Left Ventricular Assist Device-Associated Allosensitization - Much More Than a Nuisance

Abstracts S287

3-Year Actuarial Survival 3-Year Actuarial Freedom from CAV 3-Year Actuarial Freedom from NF-MACE 3-Year Actuarial Freedom from Any Treated Rejection

No DSA (n= 147)

Low Level DSA at Transplant (n= 22)

P-Value

87.8% 84.2%

94.7% 75.0%

0.383 0.527

86.2%

87.8%

0.673

75.2%

78.8%

0.827

Conclusion: In the era of virtual crossmatch, low level DSA prior to transplant does not appear to be associated with the development of CAV and poor outcomes after heart transplant. These donors, to which the potential recipient has low level DSA, should be considered for transplant. Larger numbers and longer follow-up is needed to confirm these findings. 7( 85) Perioperative Prognostic Factors for Fontan Patients Undergoing Orthotopic Heart Transplant C.J. Berg,1 B. Bauer,1 A. Hageman,2 L.C. Reardon .2  1David Geffen School of Medicine at UCLA, Los Angeles, CA; 2Ahmanson/UCLA Adult Congenital Heart Disease Center, Los Angeles, CA. Purpose: Although the Fontan procedure offers a long-term palliative option for single-ventricle patients, orthotopic heart transplantation (OHT) remains the definitive treatment for a failing Fontan circuit. We hypothesized that there are a set of perioperative variables associated with increased risk of postoperative adverse outcomes. Methods: 36 post-Fontan patients were identified as having undergone OHT at UCLA Medical Center from 1991 to 2014. Data was collected retrospectively and analyzed. The primary endpoint was designated as either perioperative mortality, extended postoperative hospital stay (> 30 days), or readmission within 2 weeks of discharge. Results: 17 of 36 patients reached the primary endpoint; 8 patients suffered perioperative death after OHT, 6 patients experienced extended hospital stays, and 4 patients were readmitted within 2 weeks after discharge. Of the patients that suffered the primary outcome, 11 of these patients had an extended preoperative hospital stay (> 10 days), 7 patients had an elevated MELD-XI score (≥ 18), and 8 patients had an extended perioperative cardiopulmonary bypass time (> 4 hours). Patients with an elevated MELD-XI score (p= 0.0128) or an extended cardiopulmonary bypass time (p= 0.0002) carried a significantly higher risk of reaching the primary endpoint. A composite scoring system of eight criteria was used to stratify the risk of patients suffering the primary endpoint. Patients with scores of ≥ 3, 2, and 0-1 had a 91.1%, 33.3%, and 25% risk of reaching the primary endpoint, respectively. Patients with a score of ≥ 3 had a relative risk of 3.6 over patients with 0-1 points (95% CI, 1.53-8.67; p= 0.0013). Conclusion: Failing Fontan patients undergoing OHT with elevated preoperative MELD-XI scores and/or extended perioperative cardiopulmonary bypass times are at greater risk of experiencing adverse outcomes after transplant. Additionally, a novel scoring system was devised for optimized risk stratification of suffering an adverse outcome after OHT, in which a score of ≥ 3 was predictive of poorer outcomes. This scoring system may allow for potential improvements in recipient evaluation during the listing process. 7( 86) Histopathological and Immunological Diagnostic Findings for Cardiac Allograft Antibody-Mediated Rejection Following Mechanical Circulatory Support K. Wassilew ,1 D. Kemper,2 N. Lachmann,3 M. Niemann,3 C. Schönemann.3   1Cardiac Pathology Unit, Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; 2Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; 3Laboratory for Tissue Typing, Institute of Transfusion Medicine and Cell Therapy, Charité- Universitätsmedizin Berlin, Berlin, Germany.

Purpose: Mechanical circulatory support (MCS) systems are widely used to bridge the failing heart to transplantation (HTx). Ongoing unspecific allosensitation on MCS support is thought to increase the incidence of antibody-mediated rejection (AMR) episodes in cardiac allografts. We aimed to investigate the correlation between histopathological and immunological diagnostic findings for cardiac AMR and pre-HTx MCS therapy. Methods: All 409 consecutive right ventricular endomyocardial biopsies (EMBs) of cardiac allografts taken between 01/2011 and 12/2012 of 220 HTx patients (58 female, age range 1-78 years, mean age 45 years) were evaluated. With regard to pre-transplant MCS treatment, patients were divided into two groups (non-MCS group n= 138 patients, MCS group n= 82 patients, mean time on MCS 298 days). When available, blood samples were scrutinized pre- and post HTX for HLA antibodies (AB) using a Luminex-based solid-phased immunoassay. Formalin-fixed paraffin-embedded tissue sections were evaluated using conventional histology (hematoxylin eosin) and immunohistochemistry (pan macrophage marker CD68 and complement split products C3d and C4d). The histological findings were scored according to the ISHLT criteria for acute cellular rejection (ACR) and AMR. The results were subjected to statistical analysis (chi-square and Cochran-Mantel-Haenzsel tests). Results: In the non-MCS group both pre- and post HTx HLA AB correlated with ACR (p= 0.034 and 0.003) and CD68 (p= 0.034 and 0.006). Subgroup analysis showed HLA AB-CL1 to correlate with CD68 (p= 0.011) and ACR (p= 0.007) in post-HTx blood samples and C3d to correlate with both preHTx HLA AB CL1 and CL2 (p= 0.042) in pre-HTx blood samples. In the MCS group the interstitial macrophage level appeared to be the only dependent variable, showing a positive correlation with pre-HTx HLA AB-CL1 (p= 0.044 vs p= 0.086). Between the MCS and non-MCS group this difference was highly significant (p= 0.007). Conclusion: Our results imply that both complement activation and HLA AB can currently not be considered helpful markers in diagnosing AMR and ACR in MCS patients. This might be explained by continuous activation of the innate immune system by macrophages in pre-transplant period. Further studies focusing on time-dependent immunological effects are warranted. 7( 87) Left Ventricular Assist Device-Associated Allosensitization - Much More Than a Nuisance B. Ko , C.A. Willis, S.G. Drakos, D. Hurst, A.G. Kfoury, G. Snow, J.C. Delgado, E.H. Hammond, C.H. Selzman, R. Alharethi, S. McKellar, J. Nativi-Nicolau, E.M. Gilbert, P. Revelo, D. Miller, B. Reid, J.C. Fang, D.D. Eckels, J. Stehlik.  U.T.A.H. Cardiac Transplant Program, Salt Lake City, UT. Purpose: The impact of immune allosensitization induced by continuous flow left ventricular assist devices (CF LVAD) on post-transplant outcomes is still controversial. And, whether LVAD allosensitization carries a different importance than allosensitization due to other etiologies is also not known. Methods: Alloantibodies were detected with single-antigen beads on Luminex platform in all patients who received heart transplant in our program from 2006 to 2014. Allosensitization was defined as calculated panel reactive antibody (cPRA) > 10%. In patients receiving CF LVADs as a bridge to transplant, cPRA was determined before CF LVAD implant and at the time of transplant, and in patients without CF LVAD at transplant listing and at the time of transplant. Antibody mediated rejection was defined as 3 or more episodes of pAMR≥ 2 detected on endomyocardial biopsies. Results: 197 patients were transplanted between 2006 and 2014, of which 78 (40%) were bridged with CF LVADs. The mean age was 52±12 years, 18% were female and 92% of women were previously pregnant. Twenty patients were sensitized at baseline, and additional 12 patients became sensitized before transplant. Among all patients, those who became newly sensitized were at the highest risk of AMR, followed by patients already sensitized at baseline - p= 0.02. In the CF LVAD group, sensitization was strongly associated with AMR (p< 0.001, Figure 1A), but not in the non-LVAD group alone (p= NS, Figure 1B). Cardiovascular mortality and all-cause mortality were numerically higher in the sensitized patients, but this relationship was not statistically significant, perhaps due to the limited number of events. Conclusion: CF LVADs lead to a high risk of AMR after transplant in the 10% of patients who developed alloantibodies after LVAD implant. CF LVAD

S288

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

associated sensitization appears to be of higher clinical significance than sensitization of other etiologies, possibly due to the temporal closeness of the newly triggered antibody production to the transplant. 

after cardiac transplantation (CTX) in relation to subsequent prognosis of the patients (pts). Methods: Retrospective analysis of CTX patients operated in one center between 2005-2010 years. EMB findings were correlated with combined end point including treated cellular rejection (ACR), AMR and graft dysfunction. EMBs were performed in prespecified intervals, all samples were evaluated by histology and immunohistochemisty. Banff classification was used for ACR diagnosis, finding of complement fragments C3d, C4d in ≥  50 % vessels was basis for AMR diagnosis. Graft dysfunction was stated when LVEF decreased ≤  40 % on echocardiography. Results: During period studied 245 CTX operations were performed. In this study we evaluated the group of 169 pts (129 men), surviving at least 12 months after CTX, with complete data from EMBs available. Fragments of C3d and/or C4d (C) in <  50 % vessels were found in EMBs of 124 (73 %) pts, in 48 % of them in combination. In 55 % of cases this finding was present more than in one EMB series. End-point (EP) was reached in 73 (43 %) of pts. Concordant finding (i.e. positive both C+EP and negative both C+EP) was found in 90 (53 %) of pts. C result predicted occurence of EP with low sensitivity and moderate specificity (48 % resp. 69 %), positive and negative predictive values were 81 % resp. 36 %. Predicted value did not improve when only repeated C positivity was considered. Conclusion: Evidence of complement activation in less than 50 % vesels is frequent EMB finding after CTX. This probably mirrors graft accomodation and is not reliable predictor of rejection and graft dysfunction. Supported by grant MZCR NT 11262-6. 7( 89) Is It Important to Reduce the Heart Rate in Patients Early After Heart Transplantation? H. Bedanova ,1 J. Ondrasek,1 P. Fila,1 V. Horvath,1 M. Orban,2 P. Nemec.1  1Center of Cardiovascular and Transplant Surgery, Brno, Czech Republic; 2ICRC, Brno, Czech Republic. Purpose: A strong correlation between lower heart rate (HR) and survival has been demonstrated in a number of studies in patients treated with heart failure, hypertension and coronary artery disease. The optimal HR for heart transplant (HTx) patients remains still unknown. The aim of our study was to evaluate association between early heart rate and survival after HTx. Methods: We retrospectively analyzed a group of 330 patients who underwent HTx in our institution from 1993 to 2013 and complete datasets, including 24-hour HR monitoring one month after HTx. Patients were divided in 2 groups: group A (n =  278) with an average 24-hour HR < 90 bpm, Group B (n =  52) with ≥  90 bpm. Results: There were no differences observed in both groups in baseline characteristics of the recipients (age, gender, diagnosis leading to HTx, order at the WL, incidence of acute rejections, and BMI). Beta-blockers were used in 53% of group A patients, and in 54% in group B. Also the characteristics of corresponding donors were similar in both groups, except of the gender distribution (group B: 2-fold female gender (p =  0.04)). One-year survival in groups A and B was 92% and 81%, respectively; 5-year survival was 79% and 60%, respectively; and 10-year survival was 66% and 50%, respectively (p =  0.001). Conclusion: Increased heart rate in the early post-transplant period was significantly associated with worse survival in patients after HTx. Female gender of donor in this context also appears to be a risk factor. According to our results, more aggressive approach in treatment of tachycardia should be beneficial for the patients after HTx.

7( 88) Significance of Subtreshold Values of Complement Activation in Myocardium After Cardiac Transplantation I. Malek ,1 T. Gazdič,2 M. Hegarová,1 L. Voska,3 J. Pirk.2  1Clinic of Cardiology, IKEM, Prague, Czech Republic; 2Clinic of Cardiovascular Surgery, IKEM, Prague, Czech Republic; 3Department of Pathology, IKEM, Prague, Czech Republic. Purpose: Evidence of complement fractions C3d, C4d in endomyocardial biopsies (EMBs) is one of the basic findings in antibody mediated rejection (AMR) diagnosis. Involvement of at least 50 % depicted vessels in considered as treshold of positivity.The importance of subtreshold values is less well documented. The aim of this paper is the evaluation of EMBs findings

7( 90) Use of Circulatory Arrest During Heart Transplantation Does Not Worsen Perioperative Survival R.A. Sorabella ,1 S. Krishnamoorthy,1 M. Najjar,1 E. Castillero,1 A. Bader,1 P. Flanagan,1 P.C. Schulze,2 D. Mancini,2 Y. Naka,1 H. Takayama,1 I. George.1  1Cardiothoracic Surgery, Columbia University College of Physicians and Surgeons, New York, NY; 2Cardiology, Columbia University College of Physicians and Surgeons, New York, NY. Purpose: Full circulatory arrest (CA) is occasionally needed during heart transplantation, either as a planned aid in complex dissection or in emergency situations. The aim of this study is to investigate indications and predictors