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Ann Thorac Surg 2005;80:29-36
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

Atrioventricular Valve Procedures with Repeat Fontan Operations: Influence of Valve Pathology, Ventricular Function, and Arrhythmias on Outcome

Constantine Mavroudis, MDa,c,*, Robert D. Stewart, MD, MPHa,c, Carl Lewis Backer, MDa,c, Barbara J. Deal, MDb,d, Luciana Young, MDb,d, Wayne H. Franklin, MD, MPHb,d

a Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois
b Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois
c Division of Cardiovascular-Thoracic Surgery, Children’s Memorial Hospital, Chicago, Illinois
d Division of Cardiology, Children’s Memorial Hospital, Chicago, Illinois

Accepted for publication January 28, 2005.

* Address reprint requests to Dr Mavroudis, Division of Cardiovascular-Thoracic Surgery, M/C 22, Children’s Memorial Hospital, 2300 Children’s Plaza, Chicago, IL 60614 (Email: cmavroudis{at}childrensmemorial.org).

Presented at the Fifty-first Annual Meeting of the Southern Thoracic Surgical Association, Cancun, Mexico, Nov 2–4, 2004.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 Acknowledgments
 References
 
BACKGROUND: The purpose of this study is to analyze atrioventricular valve procedures when performed in association with repeat Fontan operations and to determine the influence of atrioventricular valvar pathology, ventricular function, and arrhythmias on outcome.

METHODS: Between December 1994 and August 2004, 80 patients had repeat Fontan operations that included arrhythmia surgery (78 of 80), venous pathway revision (78 of 80), atrioventricular valve repair-replacement (15 of 80), and other associated procedures. Mean ages were the following: at operation, 20.3 ± 8.4 years; at prior Fontan, 7.1 ± 5.8 years. Atrioventricular valve procedures were performed on 8 functionally mitral and 7 functionally tricuspid valves. The average cross-clamp and cardiopulmonary bypass times were 61.9 ± 42.8 minutes and 218 ± 82 minutes, respectively.

RESULTS: Ventricular dysfunction (8% vs 54%, p < 0.0001), valvar dysfunction (13% vs 25%, p < 0.05), and atrial arrhythmias (18% vs 86%, p < 0.0001) increased during the preceding 12.0 ± 4.7 years before the most recent Fontan operation. Multivariate analysis for death, orthotopic cardiac transplantation (OCT), or renal dialysis showed severe ventricular dysfunction, age greater than 25 years, right or ambiguous functional ventricle, and ischemic time greater than 100 minutes to be highly significant. Notably, cardiac index, elevated end diastolic pressure, and atrial fibrillation were not predictors of outcome. Mitral valve repairs were inconsistent due to probable technical misjudgments; most tricuspid valves could not be repaired. Operative and late mortality were 1.2% and 5.0%, respectively. Emergent and late OCT were 1.2% and 3.7%, respectively.

CONCLUSIONS: Risk factors for poor outcome are severe ventricular dysfunction, right or ambiguous single ventricle, age greater than 25 years, and ischemic time greater than 100 minutes. Mitral valves are potentially more amenable to repair than are tricuspid valves. Prosthetic valve replacement should be considered when valve repair is questionable.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Discussion
 Acknowledgments
 References
 
Patients with single ventricle who have undergone a Fontan operation have lifetime risks of arrhythmias, ventricular dysfunction, atrioventricular valvar dysfunction, thromboembolism, and protein losing enteropathy [1–15]. In the modern era, staged strategies and concomitant operations have improved outcomes by correction of atrioventricular valve insufficiency, relief of outflow tract obstruction, and ventricular unloading (bidirectional Glenn) well before completion Fontan procedures [16,17]. Nevertheless, some patients still present for repeat Fontan procedures who will require atrioventricular valve repair-replacement, which oftentimes is performed in association with venous pathway revision, arrhythmia surgery, and pacemaker implantation [18–26]. The purpose of this study is to (1) determine the influence of atrioventricular valvar pathology, ventricular function, and arrhythmias on the development of atrioventricular valve insufficiency in patients who present for repeat Fontan procedures and (2) to review the outcome of those patients who had atrioventricular valve repair-replacement in association with venous pathway revision, arrhythmia surgery, pacemaker implantation, and repair of other cardiac anomalies.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Discussion
 Acknowledgments
 References
 
Study Design
The optimal study design to determine the incidence, severity, and reparative feasibility of atrioventricular valve insufficiency in single ventricle patients has yet to be implemented. Such a study would require a multiinstitutional, long-term, longitudinal registry, which would catalogue the types of diagnoses and atrioventricular valves that are most susceptible to insufficiency. Much, but not all of this information is known from autopsy studies [27]. However, the response to reparative therapy over time and at different stages of orthoterminal correction is not known. Furthermore, the types of repairs should be uniform for each type of valve: tricuspid, mitral, and common atrioventricular valves. In addition, the long-term durability of valve repair ought to be assessed as it relates to the long-term durability of prosthetic valve replacement. Variables such as the effect that the various degrees of valvar insufficiency have on atrial arrhythmias, ventricular function, pulmonary artery pressure, organomegaly, and protein-losing enteropathy, to name a few, need to be addressed.

Unfortunately, the present study has not been designed to answer all these questions. Only patients who had repeat Fontan procedures are included. Those who were treated by catheter ablation, transvenous invasive techniques, or by cardiac transplantation before repeat Fontan procedures are unknown and therefore our results may be biased in so far as all patients with operable lesions did not present for operative therapy.

Patient Characteristics
We defined our study group as those 80 consecutive patients who had repeat open heart Fontan operations between December 1994 and August 2004. This report significantly updates our prior experience (41 patients in a previous study [23]). This series includes 75 patients with Fontan conversion and arrhythmia surgery, 3 patients with atrioventricular valve replacement without venous pathway conversion (3 had arrhythmia surgery; 2 at the most recent Fontan and the other 1 at a prior Fontan), and 2 patients who had venous pathway conversion without arrhythmia surgery.

The preoperative anatomic, hemodynamic, and arrhythmia characteristics of the 80 patients at the time of the penultimate Fontan procedure are noted in Table 1, and are contrasted with the same characteristics as noted at the time of the current surgery in Table 2. The mean interval between procedures was 12.0 ± 4.7 years. A small number of patients (n = 2) had valve repair at one of the preliminary staged operations and underwent prior completion Fontan surgery without further valve intervention; five patients had failed antecedent valve repair-replacement at the preceding staging operations. Important preoperative hemodynamic and clinical findings are noted in Table 3. Hemodynamic abnormalities were present in 75 of 80 patients. Characterization of ventricular function was based on qualitative assessment by echocardiography immediately prior to surgery and at follow-up. Atrioventricular valve regurgitation was classified as mild, moderate, or severe based on the immediate preoperative echocardiographic assessment and at follow-up.


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  		Table 1. Prevalence of Ventricular Dysfunction, Tachyarrhythmias, and Atrioventricular Valve Regurgitation (AVVR) at Penultimate Fontan Operation
 

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  		Table 2. Prevalence of Ventricular Dysfunction, Tachyarrhythmias, and Atrioventricular Valve Regurgitation (AVVR) at Most Recent Fontan Operation
 

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  		Table 3. Hemodynamic and Clinical Findings at Repeat Fontan
 
These procedures were performed using the same operative principles and techniques as previously reported [18–26]. Elective femoral-femoral bypass was employed in seven patients before the resternotomy; semielective femoral-femoral bypass was instituted after partial resternotomy due to excessive bleeding or potential dangerous conditions in two patients; and urgent femoral-femoral bypass was instituted for unwanted cavitary entry in three patients.

Total cavopulmonary artery connections were performed in 78 of 80 patients (97.5%); early on by lateral tunnel (n = 8) and later by extracardiac conduits (n = 70). The remaining two had atriopulmonary revision in one and conversion to 11/2 ventricular repair in the other. The majority had associated arrhythmia surgery (78 of 80 patients [97.5%]) and pacemaker implantation (77 of 80 patients [96.3%]). The pacemakers implanted have changed over the past 10 years, reflecting surgical outcome needs as well as technologic enhancements. Initially atrial antitachycardia pacemakers were implanted, but with the decreased incidence of tachycardia associated with the more extensive right atrial maze and the need for rate responsiveness, atrial rate responsive pacemakers were implanted. Most recently, newly available dual chamber antitachycardia pacemakers have been implanted due to the potential need for ventricular pacing during late follow-up, and to avoid the risk of reoperation; most of these pacemakers are programmed for atrial pacing only. Atrioventricular valve repair-replacement was performed in 15 of 80 (18.8%) patients. Other associated procedures included ascending aortic aneurysm resection, aortic arch repair, significant pulmonary artery arterioplasty, and relief of pulmonary venous obstruction. The mean age at operation was 20.3 ± 8.4 years, the mean age at the prior Fontan procedure was 7.1 ± 5.8 years, the mean Fontan interval was 12.0 ± 4.7 years, and the mean age of onset of atrial arrhythmias was 14.1 ± 7.9 years. On the average, patients failed three antiarrhythmic medications.

The average cross-clamp time was 61.9 ± 42.8 minutes and the average cardiopulmonary bypass time was 218 ± 82 minutes (range, 75–440 minutes). Deep hypothermia and circulatory arrest was used in one patient for concomitant rerepair of the aortic arch.

Valve Repair Procedures and Prosthetic Heart Valves
Fifteen patients underwent atrioventricular repair-replacement; the clinical factors and individual critical review are summarized in Tables 4 and 5. In general, the most common lesion for mitral repair-replacement was tricuspid atresia and the most common lesion for tricuspid valve repair-replacement was hypoplastic left heart syndrome. Mitral valve repairs were performed in 6 of 8 patients; mitral valve replacements were performed in 2 of 8 patients. Tricuspid valve repairs were performed in 3 of 7 patients; tricuspid valve replacements were performed in 4 of 7 patients. In general, type of valve repair was determined by the anatomic conditions that were present: valvar clefts were sutured; annulus reducing techniques were performed by suture and ring prostheses; and valvuloplasty remodeling was performed by the Alfieri side-to-side suture technique [28]. Based on intraoperative transesophageal echocardiography, one patient with Ebstein’s anomaly had moderate tricuspid valve regurgitation after repair and underwent immediate tricuspid valve replacement. Five patients underwent valve replacement without attempted repair based on morphologic characteristics and prior replacements-repairs.


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  		Table 4. Mitral Valve Repair-Replacement for Repeat Fontan Operation
 
Statistical Analyses
Univariate analyses were performed with Fisher’s exact test or a two-tailed {chi}2 test where appropriate. Multivariate logistic regression analysis was performed with an initial model including all variables from the univariate analysis with a p value less than 0.10. Final model was achieved using backward stepwise progression. StatView statistical software (SAS Institute, Cary, NC) was used for all analyses.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Discussion
 Acknowledgments
 References
 
During the 12.0-year interim between the penultimate Fontan procedure (Table 1) and the repeat Fontan procedure that was performed at our institution (Table 2), a significant number of patients developed atrial arrhythmias (18% vs 86%, p < 0.0001), valvar dysfunction (13% vs 25%, p < 0.05), and ventricular dysfunction (8% vs 54%, p < 0.0001). There was a higher incidence of valve dysfunction in patients with right ventricular anatomy than in patients with left ventricular anatomy at the prior and at the repeat Fontan procedure (p < 0.0001).

Operative mortality was 1 of 80 (1.2%) patients. Emergent OCT occurred in 1 of 80 (1.2%). Reoperation for bleeding occurred in 1 of 80 (1.2%). Deep sternal wound infections occurred in 2 of 80 (2.5%). Acute renal failure occurred in 7 of 80 (8.7%). Chest tube duration for continued drainage was 9.3 ± 5.5 days; and length of stay was 15.2 ± 14.8 days. Late mortality was 4 of 80 (5.0%) at 6 months (ventricular failure), 8 months (ventricular failure), 1 year (renal failure), and 2 years (sudden death due to premature atherosclerotic coronary artery disease) postoperatively. Late OCT occurred in 3 of 80 (3.7%) patients due to decremental ventricular dysfunction.

Univariate analysis (Table 6) was performed to assess risk factors for death, OCT, or renal failure requiring dialysis. Importantly, preoperative cardiac index, elevated end diastolic pressure, moderate atrioventricular valve regurgitation, and atrial fibrillation were not predictors of outcome. Multivariate analysis (Table 7) showed that severe ventricular dysfunction, older age (> 25 years), right or ambiguous single ventricle, and prolonged ischemic time greater than 100 minutes are significant predictors for these adverse outcomes.


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  		Table 6. Univariate Regression Analysis of Risk Factors for Death, Transplant, or Dialysis
 

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  		Table 7. Multivariate Logistic Regression Analysis of Risk Factors for Death, Transplant, or Dialysis
 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Discussion
 Acknowledgments
 References
 
This paper demonstrates the time course for development of ventricular dysfunction, atrioventricular valve dysfunction, and arrhythmias after orthoterminal correction. Ventricular dysfunction and tachyarrhythmias progressed independently of ventricular morphology, a finding not previously reported. However, atrioventricular valve dysfunction was present significantly more often in systemic right ventricles and progressed over time [15].

Based on our results and critical analysis, mitral valve repairs seem more likely to be successful than tricuspid repairs. Of the eight mitral valves that were addressed, two had valve replacement, one for mitral stenosis due to a prior repair early in life and another due to a myxomatous valve. The other six had a potpourri of different repairs (Table 4) only two of which had an excellent outcome (Alfieri and Carpentier repairs). The others had fair results probably because of technical-judgment errors. For instance, the two patients who had cleft repairs might have benefited by the addition of an annular ring; the other patient who had an Alfieri repair would have benefited by a pledgeted suture instead of the simple suture, which dehisced. Previous reports [27, 29] have stressed that the mitral valve in patients with single ventricle is oftentimes abnormal. Nevertheless, it would appear by other reports [11] that these valves are reparable if the appropriate techniques are used. In contrast, our experience with tricuspid valve operations is somewhat different. We found that attempted repair in four patients resulted in one acceptable result. The other three had immediate valve replacement in one and continued valve dysfunction in the other two who may have benefited by valve replacement. Three patients had valve replacement as the first procedure without initial attempted repair resulting in two acceptable outcomes despite moderate ventricular dysfunction. The systemic tricuspid valve is very difficult to repair as confirmed by our small experience and as reported by others [30]. The overall number of cases in our series is small and does not lend itself to intragroup statistical analysis; however it would appear that mitral valves are potentially easier to repair than tricuspid valves and that valve replacement should be seriously considered when valve repair is questionable.

In our series, independent risk factors for poor outcome as measured by death, cardiac transplantation, or renal failure requiring dialysis were severe ventricular dysfunction, age greater than 25 years, single right or ambiguous ventricle, and prolonged ischemic time (> 100 minutes). It was surprising to find that quantitative assessment of ventricular dysfunction such as end diastolic pressure greater than 12 and measures of cardiac index were not significant predictors of outcome. We did find, however, that atrioventricular valve repair prior to the penultimate Fontan did correlate with late severe ventricular dysfunction (of 11 documented early atrioventricular valve repairs prior to the penultimate Fontan, 3 patients had late severe ventricular dysfunction versus 2 late severe ventricular dysfunction in 69 patients without early atrioventricular valve repair; p < 0.02). Clearly, a more sensitive analysis incorporating a combination of ventricular function characteristics is needed to better define which patients would benefit from repeat Fontan surgery versus cardiac transplantation.

From the outset it would seem that reoperation in patients with severe ventricular dysfunction would not be indicated. However, we reasoned that repair of valvar pathology, revision of pathway obstructions, and ablation of arrhythmias with paced regular rhythm (in some cases multiple site ventricular pacing) might improve ventricular function, as has been noted in some patients who had ablation for rapid atrial tachycardia [31, 32]. Our data indicate that isolated severe ventricular dysfunction in patients with single ventricle is unlikely to improve with the reparative procedures that have been described herein. These patients may be better served by cardiac transplantation. The difficulty is to distinguish which patients have permanent and irreversible ventricular dysfunction. Our present clinical attempts to distinguish between these groups with moderate ventricular dysfunction is to rate the temporal influence of valvar dysfunction and arrhythmias on ventricular dysfunction and make a clinical decision whether to move forward with repeat Fontan procedures or cardiac transplantation. Clearly by our analysis, moderate ventricular dysfunction was not an independent risk factor for poor outcome indicating that repeat Fontan operations can be performed safely in this population even with the addition of arrhythmia surgery and valve repair-replacement as long as the ischemic time does not exceed 100 minutes. The overall operative mortality in this entire group of repeat Fontan procedures is 1.2%, which compares favorably with other repeat Fontan series [33–39]. Even so, late deaths will occur and cardiac transplantation will be necessary in a certain number of patients. We hope to shed some light on this problem over the next few years during which time our series will mature enough to make meaningful comparisons for the long term.

We conclude that in our population of repeat Fontan patients there was a significant decrease in ventricular function and an increase in atrial arrhythmias, regardless of ventricular morphology in the interim between Fontan procedures. Atrioventricular valve dysfunction was significantly related to right ventricular morphology. Preoperative risk factors for poor outcome (death, cardiac transplantation, and renal failure requiring dialysis) include severe ventricular dysfunction, right or ambiguous single ventricle, age greater than 25 years, and ischemic time greater than 100 minutes. Mitral valves are more amenable to repair than are tricuspid valves. While valvar repair is preferable, prosthetic valve replacement should be seriously considered when valve repair is questionable.


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
Acknowledgments
 References
 
DR IRVING L. KRON (Charlottesville, VA): Gus, I want to congratulate you on wonderful results, and only 1% operative mortality is clearly a reflection of your surgical skills and selection process. I would like to comment on what you have focused on. About 10% of the patients had late heart failure-ventricular dysfunction. Was the problem the valve repair or the failing ventricle? I went through the cases, and Gus, by the way, analyzed these all beautifully, and found that valve repairs, as you mentioned, were only partially successful. It seemed like the primary valve replacements almost did better. This is counterintuitive because in the adult literature, including our own series, in patients with cardiomyopathy, valve repairs are far better than valve replacements. So what is the bottom line? When can you do a valve repair, because you now have it figured out I am sure? When do you use primary valve replacement at the time of redo? And finally, what level of ventricular dysfunction prompts primary transplant? Thank you.

DR MAVROUDIS: Thank you very much for those excellent questions. What we call severe dysfunction is based on echocardiographic analysis in a graded subjective appraisal of mild, moderate, severe ventricular dysfunction. We operate on patients with severe dysfunction when we think that the arrhythmia is a significant etiological factor for ventricular dysfunction. We add valve repair-replacement and multisite atrioventricular pacing to this therapeutic regimen with the hope that ventricular function will improve. Oftentimes this regimen is successful, but not all patients respond leaving us to ponder more the question of patient selection. We are presently looking into this very important screening process as to which patients would benefit from Fontan conversion, arrhythmia surgery, and multisite atrioventricular pacing and which patients would do better with cardiac transplantation.

Valve dysfunction in patients with single ventricle is not as straightforward as in patients with two normal ventricles. The mitral valve in tricuspid atresia is not a normal mitral valve. This has been discussed by a number of authors, notably Van Praagh [27], who thinks that during embryologic development, part of the tricuspid valve gets incorporated into the mitral valve. The valve annulus is larger, the leaflets are not normal as they are in a mitral valve, and I think that this may be one of the reasons why we haven’t had a very good repair of this valve in our series. Now, Imai from Japan has done a very good job of this and he repairs them very well; maybe he does it better than we do. In our hands it appears, at least from this data, Irv, that you are right, that probably valve replacement is better than valve repair. This is not to say that we wouldn’t try a valve repair in future patients. I am hesitant to endorse the idea of universal valve replacement in these circumstances, because for me to tell you that valve replacement is better than valve repair in every case is probably not the right message. The right message is that we ought to apply better reparative techniques, and use valve replacement when valve repair fails or when valve repair from the outset is not feasible.

DR KIRK R. KANTER (Atlanta, GA): Gus, this is a remarkable series in very high risk patients with excellent results. You categorized your valves into tricuspid and mitral, leaving out a group of patients with common atrioventricular valves as seen with unbalanced atrioventricular septal defects or heterotaxy syndrome. Did you not have any in this series or did you just not create a separate group for common AV valves? If you had any of these patients, how did you deal with those challenging valves?

DR MAVROUDIS: First of all, you have to recognize that these patients had an average age of 20 years; some of them were 35, one of them was 45 years old. Simply, that many years ago we didn’t do very well with patients with complete AV canal single ventricle type of anatomy, and that is the reason why we haven’t seen many. We saw actually one patient, who had a complete AV canal, left dominant, and had mitral valve repair at the penultimate Fontan. Over the intervening years the valve became stenotic; we replaced the mitral valve with a prosthetic valve. I imagine that more of these patients with unbalanced atrioventricular septal defects will be seen in the future, and we will use a number of techniques to repair the common atrioventricular valve, or replace it, if needed.

DR ERLE H. AUSTIN (Louisville, KY): I echo the congratulations of the other discussants. These are excellent results. In your univariate analysis, did you include the mechanism of the regurgitation? Not all pediatric echocardiographers give us the same information that we get from our adult echocardiographers as to why the valve leaks. In some cases there may be a simple cleft, which you would obviously repair. Other times you might find a very difficult valve to repair based on Carpentier’s criteria. Could you comment on that?

DR MAVROUDIS: For instance, we had two patients in our series that we did not consider to be candidates for mitral valve repair. One patient had a myxomatous mitral valve and the other had severe right ventricular dysfunction. In both cases we elected valve replacement as the best surgical approach and did not consider valve repair as an option. I think the decision as to whether to replace or repair the mitral valve depends on anatomic as well as physiologic considerations. Given that our series is so small and so varied, I do not think we can offer a clear-cut analysis as to when to repair or not to repair a mitral valve. Instead, we have written about our own experience in this paper in the hope that it will guide others to determine the proper management course in these very difficult patients.


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  		Table 5. Tricuspid Valve Repair-Replacement for Repeat Fontan Operation
 

   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 Acknowledgments
References
 
The authors thank Patricia Heraty and Melanie Gevitz for their research and editorial assistance.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 Acknowledgments
 References
 

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