Download HeartMate 3 Fully Magnetically Levitated LVAD for the Treatment of

HeartMate 3
Fully Magnetically Levitated LVAD for
the Treatment of Advanced Heart
Failure:
Results from the CE Mark Trial
Ivan Netuka, MD, Ph.D.
IKEM, Prague
Czech Republic
Principal Investigators and Sites
Friedhelm Beyersdorf, MD, PhD, Universitäts-Herzzentrum Freiburg
Bad Krozingen (Germany)
Jens Garbade, MD, PhD, Herzzentrum Leipzig (Germany)
Thomas Krabatsch, MD, PhD, Deutsches Herzzentrum Berlin (Germany)
Silvana Marasco, MD, The Alfred Hospital (Australia)
Michiel Morshuis, MD, Herz- und Diabeteszentrum NRW Clinic (Germany)
Ivan Netuka, MD, PhD, IKEM (Czech Republic)
Yuriy Pya, MD, National Research Center Cardiac Surgery (Kazakhstan)
Vivek Rao, MD, PhD, Toronto General Hospital (Canada)
Jan Schmitto, MD, PhD, Medizinische Hochschule Hannover (Germany)
Daniel Zimpfer, MD, PhD, Medical University Vienna (Austria)
Relevant Financial Relationship
Disclosure Statement
I will discuss investigational use of devices.
The following relevant financial relationships exist
related to this presentation:
Ivan Netuka, MD, PhD: Surgical Proctor and Consultant
to Thoratec Corporation, U.S.A.
Study sponsored and conducted by:
Thoratec Corporation, U.S.A.
HeartMate 3: Innovative Device Design
Full MagLev™ Flow Technology
Wide range of flow (2-10 L/min)
Artificial pulse
Larger, consistent pump gaps designed to reduce shear stress
™Full MagLev is a trademark of Thoratec Corporation
Study Overview
HeartMate 3 CE Mark Study was the first human
experience with the HeartMate 3 LVAS
Prospective, multi-center and non-randomized study
Primary objective: performance and safety at 6 months
Single entry criteria: both Bridge to Transplant (BTT) and
Destination Therapy (DT) patients
50 patients implanted in 10 centers in 6 countries
Enrollment period: June - November 2014
Study Endpoints
Primary Endpoint:
Comparison of 6-month survival to a performance goal (PG)
- HeartMate II patients in INTERMACS Registry (2012-14)
- Patients matched for age, INTERMACS profile, LVEF and excluded for
IABP usage
Secondary Endpoints:
Comparison of 6-month survival to Seattle Heart Failure Model
(SHFM) predicted survival
Adverse event rates
Functional status (NYHA Class Improvement and 6MWT test)
Quality of life (EQ-5D-5L)
Key Study Criteria
Inclusion Criteria:
NYHA IIIB or IV, or ACC/AHA Stage D
LVEF < 25%
CI ≤ 2.2 L/min/m2, while not on inotropes
Patients must meet one of the following:
- On Optimal Medical Management (OMM), based on current practice
guidelines for at least 45 out of last 60 days and are failing to respond
OR
- Inotrope dependent/unable to wean from inotropes
OR
- Listed for transplant
Exclusion Criteria:
Similar to previous VAD studies
Demographics
Parameter
N = 50
Age (years)
59 ± 13
Male
90%
BSA (m2)
2.0 ± 0.2
Ischemic etiology (%)
44%
Indication:
Bridge to Transplantation 27 (54%)
Destination Therapy 23 (46%)
INTERMACS profile:
Profile 2 5 (10%)
Profile 3 21 (42%)
Profile 4 20 (40%)
Profile 5 3 (6%)
Profile 6 1 (2%)
Baseline Hemodynamics &
Laboratory Values
Variable
N = 50 (Mean ± SD)
Pulmonary Capillary Wedge Pressure (mmHg)
22 + 9
Pulmonary Arterial Systolic Pressure (mmHg)
51 + 19
Central Venous Pressure (mmHg)
10 + 6
Cardiac Index (L/min/m2)
1.8 + 0.5
Total Bilirubin (mg/dl)
1.1 + 0.6
Blood Urea Nitrogen (mg/dl)
26 + 15
Creatinine (mg/dl)
1.3 + 0.4
Pre-Operative Risk Factors
Risk Factor
Inotropes
n (%)
29 (58%)
Stroke
2 (4%)
TIA
4 (8%)
Previous sternotomy
Left ventricular aneurysm
10 (20%)
4 (8%)
Diabetes
12 (24%)
ICD/CRT-D
39 (78%)
Implant & Patient Management
Implantation technique:
Median sternotomy on CPB
Outflow graft attachment to ascending aorta
42% concomitant cardiac surgical procedures
Anticoagulation:
Vitamin K antagonist (recommended INR 2.0 – 3.0) plus
Antiplatelet (Aspirin)
Median INR through support: 2.3 (interquartile range 1.9 – 2.7)
Primary Endpoint Analysis:
Comparison of 6-month survival to PG
HeartMate II INTERMACS Performance Goal (PG): 88%
HeartMate 3 six-month survival on LVAD support: 92%
HeartMate 3 exceeded the PG - primary endpoint met
30-day survival = 98%
6-month HeartMate 3 Actual Survival vs.
SHFM Predicted Survival on Medical Management
1.00
HM3 actuarial survival
92%
Percent Survival
0.90
Estimated SHFM
78%
0.80
0.70
Estimated hazard ratio for the HM3 = 0.34
P = 0.0093
0.60
0.50
0
1
2
3
4
5
Months
HeartMate 3 reduced the 6-month mortality risk by 66%
6
Outcomes Through 6 Months
8% (4/50) patients expired within 6 months:
Cardiac arrest after ischemic stroke (day 19)
Multi-organ failure with termination of life support (day 144)
Circulatory failure after CT contrast media anaphylaxis (day 48)
Suicide (day 113)
4% (2/50) patients transplanted prior to 6-months:
Intended transplants, day 50 & 132
Patients alive and well to date
Outcomes Through 6 Months
8% (4/50) patients expired within 6 months:
Cardiac arrest after ischemic stroke (day 19)
Multi-organ failure with termination of life support (day 144)
Circulatory failure after CT contrast media anaphylaxis (day 48)
Suicide (day 113)
4% (2/50) patients transplanted prior to 6-months:
Intended transplants, day 50 & 132
Patients alive and well to date
All Adverse Events within 6 months
Days 0 – 30
(n=50)
Event
Bleeding
Requiring Surgery
GI
Any Infection
Sepsis
Driveline
Stroke
Ischemic
Hemorrhagic
Neurologic Dysfunction*
Right Heart Failure
Requiring RVAD
Pump Malfunction
Pump Thrombosis
Hemolysis
*TIA, seizures
#
Pts
15
6
2
10
4
1
2
2
0
2
4
2
0
0
0
%
Pts
30%
12%
4%
20%
8%
2%
4%
4%
0%
4%
8%
4%
0%
0%
0%
#
Events
19
6
2
14
4
1
2
2
0
2
4
2
0
0
0
Days 0 – 180
(n=50)
#
Pts
19
7
4
18
8
5
6
4
2
4
5
2
0
0
0
%
Pts
38%
14%
8%
36%
16%
10%
12%
8%
4%
8%
10%
4%
0%
0%
0%
#
Events
35
8
6
28
8
5
6
4
2
4
5
2
0
0
0
Key Adverse Event: GI Bleeding
Days 0 – 30
(n=50)
Event
Bleeding
Requiring Surgery
GI
Days 0 – 180
(n=50)
#
Pts
15
6
%
Pts
30%
12%
#
Events
19
6
#
Pts
19
7
%
Pts
38%
14%
#
Events
35
8
2
4%
2
4
8%
6
4 patients had GI Bleeding events (8%)
Incidence of GI bleeding in continuous flow LVADs 11-25%
GI bleed event rate lower than rates published in literature
Key Adverse Event: Stroke
Days 0 – 30
(n=50)
Event
Stroke
Ischemic
Hemorrhagic
#
Pts
2
2
0
%
Pts
4%
4%
0%
Days 0 – 180
(n=50)
#
Events
2
2
0
#
Pts
6
4
2
%
Pts
12%
8%
4%
#
Events
6
4
2
4 Ischemic strokes:
2 within 30-days, procedural related events (MRS >3):
- 1 implant issue with difficulty engaging inflow conduit (day 1)
- 1 post anaphylactic shock from contrast media (day 23)
2 later strokes (day 49,176), MRS 1, one associated with infection,
patients ongoing
2 Hemorrhagic strokes:
2 later strokes (day 81, 103), MRS > 3
- 1 procedural related, post TAVI procedure (day 81)
- 1 intracerebral bleed in multiorgan failure patient (day 103)
Key Adverse Events: No Pump Malfunction,
Thrombosis, Hemolysis
Days 0 – 30
(n=50)
Event
Pump Malfunction
Pump Thrombosis
Hemolysis
#
Pts
0
0
0
%
Pts
0%
0%
0%
#
Events
0
0
0
Days 0 – 180
(n=50)
#
Pts
0
0
0
%
Pts
0%
0%
0%
#
Events
0
0
0
Incidence of pump thrombosis in currently used
continuous flow LVADs 6-12%
Key Adverse Events: No Pump Malfunction,
Thrombosis, Hemolysis
Days 0 – 30
(n=50)
Event
Pump Malfunction
Pump Thrombosis
Hemolysis
#
Pts
0
0
0
%
Pts
0%
0%
0%
#
Events
0
0
0
Days 0 – 180
(n=50)
#
Pts
0
0
0
%
Pts
0%
0%
0%
#
Events
0
0
0
Incidence of pump thrombosis in currently used
continuous flow LVADs 6-12%
Improvement in NYHA Class
By 6 months 83% patients NYHA I or II
Significant improvement (p<0.0001) over baseline
Improvement in 6MWT
28% of the patients unable to walk at baseline due to illness
At 6 months median 231 meters improvement over baseline
Improvement in Quality of Life (EuroQol)
Significant improvement from baseline to Month 3 & 6
Limitations
Non-randomized study
Performance goal – pre-specified, not propensity score
matched population
Direct comparison to contemporary publications
difficult, as both BTT and DT patients enrolled
Conclusions
Positive first experience with HeartMate 3
Primary endpoint met: 92% six-month survival exceeded
the performance goal of 88%
No hemolysis, pump thrombosis or pump exchange
Adverse event types and rates consistent with, or lower than
expected complication rates
Functional status and quality of life scores - progressive and
sustained improvement
Patient follow-up in the CE Mark Study through 2 years;
U.S. MOMENTUM 3 Study* currently enrolling
*Randomized HeartMate II vs HeartMate 3; 1,028 patients