Download HeartWare HVAD: Risk Factors for Adverse Outcomes

HeartWare HVAD:
Risk Factors for Adverse Outcomes
Mark S. Slaughter, MD
Professor and Chair
Department Cardiovascular and Thoracic Surgery
University of Louisville
Disclosures
•
•
•
•
HeartWare, Inc: research grant support
Cormatrix: research grant support
Carmat: scientific advisory board
APK: research grant support
HVAD ADVANCE Bridge to
Transplantation Study Design
• Objective: To evaluate safety & efficacy of the HeartWare HVAD®
in patients listed for cardiac transplantation
• Multi-center, prospective, non-randomized, two arm study
– HVAD (N=140) vs. Control (INTERMACS™, N=499)
• Primary endpoint: Non-inferiority to control
• First BTT using contemporaneous VAD patients as control arm
(INTERMACS™ registry)
• Primary Endpoint:
– Success at 180 days – alive on original device, transplanted, or explanted for recovery (alive
60 days post removal)
– Kaplan-Meier Survival at 180 days
• 4 CAP Installments included (Total N=242)
Aaronson, et al. Circulation. 2012;125(25):3191-200
Slaughter, et al. J Heart Lung Transpl. 2013; 32: 675-683
Patient Demographics
BTT and CAP
(N = 382)
BTT
(N = 140)
CAP
(N = 242)
53.2 ± 11.7
53.3 ± 10.3
53.1 ± 12.5
Male sex (%)
71.2%
72.1%
70.7%
Race (%)
White
Black/African American
Hispanic/Other
68.1%
26.4%
5.5%
72.1%
22.9%
5.0%
65.7%
28.5%
5.8%
Body-mass index (kg/m2)
28. 2 ± 6.1
28.5 ± 6.0
28.0 ± 6.1
2.0 ± 0.3
2.1 ± 0.3
2.0 ± 0.3
Ischemic cause of heart failure (%)
38.0%
40.7%
36.4%
Left ventricular ejection fraction (%)
17.3 ± 7.3
18.0 ± 7.1
16.9 ± 7.3
Baseline Characteristic
Age (years)
Body surface area (m2)
Patient Demographics (continued)
Baseline Characteristic
BTT and CAP
(N = 382)
BTT
(N = 140)
CAP
(N = 242)
Pulmonary artery
pressure (mmHg)
Systolic
Diastolic
48.8 ± 14.5
24.1 + 8.4
51.0 ± 15.1
25.6 + 8.9
48.1 ± 14.3
23.6 ± 8.2
Arterial blood
pressure (mmHg)
Systolic
Diastolic
Mean
103.2 ± 15.3
63.5 ± 10.6
77.5 ± 11.0
103.3 ± 15.6
63.7 ± 11.2
76.2 ± 12.1
103.7 ± 15.2
63.4 ± 10.3
78.1 ± 10.4
2.2 ± 0.6
2.1 ± 0.6
2.2 ± 0.6
II
III
IV
0.5
3.4
95.8
0.7
3.6
95.0
0.4
3.3
96.3
1
2
3
4-7
5.5
34.8
40.6
19.1
5.0
27.9
42.9
24.3
5.8
38.8
39.3
16.1
Cardiac index
(liters/min/m2)
NYHA Class (%)
INTERMACS (%)
Kaplan Meier Survival in HVAD
BTT+CAP Clinical Trial
90%
Event Free Rate
84%
79%
71%
Days
0
Patient at risk 382
Month
Survival
100%
2
356
4
305
6
261
8
218
10
191
12
165
18
114
24
74
97%
94%
90%
89%
86%
84%
79%
71%
Success Outcomes (N=382)
Endpoint
Outcome at 6 months
Success
87.6%
Transplanted or Myocardial Recovery or Alive on original device
Alive on original device
66.5%
Transplanted
20.8%
Myocardial Recovery
0.3%
Died
8.2%
Exchanged
4.2%
Mean duration of support (incl. post exchange) = 423 days
Adverse Events in BTT+CAP (N=382)
N=382 with 406.6 Patient-Years of Support
Patients with
event, n (%)
Number of
Events
Event Rate
Ventricular Arrhythmia
77 (20.2)
101
0.25
Gastrointestinal Bleeding
59 (15.4)
108
0.27
Right Heart Failure (RHF)
129 (33.8)
149
0.37
RHF Requiring RVAD
15 (3.9)
15
0.04
Ischemic Stroke
26 (6.8)
31
0.08
Hemorrhagic Stroke
32 (8.4)
34
0.08
Device Exchange for
Suspected Thrombus
16 (4.2)
17
0.04
Driveline Infection
75 (19.6)
102
0.25
Sepsis
72 (18.8)
92
0.23
Renal Failure
39 (10.2)
46
0.11
Complication
Freedom from Thrombus Events
Freedom from any thrombus event: 6 months = 96%; 1 year = 92%
Freedom from exchange for thrombus: 6 months = 98%; 1 year = 95.4%
Time to any thrombus event
Time to exchange for thrombus
Najjar, et al. J Heart Lung Transpl. 2014; 33: 23-34 (e-pub ahead of print 13 Dec 2013)
Multivariate Risk Factors for VAD
Thrombus
Najjar, et al. J Heart Lung Transpl. 2014; 33: 23-34 (e-pub ahead of print 13 Dec 2013)
Freedom from CVA
Freedom from any ICVA: 6 months = 96%; 1 year = 93%; 2 years = 88%
Freedom from HCVA: 6 months = 95%; 1 year = 90%; 2 years = 86%
ICVA
HCVA
Manuscript in preparation (Teuteberg, et al.)
Infections in BTT+CAP
• 84% driveline infections were successfully managed with antibiotics
• Driveline infections had no adverse impact on survival
• 3.5% of patients with sepsis had a device exchange for VAD
thrombus within 1 - 4 days of a sepsis diagnosis.
• 16% of sepsis events were either concurrent with or were preceded
(within 10 days) by a urinary tract infection (UTI) with positive urine
cultures.
• 17.5% of patients with sepsis died due to sepsis-related events such
as neurological events and multisystem organ failure.
• 14% of all sepsis events were associated with a stroke event (stroke
within -1 to 6 days of sepsis). Of patients with a stroke and sepsis,
70% subsequently died due to sepsis-related neurological events and
associated multisystem organ failure.
• Manuscript recently accepted by JHLT in April 2014 (John, et al.)
Gastrointestinal Bleeding in BTT+CAP
• 15.9% (59/382) patients experienced a GI bleed. Overall, the
59 patients had 108 bleeding events that resulted in 0.27 EPPY
(range 1-7 events) with 2/3 experiencing a recurrent GIB.
• Most GI bleeds (>86%) occurred >30 days post implant.
• Despite interruptions in anticoagulation in 2/3 of patients with GI
bleeds, only 8.5% had any subsequent thrombotic events.
• The most common etiology of GI bleeding was arteriovenous
malformations
• There were no deaths directly related to GI bleeding, and no
difference in overall survival between patients with and without GI
bleeding events.
• Manuscript in preparation (Goldstein, et al).
Conclusions
• ADVANCE/CAP trial met study end points
• Adverse event profile may vary between axial vs.
centrifugal pumps
• New patient/device management strategies may
reduce HVAD related adverse events