High-Output Heart Failure


Distinction Between Heart with Preserved Ejection Fraction (HFpEF), Heart Failure with Reduced Ejection Fraction (HFrEF), and High-Output Heart Failure (see Heart Failure)

  • Most Patients with Heart Failure Have Either Preserved or Reduced Ejection Fraction, While a Small Percentage Have a High Cardiac Output (CO) State with Decreased Systemic Vascular Resistance (SVR)

Etiologies of High-Output Heart Failure

  • Mayo Clinic Series of High-Output Heart Failure Patients (J Am Coll Cardiol, 2016) [MEDLINE]: n = 120
    • This Study Excluded a Number of Patient Groups with Other Etiologies of Heart Failure (Some of Which May Produce High-Output Heart Failure)
      • Congenital Etiologies of High Output
      • Hyperthyroidism (see Hyperthyroidism)
      • Iatrogenic Etiologies of High Output
        • Inotrope Administration
        • Pulmonary Vasodilator Administration
      • Physiologic Etiologies of High Output States
      • Severe Anemia (Hemoglobin <8 mg/dL) (see Anemia)
      • Cardiac Transplant (see Cardiac Transplant)
      • Cardiomyopathy
      • Constrictive Pericarditis (see Constrictive Pericarditis)
      • Left Ventricular Systolic Dysfunction (Left ventricular Ejection Fraction <45%)
      • Valvular Heart Disease
    • Most Common Etiologies of High-Output Heart Failure


General Comments

  • Many of the Following Conditions are Classified as Etiologies of “High Output Heart Failure”
    • However, this Term is a Misnomer, Since the Heart is Generally Normal (i.e. Capable of Generating a High Cardiac Output) and the Underlying Pathophysiology is Decreased Systemic Vascular Resistance, Resulting in Activation of Neurohormones Which Increase Renal Salt and Water Retention (and May Result in Hypotension)
    • Treatment with Vasodilators (Typically Used in Congestive Heart Failure) May Exacerbate the Heart Failure in These Conditions

Conditions with Predominant Peripheral Vascular Effects

  • Carcinoid Syndrome (see Carcinoid Syndrome)
    • Physiology
      • Peripheral Vasodilation with Decreased Systemic Vascular Resistance
    • Clinical
      • High Cardiac Output/Low Systemic Vascular Resistance State Has Been Reported in Some Cases (Ann Intern Med, 1994) [MEDLINE] (Neth J Med, 2002) [MEDLINE]
        • However, Heart Failure with Right Heart Valvular Fibrosis is a More Common Cardiac Presentation
  • Cirrhosis/Liver Disease (see Cirrhosis)
    • Physiology
      • Progressive Systemic Vasodilation (Especially Splanchnic) with Development of Intrahepatic/Mesenteric Arteriovenous Shunts
      • Intrapulmonary Arteriovenous Shunts (i.e. Hepatopulmonary Syndrome) May Also Occur (Echocardiography, 2006) [MEDLINE] (see Hepatopulmonary Syndrome)
    • Clinical
      • Characteristically Produces a High Cardiac Output/Low Systemic Vascular Resistance State
      • High Output Heart Failure May Occur
      • Of All of the High Output Heart Failure Conditions, Cirrhosis Generally Produces the Lowest Arterial-Venous Oxygen Difference and the Lowest Systemic Vascular Resistance
  • Erythroderma (of Any Etiology) (see Erythroderma)
    • Etiology
      • Drug Hypersensitivity Reaction
      • Psoriasis (see Psoriasis)
    • Physiology
      • Significant Cutaneous Vasodilation and Increased Blood Flow to the Skin, Resulting in Shunting of Blood Flow Through the Skin
  • Morbid Obesity (see Obesity)
    • Physiology
      • Peripheral Vasodilation with Decreased Systemic Vascular Resistance (of Unclear Etiology)
      • Leptin-Induced Expansion of Plasma Volume and Eccentric Ventricular Dilation/Hypertrophy (Circulation, 2018) [MEDLINE]
      • Obesity-Associated Hypertension (with Pressure Overload) Likely Exacerbates the Effect of Obesity on Cardiac Output (Physiol Rep, 2015) [MEDLINE]
    • Clinical
      • High Cardiac Output (Although Cardiac Output is Normal When Adjusted for Body Weight)
  • Systemic Arteriovenous Fistula (AVF) (see Systemic Arteriovenous Fistula)
    • Etiology
      • Aortocaval Fistula (Due to Spontaneous Rupture of Aortic Aneurysm)
      • Congenital Arteriovenous Fistula
      • Highly Vascular Condition/Tumor
      • Iatrogenic
        • Femoral/Radial/Ulnar Arteriovenous Fistula (Due to Arterial Access for Cardiac Catheterization for Coronary Angiogram)
        • Iliac Arteriovenous Fistula (Due to Spinal/Abdominal Surgery)
        • Renal Arteriovenous Fistula (Due to Renal Biopsy)
        • Surgically-Constructed Arteriovenous Access for Hemodialysis
        • Transjugular Intrahepatic Portosystemic Shunt (TIPS) (see Transjugular Intrahepatic Portosystemic Shunt)
      • Multiple Myeloma (see Multiple Myeloma): due to multiple minute arteriovenous fistulas in bony lesions
      • Paget Disease of the Bone (Osteitis Deformans) (see Paget Disease of Bone): due to multiple minute arteriovenous fistulas in bony lesions
      • Polyostotic Fibrous Dysplasia (McCune-Albright Syndrome): due to multiple minute arteriovenous fistulas in bony lesions
      • Trauma
        • Aortocaval Fistula
        • Bullet/Knife Wound (Particularly in the Thigh)
    • Physiology
      • High Pressure Arterial Blood is Shunted into a Low Pressure Vein, Shunting Past the Tissue Capillary Bed (and Decreasing the Systemic Vascular Resistance)
        • Subsequently, there is a Compensatory Increase in Stroke Volume, Cardiac Output, and Total Plasma Volume to Maintain Capillary Perfusion
    • Clinical

Conditions with Predominant Metabolic Effects

  • Hyperthyroidism (see Hyperthyroidism)
    • Physiology
      • Enhanced Sympathoadrenal Activation
      • Direct Myocardial Chronotropic and Inotropic Effects
      • Hyperthyroidism-Associated β-Adrenergic Stimulation Has Been Proposed to Have a Cardiotoxic Effect (Heart, 2007) [MEDLINE]
    • Clinical
      • Widened Pulse Pressure (see Widened Pulse Pressure)
      • High Cardiac Output/Low Systemic Vascular Resistance State May Occur (with High Output Heart Failure) (NEJM, 2001) [MEDLINE]
        • Sympatholytic Agents (β-Blockers) Can Partially Decrease Heart Rate and Cardiac Output, as Well as Partially Improve Pulse Pressure
      • Hyperthyroidism-Associated Hyperdynamic Right Ventricular Function (Which is Reversible with Treatment) Has Also Been Reported (Heart Lung Circ, 2017) [MEDLINE]
      • Hyperthyroidism-Associated Decreased Cardiac Output May Alternately Occur (Due to Tachycardia-Mediated Cardiomyopathy or Associated Cardiac Disease) (Heart, 2007) [MEDLINE]
      • Hyperthyroidism-Associated Reversible Right Ventricular Failure with Pulmonary Hypertension Has Also Been Reported (Am J Med Sci, 2018) [MEDLINE]
  • Myeloproliferative Disorders with Extramedullary Hematopoiesis
    • Etiology
    • Physiology
      • Increased Metabolic State with Increased Oxygen Consumption and Decreased Systemic Vascular Resistance

Conditions with Myocardial and Peripheral Vascular Effects

  • Acromegaly (see Acromegaly)
    • Epidemiology
      • Heart Failure May Be Present in Newly-Diagnosed Acromegaly
    • Physiology
      • Growth Hormone is Involved in the Maintenance of Normal Cardiac Function
  • Anagrelide (Agrylin, Xagrid) (see Anagrelide)
    • Epidemiology
    • Pharmacology
      • Phosphodiesterase III Inhibition, Resulting in Positive Inotropic/Chronotropic Effects and Vasodilation
  • Dobutamine (Dobutrex) (see Dobutamine)
    • Pharmacology
      • Myocardial β1-Adrenergic Receptor Agonist (Chronotropic/Inotropic Effects) and Vascular β2-Adrenergic/α1-Adrenergic Receptor Agonist (if Vascular β2-Adrenergic Effects Exceed α1-Adrenergic Receptor Agonist Effects, Some Peripheral Vasodilation May Occur)
  • Milrinone (see Milrinone)
    • Pharmacology
      • Phosphodiesterase Type 3 Inhibitor (Which Inhibits cAMP Degradation), Resulting in Increased Myocardial Contractility and Vasodilation
  • Mitochondrial Disease
    • Physiology
      • Altered Oxidative Metabolism
    • Clinical
      • Cardiomyopathy
      • Decreased Systemic Vascular Resistance (SVR)
      • Lactic Acidosis (see Lactic Acidosis)
  • Sepsis (see Sepsis)
    • Physiology
      • Due to Inflammatory Response (Involving TNF-α, IL-1β, IL-6, etc)
    • Clinical
      • Characteristically Produces a High Cardiac Output/Low Systemic Vascular Resistance State (Although Sepsis-Induced Myocardial Dysfunction May Alternately Occur)
      • High Output Heart Failure May Occur
  • Thiamine (Vitamin B1) Deficiency (Beriberi) (see Thiamine)
    • Epidemiology
      • Cases in Developed Countries are Generally Associated with One of the Following
    • Physiology
      • Vasodilation May Occur Due to Direct Depression of Vasomotor Function (Am J Med, 1966) [MEDLINE]
      • Thiamine Deficiency Impairs Lactate and Pyruvate Utilization by the Myocardium (These Substrates are Important for Oxidation and Energy Production in the Myocardium)
      • Thiamine Deficiency Impairs Hexose Monophosphate Shunt Function, Impairing Tissue Oxygenation
    • Clinical
      • Initially Presents with High Cardiac Output/Low Systemic Vascular Resistance State with Increased Blood Volume (Am J Med, 1966) [MEDLINE]
        • High Output Heart Failure May Occur
      • Later, Low Cardiac Output State is Observed (J Am Coll Cardiol, 1989) [MEDLINE]

Other Conditions

  • Anemia (Chronic, Severe) (see Anemia)
    • Epidemiology
      • May Occur in Patients with Beta-Thalassemia Intermedia (see Thalassemias)
    • Physiology
      • Endothelial Dysfunction, Resulting in Peripheral Vasodilation
      • Decreased Serum Viscosity, Resulting in Decreased Left Ventricular Afterload
      • Loss of Hemoglobin is Partly Compensated for by an Increase in Cardiac Output and Widening of the Arteriovenous O2 Difference
        • Severe Anemia Can Result in Left Ventricular Volume Overload and Increased Stroke Volume
    • Clinical
      • Heart Failure Generally Occurs in the Absence of Underlying Heart Disease Only with Severe Anemia (Hemoglobin <5 g/dL)
  • Anxiety or Physical/Emotional Stress (see Anxiety)
    • Physiology
      • Stress Induces Catecholamine Release, Resulting in Increased Cardiac Output and Variable Effects on Systemic Vascular Resistance
  • Chronic Pulmonary Disease (with Hypoxemia and/or Hypercapnia)
    • Epidemiology
      • Chronic Pulmonary Disease Associated with Hypoxemia and/or Hypercapnia is Associated with High Output Heart Failure
    • Physiology
      • Decreased Systemic Vascular Resistance (SVR)
      • Impaired Renal Blood Flow
      • Salt and Water Retention
    • Clinical
  • Exercise
    • Physiology
      • During Exercise, Cardiac Output Increases and Systemic Vascular Resistance Decreases
  • Fever (see Fever)
    • Physiology
      • Fever Increases Metabolic Demand and Produces Vasodilation (Especially in the Skin)
  • Hot Climate
    • Physiology
      • Hot (and Especially Humid) Environment Increases Cardiac Output (Similar to Fever)
  • Pregnancy (see Pregnancy)
    • Physiology
      • Decreased Systemic Vascular Resistance (SVR)
      • Increased Blood Volume
      • Increased Maternal Heart Rate (by 15-20 bpm)
      • Increased Metabolic Demand
      • Increased Resting Cardiac Output (to 30-50% Above Baseline)
      • Placental Blood Flow (Which May Function an Arteriovenous Shunt)


High-Output Heart Failure is Characterized by Increased Cardiac Output and Decreased Systemic Vascular Resistance (Due to Peripheral Vasodilation or Arteriovenous Fistula/Shunt)

  • Increased Cardiac Output is Related to Both Lower Arterial Afterload (Decreased Systemic Vascular Resistance) and Higher Metabolic Rate (J Am Coll Cardiol, 2016) [MEDLINE]
    • The Observed Increased Cardiac Output is Higher than that Required to Meet Metabolic Demand
  • Ineffective Blood Volume and Blood Pressure Result in the Following
    • Activation of the Sympathetic Nervous System
    • Activation of Renin-Angiotensin-Aldosterone Axis
    • Increased Serum Vasopressin (Antidiuretic Hormone) Level
  • Neurohormonal Activation Results in the Following (J Am Coll Cardiol, 2016) [MEDLINE]
    • Increased Renovascular Resistance
    • Decreased Renal Blood Flow and Glomerular Filtration Rate
    • Retention of Salt and Water
  • Chronic Volume Overload May Result in Ventricular Enlargement, Remodeling, and Heart Failure
    • Activation of Neprilysin and the Sodium-Glucose Cotransporter 2 (SGLT2) Have Been Implicated in Interstitial Fibrosis and Subsequent Ventricular Remodeling in High-Output Heart Failure

Presence of Other Cardiovascular Disease

  • The Conditions Which Provoke High-Output Heart Failure are Rarely the Sole Etiology of Heart Failure
    • In Most Patients, the High Cardiac Output Provokes Heart Failure in the Setting of Decreased Ventricular Reserve (Systolic and/or Diastolic Dysfunction) from an Underlying Cardiac Problem
    • Therefore, the Presence of High-Output Heart Failure Should Prompt a Search for Another Underlying Cardiovascular Condition, Such as the Following
      • Failing Fontan Circulation (Extracardiac Conduit or Lateral Tunnel)
      • Severe Functional Tricuspid Regurgitation (see Tricuspid Regurgitation)


Echocardiogram (see Echocardiogram)

  • Required to Assess Cardiac Function

Clinical Manifestations

Cardiovascular Manifestations

General Comments

  • Mayo Clinic Series of High-Output Heart Failure Patients (J Am Coll Cardiol, 2016) [MEDLINE]: n = 120
    • Clinical Feature
      • As Compared to Controls (and Despite Similar Ejection Fraction), Patients with High-Output Heart Failure Demonstrated the Following

Arterial Pulse Abnormalities

  • Clinical
    • Clinical Signs are Due to Increased Left Ventricular Stroke Volume
      • Bounding Pulse is with Quick Upstroke, Followed by a Rapid Collapse (Corrigan or Water Hammer Pulse)
      • Pistol-Shot Sounds May Be Auscultated Over the Femoral Arteries (Traube Sign)
      • Subungual Capillary Pulsations (Quincke Pulse)
      • Systolic Bruit May Be Heard Over the Carotid Arteries
      • Widened Pulse Pressure (Systolic – Diastolic Pressure) (see Widened Pulse Pressure)

Cardiac Exam Abnormalities

  • Clinical
    • Enlarged Apical Impulse
    • Hyperdynamic Precordium
    • Loud First Heart Sound
    • Scratchy Midsystolic Murmur (Means-Lerman Scratch) in Either the 2nd or 3rd Left Intercostal Spaces
      • Due to Rubbing Together of the Normal Pleural and Pericardial Surfaces
    • Third Heart Sound (see Third Heart Sound)
      • Due to Increased Rate of Ventricular Filling

Hemodynamic Pattern (see Hemodynamics)

  • Diagnosis/Clinical
    • Determined Using Arterial Blood Gas (ABG), Mixed/Central Venous Blood Gas (VBG), and Swan-Ganz Catheter (see Arterial Blood Gas, Venous Blood Gas, and Swan-Ganz Catheter)
      • High Cardiac Output (CO)
      • Low Systemic Vascular Resistance (SVR)
        • Of All Etiologies, Patients with Liver Disease Have the Lowest Arterial-Venous Oxygen Content Difference and the Lowest Systemic Vascular Resistance (SVR) (J Am Coll Cardiol, 2016) [MEDLINE]
      • Elevated Cardiac Filling Pressures (J Am Coll Cardiol, 2016) [MEDLINE]
      • Increased Oxygen Consumption (Due to Increased Metabolic Demand) with Increased Arterial-Venous Oxygen Difference is Present in Some Types of High-Output Heart Failure
        • Of All Etiologies, Patients with Liver Disease Have the Lowest Arterial-Venous Oxygen Content Difference and the Lowest Systemic Vascular Resistance (SVR) (J Am Coll Cardiol, 2016) [MEDLINE]
        • Of All Etiologies, Patients with Myeloproliferative Disorders Have the Highest Oxygen Consumption (Indexed to Weight) and Lowest Mixed Venous Oxygen Content (J Am Coll Cardiol, 2016) [MEDLINE]

Hypotension (see Hypotension)

  • Epidemiology
    • Arterial Blood Pressure is Either Borderline-Normal or Decreased in High-Output Heart Failure (J Am Coll Cardiol, 2016) [MEDLINE]
  • Clinical
    • XXXX

Sinus Tachycardia (see Sinus Tachycardia)

  • Epidemiology
    • XXXXX
  • Clinical
    • Heart Rate is Typically Mildly Tachycardic (Between 85-105 bpm)
      • However, Tachycardia May Be More Significant in Patients with Hyperthyroidism Due to Thyrotoxicosis
    • Tachycardia is Present During Rest, Sleep, and Exercise

Venous Abnormalities

  • Clinical
    • Cervical Venous Hum (Heard Best Over the Internal Jugular Veins, Particularly on the Right Side
    • Venous Hum May Be Heard Over the Femoral Veins

Gastrointestinal Manifestations

Abdominal Distention (see Abdominal Distention)

  • Epidemiology
    • XXXX

Neurologic Manifestations

Fatigue (see Fatigue)

  • Epidemiology
    • XXXX

Pulmonary Manifestations

Dyspnea (see Dyspnea)

  • Epidemiology
    • XXXX

Pleural Effusion (see xxxx)

  • Epidemiology
    • XXXX
  • Diagnostic
    • Transudative (see xxxx)

Pulmonary Edema

  • Epidemiology
    • XXXX
  • Clinical

Rheumatologic/Orthopedic Manifestations

Peripheral Edema (see Peripheral Edema)

  • Epidemiology
  • Clinical
    • In Addition, the Extremities are Generally Warm, Well-Perfused (Due to Peripheral Vasodilation)


Avoidance of Vasodilators

  • Vasodilators May Exacerbate High-Output Heart Failure


Mortality Rate is Related to Systemic Vascular Resistance

  • Mayo Clinic Series of High-Output Heart Failure Patients (J Am Coll Cardiol, 2016) [MEDLINE]: n = 120
    • Prognosis
      • Mortality Rate was Higher in High-Output Heart Failure, as Compared to Controls (Hazard Ratio 3.4; 95% Confidence Interval: 1.6-7.6)
      • Hemodynamics and Outcomes were Poorest in patients with the Lowest Systemic Vascular Resistance