Definitions

• Heart Failure with Preserved Ejection Fraction (HFpEF): defined as congestive heart failure with EF >50%
  • Etiology of Congestive Heart Failure with Normal Ejection Fraction
    • Atrial myxoma
    • CHF associated with high metabolic demand (high-output states): anemia, thyrotoxicosis, AVM
    • Chronic pulmonary disease with right-sided CHF (cor pulmonale)
    • Diastolic dysfunction of uncertain origin
    • Episodic or reversible LV systolic dysfunction
    • Inaccurate measurement of LVEF
    • Incorrect diagnosis of CHF
    • Obesity
    • Pericardial constriction
    • Primary valvular disease
    • Pulmonary hypertension associated with pulmonary vascular disorders
    • Restrictive (infiltrative) cardiomyopathies
      • [[Amyloidosis]]
      • [[Sarcoidosis]]
      • [[Hemochromatosis]]
    • Severe hypertension, myocardial ischemia
• Heart Failure with Borderline Preserved Ejection Fraction (HFpEF, Borderline): defined as congestive heart failure with EF 41-49%
  • Clinical characteristics are similar to patients with HFpEF
• Heart Failure with Improved Ejection Fraction (HFpEF, Improved): defined as congestive heart failure with EF >40% in patient with prior HFrEF
  • This represents the subset of HFpEF patient who previously previously had HFrEF: these patients with improvement or recovery in ejection fraction may be clinically distinct from those with persistently preserved or reduced ejection fraction
• Heart Failure with Reduced Ejection Fraction (HFrEF): defined as congestive heart failure with EF equal to or <40%

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Epidemiology

Statistics

• Lifetime Risk of Developing Congestive Heart Failure for Americans ≥40 y/o: 20%
• Incidence of Congestive Heart Failure (US): >650k new cases diagnosed annually
  • Incidence Increases with Age
• Prevalence of of Clinically Manifest Congestive Heart Failure (US): 5.1 million patients
  • Prevalence Continues to Increase
• Prevalence of Asymptomatic Left Ventricular Dysfunction: ranges from 6-21%
  • Prevalence Increases with Age
  • Left Ventricular Dysfunction Prevention Study: untreated asymptomatic left ventricular dysfunction carries a 10% risk for developing congestive heart failure symptoms and an 8% risk of death or congestive heart failure-related hospitalization annually
• Annual Costs (Heath Care + Lost Productivity) Related to Congestive Heart Failure (US): $30 Billion

Risk Factors

• Coronary Artery Disease (CAD) (see Coronary Artery Disease, [[Coronary Artery Disease]]): relative risk = 8.1
  • Most common etiology of systolic congestive heart failure in Western countries
  • Presence of athersclerotic disease (of coronary arteries, cerebral arteries, or peripheral arteries) increases the risk of developing congestive heart failure
• Cigarette Smoking (see Tobacco, [[Tobacco]]): relative risk = 1.6
• Diabetes Mellitus (DM) (see Diabetes Mellitus, [[Diabetes Mellitus]]): relative risk = 1.9
  • Diabetes mellitus is a risk factor for congestive heart failure, independent of age, hypertension, obesity, hyperlipidemia, and coronary artery disease
  • Diabetes mellitus also adversely impacts the outcome of patients with established congestive heart failure
• Valvular Heart Disease: relative risk = 1.5
• Hypertension (see Hypertension, [[Hypertension]]): relative risk = 1.4
  • Increases the risk of congestive heart failure at all ages
  • Risk of congestive heart failure increases with the degree of blood pressure elevation, older age, and longer duration of hypertension
  • Long-term treatement of both systolic and diastolic hypertension decreases the risk of congestive heart failure by 50%
• Obesity (see Obesity, [[Obesity]]): relative risk = 1.3
  • Represents a risk factor for both systolic and diastolic congestive heart failure
• Metabolic Syndrome (Any 3 of the Following -> Abdominal Adiposity + Hypertrgliglyceridemia + Low Density Lioproteinemia + Hypertension + Fasting Hyperglycemia): treatment of hypertension, hyperlipidemia, and diabetes mellitus decrease the risk of developing congestive heart failure

Relative Prevalence of Etiologies in Patients Who Initially Presented with Unexplained Dilated Cardiomyopathy (NEJM, 2000) [MEDLINE]

• Idiopathic Dilated Cardiomyopathy (50%)
• Other (10%)
• Myocarditis (9%)
• Ischemic Heart Disease (7%)
• Infiltrative Disease (5%)
• Peripartum Cardiomyopathy 4%)
• Hypertension (4%)
• Human Immunodeficiency Virus (HIV) (4%)
• Connective Tissue Disease (3%)
• Substance Abuse (3%)
• Doxorubicin (1%)

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Etiologic Classification (American Heart Association Classification, 2006) [MEDLINE]

General Comments

• Definition of Cardiomyopathy: heterogeneous group of myocardial disease associated with mechanical and/or electrical dysfunction that typically (but not invariably) exhibit inappropriate ventricular hypertrophy/dilatation
  • Cardiomyopathies May Be Either Confined to the Heart or May Be Part of a Generalized Systemic Disorder
  • Cardiomyopathies Often Lead to Cardiovascular Death or Progressive Heart Failure–Related Disability
• Result of Cardiomyopathy
  • Diastolic/Systolic Dysfunction
  • Primary Electrical Disease with Propensity for Arrhythmias
• Difficulties with Classification Schemes
  • Some Diseases Do Not Have a Uniformly Static Expression and May Evolve (Due to Remodeling and Other Factors) from One Category to Another During their Natural Clinical Course
    • Examples: hypertrophic cardiomyopathy, amyloidosis, and other infiltrative disease may progress from a non-dilated (often hyperdynamic) state with ventricular stiffness to a dilated form with systolic dysfunction
  • Quantitative Assessment of Ventricular Size is a Continuum and Patients can Vary Widely in their Degree of Dilatation (with Minimal Cavity Enlargement Early in the Course of Their Disease Process): it is often difficult to strictly differentiate dilated and non-dilated forms of cardiomyopathy

Primary Cardiomyopathies (Predominantly Involving the Heart)

Genetic

• Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (Arrhythmogenic Right Ventricular Dysplasia) (see Arrhythmogenic Right Ventricular Cardiomyopathy, [[Arrhythmogenic Right Ventricular Cardiomyopathy]])
• Conduction System Disease
  • Lenegre Disease
  • Sick Sinus Syndrome
• Glycogen Storage Diseases
  • Danon
  • PRKAG2
• Hypertrophic Cardiomyopathy
• Ion Channelopathies
  • Brugada Syndrome
  • Catecholaminergic Polymorphic Ventricular Tachycardia
  • Idiopathic Ventricular Fibrillation
  • Long-QT Syndrome
  • Short-QT Syndrome
• Left Ventricular Noncompaction
• Mitochondrial Myopathies

Mixed (Predominantly Non-Genetic; Familial Disease with a Genetic Origin has been Reported in a Minority of Cases)

• Dilated Cardiomyopathy: this is a heterogeneous group of disorders characaterized by ventricular dilation and decreased myocardial contractility in the absence of abnormal loading (valvular heart disease, hypertension)
• Restrictive Cardiomyopathy (Non-Dilated and Non-Hypertrophied)

Acquired

• Cardiomyopathy in Infants of Insulin-Dependent Diabetic Mothers
• Myocarditis (Inflammatory Cardiomyopathy) (see Myocarditis, [[Myocarditis]])
  • Epidemiology: accounts for approximately 9% of initially unexplained cardiomyopathy cases
  • Clinical
    • Acute Course: distinct onset with severe hemodynamic compromise
    • Subacute Course: indistinct onset with better tolerated left ventricular dysfunction
• Peripartum Cardiomyopathy
  • Incidence: occurs in 1:1300-1:4000 liver births
  • Risk Factors: advanced maternal age, multiparity, African descent, and long-term tocolysis
  • Clinical: left ventricular dysfunction occurs in the last trimester or early puerperium
• Tachycardia-Induced Cardiomyopathy
  • Physiology: may be caused by supraventricular tachycardias, ventricular tachycardia, ventricular pacing at high rates, or frequent premature ventricular contractions (PVC’s)
  • Clinical: degree of left ventricular dysfunction is correlated with the duration of the tachyarrhythmia
  • Treatment: often reversible (but may not be complete in some cases)
• Takotsubo Cardiomyopathy (Stress Cardiomyopathy) (see Takotsubo Cardiomyopathy, [[Takotsubo Cardiomyopathy]])
  • Epidemiology: most often affects post-menopausal women
  • Diagnosis
    • Acute reversible left ventricular dysfunction (triggered by acute emotional or physical stress) in the absence of significant coronary artery disease
    • Echocardiogram with distinctive apical ballooning
  • Clinical
    • Acute Coronary Syndrome with Transiently Elevated Cardiac Enzymes: typical presentation

Secondary Cardiomyopathies

Cardiofacial

• Lentiginosis
• Noonan Syndrome

Endocrine/Metabolic

• Acidosis (see Metabolic Acidosis-General, [[Metabolic Acidosis-General]])
• Acromegaly (see Acromegaly, [[Acromegaly]])
  • Physiology: myocardial hypertrophy with interstitial fibrosis, lympho-mononuclear cell infiltration, myocyte necrosis, and biventricular concentric hypertrophy
• Diabetes Mellitus (see Diabetes Mellitus, [[Diabetes Mellitus]])
  • Mortality Rate is Related to Hemoglobin A1C Level: inverted-U relationship with highest mortality rate with extremely low or high hemoglobin A1C levels
• Growth Hormone Deficiency: growth hormone and insulin-like growth factor 1 and required for cardiac development
• Hyperparathyroidism (see Hyperparathyroidism, [[Hyperparathyroidism]])
• Hyperthyroidism (see Hyperthyroidism, [[Hyperthyroidism]])
  • Physiology: most commonly occurs in the setting of persistent sinus tachycardia or atrial fibrillation -> consequently, may be related to the tachycardia alone
• Hypocalcemia (see Hypocalcemia, [[Hypocalcemia]])
• Hypokalemia (see Hypokalemia, [[Hypokalemia]])
• Hypophosphatemia (see Hypophosphatemia, [[Hypophosphatemia]])
• Hypothyroidism (see Hypothyroidism, [[Hypothyroidism]])
  • Clinical: both systolic and diastolic dysfunction have been reported
    • Myxedema: low cardiac output state usually results from bradycardia, decreased ventricular filling, decreased myocardial contractility and decreased myocardial work
• Hypoxia (see Hypoxemia, [[Hypoxemia]])
• Obesity (see Obesity, [[Obesity]])
  • Physiology
    • Excessive adipose tissue results in increasing circulating blood volume with resulting increased cardiac output, increased cardiac work, and hypertension
    • Possible contributions of lipotoxicity-induced cardiac myocyte injury and myocardial lipid accumulation
• Pheochromocytoma (see Pheochromocytoma, [[Pheochromocytoma]])

Endomyocardial

• Endomyocardial Fibrosis
• Hypereosinophilic Syndrome (Löeffler’s Endocarditis????) (see Hypereosinophilic Syndrome, [[Hypereosinophilic Syndrome]])

Hematologic Disease

• Anemia (see Anemia, [[Anemia]])
• Henoch-Schonlein Purpura (see Henoch-Schonlein Purpura, [[Henoch-Schonlein Purpura]])
• Sickle Cell Disease (see Sickle Cell Disease, [[Sickle Cell Disease]])

Infiltrative (Accumulation of Abnormal Substances in Extracellular Space Between Myocytes)

• Amyloidosis (see Amyloidosis, [[Amyloidosis]])
  • Epidemiology: cardiac involvement is most common with AL amyloidosis (monoclonal kappa or lambda light chains) and senile TTR amyloidosis (wild-type transthyretin) subtypes
• Gaucher’s Disease (see xxxx)
• Hunter’s Syndrome
• Hurler’s Syndrome

Infection/Inflammatory

• Hantavirus Pulmonary Syndrome (see Hantavirus, [[Hantavirus]]): unusually produces sepsis with a high SVR and low CO state
• Sarcoidosis (see Sarcoidosis, [[Sarcoidosis]])
  • Epidemiology: may affect as many as 25% of patients with systemic sarcoidosis (but is often underdiagnosed)
  • Clinical
    • Asymptomatic Left Ventricular Dysfunction
    • Atrial/Ventricular Arrhythmias
    • Atrioventricular Blocks
    • Congestive Heart Failure (CHF)
    • Sudden Cardiac Death
• Sepsis-Induced Myocardial Depression (see Sepsis, [[Sepsis]])

Ischemic

• Acute Myocardial Infarction (MI) (see Coronary Artery Disease, [[Coronary Artery Disease]])
  • Epidemiology: coronary artery disease is the most common etiology of systolic congestive heart failure (accounts for 62% of all cases)
  • Physiology: involving >40% of left ventricular myocardium or right ventricular infarction
• Myocardial Ischemia
  • Epidemiology: coronary artery disease is the most common etiology of systolic congestive heart failure (accounts for 62% of all cases)
  • Physiology: involving >40% of left ventricular myocardium
• Stunned Myocardium (from Prolonged Ischemia)
  • Cardiac Arrest (see Cardiac Arrest, [[Cardiac Arrest]])
  • Post-Cardiopulmonary Bypass (CPB) (see Cardiopulmonary Bypass, [[Cardiopulmonary Bypass]])
  • Prolonged Hypotension (see Hypotension, [[Hypotension]])

Neoplasm

• Leukemia
  • xxx
  • xxx
• Multiple Myeloma (see Multiple Myeloma, [[Multiple Myeloma]])

Neuromuscular/Neurologic

• Becker Muscular Dystrophy (see Becker Muscular Dystrophy, [[Becker Muscular Dystrophy]])
• Chronic Progressive External Opthmoplegia (Kearns-Savre)
• Duchenne Muscular Dystrophy (see Duchenne Muscular Dystrophy, [[Duchenne Muscular Dystrophy]])
• Emery-Dreifuss Muscular Dystrophy
• Familial Centronuclear Myopathy
• Fascioscapulohumeral Dystrophy (Landouzy-Dejerine)
• Friedrich’s Ataxia (see XXX)
• Humuloperitoneal Ataxia
• Juvenile Progressive Spinal Muscular Atrophy (Kugelberg-Welander)
• Limb-Girdle Muscular Dystrophy
• Myotonia Atrophica (Steinert)
• Myotonic Dystrophy (see XXX)
• Neurofibromatosis (see Neurofibromatosis, [[Neurofibromatosis]])
• Tuberous Sclerosis (see Tuberous Sclerosis, [[Tuberous Sclerosis]])

Nutritional

• Carnitine Deficiency (see Carnitine, [[Carnitine]])
  • Physiology: L-carnitine is a necessary cofactor for fatty acid oxidation
  • Clinical: progressive skeletal myopathy and cardiomyopathy
• Keshan’s Disease
• Kwashiorkor
• Niacin Deficiency (Pellagra) (see Niacin, [[Niacin]])
• Selenium Deficiency (see Selenium, [[Selenium]])
• Thiamine Deficiency (Wet Beriberi) (see Thiamine, [[Thiamine]])
• Vitamin C Deficiency (Scurvy) (see Vitamin C, [[Vitamin C]])

Rheumatologic

• Behcet’s Disease (see Behcet’s Disease, [[Behcets Disease]])
• Churg-Strauss Syndrome (see Churg-Strauss Syndrome, [[Churg-Strauss Syndrome]])
• Microscopic Polyangiitis (see Microscopic Polyangiitis, [[Microscopic Polyangiitis]])
• Polyarteritis Nodosa (PAN) (see Polyarteritis Nodosa, [[Polyarteritis Nodosa]])
• Polydermatomyositis (see Polydermatomyositis, [[Polydermatomyositis]])
• Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]])
  • Epidemiology: development of dilated cardiomyopathy is rare
  • Physiology: microvasculitis and microcirculatory disturbances, resulting in myocarditis
  • Clinical
    • Mycocarditis: myocardial disease can occur in the absence of clinical symptoms or EKG changes
    • Pericarditis
• Scleroderma (see Scleroderma, [[Scleroderma]])
  • Epidemiology
    • Rare etiology of dilated cardiomyopathy
    • May cause restrictive cardiomyopathy (see Restrictive Cardiomyopathy, [[Restrictive Cardiomyopathy]])
  • Clinical: subclinical systolic dysfunction is present in the majority of scleroderma patients
• Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]])
• Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) (see Granulomatosis with Polyangiitis, [[Granulomatosis with Polyangiitis]])

Storage (Accumulation of Abnormal Substances Intracellularly Within Myocytes)

• Fabry’s Disease
• Hemochromatosis (see Hemochromatosis, [[Hemochromatosis]])
  • Clinical: systolic or diastolic dysfunction
• Niemann-Pick Disease (see xxxx)
• Ochronosis
• Oxalosis (see Primary Hyperoxaluria, [[Primary Hyperoxaluria]])
• Pompe’s Disease (see xxxx)

Traumatic

• Cardiac Contusion (see Cardiac Contusion, [[Cardiac Contusion]])

Drug/Toxin

• 5-Fluorouracil (5-FU) (see 5-Fluorouracil, [[5-Fluorouracil]])
• Amphetamine (see Amphetamine, [[Amphetamine]])
• Anabolic Steroids (see xxxx, [[xxxx]])
• Antimony (see Antimony, [[Antimony]])
• Antracyclines
  • Epidemiology: anthracyclines most commonly cause dilated cardiomyopathy
    • However, may cause restrictive cardiomyopathy (see Restrictive Cardiomyopathy, [[Restrictive Cardiomyopathy]])
  • Daunorubicin (Daunomycin, Cerubidine) (see Daunorubicin, [[Daunorubicin]])
    • Physiology: iron-chelating agents that prevent generation of oxygen free radicals (dexrazoxane) are cardioprotective against the development of anthracycline-induced cardiomyopathy
  • Doxorubicin (Adriamycin) (see Doxorubicin, [[Doxorubicin]])
    • Physiology: iron-chelating agents that prevent generation of oxygen free radicals (dexrazoxane) are cardioprotective against the development of anthracycline-induced cardiomyopathy
• Arsenic (see Arsenic, [[Arsenic]])
• Carboxyhemoglobinemia (see Carboxyhemoglobinemia, [[Carboxyhemoglobinemia]])
• Carbon Tetrachloride (see Carbon Tetrachloride, [[Carbon Tetrachloride]])
• Catecholamines
• Chloroquine (see Chloroquine, [[Chloroquine]])
• Clozapine (Clozaril) (see Clozapine, [[Clozapine]])
• Cobalt (see Cobalt, [[Cobalt]])
• Cocaine (see Cocaine, [[Cocaine]])
  • Epidemiology: long-term cocaine abuse can produce cardiomyopathy (even in the absence of coronary artery disease, myocardial infarction, or vasculitis)
• Cyclophosphamide (Cytoxan) (see Cyclophosphamide, [[Cyclophosphamide]])
  • Epidemiology: cardiotoxicity is associated with high-dose administration
• Emetine (see Emetine, [[Emetine]])
• Ephedra (see Ephedra, [[Ephedra]])
  • Epidemiology: banned by the FDA
  • Clinical
    • Left Ventricular Systolic Dysfunction/Congestive Heart Failure
    • Sudden Cardiac Death (see Cardiac Arrest, [[Cardiac Arrest]])
• Ethanol (see Ethanol, [[Ethanol]])
  • Epidemiology: one of the most important etiologies of dilated cardiomyopathy
    • Alcoholic cardiomyopathy most commonly occurs in men 30-55 y/o who have been drinking heavily for >10 yrs
    • In contrast, mild-moderate ethanol consumption has been found to be protective against the development of congestive heart failure in poulation studies
• Hydrocarbon Intoxication (see Hydrocarbons, [[Hydrocarbons]])
• Hydroxychloroquine (Plaquenil) Intoxication (see Hydroxychloroquine, [[Hydroxychloroquine]])
• Interferons (see Interferons, [[Interferons]])
• Lead (see Lead, [[Lead]])
• Lithium (see Lithium, [[Lithium]])
• Mercury (see Mercury, [[Mercury]])
• Methamphetamine (see Methamphetamine, [[Methamphetamine]])
  • Acute Methamphetamine Intoxication
  • Chronic Methamphetamine Abuse
• Methylphenidate (Ritalin) (see Methylphenidate, [[Methylphenidate]])
• Methysergide (see Methysergide, [[Methysergide]])
• Mitomycin-C (see Mitomycin, [[Mitomycin]])
• Phenothiazines (se Phenothiazines, [[Phenothiazines]])
  • Aliphatic Compounds
    • Chlorpromazine (Thorazine, Largactil, Megaphen) (see Chlorpromazine, [[Chlorpromazine]])
    • Levomepromazine
    • Methotrimeprazine (Nozinan, Levoprome)
    • Promazine (Sparine)
    • Triflupromazine
  • Piperidines
    • Mesoridazine (Serentil) (see Mesoridazine, [[Mesoridazine]])
    • Thioridazine (Mellaril) (see Thioridazine, [[Thioridazine]])
  • Piperazines
    • Fluphenazine (Prolixin) (see Fluphenazine, [[Fluphenazine]])
    • Perphenazine (Trilafon) (see Perphenazine, [[Perphenazine]])
    • Prochloperazine (Compazine) (see Prochlorperazine, [[Prochlorperazine]])
    • Trifluoperazine (Stelazine) (see Trifluoperazine, [[Trifluoperazine]])
• Propofol Infusion Syndrome (see Propofol, [[Propofol]])
  • Physiology: rhabdomyolysis of cardiac muscle
• Taxol Derivatives (see Taxanes, [[Taxanes]])
  • Docetaxel (Taxotere) (see Docetaxel, [[Docetaxel]])
  • Paclitaxel (Taxol) (see Paclitaxel, [[Paclitaxel]])
• Trastuzumab (Herceptin) (see Trastuzumab, [[Trastuzumab]])
  • Epidemiology: risk or cardiotoxicity is increased with concomitant anthracycline administration
  • Physiology: unlike anthracycline-induced cardiotoxicity, risk of cardiomyopathy with trastuzumab does not appear to be related to cumulative dose or result in ultrastructural myocardial changes
  • Treatment: often reversible with discontinuation of trastuzumab
• Tricyclic Antidepressants (see Tricyclic Antidepressants, [[Tricyclic Antidepressants]])
  • Amitriptyline (Tryptomer, Elavil) (see Amitriptyline, [[Amitriptyline]])
  • Clomipramine (Anafranil) (see Clomipramine, [[Clomipramine]])
  • Desipramine (Norpramin, Pertofrane) (see Desipramine, [[Desipramine]])
  • Doxepin (Adapin, Sinequan) (see Doxepin, [[Doxepin]])
  • Imipramine (Tofranil, Janimine, Praminil) (see Imipramine, [[Imipramine]])
  • Nortriptyline (Pamelor, Aventyl, Norpress) (see Nortriptyline, [[Nortriptyline]])
  • Protriptyline (Vivactil) (see Protriptyline, [[Protriptyline]])
  • Trimipramine (Surmontil) (see Trimipramine, [[Trimipramine]])
• White Phosphorus Toxicity (see White White Phosphorus, [[White Phosphorus]])
• Widow Spider Bite (see Widow Spider Bite, [[Widow Spider Bite]])
  • Epidemiology: cardiomyopathy occurs rarely
• Zidovudine (Retrovir) (see Zidovudine, [[Zidovudine]])

Other

• Radiation Therapy (see Radiation Therapy, [[Radiation Therapy]]): mediastinal radiation therapy is more commonly associated with diastolic dysfunction [MEDLINE]
• Stiff Left Atrial Syndrome Following Left Atrial Catheter Ablation (see Stiff Left Atrial Syndrome, [[Stiff Left Atrial Syndrome]])
  • Epidemiology
  • Physiology

Other

Increased Afterload

• Aortic Coarctation (see Aortic Coarctation, [[Aortic Coarctation]])
• Hypertrophic Obstructive Cardiomyopathy (HOCM) (see Hypertrophic Cardiomyopathy, [[Hypertrophic Cardiomyopathy]])
• Malignant Hypertension (see Hypertension, [[Hypertension]])
  • Epidemiology: common etiology of systolic congestive heart failure (accounts for 10% of all cases)
• Severe Aortic Stenosis (see Aortic Stenosis, [[Aortic Stenosis]])

Increased Intrathoracic Pressure (with Impaired Right-Sided Venous Return)

• Herniation of Abdominal Viscera Into Thorax
• Positive-Pressure Ventilation with High Airway Pressures (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])
• Tension Pneumothorax (see Pneumothorax, [[Pneumothorax]])

Intracardiac Shunt (see Intracardiac and Extracardiac Shunt, [[Intracardiac and Extracardiac Shunt]])

• Atrial Septal Defect (ASD) (see Atrial Septal Defect, [[Atrial Septal Defect]])
• Ruptured Sinus of Valsalva Aneurysm (see Sinus of Valsalva Aneurysm, [[Sinus of Valsalva Aneurysm]])
• Ventricular Septal Defect (VSD) (see Ventricular Septal Defect, [[Ventricular Septal Defect]])
• Ventricular Septal Rupture (see Ventricular Septal Rupture, [[Ventricular Septal Rupture]])

Valvular Disease/Mechanical Disturbance

• General Comments: valvular heart disease is a common etiology of systolic congestive heart failure
• Aortic Insufficiency (AI) (see Aortic Insufficiency, [[Aortic Insufficiency]])
• Aortic Stenosis (AS) (see Aortic Stenosis, [[Aortic Stenosis]])
• Atrial Myxoma (see Atrial Myxoma, [[Atrial Myxoma]])
• Atrial Thrombus (see Intracardiac Thrombus, [[Intracardiac Thrombus]])
• Mitral Regurgitation (MR) (see Mitral Regurgitation, [[Mitral Regurgitation]])
• Mitral Stenosis (see Mitral Stenosis, [[Mitral Stenosis]])
• Papillary Muscle Dysfunction/Rupture
• Ruptured Left Ventricular Aneurysm (see Left Ventricular Aneurysm, [[Left Ventricular Aneurysm]])
• Ruptured Sinus of Valsalva Aneurysm (see Sinus of Valsalva Aneurysm, [[Sinus of Valsalva Aneurysm]])
• Tamponade (see Tamponade, [[Tamponade]])
  • Physiology: produces diastolic dysfunction
• Tricuspid Regurgitation (TR) (see Tricuspid Regurgitation, [[Tricuspid Regurgitation]])
• Ventricular Septal Defect (VSD) (see Ventricular Septal Defect, [[Ventricular Septal Defect]])

Other

• Metoclopramide (Reglan) (see Metoclopramide, [[Metoclopramide]]): due to increased aldosterone secretion, resulting in fluid retention

---

Physiology

Left Ventricular Hypertrophy

• Etiology of Left Ventricular Hypertrophy
  • Coronary Artery Disease (CAD)
  • Diabetes Mellitus (DM)
  • Hypertension
  • Valvular Heart Disease
• Degree of Left Ventricular Hypertrophy Correlates with the Risk of Heart Falure of Any Etiology: interestingly, there does not appear to be an ability to separate compensatory from pathologic left ventricular hypertrophy
• Distinguishing Systolic vs Diastolic Congestive Heart Failure
  • Mean LV Mass-Volume Ratio: mean LV mass-volume ratio is increased in diastolic congestive heart failure (2.12), as compared to systolic congestive heart failure (1.22) and controls (1.49) [MEDLINE]

---

Diagnosis

Electrocardiogram (EKG) (see Electrocardiogram, [[Electrocardiogram]])

• xxx

Serum Brain Natriuretic Peptide (BNP) or N-Terminal Pro-B-Type Natriuretic Peptide (NT-pro-BNP) (see Serum Brain Natriuretic Peptide, [[Serum Brain Natriuretic Peptide]])

• Both are derived from the 108-amino acid precursor peptide (proBNP108) that is generated by cardiac myocytes in response to myocardial stretch (and other triggers)
• BNP is elevated in both systolic and diastolic congestive heart failure
• Positive Predictive Value: lower values of BNP exclude the presence of congestive heart failure with a reasonably high positive predictive value
  • However, BNP is less specific, as there are multiple other etiologies which may elevate BNP levels

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• Acute Heart Failure
  • In Patients Presenting with Dyspnea, Measurement of BNP (or NT-ProBNP) is Useful to Support or Exclude a Diagnosis of Heart Failure (Class of Recommendation I, Level of Evidence A)
  • Measurement of Baseline BNP/NT-ProBNP and/or Cardiac Troponin on Admission to the Hospital is Useful to Establish a Prognosis in Acutely Decompensated Heart Failure (Class of Recommendation I, Level of Evidence A)
  • During a Heart Failure Hospitalization, a Predischarge BNP/NT-ProBNP Can Be Useful to Establish a Post-Discharge Prognosis (Class of Recommendation IIa, Level of Evidence B-NR)
• Chronic Heart Failure
  • Measurement of BNP/NT-ProBNP is Useful for Establishing Prognosis or Disease Severity in Chronic Heart Failure (Class of Recommendation I, Level of Evidence A)
  • In Patients with Chronic Heart Failure, Measurement of Other Clinically Available Tests, Such as Biomarkers of Myocardial Injury or Fibrosis (Soluble ST2 Receptor, Galectin-3, High-Sensitivity Cardiac Troponin, etc) in Addition to BNP/NT-ProBNP May Be Considered for Additive Risk Stratification (Class of Recommendation II1, Level of Evidence B-NR)
    • A Combination of Biomarkers May Prove to Be More Useful than Single Biomarkers

Serum Troponin (see Serum Troponin, [[Serum Troponin]])

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• Acute Heart Failure
  • Measurement of Baseline BNP (or NT-ProBNP) and/or Cardiac Troponin on Admission to the Hospital is Useful to Establish a Prognosis in Acutely Decompensated Heart Failure (Class of Recommendation I, Level of Evidence A)
• Chronic Heart Failure
  • In Patients with Chronic Heart Failure, Measurement of Other Clinically Available Tests, Such as Biomarkers of Myocardial Injury or Fibrosis (Soluble ST2 Receptor, Galectin-3, High-Sensitivity Cardiac Troponin, etc) in Addition to BNP May Be Considered for Additive Risk Stratification (Class of Recommendation II1, Level of Evidence B-NR)
    • A Combination of Biomarkers May Prove to Be More Useful than Single Biomarkers

Echocardiogram (see Echocardiogram, [[Echocardiogram]])

• xxx

6-Minute Walk Test (6MWT) (see 6-Minute Walk Test, [[6-Minute Walk Test]])

Indications

• xxxx

Cardiac Catheterization with Coronary Angiogram (see Cardiac Catheterization, [[Cardiac Catheterization]])

• xxx

Swan-Ganz Catheterization (see Swan-Ganz Catheter, [[Swan-Ganz Catheter]])

• xxx

Endomyocardial Biopsy

• xxx

Cardiopulmonary Exercise Test (see Cardiopulmonary Exercise Test, [[Cardiopulmonary Exercise Test]])

• Ventilatory Anaerobic Threshold: similar in systolic and diastolic congestive heart failure, both are decreased as compared to controls [MEDLINE]

Chest X-Ray (see Chest X-Ray, [[Chest X-Ray]])

• Cardiomegaly with usually bilateral effusions: cardiomegaly is almost always present (in absence of cardiomegaly, only 4% of effusions are due to CHF)/ pulmonary vascular congestion (may be seen)
  • Autopsy studies, 88% are bilateral/ 8% are unilateral right-sided/ 4% are unilateral left-sided (Race, 1957)
  • Mean volume on right side was only slightly greater than volume on left side: presence of highly assymmetric effusions suggests an etiology other than CHF

Chest CT (see Chest Computed Tomography, [[Chest Computed Tomography]])

• Cardiomegaly with usually bilateral effusions: cardiomegaly is almost always present (in absence of cardiomegaly, only 4% of effusions are due to CHF)/ pulmonary vascular congestion (may be seen)
  • Autopsy studies, 88% are bilateral/ 8% are unilateral right-sided/ 4% are unilateral left-sided (Race, 1957)
  • Mean volume on right side was only slightly greater than volume on left side: presence of highly assymmetric effusions suggests an etiology other than CHF

---

Clinical Manifestations

General Comments

ACCF/AHA Staging of Congestive Heart Failure (CHF) (Circulation, 2013) [MEDLINE]

• Stage A
  • Definition: at risk for heart failure but without structural heart disease or symptoms of heart failure
  • NYHA Class: N/A
• Stage B:
  • Definition: structural heart disease but without signs or symptoms of heart failure
  • New York Heart Association (NYHA) Class
    • Class I: no limitation of physical activity (ordinary physical activity does not cause symptoms of heart failure)
• Stage C: structural heart disease with prior or current symptoms of heart failure
  • Definition:
  • New York Heart Association (NYHA) Class
    • Class I: no limitation of physical activity (ordinary physical activity does not cause symptoms of heart failure)
    • Class II: slight limitation of physical activity (comfortable at rest, but ordinary physical activity results in symptoms of heart failure)
    • Class III: marked limitation of physical activity (comfortable at rest, but less than ordinary activity causes symptoms of heart failure)
    • Class IV: unable to carry on any physical activity without symptoms of heart failure or symptoms of heart failure at rest
• Stage D: refractory heart failure requiring specialized interventions
  • Definition:
  • New York Heart Association (NYHA) Class
    • Class IV: unable to carry on any physical activity without symptoms of heart failure or symptoms of heart failure at rest

Comparison of Clinical Manifestations in Systolic vs Diastolic Congestive Heart Failure

• General Comments
  • Clinical Manifestations are Very Similar for Systolic and Diastolic Heart Failure (JAMA, 2002) [MEDLINE]

Clinical Criteria for Advanced Heart Failure (European Society of Cardiology Criteria) (Circulation, 2012) [MEDLINE]

• Moderate-Severe Dyspnea/Fatigue at Rest or with Minimal Exertion (NYHA Functional Class III or IV)
• Episodes of Fluid Retention and/or Decreased Cardiac Output
• Objective Evidence of Severe Cardiac Dysfunction (at Least One of the Following)
  • LV Ejection Fraction <30%
  • Pseudonormal or Restrictive Mitral Inflow Pattern by Doppler
  • High Left and/or Right Ventricular Filling Pressures
  • Elevated BNP
• Severe Impairment of Functional Capacity (at Least One of the Following)
  • Inability to Exercise
  • 6-Minute Walk Test Distance <300 m
  • Peak Oxygen Uptake <12-14 mL/g/min
    • At Least One Hospitalization in the Past 6 Months
    • Characteristics Should Be Present Despite Optimal Medical Therapy

Cardiovascular Manifestations

• Low Cardiac Output State/Cardiogenic Shock (see Cardiogenic Shock, [[Cardiogenic Shock]])
• Ventricular Thrombus (see Intracardiac Thrombus, [[Intracardiac Thrombus]])
• Poor Tolerance of Hemodynamic Stresses: in diastolic congestive heart failure
  • Atrial Fibrillation (see Atrial Fibrillation, [[Atrial Fibrillation]]): loss of atrial contraction leads to significantly impaired ventricular filling and decreases stroke volume
  • Hypertension (see Hypertension, [[Hypertension]]): leads to increased left ventricular wall stress, which impairs myocardial relaxation
    • This is particularly true when hypertensive is abrupt and severe
  • Myocardial Ischemia: leads to increased left atrial pressures with consequent increase in pulmonary artery pressure
  • Tachycardia (see Sinus Tachycardia, [[Sinus Tachycardia]]): leads to shortened diastole, which decreases ventricular filling

Gastrointestinal/Hepatic Manifestations

• Congestive Hepatopathy (see Congestive Hepatopathy, [[Congestive Hepatopathy]])

Hematologic Manifestations

• Hypercoagulable State (see Hypercoagulable States, [[Hypercoagulable States]])
  • Deep Venous Thrombosis (DVT) (see Deep Venous Thrombosis, [[Deep Venous Thrombosis]])

Pulmonary Manifestations

Cardiac Asthma (see Obstructive Lung Disease, [[Obstructive Lung Disease]])

• Physiology: pulmonary venous hypertension
  • Mitral Stenosis: upper lobe vascular distention occurs with relative lower lobe oligemia
• Diagnosis
  • Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests, [[Pulmonary Function Tests]])
    • Mitral Stenosis: decreased FEV1, decreased FVC, and increased RV correlate with the mitral valve gradient
      • Methacholine Challenge: may be positive (likely due to dilation of bronchial vessels induced by methacholine)
  • Chest X-Ray (CXR) (zee Chest X-Ray, [[Chest X-Ray]]): left atrial enlargement
    • Double-Shadow Sign: due to enlarged LA
    • Straightened Left Heart Border: due to enlarged LA
  • Echocardiogram: diagnostic of mitral stenosis, aortic stenosis, and left-sided systolic and diastolic dysfunction
• Clinical
  • Dyspnea
  • Hemoptysis: especially seen in mitral stenosis cases
  • Wheezing

Pleural Effusion (see Pleural Effusion-Transudate, [[Pleural Effusion-Transudate]] and Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]])

• Epidemiology
  • Congestive Heart Failure is the Most Common Cause of Pleural Effusion: CHF accounts for about 500,000 cases of pleural effusion per year in the US
  • In LV Failure, Pleural Effusions Occur 8% of the Time (by Autopsy Studies, 72% Had Pleural Effusions >250 mL)
  • CHF is the Most Common Cause of Bilateral Pleural Effusion
  • Approximately 25% of Pleural Effusions in Patients with CHF are Due to Other Etiologies
• Physiology
  • Mechanism: leakage of fluid mostly from alveolar capillaries (rather than pleural capillaries) -> interstitial edema -> passage of fluid across visceral pleura into pleural space
    • In volume-loading studies in sheep, pleural fluid contains the same protein content as the lymph and interstitial edema fluid in the lung (about 25% of all the edema fluid in the lung passes into the pleural space)
    • Clearance of Fluid from Pleural Space: almost all fluid exits pleural space via parietal lymphatics (lymphatic clearance is decreased in the presence of increased systemic veous pressure)
  • Hemodynamic Correlates of Congestive Heart Failure-Associated Pleural Effusion: presence of pleural effusion by ultrasound correlates more closely with pulmonary venous pressure than with systemic venous pressure or pulmonary artery pressure
    • Effusions occur mainly with left-sided congestive heart failure and are uncommon in patients with isolated right-sided congestive heart failure
• Diagnosis
  • Need for Thoracentesis: as many as 25% of pleural effusions in patients with congestive heart failure are due to other causes -> therefore, thoracentesis may be required in the setting of fever, unilateral/asymmetric effusion, pleuritic chest pain, or absence of cardiomegaly on chest x-ray
  • Transudate: however, congestive heart failure-associated transudate may convert to an exudate over time (with a long-standing effusion) or with diuresis (even over a couple of days)
    • Appearance: usually straw-colored or yellow (although may be blood-tinged in some cases)
    • LDH Ratio: <0.6
    • Pleural Fluid LDH: <66% of upper limit of normal for serum
    • Total Protein Ratio: <0.5
    • Serum/Pleural Albumin Gradient (SPAG): may be useful in ambiguous cases to confirm that fluid is actually a transudate
      • SPAG >1.2 g/dL: confirms that fluid is a transudate
    • Cell Count/Diiff: may be PMN-predominant in some cases
• Clinical
  • Decreased Breath Sounds
  • Dullness to Percussion
  • Resting/Exertional Dyspnea: dyspnea may be out of proportion to the size of pleural effusion

Pulmonary Edema (see Pulmonary Edema, [[Pulmonary Edema]])

• Interstitial Pulmonary Edema
  • Diagnosis
    • CXR Pattern
      • Interstitial Infiltrates
      • Kerley B Lines: thickened interlobular septa (seen at periphery of lung) due to pulmonary lymphatic obstruction (associated with increased LA pressures)
• Alveolar Pulmonary Edema
  • Diagnosis
    • CXR Pattern: alveolar filling

Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

• Epidemiology
  • Left-sided congestive heart failure is the most frequent cause of pulmonary hypertension
• Physiology
  • Increased left atrial pressure -> passive backward transmission of the pressure leading to increased pulmonary artery pressure
• Diagnosis
  • Swan-Ganz Catheter: elevated pulmonary artery pressure with normal pulmonary vascular resistance (PVR)
    • In some patients with left heart disease, the elevation of pulmonary artery pressure is out of proportion to that expected from the elevation of left arterial pressure
    • In patients referred to cardiac transplant clinics, pulmonary hypertension with PVR >3.0 Wood units is reported in 19% to 35% of patients: the elevation of PAP and PVR is due to either the increase of pulmonary artery vasomotor tone and/or pulmonary vascular remodeling
• Clinical
  • Dyspnea (see Dyspnea, [[Dyspnea]])
  • Signs of Right-Sided Congestive Heart Failure
    • Peripheral Edema (see Peripheral Edema, [[Peripheral Edema]])
• Treatment: the efficacy and safety of pulmonary artery hypertension medications in this population is unclear

Other

• Resting/Exertional Dyspnea (see Dyspnea, [[Dyspnea]])
• Orthopnea (see Orthopnea, [[Orthopnea]])
• Paroxysmal Nocturnal Dyspnea (see Paroxysmal Nocturnal Dyspnea, [[Paroxysmal Nocturnal Dyspnea]])

Other Manifestations

• Fatigue (see Fatigue, [[Fatigue]])
• Peripheral Edema (see Peripheral Edema, [[Peripheral Edema]])

---

Prevention

Blood Pressure Management

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• In Patients at Increased Risk of Congestive Heart Failure, Stage A Heart Failure, the Optimal Blood Pressure in Those with Hypertension Should Be <130/80 mm Hg (Class of Recommendation I, Level of Evidence B-R)

Use of Brain Natriuretic Peptide (BNP) Screening to Prevent Congestive Heart Failure (see Brain Natriuretic Peptide, [[Brain Natriuretic Peptide]])

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• For Patients at Risk of Developing Heart Failure, BNP-Based Screening Followed by Team-Based Care, Including a Cardiovascular Specialist Optimizing Guideline-Directed Management and Therapy, Can Be Useful to Prevent the Development of Left Ventricular Dysfunction (Systolic or Diastolic) or New-Onset Heart Failure (Class of Recommendation IIa, Level of Evidence B-R)
  • Data Suggest that BNP Screening and Early Intervention May Prevent Heart Failure

---

Treatment (Stage C Heart Failure with Reduced Ejection Fraction)

Blood Pressure Management

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• Patients with HFrEF and Hypertension Should Receive Guideline-Directed Management and Therapy Titrated to Attain Systolic Blood Pressure <130 mm Hg (Class of Recommendation I, Level of Evidence C-EO)

Diuretics

Agents

• Bumetanide (Bumex) (see Bumetanide, [[Bumetanide]])
• Furosemide (Lasix) (see Furosemide, [[Furosemide]])
• Spironolactone (Aldactone) (see Spironolactone, [[Spironolactone]])
• Torsemide (Demadex, Tortas) (see Torsemide, [[Torsemide]])

Administration

• PO
• IV: may be utilized to avoid hospital admission [JCHF. 2015;():. doi:10.1016/j.jchf.2015.06.017)]

Aldosterone-Receptor Antagonists

Pharmacology

• xxxx

Agents

• Eplerenone (Inspra) (see Eplerenone, [[Eplerenone]])
• Spironolactone (Aldactone) (see Spironolactone, [[Spironolactone]])

Beta Blockers (see β-Adrenergic Receptor Antagonists, [[β-Adrenergic Receptor Antagonists]])

• Agents
  • Bisoprolol (XXXX) (see Bisoprolol, [[Bisoprolol]])
  • Carvedilol (Coreg) (see Carvedilol, [[Carvedilol]])
  • Metoprolol Succinate (Metoprolol CR/XL) (see Metoprolol, [[Metoprolol]])
• Indications
  • xxx

Digoxin (Lanoxin) (see Digoxin, [[Digoxin]])

Pharmacology

• xxxx

Renin-Angiotensin System Inhibitors

Agents

• Angiotensin Converting Enzyme Inhibitors (ACE-I) (see Angiotensin Converting Enzyme Inhibitors, [[Angiotensin Converting Enzyme Inhibitors]])
  • Captopril (Capoten) (see Captopril, [[Captopril]])
  • Enalapril (Vasotec) (see Enalapril, [[Enalapril]])
  • Fosinopril (XXX) (see Fosinopril, [[Fosinopril]])
  • Lisinopril (XXX) (see Lisinopril, [[Lisinopril]])
  • Perindopril (XXX) (see Perindopril, [[Perindopril]])
  • Quinapril (XXX) (see Quinapril, [[Quinapril]])
  • Ramipril (Altace) (see Ramipril, [[Ramipril]])
  • Trandolapril (XXX) (see Trandolapril, [[Trandolapril]])
• Angiotensin II Receptor Blockers (ARB) (see Angiotensin II Receptor Blockers, [[Angiotensin II Receptor Blockers]])
  • Candesartan (XXX) (see Candesartan, [[Candesartan]])
  • Losartan (XXX) (see Losartan, [[Losartan]])
  • Valsartan (XXX) (see Valsartan, [[Valsartan]])
• Sacubitril + Valsartan (Entresto) (see Sacubitril + Valsartan, [[Sacubitril + Valsartan]])
  • Pharmacology
    • Sacubitril: neprilysin inhibitor
    • Valsartan (see Valsartan, [[Valsartan]]): angiotensin II receptor blocker
  • Recommendations for Use: use instead of ACE inhibitor or ARB in stable mild-moderate congestive heart failure (HRrEF) with all of the following
    • Elevated Brain Natriuretic Peptide or Hospitalization for Congestive Heart Failure within the Past 12 mo
    • Estimated GFR ≥30 mL/min
    • Left Ventricular Ejection Fraction ≤40%
    • Systolic Blood Pressure ≥100 mm Hg
    • Prior Tolerance of ACE Inhibitor or ARB Therapy for at Least Weeks

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• One of the Following Clinical Strategies is Recommended to Decrease Morbidity/Mortality in Chronic HFrEF (Class of Recommendation I)
  • ACE-I Therapy (Level of Evidence A) (see Angiotensin Converting Enzyme Inhibitors, [[Angiotensin Converting Enzyme Inhibitors]])
  • ARB Therapy (Level of Evidence A) (see Angiotensin II Receptor Blockers, [[Angiotensin II Receptor Blockers]])
  • Combination Neprilysin Inhibitor + ARB Therapy (Level of Evidence for B-R)
    • Sacubitril + Valsartan (Entresto) (see Sacubitril + Valsartan, [[Sacubitril + Valsartan]])
• Angiotensin Converting Enzyme Inhibitor (ACE-I)
  • Use of ACE-I Therapy is Beneficial to Decrease Morbidity/Mortality in Chronic HFrEF in Patients with Prior/Current Symptoms of Chronic Heart Failure (Class of Recommendation I, Level of Evidence A)
• Angiotensin II Receptor Blocker (ARB)
  • Use of ARB Therapy is Recommended to Decrease Morbidity/Mortality in Patients with Prior/Current Symptoms of Chronic HFrEF Fraction Who are Intolerant to ACE-I Because of Cough or Angioedema (Class of Recommendation I, Level of Evidence A)
• Combination Neprilysin Inhibitor + Renin-Angiotensin System Inhibitor
  • In Patients with Chronic Symptomatic HFrEF Fraction NYHA Class II-III Who Tolerate an ACE-I or ARB, Replacement by an Combination Neprilysin Inhibitor + ARB is Recommended to Further Decrease Morbidity/Mortality (Class of Recommendation I, Level of Evidence B-R)
  • Combination Neprilysin Inhibitor + ARB Should Not Be Administered Concomitantly with ACE-I or Within 36 hrs of the Last Dose of an ACE-I (Class of Recommendation III = Harm, Level of Evidence B-R)
  • Combination Neprilysin Inhibitor + ARB Should Not Be Administered to Patients with a History of Angioedema (Class of Recommendation III = Harm, Level of Evidence C-EO)

Hydralazine + Isosorbide Dinitrate (see Hydralazine, [[Hydralazine]] and Isosorbide, [[Isosorbide]])

Pharmacology

• xxxx

Indications

• xxxx

Ivabradine (XXX) (see Ivabradine, [[Ivabradine]])

Pharmacology

• xxxx

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• Ivabradine Can Be Beneficial to Decrease Heart Failure Hospitalization for Patients with Symptomatic (NYHA Class II-III) Stable Chronic HRrEF (LVEF ≤35%) Who are Receiving Guideline-Directed Management and Therapy, Including a β-Blocker at Maximum Tolerated Dose, and Who are in Sinus Rhythm with a Heart Rate of ≥70 bpm at Rest (Class of Recommendation IIa, Level of Evidence B-R)

Brain Natriuretic Peptide (BNP)-Guided Therapy

• Clinical Efficacy
  • Systematic Review/Meta-Analysis (2015) [MEDLINE]: BNP-guided therapy may improve the clinical outcomes of congestive heart failure patients, if substantial reduction of BNP can be achieved

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• xxxx
  

  Statins (HMG-CoA Reductase Inhibitors) (see HMG-CoA Reductase Inhibitors, [[HMG-CoA Reductase Inhibitors]])

• Clinical Efficacy
  • No Clinical Benefit, in the Absence of Other Indications

Management of Congestive Heart Failure-Associated Pleural Effusion (see xxxx, [[xxxx]])

• Therapeutic Thoracentesis: may be required to relieve dyspnea
• Treatment of Underlying CHF: usually leads to resolution of pleural effusion within days of diuresis
• Pleurodesis: may be necessary in few cases with symptomatic persistent or recurrent effusion even after vigorous treatment of CHF
  • Talc Slurry (5g) (see Talc, [[Talc]]) or Doxycycline (5 mg/kg) (see Doxycycline, [[Doxycycline]]): preferred agents
  • Bleomycin (see Bleomycin, [[Bleomycin]]): not recommended (ineffective in a rabbit model)
• Pleuroperitoneal Shunt: alternative to pleurodesis (successfully used in a few cases)

Management of Anemia (see Anemia, [[Anemia]])

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• In patients with NYHA class II and III HF and iron deficiency (ferritin <100 ng/mL or 100 to 300 ng/mL if transferrin saturation is <20%), intravenous iron replacement might be reasonable to improve functional status and Quality of Life (Class of Recommendation IIb, Level of Evidence B-R)
  • In patients with HF and anemia, erythropoietin-stimulating agents should not be used to improve morbidity and mortality (Class of Recommendation III = No Benefit, Level of Evidence B-R)

Management of Systolic Congestive Heart Failure Associated with Predominantly Central Sleep Apnea (CSA) (see Central Sleep Apnea, [[Central Sleep Apnea]])

Modalities

• Adaptive Servo Ventilation (ASV) (see Adaptive Servo Ventilation, [[Adaptive Servo Ventilation]])

Clinical Efficacy

• SERVE-HF Trial of Adaptive Servo Ventilation in Systolic Heart Failure and Predominantly Central Sleep Apnea (NEJM, 2015) [MEDLINE]
  • Adaptive Servo Ventilation Had No Effect on the Primary End-Point, Time-to-Event: events included death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure
  • Adaptive Servo Ventilation Increased Cardiovascular and All-Cause Mortality

  Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• In Patients with NYHA Class II–IV HF and Suspicion of Sleep-Disordered Breathing or Excessive Daytime Sleepiness, a Formal Sleep Assessment is Reasonable (Class of Recommendation IIa, Level of Evidence C-LD)
• In Patients with Cardiovascular Disease and Obstructive Sleep Apnea, CPAP May Be Reasonable to Improve Sleep Quality and Daytime Sleepiness (Class of Recommendation IIb, Level of Evidence B-R)
• In Patients with NYHA Class II–IV HFrEF and Central Sleep Apnea, Adaptive Servo Ventilation Causes Harm (Class of Recommendation III-Harm, Level of Evidence B-R)

Cardiac Resynchronization Therapy (CRT) (see Cardiac Resynchronization Therapy, [[Cardiac Resynchronization Therapy]])

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Cardiac Assist Device (see Cardiac Assist Devices, [[Cardiac Assist Devices]])

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Ventricular Assist Device (VAD) (see Ventricular Assist Device, [[Ventricular Assist Device]])

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Cardiac Transplant (see Cardiac Transplant, [[Cardiac Transplant]])

Indications

Absolute

• Cardiogenic Shock Requiring Intravenous Support or Circulatory Support (Inatraortic Balloon Pump, Left Ventricular Assist Device) to Maintain Adequate Organ Perfusion
• Persistent NYHA Class IV Heart Failure Symptoms Refractory to Medical/Surgical Therapy (Including Use of Support Devices)
  • Cardiopulmonary Exercise Testing and Heart Failure Prognosis Scoring are Recommended
    • Peak Oxygen Consumption (VO2) Thresholds Suggesting Listing for Cardiac Transplant (These Apply Regardless of the Use of Cardiac Resynchronization Therapy)
      • Patient on β-Blocker: peak VO2 ≤12 mL/kg/min
      • Patients Intolerant of β-Blockers: peak VO2 ≤14 mL/kg/min
      • Young Patient (<50 y/o) or Female: peak VO2 <50% predicted
    • Sub-Maximal Cardiopulmonary Exercise Testing (Respiratory Exchange Ratio <1.05)
      • Ventilation Equivalent of Carbon Dioxide (VE/VCO2) Slope >35
    • Prognosis Scoring
      • Seattle Heart Failure Model (SHFM) Estimated 1-Year Survival of <80%
      • Heart Failure Survival Score (HFSS) in the Medium/High Risk Range
• Intractable/Severe Anginal Symptoms in Patients with Coronary Artery Disease Not Amenable to Percutaneous/Surgical Reascularization, Including Severe Transplant Coronary Artery Disease (Cardiac Allograft Vasculopathy)
• Intractable Life-Threatening Arrhythmias Unresponsive to Medical Therapy/Catheter Ablation/Surgery/Automatic Implantable Cardioverter-Defibrillator
• Selected Patients with Restrictive/Hypertrophic Cardiomyopathy and NYHA Class III-IV Heart Failure
  • Work-Up Should Identify Etiology and Exclude Constrictive Pericarditis
  • Consideration Should Include Presence of Prognostic Factors, Such as Atrial Enlargement, Left Ventricular Systolic Dysfunction, Low Cardiac Output, and Pulmonary Hypertension
  • In Patients with Hepatic Dysfunction, Liver Biopsy May Be Required to Exclude Hepatic Fibrosis/Cirrhosis
  • Bridging with Left Ventricular Assist Device (or Total Artificial Heart) May Be Utilized
  • Selected Patients with Cardiac Amyloidosis (Those without Extracardiac Amyloid with Organ Dysfunction) May Be Candidates for Cardiac Transplantation
  • Patients with Refractory Severe Heart Failure from Non-Obstructive Cardiomyopathy (Especially Those with Left Ventricular Dilation and Systolic Dysfunction) May Be Considered for Cardiac Transplant
• Other Non-Dilated Cardiomyopathy
  • Arrhythmogenic right ventricular cardiomyopathy
  • Left ventricular noncompaction
• Congenital Heart Disease
  • Groups Who May Be Considered
    • NYHA Class IV Heart Failure Not amenable to Palliative or Corrective Surgery
    • Severe Symptomatic Cyanotic Heart Disease Not Amenable to Palliation
    • Post-Fontan Procedure with Refractory Heart Failure, Persistent Protein-Losing Enteropathy, and/or Plastic Bronchitis Despite Optimal Therapy
    • Pulmonary Hypertension with Potential Risk of Developing Fixed, Irreversible PVR Elevation Which Would Preclude Cardiac Transplant in the Future
  • Patients with Significant Irreversible Pulmonary Vascular Obstructive Disease (Eisenmenger Syndrome with Severe Symptoms Despite Therapy) May Be Considered for Combined Heart-Lung Transplant
  • Cardiac Transplant Alone Should Not Be Performed in the Presence of Severe Hypoplasia of the Central/Branch Pulmonary Arteries or Veins

Relative

• Patients with Heart Failure Causing Major Limitation of Daily Activities Despite Optimal Therapy (Including a β-Blocker) with Peak VO2 of 13-14 mL/kg/min (or <55% predicted)
• Recurrent Unstable Ischemia Not Amenable to Other Interventions
• Recurrent Instability of Fluid Balance/Renal Function Not Due to Patient Noncompliance

nsufficient Indications

• Low Left Ventricular Ejection Fraction
• History of NYHA Class III-IV Symptoms of Heart Failure
• Peak VO2 >15 mL/kg/min (or >55% predicted) Without Other Clinical Indications for Cardiac Transplant

Contraindications (International Society for Heart Lung Transplantation, ISHLT, Criteria) (J Heart Lung Transplant, 2016) [MEDLINE]

Absolute

• Active Substance Abuse
  • Alcohol Abuse (see Ethanol, [[Ethanol]])
  • Drug Abuse
  • Tobacco Abuse (see Tobacco, [[Tobacco]])
• Inability to Comply with Drug Therapy
• Irreversible Pulmonary Hypertension (PVR >3 WU)
  • However, there is Variation Among Centers as to the the Exact PVR Threshold is Acceptable
  • In Addition, Heart-Lung Transplantation May Be Considered in Cases with Pulmonary Hypertension with PVR >3 WU
  • After LVAD, Hemodynamics Should Be Evaluated After 3-6 mo to Ascertain Reversibility of the Pulmonary Hypertension (Class IIa Recommendation, Level of Evidence C)
• Multisystem Disease with Severe Extracardiac Organ Dysfunction
  • Amyloidosis (see Amyloidosis, [[Amyloidosis]]): in some cases
• Severe Symptomatic Cerebrovascular Disease (Class IIb Recommendation, Level of Evidence C)
• Systemic Illness with Life Expectancy <2 yrs Despite Cardiac Transplant

Relative

• Acute Pulmonary Embolism (within 6-8 wks) (see Acute Pulmonary Embolism, [[Acute Pulmonary Embolism]])
• Age >70 y/o
  • However, Selected Patients >70 y/o May Be Considered (Class IIb Recommendation, Level of Evidence C)
• Chronic Kidney Disease (with GFR <30 mL/min) (Class IIa Recommendation, Level of Evidence C) (see Chronic Kidney Disease, [[Chronic Kidney Disease]])
• Diabetes Mellitus with End-Organ Damage Other than Non-Proliferative Retinopathy or Poor Control (HbA1c >7.5%) Despite Optimal Therapy (Class IIa Recommendation, Level of Evidence C) (see Diabetes Mellitus, [[Diabetes Mellitus]])
• Drug/Alcohol Abuse (within 6 mo)
• Frailty (Class IIb Recommendation, Level of Evidence C): unclear role in assessing transplant candidacy
  • 3 of 5 Symptoms
    • Fatigue
    • Low Level of Physical Activity
    • Muscle Loss
    • Slow Walking Speed
    • Unintentional Weight loss of ≥10 lbs within the Past Year
• Inadequate Social Support or Cognitive-Behavioral Disability/Dementia Which Might Prevent Medical Compliance (Class IIa Recommendation, Level of Evidence C)
• Infection
  • However, Selected Patients with Infection May Be Considered
• Neoplasm
  • However, Selected Patients with Neoplasms May Be Considered
• Obesity (BMI >35 kg/m2) (Class IIa Recommendation, Level of Evidence C) (see Obesity, [[Obesity]])
• Other Conditions Which Would Limit Rehabilitation Potential
  • Peripheral Arterial Disease (PAD) Not Amenable to Revascularization (Class IIb Recommendation, Level of Evidence C) (see Peripheral Arterial Disease, [[Peripheral Arterial Disease]])
• Tobacco Abuse (within 6 mo)

---

Treatment (Stage C Heart Failure with Preserved Ejection Fraction)

Blood Pressure Management

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• Patients with HFpEF and Persistent Hypertension After Management of Volume Overload Should Receive Guideline-Directed Management and Therapy Titrated to Attain Systolic Blood Pressure <130 mm Hg (Class of Recommendation I, Level of Evidence C-LD)

Aldosterone-Receptor Antagonists

Agents

• Eplerenone (Inspra) (see Eplerenone, [[Eplerenone]])
• Spironolactone (Aldactone) (see Spironolactone, [[Spironolactone]])

Recommendations (2017 Focused Update of 2013 ACCF/AHA Guideline for the Management of Heart Failure) (Circulation, 2017) [MEDLINE]

• Systolic and Diastolic Blood Pressure Should Be Controlled in Patients with HFpEF in Accordance with Published Clinical Practice Guidelines to Prevent Morbidity (Class of Recommendation I, Level of Evidence B)
• Diuretics Should Be Used for Relief of Symptoms Due to Volume Overload in Patients with HFpEF (Class of Recommendation I, Level of Evidence C)
• Coronary Revascularization is Reasonable in Patients with CAD in Whom Symptoms (Angina) or Demonstrable Myocardial Ischemia is Judged to Be Having an Adverse Effect on Symptomatic HFpEF Despite Guideline-Directed Management and Therapy (Class of Recommendation IIa, Level of Evidence C)
• Management of AF According to Published Clinical Practice Guidelines in Patients with HFpEF is Reasonable to Improve Symptomatic Heart Failure (Class of Recommendation IIa, Level of Evidence C)
• Use of β-Blockers, ACE-I’s, and ARB’s in Patients with Hypertension is Reasonable to Control Blood Pressure in Patients with HFpEF (Class of Recommendation IIa, Level of Evidence C)
• In Appropriately Selected Patients with HFpEF (EF ≥45%, Elevated BNP or Hearty Failure Admission Within 1 Year, Estimated GFR >30 mL/min, Creatinine <2.5 mg/dL, Serum Potassium <5.0 mEq/L), Aldosterone Receptor Antagonists Might Be Considered to Decrease Hospitalizations (Class of Recommendation IIb, Level of Evidence B-R)
• Use of ARB’s Might Be Considered to Decrease Hospitalizations for Patients with HFpEF (Class of Recommendation IIb, Level of Evidence B)
• Routine Use of Nitrates or Phosphodiesterase-5 Inhibitors to Increase Activity or Quality of Life in Patients with HFpEF is Ineffective (Class of Recommendation III = No Benefit, Level of Evidence XXXX)
• Routine Use of Nutritional Supplements is Not Recommended for Patients with HFpEF (Class of Recommendation XXXX, Level of Evidence XXXX)

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Prognosis

Prognostic Models in Congestive Heart Failure

Ambulatory

• Heart Failure Survival Score: all-cause mortality rate
  • Peak V ̇O2, LVEF, serum sodium, mean BP, HR, ischemic etiology, QRS duration/morphology
• Seattle Heart Failure Model: all-cause mortality rate, urgent transplantation, or LVAD implantation
  • NYHA function class, ischemic etiology, diuretic dose, LVEF, SBP, sodium, hemoglobin, percent lymphocytes, uric acid, and cholesterol

Hospitalized

• EVEREST Risk Model: combined end point of mortality or persistently poor quality of life (KCCQ <45) over the 6 mo after discharge
  • Age, diabetes, h/o stroke, h/o arrhythmia, Beta blocker use, BUN, sodium, BNP, KCCQ scores
• EFFECT: 30-day and 1 year mortality rate
  • Age, SBP, respiratory rate, sodium, hemoglobin, BUN, h/o CVA, h/o dementia, h/o COPD, h/o cirrhosis, h/o cancer
• ADHERE: in-hospital mortality rate
  • BUN
  • SBP
  • Serum Creatinine
• ESCAPE Discharge Score: 6 mo mortality rate
  • BNP
  • Cardiopulmonary Resuscitation or Mechanical Ventilation During the Hospitalization
  • BUN
  • Sodium
  • Age >70 y/o
  • Daily Loop Diuretic Dose
  • Lack of Beta Blocker
  • 6-Minute Walk Test Distance

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References

General

• Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000;342(15):1077 [MEDLINE]
• Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA. 2002 Nov 6;288(17):2144-50 [MEDLINE]
• Diastolic dysfunction after mediastinal irradiation. Am Heart J. 2005 Nov;150(5):977-82 [MEDLINE]
• Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006 Apr 11;113(14):1807-16. Epub 2006 Mar 27 [MEDLINE]
• AHA Scientific Statement: Decision making in advanced heart failure. Circulation  2012;125:1928–1952 [MEDLINE]
• Link between decisions regarding resuscitation and preferences for quality over length of life with heart failure. Eur J Heart Fail. 2012 Jan;14(1):45-53. doi: 10.1093/eurjhf/hfr142. Epub 2011 Oct 27 [MEDLINE]
• 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15;128(16):e240-327. doi: 10.1161/CIR.0b013e31829e8776. Epub 2013 Jun 5 [MEDLINE]
• The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Heart Transplantation Report–2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant. 2015 Oct;34(10):1244-54. doi: 10.1016/j.healun.2015.08.003. Epub 2015 Aug 28 [MEDLINE]
• 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017 Aug 8;136(6):e137-e161. doi: 10.1161/CIR.0000000000000509. Epub 2017 Apr 28 [MEDLINE]

Diagnosis

Brain Natriuretic Peptide (BNP) (see Brain Natriuretic Peptide, [[Brain Natriuretic Peptide]])

• Biomarker-guided therapy in chronic heart failure: a meta-analysis of randomized controlled trials. Am Heart J. 2009;158:422–30 [MEDLINE]
• B-type natriuretic peptide-guided heart failure therapy: a meta-analysis. Arch Intern Med. 2010;170:507–14 [MEDLINE]
• Does B-type natriuretic peptide-guided therapy improve outcomes in patients with chronic heart failure? A systematic review and meta-analysis of randomized controlled trials. Heart Fail Rev. 2015 Jan;20(1):69-80. doi: 10.1007/s10741-014-9437-8 [MEDLINE]

Treatment

Diuretics

• Intravenous Diuretic Therapy for the Management of Heart Failure and Volume Overload in a Multidisciplinary Outpatient Unit. JCHF. 2015;():. doi:10.1016/j.jchf.2015.06.017

Sleep-Disordered Breathing

• Adaptive servoventilation improves cardiac function and respiratory stability. Clin Res Cardiol. 2011;100:107–115 [MEDLINE]
• Adaptive servoventilation for treatment of sleep-disordered breathing in heart failure: a systematic review and meta-analysis. Chest. 2012;142:1211–1221 [MEDLINE]
• SERVE-HF Trial. Adaptive servo-ventilation for central sleep apnea in systolic heart failure. N Engl J Med 2015;373:1095-1105 [MEDLINE]

Cardiac Transplant (see Cardiac Transplant, [[Cardiac Transplant]])

• The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update. J Heart Lung Transplant. 2016;35(1):1 [MEDLINE]