Tricuspid atresia overview

# Overview
Tricuspid atresia is the fourth most common cyanotic  congenital heart disease after tetralogy of Fallot, transposition of the great arteries (TGA), and hypoplastic left heart syndrome, whether the nonoxygenated blood can not flow from right atrium to right ventricle due to nondevelopment or total agenesia of the tricuspid valve. The right ventricle is small and the pulmonary artery in some cases is hypoplastic. Atrial septal defect (ASD) or patent foramen oval (PFO) is necessary for passing the blood from the right atrium to the left system and without them the infants will not survive. The majority of infants die without palliative surgery. Tricuspid atresia was first discovered by Friedrich Ludwig kreysig in 1817, a German physician who found the obstruction between the right atrium and right ventricle in the autopsy of cyanotic infants. The classic term of tricuspid atresia was used firstly by schuberg in 1861. Tricuspid atresia occurs during prenatal development. In tricuspid atresia, there is no continuity between the right atrium and right ventricle. Inferior vena cava and superior vena cava collect venous nonoxygenated blood into the right atrium. Through atrial septal defect (ASD), blood  come into the left atrium, then left ventricle and aorta.This blood is a mixture of saturated and unsaturated O2. If there is a ventricular septal defect (VSD), this mixed blood in the left ventricle flows into the right ventricle, then via pulmonary artery reaches pulmonary bed and becomes oxygenated, then returns back into the left atrium via pulmonary veins. In diminished pulmonary blood flow whether the flow is dependent on patent ductus arteriosus (PDA), the mixed-blood in aorta flows from this passage into pulmonary artery and pulmonary bed. In the presence of normal positioning of great arteries, cyanosis is more prominent and is affected by the size of VSD. Transposition of the great arteries (TGA) and subaortic stenosis are other associated anomalies. Some Genes mutation in tricuspid valvopathy includes : missense mutation in RASA1 that regulates Ras/ERK cascade, a missense mutation in NFATC1 that downregulates the Ras/ERK pathway. Familial recurrence of tricuspid atresia is rare. Few cases of an autosomal recessive pattern of inheritance are reported.Patients with tricuspid atresia should be differentiated from other cardiac causes of cyanosis and lung olygemia include: Tetralogy of Fallot, Total anomalous pulmonary venous connection, Pulmonary atresia,  Tricuspid stenosis. Worldwide, the prevalence of tricuspid atresia is 7.8 per 100,000 persons. Tricuspid atresia is a congenital heart disease observed among infants at the time of birth.
Tricuspid atresia affects males and females equally. There is no racial predilection for tricuspid atresia. Common risk factors related to tricuspid atresia include: chromosomal abnormality, taking teratogenic medications by mother during pregnancy such asphenytoin,retinoic acid, smoking, alcohol consumption during pregnancy,  Mother comorbidities such as diabetes mellitus, hypertension, obesity, phenylketonuria, thyroid disease, epilepsy, connective tissue disorders, Infections during pregnancy such as rubella,cytomegalovirus, Coxsackie, herpes virus 6, toxoplasmosis gondi, parvovirus B19, HIV,influenza. Early clinical features in infants include cyanosis of lips and tongue, difficulty in breathing, tiring easily during feeding. The severity of cyanosis in infants with pulmonary stenosis is dependent on the amount of pulmonary blood flow passing through patent ductus arteriosus.  After physiologic closure of patent ductus arteriosus (PDA), the cyanosis will be aggravated. In patients with normal pulmonary blood flow, complications of heart failure may occur. Prognosis is generally poor without surgery  and 90% of patients will die before 10 years old. Symptoms of tricuspid atresia in neonates may include: central cyanosis in mucous membranes and tongue, poor feeding and growth retardation, difficulty in breathing, rapidheartbeats, rapid breathing.Symptoms of longstanding cyanosis and hyperviscosity syndrome as a result of secondary erythrocytosis in older children include the following: headache, alter mentation, faintness, dizziness, visual disturbances, paresthesia, tinnitus, myalgia. Patients with pulmonary stenosis and closed PAD usually appear cyanotic after birth. Conversely, patients with VSD and high pulmonary blood flow without stenotic pulmonary arteries present with signs of overt heart failure without cyanosis.In cyanotic older patients laboratory findings may include:Polycythemia due to secondary erythrocytosis, elevated prothrombin time and partial thromboplastin time, decreased levels of factors 5,7,8,9: qualitative and quantitative, platelet disorder, increased fibrinolysis and paradoxical thrombotic tendency, proteinuria, hyperuricemia, renal failure, uric acid nephrolithiasis. An ECG may be helpful in the diagnosis of tricuspid atresia. Findings on an ECG suggestive of tricuspid atresia include: left axis deviation, left ventricle hypertrophy, right atrium enlargement, left atrium enlargement. Findings on an x-ray suggestive of tricuspid atresia include: situs solitus , left-sided aortic arch, levocardia , absent main  pulmonary artery, pulmonary oligemia with decreasedvascular markings, right aortic arch in %25 of cases. Common advantages of cardiac CT scan include assessment of Fontan circuit with an injection of contrast into superior vena cava and filling of the pulmonary system, assessment of right ventricle and left ventricle morphology and function, assessment of vascular stenting patency. Cardiac MRI (CMR) is commonly used for long term management of Fontan patients.Three-dimensional echocardiography is a modality of choice for assessment of: cardiac output, anatomy of valves, anatomy of the septal structure, chamber sizing and volume, the severity of valvular regurgitation and stenosis. Catheterization may measure the gradient  between the left ventricle and left atrium in subaortic stenosis. The mainstay of therapy for the cyanotic neonate with severe  pulmonary stenosis and small-sized  VSD is using prostaglandin E1 (PGE1) for keeping patency of ductus arteriosis. For patients with heart failure symptoms initiating diuretic for reduction of congestion and then starting ACEI is recommended. Surgery is the mainstay of therapy for tricuspid atresia. In the first 8 weeks of life if there are severe Cyanosis and pulmonary obstruction and normal positioning aorta and pulmonary artery, making a shunt between systemic subclavian artery to the pulmonary artery is necessary which is called Blalock -Taussig (BT shunt). If the pulmonary artery comes from the left ventricle and is overflowed, pulmonary artery banding is useful for lowering the pulmonary blood flow. In older children, bi-direction Glenn shunt which is the connection between superior vena cava to the pulmonary artery is planned for transferring the blood to the pulmonary system. Fontan procedure is a conduit between the inferior vena cava and the pulmonary artery whether transfers the systemic venous blood to pulmonary circulation at the age of 2-3 years old. Effective measures for the primary prevention  of tricuspid atresia as prenatal screening include fetal sonography between 10-14 weeks of pregnancy for measurement of nuchal translucency thickness, fetal echocardiography between 18-22 weeks of pregnancy. Secondary prevention strategies following the Fontan procedure include serial checking EKG, Transthoracic echocardiography, Pulse oximetry, Holter monitoring, Cardiac MRI, Exercise test.

# Historical Perspective
Tricuspid atresia was first discovered by Friedrich Ludwig kreysig in 1817, a German physician who found the obstruction between the right atrium and right ventricle in the autopsy of cyanotic infants. The classic term of tricuspid atresia was used firstly by schuberg in 1861.

# Pathophysiology
Tricuspid atresia occurs during prenatal development. In tricuspid atresia, there is no continuity between the right atrium and right ventricle. Inferior vena cava and superior vena cava collect venous nonoxygenated blood into the right atrium. Through atrial septal defect (ASD), blood  come into the left atrium, then left ventricle andaorta.This blood is a mixture of saturated and unsaturated O2. If there is a ventricular septal defect (VSD), this mixed blood in the left ventricle flows into the right ventricle, then via pulmonary artery reaches pulmonary bed and becomes oxygenated, then returns back into the left atrium via pulmonary veins. In diminished pulmonary blood flow whether the flow is dependent on patent ductus arteriosus (PDA), the mixed-blood in aorta flows from this passage into pulmonary artery and pulmonary bed. In the presence of normal positioning of great arteries, cyanosis is more prominent and is affected by the size of VSD. Transpositioning great arteries (TGA) and subaortic stenosis are other associated anomalies.

# Causes
Some Genes mutation in tricuspid valvopathy includes : missense mutation in RASA1 that regulates Ras/ERK cascade, a missense mutation in NFATC1 that downregulates the Ras/ERK pathway. Familial recurrence of tricuspid atresia is rare. Few cases of an autosomal recessive pattern of inheritance are reported.

# Differentiating tricuspid atresia from Other Diseases
Patients with tricuspid atresia should be differentiated from other cardiac causes of cyanosis and lung olygemia include: Tetralogy of Fallot, Total anomalous pulmonary venous connection, Pulmonary atresia,  Tricuspid stenosis.

# Epidemiology and Demographics
Worldwide, the prevalence of tricuspid atresia is 7.8 per 100,000 persons. Tricuspid atresia is a congenital heart disease observed among infants at the time of birth.
Tricuspid atresia affects males and females equally. There is no racial predilection for tricuspid atresia.

# Risk Factors
Common risk factors related to tricuspid atresia include: chromosomal abnormality, taking teratogenic medications by mother during pregnancy such asphenytoin,retinoic acid, smoking, alcohol consumption during pregnancy,  Mother comorbidities such as diabetes mellitus, hypertension, obesity, phenylketonuria, thyroid disease, epilepsy, connective tissue disorders, Infections during pregnancy such as rubella,cytomegalovirus, Coxsackie, herpes virus 6, toxoplasmosis gondi, parvovirus B19, HIV,influenza.

# Natural History, Complications, and Prognosis
Early clinical features in infants include cyanosis of lips and tongue, difficulty in breathing, tiring easily during feeding. The severity of cyanosis in infants with pulmonary stenosis is dependent on the amount of pulmonary blood flow passing through patent ductus arteriosus.  After physiologic closure of patent ductus arteriosus (PDA), the cyanosis will be aggravated. In patients with normal pulmonary blood flow, complications of heart failure may occur. Prognosis is generally poor without surgery  and 90% of patients will die before 10 years old.

# Diagnosis

## Diagnostic Study of Choice

## History and Symptoms
Symptoms of tricuspid atresia in neonates may include: central cyanosis in mucous membranes and tongue, poor feeding and growth retardation, difficulty in breathing, rapidheartbeats, rapid breathing.Symptoms of longstanding cyanosis and hyperviscosity syndrome as a result of secondary erythrocytosis in older children include the following: headache, alter mentation, faintness, dizziness, visual disturbances, paresthesia, tinnitus, myalgia.

## Physical Examination
Patients with pulmonary stenosis and closed PAD usually appear cyanotic after birth. Conversely, patients with VSD and high pulmonary blood flow without stenotic pulmonary arteries present with signs of overt heart failure without cyanosis.

## Laboratory Findings
In cyanotic older patients laboratory findings may include:Polycythemia due to secondary erythrocytosis, elevated prothrombin time and partial thromboplastin time, decreased levels of factors 5,7,8,9: qualitative and quantitative, platelet disorder, increased fibrinolysis and paradoxical thrombotic tendency, proteinuria, hyperuricemia, renal failure, uric acid nephrolithiasis.

## Electrocardiogram
An ECG may be helpful in the diagnosis of tricuspid atresia. Findings on an ECG suggestive of tricuspid atresia include: left axis deviation, left ventricle hypertrophy, right atrium enlargement, left atrium enlargement.

## X-ray
Findings on an x-ray suggestive of tricuspid atresia include: situs solitus , left-sided aortic arch, levocardia , absent main  pulmonary artery, pulmonary oligemia with decreasedvascular markings, right aortic arch in %25 of cases.

## Echocardiography
Three-dimensional echocardiography is a modality of choice for assessment of: cardiac output, anatomy of valves, anatomy of the septal structure, chamber sizing and volume, the severity of valvular regurgitation and stenosis, Pericardial effusion.

## CT scan
Common advantages of cardiac CT scan include assessment of Fontan circuit with an injection of contrast into superior vena cava and filling of the pulmonary system, assessment of right ventricle and left ventricle morphology and function, assessment of vascular stenting patency.

## MRI
Cardiac MRI(CMR) is commonly used for long term management of Fontan patients.

## Cardiac catheterization
Catheterization may measure the gradient  between the left ventricle and left atrium in subaortic stenosis.

# Treatment

## Medical Therapy
The mainstay of therapy for the cyanotic neonate with severe  pulmonary stenosis and small-sized  VSD is using prostaglandin E1 (PGE1) for keeping patency of ductus arteriosis. For patients with heart failure symptoms initiating diuretic for reduction of congestion and then starting ACEI is recommended.

## Interventions

## Surgery
Surgery is the mainstay of therapy for tricuspid atresia. In the first 8 weeks of life if there are severe Cyanosis and pulmonary obstruction and normal positioning aorta and pulmonary artery, making a shunt between systemic subclavian artery to the pulmonary artery is necessary which is called Blalock -Taussig (BT shunt). If the pulmonary artery comes from the left ventricle and is overflowed, pulmonary artery banding is useful for lowering the pulmonary blood flow. In older children, bi-direction Glenn shunt which is the connection between superior vena cava to the pulmonary artery is planned for transferring the blood to the pulmonary system. Fontan procedure is a conduit between the inferior vena cava and the pulmonary artery whether transfers the systemic venous blood to [[pulmonary circulation at the age of 2-3 years old.

## Primary Prevention
Effective measures for the primary prevention  of tricuspid atresia as prenatal screening include fetal sonography between 10-14 weeks of pregnancy for measurement of nuchal translucency thickness, fetal echocardiography between 18-22 weeks of pregnancy.

## Secondary Prevention
Secondary prevention strategies following the Fontan procedure include serial checking EKG, Transthoracic echocardiography, Pulse oximetry, Holter monitoring, Cardiac MRI, Exercise test.