Choc cardiogénique

juin 2018

Nadia Aissaoui Réanimation médicale

Hôpital Européen Georges Pompidou Université Paris Descartes INSERM-U970, équipe 4

Diplôme d'études spécialisées complémentaires de Réanimation médicale

Plan

1. Definition and profiles

2. Epidemiology

3. Management

Resuscitation and medical therapy

‒ Inotropes/Vasopressors

‒ Revascularisation

‒ New therapies

Mechanical circulatory support

Cardiogenic shock (CS) definition

Established criteria for the diagnosis of CS are as follows:

(1) Systolic blood pressure less than 90 mmHg for 30 min or mean arterial pressure less

than 65 mmHg for 30 min or vasopressors required to achieve a blood pressure ≥ 90 mmHg;

(2) Pulmonary congestion or elevated left-ventricular filling pressures;

(3) Signs of impaired organ perfusion with at least one of the following criteria: (a)

altered mental status; (b) cold, clammy skin; (c) oliguria; (d) increased serum lactate

What are we talking about ? Spectrum of CS

Atkinson TM et al., J Am Coll Cardiol Intv 2016;9:871–83

Various profiles of severity in cardiogenic shock

Inotrope dependent

Sliding on inotropes

Refractory to inotropes

Introduction of inotropes

Various profiles of severity in cardiogenic shock

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When signs of cardiogenic shock remain despite optimal and maximal conventionnal therapy

No consensus about the definition of optimal and maximal conventionnal therapy

Refractory cardiogenic shock

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Refractory cardiogenic shock

– Multicentre, prospective, observational study conducted between 2010 and 2012

– Patients with either acute coronary syndrome (ACS) or non-ACS aetiologies were enrolled within 6 h from detection of CS: n = 219, mean age 67, 74% men

80%

11%

5%

2% 2%

Acute coronary syndrome

Worsening of chronic heart failure

Tako-Tsubo

Myocarditis Others

Etiologies

11 %

6 %

5 %

5 %

1 %

22 %25 %

25 %

,

Other

Post-cardiac arrest resuscitation syndrome

Fulminant myocarditis

cardiotoxic drug intoxication

arrythmia disorders

Pulmonary embolism

Acute myocardial infarction

Acute decompensated heart failure

Cardiogenic shock n=19,416

Etiologies of CS

Medical cardiogenic shock

– acute myocardial infarction

– fulminant myocarditis

– cardiotoxic drug intoxication

– stress-induced cardiomyopathy

– post-cardiac arrest resuscitation syndrome

– decompensated pulmonary vascular disease

– massive pulmonary embolism

– acute decompensated heart failure

Etiologies of CS

Medical cardiogenic shock

Post-surgical CS after heart surgery (including heart

transplantation)

– acute myocardial infarction

– acute decompensated heart failure

– fulminant myocarditis

– cardiotoxic drug intoxication

– stress-induced cardiomyopathy

– post-cardiac arrest resuscitation syndrome

– decompensated pulmonary vascular disease

– massive pulmonary embolism

0

10

20

30

40

50

60

70

1997-1998n=1488

1999-2000n=1760

2001-2002n=2154

2003-2004n=2448

2005-2006n=2518

2007-2008n=2661

2009-2010n=3004

2011-2012n=3383

P<0.001

Mortality of CS patients admitted in ICUs

– In-ICU Mortality during the period study : 47.4% (9 205/19 416) – Decrease : -5,6 % (95% CI, -7,7 to -3,5) from 50.3% (1997-2002) to 44.8% (2009-2012)

Puymirat E et Aissaoui N., EJHF 2016

0

10

20

30

40

50

60

70

80

90

100

1997-1998n=448

1999-2000n=462

2001-2002n=528

2003-2004n=549

2005-2006n=661

2007-2008n=638

2009-2010n=767

2011-2012n=904

0

10

20

30

40

50

60

70

80

90

100

1997-1998n=55

1999-2000n=93

2001-2002n=62

2003-2004n=58

2005-2006n=59

2007-2008n=72

2009-2010n=92

2011-2012n=94

0

10

20

30

40

50

60

70

80

90

100

1997-1998n=221

1999-2000n=240

2001-2002n=266

2003-2004n=268

2005-2006n=249

2007-2008n=286

2009-2010n=343

2011-2012n=420

0

10

20

30

40

50

60

70

80

90

100

1997-1998n=264

1999-2000n=322

2001-2002n=479

2003-2004n=510

2005-2006n=570

2007-2008n=655

2009-2010n=734

2011-2012n=663

Cardiac arrest

Myocardial infarction

Decompensated heart failure

Pulmonary embolism

P=0.85

P<0.001 P<0.001

P=0.009

Mortality according to the primary diagnosis

Puymirat E et Aissaoui N., EJHF 2016

2 main types of medical CS

Severity

Acute etiology of CS ‒ AMI ‒ Fulminant myocarditis ‒ Drug intoxication ‒ ….

INTERMACS 1/refractory CS

INTERMACS 2

High risk for severe forms of CS, even refractory CS

2 main types of medical CS

Severity

Acute etiology of CS ‒ AMI ‒ Fulminant myocarditis ‒ Drug intoxication ‒ ….

Decompensated advanced heart failure

INTERMACS 1/refractory CS

INTERMACS 2

INTERMACS 3/Inotrope dependence

High risk for severe CS, even refractory CS

More often low-out put syndrome Chronic situation

HR 1.11 (0.65-1.91) P=0.69

No cardiogenic shock Cardiogenic Shock

FAST MI 2005 : 3670 pts CS occurred in 224 (6.1%)

Alive at 30D : 3411 with 99 CS

Median follow-up was 525 (inter-quartile range, 305–1496; range, 92–2400) days

Mirabel M et al., Crit Care Med. 2011;39:1029-35

ICU survival : 68%

Long-term survival : 68%

Among 115 patients, 85 patients (75%)

died at 4 months

Circ Heart Fail. 2009;2:320-4

2 main types of medical CS

Severity

Acute etiology of CS ‒ AMI ‒ Fulminant myocarditis ‒ Drug intoxication ‒ ….

Decompensated advanced heart failure

High risk for severe CS, even refractory CS

More often low-out put syndrome Chronic situation

Long term-prognosis

Sean van Diepen et al. Circulation. 2017;136:e232-e268

Sean van Diepen et al. Circulation. 2017;136:e232-e268

“ CS is a hemodynamic problem only at the very beginning, and soon becomes a very complex

disease, with bacterial translocation, overshooting

inflammation and the development of multiple organ

failure”

Combes et al. ICM. 2016

Circulation. 2017;136:e232–e268

Cardiogenic shock management pathway

Sean van Diepen et al. Circulation. 2017;136:e232-e268

Sean van Diepen et al. Circulation. 2017;136:e232-e268

The optimal first-line vasoactive medication in CS remains unclear

Sean van Diepen et al. Circulation. 2017;136:e232-e268

Inotropes or vasopressors ?

Sean van Diepen et al. Circulation. 2017;136:e232-e268

Copyright © American Heart Association, Inc. All rights reserved.

Sean van Diepen et al. Circulation. 2017;136:e232-e268

Copyright © American Heart Association, Inc. All rights reserved.

We have to

improve the

cardiac pump

function

Effects of Inotropes on Microcirculation in CS

Plos One 2014; 9: e103978.

Thirty patients with cardiogenic shock were included

“Levosimendan did not

significantly reduce all-cause mortality at 180

days or affect any secondary clinical

outcomes”

173 deaths (26%)

185 deaths (28%)

– In the SURVIVE study population (1327), 669 (50%) had received b-blockers within 24 h prior to study drug infusion.

Mebazaa A et al., Eur J Heart Fail. 2009;11: 304-11

For patients who used beta-blockers (n = 669), mortality was significantly lower for levosimendan than dobutamine at day 5 (1.5 vs. 5.1% deaths; HR, 0.29; CI 0.11-0.78, P = 0.01).

1. Dobutamine should be used to treat low cardiac output in

cardiogenic shock (strong agreement)

2. Phosphodiesterase inhibitors or levosimendan should not be used firstline (strong agreement)

3. There is a pharmacodynamic rationale for the use of levosimendan in patients on chronic beta-blocker treatment

Sean van Diepen et al. Circulation. 2017;136:e232-e268

Copyright © American Heart Association, Inc. All rights reserved.

Sean van Diepen et al. Circulation. 2017;136:e232-e268

Copyright © American Heart Association, Inc. All rights reserved.

We have to decrease the peripheral vasodilatation

Norepinephrine in cardiogenic shock ?

De Backer D et al., N Engl J Med. 2010;362:779–89

‒ 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. ‒ The baseline characteristics of the groups were similar.

Plos One 2014; 9: e103978.

Norepinephrine infusion was associated with - no changes in heart rate, - a significant increase in CI, MAP, SVO2, LVEF, dP/dt max, and SVR - a decrease in lactate level

Beurton A et al., Shock 2016; 46; 214-218

12 pigs with AMI and CS : control group (n = 6), norepinephrine infusion (n = 6)

Tarvasmäki T et al., Crit Care. 2016;20:208

‒ The multinational CardShock study prospectively enrolled 219 patients with CS (80% ACS) ‒ Patients with adrenaline : 46 (21%)

Critical care Med, 2011 ;39:450-5.

Critical care Med, 2011 ;39:450-5.

Critical care Med, 2011 ;39:450-5.

Ten patients survived in the epinephrine group and 11 in the norepinephrine-dobutamine group

Critical care Med, 2011 ;39:450-5.

Epinephrine (adrenaline) should be restricted to patients with persistent hypotension despite adequate cardiac filling pressures and the use of other vasoactive agents, as well as for resuscitation protocols

Norepinephrine should be used to restore perfusion pressure during cardiogenic shock (strong agreement)

Epinephrine can be a therapeutic alternative to the combination of dobutamine and norepinephrine, but is associated with a greater risk of arrhythmia, tachycardia, and hyperlactatemia (weak agreement)

‒ « Inotropes, especially those with adrenergic mechanisms, can cause sinus tachycardia, may induce myocardial ischaemia and arrhythmias.

- There is long-standing concern that they may increase

mortality...”

Sean van Diepen et al. Circulation. 2017;136:e232-e268

Copyright © American Heart Association, Inc. All rights reserved.

Sean van Diepen et al. Circulation. 2017;136:e232-e268

Copyright © American Heart Association, Inc. All rights reserved.

Inhibition of systemic

inflammatory response ?

Standard therapy

N = 15

Standard therapy +

LNAM (1mg/kg and 1 mg/kg/h) N = 15

Sean van Diepen et al. Circulation. 2017;136:e232-e268

1.Frequently altered mental status does not ensure correct spontaneous breathing and preservation of the upper airway, two conditions necessary for the appropriate use of NIV 2. It may be cautiously considered in selected CS patients without severe haemodynamic instability

Suggestions for Clinical Practice

The decision to intubate patients with CS should be based on standard critical care criteria; however, clinicians should be both aware of and prepared for the potential hemodynamic deterioration associated with induction therapies, inappropriate ventilation settings, the transition from spontaneous breathing to positive-pressure ventilation, and vagal stimulation association with endotracheal tube placement

In the absence of high-quality data in the CS population, we suggest that MV modes and settings be adjusted to prevent hypoxemia and hyperoxia, to minimize patient discomfort and ventilator dyssynchrony, and to optimize hemodynamics.

Circulation. 2017;136:e232–e268

Circulation. 2017;136:e232–e268

Among patients with CS, a reported 13% to 28% develop acute kidney injury and up to 20% require renal replacement therapy

Patients needing renal replacement therapy were less likely to survive to hospital discharge and had a higher risk of long-term dialysis and mortality

Patients with CS often do not hemodynamically tolerate fluid shifts that can occur with intermittent hemodialysis.

Instead, continuous renal replacement therapy, is more commonly used for those with CS.

Renal Replacement Therapy

Lauridsen et al. Critical Care (2015) 19:452

Acute kidney injury and renal replacement therapy in CS patients

5079 CS patients with 13 % had AKI-RRT

In-hospital mortality :62 % for AKI-RRT patients, and 36 % for non-AKI-RRT patients. (relative risk = 1.70,

95 % confidence interval (CI): 1.59–1.81).

Circulation. 2017;136:e232–e268

The use of percutaneous coronary intervention dereased the

mortality of patients presenting CS after AMI

Aissaoui N, EHJ 2003 33: 2535-43

486 CS patients (1995-2005)

46.7%

22 %

33.6%

40.5%

302 CS patients (1993-1998)

Hochman J, JAMA 2001 33: 190-192

“Intensive care before coronary angiography of CS secondary to MI should be of the “scoop and run” type. What is important is to transfer the patient alive to the

coronary angiography unit without any delay as a result of an attempt at stabilization.”

Multivessel coronary artery : PCI for culprit lesion or all coronary arteries ?

Patients underwent randomization immediately after diagnostic angiography 1:1 ratio

either PCI of the culprit lesion only immediate multivessel PCI

Patients were eligible for the trial if they had acute myocardial infarction with cardiogenic shock

The composite primary end point of death or renal-replacement therapy had occurred in 158 of the 344 patients (45.9%) in the culprit-lesion-only PCI group and in 189 of the 341 patients (55.4%) in the multivessel PCI group

The place of the fibrinolysis in CS STEMI patients ?

“The ESC guidelines (2012) suggest the use of thrombolysis if angioplasty cannot be performed quickly

(within 2 h), with secondary transfer to a center with a coronary angioplasty and cardiac surgery unit”

Circulation. 2017;136:e232–e268

Various profiles of severity in cardiogenic shock

patients

Inotrope dependent

Sliding on inotropes

The most severe form : Refractory to inotropes

Introduction of inotropes

Various profiles of severity in cardiogenic shock

patients

Introduction of inotropes

Introduction of inotropes

‒ « Inotropes, especially those with

adrenergic mechanisms, can cause sinus tachycardia, may induce myocardial ischaemia and arrhythmias.

- There is long-standing concern that

they may increase mortality...”

To minimize the side effects of catecholamines ?

Thiele H, N Engl J Med. 2012 Oct 4;367(14):1287-96.

A patient was considered to be in cardiogenic shock : ‒ systolic blood pressure < 90 mm Hg for more than 30 min

or needed infusion of catecholamines to maintain SBP > 90 ‒ clinical signs of pulmonary congestion, ‒ and impaired end- organ perfusion

Not eligible for the study if ‒ resuscitation for more than 30 minutes; ‒ mechanical cause of CS ‒ onset of shock more than 12 hours before screening;

The IABP does not modify the prognosis of CS

Thiele H, N Engl J Med. 2012 Oct 4;367(14):1287-96.

Randomized prospective study - 300 pts in the IABP group - 298 pts in the control group

39,7 %

41,3 %

• Intraaortic balloon counterpulsation should not be used in cardiogenic shock in the setting of myocardial infarction managed

effectively and quickly by angioplasty (weak agreement).

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. The Impella® Recover LVAD

Reesink et al., Chest 2004, Lemaire A et al., ATS 2014, Seyfarth et al., JACC 2008

‒ Short-term left ventricular support with a flow of 2.5 or 5 l/min (Impella® 2.5 or 5.0, respectively)

‒ A microaxial rotary blood pump is

inserted through the femoral artery and passed retrogradely through the aorta into the left ventricle

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25 patients (n 13 IABP, n 12 Impella LP2.5)

Ouweneel et al. J A C C 2 0 1 7; 69: 2 7 8– 8

On the contrary, due to the limited blood blow obtained with the Impella® 2.5 device, the latter is not recommended for cardiac support during cardiogenic

shock.

Various profiles of severity in cardiogenic shock patients

Introduction of inotropes

No mechanical circulatory support

Various profiles of severity in cardiogenic shock patients

Inotrope dependent

Sliding on inotropes

The most severe form : Refractory to inotropes

Introduction of inotropes

Temporary mechanical circulatory support

Long-term

mechanical circulatory support

INTERMACS 1 and 2 patients

Introduction des inotropes Refractaire aux inotropes

Although there is no strong scientific evidence to support routine MCS therapy in

CS patients to date, it can provide emergency circulatory support while a definite solution is

sought

If temporary circulatory support is needed, the use of peripheral extracorporeal membrane oxygenation is preferred (strong agreement).

Veno-arterial Extra-corporal Membrane Oxygenation

Abrams D et al., J Am Coll Cardiol. 2014;63:2769-78

VA-ECMO provides – both respiratory and cardiac

support, – biventricular support, – is easy to insert, even at the

bedside, – stable flow rates, – and is associated with less

organ failure, after implantation compared to large biventricular assist

Day-30 survival 57 %

Schmidt M et al., EHJ published June 17, 2015

Discharge from hospital 1601 (42%)

N = 235

Reported complication rates were frequent :

- Lower extremity ischemia : 16.9%

- Fasciotomy or compartment syndrome : 10.3%

- Lower extremity amputation : 4.7%

- Stroke: 5.9%

- Major or significant bleeding : 40.8%

- Re-thoracotomy for post-cardiotomy bleeding or tamponade : 41.9%

- Significant infection : 30.4%

When ?

Etiology of CS and

Medical history

Biological data and TTE

Clinical parameters

- Clinical signs associated with rapid deterioration of cardiac function - Treatments administered and tolerance

Which parameters to consider to initiate cardiac support ?

– Liver and renal impairment

– TTE data

Before multi-organ failure

develops

3846 cardiogenic shock patients risk factors associated with mortality: – preexisting comorbidities, – pre-ECMO organ failures, – cardiac arrest, – lower pulse pressure, – lower serum bicarbonate

When to initiate ?

The Impella® 5.0 device can be used in the management of cardiogenic shock

complicating myocardial infarction if the surgical team has experience with its

placement (weak agreement).

– In-ICU survival N = 23 (57%) – D-180 survival – N=20 (50%)

Indications of Impella 5.0 in CS patients

« these systems are currently more expensive and are not adapted to patients with severe biventricular failure. »

Post-heart surgery++++

16 patients developing CS or low cardiac output syndrome after being weaned off cardiopulmonary bypass

Survival to 30 days, 3 months, and 1 year was 94%, 81%, and 75%, respectively

Complications related to Impella devices

Ouweneel DM, et al., JACC 2016

Hemolysis

Complications

Bleeding

Vascular complications

Infections

ECMO or Impella 5.0 ?

Respiratory status Right ventricular function

Surgical availabilities

ECMO and Impella

ECMO ECMO and Impella

Jouan J et al. J Heart Lung Transplant. 2010;29:135-6 Cheng A et al., ASAIO J 2013; 59: 533-6

Various profiles of severity in cardiogenic shock

patients

Inotrope dependent

Sliding on inotropes

The most severe form : Refractory to inotropes

Introduction of inotropes

Decompensated of advanced heart failure

INTERMACS 3/Inotrope dependence

Long-term ventricular assist devices

ESC/EACTS Guidelines on myocardial revascularization. EHJ 2014 Levy et al., Annals of Intensive Care 2015

Management in emergency : Cardiologists, ICU physicians

Timing of cardiac device implantation : Cardiologists, ICU physicians, Surgeons

Implantation-Management : Surgeons, ICU physicians

Decision concerning long-term assist device or heart transplantation :

Cardiologists, Transplant team, ICU physicians, Surgeons

[Tertiary centers]

Mobile Unit of Circulatory Assistance

Management of cardiogenic shock need a team with a

comprehensive, structured, multidisciplinary system of care

Key role of the intensivists

Conclusions

− Several profiles of cardiogenic shock − Major concern : mortality rate around 40 to 60 % at one-month

− Lack of evidence for medical therapy and the choice of inotrope

− Early implantation of MCS without forgetting their complications

− Impella 5.0 assists the LV whereas ECMO is an extracorporeal membrane oxygentation

− Management of cardiogenic shock need a team with a comprehensive, structured, multidisciplinary system of care

Annexes

Other therapies

Corticosteroid Insufficiency in Cardiogenic

Shock Patients

Ducrocq N et al., Shock. 2017 Dec 26.

42%

32%

Corticosteroid Insufficiency in Cardiogenic

Shock Patients : prognostic value ?

Ducrocq N et al., Shock. 2017 Dec 26.

Corticosteroid Insufficiency in Cardiogenic Shock

Patients : prognostic value ?

Ducrocq N et al., Shock. 2017 Dec 26.

Patients with a T0 TC 34 μg/dL or less and Δ max greater than 9 μg/dL appeared to have the most favorable survival (91%)

Corticosteroid therapy was associated with an increased mortality (P = .03)

• Application of hypothermia in non-resuscitated CS patients may also be beneficial from pathophysiological

considerations with multiple beneficial targets