Bild 1

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SATS 2009, Stockholm Lars H Lund Cardiogenic
Shock in Myocardial Infarction Background and
Guidelines
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• Shock - definition
• Hypoperfusion ? ?O2 delivery ? cellular
  dysfunction and metabolic acidosis, but cannot
  measure (pH?, lactate?, SVO2?) ? Organ failure
• Perfusion 8 CO x SVR

Hypovolemic ?CO ?SVR Definition 25 loss
of blood volume
Distributive ?CO ?SVR Definition SIRS /
sepsis - inflammation and - infection and -
need for dopamine, norepinephrine or
epinephrine to maintain MAP gt 60

• Cardiogenic
• ?CO
• (?SVR)
• Definition
• SHOCK trial (n302)
• registry (n1190)
• - SBP lt 90 and
• - CI lt 2.2 and
• - PCWP gt 15
• Cool extremities / oliguria
• Pulmonary edema

uptodate.com Annane, Septic Shock, Lancet
2005 Hochman, Am H J 1999, NEJM 1999
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Shock - causes
Hypovolemic ?CO ?SVR - blood loss - fluid
loss vomiting pancreatitis
cirrhosis
Distributive ?CO ?SVR - SIRS / sepsis -
anaphylaxis - drugs, sedation - neurogenic -
Addisonian crisis - Myxedema coma
Cardiogenic ?CO ?SVR Muscle - progressive
chronic HF - myocarditis - ACS - ischemia -
stunning - post-cardiotomy - post-CPR Arrhythmi
as Mechanical - ACS VSD free wall
rupture papillary / chorda rupture tamponade
- hypertrophy (obstructive) - valvular -
tamponade - pulmonary embolism - pneumothorax
uptodate.com Hollenberg, Ann Int Med
1999 Kohsaka, Arch Int Med 2005
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Causes of Cardiogenic Shock in ACS SHOCK Trial
and Registry
74.5
8.3
4.6
8
3.4
1.7
Acute MR
LV failure
RV Infarct
Cardiac Rupture
Other
VSD
Hochman, Circ. 1995
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Cardiogenic shock

• - Acute coronary syndrome is the most common
  cause of cardiogenic shock
• - Cardiogenic shock is the most common cause of
  death in ACS

ACS Incidence 0.25-1 Prevalence 2.5
5-10 of ACS Incidence probably decreasing gt40
of LV Almost equally common in NSTEMI but higher
risk profile
90-95 of ACS
No shock 1-5 annual mortality improving
Shock Mortality 80-90 in 1970s-80s 50-75 in
SHOCK era because of early reperfusion
National Registry of MI, Babaev JAMA
2005 Goldberg RJ, NEJM 1991 Lerner, Am H J
1986 AHA statistics Goldberg RJ, NEJM
1999 Goldberg RJ, Am H J 2001 Fox, JAMA
2007 Holmes DR, Circ. 1999 Jeger, Ann Int Med
2008 Uptodate.com
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Cardiogenic shock in ACS
Risk factors for shock in ACS - Lack of
reperfusion - Time to reperfusion - Age -
Diabetes - Anterior MI - Previous MI - Peripheral
vascular disease - Previous stroke - Higher
enzymes - Lower EF - Killip class - STEMI?

• Risk factors for mortality in shock and ACS
• - Lack of reperfusion
• - Time to reperfusion
• - Age
• - Previous MI
• - Mental status changes
• - Cold extremitites
• - Oliguria
• - Not STEMI
• - MAP
• - SBP
• - DBP
• - CO
• - Cardiac power (CO x MAP)
• - SVI
• - SWI
• - Left main
• - 3 vessel disease

uptodate.com Hollenberg, Ann Int Med
1999 GUSTO Hasdai, Am H J 1999 Holmes, Circ
1999 SHOCK Fincke, JACC 2004 Wong, JACC
2000 Sanborn, JACC 2003 Picard, Circ.
2003 others
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Pathophysiology - systemic
Hollenberg, Ann Int Med 1999 Sarda, R Kohsaka
Arch Int Med 2005
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Pathophysiology - molecular
Marks, J Clin Invest. 2003 Mar111(5)617-25.
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Diagnostics
Coronary angiography Echo Arterial line PA
catheter But do not delay revascularization
10
Treatment The Greatest Discoveries in Medicine
1. Sanitation 1800s. 2. Antibiotika 1928.
Fleming, penicillin from a Petri dish of bacteria
with overgrowth of penicillin-producing
fungi. 3. Anesthesia 1846 by a Boston
dentist. 4. Vaccines 1796. Edward Jenner
smallpox vaccine. 5. DNA structure 1953. James
Watson and Francis Crick. 6. Germ theory - Late
1800s. Louis Pasteur suggested that disease is
caused by exposure to microorganisms. 7. Oral
contraceptive pill 1960s. 8. Evidence-based
medicine 1990s. Understanding of association
vs. causation. The use of randomization to
eliminate confounding and blinding to eliminate
bias to produce best objective evidence from
research. Replaced subjective authority with
objective knowledge. 9. Medical imaging 1895
accidental discovery of X-ray. Since then,
computed tomography (CT scans), positron emission
(PET scans), magnetic resonance imaging (MRIs),
and ultrasound. 10. Computers in medicine
since the 1960s. Medical records, insurance,
research, drug interactions, evidence. 11. Oral
rehydration therapy 1964. Fluids and salts by
mouth to replace losses in cholera, acute
diarrhea, and other conditions. 12. Risks of
smoking 1950 in BMJ. Still kills an estimated
440,000 Americans each year. 13. Immunology
1798. Edward Jenner smallpox vaccine, allergy,
antibodies, rational drugs. 14. Chlorpromazine
(Thorazine) 1952. The first antipsychotic
medication. 15. Tissue culture 1907.
Revolutionized basic science research.
BMJ january 2007
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Applying Classification of Recommendations and
Level of Evidence
Class I Benefit gtgtgt Risk Procedure/ Treatment SHOULD be performed/ administered Class IIa Benefit gtgt RiskAdditional studies with focused objectives needed IT IS REASONABLE to perform procedure/administer treatment Class IIb Benefit RiskAdditional studies with broad objectives needed Additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED Class III Risk BenefitNo additional studies needed Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL
Level A Recommendation based on evidence from multiple randomized trials or meta-analyses Multiple (3-5) population risk strata evaluated General consistency of direction and magnitude of effect
Level B Recommendation based on evidence from a single randomized trial or non-randomized studies Limited (2-3) population risk strata evaluated
Level C Recommendation based on expert opinion, case studies, or standard-of-care Very limited (1-2) population risk strata evaluated
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Treatment
Drugs
Intensive care
ASA Heparin / LMWH (ATIII) Fondaparinux (XA,
NSTEMI) Bivalirudin (thrombin, HIT) Clopidogrel?
gpIIb/IIIa-inhibitor NSTEMI or PCI
Avoid ß-blocker Avoid ACEI Statin? Amiodarone
if needed Lower dose lidocaine
Volume management art sat 90, PCWP
18-25 Glucose control Avoid transfusion (unless
Hct lt 30) Early mechanical ventilation NaHCO3
only if pH lt 7.10-7.15
Circulatory support
Pharmacologic (?O2 consumption and
mortality) Dopamine ?afterload Norepinephrine
??afterload Dobutamine ?BP Milrinone
?BP Levosimendan ?BP but not ?O2 consumption
Stabilize with drugs? Yes if needed, But do
not delay revascularization
Mechanical IABP IA ECMO / VAD unloading
and reverse remodlling few guidelines But do not
delay revascularization
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ECMO and short-term VAD few guidelines
Impella Recover Short-term Percutanoues Axial
flow 2.5-5 L/min
ECMO
Percutaneous IABP 0.5 L/min
TandemHeart pVAD Percutanoues Centrifugal axial
flow
Centrifugal axial flow extracorporeal Bidge 3M
Sarns Medtronic Bio-Medicus Levitronix Centrimag
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Reperfusion Guidelines
ACC / AHA ESC AATS STS CTSnet EACTS
CABG Y N ? No ? ?
PCI Y Y
Heart Failure Y Y
STEMI Y Y
NSTEMI / USA Y Y
cardiologists and surgeons
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Reperfusion ACC/AHA STEMI guidelines, Antman,
Circ./JACC 2004/2008 ESC STEMI guidelines, Van
der Werf, EHJ 2008
Fibrinolysis IA lt90 min if no PCI IA lt12
hrs if no transfer PCI Same if shock
PCI IA primary PCI rescue PCI Same if
shock IA PCI better than fibrinolysis
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ACC / AHA CABG guidelines Eagle Circ./JACC 2004

• 1. No symptoms
• 2. Angina
• 3. ?LVEF
• 4. NSTEMI / USA
• Urgent CABG
• IA - L Main
• - L Main equivalent
• IB PCI suboptimal / ongoing ischemia
• IIaA proximal LAD
• IIbB 1-2 vd PCI suboptimal

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ACC / AHA CABG guidelines Eagle Circ./JACC 2004
ACC/AHA STEMI guidelines Antman Circ./JACC
2004/2008

• 1. No symptoms
• 2. Angina
• 3. ?LVEF
• 4. NSTEMI / USA
• Urgent CABG
• IA - L Main
• - L Main equivalent
• IB PCI suboptimal / ongoing ischemia
• IIaA proximal LAD
• IIbB 1-2 vd PCI suboptimal

Emergency CABG IA cardiogenic shock lt36h of
symptoms, lt18h of shock, lt age 75 IB - no PCI
and persistent pain or instability - at time of
VSD / MR repair - life-threatening V arhythmias
and L main or 3vd IIaB - no PCI and lt6-12
h ?risk day 3-7. After day 7, stable criteria
(reversible ischemia) IIIC small area at risk
and stable
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ACC / AHA CABG guidelines Eagle Circ./JACC 2004
ACC/AHA STEMI guidelines Antman Circ./JACC
2004/2008

• 1. No symptoms
• 2. Angina
• 3. ?LVEF
• 4. NSTEMI / USA
• Urgent CABG
• IA - L Main
• - L Main equivalent
• IB PCI suboptimal / ongoing ischemia
• IIaA proximal LAD
• IIbB 1-2 vd PCI suboptimal

Emergency CABG IA cardiogenic shock lt36h of
symptoms, lt18h of shock, lt age 75 IB - no PCI
and persistent pain or instability - at time of
VSD / MR repair - life-threatening V arhythmias
and L main or 3vd IIaB - no PCI and lt6-12
h ?risk day 3-7. After day 7, stable criteria
(reversible ischemia) - select patients age
75, cardiogenic shock lt36h of symptoms, lt18h of
shock IIIC small area at risk and stable
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ESC STEMI guidelines Van der Werf, EHJ 2008
CABG CABG may be indicated after failed PCI...,
Refractory symptoms after PCI, cardiogenic
shock Shock Emergency PCI or surgery may be
life-saving and should be considered at an early
stage (reference SHOCK study)
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Background early1990s 5-10 of acute coronary
syndromes result in shock 70-80
mortality 10 trials revascularization saves
lives, but selection bias

• Inclusion criteria
• Chest pain or equivalent
• 1 mm ST Elevation, Q-wave, new LBBB, or
  posterior MI with anterior 1 mm ST-depression
  and
• SBP lt 90 x 30 mins or need for vasopressor or
  IABP to SBP gt 90 and
• hypoperfusion (cool extremities or urine output lt
  30 ml/min) and
• HR gt 60 bpm and
• Cardiac index lt 2.2 and
• PCWP 15 and
• Onset of shock lt 36 hours within infarction

Hochman, Am H J 1999 Hochman, NEJM 1999
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• Exlusion criteria
• Severe systemic illness
• Active bleeding
• Mechanical cause of cardiogenic shock (included
  in registry)
• Isolated RV shock (included in registry)
• Shock from other causes
• Severe valve disease
• Dilated cardiomyopathy but not heart failure or
  previous CABG
• Onset of shock gt 36 hours within hospital
  admission

Hochman, Am H J 1999 Hochman, NEJM 1999
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The SHOCK Trial (N302) Randomization 1993 - 1998
Emergency Revascularization N 152
Medical Therapy N 150

• IABP recommended
• Thrombolytics recommended
• Delayed Revascularization after 54 hours, if
  appropriate

• PCI or CABG within 6 hours after randomization
• IABP recommended

• Primary Endpoint Overall 30 day mortality
• Seconday Endpoints 6 month and 1 year mortality

Hochman NEJM 1999
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Notable non-exlusion criteria
Hochman, NEJM 1999
24
Notable treatment
Hochman, NEJM 1999
25
Survival in the SHOCK randomized trial
P0.11
plt0.03
53
47
44
34
1 year, Hochman, JAMA 2001
30 days, Hochman, NEJM 1999
62
33
44
20
6 years, Hochman, JAMA 2006
26
Shock in STEMI and failed PCI should have
emergency CABG Convinced? Objections? - All
ansered by SHOCK Trial or Registry 50
publications
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Objection not in shock
Definition of cardiogenic shock SBP CI PCWP
Forrester lt 90 lt 2.2 gt 15 Forrester, NEJM
1976 ESC lt 90 lt 1.8 gt 20 Van der Werf, ESC
STEMI guidelines, EHJ 2008 Braunwald lt 80 lt
1.8 gt 18 Braunwalds 8th ed., 2008 Stockholms
Län lt 90 lt 2.0 gt 18 Stockholms Läns HIA
Kompendium 2009 Shock study lt 90 lt 2.2 gt 15
Hochman, Am H J 1999, NEJM 1999 low threshold
for shock or pre-shock
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Objection not in shock
Filling pressure
Normal PCWP 8-12
Elevated PCWPgt15-20
Stable 90-95 PCI CABG lt6-12h Congestion without hypotension 5 pre-shock Better survival Same benefit
Shock without congestion 1/3 Same mortality Same benefit Shock and congestion 2/3
Normal SBPgt90 CI 2,5-3,6
Backward failure - Pulmonary congestion - Early
not yet RV failure and edema
Perfusion
DecreasedSBPlt90 CIlt2,5
Forward failure SBP lt 90 Hypoperfusion (cold
extermitites, oliguria) Tachycardia ?SVR (but
mean SVR normal and 20 SIRS)
Forrester NEJM 1976, Braunwald 8th ed.,
uptodate.com, Nieminen ADHF EHJ 2005,
Gheorghiade Circ 2005, ESC STEMI guidelines 2008,
Menon JACC 2000, Menon Am J Med 2000, Kohsaka
Arch Int Med 2005
29
Objection heterogenous group
SHOCK Registry Free wall rupture and
tamponade have equal prognosis and should have
surgery Slater, JACC 2000 Acute MR has
equal prognosis and should have
surgery Thompson JACC 2000 VSD worse
prognosis and should have surgery Menon
JACC 2000 RV-shock are younger and more
single-vessel dz, but similar mortality and equal
benefit compared to LV-shock. Jacobs, JACC
2003
30
Objection can be done with PCI Yes, PCI and
CABG equal prognosis Hochman, NEJM 1999 In
trial, individual selection to PCI 60 and CABG
40. CABG had more diabetes, 3vd and LM but equal
survival White, Circ 2005 But if Lmain 30d
mortality CABG 46 PCI 86 Even though
median time from infarct was 24h for surgery and
7h for PCI. SHOCK Registry, Lee Ann Thor
Surg 2008 And, if PCI not possible or
fails dramatic survival benefit and IA
recommendation
31
Objection my patient is too old
Hochman, NEJM 1999
32
Maybe too old
- In Trial, age 75 no benefit, trend toward
harm Hochman, NEJM 1999 and JAMA 2001 - But
lower baseline risk Dzavik, Am H J 2005 - And
In registry - 1/3 are age 75 - in
hospital mortality lt age 75 45 vs 61
age 75 48 vs 81 - Covariate-adjusted more
benefit if older Dzavik, EHJ 2003 So
vital patient age 75 should be revascularized
IIa-B
33
Objection my patient is real world And not
representative of trials
Women same prognosis and same benefit Wong,
JACC 2001 Different races same prognosis and
same benefit Palmeri, Am J Card
2005 Diabetes worse prognosis but same
benefit Schindler, JACC 2000 Renal
failure included but too few for subgroup
analysis Hochman, NEJM 1999 Registry
patients excluded from trial but same
benefit Hochman, JACC 2000
34
Objection even if survives hospitalisation
poor survival
62
33
44
20
6 years, Hochman, JAMA 2006
35
Objection my patient wants Quality of Life
If survive, 87 NYHA I-II. After discharge less
deterioration of functional status and death if
revascularized Sleeper, JACC 2005 ICU and
non-cardiac complications rare. Causes of death
mainly cardiac. In 15 mo follow-up only 50
readmitted Jeger, Acute Card Care 2007
36
Objection too early cool off dont
operate on pågående infarkt Earlier
revascularization better survival Hochman
nejm 1999
37
Objection too early cool off dont
operate on pågående infarkt Earlier
revaascularization better survival Hochman
nejm 1999 Objection too late, no
point Hospital transfer same benefit despite
longer time Jeger Am H J 2006 If shock on
admission higher mortality but same benefit
Jeger EHJ 2006
38
Objection too early cool off dont
operate on pågående infarkt Earlier
revaascularization better survival Hochman
nejm 1999 Objection too late, no
point Hospital transfer same benefit from
surgery despite longer time Jeger Am H J
2006 If shock on admission higher mortality but
same benefit from surgery Jeger EHJ
2006 Yes, CABG 3-7 days post STEMI in stable
patients higher mortality than elective
CABG Stable STEMI patient 6-12 hours But,
Shock STEMI patient 53 30-day survival with
revascularization, 44 survival without So,
follow SHOCK Trial and guidelines emergency PCI
or CABG, as soon as possible lt36 h of MI and
lt18h of shock
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Centrum för mekanisk assisterad cirkulation och
Hjärttransplantation i Mälardalen
Call to action - 24-hour immediate access
to - echo - arterial line - PA
catheter - IABP - PCI - CABG - Mechanical
support THIVA / TIMA intensive care surgery
cardiology - Adherence to CABG ans STEMI
guidelines - Expansion of mechanical circulatory
support