Single Drug Immunosuppression for Infant Heart Transplant Recipients

Single Drug Immunosuppression for Infant Heart Transplant Recipients

S322 The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015 are associated with lower risk of SCD, whereas, a diagnosis of congen...

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S322

The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015

are associated with lower risk of SCD, whereas, a diagnosis of congenital heart disease (HR 1.82, 95% CI: 1.12-2.95, p= 0.016) and younger age at listing (HR 0.97, 95% CI: 0.94-0.99, p= 0.023) are associated with higher risk of SCD. Conclusion: ICD does not reduce SCD or all-cause mortality in pediatric patients awaiting transplantation. Incidence of sudden cardiac death in pediatric patients awaiting heart transplantation is low and predicted by congenital heart disease and younger age at listing. 8( 94) Variations in Criteria and Practices for Heart Transplantation Listing Among Pediatric Transplant Cardiologists A. Patel , E. Pahl, J.G. Gossett.  Pediatric Cardiology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern Feinberg School of Medicine, Chicago, IL. Purpose: Ethical issues in pediatric heart transplantation (Htx) include resourceallocation, high-risk recipients, and issues of informed consent. Few data exist on the variability of practices amongst practitioners in the current era. We aimed to understand the range of opinions about resource-allocation with attention to contraindications, outcomes, social support, adherance, and high-risk candidates. Methods: Decision making was investigated with a 47-item internet survey and vignette based questions sent to 43 pediatric transplant cardiologists in North America and United Kingdom. Contact information was obtained through professional organizations. Results: Of 43 htx cardiologists contacted, 28 (65%) responded; 20/28 (71%) fully and 8/28 (29%) partially completed the survey. Transplant volume at each institution was 10/yr (5-25). Respondants stated that a 1yr predicted survival of 70% (50-100%) was adequate to recommend listing for Htx. However, 30% of respondents would offer Htx to a medically high risk vignette (1yr survival estimated to be < 50% based on published data). Social reasons were significant enough to preclude Htx for 75% of respondents, however 75% would offer a non-adherant pt HTx and 100% would offer a HTx to a homeless pt. 80% considered a neuromuscular disease of indeterminate prognosis a relative contraindication to Htx, but 80% were willing to offer Htx to a similar pt. See Figure 1 for additional results. Conclusion: During the consent process, Htx cardiologists report discussing similar risks with exception of fertility and neurocognitive outcomes. Reported practice for offering HTx varied significantly with respect to minimal predicted 1 and 5 yr survival and contraindications to Htx. Disagreement among Htx cardiologists exists when there are concerns for non-adherance, retransplantation/rejection, and the Fontan patient with multiple morbidities. Further work is needed to undertand and develop concensus for pediatric Htx organ allocation. 

Purpose: Severe renal dysfunction may be prohibitive to HT. However, the acceptable threshold is not well defined. CKD staging has prognostic implications for the adult population, however, its influence on pediatric recipients is unknown and may be an important consideration in patient selection. Methods: 3241 HT pts were identified from UNOS (1987-2011) & stratified by CKD stage using the MDRD formula as the UNOS registry does not capture variables for pediatric GFR calculators. Exclusions: age >  17y, re-HT, multiorgan transplant/listing, & patients lost to follow-up (FU). Survival was censored at 12y & multivariate Cox proportional hazard regression models were adjusted for age, sex, diabetes, race, ischemic time, dialysis, ischemic etiology, life support, wait time & HLA mismatch. Results: CKD stages 1 (n= 2854) & 2 (n= 188) were most prevalent compared to CKD 3 (n= 71), 4 (n= 15) & 5 (113). 1066 died during the study period (31%, 45%, 55%, 67% & 45% for CKD 1-5 respectively). Crude survival is shown in Figure. Unadjusted HR for all-cause mortality (compared to CKD 1) was: CKD 2 [1.38 (1.09-1.74)*], CKD 3 [1.89 (1.36-2.62)*]; CKD 4 [2.36 (1.23-4.56)*]; CKD 5 [1.99 (1.47-2.68)*]. Adjusted multivariate analysis showed: Stage 2 [1.16 (0.87-1.53)**]; Stage 3 [1.95 (1.33-2.86)*]; Stage 4 [3.93 (1.92-8.04)*]; Stage 5 [1.91 (1.35-2.71)*]. Conclusion: CKD stage is an independent predictor of mortality post HT in pediatric recipients. CKD stages 2 - 5 have significantly worse outcomes than CKD stage 1. MDRD may be useful for risk stratification in pediatric recipients. Further studies are warranted.*p <  0.001; **p= NS 

8( 96) Single Drug Immunosuppression for Infant Heart Transplant Recipients S.M. Stack ,1 J. Eshelman,2 B.A. Pietra,3 S.D. Miyamoto,1 S.R. Auerbach.1  1Pediatric Cardiology, Children’s Hospital Colorado, Aurora, CO; 2Pharmacy, Children’s Hospital Colorado, Aurora, CO; 3Pediatric Cardiology, University of Florida, Gainesville, FL.

8( 95) Influence of Chronic Kidney Disease (CKD) in Outcomes Post Heart Transplant (HT) in Pediatric Recipients L.C. Reardon , A. Nsair, M.C. Deng, A. Ardehali, J. Alejos, E.C. DePasquale.  UCLA, Los Angeles, CA.

Purpose: Infant heart transplant (HT) recipients may have increased immune tolerance of their grafts. Thus, they may tolerate single-drug immunosuppression (SD). This study compared graft failure and mortality of patients transitioned to SD to those maintained on multi-drug immunosuppression (MD). Methods: A retrospective review of HT recipients at our institution between 1993 and 2012 was conducted. Per protocol, all patients who received a HT prior to 2 years of age and did not develop acute rejection (AR) in the 1st year post-HT were eligible for transition from MD (typically cyclosporine and azathioprine or mycophenolate mofetil) to SD (typically cyclosporine). Characteristics of SD infants (Group A) were compared to those on MD and those with AR after transition to SD (Group B). The primary outcomes were freedom from graft loss at 1 and 5 years. Univariate logisitic regression analyses were performed to identify characteristics predictive of graft loss. Time-to-event analysis was performed starting at 1 year post-HT using the log rank test and Cox proportional hazards model.

Abstracts S323 Results: 97 patients were included in Group A and 76 in Group B. Freedom from graft loss at 1 and 5 years was 94% and 76% for MD and 97% and 89% for SD, respectively (p= 0.6). Univariate analyses demonstrated higher risk of rejection in patients on a ventricular assist device (VAD) at the time of HT (p< 0.05). Conclusion: Our data demonstrate that graft survival and mortality were not significantly different for SD and MD. VAD use is associated with a greater risk of rejection. 8( 97) Risk Factors for Declining Renal Function Over Time in a Cohort of Pediatric Heart Transplant Recipients A. Kempenaar, C. Manlhiot, B.W. McCrindle, A.I. Dipchand .  Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, ON, Canada. Purpose: To determine risk factors associated with deteriorating renal function over time in a cohort of pediatric heart transplant recipients. Methods: This single center study included all patients who underwent heart transplantation (HTx) between 2001 and 2013 with at least one glomerular filtration rate (GFR) measurement by nuclear medicine scintigraphy posttransplantation (initially done 6 months after transplantation and annually thereafter). Univariable linear time-series analysis using interactions between potential covariates and time since HTx were used to determine factors associated with declining renal function over time. All regression models were adjusted for repeated measures through a compound symmetry covariance structure. Results: In total, 142 patients were included (67 males, 47%). Median age at HTx was 3.5 years (25th-75th percentile: 0.5-13.4). N= 480 GFR measurements were available for analysis (median 3 per patient, 25th-75th: 2-5) over a median of 3.5 years of follow-up (25th-75th: 1.5-6.6). The overall cohort demonstrated a mean increase in GFR over time by 2.0 (0.5) ml/min/1.73m2 per year (p< 0.001). Transplantation factors associated with faster decline of GFR over time were: later age at HTx (EST(SE): -0.3 (0.1) ml/min/1.73m2/ year, p= 0.03), female gender (-2.1 (1.0), p= 0.03), ABO compatible HTx (vs. ABO-incompatible) (-3.7 (1.1), p= 0.001). Pharmacological-related factors were: higher trough levels of cyclosporine (-0.7 (0.2)/year per 10 units) or tacrolimus (-0.7 (0.2)/year per 10 units, p< 0.001) at 3 months post-transplantation, adjunct immunosuppression with azathioprine (-2.6 (1.1)/year, p= 0.01). Adjunct immunosuppression with mycophenolate mofetil (vs. no mycophenolate mofetil) (+2.0 (1.1)/year, p= 0.06) and discharge on ACEinhibitor (vs. not) (+5.1 (0.9)/year, p< 0.001) were associated with preserved renal function. A higher number of rejection episodes during the first year post-HTx was associated with worsening renal function (-2.9 (1.2)/rejection episode, p= 0.02). Conclusion: Several subgroups are at elevated risk of deteriorating renal function over time following pediatric heart transplantation and may benefit from targeted management. Furthermore, lower levels of immunosuppression used in identified treatment regimens preserves renal function over time. 8( 98) Outcome, Prevalence and Risk Factors for Stroke Following Pediatric Heart Transplantation: An Analysis of the ISHLT Registry C. Morgan , C. Manlhiot, B.W. McCrindle, A. Dipchand.  Cardiology, Hospital for Sick Children, Toronto, ON, Canada. Purpose: In the ISHLT Registry, cerebrovascular accidents are the fifth commonest cause for mortality following pediatric heart transplantation (PHTx); but details are lacking in the reported literature. The purpose of this analysis of the ISHLT registry was to determine the prevalence, risk factors and outcomes of stroke after PHTx. Methods: Data from the ISHLT registry (1998-2010) was used to identify all patients whose primary transplantation was performed at <  18 years of age. Of the 10,441 transplants reviewed, 9,837 primary transplants and 604 retransplants were analyzed. Results: 333 patients had a stroke following PHTx; 54% were male, median age at PHTx was 6 years (0-17 years), and 44% had a diagnosis of congenital heart disease (CHD). Freedom from stoke was 99% at 1 month, 97% at 5 years, 95% at 10 years and 91% at 20 years post-PHTx. Following a stroke,

survival at 1 month, 1 year and 5 years was 83%, 69% and 55% respectively. Patients who had a stroke had an increase risk of mortality [Fig. 1; HR 1.9 (1.6-2.2), p< 0.001]. Multivariable independent risk factors for stroke included a primary diagnosis of congenital heart disease [HR 1.3 (1.0-1.6), p< 0.001], pretransplant ventilator dependence [HR 1.5 (1.1-1.9), p= 0.01], post-operative dialysis [HR 3.5 (2.5-5.0), p< 0.001], infection requiring antibiotics prior to discharge [HR 2.2 (1.72.9), p< 0.001], pacemaker implantation [HR 1.6 (1.1-2.6), p= 0.03], or drug treated hypertension [HR 1.4 (1.1-1.8), p= 0.003] during follow up. Conclusion: Stroke following pediatric heart transplantation is associated with increased mortality. Congenital heart disease portends great risk in addition to markers of increased pre- and post-transplant medical acuity. 

8( 99) Acute Pancreatitis in Pediatric Patients With Ventricular Assist Devices J.E. Ryan , W.S. Moore II, M. Priest, M.A. McCulloch, C. Pizarro, R.R. Davies.  Cardiac Center, Nemours/Alfred I duPont Hospital for Children, Wilmington, DE. Purpose: Pediatric patients undergoing ventricular assist device (VAD) implantation have multiple risk factors for pancreatitis (hemolysis, biliary stasis, medications). We sought to investigate the incidence and consequences of pancreatitis in pediatric VAD patients. Methods: A retrospective review (medications, laboratory studies, abdominal ultrasonography, nutrition strategies) was performed of all children undergoing VAD implantation at single center (2010-2014). Probability of drug-induced pancreatitis was evaluated by Naranjo Algorithm. Patients were stratified based on lipase elevation over 110mg/dL into pancreatitis (n= 9) and non-pancreatitis (n= 2) and outcomes were compared. Results: Pancreatitis occurred in 9/11 (82%) patients (3 prior to implant, 6 following). Patient complaints were nausea (5/9) and epigastric pain (1/9). Mean lipase and amylase at onset were (545±509,159±112). Mean Ranson criteria was 2.2 (2.2±1.6) with a mean predicted mortality of 24%. Pancreatitis duration exceeded 1 month in 5 (56%) patients. Opiodinduced pancreatitis was scored as “possible” in 5/9 patients. In only 2 patients were serum lipase levels correlated with LDH levels (r=  0.720, r=  0.613). Plasma free hemoglobin (PFH) levels were available in 2 patients with 4 episodes of pancreatitis; PFH was normal in 2 episodes and elevated in 2 episodes. No patient had common bile duct dilation, 6 (75%) had gallbladder sludge. All patients were made NPO. 1 patient had a central line infection. There was a trend toward higher discharge mortality among patients with pancreatitis (42.9% vs. 0.0%, p =  0.4), although length of stay did not differ (pancreatitis: 6.6±5.2 mths vs. 7.0±2.8mths). Conclusion: Pancreatitis occurs commonly in children on VAD support. It occurs independently of hemolysis or obstruction of pancreatic drainage. Treatment may compromise nutritional status and increase infectious complications. Further investigation is necessary to identify the etiology of pancreatitis in this population.