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there are a few studies demonstrating a more normal rate response and a normal maximal consumption of oxygen.87,92,95 The largest and most recent study of serial exercise tests in children demonstrated better exercise capacity associated with younger age at transplantation, especially for infants; a positive relationship between peak heart rate and time subsequent to transplantation; good exercise capacity with a mean maximum oxygen consumption of 30 mL/kg per minute at a mean of 5.5 years after transplantation; and a possible association with changes on serial studies and the presence of CAV.95 Infections Infection is a concern in all cases of solid organ transplantation and represents a significant cause of morbidity and mortality.96 Risk factors include earlier age at transplant, discrepancy between donor and recipient viral status (e.g., a CMVnegative recipient is at high risk of the disease if he or she received a CMVpositive donor), and degree of immunosuppression A report from ISHLT identified infection as being responsible for 6% of deaths occurring after transplant.2 Infection was also a significant cause of hospitalization, particularly in the first posttransplant year (19%), although by 5 years posttransplant this had fallen to 10%.2 Infections that have required hospitalization or intravenous therapy were due to bacterial infections in 43% of cases.97 Staphylococcus aureus, Klebsiella species, and Escherichia coli are common pathogens during all periods after transplantation Beyond the immediate posttransplant period, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Salmonella species are common community-acquired infections, whereas opportunistic pathogens and mycobacteria are rare Viral infections are also common, including respiratory viruses (adenovirus, influenza) and norovirus The herpesvirus group (varicella zoster, herpes simplex, cytomegalovirus, EpsteinBarr virus [EBV] and human herpesvirus type 6) are of particular importance They may cause primary or secondary infection (reactivation of latent infection), and such infections may be asymptomatic or life-threatening to the immunocompromised host EBV in particular, may cause a symptomatic primary infection and is usually the driver behind the development of PTLD Other viruses—such as human papillomavirus (warts) and molluscum contagiosum— are more of a nuisance Pneumocystis jirovecii, a fungus-like organism, is also a concern, particularly in the early posttransplant phase Prophylaxis for CMV and P jirovecii with antimicrobial agents is usually employed in the most immunosuppressed time period (the first 3 to 6 months posttransplant) to either defer or prevent infections.98,99 Children who have recurrent respiratory infections may benefit from prophylactic antibiotics and regular chest physiotherapy to prevent the development of bronchiectasis.100 Most children undergoing transplantation have not finished their routine schedule of immunizations Titers should be checked prior to transplantation Efforts should be made to immunize with as many vaccinations as feasible and developmentally appropriate prior to transplantation This is particularly important with vaccines that incorporate live viruses Vaccination schedules should be resumed approximately 6 months after transplantation Given the suppression of the immune system and the variable responses to foreign antigens, antibody titers should be checked after vaccination in order to ensure an appropriate response In general, live viral vaccines are avoided posttransplant, although there is increasing evidence and experience of their safe use in carefully selected patients.101 Renal Function Many patients have some impairment of renal function prior to transplantation In the patient with congenital heart disease, this may be due to the effects of previous cardiac surgery or cyanosis Particularly in the single-ventricle population following the Fontan procedure, systemic venous pressure may be chronically elevated In those with cardiomyopathy, inadequate cardiac output is the most common cause of impaired renal function, but this may also be due to emboli in patients on mechanical circulatory support Renal function is often further compromised in the peritransplant period, as episodes of hemodynamic instability are not uncommon An analysis from the United Network for Organ Sharing database demonstrates that dialysis in the pre- and posttransplant period is common (7% of recipients) and is more likely with ECMO, ventilator, inotrope support, infection, congenital heart disease, and a medical condition (intensive care unit home).102 The 30-day survival was lower in the dialysis group (72% vs 95%); however, dialysis had no effect on late survival conditional on surviving to 6 months Posttransplant, calcineurin inhibitors are nephrotoxic.103 The ISHLT registry reports the freedom from renal replacement therapy (defined as dialysis or transplant) as 89% at 20 years for those transplanted as infants Other age groups fared slightly worse.2 Recently strategies have utilized mammalian target of rapamycin inhibitors—either completely replacing the calcineurin inhibitor or allowing a reduction in dose.2 These strategies appear to be successful provided that renal function is only moderately reduced and the mammalian target of rapamycin inhibitors are tolerated by the patients.104 Lymphoproliferative Disorders Malignancies are another important cause of morbidity and mortality after transplantation (see Tables 67.3 and 67.4; Fig 67.30) They can occur as new events, be a reactivation of previous cancer, or result from chronic viral infections, with the latter being most important in children The reported overall incidence of malignancy is highly variable and related both to variation in definition and whether or not malignancy is reported in a time-dependent manner The reported time-unadjusted overall incidence of the most common malignancy in childhood, PTLD, ranges from 3% to 9%.2,15,105 As there is a temporal relationship to incidence, there are reports of an incidence as high as 23% to 28% in survivors more than 10 years after transplantation.16,106 Survival from the PHTS registry was 95% at 1 month, 75% at 1 year, and 67% at 5 years.15 Table 67.4 Cumulative Prevalence of Malignancy in Children After Heart Transplantation (January 1994 to June 2014) Malignancy/Type No malignancy Malignancy (all types combined) Malignancy type Lymph Other Skin Type not reported 1-Year Survivors 5451 (98.4%) 88 (1.9%) 5-Year Survivors 3072 (95.3%) 151 (4.7%) 10-Year Survivors 1281 (90.5%) 134 (9.5%) 80 0 143 10 128 Data from the registry of the International Society of Heart and Lung Transplantation J Heart Lung Transplant 2016:35(10):1185–1195