Advances In LVAD Patient Management

1. Advances In LVAD Patient Management Mark Slaughter, MD Professor of Surgery, Division of Thoracic and Cardiovascular Surgery University of Louisville Clinical Strategies to Minimize Adverse Events J101-0411

2. Minimizing LVAD Therapy Adverse Events Improvements in LVAD design and patient management strategies have led to reductions in adverse events in LVAD therapy. • Stroke • Pump failure • RV failure • Infection • Bleeding

3. HeartMate II®—Designed To Minimize Adverse Events • Sintered titanium encourages neointima formation and helps reduce the need for anticoagulation • Optimal flow dynamics reduce stroke and thrombosis risk • Small device size • Small percutaneous lead to reduce infection • Ruby bearings help dissipate heat and are designed for ultra-long lifespan

4. Design Improvements Have Resulted In Reduced Adverse Events In the recent randomized Destination Therapy trial, HeartMate II demonstrated reductions in most major adverse event categories compared with HeartMate I. Statistically significant reductions were seen for pump replacements, infection and rehospitalizations. • HeartMate II’s smaller size, smaller percutaneous lead and improved reliability contributed to these reductions HeartMate I HeartMate II HeartMate II Destination Therapy Trial Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361:2241-51.

5. Advances In Clinical Strategies Have Also Led To Reductions In Adverse Events Comprehensive guidelines have been developed collaboratively by an interdisciplinary group of professionals and published by JHLT. These guidelines were based on the initial HeartMate II experience and have been employed to improve clinical outcomes. Slaughter MS, Pagani FD, Rogers JG, et al. Clinical management of continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant. 2010;29:S1-39.

6. Assessing The Impact Of Advances In Clinical Strategies On Bridge-To-Transplantation The HeartMate II BTT post-approval study was initiated to assess outcomes in a broader patient care environment • First 169 consecutive HeartMate II patients enrolled in the INTERMACS registry listed, or likely to be listed, for transplant • 77 centers enrolled patients from April to August 2008 and were followed for at least 1 year post-implant Endpoints • The primary endpoint was survival, and secondary endpoints included adverse events reported upon occurrence and functional status using the 6-minute walk test and EuroQoL scale—determined at baseline and 3, 6, and 12 months post-implant

7. Assessing The Impact Of Advances In Clinical Strategies On Bridge-to-Transplantation HeartMate II patients enrolled in the post-approval study experienced a reduced rate of important adverse events in a broader patient care environment compared to the HeartMate II pivotal clinical trial. Pagani FD, Miller LW, Russell SD. Extended mechanical circulatory support with a continuous-flow rotary left ventricular assist device. J Am Coll Cardiol. 2009;54:312-21. Starling, Naka, Boyle, et al. JACC, in press 2010. .

8. Assessing The Impact Of Advances In Clinical Strategies On Destination Therapy To assess whether advances in clinical strategies have improved the rate of adverse events associated with Destination Therapy, HeartMate II patients enrolled in the DT pivotal trial were compared to those enrolled in the DT continued access protocol (CAP). Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361:2241-51. Park SJ. AHA Scientific Sessions, November 2010.

9. Assessing The Impact Of Advances In Clinical Strategies On Destination Therapy The CAP results show a decrease in major adverse events. * * p<0.05 ** p<0.01 ** * Park SJ. AHA Scientific Sessions, November 2010.

10. Advances In Patient Management Lower Adverse Event Rates Several advances in patient management have been made including: • Effective anti-coagulation management • Reduced heparin usage post-operatively • Percutaneous lead placement and management • Blood pressure management

11. Effective Anticoagulation Management Boyle, et al. established an evidenced-based INR target by evaluating the risk of thromboembolism and hemorrhage related to the degree of anticoagulation. • The data show that HeartMate II patients experience relatively low rates of stroke and pump thrombosis with INRs > 1.5 • Clinical experience has established recommended INR targets of 1.5 – 2.5 Boyle AJ, Russell SD, Teuteberg JJ, et al. Low thromboembolism and pump thrombosis with the HeartMate II left ventricular assist device: analysis of outpatient anti-coagulation. J Heart Lung Transplant. 2009;28:881-87.

12. Post-Op Heparin May Not Be Required Slaughter, et al. conducted a retrospective study to evaluate the effects of heparin use on thromboembolic and bleeding complications after implantation of the HeartMate II • The results indicate that patients who do not receive early post-operative anticoagulation therapy with IV heparin as a transition to warfarin and aspirin are at decreased risk of bleeding events • These patients do not appear to be at any early elevated risk of thrombotic events • Eliminating the routine use of post-operative heparin in patients with low risk of thrombosis appears to be appropriate for most cases Slaughter MS, Yoshifumi N, John R, et al. Post-operative heparin may not be required for transitioning patients with a HeartMate II left ventricular assist system to long-term warfarin therapy. J Heart Lung Transplant. 2010;29:616-24.

13. Post-Op Heparin May Not Be Required The percentage of patients requiring transfusion for bleeding from POD 3-30 was significantly lower for Group C than for Groups B and A, and a trend for less bleeding after 30 days in Group C, although not significant. • Group A: Therapeutic heparin (n=118) (8.8 pt years) • Group B: Sub-therapeutic heparin (n=178) (13.1 pt years) • Group C: No heparin (n=122) (9.0 pt years) Slaughter MS, Yoshifumi N, John R, et al. Post-operative heparin may not be required for transitioning patients with a HeartMate II left ventricular assist system to long-term warfarin therapy. J Heart Lung Transplant. 2010;29:616-24.

14. Percutaneous Lead Placement And Management The HeartMate II percutaneous lead diameter has been minimized to reduce infection risk and incorporates polyester velour to promote skin ingrowth. Best practices for percutaneous lead tunneling and immobilization have been established, leading to remarkable reductions in infection. • Percutaneous lead externalized through the abdominal wall Pelz GB, Hashmi ZA, Moraca RJ, et al. ISHLT, April 2010. Slaughter MS, Pagani FD, Rogers JG, et al. Clinical management of continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant. 2010;29:S1-39.

15. Outpatient Blood Pressure Management Continuous flow LVADs such as the HeartMate II represent an entirely new physiology • Patients that have diminished pulse pressure frequently require a doppler • Goal is to maintain mean arterial BP of 70-80 mmHg, not to exceed 90 mmHg • Use of Doppler for measurements has improved • Managing blood pressure will optimize cardiac support and may reduce hypertension-related stroke Slaughter MS, Pagani FD, Rogers JG, et al. Clinical management of continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant. 2010;29:S1-39.

16. Additional Factors Contributing To Improving Trends In Adverse Events • Improved timing of patient referral • Better patient selection • Enhanced implantation techniques • Improved post-op patient management • More experienced patient care teams and increased knowledge of continuous-flow physiology

17. HeartMate II—Ready For Usage In A Broad Patient Population • Increased knowledge of new continuous-flow pathophysiology • Well designed and reliable device • Low adverse event rates • Full set of patient management guidelines