SATS 2009, Stockholm Lars H Lund

Cardiogenic Shock in Myocardial Infarction

Background and Guidelines

Shock - definition

-Hypoperfusion  ↓O 2 delivery  cellular dysfunction and metabolic acidosis, but cannot measure (pH?, lactate?, SVO 2 ?) 

Organ failure

Perfusion ∞ 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 > 60 Cardiogenic ↓CO (↑SVR) Definition: SHOCK trial (n=302) registry (n=1190) - SBP < 90

and

- CI < 2.2

and

- PCWP > 15 Cool extremities / oliguria Pulmonary edema uptodate.com

Annane, Septic Shock, Lancet 2005 Hochman, Am H J 1999, NEJM 1999

Hypovolemic ↓CO ↑SVR - blood loss - fluid loss vomiting pancreatitis cirrhosis uptodate.com

Hollenberg, Ann Int Med 1999 Kohsaka, Arch Int Med 2005

Shock - causes

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 VSD free wall rupture papillary / chorda rupture tamponade - hypertrophy (obstructive) - valvular - tamponade - pulmonary embolism - pneumothorax

100 90 80 30 20 10 0 70 60 50 40

Causes of Cardiogenic Shock in ACS SHOCK Trial and Registry

74.5% 8.3% 4.6% 3.4% 1.7% 8% LV failure Acute MR VSD RV Infarct Cardiac Rupture Other Hochman, Circ. 1995

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% 90-95% of ACS 5-10% of ACS Incidence probably decreasing >40% of LV Almost equally common in NSTEMI but higher risk profile

No shock 1-5% annual mortality improving

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

Shock Mortality: 80-90% in 1970s-80s 50-75% in SHOCK era

because of early reperfusion

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?

uptodate.com

Hollenberg, Ann Int Med 1999 GUSTO: Hasdai, Am H J 1999 SHOCK: Holmes, Circ 1999 Fincke, JACC 2004 Wong, JACC 2000 Sanborn, JACC 2003 Picard, Circ. 2003 others

Cardiogenic shock in ACS

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 emergent revascularisation

Hollenberg, Ann Int Med 1999 Sarda, R Kohsaka Arch Int Med 2005

Pathophysiology - systemic

Pathophysiology - molecular

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

Diagnostics

Coronary angiography Echo Arterial line PA catheter

But do not delay revascularization

1. Sanitation – 1800s.

Treatment The Greatest Discoveries in Medicine:

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

Applying Classification of Recommendations and Level of Evidence

Class I Class IIa Class IIb Class III

Benefit >>> Risk Benefit >> Risk Additional studies with focused objectives needed

Procedure/ Treatment

SHOULD

be performed/ administered

IT IS REASONABLE

to perform procedure/administer treatment

Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Risk ≥ Benefit No additional studies needed

Procedure/Treatment

MAY BE CONSIDERED

Procedure/Treatment should

NOT

be performed/administered

SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL Level A: Level B: Level C:

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 Recommendation based on evidence from a single randomized trial or non-randomized studies Limited (2-3) population risk strata evaluated Recommendation based on expert opinion, case studies, or standard-of-care Very limited (1-2) population risk strata evaluated 11

Treatment

Drugs: 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 Intensive care: Volume management art sat 90%, PCWP 18-25 Glucose control Avoid transfusion (unless Hct < 30) Early mechanical ventilation NaHCO 3 only if pH < 7.10-7.15

Circulatory support: Pharmacologic (↑O 2 consumption and mortality): Dopamine: ↑afterload Norepinephrine: ↑↑afterload Dobutamine: ↓BP Milrinone ↓BP Levosimendan ↓BP but not ↑O 2 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

ECMO and short-term VAD –

few guidelines

Percutaneous IABP 0.5 L/min Impella Recover Short-term Percutanoues Axial flow 2.5-5 L/min ECMO TandemHeart pVAD Percutanoues Centrifugal axial flow Centrifugal axial flow extracorporeal Bidge 3M Sarns Medtronic Bio-Medicus Levitronix Centrimag

Reperfusion Guidelines

CABG PCI Heart Failure STEMI NSTEMI / USA Y Y Y

ACC / AHA

Y Y

ESC

Y Y N Y Y

AATS

?

STS

No

CTSnet EACTS

?

?

cardiologists and surgeons

Reperfusion

ACC/AHA STEMI guidelines, Antman, Circ./JACC 2004/2008 ESC STEMI guidelines, Van der Werf, EHJ 2008 Fibrinolysis: IA: <90 min: if no PCI IA: <12 hrs: if no transfer PCI

Same if shock

PCI: IA: primary PCI rescue PCI

Same if shock

IA: PCI better than fibrinolysis

ACC / AHA CABG guidelines Eagle Circ./JACC 2004 1. No symptoms 2. Angina 3. ↓LVEF 4. NSTEMI / USA Urgent CABG IA: IB: IIaA: IIbB: - L Main - L Main equivalent PCI suboptimal / ongoing ischemia proximal LAD 1-2 vd PCI suboptimal 5. STEMI Emergency CABG: IA: IB: cardiogenic shock <36h of symptoms, <18h of shock, < age 75 - 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 guidelines Eagle Circ./JACC 2004 1. No symptoms 2. Angina 3. ↓LVEF 4. NSTEMI / USA Urgent CABG IA: IB: IIaA: IIbB: - L Main - L Main equivalent PCI suboptimal / ongoing ischemia proximal LAD 1-2 vd PCI suboptimal ACC/AHA STEMI guidelines Antman Circ./JACC 2004/2008 5. STEMI Emergency CABG: IA: IB: Emergency CABG: cardiogenic shock <36h of symptoms, <18h of shock, < age 75 - no PCI and persistent pain or instability - at time of VSD / MR repair - life-threatening V arhythmias and L main or 3vd IA: IB: IIaB: - no PCI and <6-12 h ↑risk day 3-7. After day 7, stable criteria (reversible ischemia) cardiogenic shock <36h of symptoms, <18h of shock, < age 75 - 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 IIIC: small area at risk and stable

ACC / AHA CABG guidelines Eagle Circ./JACC 2004 1. No symptoms 2. Angina 3. ↓LVEF 4. NSTEMI / USA Urgent CABG IA: IB: IIaA: IIbB: - L Main - L Main equivalent PCI suboptimal / ongoing ischemia proximal LAD 1-2 vd PCI suboptimal ACC/AHA STEMI guidelines Antman Circ./JACC 2004/2008 5. STEMI Emergency CABG: IA: IB: IIIC: Emergency CABG: cardiogenic shock <36h of symptoms, <18h of shock, < age 75 - no PCI and persistent pain or instability - at time of VSD / MR repair - life-threatening V arhythmias and L main or 3vd IA: IB: IIaB: - no PCI and <6-12 h ↑risk day 3-7. After day 7, stable criteria (reversible ischemia) - small area at risk and stable cardiogenic shock <36h of symptoms, <18h of shock, < age 75 - 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 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)

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 < 90 x 30 mins or need for vasopressor or IABP to SBP > 90 hypoperfusion (cool extremities or urine output < 30 ml/min) HR > 60 bpm

and

Cardiac index < 2.2 PCWP ≥ 15 and

and

Onset of shock < 36 hours within infarction

and and

Hochman, Am H J 1999 Hochman, NEJM 1999

• • • • • • • • 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 1999 Hochman, NEJM 1999

The SHOCK Trial (N=302)

Randomization 1993 - 1998

Emergency Revascularization N = 152 • PCI or CABG within 6 hours after randomization • IABP recommended Medical Therapy N = 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 mortality

Hochman NEJM 1999

Notable

non

exlusion criteria Hochman, NEJM 1999

Notable

treatment

Hochman, NEJM 1999

Survival in the SHOCK randomized trial

P=0.11

53% 44%

30 days, Hochman, NEJM 1999 p<0.03

47% 34%

1 year, Hochman, JAMA 2001

33% 20% 62% 44%

6 years, Hochman, JAMA 2006

Shock in STEMI and failed PCI should have emergency CABG Convinced?

Objections?

-

All ansered by SHOCK Trial or Registry ~ 50 publications

Objection: not in shock

Definition of cardiogenic shock: Forrester: ESC: Braunwald: Stockholms Län: Shock study: SBP < 90 < 90 < 80 < 90 < 90 CI < 2.2 < 1.8 < 1.8 < 2.0 < 2.2

low threshold for shock or pre-shock

PCWP > 15 > 20 > 18 > 18 > 15 Forrester, NEJM 1976 Van der Werf, ESC STEMI guidelines, EHJ 2008 Braunwald’s 8th ed., 2008 Stockholms Läns HIA Kompendium 2009 Hochman, Am H J 1999, NEJM 1999

Objection: not in shock

Filling pressure

Normal PCWP 8-12 Elevated PCWP>15-20 Congestion without hypotension: 5% Stable: 90-95% PCI CABG <6-12h

pre-shock Better survival Same benefit

Backward failure: - Pulmonary congestion - Early: not yet RV failure and edema Shock without congestion: 1/3 Same mortality Same benefit Shock and congestion: 2/3 Forward failure: SBP < 90 Hypoperfusion (cold extermitites, oliguria) Tachycardia ↑SVR (but mean SVR normal and 20% SIRS) Forrester NEJM 1976, Braunwald 8 th 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

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

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 PCI 46% 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

Objection: my patient is too old

Hochman, NEJM 1999

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: ≥ age 75: - Covariate-adjusted

more

benefit if older 45 vs 61% 48 vs 81% Dzavik, 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 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

Objection – even if survives hospitalisation poor survival

33% 20% 62% 44%

6 years, Hochman, JAMA 2006

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 survival Hochman nejm 1999

Objection: too early ”cool off” don’t 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

Objection: too early ”cool off” don’t 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 <36 h of MI and <18h of shock

Centrum för mekanisk assisterad cirkulation och Hjärttransplantation i Mälardalen

Call to action:

- 24-hour

immediate

- echo - arterial line - PA catheter access to: - IABP - PCI - CABG - Mechanical support

THIVA / TIMA intensive care + surgery + cardiology

- Adherence to CABG ans STEMI guidelines - Expansion of mechanical circulatory support