Congenital heart disease. A concise introduction (overview)

Congenital heart disease. A concise overview

This chapter is a brief, general introduction to congenital heart disease. The diagnosis and treatment of specific congenital heart defects will be discussed in other chapters.

Definition and causes of congenital heart disease

Congenital heart disease includes cardiac lesions that are present from birth. They are anatomic malformations of the heart or great vessels which occur during intrauterine development, irrespective of the age at presentation. The most common congenital defects in humans are congenital heart defects. The overall incidence of congenital heart disease is about 1 in 100 infants (live births). The incidence of moderate to severe congenital heart disease is approximately 6/1000 infants.
Congenital heart defects are usually classified into acyanotic and cyanotic depending whether the patients clinically exhibit cyanosis. The acyanotic defects are further classified into left-to right shunt lesions and obstructive lesions. In contrast to the acyanotic defects, in cyanotic heart defects unoxygenated systemic venous blood bypasses the pulmonary circulation and gets shunted into the left side of the heart.
Remarkable improvement in outcomes for patients with congenital heart disease has occurred over the last 50 years, because of the progress in the early diagnosis and in the development of surgical or catheter-based treatment. This has resulted in a growing population of adults with congenital heart disease (approximately 85% of all newborns with congenital heart disease will reach adulthood). As a result, the number of adults with congenital heart disease is larger than the number of children with such disease.
Congenital heart disease usually results from the abnormal embryonic development of a normal cardiac structure or failure of a structure to progress beyond a certain stage of embryonic development.The causes of congenital heart disease are multiple, genetic and environmental factors affecting cardiac development in the uterus. Genetic causes include gene mutations and chromosomal anomalies. Environmental factors include viral infections in pregnancy (such as rubella), alcohol abuse during pregnancy, effects of certain drugs during pregnancy. In most cases, the cause of a congenital heart defect in a given patient is not known.
[The term " syndrome" will often be encountered in this chapter, and notably, although every doctor understands its meaning, some cannot give its exact definition. A definition of "syndrome" is a combination of symptoms, or abnormal clinical or laboratory findings that constitute a distinct clinical picture because they result from a single cause or because they very commonly occur together and have a linked etiology or pathophysiology.]

Some known causes of congenital heart disease include:

Fetal alcohol syndrome (resulting from alcohol abuse by a pregnant woman, it is associated with cardiac defects, but also non-cardiac defects, such as microcephaly, micrognathia, and growth retardation).
Maternal rubella [it can cause patent ductus arteriosus (PDA) and pulmonary stenosis and also non-cardiac lesions such as microcephaly, cataracts, and deafness]
Maternal systemic lupus erythematosus (it can cause fetal complete heart block).
Many genetic defects are associated with congenital heart disease, including:
Marfan syndrome caused by a gene mutation (it is associated with aortic dilatation and aortic regurgitation, mitral valve prolapse and regurgitation). 

Holt-Oram syndrome, also caused by a gene mutation (autosomal dominant), which is characterized by an atrial septal defect combined with skeletal anomalies of the upper extremities, such as a short thumb, or a thumb with 3 phalanges or a short antebrachium.
William's syndrome, a genetic disorder characterized by distinctive facial features ("elfin facies"), cardiovascular defects such as supravalvar aortic stenosis and other features such as neonatal hypocalcemia and later in life mild mental retardation is evident, usually with a friendly talkative personality. The inheritance is autosomal dominant.

Examples of chromosomal anomalies associated with congenital heart disease are: 
Turner syndrome (XO) is the condition in which a female is partly or completely missing an X chromosome. It is associated with coarctation of the aorta, congenital aortic stenosis and atrial septum defect (ASD).
Trisomy 21, also called Down syndrome (it is associated with endocardial cushion defects, atrial septal defect of the ostium primum type, ventricular septal defect).

General classification of congenital heart defects

Congenital heart lesions can be classified as acyanotic (defects that do not cause cyanosis) or cyanotic (defects that cause central cyanosis due to a right- to- left shunt). Cyanosis is a blue discoloration of the mucous membranes or the skin caused by an increased amount of reduced hemoglobin (hemoglobin not combined with oxygen). Central cyanosis occurs when the circulation is mixed as a result of a right-to-left shunt (pathologic flow of unoxygenated blood from a right-sided cardiac chamber to a left-sided one). 

Acyanotic congenital heart defects include:

Ventricular or atrial, or other cardiac communications with left-to-right shunting such as: ventricular septal defect [ An opening in the ventricular septum. The most common type of congenital heart disease encountered in children]
atrial septal defect [An opening in the atrial septum.The most common congenital heart defect encountered in adults, excluding mitral valve prolapse and bicuspid aortic valve]
partial anomalous pulmonary venous return, [ One or more of the pulmonary veins connect to the superior vena cava or to the right atrium.This condition has many of the physiologic characteristics of an atrial defect and it is also often associated with such a defect (in 80-90% of cases).]
patent ductus arteriosus (PDA) [PDA is the second most common congenital heart defect encountered in adults (after ASD) It is a persistent communication between the descending aorta and the left pulmonary artery at the level of the left subclavian artery. A characteristic sign usually present is a continuous murmur (heard in both systole and diastole) which is best heard on the area under the left clavicle]

Congenital abnormalities of the heart valves and great vessels, e.g:congenital aortic stenosis due to a congenital bicuspid aortic valve
[An aortic valve with two cusps instead of three. Studies have reported an incidence of about 0.5-2 % in the general population. In many- but not all- cases the valve may have a dysfunction, stenosis or regurgitation]coarctation of the aorta, [This is usually a narrowing of the descending aorta just distal to the origin of the left subclavian artery, caused by an indentation protruding in its lumen opposite to the entry of the ductus arteriosus, so-called juxtaductal aortic coarctation. Much less commonly there is an elongated, narrowed segment of the proximal descending thoracic aorta that can also involve the arch. Aortic coarctation is often associated with a bicuspid aortic valve and usually it is diagnosed in childhood because of hypertension or a heart murmur.]
congenital subvalvular aortic stenosis [This is a stenosis of the left ventricular outflow tract caused by a discrete fibrous or fibromuscular membrane, or a diffuse, fibromuscular, narrowing of the left ventricular outflow tract (like a narrow tunnel), or rarely accessory tissue on the basal anterior mitral leaflet, or an anomalous chordal attachment of the mitral valve]
 or supravalvular aortic stenosis  [A localized or diffuse narrowing of the ascending aorta distally to the superior margin of the sinuses of Valsalva, which may occur sporadically, as a manifestation of elastin arteriopathy, or as a manifestation of Williams syndrome]
pulmonary stenosis [This term is used for an obstruction (narrowing) to the right ventricular outflow, that may be located at the valvular, subvalvular, or supravalvular level. The most common form is valvular pulmonary stenosis]
congenital mitral stenosis [due to a parachute mitral valve where all chordae tendinae are connected to a single papillary muscle, congenitally dysplastic mitral valve with fused commissures, hypoplastic (small) mitral annulus or a double orifice mitral valve, or mitral stenosis due to the presence of a supravalvular ring].
 Other lesions such as 
Congenital abnormalities of the coronary arteries.
Congenitally corrected transposition of the great arteries [A rare congenital disorder, where the ventricles are in a reversed position, i.e. the right ventricle is in the position of the left ventricle, receiving blood from the left atrium and ejecting blood into the aorta, whereas the left ventricle is receiving blood from the right atrium and ejecting it into the pulmonary artery. This condition is usually diagnosed late in childhood or in early adult life, with the patient presenting with complete heart block or heart failure due to the decompensation of the right ventricle which is the systemic ventricle in this condition, supporting the systemic circulation]

Cyanotic congenital heart defects include :

The two most common in order of frequency are 
Tetralogy of Fallot (TOF) [ It is the constellation of four findings: right ventricular outflow obstruction, a large subaortic ventricular septal defect, an overriding aorta, and right ventricular hypertrophy. Frequently an atrial septum defect may coexist and then the condition is called pentalogy." Common manifestations of TOF include cyanosis, clubbing, dyspnea on exertion, hypoxic spells and squatting ]
Complete transposition of the great arteries (TGA) [ The reversal of the relation of the aorta and pulmonary artery to the ventricles, i.e the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. The common classic type of complete TGA is called d -transposition, with the aorta located anteriorly and to the right of the pulmonary artery. In cases of TGA where the aorta lies to the left of the pulmonary artery, the condition is called l -transposition.) Because in complete TGA the systemic and the pulmonary circulation are two separate circuits, defects that permit a communication of the two circulations always coexist, such as an atrial septum defect, a patent foramen ovale, a ventricular septum defect or a patent ductus arteriosus). The presence of such a communication is necessary for survival. ]
Less common malformations such as: 
Pulmonary atresia, 
Hypoplastic left heart, 
Ebstein anomaly with an ASD  [In Ebstein anomaly there is an inferior apical displacement of the septal and posterior leaflets of the tricuspid valve into the right ventricle. This results in an "atrialized" part of the right ventricle, i.e. a part of the ventricle which has become a portion of the right atrium because of the apical displacement of the tricuspid valve. The remaining right ventricle below that part is small and often dysplastic. The anterior leaflet of the tricuspid valve is large and has a sail-like appearance. Among the patients with Ebstein anomaly, 50% have a communication between the atria, i.e. a patent foramen ovale or a secundum atrial septal defect. Another abnormality that can coexist in patients with Ebstein's anomaly is Wolff-Parkinson-White syndrome since 25% of these patients have one or more accessory pathways of atrioventricular conduction].

Patients with congenital heart defects are divided into three categories according to the surgical status:
unoperated, surgically palliated (patients that have undergone operations that partially improve their condition without complete correction of their defect) or physiologically repaired (complete or near-complete surgical repair of the defect). 

General problems and complications in patients with congenital heart disease

Patients with congenital heart disease can develop various symptoms and complications. In adults with congenital heart disease, there are certain symptoms, particularly progressive dyspnea on exertion and syncope, that should prompt a thorough evaluation.
Arrhythmias present a common problem in adults with congenital heart disease. Arrhythmias in these patients often originate near the myocardial scars of previous surgical operations. The most common arrhythmias that occur, are supraventricular arrhythmias, such as atrial flutter or atrial fibrillation. 
Ventricular tachycardia (VT) may occur in adults with congenital heart disease as a late complication of prior ventriculotomy or patching of a ventricular septal defect. VT is an important arrhythmia because it can cause sudden death. In adults with corrected tetralogy of Fallot (TOF) the incidence of ventricular arrhythmias is  0.5% -5 %. Risk factors for the occurrence of ventricular arrhythmias in such patients include an older age at the time of surgical repair,  a significantly prolonged QRS interval (>180 ms) and significant dilation of the right ventricle.
Pulmonary hypertension is a common complication of certain congenital heart defects. There are two possible causes of pulmonary hypertension, depending on the type of congenital heart disease:
1. Pulmonary hypertension as a result of  pulmonary venous
hypertension due to elevated left-sided filling pressures, 
2. Pulmonary hypertension as the result of a left to right shunt, i.e an abnormal communication between the left and right heart chambers with blood flow from a left heart chamber towards a right heart chamber. This increases flow in the pulmonary arterial circulation and can result over the years in pulmonary arterial hypertension (PAH).
Shunts proximal to the tricuspid valve such as atrial septal defects or partial anomalous pulmonary venous return uncommonly result in pulmonary hypertension ( about 15 % of cases), whereas shunts distal to the tricus­pid valve, for example a large ventricular septal defect, more commonly cause pulmonary hypertension

Left to right (L-R) shunt lesions are common types of congenital heart disease. As a general rule, a significant L-R shunt is  characterized by a ratio of pulmonary flow to systemic flow 
1.5 : 1, but this rule may not apply to adults if pulmonary hypertension has developed. In such a case, the elevated pressures on the right side and the reduced right ventricular compliance gradually cause the reduction of the L-R shunt flow. When pulmonary arterial hypertension becomes severe, the L-R shunt may reverse, resulting in the development of a right to left (R-L) shunt, i.e. an abnormal flow of desaturated blood from a right heart chamber to a left heart chamber. This causes a reduction in the hemoglobin-oxygen saturation of the arterial blood (arterial desatura­tion) with the development of cyanosis, a condition called Eisenmenger syndrome.
Cyanosis in congenital heart disease occurs when persistent mixing of desaturated blood to arterial blood, due to a R-L shunt, results in hypoxemia (reduced oxygen content of the arterial blood and a fall in hemoglobin saturation with oxygen). In such cases, the body has some adaptive mechanisms to increase oxygen delivery to the tissues, such as a rightward shift in the oxyhemoglobin dissociation curve, a rise of the hematocrit (secondary erythrocytosis), and a rise in cardiac output. Chronic hypoxemia and erythrocytosis in patients with cyanotic congenital heart disease can cause the development of various complications, such as: 
 hematologic (hyperviscosity, iron deficiency, and bleeding diathesis)
 neurologic (possible complications include cerebral hemorrhage or paradoxical cerebral embolization from a venous thrombus entering the systemic circulation through a congenital heart defect)
renal (proteinuria, hyperuricemia, or renal failure)
pulmonary (pulmonary in situ arterial thrombosis, or pulmonary hemorrhage)
and rheumatologic complications (gout and hypertrophic osteoarthropathy causing arthralgias. Another musculoskeletal manifestation of cyanotic congenital heart disease is digital clubbing, which is an enlargement of the distal segments of the fingers. Clubbing is usually an indication of an underlying disease such as a cyanotic congenital heart disease, a chronic pulmonary disease or lung cancer, infective endocarditis, inflammatory bowel disease, cirrhosis of the liver. But there are also cases where clubbing is idiopathic or hereditary without any underlying disease.)
Symptoms of hyperviscosity include headaches, dizziness, visual disturbances, altered mentation, fatigue and paresthesias.
Another important issue related to congenital heart disease, is pregnancy in a woman with congenital heart disease. The presence of congenital heart disease is associated with an increased risk for peripartum complications. However, maternal congenital heart disease is not a contraindication to pregnancy unless certain high-risk features are present, such as pulmonary hypertension, cyanosis, decompensated heart failure, aortic aneurysm, severe valve disease.


Bibliography and links 

Triedman JK, Newburger JW. Trends in Congenital Heart Disease.The Next Decade. Circulation. 2016;133:2716-2733

 ESC Guidelines for the management of grown-up congenital heart disease (new version 2010)  European Heart Journal (2010) 31, 2915–2957

Congenital Heart Disease in Children

Guidelines for Evaluation and Management of Common Congenital Cardiac Problems in Infants, Children, and Adolescents
A Statement for Healthcare Professionals From the Committee on Congenital Cardiac Defects of the Council on Cardiovascular Disease in the Young, American Heart Association

Canadian cardiovascular society guidelines on the management of adult congenital heart disease 2009