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    Heart Failure

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    May.14.2024

    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 on the basis of 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 heart failure with reduced ejection fraction (left ventricular ejection fraction of 40% or less), heart failure with mildly reduced ejection fraction (left ventricular ejection fraction 41% to 49%), or heart failure with preserved ejection fraction (left ventricular ejection fraction of 50% or more) 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 angiotensin receptor–neprilysin inhibitors or ACE inhibitors/angiotensin receptor blockers, β-blockers, sodium-glucose cotransporter-2 inhibitors, and mineralocorticoid receptor antagonists for most patients, with diuretics for volume overload r2
      • Vasodilators, ivabradine, digoxin, and vericiguat may be added for appropriate patients with continued symptoms
    • Recommended medications for heart failure with preserved ejection fraction improve symptoms and function, manage co-morbidities, and reduce morbidity r3
      • Sodium-glucose cotransporter-2 inhibitors are recommended for all patients and diuretics are recommended for fluid overload
      • Additional medications that have shown benefit are angiotensin receptor–neprilysin inhibitors (or angiotensin receptor blockers if intolerant) and mineralocorticoid receptor antagonists
    • 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
    • Education, optimal management of comorbidities, and exercise are recommended for patients regardless of ejection fraction r2r3
    • 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 another indication is present (eg, atrial fibrillation, cardiac thrombus) 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 ventricular dilation, ventricular hypertrophy, or both (left, right, or biventricular) r1
    • 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 or 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 of 50% 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 r5
        • 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) r1r2r5
        • Ejection fraction of 41% to 49% that shares characteristics similar to heart failure with preserved ejection fraction and heart failure with reduced ejection fraction r5r8
        • European guidelines have additional criteria that include elevated levels of natriuretic peptides and either relevant structural heart disease or diastolic dysfunction r5
      • Heart failure with reduced ejection fraction r1r2r5
        • Ejection fraction of 40% or less r1
        • Historically described as systolic heart failure
        • Left ventricular contractility is impaired and ventricle 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 r5
        • 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 r5
        • 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 c2c3
        • Orthopnea c4
        • Paroxysmal nocturnal dyspnea c5
      • Fatigue c6
        • Exercise intolerance c7
        • Increased recovery time from activity c8
      • 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 older adults 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) c34c35
      • Wheezes c36
      • Peripheral edema, ascites, and hepatomegaly c37c38c39
      • Cachexia in advanced disease c40

    Causes and Risk Factors

    Causes

    • Most common causes of heart failure are hypertension and ischemic coronary artery disease r9r10c41c42
      • Risk of heart failure increases 8- to 10-fold after myocardial infarction r10c43
        • Patients with new onset (de novo) heart failure are more likely to present owing to acute coronary syndrome than patients with chronic heart failure r11
      • Patients with heart failure with preserved ejection fraction (usually older and female) more commonly have hypertension and less commonly have coronary artery disease c44c45
      • 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 c46
    • Other causes of heart failure with reduced ejection fraction include valvular disease and cardiomyopathies
      • Valvular disease c47c48
        • Predominantly mitral and aortic valve disease (eg, mitral regurgitation, aortic stenosis, aortic regurgitation) r12c49c50c51c52c53
      • Cardiomyopathies c54
        • 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) c55c56
        • Idiopathic dilated cardiomyopathy c57
        • Familial cardiomyopathy c58
          • 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 c59
          • 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) r14c60c61c62
          • Cardiotoxic cancer chemotherapies, particularly anthracyclines, can cause structural changes c63
            • Other therapies that are cardiotoxic include trastuzumab (especially with concomitant anthracyclines), high-dose cyclophosphamide, taxoids, mitomycin C, fluorouracil, and the interferons c64c65c66c67c68c69
          • Long-term alcohol or cocaine use may cause dilated cardiomyopathy c70c71
          • Cardiomyopathy may be caused by other drugs, many with misuse potential (eg, ephedra, anabolic steroids, amphetamines, methylphenidate) c72c73c74c75
        • Inflammatory cardiomyopathy c76
          • Immune-mediated inflammatory myocarditis c77
            • Hypersensitivity to medication (eg, sulfonamides, penicillin, methyldopa, amphotericin B, streptomycin, phenytoin, isoniazid, tetanus toxoid, hydrochlorothiazide, dobutamine, chlorthalidone) c78c79c80c81c82c83c84c85c86c87c88
            • Autoimmune disorders (eg, systemic lupus erythematosus, scleroderma) c89c90c91
          • Infective inflammatory myocarditis c92
            • Most commonly of viral origin but also can be caused by other pathogens
            • Commonly occurs in patients with HIV infection
        • Metabolic/endocrine cardiomyopathy c93c94
          • Includes cardiomyopathy caused by obesity, diabetes, hyperthyroidism, acromegaly, growth hormone imbalances, hypophosphatemia, hypocalcemia, and pheochromocytoma c95c96c97c98c99c100c101
          • 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 c102c103c104c105c106
        • Infiltration cardiomyopathy c107
          • Caused by malignancy, sarcoidosis, iron overload, or amyloidosis r5
        • Iron overload cardiomyopathy c108
          • Caused by increased iron deposition in heart. Associated with common genetic disorders (eg, primary hemochromatosis) and disorders that require lifetime transfusions (eg, thalassemia major) c109c110
        • Peripartum cardiomyopathy c111
          • 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
        • Arrhythmia-induced cardiomyopathy r2c112
          • Tachycardia, atrial fibrillation, and premature ventricular contractions may cause a dilated cardiomyopathy
            • Left ventricular myocardial dysfunction correlates with duration of tachycardia and magnitude of increased ventricular rate
            • Generally reversible with rate control
          • Right ventricular pacing, particularly substantial pacing greater than 20% to 40%, may induce cardiomyopathy r18
            • Cardiac physiologic pacing prevents or minimizes pacing-related heart failure
        • Stress cardiomyopathy (takotsubo cardiomyopathy) c113c114
          • 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 r19c115c116
    • Prevalence is 10% or more in patients aged 70 years or older r10
    Sex
    • Higher incidence in males than females by approximately 10 cases per 1000 person-years r19c117c118
    Genetics
    • Genetic loci with multiple genes and alleles with multiple mutations are involved in familial cardiomyopathies leading to heart failure r20c119
      • Underlying genetic causes include mutations in more than 30 genes encoding the sarcomere, components of the cytoskeleton, ion channels, and other elements r20
    Ethnicity/race
    • Compared with White Americans, Black Americans have higher incidence of and higher 5-year mortality from heart failure r19c120c121c122c123
      • Approximately 3% of Black adults in the United States have heart failure r10
    Other risk factors/associations
    • Atherosclerotic disease c124
    • Diabetes c125
      • Risk factor independent of age, hypertension, obesity, hypercholesterolemia, or coronary artery disease
    • Metabolic syndrome c126
    • Smoking r21c127
    • Alcohol use disorder r22c128
      • 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 r14c129c130c131c132c133c134c135c136

    Diagnostic Procedures

    Primary diagnostic tools

    • Diagnosis is suspected on the basis of thorough history and physical examination r10c137
    • 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 r2r10c138
    • Obtain 12-lead ECG as part of initial evaluation in all patients r2r8c139
    • For all patients presenting with heart failure, explore the specific cause using additional laboratory testing
      • All patients r2r10
        • Electrolyte levels, BUN and creatinine levels, and urinalysis (important for treatment decisions) c140c141c142
        • Liver function tests c143
        • Fasting lipid levels and fasting glucose level to assess cardiovascular risk factors c144c145
        • CBC, iron studies, and TSH level to exclude anemia and thyroid disease (as a cause or exacerbating factor of heart failure) c146c147c148
        • B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide c149c150
          • 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) r2r10r23r24
          • 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 r5
          • On admission to hospital for heart failure and prior to discharge, measure B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide level to inform a trajectory and help establish a postdischarge prognosis r2r24
      • 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 r2r5r8
    • Consider cardiac MRI for better assessment of myocardial structure and function, particularly if echocardiographic images are inadequate r5
    • 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 r5r25r26
    • 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
    • Because echocardiogram and natriuretic peptide levels may be nondiagnostic in heart failure with preserved ejection fraction, consider a clinical scoring system (eg, H₂FPEF) r3r27

    Laboratory

    • Routine laboratory tests r2r10
      • Obtain on presentation to assist in determining causes of heart failure, identifying risk factors, and assessing baseline kidney function
        • Comprehensive metabolic panel c151
          • Electrolyte, magnesium, calcium, BUN, and creatinine levels c152c153c154c155c156
          • Elevated liver enzyme levels may be due to hepatic congestion or dysfunction c157
        • Fasting blood glucose level c158
          • Diabetes is a common comorbidity and risk factor for heart failure
        • Fasting lipid profile c159
          • To assess risk for coronary artery disease and metabolic syndrome
        • TSH level c160
          • Thyroid disease may mimic, aggravate, or cause heart failure
        • CBC c161
          • Anemia may cause or exacerbate heart failure
        • Urinalysis c162
    • Cardiac biomarker tests r28
      • Natriuretic peptide levels c163c164
        • Hormones secreted by cardiomyocytes with myocardial stretch
        • Diagnosis during an acute episode r23r24
          • B-type natriuretic peptide level less than 100 pg/mL or N-terminal pro–B-type natriuretic peptide level less than 300 pg/mL have an excellent negative predictive value (94%-97%) to rule out heart failure
          • B-type natriuretic peptide level greater than 400 pg/mL or N-terminal pro–B-type natriuretic peptide levels above age-related cutoffs have excellent positive predictive value to diagnose heart failure
            • 450 pg/mL for patients aged younger than 50 years
            • 900 pg/mL for patients aged 50 years to 75 years
            • 1800 pg/mL for patients aged older than 75 years
          • B-type natriuretic peptide levels between 100 pg/mL and 400 pg/mL, or N-terminal pro–B-type natriuretic peptide levels between 300 pg/mL and the age-related cutoffs (450, 900, or 1800 pg/mL), are suggestive of heart failure but require additional testing
        • In nonacute situations, natriuretic peptides are primarily used for prognosis and risk stratification, but also aid in diagnosis r2r23r24
          • B-type natriuretic peptide level less than 35 pg/mL or N-terminal pro–B-type natriuretic peptide level less than 125 pg/mL indicate a diagnosis of heart failure is unlikely; levels above these thresholds are suggestive of heart failure r5r24r29
        • 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 r30
        • Note that obese patients may have falsely low natriuretic peptide levels
        • Maintain awareness that many patients with heart failure with preserved ejection fraction have natriuretic peptide levels within reference range r3
      • Cardiac troponin T or I levels c165c166c167c168
        • 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 r10c169
      • 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 r9c170
      • 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 r31r32c171
      • 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 r9
        • Heart failure with reduced or mildly 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: r33
          • Normal or near normal ejection fraction (50% or higher)
          • Abnormal mitral inflow
          • Increased atrial volume
          • Increased left ventricular mass
        • Recognize sex-specific differences in echocardiograph findings during interpretation r3
          • Females have more concentric remodeling and more impaired diastolic relaxation compared with males; left ventricular dysfunction may be underestimated
    • Cardiac MRI r2r9c172
      • 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 r2r34c173c174c175c176
    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 c177
      • 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 r35
      • Chronic obstructive pulmonary disease r36c178d1
        • 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 c179d2
        • 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 r37c180d3
        • 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 r38c181d4
        • 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 c182
        • 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 c183d5
        • 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 r35
      • Cirrhosis c184d6
        • 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 c185
        • 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: r2r10
      • Identify reversible precipitating factors
      • Relieve symptoms
      • Reduce hospitalizations
      • Restore normal oxygenation
    • For American College of Cardiology Foundation/American Heart Association stage A and B: r2
      • Reduce risk of future heart failure
      • Prevent symptoms
      • Prevent hospitalizations
    • For American College of Cardiology Foundation/American Heart Association stage C and D: r2
      • Reduce symptoms
      • Prevent hospitalizations
      • Reduce mortality

    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: r10

    • 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 r39
    • 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) r5r40
    • 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 r41
      • 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)
        • 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 r5
        • 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
    • Optimal pace and timing for guideline-directed medical therapy is unknown; however, evidence supports rapid up-titration during and immediately after hospitalization r11r42r43
      • Rapid titration of angiotensin receptor–neprilysin inhibitor or ACE inhibitor, β-blocker, and mineralocorticoid receptor blocker during the 2 days preceding discharge through 2 weeks after discharge resulted in substantially higher number of patients at goal doses of the three medications at day 90 and day 180 compared to usual care r42
        • Patients in the intensive group had a lower risk of composite of heart failure rehospitalization or death, improved signs and symptoms, improved quality of life, and similar rates of serious adverse effects at 6 months compared to usual care
        • Patients included those with reduced ejection fraction, mildly reduced ejection fraction, and preserved ejection fraction
      • Sodium-glucose cotransporter-2 inhibitors, which are recommended to prevent rehospitalization regardless of ejection fraction, can safely be initiated after discontinuation of IV agents in patients with adequate renal function r11

    Management of stable chronic heart failure r2

    • Optimal pace and timing for guideline-directed medical therapy is unknown; however, evidence suggests an additive benefit to combination therapy and a higher risk of death without optimal guideline-directed medical therapy r2r44
    • Overall management depends on disease stage
    • 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, in patients with type 2 diabetes at high risk for cardiovascular disease, and in patients with chronic coronary disease regardless of diabetes status r2r26
    • 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 r2r5
            • 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 r2r5
            • 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 within the last 3 years even if ejection fraction is not reduced r3
          • Statin r2r5
            • Indicated for patients who have history of myocardial infarction or acute coronary syndrome or for treatment of dyslipidemia; otherwise, not recommended strictly for heart failure
      • Device therapy
        • Implantable cardioverter-defibrillator for primary prevention of sudden death is recommended for patients who meet all of the following: r2
          • 40 or more days after myocardial infarction
          • Left ventricular ejection fraction 30% or less
          • New York Heart Association Class I
          • Expectation of meaningful survival for greater than 1 year
    • 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, bisoprolol, carvedilol, or sustained-release metoprolol, which are the only β-blockers proven to reduce mortality) 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 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 (hyperpolarization-activated cyclic nucleotide-gated channel blocker) 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 recommended for primary prevention of sudden cardiac death in selected patients who are expected to have meaningful survival greater than 1 year: r2
              • Patients with nonischemic dilated cardiomyopathy, with left ventricular ejection fraction 35% or less and New York Heart Association class II or III symptoms
              • Patients with ischemic heart disease at least 40 days following myocardial infarction, with left ventricular ejection fraction 35% or less and New York Heart Association class II or III symptoms
              • Patients with ischemic heart disease at least 40 days following myocardial infarction, with left ventricular ejection fraction 30% or less and New York Heart Association class I symptoms
            • Cardiac resynchronization therapy (biventricular pacing) is indicated for selected patients who have the following: r2r5
              • 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
            • Use sodium-glucose cotransporter-2 inhibitor to decrease risk of hospitalization or death r2r43
            • 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
        • Preserved ejection fraction
          • Pharmacologic therapy
            • Recommended therapies for heart failure with preserved ejection fraction improve symptoms and function, manage co-morbidities, and reduce morbidity r2r3
              • Sodium-glucose cotransporter-2 inhibitor use is recommended r3r43r45
              • Use diuretics for symptom relief r2
              • Consider adding aldosterone receptor antagonists to decrease hospitalizations in patients who meet all of the following criteria: r2r3
                • 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 adding angiotensin receptor–neprilysin inhibitor to decrease hospitalizations in women with any ejection fraction or men with ejection fraction less than 55% to 60% r2r3
                • Use angiotensin receptor blockers in individuals unable to take an angiotensin receptor–neprilysin inhibitor owing to cost or contraindication r2r3
              • Systolic and diastolic blood pressure control is particularly important
                • Diuretics, angiotensin receptor–neprilysin inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists are preferred
                • Generally avoid β-blockers owing to increased risk of intolerability, but consider in patients with coronary artery disease or atrial fibrillation with rapid ventricular response r2r3
              • Manage atrial fibrillation, if present, according to current guidelines, including anticoagulation 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 c186c187

    • ACE inhibitors c188
      • Captopril c189
        • Captopril Oral tablet; Adults: 6.25 mg PO 3 times daily, initially. Titrate dose every 1 to 2 weeks (Usual Max: 150 mg/day [Max: 450 mg/day]).
      • Enalapril c190
        • Enalapril Maleate Oral tablet; Adults: 2.5 mg PO twice daily, initially. Increase the dose every 1 to 2 weeks to the highest dosage level tolerated. Max: 20 to 40 mg/day.
      • Lisinopril c191
        • Lisinopril Oral tablet; Adults: 2.5 to 5 mg PO once daily, initially. Increase the dose every 1 to 2 weeks to the highest dosage level tolerated. Max: 20 to 40 mg/day.
    • Angiotensin receptor blockers c192
      • Candesartan c193
        • Candesartan Cilexetil Oral tablet; Adults: 4 to 8 mg PO once daily, initially. Double the dose every 1 to 2 weeks to the highest dosage level tolerated. Max: 32 mg/day.
      • Losartan c194
        • Losartan Potassium Oral tablet; Adults: 25 to 50 mg PO once daily, initially. Increase the dose every 1 to 2 weeks to the highest dosage level tolerated. Max: 50 to 150 mg/day.
      • Valsartan c195c196
        • Valsartan Oral tablet; Adults: 20 to 40 mg PO twice daily, initially. Increase the dose every 1 to 2 weeks to the highest dosage levelas tolerated. Max: 320 mg/day.
    • Angiotensin receptor–neprilysin inhibitor c197
      • Sacubitril-valsartan c198
        • Sacubitril, Valsartan Oral tablet; Adults: 49 mg sacubitril/51 mg valsartan PO twice daily, initially. Double the dose after 2 to 4 weeks as tolerated. Max: 97 mg sacubitril/103 mg valsartan PO twice daily.
    • β-Blockers c199c200
      • Bisoprolol c201c202
        • Bisoprolol Fumarate Oral tablet; Adults: 1.25 mg PO once daily, initially. Increase the dose every 2 weeks to the highest dosage level tolerated. Max: 10 mg/day.
      • Carvedilol c203c204
        • Carvedilol Oral tablet; Adults weighing 85 kg or less: 3.125 mg PO twice daily, initially. Double the dose every 2 weeks to the highest dosage level tolerated. Max: 50 mg/day.
        • Carvedilol Oral tablet; Adults weighing more than 85 kg: 3.125 mg PO twice daily, initially. Double the dose every 2 weeks to the highest dosage level tolerated. Max: 100 mg/day.
      • Metoprolol succinate c205c206
        • Metoprolol Succinate Oral tablet, extended-release; Adults: 12.5 or 25 mg PO once daily, initially. Double the dose every 2 weeks to the highest dosage level tolerated. Max: 200 mg/day.
    • Sodium-glucose co-transporter 2 inhibitor
      • For the reduction of the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in persons with heart failure
        • Dapagliflozin
          • Dapagliflozin Oral tablet; Adults: 10 mg PO once daily.
        • Empagliflozin
          • Empagliflozin Oral tablet; Adults: 10 mg PO once daily.
      • For the reduction of the risk of hospitalization for heart failure in persons with type 2 diabetes mellitus and chronic kidney disease
        • Canagliflozin
          • Canagliflozin Oral tablet; Adults: 100 mg PO once daily, initially. May increase the dose to 300 mg PO once daily if additional glycemic control is needed. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
        • Dapagliflozin
          • Dapagliflozin Oral tablet; Adults: 10 mg PO once daily.
        • Empagliflozin
          • Empagliflozin Oral tablet; Adults: 10 mg PO once daily, initially. May increase dose to 25 mg PO once daily if additional glycemic control is needed.
        • Sotagliflozin
          • Sotagliflozin Oral tablet; Adults: 200 mg PO once daily, initially. Increase the dose to 400 mg PO once daily after at least 2 weeks as tolerated. Dose may be decreased to 200 mg PO once daily as needed.
    • Aldosterone receptor antagonists c207
      • Eplerenone c208
        • 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 c209
        • Spironolactone Oral tablet; Adults: 25 mg PO once daily, initially. Increase the dose after 4 weeks as tolerated to 50 mg PO once daily.
      • Finerenone
        • Finerenone Oral tablet; Adults: 20 mg PO once daily. Adjust dose based on serum potassium concentrations every 4 weeks as needed. Dose range: 10 to 20 mg PO once daily.
    • Loop diuretics c210
      • Bumetanide c211c212
        • Bumetanide Oral tablet; Adults: 0.5 to 1 mg PO once daily, initially. 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. Repeat a second or third dose every 2 to 3 hours as needed. Max: 10 mg/day.
      • Furosemide c213
        • Furosemide Oral tablet; Adults: 20 to 80 mg PO once, initially. 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 until the desired diuretic effect is attained. Usual dose: 40 to 240 mg/day in 1 to 2 divided doses.
      • Torsemide c214
        • Torsemide Oral tablet; Adults: 10 to 20 mg PO once daily, initially. Double the dose as needed. Max: 200 mg/day.
    • Thiazide diuretics c215
      • Hydrochlorothiazide c216
        • Hydrochlorothiazide Oral tablet; Adults: 12.5 to 100 mg/day PO in single or divided doses, initially. Max: 200 mg/day.
      • Indapamide c217c218
        • Indapamide Oral tablet; Adults: 2.5 mg PO once daily, initially. Increase the dose to 5 mg PO once daily after 1 week if needed.
      • Metolazone c219
        • Metolazone Oral tablet; Adults: 5 to 20 mg PO once daily.
    • Vasodilators c220
      • Hydralazine c221
        • Hydralazine Hydrochloride Oral tablet; Adults: 25 to 50 mg PO 3 to 4 times daily, initially. Increase the dose every 1 to 2 weeks to the highest dosage level tolerated. Max: 300 mg/day.
      • Isosorbide dinitrate c222
        • Isosorbide Dinitrate Oral tablet; Adults: 20 to 30 mg PO 3 to 4 times daily, initially. Increase the dose every 1 to 2 weeks to the highest dosage level tolerated. Max: 120 mg/day.
      • Nitroglycerin c223
        • 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 c224
        • 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 c225c226
      • Ivabradine c227
        • 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 c228
      • Digoxin c229
        • 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; Older 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 c230
      • Vericiguat c231
        • 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 c232
      • Dopamine c233
        • 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 c234
        • 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 c235
        • 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 c236

    • At least 1 session of nutritional evaluation and counseling is recommended for patients with heart failure r46
      • Ensure adequate intake of macro- and micronutrients
      • Recommend DASH (Dietary Approaches to Stop Hypertension) or Mediterranean style diet of patients of normal weight r47c237c238
      • 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 r48
      • 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 r49
      • High-dose marine omega-3 supplements are recommended for patients with congestive heart disease who are taking statins and who have elevated triglycerides r49

    Exercise c239

    • Recommend exercise interventions (eg, cardiac rehabilitation), stressing full adherence to recommended regimens r2r47
      • Center-based supervised exercise training, home based with or without virtual support, and hybrid programs were all found effective in reducing hospitalizations and increasing quality of life in both short (follow-up up to 12 months) and long term (follow-up greater than 12 months) r50
    • In adults with chronic heart failure with reduced ejection fraction, evidence suggests that exercise training (eg, cardiac rehabilitation): r51
      • Reduces all-cause hospitalizations
      • Reduces hospitalizations due to heart failure in the short term
      • Improves quality of life
      • Reduces long-term mortality
    • For patients with preserved ejection fraction, exercise training has also been shown to be beneficial r52
      • Supervised exercise training is safe, improves exercise capacity (eg, peak oxygen consumption, total exercise time, 6-minute walk distance), and improves quality of life
      • Home-based training and hybrid programs have also been shown to be safe and effective in improving exercise capacity and quality of life
      • Studies have been underpowered to detect any effect on clinical outcomes such as cardiovascular events or survival
      • In the United States, insurance coverage for supervised exercise programs is less available for patients with preserved ejection than for reduced ejection fraction; clinicians may need to pursue referrals and coverage more aggressively
    • Exercise is contraindicated in life-threatening or unstable conditions, including severe decompensated heart failure r26

    General recommendations

    • Order careful intake and output measurements in acute care setting c240
    • 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 c241
    • Advise and assist with moderation or elimination of alcohol intake owing to its negative effect on ventricular systolic function c242
    • Advise and assist with smoking cessation c243d8
      • Smoking increases myocardial oxygen consumption (via increased heart rate and blood pressure) and decreases myocardial oxygen supply
    • Vaccinations
      • Patients with heart failure are recommended to receive all vaccinations for which they are eligible (eg, zoster vaccination for those aged 50 years and older), but with particular attention to respiratory diseases r53
        • Patients with heart failure are at increased risk of severe disease, hospitalization, and/or death from infections such as influenza, pneumococcal disease, respiratory syncytial virus, and COVID-19 r2
        • Vaccination against respiratory diseases has been shown to decrease morbidity and mortality, including all-cause hospitalizations and cardiovascular events r2
        • Vaccination is specifically recommended against SARS-CoV-2 (patients aged 6 months and older); influenza virus (patients aged 6 months and older); pneumococcus (patients aged 19 years and older with chronic heart diseases including heart failure); and respiratory syncytial virus (patients aged 60 years and older, or pregnant patients) r53

    Provide patients and caregivers with comprehensive education about heart failure, medication regimens, and lifestyle modifications r2c244c245

    • Educational initiatives including multimedia, phone, or text interventions, nurse-led education, and post-discharge follow-up may reduce rehospitalizations r54
    Procedures
    Implantable cardioverter-defibrillator therapy r2r5c246
    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) r2r5
      • 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 r55
    • 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 r2c247
    General explanation
    • Biventricular pacemaker is implanted to pace both right and left ventricles of the heart simultaneously 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 r56c248
    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 r57
    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 r10c249
    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% r58
    • 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 r10
    Complications
    • Vary depending on type of device
    Heart transplant r59c250
    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
    • Relative contraindications r59
      • Inability or insufficient social supports to be adherent to care
      • Diabetes with persistent poor glycemic control (hemoglobin A1c greater than 7.5%) despite optimal effort
      • Diabetes with end-organ damage other than nonproliferative retinopathy
      • Irreversible renal dysfunction (estimated GFR less than 30)
      • Severe peripheral vascular disease when rehabilitation and revascularization are not possible
      • Aged older than 70 years
      • Untreated malignancy
      • Active tobacco smoking
    • Contraindications r59
      • Active substance use disorder
      • Clinically severe, symptomatic cerebrovascular disease
      • Severe cognitive-behavioral disabilities or severe dementia
      • Severe elevated pulmonary vascular resistance
      • Severe extracardiac amyloid organ dysfunction
      • Acute fulminant hepatitis B or hepatitis C infection
      • Cirrhosis, portal hypertension, or hepatocellular carcinoma in patients with chronic hepatitis B or hepatitis C infection
    Interpretation of results
    • 1-year transplant survival rate is 90.3%; 5-year survival rate is 79.6% r2
    Complications
    • Perioperative complications including bleeding and infection
    • Organ rejection
    • Increased risk of infection, hypertension, and diabetes due to immunosuppressive drugs
    • Death

    Comorbidities

    • Hypertension c251c252
      • In the Framingham study, 91% of patients with incident heart failure had underlying hypertension r60
      • 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 r61
        • 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 r61
        • 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 r61
          • 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 r61
      • 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 r2r62
        • Add second line agents (mineralocorticoid receptor antagonists or hydralazine) as required
        • Avoid nondihydropyridine calcium channel blockers and α-blockers r41
      • For patients who have heart failure with preserved ejection fraction, diuretics, angiotensin receptor–neprilysin inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists are reasonable choices to manage blood pressure r3
    • Diabetes c253c254
      • 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 r63r64
        • Higher risk of hospitalization (up to 50% higher)r65 and rehospitalizationr66 with diabetes
        • Diabetes increases mortality risk in both ambulatory and hospitalized patients with heart failure r67
          • 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 r68r69
      • 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: r67
          • Sodium-glucose cotransporter-2 inhibitor r43
          • Angiotensin receptor–neprilysin inhibitors
          • Renin-angiotensin-aldosterone system inhibitors
          • β-Blockers
          • Ivabradine
          • Implantable cardioverter-defibrillators and cardiac resynchronization therapy
        • Sodium-glucose cotransporter-2 inhibitor are also indicated for patients who have diabetes and heart failure with mildly reduced or preserved ejection fraction r3r43
        • Use the mineralocorticoid receptor antagonist finerenone in patients with type 2 diabetes and chronic kidney disease to prevent heart failure hospitalizations r43
      • 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%-7.8%) r70
            • Recommend target hemoglobin A1C of 7% to 8% for most patients with heart failure and diabetes r67
            • Less stringent goals may be appropriate for patients with advanced stage D heart failure not pursuing mechanical circulatory support or transplant r67
          • 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 r67
          • Spironolactone may modestly worsen glycemic control in patients with diabetes mellitus and heart failure with reduced ejection fraction r67
          • 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 r67
        • 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 r71r72
          • 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 r67
            • Metformin
              • First line treatment for most patients with type 2 diabetes r73
              • 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 r3r43r74r75r76
              • 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)
          • Glucagon-like peptide-1 receptor agonists have a beneficial effect on atherosclerotic cardiovascular disease outcomes, heart failure hospitalizations, and weight loss r3
            • Use glucagon-like peptide 1 receptor agonists with caution in patients who have heart failure with reduced ejection fraction and recent decompensation r67
          • 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 r67r71
          • Do not use dipeptidyl peptidase-4 inhibitors saxagliptin or alogliptin in patients with established heart failure or those at high risk for heart failure; it is unknown whether potential increased risk of heart failure events is a class effect r3r67r71
          • Thiazolidinediones are not recommended for patients with established heart failure; both rosiglitazone and pioglitazone are associated with fluid retention and heart failure events r67r71
    • Atrial fibrillation r2c255c256d7
      • 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 r77
      • Best treatment strategies for patients with heart failure and atrial fibrillation are uncertain r78
        • 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 r79
          • 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 r80
        • 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 r81
          • Digoxin has been associated with increased mortality risk in patients with atrial fibrillation and patients with heart failure when used in high doses r82r83r84
        • 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 r85
          • Pharmacologic rhythm control options are limited to amiodarone and dofetilide in heart failure with reduced ejection fraction r81
        • 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 r86
          • 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 r87
          • For the overall population, results from CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation)r88r89 do not show improved survival with catheter ablation; detailed analysis of heart failure subgroup in the trial is ongoing and will add additional information r78
        • 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 r41
    • Coronary artery disease c257
      • 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 and ACE inhibitors are used to treat both heart failure and ischemic heart disease r90
      • Guidelines recommend against routine use of nitrates in heart failure with preserved ejection fraction; consider dihydropyridine calcium channel blockers or ranolazine r2r3
      • Revascularization may be considered r3r41
    • Anemia c258d9
      • Often normocytic and accompanied by an abnormally low reticulocyte count r91
      • 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)
      • Utilize IV iron replacement to improve functional status and quality of life in symptomatic patients with reduced or mildly reduced ejection fraction and iron deficiency (ferritin lower than 100 ng/mL or transferrin saturation less than 20%) r43r92r93
      • Consider IV iron replacement to reduce risk of heart failure hospitalization in symptomatic heart failure patients with reduced or mildly reduced ejection fraction and iron deficiency (ferritin lower than 100 ng/mL or transferrin saturation less than 20%) r43r92
      • 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 r94
        • 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 r94
    • Chronic kidney disease r95c259c260d10
      • Complex interplay between heart and kidney whereby dysfunction in 1 organ can induce or worsen dysfunction in the other r95
        • 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 r41
      • Decline of renal function may be slower with angiotensin receptor–neprilysin inhibitors compared to angiotensin receptor blockers in patients with preserved ejection fraction r3
      • Sodium-glucose cotransporter-2 inhibitors are also associated with slowing the decline in renal function r3r43
      • Use the mineralocorticoid receptor antagonist finerenone in patients with type 2 diabetes and chronic kidney disease to prevent heart failure hospitalizations r43
    • Chronic obstructive pulmonary disease c261
      • 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 c262c263
      • 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 r96
      • 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 c264
      • Most patients with heart failure also have hyperlipidemia
      • Statin therapy has not been shown to improve symptoms of heart failure r97
      • Statin therapy is recommended according to current guidelinesr98r99 for prevention of atherosclerotic cardiovascular disease; not recommended routinely for heart failure in the absence of other indications r47
    • Sleep disturbances c265
      • Common owing to orthopnea, paroxysmal nocturnal dyspnea, and nocturnal diuresis associated with diuretic use
      • In addition, obstructive sleep apnea has been noted in approximately one-third of patients with chronic heart failure r100
      • 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 r79
        • 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 r101
    • Pregnant patients r2
      • Pregnancy is generally well tolerated in patients with cardiomyopathy and New York Heart Association class 1 heart failure prepregnancy, but provide contraceptive counseling and preconception counseling regarding risks of decompensation
      • Avoid ACE inhibitors, angiotensin receptor blockers, angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, sodium-glucose cotransporter-2 inhibitors, ivabradine, and vericiguat during pregnancy owing to risk of fetal harm
      • Owing to hypercoagulability of pregnancy and with stasis due to poor ejection fraction, consider anticoagulation during pregnancy through 6 to 8 weeks postpartum in patients who have peripartum cardiomyopathy and left ventricular ejection fraction less than 30%
    • Black populations
      • Age of onset of heart failure is significantly younger in Black populations compared with White populations r10
      • Heart failure in Black populations is less likely due to ischemia and more likely due to hypertension compared with White populations r10
      • 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% in patients aged 70 years and older r10
      • 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 r10
      • 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 r10
    • Monitor electrolyte levels and renal function test results c266c267
      • At least every 6 months in clinically stable patients r10
        • Monitor more frequently if aldosterone antagonists or high-dose diuretics are used, if drug therapies are changed, or if clinical status declines r10
    • 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 c268
      • 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
          • Do not initiate eplerenone 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 r10r102c269
    • Malignant ventricular arrhythmias r102c270
      • Sustained ventricular tachycardia occurs in up to 10% of patients with advanced heart failure r102c271
      • Electrolyte disturbances, prolonged QT interval, digoxin toxicity, and myocardial ischemia are often precipitating factors for ventricular arrhythmias
    • Atrial fibrillation r102c272
      • Considered both a cause and a consequence of heart failure; present in approximately one-third of patients with heart failure r102
      • 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 r102c273
      • Annual incidence in patients with heart failure is 2% r102
      • 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 r102

    Prognosis

    • For acute decompensated heart failure
      • Prognosis of patients hospitalized with heart failure, and especially those with serial readmissions, is poor; an estimated almost 3% of patients die during hospitalization and 26% of patients die following discharge r103r104
      • Predictors for mortality in acute decompensated heart failure include older age, lower systolic blood pressure, and poor renal function (eg, higher BUN, higher creatinine) r103r104r105r106r107
      • At hospital discharge, higher levels of natriuretic peptides and smaller reduction in levels during hospitalization are correlated with poor prognosis r2r24
      • Numerous multivariable risk models (eg, EFFECTr107, 2003; ADHEREr105, 2005; GWTG-HFr104, 2010 [Get With The Guidelines - Heart Failure]; BIOSTAT-CHFr103, 2017) have been developed to improve prediction of individual prognosis r106
        • Overall, prediction of mortality is better than prediction of readmission r106r108
        • Factors that predict readmission are different from factors that predict mortality r103r106
        • GWTG-HF provides good discrimination for in-hospital mortality; BIOSTAT-CHF predicts all-cause mortality well (median follow up 21 months) r103r104r106
    • 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% r109
      • Although chronic heart failure is usually a progressively worsening condition, patients may remain stable or have improvements in ventricular remodeling with appropriate therapy r10
      • Natriuretic peptide levels correlate with prognosis in chronic heart failure regardless of ejection fraction r24
      • Numerous multivariable risk models (eg, Seattler110, 2006; CHARMr111, 2006; PARADIGMr112, 2020) have been developed to improve prediction of individual prognosis
        • Older models do not reflect current guideline-directed medical therapy
        • Many models share the following risk factors: age, sex, New York Heart Association class, body mass index, diabetes mellitus, systolic blood pressure, and renal function.
    • For preserved ejection fraction r106
      • Patients with heart failure with preserved ejection fraction have distinct clinical characteristics, but less is known regarding prognosis specific to this subpopulation than for patients with heart failure as a whole or patients with reduced ejection fraction
        • Multivariable risk models such as I-PRESERVE (for chronic heart failure with preserved ejection fraction; 2011) and ARIC (for acute hospitalization of patients with heart failure with preserved ejection fraction; 2017) have been developed to compensate r106

    Screening and Prevention

    Screening c274

    Prevention

    • All adults are recommended to follow American College of Cardiology Foundation/American Heart Association guidelines for primary prevention of cardiovascular disease r113
      • Consume a healthy diet and engage in regular physical activity c275c276
      • Smoking cessation c277
      • Weight loss if overweight or obese c278
      • Interventions (nonpharmacologic or pharmacologic) to reduce blood pressure if elevated c279
      • 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 c280
      • Control dyslipidemia with statins c281
      • For patients with diabetes, control hyperglycemia and consider sodium-glucose cotransporter-2 inhibitors to further reduce risk of heart failure c282
      • For obese patients, advise and assist with weight loss c283c284
      • For tobacco users, advise and assist with cessation c285
      • For alcohol users, advise and assist with moderation or cessation c286
      • Avoid known cardiotoxic agents (eg, cocaine, antineoplastic drugs, ephedra, cobalt, anabolic steroids, chloroquine, clozapine, amphetamines, methylphenidate, catecholamines) c287
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