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ORIGINAL ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 1  |  Page : 31-34

The Results of a 2-year Experience in Pediatric Heart Transplant in Rajaie Cardiovascular Medical and Research Center


1 Rajaee Cardiovascular, Medical and Research Center, Vali Asr Ave, Nyayesh Cross, Tehran, Iran
2 Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, University of Medical Sciences, Tehran, Iran
3 Heart Valve Disease Research Center, Rajaie Cardiovascular Medical and Research Center, University of Medical Sciences, Tehran, Iran

Date of Web Publication26-Feb-2018

Correspondence Address:
Dr. Ali Sadeghpour Tabaei
Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/rcm.rcm_36_17

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  Abstract 


Introduction: Heart transplantation is the ultimate treatment method for many infants and children with the diagnosis of cardiomyopathy or final stages of congenital heart failure. Purpose: This report provides the results of children's heart transplantation in Shahid Rajaie Heart Center during a 2-year period. Methods: Studying retrospective information of heart-transplanted children between 2012 and 2015. Results: Nineteen cases of pediatric heart transplantation were performed between 2012 and 2015 on children aged between 16 months and 14 years with an average age of 10 months. Among these, 14 (73.7%) cases were male and 5 (26.3%) cases were female. Among heart-transplanted cases, 10 (52.6%) cases were diagnosed with idiopathic dilated cardiomyopathy, 1 (5.3%) case was diagnosed with myocarditis, 7 (36.8%) cases were diagnosed with left ventricular (LV) noncompaction, and 1 (5.3%) case was diagnosed with myocarditis and LV noncompaction. After the heart transplantation, two cases suffered from pericardial effusion, three cases suffered from renal failure, three cases suffered from the right heart failure, three cases received extracorporeal membrane oxygenation, one case suffered from hypersensitivity to mycophenolate mofetil, and one case suffered from polyradiculopathy. Conclusion: Our short-term experience shows good results with low mortality rates and controlled complications of heart transplantation. Although we are in the early stages and are going through experiences, we expect to get better results given that there is an increase in the number of donors alongside improvements in immunosuppressive treatments and appropriate antibiotics.

Keywords: Cardiomyopathy, heart transplantation, pediatric


How to cite this article:
Mahdavi M, Hejri GM, Bakhshandeh H, Amin A, Tabaei AS, Dehaki MG, Hosseini S, Totonchi Z, Baharestani B. The Results of a 2-year Experience in Pediatric Heart Transplant in Rajaie Cardiovascular Medical and Research Center. Res Cardiovasc Med 2018;7:31-4

How to cite this URL:
Mahdavi M, Hejri GM, Bakhshandeh H, Amin A, Tabaei AS, Dehaki MG, Hosseini S, Totonchi Z, Baharestani B. The Results of a 2-year Experience in Pediatric Heart Transplant in Rajaie Cardiovascular Medical and Research Center. Res Cardiovasc Med [serial online] 2018 [cited 2019 Nov 22];7:31-4. Available from: http://www.rcvmonline.com/text.asp?2018/7/1/31/226166




  Introduction Top


Heart transplantation is the ultimate treatment method for many infants and children with the diagnosis of cardiomyopathy or final stages of congenital heart failure.[1],[2] According to the registry of the International Society for Heart and Lung Transplantation, 350–500 heart transplantations are performed every year in all parts of the world [3] and about 512 pediatric heart transplants were performed in 2015.[4] The first pediatric heart transplantation in our center was performed 4 years ago on a 14-year-old boy with an initial diagnosis of dilated cardiomyopathy. Due to severe complications of the transplantation, the transplant program was suspended for 2 years and was performed on 18 children from 2 years. This report provides the results of pediatric heart transplants during a 2-year period that for the first time in Iran this type of surgery was being performed on such number of children with the primary diagnosis of left ventricular (LV) cardiomyopathy, noncompaction, and myocarditis.


  Methods Top


From 2012 to 2015, pediatric heart transplantation was being performed in our center in which 18 of those cases were performed during the last 2 years. Ten patients had idiopathic dilated cardiomyopathy, one had myocarditis and LV noncompaction, seven had LV noncompaction, and one had myocarditis.

The diagnosis of all patients according to echo results was heart failure resistant to optimal guideline-directed medical therapy, and they were frequently hospitalized and received inotropic treatments. The donors' hearts were from brain-dead patients, and 100%–150% of recipient body surface areas and blood groups were compatible between the donor and the recipient.

According to the Children's Hospital of Philadelphia protocol, all patients received 600 mg/m 2 mycophenolate mofetil before transplantation, and after transplantation, all patients received mycophenolate mofetil, Solu-Medrol, tacrolimus, and antithymocyte globulin (ATG); all patients have also received prophylactic Cytomegalovirus (CMV) with ganciclovir and Pneumocystis carinii with co-trimoxazole [Table 1].
Table 1: Immunosuppression regimen for heart transplantation


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All patients were followed for signs and symptoms of rejection as well as signs of infectious complications of using immunosuppressive medications, through echocardiography, chest radiography, electrocardiography, and also laboratory findings such as tacrolimus level and checking CMV antigen. At the end of the 1st week after transplantation and after that on a regular basis, all patients underwent endomyocardial biopsy to check for organ rejection.


  Results Top


Demographic data

Nineteen cases of pediatric heart transplantation were performed between 2012 and 2015 on children, and their demographic data are shown in [Table 2].
Table 2: Demographic data


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One patient had undergone atrial septal defect closure surgery, one patient had undergone ventricular septal defect closure with Amplatzer, and one patient with LV noncompaction and Wolff–Parkinson–White and atrioventricular nodal reentrant tachycardia had undergone ablation. Before transplantation, pro-brain natriuretic peptide (proBNP) level of 12 patients was <2500 and of seven patients was >2500.

Complications after heart transplantation

Posttransplantation complications are divided into two groups of early and late complications [Table 3].
Table 3: Postoperative outcomes


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Early complications include pericardial effusion, renal failure, and right heart failure.

Pericardial effusion

Two patients suffered from pericardial effusion on days 5 and 8 after transplantation, who were recovered through pericardiocentesis.

Renal failure

Three patients suffered from renal failure and underwent dialysis on days 5, 8, and 19 after transplantation.

Right heart failure

Three patients suffered from right heart failure: two cases immediately after transplantation and one case 8 days after transplantation.

Rejection

Early-phase rejection – One case of hyperacute transplant rejection was a 12-year-old patient with symptoms of arrhythmia resistant to treatment in early hours after transplantation. The patient received extracorporeal membrane oxygenation (ECMO) and medical therapy with ATG, prednisolone, plasmapheresis, and rituximab and the biopsy result reported humoral and cellular rejection. Both cases of transplant rejection received treatments and were discharged in good general condition.

Extracorporeal membrane oxygenation

Three patients received ECMO following heart transplantation. One of the patients suffered from blood coagulation disorder due to uncontrollable bleeding in surgery room and immediately received ECMO and passed away after 7 days. One patient received ECMO after hyperacute transplant rejection immediately after transplantation that by immunosuppressive treatment and improvement of transplant rejection; the patient was taken from ECMO after 7 days. The youngest child, who underwent transplantation, received ECMO due to severe right heart failure and was taken from ECMO after improvement of right heart failure 7 days later.

Late-phase complications include infection and late-phase rejection.

Infection

One patient got CMV-Ag positive 2 months after transplantation and was treated with venous ganciclovir and then by oral valacyclovir. One of the cases suffered from diarrhea caused by giardia about 2 weeks after transplantation and was treated with furazolidone, metronidazole, and intravenous immunoglobulin (IVIG). One patient suffered from renal aspergillosis 10 months after heart transplantation and was treated with caspofungin and voriconazole. The same patient referred back with symptoms of transplant rejection and pneumonia 20 months after transplantation; after examination with bronchoalveolar lavage and diagnosis of pneumonia caused by P. carinii, mycoplasma, and CMV, the patient was treated with co-trimoxazole, dapsone, azithromycin, and ganciclovir.

Late-phase rejection

One case of transplant rejection was a 14-year-old patient that occurred 20 months after transplantation; the biopsy result reported cellular rejection. The patient was treated with pulse methylprednisolone, ATG, and IVIG.

Follow-up

We followed 18 patients with an average duration of 12 months, minimum of 1 month and maximum duration of 48 months. All patients were visited in short revisit intervals and their serum tacrolimus level and CMV-Ag were checked at each visit. They could easily contact their doctors and solve their problems. We took endomyocardial biopsy in short intervals for rejection.

Except one patient who had late rejection and life-threatening infections that were successfully controlled, we did not have any other life-threatening infections.

During the follow-up, one of the patients suffered from hypersensitivity to tacrolimus which showed digestive symptoms; symptoms were improved by replacing the medication with azathioprine. One patient suffered from hypersensitivity to mycophenolate mofetil which showed mouth sores; symptoms were improved by replacing the medication with azathioprine and the patient was discharged with good general condition. One patient suffered from radiculopathy 1.5 years after heart transplantation that was treated and improved with IVIG.

Mortality

Only one patient died early due to protein C and protein S deficiencies and coagulation problems. Although the patient was undertreated with ECMO protocol, he died due to brain death after a week of transplantation.


  Discussion Top


With the introduction of immunosuppressive cyclosporine drug in 1980 and improvements in results of heart transplantation in adults, heart transplant centers are encouraged to perform heart transplant on children, and finally, the first successful pediatric heart transplantation was performed by Bailey et al. in 1985.[1],[2] Among patients who suffer from cardiomyopathy due to various reasons, children have less chance of finding a heart donor due to their low weight and lack of appropriate donor.[5] We also faced lack of donors, and many patients in the waiting list died due to lack of proper heart donor.

With the development of surgical techniques and drug treatments, the heart transplantation results have improved. Although complications after heart transplants including transplant rejection, infection, malignant, and chronic allograft vasculopathy still exist, heart transplantation is still a treatment method to improve the quality of the patient's life.[6] Most mortalities occur during the 1st year after transplantation, and the mortality rate gradually decreases. Transplanted organ failure and surgical technique problems are responsible for 30% of deaths in this duration; multisystem failure (16%), CMV infection (14%), and transplant rejection (12%) are the other causes responsible for the death of these patients.[7] The first pediatric heart transplantation in our center was performed 4 years ago on a 14-year-old patient who suffered from severe transplant rejection and infection; due to these complications, the transplant program was suspended for 2 years and was performed on 18 children from 2 years ago. In our patients, we only had one case of death due to protein C and protein S deficiencies and problems with blood coagulation.

It seems that in the first steps of the beginning of pediatric heart transplantation, our operation room results and complications were good and similar to other expert centers.

Considering the 2-year period of heart transplantation, the average follow-up time was 12 months, except one case that the follow-up time was 48 months. Other studies with longer follow-up periods such as a study by Sarris et al. which was performed on 72 patients from 1977 to 1993, the survival rate of 1-, 5-, and 10-year olds were 75%, 60%, and 50%, respectively.[8] Several studies have examined pediatric heart transplantation on patients suffering from cardiomyopathy, myocarditis, and congenital heart failure.[1],[9] In our center, we started heart transplant program on patients suffering from cardiomyopathy, myocarditis, and LV noncompaction and postponed transplants on patients with congenital heart failure to future because of its complexities. In studies by Groetzner et al.[1] and Miana et al.,[10] they introduced infections and transplant rejection as the main cause of mortality in long-term follow-up. Considering the improvements in immunosuppressive medications and diagnostic methods and effective antibiotics, we expect to have a lower rate of mortality and infection in long-term follow-ups. Some of the problems we face in follow-ups are malignancy and graft-related vascular disorders and the need for repeating heart transplantation that must be considered in patient's follow-ups. We are currently continuing our program and we will provide a complete report about later outcomes in the near future.


  Conclusion Top


In our experiment, we had a low rate of mortality and few posttransplant complications that were controllable with good and similar operating room results with other expert centers, and we also expect to have a shorter waiting list and better results by improving our experience and better cooperation of heart donation from brain-dead patients in the near future.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Groetzner J, Reichart B, Roemer U, Reichel S, Kozlik-Feldmann R, Tiete A, et al. Cardiac transplantation in pediatric patients: Fifteen-year experience of a single center. Ann Thorac Surg 2005;79:53-60.  Back to cited text no. 1
[PUBMED]    
2.
Adwani SS, Whitehead BF, Rees PG, Whitmore P, Fabre JW, Elliott MJ, et al. Heart transplantation for dilated cardiomyopathy. Arch Dis Child 1995;73:447-52.  Back to cited text no. 2
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3.
Dipchand AI, Edwards LB, Kucheryavaya AY, Benden C, Dobbels F, Levvey BJ, et al. The Registry of the International Society for Heart and Lung Transplantation: Seventeenth official pediatric heart transplantation report-2014; Focus theme: Retransplantation. J Heart Lung Transplant 2014;33:985-95.  Back to cited text no. 3
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4.
Kaushal S, Jacobs JP, Gossett JG, Steele A, Steele P, Davis CR, et al. Innovation in basic science: Stem cells and their role in the treatment of paediatric cardiac failure – Opportunities and challenges. Cardiol Young 2009;19 Suppl 2:74-84.  Back to cited text no. 4
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5.
Jatene MB, Miana LA, Pessoa AJ, Riso A, Azeka E, Tanamati C, et al. Pediatric heart transplantation in refractory cardiogenic shock: A critical analysis of feasibility, applicability and results. Arq Bras Cardiol 2008;90:329-33.  Back to cited text no. 5
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6.
Thrush PT, Hoffman TM. Pediatric heart transplantation-indications and outcomes in the current era. J Thorac Dis 2014;6:1080-96.  Back to cited text no. 6
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7.
Dipchand AI, Kirk R, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, et al. The Registry of the International Society for Heart and Lung Transplantation: Sixteenth official pediatric heart transplantation report-2013; Focus theme: Age. J Heart Lung Transplant 2013;32:979-88.  Back to cited text no. 7
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8.
Sarris GE, Smith JA, Bernstein D, Griffin ML, Pitlick PT, Baum D, et al. Pediatric cardiac transplantation. The Stanford experience. Circulation 1994;90:II51-5.  Back to cited text no. 8
[PUBMED]    
9.
Parisi F, Carotti A, Esu F, Abbattista AD, Cicini MP, Squitieri C, et al. Intermediate and long-term results after pediatric heart transplantation: Incidence and role of pretransplant diagnosis. Transpl Int 1998;11 Suppl 1:S493-8.  Back to cited text no. 9
    
10.
Miana LA, Azeka E, Canêo LF, Turquetto AL, Tanamati C, Penha JG, et al. Pediatric and congenital heart transplant: Twenty-year experience in a tertiary Brazilian Hospital. Braz J Cardiovas Surg 2014;29:322-29.  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]


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1 Immunosuppressants
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