Patent Ductus Arteriosus (PDA)

Overview

Definition

The ductus arteriosus (DA) is a fetal blood vessel connecting the left pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy to the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy, bypassing the pulmonary circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment. Failure of the vessel to close and involute within 72 hours of birth results in a condition called patent ductus arteriosus (PDA).

Epidemiology

• Population statistics:
  • 5%–10% of all congenital heart defects (CHDs)
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 2 in 10,000 live term births 
  • Male:female ratio is 1:2
• Risk factors:
  • Prematurity Prematurity Neonatal Respiratory Distress Syndrome
  • Hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage:
    • History of perinatal asphyxia Perinatal Asphyxia Neonatal Respiratory Distress Syndrome
    • Birth at high altitude
  • Maternal factors:
    • Rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus infection
    • Phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs use
  • Genetic predisposition:
    • Positive family history Family History Adult Health Maintenance of PDA
    • DiGeorge syndrome DiGeorge syndrome DiGeorge syndrome (DGS) is a condition caused by a microdeletion at location q11.2 of chromosome 22 (thus also called 22q11.2 syndrome). There is a defective development of the third and fourth pharyngeal pouches, leading to thymic and parathyroid hypoplasia (causing T-cell immunodeficiency and hypocalcemia, respectively). DiGeorge Syndrome
    • Cri-du-chat syndrome Cri-du-chat Syndrome Cri du chat is the French term for “cat-cry” or “call of the cat.” The term refers to the cat-like cry of a pediatric patient with cri-du-chat syndrome. The condition is a rare genetic disorder caused by deletion mutations on chromosome 5. Cri-du-chat Syndrome
    • Noonan syndrome Noonan syndrome A genetically heterogeneous, multifaceted disorder characterized by short stature, webbed neck, ptosis, skeletal malformations, hypertelorism, hormonal imbalance, cryptorchidism, multiple cardiac abnormalities (most commonly including pulmonary valve stenosis), and some degree of intellectual disability. The phenotype bears similarities to that of turner syndrome that occurs only in females and has its basis in a 45, X karyotype abnormality. Noonan syndrome occurs in both males and females with a normal karyotype (46, XX and 46, xy). Mutations in a several genes (ptpn11, kras, sos1, nf1 and raf1) have been associated the ns phenotype. Mutations in ptpn11 are the most common. Leopard syndrome, a disorder that has clinical features overlapping those of noonan syndrome, is also due to mutations in ptpn11. In addition, there is overlap with the syndrome called neurofibromatosis-noonan syndrome due to mutations in nf1. Hypogonadism
    • CHARGE syndrome CHARGE Syndrome CHARGE syndrome is a rare genetic condition with autosomal dominant inheritance in which almost all body systems are affected. The acronym CHARGE stands for the constellation of clinical features seen with this condition: Coloboma, Heart defects, Atresia choanae, Growth retardation, Genetic Abnormalities, and Ear abnormalities. CHARGE Syndrome

Embryology and Pathophysiology

Embryology

• Fetal circulation Fetal circulation Prenatal and Postnatal Physiology of the Neonate:
  • In utero, lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy are fluid filled and their vasculature is vasoconstricted (oxygen comes from maternal circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment in the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity).
  • DA shunts blood from the right (R) to left (L) in the heart, bypassing high-pressure pulmonary circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment.
• After birth, DA closure is triggered by:
  • Increased systemic oxygen (O₂) concentration → decreased pulmonary blood pressure
  • Reduced prostaglandin E2 Prostaglandin E2 The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa. Fever ( PGE2 PGE2 The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa. Fever) levels due to separation from placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity 
• Closure starts at the pulmonary end and finishes at the aortic end:
  • Functional closure by 15 hours of life
  • Anatomical closure by 3rd week of life
• Histological changes turn ductus into ligamentum arteriosum Ligamentum arteriosum Prenatal and Postnatal Physiology of the Neonate.
• Failure or disruption of transition from fetal to extrauterine life results in the persistent patency of the DA.

Pathophysiology

• In PDA, the shunt reverses to L-R as pulmonary vascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing falls.
  • Increased end-diastolic volume End-diastolic volume Cardiac Cycle in left atrium and left ventricle → volume overload → dilation → heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
  • Increased pressure in pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy → pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension → respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure
• Eisenmenger’s syndrome:
  • Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension → right ventricle hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation→  increasing right-sided pressure
  • Shunt reverses to R-L, as it was in the prenatal period Prenatal period Prenatal and Postnatal Physiology of the Neonate.

Clinical Presentation

The severity of symptoms depends primarily on the degree of L-R shunt, which is dictated by size and length of the defect.

Diagnosis

• Clinical findings are confirmed by echocardiogram Echocardiogram Transposition of the Great Vessels.
• Echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA):
  • Evaluates:
    • Presence of defect
    • Hemodynamics Hemodynamics The movement and the forces involved in the movement of the blood through the cardiovascular system. Vascular Resistance, Flow, and Mean Arterial Pressure of left atrium and ventricle
    • Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) → degree of shunt and pulmonary arterial pressure Pulmonary Arterial Pressure Pulmonary Hypertension Drugs
  • All preterm infants should be screened.
• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests:
  • Normal in small shunts
  • Large shunts may show:
    • Increased pulmonary vascularization
    • Cardiomegaly Cardiomegaly Enlargement of the heart, usually indicated by a cardiothoracic ratio above 0. 50. Heart enlargement may involve the right, the left, or both heart ventricles or heart atria. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (heart failure) or several forms of cardiomyopathies. Ebstein’s Anomaly
• Electrocardiogram Electrocardiogram An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) ( ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG)):
  • Biventricular or right ventricular hypertrophy Right Ventricular Hypertrophy Tetralogy of Fallot in advanced cases

Management, Complications, and Prognosis

Management

• Observation indicated in smaller defects with no physiological changes:
  • Requires close follow-up
• Closure indicated in:
  • Moderate and large PDA
  • Small PDA with audible murmur
  • Presence of pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
  • Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
  • Respiratory compromise
  • History of infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis
• Medical therapy (pharmacological closure):
  • Decrease prostaglandin synthesis Synthesis Polymerase Chain Reaction (PCR):
    • Indomethacin Indomethacin A non-steroidal anti-inflammatory agent (nsaid) that inhibits cyclooxygenase, which is necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
    • Ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
  • Follow-up after 48 hours with echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) to ensure closure
  • Contraindicated in:
    • Cardiac defects where DA required to maintain perfusion for systemic circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment
    • Active bleeding
    • Suspicious or diagnosed necrotizing enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis
    • Impaired renal function
• Surgical therapy:
  • Indicated when medical therapy fails and/or infant > 6 kg
  • Includes percutaneous closure or surgical ligation Ligation Application of a ligature to tie a vessel or strangulate a part. Esophageal Atresia and Tracheoesophageal Fistula

Complications

• Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
• Bronchopulmonary dysplasia
• Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
• Infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis
• Post-surgery → paralysis of recurrent laryngeal nerve and stridor Stridor Laryngomalacia and Tracheomalacia

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• Spontaneous closure in up to 75% of infants if < 3 months of age
• Isolated PDA has an excellent prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas (especially small defects).

Differential Diagnosis

Continuous murmur of PDA should be differentiated from:

• Venous hum:  benign Benign Fibroadenoma, common murmur secondary to forces hitting venous walls; heard in children. A continuous murmur best heard on the right side and changes with position (unlike PDA). An echocardiogram Echocardiogram Transposition of the Great Vessels is done to confirm no pathology.
• Coronary artery Coronary Artery Truncus Arteriosus fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula: congenital vascular abnormality whereby the coronary artery Coronary Artery Truncus Arteriosus drains directly into chambers of heart without a capillary bed. Presentation includes a continuous murmur in the lower pericardium Pericardium A conical fibroserous sac surrounding the heart and the roots of the great vessels (aorta; venae cavae; pulmonary artery). Pericardium consists of two sacs: the outer fibrous pericardium and the inner serous pericardium. The latter consists of an outer parietal layer facing the fibrous pericardium, and an inner visceral layer (epicardium) resting next to the heart, and a pericardial cavity between these two layers. Heart: Anatomy. An echocardiogram Echocardiogram Transposition of the Great Vessels with Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) will show direct drainage into the chambers.
• Aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD): a defect of the aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy wherein the leaflets do not oppose perfectly, allowing blood to backflow during diastole Diastole Post-systolic relaxation of the heart, especially the heart ventricles. Cardiac Cycle. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may present with a continuous murmur and bounding pulses. Aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) is usually seen in older patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. An echocardiogram Echocardiogram Transposition of the Great Vessels can diagnose and quantify the severity of valvular defect.