sats 2009, stockholm lars h lund cardiogenic shock in myocardial infarction background and...
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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
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