Ann Thorac Surg 2004;77:889-894
© 2004 The Society of Thoracic Surgeons
Original article: cardiovascular
Outcomes of tricuspid atresia in the Fontan era
Rekwan Sittiwangkul, MDa,
Anthony Azakie, MDa,
Glen S. Van Arsdell, MDa,
William G. Williams, MDa,
Brian W. McCrindle, MD*a
a Departments of Pediatrics and Surgery, Divisions of Cardiology and Cardiovascular Surgery, The Hospital for Sick Children, University of Toronto School of Medicine, Toronto, Ontario, Canada
Accepted for publication September 5, 2003.
* Address reprint requests to Dr McCrindle, Division of Cardiology, Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G-1X8, Canada
e-mail: brian.mccrindle{at}sickkids.ca
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Abstract
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BACKGROUND: Whereas indications expand and results improve with increasing refinements to the Fontan procedure the overall impact on outcomes related to tricuspid atresia remains suboptimally defined.
METHODS: We reviewed 225 consecutive patients presenting between 1971 and 1999. All patients had classic tricuspid atresia with absent right atrioventricular connection and with D-transposition of the great arteries in 21%, pulmonary outflow obstruction in 75%, and aortic outflow obstruction in 11%.
RESULTS: Ten patients died before any intervention and 3 patients were lost to follow-up. Palliative procedures (includes 151 with systemic shunt, 27 pulmonary artery banding, 60 venous shunt) were performed in 203 patients, with 44 deaths, 8 patients awaiting Fontan, 12 patients Fontan contraindicated, and 11 patients lost-to-follow-up. A total of 137 patients had the Fontan procedure (9 patients without previous procedures) with 7 early deaths, 11 late deaths, and 3 patients progressing to heart transplantation. Total survival for the cohort was 90% at the age of 1 month, 81% at 1 year, 70% at 10 years, and 60% at 20 years with no significant change over the time period. Independent factors associated with ineligibility or death without Fontan (n = 68, 30%) included earlier birth date, lower birth weight, presence of aortic arch anomaly and greater right ventricular hypoplasia, and no palliative procedure. There were no significant changes in mortality with Fontan over the study time period with survival of 95% at 1 month, 93% at 1year, and 82% at 10 years.
CONCLUSIONS: Improvements in outcomes with tricuspid atresia will require attention to management and risk factors before Fontan.
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Introduction
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Thirty years since Fontan demonstrated that "right heart bypass" is a clinically successful approach to the management of tricuspid atresia, the Fontan procedure has been applied to a variety of congenital heart defects characterized by morphologic or functional single ventricle [1–4]. The advent of Fontan palliation has greatly improved long-term morbidity and mortality in patients with tricuspid atresia [2, 5–9]. However trends in outcomes of patients with tricuspid atresia, both before and after Fontan palliation, remain suboptimally defined.
Few studies have reported cohort analyses of an unselected consecutive series of patients presenting with tricuspid atresia [7, 10]. The purpose of this study is to determine trends in morbidity, mortality, and risk factors both before and after Fontan palliation for patients with tricuspid atresia and to help identify maneuvers that would optimize outcomes in this patient population.
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Patients and methods
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Tricuspid atresia describes a congenital cardiac malformation usually with atrial situs solitus, either complete absence of the right atrioventricular connection (left in those with mirror-image arrangement) or an imperforate connection. The left atrioventricular valve is connected to a dominant ventricle of either left, right, or indeterminate morphology [7]. Patients with double-inlet ventricle and imperforate right atrioventricular valve were excluded.
Permission to perform the health records review was obtained from the Research Ethics Board, Hospital for Sick Children, Toronto, Canada. We searched the databases of the Divisions of Cardiology and Cardiovascular Surgery and the Department of Pathology at the Toronto Hospital for Sick Children for all patients presenting with a diagnosis of tricuspid atresia between January 1971 and May 1999. Demographics, morphology, cardiac function and rhythm, clinical status, procedures, morbidity, and mortality were abstracted from records of surgery, autopsy, cardiac catheterization with angiography, prenatal and postnatal echocardiography and magnetic resonance imaging and inpatient records. Eight patients with a putative diagnosis of tricuspid atresia were excluded due to lack of sufficient data.
Included in this study were 225 patients (133 males, 92 females) whose median age at initial assessment is 33 days (range, < 1 day to 23.5 years). The mean gestational age was 39 ± 2 weeks (n = 135) and the mean birth weight was 3.1 ± 0.6 (n = 134). Cyanosis was the most common mode of presentation (n = 197, 88%), followed by congestive heart failure (n = 57, 25%), and circulatory collapse/acidosis (n = 14, 6.2%).
Electrocardiographic analysis on admission or before Fontan showed a superior leftward frontal axis (0 to -90) in 181 patients (80%), inferior leftward frontal axis (0 to + 90) in 41 patients (18%), and superior rightward axis in 3 patients. Rhythm analysis showed 209 patients (94%) had normal sinus rhythm (NSR) and no history of arrhythmia. Of the remaining 16 patients (7%), 6 had NSR with a history of tachyarrhythmia, 4 had junctional rhythm, 2 had sinus node dysfunction, 2 had NSR with Wolf–Parkinson–White, and 1 each had NSR with premature ventricular complexes and complete atrioventricular conduction block. The diagnosis was established using (n = 225) cardiac catheterization in 208 patients (93%), postnatal echocardiography in 195 (87%), prenatal echocardiography in 10 (4%) patients, and autopsy data in 43 (19%). Associated cardiovascular anomalies are shown in Table 1. All patients had an atrial septal defect which was restrictive in 37%. The vast majority (95%) also had a ventricular septal defect that was restrictive in 32%. Pulmonary outflow obstruction was present in 168 patients (75%) and 62 (28%) had a discordant ventriculo-arterial connection.
Before the Fontan procedure, the mean pulmonary artery pressure (n = 168; 130 patients suitable and 38 patients unsuitable for Fontan) was 14 ± 9 mm Hg (range, 5–70 mm Hg), the mean left ventricular end-diastolic pressure (n = 185; 129 patients suitable and 56 unsuitable for Fontan) was 7 ± 3 mm Hg (range, 0–25 mm Hg), the mean Nakata index (n = 135, 111 patients suitable, and 24 unsuitable for Fontan) was 334 ± 150 (range, 104–834), the mean Mcgoon index (n = 129, 107 patients suitable, and 22 unsuitable for Fontan) was 2.17 ± 0.58 (range, 0.91–4.52), the mean pulmonary vascular resistance index (n = 51, 42 patients suitable, and 9 unsuitable for Fontan) was 1.70 ± 1.89 U/m2 (range, 0.23–7.09), and the mean Mair index (n = 36, 29 patients suitable, and 7 unsuitable for Fontan) was 2.84 ± 1.67 (range, 0.60–9.50).
There were 221 patients who had cardiac cathetherization or postnatal echocardiography. Ventricular function was found to be normal in 207 patients (94%) and reduced in 14 patients (6%).
Extracardiac abnormalities were present in 39 patients (17%) and included urogenital abnormalities [n = 9, ambiguous genitalia (2 patients), single kidney (1 patient), horseshoe kidney (1 patient), pelvic kidney (1 patient), multicystic kidney (1 patient), double ureter (1 patient), duplicate bladder (1 patient), nephrolithiasis (1 patient)], gastrointestinal abnormalities [n = 8, tracheoesophageal fistula (3 patients), pyloric stenosis (1 patient), intestinal malrotation (1 patient), diaphragmatic hernia (1 patient), micronodular cirrhosis (1 patient), gastrointestinal reflux (1 patient)], VACTERL anomaly (n = 6), neurologic abnormalities [n = 5, severe brain anomaly (2 patients), hydrocephalus (1 patient), neonatal seizure (2 patients)], cleft lip and cleft palate (n = 3), chromosome abnormalities (n = 2, 47XXX, XY/XO), CHARGE anomaly (n = 1), choanal atresia (n = 1), retropharyngeal mass (n = 1), Noonan syndrome (n = 1), hypothyroidism (1 patient), and Sturge–Weber syndrome (n = 1). Fourteen of 39 patients (36%) had surgical procedures for extracardiac anomalies.
Data are described as frequencies, medians with ranges, and means with standard deviations as appropriate. Trends over consecutive birth cohorts were sought with Mantel–Haentsel 
-square and Kruskal–Wallis analysis of variance. Factors associated with mortality or unsuitability for Fontan procedure were sought in multiple logistic regression. Factors associated with mortality after Fontan procedure were sought with parametric modeling of time-related death in the hazard domain.
All analyses were performed using SAS statistical software Versions 7 (SAS Institute, Inc., Cary, NC) using default settings. A p value < 0.05 was set as the level of statistical significance.
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Results
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The management and outcomes for 225 patients with tricuspid atresia presenting to the Hospital for Sick Children from 1971–1999 are shown in Figure 1. There were a total of 72 deaths (32%), with 10 deaths occurring before any intervention, 44 deaths occurring after an initial palliation, 7 early deaths occurring after Fontan procedure, and 11 late deaths occurring after the Fontan procedure. Overall survival is 81%, 72%, and 64% at 1, 5, and 15 years (Fig 2).
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Fig 1. Flow diagram of overall management strategies and outcomes for patients with tricuspid atresia. (F/U = follow-up.)
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Fig 2. Time-related survival from birth for the total cohort. Circles and bars represent Kaplan–Meier estimates; solid line represents the parametric model with the dashed lines enclosing the 70% confidence limits; and numbers along the top of the bottom axis represent the number of patients at risk.
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Before Fontan at least one procedure was performed in 90% of patients (n = 203). Management before Fontan is shown in Table 2. A systemic to pulmonary artery shunt was most commonly performed, followed by balloon or surgical septectomy and pulmonary artery banding.
In 68 patients (30%), a Fontan was not performed. Ten children died before any intervention. Causes of death included sepsis in 3 patients, brain malformation in 2 patients, severe cyanosis in 2 patients, palliative care in 2 patients, and failed repair of a tracheoesophageal fistula in 1 patient. Forty-four children died after initial palliation, due to myocardial failure in 10, sudden death in 21, sepsis in 7, subaortic obstruction in 2, respiratory failure in 3, and accidental death in 1. The remaining 14 patients did not meet criteria for Fontan candidacy due to severe pulmonary artery distortion (n = 10), severe pulmonary hypertension (n = 8), poor ventricular function (n = 5), or severe atrioventricular valve regurgitation (n = 1). Independent factors associated with death before or unsuitability for the Fontan procedure (n = 68 patients) are detailed in Table 3 and include lower birth weight, earlier birth cohort, greater degree of right ventricular hypoplasia, the presence of an aortic arch lesion, and no initial intervention.
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Table 3. Independent Factors Associated With Death Before or Unsuitability for Fontan Procedure (n = 68 Patients)
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The Fontan procedure was performed in 137 (61%) of 225 patients (Fig 3). In 9 of these patients the Fontan operation was performed in a single stage without any prior palliation. The types of connections that were used for construction of a Fontan circuit changed over time. Early in the experience atriopulmonary (n = 54, 40%) or right atrioventricular conduit (n = 44,32%) connections were constructed. A lateral tunnel (n = 24, 18%) or extracardiac conduit (n = 14, 10%) connection was favored in the more recent and current eras. A fenestration was used in 33 patients (24%). With each consecutive birth cohort, the median age at which the Fontan was performed declined significantly (Table 4). Early postoperative complications were common (n = 80, 60%) and included pleural effusions (n = 34), tachyarrhythmia (n = 22), pericardial effusions (n = 13), renal failure (n = 6), complete heart block (n = 5), thromboembolic event (n = 2), and chylothorax (n = 2). Late complications developed in 45 patients (35%), including arrhythmias in 24, ventricular failure or dysfunction in 14, thromboembolic events in 9, conduit stenosis in 5, formation of pulmonary arteriovenous fistulas in 1, protein losing enteropathy in 1, and progressive subaortic obstruction in 1. Reoperation or subsequent interventions were required in 53 patients (39%). There were 7 early deaths and 11 late deaths. Survival after the Fontan procedure was 93%, 87%, and 81% at 1, 5, and 10 years (Fig 4). Two children required late heart transplantation.
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Fig 3. Flow diagram of outcomes for patients with tricuspid atresia having a Fontan operation. (F/U = follow-up.)
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Fig 4. Time-related survival from Fontan procedure. Circles and bars represent Kaplan–Meier estimates; solid line represents the parametric model with the dashed lines enclosing the 70% confidence limits; and numbers along the top of the bottom axis represent the number of patients at risk.
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Incremental risk factors for early phase mortality after the Fontan procedure include the presence of a persistent left superior vena cava (p = 0.03) and higher mean preoperative pulmonary artery pressures (p = 0.05). During the constant hazard phase, time related mortality after the Fontan procedure was adversely affected by increased age at the time of Fontan construction (p = 0.01) and the development of any late complication (p = 0.07) (Table 5). During each consecutive birth cohort, children with tricuspid atresia were more likely to have an initial assessment, have a Fontan procedure, and have a Fontan procedure at an earlier age (Table 4). Throughout each consecutive birth cohort, mortality was not significantly different.
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Comment
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This cohort analysis of 225 patients with tricuspid atresia presenting to a single institution over almost 3 decades aims to identify the clinical outcomes and risk factors for adverse events for the entire cohort. Total survival for the cohort was 81% at 1 year and 60% at 20 years. There were no significant changes in mortality with the Fontan procedure over the study time period with survival of 93% at 1 year and 82% at 10 years. Improvements in outcomes with tricuspid atresia will require attention to management and risk factors before the Fontan operation. Independent factors associated with ineligibility or death without Fontan included earlier birth date, lower birth weight, presence of aortic arch anomaly, greater right ventricle (RV) hypoplasia, and no palliative procedure. Infants with greater degrees of RV hypoplasia required earlier intervention and/or palliation suggesting greater severity of disease. Furthermore right ventricles with only mild degrees of hypoplasia may have had a greater contribution to overall ventricular systolic function.
Whereas outcomes for children with tricuspid atresia are improving, an important proportion of patients continue to die before intervention or Fontan palliation or are not suitable candidates for the Fontan procedure [10]. The management of this group of patients requires optimization in order to significantly improve overall outcomes.
Multiple procedures and interventions are required in the majority of patients before the Fontan procedure in order to regulate pulmonary blood flow, maintain an unrestrictive atrial communication, address aortic outflow obstruction, rehabilitate pulmonary artery abnormalities, and stage with cavopulmonary connections. Franklin and associates reported on 237 infants with tricuspid atresia, 86% of which were initially judged suitable for Fontan palliation [10]. Only 48% had, in fact, progressed to the Fontan operation because of early death after initial palliative procedures, sudden cardiac death, or the development of subaortic stenosis, severe pulmonary artery distortion, and/or ventricular dysfunction. In our experience 30% of children were ineligible or died without Fontan. Most of the children died after initial palliative procedures or suffered sudden death (some due to shunt complications). Other reasons for Fontan ineligibility included severe pulmonary artery distortion and/or hypertensive disease, ventricular dysfunction, and progressive subaortic stenosis.
The more common initial palliative procedures included the performance of a systemic to pulmonary artery shunt, pulmonary artery banding, a modified Norwood procedure, and enlargement of the ventricular septal defect. Reduction in mortality for these initial palliative procedures can be anticipated with improved management and experience with neonatal and infant cardiac surgery. The construction of more accurate shunts, avoidance of central shunts that may produce pulmonary overcirculation, vascular disease, and distortion of pulmonary arteries may lead to improved outcomes before Fontan. The incidence of systemic outflow obstruction in this series is 11% and was comparable to that found in autopsy series or one cohort study [10–12]. The presence of subaortic obstruction was not an independent risk factor for adverse outcomes in this patient population. Historically obstruction of the subaortic region in the setting of a single ventricle has had a negative impact on outcome, especially after banding of the pulmonary artery [10, 13–19]. Progressive subaortic stenosis leads to ventricular hypertrophy, dysfunction, and poor candidacy for or outcome after the Fontan. Staging with bidirectional cavopulmonary anastomoses and construction of a proximal pulmonary artery to aorta connection reduces the risks of acquired subaortic stenosis. In our experience aortic arch anomalies are a risk factor for death or failure to progress to a Fontan operation especially in the setting of neonatal subaortic obstruction and ventricular arterial discordance. Improving outcomes with the modified Norwood procedure may neutralize this risk factor [20, 21]. Although low birth weight babies with congenital heart defects continue to be a high risk group, delay in their operative management may only increase morbidity and mortality. With increased experience, early results with the surgical management of low birth weight babies with even complex lesions have improved [22].
Whereas mortality with Fontan procedure is low there are frequent early and late complications and ongoing morbidity. Incremental risk factors for early mortality include a persistent left-sided superior vena cava (SVC) and elevated pulmonary artery pressures before Fontan. A left-sided SVC is usually associated with bilateral SVCs, the presence of which has been shown to be a risk factor for adverse outcome after single-ventricle palliation [23]. Bilateral SVC-to-PA anastomoses are associated with central PA hypoplasia and an increased risk of thrombus formation. Modifications of surgical technique may improve flow patterns, optimize growth, and diminish the risk of thrombus formation. Anticoagulation with low molecular weight heparin (LMWH) may prevent thrombus formation. Bilateral SVCs in children with single ventricles may also be associated with viscero-atrial heterotaxy syndromes which can be complicated by extracardiac anomalies, other complex cardiovascular malformations, and worse overall prognosis.
Incremental risk factors for ongoing intermediate mortality include older age at Fontan procedure and presence of late complications including arrhythmias, ventricular dysfunction, and thromboembolic complications. Technical modifications of the Fontan procedure may improve the midterm incidence of arrhythmias and appropriate afterload reduction in the face of ventricular dysfunction may maintain ventricular function. At the Hospital for Sick Children, infants and children with single ventricle physiology and reduced ventricular function or atrioventricular (AV) valve regurgitation routinely have afterload reduction therapy with angiotensin-converting enzyme inhibitors.
Anticoagulation management of children with shunted single ventricles needs further clinical study to ascertain optimal management and prevention of thrombotic complications. Fenton and associates [24] have shown that there is a significant incidence of sudden death among infants who have undergone shunting with autopsy-proven shunt thrombosis as one of the leading causes of interim sudden death. The survival of patients discharged on aspirin (89%) was not better than that of patients discharged on no anticoagulation (88%). Four infants with sudden death had been notably irritable for 24–48 hours before death. The authors suggest that death may be preceded by unexplained irritability and such symptoms should therefore be carefully evaluated. The authors recommend the following options to reduce interim mortality: alternative regimens of anticoagulation (such as low-molecular weight heparin), alternative conduit material, and earlier reoperation. We routinely use LMWH in children with shunted single ventricles and favor earlier (3 months of age) cavopulmonary shunting. An aggressive interstage home surveillance program that includes monitoring of weight gain, hemoglobin saturation by pulse oximetry, and monitoring of poor oral intake, diarrhea, vomiting, and irritability may also reduce interim mortality. Finally in children who have poor systolic or diastolic ventricular function consideration for transplant candidacy should be given at an early stage.
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Abstract
Introduction
