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Cardiac allograft vasculopathy (CAV) in patients who have undergone heart transplantation leads to graft dysfunction and is still the major concern for long-term survival. Evaluation of coronary flow velocity reserve (CFR) has been established for diagnosis of CAV. Systemic application of adenosine vs intracoronary testing for CFR has been validated in adults; however, its accuracy in pediatric patients has not yet been proven.CFR was prospectively measured in 33 clinically asymptomatic pediatric heart transplant recipients. CFR measurements were made in the left anterior descending (LAD) artery using a 0.014-inch Doppler FloWire (Cardiometrics). CFR was defined as the ratio of hyperemic (after adenosine injection) to basal (before adenosine) average peak velocity (APV). Adenosine (Adrekar) was administered by intracoronary (15 or 30 mug bolus) and systemic (0.1 mg/kg) injection in each patient. Epicardial CAV was evaluated in coronary angiograms (Stanford criteria) and microvasculopathy was diagnosed in endomyocardial biopsies (evidence of luminal stenosis) blinded to clinical data.Thirty-three patients were included in this study. Their median age (range) was 11.9 (1.4 to 17) years and median post-transplant time 4.3 (1 to 11.7) years. Seventeen of the 33 patients had epicardial CAV (mainly peripheral obliterations or B1 and B2 lesions) and microvascular CAV. Epicardial CAV only was found in 4 patients and microvasculopathy only was present in only 1 patient. CFR was significantly reduced in patients with epicardial CAV and microvasculopathy when compared with patients without any signs of CAV: 206 +/- 53 vs 276 +/- 39 (p0.001) for the systemic application and 213 +/- 50 vs 271 +/- 45 (p = 0.004) for the intracoronary application.CFR and coronary vasoreactivity to adenosine are decreased in pediatric patients with CAV and correlate with histopathologic and angiographic evidence of microvascular disease. Measurement of CFR with intracoronary and systemic application of adenosine is comparable, while systemic application is necessary for non-invasive measurement of CFR in pediatric patients.

Purpose There is growing evidence that non-stenotic epicardial vasculopathy affects survival after heart transplantation. We have developed a model that estimates the risk of death due to vasculopathy by combining the ISHLT working formulation and the consensus statement of the German task force for cardiac allograft vasculopathy (CAV). Methods and Materials Coronary angiograms (n=996, 906 pts) performed at 30 days, 1 and 5 yrs post-transplant were evaluated according to the ISHLT (CAV0-CAV3) and the German task force (epicardial remodeling, peripheral obliteration) working formulations. Cox models were generated to estimate the risk of death, given these predictors. A combination model was designed to estimate vasculopathy-related risk of death at 10 yrs post-transplant. Results CAV0 was present in 85%, 78% and 45% of pts at 30 days, 1 year, and 5 years post-transplant; CAV1 was found in 14%, 17% and 36% of pts; CAV2 and CAV3 in 2%, 5% and 17% of pts; and remodeling was found in 10%, 18% and 45% of pts at 30 days, 1 and 5 yrs, respectively. Relative risks are presented in the table. Ten-year survival using the ISHLT classification showed sensitivity of 70%, specificity of 52% and a false classification rate of 48%. Ten-year survival as classified by epicardial remodeling showed sensitivity of 70%, specificity of 45% and a false classification rate of 43%. The combination of the ISHLT and German classification schemes had sensitivity of 88%, specificity of 29% and false classification rate of 39%. Conclusions A combination model incorporating the ISHLT working formulation and the presence of non-stenotic epicardial vasculopathy shows improved ability to identify pts at risk for death post-transplant and reduces false classification rates. 30 days 1yr 5yrs Parameter HR p HR p HR p CAV1 1.690 p 1.715 p 1.522 p=0.009 CAV2 1.765 p=0.138 2.043 p=0.063 1.928 p=0.029 CAV3 2.964 p 3.160 p 2.099 p=0.001 Remodeling 1.293 p=0.039 1.426 p=0.007 1.383 p=0.024

Non-Stenotic Coronary Vasculopathy Is Associated with Reduced Survival after Heart Transplantation N.E. Hiemann, E. Wellnhofer, C. Christan, S. Kretschmer, R. Meyer, H. Valantine, R. Hetzer, K.K. Khush. Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; Department of Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford.

performed for failed Fontan physiology.The median age at the time of the Fontan operation was 4.3 yrs and at transplantation was 11.1 yrs. The primary indications for transplant were ventricular dysfunction, plastic bronchitis, protein losing enteropathy. There were no procedural deaths. There were 3 patients (12%) that required postoperative mechanical support for early graft dysfunction. The median posttransplant ICU stay was 13.7 days. There were 2 hospital deaths (8%), both from acute graft dysfunction. Four patients (16%) died later at a mean post-transplant interval of 58 months. The 19 surviving patients have a mean follow up of 45.5 months. Overall survival for this group was 88%, 80%, and 68% at 1, 5 and 10 yrs post transplant and that compared favorably with those transplanted for cardiomyopathy. This survival was better than for those transplanted for non-Fontan CHD and this difference in survival was significant (p 0.006, log-rank test). Conclusions: Transplantation is a reasonable option for patients with a failing Fontan circulation. While the early post transplant course can be challenging the long term outcome is good and comparable to patients transplanted for cardiomyopathy.

regression/prevention of graft vasculopathy (CAD). There is little data on the use of sirolimus in the pediatric heart transplant (Tx) population. Purpose: To report our experience with sirolimus in 16 pediatric heart Tx pts. Procedures: Data were obtained by retrospective chart review. Results: There were 9 males and 7 females. Median age at review was 12.3 yr (5.1-18.0yr), and at Tx was 7.5 yr (6mo-18.0yr). Sirolimus was started at median 2.7 yr (1mo–8.2yr) post-tx and median age 11.2 yr (2.2-18.0yr). At start of sirolimus, 15 pts were on steroids, 9 on tacrolimus (FK)/mycophenolate mofetil (MMF), 5 on FK and 1 on cyclosporine (CYA)/MMF. Average sirolimus dose was 0.25 mg/kg or 7.0 mg/m, target level 10-12 g/L allowing for decreased calcineurin inhibitor dose. Sirolimus was started for mod-sev CAD (n 5, 31%), rejection (n 5, 31%), and in 6 pts for combinations of the following: CYA side-effects, FK side-effects, CAD, renal dysfunction and rejection. Six pts who received sirolimus for treatment of rejection (ISHLT 3A) showed improvement (ISHLT 0-1A/B). Three pts received sirolimus due to severely reduced renal function by glomerular filtration rate (GFR); 2 showed improvement at follow-up (GFR 43 and 32 to 67 and 106 ml/min/1.73 m, respectively) and one pt was transferred prior to follow-up. Side-effects included: abdominal pain (n 5, 31%), mouth ulcers (n 4, 26%), hyperlipidemia (n 3, 19%), anemia/ neutropenia (n 2, 12.5%), impaired linear growth (n 1, 6%), interstitial lung disease NYD (n 1, 6%). Sirolimus was discontinued due to side-effects in 3 pts. Conclusion: In this group of pediatric heart Tx recipients, sirolimus is a valuable adjunct IS agent for management of rejection, renal dysfunction, and calcineurin-inhibitor side-effects. The role of sirolimus in CAD regression and prophylaxis of both primary rejection and CAD remains to be determined.