Agreeing to Disagree: A Comparison of Antiplatelet and Anticoagulant Management Strategies at US versus International HVAD Implanting Centers

Abstracts S395 1( 106) The Effect of Cardiac Rehabilitation on Functional Capacity, Psychological Symptoms and Quality of Life in Patients with a Left Ventricular Assist Device E. Cinar,1 H. Karapolat ,1 K. Capaci,1 C. Engin,2 T. Yagdi,2 M. Ozbaran,2 S. Nalbantgil,3 M. Zoghi.3  1Department of Physical Medicine and Rehabilitation, Ege University School of Medicine, Izmir, Turkey; 2Department of Cardiovascular Surgery, Ege University School of Medicine, Izmir, Turkey; 3Department of Cardiology, Ege University School of Medicine, Izmir, Turkey. Purpose: In this prospective trial, we aimed to study the effects of cardiac rehabilitation on functional capacity, depression and quality of life, in patients with a left ventricular assist device (LVAD). We also aimed to compare the effectiveness of home and hospital based exercise programs. Methods: 42 patients who had received LVAD implants in our university hospital were included in the study. After the subjects were randomized into hospital exercise group (n= 20) and home exercise group (n= 22), they were enrolled in a cardiac rehabilitation program for 8 weeks, which lasted for one hour, three times per week in hospital and at home respectively. All subjects were assessed at baseline and 8th week. Results: In our study we detected a significant improvement in peak VO2, six minute walk test values, Minnesota living with heart failure quentionnaire and state-trait anxiety inventory in the hospital exercise group (p< 0,05). When we compared the changes seen in the parameters over time, hospital group showed significantly more improvement than the home exercise group in peak VO2, six-minute walk test, Minnesota living with heart failure questionnaire and trait anxiety subscore of the state trait anxiety inventory (p< 0,01) and FEV1(r= 0,14, p> 0,05) scores. Conclusion: End stage heart failure is increasingly being treated with LVAD implantation. Safety of cardiac rehabilitation in patients with LVAD have been proven in other studies. In this study we detected a positive effect of supervised hospital exercise program on functional capacity, quality of life and anxiety in patients with implanted LVADs. Previous studies have shown similar results regarding the efficacy of cardiac rehabilitation in both hospital and home exercise groups. But patients enrolled in these studies were mainly New York Heart Association grade 1 patients who had better functional status. In our study, exercise adherence was worse in the home exercise group. There is still need for more studies focusing on patients with LVAD and comparing the effects of home and hospital exercise programs. There is also need for more long term follow-up to show the long term efficacy of cardiac rehabilitation in LVAD patients. 1( 107) Outcomes of Ventricular Assist Device Therapy for Patients at an INTERMACS Profile 1: Single Center Experience O. Seguchi ,1 T. Fujita,2 S. Nakajima,1 H. Sunami,1 T. Sato,1 M. Yanase,1 H. Hata,3 J. Kobayashi,2 N. Fukushima,1 T. Nakatani.1  1Transplantation, National Cerebral and Cardiovascular Center, Osaka, Japan; 2Adult Cardiac Surgery, National Cerebral and Cardiovascular Center, Osaka, Japan; 3Adult Cardiac Surgery, National Cerebral and Cardiovascular Center, Osaka, Japan. Purpose: Ventricular assist device (VAD) therapy for patients at The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 are considered as challenging therapeutic strategy. Therefore, detailed analysis of outcomes of VAD therapy in INTERMACS profile 1 patients is always essential. Methods: We retrospectively reviewed medical records of patients with advanced heart failure who underwent LVAD implantation from April 2011 to June 2015 in our institution. Results: Eighty-three patients (44 at INTERMACS profile 3, 17 at INTERMACS profile 2, and 22 at INTERMACS profile 1) underwent LVAD implantation. Patients at INTERMACS profile 1 (mean age 35.8 ± 16.2, 13 males) had been supported by temporary circulatory support such as extracorporeal membrane oxygenation (ECMO, n= 1), intra-aortic balloon pumping (n= 5), and both devices (n= 16) before VAD implantation. Etiology of patients with INTERMACS profile 1 is as follows; 8 with fulminant myocarditis, 8 with dilated cardiomyopathy, 3 with dilated-phase hypertrophic cardiomyopathy, 2 with ischemic cardiomyopathy, and 1 with peripartum cardiomyopathy. With respect to the therapeutic

strategy using paracorporeal VAD (NIPRO-TOYOBO VAD), 12 patients had left VAD implantation, whereas 10 patients had biventricular VAD implantation (9 initiated their right ventricular support using an ECMO circuit). In patients at INTERMACS profile 1, five patients died within 90 days after VAD implantation (Death-group) and of the other 17 patients survived longer (Survive-group). Comparison of baseline characteristics between Death-group and Survivegroup disclosed that higher age (p= 0.007), female sex (p= 0.04), and small left ventricle (p= 0.03) were found in Death-group. Regarding mortality, patient at INTERMACS profile 1 demonstrated worse survival compared with those at profile 2 and 3 (2-year survival, 77.3% vs 94.4% vs 96.9%, respectively. p= 0.04). Conclusion: In this study, 17 of 22 INTERMACS profile 1 patients survived longer than 90 days. The survival of patients with INTERMACS profile 1 is acceptable compared with that of INTERMACS annual report. Higher age, female sex, and small left ventricle are thought to be predictive factors for poor prognosis in patients at INTERMACS profile 1 after VAD implantation. 1( 108) Agreeing to Disagree: A Comparison of Antiplatelet and Anticoagulant Management Strategies at US versus International HVAD Implanting Centers J.J. Teuteberg ,1 K.D. Aaronson,2 C. Mahr,3 H. Reichenspurner,4 T. Krabatsch,5 C.B. Patel,6 M. Strueber,7 M.S. Kiernan,8 D. Zimpfer,9 M.V. Jacoski,10 S. Schueler.11  1University of Pittsburgh Medical Center, Pittsburgh, PA; 2University of Michigan, Ann Arbor, IL; 3University of Washington, Seattle, WA; 4University Hospital Eppendorf, Hamburg, Germany; 5Deutsches Herzzentrum Berlin, Berlin, Germany; 6Duke University School of Medicine, Durham, NC; 7Spectrum Health, Grand Rapids, MO; 8Tufts Medical Center, Boston, MA; 9Medical University of Vienna, Vienna, Austria,; 10Medical Affairs, HeartWare Inc., Framingham, MA; 11Newcastle upon Tyne Freeman Hospital, Newcastle upon Tyne, United Kingdom. Purpose: There is no single accepted regimen for dosing and type of antiplatelet therapy or the goal range of anticoagulation in patients with a HeartWare® Ventricular Assist System (HVAD®) and the variability of antiplatelet and anticoagulant regimens among centers is unknown. Methods: A 33 question survey was distributed to centers who currently implant the HVAD Pump. Responses were limited to a single survey per center to avoid possible bias. Questions covered topics related to chronic anticoagulation, antiplatelet therapy, and management during surgical procedures and during bleeding events. Results: A total of 59 centers representing 18 countries and 63 U.S. centers were included. The median antiplatelet therapy dosing was substantially lower in international versus US centers, 100 mg/day v. 352 mg/day, respectively. (Figure). There were differences in the use of dual antiplatelet therapy between international and US sites: aspirin + clopidogrel (22% v. 5%) and aspirin + dipyridimole (5% v. 11%), respectively. Also, 72% non-US centers were using platelet functional assays to help guide antiplatelet therapy, compared to only 15% in the US. The most common INR range was 2.0-3.0, but 61% of non-US centers provided home monitoring devices, compared to less than 20% of US. The frequency of INR assessments at 3 months for non-US versus US was: every 3-4 days (39% v. 6%) and weekly (19% v. 55%) and biweekly (25% v. 32%). Conclusion: Centers managing HVAD patients outside of the US have a lower median target aspirin dose, are more likely to use clopidogrel in combination with aspirin and four times more likely to use platelet function testing. Although the goal INR ranges are similar, non-US centers are more likely to use home INR testing and have more frequent INR monitoring. The impact of these differences will be studied prospectively in a clinical trial examining baseline platelet reactivity and response to aspirin dosing in HVAD patients.

S396

The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016

1( 109) The Role of Neurohormonal Therapy in Patients with Left Ventricular Assist Devices R. Ghashghaei , R. Yousefzai, F. Liwinski, H. Tran, E.D. Adler.  Cardiology, University of California San Diego, San Diego, CA. Purpose: The use of Left Ventricular Assist Devices (LVADs) for the treatment of end stage heart failure continues to expand worldwide. Though the benefits of neurohormonal therapy in patients with reduced ejection fraction are well established, there is no current consensus or guidelines regarding the use of neurohormonal therapy in patients after LVAD implantation. We anticipated that heart failure patients with LVADs receiving neurohormonal therapy, compared to those without medical therapy, would have improvements in their functional status and less frequent hospitalizations at 1 year follow up. Methods: In this retrospective study, we compared the use of ACE-inhibitor and beta blocker therapy to changes in NYHA classification and heart failure hospitalizations at 1 year follow up in a cohort of 200 LVAD patients, 49% of whom were on neurohormonal therapy including both ACE inhibitors and beta blockers. Patients were matched according to their age, gender, demographics, and co-morbidities. An independent t-test was conducted to compare the mean change in NYHA classification as well as the average number of hospitalizations in LVAD patients with and without medical therapy. Results: There was no significant difference in the change in NYHA classification in those with medical therapy (M=  1.52, SD= 0.95) and in those without (M=  1.32, SD=  0.87); t(98)= 1.10, p=  0.28. However, the number of hospitalizations was significantly lower in LVAD patients with medical therapy (M=  2.12, SD=  1.89) compared to those without (M= 3.12, SD= 2.41); t(98)= 2.31, p= 0.02. Conclusion: This study suggests that neurohormonal therapy in LVAD patients may reduce hospitalizations, although it may not necessarily change functional status as measured by the NYHA classification system. Further randomized studies are required to validate these findings. 1( 110) Evaluation of Systemic Heparin vs. Bivalrudin Anticoagulation in Patients Supported by Extracorporeal Membrane Oxygenation T.J. Berei , M.P. Lillyblad, K.M. Hryniewicz, K. Wilson, R. Garberich.  Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, MN. Purpose: Anticoagulation in patients (pts) supported by extracorporeal membrane oxygenation (ECMO) plays a crucial role in minimizing circuit malfunction and thromboembolic events. Direct thrombin inhibitors have emerged as a viable option due to more steady pharmacokinetics but are much more costly. This study compared clinical outcomes, bleeding events and time within therapeutic range (TTR) between heparin or bivalirudin. Methods: We retrospectively reviewed electronic medical records of pts supported with ECMO. We divided pts into bivalirudin (gr1) and heparin group (gr2). We analyzed demographics, shock etiology, laboratory values, mortality, thromboembolic and bleeding complications, length of stay (LOS) and TTR during initial 48 hours of support. Major bleeding was defined as drop in hemoglobin of ≥  3g/dL, minor as oozing requiring bedside intervention. Vascular complications were defined as any surgical intervention. TTR was determined by an algorithm based off the Rosendaal method. Results: We evaluated 28 pts. Demographics and laboratory values are presented in Table 1.Majority of pts were in cardiogenic shock (46.4%), followed by septic shock (39.3%). Average ECMO duration was 166.1 hours. Gr 1 had higher baseline creatinine (2.0 vs 1.1, p < 0.001). Average LOS was similar (31 vs 22, p= 0.4). There were no differences for overall death (3 vs 3) or death on ECMO (3 vs 0, p= 0.2). TTR (94.3% vs. 80.1%, p =  0.2), thrombosis (0 vs 4, p= 0.1), and minor bleeding (3 vs 5, p =  0.7) favorably trended towards B. Incidence of vascular complications did not differ (7 vs 6, p= 0.7). There were no neurological complications. Conclusion: We suggest that heparin remains first-line anticoagulant in ECMO population due to its acceptable safety and efficacy profile and much lower cost when compared to bivalirudin. Larger prospective studies are needed to determine best anticoagulation strategies in pts supported with ECMO.

Demographics

Age (years) Male (%) Historyof HIT, (%) INR Hemoglobin PeakLactate PH

Bivalirudin (n= 14)

Heparin (n= 14)

P-Value

51.5 (39, 61) 8 (57.1) 0 (0) 1.55 (1.3, 2) 11.35 (10.2, 14.4) 7.5 (2.8, 9.9) 7.3 (7.2, 7.4)

62 (41, 68) 7(50.0) 0(0) 1.5 (1.3, 2) 10.8 (9.1, 13) 7.5 (2.8, 9.9) 7.4 (7.3, 7.5)

0.21 1 --0.64 0.4 0.66 0.12

1( 111) Evaluating the Safety and Efficacy of Enoxaparin in Bridging Mechanical Circulatory Support (MCS) Patients from Subtherapeutic to Therapeutic INR in an Outpatient Setting L.D. Lam ,1 U. Duong,2 L. Luu,2 K. Del Rosario,2 M. Fan,2 P. Ambrose,2 J. Moriguchi,1 A. Francisco.1  1Cedars Sinai Medical Center, Los Angeles, CA; 2UCSF School of Pharmacy, San Francisco, CA. Purpose: Mechanical circulatory support (MCS) patients require long-term anticoagulation. MCS patients with subtherapeutic INR are traditionally admitted to the hospital and bridged with unfractionated heparin (UFH). Enoxaparin is a viable alternative to UFH that offers patient convenience and decreases risk of hospital-related complications and healthcare-associated costs. The purpose of this study is to determine if enoxaparin in an outpatient setting is safe and effective in bridging MCS patients from a subtherapeutic to therapeutic INR. Methods: This IRB-approved, retrospective analysis reviewed data from January 2, 2011 to September 7, 2015. Patients at the study center who received MCS devices, were taking warfarin, and had a subtherapeutic INR during the defined time period were included. Patients were bridged with enoxaparin (n= 31 encounters) or UFH (n= 17 encounters) per physician’s discretion. The primary endpoint was safety of enoxaparin, based on major and minor bleeding events. A two-tailed Fisher’s exact test was used to compare the number of minor bleeds between the two groups. The secondary endpoint was efficacy based on thrombotic events, concurrent antiplatelet medications, drug-drug interactions with warfarin, and dosing. Hospital length of stay was measured to assess financial impact on the healthcare system. Results: The number of minor bleeds between the enoxaparin (4 events) and UFH (0 events) groups was not statistically significant (p= 0.28). No major bleeding or thrombotic events occurred in either group during treatment. Mean INR upon therapy initiation in the enoxaparin and UFH group was 1.41 +/- 0.20 and 1.39 +/- 0.18, respectively. Mean INR upon therapy discontinuation was 2.37 +/- 0.37 for the enoxaparin group and 2.06 +/- 0.20 for the UFH group. The mean enoxaparin dose was 0.88 mg/kg (range 0.47 to 1.17 mg/kg) subcutaneously twice daily. The mean length of stay for the UFH group was 8.29 days versus 0 days for the enoxaparin group. Conclusion: The results suggest that enoxaparin can be a safe, effective, and more economic alternative to UFH in bridging subtherapeutic MCS patients to therapeutic INR. 1( 112) The Role of Biventricular Assist Device on Patients with Multiorgan Failure Due to Fulminant Myocarditis: Single-Center Experience S. Nakajima ,1 N. Okada,1 K. Kuroda,1 E. Hisamatsu,1 H. Sunami,1 T. Sato,1 O. Seguchi,1 M. Yanase,1 H. Hata,2 T. Fujita,2 N. Fukushima,1 J. Kobayashi,2 T. Nakatani.1  1Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan; 2Department of Adult Cardiac Surgery, National Cerebral and Cardiovascular Center, Osaka, Japan. Purpose: In Japan, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is initially used for patients with circulatory collapse status due to fulminant myocarditis (FM) and conversion to ventricular assist device (VAD) is considered when cardiac function is not recovered. In the present