Reversal of Protein-LosingEnteropathy With CalciumReplacement in a Patient AfterFontan OperationSoo-Jin Kim, MD, In-Seung Park, MD,Jin-Young Song, MD, Jae-Young Lee, MD, andWoo-Sup Shim, MD

Department of Pediatric Cardiology, Sejong Heart Institute,Pucheon City Kyunggi-do, Korea

Protein-losing enteropathy occurs in patients followingthe modified Fontan procedure. Treatment is still contro-versial. We describe a boy who developed protein-losingenteropathy 18-months after an extracardiac Fontan pro-cedure. Treatment with calcium for hypocalcemia atten-uated the protein loss with subsequent normalization ofserum total protein and albumin levels. Decrease of oralcalcium and subsequent decrease of serum ionized cal-cium level were associated with relapse of hypoalbumin-emia. This was again treated successfully with calciumand vitamin D replacement.

(Ann Thorac Surg 2004;77:1456–7)© 2004 by The Society of Thoracic Surgeons

Protein-losing enteropathy (PLE) associated with car-diovascular disease was first noted in patients with

development of constrictive pericarditis or with long-standing congestive heart failures. It has been theorizedthat PLE results from increased systemic venous pressurethat subsequently causes lymphangiectasia. Proteins andlymphocytes leak from dilated lymphatics [1].

We report a patient who developed PLE 18-months afterthe Fontan procedure. This report is unique due to thelaboratory verification of improvement with oral calciumtherapy, relapse when weaned from therapy, and im-provement again with reinstitution of calcium therapy.

A 2-month-old boy with criss-cross heart, double outletright ventricle, and small left ventricle underwent pulmonaryartery banding procedure in April 1997, which was followedby a bidirectional cavopulmonary shunt in September 1997and extracardiac Fontan operation in August 1998.

He developed generalized edema without change incardiac function, which was revealed by echocardiographyand clinical examination at post-Fontan 18 months (Febru-ary 2000). His serum total protein and albumin levels were2.4 g/dL and 1.4 g/dL, respectively, and his fecal alfa-1antitrypsin level was 409 mg/dL. The total calcium level andionized calcium level were 8.1 mg/dL and 4.33 mg/dL,respectively. His stool alfa-1 antitrypsin level was de-

creased. Laboratory evaluation was performed to excludehypoproteinemia of nongastrointestinal origin.

Catheterization was performed, which revealed ac-ceptable hemodynamics and cardiac function (meanpressures in the Fontan conduit of 10 to 12 mm Hg,ventricular end-diastolic pressure of 8 mm Hg, goodventricular contractility).

Heparin therapy (3000 U per day subcutaneously) withintermittent intravenous albumin infusion began inMarch 2000 (1-month after the development of PLE).However, generalized edema persisted and pleural effu-sion and ascites developed. The serum total protein andalbumin level were documented to be 2.6 g/dL and 1.5g/dL, respectively. Heparin therapy failed to resolve thePLE after more than 4 months (Table 1). When theheparin therapy failed, we tried to use steroid therapybut his parents refused.

After that, he received a 20-g albumin injection twice aweek for 13 months and his total protein and albuminlevel were 2.4 to 2.7 g/dL and 1.3 to 1.7 g/dL, respectively.One day his serum total calcium and ionized calciumchecked routinely were 4.3 mg/dL and 2.67 mg/dL; 25-(OH) vitamin D3 was decreased to 3.5 ng/mL and para-thyroid hormone was increased to 114 pg/mL. He wasput on oral calcium gluconate in August 2001 (18-monthsafter development of PLE). After 4 weeks of calciummedication, the edema, pleural effusion, and ascites im-proved and he did not need further albumin infusion.The ionized calcium level was normalized within 6 weeksand, simultaneously, the total protein and albumin in-creased to nearly normal level at 8-weeks after calciummedication (Fig 1).

One-month later we decreased the calcium gluconatedose slowly. Then, the eyelid edema developed after 6weeks, and total protein and albumn level decreased to3.0 g/dL and 1.7 g/dL. The ionized calcium level was 2.8mg/dL and increased very slowly to normal level withmassive calcium and vitamin D therapy more than 10months. Although his stool alfa-1 antitrypsin level didnot normalize totally, it decreased markedly from pre-treatment value. The edema and protein and albuminlevel improved slowly. The patient has remained free ofascites, pleural effusion, and edema. Currently, he doesnot need further albumin infusion.

Comment

Enteric loss of protein with the clinical finding of diar-rhea, edema, ascites, immunodeficiency, or hypercoagu-

Accepted for publication May 15, 2003.

Address reprint requests to Dr Kim, Sejong Heart Institute, 91-121,Sosa-dong, Sosa-Ku Pucheon City, Kyunggi-do, Korea; e-mail:ksoojn@yahoo.co.kr.

Table 1. Clinical Course of the Patient

Age of the patient (months) 18 36 37 41 54 66(Fontan operation)

Total protein (g/dL) 7.2 2.4 2.9 2.6 2.1 6.9Albumin (g/dL) 4.1 1.4 1.7 1.5 1.3 3.9Ionized calcium (mg/dL) 4.2 4.3 4.1 3.8 2.6 4.2Intermittent albumin ➝Heparin infusion ➝Calcium supplement ➝

1456 CASE REPORT KIM ET AL Ann Thorac SurgREVERSAL OF PLE WITH CALCIUM REPLACEMENT 2004;77:1456–7

© 2004 by The Society of Thoracic Surgeons 0003-4975/04/$30.00Published by Elsevier Inc doi:10.1016/S0003-4975(03)00894-4

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lability is diagnosed with increasing frequency afterFontan operation. The exact pathophysiologic mecha-nism is unknown, but it is likely to be related to hemo-dynamic derangement of the intestinal circulation, sec-ondary to the Fontan physiology [2, 3].

Hypoproteinemia and PLE afflicts 7% to 10% of pa-tients following Fontan operation [4]. Previous reportsidentified the following risk factors for the developmentof PLE: elevated pulmonary arteriolar resistance (�4Wood units/m2), heterotaxia syndrome, especiallypolysplenia, anomalies of systemic venous drainage, anddecreased ventricular function with elevated left ventric-ular end-diastolic pressure (12 mm Hg) [4].

Interestingly, neither elevated pulmonary artery pres-sures, pulmonary arterial size or distorsion, nor atrioven-tricular (AV) valve regurgitation was found to signifi-cantly affect the development of this complication in ourpatient. Also, our patient had no significant hemody-namic risk factors.

This report is interesting because PLE in our patientwith hypocalcemia was recovered with calcium replace-ment. Correspondingly, recurrence developed 6 weeksafter calcium tapering.

Decreased serum total calcium level is a commonfinding in PLE and is usually attributable to hypoalbu-minemia and a decrease in the protein-bound, inactivefraction of serum calcium. Rarely, ionized calcium levelsare decreased, indicating a decrease in the active fractionof serum calcium. Cause of this finding is not known, butit is possible that calcium malabsorption may developalone or in addition to vitamin D deficiency attributableto fat-soluble vitamin malabsorption. The mechanism bywhich treatment of hypocalcemia relieve enteric proteinloss across gut mucosa in PLE is unclear. It is possiblethat the presence of ionized calcium (Ca��) on thecellular membrane of the enteric epithelium cloud allowa covalent binding with the negative charge (COOH tail)of two protein chains, therefore preventing protein en-teric loss. Thus far, it has not been investigated.

References

1. Feldt RH, Driscoll DJ, Offord KP, et al. Protein-losing enter-opathy after the Fontan operation. J Thorac Cardiovasc Surg1996;122:672–80.

2. Cohen MI, Rhodes LA, Wernosvsky G, et al. Atrial pacing: analternative treament for protein-losing entreropathy after theFontan operation. J Throac Cardiovasc Surg 2001;121:582–3.

3. Rychik J. Management of protein-losing enteropathy after theFontan procedure. Semin Thorac Cardiovasc Surg PediatrCard Surg Annu 1998;1:15–22.

4. Driscoll DJ, Offord KP, Feldt RH, et al. Five to fifteen yearfollow-up after Fonatn operation. Circulation 1992;85:469–96.

Autologous Patch Angioplasty ofthe Left Main Coronary Artery in aPediatric Patient: 7-Year Follow-UpPetros V. Anagnostopoulos, MD, Frank A. Pigula, MD,John L. Myers, MD, Lee B. Beerman, MD,Ralph D. Siewers, MD, and Sanjiv K. Gandhi, MD

Divisions of Pediatric Cardiothoracic Surgery and PediatricCardiology, Children’s Hospital of Pittsburgh, University ofPittsburgh School of Medicine, Pittsburgh, Pennsylvania, andDivision of Pediatric Cardiothoracic Surgery, PennsylvaniaState Children’s Hospital, Hershey, Pennsylvania

We present a patient who developed ischemia after anarterial switch procedure for transposition of the greatvessels secondary to left coronary artery stenosis. Theexcellent intermediate-term result of patch angioplasty ofthe left main coronary artery with the use of an internalthoracic artery patch is outlined.

(Ann Thorac Surg 2004;77:1457–9)© 2004 by The Society of Thoracic Surgeons

Accepted for publication April 9, 2003.

Address reprint requests to Dr Gandhi, Division of Cardiothoracic Sur-gery, Children’s Hospital of Pittsburgh, 3705 Fifth Ave, Pittsburgh,PA 15213; e-mail: sanjiv.gandhi@chp.edu.

Fig 1. Changes in serum albumin and ion-ized calcium concentration over time withinstitution of oral calcium supplementation.Increases in serum albumin level are fol-lowed after increased serum ionized cal-cium level and institution of calcium sup-plementation, and a marked decrease inserum albumin level after abrupt reducingdose of oral calcium supplementation isillustrated. Serum albumin levels increasedagain with increased oral calcium supplyand remained normal despite the decreasein calcium dose given.

1457Ann Thorac Surg CASE REPORT ANAGNOSTOPOULOS ET AL2004;77:1457–9 AUTOLOGOUS PATCH ANGIOPLASTY IN A PEDIATRIC PATIENT

© 2004 by The Society of Thoracic Surgeons 0003-4975/04/$30.00Published by Elsevier Inc doi:10.1016/S0003-4975(03)01262-1

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