Abstracts 7 patients who received aortic valvular repair, 2 patients developed recurrent AI on echocardiograms during average follow-up of 116 (range 25194) days. Conclusions: Additional procedure to the aortic valve at LVAD placement is feasible. Outcomes were satisfactory after aortic valve closure or repair. 550 Early Severe Post Operative Liver Dysfunction after Heartmate II® LVAD Placement: Incidence, Risk Factors, and Outcomes E.A. Ziemba,3 J.M. Aho,4 K. Liao,1 M.A. Kuskowski,5 M.M. Colvin-Adams,2 P. Echman,2 M.R. Pritzker,2 R. John.1 1University of Minnesota, Minneapolis, MN; 2University of Minnesota, Minneapolis, MN; 3University of Minnesota, Minneapolis, MN; 4Chicago Medical School, Chicago, IL; 5VA Medical Center, Minneapolis, MN. Purpose: Patients requiring left ventricular assist device (LVAD) placement often have abnormal liver function in the early post operative period. The cause is often multifactorial including right heart failure, decreased hepatic perfusion, and cellular damage from inflammatory mediators. Because liver dysfunction is often associated with poor patient outcome, the aim of this project was to study the incidence, risk factors and outcomes in patients with early post operative liver dysfunction after Heartmate II® (HMII) LVAD implantation. Methods and Materials: We retrospectively studied 57 patients that had HMII implantation as bridge to transplant (BTT) or destination therapy (DT) from April 2005 to April 2008. Early post operative liver dysfunction was defined as having a total bilirubin level of ⬎7 mg/dL (normal reference range 0-1.5 mg/dL) in the first 7 days post HMII implantation. Survival was defined as being alive or transplanted at six months post HMII. Results: Of the 57 total HMII patients, 36 underwent BTT and 21 DT. Overall age was 61 ⫾16 years, 28% were female, and heart failure etiology was ischemic in 58%. Mean pre-operative bilirubin level was 1.55 mg/dL (range 0.2-4 mg/dL). A total of 14 patients (25%) had severe post operative liver dysfunction with mean peak bilirubin of 10.18 mg/dL (range 7.217mg/dL). Overall survival 6 months post implant was 82% (47/57). The patients with early liver dysfunction had 79% survival (11/14) versus 84% in patients without dysfunction (36/43). This difference was not significant (p⫽0.7) and the presence of early post operative liver dysfunction did not decrease the odds of survival at 6 months (OR 0.71, 95%CI 0.16-3.24), p⫽0.661). Conclusions: This study confirms a relatively high incidence of liver dysfunction (very high bilirubin level) in patients after HMII LVAD implantation. Despite this, these patients continue to have an excellent 6 month survival. Thus, the impact of liver dysfunction on LVAD outcomes is probably multifactorial and deserves further evaluation. 551 Percutaneous LVAD Support in Refractory Cardiogenic Shock Rapidly and Disparately Modulates Serum Biomarkers of Apoptosis, Neurohormonal Activation, Inflammation, and Extracellular Matrix Remodeling N.R. Shah,1 M.C. Bieniarz,1 P. Loyalka,2 D.L. Mann,3 B. Kar.1,2 1Baylor College of Medicine, Houston, TX; 2Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, TX; 3Washington University School of Medicine, St. Louis, MO. Purpose: Although percutaneous LVAD (pVAD) circulatory assist devices rapidly restore blood pressure in refractory cardiogenic shock, overall morbidity and mortality in these patients remain unacceptably high for poorly understood reasons. Methods and Materials: pVAD circulatory support via the TandemHeart centrifugal pump system (CardiacAssist, Inc., Pittsburgh, PA) was used in 21 patients with refractory cardiogenic shock due to varied etiologies. Serum samples obtained from this cohort at initiation and at 24 hours of pVAD support were analyzed for soluble fas ligand (sFasL), soluble Fas receptor (sFasR), endothelin-1, high-sensitivity C-reactive protein (hsCRP), and procollagen III N-terminal peptide (PIIINP). Importantly,
S179 none of the 21 study patients received any blood products between sample collections. Results: Paired-sample t-tests were used for all analyses. sFasL (pg/mL) decreased from initiation to 24 hours (56.1 ⫹/⫺ 35.5 vs. 37.4 ⫹/⫺ 14.2; p ⬍ 0.005) of pVAD support. sFasR (pg/mL) increased from initiation to 24 hours (8883 ⫹/⫺ 3302 vs. 12618 ⫹/⫺ 8718; p ⬍ 0.038) of pVAD support. Endothelin-1 (pg/mL) decreased from initiation to 24 hours (5.02 ⫹/⫺ 3.7 vs 2.65 ⫹/⫺ 1.81; p ⬍ 0.004) of pVAD support. hsCRP (mg/dL) increased from initiation to 24 hours (7.98 ⫹/⫺ 7.42 vs. 13.32 ⫹/⫺ 8.63; p ⬍ 0.001) of pVAD support. PIIINP (ug/L) increased from initiation to 24 hours (7.16 ⫹/⫺ 4.2 vs. 8.89 ⫹/⫺ 5.49; p ⬍ 0.035) of pVAD support. Conclusions: These data suggest that acute hemodynamic support with a pVAD results in decreased neurohormonal activation (endothelin-1) and a biomarker that reflects cellular apoptosis (sFasL), but does not result in a decrease in the level of serum biomarkers that reflect ongoing cardiac remodeling (PIIINP) and/or systemic inflammation (hsCRP), which implies that adjunctive strategies that prevent inflammation and/or tissue damage may be warranted in patients who have require acute hemodynamic support with pVADs. 552 Use of Extracorporeal Membrane Oxygenation (ECMO) in Patients with Chronic Cardiomyopathy: A Word of Caution C. Bermudez,1 Y. Toyoda,1 F. Avila,1 S. Mulukutla,2 O. Marroquin,2 J. Teuteberg,2 R. Kormos.1 1University of Pittsburgh Medical Center, Pittsburgh; 2University of Pittsburgh Medical Center, Pittsburgh. Purpose: To compare results with the use of ECMO support in advanced cardiogenic shock(CS) in patients with chronic cardiomyopathy (CCM) vs those presenting with acute myocardial infarction (AMI). Methods and Materials: Of 42 patients requiring ECMO for CS (January 2003 to February 2009), 33 patients had AMI and 9 patients had known CCM (4 ischemic,3 dilated and 2 restrictive).Retrospective analysis was performed using a prospectively collected database. Results: Both groups had similar demographic carachteristics, inotropic requirement, IABP use and mechanical ventilation at initial evaluation.Renal failure at implantation was observed in 39% in AMI vs 89% of patients in CCM group (p⫽.008).Bilirrubin in CCM was 3.6 ⫾2.5 vs 1.2⫾1.1 mg/dl in AMI patients (p⫽.03). LVEF in CCM patients was12.3 ⫾3.7% vs 21⫾12.2% in AMI (p⫽.04), with RA pressure of 25⫾ 4.5 vs 17⫾ 6 mmHg (p⫽0.004) and mean PAP of 43⫾ 8 vs 34 ⫾9 mmHg (p⫽.02) in the same groups.The average support time was 77 hours (range 6-352) and 57 hours (range 9-119) in AMI and CCM groups.4/33 patients and 2/9 in AMI and CCM groups died on ECMO support.7/9 CCM and 15/33 AMI patients underwent VAD implantation. The use of BIVAD was necessary in 6/7 CCM vs 7/15 AMI patients (p⫽.009). 6/15 patients had a successful heart transplantation in AMI vs none in the CCM group. Weaning from ECMO was only possible (after revascularization) in 14 patients in AMI group. Survival curves are presented in Fig1.
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The Journal of Heart and Lung Transplantation, Vol 29, No 2S, February 2010
Conclusions: Patients with CCM supported on ECMO for acute decompensation have worse outcomes than patients supported in the presence of AMI.Significant preimplantation organ dysfunction, higher BIVAD requirement and decreased transplantation rate are surrogate markers of advanced disease.[figure1] 553 LVAD Support Results in a Significant Improvement in the Myocardial Sympathetic Nervous System, as Assessed by 123IMetaiodobenzylguanidine (123I-MIBG), Independent of Ventricular Function R.S. George,1,2 M.H. Yacoub,2 A. Cheetham,3 A. Kelion,3 E.J. Birks.1,2 1 Royal Brompton and Harefield NHS Foundation Trust, Harefield, Middlesex, United Kingdom; 2Imperial College, Harefield, Middlesex, United Kingdom; 3Royal Brompton and Harefield NHS Foundation Trust, Harefield, Middlesex, United Kingdom. Purpose: 123I-MIBG uptake improves in patients recovered with LVAD and drug combination therapy. MIBG uptake is assessed using Heart/ Mediastinum (H/M) ratio and washout rate (W/O). After drawing a region of interest (ROI) around the LV, the average myocardial counts per pixel is calculated. A large heart will have an apparent lower MIBG uptake due to lower average counts per pixel than a smaller heart despite unchanged sympathetic function. In this study we investigated whether changes in MIBG uptake in LVAD patients is secondary to reduction in LV size or improvement in the uptake mechanism itself. Methods and Materials: MIBG uptake was assessed serially in 9 LVAD patients at two time points, T1 and T2 (40 ⫾ 20 days and 289 ⫾ 84 days following device implantation, respectively). Planar scintigraphy in the anterior projection was performed at 15 minutes and 4 hours. ROI were drawn over the heart excluding the LVAD. Counts per pixel were calculated for each ROI to obtain early and delayed H/M ratios and W/O rate. To index for LV size, ROIs drawn at T1 were superimposed on acquisitions acquired at T2 and the H/M ratios and the W/O rate were re-calculated. Results: Following 289⫾84 days of LVAD support MIBG uptake increased significanlty compared to the first assessment (Early H/M, 2.2⫾0.2 vs 1.65⫾0.4, p⬍0.01; Delayed H/M ratio, 2.1⫾0.2 vs 1.6⫾0.4, p⬍0.01; W/O rate, 29⫾13.9% vs 43.5⫾24.5%, p⫽0.07). There was no significant difference between MIBG uptake measured at T2 compared to the measurements taken after superimposing the ROIs from T1 to T2 (Early H/M, 2.2⫾0.2 vs 2.2⫾0.2, p⫽0.105; Delayed H/M ratio, 2.1⫾0.2 vs 2.0⫾0.5, p⫽0.395; W/O rate, 29⫾13.9% vs 27.5⫾13.5%, p⫽0.621). Conclusions: LVAD and drug combination therapy significantly improve MIBG uptake irrespective of changes in LV size suggesting an improvement in the sympathetic nervous system. 554 A Safe and a Cost-Effective Approach for Managing Patients with Levitronix CentriMag® Short Term Devices A. Firouzi,1 R.S. George,1 K. Absalom,1 S.M. Panther,1 H. Doyle,1 A. Bashford,2 C. Bindoff,3 A. Khaghani,1 E.J. Birks.1 1Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom; 2Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom; 3Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom. Purpose: Short term left ventricular assist devices (LVADs) are being increasingly used as a bridge-to-decision (BTD), post cardiotomy or for right ventricular support (RVAD) often improving outcome but adding cost to the patient care and affecting other services. Between years 2003 and 2006, Levitronix short term device was used at our institution in 47 patients adding a total of 1,314 intensive care unit (ICU) beds (£2,299,500)* to their post operative care. The purpose of this study was to evaluate whether early ward discharge of patients with Levitronix is safe and cost effective. Methods and Materials: A ward (floor area) discharge policy was started at the beginning of April 2007 aiming to manage haemodynamically stable patients with a maximum of one organ failure on the ward. The protocol involved staff training in a multidisciplinary approach in patient management with ICU outreach involvement.
Results: Over 2 years, 18 patients (13 males) that received Levitronix were mobilised to the ward 28.6⫾42.9 days post device implantation. Levitronics was implanted in 10 as a BTD and in 8 for RVAD support. Total ward stay was 486 days. None of the patients returned to ICU for any VAD/ Levitronix related complications. All returned to ICU on either the day of explantation or transplantation. Total ICU bed days saved was 486 days saving £850,500 * and generating accommodation for 162 routine cardiac cases †. Conclusions: Ward discharge of patients with Levitronix is cost effective and safe providing they were haemodynamically stable with no respiratory complications prior to ward mobilisation. Staff training and a multidisciplinary approach is mandatory for the success of this policy. * Based on average ICU bed stay cost of £1,750 per day† Based on average of 3 ICU bed stays are required per each routine cardiac case. 555 DNA-Methylation of the Human b1-Adrenergic Receptor Core Promoter Pre and Post VAD-Support and Its Putative Role for Gene Silencing in the Terminal Failing Myocardium A. Kassner,1 B. Bohms,1 M. Morshuis,2 S. Schulte-Eistrup,2 J. Gummert,2 H. Milting.1 1Herz- und Diabeteszentrum NRW, Bad Oeynhausen, NRW, Germany; 2Herz- und Diabeteszentrum NRW, Bad Oeynhausen, NRW, Germany. Purpose: In terminal heart failure (HF) signal transduction of the badrenergic system is blunted due to downregulation of receptor protein and mRNA. We previously showed that the b1-adrenergic receptor (b1AR) protein is upregulated whereas its mRNA remained downregulated after ventricular assist device (VAD) support. We speculated that epigenetic modifications by cytosine methylations (MeCy) of the b1AR-gene (ADRB1) promotor might be responsible for the sustained downregulation of the b1AR-mRNA. Therefore, we analysed methylation of the ADRB1promotor by bisulfite sequencing. Methods and Materials: Myocardial genomic DNA (gDNA) was isolated from 10 non-failing (NF), 13 failing hearts and 5 paired samples pre- and post-VAD-support. Genomic DNA of the ADRB1 core promotor including the polymerase II binding site was analysed by bisulfite sequencing resulting in conversion of unmethylated cytosines to uracil. PCR fragments were cloned in E. coli for quantitative sequencing. Results: About 1-2% of cytosine residues were methylated within the ADRB1-promotor. We did not identify a methylation hot spot within the promotor. On average in NF, tHF, pre-VAD and post-VAD we found [% of methylcytosines; means ⫾ SD]: 1.01⫾0.56, 1.38⫾1.33 and 0.25⫾0.22 compared to 0.71⫾0.52, respectively. A correlation analysis revealed no correlation between age and MeCy in the NF-cohort whereas in HFsamples we observed a positive correlation (r2⫽0.508, p⬍0.01). Conclusions: Cytosine-methylation of the ADRB1-core-promotor is not significantly elevated in HF. The number of MeCys in the post-VADmyocardium appeared to be higher compared to corresponding pre-VADsamples, but did not reach significancy. The low abundance of MeCy within the core-promotor underlines that this part of the ADRB1-gene belongs to a CpG-island. Sustained downregulation of the b1AR-mRNA is not caused by ADRB1-promotor methylation. 556 The SWAT Team Approach for Treating the Unstable Patient in Acute Cardiopulmonary Shock D. Jaroszewski,1 C. Pierce,1 R. Scott,2 E. Steidley,2 R. Gopalan,2 P. DeValeria,1 L. Lanza,1 A. Francisco.1 1Mayo Clinic, Phoenix, AZ; 2 Mayo Clinic, Phoenix, AZ. Purpose: Transfer of patients in acute cardiogenic shock to specialty centers for definitive management may not be possible for patients unstable for transport. The SWAT team approach provides a team to the community hospital for assessment, stabilization and transfer of the patient to our facility optimizing survival to recovery or transplantation.[figure1]