para>Some infants with coexisting cardiac anomalies benefit temporarily from a PDA to provide shunting to the lungs (right-sided heart obstructions) or periphery (coarctation of the aorta). Definitive treatment should proceed as soon as feasible.
Pregnancy Considerations
Asymptomatic women with small- to moderate-sized ductus and left-to-right shunt can expect an uncomplicated pregnancy. Moderate to large unrepaired PDA with significant shunting and high pulmonary vascular resistance can complicate pregnancy, and women with right-to-left shunt are considered at high risk for significant morbidity and mortality.
EPIDEMIOLOGY
PDA is the fifth most common congenital cardiac defect in the United States, representing 5 " 10% of all congenital heart diseases.
Incidence
- Predominant age: infancy
- Predominant sex: female > male (2:1)
- 8/1,000 premature live births
- In term infants, the incidence is ~1/2,000 live births
- Occurs in up to 60% of preterm infants born at <29 weeks ' gestation (1)[A]
ETIOLOGY AND PATHOPHYSIOLOGY
- The fetal ductus arteriosus is kept open by low arterial oxygen content and vasodilators, especially circulating prostaglandin E2 (PGE2). At birth, a rise in systemic arterial oxygen tension and a decrease in circulating PGE2 induce ductal constriction.
- Closes by 24 hours in 50% of full-term neonates, by 48 hours in 90%, and by 72 hours in virtually all neonates. Ductal closure is delayed in preterm infants, and the risk of PDA is inversely proportional to gestational age.
- The main features of the natural history include spontaneous ductal closure, bacterial endocarditis, late congestive heart failure (CHF), and the development of pulmonary vascular obstructive disease.
- Prematurity, congenital
- Hypoxia, prostaglandins
Genetics
- Siblings of patients with PDA have 2 " 4% increase in frequency of PDA.
- Occurs with increased frequency in several genetic syndromes such as chromosomal aberrations (trisomy 21), single-gene mutations (Carpenter syndrome and Holt-Oram syndrome), and autosomal dominant mutations (Char syndrome)
RISK FACTORS
- Early gestational age and low birth weight
- Birth at high altitude
- Respiratory distress syndrome
- Congenital rubella and sepsis
- Antenatal NSAID exposure
GENERAL PREVENTION
- Prophylactic treatment of infants who do not develop symptomatic PDA is not recommended due to increased risk of BPD and other adverse effects associated with these drugs.
- Prophylactic IV indomethacin in preterm infants has short-term benefits, including reduction of symptomatic PDA, need for surgical ligation, and severe IVH. Unfortunately, no effect is seen on mortality/neurodevelopment and no studies show long-term outcomes.
- Similarly, prophylactic ibuprofen decreases the incidence of symptomatic PDA, the need for rescue treatment with cyclooxygenase inhibitors, and the need for surgical closure. This treatment is not recommended until long-term outcomes have been studied.
COMMONLY ASSOCIATED CONDITIONS
- Coarctation of the aorta
- Pulmonary valve stenosis/atresia
- Peripheral pulmonary stenosis (maternal rubella)
- Aortic stenosis, ventricular septal defect
- NEC in preterm infants
- IVH (intraventricular hemorrhage) (1)
- ROP (retinopathy of prematurity) (1)
- NDI (neurodevelopmental impairment) (1)
- Bronchopulmonary dysplasia
- Club feet, cataracts, blindness, systemic arterial stenosis (associated with maternal rubella)
DIAGNOSIS
HISTORY
- Children
- Many are asymptomatic
- Failure to grow, easy fatigability
- Recurrent respiratory infections
- Dyspnea on exertion
- Adults
- Leg fatigue, fatigue, syncope, exercise intolerance
- Shortness of breath, angina
PHYSICAL EXAM
- Signs (left-to-right shunt)
- Rough systolic murmur; systolic ejection click
- Continuous "machinery " murmur is heard best at left infraclavicular area (2).
- Thrill at left upper sternal border
- Bounding pulse with wide pulse pressure (2)
- Prominent, displaced apical impulse
- Diastolic flow murmur (across mitral valve)
- Tachypnea, tachycardia, diaphoresis, and rales in failure
- Signs (right-to-left shunt)
- Cyanosis and clubbing, especially lower extremities (2)
- Diastolic Graham-Steell murmur (high-velocity pulmonic insufficiency secondary to pulmonary hypertension)
- Right ventricular heave
- Signs of CHF: tachycardia, hyperactive precordium, edema, decreased urine output
DIFFERENTIAL DIAGNOSIS
- Venous hum
- Arteriovenous fistula
- Ruptured sinus of Valsalva
- Aortic insufficiency with ventricular septal defect
- Peripheral pulmonary stenosis (maternal rubella)
- Aortopulmonary fenestration
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Arterial blood gas
- Early cardiac ultrasound (clinician-performed) 3 to 12 hours after of birth is the "gold standard " for diagnosis of PDA (2,3)[A]. Infants with a small PDA have an 80% chance of spontaneous closure.
- ECG: normal if the ductus is small. Left atrial enlargement and LV hypertrophy if there is a moderate left-to-right shunt. RV hypertrophy may be present if there is PAH (2).
- Brain natriuretic peptide (BNP) levels: a useful screening tool for detecting and assessing the clinical course of PDAs
- Chest radiograph is usually normal in infants with small PDA.
- Moderate PDA: The heart is slightly enlarged and the pulmonary vascular markings are increased (2).
- Large PDA: enlargement of left ventricle and atrium and prominent pulmonary vascular markings (2)
Follow-Up Tests & Special Considerations
- Radionuclide angiography: to determine shape and size of the ductus
- Other tests: CT or MRI of the chest
Diagnostic Procedures/Other
- Doppler echocardiography: preferred procedure in confirming the diagnosis and characterizing PDA
- Cardiac catheterization and angiography: determines the degree of shunting, pulmonary pressures, and other coexisting cardiac abnormalities (2)
Test Interpretation
- Infolding of endothelial cells and migration of undifferentiated smooth muscle cells fail
- Left ventricular and atrial enlargement
- Patent ductus may have abnormal intima (maternal rubella).
TREATMENT
GENERAL MEASURES
- Appropriate health care: inpatient surgery
- Small, asymptomatic shunts may not need closure.
MEDICATION
Pharmacologic therapy is used strictly in the premature infant, and prostaglandin inhibitors are the initial intervention.
First Line
- Ibuprofen lysine (IV preparation): only for infants 500 to 1,500 g and ≤32 weeks ' gestation: Dose is 10 mg/kg IV followed by 2 doses of 5 mg/kg at 24 and 48 hours after initial dose (4)[A].
- Indomethacin 0.1 to 0.2 mg/kg/dose IV q12h for 3 doses (4)[A]
- Ibuprofen is as effective as indomethacin in closing a PDA and reduces the risk of NEC and transient renal insufficiency. Given the reduction in NEC, it is currently the drug of choice (4,5)[A].
- Indomethacin contraindications:
- Renal dysfunction, overt bleeding
- Thrombocytopenia and/or coagulation defects
- Shock, necrotizing enterocolitis
- Myocardial ischemia (6)[A]
- Contraindications for ibuprofen are similar to those for indomethacin; however, more success has been noted in treating patients in renal failure and large PDAs with ibuprofen.
- Precautions: Indomethacin reduces cerebral, GI, and renal blood flow and has been associated with isolated GI perforations. Ibuprofen is associated with a lower risk of NEC and transient renal insufficiency. However, there have been case reports of fatal pulmonary hypertension seen with ibuprofen.
Second Line
- Oral ibuprofen dosed at 10 mg/kg followed by 5 mg/kg at 24 and 48 hours is an option if the IV preparation is unavailable, but patients with borderline renal function should be evaluated and followed closely. Oral administration appears to be as effective as IV (7)[A].
- Alprostadil (prostaglandin E1) treatment to maintain patency of duct in ductal-dependent lesions
- Antibiotic prophylaxis to prevent infective endocarditis with dental, GI, GU, or respiratory tract procedures is no longer recommended unless the patient has unrepaired cyanotic congenital heart disease.
SURGERY/OTHER PROCEDURES
- Indications for PDA closure either percutaneously or surgically (1,6)[A]
- Patients with a significant left-to-right shunts who are symptomatic
- Patients with previous episodes of endocarditis regardless of the PDA size
- Persistent PDA on echocardiography despite two courses of pharmacologic treatment in preterm infants
- Complications on indomethacin, such as decreased renal output (<1 mL/kg/hr), intestinal bleeding, intestinal perforation
- Contraindications to pharmacologic intervention (severe thrombocytopenia, evolving intracranial hemorrhage, bleeding diathesis)
- Surgical transection and ligation for moderate-to-large shunts is the best option in premature infants when medical treatment has failed or is contraindicated (1)[A].
- Therapeutic catheterization is the treatment of choice for most children and adults.
- Surgical repair is recommended when PDA is too large for device closure or there is distorted ductal anatomy precluding device closure (3)[C].
- There are insufficient data to conclude whether surgical ligation or medical treatment is preferred as the initial treatment for symptomatic PDA in preterm infants (8)[A].
ALERT
PDA closure is not recommended in patients with severe pulmonary arterial hypertension and/or a right-to-left shunt due to procedural risk " the fact that the closure does not improve survival, and the shunt may be necessary to maintain cardiac output.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Pulmonary support, oxygen to correct hypoxia
- Sodium and fluid restriction (110 to 130 mL/kg)
- Use of positive end-expiratory pressure (PEEP) to improve gas exchange in infants with respiratory compromise.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Patients can be discharged from follow-up once complete closure of the ductus is documented by TTE (2)[C].
- Antibiotic prophylaxis is discontinued 6 months after PDA closure.
- Endocarditis prophylaxis is not recommended for patients with repaired defects and no residual shunt (2)[C].
Patient Monitoring
- Patients with shunts that have not been closed need to be evaluated on a regular basis to monitor for signs of cardiac overload or pulmonary vascular changes.
- Adults with Eisenmenger physiology require frequent follow-up to monitor their progression/deterioration.
PATIENT EDUCATION
For patient education materials on this topic, consult the following:
- American Heart Association: http://www.heart.org
PROGNOSIS
- Before 3 months, spontaneous closure in premature infants is nearly 73% (9) and in term infants is 40%.
- Best postoperative results if closed before age 3 years.
- Increased pulmonary vascular resistance and pulmonary hypertension are more common if closed after age 3 years.
- In adults, the prognosis depends on the condition of pulmonary vasculature and the status of the myocardium.
COMPLICATIONS
- Left-side heart failure, pulmonary hypertension
- Right-side heart hypertrophy and failure
- Eisenmenger physiology
- Bacterial endocarditis, myocardial ischemia
- Necrotizing enterocolitis
REFERENCES
11 Weisz DE, McNamara PJ. Patent ductus arteriosus ligation and adverse outcomes: causality or bias? J Clin Neonatol. 2014;3(2):67 " 75.22 Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to develop guidelines on the management of adults with congenital heart disease). Developed in collaboration with the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52(23):e143 " e263.33 Tharakan J, Venkateshwaran S. Large patent ductus arteriosus: to close or not to close. Ann Pediatr Cardiol. 2012;5(2):141 " 144.44 Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev. 2015;(2):CD003481.55 Kushnir A, Pinheiro JM. Comparison of renal effects of ibuprofen versus indomethacin during treatment of patent ductus arteriosus in contiguous historical cohorts. BMC Clin Pharmacol. 2011;11:8.66 Kluckow M, Jeffery M, Gill A, et al. A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed. 2014;99(2):F99 " F104.77 Ohlsson A, Shah SS. Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2011;(7):CD004213.88 Malviya MN, Ohlsson A, Shah SS. Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev. 2013;(3):CD003951.99 Rolland A, Shankar-Aguilera S, Diomande D, et al. Natural evolution of patent ductus arteriosus in the extremely preterm infant. Arch Dis Child Fetal Neonatal Ed. 2015;100(1):F55 " F58.
CODES
ICD10
Q25.0 Patent ductus arteriosus
ICD9
747.0 Patent ductus arteriosus
SNOMED
- Patent ductus arteriosus (disorder)
- Patent ductus arteriosus with left-to-right shunt
- Patent ductus arteriosus with right-to-left shunt (disorder)
- Patent ductus arteriosus - persisting type (disorder)
- Patent ductus arteriosus - delayed closure
CLINICAL PEARLS
- Pharmacologic closure of PDA with ibuprofen or indomethacin is done exclusively in preterm infants.
- PDA increases the incidence of necrotizing enterocolitis, pulmonary edema, and intraventricular hemorrhage in premature infants.
- Left untreated, patients develop Eisenmenger syndrome: right-to-left shunting. At this point, pulmonary vascular disease is irreversible, and closure of PDA is contraindicated (3)[A].