© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12437
Echocardiography
ECHO IN ADULT CONGENITAL HEART DISEASE
Echocardiographic Evaluation of Tetralogy of Fallot* Pooja Swamy, M.D., Aditya Bharadwaj, M.D., Padmini Varadarajan, M.D., and Ramdas G. Pai, M.D. Department of Cardiology, Loma Linda University Medical Center, Loma Linda, CA
Tetralogy of Fallot (TOF) is a cyanotic heart disease consisting of nonrestrictive ventricular septal defect, overriding aorta, pulmonary stenosis, and right ventricular hypertrophy. Early total correction is the treatment of choice and these patients with repaired TOF are increasingly seen in adult practice. This review addresses echocardiographic evaluation of TOF, corrected TOF, its sequelae and various complications. A working knowledge of TOF assessment is essential for all adult cardiologists and sonographers. (Echocardiography 2015;32:40–48) Key words: tetralogy of Fallot, echocardiography, pulmonary valve stenosis Danish anatomist Neil Stensen was the first to identify the condition in 1672. It was, however, Louis Arthur Fallot, who first described the anatomical components and pathological features of the condition. He called the condition “la maladie bleue” (blue malady) or cyanose cardiaque (cardiac cyanosis). Maude Abbott, a Canadian pioneer in pediatric cardiology used the term “tetralogy of Fallot” in 1924.1 Helen Taussig first postulated the progression of this condition resulting in cyanosis and death to be secondary to diminished pulmonary blood flow. Tetralogy of Fallot (TOF) is the most common cyanotic adult congenital heart disease with an incidence of 5 per 10,000 live births accounting for 10% of all congenital cardiac malformations and presents with equal gender prevalence. The prevalence of the condition is on the rise at the rate of 5% annually with the advent of successful corrective surgical procedures increasing the longevity of affected patients.2 When left untreated, a survival of 30% has been noted in the first decade of life that drops severely to a survival of 5% after the fourth decade. Surgical correction has proven to have a tremendous survival benefit in these patients. A thorough knowledge of the malformation and the associated pathophysiological changes prior to and at various periods after reparative or palliative surgery is crucial for a practicing cardiologist. This is particularly true for the management of a patient with TOF with cardiac or noncardiac issues when support from a regional Address for correspondence and reprint requests: Ramdas G. Pai, M.D., Professor of Medicine, Loma Linda University Medical Center, Loma Linda, CA 92354, Fax: 909-558-0903; E-mail: [email protected] *[Corrections added on 26th June 2014, after first online publication: article title was changed]
40
center for congenital heart diseases may not be available. Hence, we outline the various key aspects of the condition and its management through this review on echocardiographic evaluation of TOF. Etiology: Its exact etiology remains unclear but has been associated with chromosomal anomalies including 22q11 deletion syndrome (15% of TOF), Down syndrome, trisomy 13 and 18, maternal age >40 years, maternal diabetes mellitus, gestational exposure to hydantoin, retinoic acid, rubella and alcohol (fetal alcohol syndrome), maternal phenyl ketonuria, Alagille syndrome, and cat eye syndrome. 22q11 microdeletion (DiGeorge syndrome) is sporadic in 95% cases with remaining 5% being transmitted in an autosomal dominant fashion.3 FISH testing is widely available to test for this chromosomal abnormality and genetic counseling is offered in patients with TOF and other conotruncal anomalies. Mutation in coding region of GATA4/GATA6 (a gene encoding a zinc-finger transcription factor crucial for normal cardiogenesis) and mutations in the gene coding for transforming growth factor b2 and JAG1 have been the most recently studied genetic abnormalities to explain malformations in TOF.4,5 Essential Components of TOF: There are four essential components of TOF. A perimembranous ventricular septal defect (VSD), right ventricular outflow tract obstruction (RVOTO), an overriding aortic root, and a hypertrophied right ventricle. It has been postulated that cluster of defects caused by the anterior and cephalad migration of the infundibular septum (or its fibrous
Tetralogy of Fallot
remnant)6 while Van Praagh et al.1 believe that these are caused by the underdevelopment of the subpulmonary infundibulum. The effective rightward displacement the infundibular septum results in a malalignment of the infundibular septum with respect to the trabecular septum. This narrows the right ventricular outflow tract resulting in a larger and overriding ascending aorta and perimembranous VSD.6 Obstruction to right ventricular (RV) outflow results in RV hypertrophy.1,6 The anterocephalad deviation of the RV outlet septum and the failure of the outflow ventricular cushion to muscularize results in an infundibular septal defect (often perimembranous type of VSD). The size of this defect is variable. When there is a nonrestrictive type of septal defect, it results in equalization of the pressures between both ventricles and an unrestricted bidirectional flow between the ventricles. The impact of flow across the septum (or shunting) varies inversely with the degree of RVOTO. In a majority of patients posterior–inferior margin of the opening between the ventricles is formed by a fibrous continuity between the leaflets of the aortic and tricuspid valves. The remnant of the inter-ventricular portion of the membranous septum also forms this part of the VSD. In a minority of patients, the posteroinferior region of the defect is muscular and in such cases, the muscular tissue is formed by continuity of the posteroinferior limb of the septomarginal trabeculation with the infundibular fold. This structure protects the conduction axis in the ventricle during closure of the ventricular defect. The failure of muscularization of the outlet septum results in a fibrous band between the aortic and pulmonary valves (PVs). This forms the anterosuperior margin of the septal defect some patients of Caucasian descent, from the Far East, Central, and South America. Right ventricular outflow tract obstruction is a conotruncal developmental anomaly that occurs in the 4th–5th week of embryonic development of the heart. The level of outflow obstruction and its severity can be variable. The levels of RVOTO can occur at one or more of the following levels: (1) Right ventricular infundibulum: atretic outflow tract (2) PV: Bicuspid PV with supravalvular hypoplasia, subvalvular stenosis, or PV atresia (with or without collaterals between systemic and pulmonary vasculature) (3) Pulmonary artery (4) Branch pulmonary arteries Bronchial collaterals (systemic to pulmonary) are seen with severe RVOT obstruction/pulmo-
nary atresia. Right-sided arch occurs in about one-fifth of patients. The overriding aortic root allows blood from both ventricles due to the error in embryonic septal migration. When there is moderate to severe obstruction of the right ventricular outflow tract, there is significant right to left contributing to the blood flow into the aorta in addition to that from the left ventricle.6 Over a period of time, in unrepaired TOF, this volume overload along with intrinsic structural abnormalities of the aortic wall results in aneurysmal dilation of the aortic root. Aortic root dilatation can also be seen in repaired TOF attributed to the histological changes (medionecrosis, fibrosis, cystic medial necrosis, and elastic fragmentation) in the aortic wall. Overriding of aorta is also seen in context of a double outlet right ventricle. Right ventricular hypertrophy develops as a consequence to the increased pressure overload caused by the RVOTO and an overriding aorta. Anatomical Variants of TOF: Some of the variants of TOF include: (1) TOF with pulmonary atresia with or without major aortopulmonary collaterals. (2) TOF with absent PV, bicuspid or unicuspid PV with or without pulmonary stenosis. (3) TOF with double outlet right ventricle. (4) TOF with atrio-VSD. Associated Anomalies of TOF: Tetralogy of Fallot may be associated with a variety of congenital anomalies due to the nature of its development and the risk factors associated with its occurrence. These anomalies are summarized in Table II. Anomalous anterior descending artery deserves a special mention due to its surgical significance. It is seen in about 5–12% cases of patients with TOF. Instead of arising from the left main coronary artery, it arises from the right coronary artery and courses through the right ventricular infundibulum (RVOTO). The artery can be accidentally injured during the surgical correction of infundibular obstruction resulting in ischemia and arrhythmias. It is therefore essential to delineate the origin and course of the coronary arteries prior to surgical correction in TOF. At a similar note, it is equally important to realize that the anticipated and rare complication of transection frequently results in inadequate RVOTO release. Natural History of TOF: The variable severity of the condition and the concurrence of the associated major intra-cardiac 41
Swamy, et al.
anomalies determine the natural history or postsurgical long-term outcomes in adults with TOF. Without surgical intervention, 25% of the affected infants die in the first year of life with mortality reaching up to 40% age of 3 years; 70% by the end of first decade of life; and 90% by the end of 4th decade. Major causes of death in surgically untreated patients include hypoxic spells (62%), cerebrovascular accidents (17%), and brain abscesses (13%). With early reparative surgery in these patients there has been a sharp decline in mortality in the affected patients. As a result, we frequently encounter patients in their adulthood presenting with the complications of reparative or palliative shunt surgeries. Physiology: Ventricular septal defect in TOF is nonrestrictive leading to equal pressures in both ventricles. The direction and magnitude of flow through the defect depends on the severity of pulmonic stenosis. Moderate pulmonary stenosis (PS) is associated with a net left to right shunt at the ventricular level, and pulmonary flow exceeds systemic flow. More severe stenosis causes equal resistance to outflow into pulmonary and systemic circuits that causes bidirectional shunting. Severe obstruction to right ventricular outflow causes a large right to left shunt with markedly reduced pulmonary blood flow. Factors that can cause reduced arterial oxygen saturation are exercise-induced drop in systemic vascular resistance, hypercyanotic spells causing metabolic acidosis, and an increase in heart rate leading to increase in right to left shunt. Clinical Features and Diagnosis: About half of the patients are diagnosed antenatally by a fetal echocardiogram during pregnancy. The remaining patients are identified upon their presentation with cyanosis early in infancy or in the first few years of life. Cyanosis can be seen early in life or may develop later in life. Those who become cyanotic in adulthood typically have milder forms of the defect complex and or have a predominant left to right shunt mechanism until later in life. “Tet spells” or hypercyanotic episodes are more commonly observed in early childhood and infrequently in adulthood. The spells are typically precipitated by agitation or decreased hydration. With a decrease in systemic vascular resistance (due to decreased hydration) or an increase in pulmonary vascular resistance (resulting from infundibular muscle obstruction or spasm during agitation or crying) a significant right-to-left shunt across the VSD occurs. As a result, there is decreased pulmonary flow and increased deoxy42
genated blood flow into the systemic circulation. Central cyanosis is associated with varying degrees of hypoxia, which if left untreated can cause syncope and mortality. Congestive heart failure is a common initial presentation in infancy due to a large VSD while progressive PS develops a picture more consistent with TOF. Evolutions of Surgical Corrections of TOF: It is important for the echocardiographer to understand the various surgical procedures performed along with their time frames. In the year 1944, Helen Taussig, a cardiologist Johns Hopkins in collaboration with a surgeon, Alfred Blalock and his able surgical assistant Vivien Thomas developed creation of an “artificial ductus arteriosis” connecting the systemic circulation to the pulmonary circulation to relieve cyanosis in children with assumed TOF anatomy. This was a landmark in pediatric surgery and was the first type of palliative surgery which came to be known as “Blalock–Taussig Thomas” (BTT) shunt. This shunt established connection between the subclavian artery and the pulmonary artery.7 Very soon, the procedure became palliative not only for TOF but also for many other cyanotic congenital heart diseases. In 1946, Potts shunt was reported. This was described as an anastomosis between the descending aorta and the left pulmonary artery. The procedure was later abandoned because of the difficulty in closing the shunt at the time of complete repair. In 1962, Waterston shunt was reported and described as anastomosis between ascending aorta to pulmonary artery that was easy to perform and simple to close. In 1966, Cooley shunt was reported. It was described as an intra-pericardial anastomosis from ascending aorta to right pulmonary artery. The Potts, Waterston, and Cooley shunts were all central shunts and were less likely to thrombose compared with the relatively peripherally placed BTT shunt. The modified BTT shunt used a prosthetic tube graft interposed between the systemic artery (subclavian artery) and the pulmonary artery, instead of the direct anastomosis first described. Surgeons in the current use this modification for palliation. It was only in 1954 that Walton Lillehei of University of Minnesota performed the first total repair in 1954 using controlled cross circulation. This method used a single pump that controlled the reciprocal exchange between the patient and the donor. The commonest long-term issue after an intra-cardiac repair in TOF is progressive pulmonary regurgitation. In 1955, at the Mayo Clinic, John Kirklin and associates reported the use of a modified
Tetralogy of Fallot
Gibbons CPB circuit (Gibbon-Mayo pump oxygenator) in the open repair of complex congenital heart defects including VSD and TOF with a 60% survival rate.8 In 1970s, Bonchek and Starr evaluated the utility of surgical intervention in infancy. Among the 28 patients who had severe symptoms at the time of diagnosis and underwent immediate complete repair, the mortality was only 7%. Patient who received shunts at the time of diagnosis had a mortality of 31% (pulmonary atresia or severe hypoplasia only). The study established the superiority of complete repair at an earlier age.9 Current Surgical Trend in TOF: The timing of surgical repair is controversial and has been evolving over the years. Prior to 1970s, all patients with TOF mainly underwent palliative surgery that involved creation of a pulmonary systemic shunt followed by delayed intra-cardiac repair. After the 1970s, primary intra-cardiac repair became the treatment of choice in both symptomatic and asymptomatic patients with TOF. For the exceptional cases with hypoplastic pulmonary arteries, small-sized left ventricular (LV), anomalous origin of left coronary artery, multiple VSDs, the surgical techniques adopted in the treatment have evolved tremendously. Palliative Surgery for TOF: In the current era, palliative shunts are only performed in those who are poor candidates for intra-cardiac repair. The goal is to increase pulmonary blood flow by creating systemic artery to pulmonary artery connections. Initial Repair for TOF: Intra-cradiac surgical repair of TOF is usually performed in the first year of life; in patients who have undergone prior palliative surgery without development of pulmonary arterial hypertension; or in adults who have remained unoperated due to various circumstances. A complete TOF repair consists of two major components: Closure of the VSD: Closure is usually performed with continuous polypropylene suture, polyethylene terephthalate material, or Gore-Tex (W. L. Gore and Associates, Inc., Elkton, MD, USA) patch through either a transventricular or transatrial approach. The complications include residual VSD or leak from around the patch. Infundibular muscle may be resected if required. Inter-atrial communications are also closed with VSD closure. Relieving the RVOT obstruction: Resection of infundibular stenosis (with muscle resection if needed) is the most widely used method. When
the PV is small a right ventricular outflow augmentation with placement of a transannular patch is performed. Due to rapid growth in infancy and childhood, every attempt is made to preserve the native PV when initial intra-cardiac repair is performed in infancy. When complete repair is performed in adulthood, PV replacement is usually required if the native PV integrity is disrupted. In case of severe unresectable infundibular stenosis/pulmonary atresia or an anomalous coronary artery cruising through the infundibulum or RVOT, an extracardiac conduit with a right ventricle to pulmonary artery connection is created. It is noteworthy that though the anomalous origin of left anterior descending artery from RCA has been reported to vary from 5 to 12% in various literatures, its occurrence is in real practice relatively rare. The complications arising from its transection during the RVOTO release is detrimental though rare. The anticipation of this complication during the procedure often results in incomplete or inadequate release of RVOTO. Over the years, materials used for surgical correction of right ventricular outflow obstruction have included placement of homografts, bovine jugular valved conduits (Contegra), stentless valves, stented tissue valves, monocusp valves, mechanical valves, autologous pericardial valves, and transcatheter PVs. In 2010, the US Food and Drug Administration formally approved the Medtronic Melody (Medtronic, Minneapolis, MN, USA) Transcatheter Pulmonary Valve. This device is indicated for use as an adjunct to surgery in the management of pediatric and adult patients with the following clinical conditions: (1.) Existence of a full (circumferential) RVOT conduit that was equal to or greater than 16 mm in diameter when originally implanted and (2.) Dysfunctional RVOT conduits with a clinical indication for intervention, and either regurgitation (>moderate) or stenosis (mean RVOT gradient >35 mmHg). Adults with Corrected TOF: The long-term sequelae and complications of TOF that are surgically corrected are discussed as below. Table I summarizes these problems and with suggested management. The sequelae and complications of TOF are summarized in Table II.10 Atrial and ventricular scarring resulting in AV block, atrial flutter, and/or atrial fibrillation, ventricular tachycardia (sustained or nonsustained). Chronic pulmonary regurgitation leads to stretching of the right ventricular myocardium 43
Swamy, et al.
TABLE I Surgical Procedures for Rerepair of Tetralogy of Fallot in Adults (Adapated from ACC/AHA guidelines – Warnes et al. (2008)10 Pulmonary valve replacement (PVR) Heterograft (porcine or pericardial) or homograft Mechanical PVR in patients who require warfarin anticoagulation for other reasons. This procedure has been associated with late malfunction from pannus formation. Patch augmentation of the pulmonary annulus for proper prosthetic valve sizing Subvalvular obstruction or pulmonary artery stenosis Resection of subvalvular obstruction and/or patch augmentation of the RVOT, pulmonary annulus, main or branch pulmonary arteries Usually occurs in combination with PVR Residual/recurrent VSD closure Direct suture Patch revision AVR (tissue or mechanical) for aortic regurgitation Replacement of ascending aorta for dilatation Tube graft Bentall procedure (composite valve conduit with coronary reimplantation) Aneurysm or pseudoaneurysm formation of RVOT Resection and patch replacement Atrial arrhythmias Maze procedure or 1 of its modifications Ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation) Preoperative EP testing and ablation in the catheterization laboratory If unsuccessful, intra-operative mapping, and ablation are performed Focus is most often in the RVOT between the VSD patch and the pulmonary annulus Postoperative placement of an ICD for patients at high risk of sudden death Tricuspid valve repair for significant tricuspid regurgitation Tricuspid valve replacement for a markedly abnormal tricuspid valve Closure of residual PFO or ASD, especially if there is cyanosis, history of paradoxical embolism, or anticipated need for a permanent pacemaker or ICD. RVOT = right ventricular outflow tract; VSD = ventricular septal defect; ICD = intra-cardiac defibrillator; PFO = patent foramen ovale; ASD = atrial septal defect.
resulting in areas of inhomogeneous electrical activity. Structural changes in the myocardium along with scarring from reparative surgeries result in increased refractoriness that predisposes to reentrant electrical activity causing ventricular arrhythmias. Right ventricular dysfunction and dilatation is associated with right atrial dilatation. Right atrial dilatation and scarring from reparative surgeries result in a similar reentrant electrical activity causing atrial fibrillation, atrial flutter, and other sustained/nonsustained atrial tachyarhhythmias. Echocardiographic Features of TOF: In adults with unrepaired TOF, the key echocardiographic features are listed under main features and associated anomalies (Figs. 1–3). In adults who have undergone intra-cradiac surgical repair, an echocardiographer should look for a residual VSD, pulmonary regurgitation with associated RV dilation/dysfunction, infundibular stenosis, aortic root dilation, residual uncorrected anomalies, hypoplastic pulmonary annulus, pulmonary artery or its branches, or pulmonary artery branch stenosis. Complications related to these may unfold over time. Table II summarizes 44
the key features for a comprehensive echocardiographic examination. Transthoracic images should be obtained from all standard views, especially the suprasternal view. The latter is vital for the evaluation of the arch and its associated anomalies; systemic to pulmonary shunts and for estimating the size of the pulmonary artery branches.11 Parasternal views are important for assessment of the RVOT, PV, main pulmonary artery, VSD patch, ascending aortic size, and aortic valve (Figs. 4–5). The shortaxis view not only allows us to visualize the RVOT but also determine the size and extent of the septal defect. As mentioned earlier, RVOTO can occur at various anatomic levels and the parasternal short-axis and subcostal coronal views must be used to meticulously evaluate each potential level of obstruction. While color Doppler is useful in assessing the location of turbulent flow, continuous-wave Doppler helps in determining pressure gradients across the various levels of obstruction. Apical views are important for determining the RV size and function and the subcostal view allows visualization of the inferior venacava (IVC) size and atrial septum. Sometimes when transthoracic images are suboptimal, a transesophageal echo
Tetralogy of Fallot
TABLE II Echocardiographic Findings in TOF Uncorrected TOF
Repair-Related Findings or Long-Term Sequelae
Associated Anomalies
Large unrestrictive perimembranous VSD Overriding aorta (i.e.,
Echocardiography
ECHO IN ADULT CONGENITAL HEART DISEASE
Echocardiographic Evaluation of Tetralogy of Fallot* Pooja Swamy, M.D., Aditya Bharadwaj, M.D., Padmini Varadarajan, M.D., and Ramdas G. Pai, M.D. Department of Cardiology, Loma Linda University Medical Center, Loma Linda, CA
Tetralogy of Fallot (TOF) is a cyanotic heart disease consisting of nonrestrictive ventricular septal defect, overriding aorta, pulmonary stenosis, and right ventricular hypertrophy. Early total correction is the treatment of choice and these patients with repaired TOF are increasingly seen in adult practice. This review addresses echocardiographic evaluation of TOF, corrected TOF, its sequelae and various complications. A working knowledge of TOF assessment is essential for all adult cardiologists and sonographers. (Echocardiography 2015;32:40–48) Key words: tetralogy of Fallot, echocardiography, pulmonary valve stenosis Danish anatomist Neil Stensen was the first to identify the condition in 1672. It was, however, Louis Arthur Fallot, who first described the anatomical components and pathological features of the condition. He called the condition “la maladie bleue” (blue malady) or cyanose cardiaque (cardiac cyanosis). Maude Abbott, a Canadian pioneer in pediatric cardiology used the term “tetralogy of Fallot” in 1924.1 Helen Taussig first postulated the progression of this condition resulting in cyanosis and death to be secondary to diminished pulmonary blood flow. Tetralogy of Fallot (TOF) is the most common cyanotic adult congenital heart disease with an incidence of 5 per 10,000 live births accounting for 10% of all congenital cardiac malformations and presents with equal gender prevalence. The prevalence of the condition is on the rise at the rate of 5% annually with the advent of successful corrective surgical procedures increasing the longevity of affected patients.2 When left untreated, a survival of 30% has been noted in the first decade of life that drops severely to a survival of 5% after the fourth decade. Surgical correction has proven to have a tremendous survival benefit in these patients. A thorough knowledge of the malformation and the associated pathophysiological changes prior to and at various periods after reparative or palliative surgery is crucial for a practicing cardiologist. This is particularly true for the management of a patient with TOF with cardiac or noncardiac issues when support from a regional Address for correspondence and reprint requests: Ramdas G. Pai, M.D., Professor of Medicine, Loma Linda University Medical Center, Loma Linda, CA 92354, Fax: 909-558-0903; E-mail: [email protected] *[Corrections added on 26th June 2014, after first online publication: article title was changed]
40
center for congenital heart diseases may not be available. Hence, we outline the various key aspects of the condition and its management through this review on echocardiographic evaluation of TOF. Etiology: Its exact etiology remains unclear but has been associated with chromosomal anomalies including 22q11 deletion syndrome (15% of TOF), Down syndrome, trisomy 13 and 18, maternal age >40 years, maternal diabetes mellitus, gestational exposure to hydantoin, retinoic acid, rubella and alcohol (fetal alcohol syndrome), maternal phenyl ketonuria, Alagille syndrome, and cat eye syndrome. 22q11 microdeletion (DiGeorge syndrome) is sporadic in 95% cases with remaining 5% being transmitted in an autosomal dominant fashion.3 FISH testing is widely available to test for this chromosomal abnormality and genetic counseling is offered in patients with TOF and other conotruncal anomalies. Mutation in coding region of GATA4/GATA6 (a gene encoding a zinc-finger transcription factor crucial for normal cardiogenesis) and mutations in the gene coding for transforming growth factor b2 and JAG1 have been the most recently studied genetic abnormalities to explain malformations in TOF.4,5 Essential Components of TOF: There are four essential components of TOF. A perimembranous ventricular septal defect (VSD), right ventricular outflow tract obstruction (RVOTO), an overriding aortic root, and a hypertrophied right ventricle. It has been postulated that cluster of defects caused by the anterior and cephalad migration of the infundibular septum (or its fibrous
Tetralogy of Fallot
remnant)6 while Van Praagh et al.1 believe that these are caused by the underdevelopment of the subpulmonary infundibulum. The effective rightward displacement the infundibular septum results in a malalignment of the infundibular septum with respect to the trabecular septum. This narrows the right ventricular outflow tract resulting in a larger and overriding ascending aorta and perimembranous VSD.6 Obstruction to right ventricular (RV) outflow results in RV hypertrophy.1,6 The anterocephalad deviation of the RV outlet septum and the failure of the outflow ventricular cushion to muscularize results in an infundibular septal defect (often perimembranous type of VSD). The size of this defect is variable. When there is a nonrestrictive type of septal defect, it results in equalization of the pressures between both ventricles and an unrestricted bidirectional flow between the ventricles. The impact of flow across the septum (or shunting) varies inversely with the degree of RVOTO. In a majority of patients posterior–inferior margin of the opening between the ventricles is formed by a fibrous continuity between the leaflets of the aortic and tricuspid valves. The remnant of the inter-ventricular portion of the membranous septum also forms this part of the VSD. In a minority of patients, the posteroinferior region of the defect is muscular and in such cases, the muscular tissue is formed by continuity of the posteroinferior limb of the septomarginal trabeculation with the infundibular fold. This structure protects the conduction axis in the ventricle during closure of the ventricular defect. The failure of muscularization of the outlet septum results in a fibrous band between the aortic and pulmonary valves (PVs). This forms the anterosuperior margin of the septal defect some patients of Caucasian descent, from the Far East, Central, and South America. Right ventricular outflow tract obstruction is a conotruncal developmental anomaly that occurs in the 4th–5th week of embryonic development of the heart. The level of outflow obstruction and its severity can be variable. The levels of RVOTO can occur at one or more of the following levels: (1) Right ventricular infundibulum: atretic outflow tract (2) PV: Bicuspid PV with supravalvular hypoplasia, subvalvular stenosis, or PV atresia (with or without collaterals between systemic and pulmonary vasculature) (3) Pulmonary artery (4) Branch pulmonary arteries Bronchial collaterals (systemic to pulmonary) are seen with severe RVOT obstruction/pulmo-
nary atresia. Right-sided arch occurs in about one-fifth of patients. The overriding aortic root allows blood from both ventricles due to the error in embryonic septal migration. When there is moderate to severe obstruction of the right ventricular outflow tract, there is significant right to left contributing to the blood flow into the aorta in addition to that from the left ventricle.6 Over a period of time, in unrepaired TOF, this volume overload along with intrinsic structural abnormalities of the aortic wall results in aneurysmal dilation of the aortic root. Aortic root dilatation can also be seen in repaired TOF attributed to the histological changes (medionecrosis, fibrosis, cystic medial necrosis, and elastic fragmentation) in the aortic wall. Overriding of aorta is also seen in context of a double outlet right ventricle. Right ventricular hypertrophy develops as a consequence to the increased pressure overload caused by the RVOTO and an overriding aorta. Anatomical Variants of TOF: Some of the variants of TOF include: (1) TOF with pulmonary atresia with or without major aortopulmonary collaterals. (2) TOF with absent PV, bicuspid or unicuspid PV with or without pulmonary stenosis. (3) TOF with double outlet right ventricle. (4) TOF with atrio-VSD. Associated Anomalies of TOF: Tetralogy of Fallot may be associated with a variety of congenital anomalies due to the nature of its development and the risk factors associated with its occurrence. These anomalies are summarized in Table II. Anomalous anterior descending artery deserves a special mention due to its surgical significance. It is seen in about 5–12% cases of patients with TOF. Instead of arising from the left main coronary artery, it arises from the right coronary artery and courses through the right ventricular infundibulum (RVOTO). The artery can be accidentally injured during the surgical correction of infundibular obstruction resulting in ischemia and arrhythmias. It is therefore essential to delineate the origin and course of the coronary arteries prior to surgical correction in TOF. At a similar note, it is equally important to realize that the anticipated and rare complication of transection frequently results in inadequate RVOTO release. Natural History of TOF: The variable severity of the condition and the concurrence of the associated major intra-cardiac 41
Swamy, et al.
anomalies determine the natural history or postsurgical long-term outcomes in adults with TOF. Without surgical intervention, 25% of the affected infants die in the first year of life with mortality reaching up to 40% age of 3 years; 70% by the end of first decade of life; and 90% by the end of 4th decade. Major causes of death in surgically untreated patients include hypoxic spells (62%), cerebrovascular accidents (17%), and brain abscesses (13%). With early reparative surgery in these patients there has been a sharp decline in mortality in the affected patients. As a result, we frequently encounter patients in their adulthood presenting with the complications of reparative or palliative shunt surgeries. Physiology: Ventricular septal defect in TOF is nonrestrictive leading to equal pressures in both ventricles. The direction and magnitude of flow through the defect depends on the severity of pulmonic stenosis. Moderate pulmonary stenosis (PS) is associated with a net left to right shunt at the ventricular level, and pulmonary flow exceeds systemic flow. More severe stenosis causes equal resistance to outflow into pulmonary and systemic circuits that causes bidirectional shunting. Severe obstruction to right ventricular outflow causes a large right to left shunt with markedly reduced pulmonary blood flow. Factors that can cause reduced arterial oxygen saturation are exercise-induced drop in systemic vascular resistance, hypercyanotic spells causing metabolic acidosis, and an increase in heart rate leading to increase in right to left shunt. Clinical Features and Diagnosis: About half of the patients are diagnosed antenatally by a fetal echocardiogram during pregnancy. The remaining patients are identified upon their presentation with cyanosis early in infancy or in the first few years of life. Cyanosis can be seen early in life or may develop later in life. Those who become cyanotic in adulthood typically have milder forms of the defect complex and or have a predominant left to right shunt mechanism until later in life. “Tet spells” or hypercyanotic episodes are more commonly observed in early childhood and infrequently in adulthood. The spells are typically precipitated by agitation or decreased hydration. With a decrease in systemic vascular resistance (due to decreased hydration) or an increase in pulmonary vascular resistance (resulting from infundibular muscle obstruction or spasm during agitation or crying) a significant right-to-left shunt across the VSD occurs. As a result, there is decreased pulmonary flow and increased deoxy42
genated blood flow into the systemic circulation. Central cyanosis is associated with varying degrees of hypoxia, which if left untreated can cause syncope and mortality. Congestive heart failure is a common initial presentation in infancy due to a large VSD while progressive PS develops a picture more consistent with TOF. Evolutions of Surgical Corrections of TOF: It is important for the echocardiographer to understand the various surgical procedures performed along with their time frames. In the year 1944, Helen Taussig, a cardiologist Johns Hopkins in collaboration with a surgeon, Alfred Blalock and his able surgical assistant Vivien Thomas developed creation of an “artificial ductus arteriosis” connecting the systemic circulation to the pulmonary circulation to relieve cyanosis in children with assumed TOF anatomy. This was a landmark in pediatric surgery and was the first type of palliative surgery which came to be known as “Blalock–Taussig Thomas” (BTT) shunt. This shunt established connection between the subclavian artery and the pulmonary artery.7 Very soon, the procedure became palliative not only for TOF but also for many other cyanotic congenital heart diseases. In 1946, Potts shunt was reported. This was described as an anastomosis between the descending aorta and the left pulmonary artery. The procedure was later abandoned because of the difficulty in closing the shunt at the time of complete repair. In 1962, Waterston shunt was reported and described as anastomosis between ascending aorta to pulmonary artery that was easy to perform and simple to close. In 1966, Cooley shunt was reported. It was described as an intra-pericardial anastomosis from ascending aorta to right pulmonary artery. The Potts, Waterston, and Cooley shunts were all central shunts and were less likely to thrombose compared with the relatively peripherally placed BTT shunt. The modified BTT shunt used a prosthetic tube graft interposed between the systemic artery (subclavian artery) and the pulmonary artery, instead of the direct anastomosis first described. Surgeons in the current use this modification for palliation. It was only in 1954 that Walton Lillehei of University of Minnesota performed the first total repair in 1954 using controlled cross circulation. This method used a single pump that controlled the reciprocal exchange between the patient and the donor. The commonest long-term issue after an intra-cardiac repair in TOF is progressive pulmonary regurgitation. In 1955, at the Mayo Clinic, John Kirklin and associates reported the use of a modified
Tetralogy of Fallot
Gibbons CPB circuit (Gibbon-Mayo pump oxygenator) in the open repair of complex congenital heart defects including VSD and TOF with a 60% survival rate.8 In 1970s, Bonchek and Starr evaluated the utility of surgical intervention in infancy. Among the 28 patients who had severe symptoms at the time of diagnosis and underwent immediate complete repair, the mortality was only 7%. Patient who received shunts at the time of diagnosis had a mortality of 31% (pulmonary atresia or severe hypoplasia only). The study established the superiority of complete repair at an earlier age.9 Current Surgical Trend in TOF: The timing of surgical repair is controversial and has been evolving over the years. Prior to 1970s, all patients with TOF mainly underwent palliative surgery that involved creation of a pulmonary systemic shunt followed by delayed intra-cardiac repair. After the 1970s, primary intra-cardiac repair became the treatment of choice in both symptomatic and asymptomatic patients with TOF. For the exceptional cases with hypoplastic pulmonary arteries, small-sized left ventricular (LV), anomalous origin of left coronary artery, multiple VSDs, the surgical techniques adopted in the treatment have evolved tremendously. Palliative Surgery for TOF: In the current era, palliative shunts are only performed in those who are poor candidates for intra-cardiac repair. The goal is to increase pulmonary blood flow by creating systemic artery to pulmonary artery connections. Initial Repair for TOF: Intra-cradiac surgical repair of TOF is usually performed in the first year of life; in patients who have undergone prior palliative surgery without development of pulmonary arterial hypertension; or in adults who have remained unoperated due to various circumstances. A complete TOF repair consists of two major components: Closure of the VSD: Closure is usually performed with continuous polypropylene suture, polyethylene terephthalate material, or Gore-Tex (W. L. Gore and Associates, Inc., Elkton, MD, USA) patch through either a transventricular or transatrial approach. The complications include residual VSD or leak from around the patch. Infundibular muscle may be resected if required. Inter-atrial communications are also closed with VSD closure. Relieving the RVOT obstruction: Resection of infundibular stenosis (with muscle resection if needed) is the most widely used method. When
the PV is small a right ventricular outflow augmentation with placement of a transannular patch is performed. Due to rapid growth in infancy and childhood, every attempt is made to preserve the native PV when initial intra-cardiac repair is performed in infancy. When complete repair is performed in adulthood, PV replacement is usually required if the native PV integrity is disrupted. In case of severe unresectable infundibular stenosis/pulmonary atresia or an anomalous coronary artery cruising through the infundibulum or RVOT, an extracardiac conduit with a right ventricle to pulmonary artery connection is created. It is noteworthy that though the anomalous origin of left anterior descending artery from RCA has been reported to vary from 5 to 12% in various literatures, its occurrence is in real practice relatively rare. The complications arising from its transection during the RVOTO release is detrimental though rare. The anticipation of this complication during the procedure often results in incomplete or inadequate release of RVOTO. Over the years, materials used for surgical correction of right ventricular outflow obstruction have included placement of homografts, bovine jugular valved conduits (Contegra), stentless valves, stented tissue valves, monocusp valves, mechanical valves, autologous pericardial valves, and transcatheter PVs. In 2010, the US Food and Drug Administration formally approved the Medtronic Melody (Medtronic, Minneapolis, MN, USA) Transcatheter Pulmonary Valve. This device is indicated for use as an adjunct to surgery in the management of pediatric and adult patients with the following clinical conditions: (1.) Existence of a full (circumferential) RVOT conduit that was equal to or greater than 16 mm in diameter when originally implanted and (2.) Dysfunctional RVOT conduits with a clinical indication for intervention, and either regurgitation (>moderate) or stenosis (mean RVOT gradient >35 mmHg). Adults with Corrected TOF: The long-term sequelae and complications of TOF that are surgically corrected are discussed as below. Table I summarizes these problems and with suggested management. The sequelae and complications of TOF are summarized in Table II.10 Atrial and ventricular scarring resulting in AV block, atrial flutter, and/or atrial fibrillation, ventricular tachycardia (sustained or nonsustained). Chronic pulmonary regurgitation leads to stretching of the right ventricular myocardium 43
Swamy, et al.
TABLE I Surgical Procedures for Rerepair of Tetralogy of Fallot in Adults (Adapated from ACC/AHA guidelines – Warnes et al. (2008)10 Pulmonary valve replacement (PVR) Heterograft (porcine or pericardial) or homograft Mechanical PVR in patients who require warfarin anticoagulation for other reasons. This procedure has been associated with late malfunction from pannus formation. Patch augmentation of the pulmonary annulus for proper prosthetic valve sizing Subvalvular obstruction or pulmonary artery stenosis Resection of subvalvular obstruction and/or patch augmentation of the RVOT, pulmonary annulus, main or branch pulmonary arteries Usually occurs in combination with PVR Residual/recurrent VSD closure Direct suture Patch revision AVR (tissue or mechanical) for aortic regurgitation Replacement of ascending aorta for dilatation Tube graft Bentall procedure (composite valve conduit with coronary reimplantation) Aneurysm or pseudoaneurysm formation of RVOT Resection and patch replacement Atrial arrhythmias Maze procedure or 1 of its modifications Ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation) Preoperative EP testing and ablation in the catheterization laboratory If unsuccessful, intra-operative mapping, and ablation are performed Focus is most often in the RVOT between the VSD patch and the pulmonary annulus Postoperative placement of an ICD for patients at high risk of sudden death Tricuspid valve repair for significant tricuspid regurgitation Tricuspid valve replacement for a markedly abnormal tricuspid valve Closure of residual PFO or ASD, especially if there is cyanosis, history of paradoxical embolism, or anticipated need for a permanent pacemaker or ICD. RVOT = right ventricular outflow tract; VSD = ventricular septal defect; ICD = intra-cardiac defibrillator; PFO = patent foramen ovale; ASD = atrial septal defect.
resulting in areas of inhomogeneous electrical activity. Structural changes in the myocardium along with scarring from reparative surgeries result in increased refractoriness that predisposes to reentrant electrical activity causing ventricular arrhythmias. Right ventricular dysfunction and dilatation is associated with right atrial dilatation. Right atrial dilatation and scarring from reparative surgeries result in a similar reentrant electrical activity causing atrial fibrillation, atrial flutter, and other sustained/nonsustained atrial tachyarhhythmias. Echocardiographic Features of TOF: In adults with unrepaired TOF, the key echocardiographic features are listed under main features and associated anomalies (Figs. 1–3). In adults who have undergone intra-cradiac surgical repair, an echocardiographer should look for a residual VSD, pulmonary regurgitation with associated RV dilation/dysfunction, infundibular stenosis, aortic root dilation, residual uncorrected anomalies, hypoplastic pulmonary annulus, pulmonary artery or its branches, or pulmonary artery branch stenosis. Complications related to these may unfold over time. Table II summarizes 44
the key features for a comprehensive echocardiographic examination. Transthoracic images should be obtained from all standard views, especially the suprasternal view. The latter is vital for the evaluation of the arch and its associated anomalies; systemic to pulmonary shunts and for estimating the size of the pulmonary artery branches.11 Parasternal views are important for assessment of the RVOT, PV, main pulmonary artery, VSD patch, ascending aortic size, and aortic valve (Figs. 4–5). The shortaxis view not only allows us to visualize the RVOT but also determine the size and extent of the septal defect. As mentioned earlier, RVOTO can occur at various anatomic levels and the parasternal short-axis and subcostal coronal views must be used to meticulously evaluate each potential level of obstruction. While color Doppler is useful in assessing the location of turbulent flow, continuous-wave Doppler helps in determining pressure gradients across the various levels of obstruction. Apical views are important for determining the RV size and function and the subcostal view allows visualization of the inferior venacava (IVC) size and atrial septum. Sometimes when transthoracic images are suboptimal, a transesophageal echo
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TABLE II Echocardiographic Findings in TOF Uncorrected TOF
Repair-Related Findings or Long-Term Sequelae
Associated Anomalies
Large unrestrictive perimembranous VSD Overriding aorta (i.e.,
