The congenital heart block (CHB) is the

heart block Heart block (HB) is a disorder in the heart's rhythm due to a fault in the natural pacemaker. This is caused by an obstruction – a block – in the electrical conduction system of the heart. Sometimes a disorder can be inherited. Despite the se ...

that is diagnosed in

fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal develo ...

( in utero) or within the first 28 days after birth (neonatal period), some studies also include the diagnosis during early

childhood A child ( : children) is a human being between the stages of birth and puberty, or between the developmental period of infancy and puberty. The legal definition of ''child'' generally refers to a minor, otherwise known as a person younger t ...

to the definition of CHB. It refers to the disorder in the electrical conduction system within the heart muscle, which leads to the failure in pumping the blood efficiently into the

aorta The aorta ( ) is the main and largest artery in the human body, originating from the left ventricle of the heart and extending down to the abdomen, where it splits into two smaller arteries (the common iliac arteries). The aorta distributes ...

and the

pulmonary trunk A pulmonary artery is an artery in the pulmonary circulation that carries deoxygenated blood from the right side of the heart to the lungs. The largest pulmonary artery is the ''main pulmonary artery'' or ''pulmonary trunk'' from the heart, and ...

. The result of CHB can be first, second, or third-degree (complete)

atrioventricular block Atrioventricular block (AV block) is a type of heart block that occurs when the electrical signal traveling from the atria, or the upper chambers of the heart, to ventricles, or the lower chambers of the heart, is impaired. Normally, the sinoatr ...

(a block in the

atrioventricular node The atrioventricular node or AV node electrically connects the heart's atria and ventricles to coordinate beating in the top of the heart; it is part of the electrical conduction system of the heart. The AV node lies at the lower back section of t ...

) in which no electric signals move from the atrium to the ventricles The congenital heart block is a rare disease that affects around 1 child in every 15,000–20,000 births. However, its high mortality (which can be as high as 85% in some severe cases) makes the early diagnosis and intervention very important. CHB can be isolated, where the fetus does not suffer from any other problems, or it can be a result of other diseases either in the child or in the mother. In most cases, the congenital heart block is associated with other diseases, and therefore, the symptoms vary a lot between patients. However, low heart rate is usually the main clinical presentation that leads to the diagnosis. Also, the treatment varies as well due to the associated diseases and it can be non-invasive (medications given to the pregnant woman or to the child), or a surgery in some cases when the CHB is resulted from anatomical disorders in the heart.

Presentation

The symptoms of the congenital heart block can vary due to the underlying problems that associate / lead to the CHB, and the features of CHB reflects the other manifestations of these diseases.

Bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, ...

is usually the first symptom of CHB to be detected in utero. Due to the block in the

, less electric signals move from the

sinoatrial node The sinoatrial node (also known as the sinuatrial node, SA node or sinus node) is an oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of cells known as pacemaker cells. The sinus node is approxi ...

to the

bundle of his The bundle of His (BH) or His bundle (HB) ( "hiss"Medical Terminology for Health Professions, Spiral bound Version'. Cengage Learning; 2016. . pp. 129–.) is a collection of heart muscle cells specialized for electrical conduction. As part of ...

and its right and left branches, leading to a lower heart rate. The atrioventricular block can be first degree or much more severe like a complete atrioventricular block (third degree). In addition, several changes in the ECG can be detected. Other manifestations of the congenital heart block can be related to the impact of the maternal

autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. P ...

in the autoimmune-mediated CHB.

Fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permane ...

of the

myocardium Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle tha ...

(

Endocardial fibroelastosis Endocardial fibroelastosis (EFE) is a rare heart disorder usually occurring in children two years old and younger. It may also be considered a reaction to stress, not necessarily a specific disease. It should not be confused with endomyocardial f ...

) (EFE) is the obvious one and it occurs due to the damage caused by the maternal autoantibodies to the cardiac tissue of the fetus, and can lead to death in some cases. However, it is not a common feature of CHB. Another rare symptom that might accompany the autoimmune CHB is the disorder in the valvular function, and this happens due to the damage in the

papillary muscle The papillary muscles are muscles located in the ventricles of the heart. They attach to the cusps of the atrioventricular valves (also known as the mitral and tricuspid valves) via the chordae tendineae and contract to prevent inversion or p ...

s as a result of the maternal autoantibodies.

Causes

In some cases the reason behind CHB remains unknown but in the great majority of affected kids, this disease is associated with the transference of

from the mother during gestation or with major cardiac structural abnormalities that lead to a disturbance in the conducting signals in the

. Also, in some rare cases, the congenital heart block was linked with viral infections or treatment with specific medications.

Maternal autoimmune disease

In the autoimmune-mediated congenital heart block, autoantibodies are passively transferred through the placenta during gestation. The mother might be asymptomatic during or after pregnancy but she is usually positive to anti-Ro\SSA or anti-La\SSB antibodies. In this case, the fetus's heart is normally developed and shows no structural malformations. Just like other autoimmune diseases, the autoimmune CHB shows signs of damage resulted from the autoantibodies attacking the normal tissue of the body, inflammation and fibrosis in the fetal heart tissue are the most common ones, mainly in the atrioventricular node. These antibodies lead to irreversible injuries in the atrioventricular node which heavily compromise the efficiency of the electrical conduction system, and this results in around 18% mortality rate and 70% of the live-born kids will need early

pacemaker An artificial cardiac pacemaker (or artificial pacemaker, so as not to be confused with the natural cardiac pacemaker) or pacemaker is a medical device that generates electrical impulses delivered by electrodes to the chambers of the heart ei ...

implantation.

Anti-Ro\SSA autoantibody

This autoantibody is found in the serum of the majority of kids with autoimmune CHB, and therefore it is the one mostly linked with this disease. It attacks the proteins Ro52 and Ro60 in the antigen Ro\SSA in the fetal heart tissue.

Anti-La\SSB autoantibody

This antibody attacks the ribonucleoprotein La48 on the surface of the fetal

cardiomyocytes Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle tha ...

, the links between this autoantibody and autoimmune CHB are less strong than the anti-Ro autoantibody and it usually accompanies it in the majority of cases.
Although the autoimmune CHB has a relatively high mortality and morbidity rates, the chance of kids from -mothers positive to anti-Ro\SSA and/or anti-La\SSB antibodies- to suffer from CHB is only around 1-5%, which suggests the existence of other factors to influence the disease such as genetic and environmental factors.

Other autoantibodies

Several autoantibodies were suggested to have links with the autoimmune CHB, mainly the ones associated with the different autoimmune diseases that are common among women (such as the antibodies associated with

Systemic lupus erythematosus (SLE) Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

Rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and ...

, Progressive systemic sclerosis (PSS), and

Mixed connective tissue disease Mixed connective tissue disease, commonly abbreviated as MCTD, is an autoimmune disease characterized by the presence of elevated blood levels of a specific autoantibody, now called anti-U1 ribonucleoprotein (RNP) together with a mix of symptoms ...

). However, the role of these autoantibodies was not studied comprehensively. Also, some antigens of the fetal heart tissue (apart from the "Ro" and the "La") were studied, but no clear link with the autoimmune CHB was proven.

Congenital cardiac structural abnormalities

The presence of a cardiac structural abnormality is a major determination of the outcome of CHB. Its existence affects the conduction system of the heart and increases the mortality rate and the need for pace-maker implantation. The cardiac structural diseases that are usually associated with the congenital heart block include the left atrial isomerism with or without atrioventricular septal defect. In addition, levo transpositions of the great arteries can accompany CHB but this is less common than the first one. These developmental abnormalities can impair the conduction system of the heart by disrupting its anatomical structure.

Diagnosis

There is a difference in diagnosis between low risk pregnancies where mothers do not have (or are not aware of) any autoimmune disease, and the high risk ones where mothers are known to have a specific autoimmune disease and / or are positive to anti Ro/La autoantibodies and / or had a CHB-affected pregnancy previously. In low risk pregnancies, testing the mothers' serum is not part of the routine prenatal tests. Therefore, the congenital heart block is usually diagnosed during a routine obstetrical ultra sound. The first symptom in most cases is a slow heart rate which can be detected using fetal

echocardiogram An echocardiography, echocardiogram, cardiac echo or simply an echo, is an ultrasound of the heart. It is a type of medical imaging of the heart, using standard ultrasound or Doppler ultrasound. Echocardiography has become routinely used in ...

and Doppler ultra sound techniques between the weeks 18 - 30. The Doppler is very important to assess the level of AV block as well as to check for other cardiac structural abnormalities that might be associated with CHB such as left atrial isomerism, valvular damages and big arteries inversion, while the echocardiogram is useful to detect other complications such as the hydrops fetalis. In the absence of cardiac structural diseases, the second step to confirm the diagnosis is to test the

serum Serum may refer to: *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid * Truth serum, a drug that is likely to mak ...

of the mother for anti Ro/La autoantibodies using the enzyme-linked immunosorbent assay (

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...

). In high risk pregnancies, the diagnosis is relatively easier as fetal and maternal screenings are part of the routine monitoring of the pregnancy.

Screening

Although the chance of having kids with CHB in anti Ro/La positive mothers is relatively low (1-5%), it is recommended that all mothers with autoimmune disease to be screened and seek consultation when decide to get pregnant. For mothers with at least one CHB-affected pregnancy, with 16 - 18% recurrence chance for the directly following pregnancy and an overall 9% chance in following ones, monitoring both the mother and the fetus is crucial.

Treatment

Due to the rarity of this disease, there is a lack of comprehensive and high quality research about the different treatment options, and therefore, no specific treatment plan is followed globally. However, some studies have attempted to outline the most widely accepted approaches in dealing with CHB.

Fluorinated steroids

There is no agreement on using fluorinated

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...

s in treating CHB, and the results of the different studies are contradictory. These steroids (such as

dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cav ...

) are used when the disease is diagnosed in utero as they can cross the

placenta The placenta is a temporary embryonic and later fetal organ (anatomy), organ that begins embryonic development, developing from the blastocyst shortly after implantation (embryology), implantation. It plays critical roles in facilitating nutrien ...

without being deactivated. The main goal of using

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are in ...

s is to mitigate the

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

by decreasing the amount of anti Ro/La autoantibodies in the fetal serum. Therefore, they are used in the autoimmune-mediated CHB. Both the mother and the fetus might suffer from their

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s which can include growth problems and

adrenal insufficiency Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal gland normally secretes glucocorticoids (primarily cortisol), mineralocorticoids (primarily aldosterone), and androge ...

Beta-adrenergic agonist

Trebutaline and Sulbutamol are among the medications that have been used to treat CHB. They are used mainly to increase the heart rate in fetuses suffering from

bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, ...

. Although they showed positive results, some patients showed intolerance to their side effects.

Plasmapheresis

Plasma exchange in women positive to anti Ro/La autoantibodies has not been studied thoroughly, but it is suggested to have and effect on the titer of the antibodies in the mother's serum and therefore might have a preventive role.

Intravenous immunoglobulin

Using intravenous immunoglobulin showed some promising results in decreasing the possibility of having CHB's complications such as EFE and

cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. ...

Hydroxychloroquine

Hydroxychloroquine Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, a ...

is relatively new approach, but it showed promising results in preventing the inflammation and other injuries result from it such as fibrosis. Apart from these medications, a pace maker might be needed in around two thirds of the cases, and a procedure might be required when the heart has structural abnormalities.

Outcomes

The outcome of the congenital heart block varies a lot due to several factors, such as the associated diseases, severity of the atrioventricular block, maternal age...etc. In terms of the severity of the AV block, newborn kids with heart rate lower than 55 bpm have a negative outcome and higher chance to need pace-maker implantation, as well as kids with symptomatic bradycardia such as lower tolerance of exercises. Isolated CHB has a better prognosis than the one associated with other disorders, the presence of congenital cardiac abnormalities increases the mortality rate. Also, kids presented with

hydrops fetalis Hydrops foetalis or hydrops fetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in ...

and / or EFE and / or

have poor outcome. Some studies showed a genetic contribution to the autoimmune CHB. Among anti Ro/La positive women, older ones have higher possibility of having kids with heart block. Mortality rate in CHB increases with earlier deliveries. Kids with congenital heart block have higher chance to face health-related problems (such as

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable d ...

s) than other kids.

Epidemiology

The congenital heart block occurs in 1 child in every 15,000 to 20,000 births. More than 90% of the cases are associated with autoimmune disease and transference of maternal autoantibodies. Without considering the gender, the age of diagnosis or the associated diseases, mortality rate is around 20%. The majority of CHB-related deaths occur in the first 3 months after birth followed by fetal death, and it is less common to occur after the third month of age. Mortality rate is very high when the disease is diagnosed prenatally, and declines dramatically with older diagnosis ages. Around 60% - 70% of the patients will need pace-maker implantation regardless of the age of diagnosis. The disease seems to affect both males and females equally. The survival rate is heavily affected by the associated diseases, and it is higher in autoimmune-mediated CHB patients compared to CHB patients with congenital cardiac structural problems. Recurrence rate: mothers who had pregnancies associated with CHB, have a 16 - 18% chance of having kids with heart block in the following pregnancy. A study in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., federal district, five ma ...

showed that the vast majority of the affected mothers are of a Caucasian ethnicity, despite the fact that

Systemic Lupus Erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

(SLE) is more common among minorities.

References

{{Navbox , title = External Links , group1 = Congenital Heart Block , list1 = https://rarediseases.org/rare-diseases/heart-block-congenital/ , group2 = Heart Block Types , list2 = https://my.clevelandclinic.org/health/diseases/17056-heart-block , group3 = Congenital Heart Defects , list3 = https://www.nhlbi.nih.gov/health-topics/congenital-heart-defects and https://www.heart.org/en/health-topics/congenital-heart-defects/about-congenital-heart-defects/common-types-of-heart-defects Congenital heart defects