Patent Ductus Arteriosus

Introduction
History of the Procedure

Galen initially described the ductus arteriosus in the early first century. Harvey undertook further physiologic study in fetal circulation. However, it was not until 1888 that Munro conducted the dissection and ligation of the ductus arteriosus in an infant cadaver, and it would be another 50 years before Robert E. Gross successfully ligated a patent ductus arteriosus (PDA) in a 7-year-old child. This was a landmark event in the history of surgery and heralded the true beginning of the field of congenital heart surgery.
Problem

PDA is a persistent communication between the descending thoracic aorta and the pulmonary artery that results from failure of normal physiological closure of the fetal ductus. In normal birth weight and full-term neonates, the ductus arteriosus (DA) closes within 3 days after birth. However, the DA is patent for more than 3 days after birth in 80% of preterm neonates weighing less than 750 g and its persistent patency is associated with increased morbidity and mortality. Furthermore, in the presence of a significant left-to-right ductal shunt in low birth weight (LBW) neonates, a decreased peripheral perfusion and oxygen delivery occurs.

Although frequently diagnosed in infants, the discovery of a PDA may be delayed until childhood or even adulthood. In isolated PDA, signs and symptoms are consistent with left-to-right shunting. The shunt volume is determined by the size of the open communication and the pulmonary vascular resistance. PDA may exist with other cardiac anomalies, which must be considered at the time of diagnosis. In many cases, the diagnosis and treatment of a PDA is critical for survival in neonates with severe obstructive lesions to either the right or left side of the heart.
Frequency

PDA occurs with an incidence of approximately 1 per 2000-2500 live births, comprising 5-10% of all congenital cardiac disease. Siblings have an increased incidence, suggesting a genetic component. Rubella, in the first trimester of the mother's pregnancy, has been associated with PDA and other congenital anomalies. For unknown reasons, PDA is more common in females by a ratio of 2:1. PDA is common in premature infants and may add significantly to morbidity and mortality.
Etiology

PDA is the result of failure of the fetal ductus arteriosus to constrict and close after birth.
Pathophysiology

In the fetal circulation, the ductus arteriosus is necessary to divert blood flow from the high-resistance pulmonary vascular bed, which receives only 5-8% of the right ventricular outflow, creating a right-to-left shunt. At birth, expansion of the neonatal lungs is associated with an immediate fall in pulmonary vascular resistance. Normal ductal constriction begins at this point and reaches completion in 8-10 hours. A second stage of closure related to fibrous proliferation of the intima is complete in 2-3 weeks. Patency after 3 months is considered abnormal, and treatment should be considered at this juncture, although urgency is seldom necessary.

The ductus is a muscular artery with a thick smooth muscle layer in its medial layer. It contracts and closes within a few days after birth. A balance of factors that cause relaxation and contraction determine the vascular tone of the ductus. Major factors causing relaxation are the high prostaglandin levels, hypoxemia, and nitric oxide production in the ductus. Factors resulting in contraction include decreased prostaglandin levels, increased oxygen partial pressure, increased endothelin-1, norepinephrine, acetylcholine, bradykinin, and decreased prostaglandin E receptors. Increased prostaglandin sensitivity, in conjunction with pulmonary immaturity leading to hypoxia, contributes to the increased frequency of PDA in premature neonates.

Failure of ductus arteriosus contraction in preterm neonates has been suggested to be due to poor prostaglandin metabolism because of immature lungs. Furthermore, high reactivity to prostaglandin and reduced calcium sensitivity to oxygen in vascular smooth muscle cells contribute to contraction of the ductus. The absence of DA contraction in full-term neonates might be due to failed prostaglandin metabolism most likely caused by hypoxemia, asphyxia, or increased pulmonary blood flow, renal failure, and respiratory disorders.

COX-2 (an isoform of COX-producing prostaglandins) induction and expression might also prevent ductal closure. The activation of G protein-coupled receptors EP4 by PGE2, the primary prostaglandin regulating ductal tone leads to ductal smooth muscle relaxation.

During late gestation, the decrease in prostaglandin levels results in constriction of the ductus arteriosus. Thus, the intimal cushions come into contact and occlude the ductus lumen.

A PDA is considered pathological when it persists beyond 3 months of age or is associated with symptoms. Spontaneous closure after 5 months is rare in the full-term infant. Left untreated, patients with a large PDA are at risk to develop Eisenmenger Syndrome, in which the pulmonary vascular resistance can exceed systemic vascular resistance, and the usual left-to-right shunting reverses to a right-to-left direction. At this stage, the pulmonary vascular disease is irreversible, closure of the PDA is contraindicated, and lung transplantation may be the only hope for long-term survival.
Presentation

Signs and symptoms of PDA are the result of left-to-right shunting and are proportional to the magnitude of the blood flow through the ductus.

History

Most patients with PDA present with a machinery murmur and are asymptomatic. Neonates and infants may present with signs of heart failure including tachypnea, diaphoresis, failure to thrive, inability to feed, and irritability. They may also have a history of frequent recurrent pulmonary infections. Adults whose PDA has gone undiagnosed may present with signs and symptoms of heart failure, atrial arrhythmia, or even differential cyanosis limited to the lower extremities, indicating shunting of unoxygenated blood from the pulmonary to systemic circulation.

Physical examination

Patients typically present in good health, with normal respirations and heart rate. If the ductus is moderate or large, widened pulse pressure and bounding peripheral pulses are frequently present, reflecting increased left ventricular stroke volume and diastolic runoff of blood into the initially lower-resistance pulmonary vascular bed. Prominent suprasternal and carotid pulsations may be noted secondary to increased left ventricular stroke volume.

The continuous murmur with a machinery quality is typically loudest at the left upper and midsternal border. In patients with severe heart failure and severe elevation of pulmonary vascular resistance, no audible murmur may be present. Patients with large PDA can develop Eisenmenger pathophysiology and present with cyanosis because of reversed shunting when pulmonary arterial pressures exceed systemic pressure as described earlier.

In neonates, a heart murmur is discovered within the first few days or weeks of life. The murmur is usually recognized as systolic rather than continuous in the first weeks of life and can mimic a benign systolic murmur.

Because of changes in the pulmonary vasculature, in adults, diastolic runoff decreases to the point that only a systolic component may exist.

Furthermore, distinguishing between clinically significant and nonsignificant PDA is important. A clinically significant PDA is characterized by respiratory problems with ventilation difficulties, coupled with pulmonary congestion with tachycardia, bounding pulses, and metabolic acidosis. The left-to-right shunt leads to an increased risk of complications that include intraventricular hemorrhage, narcotizing enterocolitis, chronic lung disease, and death.
Indications

With rare exceptions, the presence of a patent ductus arteriosus (PDA) is an indication for surgical closure. In the infant, repair may be urgent for the symptomatic patient with evidence of cardiac or respiratory failure not adequately controlled with medications, or it may be delayed in the patient who is asymptomatic or well controlled on medical therapy.

Differential diagnoses
Ventricular septal defect
Aortopulmonary window (aortopulmonary fenestration)
Venous hum
Truncus arteriosus
Absent pulmonary valve syndrome
Ventricular septal defect with aortic regurgitation
Ruptured sinus of Valsalva and fistula
Systemic arteriovenous fistula
Coronary artery fistula
Pulmonary arteriovenous fistulae
Bronchial pulmonary artery stenosis
Relevant Anatomy

The patent ductus arteriosus (PDA) connects the pulmonary artery to the descending thoracic aorta, usually 2-10 mm from the aortic origin of the left subclavian artery. It is commonly 5-10 mm long and tends to be shorter in the adult. The aortic orifice tends to be wider and narrows en route to the pulmonary opening.

In the presence of complex congenital heart defects, the usual anatomy of the ductus may not be present. Anatomic abnormalities can vary widely and are common in conjunction with complex aortic arch anomalies. Structures that have been mistaken for the PDA in surgical procedures include the aorta, the pulmonary artery, and the carotid artery. The left recurrent laryngeal nerve typically arises from the vagus nerve just anterior and caudal to the ductus and loops posteriorly around the ductus to ascend behind the aorta en route to the larynx. It is the most commonly injured anatomic structure in ductal ligation. Other less commonly injured structures include the phrenic nerve and the thoracic duct.
Contraindications

The primary contraindication to repair is severe pulmonary vascular disease. If transient intraoperative occlusion of the PDA does not decrease elevated pulmonary arterial pressures with a subsequent increase in aortic pressure, then the closure must be undertaken carefully and may be contraindicated. Closure of the ductus does not reverse preexisting pulmonary vascular disease.

A subset of associated cardiac anomalies—so-called ductal-dependent lesions—depend on flow through the PDA to maintain systemic blood flow. Premature closure of the ductus without concurrent repair of the following defects is contraindicated and may be fatal:
Pulmonary artery hypoplasia
Pulmonary atresia
Tricuspid atresia
Transposition of the great arteries
Aortic valve atresia
Mitral valve atresia with hypoplastic left ventricle
Severe coarctation of the aorta

http://emedicine.medscape.com/article/162796-overview