Clinical Utility of the IMPACT Score for Mortality Prediction after Heart Transplantation: External Validation Study

Clinical Utility of the IMPACT Score for Mortality Prediction after Heart Transplantation: External Validation Study

S212 The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019 Methods: We retrospectively identified adult patients who underwent OH...

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S212

The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019

Methods: We retrospectively identified adult patients who underwent OHT from 2007-2015 and who survived ≥760 days post-OHT. Clinical characteristics and outcomes were obtained on chart review. All Allomaps and EMBx during years 2-5 were extracted from the medical record, and their clinical context reviewed to determine if they were performed routinely or were triggered by a change in clinical status defined by symptoms, imaging, or biomarkers. Significant rejection was defined as ≥2R acute cellular rejection (ACR), any antibody-mediated rejection (AMR), or treated biopsy-negative rejection. Studies within one year of a significant rejection episode were considered triggered. Patients were categorized based on whether the treating cardiologist intended to continue routine studies after the second post-OHT year. Logistic regression was used to evaluate factors predictive of surveillance strategy. Results: 217 patients met the above criteria, totaling 1,368 patient-years. 1020 studies were performed after day 760 of which 835 (81.9%) were routine (201 EMBx, 634 Allomaps). Of the routine EMbx, two (1%) demonstrated rejection—one 2R ACR and one pAMR2; both patients had BNP elevations. The remaining studies were negative for significant rejection. Routinely ordered Allomaps triggered 36 EMBx (5.7%), of which 1 (0.2%) demonstrated rejection requiring treatment. 53 patients followed a “no routine surveillance” strategy and 159 a “routine surveillance” strategy. There were no differences in heart failure hospitalization, revascularization, or death between the groups. On multivariable logistic regression, treating cardiologist was the only predictor of surveillance strategy (p<0.0001). Conclusion: Although acute rejection is rare after the second post-OHT year, routine studies were performed commonly at our institution. Treating cardiologist but not clinical risk factors predicted choice of surveillance strategy. These data do not justify routine evaluations for rejection after two years.

506 Protocol Endomyocardial Biopsy beyond Six Months - It’s Time to Move On K. Oh,1 M.H. Mustehsan,1 D.B. Sims,1 O. Saeed,1 S. Vukelic,1 J.J. Shin,1 S. Murthy,1 A. Luke,1 S.J. Forest,2 D. Goldstein,2 U. Jorde,1 and S. R. Patel.1 1Medicine, Division of Cardiology, Montefiore Medical Center/ Albert Einstein College of Medicine, Bronx, NY; and the 2Cardiovascular and Thoracic Surgery, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY. Purpose: Despite the low incidence of cardiac allograft rejection beyond 6 months after heart transplant (HTX), surveillance endomyocardial biopsy (EMB) is commonly performed up-to 1 year and beyond. We aim to investigate the value of routine EMB beyond 6 months. Methods: A single center retrospective review was conducted on all adult HTX recipients between 2008 and 2017. Patients who did not complete routine EMB beyond 6 months post-HTX were excluded. EMB results were reviewed for rejections, defined as ISHLT grade ≥ 2R or >pAMR1. Each rejection was then reviewed to determine if it was diagnosed on protocol (at 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 32, 40, and 52 weeks) or symptom-triggered EMB. Results: A total of 2714 EMBs were performed in 198 HTX recipients, characterized by median age 55 (47-63 years), 30% female, 28% African American, 65% with pre-HTX LVAD, and 30% with PRA>30% (MFI > 1000). The incidence of rejection was significantly higher during the first 6 months post-HTX (Figure 1A). Thirty-two out of 1960 EMBs from the first 6 months had rejection (1.62%), compared to 5 rejections in 755 EMBs between 6-12 months post-HTX (0.66%, p=0.05). These rejections occurred in 27 vs. 5 out of 198 patients (13.6% vs. 2.53%, p<0.0001). Importantly, protocol EMB identified the majority of rejections during the first 6 months (92.6%), but only 1 of the rejections after 6 months (p=0.002, Figure 1B). Of note, this single rejection was grade 3R, but without hemodynamic compromise or graft dysfunction, in the setting of reduced immunosuppression due to leukopenia. Conclusion: EMB was found to be a low-yield screening modality for rejection beyond 6 months post-HTX. The need for protocol EMB beyond 6 months warrants further investigation.

507 Clinical Utility of the IMPACT Score for Mortality Prediction after Heart Transplantation: External Validation Study C.D. Ortiz Bautista,1 J. Muniz Garcia,2 F. Gonzalez-Vilchez,3 J. Segovia Cubero,4 M.G. Crespo Leiro,5 R. Lopez Vilella,6 J. Gonzalez Costelo,7 E. Roig Minguel,8 J.M. Arizon Del Prado,9 J.M. Sobrino Marquez,10 I.P. Garrido Bravo,11 and J.F. Delgado Jimenez.12 1Cardiology, Hospital General Universitario Gregorio Mara~non, Madrid, Spain; 2Instituto de Investigacion Biomedica (INIBIC), Complexo Hospitalario Universitario de A Coru~na, A Coru~na, Spain; 3Cardiology, Hospital Universitario Marques de Valdecilla, Santander, Spain; 4Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain; 5Cardiology, Complexo Hospitalario Universitario de A Coru~na, A Coru~na, Spain; 6Cardiology, Hospital Universitario La Fe, Valencia, Spain; 7Cardiology, Hospital Universitario de Bellvitge, Barcelona, Spain; 8Cardiology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; 9Cardiology, Hospital Universitario Reina Sofía, Cordoba, Spain; 10Cardiology, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 11Cardiology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain; and the 12Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain. Purpose: The primary objective of this work is to externally validate the Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score in the Spanish cohort. Methods: Spanish Heart Transplant Registry data were used to identify isolated adult (>16 years) OHT performed from 2000 to 2015. Individual values of the IMPACT score were calculated for each patient. Overall 1year mortality after OHT was assessed and 1-year mortality rates between predefined IMPACT score groups (0-2pts, 3-5pts, 6-9ptos, 10-14ptos, ≥15pts) were compared. Correlation between the observed and expected mortality according to the IMPACT score was evaluated. Finally, discrimination ability was assessed by the area under the ROC curve. Results: We identified 2,814 OHT. Baseline characteristics are shown in the table. Mean value of the IMPACT score was 6.3§4.9 points. Overall 1-year survival rate was 79.1%. Kaplan-Meier 1-year survival rates by IMPACT score groups were 84.6%, 81.3%, 79.4%, 76.4% and 58.3% respectively (p <0.001). Correlation between the observed mortality in our series and that expected according to the IMPACT score was good (r=0.78), while its discrimination ability was poor (AUC=0.52). Conclusion: OHT mortality in Spain is adjusted to that expected by the IMPACT score, so there is good calibration of the predictive model. However, its predictive strength is poor and similar to that determined by chance. On the other hand, there is a lack of studies that evaluate the impact on clinical practice and outcomes of OHT. In the absence of these studies, we cannot implement the IMPACT score in our daily clinical decision making.

Baseline characteristics. 1Includes: ECMO, Abiomed BVS 5000, Levitronix, BioMedicus e Impella CP. Age (years), mean § SD Race -Caucasian, n (%) -Black, n (%) Serum Bilirrubin (mg/dl), mean § SD

N=2,814 53 § 12 2802 (99,6) 12 (0,4) 1,3 § 1,1 (continued)

Abstracts

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(Continued) Baseline characteristics. 1Includes: ECMO, Abiomed BVS 5000, Levitronix, BioMedicus e Impella CP. Creatinine clearance (ml/min), mean § SD Heart failure etiology -Idiopathic, n (%) -Ischemic, n (%) -Congenital, n (%) Dialysis pre-OHT, n (%) Infection pre-OHT, n (%) Mechanical ventilation pre-OHT, n (%) Mechanical circulatory support -No, n (%) -Intra-aortic balloon pump, n (%) -Temporary circulatory support1, n (%) -Continuous VAD, n (%) -Pulsatile VAD, n (%)

80,2 § 36,3 795 (28) 874 (31) 71 (3) 42 (2) 373 (13) 386 (14) 2061 (73,5) 432 (15,5) 282 (10) 6 (0,5) 33 (1)

509 Cardiac Transplantation across Preformed HLA-Antibody Barriers: Results of a Peritransplant Desensitization Protocol F. Ius,1 S.V. Rojas,1 T. Kaufeld,1 W. Sommer,1 C. Bara,1 J. Salman,1 T. Siemeni,1 R. Poyanmehr,1 D. Bobylev,1 M. Avsar,1 I. Tudorache,1 C.S. Falk,2 A. Haverich,1 and G. Warnecke.1 1Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany; and the 2Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany.

508 One but Not the Same: Risk Factors for Early Post-Transplant Mortality Differ between Medically Managed Patients and Those Bridged to Transplant with Left Ventricular Assist Devices L.K. Truby,1 M. Farr,2 and V.K. Topkara.2 1Duke University Medical Center, Durham, NC; and the 2Columbia University Medical Center, New York, NY. Purpose: Currently, criteria for heart transplant (HT) listing does not differ between patients medically managed versus mechanically bridged to HT. We evaluated differences in risk factors for 1-year mortality between those with and without LVAD at the time of HT. Methods: In the UNOS database we identified adult, single-organ HT recipients transplanted between 2008 and 2015. 5486 patients were propensity matched for likelihood of LVAD at the time of HT. Cox proportional hazard regression analysis was used to evaluate the hazard ratio of 1-year mortality for patients BTT with LVAD as compared to medical management across thresholds of clinically significant variables. Results: As compared to medically managed patients, those BTT with LVAD were at increased risk of 1-year post-HT mortality, with PGD being the most common cause of death. Compared to medically managed patients, BTT with LVAD was associated with increased risk of 1-year mortality at a eGFR of 40-60 mL/min/1.73m2 (HR 1.58, p=0.008) and a eGFR of < 40mL/min (HR: 1.94, p=0.010). Similar trends were observed with a BMI of 25-30 kg/m2 (HR: 1.81, p=0.033) and a BMI of > 30 kg/m2 (HR: 1.93, p<0.001). When patients were stratified by BTT status and the presence of risk factors including Age > 60, eGFR < 40 mL/min/1.73m2, and BMI > 30kg/m2 there were significant differences in 1-year mortality between medium- and high-risk medically and mechanically bridged patients, with 17.6% 1-year mortality in high-risk BTT patients compared to 10.4% in high risk medically managed patients. Conclusion: Patients bridged with mechanical support may require more careful consideration for transplant eligibility after LVAD placement in order to optimize post-HT outcomes. These findings should be taken into consideration when developing and/or refining heart systems.

Purpose: A growing number of patients awaiting heart transplantation presents with preformed anti-HLA antibodies. This allosensitization prolongs waiting times and increases morbidity and mortality. In 2017, we designed aprotocol for peritransplant desensitization of heart-transplanted patients showing preformed anti-HLA donor specific antibodies (pfDSA), i.e. a positive virtual crossmatch. The protocol included: an intraoperative single dose of the IL-6 receptor antibody Tocilizumab (10mg/kg) just before releasing the aortic clamp; 5 sessions of plasmapheresis (PE, 1 before transplantation, 1 during transplantation and 3 thereafter); an infusion (2g/kg) of IgA and IgM-enriched human immunoglobulins G (IgGAM) after the last PE; and a single Rituximab dose (375mg/m2) after IgGAM. IgGAM are repeated every 4 weeks (0.5g/kg) for a maximum of 6 months, if DSA are still positive. Aim of this study was to present the preliminary results of this peritransplant desensitization protocol. Methods: Records of heart-transplanted patients at our institution between 01/2017 and 10/2018 were reviewed. Patients with pfDSA (positive virtual crossmatch) formed the case group, remaining patients the control group. Median (IQR) follow-up amounted to 9 (5, 16) months. Results: During the study period, among the 42 transplanted patients, 9 (21%) patients formed the case group and the remaining 33 (79%) the control group. All 9 case patients showed pfDSA with >50% pre-transplant panel reactive antibodies (PRA). Pretransplant recipient and donor characteristics did not differ between groups. Post-transplant, no case patients showed severe primary graft dysfunction, but 6 (19%) control patients did (p=0.19). At treatment end, pfDSA were cleared in 4 (44%) patients. At 1-year follow-up, survival was 100% vs. 75% in case and control patients (p=0.18); freedom from biopsy-confirmed rejection (Grade >1R) was 89% vs. 92% in case (n=1) and control (n=2) patients (p=0.78); and from steroid-pulsed therapy 89% vs. 82% in case (n=1) and control (n=5) patients (p=0.76), respectively. One case patient showed minimal AMR (pAMR 1+). Conclusion: The present study showed that heart transplantation across positive crossmatch barriers can be feasible and safe. The present peritransplant desensitization protocol yielded good survival and rejection-free survival. 510 Treatment of Therapy-Resistant Hyperlipidaemia after Heart Transplant with PCSK9-Inhibitors K. Uyanik-Uenal,1 M. Stoegerer-Lanzenberger,2 K. Auersperg,1 A. Aliabadi-Zuckermann,1 G. Laufer,1 and A. Zuckermann.1 1Department of Cardiac Surgery, Medical University of Vienna (AKH), Vienna, Austria;