recent trials with durable lvads: is there a superior device?...endurance supplemental trial • the...
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Recent Trials With Durable LVADs: Is There a Superior
Device?
Francis D. Pagani MD PhDOtto Gago MD Endowed Professor of Cardiac Surgery
Michigan Medicine
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HeartMate 3 HeartMate II HVADApproved “Short Term” 2017 Approved BTT 2008 Approved BTT 2012
Approved DT 2010 Approved DT 2017
Current Device Landscape 2018
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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)
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HeartMate II HVADversus
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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
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ENDURANCE TRIAL Primary Endpoint Overall Survival
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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.
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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
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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
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Endurance Supplemental Trial
Milano et al. ISHLT April 2017
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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
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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
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HeartMate II HeartMate 3versus
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HeartMate 3 Engineering
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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.
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PRIMARY OUTCOME
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HeartMate 3: US MOMENTUM TRIALShort Term Cohort: 6 Months
Primary Endpoint Overall Survival
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Circulation. 2017;135:00–00. DOI: 10.1161/CIRCULATIONAHA.117.028303
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Circulation. 2017;135:00–00. DOI: 10.1161/CIRCULATIONAHA.117.028303
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HeartMate 3 HVADApproved “Short Term” 2017 Approved BTT 2012
Approved DT 2017
versus
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Important Challenges
• Stroke-Technology goal < 5%
• Device-related infection• Device thrombosis
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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
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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.
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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: