Risk Factors for Adverse Outcome after HeartMate II

Jennifer Cowger, MD, MS

St. Vincent Heart Center of IndianaAdvanced Heart Failure, Transplant, & Mechanical Circulatory

Support

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)

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

HMII Survival

1. Starling et al. JACC 2011;57:1890-92. Jorde, JACC 2014;63:1751-7.

HMII-BTT PostFDA1 HMII-DT PostFDA2

85% 1YRn=169 pts 74% 1YR

n=133 pts

Preoperative Correlates of Mortality for HMII

Preop HMII Risk Correlates

HMRS1 MELD2 Other- univariable1,3

Age Cr Cr RV failure PreopMCS

Albumin INR INR Vasopressors Female Sex

Center Volume Bilirubin INTERMACS profile

Destination Therapy

MELD = 9.57(logeCreatinine) + 3.78(logeBilirubin) + 11.2(logeINR) + 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;33:359-652. Cowger Matthews Circ 2010;121:214-20.

Frailty3

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

Postoperative Contributors to HMII Mortality

AE for HMII by Device IndicationPost-FDA BTT(n=169)

n (event rate) Post-FDA DT(n=247)

n (event rate)

Bleeding 75 (1.44) Bleeding 133 ( 0.84)

Infection 78 (1.00) Infection 186 (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 Failure 26 (0.18) Rt Heart Failure 44 (0.18)

Renal Failure 17 (0.13) Renal Failure 44 (0.15)

Hemolysis 5 (0.04) Hemolysis 16 (0.06)

Pump thrombosis Pump Thrombosis 9 (0.03)

Starling et al. JACC 2011;57:1890-9Uriel, JACC 2014;63:1751-7

Device Exchange

Increased Cumulative Incidence of HMII Device XC for Any Cause

Kirklin et al. JHLT 2014;33;12-22.

Device XC for ANY Cause increases Mortality

Kirklin et al. JHLT 2014;33;12-22.

HMII Device XC Increase: Driven by Thrombosis

Kirklin et al. JHLT 2014;33;12-22.

N=382 events in 6910

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

Surgical Technique and HMII Pump Migration

Taghavi, Ann Thoracic Surg 2013;96:1259-65

HMII Pump Position and Thrombosis

Inflow Angle Outflow Angle Pump Pocket Depth

Taghavi, Ann Thoracic Surg 2013;96:1259-65

Inflow Canula Angle & Thrombosis

Cannula 0.8 cm wide Ong et al. Theoretical Biology and Medical Modelling 2013;10:35

Inflow cannula depth and “washing”

ΔP=20 mmHg

Graft complications

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

Risk Correlates for Stroke

Hemorrhagic

• 1Female (HR 1.9 [1.1, 3.1])• 1Age (HR 1.9 [1.2, 3.2])

Ischemic

• 1Female (HR 1.8 [1.1, 3.3])• 1Diabetes (HR 2.0 [1.2, 3.3])• 2LDH >600 (HR 3.6 [1.6,8.0])

1. Boyle JACC 2014;63:8802. Cowger JHLT 2014. ≤65 >65≤65 >65

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/ppyBunte, JACC 2013;62:2188

Boyle JACC 2014;63:880

Bleeding on HMII

Early bleeding:• Thoracic and undetermined

Late bleeding: •GI and CNS Hazard function

Bunte, Jacc 2013;62:2188

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 ↑AVM1. Bunte, JACC 2013;62:2188

2. Boyle JACC 2014;63:880

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

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