Cardiogenic Shock in AMI

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


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.


Seyfarth et al.

IABP Mean + SD

Pulmonary wedge pressure Mean Difference

LVAD Mean + SD

Thiele et al.

Pooled

Burkoff et al.


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


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

Cardiogenic Shock in AMI

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