Initiation of a Standardized International Normalized Ratio Management Protocol Reduces Out of Range Days in an Ambulatory LVAD Population

Abstracts S443 Turkey Yuksek Ihtisas Hospital, Ankara, Turkey; 2Cardiology, Turkey Yuksek Ihtisas Hospital, Ankara, Turkey. Purpose: The Thoratec®HeartMate 3 (HM3) ventricular assist device (VAD) is a new compact, intrapericardial, centrifugal flow pump with a full magnetically levitated rotor and a wide range of operation (2-10 L/min) to accommodate a broad range of clinical needs. We analyzed our experience Heartware®VAD (HVAD) and HM3 VAD implantation through minimally invasive left thoracotomy (MILT) and J sternotomy implantation techniques Methods: Between March 2015 and October 2016, 31 patients underwent through MILT VAD implantation and were included in this study. Twenty three patients had HVAD (group A), whereas 8 patients underwent HM3 (group B). To compare outcomes of these pumps, measures were the length of entubation, haemolysis, blood loss and transfusion, intensive care unit (ICU) and hospital stay, right ventricular (RV) failure and requirement support with devices, stroke, pump thrombosis, bleending and driveline infection in hospital. Results: There was no difference in ICU length of stay (p 0,22), post-operative blood product administration (p 0,11) and total time on mechanical ventilation (p 0,46), RVF (p 0,76), duration of cardiopulmonary bypass (p 0,32). After adjusting for age, INTERMACS profile and Pennsylvania and Michigan Risk Scores, RVSWI and CVP/PCWP ratio did not differ between the two groups. In-hospital cerebrovascular events were 13% in group A and 0% in group B respectively. Conclusion: The Full MagLev technology enables rapid speed changes and allows the development of artifcial pulsatile flow and the HM3 assist system can be successfully implanted with MILT techniques. This technique has proved to be safe and reproducible, with good clinical outcome. Further large collaborative studies are needed to identify advantages of the this approach. 1( 356) Comparison of Activated Partial Thromboplastin Time (aPTT) and Anti-Factor Xa for Low Intensity Unfractionated Heparin Monitoring in Patients with Mechanical Circulatory Support Devices (MCSD) O. Volod ,1 L.D. Lam,2 M. Barglowski,1 J. Mirocha,3 C. Runyan,2 J. Moriguchi,4 L.S. Czer,4 F. Arabia.5  1Pathology, Cedars Sinai Medical Center, Los Angeles, CA; 2Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, CA; 3Cedars Sinai Research Institute, Cedars Sinai Medical Center, Los Angeles, CA; 4Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA; 5Center for Surgical Device Management, Cedars Sinai Medical Center, Los Angeles, CA. Purpose: Low intensity intravenous unfractionated heparin (LIIV-UFH) remains the mainstay therapy for bridging patients on MCS devices (MCSDs). The optimal level of anticoagulation for low intensity protocols has not been standardized. Recently, many institutions are switching from aPTT to anti-factor Xa assay (heparin assay) for UFH monitoring. There is still uncertainty if the heparin assay is superior to aPTT in MCSD patient population. We evaluated the relationship between heparin assay and aPTT for monitoring LIIV-UFH in patients with various types of MCSDs. Methods: 25 MCSD patients on LIIV-UFH intended to bridge with warfarin who underwent simultaneous aPTT and heparin assay measurements at our institution were included for retrospective analysis. Study cohort included a total of 222 paired values: 10 TAH patients (78 values), 11 HeartWare (HW) patients (100 values) and 4 HeartMate II (HMII) patients (44 values) . Only data with low intensity heparin assays between 0.10 IU/ml and 0.40 IU/ml were included. Patients INTERMACS profiles was also gathered for analysis. Results: A dose-response curve calculated from the data using regression analysis showed a high degree of variability in aPTT for a heparin assay level 0.10IU/ml- 0.40 IU/ml irrespective of the type of device: TAH r2 =  0.14, with p =  0.0009, HW r2 =  0.04 , with p =  0.060 and HMII r2 =  0.25, with p =  0.0005. The patterns of discordance were observed in both directions: supratherapeutic aPTT value (as high as 130 seconds) despite low intensity heparin level or normal aPTT ( as low as 30 seconds) despite measurable heparin level. Conclusion: Levels of aPTT were disproportionally prolonged or normal relative to the corresponding heparin assay levels in MCSD patients irrespective of the type of device or INTERMACS profiles. Concurrent use of aPTT and heparin assay to guide heparin therapy may be misleading. The heparin assay appears to be more reliable than aPTT in patients with MCSDs.

The ideal level of anticoagulation should be individually tailored. Target values of heparin assay level between 0.15 IU/ml to 0.3 IU/ml appears to be safe for bridging using low intensity heparin dose. Multicenter large studies using different instruments and reagents are necessary to establish uniform evidence - based guidelines. 1( 357) The Role of Beta Blockers in the Prevention of Gastrointestinal Bleeding After Left Ventricular Assist Device Implantation R. Kaur , R. Singh, S. Phillips, K. Abdullah, S.S. Desai, P. Shah.  Heart Failure and Heart Transplant, Inova Heart and Vascular Hospital, Fairfax, VA. Purpose: Gastrointestinal bleeding (GIB) affects between 15 to 30% of LVAD recipients. Small bowel arteriovenous malformations (AVM) have been implicated in about one-third of GIB events. It is believed that LVADs reduce pulse pressure that triggers an increase in sympathetic tone, causing smooth-muscle relaxation, arteriovenous dilation and AVM. This mechanism of AVM is also seen in patients with advanced liver disease and portal hypertension. Beta-blockers cause splanchnic vasoconstriction reducing portal and collateral blood flow. Hence, we sought to determine the role of beta-blockers in reducing the incidence of GIB in LVAD recipients. Methods: We conducted a retrospective study of patients implanted with a continuous-flow LVAD from January 2011 to June 2016 at our institution. We determined ambulatory prescription of a beta-blocker at three consecutive times points early after LVAD implant to categorize patients into two groups beta-blocker (BB) vs no beta-blocker (noBB). Incidence rates of GIB were compared between groups. Kaplan Meier methods were used to calculate GIB-free survival. The incidence and events/year were compared between both groups. Results: During the study period we implanted 172 LVADs and 148 ambulatory LVAD patients were evaluated. During a median follow-up of 2.5 years (every 3 months), 75 patients (50.7%) were on BB and 73 patients (49.3%) were not. Clinical characteristics between the BB and noBB group were similar (table with age, sex, INTERMACS profile, LVAD type, DM, HTN, AF, BTT/DT, Cr, Albumin, Bilirubin, EF, LVIDD). The survival free of GIB in the BB group was 77% and 69% in the noBB group (p =  0.344). The mean number of GIB events/year in the BB group was 0.91 compared to 1.87 in the noBB. Conclusion: Our study found a non-significant trend towards lower GIB in LVAD patients who received BB while on chronic support. Larger studies with sufficient power will need to be conducted to determine the potential mitigating effect of BB on LVAD-induced GIB.

1( 358) Initiation of a Standardized International Normalized Ratio Management Protocol Reduces Out of Range Days in an Ambulatory LVAD Population M.A. Thompson ,1 R.C. Jackson,2 M. Frakes,2 L.T. Hamann,1 R. John,3 R.J. Cogswell.4  1CV Specialty Nursing, University of MN Health, Minneapolis, MN; 2Fairview Pharmacy Services, University of MN Health, Minneapolis, MN; 3Cardiovascular Surgery, University of MN Health, Minneapolis, MN; 4Cardiology, University of MN Health, Minneapolis, MN. Purpose: Pump thrombosis remains one of the leading causes of morbidity and mortality in left ventricular assist device (LVAD) patients.

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The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017

Sub-therapeutic anticoagulation is thought to contribute to these events. In order to reduce sub-therapeutic international normalized ratios (INRs), our program developed a standardized INR management protocol. The purpose of this analysis was to determine whether implementation of this protocol decreased the number of days out of therapeutic range in our LVAD population. Methods: The protocol was initiated in May of 2014. The protocol requires more frequent INR monitoring and earlier initiation of heparin or enoxaparin in response to sub-therapeutic INRs. The percent of days within goal INR range for the population was calculated in the two years before and after initiation of the protocol using the Roosendaal Method. Results: Initiation of the protocol, which transitioned all INR management to the implanting center’s coumadin clinic, required 7 months to complete. After protocol initiation, the number of LVAD patients managed by the implanting center increased from 47 to 123. The percentage of days within goal INR range increased from 62.2 % to 73.7 % (p <  0.0001) and the percentage of days in a sub-therapeutic range decreased from 31.9% to 19.3 % (p <  0.0001). The number of INRs per patient increased from 16.9/year to 38.2/ year and the staffing required to implement this protocol increased from 2.6 to 5.2 full time employees. Conclusion: Initiating a standardized INR management protocol significantly improved the percentage of days in range and reduced sub-therapeutic INR days. This program, however, required more blood draws and pharmacy staff. Further analysis will be needed to determine whether this strategy has had a favorable impact on thrombotic complications.

1( 359) Does Aspirin Effectively Inhibit Platelet Activation During Left Ventricular Assist Device Support? F. Consolo ,1 L. Pozzi,2 G. Motolone,3 G. Sferrazza,3 M. Pieri,3 P. Della Valle,2 A. Zangrillo,1 M.J. Slepian,4 A. D'Angelo,2 F. Pappalardo.1  1Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Vita Salute University, Milano, Italy; 2Coagulation Service and Thrombosis Research Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy; 3Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milano, Italy; 4Department of Medicine and Biomedical Engineering, Sarver Heart Center, The University of Arizona, Tucson, AZ. Purpose: To evaluate the efficacy of aspirin (ASA) in inhibiting ex vivo thrombin generation in patients with durable Left Ventricular Assist Device (LVAD) and to compare the thrombin generation profile of patients administered low (100mg/day) vs high (300mg/day) ASA dose. Methods: The Thrombin Generation Test was performed on a cohort patients implanted with LVAD who did not suffer any thrombotic event (n= 14). Thrombin generation was triggered by 0.5 pmol/L Tissue Factor in normal platelet poor plasma with the addition of the patients’ purified platelets, to account for the role played by platelets in mediating thrombin generation and to exclude any influence of anticoagulation therapy (Warfarin) on the test. Patients were on different ASA dose, according to the pump model: a) HeartMate II (Thoratec Corp., USA): 100mg/day (n= 3, 21%); b) HeartMate III (St. Jude Medical Inc., USA): 100mg/day (n= 4, 29%); c) Heartware HVAD (Heartware Corp., USA): 300mg/day (n= 7, 50%). In addition, one patient with HVAD who was not on ASA because of allergy was also profiled. Results were compared with those obtained from ASA-free volunteers (controls, n= 14). Results: Following a median time of LVAD support of 210 (IQR: 138-477) days, platelet-mediated thrombin generation was comparable in ASA-treated LVAD recipients and in controls (Fig. 1A,B). Notably, the patient not on ASA (491 days of support) showed higher thrombin generation as compared to the rest of the population (Fig. 1A,B). Comparison of low vs high ASA dose revealed no differences in terms of platelet-mediated thrombin generation (Fig. 1C). Conclusion: We report that ASA inhibits ex vivo platelet-mediated thrombin generation in LVAD recipients and may eventually mitigate the risk of thrombotic complications. The thrombin generation profile of ASA-treated LVAD patients was similar to controls. Moreover, we suggest that high dose ASA does not add any significant effect in blunting platelet activation and the associated thrombin generation pattern.

1( 360) Incidence of Early Right Heart Failure After Left Ventricular Assist Device Implantation in Patients Managed without Inhaled Nitric Oxide C. Michaud , G. Marco, A. Schaap, M. Dickinson, P. Wilton.  Spectrum Health, Grand Rapids, MI. Purpose: Early right heart failure (RHF) after left ventricular assist device (LVAD) implantation is a frequent phenomenon associated with increased morbidity and mortality. Post-operative pulmonary vasodilation with inhaled nitric oxide (iNO) is an accepted standard of care to mitigate this complication, though evidence to support its use is sparse. As a costly therapy in the United States, we compared the incidence of early RHF in patients who did or did not receive iNO after LVAD implantation. Methods: All patients who received an LVAD at our institution from 2011 to 2014 were retrospectively analyzed. Patients who received RVAD or ECMO support or died within 12 hours of implant were excluded. The primary outcome was development of RHF (2012 INTERMACS definition) within 14 days of LVAD implant. Secondary outcomes included pre-operative medication and support requirements and duration of post-operative mechanical ventilation, inotrope, and vasopressor support. Results: Of 103 LVAD implants, 42 did not utilize iNO in the peri-operative period. Pre-operative cardiac and surgical histories, use of inotropes, vasopressors, and mechanical ventilation, right ventricular function on echocardiography, and pulmonary artery catheter data were similar between groups. Both groups were predominantly male with similar BMI (29 in iNO group, 28 in no-iNO group, p= 0.24) and median INTERMACS profile (2 [range 1-6] vs. 3 [1-7], p= 0.12), but patients who received iNO were older (61 vs. 55 years old, p= 0.04). Early RHF occurred in 60% of patients who received iNO and 40% of patients who did not (p= 0.06). More patients in the iNO group required subsequent RVAD support (6 vs. 0, p= 0.08) and prolonged inotropic therapy (28% vs. 12%, p= 0.05). Patients who did not receive iNO spent less time receiving mechanical ventilation (23 vs. 46 hours, p< 0.01), inotropes (127 vs. 161 hours, p= 0.03), and vasopressors (22 vs. 48 hours,