The contribution of blood product transfusions to HLA allosensitization in LVAD recipients

The Journal of Heart and Lung Transplantation Volume 22, Number 1S was detectable in the clinical setting. All cases of wearout (n⫽6) were diagnosed before circulatory support was compromised, and the pump was electively replaced or the recipient received a donor heart.

378 LEFT VENTRICULAR MECHANICAL UNLOADING DECREASES ISCHEMIC SUSCEPTIBILITY BY MODULATING ANGIOTENSIN II TYPE-2 RECEPTOR GENE EXPERSSION IN THE FAILING HEART AFTER MYOCARDIAL INFARCTION S. Horimoto, H. Horimoto, S. Mieno, K. Nakahara, Y. Nakai, M. Yoshida, S. Sasaki, Thoracic and Cardiovascular Surgery, Osaka Medical College, Takatsuki, Osaka, Japan Objectives: Left ventricular (LV) mechanical unloading is known to reduce the hemodynamic demands of the failing LV resulting in improved myocyte contractile performance. However, effects of LV unloading on susceptibility to ischemia reperfusion are left to be undefined. Recently, angiotensin II type 2 receptor (AT2R) has been shown to play an important role in myoprotective response against ischemia reperfusion injury. This study was designed to examine effects of LV unloading on angiotensin II type 2 receptor (AT2R) expression and susceptibility to ischemia reperfusion. Methods: Failing rat hearts were induced by LAD occlusion and left for two weeks (post-MI hearts), then were subjected to LV mechanical unloading for two weeks. LV unloading was acheived by heterotopic heart transplantation, in which aorta of post-MI hearts was anastomosed with the recipient’s abdominal aorta and pulmonary artery was anastomosed with the IVC. Non-MI or post-MI hearts without unloading were served as a control. Then, all hearts were isolated and subjected to 20 minutes of global ischemia and 60 minutes of reperfusion on Langendorff apparatus. LV pressures and coronary flow were measured throughout the experiment. AT2R mRNA expression in the non-infarct myocardium was determined by real time quantitative RT-PCR. Results: 1) Post-MI hearts exhibited attenuated post ischemic functional recovery associated with reduced expression of AT2R mRNA compared to non-MI hearts (0.93⫾0.42 x 107 copy* vs. 2.53⫾0.58 x 107 copy, *⫽p⬍0.05) . 2) LV unloading improved post ischemic functional recovery (74⫾6* vs. 51⫾4 %, *⫽p⬍0.05) in post-MI hearts. 3) LV unloading restored AT2R mRNA expression (2.48⫾0.96 x 10 7 copy * vs. 1.02⫾0.54 x 107 copy, *⫽p⬍0.05) in post-MI heart. Conclusions: LV mechanical unloading may decrease susceptibility to ischemia reperfusion in post-MI hearts possibly by modulating AT2R mRNA expression.

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379 DIFFERENCES IN PATIENTS WITH LEFT VENTRICULAR ASSIST DEVICE BETWEEN DILATED CARDIOMYOPATHY AND DILATED PHASE HYPERTROPHIC CARDIOMYOPATHY N. Fukushima,1 Y. Miyamoto,1 Y. Sawa,1 G. Matsumiya,1 O. Monta,1 S. Takashima,2 M. Hori,2 R. Shirakura,1 H. Matsuda,1 1Department of Surgery, Osaka University, Suita, Osaka, Japan; 2Department of Medicine, Osaka University, Suita, Osaka, Japan Background: Although clinical manifestation of dilated cardiomyopathy (DCM) and dilated phase hypertrophic cardiomyopathy (dHCM) look similar, prognosis between them has been reported to be different. In the present study, we investigated patients (pts) with DCM or dHCM who required left ventricular assist device (LVAD). Patients: 15 pts (DCM 10 and dHCM 5) underwent LVAD implantation (5 Novacor, 2 TCI-VE, 8 TCI-IP) from 1995 to 2002. 14 were male. Age at implantation in dHCM (43.0⫹/-12.4years) was significantly older than that in DCM (29.9⫹/-8.8 years). Myocardial specimens at LVAD implantation, at HTx or at death were examined. Results: 3 dHCM pts underwent HTx and 2 dHCM and 3 DCM pts died while waiting for HTx. LV diastolic dimension in dHCM (63.4⫹/-4.2 mm) was significantly shorter than that in DCM (74.1⫹/-6.8 mm) and LV ejection fraction (LVEF) in dHCM (24.8⫹/-6.0 %) was significantly larger than that in DCM (17.3⫹/-3.0 %) at the time of LVAD implantation. Although there was no significant difference in LVEF between dHCM and DCM (37.0⫹/-16.1 vs 42.3⫹/-9.6) after implantation of LVAD, the incidence of the pts whose LVEF was larger than 50 % on LVAD support in DCM (3/7) was significantly larger than that in dHCM (0/5). Although there were no differences in %fibrosis of myocardium (26.7⫹/-7.0 vs 29.4⫹/-6.5%) and serum BNP (787.7⫹/639.1 vs 761.3⫹/-624.2) between DCM and dHCM before LVAD implantation, %fibrosis (33.3⫹/-5.7%) and serum BNP (31.4⫹/-24.9 ng/ml) in DCM were significantly lower than those in dHCM (45.8⫹/5.7 % and 77.4⫹/-47.0 ng/ml) after LVAD implantation. Conclusion: These data suggested that there be some possibility of bridge to recovery in DCM but not in dHCM possibly because the myocardium in dHCM may progressively deteriorates even under volume unloading condition by LVAD. 380 THE CONTRIBUTION OF BLOOD PRODUCT TRANSFUSIONS TO HLA ALLOSENSITIZATION IN LVAD RECIPIENTS S.G. Drakos, J.C. Stringham, J.W. Long, T.C. Fuller, K.E. Nelson, J.M. Lindblom, P.A. Meldrum, E.M. Gilbert, S.A. Moore, D.G. Renlund, UTAH Cardiac Transplant Program, University of Utah School of Medicine and LDS Hospital, Salt Lake City, UT Left ventricular assist device (LVAD) implantation is associated with HLA allosensitization which may be worsened by transfusion. Methods: We reviewed 71 consecutive non-sensitized recipients of the HeartMate LVAD. Panel reactive antibody (PRA) was determined by antiglobulin cytotoxicity or flow cytometry, and correlated with transfusions of cellular blood products (cbp). All cbp were leukofiltered. Results: 54 patients (pts) received cbp while 17 received only fresh frozen plasma. There was no difference in age, gender, diagnosis, or duration of support between groups. Rates of allosensitization (PRA⬎10%) prior to transplant were similar (p⫽ns): 2 weeks

4 weeks

6 weeks

8 weeks

12 weeks

16 weeks

Transfused 9.3% (5/54) 14.8% (8/54) 22.2% (12/54) 27.8% (15/54) 31.5% (17/54) 31.5% (17/54) Not Transfused 0% (0/17) 17.6% (3/17) 29.4% (5/17) 35.3% (6/17) 52.9% (9/17) 58.8% (10/17)

Overall, 58.8% (10/17) of non-transfused pts became sensitized during support, while 35.2% (19/54) of transfused pts became sensitized

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(p⫽0.15). A PRA ⱖ90% occurred in 23.5% of non-transfused and 16.7% of transfused pts during support (p⫽0.5). With early transplants and multiparous females excluded, pts transfused with ⱖ6 units of blood developed less sensitization (PRA 0-39%) during support (78.9%, 15/19) than those with lower transfusion requirements (38.5%, 10/26, p⫽0.02). However, those not transfused but sensitized and waiting ⱖ1 year (n⫽3) eventually had a larger decline in PRA, from a peak of 77.3 ⫾ 15.2% to 28.7 ⫾ 3.5% than those who were transfused (n⫽7,from 84.6 ⫾ 20.7% to 60.9 ⫾ 23.5%, p⫽0.05) suggesting resolving reactivity. Conclusions: Perioperative transfusion of leukofiltered cbp does not worsen and may decrease sensitization seen in Heartmate LVAD recipients, but may lessen the chance of eventual resolution of PRA reactivity. Further studies are needed to characterize the reactivity and HLA specificity of antibodies in LVAD recipients receiving no cbp transfusions. 381 DIFFERENTIAL REGULATION OF CA2ⴙ-DEPENDENT ATPASEACTIVITY IN LEFT VENTRICULAR MYOCARDIUM DURING MECHANICAL CIRCULATORY SUPPORT H. Milting, A. Kassner, D. Boethig, R. Thieleczek,2 H. Koegler,3 H.E. Meyer,2 L. Arusoglu, R. Koerfer, A. El Banayosy, Clinic of Thoracic and Cardiovascular Surgery, Research Laboratory, RuhrUniversity Bochum, Heart- and Diabetescenter NRW, Bad Oeynhausen, NRW, Germany; 2Institute of Physiological Chemistry I, Ruhr-University Bochum, Bochum, NRW, Germany; 3Dept. Cardiology & Pneumology, University Goettingen, Goettingen, NS, Germany Background: Myocardial recovery is observed in some endstage heart failure patients after mechanical circulatory support. The sarcoplasmic reticulum Ca2⫹-ATPase activity is downregulated in failing myocardium and contributes to heart failure-associated contraction/relaxation abnormalities. Regulation of Ca2⫹-ATPase after mechanical support was shown to be heterogenous. Thus, we analysed Ca2⫹-ATPase activity and protein expression in paired myocardial samples of 21 patients supported by ventricular assist devices to identify factors influencing restoration of the Ca2⫹-transient after ventricular assist device support. Methods: Ca2⫹-ATPase activity was measured by a NADH-coupled reaction, SERCA2 protein was determined by westernblotting and 4-hydroxyproline by aminoacid analysis. Results: The mean Ca2⫹-ATPase activity was reduced at assist device implantation and slightly increased at transplantation, remained however significantly lower compared to non-failing donor hearts. However, the individual responses were heterogeneous. Patients with advanced age, increased left ventricular diameter and increased 4-hydroxyproline content showed downregulation of Ca2⫹-ATPase activity, whereas upregulation was found in patients with low values of these parameters after assist device support. Conclusions: Sarcoplasmic reticulum Ca2⫹-ATPase activity, influencing the myocardial Ca2⫹-transient, is not generaly restored to normal values in assist device-supported hearts, but depends on the left ventricular enddiastolic diameter, degree of ventricular fibrosis and age of the patient at the time of assist device-implantation. 382 THE HUB-AND-SPOKE SYSYTEM IN TREATING ACUTE CARDIOGENIC SHOCK: WHO SURVIVES? A.R. Kherani, F.H. Cheema, M.C. Oz, V.K. Topkara, D.A. Wilson, A.F. Cheema, M.J. Garrido, J.A. Morgan, D.W. Vigilance, Y. Naka,

The Journal of Heart and Lung Transplantation January 2003 Surgery, Columbia Univ. College of Physicians & Surgeons, New York, NY Objectives: The hub-and-spoke paradigm is a referral system that facilitates the transfer of patients in acute cardiogenic shock from spoke, community hospitals to a hub, tertiary center. This study describes these patients and tests the effectiveness of this system in treating this population. Methods: 35 spoke hospitals transferred 72 patients to a single hub from October 1993 to May 2002; they were divided into 3 groups: 1) Group A (n⫽17): status-post acute myocardial infarction (MI) and did not undergo surgical revascularization [coronary artery bypass grafting (CABG)] but instead underwent temporary left ventricular assist device placement (LVAD, n⫽3) or medical management (n⫽14). 2) Group B (n⫽26): status-post acute MI patients in shock who underwent emergent CABG at the spoke hospital prior to transfer. 3) Group C (n⫽29): suffered from postcardiotomy shock following an elective cardiac procedure at the spoke facility. Group A was the only group that did not undergo traditional cardiac surgical procedures on cardiopulmonary bypass at spoke hospitals. Results: Survival to discharge was 54% (39/72); breakdown by group is shown in Table 1. Of these patients, 46 underwent implantable LVAD placement at the hub center. Here, significant differences in survival to discharge were seen when comparing Groups A and C (p⫽0.015) and Group A with Groups B and C (p⫽0.026). End-organ function at the time of arrival at the hub center was measured by prothrombin time and creatinine, and insignificant differences were found (Table 1). Conclusion: In this small sample size, avoidance of attempted revascularization in the setting of shock led to improved survival. The postcardiotomy setting compromises later VAD implantation.

383 NOVEL APPLICATION OF THORATEC VAD AS A PARACORPOREAL TOTAL ARTIFICIAL HEART A. El-Banayosy, L. Arusoglu, M. Morshuis, L. Kizner, R. Koerfer, Cardiac Surgery, Heart Center NRW, Bad Oeynhausen, Germany Thorated VAD is a paracorporeal versatile ventricular assist device can be used for left, right or biventricular assistance. We developed a novel method to apply this system as a paracorporeal total artificial heart. This work describes our experience with the Thoratec system as a TAH. Patients and Methods: Ten patients (pts) aged between 18 and 60 yrs (median 33 yrs), nine males and one female were supported with the