Pathophysiology Coarctation aorta has no hemodynamic consequences in utero, because only 10% of the total cardiac output crosses from the ascending to the descending aorta. However after birth the ductus arteriosus and foramen ovale close, leading the whole cardiac output through the narrowed aortic segment. This leads to an increase in resistance in the left ventricular outflow tract, resulting in an elevated systolic pressure in the left ventricle and upper extremities. When coping with the elevated pressures, the left ventricle will become hypertrophic. If the coarctation is severe or in the acute phase (after birth when the ductus is closed), systolic dysfunction of the left ventricle and heart failure can occur. Most adult patients are asymptomatic unless severe hypertension is present leading to headache, epistaxis, heart failure, or aortic dissection. In addition, claudication may occur due to reduced flow to the lower extremities. Evaluation Coarctation of the aorta is easily diagnosed without invasive methods, by means of physical examination, echocardiography or MRI. The combination of weak or absent femoral arterial pulses and upper body hypertension in physical examination points into the direction of coarctation of the aorta. Nevertheless, studies have shown that the diagnosis in hypertensive patients is often missed by the referring doctor. As a consequence, a significant number of asymptomatic subjects with aortic coarctation are probably not detected until adult life, so their incidence at birth is likely to be underestimated. Late detection of subjects with aortic coarctation can have detrimental effects on survival. For, without correction, the mean life expectancy of patients with aortic coarctation is 35 years and 90% of those patients die before reaching the age of 50 years. Chest radiograph varies with age and severity of the coarctation. In infants with heart failure, the chest radiograph shows generalized cardiomegaly with increased pulmonary vascular markings due to pulmonary venous congestion. In older children and adults, the heart size may be normal but notching of the posterior one-third of the third to eighth ribs due to erosion by the large collateral arteries might be present. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 13/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Transthoracic echocardiography, including suprasternal notch views, is useful for initial imaging and hemodynamic evaluation in suspected aortic coarctation. Echocardiographic evaluation should also include measurement of the dimensions of the aortic annulus, aortic sinuses, sinotubular ridge, and ascending aorta; identification of aortic valve anatomy; determination of left ventricular size and function; and identification of any potential associated lesions such as ventricular septal defect, subvalvular aortic stenosis and mitral valve deformity. Treatment and outcome Figure 11. Schematic drawing showing surgical procedures for repair of a coarctation of the aorta. Left: an interposition graft. Middle: the extended aortic arch repair. Right: the extra-anatomical bypass. Figure 10. Schematic drawing showing surgical procedures for repair of coarctation of the aorta. Left: resection with end-to-end anastomosis. Middle: dilating technique using a patch; this technique is used in coarctations involving a long segment of the aorta. Right: the subclavian flap aortoplasty, using the left subclavian artery. Since surgical repair of aortic coarctation became available in 1944, survival of patients with aortic coarctation has dramatically improved and the number of patients who were operated on and reach adulthood is steadily increasing. However, life expectancy is still not as normal as in unaffected peers. Survival of patients operated at a median age of 16 years was 91% at 10 years, 84% at 20 years and 72% at 30 years after operation. Survival of post-coarctectomy patients is significantly affected by age at operation and nowadays early repair is advocated. Even after early repair before the age of 5 years the estimated survival is still reduced, with 91% of the operated patients alive at 20 years and 80% at 40 to 50 years after surgery. However, repair of aortic coarctation is still recommended in patients at older age when diagnosis is delayed, because it improves blood pressure regulation and is probably associated with a lower risk of cardiovascular events in later years and improved survival. There are several surgical techniques used for correction of the aortic coarctation. (Figure 10 & 11) Resection of the narrowed aortic segment with end-to-end anastomosis is the most commonly used technique. The subclavian flap aortoplasty and dilatation with a patch are not in use anymore due to a decreased blood flow in the left arm and a high rate of aneurysmatic deformation of the vessel respectively. When end-to-end anastomosis is not feasible, an interposition graft might be used instead. Sometimes a complete resection of the stenosis is not possible, for example when the carotid arteries are part of the coarctation, then an extended aortic arch repair or extra-anatomic bypass might be an appropriate choice. (Figure 7) https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 14/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Transcatheter interventions for native aortic coarctation have been used for over 20 years. Transcatheter treatment for native aortic coarctation has been shown to be feasible, relatively safe and effective at short term and intermediate follow-up and is rapidly becoming the treatment of choice. Older age, however, seems to be a risk factor for suboptimal outcome after balloon angioplasty possibly due to a more fibrotic and rigid aorta. Especially in the full grown patient, stent placement seems a particularly attractive option, resulting in an almost complete relief of the gradient in 95% of the patients. Another benefit of stent placement is the ability to address longer segment coarctations, which typically have a poorer outcome after balloon angioplasty alone. Long-term results, however, are to be awaited. Concern after surgery or catheter intervention falls chiefly in seven categories: recoarctation, aortic aneurysm formation or aortic dissection, coexisting bicuspid aortic valve, endocarditis, premature coronary atherosclerosis, cerebrovascular accidents and systemic hypertension. Transposition of the great arteries Case report Introduction Figure 13. Schematic drawing of the circulation in transposition of the great arteries. Left: normal position of the great arteries with the pulmonary and systemic circulation serially connected. Right: transposition of the great arteries with a parallel circulation. Transposition of the great arteries (TGA) accounts for 5- 8% of all congenital heart defects and occurs 2-3 times more frequently in males. TGA is best defined as a normal atrioventricular connection with an abnormal ventricular arterial connection; the morphological left atrium is connected through the left ventricle with the pulmonary artery and the morphological right atrium through the right ventricle with the aorta. (Figure Figure 12: Schematic drawing showing transposition of the great arteries. The pulmonary artery is located above the left ventricle (LV) and the aorta is located above the right ventricle (RV). https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 15/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology 12)The aorta is often located on the right side and in front of the pulmonary artery (D-TGA). In 70 percent there is an isolated form of TGA, in 30 percent the TGA is accompanied by other heart defects, like VSD or obstruction of the left ventricle outflow tract. Pathophysiology The circulation in TGA patients is not serial but parallel (Figure 13); the venous blood is returned to the systemic circulation through the right atrium and ventricle, while the arterial oxygenated blood is directed back into the pulmonary artery through the left atrium and ventricle. Due to this abnormal circulation there is severe cyanosis directly after birth, therefore it is critical for the ductus arteriosus and foramen ovale to remain open. Without treatment there is a mortality of 30% within one week, 50% within one month and 90% within one year. When an associated VSD is present the chances of survival are higher due to more shunting thus more oxygenated blood in the systemic circulation. These patients are able to reach early adulthood without corrective surgery or intervention. However the pulmonary hypertension that develops in this situation will eventually lead to severe problems. Treatment Mortality of TGA has dramatically improved from 90 percent for unoperated patients to rates of less than 5 percent following corrective surgery using the arterial switch operation. Most patients are referred for surgical repair during the first three to five days of life. The choice of surgical procedure is dependent on the presence and nature of other cardiac anomalies. In patients without any other cardiac defect (simple D-TGA), arterial switch operation is the recommended procedure. In general, the arterial switch operation has replaced the earlier atrial switch procedures developed by Mustard and Senning. In patients with D-TGA and a ventricular septal defect (VSD), the preferred procedure is arterial switch operation and VSD closure. In patients with D-TGA, large VSD, and significant pulmonary stenosis, the Rastelli procedure, an alternative surgical approach, should be considered. In some cases, arterial switch operation with or without repair of the left ventricular outflow obstruction is used. Both the arterial switch operation and Rastelli procedures are surgical anatomic corrections resulting in a morphologic left ventricle as the systemic ventricle. In comparison to atrial switch procedures, which involved the rerouting of venous return in the atria and are now only rarely performed, the arterial switch operation appears to have similar long-term survival rates with reduced long-term morbidity primarily due to a lower risk of atrial arrhythmias and heart failure. As a result, it is the recommended procedure in most patients with D-TGA. Outcome The long-term survival rates for patients with D-TGA following surgical correction are excellent for both arterial switch operation and atrial switch procedures. The long-term survival 20 years after discharge is about 95 and 80 percent for arterial switch and atrial switch respectively. Progressive congestive heart failure and sudden death are the principal causes of death. Perioperative mortality is greater in patients with complex (additional cardiac anomaly) D-TGA compared to those with simple D-TGA. There are no clinical trials comparing outcomes of arterial switch and atrial switch procedures. Reintervention is common following both approaches. Patients who undergo surgical repair for D-TGA have a reduced exercise capacity primarily due to pulmonary disease. Patients after arterial switch operation appear to have better exercise capacity than those who underwent atrial switch procedures. The decrease in exercise capacity, however, does not limit https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 16/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology ordinary activity as most patients meet the criteria for New York Heart Association functional class I. It appears that patients with D-TGA may have mild long-term neurodevelopmental impairment, most likely due to perioperative factors including hypoxemia, acidosis, cardiopulmonary bypass, and hemodynamic instability. Congenitally corrected transposition of the great arteries Congenitally corrected transposition of the great arteries Introduction The congenitally corrected transposition of the great arteries (ccTGA) is characterized by a normal anatomical position of both atria, with an abnormal connection between the atria and the ventricles. The right atrium is connected with the left ventricle and the left atrium is connected with (Figure 14) Furthermore the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. There are, in conclusion, abnormal atrioventricular connections and abnormal ventricular-arterial connections present in ccTGA. CcTGA is a very rare defect, accounting for about 1% of all congenital heart disease. the right ventricle. Pathophysiology Figure 14. Congenitally corrected transposition of the great arteries. RA, right atrium. LA, left atrium. RV, right ventricle. LV, left ventricle. p, pulmonary artery. ao, aorta. tric, tricuspid valve. The blood corrected because oxygenated blood flows through the systemic circulation and deoxygenated blood is transported to the lungs. In this particular heart defect the right ventricle functions as a systemic ventricle. With the atrioventricular valves following the position of the ventricles, the tricuspid valve is now the systemice AV-valve. flow in ccTGA is Additionally the coronary arteries are a mirror image of the normal anatomic situation. The coronary artery on the right side of the heart runs like a morphological left coronary artery; starting with a main stem which divides into a left anterior descending and circumflex branch. The coronary artery on the left is the morphological right coronary artery, which now runs around the tricuspid valve on the left. Even the conduction system is abnormal in this congenital heart defect. Normally the AV node is positioned at the base of the interatrial septum, from where the His bundle arises into the interventricular septum. Due to misalignment in ccTGA there is no bundle directly from the normal AV node into the interventricular septum. Usually there is an additional AV node located more anterior and laterally from where a long bundle arises which runs beneath the pulmonary valve leaflets into the interventricular septum. Due to the long route this bundle is rather vulnerable. Where in normal hearts the electrical activation of the ventricles in the septum runs from left to right, in ccTGA it is the exact opposite; the septum is activated from right to left, which is visible on the ECG as an abnormal initial activation. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 17/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology There is a VSD present in 60% of all ccTGA patients, who will often become symptomatic at younger age. Pulmonary valve stenosis is seen in 30 50% of patients, usually in those who already have a VSD as well. Abnormal anatomy of the tricuspid valve (M. Ebstein like) is seen in 25-30% of patients, sometimes accompanied by VSD or pulmonary valve stenosis. More than 80 percent of patients have an abnormal function of the tricuspid valve, which often becomes insufficient. Evaluation When only ccTGA is present, without other cardiac defects, the diagnosis is often not recognized until adulthood. However, when there is a VSD and/or pulmonary valve stenosis present, it presents short after birth with cyanosis and heart failure or even a total AV-block. Adult patients are usually recognized due to an abnormal ECG, abnormal chest radiograph, systolic murmur due to the regurgitation of the systemic AV-valve, occurrence of atrial tachycardia or an AV- block. Reduced exercise capacity might be present. The ECG is the most typical for ccTGA; left heart axis deviation, septum activation in mirror image (no Q-wave in I, aVL and V6, no R-top in V1) and a rather deep Q-wave in III and aVF. Echocardiography is a good diagnostic tool to review the exact anatomy. The right ventricle positioned on the left side is identified by the typical morphology of the trabeculae. Furthermore the tricuspid valve has a lower insertion compared to the mitral valve. Treatment and outcome Patients with ccTGA require lifelong follow up due to the risk of arrhythmias and associated sudden death, increase of pulmonary valve stenosis, increase of tricuspid valve regurgitation, supraventricular tachycardia, heart failure or endocarditis. Due to the complex anatomy and the low incidence of this pathology, this is best acquired at a specialised centre of congenital heart disease. Arrhythmias need treatment, preferably not with negative inotropic agents, but digoxin and possibly amiodaron are preferred. When presenting with atrial arrhythmias conversion to sinus rhythm is highly important in these patients, who are in need of their atrial kick . Many patients with ccTGA require pacemaker placement, often already in childhood or early adulthood. Frequent followup in these patients is required due to the high complication rate; dislocation of the lead which is located in the smooth-walled left ventricle and risk of infection or endocarditis. Determining the right time to replace the tricuspid valve is difficult in these patients. Preferably this is done just before the right systemic ventricle starts dilating and fails, but it remains an estimation which should be made for each individual patient. To restore normal blood flow through the ventricles, with the left ventricle functioning as the systemic ventricle, there is an option to perform a double switch operation. During this procedure both atria and both great arteries are switched, meaning a combination of the arterial switch and the atrial switch procedure. From a physiologic point of view this operation is worth considering while the left ventricle will function as systemic ventricle, however it is associated with a high perioperative mortality due to the https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 18/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology extent of surgery. Furthermore the left ventricle requires training prior to surgery, to be able to cope with the high arterial pressure after years of low pulmonary pressure. In conclusion the chance of success of this double switch operation is very low in patients above 16 years of age. Univentricular heart Case report Introduction Around 10 percent of all congenital heart defect patients have just one functioning ventricle. The other ventricle is present, however it is rudimentary or underdeveloped so it can not function normally. In utero this causes rarely any problems, due to the parallel circulation the other ventricle takes over both functions. It is after birth, if the ductus arteriosus closes, when problems arise. Pathophysiology The hypoplastic left heart syndrome (HLHS) is the most common type of univentricular heart. (Figure 15) Not only the left ventricle, but often the aortic valve, ascending aorta and aortic arch are hypoplastic as well. This will redirect blood from the left atrium into the right atrium, where is will be mixed with venous blood and pumped into the right ventricle and pulmonary artery. The whole systemic circulation depends on the shunt from pulmonary artery through the ductus arteriosus into the aorta. When the ductus starts closing the consequences are dramatic, with severe cyanosis and acidosis. Figure 15. Schematic drawing representing the hypoplastic left heart syndrome. When a hypoplastic right ventricle is present with associated atresia of the pulmonary circulation after birth will solely depend on ductus the arteriosus.When the ductus starts closing, progressive cyanosis is the main presenting symptom. the pulmonary artery, left-to-right shunt through the Other cardiac defects associated with only one functional ventricle are: tricuspid valve atresia, mitral valve atresia, severe form of Ebstein anomaly, double inlet left ventricle and unbalanced AVSD. All patients with one functioning ventricle have complete mixing of saturated and desaturated blood leading to Figure 24. Echocardiographic image of a male patient with a univentricular heart. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 19/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology chronic hypoxemia (Figure 24). Furthermore there is a chronic volume overload to the ventricle, serving as both pulmonary and systemic ventricle, leading to an early development of heart failure. Due to the obligatory intracardiac shunting the pulmonary filter is bypassed, which will increase the chance of cardiovascular accidents and brain abscesses. Treatment In case of a ductus-dependent defect initial treatment immediately after birth consists of prevention of ductus closure. At first this can be achieved pharmacologically with prostaglandin, however due to the many side effects this is no long-term solution. When there is a dependent pulmonary circulation an aortopulmonary shunt will be constructed during the first weeks of life to ensure accurate blood flow to the lungs after discontinuation of the prostaglandin. Figure 16. Schematic drawing showing the Fontan procedure. If there is a dependent systemic circulation the surgical treatment usually consists of three different steps. Since the anatomy is by no means normalized, one can not speak of a surgical correction, it is referred to as a definitive palliation. At first a Norwood or Sano procedure is performed in neonates where a neo-aorta is constructed by dividing the pulmonary artery. Second stage is the construction of a cavopulmonary shunt, also known as bidirectional Glenn shunt, which is performed at 4 -6 months of age. The third and final stage is known as Fontan procedure and performed at 18 30 months of age, where a total cavopulmonary connection is created. (Figure 16) All surgical procedures are described in more detail separately. Outcome With an expanding cohort of survivors of surgical palliation through Fontan completion, increasing information is being accumulated on the long-term morbidity of these patients. Active areas of interest include exercise tolerance, neurodevelopmental outcome, and quality of life. When assessed prospectively by formal exercise testing, children with HLHS after surgical repair showed considerable age-related decline in exercise performance. Among patients participating in treadmill or bicycle ergometry, those aged 8 to 12 performed at 70 percent of predicted peak oxygen consumption, whereas older children reached only 60 percent of predicted performance. Several reports have demonstrated significant neurodevelopmental impairment in survivors of HLHS following staged repairs or cardiac transplantation. There is a paucity of data on the quality of life for patients with HLHS. In one report of survivors and their families, parents reported poorer functional health status than patients assessed at 18 years of age. Risk factors that lower survival include noncardiac congenital anomalies and/or genetic disorder, particularly chromosomal defects, prematurity, low birth weight for gestational age, and living in a high poverty neighborhood. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 20/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology With an expanding cohort of survivors of surgical palliation through Fontan completion, increasing information is being accumulated on the long-term morbidity of these patients. Active areas of interest life. When assessed include exercise tolerance, neurodevelopmental outcome, and quality of prospectively by formal exercise testing, children with HLHS after surgical repair showed considerable age-related decline in exercise performance. Among patients participating in treadmill or bicycle ergometry, those aged 8 to 12 performed at 70 percent of predicted peak oxygen consumption, whereas older children reached only 60 percent of predicted performance. Several reports have demonstrated significant neurodevelopmental impairment in survivors of HLHS following staged repairs or cardiac transplantation. There is a paucity of data on the quality of life for patients with HLHS. In one report of survivors and their families, parents reported poorer functional health status than patients assessed at 18 years of age. Risk factors that lower survival include noncardiac congenital anomalies and/or genetic disorder, particularly chromosomal defects, prematurity, low birth weight for gestational age, and living in a high poverty neighborhood. Tetralogy of Fallot Case report Introduction In 1888 Etienne Louis Arthur Fallot described the maladie bleue as a combination of: Stenosis of the pulmonary artery (PS) Ventricular septal defect (VSD) Deviation of the origin of the aorta to the right Hypertrophic right ventricle This constellation of findings has since become known as tetralogy of Fallot (TOF). (Figure 17) The prevalence of TOF is about 3.9 per 10.000 live births. This defect accounts for about 7 to 10 percent of cases of congenital heart disease and is one of the most common congenital heart lesions requiring intervention in the first year of life. Figure 17. Schematic drawing representing the four features of tetralogy of Fallot. Anatomy https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 21/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology In fact there is only one anatomic abnormality in TOF; a misalignment of the interventricular septum. As a consequence the muscular part of the interventricular septum is not able to fuse with the cranial part of the septum (leaving a ventricular septal defect) and overriding of the aorta, which causes stenosis of the right ventricular outflow tract. The hypertrophy of the right ventricle is a direct consequence of the elevated pressure in the right ventricle due to the large unrestrictive VSD. Pathophysiology The combination of infundibular PS and a VSD causes the blood flow in utero to flow directly into the aorta, leading to a high chance of underdevelopment of the pulmonary valve and arteries. Therefore pulmonary valve stenosis and hypoplasia of the pulmonary arteries are often found in TOF patients. Stenosis at the origin or more distally of the right or left pulmonary artery are frequently found, so is total absence of (usually the left) pulmonary artery. Furthermore about 33% percent of all TOF patients has a descending aorta on the right side. The physiologic consequences of TOF are largely dependent upon the degree of right ventricular outflow obstruction. Since the VSD is typically large and unrestrictive, the pressure in the right ventricle reflects that of the left ventricle. As a result, the direction of blood flow across the VSD will be determined by the path of least resistance for blood flow, not by the size of the VSD. If the resistance to blood flow across the obstructed right ventricular outflow tract is less than the resistance to flow out of the aorta into the systemic circulation, blood will naturally shunt from the left ventricle to the right ventricle and into the pulmonary bed. In this situation, there is predominately a left-to-right shunt and the patient will be acyanotic. As the degree of right ventricular outflow obstruction increases, the resistance to blood flow into the pulmonary bed also increases. If the right ventricular obstruction is significant enough to increase resistance, it will be easier for blood to cross the VSD from the right ventricle into the left ventricle and go out the aorta, which now becomes the path of least resistance. This right-to-left shunt across the VSD will result in a large volume of desaturated blood entering the systemic circulation and cyanosis and polycythemia will ensue. One of the physiologic characteristics of TOF is that the right ventricular outflow obstruction can fluctuate. An individual with minimal cyanosis can develop a dynamic increase in right ventricular outflow tract obstruction with a subsequent increase in right-to-left shunt and the development of cyanosis. In the most dramatic situation, there can be near occlusion of the right ventricular outflow tract (RVOT) with profound cyanosis. These episodes are often referred to as "hypercyanotic spells". The exact etiology of these episodes is unclear, although there have been a number of proposed mechanisms, infundibular contractility, peripheral vasodilatation, hyperventilation, and including stimulation of right ventricular mechanoreceptors. increased Treatment Patients with TOF can undergo either palliative (shunts) or corrective (intracardiac repair) surgery. Although most children with TOF undergo intracardiac repair as their initial intervention, the principle of shunts remains an important palliative procedure for infants who may not be acceptable candidates for intracardiac repair due to prematurity, hypoplastic pulmonary arteries, or coronary artery anatomy. Shunts are constructed to increase the blood flow to the lungs, to improve the development of the pulmonary arteries. Many patients who underwent intracardiac repair initially had a palliative shunt. Blalock and Taussig first reported successful surgical palliation of TOF in 1945. The procedure, which https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 22/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology has since come to bear their names, used a subclavian artery to create an aorta-to-pulmonary artery connection. The technique has been modified and is now usually performed using a Gortex tube to create the connection. A different type of shunt is the aortopulmonary anastomis, where a direct connection between the descending aorta and left pulmonary artery (Potts) or between the ascending aorta and the right pulmonary artery (Waterston) is constructed. Intracardiac repair of TOF was reported by Lillehi in 1954. It consists of patch closure of the ventricular septal defect and enlargement of the RVOT. The latter is accomplished by relieving pulmonary stenosis, resecting infundibular and subinfundibular muscle bundles and if necessary by a transannular patch, creating unobstructed flow from the RV into the pulmonary arteries. Outcome A few decades ago the perioperative mortality in TOF patients was rather high (until 25 percent) but gradually declined to the current risk of around 3%. The survival in TOF patients after surgery is, although slightly less than the average population, considerably good. The longest follow-up cohort shows a survival rate of 85% after 35 years. However the rate of morbidity is very high in TOF patients due to a wide range of residual defects, that can increase over time. Therefore all patients with TOF require a lifelong, regular cardiologic follow up. The main complications of TOF include pulmonary regurgitation, residual right ventricular outflow tract obstruction, pulmonary hypertension and residual shunt. Intracardiac repair with a transannular RVOT patch can result in chronic severe pulmonary regurgitation. This leads to RV enlargement and patients may develop decreased exercise tolerance, right heart failure, and arrhythmias. A surgical prosthetic pulmonary valve may be necessary to restore the valve competence and improve RV function and functional status in TOF patients. Residual RVOT obstruction can persist after the original intracardiac operation due to hypertrophied subvalvar muscle, annular hypoplasia, pulmonary valve stenosis, supravalvar pulmonary stenosis, or branch pulmonary artery stenosis. Mild obstruction is usually well tolerated, but significant obstruction may require reoperation or catheter-based intervention. Relief of pulmonary artery stenosis by balloon dilation or stenting may be necessary prior to pulmonary valve replacement. Pulmonary hypertension can be present in TOF patients due to: hypoplastic pulmonary arteries with associated high vascular resistance, excessive shunting across the surgically constructed shunts (mainly Potts or Waterston shunts) or presence of multiple pulmonary artery stenosis. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 23/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology A residual VSD shunt is present in about 20 percent of all operated TOF patients, requiring a reoperation in 5 10 percent of them. Residual shunt might be due to detachment of the patch or an additional septal defect which was not recognized during surgery. Marfan syndrome Case report Introduction Figure 19. Magnetic resonance imaging of the aorta, showing aortic root dilatation in Marfan syndrome. Marfan syndrome (MFS) is an autosomal dominant condition with a reported incidence of 1 in 3000 to 5000 individuals and is one of the most common inherited disorders of connective tissue. While most MFS patients have an affected parent, around 15 30 percent have a de novo mutation. MFS is associated with a broad range of clinical symptoms and associated disorders, ranging from classic ocular, cardiovascular, and musculoskeletal abnormalities to manifestations including involvement of the lung, skin, and central nervous system. Figure 18. Echocardiographic image of aortic root dilatation in Marfan syndrome. Progressive dilatation of the ascending aorta is one of the key features, which causes a high risk of sudden death due to aortic dissection or rupture in young Marfan patients. (Figure 18 & 19) The underlying genetic defect is localised in the fibrillin gene on chromosome 15 (FBN1) in which recently around 600 different mutations are found. However in about 10% of MFS patients there is no mutation identified in the FBN1 gene, furthermore FBN1 mutations also occur across a wide range of milder phenotypes that overlap the classic Marfan phenotype. Therefore it is not possible to diagnose MFS solely with genetic information. Criteria for diagnosis of Marfan syndrome The 2010 revised Ghent criteria puts greater weight on aortic root aneurysm/dissection and ectopia lentis as the cardinal clinical features of MFS and on testing for mutations in FBN1 and other relevant genes. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 24/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology In the absence of family history of MFS, the presence of one of any of the following criteria is diagnostic for MFS: Aortic criterion (aortic diameter Z 2 or aortic root dissection) and ectopia lentis* Aortic criterion (aortic diameter Z 2 or aortic root dissection) and a causal FBN1 mutation Aortic criterion (aortic diameter Z 2 or aortic root dissection) and a systemic score 7 Ectopia lentis and a causal FBN1 mutation as defined above that has been identified in an individual with aortic aneurysm In the presence of family history of MFS (as defined by the above criteria), the presence of one of any of the following criteria is diagnostic for MFS: Ectopia lentis Systemic score 7 points* Aortic criterion (aortic diameter Z 2 above 20 years old, Z 3 below 20 years, or aortic root dissection)* For criteria with an asterisk (*), the diagnosis of MFS can be made only in the absence of discriminating features of Shprintzen-Goldberg syndrome (SGS), Loeys-Dietz syndrome (LDS), or vascular Ehlers- Danlos syndrome (vEDS) and after TGFBR1/2, collagen biochemistry, or COL3A1 testing if indicated. The revised Ghent nosology includes the following scoring system for systemic features: Wrist AND thumb sign: 3 points (wrist OR thumb sign: 1 point) Pectus carinatum deformity: 2 (pectus excavatum or chest asymmetry: 1 point) Hindfoot deformity: 2 points (plain pes planus:1 point) Pneumothorax: 2 points Dural ectasia: 2 points Protrusio acetabuli: 2 points Reduced upper segment/lower segment ratio (US/LS) AND increased arm span/height AND no severe scoliosis: 1 point Scoliosis or thoracolumbar kyphosis: 1 point Reduced elbow extension ( 170 degrees with full extension): 1 point Facial features (at least 3 of the following 5 features: dolichocephaly [reduced cephalic index or head width/length ratio], enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia): 1 point Skin striae: 1 point Myopia >3 diopters: 1 point Mitral valve prolapse (all types): 1 point A systemic score 7 indicates systemic involvement. Pathophysiology Aortic root disease, leading to aneurysmal dilatation, aortic regurgitation, and dissection, is the main cause of morbidity and mortality in the MFS. Dilatation of the aorta is found in approximately 50 percent of children with MFS and progresses with time. Approximately 60 to 80 percent of adult https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 25/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology patients with MFS have dilatation of the aortic root (with normal range adjusted for patient body surface area and age) by echocardiography, often accompanied by aortic regurgitation. Dilatation may also involve other segments of the thoracic aorta, the abdominal aorta, the root of the pulmonary artery or even the carotid and intracranial arteries. Untreated MFS is frequently associated with aortic dissection, which begins just above the coronary ostia and extends the entire length of the aorta; it is a type I dissection in the DeBakey classification or a type A in the Dailey scheme. Approximately 10 percent of dissections begin distal to the left subclavian (type III or type B) but dissection is rarely limited to just the abdominal aorta. Many patients with MFS and aortic dissection have a family history of dissection. Mitral valve prolapse (MVP) is frequently identified in patients with MFS. However, only one point in the systemic score is assigned for MVP since it is a nonspecific feature and most patients with mitral valve prolapse do not have MFS. The frequency of MVP in MFS increases with age and is greater in women. Tricuspid valve prolapse may also occur. Treatment Beta blockers decrease myocardial contractility and may also improve the elastic properties of the aorta, particularly in patients with an aortic root diameter <40 mm thereby decreasing the risk of aortic dissection and delaying the aortic dilatation. Prophylactic treatment with beta blockers is considered the standard of care in adults with MFS. Furthermore patients with MFS are advised to avoid any contact sports, exercise at maximal capacity, and isometric activities. The exact aortic root diameter at which elective surgery should be performed is uncertain. The current guidelines recommend elective operation for patients with MFS at an external diameter of 50 mm to avoid acute dissection or rupture. Indications for repair at an external diameter less than 50 mm include rapid growth (>2 mm/y), family history of aortic dissection at a diameter less than 50 mm, desire of pregnancy or presence of progressive aortic or mitral valve regurgitation. However one must take into account that a predicted aortic root diameter varies with body size and age and may be smaller in women. Smaller patients have dissection at a smaller aortic root size and 15 percent of patients with MFS have dissection at a diameter less than 50 mm.