Controversies in

Treating
Cardiogenic
Shock
Martha Burk, MD, MS
BAMC/Wilford Hall/UTHSCSA
Combined Pulmonary Fellows
Conference
Cardiogenic Shock
 Inadequate perfusion of tissue with
relatively decreased cardiac
dysfunction

 Itis the most common cause of

death in patients hospitalized for
AMI

 Treatment of AMI complicated by

cardiogenic shock remains
 Two Minute
Evidence for
Congestion
Orthopnea

Assessmen
Elevated JVP
Gallop
Edema
Ascites

t Rales
Hepatojugular reflux
Congestion at rest?

No Yes
Evidence of Low
Perfusion
No Warm and Warm and Wet
Narrow pulse pressure Dry
Pulsus paradoxus Low
Perfusion
Cool extremities
At Rest?
Altered mental status
Yes Cold and Dry Cold and Wet
Drug-related hypotension
Hyponatremia
Worsening renal function Nohria, et al JAMA 2002
Causes of Cardiogenic
Shock
 Acute MI  Myocarditis
– Pump failure  Severe septic shock
 Large infarction
 Infarct expansion
 LV outflow obstruction
 Reinfarction – Aortic stenosis
– Hypertrophic LV
 Mechanical
complications  Valvular disease
– Acute MR/papillary – Mitral stenosis
muscle rupture – Left atrial myxoma
– Ventricular wall rupture  Myocardial contusion
– Ventricular septal  Hypothyroid state
defect
– Pericardial tamponade
 Prolonged CABG
 End-stage
Adapted from UpToDate and
cardiomyopathy Hollenberg, et al Ann Intern Med 1999
Epidemiology
 Acute MI is most frequent cause
 ~10% AMI results in shock
 SHOCK
– (Should we emergently revascularize
Occluded Coronaries for shocK) trial
registry
– 1160 pts with AMI and shock
 75% with LV failure
 8% had MR
 5% had ventricular septal defect
 3% had RV failure
 2% had tamponade or cardiac rupture
 8% had shock for other reasons
– Infarctions
 55% anterior, 46% inferior
 21% posterior, 50% multiple Hollenberg, et al Ann Intern Med 1999
Davies QJ Med 2001
Mortality
 TRACE study
– Trandolapril Cardiac Evaluation protocol
– 6676 pts non-invasively managed for AMI
– 59% pts developed shock within 48 hrs
– 30 day and 6 year mortality
 Without shock 9%/45%
 With shock 62%/88%
 Euro-Heart-Survey-ACS
– 10,136 patients presenting with ACS
– 549 had cardiogenic shock on presentation
– Mortality of pts presenting with/without shock
 50%/3% with STEMI
 53%/1% with NSTEMI
Lindholm, et al European Heart Journal 2003
Iakobishvili, et al American Heart Journal 200
Mortality In TRACE

Lindholm, et al European Heart Journal 2003

Katayama, et al Circ J 2005
Pathophysiolog
y  Coronary occlusion
 Impaired coronary flow
 Infarct
 Dysfunction results in
hypotension
 Aortic pressures
<85mmHg
 Extension of
infarct/muscle necrosis
Impaired Thrombolysis
 Microthrombi develop
 Vasoconstrictors released
from microthrombi
 Vasospasm results in
increased flow resistance
 No reflow phenomenon
Davies QJ Med 2001
Neuroendocrine
Activation
 Neuroendocrine system activated
– Increase cardiac output
– Include renin, aldosterone, catecholamines,
BNP, ANP and adrenomedullin
– Adrenomedullin produced unregulated in
ischemia, hypotension
 Increased demand on myocardium
 Inadequate coronary flow
– Inability to meet increased oxygen demand
 Increased myonecrosis

Davies QJ Med 2001

Katayama, et al Internal Medicine 2004
 Regulation of
Vascular Smooth
Muscle Tone

Landry NEJM 2001

Neuroendocrine Markers of
Mortality

Katayama, et al Internal Medicine 2004

 Myocardial Dysfunction
Systolic Diastolic

↓ CO
↓ SV

↓Systemic Perfusion
Hypotension

↓ Coronary
Perfusion
Vasoconstriction Pressure
Fluid retention

Progressive
Ischemia Myocardial
Dysfunction
Death Hollenberg et al,
Annals of Internal Medicine
1999
 Ischemic myocardium

Significant
Reperfusion
Cell death residual
stenosis

Segments with Segments with Segments with

Myocardial Stunning and Hibernating
stunning Hibernation myocardium

Inotropic Relief of
No return Ischemia
Of function Support

Return of
Myocardial function
Hollenberg et al,
Annals of Internal Medicine
Reperfusion Injury
 Free radical production
 Increased neutrophil adhesion
– Complement formation
 Free fatty acid metabolism restored
– Further decreases intracellular pH
– Increased calcium influx due to Na-K exchange

 Result: further myonecrosis during first 2

hours after reperfusion

Davies QJ Med 2001

Diagnosis
 Diagnosis requires
– Documentation of myocardial
dysfunction
– Exclusion of alternative causes
 Hypovolemia
 Sepsis
 PE
 Tamponade
 Aortic dissection
 Valvular disease
Severity of Heart Failure in
AMI
Killip Classification

– Class I – Class IV
 No clinical heart failure  Cardiogenic shock
 < 5% mortality  Stuporous
– Class II  systolic BP < 90
 decreased urine
 Rales bilaterally in up to 50%
output
of lung fields
 pulmonary edema
 isolated S3
and cold clammy
 good prognosis skin
– Class III  mortality near 80%
 Rales in all lung fields
 acute mitral regurgitation
 aggressive management
required www.ahcpub.com
Management Goals
 Early recognition
 Early reperfusion
 Maintenance of adequate preload
 Decreased afterload

Pfisterer Lancet 2003

 Initial Diagnostic and Therapeutic
History and Exam
Steps
Oxygenate/Ventilate
ECG Venous access
ECHO ECG
Labs Pain control
CXR Hemodynamic support
PAC

Tissue perfusion Adequate perfusion Adequate perfusion

Remains inadequate Without congestion With pulmonary congestion
Inotropes
IABP

Reperfusion

Card cath available No card cath available

Cardiac cath Thrombolytics and IABP

Angioplasty CABG Continued Clinical management

Hollenberg, et al Ann Intern Med 1999
Utility of ECHO
 Evaluate
– LV function and myocardium at risk
– Screen for ventricular septal
rupture
– Screen for severe mitral
regurgitation
– Look for tamponade/rupture
– Assess right ventricular function
– Look for aortic dissection

Menon and Hochman Heart 2002

Echo Survival and Response
Predictors in Cardiogenic Shock
 169 pts with MI randomized w/in 12 hrs of
diagnosis of shock to receive
– early emergency revascularization
 PTCA or CABG was performed w/in 6 hrs
 IABP was recommended
– initial medical stabilization
– Echo performed w/in 24 hrs of randomization, and
7 days later
– Study designed and powered to detect 20%
difference in overall 30 day mortality
 LVEF >/= 28% and Grade 0/1 MR were
associated with improved survival
– Odds Ratio 4 and 3, respectively
Picard, et al Circulation 2003
Pulmonary Artery
Catheters

UpToDate
Importance of Position

UpToDate
Respiratory Variation With
PEEP

0 PEEP

15 PEEP

20
PEEP

UpToDate
AWP is a reliable indicator of LVEDP only when ventricular compliance is stable

UpToDate
 PACs in High
Risk Surgical
Patients
 1994 pts
– ≥60 years old
– Deemed ASA class III or IV risk
– Undergoing elective or urgent
major abdominal, thoracic,
vascular or hip frax surgery
and requiring intensive care
– Randomized to receive
treatment w/ or w/o PAC
guidance

 Conclusion
– No benefit to therapy directed
by PAC versus standard care
Class III = Severe disease, but not incapacitating
Class IV = Severe disease that is a constant threat to life

NEJM 2003
Complications of PAC
 Pneumothorax  Catheter site
 Hemothorax infection
 Hematoma  Thrombosis
 Arrhythmias  Infarction
 Heart block  Endocarditis
 Arterial laceration  Thrombocytopenia
 Pulmonary artery
perforation
 Valvular damage
Layon Chest 1999
Perioperative Use in Cardiac
Surgery
Conditions in which there is general agreement that RHC is warranted

 Differentiation between causes of low CO

– Hypovolemia v ventricular dysfunction
– Echo is inconclusive
 Differentiation between L v R heart failure
and pericardial tamponade
– Echo is inconclusive
 Guidance of management of low CO state
 Diagnosis and management of PAH in
patients with systemic hypotension and
impaired organ perfusion
J American College Cardiology 1998
 Conditions In Which
Reasonable Differences of
Opinion Exist
 Guidance of inotropic and/or vasopressor
therapy after patients with significant
cardiac dysfunction have achieved
hemodynamic stability
 Guidance of management of hypotension
and evidence of inadequate organ
perfusion when a therapeutic trial of
intravascular volume expansion and/or
vasoactive agents is associated with
moderate risk
J American College Cardiology 1998
Intra-Aortic Balloon
Pump
 Reduces systolic afterload
 Augments diastolic perfusion
pressures
 Increases cardiac output
 Improves coronary artery
perfusion
– Not true for critically stenosed vessels
 Decreases reocclusion and cardiac
events after emergency
angioplasty for AMI
 No increase in myocardial oxygen
demand
IABP
 Initially improves hemodynamic status
– Impact temporary
 80% mortality in patients with CS treated with
– IABP placement, CCU monitoring and vasopressor
 Fornaro, et al retrospectively studied 15
patients admitted for AMI with cardiogenic
shock
– All pts underwent IABP, angiography followed by
PTCA, CABG and cardiac surgery or medical
treatment
– 5 pts (33%) died
 ~18% patients in Euro-Heart-Survey
Fornaro, etinal GCS had
Ital Cardiol 1996
Iakobishvili, et al Am Heart J 2005
 Benchmark Counterpulsation
Outcomes Registry
 Prospective registry of all  21% all cause mortality
patients who receive IABPs
at participating centers  12% mortality/balloon in
1996-2001 place
 22,663 patients
– 185 US sites, 65 non-US
sites
 0.05% IABP-related
– 4314 had cardiogenic mortality
shock
– Primary endpoints  1% major limb ischemia
 Major limb ischemia
 Severe bleeding  1% severe bleeding
 IABP failure
 All cause in-hospital
mortality  4% balloon failure/leak

Cohen, et al European Heart Journal 2003

Risks of IABP
 Arterial  Miscellaneous
– Perforation – Hemorrhage
– Thrombosis – Infection
– Entrapment
– Embolization
– Limb ischemia
– Visceral ischemia
 Balloon
– Rupture
– Incorrect
positioning
– Gas embolization Overwalder The Internet Journal of
Thoracic and Cardiovascular Surgery 1999
ACC/AHA Guidelines
Class I recommendations
 STEMI patients with BP <90
– Or 30mm Hg below baseline Level B
– No response to other interventions Evidence

 STEMI patients with low output states

 As a stabilizing measure for angiography and
revascularization
Class II recommendations
 STEMI patients with refractory pulmonary
Level C
Evidence
congestion
Antman, et al JACC 2004
Reestablishing
Perfusion

NEJM 2002
Benefits of Thrombolysis in
AMI

Impact of Blood Flow on

Survival
TIMI 0 absence of any antegrade flow beyond a coronary
occlusion.
TIMI 1 faint antegrade coronary flow beyond the occlusion
although filling of the distal coronary bed is
Absolute Reduction in Mortality
incomplete.
TIMI 2 delayed or sluggish antegrade flow with complete
filling of
the distal territory.
TIMI 3 normal flow which fills the distal coronary bed
completely.
UpToDate
 TIMI 0 TIMI 1 TIMI 2 TIMI 3
Occlusion Penetration Slow Flow Normal Flow
12
9.3% P=0.003 vs TIMI 0/1
10
6.1% p<0.0001 vs TIMI 0/1
% Mortality

8 p<0.0001 vs TIMI 2

6
3.7%
4

2
10 16 33 34 44 4 8 27 13 19 9 15 18 29 34
0
GUSTO 1
GUSTO 1

GUSTO 1
German

TAM I 1-7
Team 2

German

TAM I 1-7
Team 2
Team 2
TAM I 1-7

German

TIM I 1,4
TIM I 1,4
TIM I 1,4

5,10B
5,10B
5,10B

Sample Size of Pooled Analysis: 5,498

Gibson 1998
 Both Culprit and Non-Culprit Flow are
Abnormal in Acute MI
Even PTCA of the
40 culprit artery
36.8 + 22.3
6 frames residual stenosis
35 restores flow only
30.6 + 13.4 30.6 + 14.6
30 to that observed
9 frames
in the non-culprit
25
21.0 + 3.1 (30 frames) and
CTFC

20 not to normal flow

15 (21 frames)
10
The difference
5 between culprit &
n =1,322 n = 232 n =1,589 n = 78 non-culprit flow is
0
only 6 frames; the
Culprit Culprit post Non-Culprit Normal difference
PTCA between non-
In 25% of cases, flow is slower in the non-culprit than culprit culprit and normal
In 33% of cases, flow is abnormal following stent placement flow is 9 frames

Gibson et al, JACC 1999; 34: 974-82

Thrombolytic Therapy in
CS
 Lessbenefit once cardiogenic shock
occurs
 Mortality unaffected by type of
thrombolytic
– GISSI trial 30 day mortality 70% for each
group
 Increased risk of significant bleeding with
streptokinase versus alteplase
– International Study Group
 Streptokinase v recombinant Tissue Plasminogen Activator
 Lancet 1990
Risks of Thrombolysis
Bleeding
Bleeding
Bleeding
Thrombolytic
Therapy
 Not beneficial in NSTEMI
– Coronary arteries not usually occluded
 Useful in STEMI
– IF PTCA not available within 2 hours
 ACC/AHA recommends thrombolytics
– Patients w/o contraindications
– Present w/in 12 hours of symptom onset
– Greatest benefit if given w/in 2 hours of symptoms
 Approximately 50% will achieve
normalized return of blood flow (TIMI
grade 3)
– 90% of patients undergoing PCI achieve TIMI grade
3 flow UpToDate
30 Day Mortality of Early v Late
PTCA
GUSTO-1 Trial

Berger, et al Circulation 1997

Markers of TIMI 2/3 Flow
 Decrease in chest  <50% decrease in ST
pain – AND absence of
arrhythmias at 2 hours
– TAMI study after thrombolytics
 PPV 57% TIMI 3
– Predicted LACK of TIMI 3
 NPV 86% TIMI 3
flow
 ECG changes  Sens 81%
– >50% decrease in ST  Spec 88%
elevation  PPV 87%
 in the lead with the most  NPV 83%
elevation  Mb, CK-Mb, Troponin
– PPV 66%
– Ratio of baseline/60minute
– NPV 86% myoglobin ≥4 predicts 90%
probability of TIMI 3 flow
Oldroyd Heart 2000
Is Thrombolysis
Obsolete?
 Nearly all patients with AMIs are
eligible for cardiac catheterization
 PCI identifies anatomy involved
 Acts as a triage for CT surgery
 IABPs can be placed in the cath lab
 90% pts achieve TIMI 3 flow with PCI

Grines, et al Circulation 2003

Revascularization
 SHOCK trial
– 302 pts with cardiogenic shock (largely due to LV
dysfunction) randomized to early revascularization within 6
hours, or initial medical stabilization
– Primary end point was 30 day mortality
 No survival difference at 30 days (53% v 44%)
 6 month survival 50% v 37% (p = 0.027)
– Early revascularization v initial medical stabilization
 12 month survival 47% v 34% (p = 0.025)
 At 1 year, 62% survived if TIMI flow grade 3 was achieved
v 19% survival if PTCA was unsuccessful
– Conclusion: Rapid revascularization is a survival predictor
 American College of Cardiology, American Heart
Association guidelines recommend emergency
revascularization for pts ≤ 75 years with AMI
complicated by cardiogenic shock Menon Congest Heart Fail
2003
Webb, et al J Am Coll Cardiol
Menon and Hochman Heart 2002

Barbash et al, Heart 2001

 Outcome
Predictors After
PCI Factor In p
 Retrospective Hospital
review of 113 pts Mortality 5
who underwent PCI Prior MI OR
for AMI complicated No or Yes 41%v 77 < 0.001
by shock Age (years) 4
OR
– PCI occurred w/in 12 <70 or ≥70 46 v 72 0.02
hours of sx onset
 Factors w/o impact 4
Failed OR
on survival Reperfusion
No or Yes 36 v 72 <0.001
– Gender
– Smoking status Disease
– Diabetes Single/Multivess 29 v 57 0.01
– Time to intervention el
 6, 6-12, or >12
hours Sutton, et al Heart 2005
Another Look at Outcomes,
PCI
 Patients with AMI and cardiogenic shock
– 152 underwent emergency revascularization
– 150 underwent medical stabilization
– Primary endpoint was 30 day mortality
– Secondary endpoint was 6 month survival
 Median time from AMI to shock was 5.6 hours
 Mean age of patients was 66 years
 32% patients were female
 30 day mortality (revascularization v medical
treatment)
– Not statistically significant (47 v 56%)
 6 month mortality
– 50 v 63% ( p = 0.027)

Hochman, et al NEJM 1999

Predictive Value Troponin
T

Ohman, et al NEJM 1996

2004 ACC/AHA Guidelines on
CABG
 Class I Recommendation
– STEMI
 Pts who fail angioplasty and remain hemodynamically
unstable (Level B evidence)
 At time of surgical repair of ventricular septal wall
rupture or mitral valve insufficiency
 CS pts <75 with ST elevation or LBBB (Level B) or
posterior MI who develop shock w/in 36 hrs (Level A)
– LV dysfunction
 Significant left main stenosis (Level B)
 Left main equivalent stenosis (Level B)
 Proximal LAD with 2 or 3 vessel disease
Novel Potential
Therapies
 Nitric Oxide Synthase
Inhibition
 Nitric oxide is a strong vasodilator
 Positive inotropic effect at low levels
 Negative inotropic effect at high
levels
 Large MIs are associated with NO
overproduction
 Could NO inhibition improve the
hemodynamic status of patients with
cardiogenic shock?
Nitric Oxide Synthase
Inhibitor
 30 patients with AMI and shock
– All received IABP, IVFs, pressors, and were immediately referred for
coronary catheterization
– Revascularization performed only by PCI
– Swan-Ganz catheters used after revascularizaiton
 Pts in the treatment arm received L-NAME at 1
mg/kg/h x 5 h
 Primary end point 1 month Survival 73% v 33%
– All cause 30 day mortality 1 week survival 80% v 40%
 Secondary end points 4 month survival 73% v 33%
– All cause mortality at 1 wk and 4 mos MAP improved by 25mm Hg
– Time on mechanical ventilation Urine output 210 v 110cc/h
– Time on IABP Time on IABP 59h v 103h
– Urine output at 24 hours Ventilation time 77 v 140h
– Change in cardiac index
Cotter, et al European Heart Journal 2003
Other Novel Therapies
 Monoclonal antibodies to CD11/CD18
– Inhibit neutrophil adhesion
– HALT-MI
– AMI pts from ER to cath lab
 Randomized by TIMI 0/1 flow to receive drug or
placebo
 Primary end point: size of infarct by SPECT 5-9 days
after MI and angioplasty
 No significant difference
 Na-H inhibition
– -Guardian trial showed no benefit
www.acc.org
 Assess volume status
Treat sustained arrhythmias
Mechanical ventilation as needed
Inotropic/vasopressor support
No
Acute massive ST elevation Emergency ECHO with
Extensive Q waves Color flow doppler
No ST elevation
Or new LBBB
Limited ST, Q changes
Yes
Cath lab
Immediately available
Pump failure
Yes No RV, LV, both Aortic dissection
Tamponade
Cath lab ST elevation -> Lysis
No ST elevation -> GP IIbIIIa
Acute severe MR
Aspirin, Heparin
VSR
Critical AS/MS

Rapid IABP Cardiac surgery

CABG for severe 3v dz or L main
Correct mechanical lesions
OR
Coronary angio PTCA for 1, 2, or mod 3 v CAD
Pulmonary artery cath GP IIb/IIIa antag
Coronary stent
Menon and Hochman Heart 2002
Treasures
of
San
Antonio