Recent Trials With Durable LVADs: Is There a Superior

Device?

Francis D. Pagani MD PhDOtto Gago MD Endowed Professor of Cardiac Surgery

Michigan Medicine

HeartMate 3 HeartMate II HVADApproved “Short Term” 2017 Approved BTT 2008 Approved BTT 2012

Approved DT 2010 Approved DT 2017

Current Device Landscape 2018

Recent IDE Clinical Trials in MCS

•HeartMate II Pivotal Trial for Bridge to Transplant (2008) and Destination Therapy (2010)

•ADVANCE- Pivotal Trial for HVAD for Bridge to Transplant Indication

(2012)•ENDURANCE I and ENDURANCE Supplemental Trial

- Pivotal Trial for HVAD for Destination Therapy (2017)•MOMENTUM 3

- Pivotal Trial for HeartMate 3 for Short Term and Long Term Use (2017)

HeartMate II HVADversus

5

Primary endpoint:

• Survival free of disabling stroke (mRS < 4 at 24 weeks post stroke) on the originally implanted device or transplanted or explanted due to myocardial recovery

ENDURANCE TRIAL

ENDURANCE TRIAL Primary Endpoint Overall Survival

Stroke Risk Factor Multivariable Analysis (HVAD)

8

-10 0 10 20 30 40 50 60

MAP (> 90 mmHg)

INR (≤ 2)

ASA (≤ 81 mg)

Odds Ratio P-value14.1 <0.0001

3.0 0.002

2.2 0.034

Statistically significantly more HVAD patients (7.3%, 0.07 EPPY) had a sub-therapeutic INR <2.0 compared to control patients (2.2%, 0.02 EPPY), P=0.004.

Endurance Supplemental Trial• The primary endpoint was the

incidence of neurologic injury (defined as any stroke with an MRS >0 at 24-weeks post-stroke or any transient ischemic attack (TIA) or spinal cord infarct) at 12 months, including only time on the originally implanted LVAD.

• Strokes with MRS = 0 at 24 weeks (n=13 for HVAD, n=5 for control) were not included in the primary endpoint of neurological injury

• Intervention: BP Management for the HVAD arm

Milano et al. ISHLT April 2017versus

76%87%

70% 66% 72%79% 83%

53% 54% 54%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Perc

ent o

f Sub

ject

s

B.

>100

96-100

91-95

86-90

<=85

HeartWare HVAD Control LVAD

Endurance Supplemental Trial

Milano et al. ISHLT April 2017versus

65

70

75

80

85

90

Baseline Discharge 3 Months 6 Months 12 Months

Aver

age

MAP

(mm

Hg)

A.

ENDURANCE HeartWare HVAD

ENDURANCE Control LVAD

ENDURANCE Supplemental HeartWare HVAD

ENDURANCE Supplemental Control LVAD

p = 0.0003

p = 0.0001 p = 0.0001 p = 0.0001

Endurance Supplemental Trial

Milano et al. ISHLT April 2017

Endurance Supplemental Trial

Milano et al. ISHLT April 2017

Adverse Event

Study DeviceN=308

Control DeviceN=157

P valuePatients with

eventn (%)

No. of eventsPatients with event n (%)

No. of events

Device Malfunction/Failure 74 (24.0%) 107 38 (24.2%) 47 >0.99

Hemolysis 4 (1.3%) 5 9 (5.7%) 9 0.01

StrokeIschemic Cerebrovascular EventHemorrhagic Cerebrovascular Event

TIA

52 (16.9%)40 (13.0%)16 (5.2%)13 (4.2%)

75581713

23 (14.6%)12 (7.6%)11 (7.0%)1 (0.6%)

2514111

0.600.090.530.04

Pump replacementExchange for pump thrombosis

16 (5.2%)14 (4.5%)

NA18 (11.5%)16 (10.2%)

NA0.020.03

Endurance Supplemental Trial Secondary Endpoint:(Stroke-free survival (Modified Rankin Score <4 at 24-weeks post-stroke) at two years, defined as

alive on the originally implanted device, transplanted or explanted due to patient recovery)

Milano et al. ISHLT April 2017

HeartMate II HeartMate 3versus

HeartMate 3 Engineering

MOMENTUM 3 TRIAL•The primary end point was a composite of survival free of

disabling stroke (Modified Rankin Score < 4) or survival free of reoperation to replace or remove the device (for reasons other than recovery or transplant) at 6 months after implantation.

PRIMARY OUTCOME

HeartMate 3: US MOMENTUM TRIALShort Term Cohort: 6 Months

Primary Endpoint Overall Survival

Circulation. 2017;135:00–00. DOI: 10.1161/CIRCULATIONAHA.117.028303

Circulation. 2017;135:00–00. DOI: 10.1161/CIRCULATIONAHA.117.028303

HeartMate 3 HVADApproved “Short Term” 2017 Approved BTT 2012

Approved DT 2017

versus

Important Challenges

• Stroke-Technology goal < 5%

• Device-related infection• Device thrombosis

Summary• 2017 was a progressive year for durable VAD therapy

-Optimism stemming from continued improvements in technology

-The importance of new technology significantly reducing pump thrombosis can not be understated

-Important understanding of how management practices can influence outcomes (i.e., BP control)

• Centrifugal pumps will dominate clinical use• Continued dissemination/diffusion of the therapy• Stroke and device-related infections remain important

barriers into the less ill population

Role: SpeakerDate: Thursday, March 8, 2108Session: Plenary Session: Hot Topics in Mechanical Circulatory Support for Heart and LungTitle: Recent Trials With Durable LVADs: Is There a Superior Device?Time: 8:10 a.m. - 8:30 a.m.

Dear Dr. Pagani,

We look forward to your participation in the AATS Mechanical Circulatory Support Symposium: 21st Century State of the Art Treatment of Heart and Lung Failure, taking place March 8 - 9, 2018 at the Marriott Marquis Houston in Houston, Texas.

Attached is a copy of the program agenda listing your presentation(s) date(s), time(s) and title(s). Your role for each is listed below.

Role: SpeakerDate: Thursday, March 8, 2108Session: Plenary Session: Hot Topics in Mechanical Circualtory Support for Heart and LungTitle: Recent Trials With Durable LVADs: Is There a Superior Device?Time: 8:10 a.m. - 8:30 a.m.

Role: ModeratorDate: Thursday, March 8, 2108Session: Concurrent Session IIIa: Patient Selection and Optimization for Durable MCS DevicesTime: 1:30 p.m. - 3:00 p.m.

Role: ModeratorDate: Friday, March 9, 2018Session: Concurrent Session VIIa: Debates on Controversial SubjectsTime: 9:45 a.m. - 10:45 a.m.

As you prepare your presentation slides, please keep in mind the following:•All Relevant Financial Relationships must be disclosed to learners prior to the start of the live activity. A Disclosure Statement slide must be included as the second slide for all presentations.•AATS will be using 16:9 Wide Screens. Instructions for formatting slides wide screen are attached.•You will NOT have access to “speaker notes” view in your session room – please bring a hardcopy of your notes, if needed.•Laptops are NOT allowed to be connected to the podium monitor- please bring a copy of your presentation on a USB drive.

Presentation Check In: