is associated with a complicated fetal‐to‐neonatal transition and highlight the potential for improvements of this process in infants with CHD.

We evaluated the association between cardiopulmonary bypass (CPB) time during surgery for acute type A aortic dissection (ATAAD) and mid-term survival. Data of 1122 patients who underwent surgery for ATAAD in eight Nordic centers from January 2005 to December 2014 were retrospectively analyzed. An adjusted logistic regression analysis was performed to investigate the association of incremental 30 min CPB time on 30-day mortality. In addition, the patients were divided into those that underwent surgery with >210 min (n = 369) or p < 0.001). Mid-term survival for all patients was inferior in the >210 min group as compared with the 210 min as compared with <210 min. Prolonged CPB time is associated with higher 30-day mortality and inferior mid-term survival but not with inferior reoperation-free survival after surgical repair of ATAAD.