Fundamentals of Cardiogenic Shock: Pathophysiology, Risk Factors, and Clinical Presentation

I. Epidemiology and Incidence

Cardiogenic shock (CS) complicates 5–10% of acute myocardial infarctions and is increasingly encountered in non-ischemic ICU populations. Despite advances, in-hospital mortality remains high.

Incidence:

• 5–10% of AMI patients develop CS
• Rising prevalence in decompensated chronic heart failure and myocarditis cases

Outcomes:

• In-hospital mortality: 40–60%
• One-year mortality: >50%
• Modest decline in short-term mortality with early revascularization and shock teams

Disparities:

• Geographic and resource variability in PCI access
• Socioeconomic barriers delay presentation and treatment

II. Definition and Diagnostic Criteria

CS is defined by primary cardiac pump failure leading to critical end-organ hypoperfusion. Diagnosis integrates hemodynamics, clinical signs, and laboratory markers.

Hemodynamic thresholds:

1. SBP <90 mmHg or MAP <65 mmHg (sustained or requiring support)
2. Cardiac index <2.2 L/min/m² (if measured invasively)
3. PCWP >15 mmHg (if measured, indicating congestion)

Clinical evidence of hypoperfusion:

• Altered mental status; cool, clammy extremities; oliguria (<30 mL/h)
• Elevated jugular venous pressure; pulmonary rales; S3 gallop (signs of congestion often accompany hypoperfusion)

Laboratory markers:

• Lactate >2 mmol/L; rising creatinine; metabolic acidosis

Distinction from other shock types:

• Hypovolemic: Low circulating volume (low CVP/PCWP).
• Distributive: Vasodilation (e.g., sepsis, anaphylaxis; often warm extremities initially, low SVR).
• Obstructive: Mechanical obstruction to cardiac filling or emptying (e.g., pulmonary embolism, tamponade).

SCAI Shock Stages A–E guide severity assessment and escalation planning.

III. Etiologies and Risk Factors

CS arises from acute insults on a vulnerable myocardium and is exacerbated by chronic comorbidities and social determinants.

A. Acute Precipitants

• STEMI/NSTEMI (especially large anterior MI or multivessel disease)
• Mechanical complications of MI (e.g., papillary muscle rupture, ventricular septal defect, free wall rupture)
• Sustained ventricular arrhythmias (VT/VF)
• High-grade AV block or severe bradycardia
• Acute valvular dysfunction (e.g., acute severe aortic or mitral regurgitation)
• Drug/toxin-induced myocardial depression (e.g., β-blocker overdose, calcium channel blocker overdose, anthracyclines)
• Myocarditis (fulminant)
• Takotsubo cardiomyopathy (severe variants)
• Post-operative CS after cardiac surgery or complex percutaneous interventions

B. Chronic Comorbidities

• Pre-existing heart failure (reduced myocardial reserve)
• Diabetes mellitus (associated with diffuse coronary artery disease, microvascular dysfunction, metabolic stress)
• Chronic kidney disease (contributes to volume overload, uremic cardiomyopathy, and inflammation)
• Advanced age
• Peripheral artery disease (marker of systemic atherosclerosis)

C. Social Determinants of Health

• Medication access and adherence barriers (e.g., cost, lack of insurance)
• Low health literacy leading to delayed symptom recognition and seeking care
• Socioeconomic factors (e.g., poverty, lack of transportation) contributing to delays in seeking care
• Geographic isolation from specialized cardiac centers

IV. Pathophysiology

A primary decline in cardiac output initiates a cascade of neurohormonal compensations that, while initially adaptive, ultimately worsen afterload and filling pressures, precipitating a vicious cycle of multiorgan hypoperfusion and inflammation.

• Reduced Cardiac Output: The primary insult (e.g., myocardial infarction, acute valvular failure) leads to a significant decrease in stroke volume and cardiac output.
• Systemic Hypotension & Impaired Oxygen Delivery: Low cardiac output results in decreased mean arterial pressure and reduced oxygen delivery to vital organs.
• Neurohormonal Activation:
  • Sympathetic Nervous System (SNS) Activation: Baroreceptor unloading triggers catecholamine release (epinephrine, norepinephrine), leading to tachycardia and systemic vasoconstriction (increased SVR). This increases myocardial oxygen demand on an already failing heart.
  • Renin-Angiotensin-Aldosterone System (RAAS) Activation: Reduced renal perfusion activates RAAS, leading to angiotensin II production (potent vasoconstrictor) and aldosterone release (sodium and water retention). This further increases afterload and preload.
• Elevated Filling Pressures:
  • Left Ventricular End-Diastolic Pressure (LVEDP)/Pulmonary Capillary Wedge Pressure (PCWP): Impaired LV contractility and increased afterload lead to elevated LVEDP, causing pulmonary congestion and edema.
  • Right-Sided Pressures: Left heart failure can lead to secondary right heart failure. Elevated right atrial pressure (CVP) causes systemic venous congestion (e.g., hepatic congestion, peripheral edema).
• End-Organ Hypoperfusion & Dysfunction: Persistent low cardiac output and increased vasoconstriction lead to:
  • Lactic Acidosis: Tissue hypoxia forces anaerobic metabolism.
  • Acute Kidney Injury (AKI): Reduced renal blood flow.
  • Hepatic Dysfunction (“Shock Liver”): Hypoperfusion and congestion.
  • Altered Mentation: Cerebral hypoperfusion.
• Systemic Inflammatory Response Syndrome (SIRS): Hypoperfusion and cell injury can trigger a systemic inflammatory response, further contributing to vasodilation (in later stages or mixed shock) and organ damage.

V. Clinical Presentation

CS presents with a constellation of signs and symptoms reflecting hypotension, end-organ hypoperfusion, and often volume overload. Early recognition relies on a structured assessment incorporating vital signs, physical examination, and laboratory findings.

Vital signs:

• Hypotension: Sustained SBP <90 mmHg or MAP <65 mmHg, or the need for vasopressors to maintain these levels.
• Tachycardia: Often present as a compensatory response, though bradyarrhythmias can also precipitate or worsen shock.
• Tachypnea: Due to pulmonary congestion or metabolic acidosis.
• Narrow Pulse Pressure: (Systolic BP – Diastolic BP) < 25% of SBP suggests reduced stroke volume.

Physical exam findings:

Signs of Hypoperfusion (“Cold”):

• Cool, clammy, mottled skin (especially extremities)
• Delayed capillary refill (>3 seconds)
• Altered mental status (confusion, agitation, lethargy, coma)
• Oliguria or anuria (<0.5 mL/kg/h or <30 mL/h)

Signs of Congestion (“Wet”):

• Elevated Jugular Venous Pressure (JVP) or jugular venous distension
• Pulmonary crackles or rales on auscultation
• S3 gallop (ventricular gallop)
• Peripheral edema (may be less prominent in acute CS)
• Hepatomegaly, ascites (in more chronic or right-sided failure)

Laboratory findings:

• Elevated Lactate: >2 mmol/L (serum lactate levels correlate with severity and prognosis).
• Metabolic Acidosis: Low pH and low bicarbonate on arterial blood gas (ABG).
• Rising Creatinine/BUN: Indicating acute kidney injury.
• Elevated Liver Enzymes (AST/ALT): Indicating “shock liver” or hepatic hypoperfusion.
• Elevated Cardiac Troponins: If CS is due to acute myocardial infarction.
• Elevated BNP/NT-proBNP: Indicating ventricular stretch and high filling pressures.

VI. Summary and Application

Early, structured recognition of cardiogenic shock—anchored in an understanding of its epidemiology, hemodynamic definitions, diverse etiologies, underlying pathophysiology, and classic clinical signs—is critical to prompt and effective intervention. Pharmacists and the entire interprofessional team play a pivotal role in interpreting complex data, optimizing pharmacotherapy, monitoring for efficacy and adverse effects, and coordinating care to improve outcomes in this high-risk patient population.

• Integrate epidemiologic risk factors (e.g., history of MI, HF) and hemodynamic criteria (hypotension, low cardiac index, high filling pressures) for early CS identification.
• Apply frameworks like the SCAI staging system and mnemonics such as SUSPECT CS to standardize communication, guide risk stratification, and facilitate timely escalation of care.
• Consider the impact of chronic comorbidities (diabetes, CKD) and social determinants of health (access to care, medication adherence) in both the prevention of CS and in planning comprehensive post-shock care.
• Actively liaise with the interprofessional team (physicians, nurses, respiratory therapists) to optimize pharmacotherapy (vasopressors, inotropes, diuretics), ensure appropriate monitoring (hemodynamics, labs), and contribute to shared decision-making regarding advanced therapies.

SCAI 5-Stage Classification

In 2019, the Society for Cardiovascular Angiography & Interventions (SCAI) introduced a 5-stage classification (A through E) to provide a more granular and dynamic description of shock severity. This system has been widely adopted and validated, showing a stepwise increase in mortality with each stage.