Case September 2025 - Functional PV stenosis in a premature infant

Gabriel Altit, MDCM, FRCPC, FASE - September 7, 2025

Introduction: The case of September 2025 features a premature infant with functional pulmonary atresia, illustrating the dynamic evolution of this rare physiology. Over the course of 48 hours, multiple targeted neonatal echocardiography (TNE) assessments were performed to follow the hemodynamic changes and guide management. The case allows us to revisit the rare physiology and clinical presentation of functional pulmonary atresia in preterm infants, where forward flow across the pulmonary valve is absent despite the presence of an anatomically patent valve, and pulmonary circulation becomes ductal-dependent. In this review, we approach the TNEs as we would in our neonatal hemodynamics fellowship teaching program, going through the clips briefly, interpreting the findings step by step, and integrating them into the evolving clinical context. This case emphasizes the value of structured and repeated hemodynamic assessments in tailoring therapy, optimizing right ventricular performance, and balancing systemic and pulmonary circulations. By applying precision care hemodynamics, bedside decisions were refined to match the infant’s physiology, highlighting the central role of TNE in managing complex transitional cardiovascular states.

This was an extremely premature infant born at 25 weeks’ gestation with severe intrauterine growth restriction (IUGR) and a birth weight of 550 g. The antenatal course was remarkable for prolonged anhydramnios beginning at 16 weeks, raising strong suspicion for pulmonary hypoplasia. At birth, the infant developed profound hypoxic respiratory failure. Initial resuscitation included positive pressure ventilation (PPV), endotracheal intubation, and surfactant administration. Despite these measures, oxygenation remained poor, and the infant was transitioned to high-frequency oscillatory ventilation (HFOV) with a mean airway pressure of 16 cmH₂O and volume guarantee of 2.5 mL/kg. FiO₂ remained at 100%, with oxygen saturations fluctuating around 75%. No differential saturation was observed. The clinical impression was that of severe respiratory failure with a component of acute pulmonary hypertension (persistent pulmonary hypertension of the newborn, PPHN). Inhaled nitric oxide (iNO) was initiated at 10 ppm, leading to only a transient improvement in oxygenation; escalation to 20 ppm provided no further benefit. Laboratory evaluation revealed a severe respiratory acidosis (pH 7.08, pCO₂ 84 mmHg). Vital signs included a blood pressure of 35/17 mmHg (MAP 22), heart rate 156 bpm, and temperature 36.2°C. 

Despite severe hypoxemia, perfusion and lactate levels were reassuring. A central umbilical venous line was established, though arterial line placement was unsuccessful. Chest radiography showed a bell-shaped thorax with markedly reduced lung volumes, consistent with pulmonary hypoplasia. Given the severity of hypoxemia, refractory respiratory acidosis, and suspected interplay of pulmonary hypoplasia, respiratory distress syndrome (RDS), and PPHN, the team requested a targeted neonatal echocardiography (TnECHO) at six hours of life. The primary objectives were to assess biventricular function, pulmonary pressures, ductal shunting, and systemic perfusion in order to guide hemodynamic and respiratory management. Over the next 48 hours, four sequential echocardiographic studies were performed. These serial assessments illustrate the dynamic physiology of such fragile infants and how TnECHO can be used to titrate therapy and refine clinical decision-making in real time.

Functional pulmonary valve atresia is a unique hemodynamic condition characterized by a pulmonary valve that is anatomically normal but fails to open during ventricular systole. This phenomenon is most frequently observed in infants presenting with Ebstein's anomaly (one exemple outlined in the Ebstein's anomaly section) of the tricuspid valve, a congenital heart defect affecting approximately 0.08 to 0.1 per 1000 live births and contributing to 8-12% of congenitally malformed hearts. It can also rarely occur in neonates with structurally normal hearts but poor right ventricular (RV) function with no antegrade output via the RV outflow tract (as outlined in the September 2025 case here). The valve annulus is often present and sometimes even of normal size, but the leaflets fail to open due to severe right ventricular dysfunction, elevated right ventricular end-diastolic pressures, or extreme hypoxemia and acidosis leading to a transiently closed valve. This physiology is seen most often in critically ill neonates with severe pulmonary hypertension, depressed right ventricular systolic performance, or those recovering from perinatal asphyxia.

The pathophysiology behind functional pulmonary atresia is rooted in the inability of the right ventricle to generate sufficient flow to overcome the pulmonary afterload and open the pulmonary valve. In severe Ebstein's anomaly, several factors contribute to this: a dysfunctional RV with poor contractile force, a major portion of the RV wall being severely thin, or significant tricuspid regurgitation (TR). The naturally high pulmonary vascular resistance (PVR) in the neonatal period further exacerbates this issue. Moreover, if a patent ductus arteriosus (PDA) is widely open, it transmits systemic aortic pressure to the pulmonary artery, which can then exceeds the RV pressure, thereby preventing the pulmonary valve from opening. The administration of prostaglandin E1 (PGE1), while vital for maintaining ductal patency, can paradoxically induce or worsen functional atresia by dilating the PDA excessively. The displaced tricuspid valve leaflet, characteristic of Ebstein's anomaly, can also obstruct the right ventricular outflow tract (RVOT), further diminishing the pressure proximal to the pulmonary valve. The pathophysiology of functional pulmonary atresia within normal cardiac configuration is often secondary to significant RV dysfunction, superimposed on high RV afterload. This can be nested in adverse perinatal transition with severe acidosis (which can be quite detrimental to the myocardium). 

Clinically, neonates with functional pulmonary atresia present with cyanosis, which may be mild at birth if the PDA provides adequate pulmonary blood flow. Recognizing and differentiating functional pulmonary atresia from true anatomical pulmonary atresia is paramount because their management strategies are distinctly different. Echocardiography serves as the primary diagnostic tool. Key echocardiographic features indicative of functional atresia include: a pulmonary valve that appears morphologically normal but shows no antegrade flow during systole. The valve typically appears thin and membranous, lying flat during systole rather than demonstrating the doming seen in some forms of stenosis. The presence of pulmonary regurgitation (PR), particularly with a high velocity, is a distinguishing sign, often visualized as yellow or red flow by color Doppler. In contrast, anatomical atresia typically involves a dysmorphic, thickened, and narrowed pulmonary valve annulus. A wide tricuspid valve annulus and a low tricuspid regurgitation velocity (<3.5 m/s) in a setting suggestive of pulmonary atresia can raise suspicion for functional atresia. Additionally, transient opening of the pulmonary valve with forward Doppler flow during positive pressure ventilation strongly suggests functional atresia. Fetal echocardiography in the case of Ebstein can also detect forward flow or PR through the RVOT, aiding early diagnosis. A definitive diagnostic criterion for functional atresia is the opening of the pulmonary valve in response to inhaled nitric oxide (NO), which lowers PVR, a response not seen in anatomical atresia.

The management of functional pulmonary atresia focuses on medical treatment to reduce pulmonary vascular resistance using oxygen and nitric oxide, as well as the consideration for PGE to maintain the duct open (or close monitoring to ensure that it does not close while the phenotype is not yet rescued). Crucially, no attempts should be made to surgically or interventionally open the outflow tract. Maintaining PDA patency with PGE1 may be necessary (especially if the duct becomes restrictive). Indeed, an open non-restrictive ductus will equalize pressure from the Aorta to the Pulmonary Artery. Over time, as neonatal PVR decreases, the TR decreases and the RV function improves the right ventricle might be able to generate sufficient antegrade blood flow through the pulmonary valve, potentially maintaining pulmonary circulation without the need for a PDA. In transient cases associated with severe but reversible pulmonary hypertension, restoration of forward pulmonary flow may occur within hours to days as pulmonary vascular resistance falls and right ventricular function improves. In other cases, persistence of dysfunction may lead to ongoing ductal-dependence, risk of progressive right ventricular dilation, and secondary systemic complications.