1. Risk Factors for Adverse Outcome after HeartMate II Jennifer Cowger, MD, MS St. Vincent Heart Center of Indiana Advanced Heart Failure, Transplant, & Mechanical Circulatory Support

2. Relevant Financial Relationship Disclosure Statement Jennifer A Cowger, MD, MS I will not discuss off label use and/or investigational use of the following drugs/devices: LVAD The following relevant financial relationships exist related to my role in this session: Consulting- Thoratec (unpaid)

3. FDA Approved Mechanical Circulatory Support Options in U.S in 2014 Others undergoing clinical and preclinical study HeartMate II: 17000+ implants to date world wide HeartWare HVAD Novacor

4. HMII Survival 1.Starling et al. JACC 2011;57:1890-9 2.Jorde, JACC 2014;63:1751-7. HMII-BTT PostFDA 1 HMII-DT PostFDA 2 85% 1YR n=169 pts 74% 1YR n=133 pts

5. Preoperative Correlates of Mortality for HMII

6. Preop HMII Risk Correlates HMRS 1 MELD 2 Other- univariable 1,3 AgeCr RV failurePreopMCS AlbuminINR VasopressorsFemale Sex Center VolumeBilirubinINTERMACS profile Destination Therapy MELD = 9.57(log e Creatinine) + 3.78(log e Bilirubin) + 11.2(log e INR) + 6.43 HMRS = (0.0274 x [age]) – (0.723 x [albumin g/dl]) + (0.74 x [creatinine]) + 1.136 x [INR]) + (0.807 x [center volume <15]) 1.Cowger et al J Am Coll Cardiol 2013;61:313-21 3. Dunlay, JHLT 2014;33:359-65 2.Cowger Matthews Circ 2010;121:214-20. Frailty 3

7. Predictors of Long-Term Survival Age (HR 1.3 [1.1-1.5]/10 yrs, p 0.003) Center volume >15 (HR 1.6 [1.0-2.6]) Operative Success Cowger JACC 2013;61:313-21 Survival controlling for above risks

8. Postoperative Contributors to HMII Mortality

9. AE for HMII by Device Indication Post-FDA BTT (n=169) n (event rate)Post-FDA DT (n=247) n (event rate) Bleeding75 (1.44)Bleeding133 ( 0.84) Infection78 (1.00)Infection186 (0.99) Stroke Hemorrhagic Ischemic 11 (0.08) 2 (0.01) 8 (0.06) Stroke Hemorrhagic Ischemic 29 (0.08) 19 (0.03) 10 (0.05) Rt Heart Failure26 (0.18)Rt Heart Failure44 (0.18) Renal Failure17 (0.13)Renal Failure44 (0.15) Hemolysis5 (0.04)Hemolysis16 (0.06) Pump thrombosisPump Thrombosis9 (0.03) Starling et al. JACC 2011;57:1890-9 Uriel, JACC 2014;63:1751-7 Device Exchange

10. Increased Cumulative Incidence of HMII Device XC for Any Cause Kirklin et al. JHLT 2014;33;12-22.

11. Device XC for ANY Cause increases Mortality Kirklin et al. JHLT 2014;33;12-22.

12. HMII Device XC Increase: Driven by Thrombosis Kirklin et al. JHLT 2014;33;12-22. N=382 events in 6910

13. HeartMate II: Device Configuration Flow through device impacted by: 1)Ao pressure: Hypertension 2)LVEDP: increased clot with higher LVEF or low LVEDP? 3)combined pressure loss across the inflow and outflow: graft kink, thrombus

14. Surgical Technique and HMII Pump Migration Taghavi, Ann Thoracic Surg 2013;96:1259-65

15. HMII Pump Position and Thrombosis Inflow Angle Outflow Angle Pump Pocket Depth Taghavi, Ann Thoracic Surg 2013;96:1259-65 Inflow Canula Angle & Thrombosis

16. Cannula 0.8 cm wide Ong et al. Theoretical Biology and Medical Modelling 2013;10:35 Inflow cannula depth and “washing”

17. ΔP=20 mmHg Graft complications

18. Neurologic Events 956 pts in BTT (n=405) and DT (n=551) trials Hemorrhagic stroke: 0.05 e/ppy Ischemic stroke: 0.04 e/ppy Boyle JACC 2014;63:880

19. Risk Correlates for Stroke Hemorrhagic 1 Female (HR 1.9 [1.1, 3.1]) 1 Age (HR 1.9 [1.2, 3.2]) Ischemic 1 Female (HR 1.8 [1.1, 3.3]) 1 Diabetes (HR 2.0 [1.2, 3.3]) 2 LDH >600 (HR 3.6 [1.6,8.0]) 1. Boyle JACC 2014;63:880 2. Cowger JHLT 2014. ≤65 >65

20. Major Bleeding During HMII Bunte et al (n=145) Single center study >3 u first postop week or any thereafter- 1.1 event/ppy Boyle et al (n=956) BTT and DT trial pts Bleeding > 2u- 0.67 event/ppy Bunte, JACC 2013;62:2188 Boyle JACC 2014;63:880

21. Bleeding on HMII Early bleeding : Thoracic and undetermined Late bleeding: GI and CNS Hazard function Bunte, Jacc 2013;62:2188

22. Risk factors for bleeding Age >65 yrs (HR 1.3 [1.1-1.6]) Preop HCT <31% (HR 1.31 [1.0-1.6]) ISCM (HR 1.35 [1.1-1.7]) Female sex (HR 1.45 [1.1-1.8) PA Systolic pressures: β=1.9 ±0.86 Bilirubin: β=0.71± 0.23 (p 0.002) ?Liver and RV dysfunction  ↑AVM 1. Bunte, JACC 2013;62:2188 2. Boyle JACC 2014;63:880

23. Conclusions HMII is has inherent design differences from other FDA approved devices –It is reasonable to expect different complication profiles Long term success on LVAD support is difficult to predict preoperatively and is impacted by –Operative success –Complications during VAD support –Pt comorbidities/frailty

24. Conclusions A better understanding of HMII complications will require granular data on: –Location and true burden of insitu clot formation at the time of all device explants –Preoperative comorbidities –center volume –Anticoagulation regimens