Cardiovascular Hemodynamics

Key Mechanism 1: Determinants of Cardiac Output

• Cardiac output (CO) is the product of heart rate (HR) and stroke volume (SV): CO = HR × SV
• Stroke volume is determined by three primary factors: preload, afterload, and contractility (intrinsic myocardial function)
• Preload represents the degree of myocardial fiber stretch at end-diastole, determined by ventricular end-diastolic volume (VEDV), and governed by the Frank-Starling mechanism: increased preload augments contractile force until the plateau of the curve is reached, beyond which further volume increase produces no additional force generation
• Physiologically, preload correlates with central venous pressure (CVP) on the right and pulmonary capillary wedge pressure (PCWP) on the left
• In the normal heart, CO increases proportionally with preload; however, in decompensated heart failure, the Frank-Starling curve shifts downward and leftward, such that higher filling pressures produce lower cardiac outputs

Key Mechanism 2: Vascular Resistance and Pressure-Flow Relationships

• Systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) are calculated as (Mean Pressure − Right Atrial Pressure) / Cardiac Output, with normal SVR = 800–1200 mmHg·min/L and normal PVR = 20–120 mmHg·min/L
• Resistance is inversely proportional to vessel radius to the fourth power (Poiseuille's law: R ∝ 1/r⁴), making arteriolar tone the primary determinant of systemic resistance
• Afterload represents the wall stress or tension that the myocardium must generate to eject blood, proportional to (MAP − LVEDP) × LVEDV / (2 × wall thickness); increased afterload decreases stroke volume in the setting of fixed contractility
• Compliance (change in volume per unit change in pressure) determines the relationship between filling pressure and volume; decreased compliance (as in restrictive cardiomyopathy or acute myocardial infarction) results in elevated filling pressures at reduced volumes
• The autonomic nervous system modulates both heart rate and vascular tone through sympathetic catecholamine release (increasing HR, contractility, and SVR via α and β₁ receptors) and parasympathetic vagal activity (decreasing HR)

Key Mechanism 3: Neurohumoral Regulation and Feedback Systems

• The renin-angiotensin-aldosterone system (RAAS) responds to decreased renal perfusion pressure and sympathetic stimulation by increasing angiotensin II production, which elevates SVR and promotes sodium and water retention, thereby augmenting preload
• Natriuretic peptides (atrial natriuretic peptide [ANP] and B-type natriuretic peptide [BNP]), released in response to elevated atrial stretch and ventricular wall stress, oppose RAAS activation by promoting natriuresis, vasodilation, and reduced sympathetic tone
• Endothelial dysfunction with decreased nitric oxide (NO) production and increased endothelin-1 activity promotes vasoconstriction and contributes to hypertension and heart failure progression
• Baroreceptor reflex adjusts sympathetic and parasympathetic outflow to maintain blood pressure within a narrow range; in chronic hypertension, the baroreceptor set point is reset to a higher level

Conditions Associated with Decreased Cardiac Output

• Heart failure (systolic dysfunction with reduced ejection fraction [HFrEF], diastolic dysfunction [HFpEF], or acute decompensation)
• Acute myocardial infarction with cardiogenic shock
• Cardiomyopathies (dilated, restrictive, hypertrophic, peripartum, takotsubo)
• Valvular heart disease (severe stenosis or regurgitation)
• Arrhythmias (atrial fibrillation with rapid ventricular response, ventricular tachycardia, complete heart block)
• Pericardial disease (tamponade, constrictive pericarditis)
• Pulmonary embolism with acute right ventricular dysfunction
• Sepsis with initial distributive shock despite high CO
• Severe anemia and hypoxemia

Conditions Associated with Increased Systemic Vascular Resistance

• Hypertension (essential, secondary to renal disease, endocrine dysfunction, or medications)
• Sympathomimetic agents (epinephrine, norepinephrine, dopamine)
• Vasoconstrictors (vasopressin, phenylephrine)
• RAAS activation in heart failure, renal disease, or renovascular disease
• Hypoxemia and hypercapnia
• Hypothermia
• Cocaine and amphetamine use

Conditions Associated with Decreased Systemic Vascular Resistance

• Sepsis and systemic inflammatory response syndrome (SIRS)
• Anaphylaxis with release of histamine and tryptase
• Vasodilators (nitrates, hydralazine, calcium channel blockers, ACE inhibitors)
• Hyperthermia and fever
• Pregnancy (physiologic third-trimester decrease in SVR)
• Cirrhosis with hepatic dysfunction and portal hypertension
• Thyrotoxicosis

Conditions Associated with Elevated Pulmonary Vascular Resistance

• Pulmonary hypertension (WHO Groups 1–5, including idiopathic pulmonary arterial hypertension [IPAH], left heart disease, hypoxic lung disease, chronic thromboembolic disease, and miscellaneous causes)
• Hypoxic vasoconstriction (chronic lung disease, sleep apnea, high altitude)
• Left heart failure with backward transmission of pressure
• Mitral stenosis
• Intracardiac shunts (left-to-right shunting increases PVR over time)

Cardinal Symptoms

• Dyspnea (exertional or orthopneic) reflecting elevated pulmonary capillary wedge pressure and pulmonary congestion
• Fatigue and exercise intolerance from decreased cardiac output and impaired tissue perfusion
• Syncope or presyncope indicating inadequate cerebral perfusion (common in severe aortic stenosis, hypertrophic cardiomyopathy, or arrhythmias)
• Chest pain (anginal or atypical) with myocardial ischemia
• Palpitations with tachycardia or arrhythmia
• Peripheral edema and abdominal distension from elevated systemic venous pressure and hepatic congestion

Physical Examination Findings Reflecting Hemodynamic Derangements

• Elevated jugular venous pressure (JVP) (normally <4 cm H₂O at the midaxillary line) indicating right atrial hypertension; prominent CV waves suggest tricuspid regurgitation, cannon A waves indicate atrioventricular dissociation
• Pulmonary crackles (bibasilar or diffuse) from pulmonary edema
• S₃ gallop (ventricular gallop) reflecting rapid ventricular filling in dilated ventricles
• Hepatomegaly, hepatic tenderness, and positive hepatojugular reflux indicating hepatic congestion

• Narrow pulse pressure (reduced systolic pressure minus diastolic pressure) from decreased stroke volume
• Cool extremities and delayed capillary refill from peripheral vasoconstriction and hypoperfusion
• Weak pulses (diminished amplitude)
• Tachycardia as compensatory mechanism
• Altered mental status or oliguria indicating severe hypoperfusion

• Hypertension (systolic >140 mmHg and/or diastolic >90 mmHg)
• Narrowed pulse pressure in some cases
• Vasoconstricted appearance with pale, cool skin

• Warm extremities despite hypotension
• Bounding pulses and wide pulse pressure
• Flushed appearance

• Systolic murmur of aortic stenosis (crescendo-decrescendo, radiating to neck) with delayed carotid upstroke
• Diastolic murmur of aortic regurgitation (early decrescendo)
• Holosystolic murmur of mitral regurgitation with prominent S₃
• Opening snap and diastolic rumble of mitral stenosis

Hemodynamic Assessment Approach

Laboratory Tests

• Serum lactate (elevated in hypoperfusion states, normal <2 mmol/L; >4 mmol/L associated with worse prognosis)
• Arterial blood gas (ABG) to assess oxygenation, ventilation, and acid-base status; metabolic acidosis reflects anaerobic metabolism from tissue hypoperfusion
• Troponin and myoglobin for myocardial injury
• Brain natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP): BNP >100 pg/mL or NT-proBNP >125 pg/mL suggests heart failure; higher levels correlate with worse hemodynamics and prognosis
• Complete metabolic panel for renal function, electrolytes, and hepatic congestion indicators
• Complete blood count to identify anemia

Electrocardiography (ECG)

• Identifies arrhythmias (atrial fibrillation, ventricular tachycardia, bradycardia)
• Demonstrates ischemic changes (ST-segment elevation or depression, T-wave inversions)
• Shows chamber enlargement patterns (left ventricular hypertrophy, right axis deviation)
• Documents conduction abnormalities affecting heart rate and atrioventricular synchrony

Echocardiography (Transthoracic or Transesophageal)

• Ejection fraction (EF) measurement: normal >50%, reduced EF (HFrEF) <40%, mildly reduced 40–49%, preserved EF (HFpEF) ≥50%
• Left ventricular end-diastolic dimension (LVEDD) and volumes assess chamber size
• Wall thickness identifies hypertrophy (>11 mm in men, >10 mm in women)
• Diastolic dysfunction assessment by E/e' ratio (mitral inflow early diastolic velocity [E] divided by early diastolic tissue velocity [e']; E/e' >14 suggests elevated filling pressure)
• Valvular morphology and function (stenosis severity by valve area and gradients; regurgitation by jet width, vena contracta, regurgitant volume)
• Right ventricular function and tricuspid regurgitation to estimate right atrial pressure and pulmonary artery systolic pressure
• Pericardial effusion and tamponade physiology (RV collapse, RA collapse, respiratory variation >25%)

Invasive Hemodynamic Monitoring

• Right heart catheterization (RHC) measures right atrial pressure (RAP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP or pulmonary artery occlusion pressure [PAOP]), and cardiac output (via thermodilution)
• Systemic vascular resistance (SVR) = (MAP − CVP) / CO × 80 (normal 800–1200 mmHg·min/L)
• Pulmonary vascular resistance (PVR) = (mPAP − PCWP) / CO × 80 (normal 20–120 mmHg·min/L)
• Cardiac index (CI) = CO / body surface area (normal 2.5–4.0 L/min/m²)
• Hemodynamic profiles categorized as:
• Warm and dry (normal): CO adequate, filling pressures normal (RAP <8, PCWP <18 mmHg)
• Warm and wet: elevated PCWP (>18 mmHg) despite adequate CO (often initial phase of decompensated heart failure)
• Cold and dry: reduced CO with normal filling pressures (cardiogenic shock early)
• Cold and wet: reduced CO with elevated filling pressures (decompensated cardiogenic shock)

Chest Radiography

• Pulmonary edema pattern (bilateral infiltrates, Kerley B lines, "bat wing" appearance)
• Cardiomegaly (cardiothoracic ratio >0.5)
• Pleural effusions
• Pulmonary vascular redistribution

Stress Testing and Coronary Imaging

• Exercise stress test or pharmacologic stress (dobutamine, adenosine, regadenoson) to assess for inducible ischemia
• Coronary angiography for definitive assessment of stenosis severity and therapeutic intervention

Right Heart Catheterization Diagnostic Criteria (Pulmonary Hypertension)

• Elevated mean pulmonary artery pressure (mPAP) ≥20 mmHg at rest (as of 2018 ESC guidelines)
• PVR ≥2 Wood units (>160 mmHg·min/L) for precapillary disease
• PCWP ≤15 mmHg to exclude postcapillary hypertension

Management Principles

For Decreased Cardiac Output/Cardiogenic Shock

• Inotropes for acute decompensation: dobutamine (2.5–20 μg/kg/min) increases contractility via β₁-adrenergic stimulation; milrinone (0.25–0.75 μg/kg/min) is a phosphodiesterase-3 inhibitor providing inotropy and vasodilation without tachycardia
• Vasopressors for hypotension: norepinephrine (0.01–3 μg/kg/min) preferred for sepsis and undifferentiated shock, epinephrine (0.01–0.5 μg/kg/min) for severe hypotension, dopamine (5–20 μg/kg/min) for bradycardia and hypotension
• Inodilators: levosimendan (not yet available in US) enhances contractility while reducing afterload
• Low-dose vasopressin (0.03–0.04 units/min) may supplement **norepinephrine

Complications of the hemodynamic derangement itself

• Cardiogenic shock with multiorgan failure (emergency): sustained low cardiac index drives anaerobic metabolism — signaled by rising lactate, oliguria, transaminitis (shock liver), and cool mottled extremities despite adequate filling pressures.
• Flash pulmonary edema (emergency): abrupt rise in PCWP above the plasma oncotic threshold overwhelms lymphatic clearance; signaled by hypoxemia, pink frothy sputum, and diffuse crackles.
• Type 1 cardiorenal syndrome: low forward flow plus high renal venous pressure reduces transrenal perfusion gradient; signaled by rising creatinine with bland urine sediment.
• Right ventricular failure from elevated PVR: the thin-walled RV cannot acutely generate pressure against high afterload, producing RV dilation, septal shift, and reduced LV preload — signaled by rising JVP with hypotension and clear lungs.

Complications of pharmacologic therapy

• Vasopressor-induced digital and mesenteric ischemia: unopposed α₁ vasoconstriction; signaled by acrocyanosis or abdominal pain out of proportion to exam. Extravasation of norepinephrine causes tissue necrosis — treated with local phentolamine.
• Inotrope-driven ischemia and arrhythmia: dobutamine raises myocardial oxygen demand via β₁ stimulation; signaled by new angina, ST shift, or ventricular ectopy. Milrinone accumulates in renal failure, producing prolonged hypotension.
• Nitroprusside cyanide/thiocyanate toxicity (emergency): signaled by altered mental status, lactic acidosis, and a narrowed arteriovenous oxygen difference.
• Over-diuresis: excessive preload reduction moves the patient down the Frank-Starling curve; signaled by hypotension, contraction alkalosis, hypokalemia, and hemoconcentration.
• Catastrophic hypotension from vasodilators or diuretics in preload-dependent states (emergency): tamponade, RV infarction, severe aortic stenosis, and hypertrophic cardiomyopathy with outflow obstruction.

Complications of invasive monitoring and mechanical support

• Pulmonary artery rupture (emergency): balloon overinflation in a distal branch; signaled by sudden hemoptysis — the classic lethal Swan-Ganz complication.
• Pulmonary infarction: persistent wedging occludes flow; signaled by a wedge tracing that will not revert.
• Catheter-induced arrhythmia and complete heart block: transit through the RV causes ectopy, and catheter-induced right bundle branch block in a patient with preexisting LBBB can produce complete block.
• Bloodstream infection, venous thrombosis, and knotting with prolonged catheter dwell time.
• Device complications: intra-aortic balloon pump limb ischemia; VA-ECMO raises LV afterload and can worsen pulmonary edema; Impella causes hemolysis (plasma-free hemoglobin, hematuria).

• Static filling pressures do not predict fluid responsiveness: CVP and PCWP estimate preload, not volume responsiveness. The Surviving Sepsis Campaign favors dynamic measures (passive leg raise, pulse pressure variation, stroke volume variation) over a single CVP number — a classic distractor is "give fluids because CVP is low."
• Routine pulmonary artery catheterization does not improve outcomes in decompensated heart failure (ESCAPE trial); ACC/AHA/HFSA reserve invasive hemodynamics for shock, uncertain volume status, or pre-transplant/pulmonary hypertension evaluation. If a stem gives a straightforward congested patient, the best next step is clinical assessment plus diuresis, not a Swan-Ganz.
• Mixed venous oxygen saturation (SvO₂) separates shock types: low SvO₂ with wide arteriovenous O₂ difference indicates a flow problem (cardiogenic, hypovolemic); high SvO₂ indicates impaired extraction or high output (septic, cirrhosis, thyrotoxicosis, arteriovenous fistula). This is the single most tested application of the Fick principle.
• Hypotension + elevated JVP + clear lung fields = right ventricular infarction (or tamponade/massive PE). Best next step in RV infarction is IV fluid loading and avoidance of nitrates and diuretics, which abolish the RV's preload dependence.
• Equalization of diastolic pressures with pulsus paradoxus = tamponade; **dip-and-plateau (square root sign) with Kussmaul sign** = constrictive pericarditis. Kussmaul sign is absent in pure tamponade — a favorite distractor pair.
• A giant v wave on the PCWP tracing signals acute mitral regurgitation (ruptured papillary muscle post-MI); in mitral stenosis, PCWP is elevated while LVEDP is normal, so wedge pressure overestimates LV preload.
• Avoid pure vasodilators in fixed-obstruction lesions: in severe aortic stenosis and obstructive HCM, dropping SVR cannot be compensated by increased stroke volume, causing precipitous hypotension and syncope.
• After hemodynamic stabilization, chronic HFrEF therapy is four pillars per ACC/AHA/HFSA: ARNI (or ACEI/ARB), beta blocker, MRA, and SGLT2 inhibitor. Do not start or up-titrate a beta blocker while the patient is still in cardiogenic shock.