S42 The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019
Conclusion: Our results suggest that donor T and NK cells found in the
periphery of lung transplant recipients are derived from lung parenchyma
and represent tissue-resident memory cells. This transient chimerism in
recipient blood might be clinically relevant for tolerance induction after
transplantation due to unique features of TRM T and NK cells.
78
Cardiac Allograft Vasculopathy is Linked to Impaired Generation of
Regulatory M2 Macrophages
L. Holzhauser, T. Imamura, K.A. Arnold, A. Schroeder, C. Murks, J.
Powers, T. Riley, G. Kim, J. Raikhelkar, B. Smith, A. Nguyen, S. Nathan, B.
Chung, V. Jeevanandam, N. Narang, I. Ebong, G. Sayer, N. Uriel and A.
Francis. University of Chicago, Chicago, IL.
Purpose: There is mounting evidence for the role of innate immunity in
acute cardiac allograft rejection, but this does not necessarily extend to car-
diac allograft vasculopathy (CAV) and predictors of CAV remain elusive.
We hypothesized that circulating monocytes and their derived macrophage
subtypes correlate with CAV.
Methods: 49 consecutive heart transplant recipients ≥ 2 years post-trans-
plant were enrolled. CAV was assessed on angiogram with IVUS by
ISHLT and Stanford classification grading. Peripheral blood mononuclear
cells were isolated by density gradient centrifugation, with monocytes
stained and measured by flow cytometry for classical (CD14++/CD16¡),
intermediate (CD14++/CD16+), and nonclassical (CD14lo/CD16++) sub-
types. Monocytes were cultured into macrophages, driven by M-CSF, and
assayed for polarization markers CD86 and CD206. Results were also
compared to 22 non-transplant patients with atherosclerotic coronary artery
disease (CAD) and healthy controls (no CAD).
Results: 22 patients had no significant CAV (Stanford class I-II) while 27
had significant CAV (class III-IV). Other than time since transplant (no
CAV 77§13 vs CAV 135§12 months), there were no significant differen-
ces, including immunosuppression, between the two groups. There were
no differences between monocyte subgroups in isolation, but when com-
bined with derived macrophage polarization, patients with CAV had signif-
icantly lower M2 (CD206+) macrophage production (0.19§0.04%) than
those without CAV (0.45§0.13%), p<0.05 (Figure 1a). CAV patients had
significantly lower nonclassical monocytes (1.7§0.33%) (Figure 1b) and
M2 macrophages (0.18§0.04) than those with CAD (6.3§1.0% and 0.34§
0.06) p<0.05 respectively.
Conclusion: CAV patients are characterized by reduced ability to generate
regulatory M2 macrophages. The circulating monocyte and macrophage
subtypes differ from those of native CAD and these cell-based markers
could be useful to differentiate high vs. low CAV risk phenotypes.
79
Successful Utilization of Extended Criteria Donor (ECD) Hearts for
Transplantation - Results of the OCSTM Heart EXPAND Trial to Evaluate
the Effectiveness and Safety of the OCS Heart System to Preserve and
Assess ECD Hearts for Transplantation
J.N. Schroder,1 D. D'Alessandro,2 F. Esmailian,3 T. Boeve,4 P. Tang,5 K.
Liao,6 I. Wang,7 A. Anyanwu,8 A. Shah,9 K. Mudy,10 E. Soltesz,11 and J.W.
Smith.12 1Duke University Medical Center, Durham, NC; 2Massachusetts
General Hospital, Boston, MA; 3Cedars-Sinai Medical Center, Los
Angeles, CA; 4Spectrum Health, Grand Rapids, MI; 5University of
Michigan, Ann Arbor, MI; 6University of Minnesota, Minneapolis, MN;
7
Indiana University, Indianapolis, IN; 8Mount Sinai, New York, NY;
9
Vanderbilt University, Nashville, TN; 10Minneapolis Heart Institute,
Minneapolis, MN; 11Cleveland Clinic Foundation, Cleveland, OH; and the
12
University of Washington, Seattle, WA.
Purpose: The OCS Heart EXPAND Trial is a prospective, multi-center
trial to evaluate the effectiveness of the OCSTM to resuscitate, preserve
and assess donor hearts that may not meet current standard donor heart cri-
teria for transplantation to potentially improve donor heart utilization for
transplantation.
Methods: Donor hearts were eligible if they met any of the following char-
acteristics: expected total ischemic time ≥ 4 hours or expected total ische-
mic time ≥ 2 hours plus at least one of the following risk factors: LVH, EF
40-50%, downtime ≥ 20 minutes, and age >55 yo. Hearts were perfused
and assessed on OCS Heart System from donor to recipient. Hearts were
eligible for transplantation if the following criteria were met: final OCS
Heart arterial lactate <5 mmol/L and stable OCS perfusion parameters
within recommended ranges. The primary effectiveness endpoint was a
composite endpoint of patient survival at 30 days and absence of ISHLT
severe primary heart graft dysfunction (PGD) (left or right ventricle) in the
first 24 hours post-transplantation. The secondary endpoint was the rate of
ECD heart utilization after preservation and assessment on the OCS Heart
System.
Results: 93 eligible donor hearts with a mean UNOS match run of 66
declines were assessed on OCS Heart. Donor categories were as fol-
lows: x-clamp time ≥ 4 hours 37%, LVH 23%, EF 40-50% were 23%,
downtime ≥ 20 minutes 28%, older age 13% and 33% met multiple
inclusion criteria. 75 of the 93 donor hearts were successfully trans-
planted resulting in a utilization rate of 81%. Mean OCS perfusion
time was 6.35 hours. Incidence of severe LV or RV PGD at 24 hours
was 10.7%. 30-day and 6-month survival were 94.7% and 88%
respectively.
Conclusion: The use of OCSTM Heart System resulted in high utilization of
ECD hearts with excellent short-term post-transplant outcomes, most nota-
bly a low rate of PGD. These results provide clinical evidence supporting
its use in ECD heart preservation and assessment, and may significantly
increase donor utilization for transplantation.
80
Ex-vivo Perfusion on Marginal Donors in Heart Transplantation: Clinical
Resuts and Pathological Findings
S. Sponga,1 V. Ferrara,1 A.P. Beltrami,2 A. Bonetti,2 C. Cantarutti,2
A. Caragnano,2 F. Ortolani,2 A. Lechiancole,1 R. Esposito,1 C. Di
Nora,1 V. Tursi,3 C. Nalli,1 and U. Livi.1 1Cardiothoracic Department,
Udine University Hospital, Udine, Italy; 2Medical Area Department
(DAME), Udine University Hospital, Udine, Italy; and the 3Udine
University Hospital, Udine, Italy.
Purpose: The ex-vivo normothermic perfusion in Heart Transplantation
(HTx) allows to expand the donor pool by reducing the ischemic time and
providing graft evaluation. Aim of the study was to compare the traditional
cold storage (CS) and ex-vivo normothermic perfusion (EVP) in HTx
employing marginal donors.
Methods: Since 2011, 87 HTx employing marginal donors (age>55 years;
expected ischemic time>4h; LVEF<50%; IVS>14mm; drug abuse; car-
diac arrest; CAD) in standard recipients has been performed, CS was uti-
lized in 70 cases (80%) and EVP in 17 (20%). Pre-operative data, survival
and complications at short and long term were analysed. Endomyocardial
biopsies were collected at time of organ retrieval (T0), before implantation
(T1) and after aortic declamping (T2) for light and electron mycroscopy.
Blood samples were collected at T0 and T2 from coronary sinus and
peripheral vein for metabolomic evaluation .
Results: Preoperative data were similar in the two groups. Three organs
(15%) were considered not suitable for HTx after EVP. Ischemic time and
surgical time were shorter in EVP group, which showed a better short and
long term survival: a 5-year survival of 100% vs. 94%, 82% and 73% at
30-day, 1 and 5 years respectively in CS group (p=0.06) and less overall