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Valvular Insufficiency and Heart Failure
Chapter 22
Valvular Insufficiency and Heart Failure Matthew C. Schwartz1, Andrew C. Glatz2, Matthew J. Gillespie2 1Arnold
Palmer Hospital for Children, Orlando, FL, United States; 2Children’s Hospital of Philadelphia, Philadelphia, PA, United States
INTRODUCTION Valvular insufficiency is an important cause of heart failure (HF) in children, most commonly occurring in the setting of congenital heart disease [1]. Significant insufficiency less commonly results from acquired causes including endocarditis and rheumatic heart disease or from inherited connective tissue disorders. In general, valvular insufficiency puts a significant volume load on the affected ventricle, which can lead to ventricular deterioration and HF. This chapter focuses on the causes, pathophysiology, evaluation, and treatment of HF associated with valvular insufficiency in children.
AORTIC REGURGITATION AND HEART FAILURE Etiology In children, aortic regurgitation (AR) is most typically associated with various types of congenital heart disease. AR can occur following balloon valvuloplasty for congenital aortic stenosis. AR can also develop in those with bicuspid aortic valve with no history of intervention. Patients with aortic valve leaflet prolapse due to an accompanying ventricular septal defect often exhibit AR. Various causes of aortic root dilation can also lead to AR due to annular enlargement including inherited connective tissue disorders such as Marfan syndrome or Ehlers–Danlos syndrome. Aortic root dilation and AR can also result after arterial switch and Ross operations. Acquired etiologies of AR in children are less common and include infectious endocarditis and rheumatic heart disease [2,3].
Pathophysiology HF can occur in the setting of both acute and chronic severe AR. Chronic AR leads to progressive left ventricular dilation with compensatory ventricular hypertrophy. Eventually, the dilation exceeds the degree of hypertrophy leading to elevated end-systolic wall stress and afterload. These changes cause a decrease in the systolic function of the left ventricle. If severe dilation progresses, intrinsic myocyte function is affected and irreversible injury can occur [2]. HF can ensue because pump function is diminished and because a significant amount of the ventricle’s stroke volume leaks back into the ventricle. The acute development of AR is rare in children but can lead to pronounced HF. In acute AR, the ventricle has not had time to gradually enlarge and, thus, the regurgitant volume causes an abrupt increase in left ventricular end-diastolic pressure. This increase is transmitted to the left atrium and pulmonary veins causing pulmonary edema. Also, the left ventricle is unable to acutely increase stroke volume in the setting of additional regurgitant blood, which causes a decrease in net effective forward blood flow and, thus, a decrease in cardiac output [4].
Presentation and Evaluation HF symptoms due to severe AR will be due to left-sided cardiac failure and associated pulmonary edema. Infants may develop tachypnea, respiratory insufficiency, and growth failure, while older children and adolescents can develop these symptoms as well as exercise intolerance. In those with severe AR, physical exam will include an early, medium to high frequency diastolic decrescendo murmur at the left sternal border. Because left ventricular stroke volume may be increased in the setting of a dilated ventricle, a systolic ejection murmur may also be present due to increased flow across the aortic valve. An Austin Flint murmur may also be present, a low frequency middiastolic rumble heard near the apex due to limitation in the opening of the mitral valve’s anterior leaflet from the AR jet. Pulse pressure will also be widened due to diastolic leakage of blood across the valve, and pulses may be bounding or “water hammer.” Patients who have significant HF due to AR may also exhibit tachycardia, tachypnea, and hypoxemia from pulmonary vein desaturation associated with pulmonary edema [2]. Heart Failure in the Child and Young Adult. http://dx.doi.org/10.1016/B978-0-12-802393-8.00022-3 Copyright © 2018 Elsevier Inc. All rights reserved.
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FIGURE 22.1 Transthoracic echocardiogram in the parasternal long-axis view showing severe aortic regurgitation (AR) in a 1-year-old with severe aortic stenosis who underwent balloon valvuloplasty in the neonatal period.
Echocardiography is the cornerstone for evaluating AR in children (Fig. 22.1). The anatomy of the aortic valve, the degree of AR, and the ventricular size and function can all be evaluated [5]. Echocardiographic markers of severe AR include holodiastolic flow reversal in the descending aorta, left ventricular dilation, and/or AI jet width >65% of left ventricular outflow tract diameter [2,6,7]. Magnetic resonance imaging (MRI) can also be helpful in characterizing AR by quantifying ventricular size and function as well as calculating the aortic valve regurgitant fraction [2]. Brain natriuretic peptide (BNP) and N-terminal proBNP levels can reflect the degree of neurohormonal activity in adults with HF, but these findings may not be generalizable to children [5]. Additionally, cardiac catheterization may be used as an adjunct in patient with severe AR and typically will show increased left ventricular end-diastolic pressure. As left ventricular filling pressures rise, left atrial pressure will increase and resultant increase in pulmonary vascular resistance may ensue.
Treatment Medical The left ventricle is severely volume overloaded in those patients with severe AR and HF, and diuretics and afterload reduction offer theoretical benefit. In patients who require intensive care unit admission, milrinone can be used to achieve afterload reduction, and intravenous diuretics can improve pulmonary congestion. Intubation with mechanical ventilation can also decrease left ventricular afterload and limit oxygen consumption. For outpatients with HF, diuretics can improve symptoms of pulmonary congestion, but do not prevent ongoing left ventricular dilation. If hypertension is present, it should be aggressively treated with a vasodilator such as an angiotensin-converting enzyme (ACE) inhibitor [6]. Although afterload reduction with ACE inhibitors offers theoretical benefit, it has not been clearly shown to slow the deterioration of the left ventricle in children [2]. Gisler et al. retrospectively described the course of 18 patients with isolated moderate–severe AR treated with ACE inhibitors. At a median follow-up of 2.3 years, there was no improvement in left ventricular size or shortening fraction or in the degree of AR. Adult studies also have shown variable results and suggest that vasodilator therapy cannot effectively delay need for aortic valve surgery. Evangelista et al. randomized 95 adults with asymptomatic severe AR to vasodilator therapy or placebo. The rate of aortic valve replacement was similar between groups, and there were no differences among groups in regurgitant volume, left ventricular size, or ejection fraction [8].
Invasive Given the lack of efficacy of medical therapy, aortic valve surgery is the definitive intervention for patients with HF associated with AR. Aortic valve surgery is recommended in symptomatic patients with severe AR and in asymptomatic patients with severe AR and left ventricular ejection fraction <50% or progressive left ventricular dilation [6]. In particular, progressive
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increase in the left ventricular end-systolic dimension can be an important indication for intervention as children with larger end-systolic dimensions prior to surgery may be less likely to experience recovery in left ventricular size after the operation [9]. Aortic valve surgical options include valve repair or valve replacement. Replacement options include homograft, pulmonary autograft (Ross operation), bioprosthetic valve, or mechanical valve. Choosing the best strategy is dictated by patient age, need for valve growth, risks of anticoagulation, and patient/surgeon preference. Valve repair typically involves pericardial leaflet extension and/or commissuroplasty. This option avoids anticoagulation, but it has limited longevity [10]. The Ross operation includes translocation of the pulmonary valve to the aortic position and offers good durability without the need for anticoagulation. However, the procedure can be technically demanding, and there is modest rate of autograft reintervention and right ventricular outflow tract intervention [11]. Several large series have been recently published describing long-term results of the Ross operation [12,13]. Nelson et al. described 240 patients undergoing Ross operation. Overall survival to discharge was 96%, although infants had significant mortality of 18%. Fifteen-year survival was 87% for the entire cohort and lowest for infants at 72%. At 15 years, overall freedom from left ventricular outflow tract reintervention was 59% and 85% in infants. Overall freedom from right ventricular outflow tract reintervention was 53% at 15 years, but only 19% in infants [13]. In small infants who cannot accommodate a mechanical valve and children and young adolescents wanting to avoid anticoagulation, the Ross operation is a viable option. Mechanical aortic valve replacement offers excellent longevity and durability, but anticoagulation with warfarin is required. Also, mechanical valve implantation is not an option for infants given aortic valve annular size and annular enlargement can be required in older children to facilitate placement [11]. Shanmugam et al. described 55 children who underwent aortic valve replacement with a mechanical valve. Freedom from reintervention rate was 96% at 5 years and 92% at 20 years with only 1 anticoagulation-related hemorrhage [14]. Bioprosthetic valve replacement does not require ongoing anticoagulation, but durability and longevity are limited, particularly in young children [11,15]. Similarly, replacement with homograft avoids the need for anticoagulation, but durability is very limited as are the number of possible donor grafts [11,15]. Transcatheter aortic valve replacement has become a viable option for adults who are deemed high risk for aortic valve surgery [16]. This technology shows promise, but requires extensive further study prior to its use in younger patients. Following aortic valve surgery, left ventricular size improves in most children by 6 months. Patients with persistent left ventricular dilation after surgery tend to have larger end-systolic dimension and lower ejection fraction prior to surgery [9]. In patients with severe HF associated with AR, mechanical support using extracorporeal membrane oxygenation (ECMO) or ventricular assist device (VAD) is not typically a viable option as the AR undermines the perfusion strategy. In those with severe AR who fail operative management, cardiac transplantation is also an option.
MITRAL REGURGITATION AND HEART FAILURE Etiology Similar to AR, mitral regurgitation (MR) is most commonly associated with congenital heart disease, specifically congenital valve abnormalities such as mitral arcade, parachute mitral valve, or mitral prolapse. MR can also occur in setting of endocardial inflammation from endocarditis, myocarditis, rheumatic fever, or collagen vascular disease. An infiltrative pathology from metabolic disease such as Hurler disease can also lead to insufficiency. In addition, ischemia from any cause can result in papillary muscle infarction and cause valvular leakage. Finally, annular dilation that can occur in connective tissue diseases as well as in the setting of dilated cardiomyopathy can lead to incomplete leaflet coaptation. In children, MR can also follow congenital heart surgery such as repair for congenital mitral stenosis. Patients who undergo complete atrioventricular canal repair also can develop left atrioventricular valve regurgitation after repair.
Pathophysiology The cardiac pathophysiology of MR is outlined in Fig. 22.2. Patients with severe MR have decreased cardiac output as the regurgitation “steals” blood that should be directed across the aortic valve. In acute insufficiency, left atrial pressure is increased with compromised antegrade flow into the aorta resulting in pulmonary edema and low cardiac output. In chronic MR, the regurgitation leads to increased left atrial and ventricular blood volume and dilation of the left atrium and ventricle. To reduce wall stress associated with the dilation, the ventricle will initially hypertrophy. Similar to chronic AR, progressive dilation will eventually result in irreversible ventricular injury and systolic dysfunction [17].
Presentation and Evaluation Similar to AR, severe MR can lead to left-sided cardiac failure with respiratory insufficiency and growth failure in infants and exertional issues in older children and adolescents. In severe cases, respiratory failure can occur requiring mechanical
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FIGURE 22.2 Flow diagram illustrating the pathophysiology of mitral regurgitation. CO, cardiac output; LA, left atrial; LV, left ventricle; LVH, left ventricular hypertrophy; PHTN, pulmonary hypertension; SV, stroke volume. (Adapted from Moore, et al., Critical care of patients with paediatric valvar cardiac disease, Cardiol. Young 24 (2014) 1071–1076.)
Mitral Regurgitation - Pathophysiology Regurgitation of LV SV Reduced CO & LA dilatation
LA dilatation Atrial arrhythmias, Thrombus Reactive PHTN & Right heart failure
LV volume overload LVH (concentric) & LV dilatation
LV failure Pulmonary edema, systemic hypotension
ventilation. Physical exam typically includes a holosystolic, blowing murmur best heard at the apex. If left ventricular dilation is present, the apical impulse can be displaced laterally. Patients with severe MR may have a diastolic rumble due to increased flow across the mitral valve. Patients with severe disease may also be tachycardic and tachypneic. Echocardiography is the most important modality in evaluating a patient with significant MR. Important anatomic detail can be gleaned from the echocardiogram including annular size and leaflet/subvalvar anatomy and function. Markers of severe MR in children include regurgitant jet encompassing >50% of left atrium, left atrial dilation, and left ventricular dilation [6,18,19]. Cardiac MRI can also be used to quantify the mitral valve regurgitant fraction and the left ventricular volume. Cardiac catheterization may also be helpful in the evaluation of patients with severe MR. If the left ventricle is significantly volume overloaded, left ventricular end-diastolic and left atrial pressures will be elevated. Significant elevations in left atrial pressure can cause pulmonary vascular resistance and pulmonary artery pressures to increase also.
Treatment Medical In patients with significant HF associated with MR who require intensive care unit admission, left ventricular afterload reduction and improved contractility can be useful. In theory, these measures could encourage forward flow across the aortic valve and decrease regurgitation. Milrinone is a common inotrope as it improves ventricular contractility and vasodilates to decrease afterload. Likewise, mechanical ventilation can lower afterload and decrease oxygen consumption and diuretics are useful to improve pulmonary congestion. In more stable patients, oral afterload reduction with ACE inhibitors can be used as can diuretics. Although some benefit can be seen, medical therapy has limited effectiveness in preventing progressive ventricular dilation and delaying surgery in patients with significant MR [20,21]. Knirsch et al. retrospectively compared 12 children with severe MR who were receiving ACE inhibitors with 12 who were not; left ventricular end-diastolic diameter, shortening fraction, and degree of MR were essentially unchanged between the two groups after 1 year [20].
Invasive The definitive therapy for patients with HF associated with MR is surgery. In children with severe MR, mitral valve surgery is indicated in the presence of symptoms or in asymptomatic patients with decreased left ventricular systolic function [6]. Surgical options include valve repair or replacement. Repair techniques for congenital mitral valve abnormalities have been reported with success, but repair can be challenging particularly in small infants [22,23]. When repair is not an option or unsuccessful, valve replacement with a mechanical valve is typically preferable given superior durability. With the use of mechanical valve, anticoagulation is required, and reoperation will be necessary in the setting of eventual valve failure or
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need to upsize the valve to account for somatic growth. Valve replacement can also be challenging in infants and young children due to the small size of the mitral valve annulus, and placement in the supra-annular position may be needed. Brown et al. described mitral valve replacement in nearly 100 pediatric patients with median age of 8 years. Operative mortality was 6%, and freedom from reoperation at 35 years was 63%. Factors associated with increased risk of operative death were age <2 years, presence of an atrioventricular canal defect, univentricular heart, and additional left-sided obstructive lesions [24]. Tierney et al. described mitral valve replacement in 118 children ≤5 years. The valve was placed in the supraannular position in 32%, and survival was 74% at 1 year. Risk factors for worse survival included age <1 year, presence of an atrioventricular canal defect, and additional procedure coincident with valve replacement [25]. Given the challenges associated with both repair and replacement in young children, use of stented bovine jugular venous valve (Melody valve, Medtronic, Minneapolis, Minnesota) has been employed in this population. Quinonez et al. described 11 patients with median age of 7 months who underwent surgical placement of the Melody valve in the mitral position. This valve can be serially dilated percutaneously as the child grows, a significant potential advantage of this technique [26]. The use of a pulmonary autograft (Ross II technique) in the mitral position has been described in a limited number of patients. This technique can be attractive in women who are interested in having children and in those who have failed previous mechanical valve placement due to thrombotic complications [27]. In patients with severe HF associated with MR who fail surgical intervention, cardiac transplantation can be considered, and mechanical support using ECMO or a VAD could be considered as a bridge to transplantation.
PULMONARY REGURGITATION AND HEART FAILURE Etiology In children and adolescents, isolated congenital pulmonary regurgitation (PR) is rare and PR most often results following surgical repair of conotruncal congenital heart lesions. Most commonly, patients with tetralogy of Fallot (TOF) develop chronic PR after transannular patch augmentation of the right ventricular outflow tract during TOF repair. Even patients who undergo a valve-sparing operation may develop significant PR [28]. Other lesions such as TOF with pulmonary atresia, TOF with associated coronary anomaly, or truncus arteriosus may require placement of a right ventricle to pulmonary artery conduit, which typically develops regurgitation. Patients undergoing Ross operation for aortic stenosis and/or regurgitation will also receive a conduit. Additionally, patients who undergo transcatheter pulmonary valvuloplasty can develop PR [29]. Acquired causes of PR such as endocarditis are uncommon.
Pathophysiology The degree of PR is determined by the regurgitant orifice area, right ventricular compliance, the capacitance of the pulmonary arteries, and duration of diastole. Unlike AR, the diastolic pressure difference between the main pulmonary artery and right ventricle is typically small and, thus, is not a major determinant of the degree of PR. In the case of repaired TOF, the regurgitant orifice is often large immediately after surgery. However, the impact of PR is typically small because the right ventricle is hypertrophied and noncompliant, and the heart rate is fast with shortened diastole. Over time, right ventricular compliance improves. The stroke volume of the ventricle also increases due to ongoing PR and ventricular dilation. Likewise, the heart rate slows with age, increasing length of diastole. These factors encourage a gradual increase in the degree of PR [30]. Significant PR will lead to progressive right ventricular dilation, with similar pathophysiology of left ventricular enlargement due to AR. Initially, as the ventricle dilates, compensatory hypertrophy will occur to maintain a normal mass– volume relationship. However, eventually compensatory hypertrophy will be unable to keep pace with dilation; irreversible myocardial injury can occur with resultant decreased systolic function. Fig. 22.3 depicts the pathophysiology of chronic PR after TOF repair. Also, because the right and left ventricles share myofibers, the interventricular septum, and the pericardial space, right ventricular dilation can negatively influence left ventricular systolic and diastolic function [30,31].
Presentation and Evaluation Children with chronic, severe PR are initially asymptomatic, often for 10–15 years. With progressive RV dilation and eventual systolic dysfunction, symptoms eventually occur and include exercise intolerance and arrhythmias. Negative ventricular–ventricular interaction can occur and cause left ventricular dysfunction and symptoms of left-sided HF including pulmonary edema [30]. Physical exam will show a soft diastolic, decrescendo murmur at left upper sternal border. There may also be a systolic ejection murmur at the same location due to increased right ventricular stroke volume and flow across the pulmonary valve. If right ventricular dilation is present, parasternal lift may be present.
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FIGURE 22.3 Diagram illustrating the pathophysiology of pulmonary regurgitation after tetralogy of Fallot (TOF) repair. PA, pulmonary artery; RV, right ventricle. (Adapted from Geva, et al., Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support. J. Cardiovasc. Magn. Reson. (2011) 13.)
TOF Repair
Pulmonary regurgitation
PA dilation ( capacitance)
PA pulse pressure/volume
RV dilatation
RV compliance
Pulmonary regurgitation
Echocardiography is used to characterize pulmonary valve structure and function and describe the degree of PR. In those with severe PR, the regurgitant color jet fills the right ventricular outflow tract, there is reversal of flow in the branch pulmonary arteries, and there is septal flattening during diastole [6]. However, cardiac MRI is often used to characterize the degree of PR and quantify biventricular size and systolic function. Moderate PR is considered a regurgitant fraction >25% [30]. In fact, MRI results can be very useful in risk stratification of those with repaired TOF and can provide values that are important in clinical decision-making [30,32]. Patients with indexed right ventricular end-diastolic volume >150–170 cc/ m2 may not experience normalization of right ventricular size after valve restoration [33–35]. Serum BNP can also be a useful adjunct to imaging in those with chronic PR. In those with PR related to TOF repair, BNP has been associated with NYHA functional class, right ventricular size, and severity of PR [32].
Treatment Medical There are limited data regarding medical therapy for patients with chronic PR and its associated deleterious effects on the right ventricle. The APPROPRIATE study randomized patients with repaired TOF and moderate–severe PR to Ramipril versus placebo. Most patients were asymptomatic, and there was no improvement in right ventricular ejection fraction or right ventricular end-diastolic volume at 6 months [36]. Norozi et al. randomized young adults with repaired TOF and NYHA Class one to two symptoms to bisoprolol versus placebo for 6 months and found no benefit on right ventricular ejection fraction or volume [37]. In patients with significant right-sided HF associated with lower extremity edema and/or ascites, diuretic therapy may offer some short-term symptomatic relief.
Invasive For patients with HF associated with severe PR, restoration of pulmonary valve competency is the standard of care. This can be accomplished with surgical and transcatheter techniques. Both surgical and transcatheter pulmonary valve replacement have been shown to decrease the degree of PR and right ventricular size and significantly improve HF-associated symptoms [30,38]. While right ventricular size improves including both end-diastolic and end-systolic volumes, right ventricular ejection fraction typically does not change after valve restoration [30]. There are numerous series describing the safety and efficacy of surgical pulmonary valve replacement using bioprosthetic valves, valved conduits, and homografts [11,39]. The procedure is safe with a low rate of major complication and/or early reintervention [39]. Alternatively, some patients are candidates for transcatheter pulmonary valve replacement. The Melody valve (Medtronic Inc., Minneapolis, Minnesota) is available for transcatheter pulmonary valve replacement under a Humanitarian Device Exemption in patients with a right ventricular outflow tract conduit (Fig. 22.4). Thus, patients who have undergone surgical right ventricular outflow tract palliation with homograft conduit, valved conduit, or even bioprosthetic
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(A)
(B)
FIGURE 22.4 Anteroposterior (A) and lateral (B) views of angiogram performed in distal right ventricle to pulmonary artery conduit in a 30-year-old female with repaired tetralogy of Fallot and pulmonary atresia after placement of a Melody valve in the conduit to treat severe pulmonary regurgitation. In both projections, there is no regurgitation of contrast into the right ventricle after Melody placement. Will get angio after Melody.
valve can be good candidates for percutaneous Melody valve implantation [38,40]. Patients with a native outflow tract that has not significantly dilated can also be candidates for off-label Melody valve use after outflow tract stenting [41,42]. The Sapien transcatheter valve (Edwards Lifesciences LLC, Irvine, California) has also been used in the pulmonary position and can be used in larger conduits or outflow tracts than the Melody valve, but it is only currently available in the United States as part of an investigational device exemption trial. Similar to surgical pulmonary valve replacement, Melody and Sapien valve implantation is associated with low rate of major complications and good short- and midterm success [43,44].
TRICUSPID REGURGITATION AND HEART FAILURE Etiology The most common cause of significant tricuspid regurgitation (TR) in children is Ebstein’s anomaly of the tricuspid valve. In this condition, the septal and posterior leaflets fail to delaminate during development and are adherent to the right ventricular myocardium, resulting in apical displacement of the functional tricuspid valve annulus. The anterior leaflet is redundant and “sail-like.” Significant TR can result due to abnormal leaflet coaptation [45]. Fig. 22.5 depicts a patient with significant Ebstein’s anomaly. Other patients may be born with a dysplastic tricuspid valve that does not meet criteria for Ebstein’s anomaly and may also have TR. Acquired causes such as endocarditis are rare.
Pathophysiology Neonates with severe Ebstein’s anomaly may be cyanotic due to right to left shunting at the atrial level with inadequate antegrade pulmonary blood flow due to severe TR. In other patients, ongoing severe TR will lead to right atrial and ventricular dilation. As with severe PR, eventually right ventricular systolic function can become compromised. The combination of TR and right ventricular dysfunction can limit cardiac output, especially with exercise and can lead to symptoms of right HF. Also, as the right ventricle dilates, so does the tricuspid valve annulus, leading to further TR. Right to left shunting may exist at the atrial level causing cyanosis with exertion.
Presentation and Evaluation Infants with severe Ebstein’s anomaly are symptomatic immediately. These patients may have inadequate pulmonary blood flow due to severe TR and elevated pulmonary vascular resistance and even may have “functional” pulmonary atresia requiring prostaglandin infusion. Management of these patients is complex, and a full description is beyond the scope of this chapter
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FIGURE 22.5 Transthoracic echocardiogram in the apical view showing severe tricuspid regurgitation in a 3-year-old with Ebstein’s anomaly of the tricuspid valve. RA, right atrium; RV, right ventricle; TR, tricuspid regurgitation; TV, tricuspid valve.
[46]. Older children and adolescents may develop symptoms from ongoing TR and resultant right atrial and ventricular dilation. These patients will exhibit symptoms of right-sided HF with exercise intolerance, lower extremity edema, and/or ascites. Also, given the chamber dilation and possible presence of preexcitation, arrhythmias often occur and lead to symptoms. Physical exam often reveals a low frequency holosystolic murmur at the left lower sternal border. Because right ventricular volume is increased, a systolic ejection murmur may be present at the left sternal border due to increased flow across the pulmonary valve. The second heart sound may be normal or widely split if there is significantly increased flow across pulmonary valve. In terms of evaluation, echocardiogram is the gold standard for characterizing tricuspid valve anatomy and function as well as describing the degree of TR. In those with Ebstein’s anomaly or dysplastic tricuspid valve, cardiac MRI is rarely needed [45].
Treatment Medical Patients who have significant HF associated with TR can have some symptomatic benefit from diuretics, especially if edema and ascites are present. ACE inhibitors have not been significantly investigated in those with HF associated with TR.
Invasive Surgery is indicated in those who have symptoms associated with severe TR, in those with significant cyanosis due to atrial level shunting, or in those with significant burden of atrial arrhythmias [6,45]. The nature of the surgery depends on age and size of the patient as well as tricuspid valve anatomy. Typically, tricuspid valve repair is attempted prior to valve replacement with a bioprosthetic valve. For those with Ebstein’s anomaly, tricuspid valve annuloplasty, plication of the atrialized portion of the right ventricle and right atrial reduction are often performed, although additional repair options exist including cone reconstruction [47–50]. Hetzer et al. described outcomes after tricuspid valve repair in 67 patients with Ebstein’s anomaly. The mean NYHA class improved from 3.4 to 1.3 (P < .001), and freedom from reoperation was 98% at 5 years [48]. Dearani et al. reported the Mayo Clinic’s experience with cone reconstruction in 89 patients. The series described 1 death and, at last follow-up, 87% had no or mild TR [50]. Also, patients who have only mild-moderate TR, but have significant cyanosis at rest or with exercise, can receive benefit from transcatheter closure of interatrial communication [51].
CONCLUSION Valvular insufficiency can be an important cause of HF in young children and adolescents. In these patients, insufficiency most often results from congenital valve anomalies, but postoperative regurgitation can also occur following congenital cardiac surgery. Medical therapy is typically ineffective, and surgical or transcatheter valve replacement techniques are typically the treatment of choice for pediatric patients with symptoms of HF associated with any regurgitant valve lesion.
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Bauersfeld, Angiotensin-converting enzyme inhibitors in pediatric patients with mitral valve regurgitationcase-control study and review of the literature, Congenit. Heart Dis. 5 (3) (May–June 2010) 278–284 PubMed PMID: 20576047. [21] Y. Mori, M. Nakazawa, H. Tomimatsu, K. Momma, Long-term effect of angiotensin-converting enzyme inhibitor in volume overloaded heart during growth: a controlled pilot study, J. Am. Coll. Cardiol. 36 (1) (July 2000) 270–275 PubMed PMID: 10898445. [22] G. Stellin, M.A. Padalino, V.L. Vida, G. Boccuzzo, E. Orru, R. Biffanti, et al., Surgical repair of congenital mitral valve malformations in infancy and childhood: a single-center 36-year experience, J. Thorac. Cardiovasc. Surg. 140 (6) (December 2010) 1238–1244 PubMed PMID: 20554294. [23] D. Kalfa, M. Vergnat, M. Ly, B. Stos, V. Lambert, A. Baruteau, et al., A standardized repair-oriented strategy for mitral insufficiency in infants and children: midterm functional outcomes and predictors of adverse events, J. Thorac. Cardiovasc. Surg. 148 (4) (October 2014) 1459–1466 PubMed PMID: 24667029. [24] J.W. Brown, A.C. Fiore, M. Ruzmetov, O. Eltayeb, M.D. Rodefeld, M.W. Turrentine, Evolution of mitral valve replacement in children: a 40-year experience, Ann. Thorac. Surg. 93 (2) (February 2012) 626–633 discussion 33. PubMed PMID: 22153051. [25] E.S. Selamet Tierney, F.A. Pigula, C.I. Berul, J.E. Lock, P.J. del Nido, D.B. McElhinney, Mitral valve replacement in infants and children 5 years of age or younger: evolution in practice and outcome over three decades with a focus on supra-annular prosthesis implantation, J. Thorac. Cardiovasc. Surg. 136 (4) (October 2008) 954–961 61 e1-3. PubMed PMID: 18954636. Pubmed Central PMCID: 4230576. [26] L.G. Quinonez, R. Breitbart, W. Tworetsky, J.E. Lock, A.C. Marshall, S.M. Emani, Stented bovine jugular vein graft (melody valve) for surgical mitral valve replacement in infants and children, J. Thorac. Cardiovasc. Surg. 148 (4) (October 2014) 1443–1449 PubMed PMID: 24332108.
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[27] J.W. Brown, M. Ruzmetov, M.D. Rodefeld, M.W. Turrentine, Mitral valve replacement with Ross II technique: initial experience, Ann. Thorac. Surg. 81 (2) (February 2006) 502–507 discussion 7-8. PubMed PMID: 16427839. [28] V.L. Vida, A. Guariento, B. Castaldi, M. Sambugaro, M.A. Padalino, O. Milanesi, et al., Evolving strategies for preserving the pulmonary valve during early repair of tetralogy of Fallot: mid-term results, J. Thorac. Cardiovasc. Surg. 147 (2) (February 2014) 687–694 discussion 94-6. PubMed PMID: 24314789. [29] D.M. Harrild, A.J. Powell, T.X. Tran, T. Geva, J.E. Lock, J. Rhodes, et al., Long-term pulmonary regurgitation following balloon valvuloplasty for pulmonary stenosis risk factors and relationship to exercise capacity and ventricular volume and function, J. Am. Coll. Cardiol. 55 (10) (March 9, 2010) 1041–1047 PubMed PMID: 20202522. Pubmed Central PMCID: 4235281. [30] T. Geva, Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support, J. Cardiovasc. Magn. Reson. 13 (2011) 9 PubMed PMID: 21251297. Pubmed Central PMCID: 3036629. [31] M.C. Schwartz, J.J. Rome, M.J. Gillespie, K. Whitehead, M.A. Harris, M.A. Fogel, et al., Relation of left ventricular end diastolic pressure to right ventricular end diastolic volume after operative treatment of tetralogy of fallot, Am. J. Cardiol. 109 (3) (February 1, 2012) 417–422 PubMed PMID: 22078963. [32] J. Villafane, J.A. Feinstein, K.J. Jenkins, R.N. Vincent, E.P. Walsh, A.M. Dubin, et al., Hot topics in tetralogy of Fallot, J. Am. Coll. Cardiol. 62 (23) (December 10, 2013) 2155–2166 PubMed PMID: 24076489. [33] E.R. Buechel, H.H. Dave, C.J. Kellenberger, A. Dodge-Khatami, R. Pretre, F. Berger, et al., Remodelling of the right ventricle after early pulmonary valve replacement in children with repaired tetralogy of Fallot: assessment by cardiovascular magnetic resonance, Eur. Heart J. 26 (24) (December 2005) 2721–2727 PubMed PMID: 16214832. [34] T. Oosterhof, A. van Straten, H.W. Vliegen, F.J. Meijboom, A.P. van Dijk, A.M. Spijkerboer, et al., Preoperative thresholds for pulmonary valve replacement in patients with corrected tetralogy of Fallot using cardiovascular magnetic resonance, Circulation 116 (5) (July 31, 2007) 545–551 PubMed PMID: 17620511. [35] J. Therrien, Y. Provost, N. Merchant, W. Williams, J. Colman, G. Webb, Optimal timing for pulmonary valve replacement in adults after tetralogy of Fallot repair, Am. J. Cardiol. 95 (6) (March 15, 2005) 779–782 PubMed PMID: 15757612. [36] S.V. Babu-Narayan, A. Uebing, P.A. Davlouros, M. Kemp, S. Davidson, K. Dimopoulos, et al., Randomised trial of ramipril in repaired tetralogy of Fallot and pulmonary regurgitation: the APPROPRIATE study (Ace inhibitors for Potential PRevention of the deleterious effects of Pulmonary Regurgitation in Adults with repaired TEtralogy of Fallot, Int. J. Cardiol. 154 (3) (February 9, 2012) 299–305 PubMed PMID: 20970202. [37] K. Norozi, J. Bahlmann, B. Raab, V. Alpers, J.O. Arnhold, T. Kuehne, et al., A prospective, randomized, double-blind, placebo controlled trial of beta-blockade in patients who have undergone surgical correction of tetralogy of Fallot, Cardiol. Young 17 (4) (August 2007) 372–379 PubMed PMID: 17572925. [38] M.L. O’Byrne, M.J. Gillespie, Will catheter interventions replace surgery for valve abnormalities? Curr. Opin. Cardiol. 29 (1) (January 2014) 83–90 PubMed PMID: 24281347. Pubmed Central PMCID: 4341839. [39] E.D. McKenzie, M.S. Khan, T.W. Dietzman, F.A. Guzman-Pruneda, A.X. Samayoa, A. Liou, et al., Surgical pulmonary valve replacement: a benchmark for outcomes comparisons, J. Thorac. Cardiovasc. Surg. 148 (4) (October 2014) 1450–1453 PubMed PMID: 24703628. [40] M.J. Gillespie, J.J. Rome, D.S. Levi, R.J. Williams, J.F. Rhodes, J.P. Cheatham, et al., Melody valve implant within failed bioprosthetic valves in the pulmonary position: a multicenter experience, Circ. Cardiovasc. Interv. 5 (6) (December 2012) 862–870 PubMed PMID: 23212395. [41] D.E. Boshoff, B.L. Cools, R. Heying, E. Troost, J. Kefer, W. Budts, et al., Off-label use of percutaneous pulmonary valved stents in the right ventricular outflow tract: time to rewrite the label? Catheter. Cardiovasc. Interv. 81 (6) (May 2013) 987–995 PubMed PMID: 22887796. [42] J.J. Meadows, P.M. Moore, D.P. Berman, J.P. Cheatham, S.L. Cheatham, D. Porras, et al., Use and performance of the melody transcatheter pulmonary valve in native and postsurgical, nonconduit right ventricular outflow tracts, Circ. Cardiovasc. Interv. 7 (3) (June 2014) 374–380 PubMed PMID: 24867892. [43] J.P. Cheatham, W.E. Hellenbrand, E.M. Zahn, T.K. Jones, D.P. Berman, J.A. Vincent, et al., Clinical and hemodynamic outcomes up to 7 years after transcatheter pulmonary valve replacement in the US melody valve investigational device exemption trial, Circulation 131 (22) (June 2, 2015) 1960–1970 PubMed PMID: 25944758. [44] D. Kenny, Z.M. Hijazi, S. Kar, J. Rhodes, M. Mullen, R. Makkar, et al., Percutaneous implantation of the Edwards SAPIEN transcatheter heart valve for conduit failure in the pulmonary position: early phase 1 results from an international multicenter clinical trial, J. Am. Coll. Cardiol. 58 (21) (November 15, 2011) 2248–2256 PubMed PMID: 22078433. [45] C.H. Attenhofer Jost, H.M. Connolly, J.A. Dearani, W.D. Edwards, G.K. Danielson, Ebstein’s anomaly, Circulation 115 (2) (January 16, 2007) 277–285 PubMed PMID: 17228014. [46] U.S. Boston, S.P. Goldberg, K.E. Ward, E.D. Overholt, T. Spentzas, T.K. Chin, et al., Complete repair of Ebstein anomaly in neonates and young infants: a 16-year follow-up, J. Thorac. Cardiovasc. Surg. 141 (5) (May 2011) 1163–1169 PubMed PMID: 21353250. [47] J.P. da Silva, J.F. Baumgratz, L. da Fonseca, S.M. Franchi, L.M. Lopes, G.M. Tavares, et al., The cone reconstruction of the tricuspid valve in Ebstein’s anomaly. The operation: early and midterm results, J. Thorac. Cardiovasc. Surg. 133 (1) (January 2007) 215–223 PubMed PMID: 17198815. [48] R. Hetzer, P. Hacke, M. Javier, O. Miera, K. Schmitt, Y. Weng, et al., The long-term impact of various techniques for tricuspid repair in Ebstein’s anomaly, J. Thorac. Cardiovasc. Surg. (August 14, 2015) PubMed PMID: 26349593. [49] H.N. Anderson, J.A. Dearani, S.M. Said, M.D. Norris, K.N. Pundi, A.R. Miller, et al., Cone reconstruction in children with Ebstein anomaly: the Mayo Clinic experience, Congenit. Heart Dis. 9 (3) (May–June 2014) 266–271 PubMed PMID: 24373319. [50] J.A. Dearani, S.M. Said, P.W. 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Valvular Insufficiency and Heart Failure Matthew C. Schwartz1, Andrew C. Glatz2, Matthew J. Gillespie2 1Arnold
Palmer Hospital for Children, Orlando, FL, United States; 2Children’s Hospital of Philadelphia, Philadelphia, PA, United States
INTRODUCTION Valvular insufficiency is an important cause of heart failure (HF) in children, most commonly occurring in the setting of congenital heart disease [1]. Significant insufficiency less commonly results from acquired causes including endocarditis and rheumatic heart disease or from inherited connective tissue disorders. In general, valvular insufficiency puts a significant volume load on the affected ventricle, which can lead to ventricular deterioration and HF. This chapter focuses on the causes, pathophysiology, evaluation, and treatment of HF associated with valvular insufficiency in children.
AORTIC REGURGITATION AND HEART FAILURE Etiology In children, aortic regurgitation (AR) is most typically associated with various types of congenital heart disease. AR can occur following balloon valvuloplasty for congenital aortic stenosis. AR can also develop in those with bicuspid aortic valve with no history of intervention. Patients with aortic valve leaflet prolapse due to an accompanying ventricular septal defect often exhibit AR. Various causes of aortic root dilation can also lead to AR due to annular enlargement including inherited connective tissue disorders such as Marfan syndrome or Ehlers–Danlos syndrome. Aortic root dilation and AR can also result after arterial switch and Ross operations. Acquired etiologies of AR in children are less common and include infectious endocarditis and rheumatic heart disease [2,3].
Pathophysiology HF can occur in the setting of both acute and chronic severe AR. Chronic AR leads to progressive left ventricular dilation with compensatory ventricular hypertrophy. Eventually, the dilation exceeds the degree of hypertrophy leading to elevated end-systolic wall stress and afterload. These changes cause a decrease in the systolic function of the left ventricle. If severe dilation progresses, intrinsic myocyte function is affected and irreversible injury can occur [2]. HF can ensue because pump function is diminished and because a significant amount of the ventricle’s stroke volume leaks back into the ventricle. The acute development of AR is rare in children but can lead to pronounced HF. In acute AR, the ventricle has not had time to gradually enlarge and, thus, the regurgitant volume causes an abrupt increase in left ventricular end-diastolic pressure. This increase is transmitted to the left atrium and pulmonary veins causing pulmonary edema. Also, the left ventricle is unable to acutely increase stroke volume in the setting of additional regurgitant blood, which causes a decrease in net effective forward blood flow and, thus, a decrease in cardiac output [4].
Presentation and Evaluation HF symptoms due to severe AR will be due to left-sided cardiac failure and associated pulmonary edema. Infants may develop tachypnea, respiratory insufficiency, and growth failure, while older children and adolescents can develop these symptoms as well as exercise intolerance. In those with severe AR, physical exam will include an early, medium to high frequency diastolic decrescendo murmur at the left sternal border. Because left ventricular stroke volume may be increased in the setting of a dilated ventricle, a systolic ejection murmur may also be present due to increased flow across the aortic valve. An Austin Flint murmur may also be present, a low frequency middiastolic rumble heard near the apex due to limitation in the opening of the mitral valve’s anterior leaflet from the AR jet. Pulse pressure will also be widened due to diastolic leakage of blood across the valve, and pulses may be bounding or “water hammer.” Patients who have significant HF due to AR may also exhibit tachycardia, tachypnea, and hypoxemia from pulmonary vein desaturation associated with pulmonary edema [2]. Heart Failure in the Child and Young Adult. http://dx.doi.org/10.1016/B978-0-12-802393-8.00022-3 Copyright © 2018 Elsevier Inc. All rights reserved.
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FIGURE 22.1 Transthoracic echocardiogram in the parasternal long-axis view showing severe aortic regurgitation (AR) in a 1-year-old with severe aortic stenosis who underwent balloon valvuloplasty in the neonatal period.
Echocardiography is the cornerstone for evaluating AR in children (Fig. 22.1). The anatomy of the aortic valve, the degree of AR, and the ventricular size and function can all be evaluated [5]. Echocardiographic markers of severe AR include holodiastolic flow reversal in the descending aorta, left ventricular dilation, and/or AI jet width >65% of left ventricular outflow tract diameter [2,6,7]. Magnetic resonance imaging (MRI) can also be helpful in characterizing AR by quantifying ventricular size and function as well as calculating the aortic valve regurgitant fraction [2]. Brain natriuretic peptide (BNP) and N-terminal proBNP levels can reflect the degree of neurohormonal activity in adults with HF, but these findings may not be generalizable to children [5]. Additionally, cardiac catheterization may be used as an adjunct in patient with severe AR and typically will show increased left ventricular end-diastolic pressure. As left ventricular filling pressures rise, left atrial pressure will increase and resultant increase in pulmonary vascular resistance may ensue.
Treatment Medical The left ventricle is severely volume overloaded in those patients with severe AR and HF, and diuretics and afterload reduction offer theoretical benefit. In patients who require intensive care unit admission, milrinone can be used to achieve afterload reduction, and intravenous diuretics can improve pulmonary congestion. Intubation with mechanical ventilation can also decrease left ventricular afterload and limit oxygen consumption. For outpatients with HF, diuretics can improve symptoms of pulmonary congestion, but do not prevent ongoing left ventricular dilation. If hypertension is present, it should be aggressively treated with a vasodilator such as an angiotensin-converting enzyme (ACE) inhibitor [6]. Although afterload reduction with ACE inhibitors offers theoretical benefit, it has not been clearly shown to slow the deterioration of the left ventricle in children [2]. Gisler et al. retrospectively described the course of 18 patients with isolated moderate–severe AR treated with ACE inhibitors. At a median follow-up of 2.3 years, there was no improvement in left ventricular size or shortening fraction or in the degree of AR. Adult studies also have shown variable results and suggest that vasodilator therapy cannot effectively delay need for aortic valve surgery. Evangelista et al. randomized 95 adults with asymptomatic severe AR to vasodilator therapy or placebo. The rate of aortic valve replacement was similar between groups, and there were no differences among groups in regurgitant volume, left ventricular size, or ejection fraction [8].
Invasive Given the lack of efficacy of medical therapy, aortic valve surgery is the definitive intervention for patients with HF associated with AR. Aortic valve surgery is recommended in symptomatic patients with severe AR and in asymptomatic patients with severe AR and left ventricular ejection fraction <50% or progressive left ventricular dilation [6]. In particular, progressive
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increase in the left ventricular end-systolic dimension can be an important indication for intervention as children with larger end-systolic dimensions prior to surgery may be less likely to experience recovery in left ventricular size after the operation [9]. Aortic valve surgical options include valve repair or valve replacement. Replacement options include homograft, pulmonary autograft (Ross operation), bioprosthetic valve, or mechanical valve. Choosing the best strategy is dictated by patient age, need for valve growth, risks of anticoagulation, and patient/surgeon preference. Valve repair typically involves pericardial leaflet extension and/or commissuroplasty. This option avoids anticoagulation, but it has limited longevity [10]. The Ross operation includes translocation of the pulmonary valve to the aortic position and offers good durability without the need for anticoagulation. However, the procedure can be technically demanding, and there is modest rate of autograft reintervention and right ventricular outflow tract intervention [11]. Several large series have been recently published describing long-term results of the Ross operation [12,13]. Nelson et al. described 240 patients undergoing Ross operation. Overall survival to discharge was 96%, although infants had significant mortality of 18%. Fifteen-year survival was 87% for the entire cohort and lowest for infants at 72%. At 15 years, overall freedom from left ventricular outflow tract reintervention was 59% and 85% in infants. Overall freedom from right ventricular outflow tract reintervention was 53% at 15 years, but only 19% in infants [13]. In small infants who cannot accommodate a mechanical valve and children and young adolescents wanting to avoid anticoagulation, the Ross operation is a viable option. Mechanical aortic valve replacement offers excellent longevity and durability, but anticoagulation with warfarin is required. Also, mechanical valve implantation is not an option for infants given aortic valve annular size and annular enlargement can be required in older children to facilitate placement [11]. Shanmugam et al. described 55 children who underwent aortic valve replacement with a mechanical valve. Freedom from reintervention rate was 96% at 5 years and 92% at 20 years with only 1 anticoagulation-related hemorrhage [14]. Bioprosthetic valve replacement does not require ongoing anticoagulation, but durability and longevity are limited, particularly in young children [11,15]. Similarly, replacement with homograft avoids the need for anticoagulation, but durability is very limited as are the number of possible donor grafts [11,15]. Transcatheter aortic valve replacement has become a viable option for adults who are deemed high risk for aortic valve surgery [16]. This technology shows promise, but requires extensive further study prior to its use in younger patients. Following aortic valve surgery, left ventricular size improves in most children by 6 months. Patients with persistent left ventricular dilation after surgery tend to have larger end-systolic dimension and lower ejection fraction prior to surgery [9]. In patients with severe HF associated with AR, mechanical support using extracorporeal membrane oxygenation (ECMO) or ventricular assist device (VAD) is not typically a viable option as the AR undermines the perfusion strategy. In those with severe AR who fail operative management, cardiac transplantation is also an option.
MITRAL REGURGITATION AND HEART FAILURE Etiology Similar to AR, mitral regurgitation (MR) is most commonly associated with congenital heart disease, specifically congenital valve abnormalities such as mitral arcade, parachute mitral valve, or mitral prolapse. MR can also occur in setting of endocardial inflammation from endocarditis, myocarditis, rheumatic fever, or collagen vascular disease. An infiltrative pathology from metabolic disease such as Hurler disease can also lead to insufficiency. In addition, ischemia from any cause can result in papillary muscle infarction and cause valvular leakage. Finally, annular dilation that can occur in connective tissue diseases as well as in the setting of dilated cardiomyopathy can lead to incomplete leaflet coaptation. In children, MR can also follow congenital heart surgery such as repair for congenital mitral stenosis. Patients who undergo complete atrioventricular canal repair also can develop left atrioventricular valve regurgitation after repair.
Pathophysiology The cardiac pathophysiology of MR is outlined in Fig. 22.2. Patients with severe MR have decreased cardiac output as the regurgitation “steals” blood that should be directed across the aortic valve. In acute insufficiency, left atrial pressure is increased with compromised antegrade flow into the aorta resulting in pulmonary edema and low cardiac output. In chronic MR, the regurgitation leads to increased left atrial and ventricular blood volume and dilation of the left atrium and ventricle. To reduce wall stress associated with the dilation, the ventricle will initially hypertrophy. Similar to chronic AR, progressive dilation will eventually result in irreversible ventricular injury and systolic dysfunction [17].
Presentation and Evaluation Similar to AR, severe MR can lead to left-sided cardiac failure with respiratory insufficiency and growth failure in infants and exertional issues in older children and adolescents. In severe cases, respiratory failure can occur requiring mechanical
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FIGURE 22.2 Flow diagram illustrating the pathophysiology of mitral regurgitation. CO, cardiac output; LA, left atrial; LV, left ventricle; LVH, left ventricular hypertrophy; PHTN, pulmonary hypertension; SV, stroke volume. (Adapted from Moore, et al., Critical care of patients with paediatric valvar cardiac disease, Cardiol. Young 24 (2014) 1071–1076.)
Mitral Regurgitation - Pathophysiology Regurgitation of LV SV Reduced CO & LA dilatation
LA dilatation Atrial arrhythmias, Thrombus Reactive PHTN & Right heart failure
LV volume overload LVH (concentric) & LV dilatation
LV failure Pulmonary edema, systemic hypotension
ventilation. Physical exam typically includes a holosystolic, blowing murmur best heard at the apex. If left ventricular dilation is present, the apical impulse can be displaced laterally. Patients with severe MR may have a diastolic rumble due to increased flow across the mitral valve. Patients with severe disease may also be tachycardic and tachypneic. Echocardiography is the most important modality in evaluating a patient with significant MR. Important anatomic detail can be gleaned from the echocardiogram including annular size and leaflet/subvalvar anatomy and function. Markers of severe MR in children include regurgitant jet encompassing >50% of left atrium, left atrial dilation, and left ventricular dilation [6,18,19]. Cardiac MRI can also be used to quantify the mitral valve regurgitant fraction and the left ventricular volume. Cardiac catheterization may also be helpful in the evaluation of patients with severe MR. If the left ventricle is significantly volume overloaded, left ventricular end-diastolic and left atrial pressures will be elevated. Significant elevations in left atrial pressure can cause pulmonary vascular resistance and pulmonary artery pressures to increase also.
Treatment Medical In patients with significant HF associated with MR who require intensive care unit admission, left ventricular afterload reduction and improved contractility can be useful. In theory, these measures could encourage forward flow across the aortic valve and decrease regurgitation. Milrinone is a common inotrope as it improves ventricular contractility and vasodilates to decrease afterload. Likewise, mechanical ventilation can lower afterload and decrease oxygen consumption and diuretics are useful to improve pulmonary congestion. In more stable patients, oral afterload reduction with ACE inhibitors can be used as can diuretics. Although some benefit can be seen, medical therapy has limited effectiveness in preventing progressive ventricular dilation and delaying surgery in patients with significant MR [20,21]. Knirsch et al. retrospectively compared 12 children with severe MR who were receiving ACE inhibitors with 12 who were not; left ventricular end-diastolic diameter, shortening fraction, and degree of MR were essentially unchanged between the two groups after 1 year [20].
Invasive The definitive therapy for patients with HF associated with MR is surgery. In children with severe MR, mitral valve surgery is indicated in the presence of symptoms or in asymptomatic patients with decreased left ventricular systolic function [6]. Surgical options include valve repair or replacement. Repair techniques for congenital mitral valve abnormalities have been reported with success, but repair can be challenging particularly in small infants [22,23]. When repair is not an option or unsuccessful, valve replacement with a mechanical valve is typically preferable given superior durability. With the use of mechanical valve, anticoagulation is required, and reoperation will be necessary in the setting of eventual valve failure or
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need to upsize the valve to account for somatic growth. Valve replacement can also be challenging in infants and young children due to the small size of the mitral valve annulus, and placement in the supra-annular position may be needed. Brown et al. described mitral valve replacement in nearly 100 pediatric patients with median age of 8 years. Operative mortality was 6%, and freedom from reoperation at 35 years was 63%. Factors associated with increased risk of operative death were age <2 years, presence of an atrioventricular canal defect, univentricular heart, and additional left-sided obstructive lesions [24]. Tierney et al. described mitral valve replacement in 118 children ≤5 years. The valve was placed in the supraannular position in 32%, and survival was 74% at 1 year. Risk factors for worse survival included age <1 year, presence of an atrioventricular canal defect, and additional procedure coincident with valve replacement [25]. Given the challenges associated with both repair and replacement in young children, use of stented bovine jugular venous valve (Melody valve, Medtronic, Minneapolis, Minnesota) has been employed in this population. Quinonez et al. described 11 patients with median age of 7 months who underwent surgical placement of the Melody valve in the mitral position. This valve can be serially dilated percutaneously as the child grows, a significant potential advantage of this technique [26]. The use of a pulmonary autograft (Ross II technique) in the mitral position has been described in a limited number of patients. This technique can be attractive in women who are interested in having children and in those who have failed previous mechanical valve placement due to thrombotic complications [27]. In patients with severe HF associated with MR who fail surgical intervention, cardiac transplantation can be considered, and mechanical support using ECMO or a VAD could be considered as a bridge to transplantation.
PULMONARY REGURGITATION AND HEART FAILURE Etiology In children and adolescents, isolated congenital pulmonary regurgitation (PR) is rare and PR most often results following surgical repair of conotruncal congenital heart lesions. Most commonly, patients with tetralogy of Fallot (TOF) develop chronic PR after transannular patch augmentation of the right ventricular outflow tract during TOF repair. Even patients who undergo a valve-sparing operation may develop significant PR [28]. Other lesions such as TOF with pulmonary atresia, TOF with associated coronary anomaly, or truncus arteriosus may require placement of a right ventricle to pulmonary artery conduit, which typically develops regurgitation. Patients undergoing Ross operation for aortic stenosis and/or regurgitation will also receive a conduit. Additionally, patients who undergo transcatheter pulmonary valvuloplasty can develop PR [29]. Acquired causes of PR such as endocarditis are uncommon.
Pathophysiology The degree of PR is determined by the regurgitant orifice area, right ventricular compliance, the capacitance of the pulmonary arteries, and duration of diastole. Unlike AR, the diastolic pressure difference between the main pulmonary artery and right ventricle is typically small and, thus, is not a major determinant of the degree of PR. In the case of repaired TOF, the regurgitant orifice is often large immediately after surgery. However, the impact of PR is typically small because the right ventricle is hypertrophied and noncompliant, and the heart rate is fast with shortened diastole. Over time, right ventricular compliance improves. The stroke volume of the ventricle also increases due to ongoing PR and ventricular dilation. Likewise, the heart rate slows with age, increasing length of diastole. These factors encourage a gradual increase in the degree of PR [30]. Significant PR will lead to progressive right ventricular dilation, with similar pathophysiology of left ventricular enlargement due to AR. Initially, as the ventricle dilates, compensatory hypertrophy will occur to maintain a normal mass– volume relationship. However, eventually compensatory hypertrophy will be unable to keep pace with dilation; irreversible myocardial injury can occur with resultant decreased systolic function. Fig. 22.3 depicts the pathophysiology of chronic PR after TOF repair. Also, because the right and left ventricles share myofibers, the interventricular septum, and the pericardial space, right ventricular dilation can negatively influence left ventricular systolic and diastolic function [30,31].
Presentation and Evaluation Children with chronic, severe PR are initially asymptomatic, often for 10–15 years. With progressive RV dilation and eventual systolic dysfunction, symptoms eventually occur and include exercise intolerance and arrhythmias. Negative ventricular–ventricular interaction can occur and cause left ventricular dysfunction and symptoms of left-sided HF including pulmonary edema [30]. Physical exam will show a soft diastolic, decrescendo murmur at left upper sternal border. There may also be a systolic ejection murmur at the same location due to increased right ventricular stroke volume and flow across the pulmonary valve. If right ventricular dilation is present, parasternal lift may be present.
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FIGURE 22.3 Diagram illustrating the pathophysiology of pulmonary regurgitation after tetralogy of Fallot (TOF) repair. PA, pulmonary artery; RV, right ventricle. (Adapted from Geva, et al., Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support. J. Cardiovasc. Magn. Reson. (2011) 13.)
TOF Repair
Pulmonary regurgitation
PA dilation ( capacitance)
PA pulse pressure/volume
RV dilatation
RV compliance
Pulmonary regurgitation
Echocardiography is used to characterize pulmonary valve structure and function and describe the degree of PR. In those with severe PR, the regurgitant color jet fills the right ventricular outflow tract, there is reversal of flow in the branch pulmonary arteries, and there is septal flattening during diastole [6]. However, cardiac MRI is often used to characterize the degree of PR and quantify biventricular size and systolic function. Moderate PR is considered a regurgitant fraction >25% [30]. In fact, MRI results can be very useful in risk stratification of those with repaired TOF and can provide values that are important in clinical decision-making [30,32]. Patients with indexed right ventricular end-diastolic volume >150–170 cc/ m2 may not experience normalization of right ventricular size after valve restoration [33–35]. Serum BNP can also be a useful adjunct to imaging in those with chronic PR. In those with PR related to TOF repair, BNP has been associated with NYHA functional class, right ventricular size, and severity of PR [32].
Treatment Medical There are limited data regarding medical therapy for patients with chronic PR and its associated deleterious effects on the right ventricle. The APPROPRIATE study randomized patients with repaired TOF and moderate–severe PR to Ramipril versus placebo. Most patients were asymptomatic, and there was no improvement in right ventricular ejection fraction or right ventricular end-diastolic volume at 6 months [36]. Norozi et al. randomized young adults with repaired TOF and NYHA Class one to two symptoms to bisoprolol versus placebo for 6 months and found no benefit on right ventricular ejection fraction or volume [37]. In patients with significant right-sided HF associated with lower extremity edema and/or ascites, diuretic therapy may offer some short-term symptomatic relief.
Invasive For patients with HF associated with severe PR, restoration of pulmonary valve competency is the standard of care. This can be accomplished with surgical and transcatheter techniques. Both surgical and transcatheter pulmonary valve replacement have been shown to decrease the degree of PR and right ventricular size and significantly improve HF-associated symptoms [30,38]. While right ventricular size improves including both end-diastolic and end-systolic volumes, right ventricular ejection fraction typically does not change after valve restoration [30]. There are numerous series describing the safety and efficacy of surgical pulmonary valve replacement using bioprosthetic valves, valved conduits, and homografts [11,39]. The procedure is safe with a low rate of major complication and/or early reintervention [39]. Alternatively, some patients are candidates for transcatheter pulmonary valve replacement. The Melody valve (Medtronic Inc., Minneapolis, Minnesota) is available for transcatheter pulmonary valve replacement under a Humanitarian Device Exemption in patients with a right ventricular outflow tract conduit (Fig. 22.4). Thus, patients who have undergone surgical right ventricular outflow tract palliation with homograft conduit, valved conduit, or even bioprosthetic
Valvular Insufficiency and Heart Failure Chapter | 22 303
(A)
(B)
FIGURE 22.4 Anteroposterior (A) and lateral (B) views of angiogram performed in distal right ventricle to pulmonary artery conduit in a 30-year-old female with repaired tetralogy of Fallot and pulmonary atresia after placement of a Melody valve in the conduit to treat severe pulmonary regurgitation. In both projections, there is no regurgitation of contrast into the right ventricle after Melody placement. Will get angio after Melody.
valve can be good candidates for percutaneous Melody valve implantation [38,40]. Patients with a native outflow tract that has not significantly dilated can also be candidates for off-label Melody valve use after outflow tract stenting [41,42]. The Sapien transcatheter valve (Edwards Lifesciences LLC, Irvine, California) has also been used in the pulmonary position and can be used in larger conduits or outflow tracts than the Melody valve, but it is only currently available in the United States as part of an investigational device exemption trial. Similar to surgical pulmonary valve replacement, Melody and Sapien valve implantation is associated with low rate of major complications and good short- and midterm success [43,44].
TRICUSPID REGURGITATION AND HEART FAILURE Etiology The most common cause of significant tricuspid regurgitation (TR) in children is Ebstein’s anomaly of the tricuspid valve. In this condition, the septal and posterior leaflets fail to delaminate during development and are adherent to the right ventricular myocardium, resulting in apical displacement of the functional tricuspid valve annulus. The anterior leaflet is redundant and “sail-like.” Significant TR can result due to abnormal leaflet coaptation [45]. Fig. 22.5 depicts a patient with significant Ebstein’s anomaly. Other patients may be born with a dysplastic tricuspid valve that does not meet criteria for Ebstein’s anomaly and may also have TR. Acquired causes such as endocarditis are rare.
Pathophysiology Neonates with severe Ebstein’s anomaly may be cyanotic due to right to left shunting at the atrial level with inadequate antegrade pulmonary blood flow due to severe TR. In other patients, ongoing severe TR will lead to right atrial and ventricular dilation. As with severe PR, eventually right ventricular systolic function can become compromised. The combination of TR and right ventricular dysfunction can limit cardiac output, especially with exercise and can lead to symptoms of right HF. Also, as the right ventricle dilates, so does the tricuspid valve annulus, leading to further TR. Right to left shunting may exist at the atrial level causing cyanosis with exertion.
Presentation and Evaluation Infants with severe Ebstein’s anomaly are symptomatic immediately. These patients may have inadequate pulmonary blood flow due to severe TR and elevated pulmonary vascular resistance and even may have “functional” pulmonary atresia requiring prostaglandin infusion. Management of these patients is complex, and a full description is beyond the scope of this chapter
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FIGURE 22.5 Transthoracic echocardiogram in the apical view showing severe tricuspid regurgitation in a 3-year-old with Ebstein’s anomaly of the tricuspid valve. RA, right atrium; RV, right ventricle; TR, tricuspid regurgitation; TV, tricuspid valve.
[46]. Older children and adolescents may develop symptoms from ongoing TR and resultant right atrial and ventricular dilation. These patients will exhibit symptoms of right-sided HF with exercise intolerance, lower extremity edema, and/or ascites. Also, given the chamber dilation and possible presence of preexcitation, arrhythmias often occur and lead to symptoms. Physical exam often reveals a low frequency holosystolic murmur at the left lower sternal border. Because right ventricular volume is increased, a systolic ejection murmur may be present at the left sternal border due to increased flow across the pulmonary valve. The second heart sound may be normal or widely split if there is significantly increased flow across pulmonary valve. In terms of evaluation, echocardiogram is the gold standard for characterizing tricuspid valve anatomy and function as well as describing the degree of TR. In those with Ebstein’s anomaly or dysplastic tricuspid valve, cardiac MRI is rarely needed [45].
Treatment Medical Patients who have significant HF associated with TR can have some symptomatic benefit from diuretics, especially if edema and ascites are present. ACE inhibitors have not been significantly investigated in those with HF associated with TR.
Invasive Surgery is indicated in those who have symptoms associated with severe TR, in those with significant cyanosis due to atrial level shunting, or in those with significant burden of atrial arrhythmias [6,45]. The nature of the surgery depends on age and size of the patient as well as tricuspid valve anatomy. Typically, tricuspid valve repair is attempted prior to valve replacement with a bioprosthetic valve. For those with Ebstein’s anomaly, tricuspid valve annuloplasty, plication of the atrialized portion of the right ventricle and right atrial reduction are often performed, although additional repair options exist including cone reconstruction [47–50]. Hetzer et al. described outcomes after tricuspid valve repair in 67 patients with Ebstein’s anomaly. The mean NYHA class improved from 3.4 to 1.3 (P < .001), and freedom from reoperation was 98% at 5 years [48]. Dearani et al. reported the Mayo Clinic’s experience with cone reconstruction in 89 patients. The series described 1 death and, at last follow-up, 87% had no or mild TR [50]. Also, patients who have only mild-moderate TR, but have significant cyanosis at rest or with exercise, can receive benefit from transcatheter closure of interatrial communication [51].
CONCLUSION Valvular insufficiency can be an important cause of HF in young children and adolescents. In these patients, insufficiency most often results from congenital valve anomalies, but postoperative regurgitation can also occur following congenital cardiac surgery. Medical therapy is typically ineffective, and surgical or transcatheter valve replacement techniques are typically the treatment of choice for pediatric patients with symptoms of HF associated with any regurgitant valve lesion.
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