(A) A normal postnatal heart has left-to-right shunting at PFO and PDA with the interventricular septum (IVS) bulging to the right. (B) In mild-to-moderate PPHN, the IVS can be midline with bidirectional shunts at PFO/PDA. Increased right ventricular (RV) afterload is compensated by increased RV contractility. High velocity tricuspid regurgitation (TR) is observed. (C) In severe PPHN, the PFO and PDA shunt right-to-left with IVS bulging to the left decreasing left ventricular (LV) preload. Extremely high RV afterload leads to uncoupling of RV function leading to RV dilation. An open PDA might benefit the RV by providing a pop-off mechanism to reduce RV afterload. (D) When severe PPHN is associated with LV dysfunction, pulmonary venous hypertension and high pressure in the LA leads to left-to-right shunt at PFO but right-to-left shunt at PDA. Inhaled nitric oxide (NO), as well as other therapies that lower pulmonary vascular resistance, can precipitate pulmonary edema in pulmonary venous hypertension if LV failure or other forward flow obstructions are present. In the setting of LV dysfunction, postductal systemic perfusion is supplemented by a transductal right to left shunt. Copyright Satyan Lakshminrusimha.