The arterial duct is an essential fetal structure and only becomes abnormal if it remains open after the neonatal period. Persistence of the arterial duct has been defined as continued patency in term infants older than 3 months 1. It can be defined by combining both the clinical features and anatomical measurements acquired from echocardiogram as small, moderate or large and by configuration on angiogram, as described by Krichenko et al. 2.

Isolated patent arterial duct is found in around 1 in 2000 full term infants, constituting nearly 10% of all congenital heart disease 3 and is the second most common congenital heart defect 4. The overall incidence in infants born prematurely is 8 per 1000 live births with extremely high incidence of ductal patency in low birth weight infants 1. Siassi et al. 5 reported that the incidence of patent arterial duct was 21% in a prospective study on 150 preterm infants with low birth weight. However, spontaneous delayed closure of the arterial duct occurred in 79% of their patients who survived the immediate neonatal period. The majority of reports show that there is a higher incidence in females, with a female to male ratio of ~2:1. Studies have revealed recurrence rates of between 1–5% among siblings of individuals with isolated patent arterial duct 678910. There are case reports which have shown much higher recurrence rates in individual families, suggesting different inheritance patterns in these families 11. The familial occurrence of patent arterial duct is uncommon. An epidemiology paper from Carleton covering the period between 1941–58 found only 41 families where the same cardiac defect occurred in two family members and of these only 17 had patent arterial duct 12.

Most patients are asymptomatic (when the duct is small). In a moderate-to-large duct, the patency of the arterial duct is recognised on detection of the characteristic continuous heart murmur. Often termed a "machinery murmur", this is typically loudest at the left upper chest or infraclavicular area. The precordium may be hyperactive and peripheral pulses are bounding with a wide pulse pressure. The patient may have tachycardia and in older children there may be a history of exertional dyspnoea. There may be history of prematurity, asphyxia, or maternal rubella. The baby may have fast or laboured breathing, become tired easily, or display poor growth. Large shunts may lead to failure to thrive, recurrent infection of the upper respiratory tract and congestive heart failure 1. There is a subset of patients who have been found to have a patent duct but remain asymptomatic and have no audible murmur, this group is often referred to as having a 'silent' duct.

In premature infants, there should be a high index of suspicion. Often ventilated infants with hyaline membrane disease will improve followed by an inability to wean ventilation or require increased support. There may be episodes of apnoea, bradycardia or general cardiovascular instability. Physical examination may be similar to older children with tachycardia, a continuous murmur and bounding pulses however it is not uncommon for the murmur to be only systolic.

In patients where a moderate-to-large patent duct has not been previously diagnosed, irreversible pulmonary vascular changes may occur secondary to prolonged exposure of high pulmonary flow and pressure. These changes include arteriolar medial hypertrophy, intimal proliferation and fibrosis. In this group of patients when pulmonary arterial pressure exceeds systemic pressure, the flow across the duct is reversed and is right to left. This results in the patient becoming cyanosed which may be differential with cyanosis and possibly clubbing seen in the feet but not the fingers. The murmur may disappear with accentuation of the second heart sound as a result of high pulmonary pressure. These patients will have a progressive reduction in their exercise capacity.

The arterial duct is the arterial connection between the pulmonary artery and the aorta that shunts blood away from the lungs during fetal life. In normal cardiovascular embryological development the arterial duct is formed from the sixth pair of embryonic arches. The distal portion of the left sixth arch persists as the arterial duct, connecting the left pulmonary artery with the left dorsal aorta with regression of the right distal arch. This process is completed by the 8^th week of fetal life. The duct normally constricts shortly after birth due to the postnatal drop in circulating prostaglandin E2 levels, as well as the rise in systemic oxygen tension, which induce a cytochrome P450-dependent increase in endothelin-1 in ductal smooth muscle cells 13. Subsequent to this constriction, the ductal endothelial cells detach, the subendothelial region swells leading to the formation of subintimal cushions, and the smooth muscle cells migrate to the duct region, resulting in complete ductal closure and formation of the ductal ligament 14.

In a term infant with a patent arterial duct, the structure of the ductal wall is abnormal. Histologically, the internal elastic lamina of the arterial duct is generally intact and the internal cushions are absent or less well formed than usual 15. In the premature infant, persistent patency of the arterial duct is usually a result of hypoxia or immaturity, with the duct usually having a normal structure 16.

In the majority of cases of patent arterial duct there is no identifiable cause. These cases represent the influence of multifactorial inheritance 17. Persistence of the duct is associated with chromosomal aberrations, asphyxia at birth, birth at high altitude, and congenital rubella 1. It has been suggested that there is a higher incidence in children born to mothers with TT genotype of MTHFR C677T locus involved in homocysteine metabolism 18, although there are environmental influences contributing to these findings.

Occasional cases are associated with specific genetic defects. These include chromosomal defects, such as trisomy 21 and 18, deletion syndromes 4q-, 16p13.13 (Rubinstein-Taybi) and 9p- (CHARGE). Issekutz's epidemiological study looking at infants diagnosed with CHARGE syndrome in Canada demonstrated a higher incidence of patent arterial duct in subgroup B, who present with only three or fewer major criteria 19. Familial patent arterial duct can be either isolated or part of a syndrome.

Diagnosis is usually possible based on clinical examination. The confirmation of a patent arterial duct is made with transthoracic echocardiography. In the majority of cases, cross sectional echocardiography can accurately define the presence and characteristics of a patent arterial duct. The most commonly employed views are left parasternal, high left parasternal, suprasternal and short axis views 37. The arterial duct can be measured on standard two dimensional views in the high parasternal position where it forms a 'three-legged' appearance with the pulmonary arteries. Assessment of ductal blood flow can be made using colour flow mapping (Figure 1) and pulsed wave Doppler. Particular attention should be paid to the direction and flow pattern to gain information relating to restrictive flow pattern, shunt assessment and an indirect indication of pulmonary arterial pressure. However, it may be difficult to image the ductus in older patients, transoesophageal echocardiography with colour flow mapping has shown increased sensitivity in adolescent and adult patients 3839. As pulmonary vascular resistance falls after birth, the left to right shunt increases, leading to increased pulmonary over circulation and increased pulmonary venous return. As a consequence, there is left atrial and left ventricular volume loading, seen as enlargement of the left atrium and ventricle on apical four chamber and long axis views. As a result of ventricular enlargement, there may be a degree of mitral regurgitation. The degree of volume loading can be approximated using the left atrium:aortic root ratio, a significant shunt being considered one that gives a value of > 1.3 3740. This is best assessed using the m-mode in a standard long axis view.

Diagnostic cardiac catheterisation with angiography is rarely necessitated in patients with typical clinical and echocardiographic findings. Predominately catheterisation is limited to transcatheter therapies for occlusion of the duct. In this setting, ductal anatomy is usually defined with aortography (Figure 2). The configuration of the ductus as demonstrated on the lateral angiogram can be classified as described by Krichenko et al. 2. The Type A or conical duct has a well defined aortic ampulla and constriction near the pulmonary artery end. Type B is a large duct with window-like structure, which is very short in length. Type C is a tubular duct without any constriction. Type D is the complex duct with multiple constrictions and the type E or elongated duct with constriction remote from the edge of the trachea as viewed on lateral angiography (Figure 3). This classification system allows the interventionalist to assess the size and configuration of the duct and select the most suitable occlusion device.

There have been significant advances in the understanding and identification of genetic causes of congenital heart disease in the last decade and continues to be a field which is changing rapidly 41. The recognition of subgroups of patients with a stronger genetic component to the aetiology of patent arterial duct is important for the counselling of couples with concerns regarding the risks of recurrence. The recognition of familial causes of patent arterial duct stresses the importance of a full family history and of careful examination of the facial features before estimating recurrence risk for patent arterial duct.

Antenatal diagnosis of patent arterial duct is not possible as it is a normal structure during antenatal life. At present, there are no antenatal genetic investigations that can reliably predict the patency of the arterial duct in postnatal life.

Conditions in which there are signs and symptoms of pulmonary over circulation secondary to a left to right shunt must be excluded. Other conditions may also present with a continuous murmur and bounding pulses and differentiation from an arterial duct must be made on echocardiogram. These include: coronary, systemic and pulmonary arteriovenous fistula, collateral vessels, peripheral pulmonary stenosis and ventricular septal defect with aortic regurgitation 42.

Preterm infants with symptomatic heart failure secondary to persistent patency of the arterial duct may be treated by surgical ligation or medically with conservative management and indomethacin or ibuprofen. Medical intervention is usually the treatment of choice due to the risks involved with surgical ligation. Initial conservative management involves fluid restriction and diuretic therapy with optimisation of calorie intake and ventilator support. These actions will not aid ductal closure but can improve respiratory physiology and symptoms in the short term. Indomethacin and ibuprofen act as inhibitors of prostaglandin forming cyclo-oxygenase (COX) enzymes. No statistical difference has been demonstrated between ibuprofen and indomethacin in their effectiveness in closing a patent duct 43. Indomethacin has greater inhibition of COX-1 receptors and consequently greater vasoconstrictive effects with ibuprofen offering relatively less inhibition. Both drugs have potentially serious adverse effects with indomethacin associated with renal dysfunction, necrotising enterocolitis and impairment of cerebral blood flow but potentially protective effect against intraventricular haemorrhage 4445. It has been suggested that ibuprofen may increase the risk of chronic lung disease and pulmonary hypertension has been described when ibuprofen was given prophylactically 46. Both drugs are protein bound and so in the neonate can potentially compete with bilirubin for albumin binding sites, resulting in an increase in free bilirubin and the risk of bilirubin encephalopathy 47. Timing of intervention and dosage of pharmacologic treatment remains a debated topic. Indomethacin can be given as either a short course of three doses 12 hourly or as a long course of six doses 24 hourly. There is no difference in ductal closure rates between the two but the longer course has a lower incidence of ductal reopening 4849. It is known that the optimal time for treatment is less than a week of age, however this must be balanced against treating infants and exposing them to potential side effects when the duct would have closed spontaneously. Current trends would support treatment within the first week of life and in symptomatic older infants but accepting that treatment failure and ductal reopening may well occur in the older age infants 50.

A number of infants will either not be suitable or fail medical management. These include infants with renal impairment, gastrointestinal pathology including previous necrotising enterocolitis and patients with platelet dysfunction. In such cases, surgical division and ligation is indicated for closure of a significant arterial duct. This is performed via a thoracotomy and whilst high closure rates and low mortality are reported there may be significant morbidity. These include bleeding, pneumothorax, chylothorax, infection, haemodynamic instability and thoracic scoliosis. A minimally invasive surgical approach employing video-assisted thoracic surgery (VATS) has shown early results comparable to thoracotomy including premature and low birth weight infants 5152.

In children outside of this age group, the management decisions are based on the control of symptomatic pulmonary over circulation and the lifetime risk of endocarditis. Transcatheter closure of the duct is usually offered to all children outside of the neonatal period. There have been several studies reporting excellent results with low complication rates for a variety of occluders (Figure 4a–c, 5) 53545556. Surgical ligation remains an option for those unsuitable for transcatheter closure. This is now rare with the range of occluders developed but may include very large ducts where adequate anchorage of the occluder is not possible.

The best management for the 'silent' duct remains debatable with many centres electing not to close either surgically or via catheter techniques. The risk of endocarditis is low, although studies have reported an increase in the incidence in these patients 57. This has prompted some centres to offer elective closure of the patent duct to all patients 58.

The prognosis for the untreated patent arterial duct depends largely on the size of the duct and the degree of left to right shunt and pulmonary over circulation. In preterm and low birth weight infants a patent duct is associated with significant co-morbidity and mortality due to haemodynamic instability. These include pulmonary oedema and haemorrhage, bronchopulmonary dysplasia, intraventricular haemorrhage necrotizing enterocolitis as well as congestive cardiac failure. Patients with a small duct may exhibit no symptoms and have no haemodynamic impairment, these patients have a normal prognosis but do have a lifetime risk of endocarditis. Those patients with moderate-to-large ducts with significant haemodynamic changes may present with evidence of congestive cardiac failure or in the long term may develop irreversible changes to pulmonary vascularity and pulmonary hypertension 59. Patients presenting with signs of cardiac failure would usually be offered either transcatheter or surgical closure of the duct. Irreversible pulmonary vascular changes or Eisenmenger's syndrome as a result of duct is fortunately rare, but in such cases treatment is largely supportive.

For patients who undergo transcatheter closure the immediate occlusion rates are in excess of 90% and immediate complication rates are low 535455566061. There is potential for left pulmonary artery and descending aortic obstruction in patients who are of low weight with a large duct requiring a relatively large occluder for closure. However, this is rare and normally resolves with age as vessel calibre naturally increases.

Surgical ligation and division of the arterial duct has been shown to have excellent results although is more invasive than transcatheter techniques. It remains an important treatment option for arterial ducts which are unsuitable for transcatheter closure and in premature infants in which medical management has failed. Occlusion rates are in excess of 95% with mortality figures 1–2% 62. Once the patent duct has been occluded, the long term risk of endocarditis returns to levels for the overall normal population risk. Haemodynamic changes are removed with resolution of a normal circulation.

The authors declare that they have no competing interests.

JF wrote the first draft of the manuscript. All authors revised the manuscript, read and approved the final manuscript.