The heart in congenital diaphragmatic hernia: Knowns, unknowns, and future priorities

Area of Science:

• Cardiology
• Developmental Biology
• Pediatric Surgery

Background:

• Congenital diaphragmatic hernia (CDH) is increasingly recognized to involve cardiac pathophysiology alongside lung and pulmonary vasculature abnormalities.
• Fetal cardiac morphology, including left heart hypoplasia, and early postnatal ventricular dysfunction are observed in CDH, correlating with adverse outcomes.

Purpose of the Study:

• To highlight the significant, yet incompletely understood, role of the heart in CDH pathophysiology.
• To identify key knowledge gaps including the genetic/cellular basis of cardiac dysfunction, longitudinal cardiac function, and impact on brain development.
• To emphasize the need for consensus on measuring cardiac function and pulmonary hypertension in CDH.

Main Methods:

• Review of existing investigations into cardiac morphology and function in CDH.
• Discussion of potential future research directions, including genetic and cellular studies.
• Consideration of non-invasive imaging and biomarkers for assessing cardiac function and pulmonary hypertension.

Main Results:

• Altered fetal cardiac morphology (e.g., left heart hypoplasia) is present in CDH.
• Early postnatal ventricular dysfunction is independently associated with adverse outcomes in CDH.
• Significant knowledge gaps persist regarding the genetic basis, long-term cardiac function, and systemic effects of CDH-related cardiac issues.

Conclusions:

• The heart plays a critical role in CDH pathophysiology, requiring further investigation.
• Standardized assessment of cardiac function and pulmonary hypertension is needed for individualized therapeutic strategies.
• Collaborative, multi-model approaches are essential to fully elucidate the heart's role in CDH and improve patient outcomes.