Asian Cardiovasc Thorac Ann 2001;9:312-314
© 2001 Asia Publishing EXchange Pte Ltd
Follow-Up on Heart Transplant After Left Ventricular Assist System Bridge
Norihide Fukushima, MD,
Shigeaki Ohtake, MD,
Yoshiki Sawa, MD,
Motonobu Nishimura, MD,
Goro Matsumiya, MD,
Seiji Takashima, MD1,
Masatsugu Hori, MD1,
Ryota Shirakura, MD2,
Hikaru Matsuda, MD
Department of Surgery
1 Department of Internal Medicine and Therapeutics
2 Division of Organ Transplantation Osaka University Graduate School of Medicine Osaka, Japan
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For reprint information contact: Norihide Fukushima, MD Tel: 81 6 6879 3154 Fax: 81 6 6879 3159 email: nori{at}surg1.med.osaka-u.ac.jp Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
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ABSTRACT
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The first heart transplantation permitted under the new organ transplantation law was carried out in a 47-year-old man in the dilated phase of hypertrophic cardiomyopathy. He had been on a Novacor left ventricular assist system for the previous 4 months. The posttransplant course was uneventful and he returned to work 9 months later. After 2 years of follow-up, he was in good condition and enjoyed a normal quality of life and regular work.
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INTRODUCTION
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For at least 10 years, approximately 4,000 heart transplants (HTx) have been carried out annually worldwide, including several Asian countries.1,2 Although HTx has not been performed in Japan since the first transplant in 1968, finally, the required legislation was enacted in October 1997, and the first HTx under the new law was carried out in 1999.3 The 2-year posttransplant follow-up of the patient is described in this report.
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CASE REPORT
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A 47-year-old man in the dilated phase of hypertrophic cardiomyopathy requiring hospitalization and intensive treatment, qualified as a candidate for HTx and was registered in the Japan Organ Transplantation Network. When he developed severe cardiac decompensation one year after registration, he was moved to our hospital and underwent implantation of a Novacor (Baxter Healthcare, Oakland, CA, USA) left ventricular assist system (LVAS). His post-LVAS course was uneventful. After 4 months, he underwent orthotopic HTx. As this was the first case of HTx from a brain-dead donor under the new legislation, he was kept in hospital until the risks of rejection and infection were considered negligible. He was discharged after 75 days and returned to full-time work 9 months post-HTx.
For immunosuppression, a triple-therapy regimen was started with cyclosporine, azathioprine, and steroid. As urination stopped soon after starting intravenous cyclosporine, infusion was discontinued and the drug was given orally after oral intake was started. Azathioprine was replaced with mycophenolate mofetil because of mild liver dysfunction. No episode of acute rejection greater than grade III was encountered until 20 months after HTx, so prednisolone was tapered at 6 months and the regimen at 20 months postoperatively consisted of twice daily doses of cyclosporine 250 mg, mycophenolate mofetil 1 g, and prednisolone 5 mg (Figure 1
). There was no serious episode of infection during the 2 years after HTx. The patient's serological status before LVAS implantation was negative for cytomegalovirus (CMV), but that of the donor was positive, so intravenous ganciclovir (3 mg•kg-1) was given daily for 5 days. At 43 days post-HTx, the serum level of CMV-related messenger ribonucleic acid (mRNA) was found to be elevated without any clinical manifestation or other laboratory findings of CMV disease.4 Intravenous ganciclovir (6 to 10 mg•kg-1) was given daily for 24 days and 5 g of intravenous immunoglobulin with a high CMV antibody titer was given daily for 3 days. The response was good and mRNA became undetectable with no antigenemia. Until the prednisolone dosage was reduced to 5 mg, the patient experienced 3 more episodes of positive mRNA without any clinical or laboratory indications of CMV infection (Figure 2).
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Figure 1. Triple-therapy immunosuppressive regimen with cyclosporine (CSA), prednisolone (Pred), azathioprine (AZA), and mycophenolate mofetil (MMF). Methylprednisolone (MP) was given early postoperatively. There was no evidence of rejection above International Society for Heart and Lung Transplantation (ISHLT) grade III after heart transplantation (HTx).
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Figure 2. Monitoring and prevention of cytomegalovirus disease. Ag-emia = antigenemia, GCV = ganciclovir (mg), IVIG = intravenous immunoglobulin, mRNA = messenger ribonucleic acid, NASBA = nucleic acid sequence-based amplification, PCR = protein chain reaction, WBC = white blood cell count.
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Echocardiography and cardiac catheterization at 1 and 2 years after HTx showed good cardiac function with a cardiac index of 4.2 to 4.9 L•min-1•m-2, pulmonary wedge pressure of 6 to 8 mm Hg, left ventricular ejection fraction of 75%, no mitral regurgitation, and trivial tricuspid regurgitation. Intravascular ultrasonography demonstrated no graft atherosclerosis with an intimal thickening score of 21%, although some plaques had been found on the inner surface of the left coronary arteries 3 months after HTx. Oxygen consumption at maximal exercise increased steadily from 9.7 to 17.2 mL•kg-1•min-1 after HTx. After 2 years of follow-up, the patient was in good condition and enjoyed a normal quality of life and regular work.
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DISCUSSION
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Although it has taken a long time to issue the organ transplantation law and the legislation is very stringent in Japan, the first legally approved donation of a heart and liver for transplantation took place in 1999.3 Since then, the number of Japanese people with a written consent card for organ donation has increased. In the 2 years after the first HTx, 12 organ donors have enabled the transplantation of 9 hearts, 5 single lungs, 10 livers, 17 kidneys, and 3 combined renal and pancreatic grafts.
As the donor shortage is extremely serious in Japan, the LVAS has a more important role in managing patients awaiting HTx than in other countries. Indeed, 3 of 6 patients who underwent HTx recently in Japan were bridge cases.3 The LVAS provides many advantages but also several disadvantages, such as thromboembolic events, infections, and elevation of anti-human leukocyte antigen (HLA) antibodies that may affect the outcome of a subsequent HTx.5 This patient had undergone a transfusion 4 months prior to HTx at the time of LVAS implantation, his panel-reactive antibody level was consistently 0% during the waiting period, and the T-lymphocyte crossmatch was also negative, probably because no platelets were infused at the time of LVAS implantation. Moreover, HLA mismatch on HLA-A, B, and DR loci was 2. These may have had beneficial roles in preventing acute rejection in this case. As more than 90% of adults in Japan show positive CMV serological status, CMV disease becomes serious even after routine cardiovascular operations.6,7 Therefore, early diagnosis and treatment of CMV disease is more important in Japanese posttransplant patients. We used very sensitive monitoring for CMV infection by detection of mRNA by the nucleic acid sequence-based amplification method rather than the antigenemia assay, and detection of CMV deoxyribo-nucleic acid by the protein chain reaction, as described by Aono and colleagues4 in bone marrow transplant recipients. In this case, the elevation of serum mRNA was always detected before deoxyribonucleic acid or antigenemia. Serum ribonucleic acid decreased rapidly on giving ganciclovir and immunoglobulin. This suggests that mRNA detection may be useful for predicting the development of CMV disease and monitoring the effect of antiviral therapy.4
Although the 2-year follow-up examination showed satisfactory cardiac function without any evidence of acute rejection or graft arteriosclerosis, peak oxygen consumption was subnormal but it was considered to be within the usual range for HTx recipients.8 Regarding the future of organ transplantation in Japan, this first case appears to have raised great social interest and a positive attitude towards acceptance of the transplantation of organs from a brain-dead donor. We hope HTx will soon be established as a strategy to treat end-stage cardiac failure in Japan, as in many other countries.
Presented at the 8th Annual Meeting of The Asian Society for Cardiovascular Surgery, Fukuoka, Japan, September 6–8, 2000.
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REFERENCES
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Aono T, Kondo K, Miyoshi H, Tanaka-Taya K, Kondo M, Osugi Y, et al. Monitoring of human cytomegalovirus infections in pediatric bone marrow transplant recipients by nucleic acid sequence-based amplification. J Infect Dis1998; 178;1244–9.[Medline]
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ABSTRACT
INTRODUCTION
