SATS 2009, StockholmLars H Lund

Cardiogenic Shock in Myocardial InfarctionBackground and Guidelines

Hypovolemic ↓CO ↑SVR

Definition:

25% loss of blood volume

Shock - definition

- Hypoperfusion ↓O2 delivery cellular dysfunction and metabolic acidosis, but cannot measure (pH?, lactate?, SVO2?) Organ failure

- Perfusion ∞ CO x SVR

Distributive ↑CO ↓SVR

Definition:

SIRS / sepsis:- inflammation and- infection and- need for dopamine, norepinephrine or epinephrine to maintain MAP > 60

Cardiogenic ↓CO (↑SVR)

Definition:

SHOCK trial (n=302)registry (n=1190)

- SBP < 90 and - CI < 2.2 and - PCWP > 15

Cool extremities / oliguriaPulmonary edema

uptodate.comAnnane, Septic Shock, Lancet 2005Hochman, Am H J 1999, NEJM 1999

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

Arrhythmias

Mechanical- ACS

VSDfree wall rupturepapillary / chorda rupturetamponade

- hypertrophy (obstructive)- valvular- tamponade- pulmonary embolism- pneumothorax

Shock - causes

uptodate.comHollenberg, Ann Int Med 1999Kohsaka, Arch Int Med 2005

Causes of Cardiogenic Shock in ACS SHOCK Trial and Registry

Hochman, Circ. 1995

0

10

20

30

40

50

60

70

80

90

100

AcuteMR

LVfailure VSD

RVInfarct

CardiacRupture Other

74.5%

8.3% 4.6% 3.4% 1.7% 8%

- Acute coronary syndrome is the most common cause of cardiogenic shock

- Cardiogenic shock is the most common cause of death in ACS

ACSIncidence: 0.25-1%Prevalence: 2.5%

National Registry of MI, Babaev JAMA 2005Goldberg RJ, NEJM 1991Lerner, Am H J 1986AHA statisticsGoldberg RJ, NEJM 1999Goldberg RJ, Am H J 2001Fox, JAMA 2007Holmes DR, Circ. 1999Jeger, Ann Int Med 2008Uptodate.com

No shock1-5% annual mortalityimproving

ShockMortality:80-90% in 1970s-80s50-75% in SHOCK era

because of early reperfusion

5-10% of ACSIncidence probably decreasing>40% of LVAlmost equally common in NSTEMI but higher risk profile

90-95% of ACS

Cardiogenic shock

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- LVEF- Moderate-severe MR

But all have benefit from emergentrevascularisation

uptodate.comHollenberg, Ann Int Med 1999GUSTO:

Hasdai, Am H J 1999Holmes, Circ 1999

SHOCK:Fincke, JACC 2004Wong, JACC 2000Sanborn, JACC 2003Picard, Circ. 2003others

Cardiogenic shock in ACS

Pathophysiology - systemic

Hollenberg, Ann Int Med 1999Sarda, RKohsaka Arch Int Med 2005

Marks, J Clin Invest. 2003 Mar;111(5):617-25.

Pathophysiology - molecular

Coronary angiography

EchoArterial linePA catheter

But do not delay revascularization

Diagnostics

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

TreatmentThe Greatest Discoveries in Medicine:

11

Class I Benefit >>> Risk

Procedure/ Treatment SHOULD be performed/ administered

Class IIa Benefit >> 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

Applying Classification of Recommendations and Level of Evidence

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

ASA

Heparin / LMWH (ATIII)Fondaparinux (XA, NSTEMI)Bivalirudin (thrombin, HIT)

Clopidogrel?

gpIIb/IIIa-inhibitor NSTEMI or PCI

Avoid β-blocker

Avoid ACEI

Statin?

Amiodarone if needed

Lower dose lidocaine

Volume managementart sat 90%, PCWP 18-25

Glucose control

Avoid transfusion (unless Hct < 30)

Early mechanical ventilation

NaHCO3 only if pH < 7.10-7.15

Treatment

Circulatory support:Pharmacologic (↑O2 consumption and mortality):

Dopamine: ↑afterloadNorepinephrine: ↑↑afterloadDobutamine: ↓BPMilrinone ↓BPLevosimendan ↓BP but not ↑O2 consumption

Stabilize with drugs?Yes if needed, But do not delay revascularization

Mechanical:

IABP: IA

ECMO / VAD:unloading and reverse remodllingfew guidelines

But do not delay revascularization

Drugs: Intensive care:

Impella RecoverShort-termPercutanouesAxial flow2.5-5 L/min

ECMO and short-term VAD – few guidelines

Centrifugal axial flow extracorporealBidge

3M Sarns

MedtronicBio-Medicus

Levitronix Centrimag

PercutaneousIABP0.5 L/min

ECMO

TandemHeart pVADPercutanouesCentrifugal axial flow

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

Reperfusion

ACC/AHA STEMI guidelines, Antman, Circ./JACC 2004/2008ESC STEMI guidelines, Van der Werf, EHJ 2008

Fibrinolysis:

IA: <90 min: if no PCIIA: <12 hrs: if no transfer PCISame if shock

PCI:

IA: primary PCIrescue PCI

Same if shock

IA: PCI better than fibrinolysis

ACC / AHA CABG guidelinesEagle 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 ischemiaIIaA: proximal LADIIbB: 1-2 vd PCI suboptimal

5. STEMI

Emergency CABG:

IA: cardiogenic shock <36h of symptoms, <18h of shock, < age 75IB: - 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 <6-12 h↑risk day 3-7. After day 7, stable criteria (reversible ischemia)

IIIC: - small area at risk and stable

ACC / AHA CABG guidelinesEagle 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 ischemiaIIaA: proximal LADIIbB: 1-2 vd PCI suboptimal

5. STEMI

Emergency CABG:

IA: cardiogenic shock <36h of symptoms, <18h of shock, < age 75IB: - 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 <6-12 h↑risk day 3-7. After day 7, stable criteria (reversible ischemia)

IIIC: - small area at risk and stable

ACC/AHA STEMI guidelinesAntman Circ./JACC 2004/2008

Emergency CABG:

IA: cardiogenic shock <36h of symptoms, <18h of shock, < age 75IB: - 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 <6-12 h↑risk day 3-7. After day 7, stable criteria (reversible ischemia)

IIIC: small area at risk and stable

ACC / AHA CABG guidelinesEagle 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 ischemiaIIaA: proximal LADIIbB: 1-2 vd PCI suboptimal

5. STEMI

Emergency CABG:

IA: cardiogenic shock <36h of symptoms, <18h of shock, < age 75IB: - 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 <6-12 h↑risk day 3-7. After day 7, stable criteria (reversible ischemia)

IIIC: - small area at risk and stable

ACC/AHA STEMI guidelinesAntman Circ./JACC 2004/2008

Emergency CABG:

IA: cardiogenic shock <36h of symptoms, <18h of shock, < age 75IB: - 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 <6-12 h↑risk day 3-7. After day 7, stable criteria (reversible ischemia)- select patients ≥ age 75, cardiogenic shock <36h of symptoms, <18h of shock

IIIC: small area at risk and stable

ESC STEMI guidelinesVan 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)

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 < 90 x 30 mins or need for vasopressor or IABP to SBP > 90 and

• hypoperfusion (cool extremities or urine output < 30 ml/min) and

• HR > 60 bpm and

• Cardiac index < 2.2 and

• PCWP ≥ 15 and

• Onset of shock < 36 hours within infarction Hochman, Am H J 1999Hochman, NEJM 1999

Background early1990s: 5-10% of acute coronary syndromes result in shock70-80% mortality~10 trials revascularization saves lives, but selection bias

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 > 36 hours within hospital admission

Hochman, Am H J 1999Hochman, NEJM 1999

The SHOCK Trial (N=302)Randomization 1993 - 1998

Emergency RevascularizationN = 152

• PCI or CABG within 6 hours after randomization

• IABP recommended

Medical TherapyN = 150

• IABP recommended• Thrombolytics

recommended• Delayed Revascularization

after 54 hours, if appropriate

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

mortalityHochman NEJM 1999

Hochman, NEJM 1999

Notable non-exlusion criteria

Hochman, NEJM 1999

Notable treatment

6 years, Hochman, JAMA 2006

1 year, Hochman, JAMA 200130 days, Hochman, NEJM 1999

47%

34%

62%

p<0.03

44%33%

20%

P=0.11

53%

44%

Survival in the SHOCK randomized trial

Shock in STEMI and failed PCIshould have emergency CABG

Convinced?

Objections?

- All ansered by SHOCK Trial or Registry~ 50 publications

Objection: not in shock

Definition of cardiogenic shock:

SBP CI PCWPForrester: < 90 < 2.2 > 15 Forrester, NEJM 1976

ESC: < 90 < 1.8 > 20 Van der Werf, ESC STEMI guidelines, EHJ 2008

Braunwald: < 80 < 1.8 > 18 Braunwald’s 8th ed., 2008

Stockholms Län: < 90 < 2.0 > 18 Stockholms Läns HIA Kompendium 2009

Shock study: < 90 < 2.2 > 15 Hochman, Am H J 1999, NEJM 1999

low threshold for shock or pre-shock

Backward failure:- Pulmonary congestion- Early: not yet RV failure and edema

Forward failure:SBP < 90Hypoperfusion (cold extermitites, oliguria)Tachycardia↑SVR (but mean SVR normal and 20% SIRS)

Filling pressure

ElevatedPCWP>15-20

NormalPCWP 8-12

Pe

rfu

sio

n

No

rma

l S

BP

>9

0C

I 2

,5-3

,6

De

cre

ase

dS

BP

<9

0

CI<

2,5

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

Stable: 90-95%PCI

CABG <6-12h

Congestion without hypotension: 5%

pre-shock

Better survival

Same benefit

Shock without congestion:

1/3

Same mortality

Same benefit

Shock and congestion:

2/3

Objection: not in shock

Objection: heterogenous group

SHOCK Registry:

Free wall rupture and tamponade have equal prognosis and should have surgerySlater, JACC 2000

Acute MR has equal prognosis and should have surgeryThompson JACC

2000

VSD worse prognosis and should have surgeryMenon JACC

2000

RV-shock are younger and more single-vessel dz, but similar mortality and equal benefit compared to LV-shock.

Jacobs, JACC 2003

Objection: can be done with PCI

Yes, PCI and CABG equal prognosisHochman, 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

Hochman, NEJM 1999

Objection: my patient is too old

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: < age 75: 45 vs 61%≥ age 75: 48 vs 81%

- Covariate-adjusted more benefit if olderDzavik, EHJ 2003

So vital patient ≥ age 75 should be revascularized: IIa-B

Objection: my patient is ”real world”And not representative of trials

Women same prognosis and same benefitWong, JACC 2001

Different races same prognosis and same benefitPalmeri, Am J Card 2005

Diabetes worse prognosis but same benefitSchindler, JACC 2000

Renal failure included but too few for subgroup analysisHochman, NEJM 1999

Registry patients excluded from trial but same benefitHochman, JACC 2000

Objection – even if survives hospitalisationpoor survival

6 years, Hochman, JAMA 2006

62%

44%33%

20%

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

Objection: too early”cool off”don’t operate on ”pågående infarkt”

Earlier revascularization better survivalHochman nejm 1999

Objection: too early”cool off”don’t operate on ”pågående infarkt”

Earlier revaascularization better survivalHochman nejm 1999

Objection: too late, no point

Hospital transfer same benefit despite longer timeJeger Am H J 2006

If shock on admission higher mortality but same benefit Jeger EHJ 2006

Objection: too early”cool off”don’t operate on ”pågående infarkt”

Earlier revaascularization better survivalHochman nejm 1999

Objection: too late, no point

Hospital transfer same benefit from surgery despite longer timeJeger 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 CABGStable 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<36 h of MI and <18h of shock

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

Centrum för mekanisk assisterad cirkulation och Hjärttransplantation i Mälardalen