Download Support Devices for Acute CHF Destination LVADs to exclude

Support Devices for Acute CHF
Destination LVADs to exclude Transplant
Expectations, Indications, Benefits ,Risks
Donna Mancini, MD
Mt Sinai School of Medicine
Conflict of Interest
• None
Refractory cardiogenic Shock
• 1. Use of temporary percutaneous devices in AHF/cardiogenic shock
• 2. Durable devices for Destination therapy
Cardiogenic Shock Definition (SHOCK Trial)
• Hypotension systolic BP < 90 mm Hg for > 30 min or mean BP 30 mm
Hg lower than baseline
• Need for pharmacologic or IABP support to maintain SBP > 90
• End organ hypoperfusion
•
•
•
•
•
Cool extremities
Urine output < 30 cc/hr
Altered mental status
Lactate > 2 mmol/l
Pulmonary congestion
• Hemodynamic criteria
• CI < 2.2 l/min/m2 and PCW >15 mm Hg
Etiology of Cardiogenic Shock
• Acute Myocardial Infarction
•
•
•
•
Large infarct
Moderate or small infarct w pre existing LV dysfn
Mechanical complication of MI- acute MR, VSD, LV rupture
RV infarct
• End Stage Cardiomyopathy
• Myocarditis
• Valvular Heart Disease
• Stress induced cadiomyopathy
• Cardiac Tamponade
Cardiogenic Shock
• AMI occurs in 1 million patients in US and 8 million patients annually
worldwide
• Cardiogenic Shock occurs in 4-12% of AMI patients
• 1 yr Mortality rate is about 65%
• IABP-SHOCK II trial failed to show 30 day survival benefit in AMI
patients w cardiogenic shock supported by IABP
• Shift now is to examine use of other percutaneous devices in these
patients
The downward spiral of refractory cardiogenic shock
SIRS
Shock Trial
Hochman JAMA 2001;285:190
SHOCK II Trial 2012
Thiele NEJM 2012;367:1287
Non Selective
NOS inhibitor
Cardiogenic Shock
IABP
ECMO
LV to Aorta
LA-Aorta
Short Term Mechanical Circulatory Support Devices
V-A
IABP
ECMO
TandemHeart
Impella
Afterload
Reduced
Increased
Increased
Neutral
LV stroke volume
Slight increase
Reduced
Reduced
Reduced
Coronary
perfusion
Slight increase
Unknown
Unknown
Unknown
LV pre-load
Slightly reduced
Reduced
Reduced
Slightly reduced
PCW pressure
Slightly reduced
Reduced
Reduced
Slightly reduced
Peripheral tissue
perfusion
No significant
increase
Improved
Improved
Improved
VA ECMO
Elastase EDV to ESP
EDP and arterial elastase
as ECMO flow
TPR
ECMO + IABP
Ecpella
J Am Coll Cardiol. 2015;66(23):2663-2674.
KVAD = ECMO+ mini LVAD
Koji Takeda Md, Phd
Axillary outflow
Oxygenator
Pulmonary
unloading
Centrimag pump
Femoral v.
drainage
RV unloading
LV apical cannula through
mini-thoracotomy
LV unloading
Tandem Heart
LA to Ao
J Am Coll Cardiol. 2015;66(23):2663-2674.
.
Effect of LV to arterial MCS
Impella; durable VADs
J Am Coll Cardiol. 2015;66(23):2663-2674.
Randomized trials of Percutaneous MCS vs IABP in AMI
Tandem Heart n=41
Tandem Heart n=33
Impella 2.5 n=26
3 trials totaling
100 patients
Reyentovich, A. et al. (2016)
Nat. Rev. Cardiol.
Randomized trials of Percutaneous MCS vs IABP in AMI
Reyentovich, A. et al. (2016)
Nat. Rev. Cardiol.
Guideline Recommendations of Short Term Mechanical
Assist Devices in Cardiogenic shock
ACC/AHA/SCAI
ESC/EACTS
IABP
Class IIA
Hemodynamic instability
after AMI
IIb
Hemodynamic
instability after AMI
ECMO
none
none
none
ECMO implantation
should be considered
for temporary support
in patients with acute
heart failure with
potential for functional
recovery following
revascularization.
Tandem Heart
IIB
Same as IABP
IIb
Routine use of
percutaneous
centrifugal pumps is not
recommended.
Impella
IIB
Same as IABP
none
none
Evolution of Heart Failure Classification
ACC/AHA Stages: One-way progression
A
Risk
B
Asx
Structural dx
D= IV sx
C
Sx ever
Refractory to
Optimal Med Rx
NYHA Symptom Class:
Back and forth
NYHA I
II
III
NYHA
IV
e.g. Tx, VAD,
Continuous
Inotropes only
indicated for
Stage D
INTERMACS
Profiles
INTERMACS: Interagency Registry for Mechanically
Assisted Circulatory Support
Green Bars
DT
LVAD vs Tx
LVAD
Body Size
Tx
Age
Still w limits All sizes
BSA<1.3 ??
No age limit 70
RV failure
RVSWI
PVR< 6 Wood U
Restrictive CM Inadequate
Yes
Urgent
Situations
Assess Neuro
Status
Yes
No
Yes
No
Patient Selection for VADs
• Severity of CHF
• INTERMACS; HFSS; Seattle HFM
• Exclude significant co-morbidity:
if unclear  support with short term device
• Assess need for biventricular support
• Assess need for short vs long term support
• Assess peri-operative risk
 No severe end-organ dysfunction/failure
 Ability to tolerate anticoagulant or antiplatelet therapieswithout plans for
correction
NYHA
CLASS
ADULT PROFILES
IV Ino
IABP/V
ent
Official Shorthand
INTERMACS
LEVEL 1
X
X
“Crash and burn”
IV
INTERMACS
LEVEL 2
X
X
“Sliding fast” on inotropes
IV
INTERMACS
LEVEL 3
X
“Stable” Continuous Ino-”Dependent”
*
IV
INTERMACS
LEVEL 4
Resting symptoms on oral therapy at
home.
ambul
IV
INTERMACS
LEVEL 5
“Housebound”,
Comfortable at rest, symptoms with
minimum activity ADL
ambuI
IV
INTERMACS
LEVEL 6
“Walking wounded”-ADL possible but
meaningful activity limited
IIIB
INTERMACS
LEVEL 7
Advanced Class III
III
HeartMate IITM LVAS
The HeartMate II LVAS (St. Jude Medical, Inc.) is a mechanical
bearing axial continuous-flow blood pump;
only device in the US approved for both Bridge-To-Transplant
(BTT) and Destination Therapy (DT) patients
Mehra MR, Naka Y, et al. Published Nov 16, 2016 at
NEJM.org
Estep J JACC 2015;66:1748
Estep J JACC 2015;66:1748
Adverse Events in ROADMAP
Adverse Events
OMM (n = 103)
LVAD (n = 94)
DT Trial§(EPPY)
Bleeding
1 (1) [0.02]
44 (47) [1.22]‡
GI bleeding
1 (1) [0.02]
29 (31) [0.76]‡‖
Driveline infection
—
9 (9.6) [0.14]‡
0.22
Pump thrombus
—
6 (6.4) [0.08]†
0.07¶
Pump exchange yr 1
—
4 (4.3)
2.10%
Stroke
2 (2) [0.02]
8 (8.5) [0.09]∗
0.08
Arrhythmias VT/VF
6 (5.8) [0.12]
17 (18.1) [0.23]∗
0.46
Worsening HF#
36 (35) [0.68]
10 (10.6) [0.12]‡
—
Rehospitalizations
64 (62) [1.43]
75 (79.8) [2.49]‡
2.64∗∗
Composite event rate††
39 (38) [0.83]
62 (66) [1.89]‡
Relative Risk (95% CI):
OMM/LVAD: 0.44 (0.35).56)
1.13
—
2.09
HeartMate 3TM LVAS Magnetic
HeartMate
II LVAS
Levitation Technology
•
•
•
Wide
blood-flow
passages
to reduce
shear stress
The
HeartMate
3 LVAS
(St. Jude
Medical,
Inc.) is a
centrifugal-flow, fully magnetically levitated blood pump
Frictionless with absence of mechanical bearings
engineered to minimize destruction of red blood cells and
Intrinsic Pulse designed tothrombosis
reduce stasis and avert thrombosis
Mehra MR, Naka Y, et al. Published Nov 16, 2016 at
NEJM.org
Target Population
• Patients with advanced heart failure and
severe limitations (NYHA IIIB or IV),
refractory to standard medical therapy and
deemed as necessary candidates for left
ventricular assist device implantation,
irrespective of the intended goal of pump
support (BTT or DT)
• Key exclusion criteria included planned
biventricular support, irreversible end-organ
dysfunction, or active infection
Study Design
Patient meets
MOMENTUM 3
eligibility
criteria?
HeartMate II
HeartMate 3
Randomization
1:1
Short Term (ST) Cohort
N=294
6-month follow-up
Intent-to-Treat (ITT) Population
N=294
HeartMate 3
N=152
HeartMate II
N=142
Treatment failures
Full Study Cohort
N=1028
24-month follow-up for
powered secondary endpoint
Treatment failures
(not treated with study device)
(not treated with study device)
N=1
N=4
Death: 1
As Treated Population
N=289
Long Term (LT) Cohort
N=366
24-month follow-up
Implanted with
HeartMate 3
N=151
Implanted with
HeartMate II
N=138
No LVAD implant: 1
Withdrawal of consent: 1
Transplant: 1
Implanted with non-study LVAD:
1
Study Endpoint
• Primary Endpoint (composite, by ITT):
• Survival at 6 months free of disabling stroke
(modified Rankin score >3) or reoperation to
replace or remove the pump (other than for
recovery)
• Demonstration of non-inferiority of HeartMate
3™ LVAS to HeartMate II™ LVAD
Caution – HeartMate 3 LVAS is an investigational device. Limited by Federal (United States) law to investigational use
SJM-HM3-1116-0003 | Item approved for global use.
Baseline Characteristics
Characteristic
Age - years
Mean
Left ventricular ejection fraction - %
Male sex - no. (%)
Race – no. (%)
White
Black or African American
Other*
Body surface area - m2
Ischemic cause of heart failure - no. (%)
History of stroke - no. (%)
Concomitant medication or intervention - no (%)
Intravenous inotropic agents
IABP
INTERMACS 2
INTERMACS 3
Bridge to Transplant (BTT)
Bridge to Candidacy
Destination Therapy (DT)
HeartMate 3
(n=152)
HeartMate II
(n=142)
60 ± 12
17.1 ± 5.0
121 (80)
59 ± 12
17.3 ± 4.9
114 (80)
104 (68)
37 (24)
11 (8)
2.1 ± 0.3
68 (45)
12 (8)
107 (75)
24 (17)
11 (8)
2.1 ± 0.3
72 (51)
14 (10)
132 (87)
18 (12)
50 (33)
76 (50)
41 (27)
27 (18)
121 (85)
21 (15)
44 (31)
69 (49)
37 (26)
27 (18)
84 (55)
78 (55)
Primary End Point Analysis (ITT)
Survival at 6 months free of disabling stroke or
reoperation to replace or remove the pump
1.00
HeartMate 3
Probability of Event Free Survival
86%
0.80
HeartMate II
77%
0.60
Non-inferiority Analysis
Absolute difference +9.4% (95% LCB -2.1%), P<0.0001
0.40
Superiority Analysis
HR 0.55, (95% CI 0.32-0.95), P=0.037
0.20
0.00
no. at risk
HeartMate 3 152 0
HeartMate II
142
146
125
1 138
119
1352
116
130
110
Months
3 128
106
1274
103
5
6
Primary Endpoint (ITT)
HeartMate 3
(n=152)
n (% [95%CI])
HeartMate II
(n=142)
n (% [95%CI])
Superiority Analysis
Survival free from disabling stroke and
reoperation to repair or replace the LVAD at 6
months
Hazard Ratio†
P
value
131 (86.2 [80 - 91])
109 (76.8 [69 - 83])
0.55 (0.32 - 0.95) 0.037
1(1[0-4])
4 (3 [1 - 7])
0.23 (0.03 – 2.09)
0.15
Disabling stroke (Rankin Score > 3)
6 (4 [1 - 8])
4 (3 [1 - 7])
1.31 (0.37 - 4.64)
0.59
Reoperation to repair or replace pump*
1 (1 [0 - 4])
11 (8 [4 - 13])
0.08 (0.01 - 0.60)
0.002
13 (9 [5 - 14])
14 (10 [6 - 16])
0.82 (0.38 - 1.73)
0.70
First event that prevented patient from
reaching the primary endpoint
Did not receive assigned pump
Death within 180 days after implant
†Hazard
ratios were calculated with the use of Cox regression.
* includes two cases of urgent heart transplant due to device malfunction in the axial-flow pump group
CI denotes confidence interval and LVAD left ventricular assist device
Caution – HeartMate 3 LVAS is an investigational device. Limited by Federal (United States) law to investigational use
SJM-HM3-1116-0003 | Item approved for global use.
*
Conclusions
• Short and long term mechanical support devices are being used for
the treatment of cardiogenic shock and Stage D Heart Failure
• There are continued improvements in pump design
• Short term devices have not yet been shown to improve survival in
cardiogenic shock but clearly provide greater hemodynamic support
• Adverse events remain common in the use of durable device support