M Khurram

Development of an ex vivo technique to achieve reanimation of hearts sourced from a porcine donation after circulatory death model

BACKGROUND This study reports on the development of a novel method for achieving ex vivo reanimation of hearts from a porcine donation after circulatory death (DCD) model without the use of donor pretreatment. METHODS Porcine hearts (n = 23) were procured 10-29 min after confirmation of asystole. All hearts underwent initial flush with AQIX RS-I solution (London, UK). A 2-h preservation period followed: group 1 hearts (n1-n11) were preserved using static cold storage, group 2 hearts (n12-n17) were preserved using oxygenated, hypothermic machine perfusion (MP), and group 3 hearts (n18-n23) were subjected to retrograde oxygen persufflation. Reperfusion was performed on a Langendorff modification of a Model 33 Functional Circulation circuit. In hearts n16-n23, a dialysis circuit was incorporated into the circuit to facilitate removal of metabolites. The experimental protocol was allowed to follow an evolutionary course, with the aim of achieving greater success with reanimation. RESULTS In group 1 (static cold storage), 7 of the 11 hearts (63.6%) achieved reanimation on the ex vivo circuit. Two of the six hearts (33.3%) in group 2 (MP) were successfully reanimated. All the six hearts (100%) in group 3 (persufflation) were successfully reanimated. The period of sustained reanimation increased when dialysis was incorporated into the circuit with a maximum of 300 min. CONCLUSIONS Porcine DCD hearts after 29 min of warm ischemia can be reanimated using the method described. A mechanism of reoxygenation (oxygenated MP or coronary sinus oxygen persufflation) during preservation appears mandatory for hearts from DCDs. Persufflation was associated with a higher probability of successful reanimation. Dialysis in the warm phase was useful in removing metabolites that could interfere with reanimation. The results demonstrate the potential of DCDs to counter the decline affecting heart transplantation.

Behaviour of transplanted tumours and role of matching in rejection

BACKGROUND Tumour transfer/development is one of the more serious risks associated with transplantation. The behaviour of a tumour can be unpredictable in immunosuppressed recipients. We report a highly sensitive method to monitor tumour behaviour in real time in a rodent tumour transplant model. This paper also explores the effect of MHC matching on tumour growth among control and immunosuppressed hosts. METHODS Luciferase expressing Wistar rat kidney tumour cells were transplanted into either Wistar or Lewis recipients which mimic a well and poorly matched combination to assess the effects of MHC matching on transplanted tumour cells. Experimental groups included controls with no immunosuppression and animals immunosuppressed with cyclosporine. The latter group was further divided into a continuous treatment group which received four weeks of immunosuppression and a treatment withdrawal group where immunosuppression was stopped after two weeks to assess the effects of rejection on tumour growth. RESULTS All the tumour cells were rejected in the control animals that received no immunosuppression, within 2 weeks among well-matched combination and within one week in the poorly matched combination (p 0.001). The transplanted tumour cells continued to grow in both well-matched and poorly matched groups who were treated with cyclosporine, but growth was significantly faster in the well-matched combination (p 0.033). After treatment withdrawal the tumour cells were rejected in all the animals of the poorly matched group compared to 50% in well matched animals within the four-week study period (p 0.039). CONCLUSION In the absence of immunosuppression the hosts reject the transplanted tumour cells, and the anti-tumour response is stronger when there is a greater mismatch in MHC with the recipient. In the presence of cyclosporine immunosuppression the tumour continues to grow, however, after withdrawal of the immunosuppression, tumour clearance is quicker in the poorly matched background. This data supports the idea of expansion of the donor pool by using kidneys after ex vivo resection of small renal tumours and that these organs should be transplanted into a less well-matched HLA recipient. We hypothesise that should a tumour recurrence occur a poorly matched recipient could clear the tumour through withdrawal of immunosuppression.

Resuscitation of Marginal Hearts Using Ex Vivo Perfusion

B1230 Complicated Ventricular Assist Device Patients With Good PostTransplant Outcomes Supports 1A Upgrade. J. Moriguchi, F. Arabia, R. Jocson, J. Patel, M. Kittleson, Z. Yu, F. Liou, M. Siu, L. Czer, D. Chang, A. Trento, J. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA. Purpose: Currently, patients (pts) awaiting heart transplant (HTx) on Ventricular Assist Device (VAD) and listed as status 1B are allowed 30 days of status 1A time. However, if these pts develop complications while on the heart transplant waitlist then they are elevated to status 1A due to high risk of poor outcome while waiting. It has not been well established if complicated VAD pts have compromised outcomes after HTx compared to non-complicated VAD pts electively listed 1A. Methods: Between 2007 and 2012 we evaluated 72 pts awaiting status 1A for HTx on VAD. All pts were assessed for complications while on the waitlist as defi ned by the new “Guidance Regarding Adult Heart Status 1A(b) Device-Related Complications”. Pts were then divided into those that developed VAD complications and were subsequently upgraded to status 1A while on the waitlist and those who did not develop complications but had upgraded to status 1A using elective time. Post-HTx outcomes including 3-year (yr) Actuarial Survival, freedom from Cardiac Allograft Vasculopathy (CAV) and freedom from Non-fatal Major Adverse Cardiac Events (NF-MACE: Myocardial Infarction, Congestive Heart Failure, angioplasty, pacemaker/ICD, stroke) at 3 yrs along with 1-yr freedom from any treated rejection and rehospitalization were assessed. Results: 15 VAD pts developed complications while awaiting HTx, allwere status 1A at the time of HTx. 57 non-complicated VAD pts listed status 1A underwent HTx during the same period. Complicated VAD pts had comparable 3 yr post-HTx outcomes compared to noncomplicated VAD pts. 1 yr freedom from any rejection were also similar between the two groups. Complicated VAD pts had numerically lower freedom from re-hospitalization 1 year post-HTx (See Table). Complicated VAD (n=15) Non-Complicated VAD (n=57) Log-rank p-value 1 Year Freedom from Any Treated Rejection 93.3% 84.2% 0.39 1 Year Freedom from Rehospitalization 86.7% 87.7% 0.87 3 Year Actuarial Survival 93.3% 93.0% 0.99 3 Year Freedom from CAV 93.3% 89.5% 0.65 3 Year Freedom from NFMACE 66.7% 80.7% 0.21 Conclusion: VAD pts who developed complications vs. those without complications while on the HTx waitlist appear to have comparable post-HTx outcomes. This fi nding supports upgrading these pts to status 1A listing pre-HTx as they have acceptable post-HTx outcomes. DISCLOSURES: Moriguchi, J.: Grant/Research Support, Thoratec, Syncardia Inc. Arabia, F.: Other, Syncardia, Consultant. Patel, J.: Grant/Research Support, Alexion Pharmaceuticals. Chang, D.: Stockholder, Abbot Pharmaceuticals, ABBV. Kobashigawa, J.: Grant/Research Support, XDx Inc., Novartis. Abstract# B1231 Right Ventricular Assist Device Support After Continuous Flow Left Ventricular Assist Device Implantation: Predicting a Poor Predictor. S. Singh,1 R. Hernandez,2 J. Anand,1 A. Baldwin,2 E. Sandoval-Martinez,2 W. Cohn,1 O. Frazier,2 H. Mallidi.1 1Department of Surgery, Baylor College of Medicine, Houston, TX; 2Center for Circulatory Support, Texas Heart Institute, Houston, TX. Purpose: Demographic, perioperative and late clinical outcomes in patients who require right ventricular assist device (RVAD) support after left ventricular assist device (LVAD) implantation, has not been well described. Predictive tools of RVAD after LVAD are based on univariate models from combined pulsatile and continuous fl ow (CF) VAD patients. Multivariable models have been inconsistent in predictors elucidated. We aimed to review contemporary CF LVADs with long term follow-up, to determine the predictors of RVAD need after CF LVAD, and the impact on mid and long term survival. Methods: A retrospective review of a single center was done. All HeartMate II CF LVADs (2003-2012) were identifi ed. Patients were stratifi ed by whether they received a RVAD after LVAD implant. Descriptive univariate statistics, multivariate regression and survival analysis were performed. Results: We identifi ed 294 patients; 26 (8.8%) required a RVAD. Mean follow up was 2.5 years (maximum 8 years). Late survival was worse in those who received a RVAD (15% vs 76%, p<0.001). Receiving an RVAD was an independent predictor of mortality (HR 2.4, 95% CI 3.7-40, p<0.001). Patients who required a RVAD had similar demographics and preoperative characteristics, however more likely to be: bridge to transplant (69% vs 46%, p=0.03), intubated pre-operatively (31% vs 12%, p=0.008), on temporary circulatory support preop (27% vs 8%, p=0.09) and had higher preoperative bilirubin and AST. RVAD patients more often required redo sternotomy (69% vs 39%, p=0.003). In-hospital outcomes included longer ventilator support (30+50 vs 9+17 days, p<0.001). Multivariable regression analysis found signifi cant independent predictors of getting a RVAD after LVAD implant to be redo sternotomy (HR 1.5, 95% CI 1.3-9.3, p=0.002) and pre-operative temporary circulatory support (HR 1.3, 95% CI 1.2-9.6, p=0.01). Conclusion: This is the largest series of patients with contemporary CF LVADs and long term follow-up. RVAD requirement after LVAD purports very poor early, mid and long term survival. Redo sternotomy and pre-operative temporary circulatory support were independent predictors of RVAD requirement, which along with univariate variables identifi ed above, may be used to identify and stratify this high risk cohort. B1231 Right Ventricular Assist Device Support After Continuous Flow Left Ventricular Assist Device Implantation: Predicting a Poor Predictor. S. Singh,1 R. Hernandez,2 J. Anand,1 A. Baldwin,2 E. Sandoval-Martinez,2 W. Cohn,1 O. Frazier,2 H. Mallidi.1 1Department of Surgery, Baylor College of Medicine, Houston, TX; 2Center for Circulatory Support, Texas Heart Institute, Houston, TX. Purpose: Demographic, perioperative and late clinical outcomes in patients who require right ventricular assist device (RVAD) support after left ventricular assist device (LVAD) implantation, has not been well described. Predictive tools of RVAD after LVAD are based on univariate models from combined pulsatile and continuous fl ow (CF) VAD patients. Multivariable models have been inconsistent in predictors elucidated. We aimed to review contemporary CF LVADs with long term follow-up, to determine the predictors of RVAD need after CF LVAD, and the impact on mid and long term survival. Methods: A retrospective review of a single center was done. All HeartMate II CF LVADs (2003-2012) were identifi ed. Patients were stratifi ed by whether they received a RVAD after LVAD implant. Descriptive univariate statistics, multivariate regression and survival analysis were performed. Results: We identifi ed 294 patients; 26 (8.8%) required a RVAD. Mean follow up was 2.5 years (maximum 8 years). Late survival was worse in those who received a RVAD (15% vs 76%, p<0.001). Receiving an RVAD was an independent predictor of mortality (HR 2.4, 95% CI 3.7-40, p<0.001). Patients who required a RVAD had similar demographics and preoperative characteristics, however more likely to be: bridge to transplant (69% vs 46%, p=0.03), intubated pre-operatively (31% vs 12%, p=0.008), on temporary circulatory support preop (27% vs 8%, p=0.09) and had higher preoperative bilirubin and AST. RVAD patients more often required redo sternotomy (69% vs 39%, p=0.003). In-hospital outcomes included longer ventilator support (30+50 vs 9+17 days, p<0.001). Multivariable regression analysis found signifi cant independent predictors of getting a RVAD after LVAD implant to be redo sternotomy (HR 1.5, 95% CI 1.3-9.3, p=0.002) and pre-operative temporary circulatory support (HR 1.3, 95% CI 1.2-9.6, p=0.01). Conclusion: This is the largest series of patients with contemporary CF LVADs and long term follow-up. RVAD requirement after LVAD purports very poor early, mid and long term survival. Redo sternotomy and pre-operative temporary circulatory support were independent predictors of RVAD requirement, which along with univariate variables identifi ed above, may be used to identify and stratify this high risk cohort. Abstract# B1232 Sensitization After Heartmate II Implantation Reduces Transplant Access. P. Kimball, F. McDougan, M. Flattery, K. Shah. Surgery, VCU Hospitals, Richmond, VA. Background. Various ventricular assist devices are used as bridges to heart transplantation (HT). However, VAD implantation with concomittant blood transfusions (BT) may increase patient allosensitization and reduce access to HT. We evaluated the impact of Heartmate II implantation upon sensitization and transplant rate within 12 months of implant. Methods. Between 2009-12, 63 patients received HMII. PRA, anti-HLA specifi city and strength index (MFI) were measured before and approximately 3 months after HMII placement using single antigen bead luminex. Results. Comparison of pre vs. post-HMII sensitization showed that implantation increased the number of patients with PRA>10% (25% vs. 40%, p<0.05) and increased PRA against Class I (4%±2 vs. 41%±30, p<0.05) and Class II (4%±2 vs. 56%±25, p<0.05). Because 60% of HMII recipients maintained a stable PRA<10%, we partitioned patients into those with post-HMII PRA<10% (Group 1) vs. >10% (Group 2). Fewer Group 1 than Group 2 patients had specifi cities against Class I (18% vs. 57%, p<0.05) or Class II (11% vs. 32%, p<0.05). In addition, antibody MFIs were signifi cantly lower (p<0.05) for Group 1 vs. 2 patients against Class I (1000 vs. 24000) or Class II (1000 vs. 2000). Although 80% of patients in both groups received BTs, fewer BTs were received by Group 1 vs. Group 2 (2.8±3 vs. 5.2±3, p<0.05). Twelve month clinical outcomes differed between Groups. Mortality was lower among Group 1 vs. Group 2 (6.4% vs. 12.5%, p<0.05). Although 1-yr transplan

Donation after cardiac death: Can hearts be sucessfully reanimated?

RO-194 – Classification at 6 weeks and fibrosis/atrophy at one year Variables at one year Classification of biopsies at 6 weeks p (neg vs. bord) p (neg vs. rej) p (bord vs. rej) Negative (n=100) Borderline (n=43) Rejection (n=14) Interstitial fibrosis 0.80 (0.71) 0.91 (0.43) 0.71 (0.47) 0.36 0.66 0.17 Tubular atrophy 1.03 (0.63) 0.98 (0.34) 0.71 (0.46) 0.60 0.073 0.028 Mean (SD). were placed on MPP (pulsatile perfusion machine, RM3) and all patients received the same immunosuppressive treatment. Estimated MDRD and inuline clearance were analysed until 36 months after transplantation and systematic biopsies were performed at M3 and M12 to evaluate the chronic interstitial fibrosis (IF) by colour image quantification. Our experience with RM3 perfusion machine leads us to perform a SKG when the resistance index (RI) is lower than 0.4 after 6 hours of perfusion and a DKG when the RI is between 0.4 and 0.6. Donor’s and recipient’s characteristic (mean age, gender), mean numbers of HLA mismatch were not significantly different. The mean duration time of MPP and the mean warm ischemic time were higher in the DKG than in the SKG group (1319 vs 689 min, p= 0.05 and 105 vs 121 min, p=0.017). Patient and graft survivals were 100% in both groups. PNF (not observed in our cohort) and DGF rate were not statistically different between the 2 groups (100% vs 78%). Acute rejection rate was not different between the groups. Graft outcomes and IF results are reported table 1. Table 1. Evolution of graft function and histology

Large animal renal allotransplantation; a porcine recovery model to assess delayed graft function

RO-194 – Classification at 6 weeks and fibrosis/atrophy at one year Variables at one year Classification of biopsies at 6 weeks p (neg vs. bord) p (neg vs. rej) p (bord vs. rej) Negative (n=100) Borderline (n=43) Rejection (n=14) Interstitial fibrosis 0.80 (0.71) 0.91 (0.43) 0.71 (0.47) 0.36 0.66 0.17 Tubular atrophy 1.03 (0.63) 0.98 (0.34) 0.71 (0.46) 0.60 0.073 0.028 Mean (SD). were placed on MPP (pulsatile perfusion machine, RM3) and all patients received the same immunosuppressive treatment. Estimated MDRD and inuline clearance were analysed until 36 months after transplantation and systematic biopsies were performed at M3 and M12 to evaluate the chronic interstitial fibrosis (IF) by colour image quantification. Our experience with RM3 perfusion machine leads us to perform a SKG when the resistance index (RI) is lower than 0.4 after 6 hours of perfusion and a DKG when the RI is between 0.4 and 0.6. Donor’s and recipient’s characteristic (mean age, gender), mean numbers of HLA mismatch were not significantly different. The mean duration time of MPP and the mean warm ischemic time were higher in the DKG than in the SKG group (1319 vs 689 min, p= 0.05 and 105 vs 121 min, p=0.017). Patient and graft survivals were 100% in both groups. PNF (not observed in our cohort) and DGF rate were not statistically different between the 2 groups (100% vs 78%). Acute rejection rate was not different between the groups. Graft outcomes and IF results are reported table 1. Table 1. Evolution of graft function and histology

Using dialysis for prolonged ex vivo warm reperfusion of DCD hearts

RO-194 – Classification at 6 weeks and fibrosis/atrophy at one year Variables at one year Classification of biopsies at 6 weeks p (neg vs. bord) p (neg vs. rej) p (bord vs. rej) Negative (n=100) Borderline (n=43) Rejection (n=14) Interstitial fibrosis 0.80 (0.71) 0.91 (0.43) 0.71 (0.47) 0.36 0.66 0.17 Tubular atrophy 1.03 (0.63) 0.98 (0.34) 0.71 (0.46) 0.60 0.073 0.028 Mean (SD). were placed on MPP (pulsatile perfusion machine, RM3) and all patients received the same immunosuppressive treatment. Estimated MDRD and inuline clearance were analysed until 36 months after transplantation and systematic biopsies were performed at M3 and M12 to evaluate the chronic interstitial fibrosis (IF) by colour image quantification. Our experience with RM3 perfusion machine leads us to perform a SKG when the resistance index (RI) is lower than 0.4 after 6 hours of perfusion and a DKG when the RI is between 0.4 and 0.6. Donor’s and recipient’s characteristic (mean age, gender), mean numbers of HLA mismatch were not significantly different. The mean duration time of MPP and the mean warm ischemic time were higher in the DKG than in the SKG group (1319 vs 689 min, p= 0.05 and 105 vs 121 min, p=0.017). Patient and graft survivals were 100% in both groups. PNF (not observed in our cohort) and DGF rate were not statistically different between the 2 groups (100% vs 78%). Acute rejection rate was not different between the groups. Graft outcomes and IF results are reported table 1. Table 1. Evolution of graft function and histology

A Novel Perfusion Fluid for DCD Donor Kidneys; Better as a Flush or a Storage Medium?

P-037 – Table 1. Patient characteristics of reported cases of patients with AHD who received OLT ID Paper Ref. Age at LT Sex Cirrhosis etiology Clinical status before LT Clinical status after LT Follow up 1 Parkes et al., 1970 56 M N/A HE Cognitive impairment and movement disorder

An Ex Vivo Model For Reanimating Porcine Hearts Sourced From Donors After Cardiac Death.

P-037 – Table 1. Patient characteristics of reported cases of patients with AHD who received OLT ID Paper Ref. Age at LT Sex Cirrhosis etiology Clinical status before LT Clinical status after LT Follow up 1 Parkes et al., 1970 56 M N/A HE Cognitive impairment and movement disorder

Preservation of Donation After Cardiac Death Hearts Using Oxygenated, Hypothermic Machine Perfusion

P-037 – Table 1. Patient characteristics of reported cases of patients with AHD who received OLT ID Paper Ref. Age at LT Sex Cirrhosis etiology Clinical status before LT Clinical status after LT Follow up 1 Parkes et al., 1970 56 M N/A HE Cognitive impairment and movement disorder