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

Abstract

There is growing recognition that the heart is a key contributor to the pathophysiology of congenital diaphragmatic hernia (CDH), in conjunction with developmental abnormalities of the lung and pulmonary vasculature. Investigations to date have demonstrated altered fetal cardiac morphology, notably relative hypoplasia of the fetal left heart, as well as early postnatal right and left ventricular dysfunction which appears to be independently associated with adverse outcomes. However, many more unknowns remain, not least an understanding of the genetic and cellular basis for cardiac dysplasia and dysfunction in CDH, the relationship between fetal, postnatal and long-term cardiac function, and the impact on other parts of the body especially the developing brain. Consensus on how to measure and classify cardiac function and pulmonary hypertension in CDH is also required, potentially using both non-invasive imaging and biomarkers. This may allow routine assessment of the relative contribution of cardiac dysfunction to individual patient pathophysiological phenotype and enable better, individualized therapeutic strategies incorporating targeted use of fetal therapies, cardiac pharmacotherapies, and extra-corporeal membrane oxygenation (ECMO). Collaborative, multi-model approaches are now required to explore these unknowns and fully appreciate the role of the heart in CDH.

Inotropic score and vasoactive inotropic score as predictors of outcomes in congenital diaphragmatic hernia: A single center retrospective study

“…This pulmonary vasculature is maladaptive and maldeveloped as a result of this prenatal insult, thus leading to pulmonary hypertension. The resultant reduced pulmonary blood flow in the setting of this pulmonary hypertension causes decreased pulmonary venous return to the left atrium, and ultimately can lead to postnatal systemic hypotension ( 15 , 17 ). The RV dilation and hypertrophy alter the myocardial contractility as ventricular inter-dependence is compromised due to septal displacement.…”

“…Left ventricular hypoplasia is thought to be a product of mechanical compression of the fetal heart by the herniated contents in the thoracic cavity ( 19 ). Re-direction of ductus venosus and inferior vena cava (IVC) flow away from the foramen ovale leads to decreased LV preload and inadequate fetal myocardial growth ( 15 , 20 ). Additionally, postnatal stress with elevated systemic vascular resistance (SVR) after placental separation further worsens ventricular dysfunction and is associated with adverse postnatal outcomes ( 14 , 16 , 21 , 22 ).…”

“…The RV dilation and hypertrophy alter the myocardial contractility as ventricular inter-dependence is compromised due to septal displacement. With inadequate RV contractility and increased RV afterload, a vicious cycle of decreased pulmonary blood flow, with further reduction in pulmonary venous return, and thus lower LV preload with resultant systemic and coronary hypoperfusion and worsening myocardial contractility ensues ( 15 , 17 , 23 ).…”

“…Various fetal and postnatal mechanisms for LV dysfunction in the CDH population have been hypothesized, such as underdeveloped left sided cardiac structures, increased SVR and ventricular interdependence (15)(16)(17). Early fetal echocardiograms show evidence of smaller left heart structures (16,18).…”

Early Ductal Shunting Patterns in Neonates with Congenital Diaphragmatic Hernia Predict Clinical Outcomes

“…Subsequent left ventricle (LV) dysfunction may ensue via the ventricular interdependence between the RV and LV as both ventricles share the interventricular septum (IVS), encircling myocardial bers, and the pericardium. 19 Acute dilation of the RV also results in bulging of the IVS into the left ventricular chamber, thus impairing LV diastolic lling and elevating LV end-diastolic pressure (LVEDP). In normal conditions, the IVS contributes to both LV and RV functions and is responsible for one-third of RV stroke work.…”