1.
Abstracts S89
fraction (LVEF) >50%, a final resulting LVEF>40% and a decrease in
LV end-systolic volume >25% (i.e. “Responders”). LV myocardium was
obtained at the time of LVAD implantation. Illumina platform was used for
microarray screening of the myocardial tissue. Myocardial mRNA levels of
cytokines were quantified by RT-qPCR. Phosphorylated protein levels of
transcription factors were measured by Western Blot.
Results: Eleven patients met the criteria of response (i.e. 16% “Responders”).
Microarray gene expression screening in the 11 Responders versus 11 age-,
gender- and HF etiology- matched Non-responders showed that 20% of
the differentially expressed genes were involved in inflammatory cellular
pathways. The mRNA tissue levels of CCL2, CCL8 and TNFa were signifi-
cantly decreased in Responders (n=11) compared to the total cohort of Non-
responders (n=57). Also, phosphorylated Stat 3, a transcription factor that
controls the expression of multiple cytokines was significantly down regu-
lated at the myocardium of Responders (n=11) vs Non Responders (n=57)
(0.8 ± 0.2 vs 1.9 ± 0.4 AU, respectively, p=0.02). On the contrary, phospho-
rylated p65-NFkB was not differentially expressed between the two groups.
Conclusion: Cytokine mRNA levels are significantly decreased in the myo-
cardium of Responders suggesting that decreased inflammatory burden cor-
relates with myocardial structural and functional improvement after LVAD
unloading. Stat 3 could be a key coordinator of the differential inflamma-
tory response and it could serve as a potential therapeutic target to enhance
myocardial recovery following mechanical unloading of the failing heart.
(225)
Thymosin β4 and Its Cleavage Product Ac-SDKP Are Down-Regulated
in Left Ventricular Myocardium of Patients With Advanced Heart
Failure
H.N. Sabbah, R.C. Gupta, V. Singh-Gupta. Medicine, Henry Ford Hospital,
Detroit, MI.
Purpose: Thymosin β4 (Tβ4) is a 43 amino acid peptide and has been shown
to promote angiogenesis, suppress pro-inflammatory cytokines and protect
cardiomyocytes from apoptosis and oxidative stress injury. The Tβ4 cleavage
product Ac-SDKP is a tetrapeptide (Acetyl-Ser-Asp-Lys-Pro) that has been
shown to inhibit collagen production by fibroblasts and collagen deposition
in the LV of rats with hypertension or myocardial infarction. In the setting
of chronic heart failure (HF), LV dysfunction and chamber remodeling are
associated with interstitial fibrosis, reduced capillary density, cardiomyocyte
apoptosis and increased production of reactive oxygen species (ROS). We
previously showed that both Tβ4 and Ac-SDKP are down-regulated in dogs
with experimentally-induced HGF. This study tested the hypothesis that pro-
tein levels of both Tβ4 and its cleavage productAc-SDKP are down-regulated
in LV myocardium of patients with advanced HF.
Methods: Fresh LV tissue was obtained from the LV free wall of 6 explanted
failed human hearts (3 with ischemic cardiomyopathy, ICM, and 3 with
idiopathic dilated cardiomyopathy, IDC) and from 4 donor hearts (DNR)
deemed not suitable for transplantation. Protein levels of Tβ4 was determined
by Western blotting and bands quantified in densitometric units (du). Levels
of Ac-SDKP were determined by ELISA and expressed in ng/mg protein.
Results: Protein level of Tβ4 was significantly lower in explanted failing
hearts compared to DNR hearts (0.22 ± 0.01 vs. 0.56 ± 0.02 du, p<0.05).
Similarly, levels of Ac-SDKP were significantly lower in explanted failing
hearts compared to DNR hearts (85 ± 10 vs. 207 ± 12 ng/mg protein, p<0.05).
The magnitude of down-regulation of Tβ4 and Ac-SDKP in failing hearts
was similar for both ICM and IDC (Tβ4: ICM 0.24 ± 0.02 vs. IDC 0.20 ±
0.01 du; Ac-SDKP: ICM 84 ± 20 vs. IDC 61 ± 8 ng/mg).
Conclusion: Protein levels of Tβ4 and its cleavage tetrapeptide Ac-SDKP
are markedly down-regulated in LV myocardium of explanted failing human
hearts regardless of the etiology of HF. These findings are in-line with the
reported increase of pro-inflammatory cytokines, interstitial fibrosis, cardio-
myocyte apoptosis, and ROS formation as well as reduced capillary density
in failing human hearts. The findings support the therapeutic targeting of Tβ4
and Ac-SDKP as potential treatment for chronic HF.
(226)
Myocardial Lipid Metabolism in the End-Stage Failing: Heart: Evidence
for an Energy-Starved State
J.E. Rame,1 K. Bedi,1 N. Snyder,2 J. Brandimarto,2 C. Mesaros,2
E.Y. Birati,1 I.A. Blair,2 K.B. Margulies.1 1Cardiovascular Institute,
(223)
Virtual Implantation of the 50cc Total Artificial Heart
R.A. Moore, P.C. Madueme, A. Lorts, D.L. Morales, M.D. Taylor.
The Heart Institute, Cincinnati Children’s Hospital Medical Center,
Cincinnati, OH.
Purpose: Our group previously described successful use of virtual implan-
tation of the 70cc Total Artificial Heart (TAH) to predict safe placement in
small-size patients not meeting standard fit criteria. With the new 50cc TAH,
there is an opportunity for broader use of the TAH device in pediatric patients
with biventricular heart failure. The proposed fit criteria for the 50cc TAH
(BSA 1.2-1.6 m2) has not been tested in actual patients. The study objective
was to determine the efficacy of virtual implantation of the 50cc and 70cc
TAH in a cohort of pediatric heart failure patients and compare virtual fit
results with proposed fit criteria.
Methods: A chest CT of each patient was rendered for 3D display of the
thoracic cage and intrathoracic structures. 3D-rendered representations of
the 50cc and 70cc TAH devices were tested using virtual implantation of the
device into the thoracic cage of each patient. The devices were assessed for
intersection with the thoracic cage and intrathoracic structures. The results of
the virtual implantation were compared to standard sizing of the 70cc device
and the proposed criteria for each device.
Results: Fifteen patients (age 3-34 years; BSA 0.67-1.99 m2), being evalu-
ated for mechanical support as bridge-to-heart transplantation, underwent vir-
tual implantation of the 50cc and 70cc TAH. Successful virtual fit was defined
as no evidence of device intersection with the thoracic cage or important
intrathoracic structures.Virtual implantation of the 50cc TAH was successful
in 80% of the patient cohort compared to 33% for the larger 70cc TAH. The
50cc TAH proposed criteria matched well with the virtual implantation results
for this cohort with 85% concordance. The virtual implantation demonstrated
device fit in 2 patients outside the proposed sizing criteria.
Conclusion: Virtual TAH device implantation previously demonstrated suc-
cessful prediction of device size compatibility. With the introduction of the
new 50cc TAH device, this method can establish eligibility criteria for device
placement in the pediatric population.
(224)
Cytokine Expression in the Myocardium Correlates With Cardiac
Structural and Functional Improvement Induced By Mechanical
Unloading in Chronic Heart Failure
N. Diakos, L. McCreath, S. Navankasattusas, A. Catino, J. Stehlik,
A.G. Kfoury, C. Selzman, A. Koliopoulou, S.H. McKellar, D. Budge,
K. Skedros, A. Ragnhildstveit, M. Al-Sari, U. Lam, J. Fang, D. Li,
S.G. Drakos. U.T.A.H. Cardiac Transplant Program, Salt Lake City, UT.
Purpose: Inflammation plays a key role in the pathophysiology of heart fail-
ure (HF). Prior studies have shown correlation between systemic cytokines
and adverse outcomes of HF patients. We hypothesized that inflammatory
burden could correlate with the ability of the failing human heart to improve
its endogenous function after mechanical unloading induced by left ventricu-
lar assist devices (LVAD).
Methods: We prospectively examined 68 patients supported with durable
LVAD. Left ventricular function was serially evaluated using echocardi-
ography with LVAD turn-down. LVAD- induced myocardial functional
“response” was defined as a relative increase in left ventricular ejection

2.
S62 The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
better understand the degree and type of mismatches that impact transplant
survival.
(147)
MELD-XI Score Predicts Early and Late Mortality in Patients Following
Heart Transplantation
J.C. Grimm,1 J. Magruder,1 V. Valero 3rd,1 A. Kilic,1 G.J. Whitman,1
R.J. Tedford,2 S.D. Russell,2 A.S. Shah,1 C.M. Sciortino.1 1Surgery,
The Johns Hopkins Medical Institution, Baltimore, MD; 2Medicine,
The Johns Hopkins Medical Institution, Baltimore, MD.
Purpose: The Model for End-stage Liver Disease eXcluding INR (MELD-XI)
score has been validated as an accurate predictor of outcomes in heart fail-
ure patients, but its utility in orthotopic heart transplant (OHT) recipients is
unknown. Accordingly, we sought to determine the risk-adjusted influence
of an elevated MELD-XI score on early and late mortality following OHT.
Methods: The United Network for Organ Sharing database was queried
for adult (>18 years) patients undergoing OHT between 2002 and 2012.
A MELD-XI score (incorporating serum creatinine and bilirubin) was cal-
culated. Stratification into “high” and “low” MELD-XI cohorts based on a
previously established threshold score of 17 was performed. Patient specific
characteristics, intraoperative variables and postoperative outcomes were
compared between the two cohorts. Thirty-day, 1-year and 5-year multi-
variable Cox hazard regression models were constructed to determine the
risk-adjusted impact of a “high” MELD-XI score on mortality. Kaplan Meier
estimates were utilized to compare unadjusted survival.
Results: Of the 27,126 patients that met criteria for inclusion, 22% (6,048)
had MELD-XI scores >17. Thirty-day (p<0.001), 1-year (p<0.001) and
5-year (p<0.001) survival was statistically different between the score cohorts.
Additionally, a “high” MELD-XI score was an independent predictor of 30-day
(HR: 1.75, CI: 1.52-2.02; p<0.001), 1-year (HR: 1.62, CI: 1.48-1.77; p<0.001)
and 5-year (HR: 1.33, CI: 1.25-1.43; p<0.001) mortality after adjustment with
a combination of recipient, donor and transplant specific variables. This cohort
also experienced an increased incidence of postoperative renal failure (11.7%
v. 6.5%; p<0.001) and stroke (3.3% v. 2.2%; p<0.001).
Conclusion: This is the largest known study demonstrating the unique appli-
cation of the MELD-XI scoring system in predicting early and late mortality
in patients following OHT. The MELD-XI provides another preoperative
metric to improve patient selection and, thus, optimize organ allocation.
(148)
Restoration of Pulsatile Flow Leads to a Reduction in Sympathetic
Nerve Activity Among Patients With Continuous-Flow Left Ventricular
Assist Devices
W.K. Cornwell,1 T. Tarumi,2 A. Stickford,2 J. Kibe,3 C. Fitzsimmons,3
J. Moore,2 M. Roberts,2 R. Parker,2 D. Markham,4 M. Drazner,1
B. Levine.2 1Cardiology, Univ of Texas SW, Dallas, TX; 2Institute of
Exercise and Environmental Medicine, Dallas, TX; 3Cardiology, Univ of
Texas SW, Coppell, TX; 4Cardiology, Emory University, Atlanta, GA.
Purpose: We previously demonstrated that sympathetic nerve activity (SNA)
is markedly elevated in patients with continuous-flow (CF) left ventricular
assist devices (LVADs). In the current study, we sought to determine whether
the restoration of pulsatile flow leads to reductions in SNA in these patients.
Methods: Eight male and two female subjects (56±11 years) with Heartmate
II, CF-LVADs underwent hemodynamic and sympathetic neural assessment.
Beat-to-beat blood pressure and muscle (M) SNA, (measured directly via
microneurography) were continuously recorded to determine steady-state
(145)
Cardiac Allograft Vasculopathy in Redo-Transplants: Is It More or Less
(or) the Same the Second Time around?
L. McCreath, R. McCubrey, J. Folsom, S. Wright, J. Stehlik, D. Budge,
S.H. McKellar, M. Everitt, G. Snow, B. Reid, K. Skedros, A. Ragnhildstveit,
K. Afshar, J. Nativi, S.G. Drakos, A.G. Kfoury. UTAH Cardiac Transplant
Program, Salt Lake City, UT.
Purpose: CardiacAllograftVasculopathy (CAV) continues to hinder the long
term success of heart transplant recipients. Redo-transplantation is currently
the only definitive treatment for advanced CAV. Whether these patients are at
similar CAV-risk with the second transplant remains unknown and the topic
of interest in this study.
Methods: The UTAH Cardiac Transplant database was queried for all patients
who were retransplanted from 1985 to 2011. Heart recipients who did not
have CAV as an indication for redo-transplantation were excluded. CAV
diagnosis was made by coronary angiography and based on the 2010 ISHLT
standardized nomenclature for CAV. Patient demographics, rejection history,
and CAV incidence were analyzed.
Results: Of the 1,169 eligible patients, 135 (11.5%) developed CAV post their
first transplant; 78 cases within 10 years and 54 beyond 10 years. The mean
time to CAV was 6.58 years. Of the 135 patients who developed CAV, only 21
(15.5%)endeduprequiringaredo-transplant.Ofthe21patientsretransplanted,4
(19.0%) developed CAV again; 2 patients within 10 years and 2 patients beyond
10 years.The incidence of CAV was statistically similar (p=NS) between 1st and
redo-transplant. Baseline characteristics (see table) are included.
Conclusion: Our results indicate that CAV is as likely to develop in redo-
transplants despite recent advances in immunosuppression and the standard-
ized use of lipid-lowering agents.Although outcomes in redo-transplantation
for the indication of CAV are favorable, efforts to better understand and
minimize CAV are needed, especially in the face of scarce donor organs.
(146)
Influence of HLA Mismatch on Outcomes After Heart Transplantation:
UNOS Registry Data
K. Pandya, J. Zhang, M. Hickey, A. Nsair, A. Baas, M. Cadeiras, D. Cruz,
L. Reardon, M. Deng, A. Ardehali, E. Reed, E. Depasquale. Advanced
Heart Failure and Cardiac Transplantation, University of California,
Los Angeles, Los Angeles, CA.
Purpose: HLA matching has been shown to improve survival in renal trans-
plants, however, is not currently a major consideration in heart transplanta-
tion (HT). We sought to evaluate the impact of HLA mismatch on long term
outcomes after heart transplantation.
Methods: 37516 patients were identified from the UNOS registry (1987-
2014) and stratified by number of HLA mismatches (> 3 vs ≤ 3). Exclusions:
age < 18, multiorgan or re-HT. Survival was censored at 12-y. Multivariate
Cox proportional hazard regression models were adjusted for age, sex, DM,
race, ischemic time, dialysis, etiology, life support and wait times.
Results: 5791 were identified with ≤ 3 HLA mismatches compared to
31720 with > 3 HLA mismatches. Mean age was 52.1 ± 11.7 years (p=NS
between groups). Most common etiologies were dilated (42%) and ischemic
cardiomyopathy (41%). Mean follow up was 6.4 ± 5.6 years. Number of
mismatches by HLA loci (> 3 vs ≤ 3): A Locus [1.5 ± 0.6 vs 0.7 ± 0.6], B
Locus [1.8 ± 0.4 vs 1.1 ±0.6] and DR Locus [1.6 ± 0.5 vs 0.9 ± 0.6] (p 3,
respectively). Crude 1, 5, 10 year survival was: HLA mismatch ≤ 3 [88, 73,
52%] vs HLA mismatch > 3 [87, 71, 51%] (log-rank, p=0.006). Multivariate
Cox regression analysis yielded a hazard ratio of 1.07 (CI 1.02 -1.12).
Conclusion: HT recipients with fewer mismatches appear to have small
but significantly improved outcomes. Further study is warranted to

3. The first study was conducted to determine if inflammatory affliction would correlate
with the ability of the failing human heart to improve its endogenous function after
mechanical unloading induced by left ventricular assist devices. Our findings suggested
the correlation existed and occurred due to significantly decreased cytokine mRNA levels
in the myocardium of responders. Duration: 1.47 years
The context of the second study was to establish whether heart transplant recipients are at
similar CAV-risk with the second transplant. We concluded that CAV is as likely to
develop in redo-transplants despite recent advances in immunosuppression and the
standardized use of lipid-lowering agents. Duration: 2.13 years
These research studies were collaboratively conducted with researches, physicians, and
surgeons each contributing a role pertaining to their individual skills. My role consisted
of maintaining/ organizing clinical databases and tissue samples, running westerns,
protein assays, RNA sequencing, murine TAC surgeries, and collecting/ harvesting
cardiac tissue during Heart Transplants & LVAD surgeries.
Both studies were submitted and published through the International Society for Heart
and Lung Transplantation
(1) Published in the Journal of Heart and Lung Transplantation Title: Cytokine
Expression in the Myocardium Correlates With Cardiac Structural and Functional
Improvement Induced By Mechanical Unloading in Chronic Heart Failure. April 2015,
Volume 34, Issue 4, Supplement, Page S89.
Linkhttp://dx.doi.org/10.1016/j.healun.2015.01.237
(2) Title: Cardiac Allograft Vasculopathy in Redo-Transplants: Is It More or Less (or) the
Same the Second Time around? April 2015, Volume 34, Issue 4, Supplement, Page S62.
Link: http://dx.doi.org/10.1016/j.healun.2015.01.157
________________________________________________________________________
Research Mentors:
Stavros G. Drakos, MD/PhD is an Associate Professor of Cardiology with Tenure and the
Medical Director of the Cardiac Mechanical Support Program.
Phone Number: 801-5852340
Email: stavros.drakos@hsc.utah.edu
Dean Li, Vice Dean for Research, School of Medicine Director, Molecular Medicine Program
Interim Co-Chair, Department of Physiology Chief Scientific Officer for U of U Health Sciences
Phone number: 801-587-8294
Email: dean.li@u2m2.utah.edu