Surgical valve replacement in adults late after total cavo-pulmonary connection/Fontan procedure

Abstract

OBJECTIVES

There is dearth of data on long-term outcomes of systemic semilunar (SS) or atrioventricular (AV) valve operation in adult patients with a Fontan circulation. We describe a single-centre experience of adults who underwent valve surgery late after a Fontan procedure.

METHODS

We retrospectively reviewed all patients with a Fontan circulation who had a reoperation for severe valve disease during adulthood in our centre. Demographic, anatomical, clinical and periprocedural data and long-term outcome were retrospectively retrieved from our dedicated electronic hospital database and examined.

RESULTS

Out of 233 adults with a Fontan operation, 8 (7 males [88%]) had valve surgery during the study period. Indication for surgery was severe symptomatic valve regurgitation in all patients (of the SS valve in seven cases and of the left AV valve in 1). Mechanical prosthesis was implanted in all cases. At a median follow-up of 10 years (interquartile range 5–20), one patient died due to hepatitis C virus infection. All the remaining 7 patients experienced a significant improvement of the New York Heart Association class compared to the pre-operative state (P = 0.015); echocardiography showed stable systemic ventricle ejection fraction in absence of volume overload (50.1 ± 7.9% vs 51.6 ± 8.7%, P = 0.399) and well-functioning prostheses. No patient needed further operation nor heart transplantation.

CONCLUSIONS

Surgical SS valve replacement late after a Fontan operation in highly selected adult patients with valvular regurgitation performed in a tertiary dedicated centre resulted to be safe in our population and conveyed clinical benefit. Close monitoring of all Fontan patients developing valvular dysfunction is warranted, whereas future prospective research may refine selection criteria, optimal timing and outcomes.

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INTRODUCTION

The number of patients with a Fontan circulation reaching adulthood is growing and the presence of significant valve disease is more frequently observed. The optimal timing of cardiac surgical reoperation remains unclear. Evidence about the outcomes of systemic semilunar (SS) or atrioventricular (AV) valve operation in such adult patients is limited.

We describe a single-centre experience of adult patients with a Fontan circulation who underwent surgical reoperation of a cardiac valve, focusing on the indication, surgical details and short- and long-term clinical outcomes.

METHODS

This is a single tertiary centre retrospective study of all adult patients (aged >16 years) with a Fontan circulation, who had a reoperation for severe valve disease in adulthood between November 1999 and November 2021. Considering the paucity of data regarding the specific management of valve regurgitation in adults with a single ventricle physiology and the peculiarity of Fontan circulation and anatomy, which may further increase the well-known risks associated with resternotomy, and delicate cardiopulmonary physiology, accurate patient selection was performed and discussed in a multidisciplinary meeting, providing a ‘personalized’ approach. In out cohort, surgery for heart valve disease was reserved for symptomatic patients with echocardiographic evidence of severe valve disease without clinical or echocardiographic features of end-stage heart failure [New York Heart Association (NYHA) class <IV, systemic ventricle ejection fraction (EF) at most moderately impaired]. In case of SS valve severe regurgitation, also severe aortic root/ascending aorta dilation was considered.

Demographic, anatomical, clinical and periprocedural data and long-term outcome were examined. Data were retrospectively retrieved from our dedicated electronic hospital database. Mortality data were identified from electronic hospital records, automatically linked to the office of National statistics, which registries all UK deaths and are complete. As this is a retrospective study and original data were collected for routine clinical care and administration purposes, individual informed consent was not required (UK National Research Ethics Service guidance). The study was performed according to the Declaration of Helsinki.

Statistical analysis

Continuous variables were expressed as mean ± standard deviation or as median with interquartile range (IQR), as appropriate. Categorical data were expressed as number with percentages. A paired t-test was used to compare pre-operative and follow-up SVEF, while the Wilcoxon signed-rank test was used to compare pre-operative and follow-up NYHA class. A P-value <0.05 was considered statistically significant. All analyses were performed using SPSS (SPSS version 26, Inc., Chicago, IL, USA) statistical software.

RESULTS

Out of 233 adults (116 [49.8%] female) with a Fontan circulation, we identified eight patients who had valve surgery at age 26 ± 9.8, 11 ± 8.1 years from the original total cavopulmonary connection (TCPC) (5 [62.5%]) or TCPC conversion (3 [27.5%]). Valve surgery represented the sixth and fifth intervention for three patients and the fourth and third resternotomy for the remainder.

Demographic, surgical indication, type of operation

Baseline demographics and clinical characteristics are presented in Table 1. Seven patients were male (88%); the mean age at the time of Fontan operation was 14 ± 10 years. Primary congenital heart disease was tricuspid atresia in five patients (63%), pulmonary atresia in 3 (38%) with straddling right AV valve in 2. Systemic ventricular morphology was predominantly left (7 patients, 88%), whereas 4 patients had transposed great arteries with anterior and rightward aorta.

Seven patients had a TCPC with extracardiac conduit (ranging in size from 20 to 24 mm), whereas 1 had a lateral tunnel Fontan. Five patients had fenestration at the time of Fontan procedure, one of whom had transcatheter closure prior to valve surgery, such that at the time of valve surgery four patients had a patent fenestration. Two patients had previous pacemaker implantation for symptomatic bradyarrhythmia.

The pre-operative NYHA class was II in two patients and III in six, with mean echocardiographic SVEF 51.6 ± 8.7% (Table 2).

Indication for repeat surgery was symptoms (i.e. worsening NYHA class, objective reduction in exercise capacity) associated with semilunar valve aortic regurgitation in seven cases, pulmonary valve incompetence in 1 (Damus–Kaye–Stansel procedure with a hypoplastic aortic root), and severe left AV valve regurgitation in one. Among the seven patients with semilunar valve incompetence, important root dilatation (ranging 55–68 mm) was present in 4; they also had a previous composite root replacement with one patient having aortic valve repair. In all cases a mechanical prosthesis was implanted.

One patient, who had arch reconstruction at the time of valve replacement, had synchronous repair of iatrogenic bronchial injury.

Surgery outcomes and survival

Table 3 depicts follow-up information for each patient. There was no surgery-related perioperative mortality. The median bypass time was 202 min with a median cross-clamp time of 114 min. Circulatory arrest to replace a segment of the aortic arch was required in four patients, with a mean arrest time of 28.5 ± 13.9 min. Antegrade cerebral perfusion used in the remaining cases. Patients were cooled to a nadir temperature of 28–32 degrees, unless circulatory arrest was required. One patient had additional replacement of an epicardial pacing system for existing heart block. Pleural drains were placed in all patients and removed after a mean of 5.5 days (IQR 4–8). Post-operative complications included: left recurrent laryngeal nerve injury in one patient, prolonged chest tube drainage (>10 days) in one, post-operative renal replacement therapy in one and temporary tracheostomy in one. All patients were transfused with blood or clotting products. The median in-hospital stay was 27 days (IQR 13–49).

The single patient who had left AV valve replacement died of hepatocarcinoma related to long-standing and reactivated hepatitis C virus infection 2 years after the operation. At a median follow-up of 10 years (IQR 5–20), 3/7 of the remaining patients were in class NYHA I and four in NYHA II, representing significant improvement compared to the pre-operative state (P = 0.015). Echocardiography showed stable SVEF compared to baseline (50.1 ± 7.9% vs 51.6 ± 8.7%, P = 0.399), in the absence of volume overload, with valve prosthesis well positioned and functioning in all patients (mean gradient 16 ± 4.4 mmHg). None of the patients needed further operation or heart transplantation during the study period.

DISCUSSION

Our case series provides evidence that in selected adult patients with a Fontan circulation, surgical valve replacement is safe and confers symptomatic improvement with good longer-term outcome (Central Image). This is a particularly important finding as survival for patients undergoing a Fontan procedure in the current era can reach 85% at 20 years [1, 2]. There was no cardiac-related mortality in this selected adult cohort of patients and the SVEF at follow-up remained stable. Moreover, there was a significant clinical improvement, as testified by the significant difference in pre- and post-operative NYHA class.

Over the past two decades, the number of adults with a Fontan circulation has significantly increased, due to both extended indication for this path to a wider spectrum of complex congenital heart diseases and to improvements in clinical and surgical management [3, 4].

This makes it of utmost importance to increase knowledge not only about surgery-related complications but also concerning clinical evolution and possible issues that could manifest over time. Long-term treatment options for these patients are limited. Benefit from new drugs such as sacubitril/valsartan or dapaglifozin still needs to be confirmed, albeit some initial data seem to be encouraging [5, 6]. While cardiac transplantation remains a valid, definitive strategy to treat end-stage heart failure and its complications in these patients; this needs to be considered in the context of a shortage of available organs and the higher percentage of human leucocyte antigen antibodies in these patients, due to previous operations and blood transfusion.

Moreover, patients with a Fontan circulation often have other organs dysfunction, which makes transplant more challenging and, in some, contraindicated.

It is paramount to optimize haemodynamics in this growing cohort of patients. Many percutaneous interventions are performed were possible to relieve obstruction [6], whereas catheter ablations are employed to control cardiac rhythm, maintain AV synchrony and pharmacotherapy to optimize preload and potentially improve transpulmonary flow. While repeat valve surgery can be high risk in these patients, it can allow for further optimization of the circulation [7], improving symptoms and halting or reversing the ventricular dilation seen with severe AV or SS valve regurgitation that is associated with significant mortality in patients with a Fontan circulation [3, 8–10]. Most of available data about valvular surgery in patients with single ventricle physiology come from paediatric populations. Wong et al. [11] described unfavourable outcomes in children with a Fontan circulation operated on for severe AV valve regurgitation. Alshami et al. [12] described adverse outcomes in a paediatric population with single ventricle physiology operated on for either AV valve or SS valve regurgitation. In particular, the outcome was worse in patients who underwent AV valve replacement [12].

At present, there is a paucity of data concerning cardiac reoperation outcomes in adult Fontan patients, excluding TCPC conversion or revision.

Nakayama et al. [13] reported excellent 10-year outcomes in the subgroup of Fontan adults who underwent valvular intervention.

Bobylev et al. [14] reported an interesting case of semilunar valve replacement with decellularized homograft after a Damus–Kaye–Stansel anastomosis and Fontan procedure, with evidence of good clinical status and normal valve prosthesis functioning at 2-year follow-up.

An interesting case series was published by the Mayo Clinic Group [15]; the authors reported that in their 47-year experience, 15 out of 1176 patients required SS valve intervention, of which 2 were performed at the time of initial Fontan and 13 during follow-up. Cardiac reoperation was required in five cases and six deaths were reported. The remaining nine patients were followed up for a median of 11 years, during which no major adverse cardiovascular events occurred, and valvular function remained satisfactory. Compared to the Mayo Clinic experience [15], our surgical valve reintervention with SS replacement was more frequent over time (7 out of 233 [3%] vs 15 out of 1176 [1.3%]). Similarly to the Mayo Clinic experience [15], there was no perioperative death. Longer-term mortality in our cohort was lower (1 out of 8 [13%] vs 6 out of 15 [40%]), with no cardiovascular deaths, while in their report four patients died due to cardiac or cardiac-related adverse events. In addition, in our population, SVEF remained stable during follow-up in all patients, while colleagues at the Mayo Clinic reported three cases of SVEF drop [15]. To conclude, in our series, no patient required repeat cardiac surgery, whereas 5 patients from the Mayo cohort required reoperation. Patient selection and timing are likely to have contributed to this. Prospective large studies are warranted to establish the optimal timing for intervention.

Limitations

We acknowledge that the present study has some limitations. First, the retrospective design and the small patients population enrolled in a single centre could have influenced our results. However, the population of adults with a Fontan circulation operated on for valve regurgitation in our centre in proportion is greater than the largest adult cohort described until now by the Mayo Clinic [15]. Nevertheless, our study is mainly meant to be descriptive rather than conclusive about the scarcely investigated issue of valve surgery outcomes in adults with Fontan circulation. In the current era, transplant seems to be the only definitive option for these patients, even though access to this treatment is often limited by the presence of significant comorbidities at a young age, relative contraindication given by elevated antibodies, and collaterals. Moreover, the availability of a congenital surgeon is requested by the transplant team. Valve surgery is a rare operation in adults with a single ventricle physiology, often not performed due to the dearth of data in literature. Our paper wants to support the concept that these patients, when properly selected, may benefit from valve surgery, although it remains a high-risk operation.

In addition, the lack of novel heart failure medications during the timespan of our study could have influenced our results. However, we cannot assume that these drugs would have changed the prognosis of our patients, as there is still a lack of data about their safety and efficacy in adults with a Fontan circulation.

To conclude, we acknowledge that the wide diversity of follow-up length among our patients may prevent from establishing the timing of improvement and from performing specific analyses. However, reporting also the outcome of patients operated on more than 15 years ago may suggest the persistence of good clinical status even over a very long period of time.

CONCLUSIONS

Surgical SS valve replacement late after a Fontan operation in highly selected adult patients with valvular regurgitation performed in a tertiary dedicated centre resulted in being safe in our population and conveyed clinical benefit. Close monitoring of all Fontan patients developing valvular dysfunction is paramount, and future prospective and multicentric research is warranted to refine selection criteria, optimal timing and outcomes.

FUNDING

None declared.

Conflict of interest: none declared.

DATA AVAILABILITY

The data underlying this article are available in the article.

Author contributions

Veronica Lisignoli: Data curation; Writing—original draft. Giulia Iannaccone: Data curation; Formal analysis; Project administration; Writing—original draft. Michael Murphy: Methodology; Validation; Writing—review & editing. Polona Kacar: Data curation. Sara Moscatelli: Data curation. Wei Li: Supervision; Writing—review & editing. Darryl Shore: Supervision; Writing—review & editing. Michael A. Gatzoulis: Supervision; Validation; Visualization; Writing—review & editing. Claudia Montanaro: Conceptualization; Methodology; Project administration; Supervision; Validation; Writing—review & editing

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Jürgen Hörer and the other anonymous reviewers for their contribution to the peer review process of this article.

REFERENCES

ABBREVIATIONS

ABBREVIATIONS
 
• EF

  Ejection fraction

 
• IQR

  Interquartile range

 
• NYHA

  New York Heart Association

 
• TCPC

  Total cavopulmonary connection

Author notes