Author + information
- Received August 3, 2005
- Revision received December 5, 2005
- Accepted December 30, 2005
- Published online May 16, 2006.
- Salvatore Giannico, MD⁎,⁎ (, )
- Fatma Hammad, MD†,
- Antonio Amodeo, MD⁎,
- Guido Michielon, MD⁎,
- Fabrizio Drago, MD⁎,
- Attilio Turchetta, MD†,
- Roberto Di Donato, MD⁎ and
- Stephen P. Sanders, MD, FACC⁎
- ↵⁎Reprint requests and correspondence:
Dr. Salvatore Giannico, Pediatric Cardiology-Bambino Gesŭ Hospital, Piazza Sant’Onofrio, 4-00165 Rome, Italy.
Objectives We sought to evaluate the mid-term outcome of hospital survivors with extracardiac Fontan circulation.
Background Few data exist about the mid-term and long-term results of the extracardiac Fontan operation.
Methods From November 1988 to November 2003, 221 patients underwent an extracardiac Fontan procedure as primary (9 patients) or secondary (212 patients) palliation, at a mean age of 72.2 months (range 13.1 to 131.3 months). A total of 165 of 193 early survivors underwent programmed noninvasive follow-up evaluations and at least one cardiac catheterization.
Results The overall survival, including operative deaths, was 85% at 15 years. Freedom from late failure among hospital survivors is 92% at 15 years. A total of 127 of 165 survivors (77%) were in New York Heart Association functional class I. The incidence of late major problems was 24% (42 major problems in 36 of 165 patients): 19 patients had arrhythmias (11%), 5 patients had obstruction of the extracardiac conduit (3%) and 6 of the left pulmonary artery (3.5%), and 5 patients experienced ventricular failure (3%), leading to heart transplantation in 3 patients. Protein-losing enteropathy was found in two patients (1%). The incidence of late re-interventions was 12.7% (21 of 165 patients, including 15 epicardial pacemaker implantations). Four patients died (2.3%), two after heart transplantation.
Conclusions After 15 years of follow-up, the overall survival, the functional status, and the cardiopulmonary performance of survivors of the extracardiac Fontan procedure compare favorably with other series of patients who underwent the lateral tunnel approach. The incidence of late deaths, obstructions of the cavopulmonary pathway, re-interventions, and arrhythmias is lower than that reported late after other Fontan-type operations.
Before the Fontan operation, complex cardiac anomalies that were unsuitable for biventricular repair were palliated by pulmonary artery banding or systemic-to-pulmonary shunts. Nevertheless, the life expectancy was only two to three decades.
The introduction of the Fontan operation dramatically changed the management of patients with a functional single ventricle. Thirty-four years after the first description of total right heart bypass (1), one or another modification of the Fontan operation has become one of the most frequently performed operations for congenital heart disease. The separation of systemic and pulmonary venous returns results in near-normal systemic oxygen saturation and normalizes the volume work of the systemic ventricle. Now children, adolescents, and adults with a functional single ventricle can experience a normal lifestyle.
This extensive application of the Fontan principle is currently under intensive scrutiny. After the earlier pessimistic reports about long-term outcome (2–4) and the more recent experience reported by Gentles et al. (5), it remains unclear whether the Fontan principle provides satisfactory palliation for patients with a single ventricle, and if so, which operative strategy affords the best late outcome.
Since 1988, right heart bypass has been accomplished by means of a total cavopulmonary connection (6), achieved using a lateral tunnel, an intra-atrial conduit, or an extracardiac conduit. We have reported the technical advantages (7), the hemodynamic benefits, and the patterns of cavopulmonary flow of the extracardiac Fontan procedure (8), as well as its application in complex cardiac anomalies (9,10). Physical models as well as mathematical models have confirmed the hemodynamic benefits of the extracardiac Fontan procedure (11).
The feasibility of a fenestration in the extracardiac Fontan connection as well as the potential for conversion of a previous atriopulmonary connection have been reported (12–15).
The potential advantages of the extracardiac Fontan procedure include avoidance of myocardial ischemia (aortic cross-clamping), atriotomy, and intra-atrial suture lines, as well as the feasibility of early or late fenestration. However, the capacity of this procedure to reduce late atrial arrhythmias and the longevity of the extracardiac conduit remain unproven (16–19). We reviewed our total experience with the extracardiac Fontan procedure and report mid-term results in the first 193 survivors.
All patients who underwent a primary or secondary extracardiac Fontan procedure at Bambino Gesŭ Pediatric Hospital between November 1988 and November 2003 were identified by searching the computer database of the Follow-Up Unit of Congenital Cardiac Patients. The medical records of each patient were reviewed, and the following information was collected: clinical status, medication, cardiovascular test results including electrocardiogram, Holter monitoring, exercise test, echocardiogram, cardiac magnetic resonance imaging (MRI), and cardiac catheterization. The scheduled tests performed in the Follow-Up Unit are reported in Table 1.In addition, complications, interventional catheterization procedures, and surgical procedures were recorded.
An age- and gender-matched control population was identified for comparison of cardiovascular test results (20,21). The control group of normal children are one from our laboratory (20) and one from another institution (21).
A maximal exercise stress test was performed in patients over five years of age following the Bruce protocol once per year. Lung function testing was performed in all patients by a pneumotachograph, measuring the best of three consecutive flow-volume curves. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced expiratory flow were considered as absolute values and as percentages of predicted values. Magnetic resonance imaging was performed in all patients as previously reported (10). Postoperative cardiac catheterization and angiography were performed at least once in all survivors following our protocol (8).
Numeric data are presented as mean value ± 1 SD. The primary outcome variable in this study was survival with an intact Fontan circulation. Failure was defined as death or takedown of the Fontan circulation to an aortopulmonary or cavopulmonary shunt, or heart transplantation. Early failure was defined as death or takedown within 30 days from surgery or death before hospital discharge. Secondary end points were functional class, prevalence of arrhythmias, and late complications of the Fontan circuit resulting in interventional procedures. Survival data and probability of freedom from time-related events were analyzed by the product limit method of Kaplan and Meier.
Normograms of the hazard functions for the following end points were obtained: death or heart transplantation, obstruction of the cavopulmonary pathway, arrhythmia, re-intervention, and pacemaker implantation.
Comparisons of rest and exercise values between the control and the extracardiac Fontan groups were made using a two-tailed ttest for unpaired data. Statistical analysis was conducted with SAS 1998 statistical software (SAS Institute Inc., Cary, North Carolina).
From November 1988 to November 2003, 221 patients, mean age 6 years (range 1 to 10.9 years), underwent an extracardiac Fontan operation at our institution. An extracardiac conduit or a direct anastomosis was used to connect the inferior vena cava to the pulmonary artery in all cases (7). The superior vena cava was anastomosed to the ipsilateral pulmonary artery either at the time of the Fontan operation (nine patients) or as a bidirectional cavopulmonary anastomosis performed previously. The 60 patients with complex cardiac anomalies who underwent surgery between 1988 and 1995 represent a subgroup previously reported (10).
During this period, 16 additional patients underwent a Fontan operation using another technique (lateral tunnel in nine and atriopulmonary connection in seven patients). Selection was based on the surgeon’s preference. This number of patients is insufficient for comparison with the extracardiac Fontan group. This group will not be described further.
Of the initial 221 patients, 193 survived to hospital discharge with the Fontan circulation intact, 22 died early postoperatively, and 6 patients survived an emergency takedown of the Fontan procedure. The early failure rate decreased from 14.8% (17 of 115 patients) in the first 10 years to 4.7% (5 of 106 patients) in the last 5 years. The mean follow-up was 63 months, and the median follow-up was 50 months (range 1 to 179 months). For 36 patients the follow-up was longer than 10 years. The total follow-up was 1,122 patient/years. A total of 28 of 193 patients were lost to follow-up because they returned to their country of origin during follow-up. Preoperative diagnoses in 193 early survivors (165 in follow-up and 28 lost to follow-up) are summarized in Table 2.We analyzed the clinical data of patients lost to follow-up, including age, disease, time of the extracardiac Fontan procedure, type of conduit used, early postoperative data, and early follow-up data. The patients lost to follow-up did not differ significantly from the other survivors.
A total of 9 of 193 survivors underwent an extracardiac Fontan procedure as the primary surgical procedure. Previous surgical procedures of the survivors in follow-up are reported in Table 3and reflect our policy of a staging toward a Fontan procedure (22–24).
In 10 patients, a previous atriopulmonary connection was converted to an extracardiac Fontan because of obstruction of the Fontan pathway or persistent atrial arrhythmias (15,25). The additional surgical procedures performed at the time of the extracardiac Fontan are reported in Table 3.
Dacron conduits were used until 1997 (N = 43). Also, before 1997 an aortic homograft was used in three patients. Since 1997 we have used only polytetrafluoroethylene Gore-Tex conduits (N = 113) to minimize the risk of peel formation (10). The range of conduit sizes was 16 to 24 mm. In four patients, the inferior vena cava was anastomosed directly to the right pulmonary artery (26). In three other patients, the superior vena cava was connected to the left pulmonary artery and the inferior vena cava was connected to the right pulmonary artery (27).
The extracardiac conduit was fenestrated in 52 of 193 early survivors using a small Gore-Tex conduit interposed between the extracardiac conduit and the atrial wall or a 4-mm direct connection between the side of the conduit and the atrial wall. The main indication for a fenestrated extracardiac Fontan was the small size of the pulmonary arteries. Myocardial ischemia (aortic cross-clamping) was avoided in 128 of 193 patients.
Of the 165 early survivors in follow-up, 127 (77%) are in New York Heart Association functional class I, 31 patients (19%) are in class II, and 5 patients (3%) are in class III. All 165 patients in follow-up received oral anticoagulation agents for at least six months after surgery and subsequently antiaggregate therapy with aspirin. No patient had a bleeding complication of the anticoagulant therapy. A total of 98 of 165 patients enrolled were taking medications, including digoxin, furosemide angiotensin-converting enzyme inhibitors, and antiarrhythmic drugs. Thirty-six patients (22% of the 165 survivors) experienced 42 major late complications (Fig. 1).The overall freedom from failure of the Fontan procedure (early and late) by Kaplan-Meier curve is 89% at 5 years and 85% at 10 and 15 years. Freedom from late failure among those who survived to hospital discharge with the Fontan circulation intact is 94.2% at 10 years and 92.2% at 15 years (Fig. 2).
Exercise tolerance and lung function test
Maximal exercise stress testing showed a moderate reduction of exercise tolerance (62.4% of predicted value, range 58% to 65%). The heart rate at the peak of exercise was significantly lower than in the control group (161 ± 19 beats/min; control subjects, 182 ± 6 beats/min; p < 0.001) as was the maximal systolic arterial pressure (116 ± 10 mm Hg; control subjects, 130 ± 9 mm Hg, p < 0.005). Systemic oxygen saturation decreased during exercise from 92% to 88% (mean value) in the patients without fenestration and from 89% to 80% (mean value) in the six patients with the fenestration left open. The level of exercise tolerance remained stable during follow-up in 127 of 165 (77%) patients without major late complications (Table 4).Exercise tests were not performed regularly in the 38 patients with late complications or late deaths, or if performed, the results were too variable to permit detection of a trend. Measures of the cardiac output and the oxygen consumption during the stress test were obtained in 64 of 165 patients. Cardiac output increased from 3.04 ± 0.75 l/min to 4.5 ± 2.02 l/min at maximal exercise.
A restrictive ventilatory pattern, defined as FVC and FEV1 <80% of predictive, with FEV1/FVC > 80% of predicted, was identified in 45 patients during follow-up (mild in 27 patients and moderate in 18 patients). In most of these patients, previous cardiothoracic surgical procedures are the most likely cause. Four patients had an obstructive ventilatory pattern, defined as FVC > 80% of predicted but FEV1 and FEV1/FVC <80% of predicted.
Conduit function assessment
In 154 of 165 survivors, echocardiography showed laminar, predominantly diastolic, cavopulmonary flow with typical respiratory variation. In these patients, MRI imaging showed uniform reduction of the internal conduit diameter of 17.2 ± 6.4% during the first 6 months with no progression over the following years (17.5 ± 5.8%, p = not significant). In all survivors in follow-up, we analyzed at least two MRI images (the first within six months of the Fontan procedure and the second at least two years later). In 108 of 165 patients, an additional MRI was analyzed an average of 2 years after the second examination.
Angiography of the cavopulmonary pathway indicated no thrombus formation among survivors and no graft stenosis in 154 of 165 survivors. The remaining 11 patients had obstruction of the cavopulmonary pathway. In five patients (3%), there was a significant obstruction of the extracardiac conduit (Table 5).Echocardiographic Doppler patterns of the flow inside the conduit were different in the five patients with conduit stenosis: forward flow was laminar during a normal inspiratory phase, but showed turbulent features with increased Doppler velocities during a forced, deep inspiration. Three of these five patients underwent successful stent implantation, and one patient underwent successful balloon angioplasty. The remaining patient with calcification of a 16-mm homograft conduit underwent surgical replacement, performed without aortic cross-clamping and completed with normothermic circulation and a beating heart (Table 5). One patient had both conduit stenosis (resolved by balloon angioplasty) and left pulmonary artery stenosis treated successfully by stent implantation. Six survivors presented late with stenosis of the left pulmonary artery. Four patients underwent successful stent implantation, and two underwent percutaneous balloon angioplasty with clinical improvement. Cumulative freedom from cavopulmonary pathway obstruction was 96% at 5 years, 93.3% at 10 years, and 89% at 15 years (Fig. 3).There was no significant relationship between the size of the conduit and late outcome.
Twenty-one patients had mild-to-moderate regurgitation and three had moderate regurgitation of a common atrioventricular valve. Three patients with hypoplastic left heart syndrome had severe tricuspid regurgitation leading to valve annuloplasty at the time of the extracardiac Fontan procedure. Six patients had mild-to-moderate aortic insufficiency. Four of these had undergone surgical repair of the aortic valve at the time of the extracardiac Fontan procedure, and one subsequently underwent aortic valve replacement.
Five patients (3%) showed signs of ventricular failure (high caval and pulmonary mean pressures, high end-diastolic ventricular pressure). Two of them are receiving anticongestive therapy. The other three underwent heart transplantation with two hospital deaths.
In all survivors with a fenestration, the small conduit interposed between the main conduit and the atrial wall or the 4-mm circular hole was easily visualized by echocardiography in the subcostal or apical four-chamber view. The flow across the fenestration was continuous and laminar in the first 15 to 20 days after surgery and became turbulent and subsequently absent in the small conduit at the end of the first month because of the spontaneous closure of the fenestration.
A total of 29 of 52 fenestrations had spontaneously closed at the echocardiographic or catheterization study, at a mean of 2 months after the fenestrated Fontan procedure. Transcatheter complete occlusion was performed in 17 of 23 patients with open fenestration 6 to 18 months later. In the remaining six patients, the fenestration was left open because of the hemodynamic data. The spontaneous or transcatheter occlusion of the fenestration produced a significant increase of the systemic oxygen saturation (from 85% to 93%), but there was no evident relationship with late outcome.
The predominant rhythm was sinus in 127 of 165 survivors and junctional in 38 patients with moderate nocturnal bradycardia caused by sinus node dysfunction.
Nineteen patients (11% of the 165 survivors) had late arrhythmias. Three of 19 underwent epicardial pacemaker implantation because of progressive complete atrioventricular block associated with an L ventricular loop. Nine of 19 patients had an epicardial pacemaker implanted to treat sinus node dysfunction, according to current guidelines (28).
Seven of 19 patients had atrial arrhythmias (recurrent atrial flutter or fibrillation, or paroxysmal supraventricular tachycardia), late after the Fontan procedure. All patients had symptoms of heart failure and/or low cardiac output during the episodes of atrial arrhythmia. All seven patients were treated medically, and three underwent pacemaker implantation because of drug-induced bradycardia. One of these latter three patients subsequently underwent successful heart transplantation. Kaplan-Meier cumulative freedom from arrhythmias was 91% at 5 years, 87.4% at 10 years, and 83.8 at 15 years (Fig. 4).
Uncommon cardiac-related events
At 18 and 22 months after the extracardiac Fontan operation, protein losing-enteropathy developed in two patients, one with hypoplastic left heart syndrome and the other with asplenia syndrome. Cerebral thromboembolism occurred in one patient in association with bacterial endocarditis of the common atrioventricular valve.
In one patient with tricuspid atresia and transposition of the great arteries, severe subaortic stenosis developed 10 months after the extracardiac Fontan (performed as primary palliation), and the patient underwent successful surgical relief of the obstruction. One patient underwent a successful aortic valve replacement for severe aortic regurgitation 118 months after the Fontan operation.
Catheter-based re-interventions (dilation or stent implantation) were performed in 10 patients for conduit stenosis, left pulmonary artery stenosis, or both (Table 6).Six patients underwent surgical re-interventions for hemodynamic or anatomic problems, including one conduit replacement, three heart transplantations, one subaortic stenosis resection, and one aortic valve replacement. An epicardial pacemaker was implanted for bradyarrhythmia, heart block, or to permit drug treatment of atrial tachyarrhythmias in 15 patients (re-interventions for rhythm disturbances). Kaplan-Meier cumulative freedom from all re-interventions is 81% at 10 years and 69.4% at 15 years (Fig. 5).Kaplan-Meier cumulative freedom from pacemaker implantation (the most frequent reoperation) was 88.7% at 10 years and 76.2% at 15 years (Fig. 6).Kaplan-Meier cumulative freedom from catheter-based re-interventions is shown in Figure 3.
There were four late deaths. Two patients with a pacemaker died suddenly at home. Two deaths occurred after heart transplantation.
Postoperative physiology of extracardiac Fontan
Our series of survivors with an extracardiac Fontan circulation is the largest series reported in the literature and has the longest follow-up. The overall survival (including hospital deaths) in our patients is 85% at 10 and 15 years, comparable with those reported for intra-atrial cavopulmonary connections (2–5) (Table 7).However, actuarial survival for those discharged from the hospital with the extracardiac Fontan intact is 92.2% at 15 years. Further, 77% of 165 survivors in regular follow-up have no symptoms during normal daily life, with a satisfactory exercise tolerance and a mild exercise-induced decrease in systemic saturation, common after a Fontan procedure (29).
Cardiopulmonary function after Fontan procedures depends on several factors, all influencing the dynamics of cavopulmonary flow. Our echocardiographic Doppler studies confirm that forward cavopulmonary flow is predominantly an early diastolic event, in contrast to what occurs in atriopulmonary connections. This hemodynamic model with blood flowing from venae cavae to the pulmonary artery through a tubular system, interposed between the systemic and pulmonary capillary beds, reduces energy loss, especially compared with the atriopulmonary connection. This model emphasizes the potential role of diastolic ventricular performance (as a suction pump) in Fontan circulation (8–30). Further invasive studies with a simultaneous measurement of the forward cavopulmonary flow and the ventricular diastolic pressure variations should help to define the role of the diastolic ventricular performance.
Experimental or computerized fluid dynamics studies suggest that all types of cavopulmonary connection are efficient for reducing energy losses (31,32), but the extracardiac conduit seems to provide the least fluid energy dissipation at all flow rates and especially at high flows (33). Moreover, the spatial arrangement of the extracardiac conduit that minimizes energy loss is with the conduit oriented to the left pulmonary artery and the superior vena cava to the right pulmonary artery. This spatial arrangement produces a beneficial vortex that facilitates cavopulmonary forward flow, especially at high flow rates (11).
Our results in the subgroup of 10 patients who underwent revision of a previous atriopulmonary connection to an extracardiac Fontan circulation are promising. If these observations are corroborated by further experience, more failed atriopulmonary Fontan patients could be converted to an extracardiac Fontan procedure as an alternative to heart transplantation.
The typical respiratory variations of the cavopulmonary flow, analyzed by echocardiographic Doppler in our patients early after the surgery (8), were also seen later in follow-up and show that pulmonary flow is clearly dependent on respiratory motion (inspiratory suction). This respiratory mechanism becomes crucial during exercise to increase cavopulmonary flow, probably because the increased resting venous tone in patients with Fontan procedures may limit their ability to mobilize blood from capacitance vessels during exercise (34).
Late complications of extracardiac Fontan
Extracardiac conduit obstruction
The longevity of the extracardiac conduit remains the most controversial aspect of this surgical option. In our series of the 165 survivors, including the 36 patients with the longest follow-up (more than 10 years), conduit obstruction has developed in only 5 patients. The mechanism of late conduit obstruction is likely longitudinal torsion of the conduit during rapid somatic growth in height. The facility with which this obstruction can be treated by stent placement supports this mechanism. Further, serial MRI data show no decrease in the internal diameter of the conduit after the first six months.
Late pulmonary artery stenoses
It is interesting that late stenosis was seen only in the left pulmonary artery in our series. These stenoses were probably related to residual ductal tissue and become more evident with the growth of the patients. Further, any central stenosis of the right pulmonary artery would likely have been treated at the time of the Glenn anastomosis or at the time of the placement of the inferior vena cava to right pulmonary artery conduit.
A significant reduction of late atrial arrhythmias is probably the most important potential benefit of this procedure (10,12–19). Although the impact of atrial arrhythmias on survival in patients with the Fontan procedure is not yet clear, the development of supraventricular tachycardia or atrial flutter/fibrillation exposes long-term survivors to serious morbidity. Kaplan-Meier estimates of freedom from atrial tachyarrhythmias vary widely from 12.5% to 80%, depending on the Fontan population and the time of the follow-up (35–39). Antiarrhythmic drug therapy, antitachycardia pacing, and more recently radiofrequency ablation have proved useful in controlling the arrhythmias (40). Otherwise untreatable arrhythmias have been successfully treated in some patients by the Mavroudis procedure (41).
The Kaplan-Meier estimates of freedom from arrhythmias in our series is 83.8% at 15 years. This rate is acceptably low compared with the incidence of atrial arrhythmias after atriopulmonary connection (up to 40%) (2–4,40) or after total cavopulmonary intra-atrial connection (up to 20%) (35–39), although the comparison of series is difficult because of different durations of follow-up.
Our satisfactory long-term data are similar to mid-term results reported in 2001 (16,17) and more recently by Nakano et al. (19), showing a lower morbidity from arrhythmias than with the lateral tunnel. These last investigators reported that “the lateral tunnel procedure itself was a predictor of postoperative supraventricular arrhythmias” and these arrhythmias were more frequent in patients with a higher dilatation ratio of the tunnel and higher plasma atrial natriuretic peptide level. These data suggest that chronic stretch of the atrial wall could be an arrhythmogenic stimulus in the lateral tunnel compared with the extracardiac conduit. These protective effects of an extracardiac procedure on the development of late arrhythmias might be further explained by the avoidance of atriotomy and intra-atrial suture lines.
Nine percent (15 of 165) of the re-interventions in these patients were attributable to the lack of a transvenous approach to the atria and the need for surgical positioning of the pacing leads. Surgical re-intervention for late obstruction of the extracardiac conduit, the more controversial aspect of this procedure, occurred in only a single patient. Ten additional patients with conduit or left pulmonary artery stenosis underwent successful balloon dilation or stent implantation.
The poor results of the heart transplantation after extracardiac Fontan in our series (two of three patients died) confirm that patients with Fontan failure should be considered high-risk candidates for transplantation, as recently reported (42). The alternative approach (bidirectional cavopulmonary anastomosis with additional source of pulmonary blood flow) could represent the best bridge to heart transplantation, by lowering inferior vena caval pressure and preserving hepatic and renal function (42).
The late deaths occurred after heart transplantation (two patients) and in two patients with a pacemaker who died suddenly at home. The exact cause of death in these patients is unknown.
The most important limitation of this study is the number of patients lost to follow-up. However, the patients lost to follow-up were not significantly different in any way from the entire group.
After 15 years of follow-up, the overall survival, the functional status, and the cardiopulmonary performance of survivors of the extracardiac Fontan procedure compare favorably with these parameters in others series of patients who underwent surgery with the lateral tunnel approach. The incidence of late deaths, obstructions of cavopulmonary pathway, re-interventions, and arrhythmias is lower than that reported by others investigators late after other Fontan-type operations.
The authors thank Miss Orietta Castellacci for the editing of the manuscript.
This paper is dedicated to the memory of the late Dr. Cosimo Squitieri.
- Abbreviations and Acronyms
- forced expiratory volume in 1 s
- forced vital capacity
- magnetic resonance imaging
- Received August 3, 2005.
- Revision received December 5, 2005.
- Accepted December 30, 2005.
- American College of Cardiology Foundation
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