Heart-Lung Transplantation

Abstracts S191 serum by ELISA (Eisai, Tokyo, Japan) The association of KL-6 serum levels at baseline with the survival after lung transplantation was analyzed using Kaplan-Meier analysis. The predictive accuracy of the model was tested by the Cox-Regression and Harrell´s C-statistic. Results: The overall survival in 6 years was 53%. The ROC-curve analysis showed a KL-6 baseline serum level of 305 U/ml as the best cut-off value for the prediction of survival. Patients with KL-6 serum level higher than 305 U/ml showed a worse survival (p < 0.016) compared to those with lower levels. In multivariate analysis, a model based on FEV1 decline and serum KL-6 levels showed a stronger predictive value for survival than FEV1 decline alone (C-Index= 0.702, p= 0.0001 und C-Index= 0.687, p= 0.0003). Conclusion: It can be suggested that high serum levels of KL-6 after lung transplantation are associated with a poor outcome in lung transplant recipients. The combination of KL-6 serum levels and FEV1 decline has a better prognostic accuracy than FEV1 decline alone. 5 ( 11) Evolving Experience of Treating Antibody-Mediated Rejection Following Lung Transplantation S. Otani ,1 A.K. Davis,2 L. Cantwell,3 S. Ivulich,4 M.A. Paraskeva,1 G.I. Snell,1 G.P. Westall.1  1Lung Transplant Service, Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Australia; 2Haematology, Alfred Hospital, Melbourne, Australia; 3National Transplant Services, Australian Red Cross Blood Services, Melbourne, Australia; 4Pharmacy, Alfred Hospital, Melbourne, Australia. Purpose: The importance of antibody-mediated rejection (AMR) following lung transplantation remains contentious. In particular, the diagnostic criteria suggested to define AMR, namely the presence of donor-specific antibodies (DSA), C4d immunoreactivity, histological features and allograft dysfunction are not always readily applicable or confirmatory in lung transplantation. In this study, we reviewed our evolving experience related to the diagnosis and treatment of AMR in lung transplant recipients from 2009 to 2012. Methods: In a retrospective single-center study of 255 lung transplant recipients, we identified patient in whom a clinical diagnosis of AMR was made, and define the immunological, histological, clinical features, as well as the therapeutic response of this cohort. Results: We identified 15 lung transplant recipients who were clinically diagnosed with AMR and underwent combination therapy with high-dose intravenous corticosteroid, intravenous immunoglobulin, plasmapheresis and Rituximab. Histological and C4d abnormalities were rarely observed. Following therapy, while the total number of the original DSA dropped by 36%, and the mean fluorescence intensity (mfi) of the originally observed DSA decreased from 7627 ± 6722 to 4281 ± 6319 (p < 0.001), clinical outcomes were overall disappointing with 13 of 15 patients progressing to either chronic lung allograft dysfunction (8 bronchiolitis obliterans syndrome, 5 restrictive allograft syndrome) or death within 12 month. An observed drop in mfi of 20% for class II DSA was associated with a clinical response to therapy (p= 0.035). Conclusion: AMR in lung transplantation remains both a diagnostic and therapeutic challenge. The presence of DSA in patients with otherwise unexplained graft dysfunction is associated with poor long-term outcomes.

5( 12) Long-Term Successful Outcomes From Kidney Transplantation Following Lung/Heart-Lung Transplantation S. Otani ,1 B.J. Levvey,1 G.P. Westall,1 M.A. Paraskeva,1 H.M. Whitford,1 T. Williams,1 R. Walker,2 S. Menahem,2 G.I. Snell.1  1Lung Transplant Service, Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Australia; 2Renal Medicine, Alfred Hospital, Melbourne, Australia. Purpose: Renal dysfunction is common after lung and heart-lung transplant(LTx, HLTx), limiting recipient survival and quality of life. This study analyzes the outcomes of simultaneous or late kidney transplant(KTx) following LTx/HLTx. Methods: From a single center retrospective chart-review of 999 LTx/HLTx patients, we identified 11 patients requiring simultaneous or late KTx. Results: Two patients underwent simultaneous deceased donor LTx and KTx from lymphangioleiomyomatosis (LAM) (LTx, n= 1) and cystic fibrosis (CF) (HLTx, n= 1). Eight patients [congenital heart disease(CHD) n= 4; CF n= 4; pulmonary fibrosis(IPF) n= 1] underwent LTx (n= 4 ) or HLTx (n= 4), followed by elective living donor KTx (including one from an ABO incompatible parent). One additional patient (CHD) underwent a late deceased donor KTx. The indication for KTx was calcineurin inhibitor toxicity/hypertension (n= 7) alone, or in combination with diabetes (n= 3), nephrolithiasis (n= 2), IgA nephropathy, BK nephropathy and post-strep glomerular nephritis (GN). The median time from LTx/HLTx to KTx was 127 (23 -263) months. Eight patients were dialysed preKTx. Kidney graft loss occurred via BK nephropathy in one patient at 51 months. At a median follow-up of 45 (1-157) months, the median serum Cr is currently 112 μ mol/L (n= 7). The median FEV1 six months pre and post staged KTx were 2.17L and 2.24L, respectively (n= 6). Acute lung rejection was seen in one patient. No acute kidney rejection has been detected. Three patients died from: sepsis day 4 (late group CHD HLTx), iatrogenic hemorrhage day 30 (simultaneous CF LTx) and transplant coronary disease 96 months (late IPF HLTx). Eight patients are currently alive and well. Conclusion: Simultaneous and late deceased donor KTx are challenging in the setting of LTx. By contrast, late living related KTx after LTx is associated with excellent long-term survival and acceptable kidney and lung allograft function. In late KTx an absent or short period of dialysis was associated with best outcomes.

Kidney and lung/ heart-lung transplantation

Case

Type of Age (KTx), thoracic Gender Tx

Indication Time from of thoracic thoracic Tx Tx to KTx Cause of kTx

Follow up Complications after KTx

Simultaneous 17F KTx 1

Bilateral CF LTx

-

Diabetes

Lung allograft 1m Died failure from iatrogenic hemorhage

Simultaneous 47F KTx 2

Bilateral LAM LTx

-

Angioliponas

Uretovesicular 1y11m stenosis Alive&well

Late KTx 1 (1st KTx)

46F

HLTx

CHD

12y7m

Cyclosporine

Kidney graft 4y3m loss (BK Kidney nephropathy ) graft loss

Late KTx 1 (2nd KTx)

55F

HLTx

CHD

21y10m

BK nephropathy

Late KTx 2

53M

HLTx

IPF

8y11m

Cyclosporine

Late KTx 3

32M

Bilateral CF LTx

3y11m

Cyclosporine

9y9m Alive&well

Late KTx 4

29M

Bilateral CF LTx

5y11m

Recurrence of focal segmental glomerulosclerosis (Sirolimus)

8y3m Alive&well

Late KTx 5

27M

Bilateral CF LTx

8y2m

IgA nephropathy, Nephrolithiasis, Diabetes

3y2m Alive&well

Late KTx 6

37M

HLTx

17y9m

Cyclosporine

2y10m Alive&well

Late KTx 7

35F

Bilateral CF LTx

1y11m

Post-strep GN, Diabetes, Tacrolimus

Acute lung rejection

5m Alive&well

Late KTx 8

39M

HLTx

CHD

17y

Cyclosporine

Leak of ureteric anastmosis

4d Died from sepsis

Late KTx 9

21F

HLTx

CF

7y7m

Nephrolithiasis, Diabetes

CHD

6m Alive&well Cardiac allograft failure

13y1m Died from transplant coronary disease

1m Alive&well

S192

The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014

5( 13) Influence of Intraoperative Hemodynamic Factors on the Development of Acute Kidney Injury in Lung Transplantation R. Romano ,1 I. Wong,2 L. Thakuria,2 F. De Robertis,3 T. Bahrami,3 M. Amrani,3 S. Kaul,3 D. Hall,3 A. Reed,3 M. Carby,3 A. Simon,3 N. Marczin.1   1Anaesthetics, Imperial College London, London, United Kingdom; 2Imperial College London, London, United Kingdom; 3Royal Brompton and Harefield NHS Foundation Trust, Harefield, United Kingdom. Purpose: Postoperative renal dysfunction requiring renal replacement therapy occurs frequently following lung transplantation (LT) with impact on perioperative and early mortality. Beyond preoperative factors, intraoperative events may also contribute to renal problems. In search of intraoperative determinants of postoperative renal dysfunction, we have evaluated the impact of hypotension episodes (HE) and requirement for vasoactive support and usage of blood products on the development of postoperative AKI in patients undergoing bilateral sequential lung transplantation. Methods: HE lasting longer than 15 min were graded according to blood pressure targets from the electronic database record (IntelliSpace Critical Care and Anaesthesia) of 60 patients between July 2010 and April 2013 at Harefield Hospital. Vasoactive support was documented at arrival to ICU. The development of AKI was monitored during the first 3 postoperative days using AKI Network (AKIN) criteria. Results: The development of AKI was associated with more HE below the target mean arterial blood pressure of 70 mmHg (16.7 ± 8.4 vs 11.1± 3.0 p= 0.019). In addition, the frequency of HE was also related to the grading of AKI (11.1 ± 3.0; 13.0 ± 5.2; 15.0 ± 7.9 and 19.9 ± 9.5 for AKI 0, 1, 2 and 3, respectively , p= 0.013). Similarly, episodes of mean arterial blood pressure < 60 mmHg was also different between AKI and no AKI groups (5.7 ± 5.6 vs 2.1 ± 1.9, p= 0.042). HE in patients subjected to cardiopulmonary bypass was higher (16.9 ± 9.1 vs 11.5 ± 6.8 for MAP< 70 and 6.0 ± 5.6 vs 1.6 ± 1.9 for MAP< 60, p= 0.001) associated with higher incidence of grade 3 AKI (51.1% vs 7.7). Regarding vasoactive support, the use of milrinone, noradrenaline and vasopressin was higher in patients who developed AKI. AKI was also associated with higher use of blood products (5.2 vs 2.9 U for red blood cells; 2.6 vs 1.4 U for plasma and 1.3 vs 0.57 U for platelets). Conclusion: This study highlights the potential role of intraoperative factors in the development of AKI following LT. Lasting intraoperative hypotension requiring higher doses of vasoactive support, the use of cardiopulmonary bypass and increased blood transfusion appear to be associated with higher incidence and severity of AKI. These may have important implications to overall intraoperative management of LT. 5( 14) Outcome After Transplantation of Lungs Evaluated With Ex-Vivo Lung Perfusion A. Wallinder ,1 S. Ricksten,2 G.C. Riise,3 T. Nilsson,4 G. Dellgren.3   1Dep. of Cardiothoracic surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; 2Cardiothoracic Anesthesia and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden; 3Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden; 4Cardiothoracic Anaesthesia and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden. Purpose: Ex vivo lung perfusion (EVLP) has emerged as a reliable method for evaluation of rejected donor lungs and is now adopted by several institutions. We reviewed clinical outcome in patients transplanted with EVLP evaluated lungs at our centre and compared results to contemporary controls. Methods: Lungs deemed unsuitable for donation but with potential for improvement underwent EVLP and were transplanted if preset criteria was fulfilled. Clinical outcome was reviewed and compared to consecutive patients transplanted during the same time period with conventional donor lungs (CONV). Results: 22 donor lungs were initially rejected for Lung transplantation (Ltx) due to inferior PaO2/FiO2 ratio (n=  15), bilateral infiltrate on chest x-ray (n= 11) or on going ECMO (n= 1). Four double lungs and two single lungs were deemed unsuitable for transplantation. 18 recipients from the regular waiting list underwent either lobar (n= 1) single (n= 4) or double (n= 13) LTx with EVLP-treated lungs. Data was compared to 85 consecutive recipients of

non-EVLP lungs. Primary graft dysfunction >  grade 1 at 72 hours occurred in 16% of patients in the EVLP group and 12% in the CONV group. Median ICU stay was for the EVLP group 73 hours (range, 36-936) and for CONV group51 hours (range, 19-1632), p= 0.58. There was no difference in length of hospital stay (p=  0.21). Survival, free from graft-loss, was 83% at one year in the EVLP group and 85% in the CONV group (fig. 1). Between 12 and 18 months one recipient in the EVLP group was re-transplanted and one patient transplanted with lobes died from a pulmonary embolization. At 12 months median FEV 1.0 (% of predicted) was 98% (EVLP) and 96% (CONV) for double lung recipients compared to 53% (EVLP) and 59% (CONV) for single lung recipients. Conclusion: Results after transplantation of lungs after EVLP seem noninferior to results after conventional transplantation. This finding is congruent with data from other centres. 5( 15) Is Routine Screening for Community-Acquired Respiratory Virus Infections in Lung Transplant Recipients Worthwhile? M. Greer ,1 T. Fühner,1 I. Tudorache,2 G. Warnecke,2 A. Haverich,2 T. Welte,1 J. Gottlieb.1  1Respiratory Medicine, Hanover Medical School, Hannover, Germany; 2Cardiac, Thoracic, Transplantation and Vascular Surgery, Hanover Medical School, Hannover, Germany. Purpose: Community-acquired respiratory virus (CARV) infections increase morbidity and mortality among lung transplant (LTx) recipients. Reported prevalence rates approach 9%, with detection traditionally relying on antigen testing e.g. immunofluorescence assays (IFT). Recently multiplex-PCR (mPCR) has shown better sensitivity in virus detection. Data evaluating the value of screening patients for latent CARV infections and their impact is limited. This study evaluates the utility of screening LTx recipients for CARV infections. Methods: Retrospective review of all outpatient bronchoscopies on LTx recipients at our Institution between 01.08.2012 and 10.10.2013 was performed. Structured patient questionnaires, routine laboratory, blood gas, spirometry and chest x-rays were evaluated. Bronchoscopies were performed as part of our surveillance programme, elective control procedures or unplanned procedures necessary due to new symptoms, ≥ 10% loss in FEV1, raised inflammatory indices or x-ray change. Bronchoalveolar Lavage (BAL) was performed in all cases and samples sent for microbiological and virological assessment. IFT assays for CARV were performed on all samples. A negative IFT in symptomatic patients resulted in mPCR analysis. Results: 541 patients underwent 1,705 bronchoscopies, of which 773 (45%) were indicated. Median number of procedures was 2 [IQR 1-4] per patient, at median 12.2 [IQR 4.0-27.7] months post-LTx. 177 (10.4%) CARV infections were identified: IFT 87, mPCR 93. Paramyxoviruses accounted for 113/177 (64%) of CARV infections. Eighteen patients (10%) denied symptoms, but exhibited deteriorated lung function or raised CRP. Only 2/630 (0.3%) asymptomatic patients with normal CRP and FEV1 values tested positive. Symptomatic CARV infection increased the likelihood of persisting ≥ 10% FEV1 loss (34 vs. 21%; p= 0.001) at follow-up. Clinically asymptomatic infections demonstrated similar clinical course to CARV negative patients (≥ 10% FEV1 loss; 25 vs. 20%; p= 0.76). Conclusion: Virology screening in asymptomatic stable LTx patients appears unnecessary. Structured history-taking and evaluation of laboratory and spirometry data reliably predicts patients at-risk. Asymptomatic CARV infections appear rare and of limited consequence. 5( 16) A Peritransplant Strategy in Lung Transplant Recipients with Preformed HLA Donor-Specific Antibodies (pDSA) F. Parquin , J. Devaquet, A. Si Larbi, E. Cuquemelle, A. Roux, C. Cerf, C. Picard.  Lung Transplant Group, Hopital Foch, Suresnes, France. Purpose: pDSA are associated with acute antibody mediated rejection (AMR) and poor graft outcome after kidney and cardiac transplantation, the risk increasing with the pDSA strenght. Therefore, peritransplant regimen based on combination of plasmapheresis, intravenous immunoglobulin (ivIg) and anti CD20 were successfully developed in presensitised patients (pts) to overcome positive virtual crossmatch. We applied this strategy in lung