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Cardiogenic shock in acute myocardial infarction: clinical outcome and predictors

Vis, M.M.

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Citation for published version (APA):Vis, M. M. (2012). Cardiogenic shock in acute myocardial infarction: clinical outcome and predictors.

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Download date: 21 Apr 2020

https://dare.uva.nl/personal/pure/en/publications/cardiogenic-shock-in-acute-myocardial-infarction-clinical-outcome-and-predictors(b7d2af35-c6d5-4248-b283-7445919b83d2).html

M. Marije Vis

Jan J. Piek

José P.S. Henriques

CHAP05p074_099MarijePS 11-10-2012 00:55 Pagina 76

P A R T I I C H A P T E R

Cardiogenic shock:

role of revascularization

Minerva Cardioangiologica, 2011;59(1):75-87

5


A B S T R A C T

The most common cause of cardiogenic shock is myocardial ischemia developing

early or late in the course of acute myocardial infarction. The incidence of cardio-

genic shock (CS) is around 7% in ST-segment elevation myocardial infarction

(STEMI) patients and has remained constant over the last 20 years. Therapy

should be chain based by increased patient’s awareness. Early and prehospital

diagnosis and treatment, with prompt transfer to a catheterization laboratory.

Early revascularization is the cornerstone treatment of acute myocardial infarction

complicated by cardiogenic shock. According to the guidelines, revascularization is

effective up to 36 hours after the onset of CS and preformed within 18 hours after

the diagnosis of CS. Primary percutaneous coronary intervention (PCI) is the most

efficient and easily available therapy to restore coronary flow in the infarct related

artery. Although recommended, there is little evidence that immediate multivessel

PCI is beneficial for CS. The growing numbers of reports suggest staged PCI pro-

cedures or CABG is preferred in CS patients with significant LM disease or 3-ves-

sel disease. The use of hemodynamic support with newly available percutaneous

left ventricular unloading devices may herald a new era enabling preservation of

adequate perfusion to other vital organs such as the brain, kidney and bowel.

Despite all current efforts, in-hospital mortality for CS remains around 50%.

However, long-term outcome and quality of life in hospital survivors is similar to

patients with ST-segment elevation myocardial infarction patients presenting wit-

hout CS.

CARD IOGEN I C SHOCK IN ACUTE MYOCARD IA L INFARCT ION

P A R T I I ANG IOGRAF I C PARAMETERS IN CARD IOGEN I C SHOCK

78


C A R D I O G E N I C S H O C K

Cardiogenic shock is still the leading caus of in-hospital mortality for patients admit-

ted with acute myocardial infarction, both ST-segment elevation myocardial infarc-

tions (STEMI) as nonSTEMI, with diffuse subendocardial ischemia.1 Due to impro-

vement in therapy, mortality in STEMI patients without cardiogenic shock (CS) had

declined over the years. In the early days mortality was around 30%, with bed rest

as the only therapeutic modality. In the sixties mortality dropped to 13-15%, when

coronary care units appeared with possibility of hemodynamic monitoring, defibril-

lation and B-blockers prescription.2 Nowadays mortality is around 6% in the era of

early revascularization (ERV) (F IGURE 1 ).3-20

Despite improved strategies for acute STEMI, the incidence of cardiogenic shock in

STEMI patients at presentation has remained constant over the last 20 years and is

still around 7%.3 Only recently, some reports show a decline in the incidence of CS,

mainly due to less delayed CS after hospital admission, parallel with an increase of

pre-hospital triaging systems and primary PCI.3-6 Early revascularization (ERV) dec-

reases cardiogenic shock late in the course of acute myocardial infarction. Once CS

has been diagnosed in –hospital mortality remains still unacceptably high around

50%.5 Although in hospital mortality is still very high in these patients, long term

survival after hospital discharge is comparable to STEMI patients without CS on

admission with an annual mortality between 2- 4%.7,8 Development ofcardiogenic


CARD IOGEN I C SHOCK : ROLE OF REVASCULAR I ZAT ION C H A P T E R 5

79

4 0

3 0

2 0

1 0

0

Bed rest30%

DefibriliationHemodynamic

MonitoringB-Blockade

13-15% AspirinPCI,Lysis

5.0-6.5%

Pre-CCU Era CCU Era Reperfusion Era

F IGURE 1 Consequences of STEMI: early mortality risk over the last decades.

CCU= Coronary Care Unit, Adapted from Antman EM 2.0

30-d

aym

orta

lity

(30%

)


shock may result from ischemic and non ischemic conditions leading to global or

regional pump failure or ischemic or non ischemic mechanical complications

(TABLE I).

The focus of this review is the role of revascularization in reversing CS due to ische-

mic heart disease.

PAT H O F YS I O LO GY O F C A R D I O G E N I C S H O C K

Cardiogenic shock is defined as systemic hypoperfusion induced by left ventricular

(LV) failure in spite of adequate LV-filling pressure. The classic criteria for CS are

shown in TABLE I I .9 When over 40% of myocardium is ischemic or necrotic a mis-

match between oxygen supply and demand leads to a downward spiral of low car-



80

TABLE 1 Causes of Cardiogenic Shock

1 P U M P F A I L U R E :

Large Infarction

Smaller infarction with pre-existing disease

Right Ventricular failure

2 M E C H A N I C A L C O M P L I C A T I O N S

Papillary muscle rupture

Ventricular septal defect

Cardiac rupture

Tamponade

3 O T H E R P R I M A R Y C A R D I A C C O N D I T I O N S

Myocarditis

Acute stress cardiomyopathy

End-stage cardiomyopathy

Left ventricular outflow tract obstruction

Valvular disease

Arrhythmias

4 O T H E R C O N D I T I O N S

Trauma with myocardial contusion

Septic shock with myocardial depression

Aortic dissection with acute aortic regurgitation


diac output reduced antegrade and collateral coronary perfusion. Decreased tissue

perfusion results in anaerobic metabolism with formation of lactate in the affected

hypoxic cells. Lactate acidosis consequently leads to myocardial cell membrane dys-

function, leakage of toxins into the circulation resulting in endothelial dysfunctions.

Apoptosis of myocardial cells leads also to a systemic inflammatory response syn-

drome (F IGURE 2 ).

In circulatory failure, all compensatory mechanisms aim to preserve end organ per-

fusion. There is a clear hierarchy in preserving sufficient circulation to those organs

that least withstand ischemia. This hierarchical order in preserving adequate circu-

lation is brain, heart, kidney, bowel, before all other organs are supplied.

Sympathetic activation to compensate low Cardiac Output (CO) and maintain

blood pressure leads to peripheral vasoconstriction and progressive capillary dys-

function with peripheral pooling of blood. Inadequate flow especially to the brain

and kidneys leads to irreversible damage and death. As brain function is the most



81

Systemic Inflammatoryresponse syndrome(IL-6, TNF-a, NO)

↓ Cardiac output↓ Stroke volume

↑ LVEDP Pulmonarycongestion

↓ Coronary PerfusionPressure

↓ Systemic Perfusion

Hypotension

Hypoxemia

Compensatoryvasoconstriction

Myocordial infarction

Myocordial dysfunction

Systolic Diastolic

Ischemia Relief of ischemia

SURVIVAL with GOOD QUALITY of LIFEDEATH

Progressivemyocardialdysfunction

Revascularization

F IGURE 2 Pathofysiology of the different mechanisms leading to cardiogenic shock.

Adapted from Hochman and Hollenberg et al. Circulation. 2008;117:686-697




82

important function by which human life is determined, preservation of flow to the

brain should intuitively be the most important target. However, until recently the

only true option these patients had in deplorable conditions was by recovery of suf-

ficient native heart function to maintain end organ perfusion. From this point of

view, only early revascularization holds the premis of recovery.

AC U T E MYO C A R D I A L I N FA RC T I O N A N D C A R D I O G E N I C S H O C K A L E RT P L A N

The cornerstone of preventing cardiogenic shock is early revascularization. Only a

chain approach, with rapid evaluation and prompt initiation of supportive therapy

with the purpose to shorten total ischemic time and consequently duration of cardi-

ogenic shock, will lead to improved outcome. (F IGURE 3). The first step in this

approach is timely recognition of signs and symptoms of acute myocardial infarcti-

on, for both patients and physicians or paramedics. The general public can be edu-

cated, by repeated public campaigns, when and how to search for medical help.

Furthermore, easy access to medical care will enable early reporting and presentati-

on of STEMI patients and thereby reducing the chance of developing CS.

Pre-hospital or in ambulance diagnosis of STEMI and prompt treatment with anti-

thrombotic agents is likely to further decline the incidence of CS at presentation. In

patients with acute STEMI, rapid transportation to tertiary canters with 24/7 avai-

lability for immediate revascularization is mandatory, and if necessary prompt per-

cutaneous mechanical support can be started.

Risk stratification for those at risk for developing shock, is likely to have an impor-

tant impact on survival (as early diagnosis of acute myocardial infarction had had).

Therefore, it is of major importance to study those at risk to develop cardiogenic

shock. This may reduce the incidence of cardiogenic shock on admission as well as

the development of CS even after reperfusion or early indentify those at risk for

further deterioration after initial therapy has been administered.

R I S K ST R AT I F I C AT I O N

There are a number of risk factors associated with extended left ventricular dysfunc-

tion and development of cardiogenic shock.

Older patients tend to have longer delay before calling for assistance.10 Women are

known to have a delay of around 30 minutes compared with men before seeking




83

medical care. The average age of women with their index myocardial infarction is

higher. As a result, the Shock registry registered more women (43%) in cardiogenic

shock compared to only 20-25% women reported in regular AMI patient cohorts.

Also, their clinical presentation is different leading to both patient and doctors

delay.

Some classical risk factors associated with higher mortality in STEMI patients are

also risk factors for cardiogenic shock (CS).11 For example, patients with diabetes

Symptoms Characteristic Hemodynamics ECG

patients with CS (prone) symptoms: calling for help

In ambulance triage

ECG data transmission to tertiary centre cardiologist: decision STEMI and/ or CS (prone)

In ambulance administratin of anti-thormbotic regimens(and inotropic agents if RR < 100 mmHg)

Immediate CAG with intention to ERV who develop shock within 36 hours of MI andwho are suitable for revascularisation that can be performed within 18 hours of shock

Chest pain

alteration in mental status

Cool & clammy extremities

sweating

Older age

Female gender

Former myocardialinfarction

known glucose intolerance/ diabetes mellitus

Former PCI + stent

Systolic pressure < 100 mmHg

Drop of mean arterialpressure > 30 mmHg

Killip class > I

Cyanosis

Pulse > 100/min or < 40/min

HR > 100/min or < 40/min

Longer QRS-duration

New LBBB

Pathological Q-waves

LAD related infarction

≥ 1 mm extensiveST- segment ↑

Diffuse subendocardial ischemia

F IGURE 3 Suggested cardiogenic shock alert plan


mellitus, usually older and more often female, have a higher incidence of CS when

compared with patients without diabetes mellitus. Also patients with multivessel

disease or previous myocardial infarction and kidney dysfunction, both conditions

being associated with diabetes as well, are a subset of patients with higher risk for

CS and death. Also, anemia has been associated with poor outcome in heart failure

and in CS patients.12-14 Clinical characteristics represented by higher Killip class and

higher heart rate contribute to worse prognosis. (TABLE 2, 3 ).15,16

Recognizing all of these signs of (pre) shock can lead to an earlier diagnosis (dia-

gnostic tests to confirm the clinical setting) and initiation of more intensive treat-

ment. As previously mentioned, pre-hospital medical treatment leads to earlier

reperfusion of the myocardium.



84

TABLE 2 Classic criteria cardiogenic shock according to the SHOCK trial

1 S Y S T E M I C H Y P O T E N S I O N W I T H A D E Q U A T E F I L L I N G P R E S S U R E

systolic pressure < 90mmHg or vasopressors or IABP to maintain blood pressure ≥ 90 mmHg

LV end diastolic pressure > 18 mmHg or RV end diastolic pressure > 15 mmHg

Drop of mean arterial pressure > 30 mmHg

2 P E R S I S T E N T H Y P O T E N S I O N > 3 0 M I N U T E S

3 P O O R S Y S T O L I C C A R D I A C F U N C T I O N

CI < 1.8 L/min/m2 or CI < 2.2 L/min/m2 with support

4 T I S S U E H Y P O P E R F U S I O N

Brain: alteration in mental status

Kidney: oligurie < 30 ml/hr

Skin: cool and clammy extrimities, cyanosis, sweating

TABLE 3 Killip classification & approximate mortality (%) in early revascularisation era

Killip class I: no clinical signs of heart failure (3%)

Killip class II: rales or crackles in lungs, an S3 gallop, elevated jugular venous pressure (9%)

Killip class III: acute pulmonary edema (20%)

Killip class IV: cardiogenic shock or hypotension (systolic blood pressure < 90 mmHg)

peripheral vasoconstriction (oliguria, cyanosis or sweating) (40%)

Extracted from Killip T, Kimball JT (oct 1967). Treatment of myocardial infarction in a coronary care unit.

A two year experience with 250 patients. Am J Cardiol. 20(4):457-64




85

R I S K A SS E SS M E N T I N C S W I T H ECG

As the electrocardiogram is one of the first diagnostic tools for early risk assessment,

it is of value to understand what features are associated with reduced clinical outco-

me or development of CS.

Heartrate (<40/min or >100/ min)

ST segment elevation revealing transmural ischemia.

Localization of myocardial infarction (inferior vs. anterior)

Diffuse subendocardial ischemia (sum of ST-depression).

Longer QRS duration

New left bundle branch block

Right bundle branch block with left axis deviation

Signs of global ischemia such as ST segment elevation in AvR

R I S K A SS E SS M E N T I N C S W I T H EC H O C A R D I O G R A P H Y

When patients present with acute inferior wall infarction and CS, especially when

the right coronary artery is involved, right ventricular failure may be part of the

acute CS presentation. This condition usually responds quite well to adequate intra-

venous fluid administration and mild inotropic medication and resolves after ade-

quate reperfusion. When more severe CS is present in inferior wall infarction, addi-

tional conditions need to be considered. Patients may have had prior (anterior)

myocardial infarction or a concomitant mechanical complication should be suspec-

ted. One of the most important and easily available techniques is echocardiography.

A transthoracic echocardiogram may sometimes not reveal subtle findings but will

discriminate between severe left ventricular dysfunction or other reason for circula-

tory distress. When patient are on mechanical ventilation additional transoesopha-

geal echocardiography is essential, as this may reveal more details and there is no

real drawback in using a transoesophageal probe in already intubated patients.

Clearly the need for intubation is usually a sign of worsening circulatory conditions

requiring complete disclosure of myocardial function.

Besides revealing structural disease such as valvular disease it may give important

information about filling pressures. A short mitral deceleration time (≤140 ms) is

highly predictive of pulmonary capillary wedge pressure ≥ 20 mmHg in CS.17 Of

note, the importance of echocardiography is much higher than the introduction of


a pulmonary artery catheter. There is no strong support for the latter to improve cli-

nical outcome. The goal is to understand the origin of CS and potentially treat the

underlying disease while a monitoring catheter will only monitor the patient.

C U R R E N T T H E R A P E U T I C MO DA L I T I E S

As mentioned before, the only approach of reversing ischemic induced CS is revas-

cularization. Other supportive therapeutic modalities (pharmotherapeutic agents

and mechanical support) are necessary to improve hemodynamic flow and perfusi-

on. When pondering on the importance of brain and other end-organ perfusion,

one might speculate if mechanical support might be even more important compa-

red with early revascularization. Nevertheless, currently only recovery of sufficient

native myocardial function is the real option for all patients. There is only one

method: revascularization.

RO L E O F R E VA S C U L A R I ZAT I O N

The SHould we emergently revascularize Occluded Coronaries for cardiogenic

shocK (SHOCK) was the first prospective multicenter trial comparing emergency

revascularization (PCI or CABG) with initial medical stabilization.18 There was a sig-

nificant benefit in survival in the ERV group on long term (> 6 months) survival.

Although this trial has been seen as landmark trial in CS patients, few notes are in

place. First of all, the trial was designed to show a survival benefit at 30 days after

the initial event. After 30 days there was no significant difference. Additionally even

after 6 months, although a significant difference in survival was observed, it was con-

siderably smaller than the originally assumed mortality difference at 30 days.9,18,19

A total of 302 patients from 30 sites were randomized over the period of 5 years,

resulting in an average of 2 pt/years (10/centre in 5 years). Nevertheless, this was the

first trial showing that an available strategy resulted in higher survival compared

with a conservative approach.

Consequently, the AHA guideline recommends ERV, PCI or CABG, for patients

presenting with ST elevation or LBBB who develop shock within 36 hours of acute

myocardial infarction and are suitable for revascularization that can be performed

within 18 hours of shock.20 For all patients less than 75 years old and those over 75

years old with good functional status emergency revascularization is recommended.



86


I M M E D I AT E CO RO N A RY A N G I O G R A P H Y B A S E D T H E R A P Y I N C S

Coronary angiography gives detailed information concerning severity of coronary

artery disease (CAD) for further risk stratification and therapy. (F IGURE 4 )

Angiographic findings in the SHOCK trial showed highest mortality in LM disease

as culprit artery. In half of the patients the IRA was the left coronary descending

artery (LAD). Multivessel disease (MVD) was identified in over 50% of cases and

showed worse prognosis compared to single vessel disease.21 The initiation of cardi-

ogenic shock in acute STEMI is due to an occlusion of a coronary artery. In electro-

cardiographic confirmed STEMI, a total 20-30% of patients have spontaneous

reperfusion with already open coronary arteries on immediate angiography, when

in ambulance anti thrombotic medication has been administered. In patients pre-

senting with CS this is 10% at best. Coronary occlusions on the initial angiogram are

associated with CS and reduced survival. Therefore, immediate transportation to

tertiary centers with 24/7 availability of a catheterization laboratory and comple-

mentary cardiothoracic surgery is the optimal regimen.



87

Fibrinolytic therapy should be administered to those patients who are not candidates for early revascularization and who do not have a contraindicating to fibrinolysis.

GENERALsystolic pressure < 100 mmHg: Dopamine

systolic pressure < 70 mmHg: NorepinephrineIABP

CAG

Failed PCI

Moderate: 1(sub) totalocclusion and < 90% stenosis in nonculprit

major vessels

Severe: 2 (sub) totalocclusions or > 90%

stenosis in 2 nonculpritmajor vessels

1-vessel 2-vessel 3-vessel LM

PCI IRA PCI IRA + delayed PCI PCI IRA+ delayed CABG Immediate CABG

F IGURE 4 Revascularization strategy. Adapted from the ACC/AHA/ESC guidelines.20,29


P C I A N D C A B G T H E R A P Y R E S U LT S

Primary percutaneous coronary intervention (PCI) is the most efficient and easily

available therapy to restore coronary flow in the infarct related artery (IRA). It is

superior to thrombolysis, which only leads to successful reperfusion in 40-50% of all

cases with CS and has not shown to lead to improved survival compared to conven-

tional therapy for CS STEMI patients.22 Clearly, PCI is the cornerstone therapy for

all STEMI patients including those in CS.

As single vessel disease is currently treated with primary PCI, the issue for acute sur-

gical revascularization, only arise in the case of multivessel disease on the initial

angiogram. Multivessel disease (MVD) was seen over 50% of cases in the SHOCK

trial as well as in other reports. Patients with MVD had worse clinical outcome com-

pared to single vessel disease.21 MVD is correlated to worse LV function at baseline.

As restoration of coronary blood flow to the ischemic myocardium has been the

rationale for treatment, many MVD patients underwent additional PCI or CABG.

However, there is no evidence that additional revascularization in MVD patients

results in superior clinical outcome.23 Recently, our group has identified that that the

impact of MVD on mortality is mainly determined by the presence of a chronic total

occlusion (CTO) in a non-IRA.24-27 A CTO was found to be an independent predic-

tor of both short- and long-term mortality. It is associated not only with poor LV

function immediately after the index event, but also with a higher rate of a further

deterioration of LV function. Even in a STEMI CS cohort of 292, only the presence

of a CTO is an independent predictor for mortality and MVD without a CTO was

no longer an independent predictor.25

Multivessel PCI in MVD is only recommended by the AHA/ACC/ESC guidelines

in case of persistent CS after primary PCI. Early multivessel PCI is associated with

higher rate of complications probably due to adverse thrombotic events in a pro-

thrombotic environment.28,29 Furthermore, implanting stents while in cardiogenic

shock holds the risk of under deployment of stents with higher risk for stent throm-

bosis. Staged PCI procedures or CABG is preferred in patients with significant LM

disease or 3-vessel disease. Of note, in the SHOCK trial patients were treated with

an aim to complete revascularization. Therefore, 37% of these very poor patients

underwent immediate surgical revascularization. Surprisingly, patients treated with

CABG has comparable outcomes with PCI patients, while those treated with surge-



88


ry were in worse condition.30 One of the reasons for this relatively good outcome of

CABG patients may have had to do with the fact that the severity and presence of a

CTO were importantly stratified for either strategy, with a larger amount of comple-

te revascularization in the group selected for CABG.

Furthermore, the presence of a CTO is associated with a further decrease of LV

function during hospitalization as well as follow up.31 In case of a concomitant CTO

our data might support a strategy to recanalize a CTO in the non- IRA within the

first week or early thereafter after the index myocardial infarction. This strategy is

currently being tested in the global Explore trial.32

The ACC/AHA practice guidelines recommend immediate CABG for LM or 3 VD.

However, daily clinical practice is different. Even in the SHOCK trial administered

therapy was somewhat different as pre- specified and recommended per protocol.

As there seems to be a discrepancy between the guidelines and daily clinical practi-

ce, one may wonder about potential explanations. Either the guidelines should be

reinforced more strongly or the daily clinical practice does not support this strate-

gy. Additionally, as mentioned, multivessel PCI or CABG has not shown to lead to

better clinical outcome with similar, very high mortality rates. Also, it is important

to keep in mind the fact that the SHOCK trial was in fact a per protocol negative

trial, with (although a statistically significant) only a mild difference in mortality and

only after 1 year ( 53,3 vs 66,4 %, P<0.03).33

WH E R E S H O U L D W E G O TO I N PAT I E N TS W I T H MU LT I V E SS E L D I S EA S E

I N DA I LY C L I N I C A L P R AC T I C E ? C A B G O R P C I ?

According to the SHOCK trial, complete revascularization has beneficial effect on

long term survival.34 In the SHOCK trial both emergency CABG and PCI showed

comparable results in survival and quality of life on the long term. Another series of

emergency CABG in CS patients showed a better in hospital survival when a bea-

ting heart procedure was used. Also a 6-fold higher usage of a left internal mamma-

ry artery graft was seen which might explain the better survival on the long term.35

Staged PCI procedures might be considered as a good alternative in 3 VD and LM

disease. Nevertheless, one needs to keep in mind that it is all about the culprit arte-

ry in acute myocardial infarction. Our AMC revascularization strategy is therefore

more focused on treating the culprit artery and not only seldom treat CS patients



89


with immediate or delayed CABG (F IGURE 5 ). Our strategy may in fact be more in

line with current daily practice in the majority of tertiary hospitals. In addition,

during the decision making process one may keep in mind that a high Syntax score

will direct to a more complicated PCI with possibility of not achieving full revascu-

larization (F IGURE 6 ) .

Primary PCI has evolved, including the introduction of stents and platelet glycopro-

tein IIb/IIIa receptor inhibitors (GPI). Although intracoronary stenting has not

showed to impact on survival, it reduces recurrent myocardial infarction and target

vessel revascularization.36 Contrariwise, it may hold a higher risk for stent thrombo-

ses, associated with a worse clinical outcome.



90

GENERALsystolic pressure < 100 mmHg: Dopamine

systolic pressure < 70 mmHg: NorepinephrineConsider percutaneous implantable LVAD (impella 2,5 or 5,0)

CAG

Failed PCI

Moderate: 1(sub)total occlusion

and < 90% stenosisin nonculprit major vessels

Severe: 2 (sub) total occlusions

or > 90% stenosis in 2 nonculprit major vessels

TIMI flow IRA

0+1 2+3

Individualdecisionbased on

area at riskand/or highSyntax score

1-vessel 2-vessel 3-vessel LM

PCI IRA PCI IRA + clinically driven (delayed) PCIImmediate/

delayedCABG

F IGURE 5 Revascularization strategy according to daily practice at the Academical Medical Center.


The administration of GPI results in a higher rate of TIMI 3 flow after PCI which

has been shown to be one of the most important prognostic factors for survival,

especially in CS. Not only does pre-treatment with GPI lead to higher rates of TIMI

3 flow, also administration before arrival on the cath-lab or in the ambulance results

in a higher rate of TIMI 3 flow on the initial angiogram before PCI.37

Restoration of coronary flow, in cardiogenic shock due to ischemia, is apparently

not sufficient in these critically ill patients. Besides ERV probably a combination

with intensive medical - and left ventricular (LV) mechanical support might be

necessary in improving survival on the long term.

M EC H A N I C A L S U P P O RT

The guidelines recommend Intra Aortic Balloon Pump (IABP) therapy when CS

persists and is not quickly reversed with pharmacological therapy. The IABP redu-

ces afterload, leading to reduced LV wall stress, higher CO and less oxygen demand.

Furthermore, diastolic augmentation with elevated diastolic coronary inflow leads

to better oxygen supply. Both the GUSTO and SHOCK trial showed a trend

towards improved survival. However, a recent meta analysis did not show any bene-



91

F IGURE 6 Syntax score adapted from Eurointervention 2005.10.

Dominance

Calc

ifica

tion

Thrombus

BifurcationTortuosity

Tota

l Occ

lusion

Number& locationof lesions Left Main

3Vessel

S Y N TA XS C O R E


fit and in fact, patients treated with an IABP had more often severe complications.38

The most used percutaneous LV unloading devices that may serve as bridge- to-

recovery (or to decision) are the TandemHeart (Cardiac Assist, Inc, Pittsburgh, Pa)

and the Impella 2.5 (Abiomed, Inc, Danvers, Mass). The TandemHeart pVAD is an

extra corporeally continuous-flow assist device. The pump is capable of delivering

blood flow up to 5.0 liters per minute. TandemHeart pVAD provides short-term

support from a few hours up to 14 days. Another easily insertable LVAD is the

Impella 2.5 in the left ventricle, generating flows up to 2.5 L/min. It directly unlo-

ads the left ventricle, reduces myocardial workload and oxygen consumption. It inc-

reases cardiac output and coronary and end-organ perfusion. Both LVADs at least

partly support circulation by draining blood from the left side of the heart and retur-

ning oxygenated blood to the systemic arteries. LVAD therapy results in a higher

cardiac power index compared with IABP.39 Cardiac power is the product of cardiac

index and mean arterial pressure. Cardiac power output and index were the most

important independent predictors of in-hospital mortality in the SHOCK trial.

40Although promising techniques, there are no studies yet showing a better clinical

outcome when treated with any of these devices.

Another support system is extracorporeal membrane oxygenation (ECMO). An

ECMO machine is similar to a heart-lung machine. The ECMO machine continu-

ously pumps blood from the patient through a “membrane oxygenator” that imita-

tes the gas exchange process of the lungs. In a small series of 5 patients, it immedia-

tely stabilized circulation and organ perfusion before a LVAD was implanted. After

continuation for 3 days as support for RV failure it could be stopped safely with pre-

served organ function. The bleeding complications and the LV overloading effects

seem to limit its widespread usage.41

I N OT RO P I C AG E N TS

In reaction to extensive myocardial depression due to ischemia or necrosis , com-

pensatory mechanisms are activated in order to prevent further damage to the heart

and end organs. Insight into these acute phase reactions might lead to new treat-

ment modalities. A variety of mechanisms and factors play an important role not

only in the genesis of shock but also in outcome after shock.

The neurohumoral reaction to hypo perfusion is release of catecholamine, angioten-



92


sine II (ACE II), vasopressin and retention of salt and water. Catecholamines increa-

se contractility and elevate periferal vasoconstriction. ACE II and vasopressin

improve peripheral and coronary blood flow but a negative side effect is the increa-

se in afterload leading to a higher myocardial oxygen demand with a toxic effect.

This is probably why higher dose of inotropic agents are associated with poorer

outcome.42

The cytokine system also plays an important role. Activation of this systemic inflam-

matory stress syndrome (SIRS) with symptoms as fever, elevated white blood count

and CRP can lead to lower inappropriate systemic vascular resistance, similar to

sepsis, with persistent cardiogenic shock. Thusfar iNOS inhibition has failed to

show any improvement in clinical outcome.43 The TRIUMPH trial not only showed

that targeting this pathway did not result in improved clinical outcome, it also show-

ed that increase of cardiac output by whatever agent is not necessarily associated

with improved clinical outcome.

F U T U R E D I R EC T I O N S

Improving early pre-hospital identification, presentation and therapy will be the

cornerstone by which we can reduce the occurrence of and fatality rate in CS.

Immediate transport to a catheterization laboratory and appropriate and state-of-

the-art revascularization is mandatory. When CS develops prompt additional tes-

ting to elucidate the underlying diagnosis of cardiogenic shock is mandatory.

Echocardiography has a cornerstone role. In addition, known or new (bio)markers

may identify patients at risk for developing CS.44

It is likely that with the arrival of newer, more potent and safe percutaneous circu-

latory support devices we need to re-engineer the strategy in these CS patients.

Early and adequate circulatory support and LV unloading may enable not only to

open up the infarct related artery but perhaps also full revascularization even in case

of a CTO. Furthermore prolonged LVAD support might lead to less activation of

SIRS. Therefore in STEMI patients with CS , the paradigm may shift from “time-

to-balloon” to “time-to-circulatory support”.

Although CS is usually a disease of the left ventricle and left coronary artery, a total

of 38% in STEMI patients admitted with CS, have RV-failure.45 The only adequate

therapy now available is inototropic infusion when adequate filling pressure of 15



93


mmHg has been achieved by fluid infusion. Higher pressures in combination with

fluid infusion will lead to shifting of the interventricular septum, limited filling of the

LV and lower CO. Currently there are no specific percutaneous cardiac assist devi-

ces for right ventricular failure. The first in man study of the newly designed RV

Impella for right ventricular support is therefore eagerly awaited.

Nevertheless, the above mentioned visions may prove to be only futuristic.

Currently, prompt restoration of the infarct related artery is the single most impor-

tant therapy and additional revascularization in MVD patients should be only care-

fully considered.

C O N C L U S I O N S

Cardiogenic shock is a syndrome of the failing heart. The most common cause of

cardiogenic shock is ischemia developing early or late in the course of acute myo-

cardial infarction. Early revascularization has been proven to be effective in the tre-

atment of acute myocardial infarction. Since the rise of primary PCI, the develop-

ment of cardiogenic shock late in the course of MI has declined. Therapy should be

chain based, starting with educating the patient, early diagnosis and treatment befo-

re arrival at an emergency catheterization laboratory with all facilities. Immediate

transportation to a tertiary center with availability to perform primary PCI is man-

datory. The so called rise of the percutaneous LVAD machines potentially herald a

new era. Although in hospital mortality remains high we have to bear in mind that

long term outcome is comparable to STEMI patients without CS with good quality

of life.



94


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