Non-ischemic left ventricular dysfunction after pediatric cardiac transplantation: treatment with plasmapheresis and OKT3.

BACKGROUND: Acquired left ventricular dysfunction after pediatric cardiac transplantation is associated with a high mortality rate. It often occurs without biopsy evidence of cellular rejection or severe transplant coronary arteriopathy. METHODS: We employed a protocol for treatment of acquired, non-ischemic left ventricular dysfunction utilizing plasmapheresis, monoclonal anti-T-cell antibody (OKT3), cyclophosphamide and steroids, regardless of the results of endomyocardial biopsy. Left ventricular dysfunction was defined as an echocardiographic shortening fraction of <29% and/or symptoms of congestive heart failure requiring inotropic support. Transplant coronary arteriopathy was excluded by coronary angiography in all cases. RESULTS: Ten pediatric heart transplant recipients were treated for 13 episodes of non-ischemic left ventricular dysfunction. Biopsy scores were low grade (ISHLT Grade 1A or 1B) in 8 episodes. Eight of 10 patients had a history of non-compliance in regularly taking immunosuppressant medications. Inotropic support was required in 9 of 13 cases, with a median duration of 5 days. Median left ventricular shortening fraction was 17% at time of presentation. Normalization of shortening fraction occurred a median of 40 days from the start of treatment. Survival to hospital discharge occurred in 11 of 13 (85%) patients. Long-term patient survival, however, was only 50% at 24 months after presentation with a first episode of acquired left ventricular dysfunction. CONCLUSIONS: Use of plasmapheresis, OKT3, cyclophosphamide and steroids resulted in successful short-term reversal of non-ischemic left ventricular dysfunction in pediatric heart transplant patients, but long-term survival remained poor.

Rejection is reduced in thoracic organ recipients when transplanted in the first year of life.

BACKGROUND: Infant heart transplant recipients have been reported to have decreased rates of rejection when clinical criteria are used for diagnosis. This study compares the rates of acute episodes of rejection in heart and lung transplant recipients transplanted in the first year of life to those of older recipients utilizing pathologic criteria. METHODS: Records of 100 consecutive lung transplant recipients (cystic fibrosis patients excluded) and 107 consecutive heart transplant recipients were reviewed with respect to: time to first rejection; total number; single versus multiple; and early (<90 days) versus late (>180 days) biopsy-proven rejection episodes. Rejection was defined as ISHLT biopsy Grade 3A or A2 for heart and lung transplant recipients, respectively. Biopsy and immunosuppression protocols were similar between groups. RESULTS: Kaplan-Meier analysis for freedom from rejection showed infant heart recipients were more often rejection-free (p = 0.004) as were infant lung recipients (p = 0.0001). Multivariate analysis revealed age at transplant as the most significant factor in predicting time to first rejection (age <1 year: risk ratio 0.19 [0.068-0.54] for lung transplant recipients and risk ratio 0.46 [0.27-0.78] for heart transplant recipients). Early rejection episodes occurred with less frequency in both the infant heart (19 of 63 [30%] versus 24 of 44 [50%]; p = 0.016) and lung (3 of 26 [12%] versus 63 of 74 [85%]; p = 0.001) groups. Late episodes of rejection were also less frequent in infant heart (4 of 53 [8%] versus 10 of 36 [28%], p = 0.016) and lung (0 of 23 [0%] versus 29 of 65 [45%]; p = 0.001) recipients. Multiple (> or =2) rejection episodes occurred less in infant heart (4 of 63 [6%] versus 9 of 41 [22%]; p = 0.037) and lung recipients (0 of 26 [0%] versus 17 of 74 [23%]; p = 0.003). CONCLUSIONS: These results demonstrate that age of <1 at time of thoracic transplantation confers significant protection from early, late and multiple episodes of acute rejection, as well as significantly greater freedom from rejection and time to first rejection.