Cardiology Patient Page
Tetralogy of Fallot Patricia O’Brien, MSN, CPNP-AC; Audrey C. Marshall, MD
C
ongenital heart defects result from abnormal changes in the structure of the heart that occur early in pregnancy and are present at birth. They are the most common birth defects, occurring in about 1 in 125 births. Tetralogy of Fallot (TOF) is a common defect in which obstruction to the flow of blood from the heart to the lungs causes low oxygen levels in the blood. Open heart surgery to correct the heart defect is the only treatment that gives long-term survival.
What Is TOF? TOF is a defect combining 4 abnormalities that are all related (Figure): 1. Right ventricular outflow tract obstruction. The connection between the right ventricle of the heart and the lungs is narrowed, and the blood flow to the lungs is reduced. The main area of narrowing is under the pulmonary valve, caused by thick muscle in this area. The valve may also be narrow (stenotic), and the pulmonary artery may also be small (hypoplastic).
2. Ventricular septal defect. There is a hole in the wall (septum) between the right and left ventricles (pumping chambers) of the heart. 3. Overriding of the aorta. The major blood vessel from the heart to the body, the aorta, is positioned more rightward than normal and sits above the ventricular septal defect. 4. Hypertrophy of the right ventricle. The right ventricle is more muscular than normal as a result of the right ventricular outflow tract obstruction and the need to pump harder. TOF can be seen with other heart defects, but this Cardiology Patient Page focuses on the most common form, TOF with pulmonary stenosis. TOF occurs equally in boys and girls and in all races and ethnic groups. It is associated with several genetic conditions, including trisomy 21 (Down syndrome), and with deletions on chromosome 22 and may occur with other birth defects such as cleft lip and palate. If a parent or sibling has TOF, other children in the family also have
a higher-than-average chance of having this heart defect.
How Is TOF Diagnosed? Many newborns with TOF will have lower measured oxygen levels than normal or may have visibly blue lips or nail beds (called cyanosis). It is now recommended that newborns get screened for heart disease by having their oxygen levels measured by a machine called a pulse oximeter before going home. A heart murmur (abnormal heart sounds caused by turbulent blood flow) may be heard with a stethoscope. An echocardiogram, an ultrasound that gives detailed images of the heart, is necessary to confirm the diagnosis. Today, many infants are diagnosed with a heart defect before birth by an ultrasound during pregnancy. Symptoms vary, depending on the severity of obstruction to blood flow to the lungs. Some infants appear blue soon after birth because of severe obstruction, whereas others with less obstruction are a normal pink color. The obstruction generally gets worse over time, so blue lips may
The information contained in this Circulation Cardiology Patient Page is not a substitute for medical advice, and the American Heart Association recommends consultation with your doctor or healthcare professional. From the Department of Nursing/Patient Services, Cardiovascular Program, Boston Children’s Hospital, Boston, MA (P.O.); and Department of Pediatrics, Harvard Medical School, and Cardiac Catheterization Laboratory, Department of Cardiology, Boston Children’s Hospital, Boston, MA (A.C.M.). Correspondence to Patricia O’Brien, MSN, CPNP-AC, Department of Nursing/Patient Services, Cardiovascular Program, Boston Children’s Hospital. E-mail [email protected] (Circulation. 2014;130:e26-e29.) © 2014 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.113.005547
Downloaded from http://circ.ahajournals.org/ at CONS e26 CALIFORNIA DIG LIB on December 9, 2014
O’Brien and Marshall Tetralogy of Fallot e27
Figure. Diagram of normal heart contrasted with heart defects associated with Tetralogy of Fallot. From Boston Children’s Hospital Web site.
first appear at several months of age. Some infants with mild obstruction may never be blue (“pink Tets”) and may have signs of too much blood flow to the lungs (rapid breathing, poor feeding, and slow weight gain), much like an infant with only a ventricular septal defect. Most newborns with TOF are well, with normal breathing and feeding, and can be discharged home with
surgery planned several months later. Premature infants or newborns with other major medical problems that put them at higher risk may do better avoiding a full repair and instead having a temporary procedure if they have severe obstruction (Table 1).
Hypercyanotic Spells Infants with TOF may have hypercyanotic spells (“Tet spells”), episodes in
which they become intensely blue with deeper and faster breathing. Most common between 2 and 4 months of age, spells occur more often in the morning with crying, feeding, or stooling or at times of stress, or they can be triggered by dehydration. Treatment includes calming the baby and holding the baby in a position with knees up touching the chest. This changes the blood flow pattern in the heart and may relieve the
Table 1. Treatments for Tetralogy of Fallot With Pulmonary Stenosis Age
Characteristics
Treatments
Newborn
Severe cyanosis in newborns at higher risk for complete repair: premature infants, infants with other birth defects, very ill infants
TEMPORARY PROCEDURES: SURGERY: Shunt procedure: Gore-Tex tube from an artery off the aorta to the pulmonary artery to provide blood flow to the lungs CATHETERIZATION: dilation of the pulmonary valve
3–6 mo
Open heart surgery, heart-lung bypass
SURGERY: complete repair: 1. Close the VSD with a patch so that the aorta comes from the left ventricle 2. Remove extra-thick muscle in the right ventricle below the valve 3. Repair narrow pulmonary valve a. Valve-sparing technique for mild obstruction: pulmonary valve is dilated b. Transannular patch for severe obstruction: larger patch going across the pulmonary valve extending from the right ventricle to the pulmonary artery that destroys the pulmonary valve 4. Patch the right ventricle to relieve obstruction In 5% of patients, an abnormal coronary artery (supplies blood to heart muscle) crosses the area where the patch would go. In that case, repair is done with a conduit (tube) from right ventricle to main pulmonary artery
Type of surgical repair depends on child’s anatomy
Adolescents and adults
Progressive leaking of the pulmonary valve and dilation of the right ventricle Narrow pulmonary valve or pulmonary artery
SURGERY: pulmonary valve replacement with tissue valve CATHETERIZATION: balloon dilate pulmonary valve or pulmonary artery
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on December 9, 2014
e28 Circulation July 22, 2014
spell. If there is no improvement in a few minutes, call 9-1-1. Rarely, spells can cause babies to pass out or to have a seizure or a stroke. If a spell occurs, surgery is performed soon to prevent further spells.
Surgical Treatment Most infants have a surgical repair at 3 to 6 months of age. Surgery is done through an incision in the center of the chest along the sternum (breastbone), and the heart-lung bypass machine is used to support the circulation during the operation (Table 1). Infants are usually in the hospital for about a week and fully recover in 4 to 6 weeks. Surgical results are excellent, with a less than 2% surgical mortality and very good long-term outcomes. After surgery, infants are in the intensive care unit for several days, are on a ventilator to help them breathe, and receive medicines to help the heart recover from surgery. A problem seen early after surgery can be fluid overload in the lungs and body because the right ventricle is not pumping effectively as it recovers. Medicines called diuretics are used to help get rid of extra fluid. Problems with abnormal heartbeats (rhythm problems) may also occur after surgery because of swelling or injury to the electric system of the heart, which runs next to the ventricular septal defect. Rarely, a pacemaker may be needed if the rhythm does not return to normal.
Long-Term Concerns During childhood, most children do very well, with normal growth and development, but need regular cardiology care (Table 2). However, even successful surgery does not result in a totally normal heart. The right ventricular outflow tract often has some degree of obstruction, and the pulmonary valve does not function normally. As a result of most surgical repairs, the valve leaflets cannot close completely, allowing blood to leak back into the right ventricle (called pulmonary regurgitation).
Table 2. Future Care Few children have symptoms, and most may participate in normal activities without restriction Medical care involves regular (yearly) evaluations by the cardiologist with electrocardiograms and echocardiograms to monitor for cardiac concerns that may occur late after repair Continued or progressive obstruction in the right ventricle Continued or progressive obstruction across the pulmonary arteries Leaking (regurgitation) of the pulmonary valve Increasing dilation of the right ventricle and decreased ventricle function Dilation of the aorta (rarely needs treatment) Rhythm problems Ventricular tachycardia: dangerous fast rhythm Abnormal slow rhythms: need for pacemaker Heart-healthy lifestyle is encouraged Healthy diet and appropriate weight for age Regular exercise No smoking Regular dental care is necessary Higher incidence of learning and behavioral problems is observed Attention deficit–hyperactivity disorder, learning disabilities, speech delays, etc Early assessment and treatment Adolescents are prepared to become more responsible for their own health care Learn more about tetralogy of Fallot and long-term issues Assume more responsibility for care over time Most will achieve normal adult lifestyle (eg, work full-time, have children)
Pulmonary regurgitation is well tolerated in children, but over many years, the right ventricle may dilate and stretch in some patients. The right ventricle may pump less effectively, which increases the risk of rhythm problems and may decrease exercise ability. Early signs of trouble from pulmonary regurgitation are seen on echocardiograms and are further evaluated with magnetic resonance imaging. Magnetic resonance imaging is an imaging study done inside a magnet that allows very detailed pictures and measurements of the heart structures. Surgical replacement of the pulmonary valve with a tissue valve is considered for patients with progressive right ventricular dilation. This is a low-risk open heart procedure done on the heart-lung bypass machine; the usual hospital stay is less than a week; and recovery is in 6 to 8 weeks. Abnormal rhythm problems, especially a very rapid heart rate called ventricular tachycardia, which can be
life-threatening, can occur years after TOF repair. More common in those with significant obstruction in the right ventricle, symptoms include dizziness, fainting, or palpitations (irregular or rapid heartbeat). Treatments may include medications or further procedures.
Summary TOF is a congenital heart defect that results in decreased blood flow to the lungs and is successfully repaired by surgery in infancy, allowing most patients a normal lifestyle. Lifelong follow-up is important to watch for problems such as an abnormal heart rhythm, leaking of the pulmonary valve, or poor function of the right ventricle. Continued research leading to new knowledge and treatments for congenital heart disease will improve the care of children in the future.
Disclosures None.
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on December 9, 2014
O’Brien and Marshall Tetralogy of Fallot e29
Additional Resources Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor JW, Mussatto KA, Uzark K, Goldberg CS, Johnson WH, Li J, Smith SE, Bellinger DC, Mahle WT. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: Scientific Statement from the American Heart Association. Circulation. 2012;126:1143–1172.
Sable C, Foster E, Uzark K, Bjornsen K, Canobbio MM, Connolly HM, Graham TP, Gurvitz MZ, Kovics A, Meadows AK, Reid GT, Reiss JG, Rosenbaum KN, Sagerman PJ, Saidi A, Schonberg R, Shah S, Tong E, Williams RG. Best practices in managing transition to adulthood for adolescents with congenital heart disease: the transition process and medical and psychosocial issues: a Scientific Statement
from the American Heart Association. Circulation. 2011;123:1454–1485. Adult Congenital Heart Association Web site. www.achaheart.org. American Heart Association Web site. www. heart.org. Boston Children’s Hospital Web site. www.childrenshospital.org.
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on December 9, 2014
Tetralogy of Fallot Patricia O'Brien and Audrey C. Marshall Circulation. 2014;130:e26-e29 doi: 10.1161/CIRCULATIONAHA.113.005547 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/130/4/e26
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on December 9, 2014
Tetralogy of Fallot Patricia O’Brien, MSN, CPNP-AC; Audrey C. Marshall, MD
C
ongenital heart defects result from abnormal changes in the structure of the heart that occur early in pregnancy and are present at birth. They are the most common birth defects, occurring in about 1 in 125 births. Tetralogy of Fallot (TOF) is a common defect in which obstruction to the flow of blood from the heart to the lungs causes low oxygen levels in the blood. Open heart surgery to correct the heart defect is the only treatment that gives long-term survival.
What Is TOF? TOF is a defect combining 4 abnormalities that are all related (Figure): 1. Right ventricular outflow tract obstruction. The connection between the right ventricle of the heart and the lungs is narrowed, and the blood flow to the lungs is reduced. The main area of narrowing is under the pulmonary valve, caused by thick muscle in this area. The valve may also be narrow (stenotic), and the pulmonary artery may also be small (hypoplastic).
2. Ventricular septal defect. There is a hole in the wall (septum) between the right and left ventricles (pumping chambers) of the heart. 3. Overriding of the aorta. The major blood vessel from the heart to the body, the aorta, is positioned more rightward than normal and sits above the ventricular septal defect. 4. Hypertrophy of the right ventricle. The right ventricle is more muscular than normal as a result of the right ventricular outflow tract obstruction and the need to pump harder. TOF can be seen with other heart defects, but this Cardiology Patient Page focuses on the most common form, TOF with pulmonary stenosis. TOF occurs equally in boys and girls and in all races and ethnic groups. It is associated with several genetic conditions, including trisomy 21 (Down syndrome), and with deletions on chromosome 22 and may occur with other birth defects such as cleft lip and palate. If a parent or sibling has TOF, other children in the family also have
a higher-than-average chance of having this heart defect.
How Is TOF Diagnosed? Many newborns with TOF will have lower measured oxygen levels than normal or may have visibly blue lips or nail beds (called cyanosis). It is now recommended that newborns get screened for heart disease by having their oxygen levels measured by a machine called a pulse oximeter before going home. A heart murmur (abnormal heart sounds caused by turbulent blood flow) may be heard with a stethoscope. An echocardiogram, an ultrasound that gives detailed images of the heart, is necessary to confirm the diagnosis. Today, many infants are diagnosed with a heart defect before birth by an ultrasound during pregnancy. Symptoms vary, depending on the severity of obstruction to blood flow to the lungs. Some infants appear blue soon after birth because of severe obstruction, whereas others with less obstruction are a normal pink color. The obstruction generally gets worse over time, so blue lips may
The information contained in this Circulation Cardiology Patient Page is not a substitute for medical advice, and the American Heart Association recommends consultation with your doctor or healthcare professional. From the Department of Nursing/Patient Services, Cardiovascular Program, Boston Children’s Hospital, Boston, MA (P.O.); and Department of Pediatrics, Harvard Medical School, and Cardiac Catheterization Laboratory, Department of Cardiology, Boston Children’s Hospital, Boston, MA (A.C.M.). Correspondence to Patricia O’Brien, MSN, CPNP-AC, Department of Nursing/Patient Services, Cardiovascular Program, Boston Children’s Hospital. E-mail [email protected] (Circulation. 2014;130:e26-e29.) © 2014 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.113.005547
Downloaded from http://circ.ahajournals.org/ at CONS e26 CALIFORNIA DIG LIB on December 9, 2014
O’Brien and Marshall Tetralogy of Fallot e27
Figure. Diagram of normal heart contrasted with heart defects associated with Tetralogy of Fallot. From Boston Children’s Hospital Web site.
first appear at several months of age. Some infants with mild obstruction may never be blue (“pink Tets”) and may have signs of too much blood flow to the lungs (rapid breathing, poor feeding, and slow weight gain), much like an infant with only a ventricular septal defect. Most newborns with TOF are well, with normal breathing and feeding, and can be discharged home with
surgery planned several months later. Premature infants or newborns with other major medical problems that put them at higher risk may do better avoiding a full repair and instead having a temporary procedure if they have severe obstruction (Table 1).
Hypercyanotic Spells Infants with TOF may have hypercyanotic spells (“Tet spells”), episodes in
which they become intensely blue with deeper and faster breathing. Most common between 2 and 4 months of age, spells occur more often in the morning with crying, feeding, or stooling or at times of stress, or they can be triggered by dehydration. Treatment includes calming the baby and holding the baby in a position with knees up touching the chest. This changes the blood flow pattern in the heart and may relieve the
Table 1. Treatments for Tetralogy of Fallot With Pulmonary Stenosis Age
Characteristics
Treatments
Newborn
Severe cyanosis in newborns at higher risk for complete repair: premature infants, infants with other birth defects, very ill infants
TEMPORARY PROCEDURES: SURGERY: Shunt procedure: Gore-Tex tube from an artery off the aorta to the pulmonary artery to provide blood flow to the lungs CATHETERIZATION: dilation of the pulmonary valve
3–6 mo
Open heart surgery, heart-lung bypass
SURGERY: complete repair: 1. Close the VSD with a patch so that the aorta comes from the left ventricle 2. Remove extra-thick muscle in the right ventricle below the valve 3. Repair narrow pulmonary valve a. Valve-sparing technique for mild obstruction: pulmonary valve is dilated b. Transannular patch for severe obstruction: larger patch going across the pulmonary valve extending from the right ventricle to the pulmonary artery that destroys the pulmonary valve 4. Patch the right ventricle to relieve obstruction In 5% of patients, an abnormal coronary artery (supplies blood to heart muscle) crosses the area where the patch would go. In that case, repair is done with a conduit (tube) from right ventricle to main pulmonary artery
Type of surgical repair depends on child’s anatomy
Adolescents and adults
Progressive leaking of the pulmonary valve and dilation of the right ventricle Narrow pulmonary valve or pulmonary artery
SURGERY: pulmonary valve replacement with tissue valve CATHETERIZATION: balloon dilate pulmonary valve or pulmonary artery
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on December 9, 2014
e28 Circulation July 22, 2014
spell. If there is no improvement in a few minutes, call 9-1-1. Rarely, spells can cause babies to pass out or to have a seizure or a stroke. If a spell occurs, surgery is performed soon to prevent further spells.
Surgical Treatment Most infants have a surgical repair at 3 to 6 months of age. Surgery is done through an incision in the center of the chest along the sternum (breastbone), and the heart-lung bypass machine is used to support the circulation during the operation (Table 1). Infants are usually in the hospital for about a week and fully recover in 4 to 6 weeks. Surgical results are excellent, with a less than 2% surgical mortality and very good long-term outcomes. After surgery, infants are in the intensive care unit for several days, are on a ventilator to help them breathe, and receive medicines to help the heart recover from surgery. A problem seen early after surgery can be fluid overload in the lungs and body because the right ventricle is not pumping effectively as it recovers. Medicines called diuretics are used to help get rid of extra fluid. Problems with abnormal heartbeats (rhythm problems) may also occur after surgery because of swelling or injury to the electric system of the heart, which runs next to the ventricular septal defect. Rarely, a pacemaker may be needed if the rhythm does not return to normal.
Long-Term Concerns During childhood, most children do very well, with normal growth and development, but need regular cardiology care (Table 2). However, even successful surgery does not result in a totally normal heart. The right ventricular outflow tract often has some degree of obstruction, and the pulmonary valve does not function normally. As a result of most surgical repairs, the valve leaflets cannot close completely, allowing blood to leak back into the right ventricle (called pulmonary regurgitation).
Table 2. Future Care Few children have symptoms, and most may participate in normal activities without restriction Medical care involves regular (yearly) evaluations by the cardiologist with electrocardiograms and echocardiograms to monitor for cardiac concerns that may occur late after repair Continued or progressive obstruction in the right ventricle Continued or progressive obstruction across the pulmonary arteries Leaking (regurgitation) of the pulmonary valve Increasing dilation of the right ventricle and decreased ventricle function Dilation of the aorta (rarely needs treatment) Rhythm problems Ventricular tachycardia: dangerous fast rhythm Abnormal slow rhythms: need for pacemaker Heart-healthy lifestyle is encouraged Healthy diet and appropriate weight for age Regular exercise No smoking Regular dental care is necessary Higher incidence of learning and behavioral problems is observed Attention deficit–hyperactivity disorder, learning disabilities, speech delays, etc Early assessment and treatment Adolescents are prepared to become more responsible for their own health care Learn more about tetralogy of Fallot and long-term issues Assume more responsibility for care over time Most will achieve normal adult lifestyle (eg, work full-time, have children)
Pulmonary regurgitation is well tolerated in children, but over many years, the right ventricle may dilate and stretch in some patients. The right ventricle may pump less effectively, which increases the risk of rhythm problems and may decrease exercise ability. Early signs of trouble from pulmonary regurgitation are seen on echocardiograms and are further evaluated with magnetic resonance imaging. Magnetic resonance imaging is an imaging study done inside a magnet that allows very detailed pictures and measurements of the heart structures. Surgical replacement of the pulmonary valve with a tissue valve is considered for patients with progressive right ventricular dilation. This is a low-risk open heart procedure done on the heart-lung bypass machine; the usual hospital stay is less than a week; and recovery is in 6 to 8 weeks. Abnormal rhythm problems, especially a very rapid heart rate called ventricular tachycardia, which can be
life-threatening, can occur years after TOF repair. More common in those with significant obstruction in the right ventricle, symptoms include dizziness, fainting, or palpitations (irregular or rapid heartbeat). Treatments may include medications or further procedures.
Summary TOF is a congenital heart defect that results in decreased blood flow to the lungs and is successfully repaired by surgery in infancy, allowing most patients a normal lifestyle. Lifelong follow-up is important to watch for problems such as an abnormal heart rhythm, leaking of the pulmonary valve, or poor function of the right ventricle. Continued research leading to new knowledge and treatments for congenital heart disease will improve the care of children in the future.
Disclosures None.
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on December 9, 2014
O’Brien and Marshall Tetralogy of Fallot e29
Additional Resources Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor JW, Mussatto KA, Uzark K, Goldberg CS, Johnson WH, Li J, Smith SE, Bellinger DC, Mahle WT. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: Scientific Statement from the American Heart Association. Circulation. 2012;126:1143–1172.
Sable C, Foster E, Uzark K, Bjornsen K, Canobbio MM, Connolly HM, Graham TP, Gurvitz MZ, Kovics A, Meadows AK, Reid GT, Reiss JG, Rosenbaum KN, Sagerman PJ, Saidi A, Schonberg R, Shah S, Tong E, Williams RG. Best practices in managing transition to adulthood for adolescents with congenital heart disease: the transition process and medical and psychosocial issues: a Scientific Statement
from the American Heart Association. Circulation. 2011;123:1454–1485. Adult Congenital Heart Association Web site. www.achaheart.org. American Heart Association Web site. www. heart.org. Boston Children’s Hospital Web site. www.childrenshospital.org.
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on December 9, 2014
Tetralogy of Fallot Patricia O'Brien and Audrey C. Marshall Circulation. 2014;130:e26-e29 doi: 10.1161/CIRCULATIONAHA.113.005547 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/130/4/e26
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on December 9, 2014
