Patent Ductus Arteriosus: Diagnosis and Management and Recent Data

The diagnosis and management of Patent Ductus Arteriosus (PDA) vary significantly based on the patient’s age—ranging from the extremely preterm neonate to the adult—and the hemodynamic impact of the shunt.

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Diagnosis

Clinical Presentation

The clinical hallmark of a hemodynamically significant PDA is a continuous “machinery” murmur heard best at the left upper sternal border. In neonates and infants with large shunts, other findings include:

• Bounding pulses (due to a wide pulse pressure from diastolic runoff into the pulmonary circulation).
• Active precordium and signs of congestive heart failure (tachypnea, poor feeding, failure to thrive).
• Differential cyanosis (if pulmonary hypertension leads to a right-to-left shunt, affecting the lower body more than the upper body).

Echocardiography (Gold Standard)

Transthoracic echocardiography (TTE) is the definitive diagnostic tool. Key parameters used to assess hemodynamic significance include:

• Ductal Diameter: Often measured at the narrowest point (pulmonary end). A diameter >1.5 mm in preterm infants is often considered significant.
• Shunt Direction and Velocity: Predominantly left-to-right flow with low velocity suggests a large, unrestrictive ductus.
• LA/Ao Ratio: A left atrium to aortic root ratio >1.5 indicates significantly high pulmonary blood flow and left heart volume overload.
• Diastolic Flow Reversal: Retrograde flow in the descending aorta or mesenteric arteries indicates “ductal steal,” compromising systemic perfusion.

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Management Strategies

1. Conservative Management

In recent years, particularly for preterm infants (<32 weeks), there has been a significant shift toward conservative or expectant management. Emerging trial evidence suggests that early routine pharmacological closure does not improve outcomes like bronchopulmonary dysplasia (BPD) or mortality and may, in some cases, be associated with increased risks. Conservative measures include:

• Fluid restriction and optimized PEEP/ventilatory support.
• Wait-and-watch approach, as many PDAs close spontaneously even in extremely low birth weight infants.

2. Pharmacological Closure

Indicated primarily in symptomatic preterm infants when conservative measures fail.

• NSAIDs: Indomethacin and Ibuprofen are traditional first-line agents. They act by inhibiting prostaglandin synthesis.
• Paracetamol (Acetaminophen): Increasingly used as an alternative with a potentially better safety profile regarding renal and gastrointestinal side effects, though its efficacy compared to Ibuprofen remains a subject of ongoing clinical debate.

3. Transcatheter Device Closure

This is the procedure of choice for most children and adults.

• Devices: Tools like the Amplatzer Piccolo Occluder have expanded the feasibility of percutaneous closure to very low birth weight infants (>700 – 800 g).
• Technique: Usually performed via venous access (antegrade) or arterial access (retrograde). Recent data highlights the safety of “venous-only” access to minimize arterial complications in small infants.

4. Surgical Ligation

Reserved for cases where transcatheter closure is technically impossible, such as:

• Extremely small infants where even specialized devices cannot be safely deployed.
• Ductal anatomy (e.g., very short or window-like) that is not amenable to device occlusion.
• Failure of medical therapy in a critically ill neonate.

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The PDA Randomized Clinical Trial

This multicenter, randomized clinical trial published in JAMA randomized 482 extremely preterm infants to either expectant management or active treatment (ibuprofen, indomethacin, or paracetamol). The study found no significant difference in the composite primary outcome of death or bronchopulmonary dysplasia at 36 weeks. Critically, mortality was significantly lower in the expectant management group (4.1%) compared to the active treatment group (9.6%), with a lower incidence of infections resulting in death in the expectant group.

A meta-analysis of 10 RCTs involving 2,035 infants, published in JAMA Pediatrics found that the incidence of death or moderate-to-severe BPD was higher in the active treatment group compared to the expectant management group.

BeNeDuctus Trial

The BeNeDuctus trial is a landmark study that has fundamentally challenged the long-standing “rush to close” approach for Patent Ductus Arteriosus (PDA) in extremely preterm infants. Expectant management was found to be non-inferior to early ibuprofen treatment. The primary outcome occurred in 46.3% of the expectant management group compared to 63.5% in the early ibuprofen group. The composite primary outcome included necrotizing enterocolitis (Bell’s stage IIa or higher), moderate to severe bronchopulmonary dysplasia, or death at 36 weeks’ postmenstrual age. It was multicenter, noninferiority trial, of infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<28 weeks’ gestational age).

Baby-OSCAR trial

The Baby-OSCAR (Outcome after Selective early Closure of Arterial duct) trial is one of the definitive studies that helped shift neonatal practice toward a more conservative approach regarding Patent Ductus Arteriosus. There was no significant difference in the composite outcome of death or moderate-to-severe BPD at 36 weeks of postmenstrual age. The trial reinforced that early treatment with ibuprofen does not provide a clear clinical benefit over waiting, even when the PDA appears hemodynamically significant on early echocardiography.