English

ThisiscontentfromClinicalKey

Want more answers?

Sign up for your free ClinicalKey trial today!  Your first step in getting the right answers when you need them. ClinicalKey is a clinical knowledge solution designed to help healthcare professionals and students find the right answers by providing in-depth, evidence-based knowledge – all from one resource.

Sep.14.2022

Heart Failure

Synopsis

Key Points

  • Heart failure is a clinical syndrome characterized by structural or functional impairment of ventricular filling or ejection of blood resulting in insufficient perfusion to meet metabolic demands and clinically manifested as edema, dyspnea, and fatigue
  • Diagnosis is suspected based on thorough history and physical examination. Measurement of natriuretic peptide levels, 2-dimensional echocardiography with Doppler flow imaging, and chest radiography support diagnosis of heart failure
  • Functionally categorized as either heart failure with reduced ejection fraction (left ventricular ejection fraction of 40% or less) or heart failure with preserved ejection fraction (left ventricular ejection fraction of 50% or more). Patients with values of 41% to 49% are classified as having mildly reduced ejection fraction r1
  • Coronary artery disease is the predominant cause of heart failure with reduced ejection fraction, which most commonly results in left ventricular dilation; hypertension is the predominant cause of heart failure with preserved ejection fraction, which is usually associated with left ventricular hypertrophy
  • Treatment of heart failure with reduced ejection fraction depends on disease stage and functional classification; recommended pharmacologic classes include ACE inhibitors or angiotensin receptor–neprilysin inhibitors, β-blockers, sodium-glucose cotransporter-2 inhibitors, and aldosterone antagonists for most patients, with diuretics for volume overload r2
    • Angiotensin receptor blockers or angiotensin receptor–neprilysin inhibitors may be indicated instead of ACE inhibitors in select patients
    • Vasodilators, ivabradine, digoxin, and vericiguat may be added for appropriate patients with continued symptoms
  • Recommended therapies for heart failure with preserved ejection fraction are symptom-directed or for management of comorbidities, especially hypertension r2
    • Although diuretics are recommended for fluid overload, there is no evidence that other treatments recommended for heart failure with reduced ejection fraction are efficacious for heart failure with preserved ejection fraction
    • Recent clinical trials suggest sodium-glucose cotransporter-2 inhibitors should be considered in heart failure with preserved ejection fraction r3
  • Device therapy (with implantable cardioverter-defibrillator or cardiac resynchronization device) is sometimes indicated as adjunctive therapy in select patients; temporary inotrope support, mechanical circulatory support with a ventricular assist device, and heart transplant are indicated in select advanced cases refractory to other treatment
  • Complications include malignant ventricular arrhythmias, atrial fibrillation, and thromboembolic events
  • Prognosis of patients hospitalized with heart failure, and especially those with serial readmissions, is poor r2
    • Mortality rate for patients with heart failure is approximately 40% within 5 years of diagnosis; for those with advanced heart failure,1-year survival rate is 50% r4

Urgent Action

  • Life-threatening conditions (eg, acute coronary syndromes, cardiac arrhythmias) may precipitate acute decompensated heart failure and must be treated emergently

Pitfalls

  • Treatment of advanced heart failure is often palliative; reevaluation of quality of indicators is necessary to avoid prolongation of futile efforts
  • There is no evidence of benefit from antiplatelet drugs (including aspirin) in patients with chronic stable heart failure unless concomitant coronary artery disease is present. Likewise, oral anticoagulants are not recommended unless atrial fibrillation or known cardiac thrombus is present r5

Terminology

Clinical Clarification

  • Heart failure is a complex clinical syndrome caused by structural or functional impairment of ventricular filling or ejection of blood resulting in insufficient perfusion to meet metabolic demands
  • Characterized by progressive cardiac remodeling with left ventricular dilation, left ventricular hypertrophy, or both
  • Cardinal clinical manifestations include pulmonary and/or systemic venous congestion and/or inadequate peripheral oxygen delivery with edema, dyspnea, and fatigue

Classification

  • Staging by American College of Cardiology Foundation/American Heart Association guideline (according to structure and progression of disease as evidenced by ECG and echocardiography) r2
    • Stage A (at risk for heart failure)
      • At high risk for heart failure without structural heart disease, symptoms, or cardiac biomarkers of stretch or injury on the basis of risk factors of the following:
        • Hypertension
        • Atherosclerotic cardiovascular disease
        • Diabetes
        • Metabolic syndrome and obesity
        • Genetic variant for cardiomyopathy
        • Family history of cardiomyopathy
        • Exposure to cardiotoxic agents
    • Stage B (pre–heart failure)
      • No signs and symptoms of heart failure but 1 of the following:
        • Structural heart disease
          • Reduced ejection fraction, reduced strain
        • Ventricular hypertrophy
        • Chamber enlargement
        • Wall motion abnormalities
        • Valvular heart disease
      • Evidence for increased filling pressures
        • By invasive hemodynamic measurements
        • By noninvasive imaging results suggesting elevated filling pressures (eg, Doppler echocardiography)
      • Patients with risk factors and 1 of the following, in the absence of competing diagnoses (eg, acute coronary syndrome, chronic kidney disease, pulmonary embolism, myopericarditis):
        • Increased levels of B-type natriuretic peptide or
        • Persistently elevated cardiac troponin
    • Stage C (symptomatic heart failure)
      • Structural heart disease with prior or current symptoms of heart failure
    • Stage D (advanced heart failure)
      • Marked symptoms that interfere with daily life and with recurrent hospitalizations despite optimal goal-directed medical therapy
  • Functional classification by New York Heart Association (based on symptom severity) r6
    • Class I
      • Heart disease with no symptoms or limitations with ordinary physical activity
    • Class II (mild)
      • Comfortable at rest, but mild symptoms of heart failure during ordinary activity
    • Class III (moderate)
      • Comfortable at rest, but severe symptoms of heart failure with ordinary activity or symptoms with even minimal exertion
    • Class IV (severe)
      • Symptoms at rest
      • Unable to carry on any physical activity without symptoms, mostly bedbound
  • Classification based on ejection fraction
    • Heart failure with preserved ejection fraction r1
      • Approximately half of all patients with heart failure r7
      • Ejection fraction o50% or more r2r8
      • Filling of ventricles is impaired owing to abnormal relaxation or stiffness and decreased diastolic distensibility
      • Historically described as diastolic heart failure
      • European guidelines have additional criteria that include elevated levels of natriuretic peptides and either relevant structural heart disease or diastolic dysfunction r9
      • Patients often have left atrial enlargement and increased left ventricular wall thickness but usually do not have left ventricular dilation
    • Heart failure with mildly reduced ejection fraction (previous terminology was heart failure with mid-range or borderline ejection fraction) r1r2r9
      • Ejection fraction of 41% to 49% that shares characteristics similar to heart failure with preserved ejection fraction and heart failure with reduced ejection fraction r8r9
      • European guidelines have additional criteria that include elevated levels of natriuretic peptides and either relevant structural heart disease or diastolic dysfunction r9
    • Heart failure with reduced ejection fraction r1r2r9
      • Ejection fraction of 40% or less r1
      • Historically described as systolic heart failure
      • Left ventricular contractility is impaired and is often dilated
    • Heart failure with improved ejection fraction r1
      • Symptomatic heart failure with a baseline left ventricular ejection fraction of 40% or less, a 10-point or greater increase from baseline left ventricular ejection fraction, and a second measurement of left ventricular ejection fraction greater than 40%
      • New, distinct classification
  • Classification based on timeline
    • New (de novo) heart failure r9
      • Acute onset
        • May present suddenly as a result of acute insult (eg, myocardial infarction)
      • Subacute onset
        • Gradual onset of symptoms
        • Occurs when transitioning from asymptomatic to symptomatic heart failure
    • Chronic heart failure r9
      • Stable
        • Treated heart failure; signs and symptoms are unchanged for more than 1 month (ie, compensated)
      • Decompensated
        • Symptomatic deterioration of stable chronic heart failure, often requiring hospitalization
        • Decompensation may occur acutely owing to a precipitating event (eg, myocardial infarction, atrial fibrillation, noncompliance with medical therapy) or may occur subacutely

Diagnosis

Clinical Presentation

History

  • Common symptoms of heart failure include:
    • Dyspnea c1
      • Dyspnea on exertion; dyspnea at rest often occurs in advanced heart failure c2c3c4
      • Orthopnea c5
      • Paroxysmal nocturnal dyspnea c6
    • Fatigue c7
      • Exercise intolerance c8
      • Increased recovery time from activity
    • Peripheral edema c9
      • Ankle swelling c10
    • Ascites causing any of the following: c11
      • Anorexia c12
      • Early satiety c13
      • Gastrointestinal discomfort c14
      • Increased abdominal girth c15
      • Scrotal swelling c16
    • Change in weight c17
      • Rapid weight gain suggests volume overload c18
      • Weight loss may occur in advanced disease c19
  • Other symptoms of heart failure may include:
    • Nonproductive cough during recumbency c20
    • Confusion, especially in elderly people c21
    • Palpitations c22
    • Syncope c23
  • Family history of cardiomyopathy may suggest underlying cause; ask patient about heart failure in family members going back 3 generations c24

Physical examination

  • Specific signs include:
    • Prominent jugular venous distention c25
    • Positive hepatojugular reflux c26
    • Laterally displaced apical impulse c27
    • Presence of S₃ gallop with systolic heart failure; may have S₄ gallop with diastolic heart failure c28c29
  • Less specific signs include the following (may be associated with many other conditions):
    • Tachypnea and tachycardia c30c31
    • Narrow pulse pressure c32
    • Cool extremities c33
    • Crackles/rales (may be absent in advanced chronic heart failure) c34
    • Wheezes c35
    • Peripheral edema, ascites, and hepatomegaly c36
    • Cachexia in advanced disease c37

Causes and Risk Factors

Causes

  • Most common causes of heart failure are hypertension and ischemic coronary artery disease r10r11
    • Risk of heart failure increases 8- to 10-fold after myocardial infarction r11c38
    • Patients with heart failure with preserved ejection fraction (usually older and female) more commonly have hypertension and less commonly have coronary artery disease c39c40
    • Patients who have heart failure with reduced ejection fraction are more likely to have coronary artery disease (approximately two-thirds of cases), with hypertension a contributing factor
  • Other causes of heart failure with reduced ejection fraction include valvular disease and cardiomyopathies
    • Valvular disease c41
      • Predominantly mitral and aortic valve disease (eg, mitral regurgitation, aortic stenosis, aortic regurgitation) r12c42c43c44c45c46
    • Cardiomyopathies c47
      • Idiopathic dilated cardiomyopathy c48
        • Large group of dissimilar myocardial disorders with common characteristics including ventricular dilation and depressed myocardial contractility in absence of abnormal loading conditions (eg, hypertension, valvular disease)
      • Familial cardiomyopathy c49
        • 2 closely related family members must meet criteria for idiopathic cardiomyopathy r13
        • A substantial percentage of what were once presumed idiopathic cardiomyopathies or peripartum cardiomyopathies are now recognized as having a genetic basis r13
      • Toxic cardiomyopathy c50
        • Heart failure may result from toxic effect on cardiac preload, cardiac afterload, or myocardial contractility r14
        • Heart failure may be reversible (eg, secondary to propofol), irreversible (eg, secondary to doxorubicin), or either (eg, secondary to cyclophosphamide) r14c51c52c53
        • Cardiotoxic cancer chemotherapies, particularly anthracyclines, can cause structural changes c54
          • Other therapies that are also cardiotoxic include trastuzumab (especially with concomitant anthracyclines), high-dose cyclophosphamide, taxoids, mitomycin C, fluorouracil, and the interferons
        • Long-term alcohol or cocaine use may cause dilated cardiomyopathy c55c56
        • Cardiomyopathy may be caused by other drugs, many with misuse potential (eg, ephedra, anabolic steroids, amphetamines, methylphenidate)
      • Inflammatory cardiomyopathy c57
        • Immune-mediated inflammatory myocarditis c58
          • Hypersensitivity to medication (eg, sulfonamides, penicillin, methyldopa, amphotericin B, streptomycin, phenytoin, isoniazid, tetanus toxoid, hydrochlorothiazide, dobutamine, chlorthalidone) c59c60c61c62c63c64c65c66c67
          • Autoimmune disorders (eg, systemic lupus erythematosus, scleroderma) c68c69c70
        • Infective inflammatory myocarditis c71
          • Most commonly of viral origin but also can be caused by other pathogens
          • Commonly occurs in patients with HIV infection
      • Metabolic/endocrine cardiomyopathy c72c73
        • Includes cardiomyopathy caused by obesity, diabetes, hyperthyroidism, acromegaly, growth hormone imbalances, hypophosphatemia, hypocalcemia, and pheochromocytoma
        • Also includes cardiomyopathy caused by nutritional deficiencies (eg, thiamine deficiency, selenium deficiency), which may be seen in patients with chronic alcohol use disorder and anorexia nervosa c74c75c76
      • Infiltration cardiomyopathy c77
        • Caused by malignancy, sarcoidosis, iron overload, or amyloidosis r9
      • Iron overload cardiomyopathy c78
        • Caused by increased iron deposition in heart. Associated with common genetic disorders (eg, primary hemochromatosis) and disorders that require lifetime transfusions (eg, thalassemia major)
      • Peripartum cardiomyopathy c79
        • Left ventricular dysfunction occurs typically in third trimester of pregnancy or in immediate postpartum period r15
        • Incidence varies from 0.2% to 3% of live births worldwide, depending on region r16
        • Prognosis is directly related to degree of recovery to near baseline left ventricular function; mortality rates are high r17
      • Tachycardia-related cardiomyopathy c80
        • Left ventricular myocardial dysfunction correlates with duration of tachycardia and magnitude of increased ventricular rate
        • Generally reversible with rate control
      • Stress cardiomyopathy (takotsubo cardiomyopathy) c81c82
        • Acute reversible left ventricular dysfunction in the absence of significant coronary artery disease; triggered by acute emotional or physical stress
        • Characteristic apical ballooning is present
        • Often affects postmenopausal patients

Risk factors and/or associations

Age
  • Incidence increases with age, from approximately 20 cases per 1000 person-years among those aged 65 to 69 years to more than 80 cases per 1000 person-years among those aged 85 years or older r18c83c84
  • Prevalence is 10% or more in patients aged 70 years or older r11
Sex
  • Higher incidence in males than females by approximately 10 cases per 1000 person-years r18c85c86
Genetics
  • Genetic loci with multiple genes and alleles with multiple mutations are involved in familial cardiomyopathies leading to heart failure r19c87
    • Underlying genetic causes include mutations in more than 30 genes encoding the sarcomere, components of the cytoskeleton, ion channels, and other elements r19
Ethnicity/race
  • Compared with White Americans, Black Americans have higher incidence of and higher 5-year mortality from heart failure r18c88c89c90c91
    • Approximately 3% of Black adults in the United States have heart failure r11
Other risk factors/associations
  • Atherosclerotic disease c92
  • Diabetes c93
    • Risk factor independent of age, hypertension, obesity, hypercholesterolemia, or coronary artery disease
  • Metabolic syndrome c94
  • Smoking r20c95
  • Alcohol use disorder r21c96
    • Significant negative correlation between ejection fraction and lifetime alcohol intake
    • Positive correlation between left ventricular mass and lifetime alcohol consumption
  • Exposure to drugs or toxins associated with cardiotoxicity, including cancer chemotherapies (eg, anthracyclines, trastuzumab), drugs of abuse (eg, cocaine, amphetamines, anabolic steroids), and others r14c97c98c99c100c101c102c103c104

Diagnostic Procedures

Primary diagnostic tools

  • Diagnosis is suspected based on thorough history and physical examination r11c105
  • Obtain chest radiograph in acutely dyspneic patients to identify pulmonary edema and assess heart size. In nonacute diagnostic settings, chest radiograph is also recommended to detect or exclude alternative causes of symptoms r2r11
  • Obtain 12-lead ECG as part of initial evaluation in all patients r2r8c106
  • For all patients presenting with heart failure, explore the specific cause using additional laboratory testing
    • All patients r2r11
      • Electrolyte levels, BUN and creatinine levels, and urinalysis (important for treatment decisions) c107c108c109
      • Liver function tests
      • Fasting lipid levels and fasting glucose level to assess cardiovascular risk factors
      • CBC, iron studies, and TSH level to exclude anemia and thyroid disease (as a cause or exacerbating factor of heart failure) c110c111
      • B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide c112
        • Obtain for all patients with symptoms suggesting acute heart failure
          • American College of Cardiology Foundation, American Heart Association, and Heart Failure Society of America guidelines recommend measuring B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide level to support clinical decision making, especially in the setting of clinical uncertainty (in both ambulatory and hospitalized patients) r2r11r22
        • When making initial diagnosis:
          • Negative predictive value exceeds positive predictive value. Negative predictive value is best used to rule out rather than rule in the diagnosis on initial evaluation
          • European Society of Cardiology guideline recommends obtaining these measurements to help establish initial working diagnosis and identify patients who require further cardiac investigation. If values are below cutoff point, echocardiography is not needed r9
        • On admission to hospitalization for heart failure and predischarge, measure B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide level to inform a trajectory and help establish a postdischarge prognosis r2
    • Patients with acute decompensated heart failure:
      • On admission to hospital, measure baseline levels of natriuretic peptide biomarkers and/or cardiac troponin to help establish a prognosis r2
  • Obtain transthoracic 2-dimensional echocardiogram with Doppler flow studies for all patients with suspected heart failure r2r8r9
  • Consider cardiac MRI for better assessment of myocardial structure and function, particularly if echocardiographic images are inadequate r9
  • Noninvasive (eg, myocardial perfusion/ischemia imaging) and/or invasive (eg, coronary angiography) cardiac evaluation is not routine, but it is recommended for new-onset heart failure in the setting of known or suspected coronary artery disease or ischemic symptoms r9r11r23
  • Hemodynamic monitoring via pulmonary artery catheter (right-sided heart catheterization) is not routine, but it may be indicated in critically ill patients and in some noncritically ill patients to obtain additional information r2
  • Consider genetic testing for first-degree relatives of patients with genetic or inherited cardiomyopathies. Referral for genetic counseling is reasonable for selected patients with nonischemic cardiomyopathy to identify conditions that could guide treatment for patient and family members r2

Laboratory

  • Routine laboratory tests r2r11
    • Obtain on presentation to assist in determining causes of heart failure, identifying risk factors, and assessing baseline kidney function
      • Comprehensive metabolic panel c113
        • Electrolyte, magnesium, calcium, BUN, and creatinine levels c114c115c116c117c118
        • Elevated liver enzyme levels may be due to hepatic congestion or dysfunction c119
      • Fasting blood glucose level c120
        • Diabetes is a common comorbidity and risk factor for heart failure
      • Fasting lipid profile c121
        • To assess risk for coronary artery disease and metabolic syndrome
      • TSH level c122
        • Thyroid disease may mimic, aggravate, or cause heart failure
      • CBC c123
        • Anemia may cause or exacerbate heart failure
      • Urinalysis c124
  • Cardiac biomarker tests r24
    • Natriuretic peptide levels c125c126
      • Hormones secreted by cardiomyocytes with myocardial stretch
      • Elevated B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide levels support the diagnosis of heart failure in cases of diagnostic uncertainty (eg, if echocardiography is nondiagnostic) or if echocardiography is not available r22
        • B-type natriuretic peptide level of 100 pg/mL or more for acute onset or 35 pg/mL or more for nonacute onset suggests heart failure
        • N-terminal pro–B-type natriuretic peptide level of 300 pg/mL or more for acute onset or 125 pg/mL or more for nonacute onset suggests heart failure
      • High degree of sensitivity but low degree of specificity for heart failure; natriuretic peptide levels may be elevated owing to other cardiac and noncardiac causes r25
      • Note that obese patients may have falsely low natriuretic peptide levels
    • Cardiac troponin T or I levels c127c128c129c130
      • Elevated levels:
        • May reflect acute coronary syndrome
        • Are often associated with severe heart failure without an obvious acute ischemic process
      • Decreasing cardiac troponin levels over time suggest improving heart failure and are associated with better prognosis

Imaging

  • Chest radiography r11c131
    • Indicated for suspected new-onset heart failure and acute decompensated heart failure r2
    • Posteroanterior and lateral chest views are recommended; supine chest radiography has limited value
    • Has low sensitivity and specificity for heart failure; useful in identifying an alternative pulmonary process causing patient's symptoms and signs
    • Cardiomegaly and/or pulmonary venous congestion are suggestive of heart failure
      • Characteristic findings are cardiac chamber enlargement, increased pulmonary venous pressure, interstitial or alveolar edema, and valvular or pericardial calcification
      • Increased pulmonary venous pressure may be seen as:
        • Redistribution of blood flow from base of lung to apex
        • Linear densities reflecting interstitial edema
        • Bilateral perihilar haziness in a butterfly pattern

Functional testing

  • ECG r10c132
    • Perform 12-lead ECG initially on all patients presenting with symptoms of heart failure r2
    • Very few patients who have heart failure with systolic dysfunction will have a completely normal ECG result. If results are normal, consider other causes of symptoms. Routine ECG is performed primarily to identify those patients and to detect other abnormalities that may need investigation or treatment
    • No particular ECG feature is specific to heart failure
      • Left ventricular hypertrophy may be evident on ECG
      • Q waves indicate myocardium loss due to previous infarction
      • Atrial and ventricular arrhythmias are common
  • 2-dimensional echocardiography with Doppler flow imaging r26r27c133
    • 2-dimensional echocardiography displays cross-sectional view of beating heart, including chambers of heart, valves, and major blood vessels; Doppler flow imaging evaluates blood flow
      • Provides essential information on chamber volumes, wall thickness, wall motion abnormalities, and valve structure
      • Left ventricular ejection fraction and cardiac output can be estimated
      • Diastolic and systolic function of heart can be assessed
      • Pulmonary capillary wedge pressure can be estimated
      • Transthoracic echocardiography is preferred method
        • Transesophageal echocardiography is an alternative if transthoracic route is nondiagnostic owing to inadequate transthoracic window, which may occur in patients who are obese, have chronic lung disease, and require mechanical ventilation
    • Interpretation r10
      • Heart failure with reduced ejection fraction (left ventricular systolic dysfunction) is suggested by:
        • Ejection fraction less than 50%
        • Hypokinesis, akinesis, or dyskinesis
        • Increased left ventricular diameter and volume
        • Decreased outflow velocity
      • Heart failure with preserved ejection fraction (left ventricular diastolic dysfunction) is suggested by: r28
        • Normal or near normal ejection fraction (50% or higher)
        • Abnormal mitral inflow
        • Increased atrial volume
        • Increased left ventricular mass
  • Cardiac MRI r2r10c134
    • Alternative to echocardiography for assessing left ventricular volume and ejection fraction; may be used if echocardiography is not diagnostic
    • Provides high anatomic resolution of all aspects of the heart and surrounding structures and can yield additional information on myocardial perfusion, viability, and fibrosis
    • Can identify inflammatory and infiltrative causes and provide prognostic information
    • Less accurate than echocardiography with high heart rates
    • Contraindications include metal implants or severe kidney disease, which preclude use of contrast solution

Procedures

Cardiac catheterization with coronary angiography r2r29c135c136c137c138
General explanation
  • Catheters are placed percutaneously in peripheral blood vessels and advanced into central circulation
  • Measures intravascular pressure, oxygen saturation in heart and great vessels, and cardiac contractility and function
  • Angiography delineates anatomic structures and coronary artery patency
  • Usually performed under light sedation
Indication
  • Patients who have heart failure with anginal symptoms r2
  • May be useful for patients with new-onset heart failure but no anginal symptoms r2
Contraindications
  • Severe comorbidities that would preclude revascularization (eg, renal, hepatic, or pulmonary failure or malignancy)
  • Contrast medium allergy
  • Severe anemia
  • Uncontrolled coagulopathy
  • Hemodynamic instability
  • Acute stroke
  • Active infection, sepsis
  • Pregnancy
  • Uncooperative patient
Interpretation of results
  • Can identify ischemic causes for systolic or diastolic dysfunction
Complications
  • Uncommon
    • Stroke
    • Myocardial infarction
    • Bleeding/hematoma
    • Thromboembolism
    • Arrhythmia
    • Allergic reaction to contrast medium
    • Blood vessel perforation
    • Death

Other diagnostic tools

  • Genetic testing
    • Contributes to risk stratification and has implications for treatment, currently most often for decisions regarding defibrillators for primary prevention of sudden death and regarding exercise limitation for hypertrophic cardiomyopathy r2
    • Offer genetic screening and counseling for first-degree relatives of patients with genetic or inherited cardiomyopathies and for select patients with nonischemic cardiomyopathies r2
    • Some genes implicated in inherited dilated, restrictive, and hypertrophic cardiomyopathies for which genetic testing is available include: r2
      • TTN, encoding the large structural protein titin; truncation variants are implicated in dilated cardiomyopathy
      • LMNA, encoding lamin A/C, associated with conduction block and atrial arrhythmias as well as ventricular arrhythmias
      • Mutations in various desmosomal protein variants (eg, DSP) implicated in arrhythmogenic right ventricular cardiomyopathy
      • Mutations in FLNC (encoding filamin-C) have been associated with skeletal myopathies and with isolated cardiomyopathy with ventricular arrhythmias

Differential Diagnosis

Most common

  • Conditions that cause dyspnea r30
    • Chronic obstructive pulmonary disease r31c139d1
      • Group of chronic and progressive pulmonary diseases (emphysema and chronic bronchitis) that limit airflow; occur nearly exclusively in smokers
      • Similar feature: chronic dyspnea
      • Differing features: great variation of dyspnea from day to day, productive cough, rhonchi and/or expiratory wheezing on auscultation, hyperinflation (barrel chest), and hyperresonant chest sounds
      • Diagnosis: spirometry shows decreased pulmonary function; chest radiography may show diaphragm flattening, increased retrosternal air space, or bronchovascular markings
      • Chronic obstructive pulmonary disease may coexist with heart failure
    • Asthma c140d2
      • Chronic inflammatory condition of airways that produces edema and bronchoconstriction; episodes are often caused by triggers (eg, allergens, exercise, infection)
      • Similar features: wheezing and dyspnea
      • Differing features: typically earlier age of onset; episodic and reversible symptoms of airflow obstruction, often after triggers; and chest tightness
      • Diagnosis: spirometry with postbronchodilator response; chest radiograph may show hyperinflation
    • Pulmonary embolism r32c141d3
      • Pulmonary artery or branch artery is suddenly occluded, most often because of a dislodged thrombus
      • Similar features: dyspnea, tachypnea, and tachycardia
      • Differing features: abrupt onset of chest pain, which may be pleuritic; hypoxia; and sometimes hemoptysis
      • Diagnosis: CT angiography detects pulmonary emboli; D-dimer levels are elevated
    • Myocardial infarction r33c142d4
      • Myocardial necrosis resulting from occlusion of coronary artery
      • Similar features: dyspnea and fatigue
      • Differing features: retrosternal chest pain or pressure (radiating to neck, jaw, shoulder, or arm) is typical; atypical presentation without chest pain may occur in female patients, older patients, and those with diabetes
      • Diagnosis: ECG shows ST elevation, ST depression, or T-wave inversion; cardiac troponin levels are elevated
    • Pneumonia c143
      • Acute inflammation of lung tissue caused by infection
      • Similar features: tachypnea, tachycardia, rales, and wheezing
      • Differing features: productive cough, fever and rigors, rhonchi, and hypoxia
      • Diagnosis: chest radiograph shows lobar or lobular consolidation; viral or atypical bacterial pneumonias often appear as interstitial infiltrates
    • Acute respiratory distress syndrome c144d5
      • Severe and often fatal acute respiratory failure; characterized by diffuse inflammatory lung injury rapidly progressing to increased pulmonary vascular permeability, increased lung weight, and hypoxemia
      • Similar features: dyspnea, cough, tachypnea, tachycardia, and pulmonary edema
        • Cardiogenic and noncardiogenic pulmonary edema can coexist
      • Differing features: cardiac biomarker levels are less likely to be elevated; echocardiographic findings are more likely to be within reference range
      • Diagnosis: history, physical examination, arterial blood gas levels, and chest radiography or CT
        • Criteria include:
          • Timing of symptoms (within 1 week of a known clinical insult such as pneumonia, sepsis, or trauma)
          • Hypoxemia (as shown by blood gas levels)
          • Bilateral opacities not otherwise explained and not cardiogenic in nature
          • Respiratory failure or pulmonary edema not fully explained by heart failure or fluid overload
  • Conditions that cause edema r30
    • Cirrhosis c145d6
      • Irreversible liver disease caused by long-term excessive alcohol intake, viral hepatitis, or other reason
      • Similar features: peripheral edema and ascites; dyspnea may be present because of ascites
      • Differing features: stigmata of liver disease are usually present; liver function test results are outside reference range
      • Diagnosis: abdominal sonography or other abdominal imaging shows liver nodularity and features of portal hypertension; definitive diagnosis is by liver biopsy
    • Nephrotic syndrome c146
      • Renal disease affecting kidney basement membrane, resulting in heavy proteinuria and hypoalbuminuria
      • Similar features: peripheral edema (including edema of face/eyes) and ascites
      • Differing features: dyspnea may occur but is usually exertional only and associated with pleural effusion and very low protein levels
      • Diagnosis: high random urine protein to creatinine ratio is suggestive; protein excretion of 3.5 g or more per 24 hours confirms. Renal biopsy confirms renal pathology

Treatment

Goals

  • For acute decompensated heart failure or de novo heart failure: r2r11
    • Identify reversible precipitating factors
    • Relieve symptoms
    • Reduce hospitalizations
    • Restore normal oxygenation

Disposition

Admission criteria

Patients with de novo acute heart failure or acute decompensated heart failure: admit for appropriate laboratory tests, imaging, and start of treatment

Specific heart failure admission indications include: r11

  • Evidence or suspicion of acute coronary syndromes
  • Respiratory distress and/or pulmonary edema
  • Hemodynamically significant arrhythmias
  • Syncope or symptomatic hypotension
  • Worsening renal function
  • Altered mentation
Criteria for ICU admission r34
  • Respiratory failure needing advanced respiratory support including endotracheal intubation and noninvasive positive pressure ventilation
  • Hemodynamic instability needing pharmacologic or mechanical support

Recommendations for specialist referral

  • Cardiologist for diagnostic evaluation of heart failure causes and optimization of medical management
  • Cardiothoracic surgeon for coronary revascularization surgery and/or ventricular assist device
  • Electrophysiologist for implantation of cardiac defibrillator and/or cardiac resynchronization therapy
  • Transplant specialist for heart transplant and management of immunosuppressant therapy
  • Nephrologist for associated kidney disease and treatment with ultrafiltration
  • Geriatrician for critical decisions on older patients with multiple comorbidities
  • Palliative care specialist for end-of-life decisions
  • Genetic counselor to identify inherited or genetically based cardiomyopathies

Treatment Options

Management of acute heart failure (either decompensated or de novo)

  • Obtain IV access and begin supplemental oxygen via noninvasive positive pressure ventilation (eg, CPAP, high-flow nasal canula, BPAP) r9r35
  • Identify and manage immediate life-threatening conditions, if present (eg, unstable arrhythmia, acute coronary syndrome) r2
    • May require advanced cardiac life support (eg, endotracheal intubation, cardioversion, cardiac pacing) depending on organ system dysfunction
    • May require cardiac catheterization and percutaneous coronary intervention
  • Identify and manage other potential precipitating causes of decompensation, including: r2
    • Uncorrected high blood pressure r36
    • Atrial fibrillation and other arrhythmias
    • Acute or worsening valvular disease
    • Medication nonadherence
    • Recent addition of negative inotropic drugs
    • Dietary sodium indiscretion
    • Acute kidney injury or worsening chronic kidney disease
    • Anemia
    • Acute infection
    • Thyroid disorders
    • Excessive alcohol intake or illicit drugs
  • Alleviate symptoms
    • Provide loop diuretics and monitor urine output for all patients with evidence of fluid overload r2
      • If patient is already using outpatient loop diuretic therapy, give an initial IV dose that equals or exceeds the long-term oral daily dose
      • Short-term infusion of inotropic agents, in addition to loop diuretic, may improve diuresis in patients with hypotension and evidence of hypoperfusion (cardiogenic shock)
      • May consider a vasopressor for patients who have persistent evidence of cardiogenic shock despite inotrope use or the use of mechanical circulatory support or intra-aortic balloon pump temporarily while treatment is being administered r9
      • Consider ultrafiltration if diuretic strategies are unsuccessful
    • In patients hospitalized with volume overload and severe hyponatremia who do not respond to free water restriction, consider vasopressin antagonists r2
    • If patient is not hypotensive and diuresis is inadequate, consider adjuvant therapy with a vasodilator (eg, IV nitroglycerin, nitroprusside) to relieve dyspnea r2
      • Use vasodilators with caution in patients with preserved ejection fraction who are typically more volume sensitive r2
    • Invasive hemodynamic monitoring with pulmonary artery catheter is not routine but may help guide therapeutic decision-making if persistent symptoms or volume status is uncertain r2
    • Begin β-blocker therapy at low dose after optimization of volume status and discontinuation of IV agents r2

Management of stable chronic heart failure depends on disease stage r2

  • Stage A (at high risk for heart failure without structural heart disease or symptoms, based on risk factors of hypertension, dyslipidemia, diabetes, and obesity)
    • Manage comorbid hypertension, lipid disorders, diabetes, obesity, and atherosclerotic cardiovascular disease according to relevant guidelines r2
    • Counsel and assist patient with smoking cessation, alcohol restriction or discontinuation, and cardiotoxic agent avoidance r2
    • Use sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes and established cardiovascular disease or in those at high risk for cardiovascular disease r2
  • Stage B (structural heart disease, such as ventricular remodeling, left ventricular hypertrophy, or ventricular dilation, without signs and symptoms of heart failure) r2
    • All recommendations for patients with stage A heart failure also apply to those with stage B heart failure; in addition, the following apply: r2
      • Pharmacologic therapy
        • ACE inhibitor r2
          • Prevents symptoms and reduces mortality in New York Heart Association class I heart failure by inhibiting the renin-angiotensin-aldosterone system; decreases cardiac remodeling
          • Indicated for all patients with reduced ejection fraction
        • Angiotensin receptor blocker
          • Indicated in patients with recent myocardial infarction and left ventricular ejection fraction 40% or less if intolerant of ACE inhibitor r2
        • β-Blocker r2
          • Prevents symptoms and reduces mortality by blocking catecholamines and slowing heart rate, which allows for improved ventricular filling; improves ejection fraction
          • Indicated for all patients with reduced ejection fraction (in conjunction with ACE inhibitor), unless specific contraindications exist
          • Consider for patients with history of myocardial infarction even if ejection fraction is not reduced r5
        • Statin r2r5
          • Indicated for all patients who have history of myocardial infarction or acute coronary syndrome; otherwise, not recommended strictly for heart failure
    • Device therapy
      • Implantable cardioverter-defibrillator for primary prevention of sudden death is reasonable in selected patients with history of myocardial infarction, asymptomatic ischemic cardiomyopathy, and expectation of meaningful survival for greater than 1 year r2
        • Applies only to patients with left ventricular ejection fraction 30% or less in stage B pre–heart failure
  • Stage C (structural heart disease with prior or current symptoms of heart failure)
    • All recommendations for patients with stage A also apply to those with stage C heart failure; in addition, the following apply: r2
      • Reduced ejection fraction
        • Pharmacologic therapy
          • Inhibition of renin-angiotensin-aldosterone system with ACE inhibitor, angiotensin receptor blocker, or angiotensin receptor–neprilysin inhibitor—in conjunction with evidence-based β-blockers and aldosterone antagonists in selected patients—is recommended for patients with chronic heart failure with reduced ejection fraction r2
            • Use ACE inhibitor for patients with current or prior symptoms of chronic heart failure with reduced ejection fraction; confers morbidity and mortality benefit r2
              • No superior morbidity or mortality benefit is associated with any specific ACE inhibitor r2
              • Do not give ACE inhibitor to patients with history of angioedema r2
            • Use angiotensin receptor blocker for patients with prior or current symptoms of chronic heart failure with reduced ejection fraction who are intolerant to ACE inhibitors owing to cough or angioedema. This medication also confers morbidity and mortality benefit r2
            • In patients with chronic symptomatic heart failure with reduced ejection fraction (New York Heart Association class II or III) who tolerate an ACE inhibitor or angiotensin receptor blocker, it is recommended to replace these medications with an angiotensin receptor–neprilysin inhibitor to further reduce morbidity and mortality r2
              • Do not give angiotensin receptor–neprilysin inhibitor concomitantly with ACE inhibitors or within 36 hours of last dose of ACE inhibitor (unacceptable risk of angioedema) r2
              • Do not give angiotensin receptor–neprilysin inhibitor to patients with history of angioedema r2
          • Use β-blocker in all patients (eg, 1 of the 3 β-blockers proven to reduce mortality: bisoprolol, carvedilol, or sustained-release metoprolol) r2
          • Use sodium-glucose cotransporter-2 inhibitors in all patients with symptomatic chronic heart failure with reduced ejection fraction, including those without diabetes, to reduce hospitalization for heart failure and cardiovascular mortality r2
            • Use dapagliflozin or empagliflozin, which have been proven to reduce risk of heart failure hospitalization and death r37r38
          • Use aldosterone receptor antagonists (ie, mineralocorticoid receptor antagonists) in selected patients, including: r2
            • Patients with New York Heart Association class II to IV heart failure with left ventricular ejection fraction of 35% or less, to reduce morbidity and mortality r2
              • Patients with class II heart failure should have history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels to be considered for aldosterone receptor antagonists r2
            • To use these, estimated GFR should be more than 30 mL/minute/1.73 m² and potassium level should be less than 5 mEq/L r2
          • Ivabradine can help reduce hospitalization for selected patients r2
            • Symptomatic (New York Heart Association class II or III) stable chronic heart failure with reduced ejection fraction in which left ventricular ejection fraction is 35% or less, andr2
            • Already receiving maximally tolerated β-blocker, ACE inhibitor, angiotensin receptor blocker, or angiotensin receptor–neprilysin inhibitor and mineralocorticoid receptor antagonist, andr2
            • In sinus rhythm with heart rate of 70 or more beats per minute at rest r2
            • Reduces heart rate by selective inhibition of alternative sinoatrial node current
          • Use diuretics in all patients with evidence of fluid retention, unless contraindicated, to improve symptoms r2
            • Loop diuretics are preferred unless patient is hypertensive and has only mild fluid retention, in which case thiazide diuretics may be reasonable
            • No differences between specific loop diuretics in their effects on symptoms or survival
          • Consider hydralazine plus isosorbide dinitrate for persistently symptomatic Black patients (New York Heart Association class III or IV) despite concomitant use of ACE inhibitors, β-blockers, and aldosterone receptor antagonists r2
          • Can consider digoxin (unless contraindicated) for additional symptom relief; use caution in patients taking other drugs that can depress sinus or atrioventricular nodal function or affect digoxin levels (eg, amiodarone, β-blocker) r2
          • Can consider vericiguat, an oral soluble guanylate cyclase stimulator, in high-risk patients with heart failure with reduced ejection fraction and recent worsening of heart failure and who are already on goal-directed medical therapy to reduce heart failure hospitalization and cardiovascular death
          • Manage atrial fibrillation, if present, according to current guidelines, including anticoagulation r2d7
        • Device therapy
          • Implantable cardioverter-defibrillator therapy is indicated for primary prevention of sudden cardiac death in selected patients with left ventricular ejection fraction 35% or less who are expected to live longer than 1 year r2r9
          • Cardiac resynchronization therapy (biventricular pacing) is indicated for selected patients who have the following: r2r9
            • Left ventricular ejection fraction 35% or less
            • Sinus rhythm
            • Left bundle branch block with QRS duration of 150 milliseconds or longer
            • New York Heart Association class II, class III, or ambulatory class IV symptoms on optimal medical therapy
      • Mildly reduced ejection fraction
        • Pharmacologic therapy
          • Use diuretics in all patients with congestion to alleviate signs and symptoms as needed r2
          • Consider adding a drug from any of the following classes to reduce risk of heart failure hospitalization and death: r2
            • ACE inhibitor or angiotensin receptor blockers
            • β-Blocker
            • Mineralocorticoid receptor antagonist
            • Angiotensin receptor–neprilysin inhibitor
            • Sodium-glucose cotransporter-2 inhibitor (eg, empagliflozin, which has specifically been proven to reduce risk of heart failure, hospitalization, and death when ejection fraction is higher than 40%) r3
      • Preserved ejection fraction
        • Pharmacologic therapy
          • Recommended therapies for heart failure with preserved ejection fraction are symptom-directed or used for management of comorbidities r2
            • Use diuretics for symptom relief r2
            • Systolic and diastolic blood pressure control is particularly important; β-blockers, ACE inhibitors, and angiotensin receptor blockers are reasonable choices r2
            • Manage atrial fibrillation, if present, according to current guidelines, including anticoagulation r2
            • Can consider angiotensin receptor blockers to decrease hospitalizations r2
            • Consider aldosterone receptor antagonists to decrease hospitalizations in patients who meet all of the following criteria: r2
              • Ejection fraction 45% or higher
              • Elevated B-type natriuretic peptide levels or heart failure admission within previous 1 year
              • Estimated GFR higher than 30 mL/minute/1.73 m²
              • Creatinine level lower than 2.5 mg/dL
              • Potassium level lower than 5 mEq/L
            • Consider sodium-glucose cotransporter-2 inhibitors (eg, empagliflozin, which has specifically been proven to reduce risk of heart failure hospitalization and death when ejection fraction is higher than 40%) r3r9
            • Consider angiotensin receptor–neprilysin inhibitor to decrease hospitalizations r2
          • Refer for coronary revascularization patients with angina or demonstrable cardiac ischemia despite medical management of heart failure r2
  • Stage D (symptoms refractory to optimal goal-directed medical therapy; also known as advanced heart failure or end-stage heart failure)
    • Carefully reconsider diagnosis to ensure that there are no remedial or alternative causes for symptoms before labeling the condition refractory heart failurer2
    • Treatment of advanced heart failure is often palliative; reevaluate quality of indicators to avoid prolongation of futile efforts
    • Pharmacologic therapy r2
      • Use IV inotropic support with dopamine (also promotes renal blood flow at low doses), dobutamine, or milrinone to maintain systemic perfusion and preserve end-organ performance r2
        • As short-term therapy (until resolution of acute precipitating event)
        • As bridge therapy (for patients waiting for mechanical circulatory support or heart transplant)
        • As long-term palliative/destination therapy (for patients ineligible for mechanical circulatory support or heart transplant)
    • Mechanical circulatory support r2
      • Temporary ventricular assist devices (percutaneous and extracorporeal) are indicated as bridge therapy, allowing time for either improvement or clinical decision making for carefully selected patients with reduced ejection fraction and marked hemodynamic compromise
      • Durable mechanical circulatory support can prolong survival for carefully selected patients with severe heart failure with reduced ejection fraction (destination therapy)
    • Heart transplant r2
      • Indicated for carefully selected patients with stage D heart failure despite optimal medical therapy, device therapy, and surgical management
      • Donated hearts are scarce; bridge therapy must maintain patient during wait for transplant

Drug therapy c147c148

  • ACE inhibitors c149
    • Captopril c150
      • Captopril Oral tablet; Adults: 6.25 mg PO 3 times daily, initially. Increase the dose as tolerated. Max: 50 mg PO 3 times daily.
    • Enalapril c151
      • Enalapril Maleate Oral tablet; Adults: 2.5 mg PO twice daily, initially. Increase the dose as tolerated. Max: 10 to 20 mg PO twice daily.
    • Lisinopril c152
      • Lisinopril Oral tablet; Adults: 2.5 to 5 mg PO once daily, initially. Increase the dose as tolerated. Max: 20 to 40 mg/day.
  • Angiotensin receptor blockers c153
    • Candesartan c154
      • Candesartan Cilexetil Oral tablet; Adults: 4 to 8 mg PO once daily, initially. Double the dose every 2 weeks as tolerated. Max: 32 mg/day.
    • Losartan c155
      • Losartan Potassium Oral tablet; Adults: 25 to 50 mg PO once daily, initially. Increase the dose as tolerated. Max: 50 to 150 mg/day.
    • Valsartan c156c157
      • Valsartan Oral tablet; Adults: 20 to 40 mg PO twice daily, initially. Increase the dose as tolerated. Max: 160 mg PO twice daily.
  • Angiotensin receptor–neprilysin inhibitor
    • Do not give angiotensin receptor–neprilysin inhibitor concomitantly with ACE inhibitors or within 36 hours of the last dose of ACE inhibitor (unacceptable risk of angioedema) r2
    • Sacubitril-valsartan c158
      • Sacubitril, Valsartan Oral tablet; Adults: 49/51 mg sacubitril/valsartan PO twice daily, initially. Double the dose after 2 to 4 weeks as tolerated. Max: 97/103 mg sacubitril/valsartan PO twice daily.
  • β-Blockers c159c160
    • Bisoprolol c161c162
      • Bisoprolol Fumarate Oral tablet; Adults: 1.25 mg PO once daily for 48 hours, then 2.5 mg PO once daily for first month, then 5 mg PO once daily. Max: 10 mg PO once daily.
    • Carvedilol c163c164
      • Carvedilol Oral tablet; Adults weighing more than 85 kg: 3.125 mg PO twice daily for 2 weeks, initially. Increase the dose after 2 weeks as tolerated to 6.25, 12.5, 25, and then 50 mg PO twice daily.
      • Carvedilol Oral tablet; Adults weighing 85 kg or less: 3.125 mg PO twice daily for 2 weeks, initially. Increase the dose after 2 weeks as tolerated to 6.25, 12.5, and then 25 mg PO twice daily.
    • Metoprolol succinate c165c166
      • Metoprolol Succinate Oral tablet, extended-release; Adults: 12.5 or 25 mg PO once daily for 2 weeks, initially, in persons with NYHA class III or IV heart failure or NYHA class II heart failure, respectively. Double the dose every 2 weeks as tolerated, up to the target dosage of 200 mg PO once daily.
  • Aldosterone receptor antagonists c167
    • Eplerenone c168
      • Eplerenone Oral tablet; Adults: 25 mg PO once daily, initially. Increase the dose within 4 weeks as tolerated to 50 mg PO once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Spironolactone c169
      • Spironolactone Oral tablet; Adults: 12.5 to 25 mg PO once daily, initially. May increase the dose to 50 mg PO once daily, if tolerated and clinically indicated.
  • Loop diuretics c170
    • Bumetanide c171c172
      • Bumetanide Oral tablet; Adults: 0.5 to 1 mg PO once daily, initially. May repeat a second or third dose every 4 to 5 hours as needed. Usual dose: 0.5 to 2 mg/day. Max: 10 mg/day.
      • Bumetanide Solution for injection; Adults: 0.5 to 1 mg IV/IM once, initially. May repeat a second or third dose every 2 to 3 hours as needed. Max: 10 mg/day.
    • Furosemide c173
      • Furosemide Oral tablet; Adults: 20 to 80 mg PO once, initially. May repeat the dose or increase by 20 to 40 mg/dose every 6 to 8 hours as needed. Usual dose: 40 to 240 mg/day in 1 to 2 divided doses. Max: 600 mg/day.
      • Furosemide Solution for injection; Adults: 20 to 40 mg IV/IM once, initially. May repeat the dose or increase by 20 mg/dose every 2 hours as needed.
    • Torsemide
      • Torsemide Oral tablet; Adults: 10 to 20 mg PO once daily, initially. Double the dose as needed. Max: 200 mg/day.
  • Thiazide diuretics c174
    • Hydrochlorothiazide c175
      • Hydrochlorothiazide Oral tablet; Adults: 12.5 to 100 mg/day PO in single or divided doses.
    • Indapamide c176c177
      • Indapamide Oral tablet; Adults: 2.5 mg PO once daily, initially. May increase the dose to 5 mg PO once daily after 1 week if needed.
    • Metolazone c178
      • Metolazone Oral tablet; Adults: 5 to 20 mg PO once daily.
  • Vasodilators c179
    • Hydralazine c180
      • Hydralazine Hydrochloride Oral tablet; Adults: 25 to 50 mg PO 3 to 4 times daily, initially. May increase the dose by 25 mg/dose weekly as tolerated. Max: 100 mg PO 3 times daily.
    • Isosorbide dinitrate c181
      • Isosorbide Dinitrate Oral tablet; Adults: 20 to 30 mg PO 3 to 4 times daily, initially. May increase the dose weekly as tolerated. Max: 40 mg PO 3 times daily.
    • Nitroglycerin c182
      • Nitroglycerin Solution for injection; Adults: 5 mcg/minute continuous IV infusion, initially. Titrate by 5 mcg/minute every 3 to 5 minutes to clinical response, or a dose of 20 mcg/minute. May further titrate by 10 mcg/minute, and if the desired effect is still not achieved, by 20 mcg/minute. Max titration: 20 mcg/minute every 3 to 5 minutes. Usual dose range: 5 to 100 mcg/minute. Max: 200 mcg/minute.
    • Nitroprusside c183
      • Sodium Nitroprusside Solution for injection; Adults: 0.3 to 0.5 mcg/kg/minute continuous IV infusion, initially. Titrate by 0.5 mcg/kg/minute every 5 minutes until desired effect or blood pressure cannot be further reduced without compromising organ perfusion. Max: 10 mcg/kg/minute for 10 minutes.
  • Hyperpolarization-activated cyclic nucleotide–gated channel blocker c184c185
    • Ivabradine c186
      • Ivabradine Oral tablet; Adults: 5 mg PO twice daily, initially. Adjust the dose after 2 weeks and thereafter as needed based on heart rate and tolerability. Max: 7.5 mg PO twice daily.
  • Digitalis glycoside c187
    • Digoxin c188
      • Digoxin Oral tablet; Adults: 3.4 to 5.1 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 6 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. Round dose to the nearest whole/half tablet.
      • Digoxin Oral tablet; Geriatric Adults: 3.4 to 5.1 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 6 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. Round dose to the nearest whole/half tablet. Usual Max: 0.125 mcg/day.
  • Guanylate cyclase stimulator
    • Vericiguat
      • Vericiguat Oral tablet; Adults: 2.5 mg PO once daily, initially. Double the dose approximately every 2 weeks as tolerated to the target dose of 10 mg PO once daily.
  • Inotropic agents c189
    • Dopamine c190
      • Dopamine Hydrochloride Solution for injection; Adults: 2 to 5 mcg/kg/minute continuous IV infusion, initially. Titrate by 5 to 10 mcg/kg/minute until goal hemodynamic and/or renal response is attained. Usual dose: 5 to 15 mcg/kg/minute. Max: 50 mcg/kg/minute
    • Dobutamine c191
      • Dobutamine Hydrochloride Solution for injection; Adults: 0.5 to 1 mcg/kg/minute continuous IV infusion. Titrate every few minutes to clinical response. Usual dose: 2 to 20 mcg/kg/minute. Max: 40 mcg/kg/minute.
    • Milrinone c192
      • Milrinone Lactate Solution for injection; Adults: 50 mcg/kg IV loading dose, then 0.125 to 0.75 mcg/kg/minute continuous IV infusion.

Nondrug and supportive care

Dietary recommendations

  • At least 1 session of nutritional evaluation and counseling is recommended for patients with heart failure r39
    • Ensure adequate intake of macro- and micronutrients
    • Recommend DASH (Dietary Approaches to Stop Hypertension) or Mediterranean style diet of patients of normal weight r40
    • Recommend weight loss of 5% to 10% for patients with BMI 35 kg/m² or higher
    • Aim for protein intake of at least 1.1 g/kg/day for patients with malnutrition or cachexia (develops in 10%-20% of patients with heart failure)
    • Consider some degree of sodium restriction (eg, less than 3 g/day) for patients with stage C and D heart failure while noting that evidence is lacking for this recommendation
      • American College of Cardiology Foundation/American Heart Association guideline recommends restricting sodium to 1500 mg/day or less for patients with stage A and B heart failure
  • American Heart Association recommends 1 to 2 meals of seafood per week be included to reduce risk of congestive heart failure, coronary heart disease, ischemic stroke, and sudden cardiac death r41
    • Marine omega-3 supplementation of 1 g/day is recommended for primary prevention for individuals who do not consume at least 1.5 fish or seafood meals per week r42
    • High-dose marine omega-3 supplements are recommended for patients with congestive heart disease who are taking statins and who have elevated triglycerides r42

Exercise

  • For adults with congestive heart failure and heart failure with reduced ejection fraction, recommend exercise interventions (eg, cardiac rehabilitation), stressing full adherence to recommended regimens r40
  • In adults with chronic heart failure with reduced ejection fraction, evidence suggests that exercise training (eg, cardiac rehabilitation): r43
    • Reduces all-cause hospitalizations
    • Reduces hospitalizations due to heart failure in the short term
    • Improves quality of life
    • Reduces long-term mortality

General recommendations

  • Order careful intake and output measurements in acute care setting c193
  • Order daily weight monitoring on inpatient and outpatient basis; have patient or caregiver notify physician for overnight gain of 0.9 kg or more or 1-week gain of 2.3 kg or more c194
  • Advise and assist with moderation or elimination of alcohol intake owing to its negative effect on ventricular systolic function c195
  • Advise and assist with smoking cessation c196d8
    • Smoking increases myocardial oxygen consumption (via increased heart rate and blood pressure) and decreases myocardial oxygen supply
  • Vaccinations
    • Pneumococcal vaccine and annual influenza vaccine are recommended unless contraindicated c197c198
    • COVID-19 vaccination is strongly recommended for all transplant candidates or transplant recipients. In all other patients, administer COVID-19 vaccination in accordance with age-specific CDC recommendations r44r45

Provide patients and caregivers with comprehensive education about heart failure, medication regimens, and lifestyle modifications r2c199c200

Procedures
Implantable cardioverter-defibrillator therapy r2c201
General explanation
  • Cardioverter-defibrillator is implanted to perform cardioversion, defibrillation, and pacing of heart and thereby reduce sudden death from cardiac arrhythmias
  • Decision to implant cardioverter-defibrillator is made by cardiologist or electrophysiologist
Indication
  • Primary prevention of sudden death in selected patients who have heart failure with reduced ejection fraction (European guidelines differ slightly) r5
    • Left ventricular ejection fraction of 35% or less caused by prior myocardial infarction with New York Heart Association class II or III symptoms on optimal medication therapy
    • Left ventricular ejection fraction of 30% or less caused by prior myocardial infarction with New York Heart Association class I symptoms on optimal medication therapy
    • Left ventricular ejection fraction of 40% or less with sustained ventricular tachycardia or inducible ventricular fibrillation on electrophysiology study
    • Left ventricular ejection fraction of 35% or less with nonischemic dilated cardiomyopathy and New York Heart Association class II or III symptoms on optimal medication therapy
  • Secondary prevention of sudden death in selected patients with heart failure
    • Prior cardiac arrest
    • Sustained ventricular arrhythmias
Contraindications
  • Less than 40 days after myocardial infarction
    • Less than 90 days after revascularization
  • Life expectancy of less than 1 year of meaningful survival
Interpretation of results
  • Decrease in mortality from sudden cardiac death associated with arrhythmias r2
Complications r46
  • Bleeding or pneumothorax related to procedural access
  • Infection
  • Lead malfunction, including oversensing (delivery of inappropriate shocks) and undersensing (not delivering a shock when indicated)
  • Generator malfunction
Cardiac resynchronization therapy r2c202
General explanation
  • Biventricular pacemaker is implanted to pace both right and left ventricles of the heart simultaneously in order to improve ventricular contractility and function, reverse ventricular remodeling, and diminish secondary mitral regurgitation
Indication
  • Patients who have: r2
    • Left ventricular ejection fraction of 35% or less with sinus rhythm
    • Left bundle branch block with QRS interval of 150 milliseconds or more
    • New York Heart Association class II, class III, or ambulatory class IV symptoms on optimal medication therapy
  • May also be useful in: r2
    • Patients who, despite optimal medication therapy, have left ventricular ejection fraction of 35% or less with sinus rhythm; non–left bundle branch block with QRS interval of 150 milliseconds or more; and class III or ambulatory class IV symptoms
    • Patients who, despite optimal medication therapy, have left ventricular ejection fraction of 35% or less with sinus rhythm; left bundle branch block with QRS interval of 120 to 149 milliseconds; and class II, class III, or ambulatory class IV symptoms
    • Patients with atrial fibrillation who, despite optimal medication therapy, have left ventricular ejection fraction of 35% or less and
      • In whom right ventricular pacing is required, or
      • Meet other cardiac resynchronization therapy requirements and in whom rate control medication or atrioventricular nodal ablation allows virtually 100% ventricular pacing with cardiac resynchronization therapy
Contraindications
  • Functional status or life expectancy reduced by noncardiac chronic comorbidities
Interpretation of results
  • Decrease in mortality and functional improvements in oxygen consumption, exercise tolerance, and quality of life r2
Complications
  • Bleeding or pneumothorax related to procedural access
  • Infection
  • Lead failure
  • Generator failure
Ultrafiltration r47c203
General explanation
  • Renal replacement therapy to mechanically remove fluid from body by using hydrostatic pressure across a semipermeable membrane to separate isotonic plasma water from blood r48
Indication
  • Used for selected patients with advanced heart failure, diuretic resistance, and worsening renal function
Contraindications
  • Inability to take required anticoagulants
Interpretation of results
  • Weight loss and improvement of symptoms (eg, improved dyspnea) are positive results
Complications
  • Bleeding
  • Infection
  • Hypotension
Mechanical circulatory support r11c204
General explanation
  • Ventricular assist device provides hemodynamic support in patients with end-stage heart failure refractory to medical therapy by restoring cardiac output, improving end-organ function, and promoting physiologic recovery
  • May be extracorporeal (temporary) or implanted (permanent); may use left ventricular or biventricular modes
Indication
  • Patients who have end-stage heart failure with reduced left ventricular ejection fraction refractory to optimal medication therapy
  • May be considered a bridge to transplant (temporary) or a destination therapy (permanent) in patients who are not transplant candidates
Contraindications
  • Complex; include lack of family support system
Interpretation of results
  • Prolonged survival; 6-month survival while supported on a device has been measured as approximately 75% r49
  • In 1 study, the 1-year survival rate for those on a left ventricular assist device with medical therapy was 52% versus 25% for those on medical therapy alone r11
Complications
  • Vary depending on type of device
Heart transplant r11c205
General explanation
  • Surgical procedure in which failing heart is removed and replaced with healthy donor heart; curative of refractory end-stage heart failure
Indication
  • Patients with end-stage heart failure with functional limitations refractory to optimal medication therapy
Contraindications
  • Advanced age
  • Obesity
  • Diabetes with widespread microvascular complications
  • Irreversible pulmonary disease or acute pulmonary emboli
  • Irreversible chronic kidney disease
  • Infection
  • Malignancy
  • Smoking
  • Polysubstance abuse
  • Other psychosocial comorbidities that would limit survival
Interpretation of results
  • 1-year transplant survival rate is 88%; 5-year survival rate is 72% r11
Complications
  • Perioperative complications including bleeding and infection
  • Organ rejection
  • Increased risk of infection, hypertension, and diabetes due to immunosuppressive drugs
  • Death

Comorbidities

  • Hypertension c206c207
    • In the Framingham study, 91% of patients with incident heart failure had underlying hypertension r50
    • Control of hypertension is important for all patients with heart failure and is the primary management strategy for those with preserved ejection fraction r2
    • Treatment goals r51
      • In patients at increased risk for heart failure (stage A heart failure), blood pressure of less than 130/80 mm Hg is optimal in those with hypertension as a novel strategy to prevent progression to symptomatic heart failure r51
      • For patients who have heart failure with reduced ejection fraction and hypertension, prescribe guideline-directed management and titrate therapy to attain systolic blood pressure less than 130 mm Hg r51
        • This is a threshold now associated with improved clinical outcomes but not yet proven by randomized clinical trials in a population with heart failure
      • For patients who have heart failure with preserved ejection fraction and persistent hypertension after management of volume overload, prescribe guideline-directed management and titrate therapy to attain systolic blood pressure less than 130 mm Hg r51
    • For patients in all stages of heart failure with reduced ejection fraction, antihypertensive therapy with a diuretic (if required for volume overload), an ACE inhibitor/angiotensin receptor blocker or angiotensin receptor–neprilysin inhibitor, and a β-blocker is recommended based on high-quality, randomized controlled data r2r52
      • Second line agents (mineralocorticoid receptor antagonists or hydralazine) are added as required
      • Avoid nondihydropyridine calcium channel blockers and α-blockers r36
    • For patients who have heart failure with preserved ejection fraction, β-blockers, ACE inhibitors, angiotensin receptor blockers, and possibly angiotensin receptor–neprilysin inhibitors are reasonable choices to manage blood pressure r2
  • Diabetes c208c209
    • Risk factor for, and common comorbidity of, heart failure
      • Each condition independently increases risk for the other
      • Patients with diabetes without symptomatic heart failure often have subclinical abnormalities of cardiac structure and function
    • Having both conditions is associated with worse clinical outcomes
      • Health-related quality of life is worse than for patients with heart failure alone r53r54
      • Higher risk of hospitalization (up to 50% higher)r55 and rehospitalizationr56 with diabetes
      • Diabetes increases mortality risk in both ambulatory and hospitalized patients with heart failure r57
        • Overall mortality risk is similar risk for both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction
        • Cardiovascular mortality risk is higher for patients with diabetes and heart failure with preserved ejection fraction as compared to heart failure with reduced ejection fraction r58r59
    • Management of heart failure in diabetes
      • Based on benefit in patients who have heart failure with reduced ejection fraction (regardless of diabetes status), these therapies should routinely be implemented in patients with diabetes and heart failure with reduced ejection fraction who meet guideline indications: r57
        • Renin-angiotensin-aldosterone system inhibitors
        • Angiotensin receptor–neprilysin inhibitors
        • β-Blockers
        • Ivabradine
        • Implantable cardioverter-defibrillators and cardiac resynchronization therapy
    • Management of diabetes in heart failure
      • Consider glycemic goals and the impact of heart failure medications on glycemic control
        • Moderate, rather than intensive, glycemic control may be optimal for patients with diabetes and heart failure
          • U-shaped relationship between mortality and hemoglobin A1C in patients with heart failure (lowest risk of death with modest glucose control and hemoglobin A1C of 7.1% to 7.8%) r60
          • Recommend target hemoglobin A1C of 7% to 8% for most patients with heart failure and diabetes r57
          • Less stringent goals may be appropriate for patients with advanced stage D heart failure not pursuing mechanical circulatory support or transplant r57
        • ACE inhibitors, angiotensin receptor blockers, and angiotensin receptor–neprilysin inhibitors have favorable effects on the development of diabetes mellitus and glycemic control in patients with heart failure with reduced ejection fraction r57
        • Spironolactone may modestly worsen glycemic control in patients with diabetes mellitus and heart failure with reduced ejection fraction r57
        • Carvedilol may be preferable to metoprolol succinate and bisoprolol for patients with heart failure with reduced ejection fraction and diabetes mellitus with poor glycemic control r57
      • Management of type 1 diabetes in patients with heart failure is same as for patients without heart failure
      • In patients with type 2 diabetes, consider the effect of specific glucose-lowering pharmacotherapies on cardiovascular outcomes r61r62
        • In patients at high risk for heart failure and those with established heart failure, metformin and sodium-glucose cotransporter-2 inhibitors are preferable to use over sulfonylurea drugs r57
          • Metformin
            • First line treatment for most patients with type 2 diabetes r63
            • Reduced mortality and a small reduction in all-cause hospitalization in patients with heart failure compared with control subjects
            • Lower risk of heart failure hospitalization than with sulfonylurea drugs
          • Sodium-glucose cotransporter-2 inhibitors
            • First class of glucose-lowering agents demonstrated to reduce heart failure symptoms, risk of heart failure hospitalization, and death in patients with diabetes, with and without established diagnosis of heart failure at baseline r64r65r66
            • Empagliflozin, canagliflozin, and dapagliflozin are recommended for treatment of type 2 diabetes in patients with known atherosclerotic cardiovascular disease, patients older than 50 years with additional risk factors for atherosclerotic heart disease, and those with mild-moderate heart failure with reduced ejection fraction r38r65r67r68r69r70
              • Also recommended in patients without type 2 diabetes who have mild to moderate heart failure with reduced ejection fraction as associated with reduced symptoms, hospitalizations, and cardiac mortality r38r71
            • Cardiovascular benefit must be balanced with potential risks, including genital candidiasis and other rare potential complications (ie, euglycemic diabetic ketoacidosis, lower-limb amputation, fractures associated with canagliflozin)
        • Insulin may be considered; use with caution and close monitoring only if adequate glycemic control cannot be achieved with metformin and sodium-glucose cotransporter-2 inhibitors; associated with weight gain and increased risk of hypoglycemia r57r62
        • Glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase-4 inhibitors sitagliptin and linagliptin have a neutral effect on heart failure. Do not use dipeptidyl peptidase-4 inhibitor saxagliptin in patients with established heart failure or those at high risk for heart failure r57r62
          • Use glucagon-like peptide 1 receptor agonists with caution in patients who have heart failure with reduced ejection fraction and recent decompensation. There are no data to guide use of these medications in heart failure with preserved ejection fraction r57
        • Thiazolidinediones are not recommended for patients with established heart failure; both rosiglitazone and pioglitazone are associated with fluid retention and heart failure events r57r62
  • Atrial fibrillation r2c210c211
    • Heart failure and atrial fibrillation have a bidirectional association, share many of the same risk factors, and frequently complicate each other
    • Heart failure with atrial fibrillation is associated with worse outcomes, including increase in stroke severity and all-cause mortality. Female patients have worse outcomes than male patients r72
    • Best treatment strategies for patients with heart failure and atrial fibrillation are uncertain r73
      • Approach (rate control versus restoration of sinus rhythm) may be individualized depending on whether atrial fibrillation is resulting from or contributing to progression of underlying cardiac failure r74
        • Recent data suggest that early rhythm control (atrial fibrillation present for less than 1 year) in high-risk patients, including those with heart failure, may be beneficial in reducing composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome r75
      • Rate control is typically accomplished with β-blockers in patients with heart failure
        • Nondihydropyridine calcium channel blockers are contraindicated in patients with left ventricle systolic dysfunction but are reasonable when systolic function is preserved r76
        • Digoxin has been associated with increased mortality risk in patients with atrial fibrillation and patients with heart failure when used in high doses r77r78r79
      • Atrial Fibrillation and Congestive Heart Failure Trial showed that pharmacologic rhythm control is not superior to rate control strategy for preventing cardiac death. Consider rhythm control strategy for patients who remain symptomatic despite rate control alone r80
        • Pharmacologic rhythm control options are limited to amiodarone and dofetilide in heart failure with reduced ejection fraction r76
      • Catheter ablation (pulmonary vein isolation) may be superior to both pharmacologic rate and rhythm control in patients with both heart failure and atrial fibrillation
        • CASTLE-AF trial (Catheter Ablation versus Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation) results showed that, for patients with heart failure with reduced ejection fraction, atrial fibrillation catheter ablation was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure r81
        • Catheter ablation appears to be similarly effective for atrial fibrillation (eg, freedom from recurrent atrial arrhythmia, improvements in New York Heart Association functional class, symptom severity) in both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction r82
        • For the overall population, results from CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation)r83r84 do not show improved survival with catheter ablation; detailed analysis of heart failure subgroup in the trial is ongoing and will add additional information r73
      • Atrioventricular nodal ablation and cardiac resynchronization device placement can be useful if other methods fail r2
    • Anticoagulation is typically indicated for the prevention of thromboembolic complications based on CHA₂DS₂-VASc scoring system r36
  • Coronary artery disease c212
    • Present in approximately two-thirds of patients with heart failure
    • Evaluate patients with heart failure with reduced ejection fraction for coronary artery disease and treat accordingly
    • β-Blockers, nitrates, and ACE inhibitors are used to treat both heart failure and ischemic heart disease r85
    • Revascularization may be considered r36
  • Anemia c213
    • Often normocytic and accompanied by an abnormally low reticulocyte count r86
    • Associated with an increased risk of hospitalization and mortality and decreased exercise capacity and quality of life
    • Correct any specific underlying cause (eg, iron, vitamin B₁₂, folate deficiency)
    • In symptomatic patients with ejection fraction 45% or less and iron deficiency (ferritin lower than 100 ng/mL or 100-300 ng/mL if transferrin saturation is less than 20%), consider IV iron replacement to improve functional status and quality of life r9r87r88
    • In symptomatic heart failure patients recently hospitalized for heart failure and with ejection fraction less than 50% and iron deficiency (serum ferritin less than 100 ng/mL or serum ferritin of 100-299 ng/mL with transferrin saturation less 20%), consider IV iron replacement to reduce risk of heart failure hospitalization r9r88
    • Patients with heart failure and symptomatic anemia may require RBC transfusion; in patients without symptoms due to anemia, a restrictive transfusion strategy (at hemoglobin levels of 7-8 g/dL) is recommended r89
      • Care must be taken to monitor volume status and avoid overload when transfusion is administered
    • Do not use erythropoietin-stimulating agents to improve morbidity and mortality in patients with anemia and heart failure r89
  • Chronic kidney disease r90c214c215
    • Complex interplay between heart and kidney whereby dysfunction in 1 organ can induce or worsen dysfunction in the other r90
      • Chronic heart failure resulting in chronic kidney disease is described as chronic cardiorenal syndrome
      • Chronic kidney disease resulting in chronic heart failure is described as chronic renocardiac syndrome
    • GFR is reduced in most patients with advanced heart failure
    • Reduced renal function is strongly prognostic of poor outcome
    • Avoid treatment with nephrotoxic agents r36
  • Chronic obstructive pulmonary disease c216
    • Present in approximately one-third of patients with heart failure
    • Associated with poorer functional status and prognosis
    • β-Blockers may exacerbate bronchospasm; oral corticosteroids can lead to sodium and fluid retention and thus worsen congestive symptoms
  • Depression c217c218
    • Major depression is common in patients with heart failure during hospitalization and is often not recognized
    • Associated with nonadherence to heart failure therapy and worse prognosis r91
    • Avoid tricyclic antidepressants in patients with heart failure owing to association with cardiovascular adverse effects; selective serotonin reuptake inhibitors are a safer alternative for these patients
  • Hyperlipidemia c219
    • Most patients with heart failure also have hyperlipidemia
    • Statin therapy has not been shown to improve symptoms of heart failure r92
    • Statin therapy is recommended according to current guidelinesr93 for prevention of atherosclerotic cardiovascular disease; not recommended routinely for heart failure in the absence of other indications r40
  • Sleep disturbances c220
    • Common owing to orthopnea, paroxysmal nocturnal dyspnea, and nocturnal diuresis associated with diuretic use
    • In addition, obstructive sleep apnea has been noted in about one-third of patients with chronic heart failure r94
    • In patients with New York Heart Association class II through IV heart failure who are suspected to have sleep disordered breathing or excessive daytime sleepiness, consider formal sleep assessment r2
    • In patients with cardiovascular disease and obstructive sleep apnea, consider CPAP to improve sleep quality and alleviate daytime sleepiness r2

Special populations

  • Female patients
    • In general, female patients with heart failure have a survival advantage compared with male patients r74
      • Female patients are more likely to have nonischemic heart failure than male patients
    • Digoxin is associated with increased risk for death in female patients compared with male patients, presumably owing to increased serum digoxin levels related to decreased lean body mass and renal function
    • Benefits of treatment with ACE inhibitors, angiotensin receptor blockers, and β-blockers are observed at lower dosages than required by male patients r95
  • Black populations
    • Age of onset of heart failure is significantly younger in Black populations compared with White populations r11
    • Heart failure in Black populations is less likely due to ischemia and more likely due to hypertension compared with White populations r11
    • Morbidity and mortality are higher in Black populations than in White populations r2
    • ACE inhibitors are less effective and carry increased risk of angioedema in Black patients with heart failure compared with White patients with heart failure r2
    • Use hydralazine and isosorbide dinitrate in addition to, or in place of, ACE inhibitors for Black patients with disease of New York Heart Association class II or higher r2
  • Older patients
    • Heart failure is associated with increased morbidity and mortality in older patients; median survival is 2.5 years after hospitalization for heart failure, with a 1-year mortality rate of 25% r11
    • During treatment with ACE inhibitors, β-blockers, and diuretics, it is imperative to monitor volume status, postural hypotension, and cerebrovascular symptoms

Monitoring

  • At each outpatient encounter, assess:
    • Symptoms, activity level, and functional capacity r11
    • Vital signs and volume status (ie, weight change, estimation of jugular venous pressure, presence of peripheral edema or orthopnea) r2
    • Adherence to recommended treatment and therapeutic efficacy r11
  • Monitor electrolyte levels and renal function test results c221c222
    • At least every 6 months in clinically stable patients r11
      • Monitor more frequently if aldosterone antagonists or high-dose diuretics are used, if drug therapies are changed, or if clinical status declines r11
  • Serial measurements of B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide level are not routinely recommended for guiding optimal therapy in patients with heart failure r2
    • Usefulness of routine serial measurement is not established
    • Measurement of levels at time of admission for purpose of diagnosis and prognosis or to determine disease severity at time of hospital admission has been established r2
  • Serial echocardiograms to monitor ejection fraction and severity of structural remodeling are not routinely recommended, but they may be useful in select patients: r2
    • In those with change in clinical status (significant improvement or worsening)
    • In those with change in treatment
    • In those who may be candidates for device therapy
  • Drug therapy monitoring
    • Monitoring of drug therapy is complex and dependent upon concomitant medications and comorbid conditions. For complete recommendations on individual agents, refer to product labeling or guidelines
    • ACE inhibitors, angiotensin receptor blockers, and angiotensin receptor–neprilysin inhibitors
      • At baseline and periodically thereafter, monitor serum creatinine, potassium, and sodium levels as well as blood pressure for all agents in these classes
    • β-Blockers
      • Routinely monitor blood pressure and heart rate
    • Aldosterone receptor antagonists
      • At baseline, 1 week, and periodically thereafter, monitor serum potassium levels
        • Eplerenone should not be initiated in patients with serum potassium level greater than 5 mEq/L
        • While on therapy with either eplerenone or spironolactone, dosage adjustments are recommended for elevated potassium
      • At baseline and periodically thereafter, monitor serum creatinine level, blood pressure, and weight
    • Diuretics
      • At baseline and periodically thereafter, monitor serum creatinine and electrolyte levels and blood pressure
      • Toxicity with loop diuretics has been associated with ototoxicity and hearing loss. Monitor patients for alterations in hearing periodically
    • Vasodilators
      • At baseline and periodically thereafter, monitor blood pressure, heart rate, and serum creatinine level
      • For continuous intravenous infusion therapies, continuous blood pressure monitoring is recommended
    • Digoxin
      • At baseline and periodically thereafter, monitor ECG, electrolyte (eg, potassium, magnesium, calcium) levels, and serum creatinine level
      • Therapeutic drug monitoring may be used to guide therapy. For heart failure indications, a therapeutic range of 0.5 to 1 ng/mL is recommended
    • Guanylate cyclase stimulators
      • At baseline and periodically thereafter, monitor blood pressure and CBC
      • Vericiguat is contraindicated in pregnancy; confirmation of negative pregnancy test result is recommended in patients of childbearing age
    • Inotropic agents
      • Continuous IV infusion of inotropic agents requires monitoring of heart rate and blood pressure. Periodic evaluation of serum creatinine level is also recommended

Complications and Prognosis

Complications

  • Premature death due to pump failure r11r96c223
  • Malignant ventricular arrhythmias r96c224
    • Sustained ventricular tachycardia occurs in up to 10% of patients with advanced heart failure r96c225
    • Electrolyte disturbances, prolonged QT interval, digoxin toxicity, and myocardial ischemia are often precipitating factors for ventricular arrhythmias
  • Atrial fibrillation r96c226
    • Considered both a cause and a consequence of heart failure; present in about one-third of patients with heart failure r96
    • Mitral valve disease, thyroid disease, sinus node disease, and myocardial infarction are predisposing factors for atrial fibrillation; atrial fibrillation after myocardial infarction with severe left ventricular dysfunction carries a poor prognosis
    • Concurrent heart failure and atrial fibrillation place patient at high risk for thromboembolic events (eg, transient ischemic attack, stroke, deep vein thrombosis)
  • Thromboembolic events r96c227
    • Annual incidence in patients with heart failure is 2% r96
    • Caused by blood stasis in dilated cardiac chamber, wall motion abnormalities, atrial fibrillation, and immobility
    • Risk of stroke in patients with severe heart failure is 4% compared with less than 0.5% in those without heart failure r96

Prognosis

  • For acute decompensated heart failure
    • Prognosis of patients hospitalized with heart failure, and especially those with serial readmissions, is poor
    • Best single predictor for mortality in acute decompensated heart failure is high BUN level (43 mg/dL or more) at admission, followed by low systolic blood pressure (less than 115 mm Hg) and then by high level of serum creatinine (2.75 mg/dL or more) r97
    • Predictive multivariable models have been developed to improve prediction of individual prognosis
      • ADHERE classification, based on ADHERE registry data (Acute Decompensated Heart Failure National Registry) r97
      • EFFECT risk score, based on data from EFFECT study (Enhanced Feedback for Effective Cardiac Treatment) r98
  • For chronic heart failure
    • Mortality rate for patients with heart failure is approximately 40% within 5 years of diagnosis r4
    • For patients with advanced heart failure, 1-year survival rate is 50% r99
    • Although chronic heart failure is usually a progressively worsening condition, patients may remain stable or have improvements in ventricular remodeling with appropriate therapy r11
    • Predictive multivariable models have been developed to improve prediction of individual prognosis
      • Seattle Heart Failure Model r100
      • Heart Failure Survival Score r101
      • CHARM risk score, based on data from CHARM trials (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) r102
      • I-PRESERVE score (for heart failure with preserved ejection fraction only), based on data from I-PRESERVE trial (Irbesartan in Heart Failure With Preserved Systolic Function) r103

Screening and Prevention

Screening c228

Prevention

  • All adults are recommended to follow American College of Cardiology Foundation/American Heart Association guidelines for primary prevention of cardiovascular disease r104
    • Consume a healthy diet and engage in regular physical activity
    • Smoking cessation
    • Weight loss if overweight or obese
    • Interventions (nonpharmacologic or pharmacologic) to reduce blood pressure if elevated
    • Statin therapy in patients with elevated LDL-C, with diabetes, or aged 40 to 75 years with elevated risk of atherosclerotic cardiovascular disease
  • American College of Cardiology Foundation/American Heart Association guideline recommends that patients at high risk for developing heart failure (stage A) control specific modifiable risk factors r2
    • Control hypertension with diuretics, ACE inhibitors, angiotensin receptor blockers, and/or β-blockers c229
    • Control dyslipidemia with statins c230
    • For patients with diabetes, control hyperglycemia and consider sodium-glucose cotransporter-2 inhibitors to further reduce risk of heart failure c231
    • For obese patients, advise and assist with weight loss c232c233
    • For tobacco users, advise and assist with cessation c234
    • For alcohol users, advise and assist with moderation or cessation c235
    • Avoid known cardiotoxic agents (eg, cocaine, antineoplastic drugs, ephedra, cobalt, anabolic steroids, chloroquine, clozapine, amphetamines, methylphenidate, catecholamines) c236
Bozkurt B et al: Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. J Card Fail. ePub, 202133663906Heidenreich PA et al. 2022 AHA/ACC/HFSA Guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263-42135379503Anker SD et al: Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 385(16):1451-61, 202134449189Benjamin EJ et al: Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. ePub, 201728122885Ponikowski P et al: 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 18(8):891-975, 201627207191Goldman L et al: Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale. Circulation. 64(6):1227-34, 19817296795Udelson JE: Heart failure with preserved ejection fraction. Circulation. 124(21):e540-3, 201122105201Ezekowitz JA et al: 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of heart failure. Can J Cardiol. 33(11):1342-433, 201729111106McDonagh TA et al: 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 42(36):3599-726, 202134447992Shamsham F et al: Essentials of the diagnosis of heart failure. Am Fam Physician. 61(5):1319-28, 200010735340Heart Failure Society of America et al: HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. 16(6):e1-194, 201020610207Boudoulas H et al: Valvular heart disease: the influence of changing etiology on nosology. J Heart Valve Dis. 3(5):516-26, 19948000586Hershberger RE et al: Genetic Evaluation of Cardiomyopathy-A Heart Failure Society of America Practice Guideline. J Card Fail. 24(5):281-302, 201829567486Feenstra J et al: Drug-induced heart failure. J Am Coll Cardiol. 33(5):1152-62, 199910193711Jha N et al: Peripartum cardiomyopathy. Heart Fail Rev. 26(4):781-797, 202133438106Cemin R et al: Peripartum cardiomyopathy: moving towards a more central role of genetics. Curr Cardiol Rev. 9(3):179-84, 201323909634Bauersachs J et al: Pathophysiology, diagnosis and management of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy. Eur J Heart Fail. 21(7):827-843, 201931243866Curtis LH et al: Incidence and prevalence of heart failure in elderly persons, 1994-2003. Arch Intern Med. 168:418-24, 200818299498Sturm AC: Genetic testing in the contemporary diagnosis of cardiomyopathy. Curr Heart Fail Rep. 10(1):63-72, 201323135967Leone A: Toxics of tobacco smoke and cardiovascular system: from functional to cellular damage. Curr Pharm Des. 21(30):4370-9, 201526234797Urbano-Marquez A et al: The effects of alcoholism on skeletal and cardiac muscle. N Engl J Med. 320(7):409-15, 19892913506Chow SL et al: Role of biomarkers for the prevention, assessment, and management of heart failure: a scientific statement from the American Heart Association. Circulation. 135(22):e1054-91, 201728446515Harjola VP et al: Acute coronary syndromes and acute heart failure: a diagnostic dilemma and high-risk combination. A statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 22(8):1298-314, 202032347648Drexler B et al: Quantifying cardiac hemodynamic stress and cardiomyocyte damage in ischemic and nonischemic acute heart failure. Circ Heart Fail. 5(1):17-24, 201221976469McKie PM et al: B-type natriuretic peptide as a biomarker beyond heart failure: speculations and opportunities. Mayo Clin Proc. 80(8):1029-36, 200516092582American College of Cardiology Foundation Appropriate Use Criteria Task Force et al: ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echocardiography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance endorsed by the American College of Chest Physicians. J Am Coll Cardiol. 57(9):1126-66, 201121349406Anagnostopoulos C et al: Non-invasive investigations. Br Med Bull. 59:29-44, 200111756202Nagueh SF et al: Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 29(4):277-314, 201627037982Amsterdam EA et al: 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 130(25):e344-426, 201425249585Teichman SL et al: Challenges in acute heart failure clinical management: optimizing care despite incomplete evidence and imperfect drugs. Crit Pathw Cardiol. 14(1):12-24, 201525679083Poon CS et al: Submissive hypercapnia: why COPD patients are more prone to CO₂ retention than heart failure patients. Respir Physiol Neurobiol. 216:86-93, 201525891787van der Hulle T et al: Recent developments in the diagnosis and treatment of pulmonary embolism. J Intern Med. 279(1):16-29, 201626286356Stillman AE et al: Assessment of acute myocardial infarction: current status and recommendations from the North American Society for Cardiovascular Imaging and the European Society of Cardiac Radiology. Int J Cardiovasc Imaging. 27(1):7-24, 201120972835Smith G et al: ABC of intensive care: criteria for admission. BMJ. 318(7197):1544-7, 199910356016Scott MC et al: Congestive heart failure. Emerg Med Clin North Am. 33(3):553-62, 201526226866Hollenberg SM et al: 2019 ACC expert consensus decision pathway on risk assessment, management, and clinical trajectory of patients hospitalized with heart failure: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 74(15):1966-2011, 201931526538Packer M et al: Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 383(15):1413-1424, 202032865377McMurray JJV et al: Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 381(21):1995-2008, 201931535829Vest AR et al: Nutrition, obesity, and cachexia in patients with heart failure: a consensus statement from the Heart Failure Society of America Scientific Statements Committee. J Card Fail. 25(5):380-400, 201930877038Bozkurt B et al: Contributory risk and management of comorbidities of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in chronic heart failure: a scientific statement from the American Heart Association. Circulation. 134(23):e535-78, 201627799274Rimm EB et al: Seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease: a science advisory from the American Heart Association. Circulation. 138(1):e35-e47, 201829773586O'Keefe EL et al: Sea change for marine omega-3s: randomized trials show fish oil reduces cardiovascular events. Mayo Clin Proc. 94(12):2524-33, 201931627938Long L et al: Exercise-based cardiac rehabilitation for adults with heart failure. Cochrane Database Syst Rev. 1:CD003331, 201930695817American Society of Transplantation: ASTS, AST, and ISHLT Joint Statement on COVID-19 Vaccination in Organ Transplant Candidates and Recipients. AST website. Updated March 13, 2022. Accessed September 8, 2022. https://www.myast.org/joint-statement-about-covid-19-vaccination-organ-transplant-candidates-and-recipientshttps://www.myast.org/joint-statement-about-covid-19-vaccination-organ-transplant-candidates-and-recipientsCDC: Interim COVID-19 Immunization Schedule for 6 Months of Age and Older. CDC website. Updated August 22, 2022. Accessed September 2, 2022. https://www.cdc.gov/vaccines/covid-19/downloads/COVID-19-immunization-schedule-ages-6months-older.pdfhttps://www.cdc.gov/vaccines/covid-19/downloads/COVID-19-immunization-schedule-ages-6months-older.pdfEzzat VA et al: A systematic review of ICD complications in randomised controlled trials versus registries: is our "real-world" data an underestimation? Open Heart. 2(1):e000198, 201525745566Fiaccadori E et al: Ultrafiltration in heart failure. Am Heart J. 161(3):439-49, 201121392597Zafar MR et al: Pharmacological and non-pharmacological strategies for volume overload in acute decompensated congestive heart failure: a review article. Cureus. 12(2):e6952, 202032190502Kirklin JK et al: Mechanical circulatory support: registering a therapy in evolution. Circ Heart Fail. 1(3):200-5, 200819808290Levy D et al: The progression from hypertension to congestive heart failure. JAMA. 275(20):1557-62, 19968622246Whelton PK et al: 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 138(17):e426-83, 201830354655Slivnick J et al: Hypertension and heart failure. Heart Fail Clin. 15(4):531-41, 201931472888Allen LA et al: Identifying patients hospitalized with heart failure at risk for unfavorable future quality of life. Circ Cardiovasc Qual Outcomes. 4(4):389-98, 201121693723Fotos NV et al: Health-related quality of life of patients with severe heart failure. A cross-sectional multicentre study. Scand J Caring Sci. 27(3):686-94, 201323004008Dunlay SM et al: Hospitalizations after heart failure diagnosis a community perspective. J Am Coll Cardiol. 54(18):1695-702, 200919850209Arora S et al: Etiologies, trends, and predictors of 30-day readmission in patients with heart failure. Am J Cardiol. 119(5):760-9, 201728109560Dunlay SM et al: Type 2 diabetes mellitus and heart failure: a scientific statement from the American Heart Association and the Heart Failure Society of America: this statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guideline update. Circulation. 140(7):e294-e324, 201931167558MacDonald MR et al: Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J. 29(11):1377-85, 200818413309Kristensen SL et al: Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction: a report from the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction). Circulation. 135(8):724-35, 201728052977Aguilar D et al: Relationship of hemoglobin A1C and mortality in heart failure patients with diabetes. J Am Coll Cardiol. 54(5):422-8, 200919628117Davies MJ et al: Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 41(12):2669-701, 201830291106Cosentino F et al: 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 41(2):255-323, 202031497854Das SR et al: 2020 Expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 76(9):1117-45, 202032771263Nassif ME et al: A review of cardiovascular outcomes trials of glucose-lowering therapies and their effects on heart failure outcomes. Am J Cardiol. 124 Suppl 1:S12-9, 201931741435McDonald M et al: CCS/CHFS heart failure guidelines update: defining a new pharmacologic standard of care for heart failure with reduced ejection fraction. Can J Cardiol. 37(4):531-46, 202133827756Nassif ME et al: Dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction: the DEFINE-HF trial. Circulation. 140(18):1463-76, 201931524498Fitchett D et al: Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME trial. Eur Heart J. 37(19):1526-34, 201626819227Rådholm K et al: Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS program. Circulation. 138(5):458-68, 201829526832Fitchett D et al: Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalization across the spectrum of heart failure risk in the EMPA-REG OUTCOME® trial. Eur Heart J. 39(5):363-370, 201829020355Kosiborod MN et al: Effects of dapagliflozin on symptoms, function, and quality of life in patients with heart failure and reduced ejection fraction: results from the DAPA-HF Trial. Circulation. 141(2):90-9, 202031736335Petrie MC et al: Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes. JAMA. 323(14):1353-68, 202032219386Madan N et al: Atrial fibrillation and heart failure in women. Heart Fail Clin. 15(1):55-64, 201930449380Carlisle MA et al: Heart failure and atrial fibrillation, like fire and fury. JACC Heart Fail. 7(6):447-56, 201931146871Cleland JGF et al: The year in cardiology: heart failure. Eur Heart J. 41(12):1232-48, 202031901936Kirchhof P et al: Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med. 383(14):1305-16, 202032865375January CT et al: 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 130(23):2071-104, 201424682348Ahmed A et al: Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J. 27(2):178-86, 200616339157van Veldhuisen DJ et al: Digoxin for patients with atrial fibrillation and heart failure: paradise lost or not? Eur Heart J. 34(20):1468-70, 201323324547Vamos M et al: Digoxin-associated mortality: a systematic review and meta-analysis of the literature. Eur Heart J. 36(28):1831-8, 201525939649Roy D et al: Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 358(25):2667-77, 200818565859Marrouche NF et al: Catheter ablation for atrial fibrillation with heart failure. N Engl J Med. 378(5):417-27, 201829385358Black-Maier E et al: Catheter ablation of atrial fibrillation in patients with heart failure and preserved ejection fraction. Heart Rhythm. 15(5):651-7, 201829222043Mark DB et al: Effect of catheter ablation vs medical therapy on quality of life among patients with atrial fibrillation: the CABANA randomized clinical trial. JAMA. 321(13):1275-85, 201930874716Packer DL et al: Effect of catheter ablation vs antiarrhythmic drug therapy on mortality, stroke, bleeding, and cardiac arrest among patients with atrial fibrillation: the CABANA randomized clinical trial. JAMA. 321(13):1261-74, 201930874766Pepine CJ et al: How do we best treat patients with ischemic heart disease? Circulation. 98(19):1985-6, 19989808592Cheitlin MD et al: ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography). J Am Soc Echocardiogr. 16(10):1091-110, 200314566308Anand IS et al: Anemia and iron deficiency in heart failure: current concepts and emerging therapies. Circulation. 138(1):80-98, 201829967232Ponikowski P et al: Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet. 396(10266):1895-1904, 202033197395Qaseem A et al: Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 159(11):770-9, 201324297193Rangaswami J et al: Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 139(16):e840-78, 201930852913Carney RM et al: Depression and coronary heart disease: a review for cardiologists. Clin Cardiol. 20(3):196-200, 19979068903van der Harst P et al: Statins in the treatment of heart failure. Circ Heart Fail. 3(3):462-4, 201020484198Grundy SM et al: 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 139(25):e1046-81, 201930565953MacDonald M et al: The current prevalence of sleep disordered breathing in congestive heart failure patients treated with beta-blockers. J Clin Sleep Med. 4(1):38-42, 200818350960Santema BT et al: Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study. Lancet. 394(10205):1254-63, 201931447116Watson RD et al: ABC of heart failure: clinical features and complications. BMJ. 320(7229):236-9, 200010642237Fonarow GC et al: Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA. 293(5):572-80, 200515687312Canadian Cardiovascular Outcomes Research Team: EFFECT Heart Failure Mortality Prediction. CCORT website. Accessed September 8, 2022. http://www.ccort.ca/Research/CHFRiskModel.aspxhttp://www.ccort.ca/Research/CHFRiskModel.aspxYang J et al: Heart failure: advanced development in genetics and epigenetics. Biomed Res Int. 2015:352734, 201525949994University of Washington: Seattle Heart Failure Model. University of Washington website. Accessed September 8, 2022. http://depts.washington.edu/shfm/http://depts.washington.edu/shfm/Aaronson KD et al: Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation. Circulation. 95(12):2660-7, 19979193435Pocock SJ et al: Predictors of mortality and morbidity in patients with chronic heart failure. Eur Heart J. 27(1):65-75, 200616219658Komajda M et al: Factors associated with outcome in heart failure with preserved ejection fraction: findings from the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-PRESERVE). Circ Heart Fail. 4(1):27-35, 201121068341Arnett DK et al: 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 74(10):1376-414, 201930894319
;