Download LionHeart LVAS - Penn State Hershey Medical Center

Destination Therapy with a Totally
Implantable Left Ventricular Assist Device
System: Results of the LionHeart CUBS Trial
John P. Boehmer, M.D.
Penn State College of Medicine
Aly El-Banayosy, Reiner Koerfer, Latif Arusoglu, Bad Oeynhausen Heart Center, Bad Oeynhausen,
Germany; Rolald Hetzer, Yuguo Weng, Michael Jurmann, Deutsches Herzzentrum Berlin, Berlin,
Germany; Mario Vigano, Mauro Rinaldi, Policlinico San Matteo, Pavia, Italy; Alain Pavie, Pascal
LePrince, La Pitie Hospital, Paris, France; Ernest Wolner, Georg Wieselthaler, University of Vienna,
Vienna, Austria; Ludwig vonSegesser, CHUV Hospital Vaudois, Lusanne, Switzerland; Thorsten
Whaler, Ulrich Franke, Klinikum der Friedrich Schiller Universitat, Jena, Germany; Walter E Pae, Jr;
Penn State College of Medicine, Hershey, PA
LionHeart LVAS
• Destination Therapy
Device
• Evolution of Thoratec
Pneumatic VAD
• Fully Implanted with
Transcutaneous
Energy Transmission
(no percutaneous lead)
• Fully Automatic
Cardiac Output Control
• Modular Design
Clinical Utility Baseline Study
(CUBS)
Purpose…. to determine the safety and
performance of the LionHeart LVAS to
serve as a permanent method of
circulatory support for patients with endstage heart failure who are ineligible for
heart transplantation
CUBS Trial:
Overview and Duration
• Prospective, single-arm, multicenter study
• Enroll 30-40 patients at European centers
with at least one year follow-up
• Primary endpoints safety and performance
based on comparison to historical controls
• Study period was from October 1999 to
December 2002….3960 pt. days
Patient Selection CUBS Trial
Key Inclusion Criteria
• LVEF < 30% within 90 days prior to
enrollment
• NYHA class IV heart failure under tailored
medical management
• Heart failure for 6 weeks
• Peak O2 by CPX < 14cc/kg/min or unable to
exercise
• Ineligible for heart transplantation
• Good communication skills
Patient Selection CUBS Trial
Key Exclusion Criteria
• BSA < 1.5 m2 or > 2.25 m2
• Severe COPD (FEV1 < 1.2 L/min or <40%
predicted)
• Fixed pulmonary HTN (> 6 Woods units)
• Severe renal dysfunction (Cr > 3.0 mg/dL or
requiring ongoing hemodialysis)
• CVA within past 6 months or impending CVA
• Inability to relocate within 4 hours of the
implanting site
Patient Selection CUBS Trial
Changes to Inclusion/Exclusion Criteria
• Inclusion Criteria
– Remove poor prognostic indicators (simplify
screening)
– Remove criterion for low CI (simplify screening)
• Exclusion Criteria
– Renal dysfunction modified to serum Cr < 2.0
mg/dL within 7 days of implant and no
hemofiltration in that time period
– Add criterion for carotid artery duplex without
hemodynamically significant lesion
CUBS: Patients
• 26 male patients enrolled
• Three were ineligible, but received the device
– CVVHD at time qualifying creatinine was drawn
– Pulmonary hypertension > 6 Wood units
– Metastatic thyroid cancer with poor prognosis
• Reasons not eligible for heart transplant
– Age > 65 years
– Systemic lupus erythematosis
– Insulin dependent diabetes with end-organ
dysfunction
CUBS Study Group
• Bad Oeynhausen Heart Center…Korfer, El-Banayosy,
Arusoglu….9
• Deutsches Heart Center Berlin…Hetzer, Weng,
Jurmann….3
• Policlinico san Matteo, Pavia…Vigano, Rinaldi…4
• LaPitie Hospital, Paris.. Pavie, LaPrince… 3
• University of Vienna… Wolner, Wieselthaler… 1
• CHUV University Hospital Vaudois, Lausanne…
vonSegesser….1
• Klinikum der Friedrich Schiller Universitat,
Jena…Whaler, Franke….1
CUBS: Patients
LionHeart
CUBS
N = 26
LionHeart
CUBS
N = 23
REMATCH
OMM
N = 61
REMATCH
LVAD
N = 68
64 + 6.2
65 + 4.2
68 + 8.2
66 + 9.1
Male (%)
100
100
82
78
Ischemic (%)
58
61
69
78
LVEF
22 + 5.0
22 + 5.1
17 + 4.5
17 + 5.2
BP systolic
(mm Hg)
104 + 17
104 + 18
103 + 17
101 + 15
BP diastolic
(mm Hg)
62 + 12
62 + 12
62 + 11
61 + 10
Age (years)
CUBS: Patients
LionHeart
CUBS
N = 26
LionHeart
CUBS
N = 23
REMATCH
OMM
N = 61
REMATCH
LVAD
N = 68
PCWP (mm Hg)
24 + 8.0
24 + 8.3
24 + 7.4
25 + 9.9
CI (L/min/m2)
1.7 + 0.4
1.7 + 0.4
2.0 + 0.6
1.9 + 1.0
ACEI (%)
89
87
51
62
Beta blocker
68
72
20
24
Inotropic agents (%)
52
45
72
65
9.5 + 3.0
9.4 + 2.9
--
9.2 + 2.0
Peak VO2
Survival
Survival in the CUBS Trial
100
90
80
70
60
50
40
30
20
10
0
41% (20-61%)
34% (13-55%)
0
6
12
18
Months
24
30
Survival in the CUBS Trial
REMATCH
CUBS
100
100
80
41%
34%
60
40
20
Survival (%)
Survival (%)
80
60
LV assist device
40
20
25%
Medical therapy
0
0
6
12
18
Months
24
30
23%
52%
0
0
6
12
8%
18
Months
24
30
Survival Conditional on Discharge
2 Year Survival
120 Day Survivors
Percent Survival
100
90
80
70
60
50
40
30
20
10
0
0
4
8
12
Months
16
20
24
CUBS: Cause of Death
Sepsis
Device failure
Cerebrovasc. disease
Other cardiovascular
Cardiac procedure
Perioperative bleeding
Non-periop bleeding
Total
<6 mo
>6 mo
Total
3
1
4
0
2*
2*
0
0
0
4
1
5
1
0
1
2
0
2
2
0
2
12
4
16
* - Sac failures occurred beyond 2 years, as anticipated
Serious Adverse Events*:
CUBS
OVERALL
DEVICE RELATED
Freq.
N
Rate
Freq.
N
Rate
Neurologic dysfunction
12
11
0.6924
1
1
0.0577
Non-neurologic bleed
8
7
0.4616
0
0
0
Perioperative bleed
3
3
0.1731
3
3
0.1731
Local infection
4
4
0.2308
4
4
0.2308
Pump pocket infection
1
1
0.0577
1
1
0.0577
Sepsis
3
3
0.1731
1
1
0.0577
Device Failure
2
2
0.1154
2
2
0.1154
Events
*Rate/pt.-year
Serious Adverse Events*:
REMATCH LVAD vs. CUBS
LionHeart
CUBS
(N=23)
REMATCH
LVAD
(N=68)
Neurologic dysfunction
0.69
0.39
Non-neurologic bleeding
0.40
0.56
Perioperative bleed
0.17
0.46
Local infection
0.23
0.39
Pump pocket infection
0.06
0.14
Sepsis
0.17
0.60
Device failure
0.12
0.08
EVENT
*Rate/pt.-year
CUBS:
Adverse Events Related to LVAD
CUBS
N = 23
0.34
REMATCH
N = 68
Perioperative bleeding
0.23
0.46
Device infection
0.17
0.41
Infection of pump interior
0.00
0.23
LVAD malfunction
*Rate/pt.-year
0.75
CUBS: Major Serious AEs by Type
0.35
Infection AEs
Rate AE/30 pt days
0.3
Bleeding AEs
0.25
Neuro
0.2
0.15
0.1
0.05
0
0-30 days
31-90 days
91-180 days
Days from enrollment
181-365 days
Summary: Clinical Experience
• A compliance
chamber is feasible
• Transcutaneous
energy transmission
of this magnitude is
possible
• Excellent mobility
including swimming
and bathing
Summary: Clinical Experience
• Overall adverse event rate appears
comparable to prior benchmark
• Excellent device reliability – two sac failures
at 2 & 2.5 years, one motor controller failure,
but importantly, no pump changes up to two
years (expected sac life)
• Minimal device related pocket infections
• Actuarial survival approximately 86% at 1
month, 45% at 6 months, 41% at 1year and
34% at 2 years