Patent ductus arteriosus

Patent ductus arteriosus (PDA) occurs in 5-10% of all congenital heart defects, excluding premature infants. PDAs are very common in preterm babies and can have significant physiological effects. 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 ductus arteriosus to close 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 low¹.

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%)².

Epidemiology³

• The factors responsible for persistent patency of ductus arteriosus in term babies are not completely understood but genetic factors and intrauterine infection are likely to play a role.

• The reported incidence varies widely because of methodological variations in the population studied and definition of PDA.

• 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.

• It affects girls twice as often as boys but in congenital rubella syndrome the sex incidence is equal.

Risk factors¹

• Most cases are thought to be multifactorial due to combination of genetic predisposition and a critically timed environmental exposure such as asphyxia during delivery, rubella infection during pregnancy or unknown viral infections or chemicals.

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

• Exposure of a fetus to valproic acid in pregnancy.

• Birth at high altitude - because of exposure to low oxygen tension.

Presentation

History

• Patients with a small PDA are usually 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.

• The precordium is hyperactive and a systolic thrill may be present at the upper left sternal border.

• The first heart sound is normal but the second is often obscured by the murmur.

• A grade 1 to 4/6 continuous ('machinery') murmur is best audible at the left infraclavicular area or 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.

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

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).

Investigations⁴

The only investigation needed to confirm the diagnosis and significance of PDA is echocardiograpy. 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.

Management

• Indometacin is ineffective in term infants with PDA and should not be used. Medical management is limited to use of decongestive measures such as diuretics in those with features of heart failure.

• 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 age⁴.

• 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 procedure⁵. 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 infection⁴.

• 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)⁶.

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 disease³.

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 complications².

• 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.

• Management of PDA in the preterm infant remains controversial, with diverse approaches ranging from very conservative management to aggressive early closure of the duct pharmacologically or surgically⁷.

• 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 dysplasia⁸.

• 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 choice⁹.

• Moderate-quality evidence suggests that paracetamol is as effective as ibuprofen. However further trials are required before any recommendations for the routine use of paracetamol can be made¹⁰.

• Surgical ligation of the duct is 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 ligation¹¹.

• Echocardiography-guided catheter closure of the ductus in small preterm babies in the neonatal intensive care unit has been reported from Oxford¹².

• PDA is commonly diagnosed in extremely preterm infants and is associated with numerous pathologies, including chronic lung disease (CLD), NEC and intraventricular haemorrhage (IVH). The evidence for some of these associations is conflicting and as association does not imply causation these should not be labelled as complications of PDA⁷.