Pharmacological Strategies &

Mechanical Support
in Cardiogenic Shock

Ronggo Prakoso
 Introduction
• Cardiogenic shock is defined as a primary cardiac disorder that results
in both clinical and biochemical evidence of tissue hypoperfusion.
• Clinical criteria include:
• a systolic blood pressure ≤ 90 mm Hg for ≥ 30 minutes or
• support to maintain systolic blood pressure > 90 mm Hg and
• urine output ≤ 30 mL/hr or cool extremities.
• Hemodynamic criteria include:
• a depressed cardiac index ( ≤ 2.2 l/min/m2 body surface area) and
• an elevated pulmonary-capillary wedge pressure > 15 mm Hg.

Cardiogenic Shock
Kosaraju A, Pendela VS, Hai O.
ID: NBK482255PMID: 29489148, StatPearls Publishing LLC.2023
 Definition
Clinical Trial Cardiogenic Shock Criteria
(Guideline)
SHOCK Trial SBP <90 mm Hg for >30 min or vasopressor support to maintain SBP >90 mm Hg
Evidence of end‐organ damage (UO <30 mL/h or cool extremities)
(1999) Hemodynamic criteria: CI <2.2 and PCWP >15 mm Hg
IABP‐SOAP II MAP <70 mm Hg or SBP <100 mm Hg despite adequate fluid resuscitation (at least 1 L of
crystalloids or 500 mL of colloids)
(2012) Evidence of end‐organ damage (AMS, mottled skin, UO <0.5 mL/kg for 1 h, or serum lactate
>2 mmol/L)
EHS‐PCI SBP <90 mm Hg for 30 min or inotropes use to maintain SBP >90 mm Hg
Evidence of end‐organ damage and increased filling pressures
(2012)
ESC‐HF Guidelines SBP <90 mm Hg with appropriate fluid resuscitation with clinical and laboratory evidence of
end‐organ damage
(2016) Clinical: cold extremities, oliguria, AMS, narrow pulse pressure. Laboratory: metabolic acidosis,
elevated serum lactate, elevated serum creatinine
KAMIR‐NIH SBP <90 mm Hg for >30 min or supportive intervention to maintain SBP >90 mm Hg
Evidence of end‐organ damage (AMS, UO <30 mL/h, or cool extremities)
(2018)
Cardiogenic Shock
Vahdatpour C, Collins D, Goldberg S
DOI: 10.1161/JAHA.119.011991
The most common causes of cardiogenic shock:
• Acute myocardial ischemia ((related coronary)(AMICS))
• Contractility defect: ischemic and non-ischemic cardiomyopathy, arrhythmias, septic
shock with myocardial depression, myocarditis
• Mechanical defect: acute mitral regurgitation (papillary muscle rupture), ventricular wall
rupture (septal or free wall), cardiac tamponade, left ventricular outflow obstruction
(hypertrophic obstructive cardiomyopathy [HOCM], aortic stenosis [AS]), Left ventricular
inflow obstruction (MS, atrial myxoma)
• Aortic dissection
• Pulmonary embolus (right ventricular with or without left ventricular failure)
• Right ventricular failure
• Other causes include cardiotoxic drugs (doxorubicin), medication overdose (beta/calcium
channel blockers), metabolic derangements (acidosis), electrolyte abnormalities (calcium
or phosphate)

Cardiogenic Shock
Kosaraju A, Pendela VS, Hai O.
ID: NBK482255PMID: 29489148, StatPearls Publishing LLC.2023
 Epidemiology
• The incidence of cardiogenic shock is in decline, which can be attributed to
increased rates of use of primary percutaneous coronary intervention (PCI)
for acute MI. However, approximately 5-8% of STEMI and 2-3% of NON-
STEMI cases can result in cardiogenic shock. This can translate to 40,000 to
50,000 cases per year in the United States.
Cardiogenic shock has a higher incidence in the following classes of patients:
• Elderly population
• Patient population with diabetes
• Prior history of left ventricular injury
• Female gender

Cardiogenic Shock
Kosaraju A, Pendela VS, Hai O.
ID: NBK482255PMID: 29489148, StatPearls Publishing LLC.2023
 Pathophysiology
The pathophysiology of cardiogenic shock is complex and not fully understood. Ischemia to the
myocardium causes derangement to both systolic and diastolic left ventricular function, resulting in a
profound depression of myocardial contractility. This, in turn, leads to a potentially catastrophic and
vicious spiral of reduced cardiac output and low blood pressure, perpetuating further coronary ischemia
and impairment of contractility. Several physiologic compensatory processes ensue. These include:
• The hallmark is activation of the sympathetic system leading peripheral vasoconstriction and vital end-
organ damage, which stems from ineffective stroke volume and insufficient circulatory compensation.
Compensatory peripheral vasoconstriction may initially improve coronary and peripheral perfusion,
however it contributes to increased cardiac afterload that overburdens damaged myocardium
• Tachycardia increases myocardial oxygen demand and subsequently worsens myocardial ischemia.
• These compensatory mechanisms are subsequently counteracted by pathologic vasodilation that occurs
from the release of potent systemic inflammatory markers such as interleukin-1, tumor necrosis factor-
a, and interleukin-6. Additionally, higher levels of nitric oxide and peroxynitrite are released, which also
contribute to pathologic vasodilation and are known to be cardiotoxic.
Unless interrupted by adequate treatment measures, this self-perpetuating cycle leads to global
hypoperfusion and the inability to effectively meet the metabolic demands of the tissues, progressing to
multiorgan failure and eventually death.
Cardiogenic Shock
Kosaraju A, Pendela VS, Hai O.
ID: NBK482255PMID: 29489148, StatPearls Publishing LLC.2023
 Important Point

Ea1 Ea2

LVEDP2
LVEDP1

Cardiac System
Vascular System
• Decrease Emax (preload-independent LV contractility)
• Incease Peripheral Vascular Resistance
• Incease Ea (steeper Ea) represent increase LV afterload • maintain coronary and organ perfusion
• Increased LVEDP • Dearrangement compensation lead to hipoperfusin
• Decrease SV • Increased Cardiac Afterload & Myocard workload
JACC VOL. 73, NO. 6, 2019 Guglin et al. 699 FEBRUARY 19, 2019:698–716
 Diagnostic Evaluation of Cardiogenic Shock
includes the following:
• Complete blood picture, comprehensive metabolic panel, magnesium, phosphorous,
coagulation profile, thyroid-stimulating hormone
• Arterial blood gas
• Lactate
• Brain natriuretic peptide
• Cardiac enzyme test
• Chest x-ray
• Electrocardiogram
• Two-dimensional echocardiography
• Ultrasonography to guide fluid management
• Coronary angiography
Cardiogenic Shock
Kosaraju A, Pendela VS, Hai O.
ID: NBK482255PMID: 29489148, StatPearls Publishing LLC.2023
 mind map: critical care management
of cardiogenic shock

• Role of Intensivist
• Achieving Euvolemia
• Inotropes & Vasopressor
• Mechanical Ventilation
• CRRT
• End Organ Protection
• Role of Cardiac Anesthesiologist
• central gatekeepers of optimal outcomes for
high-risk individuals, determining variation in
the types of shock & etiologies of decreased
CO
• Role of Cardiologist/Cardiac Surgeon
• central to device selection and
implementation of temporary mechanical
circulatory support devices (tMCS)
Massod F et al
METHODIST DEBAKEY CARDIOVASC J | 16 (1) 2020
 The goal of medical management is to restore cardiac
output and prevent irreversible end-organ damage rapidly.
(1)
The optimal choice of a vasoactive agent in cardiogenic shock is unclear.
• Norepinephrine is preferred over dopamine in patients with severe hypotension (SBP < 70 mmHg) or
hypotension unresponsive to other medications
• dopamine associated with higher rates of arrhythmias & a higher risk of mortality in this patient
population.
• norepinephrine can cause tachycardia and increased myocardial O 2 demand in patients with
recent MI.
• Dobutamine (beta-1 & beta-2 agonist propertiesis) widely used, which improve myocardial contractility,
lower left ventricular end-diastolic pressure, and increased cardiac output.
• Milrinone, also a widely used inotrope, has been shown to reduce left ventricular filling pressures

Cardiogenic Shock
Kosaraju A, Pendela VS, Hai O.
ID: NBK482255PMID: 29489148, StatPearls Publishing LLC.2023
 Sustained Sympathetic Activation Leads to
β-Adrenergic Reseptor Desensitization/Down Regulation
• β-AR desensitization/down-regulation diminishes
adrenergic signaling & cardiac contractile reserve 
conventionally considered to be detrimental in HF
progression
• RyR2 dysfunction and Ca2+ leak deplete SR Ca2+
store, diminish Ca2+ release in systole and elevate
Ca2+ levels in diastole thus not only impairing both
systolic & diastolic ventricular function promote
triggered activity & arrhythmogenesis as a cause of
sudden death
• β-ARs desensitization/down-regulation, by
diminishing adrenergic signalling (may act in a way
similar to a β-AR blocker), helps to attenuate RyR2
dysfunction & Ca2+leak, protecting the heart from
developing serious cardiac arrhythmias  sudden
cardiac death Mahmood A, Ahmed K & Zhang Y
Frontiers in Cardiovascular Medicine
1 July 2022 doi: 10.3389/fcvm.2022.925692
 Role of Sarco/endoplasmic reticulum Ca2+-ATPase
SERCA in Cardiac Function

Li C, et al
Redox Biology 36 (2020) 101659
 Role of SERCA & RyR2 in Calcium Homeostasis

Wang R; REVIEW
published: 09 June 2020 doi: 10.3389/fphar.2020.00872
 Any Breakthrough?
• Levosimendan (LS) has been progressively used for the treatment of patients
developing acute as well as chronic or advanced cardiac dysfunction as a
better inotropic agent in terms of its ability to increase the cardiac output in
an acutely or chronically decompensated heart without an increase in the
myocardial oxygen demand.

Molecular Targets Pharmaceutical Results

By specifically binding to calcium-saturated cardiac
troponin C, calcium sensitization of the contractile
machinery is achieved
ATP-sensitive channels on vasculature’s
smooth muscle open
Activation of the ATP-sensitive potassium channels
in the mitochondria
Inotropy with no rise in calcium transient or oxygen
consumption; anti-stunning impact
Vasodilation (includes coronary arteries as
well); elevated end-organ perfusion
Cardiovascular and organ (heart) protection;
ischemic impact prevention
Mechanism of Action
 The goal of medical management is to restore cardiac
output and prevent irreversible end-organ damage rapidly.
(2)
• Fibrinolytic therapy should be administered to patients who are unsuitable candidates for
either percutaneous coronary intervention or coronary artery bypass graft if there are no
contraindications.
• Patients with MI or ACS are given aspirin and heparin. They have been shown to be
effective in reducing mortality.
• Diuretics (furosemide) play a role in decreasing plasma volume & edema;
• thereby decreasing cardiac output & blood pressure, lowering compensatory
mechanism in peripheral vascular resistance.
• continuous therapy, extracellular fluid and plasma volumes return almost to
pretreatment levels.

Cardiogenic Shock
Kosaraju A, Pendela VS, Hai O.
ID: NBK482255PMID: 29489148, StatPearls Publishing LLC.2023
 Integrated Action Plan
Procedures
• Central line placement plays a role in fluid resuscitation, access for multiple infusions, and allows invasive
monitoring of central venous pressure.
• Arterial line placement is useful in providing continuous blood pressure monitoring, especially in patients
requiring inotropic agents.
• Mechanical ventilation is indicated in patients with cardiogenic shock for oxygenation and airway
protection.
Percutaneous Coronary Intervention and Coronary Artery Bypass
• Primary percutaneous coronary intervention (PCI) should be performed, irrespective of time delay from
the onset of myocardial infarction
• Urgent coronary artery bypass grafting is indicated in patients with coronary anatomy not amenable to PCI.
Damage/Source Control
Implementation of temporary mechanical circulatory support devices (tMCS)

Cardiogenic Shock
Kosaraju A, Pendela VS, Hai O.
ID: NBK482255PMID: 29489148, StatPearls Publishing LLC.2023
 temporary Mechanical Circulatory Support devices
(tMCS)
Ideal Principle Mechanism of tMCS: • IABP
• Unloading LV Mechanically: • Percutaneus VAD
• Increasing SV/CO
• ECMO & E-CPR
• Afterload reduction
• Decrease Cardiac Workload, Myocard DO2, Avoid
Tachyarrhitmia (resting the heart)
• Increase O2 suplly (coronary perfusion)
• End Organ Protection (maintain organ perfusion)
• Increasing MAP, avoid pre organ vasoconstriction,
avoid venous congestion
Cardiogenic Shock
Kosaraju A, Pendela VS, Hai O.
ID: NBK482255PMID: 29489148, StatPearls Publishing LLC.2023
 Intra-Aortic Balloon
Counterpulsation (IABP)
Dual Effect
• Balloon inflation (immediately after AV closure)
• Increase diastolic pressure
• Increase mean arterial pressures
• Improves coronary perfusion
• Balloon deflation (just before AV opening)
• Reduction in left ventricle afterload (LVEDP by 6%)
• Decrease in LV end systolic pressure (by 18)
• Passively augments Stroke Volume (SV by 14%)
Primary Hemodynamic objectives of the IABP:
• increase in myocardial oxygen supply
• decrease in oxygen demand
• Decrease in Sistolic Blood & Pulmonary Capillary
Wedge Pressure (Clinically)
• optimization of end-organ perfusion
• Increase in Diastolic Blood & Mean Arterial Pressure
Kimman JR et al (Clinically)
Curr Heart Fail Rep (2020) 17:147-60
https://doi.org/10.1007/s11897-020-00480-0

Recent Statistic Outcome
• In 2015;a meta-analysis-efficacy IABP in AMI- placement in European guidelines
(12 RCTs with 2123 patients) concluded that
IABP had NO statistically significant effect on decompensated HF with cardiogenic shock)
mortality
• In other meta-analysis of 16 RCTs, prophylactic
use of IABP during high-risk PCI was Showed
NO decrease in:
• 30-day or 6-month all-cause mortality,
• re-infarction, stroke/ transient ischemic
attack (TIA),
• HF,
• repeat revascularization, embolization,
• arrhythmia
Kimman JR et al
Curr Heart Fail Rep (2020) 17:147-60
https://doi.org/10.1007/s11897-020-00480-0
A final indication includes mechanical complications of
AMI (i.e., VS or free wall rupture, IMR) as a bridge to
surgical repair (class IIa/C) recommendation for IABP
non-ACS CS group (also defined as ADHF-CS: acute
compared to inotropes treatment only:
After 48 h, IABP group had significant;
• higher central venous oxygen saturation,
• better increase in cardiac power output,
• lower NT-pro BNP levels,
• more negative cumulative fluid balance,
• better decrease in dyspnea severity score,
• increase MAP, decrease mean PAP & PCWP,
• fewer patients ended up with moderate to severe MR,
• lower major adverse cardiovascular events, death, HF, re-
hospitalization or TIA/stroke & mortality at 90 days
 Impella
A percutaneous system that consist of a micro-axial
pump
• 9 Fr catheter & pump at insertion
• Pump expand to 18 Fr
• Design for flows > 3,5 L/min
It pulls blood from LV and expels it into ascending Input
aorta, allowing heart to rest while it pumps blood into
vital organ such as brain & kidney.
• Provide left ventricular unloading
• Reduction of left ventricle end diastolic pressure
(LVEDP)
• Lowering myocardial O2 demand

IJC Heart & Vasculature 40 (2022) 101007

Statistic Review

• Short-term mortality of patients

treated with Impella device was
47.0% (95% CI 43.6–50.4%)
• Vascular access complications
occurred in 6.4% (4.8–8.1%),
major bleeding was observed in
16.4% of cases (12.4– 20.5%)
• no significant difference in
short-term 30-d all-cause
mortality versus use of IAPB
EARLIER
pre-PCI weof act
insertion in CS,
Impella wasBETTER outcomes
significantly associated are to beclinical
to better expected
outcomes. IJC Heart & Vasculature 40 (2022) 101007
Extra Corporeal Membran Oxygenator (ECMO)
• Previously as salvation for Post Cardiotomy Syndrome
(Central VA-ECMO)
• Temporary support in patients with high risk of
mortality, bridges time for:
• recovery,
• permanent assist,
• transplantation
• Suitable for CS due to:
• LV failure,
• RV failure,
• biVentriculer failure
• Severe refractory ventricular tachyarrhytmia undergo ablation
• ECMO-CPR
OVERVIEW

JACC VOL. 73, NO. 6, 2019 Guglin et al. 699 FEBRUARY 19, 2019:698–716
 Dramatic Increase in the Use of ECMO in cardiology,
the Reason:

There are several reasons behind the Availability of durable membranes

and portable circuits
• Ability of VA-ECMO to provide left, right, and biventricular support
• Ease of implantation in the catheterization laboratory or at the bedside
• Increased familiarity with the technology by cardiologists and surgeons
• The need for a short-term bridge to transplantation or mechanical support
• Progress in durable mechanical circulatory support devices, which enables
ECMO use as bridge to a left ventricular assist device (LVAD)
• Financial incentives

JACC VOL. 73, NO. 6, 2019 Guglin et al. 699 FEBRUARY 19, 2019:698–716
Comparison

JACC VOL. 73, NO. 6, 2019 Guglin et al. 699 FEBRUARY 19, 2019:698–716
Unloading LV & LV Afterload
 e ?
om
u tc
O Sasa Rajsic, Benedikt Treml, Dragana Jadzic, Robert Breitkopf,
Christoph Oberleitner, Marina Popovic Krneta and Zoran Bukumiric

• Thirty-two studies comprising 12756 patients (1994-2019)

• In hospital mortality was 62% (pooled estimate, 8493/12756)
• More than one-third of patients died during ECMO support.
• The most frequent complications were
• renal failure (51%, 693/1351)  (44%, 4879/11186) need renal replacement therapy
• bleeding (49%, 1971/4523); Surgical 14.9% and cannulation site bleeding 16.8%
• Neurological complications; cerebral bleeding occurring (5.6%) & ischemic stroke (9.8%) of patients
• Factors associated with in-hospital mortality were :
• age over 60 years,
• shorter ECMO duration and
• presence of infection
Rajsic et al. Annals of Intensive Care (2022) 12:93
https://doi.org/10.1186/s13613-022-01067-9
 Prognosis
Cardiogenic shock carries a poor prognosis and is the leading cause of death in
patients with an acute MI. Close to 80% of patients die despite optimal treatment.
Complications associated with cardiogenic shock include:
• Dysrhythmias
• Cardiac arrest
• Renal failure
• Ventricular aneurysm
• Stroke
• Thromboembolism
• Death
While the in-hospital mortality has improved, the 6-12 month mortality in
cardiogenic shock has remained unchanged at >50% over the past 2 decades.
Cardiogenic Shock
Kosaraju A, Pendela VS, Hai O.
ID: NBK482255PMID: 29489148, StatPearls Publishing LLC.2023
 Conclusion
• Cardiogenic shock is a life-threatening disorder and main cause of
death after an acute MI. Even in the best of hands & latest treatment,
the condition carries a mortality rate in excess of 30%.
• Because cardiogenic shock affects almost every other organ in the
body, the condition is best managed by an interprofessional team that
also includes ICU, nephrologist, pulmonologist, and internist should
be involved to ensure optional care.
• Neither pharmacological therapy nor mechanical circulatory support
are proven to be ideal treatment, combination and selection more
beneficial to improve outcome whether protocols and techniques
must be developed to reduce the rate of adverse events
Terima Kasih
Just because
you can,
doesn’t mean
you should
Do No HARM