Cardiac function in congenital diaphragmatic hernia : a longitudinal perspective

<p dir="ltr"><b>Background</b></p><p dir="ltr">Congenital diaphragmatic hernia (CDH), occurring in approximately 1 in 3,000 live births, remains a life-threatening condition despite advances in neonatal care. In recent years, cardiac function has been increasingly recognized as an important marker of disease severity. Current knowledge emphasizes the complex interplay between pulmonary hypoplasia, pulmonary hypertension, and biventricular dysfunction, and their impact on outcomes. Speckle-tracking echocardiography has emerged as a reproducible and user-friendly method for assessing myocardial strain, but its applicability and clinical value in CDH are uncertain, and published studies are limited by small sample sizes. It is plausible that severe illness in the neonatal period, accompanied by cardiac dysfunction, have lasting effects on cardiac performance and cardiovascular morbidity. However, little is known about cardiac function in older children and adolescents with CDH, and evidence on long-term cardiovascular morbidity is scarce.</p><p dir="ltr"><b>Aims</b></p><p dir="ltr">To explore cardiac function in children, adolescents, and young adults with CDH. To evaluate myocardial strain as a potential marker of disease severity. Further, to assess long-term cardiovascular morbidity in children and young adults with CDH.</p><p dir="ltr"><b>Method</b></p><p dir="ltr">Four studies were conducted using different methodological designs. In a registry-based study, we investigated whether children and young adults born with CDH had a higher risk of developing cardiovascular diagnoses compared with matched controls. A retrospective cohort study described cardiac function measured using strain and examined whether cardiac dysfunction correlated with prolonged length of stay (LOS) in the pediatric intensive care unit (PICU). A prospective study included a similar cohort of neonates born with CDH, aiming to describe cardiac function using strain analysis and to examine its association with LOS and milrinone use. Lastly, the thesis included an exploratory randomized crossover study that explored cardiac function in adolescents born with CDH and assessed cardiopulmonary responses to beetroot juice intake.</p><p dir="ltr"><b>Results</b></p><p dir="ltr">Individuals with CDH had markedly increased mortality in infancy and a higher risk of cardiovascular morbidity, including pulmonary hypertension, arrhythmia, and systemic hypertension, during follow-up. Neonates demonstrated impaired cardiac function at birth, with reduced left ventricle (LV), right ventricle, and atrial strain. LV dysfunction and smaller LV size were associated with longer intensive care. Although cardiac function improved over the first weeks of life, values remained below those of controls, and low LV strain values correlated with prolonged ventilation and stay in intensive care. Pharmacological support with milrinone was linked to longer intensive care overall, though early administration appeared beneficial. In adolescence, lower LV strain values than in controls were observed. In contrast to controls, who exhibited reduced exercise blood pressure and improved peak oxygen delivery, the CDH group showed no cardiovascular response to beetroot juice.</p><p dir="ltr"><b>Conclusion</b></p><p dir="ltr">The findings show that newborns with CDH have impaired cardiac function, and that the degree of cardiac dysfunction, measured using strain, correlates with a longer stay in the PICU. Early assessment of cardiac function may help guide treatment and potentially shorten the duration of intensive care. We found that cardiac function, measured using strain, improved but remained lower compared with in controls at one month of age and in adolescence. In adolescents with CDH, no cardiovascular response to organic nitrate intake was observed, in contrast to in the control group. These findings may help explain the increased risk of cardiovascular morbidity observed in this population and highlight the importance of systematic cardiovascular assessment and follow-up in individuals with CDH.</p><h3>List of scientific papers</h3><p dir="ltr">I. Hidden cardiovascular morbidity in children and young adults born with congenital diaphragmatic hernia: A population-based study. Tyden KO, Nordenstam F, Frenckner B, Burgos CM. J Pediatr Surg. 2022;57(11):510-5. <a href="https://doi.org/10.1016/j.jpedsurg.2022.03.028" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.jpedsurg.2022.03.028</a></p><p dir="ltr">II. Left atrial strain in neonates with congenital diaphragmatic hernia and length of stay in pediatric intensive care unit. Tyden KO, Mesas Burgos C, Jonsson B, Nordenstam F. Front Pediatr. 2024;12:1404350. <a href="https://doi.org/10.3389/fped.2024.1404350" rel="noreferrer" target="_blank">https://doi.org/10.3389/fped.2024.1404350</a></p><p dir="ltr">III. Cardiac function in children with congenital diaphragmatic hernia: cardiac strain at birth and at 2-5 weeks of age. Tyden KO, Magnusson K, Burgos CM, Jonsson B, Nordenstam F. Front Pediatr. 2025;13:1598695. <a href="https://doi.org/10.3389/fped.2025.1598695" rel="noreferrer" target="_blank">https://doi.org/10.3389/fped.2025.1598695</a></p><p dir="ltr">IV. Cardiac and Pulmonary Function in Teenagers with Congenital Diaphragmatic Hernia: A Matched-Control Study with a Double-Blinded Beetroot Juice Crossover. Tyden KO, Sorqvist E, Burgos CM, Carlstrom M, Nordenstam F. [Manuscript]</p>