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Update on the Treatment of Cardiogenic Shock in Acute MI
Daniel Burkhoff MD PhD Adjunct Associate Professor of Medicine
Columbia University
Disclosures: Employee of HeartWare; Educational Grant Abiomed
Faculty Disclosure
Company Nature of Affiliation Unlabeled Product Usage
HeartWare Employee None
Abiomed Educational Grant None
Thirty-Year Trends (1975 to 2005) in the Magnitude of, Management of, and Hospital Death Rates Associated
With Cardiogenic Shock in Patients With Acute Myocardial Infarction
Goldberg et al, Circulation 2009;119:1211-1219
Copyright American Heart Association, Inc. All rights reserved.
Perc
ent A
MI w
ith C
GS
Thirty-Year Trends (1975 to 2005) in the Magnitude of, Management of, and Hospital Death Rates Associated
With Cardiogenic Shock in Patients With Acute Myocardial Infarction
Goldberg et al, Circulation 2009;119:1211-1219
Copyright American Heart Association, Inc. All rights reserved.
Mor
talit
y (%
)
In-hospital Mortality + Treatment Trends
0
10
20
30
40
50
60
70
80
1997 1999 2001 2003 2005
%
Cardiogenic Shock (Total)
Cardiogenic Shock at admission (p=0.009)
Cardiogenic after admission (p=0.094)
Jeger et al. Ann Int Med 2008;149:618-626
0
10
20
30
40
50
60
70
80
1997 1999 2001 2003 2005
%
PCI (p
6
EARLY REVASCULARIZATION IN ACUTE MYOCARDIAL INFARCTION COMPLICATED BY CARDIOGENIC SHOCK
Hochman et al, NEJM 1999;341
ERV (N=152)
IMS (N=150)
Years From Randomization
Prop
ortio
n Al
ive
0 1 2 3 4 5 6 0.0
0.2
0.4
0.6
0.8
1.0 Log-Rank p = .024 30 days
SHOCK Trial
Hochman J. JAMA 2001; 285: 190-192
CPO and Survival in CGS/AMI
Cardiac Power Output (Watts)
Estim
ated
In-H
ospi
tal
Mor
talit
y (%
)
Fincke et al. (JACC 2004)
Meta-analysis of Percutaneous LVAD in CGS
Cheng et al, European Heart Journal 2009;30:2102-2108
* Not reported whether the envelopes were opaque and sequentially numbered. IABP, intra-aortic balloon pump; LVAD, left ventricular assist device.
Table 1. Study characteristics of included trials Thiele et al.
Burkhoff et al.
Seyfarth et al.
Percutaneous LVAD used TandemHeart TandemHeart Impella LP25
Control IABP IABP IABP Total number of patients 41 33 26
Setting Single-centre Multi-centre Two-centre Randomization Yes Yes Yes Sequence generation Drawing
Envelopes Not reported Not reported
Concealment of allocation
Sealed envelopes Not reported Not reported
Blinding Not possible Not possible Not possible Handling of patient attrition
Complete follow-up Complete follow-up Complete follow-up
Hemodynamics
Cheng et al, European Heart Journal 2009;30:2102-2108
Cardiac index Mean Difference
LVAD Mean + SD
Thiele et al.
Pooled
Burkoff et al.
P(heterogeneity) = 0.22 l2 = 34.0%
Seyfarth et al.
IABP Mean + SD
Mean Arterial Pressure Mean Difference
LVAD Mean + SD
Thiele et al.
Pooled
Burkoff et al.
P(heterogeneity) = 0.10 l2 = 55.9%
Seyfarth et al.
IABP Mean + SD
Pulmonary wedge pressure Mean Difference
LVAD Mean + SD
Thiele et al.
Pooled
Burkoff et al.
P(heterogeneity) = 0.01 l2 = 76.6%
Seyfarth et al.
IABP Mean + SD
Favors IABP Favors LVAD
2.3 + 0.6 2.2 + 0.6 2.2 + 0.6
1.8 + 0.4 2.1 + 0.2 1.8 + 0.7
0.55 (0.23-0.87) 0.16 (-0.14-0.46) 0.35 (-0.16-0.88) 0.35 (0.09-0.61)
-2 -1 0 1 2
76 + 10 91 + 16 87 + 18
70 + 16 72 + 12 71 + 22
0.55 (-2.9-13.9) 18.6 (9.4-27.9) 16.0 (0.5-31.5) 12.8 (3.6-22.0)
-50 -25 0 Favors IABP Favors LVAD
25 50
-20 -10 0 Favors LVAD Favors IABP
16 + 5 16 + 4 19 + 5
22 + 7 25 + 3 20 + 6
-5.6 (-9.2 to -2.1) -8.4 (-11.0 to -5.8) -1.0 (-5.2-3.2) -5.3 (-9.4 to -1.2)
10 20
30 Day Mortality
Cheng et al, European Heart Journal 2009;30:2102-2108
30-day Mortality Relative Risk
LVAD n/N
Thiele et al.
Pooled
Burkhoff et al.
P(heterogeneity) = 0.83 l2 = 0%
Seyfarth et al.
IABP n/N
9/19
6/13
5/14
6/13
0.95 (0.48-1.90)
1.33 (0.57-3.10)
1.00 (0.44-2.29)
1.06 (0.68-1.66)
0.1 1 10
Favors IABP Favors LVAD
9/21 9/20
24/53 20/47
Randomized Studies in Cardiogenic Shock Trial n/N n/N Relative Risk 95% CI Relative Risk 95% CI
0 0.5 1 2 3
Follow-up
Revascularization (PCI/CABG) SHOCK SMASH Total
76/152 22/32 103/184
83/149 18/23 117/172
0.80 (0.66;0.98) 0.87 (0.66;1.29) 0.82 (0.70;0.98)
1-year 30 days
Early revascularization better
Medical treatment better
0.75 1.5 2.5 0.25
Norepinephrine better
0.75 (0.55;0.93) 64/145 50/135 28 days Dopamine better
Catecholamines SOAP II (CS Subgroup)
In-hospital 15/40 13/40 1.15 (0.59;2.27) Up-stream Abciximab better
Standard treatment better
Glycoprotein IIb/IIIa-Inhibitors PRAGUE-7
30 days 30 days 30 days
97/201 24/59 4/15 125/275
76/180 7/20 10/15 93/215
1.14 (0.91;1.45) 1.16 (0.59;2.69) 0.40 (0.13;1.05) 1.05 (0.85;1.29)
NO Synthase inhibition better
Placebo better
NO Synthase Inhibitors TRIUMPH SHOCK-2 Cotter et al Total
30 days 7/19 6/21
IABP better
Standard treatment better
1.28 (0.45;3.72) IABP IABP-SHOCK I
30 days 30 days 30 days
9/21 9/19 6/13 24/53
9/20 5/14 6/13 20/47
0.95 (0.48;1.90) 1.33 (0.57-3.10) 1.00 (0.44-2.29) 1.06 (0.68-1.66)
LVAD better
IABP better
LVAD Thiele et al Burkhoff et al Seyfarth et al Total
Thiele et al. Eur Heart J 2010,31:1828-1835
DSMB: Kurt Huber Ferenc Follath Bernhard Maisch Johannes Haerting Steering committee: Holger Thiele Karl Werdan Uwe Zeymer Gerhard Schuler Support + Patronage:
IABP-Shock-II Trial
IABP Shock-II Primary Study Endpoint (30-Day Mortality)
Mor
talit
y (%
)
Thiele et al. NEJM 2012;367:1287-1296
Time after Randomization (Days)
P=0.92 by log-rank test Relative risk 0.96; 95% CI 0.79-1.17; P=0.69 by Chi2-Test
Control 41.3%
IABP 39.7%
0
10
20
30
40
50
0 5 10 15 20 25 30
Thiele et al, Lancet, Volume 382, Issue 9905, 2013, 1638 - 1645
IABP Shock-II Primary Study Endpoint (30-Day Mortality)
16
Indication Assist device
ESC/EACTS [1, 2] ACCF/AHA/SCAI [3-6]
Cardiogenic shock
IABP Class IIb (B) Intra-aortic balloon pumping may be considered.
Class IIa [B] The use of intra-aortic balloon pump (IABP) counterpulsation can be useful for patients with cardiogenic shock after STEMI who do not quickly stabilize with pharmacological therapy.
Other devices
Class IIb (C) LV assist devices may be considered for circulatory support in patients in refractory shock.
Class IIb [C] Alternative LV assist devices for circulatory support may be considered in patients with refractory cardiogenic shock.
EU and US Guideline Recommendations
Burkhoff et al. Chapter 27: Percutaneous Circulatory Support: Intra-aortic Balloon Counterpulsation, Impella, TandemHeart, and Extracorporeal Bypass In: Baim & Grossmans Cardiac Catheterization, Angiography, and Intervention,, 8th Edition, Editor: Mauro Moscucci
17
Review and Comparison of Cardiac Support Strategies
Strategy Therapy / Device Mechanism
Medical Management Inotropes / Pressors Increase Contractility, HR,
TPR
Counterpulsation IABP Aortic Pressure Augmentation
Extracorporeal Bypass Pump
TandemHeart LA -> AO flow ECMO RA -> AO flow
Implantable Transvalvular Pump
Impella 2.5/4.0/5.0 LV -> AO flow
0 25 50 75 100 125 150 0
25
50
75
100
125
150
LV Volume (ml)
LV P
ress
ure
(mm
Hg)
18 Pressure-Volume Loops and Relationships
0 50 100 150 0
25
50
75
100
125
150
LV Volume (ml)
LV P
ress
ure
(mm
Hg)
Ees Ees
19 Contractility
20
Left Ventricular Volume
Left
Ven
tric
ular
Pre
ssur
e
SW
Cardiac Power Output (CPO)
CPO = SW*HR MAP*SV*HR
21
Left Ventricular Volume
Left
Ven
tric
ular
Pre
ssur
e
SW
PE
Determinants of Myocardial Oxygen Consumption
PVA = PE+SW Heart Rate
Contractility
Balance between Energy Supply and Demand and its Impact on Myocardial and Vascular Properties
23
Hemodynamic principles provide important insights into different forms of mechanical circulatory support (MCS) in
various clinical settings
24
A Typical Case of CGS in AMI
59 year old man, multiple cardiac risk factors NSTEMI, EF 15% Cath: Diffuse disease in LCx and LAD 100% RCA with diffuse disease Hemodynamics: HR: 122 CVP: 11 PAP: 37/29 (31) PCWP: 22 AoP: 75/53 (62) CO/CI: 3.2/1.8 CPO: 0.44 Watts
25
Harvi
Interactive, simulation-based textbook for the iPad
(for iPad 2, 3, mini)
26
ECMO vs Direct LV Unloading
ECMO Provides effective cardiac support, especially in the
setting of RV failure Improved systemic oxygenation CAUTION: LV can be overloaded and pulmonary
edema can be exacerbated Transvalvular Percutaneous LVAD Improves systemic hemodynamics Unloads the LV Oxygenation can be improved secondary to
reduced PCWP
Conclusions: CGS in AMI
There is no unequivocal benefit to LV support in CGS
IABP is clearly not the answer (though may be useful to increase coronary flow with no reflow or residual stenosis)
LVAD support makes most sense upfront in hypotensive patients for PCI to support the procedure and allow decisions for possible bridging
ECMO is best for total crash and burns
Update on the Treatment of Cardiogenic Shock in Acute MIFaculty DisclosureSlide Number 3Slide Number 4In-hospital Mortality + Treatment TrendsSlide Number 6SHOCK TrialCPO and Survival in CGS/AMIMeta-analysis of Percutaneous LVAD in CGSHemodynamics30 Day MortalityRandomized Studies in Cardiogenic ShockIABP-Shock-II Trial IABP Shock-IIPrimary Study Endpoint (30-Day Mortality)Slide Number 15Slide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20Slide Number 21Slide Number 22Slide Number 23Slide Number 24Slide Number 25Slide Number 26Conclusions: CGS in AMI