Surgical Management of the Failing Systemic Ventricle

Chapter 48

Surgical Management of the Failing Systemic Ventricle Jack Wallen1, James S. Tweddell1,2 1Cincinnati

Children’s Hospital Medical Center, Cincinnati, OH, United States; 2University of Cincinnati, Cincinnati, OH, United States

INTRODUCTION Heart failure (HF) is a complex physiologic phenomenon that, prior to the modern era, was poorly understood despite being widely recognized. The typical symptoms of dyspnea, cachexia, and edema were known in antiquity and were a portent of death. Today, it is recognized as a progressive clinical syndrome with a variety of etiologies and pathophysiologies and is becoming better understood at a molecular level. Compared to older patients, HF in children and young adults not only includes many of the same diagnoses but also the sequelae of complex congenital heart disease. Many of these are rare conditions and defy a simple classification system. All of congenital heart surgery may be considered as treatment for or prevention of HF. In this chapter, we will focus on emerging surgical strategies for the systemic right ventricle, the failing Fontan, and the borderline left ventricle.

THE SYSTEMIC RIGHT VENTRICLE The right ventricle is the systemic or subaortic ventricle among patients with congenitally corrected transposition of the great vessels (discordant connections at both the atrioventricular and ventriculoarterial junctions) and among patients who have undergone atrial level correction of transposition of the great vessels (ventriculoarterial discordance). Conditions in which the right ventricle serves as the systemic pumping chamber are commonly complicated by the development of right ventricular failure and tricuspid valve regurgitation. The left ventricle is a highly preserved in vertebrate evolution and is well suited for the prolonged pressure work of the systemic circulation. The right ventricle is a more recent evolutionary adaptation of the bulbus cordis and is better suited to serve as a low pressure, volume pump [1]. The anatomic differences between the left and right ventricles have been summarized by Van Praagh and colleagues (Table 48.1) [2]. The right ventricle differs from the left ventricle in both anatomy and geometry. Whereas the LV has three layers of myofibrils, the RV has only two [3]. The compact myocardium (stratum compactum) of the left ventricle is much thicker in relation to the spongy myocardium (stratum spongiosum) in the right ventricle. The atrioventricular valves have important differences. There are two papillary muscles attaching the mitral valve chords to the left ventricle free wall without attachment to the septum. In contrast, the papillary muscles of the right ventricle are multiple and small with both septal and free wall attachments. The attachments of the tricuspid valve to both the septum and free wall may predispose the tricuspid valve to the development of regurgitation with right ventricular dilatation. Indeed, tricuspid regurgitation and failure of the systemic right ventricle occur together [4–6]. The overall frequency of HF in a cohort of 188 adult patients with systemic right ventricles or single ventricle was 32% [7]. Interestingly, when analyzed according to anatomy, the frequencies were 22% in patients with TGA palliated with a Mustard operation, 32.3% for patients with ccTGA, and 40% for patients with a Fontan procedure. Mortality among symptomatic patients was 47.1% versus 5% among asymptomatic patients. Norozi et al. also found a higher incidence of HF in patients with TGA and atrial correction (30.8%) and single ventricle (47.1%) [8]. Placing the RV in the subaortic position increases the risk of systolic ventricular dysfunction. Survival to adulthood for patients with a systemic right ventricle is about 80% with similar survival between those ccTGA and those after the atrial level switch operation for D-TGA [9]. Medical therapy generally mirrors that of treatment of acquired HF with little evidence of success [3]. Surgical strategies may be directed at the tricuspid valve, pulmonary artery banding including retraining of the left ventricle and resynchronization therapy. Heart Failure in the Child and Young Adult. http://dx.doi.org/10.1016/B978-0-12-802393-8.00048-X Copyright © 2018 Elsevier Inc. All rights reserved.

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TABLE 48.1  Characteristic

Left Ventricle

Right Ventricle

Cavity

Cylindric

Crescentic

Contraction patter

Concentric

Bellows-like

Inlet and outlet valves

Close proximity

Distant

Coronary artery supply

Two coronary arteries

One coronary artery

Developmental origin

Primitive ventricle

Bulbus cordis

Atrioventricular valve

Closure for circular orifice

Closure for crescentic orifice

Papillary muscles

Two large papillary muscles

Multiple small papillary muscles

FIGURE 48.1  Survival after tricuspid valve replacement among patients with congenitally corrected transposition stratified by preoperative systemic right ventricular ejection fraction (EF). Poor systemic right ventricular EF was a risk factor for mortality. Reproduced with permission from: F.P. Mongeon, H.M. Connolly, J.A. Dearani, Z. Li, C.A. Warnes, Congenitally corrected transposition of the great arteries ventricular function at the time of systemic atrioventricular valve replacement predicts long-term ventricular function, J. Am. Coll. Cardiol. 57 (20) (2011) 2008–2017.

Tricuspid Valve Surgery Tricuspid valve regurgitation results in excess volume loading of the systemic right ventricular dysfunction and accelerates development of dysfunction. Surgery directed at the TV should eliminate excess volume loading and stabilize RV function and therefore improve long-term outcome [10]. Tricuspid repair for the patient with a systemic RV is technically difficult. The intermediate outcomes are unsatisfactory and fail to achieve long-term tricuspid valve competence [11]. Therefore tricuspid valve replacement is recommended over repair. Significant RV dysfunction (ejection fraction (EF) <40%) at the time of tricuspid valve replacement is an important risk factor for survival and persistent dysfunction and TV replacement should be considered before RV dysfunction develops (Fig. 48.1) [12].

Pulmonary Artery Banding for the Failing Systemic Right Ventricle Pulmonary artery banding may be used in the traditional way in neonates and infants with ccTGA and D-TGA with a ventricular septal defect (VSD) for relief of congestive HF and prevention of pulmonary artery hypertension in advance of definitive repair. It is also applied to children, teenagers, and adults with systemic right ventricles without a significant VSD to improve tricuspid valve function and retrain the left ventricle. The technique was initially pioneered in hopes of retraining the left ventricle in anticipation of anatomic repair, but it became apparent that by increasing afterload to the morphologic LV, the interventricular septum is shifted toward the RV and results in better coaptation of the tricuspid valve. The pulmonary artery band applies afterload to the morphologic left ventricle and care must be taken to avoid inducing pulmonary ventricular failure, including close monitoring of hemodynamics and intraoperative echo while the band is applied [1,13].

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The pressure in the morphologic LV is raised to 50%–75% of systemic pressure while monitoring the central venous pressure and mitral valve by echo. Elevation of central venous pressure or the development of mitral regurgitation would suggest the band is too tight and should be loosened. Some groups have experimented with dilatable PABs that would allow for catheter dilatation to allow the band to be loosened as patients grow. The results with anatomic repair following left ventricular retraining are mixed and patients who have undergone retraining are at increased risk of mortality [14]. Different techniques of retraining have been suggested without an obviously superior method [13,15]. Older age, greater than 12 years, appears to be an important factor predicting the inability to retrain the LV and achieve a durable anatomic repair. Reports have shown that maintenance of the pulmonary artery banding resulted in sustained improvement in RV function and tricuspid regurgitation [16,17]. These data suggest that banding alone may be a reasonable end point, particularly for the patient >12 years of age for whom banding has resulted in improvement in TR and stabilization of RV function.

Cardiac Resynchronization Therapy Cardiac resynchronization therapy (CRT) is well established as an effective treatment for adults with symptomatic morphologic left ventricular failure that is refractory to medical therapy [18]. The efficacy of CRT in CHD patients with HF is less clear [19–21]. Despite these differences, there are reports of reductions in QRS duration of 19%–24%, increases in LVEF of 26%–52%, and improved New York Heart Association (NYHA) functional classification in children with failing morphologic LV [22–24]. The proportion of nonresponders in these studies ranged from 12% to 16%, which is generally lower than that reported in studies in adults. As anticipated the response to CRT in CHD patients is dependent on systemic ventricular morphology. In a retrospective analysis of 20 patients with QRS duration >130 ms who underwent CRT, responses were compared in three groups: systemic LV, systemic RV, and biventricular repairs [25]. Overall, systemic ventricular end-diastolic volume index (EDVI), plasma B-type natriuretic peptide levels, and NYHA class improved with CRT by 6 months following device implantation. However, although QRS duration was significantly reduced in all three morphologic groups, no improvement in EDVI or ventricular EF was seen in those with a systemic RV. Other groups have also shown a reduced response to CRT in patients with systemic RV compared with systemic LV [23,24,26]. Dubin et al. found that CRT was associated with a 13% increase in EF in 14 of 17 patients with systemic RVs, which is comparable to the (nonsignificant) 14% increase seen by Sakaguchi and colleagues [22,25]. All these studies suffer the limitations of small size and retrospective analysis. Recommendations for optimal placement of CRT pacing leads in systemic RV patients have recently been made [27]. The reason(s) for the diminished benefit of CRT in CHD patients with systemic RV are unclear but may be related to generally older age in the patients with systemic RV at the time of device implantation. Furthermore, alterations in the pattern of ventricular contraction in the systemic RV compared with the normal RV have been found, suggesting an adaptive change in contractile elements to the systemic load [28].

THE FAILING FONTAN Since the original description of the procedure in 1971, surgical creation of a Fontan circulation has undergone several modifications. Originally described for the repair of tricuspid atresia, The Fontan operation involved the creation of an atriopulmonary (AP) connection by isolating the right atrial chamber by closing the atrial septal defect and the tricuspid valve. It became evident that the atrium did not become “ventricularized” and serve as a pumping chamber following this operation. Since this initial description, two major surgical modifications have been introduced; the lateral tunnel technique and the extracardiac conduit (Fig. 48.2). These modifications are based on the hydrodynamic studies of deLeval that showed that greater efficiency and the lowest energy loss was achieved with a Fontan circuit of uniform caliber with minimal acute angles [29]. Significantly better 15-year survival following lateral tunnel (94%) versus classic Fontan (81%) procedures has been reported [30]. More recent analysis of registry data of 1006 patients who underwent a Fontan procedure showed Kaplan–Meier estimates of survival at 15, 20, and 25 years were 93%, 90%, and 83%, respectively [31]. Pundi et al. recently published follow-up data of 1052 patients who underwent a Fontan operation at the Mayo Clinic between 1973 and 2012 [32]. Overall 10-, 20-, and 30-year survival was 74%, 61%, and 43%, respectively. This represents remarkable progress compared with the 26% 1-year mortality reported in the first generation of tricuspid atresia patients undergoing this procedure [33]. When survival data were broken down by type of Fontan procedure performed (AP connection, lateral tunnel, extracardiac conduit), a significant benefit was seen in those patients receiving an extracardiac conduit (Fig. 48.3) [32]. The original selection criteria for a Fontan procedure in patients with tricuspid atresia were defined by Choussat and Fontan and became known as the “10 commandments” (Table 48.2) [34]. Current selection criteria include competent,

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FIGURE 48.2  Types of Fontan procedures. (A) Atriopulmonary connection, (B) lateral tunnel, (C) extracardiac conduit. Reproduced with permission from: Y. d’Udekem, A.J. Iyengar, A.D. Cochrane, et al., The Fontan procedure: contemporary techniques have improved long-term outcomes, Circulation 116 (11 Suppl.) (2007) I157–I164. FIGURE 48.3  Survival by Fontan procedure performed. Reproduced with permission from: K.N. Pundi, J.N. Johnson, J.A. Dearani, et al., 40-Year follow-up after the Fontan operation: long-term outcomes of 1,052 patients, J. Am. Coll. Cardiol. 66 (15) (2015) 1700–1710.

TABLE 48.2  “10 Commandments” for Fontan Suitability Age > 4 years Sinus rhythm Normal systemic venous return Normal right atrial volume Low mean pulmonary artery pressure (≤15 mmHg) Pulmonary resistance <4 WU/m2 Adequate pulmonary artery size (PA/Ao ratio > 0.75) Normal left-ventricular function (ejection fraction ≥60%) Competent mitral valve No distortion of pulmonary artery following BT shunt

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nonstenotic, or repairable AV valve; good ventricular function with unobstructed ventricular outflow; and a satisfactory pulmonary vascular bed; nonstenotic pulmonary arteries; normal pulmonary vascular resistance (PVR) (less than 2.5 WU/ m2) and unobstructed pulmonary venous return [35].

Fontan Physiology The goal of the Fontan circulation is to provide adequate pulmonary blood flow and systemic ventricular preload, despite bypass of the subpulmonary ventricle without a significant elevation in venous pressures. By separating the systemic and pulmonary venous circulations, cyanosis is relieved and ventricular volume load is reduced. Complications are related to elevations in venous pressure, venous congestion, and reduced cardiac output. These complications can manifest as Early and late mortality Exercise intolerance l Cardiomegaly l Ventricular dysfunction/HF l Rhythm/conduction disturbances l Hepatomegaly l Protein-losing enteropathy (PLE) l Plastic bronchitis l Venous thrombi/thromboembolism l Ascites l Peripheral edema l l

Exercise capacity in Fontan patients, measured by peak oxygen consumption (VO2) at a mean age of 14 years, is reduced to 65% of that predicted for age and gender [36]. With increasing age through adolescence and into adulthood, exercise capacity will fall even farther, by approximately 2.6% per year [37]. A fall in peak VO2 to approximately 50% predicted correlates with the development of symptoms of HF in adult congenital heart patients, implying that Fontan patients can expect to reach this critical value in their 20s [38].

The Failing Fontan The benefits of palliating patients with a Fontan procedure are well established. Despite the impressive survival outcomes reported during long-term follow-up, at its core the Fontan circulation is hemodynamically imperfect. While cyanosis is eliminated by redirecting systemic venous return directly to the pulmonary circulation, without the benefit of a prepulmonary ventricle, this passive flow leads to greatly elevated central venous pressures, in the region of 10–15 mmHg. This passive flow also results in a restricted return to the systemic ventricle, dramatically reducing preload. This is associated with a reduced cardiac output in Fontan patients compared with patients with two functional ventricles [39]. Preload is determined by transpulmonary flow, which in turn is determined by the transpulmonary gradient and PVR. TPG = mean PA pressure − LA pressure



PVR = 80 × TPG CO



PVR is expressed in Wood units (1WU = 1 mmHg min/L = 80 dyne s/cm5); CO, cardiac output. Numerous lines of evidence support the idea that PVR is the major determinant of cardiac output in Fontan patients. For example, negative pressure ventilation increased cardiac index by approximately 40% compared with positive pressure ventilation in Fontan patients [40]. Fenestration of the Fontan conduit, allowing a fraction of the venous return to bypass the pulmonary vascular bend particularly when PVR may be elevated, significantly improved CO [41,42].

Long-Term Sequelae of Fontan Circulation The palliative, rather than curative, nature of the Fontan operation has long been recognized [43]. Fontan palliation has been a significant surgical success since its inception, with excellent survival in the modern era. Nevertheless, long-term consequences are well recognized and represent a significant source of hospitalization. Regular follow-up with a team experienced in the care of complex CHD, specifically single-ventricle physiology, is mandatory, particularly for potentially

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reversible causes of Fontan failure. The American Heart Association recommends that the Fontan patient should be evaluated for the following [44]: Ventricular dysfunction Arrhythmias l Fontan pathway thrombus l Inflow/outflow obstruction l PLE l Valve dysfunction l Residual right-to-left shunts l Elevated systemic vascular resistance l Elevated systemic venous pressure l Plastic bronchitis l l

An in-depth discussion of the medical management of these patients is beyond the scope of this chapter but may involve ACE inhibitors, β-blockers, diuretics, and digoxin. Currently, there are no guidelines that specifically address the problem of HF in patients with CHD, and the efficacy of standard HF management strategies in these select patients is unknown. As stated recently by the American Heart association “…extrapolation from HF data and guidelines in adult acquired heart disease requires that we assume that the mechanisms, surrogate end points, and responses to therapy are sufficiently similar in CHD, which may not be the case” [44].

Treatment of Late Complications Following Single Ventricle Palliation Protein-Losing Enteropathy Enteric loss of serum proteins, including albumin, immunoglobulins, and clotting factors, is characteristic of PLE. The resultant hypoproteinemia leads to peripheral edema, ascites, pleural effusions, diarrhea, malabsorption, and cachexia. First reported in a 7-year-old patient 1-year after Fontan operation, the incidence of PLE ranges from 3.7% to 15% [45–48]. Risk factors for PLE include non-LV anatomy for single ventricles, prolonged hospital stay, postoperative renal failure, and prolonged cardiopulmonary bypass times [47,49]. Historically, PLE has been a much feared complication, with a median survival following diagnosis of 5 years [32,46]. However, analysis of a cohort of 42 Fontan patients with PLE operated in the current era (1992–2010) found survival rates of 88% and 72% at 5 and 10 years, respectively [50]. Aggressive surgical and interventional management of these patients may account for the improved survival following diagnosis. PLE is an independent predictor of death associated with HF in these patients [51]. Factors associated with worse outcome following a diagnosis of PLE include elevated Fontan pressures (>15 mmHg), NYHA class > II, elevated PVR and elevated serum creatinine, EF <55%, low cardiac index, and low mixed venous saturations. Symptoms of PLE develop when the intestinal loss of proteins exceeds the synthetic capacity of the patient. A multifactorial mechanism for PLE has been proposed: Fontan physiology results in a chronic state of reduced cardiac index, with an increase in mesenteric vascular resistance and venous congestion and resultant diminished perfusion. This, coupled with the chronic inflammatory state seen in patients with HF, results in the release of proinflammatory mediators (including TNF-α), which activates matrix-metalloprotienases leading to the removal of membrane proteins, including the glycosaminoglycan heparan sulfate [52,53]. This alters the membrane integrity of enterocytes and leads to intestinal protein leak. Interestingly, a possible genetic predisposition to developing PLE has been observed [53]. Medical management of PLE should focus on dietary modifications, the management of HF, and relief of symptoms [50,54,55]. Diets should be sodium restricted, low-fat, high protein, and high medium-triglycerides. Periodic supplementation with intravenous albumin may be required for severe protein loss. Medical management alone of Fontan patients with PLE resulted in symptomatic improvement in 47% [50]. Virtually all patients should receive treatment for edema using diuretics. Angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, corticosteroids, and the entericspecific steroid budesonide are also useful. Pulmonary vasodilators such as sildenafil and bosentan have also been effective. Octreotide is a somatostatin analogue shown to reduce lymphatic flow and has been used successfully to treat PLE in a small case series (n = 3) of Fontan patients [56]. Subcutaneous unfractionated heparin has been investigated for symptomatic improvement and elevation in serum protein [57,58].

Arrhythmias Late arrhythmias have been documented in 11%–52% of Fontan patients [48,59–63]. Arrhythmias are a significant contributor to morbidity. Atrial tachyarrhythmias predominate, with intraatrial reentrant tachycardia (IART) the most

Surgical Management of the Failing Systemic Ventricle Chapter | 48  645

frequent, occurring in up to 40% of Fontan patients by 25 years [64]. IART refers to any macro reentrant atrial arrhythmia, including typical atrial flutter. The management of these arrhythmias is difficult and may involve catheter ablation, a surgical maze procedure, and device therapy [65]. The etiology of these arrhythmias is likely multifactorial, involving sinus node dysfunction, the presence of atrial suture lines, and elevated atrial pressures in the Fontan circulation. These factors may be mitigated in patients who received an extracardiac conduit procedure, which reduces the number of atrial suture lines and lowers atrial pressures compared with the lateral tunnel procedure. However, in a recent multicenter retrospective cohort study of 1271 of patients who underwent a Fontan procedure (669 extracardiac, 602 lateral tunnel), no difference was found in the incidence of late (>30 days) arrhythmia [66]. There was a higher incidence of early (<30 days) bradyarrhythmias in the extracardiac (11%) versus lateral tunnel (4%) groups. Apart from surgical issues, underlying conduction abnormalities, primarily macroreentrant, and AV nodal reentry have been identified as potential mechanisms for these tachyarrhythmias [67]. A number of risk factors for the development of supraventricular tachycardia have been identified in these patients, including AP Fontan, low functional status, sinus node dysfunction, and nonsustained atrial tachycardia [64,68–70]. Interestingly, the risk of developing IART after the Fontan procedure is biphasic, with increased risk in the first 2 years following the procedure, followed by a decline from years 4 to 6, then rising steadily [68]. Medical management should be the first line of therapy for patients with arrhythmias. Radiofrequency ablation has been used to treat these patients, with complete or partial procedural success in 87.5% [67]. Of these, 50% eventually had recurrence of their arrhythmia within 18 months of the ablation. Others have observed similar high rates of recurrence following ablation in Fontan patients [71,72]. Patients with atrial tachyarrhythmias reported symptoms including palpitations (62%), fatigue (44%), dyspnea (23%), edema (21%), presyncope (21%), and syncope (3%) [69]. These patients were also more likely to have HF and atrial thrombus.

Surgical Management of the Failing Fontan The term “Failing Fontan” refers to the clinical scenario that includes rhythm disturbances, constitutional effects (exercise intolerance, growth failure), thrombosis in the Fontan circuit, cirrhosis, ascites, PLE, plastic bronchitis, and ventricular failure. Systemic ventricular failure occurs in up to 40% of adult Fontan patients [7]. There are three widely accepted surgical options for management of this condition: Fontan takedown, Fontan conversion, and cardiac transplantation. Mechanical circulatory support for the failing Fontan is also an option, whether in the form of ECMO or VAD support [73]. This topic is discussed in detail elsewhere in this textbook.

Fontan Takedown Catastrophic acute failure of the Fontan circulation requiring takedown is a rare event in the current era [30,74,75]. Referred to as early Fontan failure, this involves a postoperative state characterized by systemic malperfusion, elevated Fontan circuit pressures, and large volume requirements, which is unresponsive to inotropic support and carries a high risk for mortality. When recognized, rescue options include either ECMO support or surgical Fontan takedown to an intermediate palliative circulatory state (systemic-pulmonary arterial shunt and bidirectional Glenn). High mortality rates have been reported following Fontan takedown. The Boston group reported on 53 patients who underwent Fontan takedown from 1979 to 2006 of whom 43 underwent takedown within 1 month of Fontan creation [76]. The most common indications for takedown were high PVR leading to elevated Fontan pressure/low cardiac output, PA obstruction/hypoplasia, and persistent pleural or pericardial effusions or ascites. Early (<30 day) mortality among the 53 patients was 45%. Other risk factors for early death following Fontan takedown included circulation other than bidirectional Glenn prior to Fontan creation, AP connection, fenestrated Fontan, and systemic RV. Of the survivors, 66% ultimately underwent recreation of the Fontan circulation at a median 4.6 years (range, 0.6–13.1 years) after takedown. Three quarters of patients who received a redo Fontan had medical or technical factors that likely contributed to their initial Fontan failure, most commonly PA stenosis or discontinuity. Three patients underwent cardiac transplantation for persistent ventricular dysfunction. In a small series of 14 patients that underwent Fontan takedown between 1980 and 2007 at Royal Children’s Hospital, Melbourne, hospital mortality was 36% [77]. Compared with the overall cohort of Fontan patients, those who underwent takedown had pre-Fontan PA pressures that were 14% higher (13.8 vs. 12.1 mmHg). There were no late deaths or cardiac transplants, and only two survivors later underwent ECC Fontan creation. Overall, these studies suggest that Fontan takedown in cases of early failure is a rare event that is associated with significant risk despite surgical intervention. However, Fontan takedown does serve to stabilize the circulation of a certain group of patients and does not preclude the possibility of future recreation of a Fontan circulation, particularly in patients with readily correctible factors that contributed to early Fontan failure.

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Fontan Conversion An AP anastomosis is associated with late complications including atrial dilation, thrombus, and arrhythmias, leading to reduced cardiac output and decreased quality of life. Development of the total cavopulmonary connection (lateral tunnel and extracardiac conduit Fontan) has superseded the classic technique. Laks and colleagues developed the Fontan conversion procedure and reported on the outcome of three patients with AP Fontan with atrial tachyarrhythmias unresponsive to medical therapy who were surgically converted to a lateral tunnel Fontan circulation [78]. This operation resulted in marked clinical improvement in a majority of patients [79,80]. Intraoperative electrophysiology mapping and cryoablation of arrhythmia circuits was added to Fontan conversion surgery [81]. While early reports of Fontan conversion had mixed results with some centers reporting mortality as high as 33% and high arrhythmia recurrence with refinement of indications and technique results have improved and current midterm results are encouraging. Several institutions report 5-year survival >90% and 10-year survival >80% [78,82–90]. It is evident that Fontan conversion is associated with acceptable risk and provides functional improvement in patients who undergo this procedure when combined with antiarrhythmia procedures [91,92]. Patient selection for Fontan conversion is crucial to optimizing outcome. The Mayo Clinic analyzed the outcomes of 70 patients who underwent conversion of AP Fontan from 1994 to 2011 and found a 14% mortality rate [93]. Multivariate analysis showed that only age greater than 27 years, male sex, lack of antiarrhythmia surgery, and AV valve regurgitation were predictive of death. Deal et al. found right ventricular morphology, ascites, PLE, prolonged CPB time, and biatrial arrhythmia operation to be independent risk factors for cardiac death or transplantation in their series of 140 Fontan conversions [90]. Cardiopulmonary exercise testing has been shown to be predictive of perioperative survival following Fontan conversion, with baseline peak VO2 less than 14 mL/kg/min an independent predictor of death, along with male sex, age greater than 25, and AV valve regurgitation [94]. Van Melle et al. reported the outcome of 225 failing Fontan patients who underwent either takedown (n = 38), conversion (n = 137), or transplantation (n = 50) surgery at 22 European centers [95]. Kaplan–Meier survival estimates showed no difference between transplant and conversion patients (P = .13) but decreased ventricular function was an independent risk factor for poor outcome in the conversion group. These findings suggest that Fontan conversion is most likely to be successful in patients with preserved single ventricle function and that delaying Fontan conversion surgery until the onset of organ dysfunction is detrimental to the outcome.

Cardiac Resynchronization Therapy CRT was discussed earlier as a surgical treatment for the failing systemic right ventricle and is well established as an effective treatment for adults with symptomatic HF that is refractory to medical therapy, who have both left ventricular dysfunction and dyssynchrony secondary to left bundle-branch block (LBBB). CRT is recommended for patients with systolic dysfunction (LVEF ≤35%), sinus rhythm, LBBB pattern with QRS duration ≥150 ms, and NYHA class II, III, or ambulatory IV symptoms on guideline directed medical therapy [18]. CRT is not recommended for patients with no or minimal symptoms and non-LBBB pattern with QRS duration <150 ms or for those in whom survival of less than 1 year is expected. The efficacy of CRT in CHD patients with HF is less clear, due to the variety of cardiomyopathies found in the pediatric population (e.g., associated with CHD, noncompaction, muscular dystrophy, etc.) and because the incidence of LBBB pattern in these patients is rare [19–21]. Despite these differences, studies of the effects of CRT in children have reported significant reductions in QRS duration of 19%–24%, increases in LVEF of 26%–52%, and improved NYHA functional classification [22–24]. The proportion of nonresponders in these studies ranged from 12% to 16%, which is generally lower than that reported in studies in adults. High-quality studies identifying patients with congenital heart disease and HF who should receive CRT are not available, and the benefit of CRT among patients with a failed Fontan is isolated to case reports [96–99]. Nevertheless, single-ventricle dysfunction with a prolonged QRS duration would seem to be a reasonable indication for a trial of multisite pacing. The potential benefits must be balanced against the technical challenges in complex and fragile patients with multiple prior surgeries and abnormal native conduction pathways that make precise lead placement challenging.

Cardiac Transplantation for Failing Fontan Indications for OHT include patients with refractory severe HF who will not benefit from further medical or surgical intervention, and patients with normal ventricular function but with PLE or plastic bronchitis despite optimal medical/surgical therapy [73]. The International Society for Heart Lung Transplantation advised that congenital heart disease patients be listed for heart transplant if they have “…certain anatomic and physiologic conditions with or without associated ventricular dysfunction. These conditions may include… persistent protein-losing enteropathy and/or plastic bronchitis associated

Surgical Management of the Failing Systemic Ventricle Chapter | 48  647

with CHD despite optimal medical-surgical therapy…” [100,101]. Analysis of the UNOS database shows that the number of adults with CHD who undergo heart transplant has risen steadily over time [102]. The prevalence of heart transplant among adult patients with congenital heart disease has increased 41% since 1999 [103]. This patient population represents a unique challenge to the cardiac transplant team; patients have typically undergone prior cardiac surgeries (often multiple) and have been exposed to blood products resulting in the presence of human leukocyte antigen antibodies and a high PRA. These factors increase both the risk and complexity of transplant surgery, can affect the length of time on a transplant waiting list, and make the management of these patients afterward more difficult. Transplantation in the patient with a failing Fontan circulation is typically indicated for the presence of PLE, plastic bronchitis, and HF. Fontan patients are at greater risk for early and ongoing mortality following heart transplantation. The results of studies of outcome of transplantation for the Fontan procedure are summarized in Table 48.3 [104]. Early mortality in multiinstitutional studies is between 10% and 20%. This contrasts sharply with the 94.4% 30-day survival seen in two-ventricle patients undergoing cardiac transplantation for HF [105]. 1 and 5-year survival is lower in Fontan patients undergoing heart transplant compared with other CHD patients (non-Fontan 83% and 74% vs. 71% and 60% Fontan, respectively, P = .006) [106]. Compared with other CHD patients who received a transplant, the survival in Fontan patients is significantly worse (Fig. 48.4). A number of risk factors for mortality following transplantation have been identified. The most common cause of death in Fontan patients was infection (30%), followed by early graft failure (17%), and rejection (13%) [107]. Other factors that have been identified as risk factors for posttransplant mortality include early Fontan failure, PLE, Fontan obstruction, earlier era of transplant, renal failure, pretransplant ECMO, and pretransplant mechanical ventilation [108–111]. The presence of PLE combined with the use of posttransplant immunosuppression likely accounts for the finding that infection is a significant cause of postoperative death in this group of patients. There may be room for cautious optimism, Davies et al. retrospectively compared the outcomes of primary cardiac transplantation of 43 Fontan patients with 129 with other forms of CHD (TGA, tetralogy of Fallot, pulmonary atresia, pulmonary stenosis, tricuspid atresia, HLHS) [112]. The mean interval between the Fontan procedure and transplantation was 8.6 years (range, 6 days to 24.5 years). While earlier mortality was higher in the Fontan group late mortality was similar between the Fontan group and those with other forms of CHD, suggesting that if anatomic barriers, physiologic and immunologic challenges can be overcome the results of transplantation may be satisfactory. The benefits of cardiac TABLE 48.3  Outcomes Following Cardiac Transplantation in Failing Fontan Patients

Single-center

Multicenter

Author

N

Early Mortality

5-Year Survival

Davies et al. [112]

43

25%

58.7%

Backer et al. [110]

22

23%

66%

Jayakumar et al. [114]

24

38%

57%

Lamour et al. [125]

8

38%

60%

Petko et al. [126]

9

44%

50%a

Michielon et al. [105]

6

67%

68%

Bhama et al. [127]

5

60%

N/A

Kanter [113]

9

11%

70.8%

Mitchell et al. [128]

14

7%

N/A

Gamba et al. [129]

14

14%

77%

Bernstein et al. [107]

70

20% (6 months)

68%

Lamour et al. [106]

107

≈20%

60%

Kovach et al. [111]

194

≈13%

N/A

Michielon et al. [108]

61

18.3%

73%

Only those patients with failing Fontan physiology who underwent cardiac transplantation are included. aLate interval not specified. Modified from D.C. Mauchley, M.B. Mitchell, Transplantation in the fontan patient, Semin. Thorac. Cardiovasc. Surg. Pediatr. Card. Surg. Annu. 18 (1) (2015) 7–16.

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FIGURE 48.4  Posttransplant survival in Fontan versus non-Fontan CHD patients. Reproduced with permission from: J.M. Lamour, K.R. Kanter, D.C. Naftel, et al., The effect of age, diagnosis, and previous surgery in children and adults undergoing heart transplantation for congenital heart disease, J. Am. Coll. Cardiol. 54 (2) (2009) 160–165.

transplantation in patients with failing Fontan physiology can be dramatic. In those patients that survived the early posttransplant period, resolution of PLE was seen in more than 85% [107,110,113,114]. Michielon et al. showed that the greatest survival benefit of cardiac transplant occurred in patients with late (>2 years after Fontan procedure) failure and poor ventricular function, in whom the 5-year survival exceeded 90% [108].

THE BORDERLINE LEFT VENTRICLE The challenging long-term outlook for the individual palliated with a Fontan has been the motivation to test the boundaries of achieving a two-ventricle circulation among a subgroup of patients with small left-sided structures such as nonapex forming left ventricle with coarctation, Shone complex and right dominant unbalanced atrioventricular septal defect. In contrast to the patient with right heart hypoplasia such pulmonary atresia with intact septum where the decision concerning candidacy for a 2-ventricle repair is routinely deferred past the newborn period, for the patient with left heart hypoplasia, especially with arch hypoplasia with ductal-dependent systemic blood flow, neonatal palliation is necessary and incorrect choices concerning candidacy for two-ventricle repair are associated with increased mortality [115]. Decision-making can be challenging as the potential dimension of the left-sided structures is difficult to determine in the face of a volume loaded right ventricle [116–119]. Primary repair of infants with borderline LV undergoing endocardial fibroelastosis (EFE) resection has been reported [120]. The EFE results in diastolic dysfunction (Fig. 48.5). The results were excellent in this group of patients but it is noteworthy that the median follow-up is less than 3 years and the patients had mild LV hypoplasia suggesting that proper selection is important to success. Postnatal improvement in diastolic function and the potential for catch-up growth have motivated a strategy of staged biventricular conversion. A subset of patients with hypoplastic left heart structures who underwent single ventricle palliation may be eligible for later biventricular conversion and a potential improvement in long-term outcome. Risk factors for poor long-term outcomes following single-ventricle repair include genetic syndromes, tricuspid regurgitation, right ventricular dysfunction, and elevated PVR. Biventricular conversion involves takedown of the aortopulmonary anastomosis and reestablishing separate systemic and pulmonary circulations. This may require aortic arch reconstruction and a Rastelli-type baffle with a pulmonary artery conduit. Additional procedures may include aortic or mitral valve repair, closure of atrial septal defects, and resection of EFE. Determining which patients are suitable for biventricular conversion is complex. Several scoring systems have been developed to determine which neonates with borderline hypoplastic left heart structures are candidates for initial biventricular repair, but these do not apply to patients already palliated to a single ventricle physiology [121]. Factors that must be assessed in making the decision to pursue biventricular conversion following single-ventricle repair include the size and function of left-sided structures, typically based on echocardiography and cardiac MRI. The presence of a small mitral valve and/or EFE must be approached with caution but may possibly be addressed at the time of surgery. Preoperative cardiac catheterization is important to evaluate left atrial pressures, which will rise on establishing biventricular physiology. The optimal timing of conversion in suitable candidates is unclear. Boston Children’s Hospital retrospectively analyzed the outcome of biventricular conversion in 28 patients initially palliated with single-ventricle repair [122]. Reconstruction of the aorta involved direct anastomosis (with or without patch enlargement) or the Ross procedure, while right ventricular outflow was established using homograft conduits or direct anastomosis of the pulmonary artery. Caval reanastomosis to the right atrium was established. Median postoperative ICU stay was 18 days (range, 3 days to 2.9 years), and ECMO support was required in 11%. Median age at conversion was 42 months (range, 4–95 months) but tended to be younger in those with unbalanced complete atrioventricular canal defect

Surgical Management of the Failing Systemic Ventricle Chapter | 48  649

(A)

(B)

FIGURE 48.5  Endocardial fibroelastosis (EFE) results in diastolic dysfunction. MRI images depicting circumferential EFE before LV rehabilitation (A) and residual EFE along the interventricular septum on follow-up MRI (B). Reproduced with permission from: S.M. Emani, E.A. Bacha, D.B. McElhinney, et al., Primary left ventricular rehabilitation is effective in maintaining two-ventricle physiology in the borderline left heart, J. Thorac. Cardiovasc. Surg. 138 (6) (2009) 1276–1282.

(median, 11.3 months) versus those with HLHS (median age 46.5 months). After median follow-up of 31.7 months, survival was 89.3%, while 61% required either catheter-based or surgical reintervention. Left-ventricular volume increased significantly compared with the preconversion volumes. Long-term outcomes are required to determine the utility of biventricular conversion in these patients. The hybrid approach to HLHS, maintenance of ductal patency with a stent, atrial septal defect creation, and branch pulmonary artery banding, results in relief of prostaglandin-dependent systemic circulation and control of pulmonary blood flow has the same as the Norwood procedure without the use of cardiopulmonary bypass [123]. Patients with small leftsided heart structures may be initially palliated with the hybrid procedure and if adequate growth of left heart structures occurs, these patients can undergo biventricular repair, which involves the repair of any intracardiac defects such as VSDs, arterial switch as needed, enlargement of LVOT (e.g., Ross Konno), and reconstruction of the RVOT. This strategy has been pursued by the group in Geissen, Germany, who reported on 40 patients undergoing biventricular repair following initial hybrid palliation [124]. They reported significant growth of left-sided structures (aortic and mitral valve diameters, ratio of LV to RV length) following the hybrid procedure. Median survival in this cohort was 7.9 years; the mortality rate following biventricular conversion was 10%. Strategies for management of the borderline LV remain are isolated to single institution experience with small patient groups with a broad spectrum of primary diagnoses. The publications are single armed uncontrolled case series and follow-up is short. In addition, to a high rate of reintervention, there are long-term issues related to persistent diastolic dysfunction with poor exercise tolerance and most concerning pulmonary hypertension that may make the patients high risk for heart transplantation. Given the small numbers encountered even at large centers, high-quality multiinstitutional studies will be necessary to define the selection criteria and techniques to achieve the optimal outcome for the individual with a borderline LV.

CONCLUSION HF in children resulting from congenital heart disease represents a major health care burden. Again, all of congenital heart surgery may be considered as treatment for or prevention of HF. In this chapter we have focused on emerging surgical strategies for the systemic right ventricle, the failing Fontan and the borderline left ventricle. Improvement in outcome for this patient population will depend on ongoing research to identify the causes of structural heart disease and myocardial dysfunction at the cellular and tissue level. In addition, while we work to identify the mechanisms of the cause of CHD we need to obtain more complete and better patient level data to help us guide our therapies and identify new strategies.

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Surgical Management of the Failing Systemic Ventricle Chapter | 48  653

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654  SECTION | IV  Cardiac Surgery and Pediatric Heart Failure

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