Overview
Definition
The ductus arteriosus (DA) is a fetal blood vessel connecting the left pulmonary artery to the aorta, bypassing the pulmonary circulation. 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: 2 in 10,000 live term births
- Male:female ratio is 1:2
- Risk factors:
- Prematurity
- Hypoxia:
- History of perinatal asphyxia
- Birth at high altitude
- Maternal factors:
- Rubella Rubella Rubella (also known as German measles or three-day measles) is caused by a single-stranded, positive-sense RNA virus of the Togaviridae family. Rubella only infects humans and spreads prenatally via vertical transmission or postnatally via droplet contact. Congenital rubella is associated with a classic triad of symptoms: cataracts, cardiac defects, and deafness. Infection in children and adults may be mild and present with constitutional symptoms along with a viral exanthem. Rubella Virus infection
- Phenytoin use
- Genetic predisposition:
- Positive family history 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
- 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:
- 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 are fluid filled and their vasculature is vasoconstricted (oxygen comes from maternal circulation in the placenta Placenta The placenta consists of a fetal side and a maternal side, and it provides a vascular communication between the mother and the fetus. This communication allows the mother to provide nutrients to the fetus and allows for removal of waste products from fetal blood. Placenta, Umbilical Cord, and Amniotic Cavity).
- DA shunts blood from the right (R) to left (L) in the heart, bypassing high-pressure pulmonary circulation.
- After birth, DA closure is triggered by:
- Increased systemic oxygen (O2) concentration → decreased pulmonary blood pressure
- Reduced prostaglandin E2 (PGE2) levels due to separation from placenta Placenta The placenta consists of a fetal side and a maternal side, and it provides a vascular communication between the mother and the fetus. This communication allows the mother to provide nutrients to the fetus and allows for removal of waste products from fetal blood. 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.
- 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
Vascular Resistance
Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Vascular resistance is directly related to the diameter of the vessel (smaller vessels have higher resistance).
Vascular Resistance, Flow, and Mean Arterial Pressure falls.
- Increased end-diastolic volume in left atrium and left ventricle → volume overload → dilation → heart failure
- Increased pressure in pulmonary artery → 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 → right ventricle hypertrophy→ increasing right-sided pressure
- Shunt reverses to R-L in the prenatal period.
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.
| Degree of shunt | Clinical presentation | Physical examination |
|---|---|---|
| Small shunt |
|
Murmur:
|
| Moderate shunt |
|
|
| Large shunt | Infant:
|
|
Phonocardiograms of abnormal
heart sounds
Heart sounds
Heart sounds are brief, transient sounds produced by valve opening and closure and by movement of blood in the heart. They are divided into systolic and diastolic sounds. In most cases, only the first (S1) and second (S2) heart sounds are heard. These are high-frequency sounds and arise from aortic and pulmonary valve closure (S1), as well as mitral and tricuspid valve closure (S2).
Heart Sounds caused by the following cardiac defects:
aortic regurgitation
Aortic regurgitation
Aortic regurgitation (AR) is a cardiac condition characterized by the backflow of blood from the aorta to the left ventricle during diastole. Aortic regurgitation is associated with an abnormal aortic valve and/or aortic root stemming from multiple causes, commonly rheumatic heart disease as well as congenital and degenerative valvular disorders.
Aortic Regurgitation,
mitral valve prolapse
Mitral valve prolapse
Mitral valve prolapse (MVP) is the most common cardiac valvular defect, and is characterized by bulging of the mitral valve (MV) cusps into the left atrium (LA) during systole. Mitral valve prolapse is most commonly due to idiopathic myxomatous degeneration. Patients are typically asymptomatic.
Mitral Valve Prolapse,
mitral stenosis
Mitral stenosis
Mitral stenosis (MS) is the narrowing of the mitral valve (MV) orifice, leading to obstructed blood flow from the left atrium (LA) to the left ventricle (LV). Mitral stenosis is most commonly due to rheumatic heart disease. Mitral stenosis leads to impaired LV diastolic filling, increased LA pressure, and LA dilation.
Mitral Stenosis (MS),
aortic stenosis
Aortic stenosis
Aortic stenosis (AS), or the narrowing of the aortic valve aperture, is the most common valvular heart disease. Aortic stenosis gradually progresses to heart failure, producing exertional dyspnea, angina, and/or syncope. A crescendo-decrescendo systolic murmur is audible in the right upper sternal border.
Aortic Stenosis (AS),
tricuspid regurgitation
Tricuspid regurgitation
Tricuspid regurgitation (TR) is a valvular defect that allows backflow of blood from the right ventricle to the right atrium during systole. Tricuspid regurgitation can develop through a number of cardiac conditions that cause dilation of the right ventricle and tricuspid annulus. A blowing holosystolic murmur is best heard at the left lower sternal border.
Tricuspid Regurgitation, hypertrophic obstructive
cardiomyopathy
Cardiomyopathy
Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease).
Overview of Cardiomyopathies (HOCM),
atrial septal defect
Atrial Septal Defect
Atrial septal defects (ASDs) are benign acyanotic congenital heart defects characterized by an opening in the interatrial septum that causes blood to flow from the left atrium (LA) to the right atrium (RA) (left-to-right shunt).
Atrial Septal Defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA)
Diagnosis
- Clinical findings are confirmed by echocardiogram.
- Echocardiography:
- Evaluates:
- Presence of defect
- Hemodynamics of left atrium and ventricle
- Doppler → degree of shunt and pulmonary arterial pressure
- All preterm infants should be screened.
- Evaluates:
- Chest X-ray:
- Normal in small shunts
- Large shunts may show:
- Increased pulmonary vascularization
- Cardiomegaly
-
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.
Normal 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.
Normal Electrocardiogram (ECG)):
- Biventricular or right ventricular hypertrophy in advanced cases
Echocardiogram showing PDA:
An echocardiogram depicting PDA with a small shunt (white arrow) found incidentally in a patient with
Kawasaki disease
Kawasaki disease
Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome or infantile polyarteritis, is a medium-sized necrotizing febrile vasculitis that affects children < 5 years of age. Multiple systems are involved but the most serious is the predilection of the coronary arteries.
Kawasaki Disease
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
- Respiratory compromise
- History of infective endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
- Medical therapy (pharmacological closure):
- Decrease prostaglandin synthesis:
- Indomethacin
- Ibuprofen
- Follow-up after 48 hours with echocardiography to ensure closure
- Contraindicated in:
- Cardiac defects where DA required to maintain perfusion for systemic circulation Systemic circulation Circulation is the movement of blood throughout the body through one continuous circuit of blood vessels. Different organs have unique functions and, therefore, have different requirements, circulatory patterns, and regulatory mechanisms. Systemic and Special Circulations
- Active bleeding
- Suspicious or diagnosed necrotizing enterocolitis Necrotizing enterocolitis Necrotizing enterocolitis (NEC) is an intestinal inflammatory process that can lead to mucosal injury and necrosis. The condition is multifactorial, with underlying risk factors that include prematurity and formula feeding. The clinical presentation varies in severity from feeding intolerance, acute findings on abdominal exam, and systemic symptoms. Necrotizing Enterocolitis
- Impaired renal function
- Decrease prostaglandin synthesis:
- Surgical therapy:
- Indicated when medical therapy fails and/or infant > 6 kg
- Includes percutaneous closure or surgical ligation
Complications
- Pulmonary hypertension
- Bronchopulmonary dysplasia
- Congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure
- Infective endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
- Post-surgery → paralysis of recurrent laryngeal nerve and stridor
Prognosis
- Spontaneous closure in up to 75% of infants if < 3 months of age
- Isolated PDA has an excellent prognosis (especially small defects).
Differential Diagnosis
Continuous murmur of PDA should be differentiated from:
- Venous hum: benign, 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 is done to confirm no pathology.
- Coronary artery fistula: congenital vascular abnormality whereby the coronary artery drains directly into chambers of heart without a capillary bed. Presentation includes a continuous murmur in the lower pericardium. An echocardiogram with Doppler will show direct drainage into the chambers.
- Aortic regurgitation: a defect of the aortic valve wherein the leaflets do not oppose perfectly, allowing blood to backflow during diastole. Patients may present with a continuous murmur and bounding pulses. Aortic regurgitation is usually seen in older patients. An echocardiogram can diagnose and quantify the severity of valvular defect.
References
- Thomas D. and Anne K. (2020). Clinical manifestations and diagnosis of patent ductus arteriosus in term infants, children, and adults. UpToDate. Retrieved January 09, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-patent-ductus-arteriosus-in-term-infants-children-and-adults
- Bernstein, D. (2020). General principles of treatment of congenital heart disease. In R. M. Kliegman MD, J. W. St Geme MD, N. J. Blum MD, Shah, Samir S., MD, MSCE, Tasker, Robert C., MBBS, MD & Wilson, Karen M., MD, MPH (Eds.), Nelson textbook of pediatrics (pp. 242–2436.e1) doi:http://dx.doi.org/10.1016/B978-0-323-52950-1.00461-2. Retrieved January 31, 2021, from https://www.clinicalkey.es/#!/content/3-s2.0-B9780323529501004612
- Benitz, W. E., & Bhombal, S. (2020). Patent ductus arteriosus. In Martin, Richard J., MBBS, FRACP, Fanaroff, Avroy A., MD, FRCPE, FRCPCH & Walsh, Michele C., MD, MSE (Eds.), Fanaroff and martin’s neonatal-perinatal medicine (pp. 1334–1341) doi:http://dx.doi.org/10.1016/B978-0-323-56711-4.00074-2. Retrieved January 31, 2021, from https://www.clinicalkey.es/#!/content/3-s2.0-B9780323567114000742
- Gillam-Krakauer, M., & Reese, J. (2018). Diagnosis and Management of Patent Ductus Arteriosus. NeoReviews, 19(7), e394–e402. DOI:10.1542/neo.19-7-e394. Retrieved January 31, 2021, from https://pubmed.ncbi.nlm.nih.gov/30505242/
