Congenital heart defect

A congenital heart defect (CHD), also known as a congenital heart anomaly, congenital cardiovascular malformation, and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular disease. Signs and symptoms depend on the specific type of defect. Most congenital heart defects are not associated with other diseases. A complication of CHD is heart failure.

Congenital heart defects are the most common birth defect. In 2015, they were present in 48.9 million people globally. They affect between 4 and 75 per 1,000 live births, depending upon how they are diagnosed. In about 6 to 19 per 1,000 they cause a moderate to severe degree of problems.

The cause of a congenital heart defect is often unknown. Risk factors include certain infections during pregnancy such as rubella, use of certain medications or drugs such as alcohol or tobacco, parents being closely related, or poor nutritional status or obesity in the mother. Having a parent with a congenital heart defect is also a risk factor. or a heart transplant may be required. Some children have no signs while others may exhibit shortness of breath, cyanosis, fainting, heart murmur, under-development of limbs and muscles, poor feeding or growth, or respiratory infections. Congenital heart defects cause abnormal heart structure resulting in production of certain sounds called heart murmur. These can sometimes be detected by auscultation; however, not all heart murmurs are caused by congenital heart defects.

Associated conditions

Congenital heart defects are associated with an increased incidence of seven other specific medical conditions, together being called the VACTERL association:

V — Vertebral anomalies
A — Anal atresia
C — Cardiovascular anomalies
T — Tracheoesophageal fistula
E — Esophageal atresia
R — Renal (Kidney) and/or radial anomalies
L — Limb defects

Ventricular septal defect (VSD), atrial septal defect (ASD), and tetralogy of Fallot (ToF) are the most common congenital heart defects seen in the VACTERL association.

Causes

The cause of congenital heart disease may be genetic, environmental, or a combination of both. They are described in the table below.

{| class="wikitable"

!Genetic lesions

!Attributable percent

!Examples

!Primary genetic testing method

|Aneuploidies

|5–8%

|Survivable autosomal trisomies (chromosomes 13, 18, 21), chromosome X monosomy (Turner syndrome)

|Karyotyping

|Copy number variants

|10–12%

|22q11.2 deletion/duplication (velocardiofacial/DiGeorge syndrome), 1q21.1 deletion/duplication, 8p23.1 deletion/duplication, 15q11.2 deletion (Burnside-Butler syndrome)

|Array comparative genomic hybridization (also known as chromosomal microarray analysis)

|Inherited protein-coding single nucleotide variant (SNV) or small insertion/deletion (indel)

|3–5%

|Holt–Oram syndrome, Noonan syndrome, Alagille syndrome

|Gene panel

|De novo protein-coding SNV or indel

|~10% Several proteins that interact with MYH6 are also associated with cardiac defects. The transcription factor GATA4 forms a complex with the TBX5 which interacts with MYH6. Another factor, the homeobox (developmental) gene, NKX2-5 also interacts with MYH6. Mutations of all these proteins are associated with both atrial and ventricular septal defects; In addition, NKX2-5 is associated with defects in the electrical conduction of the heart and TBX5 is related to the Holt–Oram syndrome which includes electrical conduction defects and abnormalities of the upper limb. The Wnt signaling co-factors BCL9, BCL9L and PYGO might be part of these molecular pathways, as when their genes are mutated, this causes phenotypes similar to the features present in Holt-Oram syndrome. Another T-box gene, TBX1, is involved in velo-cardio-facial syndrome DiGeorge syndrome, the most common deletion which has extensive symptoms including defects of the cardiac outflow tract including tetralogy of Fallot. || || || ||Upper limb abnormalities || Small or absent thymus <br /> Small or absent parathyroids <br /> Facial abnormalities

The notch signaling pathway, a regulatory mechanism for cell growth and differentiation, plays broad roles in several aspects of cardiac development. Notch elements are involved in determination of the right and left sides of the body plan, so the directional folding of the heart tube can be impacted. Notch signaling is involved early in the formation of the endocardial cushions and continues to be active as the develop into the septa and valves. It is also involved in the development of the ventricular wall and the connection of the outflow tract to the great vessels. Mutations in the gene for one of the notch ligands, Jagged1, are identified in the majority of examined cases of arteriohepatic dysplasia (Alagille syndrome), characterized by defects of the great vessels (pulmonary artery stenosis), heart (tetralogy of Fallot in 13% of cases), liver, eyes, face, and bones. Though less than 1% of all cases, where no defects are found in the Jagged1 gene, defects are found in Notch2 gene. In 10% of cases, no mutation is found in either gene. For another member of the gene family, mutations in the Notch1 gene are associated with bicuspid aortic valve, a valve with two leaflets instead of three. Notch1 is also associated with calcification of the aortic valve, the third most common cause of heart disease in adults.

Mutations of a cell regulatory mechanism, the Ras<nowiki>/</nowiki>MAPK pathway are responsible for a variety of syndromes, including Noonan syndrome, LEOPARD syndrome, Costello syndrome and cardiofaciocutaneous syndrome in which there is cardiac involvement. While the conditions listed are known genetic causes, there are likely many other genes which are more subtle. It is known that the risk for congenital heart defects is higher when there is a close relative with one. Alcohol exposure in the father also appears to increase the risk of congenital heart defects.

Being overweight or obese increases the risk of congenital heart disease. A distinct physiological mechanism has not been identified to explain the link between maternal obesity and CHD, but both pre-pregnancy folate deficiency and diabetes have been implicated in some studies.

Twins and Multiple Births

Congenital heart defects happen more often in twins than in single babies. Monochorionic twins, who share a placenta, have a greater risk of these heart defects compared to dichorionic twins, who have their own placentas. A systematic review and meta-analysis of four studies conducted in 2007 showed a 9-fold increase in CHD risk in MC twins compared to singletons.

Mechanism

There is a complex sequence of events that result in a well formed heart at birth and disruption of any portion may result in a defect. The orderly timing of cell growth, cell migration, and programmed cell death ("apoptosis") has been studied extensively and the genes that control the process are being elucidated.

Around day 15 of development, the cells that will become the heart exist in two horseshoe shaped bands of the middle tissue layer (mesoderm),

At day 22, the circulatory system is bilaterally symmetrical with paired vessels on each side and the heart consisting of a simple tube located in the midline of the body layout. The portions that will become the atria and will be located closest to the head are the most distant from the head. From days 23 through 28, the heart tube folds and twists, with the future ventricles moving left of center (the ultimate location of the heart) and the atria moving towards the head. Spitzer (1923) treats them as returns to one of the phylogenesis stages. Krimski (1963), synthesizing two previous points of view, considered congenital heart diseases as a stop of development at the certain stage of ontogenesis, corresponding to this or that stage of the phylogenesis. Hence, these theories can explain feminine and neutral types of defects only.

Diagnosis

Many congenital heart defects can be diagnosed prenatally by fetal echocardiography. This is a test which can be done during the second trimester of pregnancy, when the woman is about 18–24 weeks pregnant. It can be an abdominal ultrasound or transvaginal ultrasound.

If a baby is born with cyanotic heart disease, the diagnosis is usually made shortly after birth due to the blue colour of their skin (called cyanosis)..

Newborn screening and early detection

Early detection of critical congenital heart disease (CCHD) in patients with CHD is important for reducing morbidity and mortality, as it allows for timely treatment and may help prevent future complications. Despite the use of standard screening tests such as prenatal ultrasound and physical examination, many cases of CCHD are missed during initial evaluation. Pulse oximetry is a non-invasive and reliable method that measures oxygen levels in the blood. The pulse oximeter is placed on the right hand and one foot to obtain oxygen saturation measurements.

Hypoplasia

Hypoplasia can affect the heart, typically resulting in the underdevelopment of the right ventricle or the left ventricle. This causes only one side of the heart to be capable of pumping blood to the body and lungs effectively. Hypoplasia of the heart is rare but is the most serious form of CHD. It is called hypoplastic left heart syndrome when it affects the left side of the heart and hypoplastic right heart syndrome when it affects the right side of the heart. In both conditions, the presence of a patent ductus arteriosus (and, when hypoplasia affects the right side of the heart, a patent foramen ovale) is vital to the infant's ability to survive until emergency heart surgery can be performed, since without these pathways blood cannot circulate to the body (or lungs, depending on which side of the heart is defective). Hypoplasia of the heart is generally a cyanotic heart defect.

Obstructive defects

Obstructive defects occur when heart valves, arteries, or veins are abnormally narrow or blocked. Common defects include pulmonic stenosis, aortic stenosis, and coarctation of the aorta, with other types such as bicuspid aortic valve stenosis and subaortic stenosis being comparatively rare. Any narrowing or blockage can cause heart enlargement or hypertension.

Septal defects

The septum is a wall of tissue which separates the left heart from the right heart. Defects in the interatrial septum or the interventricular septum allow blood to flow from the left side of the heart to the right, reducing the heart's efficiency. although approximately 30% of adults have a type of atrial septal defect called probe patent foramen ovale. An atrioventricular septal defect is more complex involving an atrial septal defect, a ventricular septal defect, and irregularities in the heart valves.

Cyanotic defects

Cyanotic heart defects are called such because they result in cyanosis, a bluish-grey discoloration of the skin due to a lack of oxygen in the body. Such defects include persistent truncus arteriosus, total anomalous pulmonary venous connection, tetralogy of Fallot, transposition of the great vessels, and tricuspid atresia.

Mental health

Supporting people with chronic diseases such as congenital heart disease with emotional problems and mental health is a treatment consideration. Since some people with congenital heart disease have a lower quality of life that is related to their condition, some people may struggle with finding a job, engaging in physical exercise, with their fertility, and clinical depression as examples. An estimated 31% of adults with congenital heart disease also have mood disorders.

For congenital heart defects that arise without a family history (de novo), the recurrence risk in offspring is 3–5%. This risk is higher in left ventricular outflow tract obstructions, heterotaxy, and atrioventricular septal defects.

References

External links

Congenital heart disease information for parents.

Somerville Heart Foundation website. For support and advice for patients of CHD of all ages in the UK.