Curr Treat Options Cardio Med (2014) 16:314 DOI 10.1007/s11936-014-0314-5

Adult Congenital Heart Disease (A Bhatt and K Niwa, Section Editors)

Pulmonic Regurgitation and Management Challenges in the Adult with Tetralogy of Fallot Emily Ruckdeschel, MD Joseph D. Kay, MD* Address *University of Colorado, Denver ACHD Program, Leprino Office Building, B132, 12401 East 17th Avenue, Room 534, Aurora, CO 80045, USA Email: [email protected]

Published online: 30 April 2014 * Springer Science+Business Media New York 2014

This article is part of the Topical Collection on Adult Congenital Heart Disease Keywords Tetralogy of Fallot I Pulmonary valve replacement I Adult congenital heart disease I Pulmonary valve regurgitation I Congenital heart disease

Opinion statement Patients with tetralogy of Fallot (TOF) are living longer than ever because of advances in surgery in childhood since the 1950s. However, surgery in childhood is not a cure and remains only a palliative procedure because almost all patients will require further intervention throughout life. The most common intervention required in adulthood is pulmonary valve replacement (PVR) because of residual pulmonary regurgitation leading to right ventricular dilation and eventual dysfunction. The most appropriate timing for PVR remains difficult to determine and is based on many factors. Our practice is to weigh not only objective factors such as right ventricular size and function but also careful objective assessment of the patient’s current quality of life and functional status.

Introduction Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease at birth and occurs at a rate of 0.28 0.48 per 1000 live births [1, 2]. It also continues to be most common cyanotic congenital heart defect with survival into adulthood. Survival is now expected into adulthood, and accounts for 3.5 % 10 % of all congenital defects. There is equal

prevalence regardless of sex, ethnicity, or race. The etiology of TOF is likely multifactorial and contains some genetic component given its increase prevalence in offspring of parents with TOF. However, there is also likely an environmental component given its association with maternal diabetes, protein losing enteropathy, retinoic acids, and trimethadione [3].

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Pathology Tetralogy of Fallot, first described by Thomas B Peacock in his 1858 textbook Malformations of the Heart, and later more precisely defined by Etienne-Louis Arthur Fallot in 1888 [4], consists of four anatomical features; subpulmonary infundibular stenosis, ventricular septal defect, rightward deviation of the aorta (overriding aorta), and right ventricular (RV) hypertrophy. All patients with TOF have deviation of the outlet or conal septum causing subpulmonary stenosis, but there can be variations in the degree of pulmonary stenosis from mild to complete atresia of the pulmonary valve and main pulmonary artery, all with varying degree of aortic override of the ventricular septum [2, 3]. There are also variable degrees of stenosis of the branch and main pulmonary arteries. In the cases of pulmonary valve atresia, there is complete absence of the main pulmonary artery, and pulmonary blood flow is acquired through aortic to pulmonary collaterals or a patent ductus arteriosus for postnatal survival. Other commonly associated cardiac abnormalities include coronary anomalies. Specifically, origin of the left anterior descending (LAD) coronary artery off the right coronary artery or right sinus of Valsalva occurs in about 5 % of patients with TOF [4]. This LAD course over the right ventricular outflow tract (RVOT) makes surgical intervention challenging and failure to identify this anomaly could lead to LAD injury and myocardial infarction. Rarely, there is a single origin of the coronary arteries. A right aortic arch is present in 25 % of patients with TOF and is more frequently associated with a 22q11 chromosomal deletion. This deletion is autosomal dominant and may be associated with T cell deficiency and altered calcium homeostasis. Atrial septal defects may be identified in over 80 % of individuals with TOF [5]. Historically, surgeons would intentionally allow an atrial septal defect (ASD) to persist in order to assist the right ventricle in the postoperative setting. These defects when present in adulthood can complicate TOF physiology with bidirectional shunt, risk of paradoxical embolus, exertional hypoxemia in the setting of a weak right ventricle, and additional volume load to an already dilated right ventricle. Lastly, persistent left superior vena cava occurs in 11 % of patients usually draining to the coronary sinus (a benign entity) but may rarely drain directly in the left atrium [5].

Surgical Palliation Presentation of unrepaired tetralogy of Fallot in adulthood is relatively rare in the modern age in western countries. Surgical palliation of TOF began in the 1940s with the goal of improving pulmonary blood flow and reducing cyanosis. The initial cohort of individuals who underwent surgery often had a palliative shunt performed prior to complete repair. The first systemic to pulmonary arterial shunt was performed by Alfred Blalock at Johns Hopkins in 1944 consisting of anastomosis of the subclavian artery to a branch pulmonary artery, later termed the classic Blalock–Taussig shunt. Direct anastomosis of the ascending or descending aorta to the pulmonary artery (Waterston and Potts shunts respectively) was also used in this era. Although

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these latter shunts avoided injury to a subclavian artery, controlling the amount of pulmonary blood flow was difficult, and when left in place for longer periods of time, led to excessive pulmonary blood flow and pulmonary arterial hypertension in that lung. The Potts shunt was notoriously challenging to close from a median sternotomy at time of complete repair in TOF, therefore, was occasionally still patent into adulthood in this cohort. If a palliative shunt is currently needed, most centers today perform a modified Blalock–Taussig shunt, which consists of a synthetic tube graft connecting the subclavian artery to a branch pulmonary artery. Of note, individuals in the first era of surgery were frequently repaired at an older age, had a longer period of cyanosis and RVOT obstruction, and had systemic to pulmonary arterial shunt flow to the lungs for many years. These factors frequently lead to complications in adult life. Although surgical “repair,” consisting of ventricular septal defect closure and relief of the RVOT obstruction began in the 1950s shortly after the development of cardiopulmonary bypass, attempts at primary repair of TOF early in life did not begin until the 1970s and were not routine until the 1990s [6]. Primary “repair” consists of ventricular septal defect (VSD) closure and relief of RVOT obstruction. The extent of surgery is dependent upon the severity of the underlying disease. Historically, the importance of pulmonary regurgitation after complete repair was not well understood, and many children and their parents were informed that this surgery fixed the child’s problem. “Complete” repairs most commonly utilized a transannular patch that enlarged the RVOT and the pulmonary valve annulus leaving patients with often times significant pulmonary regurgitation. Modern surgical techniques are geared toward sparring of the pulmonary valve when possible and are most often performed in the first year of life. Though current surgical techniques result in excellent long-term survival (995 %), it is not without sequalae [7]. Pulmonary regurgitation continues to be the most common complication for individuals with repaired TOF. Untreated, moderate to severe pulmonic regurgitation often leads to RV dilation and dysfunction. Branch pulmonary artery stenosis and residual RVOT obstruction can also occur in this patient population leaving the right ventricle to face a combined pressure and volume overload. Late electrical issues include atrial to ventricular (AV) block, atrial arrhythmias, ventricular arrhythmias, and sudden cardiac death. Aortic root dilation is also noted with age in TOF, though the risk of aortic dissection remains low. The most common cause for surgical reintervention in adults with TOF is pulmonary regurgitation. However, the timing of replacing the pulmonary valve is complex and controversial. Over the last 10 years, there has been a growing body of evidence to help better determine the best time for intervention but this remains a complicated issue.

Follow-up There is a high rate of adult patients with congenital heart disease being lost to cardiac follow-up which ranges from 24 % 60 % depending upon the severity of heart lesions [8, 9]. Many of these patients are under the impression, (and in many cases were informed so), that they were cured with their surgery as a child. Patients who fail to follow-up with congenital heart

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Curr Treat Options Cardio Med (2014) 16:314 disease specialists or community cardiologists are at increased risk for poor outcomes and lack of appropriate interventions [8, 10]. By the time these patients present for medical attention (often for heart failure symptoms or arrhythmia), they frequently have developed severe RV dilation or irreversible RV dysfunction and may no longer have significant clinical improvement after surgical intervention. Patients with complex congenital heart disease should be followed by cardiologists with expertise in adults with congenital heart disease for the entirety of their lives [11]. It is recommended that all patients with repaired TOF have at least annual follow- up with a cardiologist with expertise in adult congenital heart disease (ACHD). They should undergo routine imaging with either echocardiogram or magnetic resonance imaging (MRI) performed by staff with experience in performing as well as interpreting these more complex studies. Additional testing including Holter monitoring and cardiopulmonary exercise testing will often also be indicated. Genetic syndromes should be evaluated for and if identified, patients should meet with a geneticist if considering pregnancy [11].

Imaging Techniques (Fig. 1) The right ventricle can be challenging to image using echocardiography because of its location and geometry. Significant RV dilation and history of prior surgery can impair transthoracic echocardiogram quality. This may limit accurate estimation of RV size and function, essential in determining timing of PVR. Some echocardiographic measures such as the Tei index and myocardial performance index show promise for assessing RV function [12]. In patients with repaired

Fig. 1. Assessment of pulmonary regurgitation by MRI and echocardiogram. Panel A and B demonstrating measurement of pulmonary regurgitation by cardiac MRI using phase contrast analysis of flow (antegrade and retrograde). Panel A showing magnitude image of pulmonary artery and contour (green circle). Panel B showing phase contrast analysis of systolic and diastolic flow consistent with severe pulmonary regurgitation. Panel C and D demonstrating evaluation of pulmonary regurgitation by echocardiography. Panel C showing color Doppler of severe pulmonary regurgitation. Panel D showing pulsed-wave doppler with equivalent size and density of systolic and diastolic flow, with diastolic flow terminating in early to mid-diastole secondary to equalization of pulmonary artery end diastolic and RV end diastolic pressures, consistent with severe pulmonary regurgitation.

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TOF, a RV myocardial performance index of 90.40 has been shown to be 81 % sensitive and 85 % specific to diagnose a RV ejection fraction of less than 35 % (as measured by cardiac MRI) [12]. In younger patients, assessment of RV volume with three-dimensional echocardiography has good correlation with cardiac MRI imaging [13•]. Finally, parasternal short axis measurement of RV and RV outflow tract diameters can predict the RV end diastolic volume (RVEDV) comparably to cardiac MRI [14]. Despite these advances in echocardiography, cardiac MRI is the gold standard for imaging in TOF. Ventricular volume and function, valvular gradients, and regurgitant fractions, associated congenital anomalies and post operative anatomy can all be reliably assessed with cardiac MRI. Image quality is excellent in spite of body habitus or previous surgery, and coronary anatomy, pulmonary arterial pathology, and relationship of the RVOT to the sternum, all essential preoperative considerations can be concomitantly assessed without exposure to radiation. Though its clinical relevance is not yet well determined, the degree of myocardial scarring and fibrosis can be assessed as well. The drawbacks of cardiac MRI are cost, time, and patient discomfort. Cardiac MRIs may last anywhere from 1 to 2 h and can be associated with significant anxiety from claustrophobia, with many patients not eligible to MRI evaluation secondary to previously placed pacemakers or implantable defibrillators. Cardiac computed tomography (CT) is an alternative to cardiac MRI in centers where there is CT-based expertise. It allows for similar anatomic and functional assessment, and provides the additional benefit of assessment for coronary atherosclerosis, important in older adults with TOF. Despite the newer technologies of flash CT, which allow a significant reduction in radiation dose, cardiac CT is not recommended for annual assessment, however, may be an important alternative imaging modality in patients who have already been identified as likely operative candidates for pulmonic valve replacement. Current recommendations are for imaging by some modality at least every year.

Pulmonary Regurgitation Current surgical practice is aimed at sparing the pulmonary valve even to the extent of leaving some degree of pulmonary stenosis to avoid significant pulmonary regurgitation (PR). Historically, there was less concern about the long-term consequence of pulmonary regurgitation creating a generation of individuals with TOF, now in their young and mid adult ages, with significant PR. Many factors contribute to the development and progression RV dilation and extent of pulmonary regurgitation. These include type of surgical repair (transannular patch and residual branch pulmonary artery stenosis leading to more rapid RV dilation compared), as well as underlying pulmonary valve morphology, compliance of the right ventricle [15]. Specifically, repair with a transannular patch repair would frequently leave patients with a significant degree of pulmonary regurgitation. Pulmonary regurgitation leads to progressive dilation and dysfunction of the right ventricle, which may worsen tricuspid valve regurgitation, creating an additional

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Curr Treat Options Cardio Med (2014) 16:314 volume load on the right ventricle [16]. Long-term PR can become symptomatic with right heart failure, arrhythmias, exercise intolerance, and death. Chronic PR leads to an increased volume load on the right ventricle, which results in increases of end diastolic volumes and later, end systolic volumes. Over time, there is progressive worsening of systolic function, which is usually asymptomatic until severe dysfunction occurs. The right ventricle is hypertrophied initially in these patients secondary to RVOT obstruction, which may lead to increased oxygen demand. The long-term volume load of pulmonary regurgitation leads to progressive dilation and fibrosis of the right ventricle from chronic myocardial ischemia. Right ventricular dysfunction may adversely affect left ventricular function as well [17]. Lastly, concomitant right atrial enlargement increases the frequency of late atrial arrhythmias in addition to the ventricular arrhythmias resulting from RV abnormalities.

Arrhythmia There is a significant burden of arrhythmia in patients with repaired TOF. A multi-institutional study of adult patients with repaired TOF showed that 43 % had sustained arrhythmia or required arrhythmia intervention [18]. Atrial tachyarrhythmias occurred in 20 % of patients. Intra-atrial reentrant tachyarrhythmias are associated with right atrial enlargement, hypertension, and the number of prior cardiac surgeries. Atrial fibrillation is associated with older age, lower left ventricular ejection fraction, and left atrial dilation. Ventricular arrhythmias occurred in 14.6 % of patients and were associated with the number of prior cardiac surgeries, QRS duration, and left ventricular diastolic dysfunction [18]. Progressive conduction disorders are known to occur late after TOF repair regardless of type of initial repair [17]. There is progressive prolongation of PR interval and QRS duration over time, which is not necessarily ameliorated by pulmonary valve replacement [17]. Sudden cardiac death is the most common cause of cardiac death in patients with TOF, though overall the rates are relatively low with an annual incidence 0.15 % [19, 20]. The rates of sustained ventricular tachycardia and ventricular arrhythmias are 11.9 % and 8.3 %, respectively, 35 years after corrective surgery [21]. Ventricular arrhythmias are a complication of both repaired and unrepaired TOF, with nearly 60 % of patients with unrepaired or partially palliated TOF demonstrating significant ventricular arrhythmia. In individuals who have undergone complete repair of TOF, repair at a later age is associated with increased ventricular arrhythmia burden [22]. These rates have likely improved with modern surgical repair but still remain high despite good surgical outcomes. Ventricular arrhythmias are attributed to areas of surgical scar and unfavorable hemodynamics. QRS duration (9180 ms), annual rate of change in QRS duration, pulmonary regurgitation, and older age at repair are risk factors for ventricular arrhythmia [21]. Clinical arrhythmia has also been associated with fibrosis of the right ventricle (late gadolinium enhancement on cardiac MRI) [23]. Left ventricular disease is also a risk factor for ventricular arrhythmia in TOF. Both longitudinal strain and diastolic dysfunction of the left ventricle are predictive of ventricular arrhythmia [24] and sudden cardiac death [25].

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The mortality rate for individuals with TOF remains low, and predicting appropriate candidates for primary prevention internal cardiac defibrillators (ICDs) is challenging. Algorithms using appropriateness criteria for ICDs in patients with reduced left ventricular fraction and known clinical risk factors for VT in patients with TOF help to better identify those patients at high risk for ventricular tachycardia and sudden cardiac death [24]. EP studies reveal that inducible monomorphic VT and polymorphic VT are associated with high rates of subsequent events including sustained ventricular tachycardia and sudden cardiac death and may be useful in select cases [26]. However, patients with TOF who have ICDs implanted for either primary or secondary prevention experience high rates of inappropriate in addition to appropriate shocks. Therefore, careful consideration in each individual TOF case with a multidisciplinary team and review of hemodynamics and imaging for potential rectifiable stimuli for arrhythmia (areas of scar, uncorrected severe PR, coronary artery disease) and potential risk factors for inappropriate shocks (known rapid atrial tachyarrhythmia) is essential [27]. Unfortunately, pulmonic valve replacement alone has not been shown to reduce the risk of ventricular arrhythmia related death [28]. This likely reflects the complex nature of arrhythmia development in TOF. Small studies have shown that pulmonary valve replacement with concomitant cryoablation may reduce the risk of recurrent atrial and ventricular arrhythmias [29]. Some centers perform preoperative EP evaluation to assess for individuals with inducible ventricular tachycardia who may benefit from cryoablation of the RVOT. Other centers perform cryoablation at the time of PVR in all TOF individuals. Further research is greatly needed to determine whether postsurgical EP study for inducible VT is a cost-effective approach with a favorable risk benefit ratio. At this time, it is not clear that the prevention of sudden cardiac death events is significant enough to outweigh the risks of inappropriate shocks, or appropriate shocks for rhythm, which may have been hemodynamically well tolerated.

Aortic Root Dilation Aortic root dilation is common in patients with conotruncal abnormalities including TOF and may be due to an intrinsic aortopathy [30]. Progressive aortic root dilation leads to aortic regurgitation in 15 %–18 % of patients with TOF [31]. Higher rates of aortic root dilation are seen in those with pulmonary atresia, severe RVOT obstruction, right aortic arch, and longer duration of shunt palliation and may be an effect of increased aortic blood flow. Aortic root dissection has been seen only in case reports, and the majority of individuals do not experience aortic events. Although beta-blocker therapy has recommended in other patients with intrinsic aortopathy, such as Marfan’s Syndrome, there is not yet any data to suggest this is helpful in patients with TOF. In addition, it is unclear if there would be benefit to repair these patients at a lower aortic root diameter, such as done with other patients with aortopathy, or wait until larger diameters as is done in patients without coexisting abnormalities.

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Benefits of Pulmonary Valve Replacement Pulmonary valve replacement, either surgical or percutaneous has been shown to have low mortality (G2 %) and morbidity and good long-term outcomes [7, 32, 33, 34••]. Risk factors for adverse outcomes in patients undergoing pulmonary valve replacement include concomitant surgery, prolonged hospitalization, preoperative arrhythmias, and New York Heart Association class [35•]. Decrease in right ventricular end diastolic volume (RVEDV) and end systolic volume (RVESV) has been documented after surgical pulmonary valve replacement. This occurs relatively quickly after pulmonary valve replacement, whereas markers of RV diastolic dysfunction improve slowly over time [36]. Despite improvement in RV dilation, there has not yet been documented any clear improvement in RV ejection fraction [32, 33]. However, in adults with RVEDV 9163 170 mL/m2 or RVESV 980 mL/m2, volumes do not return to normal after pulmonary valve replacement and this guides timing of replacement [37••, 38•]. Left ventricular hemodynamics have been shown to benefit as well. Left ventricular ejection fraction is improved in patients who undergo pulmonary valve replacement that is likely related to decreased volume load and dilation of the right ventricle [39, 40]. In addition, patients have improved functional status with documented improvement in ability index and New York Heart Association class [32, 40]. However, significant objective improvement on exercise stress testing has not been demonstrated in all cases [41, 42]. Despite improvement in hemodynamics and symptoms, pulmonary valve replacement has not yet been shown to have a mortality benefit. Ventricular and atrial tachyarrhythmias have not been shown to be significantly reduced by pulmonary valve replacement alone [28]. However, in combination with intraoperative cryoablation, pulmonary valve replacement has been associated with a decrease in both atrial and ventricular arrhythmias [43].

Surgical Considerations Surgical pulmonary valve replacement can be completed with mechanical prostheses, homografts, heterografts, valved conduits, and autologous pericardial valves. Mechanical valves are rarely used in the pulmonary position secondary to historically high rates of thromboembolic events and valve failure [44]. More recent studies have shown that with proper surgical technique and appropriate anticoagulation mechanical valves offer good longterm options with less development of stenosis and regurgitation [45]. Despite this, they remain rarely used in the modern surgical era. Surgical valve replacement offers advantages in some regard in that other hemodynamically significant lesions can be addressed and intraoperative cryoablation can be performed at the same time. There is no clear benefit of one prosthetic valve type over another though in cases of significant RVOT dilation there may be benefit in the use of a stented prosthesis [44]. New self- expanding tissue

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valves are being utilized for off-pump pulmonary valve replacements with promising initial results that reduce surgical time, blood loss, and need for blood products [46]. In the last decade, there has been an increasing use of percutaneously placed valves [47]. The most common percutaneously placed valve in the pulmonary position currently in use is the Melody valve (Medtronic, Minneapolis, MN), which is a valved bovine jugular vein that is mounted on a balloon expandable stent and can be placed via venous access. Percutaneous valves are currently limited to patients with prior conduits in place and are not approved in the United States for use in native RV outflow tracts. The size of the prior conduit is also limiting with G16 mm being prohibitively small. Although there is no absolute upper limit of valve size in which a Melody valve can be implanted, enough narrowing must have occurred to allow anchoring of the valve in place. At the time of implantation, a balloon sized valve of 922 mm may be too large. However, on a limited basis they have been used successfully in native RV outflow tracts and larger conduits that have significant stenosis. There are other percutaneous valves available now for potential pulmonic position placement. Early studies demonstrated that there was a relatively low complication rate with improvement in pulmonary stenosis and regurgitation with transcatheter therapy [47, 48]. Overall, the initial short- and medium-term results have had good procedural success. There was decrease in RVOT obstruction when present prior to valve placement and a reduction and RVEDV after 6 months [34••]. There have also been shown to be a modest improvement in objective and subjective exercise capacity in patients who have undergone percutaneous pulmonary valve replacement as well MRI measured improvement in RV volumes [49, 50]. Ideally, use of the transcatheter valve will reduce the total number of surgeries that patients will need through their lifetime. Patients who have had multiple sternotomies are at higher risk for operative complications and may be good candidates for the procedure. It does limit other interventions at the time of valve replacement. Major risks of the procedure include conduit rupture, stent fracture, and coronary artery compression. Cost analysis shows that the percutaneous pulmonary valve insertion is associated with a relatively small increase in treatment management cost [51]. However, there has been documented endocarditis in all major trials of the transcatheter pulmonary valve in North America and Europe [52••]. As follow-up for this valve remains relatively limited, it is yet unclear whether rates of endocarditis are higher in patients who have received a transcatheter valve compared with those with surgical repair.

Pregnancy with Pulmonary Regurgitation Patients with TOF and pulmonary regurgitation generally tolerate pregnancy well. As with all patients with congenital heart disease, there is an increased risk of their offspring having some form of congenital heart disease. There is also an increased risk of fetal loss. Poor outcomes in this patient population have been shown to be associated with severe pulmonary hypertension, left ventricular dysfunction, and severe pulmonary regurgitation with RV dysfunc-

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Curr Treat Options Cardio Med (2014) 16:314 tion [53]. In addition, maternal use of cardiovascular medications is associated with pregnancy outcome and maternal cardiovascular events during pregnancy are associated with fetal events [54]. Small studies have noted worsening of RV remodeling (increased RVEDV) in women with repaired TOF who have undergone pregnancies, though this was not associated with a decrease in RV function [55]. We generally recommend a thorough evaluation prior to considering pregnancy to assess ventricular function and valvular competence. In addition, we recommend that patient undergo cardiopulmonary stress testing, which has been shown to be predictive of pregnancy outcomes in women with congenital heart disease and their infants [56].

Timing of Pulmonary Valve Replacement Despite continued research into the topic, there is not yet a clear recommendation as to when to replace a pulmonary valve in patients with repaired TOF. It is our practice to take into consideration both objective and subjective measurements of cardiac function. Most consider it reasonable for pulmonary valve replacement in patients with moderate to severe PR who are symptomatic, regardless of RV size or function. In addition, patients with moderate to severe PR who require surgical intervention for other hemodynamically significant lesions or patients with moderate to severe PR and difficult to control arrhythmias in the setting of RV dilation or dysfunction should be considered for pulmonary valve replacement. It is less clear how to treat the patient with severe pulmonary regurgitation without symptoms. In those with progressive dilation or RV dysfunction it is reasonable to refer for pulmonary valve replacement prior to the onset of symptoms. In those asymptomatic patients with severe pulmonary regurgitation and stable RV dilation, there currently is no clear benefit to pulmonary valve replacement. Although pulmonary valve replacement remains currently is a low risk surgery in the modern era, these bioprosthetic pulmonary valves have a finite lifespan, with most lasting on average 15 years when placed in young adults [57]. The development of the percutaneous pulmonic valve has decreased the threshold of many providers and programs for when to place the first surgical prosthetic valve. It remains to be seen if such an approach will have an impact in decrease late complications such as arrhythmias and RV dysfunction.

Compliance with Ethics Guidelines Conflict of Interest Dr. Emily Ruckdeschel declares no conflicts of interest. Dr. Joseph Kay is on the medical advisory board for the Adult Congenital Heart Association. Their mission is to improve care and access to care for adult with congenital heart disease. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

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References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.

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van der Linde D, Konings EE, Slager MA, et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58:2241–7. Bashore TM. Adult congenital heart disease: right ventricular outflow tract lesions. Circulation. 2007;115:1933–47. Moss AJ, Allen HD. Moss and Adams' heart disease in infants, children, and adolescents: including the fetus and young adult. 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins; 2008. Fallot A. Contribution a l'anatomie patholgique de la malldie blue (cyanosecardiaque). Marseilles Med. 1888;418–420. Rao BN, Anderson RC, Edwards JE. Anatomic variations in the tetralogy of Fallot. Am Heart J. 1971;81:361–71. Bacha EA, Scheule AM, Zurakowski D, et al. Longterm results after early primary repair of tetralogy of Fallot. J Thorac Cardiovasc Surg. 2001;122:154–61. Hickey EJ, Veldtman G, Bradley TJ, et al. Late risk of outcomes for adults with repaired tetralogy of Fallot from an inception cohort spanning four decades. Eur J Cardiothorac Surg. 2009;35:156–64. discussion 164. Wray J, Frigiola A, Bull C. (ACoRN) ACHdRN. Loss to specialist follow-up in congenital heart disease; out of sight, out of mind. Heart. 2012;99(7):440–1. Mackie AS, Rempel GR, Rankin KN, Nicholas D, Magill-Evans J. Risk factors for loss to follow-up among children and young adults with congenital heart disease. Cardiol Young. 2012;22:307–15. Yeung E, Kay J, Roosevelt GE, Brandon M, Yetman AT. Lapse of care as a predictor for morbidity in adults with congenital heart disease. Int J Cardiol. 2008;125:62–5. Williams RG, Pearson GD, Barst RJ, et al. Report of the National Heart, Lung, and Blood Institute Working Group on research in adult congenital heart disease. J Am Coll Cardiol. 2006;47:701–7. Yasuoka K, Harada K, Toyono M, Tamura M, Yamamoto F. Tei index determined by tissue Doppler imaging in patients with pulmonary regurgitation after repair of tetralogy of Fallot. Pediatr Cardiol. 2004;25:131–6.

13.•

Dragulescu A, Grosse-Wortmann L, Fackoury C, et al. Echocardiographic assessment of right ventricular volumes after surgical repair of tetralogy of Fallot: clinical validation of a new echocardiographic method. J Am Soc Echocardiogr. 2011;24:1191–8. This article highlights potentially new objective methods of tracking right ventircular function in this population, as a possible better means of knowing when the right ventricle is start to fail and may require repeat advanced imaging such as cardiac MRI. 14. Chaowalit N, Durongpisitkul K, Krittayaphong R, Komoltri C, Jakrapanichakul D, Phrudprisan S. Echocardiography as a simple initial tool to assess right ventricular dimensions in patients with repaired tetralogy of Fallot before undergoing pulmonary valve replacement: comparison with cardiovascular magnetic resonance imaging. Echocardiography. 2012 15. Kang IS, Redington AN, Benson LN, et al. Differential regurgitation in branch pulmonary arteries after repair of tetralogy of Fallot: a phase-contrast cine magnetic resonance study. Circulation. 2003;107:2938–43. 16. Berman W, Fripp RR, Rowe SA, Yabek SM. Congenital isolated pulmonary valve incompetence: neonatal presentation and early natural history. Am Heart J. 1992;124:248–51. 17. Massin MM, Malekzadeh-Milani SG, Schifflers S, Dessy H, Verbeet T. Long-term electrocardiographic follow-up after repair of tetralogy of Fallot. Ann Noninvasive Electrocardiol. 2011;16:336–43. 18. Khairy P, Hosn JA, Broberg C, et al. Multicenter research in adult congenital heart disease. Int J Cardiol. 2008;129:155–9. 19. Silka MJ, Hardy BG, Menashe VD, Morris CD. A population-based prospective evaluation of risk of sudden cardiac death after operation for common congenital heart defects. J Am Coll Cardiol. 1998;32:245–51. 20. O'Meagher S, Choudhary P, Duflou J, Puranik R, Celermajer DS. Causes of death in tetralogy of Fallot in adults—an autopsy study. Int J Cardiol. 2013;168:1547–8. 21. Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet. 2000;356:975–81.

314, Page 12 of 13 22.

Deanfield JE, McKenna WJ, Presbitero P, England D, Graham GR, Hallidie-Smith K. Ventricular arrhythmia in unrepaired and repaired tetralogy of Fallot. Relation to age, timing of repair, and haemodynamic status. Br Heart J. 1984;52:77–81. 23. Babu-Narayan SV, Kilner PJ, Li W, et al. Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults with repaired tetralogy of fallot and its relationship to adverse markers of clinical outcome. Circulation. 2006;113:405–13. 24. Khairy P, Dore A, Poirier N, et al. Risk stratification in surgically repaired tetralogy of Fallot. Expert Rev Cardiovasc Ther. 2009;7:755–62. 25. Diller GP, Kempny A, Liodakis E, et al. Left ventricular longitudinal function predicts life-threatening ventricular arrhythmia and death in adults with repaired tetralogy of fallot. Circulation. 2012;125:2440–6. 26. Khairy P. Programmed ventricular stimulation for risk stratification in patients with tetralogy of Fallot: a Bayesian perspective. Nat Clin Pract Cardiovasc Med. 2007;4:292–3. 27. Khairy P, Harris L, Landzberg MJ, et al. Implantable cardioverter-defibrillators in tetralogy of Fallot. Circulation. 2008;117:363–70. 28. Harrild DM, Berul CI, Cecchin F, et al. Pulmonary valve replacement in tetralogy of Fallot: impact on survival and ventricular tachycardia. Circulation. 2009;119:445–51. 29. Karamlou T, Silber I, Lao R, et al. Outcomes after late reoperation in patients with repaired tetralogy of Fallot: the impact of arrhythmia and arrhythmia surgery. Ann Thorac Surg. 2006;81:1786–93. discussion 1793. 30. Stulak JM, Dearani JA, Burkhart HM, Sundt TM, Connolly HM, Schaff HV. Does the dilated ascending aorta in an adult with congenital heart disease require intervention? J Thorac Cardiovasc Surg. 2010;140:S52–7. discussion S86 91. 31. Niwa K. Aortic root dilatation in tetralogy of Fallot long-term after repair—histology of the aorta in tetralogy of Fallot: evidence of intrinsic aortopathy. Int J Cardiol. 2005;103:117–9. 32. Graham TP, Bernard Y, Arbogast P, et al. Outcome of pulmonary valve replacements in adults after tetralogy repair: a multi-institutional study. Congenit Heart Dis. 2008;3:162–7. 33. Cheung EW, Wong WH, Cheung YF. Meta-analysis of pulmonary valve replacement after operative repair of tetralogy of fallot. Am J Cardiol. 2010;106:552–7. 34.•• McElhinney DB, Hellenbrand WE, Zahn EM, et al. Short- and medium-term outcomes after transcatheter pulmonary valve placement in the expanded multicenter US melody valve trial. Circulation. 2010;122:507–16.

Curr Treat Options Cardio Med (2014) 16:314 This article represents the critical trial of MELODY valve insertion in the United States that lead to FDA humanitarian Device exemption approval at the end of 2009. While not a randomized controlled study, it demonstrated safety, but some late problems with the trans catheter vavle that warrents careful follow-up after valve implantation. 35.• Jain A, Oster M, Kilgo P, et al. Risk factors associated with morbidity and mortality after pulmonary valve replacement in adult patients with previously corrected tetralogy of Fallot. Pediatr Cardiol. 2012;33:601–6. This paper shows the approximate morbidity and mortality with surgical pulmonary valve replacement in the most modern era. 36. van Straten A, Vliegen HW, Lamb HJ, et al. Time course of diastolic and systolic function improvement after pulmonary valve replacement in adult patients with tetralogy of Fallot. J Am Coll Cardiol. 2005;46:1559–64. 37.•• Therrien J, Provost Y, Merchant N, Williams W, Colman J, Webb G. Optimal timing for pulmonary valve replacement in adults after tetralogy of Fallot repair. Am J Cardiol. 2005;95:779–82. While not a recent paper in the last 5 years, this paper still remains the corner stone as to understanding of optimal timing of pulmonary valve replacement to prevent permanent irreversible RV remodeling from pulmonary insufficiency, and most centers still point to these values as RV volumes in which elective pulmonary vlave replacment should be considered. 38.• Lee C, Kim YM, Lee CH, et al. Outcomes of pulmonary valve replacement in 170 patients with chronic pulmonary regurgitation after relief of right ventricular outflow tract obstruction: implications for optimal timing of pulmonary valve replacement. J Am Coll Cardiol. 2012;60:1005–14. This paper continues to help us understand the optimal timing of surgcial PVR, validating previous publisehed reports. 39. Chalard A, Sanchez I, Gouton M, et al. Effect of pulmonary valve replacement on left ventricular function in patients with tetralogy of Fallot. Am J Cardiol. 2012;110:1828–35. 40. Shiokawa Y, Sonoda H, Tanoue Y, Nishida T, Nakashima A, Tominaga R. Pulmonary valve replacement long after repair of tetralogy of Fallot. Gen Thorac Cardiovasc Surg. 2012;60:341–4. 41. Tsang FH, Li X, Cheung YF, Chau KT, Cheng LC. Pulmonary valve replacement after surgical repair of tetralogy of Fallot. Hong Kong Med J. 2010;16:26– 30. 42. Eyskens B, Reybrouck T, Bogaert J, et al. Homograft insertion for pulmonary regurgitation after repair of tetralogy of fallot improves cardiorespiratory exercise performance. Am J Cardiol. 2000;85:221–5.

Curr Treat Options Cardio Med (2014) 16:314 43.

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Therrien J, Siu SC, Harris L, et al. Impact of pulmonary valve replacement on arrhythmia propensity late after repair of tetralogy of Fallot. Circulation. 2001;103:2489–94. Davlouros PA, Karatza AA, Gatzoulis MA, Shore DF. Timing and type of surgery for severe pulmonary regurgitation after repair of tetralogy of Fallot. Int J Cardiol. 2004;97 Suppl 1:91–101. Dos L, Teruel L, Ferreira IJ, et al. Late outcome of Senning and Mustard procedures for correction of transposition of the great arteries. Heart. 2005;91:652–6. Chen Q, Turner M, Caputo M, Stoica S, Marianeschi S, Parry A. Pulmonary valve implantation using selfexpanding tissue valve without cardiopulmonary bypass reduces operation time and blood product use. J Thorac Cardiovasc Surg. 2013;145:1040–5. Bonhoeffer P, Boudjemline Y, Qureshi SA, et al. Percutaneous insertion of the pulmonary valve. J Am Coll Cardiol. 2002;39:1664–9. Lurz P, Coats L, Khambadkone S, et al. Percutaneous pulmonary valve implantation: impact of evolving technology and learning curve on clinical outcome. Circulation. 2008;117:1964–72. Batra AS, McElhinney DB, Wang W, et al. Cardiopulmonary exercise function among patients undergoing transcatheter pulmonary valve implantation in the US Melody valve investigational trial. Am Heart J. 2012;163:280–7. Khambadkone S, Coats L, Taylor A, et al. Percutaneous pulmonary valve implantation in humans: results in 59 consecutive patients. Circulation. 2005;112:1189–97. Raikou M, McGuire A, Lurz P, Bonhoeffer P, Wegmueller Y. An assessment of the cost of percu-

Page 13 of 13, 314 taneous pulmonary valve implantation (PPVI) versus surgical pulmonary valve replacement (PVR) in patients with right ventricular outflow tract dysfunction. J Med Econ. 2011;14:47–52. 52.•• McElhinney DB, Benson LN, Eicken A, Kreutzer J, Padera RF, Zahn EM. Infective endocarditis after transcatheter pulmonary valve replacement using the Melody valve: combined results of 3 prospective North American and European studies. Circ Cardiovasc Interv. 2013;6:292–300. This paper highlights the 2007 AHA guidelines in which SBE prophylaxis is still required for those with artifical valve insertion, and how providers need to follow these patients closely in the event if infections and fevers. 53. Veldtman GR, Connolly HM, Grogan M, Ammash NM, Warnes CA. Outcomes of pregnancy in women with tetralogy of Fallot. J Am Coll Cardiol. 2004;44:174–80. 54. Balci A, Drenthen W, Mulder BJ, et al. Pregnancy in women with corrected tetralogy of Fallot: occurrence and predictors of adverse events. Am Heart J. 2011;161:307–13. 55. Assenza G, Cassater D, Landzberg M, et al. The effects of pregnancy on right ventricular remodeling in women with repaired tetralogy of Fallot. Int J Cardiol. 2013;168(3):1847–52. 56. Lui GK, Silversides CK, Khairy P, et al. Heart rate response during exercise and pregnancy outcome in women with congenital heart disease. Circulation. 2011;123:242–8. 57. Yemets IM, Williams WG, Freedom RM, et al. Pulmonary valve replacement late after repair of tetralogy of Fallot. Ann Thorac Surg. 1997;64(2):526–30.

Pulmonic regurgitation and management challenges in the adult with tetralogy of fallot.

Patients with tetralogy of Fallot (TOF) are living longer than ever because of advances in surgery in childhood since the 1950s. However, surgery in c...
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