Surgical management of failing Fontan circulation: results from 30 cases with 285 patient-years follow-up

Abstract

 

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OBJECTIVES

Fontan patients are known to suffer from clinical attrition over the years, which has been characterized as Fontan failure. We sought to evaluate the clinical outcomes of such Fontan patients undergoing surgical management in a 25-year, single-centre experience.

METHODS

A retrospective single-centre analysis of patients undergoing surgical treatment for failing Fontan between 1995 and 2020, including any reoperations when ventricular function was preserved, or a heart transplant (HTx), when ventricular contractility was impaired. We analysed survival, indications for surgery and early and late complication rates.

RESULTS

We collected 30 patients (mean age 24.7 years) who required surgery after a mean time of 19.3 years from the original Fontan procedure: Fontan conversion in 21 (70%, extracardiac conduit in 19, lateral tunnel in 2), a HTx in 4 (13.3%) and other reoperations in 5 (16.7%). The most common indications for surgery were tachyarrhythmias (63.3%) and severe right atrial dilatation (63.3%). Overall survival at the 1-, 5-, 10- and 20-year follow-up examinations were 75.9% [95% confidence interval (CI): 91.4–60.4%], 75.9% (95% CI: 91.4–60.4%), 70% (95% CI: 78–52%) and 70% (95% CI: 78–52%), respectively. The most frequent complications were postoperative tachyarrhythmias (50%) and late Fontan-associated liver disease (56.5%). HTx and Fontan conversion provided comparably good outcomes compared to other reoperations (P = 0.022).

CONCLUSIONS

Surgery for failing Fontan can be performed effectively with overall good long-term survival. However, early and late morbidities are still a significant burden. Because other reoperations performed when patients presented with contraindications for a HTx have carried high mortality, close clinical follow-up is mandatory, and an earlier indication for Fontan conversion or a HTx is advisable to optimize outcomes.

INTRODUCTION

Since its first description in 1971, the Fontan operation has enabled thousands of children to survive life-threatening congenital heart diseases and reach adulthood. The limitations of the original atriopulmonary (AP) techniques, such as arrhythmias, right atrium (RA) dilatation and thrombosis and chronic systemic venous hypertension, are well known. Despite all the technical refinements of the AP connection described through the years, this ingenious procedure has shown the late drawbacks of an unnatural circulation, characterized by coexisting elevated systemic and pulmonary venous pressures and reduced cardiac output, i.e. Fontan paradox, resulting finally in the failing Fontan [1–8].

A heart transplant (HTx) remains the definitive treatment for failing Fontan, with encouraging midterm and long-term results [9–14]. However, timing and indications for an HTx in the Fontan population are still controversial. In fact, it is often hard to list for transplant a patient who is seemingly doing well but slowly declining, On the contrary, waiting too long can create situations in which the transplant risk becomes too high due to the advanced chronic multi-organ dysfunction peculiar to such patients. In addition, the high rate of human leucocyte antigen sensitization and the scarcity of adequate donors may severely affect the post-transplant outcome.

To minimize Fontan failure drawbacks and postpone an HTx, a pioneering surgical conversion to total cavopulmonary connection (TCPC) was introduced by Mavroudis [4] in patients with a preserved ventricular function and an AP connection. The better haemodynamic efficiency of TCPC is the rationale of the Fontan conversion surgery, which has been adopted by several centres worldwide, with encouraging early results [4–7] and with effective prolongation of Fontan longevity.

We report our institutional experience with surgical management of patients with failing Fontan since 1995, comprehensive of Fontan conversion and HTx, highlighting indications and outcomes.

MATERIALS AND METHODS

Patients

This is a retrospective observational single-centre study of patients with failing Fontan, unresponsive to medical therapy, who required surgical management between July 1995 and July 2020. The study was approved by our institutional ethics committee (protocol nt42n/AO/20); the need for patient consent was waived.

Failing Fontan circulation was defined as the presence of ≥1 of the following: New York Heart Association (NYHA) functional class > II; drug-refractory arrhythmias; RA thrombosis or systemic embolism; severe RA dilatation; haemodynamic obstruction in the Fontan circuit (either on the systemic or pulmonary side); protein-losing enteropathy (PLE); severe atrioventricular valve regurgitation; and portal hypertension with Fontan-associated liver disease (FALD).

If the original Fontan procedure was an AP variant, with preserved single-ventricle function [ejection fraction (EF) > 50%], a conversion to TCPC [by means of a lateral tunnel (LT) or an extracardiac conduit (ECC)] was indicated. On the contrary, an HTx was indicated when ventricular function was impaired (EF < 40%) or if the patient had already been converted to TCPC.

Other types of surgical procedures were performed when a residual defect was considered amenable to effective surgical management or if contraindications for an HTx or conversion were evident. Consequently, patients were divided into 3 study groups according to the type of surgical approach: Fontan conversion, HTx and other reoperations. Clinical and follow-up data were collected from patient records. Early adverse events (AE) included effusions (pleural/pericardial/ascites); arrhythmias and onset of complete atrioventricular block (AVB); acute kidney injury (AKI); bleeding; infections; abdominal disease; and liver failure. Late AE were FALD (defined by ≥2 of the following: spleen diameter >12 cm; portal vein diameter >12 mm; slow portal vein flow; oesophageal varices); tachyarrhythmias; PLE; need of a pacemaker implant; need for reoperation; and death.

Primary outcomes were survival (defined as time from surgery to death; patients without the event of interest were censored at the last available follow-up) and onset of AE; the secondary outcome was NYHA functional class status at the last follow-up.

Surgery

Fontan conversion was accomplished as described elsewhere [4]: on cardiopulmonary bypass, the AP connection was taken down, and the Fontan circuit was restored using an LT with heterologous pericardium or ECC (most recently) using a polytetrafluoroethylene tube graft (size range 18–26 mm, median 22 mm). In addition we performed RA reduction plasty in severely dilated atria to prevent RA thrombosis; atrial cryo- or radiofrequency ablation in all patients presenting with untreatable supraventricular tachyarrhythmias; epicardial atrioventricular leads were routinely implanted after 2008, whereas a pacemaker was implanted on demand (i.e. preoperative advanced AVB, onset of AVB after ablation procedure).

When an HTx was required, it was performed through a standard bicaval technique, with pulmonary artery patch plasty whenever necessary.

Statistical analyses

Data are summarized as mean [standard deviation (SD)] or median [interquartile range] for continuous variables, as counts and percentages for categorical variables. The normality of quantitative variables was checked by graphical assessment. Quantitative variables were compared across groups with the Kruskal–Wallis test and categorical variables, with the Fisher’s exact test. Survival was estimated with the Kaplan–Meier method along with the 95% confidence interval (CI) at 1, 5, 10 and 20 years of follow-up. Comparison between groups was made with the log-rank test. Due to the low numerosity and the high incidence of AE, the Kaplan–Meier estimates of freedom from AE were not formulated. Significance was set at P-value <0.05. Analyses were performed using SPSS 23.0 (IBM Corporation, Armonk, NY, USA).

RESULTS

Baseline characteristics

Thirty patients [63.3% men; mean age, 24.7 (SD: 8.5) years] required a surgical reoperation for failing circulation at a mean interval of 19.3 (SD: 9) years from the original Fontan procedure. According to our data, the estimated prevalence of Fontan failure in the 1995–2020 time frame was 30/216 (13.8%). The most common anatomical diagnosis was tricuspid atresia (60%), followed by double inlet left ventricle (13.3%; Table 1).

The original Fontan operation comprised an AP connection (Kreutzer or Bjork variants) in 22 (73.3%) patients, an LT in 6 (20%) and an ECC in 2 (6.7%). The most frequent indications for reoperation were refractory arrhythmias in 19 (63.3%), severe RA dilatation in 19 (63.3%) and NYHA functional class > II in 15 (50%; Table 1). Twenty-seven patients (90%) had >1 indication.

Surgical management comprised HTx in 4 patients (13.3%) and conservative surgery in 26, including conversion to TCPC in 21 (70%; ECC in 19, 63.3%, LT in 2, 6.7%) and other procedures in 5 (16.7%, Table 1). Among the latter, we performed a Fontan takedown to a one-and-a-half ventricle repair after a Bjork AP connection in 1 patient; aortic valve replacement, subaortic resection and pacemaker implant in 1; paracorporeal left ventricular assist device implant in 1; subaortic stenosis resection, aortic valve and ascending aorta replacement in 1; neoaorta pseudoaneurysm resection in 1 (Supplementary Material, Table S1). Most patients undergoing Fontan revision had an associated radiofrequency or cryoablation procedure and a pacemaker implant (Table 2).

All patients undergoing an HTx presented with lower mean age at reoperation [15.5 years (SD: 3.7); P = 0.050] compared to those having conservative surgery. In particular, in the HTx group, a dominant LV morphology was less frequent (50% vs 95.2%; Fontan conversion, vs 80%; other surgery; P = 0.038). Of note, PLE as an indication for surgery was more common in the HTx group (50%) than in the Fontan conversion (4.8%) and other surgery (0%) groups (P = 0.049; Table 1).

Early outcomes

Perioperative variables are presented in Table 2. Noticeably, Fontan conversion was associated with a significantly lower aortic cross-clamp time (P = 0.043), whereas patients undergoing other surgery had a longer stay in the intensive care unit (P = 0.013) compared with the other groups.

Early complications occurred in most patients (96.7%) in all groups. Overall, the most common complications were supraventricular tachyarrhythmias (15 patients, 50%), effusions (11, 36.7%) and AKI (8, 26.7%). Other complications (i.e. pneumothorax, cardiogenic shock, liver failure, drug-induced hypothyroidism, graft rejection, limb ischaemia and cerebral haemorrhage) occurred in 11 (36.7%). Different surgical strategies did not seem to significantly influence the onset of early AE (Table 3).

Overall, 7 operative deaths occurred after a median time of 4.8 (1–5.2) months. Three patients in our early experience died after Fontan conversion (ECC thrombosis in 2, sepsis in 1). Another patient died 2 weeks after an HTx of rejection. The last 3 deaths occurred in patients who underwent conservative surgery other than conversion and who were not eligible for an HTx. In detail, 1 patient with hypoplastic left heart syndrome and single-lung Fontan developed congestive heart failure after repair of an aortic pseudoaneurysm and died suddenly during an anaesthesia procedure. The second patient with tricuspid atresia and preoperative compromised liver function, died after subaortic stenosis resection, aortic valve and ascending aorta replacement, because of the onset of disseminated coagulopathy and portal thrombosis. The last patient had undergone an extracardiac TCPC at 17 years of age because of a long history of pulmonary hypertension since childhood, which eventually responded to chronic pulmonary vasodilator therapy. However, 2 years later, he developed ventricular dysfunction and AKI and had a left ventricular assist device implanted. He died 1 month later of a massive cerebral haemorrhage while on support (Supplementary Material, Table S1).

Late outcomes

At a median follow-up of 8.4 years (1–5; 100% completeness), 9 patients (39.1%) required interventional procedures, and 4 (17.4%) underwent reoperation (Table 3). In particular, 2 patients developed progressive single-ventricle failure (1 after one-and-a-half ventricle repair and 1 after Fontan conversion) and underwent an HTx 2 and 9 years after the redo-Fontan operation, respectively. The second patient died 2 months later of recurrent infections and interstitial lung disease; it is of note that this patient had a preoperative diagnosis of PLE.

Twenty-one patients (92.3%) developed late AE. The most frequent were FALD in 13 (56.5%), persistent supraventricular tachiarrhythmias in 12 (52.2%) and other various AE (lymphocytopenia, Hepatitis C virus hepatitis, transient ischaemic attack and limb ischaemia) occurred in 8 (34.8%). Surgical strategies did not influence the late complications rate, although none of the patients who had an HTx presented with FALD (versus 66.7% in the Fontan conversion and 50% in the other surgery groups; P = 0.068; Table 3).

Among the 22 long-term survivors, 20 (90.9%) are in NYHA functional class I-II and are on medical therapy. As described in Table 4, it is noticeable that the mean Fibroscan value in patients after an HTx is significantly lower (normalized) compared to patients with persisting Fontan circulation after conservative surgery [9.8 (SD: 4.6) kPa vs 27.1 (SD: 9.7) kPa; P = 0.003].

Overall survival at the 1-, 5-, 10- and 20-year follow-up was 75.9% (95% CI: 91.4–60.4%), 75.9% (95% CI: 91.4–60.4%), 70% (95% CI; 78–52%) and 70% (95% CI: 78–52%), respectively (Fig. 1). Of note, survival in patients who underwent Fontan conversion or an HTx was statistically higher than in the “other surgery” group (P = 0.022, Fig. 2).

DISCUSSION

It is now clear that failing of Fontan circulation is inevitable [1, 2], and in our experience, it has occurred about 20 years after the initial operation, as reported elsewhere [1, 4–7]. This confirms that Fontan palliation is effective, since once a patient has survived the teenage years, the longevity as adult is quite good. This long-term palliation actually allows the growth of children with complex congenital heart diseases to adult age when an HTx is a potential final treatment. However, it is evident that long-term survival is limited.

In this 25-year experience with surgical treatment of patients with Fontan failure, we report satisfactory long-term outcomes and acceptable mortality, with a 20-year survival of about 70%, similar to that reported elsewhere for the Fontan population [1, 4–7, 16, 18–22]. However, the incidence of early and late complications has been consistent in this series. Of note, paroxysmal supraventricular tachyarrhythmias persisted in several patients, which may trigger a second Fontan failure [15, 16].

In our experience, the type of original Fontan and the extant ventricular function have driven the surgical strategy. When the single-ventricle function is preserved, a surgical Fontan conversion is advisable, the rationale being to prolong Fontan longevity and to postpone the final, not unexpected, stage (transplant), which remains a time-limited option. In fact, the potential long-term morbidities related to immunosuppression therapy and the risk of graft rejection can reduce consistently the long-term survival in Fontan patients after an HTx [14]. This approach seems to be effective, because at a median follow-up of 10 years, late survivors after Fontan conversion present with preserved ventricular function and exercise capacity, in most cases, similar to those registered in not-failing Fontan patients [24, 25].

In our series, an early (NYHA functional class II) Fontan conversion has become a low-mortality strategy because no death has been recorded in the last 20 years, although several morbidities occurred (Table 3). It is noticeable that all 3 operative deaths occurred at the beginning of our experience, in patients who presenting with NYHA functional class III-IV and severely compromised clinical conditions. A learning curve is evident, and it is needed to improve either the surgical technique or the perioperative clinical management, which are often complicated in these patients. The main indications for Fontan conversion were drug-resistant supraventricular arrhythmias and severe RA dilatation, which represent a common combination after an AP Fontan [1–3, 15, 16], where atrial hypertension and dilatation stimulate intra-atrial macro-reentrant tachycardias, which respond poorly to catheter ablation.

It is worth mentioning that a previous Fontan conversion has not precluded a subsequent HTx as a final expected step. A Fontan conversion remains a palliation of a palliative operation whose aim is to postpone as late as possible the last final palliation, i.e. an HTx. In our series, the HTx was performed in fewer cases (13%) than reported by other authors [6]. All these patients presented with a single-ventricle EF < 40% or had already undergone a TCPC, or developed PLE, which is a clear indication for an HTx [17]. Also, as described elsewhere [6, 9, 12], patients who required an HTx presented with failure of the Fontan circulation significantly earlier than those who underwent conservative strategies (P = 0.050; Table 1). Interestingly, left ventricular morphology of the dominant ventricle was less frequently represented than in the other groups (P = 0.038), in whom it might have played a protective role, and in whom surgery was postponed [18]. Operative mortality was 25% in this limited series, which is slightly higher but similar to results from other larger studies [14]. As outlined elsewhere [6], there were no significant differences between conversion and HTx. However, a low operative mortality (3.7%) was reported by Kanter et al. [10], whose single-institution experience demonstrates that a careful selection of failing Fontan patients and an experienced congenital surgical team can achieve successful HTx rates even in such complex patients. Although our series may suffer from small numbers of patients and its retrospective nature, our surgical experience demonstrates that survival of patients who underwent other conservative reoperations is significantly lower compared to those who had Fontan conversion and an HTx (P = 0.022) (Fig. 2). In fact, 3 patients died early because of a late referral and a severely compromised clinical status (severe liver dysfunction in 2, pulmonary hypertension in 1), which contraindicated an HTx.

Because the Fontan circulation is at risk of the so-called Fontan attrition in the long term, we advocate a close, proactive clinical follow-up to evaluate the correct timing for a conversion or an HTx in these patients, to further prolong their life. We believe that an early HTx is advisable in all Fontan patients to avoid a no-return point, in which a rescue surgery has very poor results, and the progressive multiorgan impairment that can become a contraindication for an HTx. Unfortunately, specific guidelines for an HTx in Fontan patients are still missing and should be promptly described to improve outcomes in such difficult patients.

Lastly, we found that 56.5% of our patients presented with FALD caused by systemic chronic venous hypertension [1–3], which is recognized in an increasing number of patients at long-term follow-up. Over the last decades, several studies have tried to identify a relationship between haemodynamics and extent of liver fibrosis in Fontan patients, but the findings have been discordant [26–28]. In our experience, non-invasive transient elastography correlated well with the post-mortem pathological features [29], and we currently use it to evaluate FALD severity in our routine clinical check-ups of Fontan patients. This method may be helpful to prevent advanced liver disease, which can significantly affect long-term outcome. Noticeably, the mean liver elastography values in patients who received a transplant were normal, and none of them had a recurrence of FALD (Table 3). This result might suggest the reversibility of FALD with an HTx, which normalizes haemodynamic circulation, as supported by recent reports in the literature [23], which shows liver magnetic resonance imaging and VAST score improvement after an HTx. The issue that remains unsolved is until when and if FALD is reversible. Further, larger studies are needed to answer this question.

Limitations

This study presents the intrinsic limitation of a single-centre retrospective analysis with a small number of patients, which limits the statistical power of the analyses. The small numbers in the study groups and the different (although not statistically relevant) follow-up times should dictate particular attention to comparing the incidence of AE and late outcomes. Comparisons between groups were not made to demonstrate the superiority of one technique over another. Rather, the goal was to highlight the fact that a late referral (i.e. compromised clinical conditions, NYHA functional class IV) inevitably leads to worse outcomes.

The assessment of hepatic function with liver elastography prior to surgery was not available at the beginning of our experience, so we cannot prove if surgery has truly modified liver prognosis. Also, the statistically significant difference we registered between transplanted and not transplanted patients may only suggest a possible role of an HTx in restoring “normal” liver conditions.

CONCLUSIONS

Failing Fontan circulation can be managed surgically with satisfactory long-term survival by an HTx and Fontan conversion. However, early and late complications are frequent. Fontan conversion allowed most patients to postpone the need for an HTx, thereby preserving native heart function. Surgical procedures in decompensated Fontan patients carry a high operative risk. A close, accurate follow-up is mandatory to refer patients earlier to surgery and optimize outcomes. In particular, the appropriate timing for an HTx needs to be defined.

SUPPLEMENTARY MATERIAL

Supplementary material is available at EJCTS online.

Conflict of interest: none declared.

Author contributions

Massimo A. Padalino: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Resources; Supervision; Validation; Visualization; Writing—original draft; Writing—review & editing. Matteo Ponzoni: Conceptualization; Data curation; Investigation; Methodology; Writing—original draft; Writing—review & editing. Biagio Castaldi: Investigation; Writing—review & editing. Liliana Chemello: Investigation; Writing—review & editing. Loira Leoni: Investigation; Writing—review & editing. Giuseppe Toscano: Investigation. Gino Gerosa: Supervision. Giovanni Di Salvo: Investigation; Supervision; Validation; Visualization; Writing—review & editing. Vladimiro L. Vida: Investigation; Supervision; Validation; Writing—review & editing.

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Constantine Mavroudis, Yoshihiro Oshima and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.

REFERENCES

ABBREVIATIONS

 
• AKI

  Acute kidney injury

 
• AE

  Adverse events

 
• AP

  Atriopulmonary

 
• AVB

  Atrioventricular block

 
• CI

  Confidence interval

 
• ECC

  Extracardiac conduit

 
• EF

  Ejection fraction

 
• FALD

  Fontan-associated liver disease

 
• HTx

  Heart transplant

 
• LT

  Lateral tunnel

 
• NYHA

  New York Heart Association

 
• PLE

  Protein-losing enteropathy

 
• RA

  Right atrium

 
• SD

  Standard deviation

 
• TCPC

  Total cavopulmonary connection

Author notes