Heart transplantation and mitral valve repair in pediatric patients with refractory heart failure

Heart Transplantation

Heart Transplantation and Mitral Valve Repair in Pediatric Patients With Refractory Heart Failure S.-S. Wang, R.-B. Hsu, Y.-S. Chen, W.-J. Ko, N.-K. Chou, H.-Y. Yu, S.-H. Chu, C.-S. Liau, and Y.-T. Lee

H

EART TRANSPLANTATION (HT) is an effective therapeutic modality for infants and children with end-stage or inoperable cardiac disease.1–3 Because of the shortage of donors, many patients die during the waiting period.4 There is also considerable donor-recipient body weight (BW) discrepancy in small children. Nontransplant cardiac operations,5,6 have been introduced to treat refractory heart failure (RHF). Yet its clinical effects in small children was not well established.7 The aim of this paper was to evaluate the effect of HT and mitral repair (including Batista operation) in pediatric patients with RHF. MATERIALS AND METHODS From March 1995 to February 2002, 149 patients underwent HT at the National Taiwan University Hospital. Among them, nine pediatric patients (age at transplantation less than 16 years) underwent orthotopic HT (OHT) for RHF. The clinical characteristics are shown in Table 1. There were four boys and five girls. The ages of the recipients ranged from 5 months to 14 years, 8 months with a mean of 5 years, 11 months ⫾ 5 years, 1 month. The ages of the donors ranged from 1 year to 18 years old with a mean of 10 ⫾ 7 years. The BW of recipient ranged from 4 to 40 kg with a mean of 16 ⫾ 11 kg. The BW of the donors ranged from 10 to 56 kg with a mean of 32 ⫾ 19 kg. The body height of recipients ranged from 53 to 154 cm with a mean of 102 ⫾ 30 cm. The underlying disease was dilated cardiomyopathy (CM) in four (among the four, one underwent mitral valve repair 5 months before OHT, another underwent Batista5 operation 7 months before OHT), restrictive CM in two, complex congenital heart diseases (CHD) in one (this 7-year-old girl with transposition of great artery and pulmonary atresia underwent a Blalock-Taussig shunt for palliation at 1 and 2 years of age, respectively, and a bidirectional Glenn shunt at 6 years), hypertrophic CM in one, and Kawasaki disease with coro© 2003 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 35, 463– 465 (2003)

nary aneurysms and total occlusion of left anterior descending coronary (LAD) artery in one. Among the nine patients, two with dilated CM with moderate to severe mitral regurgitation underwent mitral valve repair before OHT. One was a 10-kg boy age 2 years, 6 months (case 8). He was intubated for intractable heart failure under maximal doses of catecholamine including epinephrine, dobutamine, dopamine, and milrinone. Echocardiographic examinations revealed left ventricular ejection fraction (LVEF) of 25% and left ventricular end diastolic dimension (LVEDD) of 52 mm. Cardiac catheterization revealed pulmonary artery pressure of 58/30 mm Hg with O2 saturation of 32%, while left ventricular pressure was 65/23 mm Hg and aortic pressure 61/48 mm Hg. Because no suitable donor was available and was impending, renal failure he underwent emergency mitral valve surgery. The mitral valve was reconstructed with Alfieri’s repair and Wooler’s annuloplasty. He was discharged with LVEDD of 45 mm and LVEF of 28% 1 month after surgery. However, he suffered from heart failure and underwent OHT 5 months after mitral valve repair. The other was a 12-kg girl at the age of 3 years, 4 months (case 5). Exertional dyspnea occurred at 5 months old when she got viral myocarditis. Serial echocardiographic examinations revealed LVEDD of 36 mm at the age of 7 months and 74 mm at 40 months old, and LVEF decreased from 41% to 10%. Because of intractable heart failure on multiple inotropic drips, she underwent Batista operation. She was discharged with LVEDD of 58 mm and LVEF of 28% 1 month after

Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. Address reprint requests to Shoei-Shen Wang, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan. 0041-1345/03/$–see front matter doi:10.1016/S0041-1345(02)03985-4 463

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WANG, HSU, CHEN ET AL Table 1. Clinical Characteristics of the Nine Pediatric Patients

Case

Age

Donor Age Height Weight (Year) Sex (cm) (kg)

Donor Weight (kg)

Underlying Disease

Ischemic Time (Minutes)

1

9 years, 7 months

15

F

125

23

56

Dilated CM

52

2

1 years, 2 months

7

M

80

6

20

Dilated CM

200

3

6 years, 8 months

8

F

115

17

26

340

4

14 years, 8 months

18

F

154

40

56

TGA ⫹ PA s/p BT shunt, Glenn shunt Restrictive CM

120

5 6 7 8 9

3 years, 4 months 5 months 3 years, 3 months 2 years, 6 months 11 years, 11 months

16 7 17 1 7

F M M M F

93 53 90 86 119

12 4 12 10 24

42 10 50 12 20

Dilated CM s/p Batista Hypertrophic CM Kawasaki s/p CABG on ECMO Dilated CM s/p MR Restrictive CM

218 110 214 236 257

Complications

Moderate rejection 2 months after OHT PTLD 8 months after OHT, CMV infection 1 year after OHT CMV infection 9 months after OHT Humoral rejection 2 weeks after OHT Nil Nil Mortality 23 days after OHT Nil Recurrent ascites 1 day after OHT

F, female; CM, cardiomyopathy; OHT, orthotopic heart transplantation; M, male; PTLD, posttransplant lymphoproliferative disease; CMV, cytomegalovirus; TGA, transposition of great artery; PA, pulmonary atresia; s/p, status post; BT, Blalock-Taussig; CABG, coronary artery bypass grafting; ECMO, extracorporeal membrane oxygenation; MR, mitral repair.

surgery. However, she suffered from heart failure 6 months after surgery and underwent OHT 7 months after Batista operation. Before OHT, all patients were in New York Heart Association functional class IV and the patient with Kawasaki disease (case 7) was receiving extracorporeal membrane oxygenation (ECMO) support. All patients underwent OHT with traditional right atrial anastomosis except the patient with complex CHD (case 3), who underwent bicaval anasotomosis.8 After OHT all patients received the same immunosuppressive protocol: antithymocyte globulin and methylprednisolone for induction, and triple therapy with azathioprine, prednisolone, and cyclosporine or tacrolimus as maintenance therapy. All patients were regularly followed up, including echocardiography and endomyocardial biopsy. The data are presented as mean values ⫾ standard deviation.

RESULTS

One of the nine pediatric patients died after OHT. This 3-year-old boy with Kawasaki disease (case 7) underwent coronary artery bypass grafting (left internal mammary artery to LAD, right gastroepiploic artery to right coronary artery) 2 days before OHT and was on ECMO. He finally died of multiple organ failure 23 days after OHT. The operative mortality was 11%. All the other eight patients survived the transplantation and are well now. The actuarial 7-year survival rate was 89%. Except the 12-year-old girl with restrictive CM (case 9), all the other eight patients received an oversized donor heart and the donor-recipient BW ratio was up to 4.2 in case 7. Despite this significant BW discrepancy, however, the heart size ratio showed no significant difference. No technical problems were noted during OHT. The ischemic time of the donor heart ranged from 52 to 340 minutes with a mean of 194 ⫾ 87. The cardiopulmonary bypass time ranged from 103 to 346 minutes with a mean of 178 ⫾ 68. The operation time from skin to skin ranged from 240 to 780 minutes with a mean of 429 ⫾ 179.

All patients showed a dramatic improvement in LVEF to greater than 60% 1 month after OHT. Cardiac function during serial follow-up (1 month to 6 years) revealed normal systolic and diastolic function. No anticongestive medication was required. None suffered from severe rejection. One (case 1) suffered from grade 2 moderate rejection and was cured with tacrolimus, muromonoab-CD3, and methylprednisolone. Another (case 4) suffered from acute humoral rejection, which was controlled with tacrolimus and mycophenolate mofetil. Epstein-Barr virus associated posttransplant lymphoproliferative disease was diagnosed by cervical lymph node biopsy in a 2-year-old boy (case 2) 8 months after OHT. He was successfully treated with intravenous immunoglobulin, ␣-interferon, acyclovir, and reduced cyclosporine dose. Cytomegalovirus infection was also noted in this patient 1 year after OHT. Another girl with complex congenital heart disease (case 3) also suffered from cytomegalovirus infection 9 months after OHT. Both were controlled with gancyclovir. DISCUSSION

Heart transplantation is the treatment of choice for endstage myocardial failure, both in adults and children.1–3 Wider application of pediatric HT is limited by the shortage of appropriate donor organs.9 Donor-recipient BW mismatch is common. Usually the larger the donor relative to the recipient, the better result.1 In this study, eight of nine patients received oversized heart transplants, which did not show disturbed heart or lung function posttransplantation. Because of severe cardiomegaly of recipients with RHF, an oversized donor may not be a contraindication, and can be used with donor/recipient BW ratio up to 4.2 without a heart size discrepancy. Preoperative evaluation of the heart size of the donor and recipient with chest X-ray or echocardiographic examination is crucial.

HEART TRANSPLANTATION IN PEDIATRIC PATIENTS

Although pediatric heart transplantation has gained popularity with improved early results and long-term outcomes,1,9 it is restricted by the donor shortage. Our policy to treat the patient with intractable heart failure and immediate threat to death was to apply nontransplant cardiac surgery as a bridge to HT,10 –12 including mitral vale repair, Batista operation,5 ECMO, or ventricular assist devices. Batista operation required left ventriculectomy and mitral repair. It is not restricted by donor sources. In this study, case 5 underwent Batista operation for RHF, which was the first pediatric case of Batista operation in Taiwan. After operation, the cardiac function improved with the LVEF, increasing from 10% to 28%. However, intermittent intravenous inotropic agents were sometimes required, and finally she underwent OHT 7 months after Batista operation. It is concluded that either mitral valve repair alone or Batista operation can be used as a bridge to transplantation in pediatric patients. The results of heart transplantation for pediatric patients with RHF are satisfactory, with an

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operative mortality of 11% and a 7-year survival rate of 89%. REFERENCES 1. Hosenpud JD, Bennett LE, Keck BM, et al: J Heart Lung Transplant 20:805, 2001 2. Wang SS, Chu SH, Ko WJ: Transplant Proc 28:1733, 1996 3. Wang SS, Chu SH: Artif Organs 20:1325, 1996 4. Wang SS, Chou NK, Hsu RB, et al: Transplant Proc 32:1527, 2000 5. Batista RJV, Verde J, Nevy P, et al: Ann Thorac Surg 64:634, 1997 6. Bolling SF, Pagani FD, Deeb GM, et al: J Thorac Cardiovasc Surg 115:381, 1998 7. Varicella A, Gundry SR, Larsen RL, et al: Ann Thorac Surg 69:1253, 2000 8. Wang SS, Chu SH, Hsu RB, et al: Transplant Proc 32:2396, 2000 9. Dellgren G, Koirala B, Sakopoulus A, et al: J Thorac Cardiovasc Surg 121:782, 2001 10. Wang SS, Chen YS, Ko WJ, et al: Artif Organs 20:1287, 1996 11. Wang SS, Chu SH, Ko WJ, et al: Transplant Proc 30:3401, 1998 12. Wang SS, Ko WJ, Chen YS, et al: Artif Organs 25:599, 2001