Practice EssentialsTetralogy of Fallot (TOF) (pronounced te-tral-uh-jee of Fal-oh), one of the most common congenital heart disorders, comprises right ventricular (RV) outflow tract obstruction (RVOTO) (infundibular stenosis), ventricular septal defect (VSD), aorta dextroposition (overriding aorta), and RV hypertrophy (see the image below). The mortality rate in untreated patients reaches 50% by age 6 years, but in the present era of cardiac surgery, children with simple forms of tetralogy of Fallot enjoy good long-term survival with an excellent quality of life. Show
However, it is important to understand that corrective surgery for tetralogy of Fallot performed in childhood is not curative surgery. As a result, many children with repaired tetralogy of Fallot survive into adulthood and are seen at cardiology clinics. [1, 2] Some patients who never underwent surgery for mild tetralogy during childhood may present as adults with a variety of symptoms, and other patients who may only have had a palliative procedure (eg, shunt placement) can also present as adults. [3] Anatomic findings in tetralogy of Fallot are depicted.Signs and symptoms of tetralogy of FallotThe clinical features of tetralogy of Fallot in the adult are directly related to the severity of the anatomic defects and may include the following:
Infants, however, often display the following:
Physical findings in adults include the following:
See Presentation for more detail. Diagnosis of tetralogy of FallotIn adult patients, the following laboratory studies may be helpful:
Imaging studies include the following:
Chest radiographs have the following attributes:
Echocardiography has the following attributes:
MRI has the following attributes:
Cardiac catheterization is useful in any of the following settings:
Cardiac catheterization allows the following:
See Workup for more detail. See also the Guidelines section for the 2018 American Heart Association/American College of Cardiology (AHA/ACC) recommendations for the management of adults with tetralogy of Fallot. Treatment of tetralogy of FallotFor adults with acute cyanosis, place them in a knee-chest position. In addition, provide/administer the following:
Most symptomatic adults with tetralogy of Fallot require some type of surgical intervention. Pulmonary valve replacement is the most common procedure performed, usually under cardiopulmonary bypass. Factors that increase the risk for surgery in adult patients with tetralogy of Fallot include the following:
See Treatment and Medication for more detail, as well as the Guidelines section for the 2018 American Heart Association/American College of Cardiology (AHA/ACC) recommendations for the management of adults with tetralogy of Fallot. BackgroundTetralogy of Fallot (TOF) (pronounced te-tral-uh-jee of Fal-oh) is one of the most common congenital heart disorders (CHDs). This condition is classified as a cyanotic heart disorder, because tetralogy of Fallot results in an inadequate flow of blood to the lungs for oxygenation (right-to-left shunt) (see the following image). Patients with tetralogy of Fallot initially present with cyanosis shortly after birth, thereby attracting early medical attention. In most cases, the cyanosis does not present for a few weeks or months after birth; however, infants born with transposition of the great vessels usually present with cyanosis immediately after birth. Anatomic findings in tetralogy of Fallot are depicted.Typical featuresThe four features typical of tetralogy of Fallot include right ventricular (RV) outflow tract obstruction (RVOTO) (infundibular stenosis), ventricular septal defect (VSD), aorta dextroposition (overriding aorta), and right ventricular hypertrophy. Occasionally, a few children also have an atrial septal defect (ASD), which makes up the pentad of Fallot. The basic pathology of tetralogy is due to the underdevelopment of the RV infundibulum, which results in an anterior-leftward malalignment of the infundibular septum. This malalignment determines the degree of RVOTO. The clinical features of tetralogy of Fallot are generally typical, and a preliminary clinical diagnosis can almost always be made. Because most infants with this disorder require surgery, it is fortunate that the availability of cardiopulmonary bypass (CPB), cardioplegia, and surgical techniques is now well established. Most surgical series report excellent clinical results with low morbidity and mortality rates. Surgery in infancyThe first surgery to repair tetralogy of Fallot consisted of placement of a shunt to relieve the cyanosis. Primary repair is currently recommended within the first 12 months of life; in general, excellent results are obtained at most centers. Ever since primary repair of tetralogy of Fallot became the standard of care nearly 30 years ago, more adult patients with repaired tetralogy of Fallot in early childhood are living longer, [1, 2] and they are being seen at many cardiac clinics. Some patients who never underwent surgery for mild tetralogy during childhood may present as adults with a variety of symptoms, and other patients who may only have had a palliative procedure (eg, shunt placement) can also present as adults. [3] What happens years after surgical repair?It is important to understand that corrective surgery for tetralogy of Fallot performed in childhood is not curative surgery. Rather, this procedure only corrects the anatomic defects—without changing the progression of the disease or addressing the consequences of using a patch. As a result, these individuals develop new symptoms and eventually present to the cardiology clinic with diverse symptoms. Thus, most pediatric surgeons consider the initial surgery for tetralogy of Fallot to be long-term palliation, not definitive surgery. With advancing age, children with tetralogy of Fallot who had corrective surgery are usually asymptomatic for the first decade after the initial procedure. Thereafter, they develop adverse myocardial problems, the majority of which involve varying degrees of pulmonary valve insufficiency, which, in turn, can lead to RV overload and RV distention and failure. [7] RV enlargement also leads to the development of atrial and ventricular arrhythmias, which, if not recognized early, are a common cause of high morbidity and mortality. An estimated one third of adults with tetralogy of Fallot experience atrial and ventricular arrhythmias over a period of 2-3 decades. The incidence of sudden death ranges from 6% to 9% in patients who develop these arrhythmias. [8] Another concern regarding patients with tetralogy of Fallot is that many are lost to follow-up as they become adults, and thus the opportunity to manage complications before they become irreversible can be missed. Several surveys indicate that many children with repaired tetralogy of Fallot feel fine after surgery, believe that they are cured, and then stop seeing their cardiologist. In other cases, the primary care provider is unaware of the need to follow these patients, owing to the erroneous belief that surgery is curative. See also Tetralogy of Fallot With Pulmonary Stenosis, Tetralogy of Fallot With Pulmonary Atresia, and Tetralogy of Fallot With Absent Pulmonary Valve. Historical informationLouis Arthur Fallot, after whom the name tetralogy of Fallot is derived, was not the first person to recognize the condition. Stensen first described it in 1672; however, it was Fallot who first accurately described the clinical and complete pathologic features of the defects. Although the disorder was clinically diagnosed much earlier, no treatment was available until the 1940s. Cardiologist Helen Taussig recognized that cyanosis progressed and inevitably led to death in infants with tetralogy of Fallot. She postulated that the cyanosis was due to inadequate pulmonary blood flow. Her collaboration with Alfred Blalock led to the first type of palliation for these infants. In 1944, Blalock operated on an infant with tetralogy of Fallot and created the first Blalock-Taussig shunt between the subclavian artery and the pulmonary artery (see the image below). This image shows completed blocking with a Taussig shunt.The pioneering Blalock-Taussig shunt surgical technique opened a new era in neonatal cardiac surgery. Development of the Potts shunt (from the descending aorta to the left pulmonary artery), the Glenn shunt (from the superior vena cava to the right pulmonary artery), and the Waterston shunt (from the ascending aorta to the right pulmonary artery) followed. Scott performed the first open correction in 1954. Less than 6 months later, Lillehei performed the first successful open repair for tetralogy of Fallot using controlled cross-circulation, with another patient serving as oxygenator and blood reservoir. The following year, with the advent of cardiopulmonary bypass by Gibbons, another historic era of cardiac surgery was established. Since then, numerous advances in surgical technique and myocardial preservation have evolved in the treatment of tetralogy of Fallot. AnatomyThe classic anatomic features of adult patients with tetralogy of Fallot (TOF) are no different from those seen in pediatric patients, such as the following [9] :
AortaThe aorta in patients with tetralogy of Fallot is hugely dilated and overrides the diminutive pulmonary artery. In about 25% of cases, the aorta arises from a right-sided aortic arch. Because of this feature and overriding of the septum, about 50% of the blood flow from the aorta arises from the RV via the large perimembranous VSD. RVOTOIn the majority of adults with tetralogy of Fallot, there is resistance to RV emptying. The obstruction is caused by the anterior displacement and rotation of the infundibular septum which narrows the outflow tract. The infundibular obstruction may be associated with pulmonary valve stenosis or atresia, which results in further outflow tract obstruction. Pulmonary arteriesThe size of the pulmonary arteries in tetralogy of Fallot vary in size and distribution. In most cases, the vessels are hypoplastic but can be atretic in severe cases. An almost universally common feature of tetralogy of Fallot is reduced blood flow in the pulmonary arteries and, hence cyanosis. There are also reported cases of an absent left pulmonary artery. In close to three quarters of patients with TOF, there is pulmonary valve stenosis, which is often due to leaflet tethering rather than commissural fusion. In virtually all such cases, the pulmonary annulus is narrowed. Associated anomaliesAssociated heart defects are very common in tetralogy of Fallot. Some patients may have an atrial septal defect, often referred to as part of the pentad of Fallot. Other common defects include a patent ductus arteriosus, muscular VSD, atrioventricular septal defects, anomalous coronary arteries, anomalous pulmonary venous return, absent pulmonary valve, aortic incompetence, and aortopulmonary window. [10, 11] Etiology and PathophysiologyPathophysiology in pediatric patients with tetralogy of FallotThe cause(s) of most congenital heart diseases (CHDs) are unknown, although genetic studies suggest a multifactorial etiology. Methylene tetrahydrofolate reductase (MTHFR) gene polymorphism may be a susceptibility gene for tetralogy of Fallot (TOF). [12, 13] More recently, it appears that VEGF genetic polymorphisms, -2578C>A and -634C>G, may be associated with an increased risk for tetralogy of Fallot, whereas the risk is potentially reduced with 936C>T polymorphism. [14] Prenatal factors associated with a higher incidence of tetralogy of Fallot include maternal rubella (or other viral illnesses) during pregnancy, poor prenatal nutrition, maternal alcohol use, maternal age older than 40 years, maternal phenylketonuria (PKU) birth defects, and diabetes. Children with Down syndrome also have a higher incidence of tetralogy of Fallot, as do infants with fetal hydantoin syndrome or fetal carbamazepine syndrome. In addition, as one of the conotruncal malformations, tetralogy of Fallot can be associated with a spectrum of lesions known as CATCH 22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia). Cytogenetic analysis may demonstrate deletions of a segment of chromosome band 22q11 (DiGeorge critical region). Ablation of cells of the neural crest has been shown to reproduce conotruncal malformations. These abnormalities are associated with the DiGeorge syndrome and branchial arch abnormalities. The hemodynamics of tetralogy of Fallot depend on the degree of right ventricular (RV) outflow tract obstruction (RVOTO). The ventricular septal defect (VSD) is usually nonrestrictive, and the RV and left ventricular (LV) pressures are equalized. If the obstruction is severe, the intracardiac shunt is from right to left, and pulmonary blood flow may be markedly diminished. In this instance, blood flow may depend on the patent ductus arteriosus (PDA) or bronchial collaterals. Pathophysiology in the adult with tetralogy of FallotPreviously, clinicians often ordered routine echocardiograms in adult patients with tetralogy of Fallot who were followed in the clinic following surgery in infancy. At that time, it was felt that, as in cases of tricuspid regurgitation, pulmonary valve insufficiency was a relatively benign and inconsequential observed entity. Because most affected patients were not symptomatic, they were never treated. However, observation of these patients over time revealed that they began to develop severe RV dysfunction and arrhythmias. The RV dilatation from the pulmonary valve insufficiency is associated with fibrosis and severe myocardial damage, which then often lead to a decrease in exercise endurance, and the majority of patients soon develop ventricular arrhythmias. [15] Initially most patients with chronic RV function are asymptomatic, but as the compensatory mechanisms fail and the ejection fraction decreases, symptoms start to appear. If the condition is not treated at this stage, the RV dysfunction is irreversible. The arrhythmias occur as a result of progressive dilatation and stretching of the right atrium and RV. ArrhythmiasAtrial arrhythmias of clinical significance are chiefly of the reentry type, but they may also include atrial tachycardia and atrial fibrillation. These atrial arrhythmias occur in 10-35% of patients with repaired tetralogy of Fallot. [16] Ventricular arrhythmias and sudden death are also known to occur in those with repaired tetralogy of Fallot. Case studies have revealed that patients who experience sudden death often have moderate to severe pulmonary valve insufficiency at the time of death. Ventricular arrhythmias tend to be less common in patients with mild pulmonary valve insufficiency. Overall, the risk of late sudden death is many times greater in patients who survive tetralogy of Fallot surgery than in their age-matched counterparts. [17] EpidemiologyTetralogy of Fallot (TOF) represents approximately 7%-10% of congenital heart diseases (CHDs), [2] and it is the most common cyanotic CHD, with 0.23-0.63 cases per 1,000 births. [1] This disorder accounts for one third of all CHD in patients younger than 15 years; in adults, tetralogy of Fallot has an estimated prevalence of 1 in 3,500 to 1 in 4,300 people. [2] In most cases, tetralogy of Fallot is sporadic and nonfamilial. The incidence in siblings of affected parents is 1-5%, and it occurs more commonly in males than in females. The disorder is associated with extracardiac anomalies such as cleft lip and palate, hypospadias, and skeletal and craniofacial abnormalities. Genetic studies indicate that in some patients with tetralogy of Fallot, there may be 22q11.2 deletion and other submicroscopic copy number alterations. [18] Adult patients with tetralogy of Fallot currently represent a very large group of patients who underwent congenital heart surgery in early life. Although the exact number of these adults is not known, because many are lost to follow-up or have never been followed, it is estimated that over two thirds of affected children who undergo repair of tetralogy of Fallot in early childhood will reach adulthood, with one study showing 94% survival rate of 168 patients aged 16 years and older who underwent simple repair. [17] For individuals born with this condition, the 30-year survival is above 75%, provided these individuals have been clinically followed. Limited data to date reveal that adult tetralogy of Fallot is equally common in both sexes. The majority of adult patients with repaired tetralogy of Fallot present after the second or third decade of life. Males and females appear to be equally affected with symptoms as they age. [19] PrognosisIn the present era of cardiac surgery, children with simple forms of tetralogy of Fallot (TOF) enjoy good long-term survival with an excellent quality of life. Late outcome data suggest that most survivors are in New York Heart Association (NYHA) classification I, although maximal exercise capability is reduced in some. About 75% infants who undergo repair during infancy will survive to reach their second to third decade of life without major consequences. However, after the first two decades of life, symptoms start to appear due to pulmonary valve regurgitation. By the fourth decade of life, most survivors are symptomatic. Adult patients with tetralogy of Fallot who undergo surgery again are usually symptom free for 10-15 years, but by the time they reach their fifth decade, even these patients begin to have symptoms. [17] Although the second surgery reduces the rate of death, the majority of these individuals have a shorter lifespan than age-matched control subjects without a history of congenital heart disease. Adults with recalcitrant arrhythmias and right heart failure have the worst prognosis. Sudden death from ventricular arrhythmias has been reported in 1-5% of patients at a later stage in life, and the cause remains unknown. It has been suspected that ventricular dysfunction may be the cause. One study found left ventricular longitudinal dysfunction to be associated with a greater risk of developing life-threatening arrhythmias. [20] Continued cardiac monitoring into adult life is necessary. For some time, it has been suspected that certain children may have inherited a predispostion to developing long QT syndrome. A 2012 study by Chiu confirmed this suspicion. [21] Most individuals who survive to age 30 years develop congestive heart failure (CHF), although individuals whose shunts produce minimal hemodynamic compromise have been noted, albeit rarely, and these individuals achieve a normal life span. Survival of patients into their 80s have been reported. Due to advanced surgical techniques, a 40% reduction in deaths associated with tetralogy of Fallot was noted from 1979 to 2005. [19] ComplicationsAdults with repaired tetralogy of Fallot during infancy can present with the following complications later in life:
See Surgical Complications in patients with repaired tetralogy of Fallot.
Author Coauthor(s) Mary C Mancini, MD, PhD, MMM Mary C Mancini, MD, PhD, MMM is a member of the following medical societies: American Association for Thoracic Surgery, American College of Surgeons, American Surgical Association, Phi Beta Kappa, Society of Thoracic Surgeons Disclosure: Nothing to disclose. Chief Editor Yasmine S Ali, MD, MSCI, FACC, FACP Assistant Clinical Professor of Medicine, Vanderbilt University School of Medicine; President, LastSky Writing, LLC Yasmine S Ali, MD, MSCI, FACC, FACP is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, American Medical Writers Association, National Lipid Association, Tennessee Medical Association Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: LastSky Writing;Philips Healthcare;M Health;Athena Health;PeerView Institute;Verywell Health; HealthCentral;MedEdicus;Pharmaceutical Training Institute;Elsevier;MedStudy;North American Thrombosis Forum;WellnessVerge;Prose Media; AKH, Inc.<br/>Serve(d) as a speaker or a member of a speakers bureau for: North American Thrombosis Forum. Acknowledgements David FM Brown, MD Associate Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair, Department of Emergency Medicine, Massachusetts General Hospital David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine Disclosure: lippincott Royalty textbook royalty; wiley Royalty textbook royalty David A Donson, MD Assistant Medical Director, Department of Emergency Medicine, Maimonides Medical Center David A Donson, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Theodore J Gaeta, DO, MPH, FACEP Clinical Associate Professor, Department of Emergency Medicine, Weill Cornell Medical College; Vice Chairman and Program Director of Emergency Medicine Residency Program, Department of Emergency Medicine, New York Methodist Hospital; Academic Chair, Adjunct Professor, Department of Emergency Medicine, St George's University School of Medicine Theodore J Gaeta, DO, MPH, FACEP is a member of the following medical societies: Alliance for Clinical Education, American College of Emergency Physicians, Clerkship Directors in Emergency Medicine, Council of Emergency Medicine Residency Directors, New York Academy of Medicine, and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Ronald J Oudiz, MD, FACP, FACC, FCCP Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Director, Liu Center for Pulmonary Hypertension, Division of Cardiology, LA Biomedical Research Institute at Harbor-UCLA Medical Center Ronald J Oudiz, MD, FACP, FACC, FCCP is a member of the following medical societies: American College of Cardiology, American College of Chest Physicians, American College of Physicians, American Heart Association, and American Thoracic Society Disclosure: Actelion Grant/research funds Clinical Trials + honoraria; Ikaria Grant/research funds Clinical Trials + honoraria; Gilead Grant/research funds Clinical Trials + honoraria; Pfizer Grant/research funds Clinical Trials + honoraria; United Therapeutics Grant/research funds Clinical Trials + honoraria; Lilly Grant/research funds Clinical Trials + honoraria; Lung LLC Clinical Trials + honoraria; Bayer Grant/research funds Consulting; Medtronic Consulting fee Consulting; Novartis Consulting fee Consulting Kurt Pflieger, MD, FAAP Active Staff, Department of Pediatrics, Lake Pointe Medical Center Kurt Pflieger, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Emergency Physicians, American Heart Association, and Texas Medical Association Disclosure: Nothing to disclose. Gary Edward Sander, MD, PhD, FACC, FAHA, FACP, FASH Professor of Medicine, Director of CME Programs, Team Leader, Root Cause Analysis, Tulane University Heart and Vascular Institute; Director of In-Patient Cardiology, Tulane Service, University Hospital; Visiting Physician, Medical Center of Louisiana at New Orleans; Faculty, Pennington Biomedical Research Institute, Louisiana State University; Professor, Tulane University School of Medicine Gary Edward Sander, MD, PhD, FACC, FAHA, FACP, FASH is a member of the following medical societies: Alpha Omega Alpha, American Chemical Society, American College of Cardiology, American College of Chest Physicians, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Heart Association, American Society for Pharmacology and Experimental Therapeutics, American Society of Hypertension,American Thoracic Society, Heart Failure Society of America, Louisiana State Medical Society, National Lipid Association, and Southern Society for Clinical Investigation Disclosure: Forest Labs Honoraria Speaking and teaching Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management position; ProceduresConsult.com Royalty Other Mark Spektor, DO Medical Director, Department of Emergency Medicine, Maimonides Medical Center Mark Spektor, DO is a member of the following medical societies: American College of Emergency Physicians, American College of Physician Executives, and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Which symptom set is most indicative of tetralogy of Fallot?The most common signs and symptoms seen for a newborn with tetralogy of Fallot include: 1) a loud heart murmur (systolic ejection murmur at the left upper sternal border due to pulmonic stenosis and/or holosystolic murmur at the left mid sternal border due to a ventricular septal defect); and 2) cyanosis.
What clinical manifestation of tetralogy of Fallot should the nurse expect when caring for an infant with this diagnosis?Infants with tetralogy of Fallot can have a bluish-looking skin color―called cyanosis―because their blood doesn't carry enough oxygen. At birth, infants might not have blue-looking skin, but later might develop sudden episodes of bluish skin during crying or feeding. These episodes are called tet spells.
What is the most common complication of tetralogy of Fallot?What are possible complications of tetralogy of Fallot?. Blood clots (which may be in the brain causing stroke). Infection in the lining of the heart and heart valves (bacterial endocarditis). Abnormal heart rhythms (arrhythmias). Heart failure.. Death.. What are the four cardinal features of tetralogy of Fallot?The four cardinal features of tetralogy of Fallot include right ventricular outflow tract obstruction, ventricular septal defect, right ventricular hypertrophy, and aortic override of the septal defect.
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