Protein‐Losing Enteropathy after Fontan Operation

Protein‐losing enteropathy (PLE) is a poorly understood and enigmatic disease process affecting patients with single ventricle after Fontan operation. In those afflicted, PLE after Fontan operation results in significant morbidity and mortality. The pathophysiology of the disease is unknown; however, a proposed mechanism incorporates a combination of phenomena including: (1) altered hemodynamics, specifically low cardiac output; (2) increased mesenteric vascular resistance; (3) systemic inflammation; and (4) altered enterocyte basal membrane glycosaminoglycan make‐up. A paradigm for the clinical management of PLE after Fontan operation is proposed.     

Steroid Pulse Therapy for Protein‐losing Enteropathy after the Fontan Operation

A 19‐year‐old male with Fontan circulation developed protein‐losing enteropathy associated with acute enteritis. Although his central venous pressure was in the normal range, subcutaneous high molecular heparin injection and oral predonisolone administration were not effective. We initiated intravenous high‐dose methyl‐predonisolone (15 mg/kg/day) for 3 days followed by oral predonisolone (0.5 mg/kg/day) for 4 days and repeated the course in 2 weeks. The serum protein and albumin increased to the normal level at 2 months after pulse therapy. The patient has not shown any recurrence of such protein‐losing enteropathy for 2 years without any steroid agents.     

The Use of Octreotide to Successfully Treat Protein‐losing Enteropathy Following the Fontan Operation

Octreotide has had limited use for the treatment of protein‐losing enteropathy following the Fontan operation. We describe three cases where subcutaneous octreotide was successfully used to treat refractory protein‐losing enteropathy following the Fontan operation. Patients received octreotide therapy for a period of 14–28 months. Octreotide was discontinued in one patient due to symptomatic cholelithiasis; this patient died 7 months after treatment was discontinued. Octreotide may be a useful treatment in these patients, but further study on its efficacy and mechanism of action is needed.     

The Role of Iron Deficiency in Protein‐losing Enteropathy Following the Fontan Procedure

We describe the case of an adult who developed protein‐losing enteropathy 21 years after having undergone a Fontan procedure. Investigations revealed iron deficiency anemia which was treated with intravenous iron sucrose leading to resolution of both the anemia as well as symptoms of protein‐losing enteropathy.     

Protein‐losing Enteropathy after the Total Cavopulmonary Connection: Impact of Intravenous Immunoglobulin

Objective. Despite multiple treatment modalities, protein‐losing enteropathy remains a serious complication to Fontan‐type operations. Observations suggest inflammation to be involved in the pathogenesis of this condition, and immunomodulating treatment with high‐dose intravenous immunoglobulin may modify the condition positively. Patients. Four patients with protein‐losing enteropathy occurring after the total cavopulmonary connection, presenting with edema, hypoalbuminemia, and hypogammaglobulinemia, received intravenous immunoglobulin replacement therapy. Interventions. Standard replacement dose (1 g/kg) was used with intervals between infusions adjusted according to albumin and gamma globulin levels. Treatment periods ranged from 1 year to 5.3 years. Results. Intravenous immunoglobulin treatment was associated with significant increase in plasma albumin and to some extent in immunoglobulin G levels, as well as resolution of edema and the children started to thrive normally. During treatment, no serious infections or serious side effects were seen. Additional follow‐up intervals ranged from 2 years to 2.8 years, during which only one episode of clinical relapse was registered and treated. Conclusions. We find the increase in albumin level and the resolution of protein‐losing enteropathy symptoms after treatment with intravenous immunoglobulin of particular interest considering this serious complication to Fontan‐type operations.     

Lymphatic Obstruction and Protein‐losing Enteropathy in Patients with Congenital Heart Disease

Objective. Protein‐losing enteropathy (PLE) is a known complication of surgical procedures for congenital heart disease. The pathogenesis and pathophysiology of PLE remain poorly understood. However, lymphatic insufficiency appears central to the disease process. We sought to investigate the role of lymphatic obstruction and central venous catheter‐related central venous thrombosis in patients with congenital heart disease and PLE. Design. A case‐control study design was constructed consisting of patients with congenital heart disease and PLE and 2:1 matched controls having undergone the same definitive surgical procedure. Obstruction to lymphatic return was considered present if the thoracic duct was ligated, or if there was complete central venous obstruction at the usual site of thoracic duct drainage. Results. Obstruction to lymphatic return was identified in 4 of 16 cases (25%) and 1 of 32 controls (4%), P = .06. There was no association between PLE and central venous catheter use or duration, and no discriminating characteristics between cases and controls with respect to anatomy, pre‐Fontan hemodynamic variables, operative or perioperative factors, or hemodynamic variables at the time of PLE diagnosis. Mortality for patients with PLE was 25% compared with 9% in controls (P = not significant). Long‐term resolution of PLE was obtained in six patients (38%). Conclusion. There is a high prevalence of apparent lymphatic obstruction in patients with congenital heart disease and PLE, suggesting that physical lymphatic obstruction may play an important, and previously unrecognized role in the development of PLE in patients with complex congenital heart disease.     

Rational Approach to Surgical Management of Complex Forms of Double Outlet Right Ventricle with Modified Fontan Operation

Objective. Surgical alternatives to biventricular repair of complex forms of double outlet right ventricle (DORV) remain controversial. The available knowledge of the Fontan operation (FO) for children with this anomaly is limited. The aim of this report is to analyze the results and risk factors of the FO performed as an alternative to the biventricular repair of complex DORV. Methods. Between 1980 and 2007, 47 patients with complex forms of DORV underwent a modified FO. Concomitant defects included noncommitted, subpulmonary or multiple ventricular septal defects, anomalies of atrioventricular valves and/or caval veins, and ventricular hypoplasia. Thirty‐five of 45 patients (77%) have undergone a hemi‐Fontan and 35 patients (77%; 10 children without previous hemi‐Fontan) have had a completion FO without mortality or Fontan takedown. Risk factors for adverse outcomes were determined by multivariate analyses. Results. There were no early but six late deaths. The follow‐up period ranged from 1 year to 25 years (mean 10.0 ± 6.5). The actuarial survival was 93% at 1 year, 87% at 10, 15, and 25 years. Multivariate analysis identified preoperative left or common atrioventricular valve insufficiency (P = .001) and decreased left ventricular ejection fraction (<50%) (P = .02) as risk factors for late death and/or morbidity. The only risk factor for a late adverse outcome and poor functional status was increased preoperative pulmonary vascular resistance (>4.0 Woods units/m²) (P = .005). Conclusion. FO provides good early‐ and mid‐term results in the treatment of complex forms of DORV. The increased preoperative pulmonary vascular resistance was a significant negative risk factor for adverse outcome in this patient population.     

Oral Budesonide as a Therapy for Protein‐Losing Enteropathy in Patients Having Undergone Fontan Palliation

Background. Protein‐losing enteropathy is associated with Fontan palliation for single‐ventricle physiology and has been difficult to treat. Limited data suggest the successful use of oral budesonide (Entocort, AstraZeneca) as a palliative measure. Methods. We examine our single‐institution retrospective experience in eight patients who were treated with this therapy. Results. Median pretherapy albumin level was 1.7 g/dL (range 1.0–2.7 g/dL), 3 months after therapy was 3.1 g/dL (range 2–4.8 g/dL), and by the end of the first year was 3.4 g/dL (range 2.1–5.3 g/dL). All patients had at least a transient improvement, and at latest follow‐up (median 29 months, range 3–51 months) five patients remain on therapy. Five of eight patients had required pretherapy albumin transfusions; one patient required albumin infusions after therapy. Four patients had side effects associated with the medication. Conclusions. Oral budesonide is an additional therapy that has the potential to improve symptoms and delay need for heart transplantation in this patient population.     

Recurrent Exacerbations of Protein-losing Enteropathy after Initiation of Growth Hormone Therapy in a Fontan Patient Controlled with Spironolactone

Protein-losing enteropathy (PLE) is a rare, but serious complication in single ventricle patients after Fontan palliation, and is associated with a 5-year mortality of 46%. We describe a patient with PLE after Fontan palliation who achieved remission with high-dose spironolactone (an aldosterone antagonist), but had three exacerbations each temporally correlated with the use of growth hormone (an aldosterone agonist). Because of the opposing mechanisms of action of these two medications, caution might be indicated when using growth hormone for patients with PLE who are successfully treated with spironolactone.     

Clinical Outcomes and Improved Survival in Patients With Protein-Losing Enteropathy After the Fontan Operation

Background

Patients with protein-losing enteropathy (PLE) following the Fontan operation have a reported 50% mortality at 5 years after diagnosis.

Objectives

The aim of this study was to review outcomes in patients with PLE following the Fontan operation.

Methods

From 1992 to 2010, 42 patients (55% male) with PLE following the Fontan operation were identified from clinical databases at the Mayo Clinic. Data were collected retrospectively.

Results

Mean age at PLE diagnosis was 18.9 ± 11.0 years. Initial Fontan operation was performed at 10.1 ± 10.8 years of age. Mean time from Fontan operation to PLE diagnosis was 8.4 ± 14.2 years. Survival was 88% at 5 years. Decreased survival was seen in patients with high Fontan pressure (mean >15 mm Hg; p = 0.04), decreased ventricular function (ejection fraction <55%; p = 0.03), and New York Heart Association functional class >2 at diagnosis (p = 0.04). Patients who died had higher pulmonary vascular resistance (3.8 ± 1.6 Wood units [WU] vs. 2.1 ± 1.1 WU; p = 0.017), lower cardiac index (1.6 ± 0.4 l/min/m² vs. 2.7 ± 0.7 l/min/m²; p < 0.0001), and lower mixed venous saturation (53% vs. 66%; p = 0.01), compared with survivors. Factors were assessed at the time of PLE diagnosis. Treatments used more frequently in survivors with PLE included spironolactone (21 [68%]), octreotide (7 [21%]), sildenafil (6 [19%]), fenestration creation (15 [48%]), and relief of Fontan obstruction (7 [23%]).

Conclusions

PLE remains difficult to treat; however, in the current era, survival has improved with advances in treatment. Further study is needed to better understand the mechanism of disease and ideal treatment strategy.     

Outcome of early and late onset Fontan operation in patients with univentricular heart repair

ObjectiveTo evaluate our experience in the Fontan procedure comparing those below and above 6 years of age.MethodsA review of our clinical database was conducted to identify the patients who received extracardiac Fontan between 2002 and 2010. All demographic, echocardiographic, surgical, haemodynamic and follow-up data were collected. The overall mortality was defined as death occurring from the time of surgery to the most recent follow-up. Early postoperative death was defined as death occurring during admission or within 30 days from the operation. Seventy-six patients with functionally univentricular hearts were included in the study. Patients were divided into two groups. Group A included patients who had received extracardiac Fontan at the age of 6 years or less, whereas group B included patients who had received extracardiac Fontan at an age of more than 6 years.ResultsThe overall hospital mortality was 7.9% (10.2% in group A and 5.9% in group B). No statistically significant difference was seen between the two groups regarding the postoperative mortality including thrombosis, stroke, chylothorax, bleeding, pericardial effusion, wound infection, serious postoperative arrhythmias and protein losing enteropathy. On the other hand the mechanical ventilation duration, duration of hospital and ICU stay, duration of the chest tubes and the postoperative saturation was not significant between the two groups.ConclusionsThe age of the patient at the time of Fontan surgery does not affect the results, in terms of both morbidity and mortality.     

Hyponatremia and Its Association with the Neurohormonal Activity and Adverse Clinical Events in Children and Young Adult Patients after the Fontan Operation

Background. Hyponatremia (HN) is relatively common in adults with congenital heart disease and is a powerful predictor of mortality. However, the precise relationship of HN to the Fontan pathophysiology remains unknown. Purpose. Our study aimed to clarify the association of HN to the Fontan pathophysiology. Methods and Results. We measured the plasma sodium (Na) level in 169 consecutive Fontan patients (78 children) and HN (≤137 mEq/L) was observed in 50 patients (30% of the total patients, 31% of the children). The HN patients showed a lower peak oxygen uptake (VO₂) with a greater New York Heart Association class (P < .0001). The plasma level of norepinephrine (NE), rennin activity (PRA), arginine vasopressin, central venous pressure (CVP) and medications were associated with the Na levels and the NE, PRA, and diuretic use were the independent determinants (P < .01?.0001). The plasma B‐type natriuretic peptide was not correlated with the Na levels. In the children, diuretic use and the PRA independently determined the Na levels without any association to the CVP or peak VO₂. During a median follow‐up of 2.1 years, the HN in addition to the CVP and peak VO₂ independently predicted the unscheduled hospitalizations in all patients, while the HN was the only independent predictor of the hospitalizations in the adult patients (hazard ratio: 3.1, 95% confidence interval 1.2–8.0, P= .021). Conclusions. Child and adult Fontan patients exhibited a high prevalence for HN that closely reflected some neurohumoral activation and predicted adverse clinical events, especially in adult Fontan patients.     

Intra‐aortic Balloon Pump Use in the Failing Fontan Circulation

Acute cardiogenic shock in patients with Fontan physiology, while uncommon, is associated with devastating outcomes. Management of these patients is increasingly relying on the use of mechanical support. The use of intra‐aortic balloon pump is underutilized. This report highlights the successful use of this modality in an adult with Fontan physiology and reviews the literature on this approach in such patients.