Access Matters: Survival Advantage with Minimally Invasive Implantation of LVAD as Destination Therapy

Abstracts S53 1( 21) Cost-Effectiveness of a Blood-Based Biomarker Compared to Endomyocardial Biopsy for the Diagnosis of Acute Allograft Rejection Z. Hollander ,1 T.H. Mohammadi,2 S. Assadian,1 J.E. Wilson-McManus,1 K.K. Lam,1 R.T. Ng,3 W. McMaster,4 P.A. Keown,4 B.M. McManus,3 C. Marra.5  1PROOF Centre of Excellence, Vancouver, BC, Canada; 2Centre for Health Evaluation & Outcome Sciences, Vancouver, BC, Canada; 3University of BC & PROOF Centre of Excellence, Vancouver, BC, Canada; 4University of British Columbia, Vancouver, BC, Canada; 5School of Pharmacy, Memorial University, St. John’s, NL, Canada. Purpose: Endomyocardial biopsy is the gold standard for diagnosing acute rejection in heart transplant patients. Based on patient surveys, one of the most important improvements in transplant patient management would be the replacement of biopsy by a minimally invasive test. Gene expression profiles in peripheral blood of cardiac transplant patients have the potential to be used to monitor for absence of acute allograft rejection. Thus, could lead to significant reduction in the number of biopsies. The purpose of this work was to evaluate the incremental costs and effectiveness of using a blood-based test versus endomyocardial biopsy in the detection of acute cardiac allograft rejection. Methods: A discrete event simulation model was developed to assess the cost effectiveness of a blood test guiding biopsy versus biopsy alone to detect acute allograft rejection for the first 5 years after heart transplantation. Published utility estimates, probabilities of medical events and complications, and direct medical costs in 2012 US dollars were used in the model. The performance characteristics of the gene expression based blood test to rule out rejection from a validation study were used. Costs and quality-adjusted life-years (QALYs) were discounted at a 3% annual rate in the base case analyses. Results: Using a blood test to guide biopsy as compared to biopsy alone in heart transplantation resulted in cost savings of $27,244 and QALY gains of 0.046 on average per patient for the first 5 years post-transplant. Results were robust in wide-ranging probabilistic and univariate sensitivity analyses. Conclusion: Compared to the current standard practice of using endomyocardial biopsy for the diagnosis of acute allograft rejection after cardiac transplantation, the use of an effective blood test provides beneficial clinical outcomes and healthcare cost savings. In addition, a blood-based monitoring test would decrease the number of biopsies that patients would have to undergo, thus improving their quality of life. 1( 22) Access Matters: Survival Advantage with Minimally Invasive Implantation of LVAD as Destination Therapy V. Tarzia ,1 M. Di Mauro,2 G. Bortolussi,1 J. Bejko,1 D. Marinelli,2 M. Foschi,2 M. Maccherini,3 S. Bernazzali,3 M. Maiani,4 V. Tursi,4 P. Agostoni,5 A. Apostolo,5 F. Alamanni,5 U. Livi,4 G. Sani,3 T. Bottio,1 G. Di Giammarco,2 G. Gerosa.1  1Cardiac Surgery, University of Padova, Padova, Italy; 2Cardiac Surgery, University of Chieti, Chieti, Italy; 3Cardiac Surgery, University of Siena, Siena, Italy; 4Cardiac Surgery, University of Udine, Udine, Italy; 5Cardiac Surgery, University of Milano, Milano, Italy. Purpose: It is well known that, in selected patients, survival with LVAD as destination therapy (DT) is able to compete with heart transplantation. Patient selection is usually based on recognized pre-operative parameters. However, the impact of surgical technique is often neglected. The aim of this “all-comers” study is to evaluate long-term clinical outcome of patients with Jarvik 2000 LVAD as DT or bridge-to-candidacy (BTC), in relation to known risk factors, as well as implantation technique. Methods: From October 2008 to October 2015, 124 adult patients with endstage heart failure were implanted with Jarvik 2000 LVAD in 5 Italian centers. All devices had retro-auricular pedestal as driveline exit-site. One hundred-two implants were intended as DT (87) or BTC (15). Relevant clinical variables, laboratory tests, operative details and long-term survival were retrospectively analyzed. Results: Mean age was 62±7 years, 13 were females, and 32% were classified as INTERMACS level I-II. Seventy-three patients were implanted via conventional access, including left thoracotomy and full sternotomy, while the remaining 29 were implanted via minimally invasive approach. No differences were found between the two groups regarding pre- and intra-operative data. Overall survival was 61±5%, 47±6% and 41±6% at 1, 2 and 3 years, respectively. At Coxanalysis, risk factors for lower long-term survival were: higher pre-operative

bilirubin (HR= 1.016; 95CL 1.003-1.033, p-value=  0.039), INTERMACS class 1-2 (HR= 4.4; 1.7-11.2, p-value= 0.002); conversely, minimally invasive approach was a protective factor (HR= 0.18; 0.05-0.69, p-value=  0.011). AUC of the final model was 0.76. Survival at 1, 2 and 3 years was significantly higher with the minimally-invasive approach (74±8%, 59±5% and 59±4%) compared to the standard technique (56±6%, 42±6% and 37±6%). Conclusion: Patients treated with Jarvik 2000 LVAD as DT or BTC achieved a satisfactory long-term survival. In our “all-comers” experience, minimally-invasive implantation technique has proved to be beneficial in this subset of patients, therefore its application should be largely extended even to this population. 1( 23) Heparin-Free Off-Pump LVAD Implantation Reduces Early Adverse Events Compared with On-Pump Implantation S.K. Balasubramanian , E. Pavlushkov, S. Pettit, C. Lewis, Y. Abu-Omar, M. Berman, J.K. Parameshwar, S. Tsui.  Transplantation, Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom. Purpose: Left ventricular assist device implantation is associated with a relatively high incidence of bleeding and right ventricular failure (RVF). These adverse events increase resource use, hospital stay and compromise survival. An off-pump implant technique without using intra-operative systemic heparin was developed to reduce these adverse events. Early outcomes of patients implanted with the HeartWare HVAD using cardiopulmonary bypass (CPB) or the heparin-free off-pump implant technique were compared. Methods: A retrospective analysis of 57 consecutive patients who underwent HeartWare HVAD implantation from October 2009 to October 2015 was carried out. Demographic and perioperative clinical variables were analyzed using Fisher’s exact test and Wilcoxon Rank-Sum test. Results: HeartWare HVADs were implanted using CPB (Group CPB, n =  34) or the heparin free off pump technique (Group HFOP, n = 23); in the latter group, 7 were performed with a full sternotomy and 16 with minimal access using hemi-sternotomy plus left anterior thoracotomy. All patients required inotropic therapy for stage-D heart failure. Group HFOP had significantly higher pre-operative mean transpulmonary gradient and higher INTERMACS profile. In the peri-implant period, 13 (56.5%) patients in the HFOP group did not require Red Cell transfusion and none required FFP or platelet transfusion. Post-operatively, Group CPB had significantly higher rate of hemorrhage (P= 0.007), chest re-exploration (P= 0.002), Red Cell (P= 0.013) and blood products (P= 0.002) transfusion. There was a trend towards shorter ICU stay and lower incidence of RVF in the HFOP group. Overall 30-day and 1-year survivals were 96.4% and 81% respectively with no difference between groups. Conclusion: HFOP implantation of HVAD in patients with higher INTERMACS profile is associated with less bleeding, blood product usage and a trend towards less RV failure and shorter ICU stay. Use of this technique should be further explored in a larger clinical trial.

HVAD Table

Clinical Variables Age Sex (Male) Dilated cardiomyopathy Preoperative TPG (mm Hg) INTERMACS Profile Inotropes duration (days) Red blood cells (ml) Platelets (ml) Fresh frozen Plasma (ml) Re-exploration of chest Post-operative   hemorrhage (ml) Need for RVAD Need of Ventilation (Hours) ICU stay (days) Late drive line infection Late bleeding complications 30-day mortality One year survival

Group HFOP (N=  23) Mean ± SD

Group CPB (N= 34) Mean ± SD

P-Value

50.3 ± 15.0 82.6% 43.7% 15.7±4.6 2.3±0.48 7.2 ± 6.5 399.3 ± 693.7 0 0 4.3% 202.4 ± 105.2

48.3 ± 9.7 76.5% 56.2% 12.6 ± 4.1 1.8 ±0.69 8.8 ± 6.7 1992.5 ±3488.6 315.1 ± 410.9 320.9 ± 559.0 41.2% 476.2 ± 239.4

0.576 0.744 0.796 0.012 0.018 0.357 0.013 0.005 0.002 0.002 0.007

4.3% 33.9 ± 35.3 8.8 ± 5.3 17.0% 8.7% 4.3% 82.6%

23.5% 45.9 ± 33.8 12.2 ± 7.6 20.5% 14.7% 2.9% 79.4%

0.069 0.215 0.0595 1 0.689 1 1