Ann Thorac Surg 2006;82:e39-e40
© 2006 The Society of Thoracic Surgeons
Case Reports
Resolution of Protein-Losing Enteropathy and Normalization of Mesenteric Doppler Flow With Sildenafil After Fontan
Orhan Uzun, MDa,*,
Joon Kwang Wong, MBBSa,
Vinaj Bhole, MRCPb,
Oliver Stumper, PhD, MDb
a Department of Pediatric Cardiology, University Hospital of Wales, Cardiff, United Kingdom
b Department of Pediatric Cardiology, Birmingham Children’s Hospital, Birmingham, United Kingdom
Accepted for publication August 23, 2006.
* Address correspondence to Dr Uzun, University Hospital of Wales, Department of Paediatric Cardiology, Heath Park, Cardiff, CF 14 4XW, United Kingdom (Email: uzun{at}cf.ac.uk).
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Abstract
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A 9.5-year-old girl after Fontan procedure for hypoplastic left heart syndrome had recurrent protein-losing enteropathy (PLE) develop 2 months after partial catheter closure of the Fontan fenestration. Despite satisfactory hemodynamic measurements under general anesthesia, we postulated that she suffered from increased pulmonary vascular reactivity and commenced her on Sildenafil treatment. After 6 weeks of oral Sildenafil treatment, her serum albumin and the fecal alpha-1-antitrypsin levels normalized, and her exercise tolerance had increased. There was also an improvement of the mesenteric arterial flow patterns on Doppler studies. Sildenafil should be considered in the treatment of PLE after the Fontan procedure.
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Introduction
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Protein-losing enteropathy (PLE) is a well-recognized complication after the Fontan procedure. Treatment options are limited and the outcome is generally poor with mortality rates of up to 50% over 5 years [1, 2]. Protein-losing enteropathy usually presents with loose stools and peripheral edema. The diagnostic features include decreased serum albumin levels < 30 g/L and increased fecal excretion levels of alpha-1-antitrypsin [3, 4]. A high protein and medium chain triglyceride diet may give some symptomatic relief. Various success rates have been reported with the use of medium-term steroid or heparin treatment and cardiac pacing [5–7]. In resistant cases, transcatheter Fontan fenestration or surgical revision is suggested [8]. Heart transplantation is considered to be the last option.
A 9.5-year-old girl with hypoplastic left heart syndrome had undergone a three-stage Norwood operation. At age 4 she underwent a nonfenestrated Fontan procedure. Preoperative cardiac catheterization revealed mean pulmonary artery pressures of 10 mm Hg and a transpulmonary gradient of 3 mm Hg. The postoperative course was uneventful. Two years after the Fontan operation she presented with a migrating edema and loose stools. Initial investigation revealed PLE with a serum albumin of 29 g/L and increased excretion of alpha-1-antitrypsin in her stool. She was treated with high protein and medium chain triglyceride diet, steroids, and heparin without success. Repeat cardiac catheterization under general anesthesia suggested very satisfactory baseline hemodynamics with Fontan pressures of 14 mm Hg and a transpulmonary gradient of 4 mm Hg. However, it was noted that the atrial septal defect was small and could potentially cause restriction to pulmonary venous return during periods of increased cardiac output. During dobutamine infusion, inferior vena cava pressure rose from a mean of 15 mm Hg to 21 mm Hg, and a gradient of 4 mm Hg across the atrial septum was unmasked. Thus she underwent atrial septectomy and conversion to an extracardiac fenestrated Fontan. She improved rapidly thereafter and the PLE resolved. She was maintained on diuretic, angiotensin-converting enzyme inhibitor, and warfarin therapy. Her resting saturations were stable at 85% breathing room air.
Two years after the Fontan revision, she complained of increasing effort intolerance and cyanosis with resting saturations of 78%. She managed only 6 minutes of a modified exercise test with saturations of 70% at peak exercise. Repeat cardiac catheterization documented very satisfactory Fontan pathways and hemodynamics both at rest (13 mm Hg, mean pulmonary artery pressure) and during catheter test occlusion (14 mm Hg, mean pulmonary artery pressure) of the fenestration. To improve her cyanosis and effort tolerance, the Fontan fenestration was partially closed using a custom-made Cardia (Cardia, Inc, Burnsville, MN) occlusion device designed to allow for a reduction in the right-to-left shunt. She was discharged home the following day with resting saturations of 92% breathing room air. She initially had improved exercise tolerance (15 mins, saturation 83% at peak exercise), but represented to our unit some 3 months after the procedure with signs of PLE. Her serum albumin level was 29 g/L and her fecal alpha-1-antitrypsin level was 2.37 mg/g (normal values, 0.04–0.43 mg/g) [3, 4], documenting recurrence of her PLE. Thus she was recommenced on high protein and medium chain triglyceride diet. Her echocardiogram showed good ventricular function, mild tricuspid regurgitation, a small persistent right-to-left shunt across the previously placed partial occlusion device with a peak velocity of 1.6 m/s, suggesting an increased transpulmonary gradient. Doppler evaluation of the mesenteric arterial flow patterns documented a loss of the diastolic component, suggesting elevated mesenteric vascular resistance (Fig 1A) [9]. In this setting it was elected to start her on a pulmonary vasodilator drug. A trial of sildenafil at 0.5 mg/kg/dose, 4 times a day, with rapid increase to a maximum of 1.5 mg/kg/dose was commenced. Two weeks after initiation of treatment with oral sildenafil her edema gradually disappeared. Serum albumin levels increased and fecal alpha-1-antitrypsin levels decreased. Three weeks into the treatment her serum albumin levels were normalized (from 29 g/L baseline to 43 g/L). Her fecal alpha-1-antitrypsin levels returned to within normal range (0.36 mg/g) 6 weeks after the initiation of oral sildenafil treatment (Fig 2). Repeat Doppler interrogation of the superior mesenteric artery showed a normalized pattern with the reappearance of continuous flow in diastole (Fig 1B). There was also a reduction in the Doppler velocity across the partially occluded fenestration from 1.6 m/s to 1 m/s, suggesting a reduction in the transpulmonary gradient. She remained in remission to date with saturation of 94% and serum albumin levels of 45 g/L, and she continues on 1 mg/kg/dose sildenafil 3 times a day.
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Fig 1. (A) Doppler flow profile of superior mesenteric arterial flow after recurrence of protein-losing enteropathy. (B) Note the absence of diastolic flow. With resolution of the protein-losing enteropathy on sildenafil treatment there is reappearance of a normal continuous flow pattern.
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Comment
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Protein-losing enteropathy occurs in as many as 5% of patients after the Fontan procedure. It is one of the most debilitating complications of the Fontan procedure with very disappointing response to drug treatment and high mortality [1, 2]. The cause is not fully explained. Increased pressure within the Fontan circuit counteracting the passive inferior vena caval flow against gravity may hinder intestinal circulation with resultant loss of anatomic integrity of the highly delicate intestinal villi. Increased resistance to mesenteric arterial flow evidenced by a loss of diastolic flow has been documented [9]. Various treatment modalities have been reported and were applied in our patient. The recurrence of PLE after partial closure of the Fontan fenestration, despite satisfactory baseline hemodynamics under general anesthesia and the finding of high-velocity flow patterns across the residual fenestration and a loss of the diastolic component of mesenteric arterial flow patterns, suggested an increased pulmonary and mesenteric vascular reactivity. Thus the use of a potent pulmonary vasodilator such as sildenafil seemed to be indicated. Sildenafil also decreases mesenteric arterial resistance and increases arterial mesenteric blood flow [9].
There has been complete resolution of PLE and improved exercise tolerance in our patient during the 6 months of treatment with sildenafil. This effect is likely to be due to a combination of actions including a reduction of pulmonary vascular resistance (as evidenced by reduction of trans-fenestration Doppler velocity) as well as dilating the mesenteric vessels with resultant increase in mesenteric arterial flow. No side effects were observed.
In conclusion, sildenafil should be considered in the treatment of PLE in cases with satisfactory Fontan pathways and baseline hemodynamics, but signs of increased pulmonary and mesenteric vascular resistance.
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Acknowledgments
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We are grateful for the support and contribution by the Medical Physics Department at the University Hospital.
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References
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- Feldt RH, Driscoll DJ, Offord KP, et al. Protein-losing enteropathy after the Fontan operation J Thorac Cardiovasc Surg 1996;112:672-680.[Abstract/Free Full Text]
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- Rychik J, Piccoli D, Barber G. Usefulness of corticosteroid therapy for protein-losing enteropathy after the Fontan procedure Am J Cardiol 1991;68:819-821.[Medline]
- Donnelly J, Rosenthal A, Castle V, et al. Reversal of protein-losing enteropathy with heparin therapy in three patients with univentricular hearts and Fontan palliation J Pediatr 1997;130:474-478.[Medline]
- Cohen MI, Rhodes LA, Wernovsky G, et al. Atrial pacing: an alternative treatment for protein-losing enteropathy after the Fontan operation J Thorac Cardiovasc Surg 2001;121:582-583.[Free Full Text]
- Rychik J, Gui-Yang S. Relation of mesenteric vascular resistance after Fontan operation and protein-losing enteropathy Am J Cardiol 2002;90:672-674.[Medline]
- Michelakis E, Tymchak W, Lien D, et al. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide Circulation 2002;105:2398-2403.[Abstract/Free Full Text]
- Jackson G, Benjamin N, Jackson N, et al. Effects of sildenafil citrate on human hemodynamics Am J Cardiol 1999;83:13C-20C.[Medline]
- Ostrow AM, Freeze H, Rhychik J. Protein losing enteropathy after Fontan operation: Investigation into possible pathophysiologic mechanisms Ann Thorac Surg 2006;82:695-701.[Abstract/Free Full Text]
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Abstract
Introduction
