Abstract
Heart transplantation is an option for children with complex congenital heart disease and cardiomyopathies. A patient's quality of life and long-term survival depend on successful management of the surgical complications and adverse side effects of immunosuppression. The purpose of this review was to summarize the practical management of postoperative care in this patient population and to make recommendations for the future.
Heart Transplantation; Children; Immunosuppression; Rejection; Postoperative Care
INTRODUCTION
Heart transplantation is a therapeutic option for complex congenital heart disease and treatment-refractory cardiomyopathies. Some of the factors that affect the success of this procedure were reviewed, including the indication criteria for recipients and donors, immediate postoperative management, immunosuppression, complications and survival.
The main indications for heart transplantation are as follows: severe ventricular dysfunction
despite optimized drug therapy in patients with cardiomyopathies or who have undergone corrective
surgery for congenital heart disease; treatment-refractory malignant arrhythmias; complex congenital
heart disease not surgically repaired; unresectable cardiac tumors causing ventricular outlet
obstruction; unacceptable quality of life; heart failure stages C and D; oxygen consumption less
than 50% predicted for age; and progressive pulmonary hypertension that prevents heart
transplantation (11. Sociedade Brasileira de Cardiologia. I Diretriz para transplante cardíaco.
Arq Bras Cardiol. 1999;73(supl. 5):1-55.
2. Azeka E. Heart transplantation in children: the immediate postoperative period.
In: Auler Junior JO, Oliveira AS, eds. Postoperative Thoracic and Cardiovascular Surgery. Porto
Alegre: Artmed; 2004. p. 384-391.-33. Bacal F, Neto JD, Fiorelli AI, Mejia J, Marcondes-Braga FG, Mangini S, et al.
[II Brazilian Guidelines for Cardiac Transplantation]. Arq Bras Cardiol. 2010;94(1
Suppl):e16-76.).
The principal indications for transplantation in congenital heart disease are as follows:
hypoplastic left heart syndrome with right ventricular dysfunction; pulmonary atresia with
significant obstructive anomalies of the coronary arteries; interrupted aortic arch with severe
subaortic obstruction; severe unbalanced atrioventricular septal defect; various single ventricle
defects with subaortic obstruction; and severe Ebstein's anomaly. Dilated cardiomyopathies
occur most frequently, followed by restrictive cardiomyopathies (11. Sociedade Brasileira de Cardiologia. I Diretriz para transplante cardíaco.
Arq Bras Cardiol. 1999;73(supl. 5):1-55.
2. Azeka E. Heart transplantation in children: the immediate postoperative period.
In: Auler Junior JO, Oliveira AS, eds. Postoperative Thoracic and Cardiovascular Surgery. Porto
Alegre: Artmed; 2004. p. 384-391.
3. Bacal F, Neto JD, Fiorelli AI, Mejia J, Marcondes-Braga FG, Mangini S, et al.
[II Brazilian Guidelines for Cardiac Transplantation]. Arq Bras Cardiol. 2010;94(1
Suppl):e16-76.
4. Boucek MM, Edwards LB, Keck BM, Trulock EP, Taylor DO, Mohacsi PJ, et al. The
Registry of the International Society for Heart and Lung Transplantation: Fifth Official Pediatric
Report - 2001 to 2002. J Heart Lung Transplant. 2002;21(8):827-40,
http://dx.doi.org/10.1016/S1053-2498(02)00496-5.
http://dx.doi.org/10.1016/S1053-2498(02)...
5. Shaddy RE, Parisi F. Pediatric heart transplantation. In: Allen HD, Driscoll DJ,
Shaddy RE, Feltes T, eds. Moss and Adams' Heart Disease in Infants, Children, and Adolescents,
Including the Fetus and Young Adult, 7th Edition. Philadelphia: Lippincott, Williams and Wilkins;
2001. p. 1384-1400.-66. Azeka E, Franchini Ramires JA, Valler C, Alcides Bocchi E. Delisting of infants
and children from the heart transplantation waiting list after carvedilol treatment. J Am Coll
Cardiol. 2002;40(11):2034-8, http://dx.doi.org/10.1016/S0735-1097(02)02570-6.
http://dx.doi.org/10.1016/S0735-1097(02)...
).
The contraindications for heart transplantation are the following: uncontrolled systemic
infection and sepsis; irreversible pulmonary hypertension despite pulmonary vascular reactivity
tests; multiple organ failure; complex genetic syndromes; severe central nervous system
abnormalities; psychiatric disorders; prematurity; uncontrolled malignancy; and progressive systemic
disease with early mortality (genetic, metabolic and mitochondrial syndromes) (11. Sociedade Brasileira de Cardiologia. I Diretriz para transplante cardíaco.
Arq Bras Cardiol. 1999;73(supl. 5):1-55.
2. Azeka E. Heart transplantation in children: the immediate postoperative period.
In: Auler Junior JO, Oliveira AS, eds. Postoperative Thoracic and Cardiovascular Surgery. Porto
Alegre: Artmed; 2004. p. 384-391.
3. Bacal F, Neto JD, Fiorelli AI, Mejia J, Marcondes-Braga FG, Mangini S, et al.
[II Brazilian Guidelines for Cardiac Transplantation]. Arq Bras Cardiol. 2010;94(1
Suppl):e16-76.-44. Boucek MM, Edwards LB, Keck BM, Trulock EP, Taylor DO, Mohacsi PJ, et al. The
Registry of the International Society for Heart and Lung Transplantation: Fifth Official Pediatric
Report - 2001 to 2002. J Heart Lung Transplant. 2002;21(8):827-40,
http://dx.doi.org/10.1016/S1053-2498(02)00496-5.
http://dx.doi.org/10.1016/S1053-2498(02)...
).
The preoperative evaluation includes the determination of the pulmonary vascular resistance
index. Children with pulmonary vascular resistance indices greater than 6 Wood units/m2
are more susceptible to the development of right ventricular dysfunction and mortality. Currently,
inhaled nitric oxide and sildenafil citrate are administered postoperatively to reduce the risk of
pulmonary hypertension crises (77. Bando K, Konishi H, Komatsu K, Fricker FJ, del Nido PJ, Francalancia NA, et al.
Improved survival following pediatric cardiac transplantation in high-risk patients. Circulation.
1993;88(5 Pt 2):II218-23.
8. Addonizio LJ, Gersony WM, Robbins RC, Drusin RE, Smith CR, Reison DS, et al.
Elevated pulmonary vascular resistance and cardiac transplantation. Circulation. 1987;76(5 Pt
2):V52-5.
9. Azeka E, Marcial MB, Camargo PR, Kajita L, Aliman AC, Auler JO. [Hemodynamic
evaluation and clinical outcome of children with severe dilated cardiomyopathy eligible for heart
transplantation]. Arq Bras Cardiol. 1998;71(5):661-6.-1010. Azeka E, Costa Auler JO Jr, Kajita L, Alliman AC, Franchini Ramires JA, Ebaid M.
Effects of low doses of inhaled nitric oxide combined with oxygen for the evaluation of pulmonary
vascular reactivity in patients with pulmonary hypertension. Pediatr Cardiol. 2002;23(1):20-6,
http://dx.doi.org/10.1007/s00246-001-0006-2.
http://dx.doi.org/10.1007/s00246-001-000...
).
The donor's weight is another important consideration. It is recommended that the donor weigh up to three times as much as the recipient (1111. Fricker FJ, Armitage JM. Heart and heart -lung transplantation in children and adolescents. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Moss' Heart disease in infants, children, and adolescents including the fetus and young adult. Baltimore, Williams & Wilkins, 1995.495-10.). If the donor weighs more than the recipient, the latter may develop a syndrome characterized by hypertension, elevated intracranial pressure and altered consciousness due to the higher stroke volume of the donor's heart (1111. Fricker FJ, Armitage JM. Heart and heart -lung transplantation in children and adolescents. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Moss' Heart disease in infants, children, and adolescents including the fetus and young adult. Baltimore, Williams & Wilkins, 1995.495-10.).
Ischemic time must be carefully monitored; ischemic times greater than three to four hours are
associated with high mortality in the first 30 days because of primary graft failure (1111. Fricker FJ, Armitage JM. Heart and heart -lung transplantation in children and
adolescents. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Moss' Heart disease in
infants, children, and adolescents including the fetus and young adult. Baltimore, Williams &
Wilkins, 1995.495-10.
12. Dipchand A, et al. Hospital for Sick Children Heart Transplant Program. Clinical
Protocols. 2011.-1313. Azeka E, Marcial MB, Jatene M, Auler JO Jr, Ramires JA. Eight-year experience of
pediatric heart transplantation: clinical outcome using non-invasive methods for the evaluation of
acute rejection. Pediatr Transplant. 2002;6(3):208-13,
http://dx.doi.org/10.1034/j.1399-3046.2002.01075.x.
http://dx.doi.org/10.1034/j.1399-3046.20...
).
The panel reactive antibody (PRA) test indicates the percentage of the recipient's
antibodies that react with human leukocyte antigen (HLA), and patients with elevated PRA scores are
termed “sensitized”. Therefore, it is crucial to review the medical histories of both
the donor and the recipient, including blood product transfusions and previous procedures (1414. Pediatric heart transplantation protocol. Revised June 2002. Loma Linda: Loma
Linda International Heart Institute, Loma Linda University Medical Center and Children's
Hospital Transplantation Institute Cardiac Transplant Program; 2002.-1515. Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda
conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol.
1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
http://dx.doi.org/10.1016/0735-1097(93)9...
). After the
transplantation team has been notified of a potential donor, a virtual crossmatch between the
recipient and donor is performed, and the transplantation procedure begins, according to the results
of crossmatch.
During the immediate postoperative period, the main complications are primary graft failure, right ventricular failure, pulmonary hypertension crisis, rejection and infection.
The primary objective in the immediate postoperative period is maintaining adequate cardiac output because of denervation and ischemic time. The dependence on vasoactive drugs occurs mainly in the first days post-transplantation; it is recommended that these drugs be administered by continuous infusion during the first 72 hours after surgery (1111. Fricker FJ, Armitage JM. Heart and heart -lung transplantation in children and adolescents. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Moss' Heart disease in infants, children, and adolescents including the fetus and young adult. Baltimore, Williams & Wilkins, 1995.495-10.). The vasoactive drugs of choice are dobutamine, milrinone, Isuprel and epinephrine (1111. Fricker FJ, Armitage JM. Heart and heart -lung transplantation in children and adolescents. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Moss' Heart disease in infants, children, and adolescents including the fetus and young adult. Baltimore, Williams & Wilkins, 1995.495-10.). The following parameters should be monitored during the administration of vasoactive drugs: temperature, heart rate, respiratory rate, blood pressure, central venous pressure, left atrial pressure, mean pulmonary artery pressure, urine output and venous oxygen saturation.
Primary graft failure is a major cause of immediate mortality (prior to 30 days) after heart
transplantation (1515. Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda
conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol.
1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
http://dx.doi.org/10.1016/0735-1097(93)9...
). The treatment consists in some cases
the use of mechanical circulatory support or retransplantation. Prolonged ischemic time is a primary
risk factor for primary graft failure (22. Azeka E. Heart transplantation in children: the immediate postoperative period.
In: Auler Junior JO, Oliveira AS, eds. Postoperative Thoracic and Cardiovascular Surgery. Porto
Alegre: Artmed; 2004. p. 384-391.).
Pulmonary hypertension can be assessed by measuring the pulmonary artery pressure and the right
atrial pressure. Right ventricular dysfunction and tricuspid regurgitation secondary to pulmonary
hypertension can be monitored with echocardiography. Drugs such as non-selective systemic
vasodilators (sodium nitroprusside) and inhaled nitric oxide (in selected cases) are used in
combination with inotropic drugs, such as dobutamine and milrinone. Milrinone reduces pulmonary and
systemic vascular resistance and provides non-adrenergic inotropic support. In cases of severe right
ventricular failure, extracorporeal membrane oxygenation may be indicated, but it increases the risk
of bleeding and neurological complications (1515. Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda
conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol.
1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
http://dx.doi.org/10.1016/0735-1097(93)9...
16. Azeka E. Heart transplant in children: clinical analysis of evolution [PhD
in Cardiology]. São Paulo: Faculty of Medicine, USP; 1998.
17. Chinnock RE, Larsen RL, Emery JR, Bailey LL. Pretransplant risk factors and
causes of death or graft loss after heart transplantation during early infancy. Pediatric Heart
Transplant Team, Loma Linda. Circulation. 1995;92(9 Suppl):II206-9,
http://dx.doi.org/10.1161/01.CIR.92.9.206.
http://dx.doi.org/10.1161/01.CIR.92.9.20...
18. Tweddell JS, Canter CE, Bridges ND, Moorhead S, Huddleston CB, Spray TL.
Predictors of operative mortality and morbidity after infant heart transplantation. Ann Thorac Surg.
1994;58(4):972-7, http://dx.doi.org/10.1016/0003-4975(94)90440-5.
http://dx.doi.org/10.1016/0003-4975(94)9...
19. Heck CF, Shumway SJ, Kaye MP. The Registry of the International Society for
Heart Transplantation: sixth official report—1989. J Heart Transplant.
1989;8(4):271-6.-2020. Kawauchi M, Gundry SR, de Begona JA, Fullerton DA, Razzouk AJ, Boucek M, et al.
Prolonged preservation of human pediatric hearts for transplantation: correlation of ischemic time
and subsequent function. J Heart Lung Transplant. 1993;12(1 Pt 1):55-8.).
Patients with chronic congestive heart failure may exhibit elevated systemic vascular resistance,
which can lead to paradoxical hypertension in the postoperative period. Sodium nitroprusside and
angiotensin inhibitors are drugs used to manage systemic hypertension (1515. Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda
conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol.
1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
http://dx.doi.org/10.1016/0735-1097(93)9...
).
Hypertension caused by cyclosporine may develop in the first weeks to months after
transplantation, independent of nephrotoxicity. This complication may even occur years later and
cause worsening renal function. The mechanisms of cyclosporine-induced hypertension remain unclear.
Some studies have reported hypertensive patients with no renal function changes (1111. Fricker FJ, Armitage JM. Heart and heart -lung transplantation in children and
adolescents. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Moss' Heart disease in
infants, children, and adolescents including the fetus and young adult. Baltimore, Williams &
Wilkins, 1995.495-10.,1515. Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda
conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol.
1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
http://dx.doi.org/10.1016/0735-1097(93)9...
).
Prophylactic therapy is used to prevent bacterial, cytomegaloviral (CMV), toxoplasmosis and fungal infections (2121. Schowengerdt KO, Naftel DC, Seib PM, Pearce FB, Addonizio LJ, Kirklin JK, et al. Infection after pediatric heart transplantation: results of a multiinstitutional study. The Pediatric Heart Transplant Study Group. J Heart Lung Transplant. 1997;16(12):1207-16.-2222. Schowengerdt KO, Azeka E. Infection Following Pediatric Heart Transplantation. In: Canter CE, Kirklin JK, eds. ISHLT Monograph Series Volume 2: Pediatric Heart Transplantation, 1st Edition. Philadelphia: Elsevier; 2007. p.157-71.). The choice of immunosuppressive regimens varies among transplant centers. Immunosuppression protocols for children may or may not include corticosteroids. A triple (calcineurin inhibitor, cytostatic agent and steroids) or double regimen (calcineurin inhibitor and cytostatic agent) may be employed, with or without induction therapy with antithymocyte globulin.
The most common calcineurin inhibitors are cyclosporine and tacrolimus. Cyclosporine is initiated
preoperatively and discontinued during the cardiopulmonary bypass; after surgery, it is then
readministered intravenously at a continuous dose of 0.1 mg/kg/h until the endotracheal tube is
removed from the patient. Following tube removal, pediatric patients are administered oral
cyclosporine at an initial dose of 5 mg/kg/day, which is adjusted according to the serum
cyclosporine level, which is normally between 250 and 300 ng/ml. In patients with cyclosporine
toxicity, tacrolimus is administered at oral dose of 0.15 to 0.3 mg/kg/day (1414. Pediatric heart transplantation protocol. Revised June 2002. Loma Linda: Loma
Linda International Heart Institute, Loma Linda University Medical Center and Children's
Hospital Transplantation Institute Cardiac Transplant Program; 2002.). Branco et al. (2323. Branco KC, Azeka E, Trindade E, Galas FR, Hajjar LA, Benvenuti L, et al. The
impact of tacrolimus as rescue therapy in children using a double immunosuppressive regimen after
heart transplantation. Transplant Proc. 2012;44(8):2483-5,
http://dx.doi.org/10.1016/j.transproceed.2012.07.139.
http://dx.doi.org/10.1016/j.transproceed...
) reported good
outcomes after converting from cyclosporine to tacrolimus in cases of toxicity and refractory
rejection of cyclosporine.
A cytostatic drug, such as azathioprine, is administered at a oral dose of 1 to 3 mg/kg/day. The total number of leukocytes is then monitored; a value greater than 4000 cells/mm3 is required. Mycophenolate may be administered instead of azathioprine. Mycophenolate acts by inhibiting the proliferation of lymphocytes; it can lead to bone marrow suppression. The main side effect is gastrointestinal symptoms.
In addition to cytostatic agents and calcineurin inhibitors, thymoglobulin and methylprednisolone are commonly administered. The methylprednisolone dosage is based on the child's weight.
The main complications that can occur post-transplantation are described below.
REJECTION
Acute rejection is the most common complication of transplantation. Its incidence is high during
the first four months post-transplantation. Endomyocardial biopsy is a diagnostic method that shows
the degree and type of rejection (2424. Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al.
Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of
heart rejection. J Heart Lung Transplant. 2005;24(11):1710-20,
http://dx.doi.org/10.1016/j.healun.2005.03.019.
http://dx.doi.org/10.1016/j.healun.2005....
). However, acute
rejection in children is commonly diagnosed using noninvasive methods (22. Azeka E. Heart transplantation in children: the immediate postoperative period.
In: Auler Junior JO, Oliveira AS, eds. Postoperative Thoracic and Cardiovascular Surgery. Porto
Alegre: Artmed; 2004. p. 384-391.,2525. Chinnock RE. Pediatric heart transplantation at Loma Linda: 1985 to 1996. Clin
Transpl. 1996:145-51.); such as clinical symptoms,
conventional electrocardiogram, Doppler and tissue echocardiography, gallium-67 scintigraphy and BNP
levels. The clinical signs of acute rejection include cardiac arrhythmias and symptoms of congestive
heart failure, along with nonspecific signs, such as irritability and anorexia (1414. Pediatric heart transplantation protocol. Revised June 2002. Loma Linda: Loma
Linda International Heart Institute, Loma Linda University Medical Center and Children's
Hospital Transplantation Institute Cardiac Transplant Program; 2002.). An electrocardiogram showing a decrease in the sum of the QRS
voltages greater than 20% may indicate acute rejection. Echocardiography may also show ventricular
dysfunction, increased cavity diameter, septum and posterior wall thickness, atrioventricular valve
insufficiency, pericardial effusion and changes in ventricular diastolic function.
The treatment for acute rejection consists of maintaining the rejection immunosuppression regimen (1414. Pediatric heart transplantation protocol. Revised June 2002. Loma Linda: Loma Linda International Heart Institute, Loma Linda University Medical Center and Children's Hospital Transplantation Institute Cardiac Transplant Program; 2002.). In patients with stable hemodynamic parameters, methylprednisolone is administered for four days. In cases in which the child needs vasoactive drugs and ventricular dysfunction is demonstrated by echocardiography, antithymocyte globulin preparation is administered in addition to methylprednisolone. Antithymocyte globulin is used for seven to ten days, and it is monitored by measuring the level of T lymphocytes in the peripheral blood; the requirement is fewer than 150 cells/mm3 by flow cytometry.
Irradiation of lymphocytes (ILT) and methotrexate are used as rescue therapeutic options in patients with refractory rejection.
Humoral rejection is diagnosed by microscopic and immunofluorescence analyses of endomyocardial
biopsy specimens (2424. Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al.
Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of
heart rejection. J Heart Lung Transplant. 2005;24(11):1710-20,
http://dx.doi.org/10.1016/j.healun.2005.03.019.
http://dx.doi.org/10.1016/j.healun.2005....
). Immunofluorescence findings may also
indicate immunoglobulin and complement deposition in the vascular endothelium and evidence of
endothelial cell swelling. Humoral rejection is associated with sensitized patients, high mortality,
graft vascular disease development and poor survival (1212. Dipchand A, et al. Hospital for Sick Children Heart Transplant Program. Clinical
Protocols. 2011.,1515. Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda
conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol.
1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
http://dx.doi.org/10.1016/0735-1097(93)9...
,2424. Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al.
Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of
heart rejection. J Heart Lung Transplant. 2005;24(11):1710-20,
http://dx.doi.org/10.1016/j.healun.2005.03.019.
http://dx.doi.org/10.1016/j.healun.2005....
).
Treatments for humoral rejection include methylprednisolone, cyclophosphamide, immunoglobulin,
rituximab and plasmapheresis (1212. Dipchand A, et al. Hospital for Sick Children Heart Transplant Program. Clinical
Protocols. 2011.,1515. Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda
conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol.
1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
http://dx.doi.org/10.1016/0735-1097(93)9...
).
Hyperacute rejection is a form of humoral rejection that occurs immediately after transplantation
and is mediated by preformed antibodies (1515. Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda
conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol.
1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
http://dx.doi.org/10.1016/0735-1097(93)9...
). These
antibodies result from previous exposure to human antigens (e.g., during pregnancy or blood
transfusions), and they act directly against antigens in the transplanted heart. Patients with
hyperacute rejection have poor prognoses and usually require assisted circulation because of severe
ventricular dysfunction.
INFECTION
The infectious process represents a major cause of death in the first year after transplantation. Schowengerdt et al. (2121. Schowengerdt KO, Naftel DC, Seib PM, Pearce FB, Addonizio LJ, Kirklin JK, et al. Infection after pediatric heart transplantation: results of a multiinstitutional study. The Pediatric Heart Transplant Study Group. J Heart Lung Transplant. 1997;16(12):1207-16.) reported that among 332 patients undergoing heart transplantation, there were 276 episodes of infection: 164 (60%) bacterial, 51 (18%) CMV, 19 (7%) fungal and 7 (2%) protozoal. Bacterial infections occur more commonly in children under six months of age at transplant, comprising 73% of all infections in this age group, compared with 49% in children older than six months. The highest incidence of bacterial infection occurs during the first month after transplantation. The most common infections are bronchopneumonia and bacteremia. CMV is responsible for 59% of all viral infections, with the highest risk in the first two months after transplantation. Factors associated with CMV infection include age, mechanical ventilation, CMV serologic status disparity (a positive donor and a negative recipient) and prolonged ischemic time.
HYPERTENSION
Hypertension is a frequent complication, occurring in approximately 60% of patients within five
years after transplantation (44. Boucek MM, Edwards LB, Keck BM, Trulock EP, Taylor DO, Mohacsi PJ, et al. The
Registry of the International Society for Heart and Lung Transplantation: Fifth Official Pediatric
Report - 2001 to 2002. J Heart Lung Transplant. 2002;21(8):827-40,
http://dx.doi.org/10.1016/S1053-2498(02)00496-5.
http://dx.doi.org/10.1016/S1053-2498(02)...
).
GRAFT VASCULAR DISEASE
Graft vascular disease, one of the main factors limiting long-term survival, may be related to
both immunological and non-immunological factors. Dobutamine stress echocardiography has been used
as a noninvasive diagnosis method; however, coronary angiography and intravascular ultrasonography
are currently the methods of choice. The potential risk factors for graft vascular disease are older
age and an increased number of rejections (2525. Chinnock RE. Pediatric heart transplantation at Loma Linda: 1985 to 1996. Clin
Transpl. 1996:145-51.
26. Azeka E. Coronary heart disease after pediatric heart transplant
[Habilitation thesis]. São Paulo: Faculty of Medicine, USP; 2005.
27. Chinnock RE, Baum MF, Larsen R, Bailey L. Rejection management and long-term
surveillance of the pediatric heart transplant recipient: the Loma Linda experience. J Heart
Lung Transplant. 1993;12(6 Pt 2):S255-64.
28. Kirk R, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, et al.
The Registry of the International Society for Heart and Lung Transplantation: Fourteenth Pediatric
Heart Transplantation Report—2011. J Heart Lung Transplant. 2011;30(10):1095-103,
http://dx.doi.org/10.1016/j.healun.2011.08.005.
http://dx.doi.org/10.1016/j.healun.2011....
-2929. Azeka E, Auler Júnior JO, Fernandes PM, Nahas WC, Fiorelli AI, Tannuri U,
et al. Registry of Hospital das Clínicas of the University of São Paulo Medical School:
first official solid organ and tissue transplantation report - 2008. Clinics. 2009;64(2):127-34,
http://dx.doi.org/10.1590/S1807-59322009000200010.
http://dx.doi.org/10.1590/S1807-59322009...
).
TUMOR
The occurrence of tumors after heart transplantation is termed post-transplant
lymphoproliferative disease. These tumors are predominantly of a B cell lineage and are usually
triggered by Epstein-Barr virus. This disease may occur in 5% of patients within five years after
transplantation (2525. Chinnock RE. Pediatric heart transplantation at Loma Linda: 1985 to 1996. Clin
Transpl. 1996:145-51.,2929. Azeka E, Auler Júnior JO, Fernandes PM, Nahas WC, Fiorelli AI, Tannuri U,
et al. Registry of Hospital das Clínicas of the University of São Paulo Medical School:
first official solid organ and tissue transplantation report - 2008. Clinics. 2009;64(2):127-34,
http://dx.doi.org/10.1590/S1807-59322009000200010.
http://dx.doi.org/10.1590/S1807-59322009...
).
RENAL COMPLICATIONS
Nephrotoxicity can be caused by the chronic use of calcineurin inhibitors. Patients may develop
severe renal failure, which is defined as the need for dialysis or transplant (1515. Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda
conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol.
1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
http://dx.doi.org/10.1016/0735-1097(93)9...
,2828. Kirk R, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, et al.
The Registry of the International Society for Heart and Lung Transplantation: Fourteenth Pediatric
Heart Transplantation Report—2011. J Heart Lung Transplant. 2011;30(10):1095-103,
http://dx.doi.org/10.1016/j.healun.2011.08.005.
http://dx.doi.org/10.1016/j.healun.2011....
).
DYSLIPIDEMIA
Dyslipidemia is a common complication after cardiac transplantation. Studies have produced
conflicting results regarding the association between dyslipidemia and immunosuppressive drugs in
children (1515. Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda
conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol.
1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
http://dx.doi.org/10.1016/0735-1097(93)9...
,2323. Branco KC, Azeka E, Trindade E, Galas FR, Hajjar LA, Benvenuti L, et al. The
impact of tacrolimus as rescue therapy in children using a double immunosuppressive regimen after
heart transplantation. Transplant Proc. 2012;44(8):2483-5,
http://dx.doi.org/10.1016/j.transproceed.2012.07.139.
http://dx.doi.org/10.1016/j.transproceed...
).
SURVIVAL
As reported in the twelfth official pediatric registry of the International Society for Heart and
Lung Transplantation (ISHLT) (2828. Kirk R, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, et al.
The Registry of the International Society for Heart and Lung Transplantation: Fourteenth Pediatric
Heart Transplantation Report—2011. J Heart Lung Transplant. 2011;30(10):1095-103,
http://dx.doi.org/10.1016/j.healun.2011.08.005.
http://dx.doi.org/10.1016/j.healun.2011....
), the median patient
survival depends on the patient's age at the transplant. In our setting, 133 patients (4 were
young adults) underwent transplantation, and five underwent re-transplantation. Eighty-five patients
were alive from October 30, 1992 to November 3, 2013.
REFERENCES
-
1Sociedade Brasileira de Cardiologia. I Diretriz para transplante cardíaco. Arq Bras Cardiol. 1999;73(supl. 5):1-55.
-
2Azeka E. Heart transplantation in children: the immediate postoperative period. In: Auler Junior JO, Oliveira AS, eds. Postoperative Thoracic and Cardiovascular Surgery. Porto Alegre: Artmed; 2004. p. 384-391.
-
3Bacal F, Neto JD, Fiorelli AI, Mejia J, Marcondes-Braga FG, Mangini S, et al. [II Brazilian Guidelines for Cardiac Transplantation]. Arq Bras Cardiol. 2010;94(1 Suppl):e16-76.
-
4Boucek MM, Edwards LB, Keck BM, Trulock EP, Taylor DO, Mohacsi PJ, et al. The Registry of the International Society for Heart and Lung Transplantation: Fifth Official Pediatric Report - 2001 to 2002. J Heart Lung Transplant. 2002;21(8):827-40, http://dx.doi.org/10.1016/S1053-2498(02)00496-5.
» http://dx.doi.org/10.1016/S1053-2498(02)00496-5 -
5Shaddy RE, Parisi F. Pediatric heart transplantation. In: Allen HD, Driscoll DJ, Shaddy RE, Feltes T, eds. Moss and Adams' Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult, 7th Edition. Philadelphia: Lippincott, Williams and Wilkins; 2001. p. 1384-1400.
-
6Azeka E, Franchini Ramires JA, Valler C, Alcides Bocchi E. Delisting of infants and children from the heart transplantation waiting list after carvedilol treatment. J Am Coll Cardiol. 2002;40(11):2034-8, http://dx.doi.org/10.1016/S0735-1097(02)02570-6.
» http://dx.doi.org/10.1016/S0735-1097(02)02570-6 -
7Bando K, Konishi H, Komatsu K, Fricker FJ, del Nido PJ, Francalancia NA, et al. Improved survival following pediatric cardiac transplantation in high-risk patients. Circulation. 1993;88(5 Pt 2):II218-23.
-
8Addonizio LJ, Gersony WM, Robbins RC, Drusin RE, Smith CR, Reison DS, et al. Elevated pulmonary vascular resistance and cardiac transplantation. Circulation. 1987;76(5 Pt 2):V52-5.
-
9Azeka E, Marcial MB, Camargo PR, Kajita L, Aliman AC, Auler JO. [Hemodynamic evaluation and clinical outcome of children with severe dilated cardiomyopathy eligible for heart transplantation]. Arq Bras Cardiol. 1998;71(5):661-6.
-
10Azeka E, Costa Auler JO Jr, Kajita L, Alliman AC, Franchini Ramires JA, Ebaid M. Effects of low doses of inhaled nitric oxide combined with oxygen for the evaluation of pulmonary vascular reactivity in patients with pulmonary hypertension. Pediatr Cardiol. 2002;23(1):20-6, http://dx.doi.org/10.1007/s00246-001-0006-2.
» http://dx.doi.org/10.1007/s00246-001-0006-2 -
11Fricker FJ, Armitage JM. Heart and heart -lung transplantation in children and adolescents. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Moss' Heart disease in infants, children, and adolescents including the fetus and young adult. Baltimore, Williams & Wilkins, 1995.495-10.
-
12Dipchand A, et al. Hospital for Sick Children Heart Transplant Program. Clinical Protocols. 2011.
-
13Azeka E, Marcial MB, Jatene M, Auler JO Jr, Ramires JA. Eight-year experience of pediatric heart transplantation: clinical outcome using non-invasive methods for the evaluation of acute rejection. Pediatr Transplant. 2002;6(3):208-13, http://dx.doi.org/10.1034/j.1399-3046.2002.01075.x.
» http://dx.doi.org/10.1034/j.1399-3046.2002.01075.x -
14Pediatric heart transplantation protocol. Revised June 2002. Loma Linda: Loma Linda International Heart Institute, Loma Linda University Medical Center and Children's Hospital Transplantation Institute Cardiac Transplant Program; 2002.
-
15Miller LW, Schlant RC, Kobashigawa J, Kubo S, Renlund DG. 24th Bethesda conference: Cardiac transplantation. Task Force 5: Complications. J Am Coll Cardiol. 1993;22(1):41-54, http://dx.doi.org/10.1016/0735-1097(93)90814-H.
» http://dx.doi.org/10.1016/0735-1097(93)90814-H -
16Azeka E. Heart transplant in children: clinical analysis of evolution [PhD in Cardiology]. São Paulo: Faculty of Medicine, USP; 1998.
-
17Chinnock RE, Larsen RL, Emery JR, Bailey LL. Pretransplant risk factors and causes of death or graft loss after heart transplantation during early infancy. Pediatric Heart Transplant Team, Loma Linda. Circulation. 1995;92(9 Suppl):II206-9, http://dx.doi.org/10.1161/01.CIR.92.9.206.
» http://dx.doi.org/10.1161/01.CIR.92.9.206 -
18Tweddell JS, Canter CE, Bridges ND, Moorhead S, Huddleston CB, Spray TL. Predictors of operative mortality and morbidity after infant heart transplantation. Ann Thorac Surg. 1994;58(4):972-7, http://dx.doi.org/10.1016/0003-4975(94)90440-5.
» http://dx.doi.org/10.1016/0003-4975(94)90440-5 -
19Heck CF, Shumway SJ, Kaye MP. The Registry of the International Society for Heart Transplantation: sixth official report—1989. J Heart Transplant. 1989;8(4):271-6.
-
20Kawauchi M, Gundry SR, de Begona JA, Fullerton DA, Razzouk AJ, Boucek M, et al. Prolonged preservation of human pediatric hearts for transplantation: correlation of ischemic time and subsequent function. J Heart Lung Transplant. 1993;12(1 Pt 1):55-8.
-
21Schowengerdt KO, Naftel DC, Seib PM, Pearce FB, Addonizio LJ, Kirklin JK, et al. Infection after pediatric heart transplantation: results of a multiinstitutional study. The Pediatric Heart Transplant Study Group. J Heart Lung Transplant. 1997;16(12):1207-16.
-
22Schowengerdt KO, Azeka E. Infection Following Pediatric Heart Transplantation. In: Canter CE, Kirklin JK, eds. ISHLT Monograph Series Volume 2: Pediatric Heart Transplantation, 1st Edition. Philadelphia: Elsevier; 2007. p.157-71.
-
23Branco KC, Azeka E, Trindade E, Galas FR, Hajjar LA, Benvenuti L, et al. The impact of tacrolimus as rescue therapy in children using a double immunosuppressive regimen after heart transplantation. Transplant Proc. 2012;44(8):2483-5, http://dx.doi.org/10.1016/j.transproceed.2012.07.139.
» http://dx.doi.org/10.1016/j.transproceed.2012.07.139 -
24Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. 2005;24(11):1710-20, http://dx.doi.org/10.1016/j.healun.2005.03.019.
» http://dx.doi.org/10.1016/j.healun.2005.03.019 -
25Chinnock RE. Pediatric heart transplantation at Loma Linda: 1985 to 1996. Clin Transpl. 1996:145-51.
-
26Azeka E. Coronary heart disease after pediatric heart transplant [Habilitation thesis]. São Paulo: Faculty of Medicine, USP; 2005.
-
27Chinnock RE, Baum MF, Larsen R, Bailey L. Rejection management and long-term surveillance of the pediatric heart transplant recipient: the Loma Linda experience. J Heart Lung Transplant. 1993;12(6 Pt 2):S255-64.
-
28Kirk R, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, et al. The Registry of the International Society for Heart and Lung Transplantation: Fourteenth Pediatric Heart Transplantation Report—2011. J Heart Lung Transplant. 2011;30(10):1095-103, http://dx.doi.org/10.1016/j.healun.2011.08.005.
» http://dx.doi.org/10.1016/j.healun.2011.08.005 -
29Azeka E, Auler Júnior JO, Fernandes PM, Nahas WC, Fiorelli AI, Tannuri U, et al. Registry of Hospital das Clínicas of the University of São Paulo Medical School: first official solid organ and tissue transplantation report - 2008. Clinics. 2009;64(2):127-34, http://dx.doi.org/10.1590/S1807-59322009000200010.
» http://dx.doi.org/10.1590/S1807-59322009000200010
-
No potential conflict of interest was reported.
Publication Dates
-
Publication in this collection
Jan 2014