Patent ductus arteriosus

What is patent ductus arteriosus?

Patent ductus arteriosus (PDA) occurs in 5-10% of all congenital heart defects occurring in babies born at term.

PDAs are very common in preterm babies; 70% of babies born weighing less than 1 kg will have a PDA on day 7 of life.¹ 50% of babies born at less than 26 weeks will have a PDA at 2 months of age.²

It is important to recognise that PDA in the preterm infant and PDA in term babies and older children are two very distinct conditions with different implications and management. This article primarily focuses on the PDA as a congenital heart defect, with a separate section dealing with PDA in preterm babies at the end.

Physiology

The ductus arteriosus is, in developmental terms, a remnant of the sixth aortic arch and connects the pulmonary artery to the proximal descending aorta just after the left subclavian artery origin. It is a normal structure in fetal life.

In utero the lungs are not expanded. Gas exchange occurs at the placenta and only about 10% of the circulation passes through the lungs. The ductus arteriosus connects the pulmonary artery to the aorta to shunt most of the blood away from the lungs. After delivery it closes and the blood passes through the opened lungs. Failure of the closure of the ductus arteriosus can lead to overloading of the lungs. The shunt is left to right unless pulmonary hypertension occurs and pulmonary pressure exceeds systemic pressure.

After birth the ductus closes functionally in 12-18 hours and anatomically in 2-3 weeks. If it remains open beyond three months of life in preterm infants and beyond one year of life in full-term infants it is termed as persistent patency of ductus arteriosus because the incidence of spontaneous closure beyond these time limits is very low.

The ductus arteriosus is likely to close without treatment in most infants born at gestational age over 28 weeks (73%), and those with birth weight over 1000 g (94%).³

How common is patent ductus arteriosus? (Epidemiology)

• In babies born at term the incidence is reported as 1 in 2,000 births which accounts for 5-10% of all congenital heart defects. If children with silent PDA (discovered incidentally by echocardiography done for another purpose) are included, the incidence increases to 1 in 500 births.²

• It affects girls twice as often as boys.

Risk factors⁴

• Genetic syndromes such as trisomy 21 and Holt-Oram syndrome.

• Exposure of a fetus to valproic acid, cocaine, calcium channel blockers or magnesium in pregnancy.¹

• Maternal diabetes.¹

• Extreme prematurity.

• Respiratory distress syndrome.

• Neonatal sepsis.

• Birth at high altitude.

• Neonatal administration of loop diuretics, aminoglycosides, cimetidine, heparin or excessive fluids.¹

Patent ductus arteriosus symptoms (presentation)

History

• Patients with a small PDA are often asymptomatic.

• A large-shunt PDA may cause lower respiratory tract infection as well as feeding difficulties and poor growth during infancy, with failure to thrive because of heart failure.

Examination

• If the pulmonary circulation is markedly overloaded there will be tachycardia, tachypnoea and a wide pulse pressure.

• Peripheral pulses are bounding as the run-off into the pulmonary circulation drops the diastolic pressure and causes a wide pulse pressure.

• Hypotension is often present in babies <1 kg in weight.¹

• A grade 1 to 4/6 continuous ('machinery') murmur may be heard, best audible at the left infraclavicular area or upper left sternal border and radiating through to the back.

• However, a PDA may cause a systolic murmur with a normal first heart sound, rather than the classic continuous murmur.

• A systolic thrill may be present at the upper left sternal border.

• In the case of a large PDA shunt, a diastolic mitral rumble may be heard because of the high flow rate across the mitral valve.

• Patients with a small PDA do not have the above-mentioned findings.

Differential diagnosis

A number of conditions present with a murmur similar to the continuous murmur of PDA or with bounding pulses, and require differentiation from PDA. These include:

• Coronary arteriovenous fistula.

• Systemic arteriovenous fistula.

• Pulmonary arteriovenous fistula.

• Venous hum.

• Fallot's tetralogy (with absent pulmonary valve).

• Ruptured aneurysm of the sinus of Valsalva (seen in Marfan's syndrome).

• Aortopulmonary septal defect (aortopulmonary window).

Investigations

The only investigation needed to confirm the diagnosis and significance of PDA is echocardiography. Occasionally, CXR and ECG are also performed.

• Echocardiography confirms the diagnosis and characterises the anatomy and physiology of the PDA. A complete echocardiogram includes measurement of cardiac chambers and function, two-dimensional imaging of PDA anatomy and Doppler assessment to define PDA shunt flow. The ratio of left atrial size to aortic root size can be used to estimate the degree of PDA shunt.

• If the shunt is significant, CXR will show enlargement of the pulmonary arteries, veins, left atrium and left ventricle. Such features usually require a ratio of pulmonary flow to systemic flow of at least 2:1. In older people a PDA may be calcified and visible on a plain film.

• ECG is often normal in small or moderate PDA but there may be signs of left ventricular hypertrophy (LVH). A large PDA may be associated with signs of biventricular hypertrophy (BVH) and in those with pulmonary hypertension, right ventricular hypertrophy (RVH) may be present.

Treatment of patent ductus arteriosus

• In term or near-term infants, conservative management may be sufficient whilst awaiting spontaneous closure. This may involve careful fluid restriction and increasing peak end-expiratory pressure to treat pulmonary oedema in infants with a large PDA.¹

• Indometacin is ineffective in term infants with PDA and should not be used. However, indometacin, ibuprofen or paracetamol may be effective in preterm infants.

• PDA closure is indicated for any symptomatic infant, child or adult (with exclusion of those with fixed high pulmonary vascular resistance). Closure is also indicated in asymptomatic patients with left heart volume load. This can be done either by surgery or interventional techniques at any age.²

• Surgical closure is reserved for patients in whom a non-surgical closure technique is not considered applicable. In infants with heart failure or pulmonary hypertension, surgery is performed on an urgent basis. The standard surgical procedure is ligation and division of the ductus through left posterolateral thoracotomy without cardiopulmonary bypass.

• In asymptomatic well infants, current practice is to wait until 1 year of age, with regular echocardiographic evaluation to check for spontaneous closure of the PDA. If the duct is still patent at 1 year of age it can be closed usually by occlusion at cardiac catheterisation (endovascular occlusion). National Institute for Health and Care Excellence (NICE) guidance has been produced and considers that current evidence on the safety and efficacy of endovascular occlusion of PDA appears to support the use of this procedure.⁵ The procedure should be performed in units where there are arrangements for cardiac surgical support in the event of complications. The choice of device depends largely on the size of PDA.

• Serious complications of transcatheter closure of PDA are rare and include device embolisation, femoral artery or vein thrombosis related to vascular access and infection.⁶

• Whilst the ductus arteriosus is patent then the risk of endocarditis should be considered (there is no increased risk of endocarditis once repair is complete). Routine antibiotic prophylaxis is not indicated but during invasive procedures (eg, urinary or gastrointestinal procedures) involving areas of sepsis, suitable antibiotics should be given promptly (to cover all the likely organisms, including any known to cause endocarditis).⁷

Complications

Many patients with small PDAs do not have any haemodynamic overload and apart from the risk of endarteritis have a normal prognosis. Those with significant left heart volume load can develop congestive heart failure or irreversible pulmonary vascular disease.¹

Prognosis

• In most older patients successful closure of the PDA can be achieved without complications, and long-term follow-up is not required.

• Children who have had a PDA closed need no further restrictions on their lives.

Patent ductus arteriosus in preterm neonates

The ductus arteriosus remains patent at day 4 after birth in about 10% of preterm infants born at 30-37 weeks of gestational age, 80% of those born at 25-28 weeks, and 90% of those born at 24 weeks. At day 7 after birth, these rates decline to approximately 2%, 65%, and 87%, respectively. Therefore, extremely preterm infants born at gestational age of less than 28 weeks are at the highest risk of developing a haemodynamically significant PDA and the related complications.³

• In a preterm infant, PDA should be suspected if the respiratory distress because of hyaline membrane disease does not improve or worsens after initial improvement and the baby cannot be weaned off the ventilator.

• In the premature infant of low birth weight, the classical signs are usually absent. The continuous murmur is rarely heard. There may be a rough systolic murmur along the left sternal border but a small baby with a large PDA and significant pulmonary over-circulation may have no murmur. Physical examination commonly reveals bounding peripheral pulses, a hyperactive precordium, and tachycardia with or without gallop rhythm.

• In a premature baby, the ECG is not diagnostic. It is usually normal but may show LVH.

• The diagnosis is confirmed by echocardiography which not only allows the PDA to be visualised, but also assesses the haemodynamic significance of the PDA.

• The optimal treatment strategy for PDA in preterm infants has been controversial.

• There is now good evidence of a lower risk of deaths for premature infants who receive treatment for their PDA.⁸

• In the latest study, there was a significant reduction in mortality for preterm infants whose PDAs were treated (medically or surgically) but this was largely in the subgroup who required intensive ventilation.⁸

• Infants born at or above 30 weeks gestation at birth seldom require treatment for ductus closure. Prophylactic indometacin has been shown to reduce mortality and bronchopulmonary dysplasia.⁹

• Indometacin is used as standard therapy to close a PDA but is associated with reduced blood flow to several organs. Ibuprofen is as effective as indometacin in closing a PDA. Ibuprofen reduces the risk of necrotising enterocolitis (NEC) and transient renal insufficiency. Therefore, of these two drugs, ibuprofen appears to be the drug of choice¹⁰although recent studies suggest that indometacin may be safer than previously thought.¹

• Paracetamol is now thought to have similar efficacy to both ibuprofen and indometacin. It seems to be less effective in those infants who had previously been given ibuprofen or indometacin. Liver enzymes required monitoring for toxicity.¹

• Surgical ligation of the duct has historically been well tolerated but was associated with significant morbidity (hypotension, pneumothorax, vocal cord paralysis) and mortality. One study reported a one-year mortality of 12.8% and a 32% incidence of neurodisability in survivors undergoing duct ligation.¹¹

• Transcatheter closures have become the procedure of choice for definitive PDA closure in adults, children and infants >6 kg but are increasingly being used in smaller infants.²¹²