Heart Failure

History

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

Physical examination

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

Causes

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

Risk factors and/or associations

Primary diagnostic tools

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

Laboratory

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

Imaging

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

Functional testing

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

Procedures

Other diagnostic tools

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

Most common

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

Admission criteria

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

Specific heart failure admission indications include: ^r11

• Evidence or suspicion of acute coronary syndromes
• Respiratory distress and/or pulmonary edema
• Hemodynamically significant arrhythmias
• Syncope or symptomatic hypotension
• Worsening renal function
• Altered mentation

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

Drug therapy ^c147c148

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

Nondrug and supportive care

Dietary recommendations

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

Exercise

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

General recommendations

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

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

Comorbidities

• Hypertension ^c206c207
  • In the Framingham study, 91% of patients with incident heart failure had underlying hypertension ^r50
  • Control of hypertension is important for all patients with heart failure and is the primary management strategy for those with preserved ejection fraction ^r2
  • Treatment goals ^r51
    • In patients at increased risk for heart failure (stage A heart failure), blood pressure of less than 130/80 mm Hg is optimal in those with hypertension as a novel strategy to prevent progression to symptomatic heart failure ^r51
    • For patients who have heart failure with reduced ejection fraction and hypertension, prescribe guideline-directed management and titrate therapy to attain systolic blood pressure less than 130 mm Hg ^r51
      • This is a threshold now associated with improved clinical outcomes but not yet proven by randomized clinical trials in a population with heart failure
    • For patients who have heart failure with preserved ejection fraction and persistent hypertension after management of volume overload, prescribe guideline-directed management and titrate therapy to attain systolic blood pressure less than 130 mm Hg ^r51
  • For patients in all stages of heart failure with reduced ejection fraction, antihypertensive therapy with a diuretic (if required for volume overload), an ACE inhibitor/angiotensin receptor blocker or angiotensin receptor–neprilysin inhibitor, and a β-blocker is recommended based on high-quality, randomized controlled data ^r2r52
    • Second line agents (mineralocorticoid receptor antagonists or hydralazine) are added as required
    • Avoid nondihydropyridine calcium channel blockers and α-blockers ^r36
  • For patients who have heart failure with preserved ejection fraction, β-blockers, ACE inhibitors, angiotensin receptor blockers, and possibly angiotensin receptor–neprilysin inhibitors are reasonable choices to manage blood pressure ^r2
• Diabetes ^c208c209
  • Risk factor for, and common comorbidity of, heart failure
    • Each condition independently increases risk for the other
    • Patients with diabetes without symptomatic heart failure often have subclinical abnormalities of cardiac structure and function
  • Having both conditions is associated with worse clinical outcomes
    • Health-related quality of life is worse than for patients with heart failure alone ^r53r54
    • Higher risk of hospitalization (up to 50% higher)^r55 and rehospitalization^r56 with diabetes
    • Diabetes increases mortality risk in both ambulatory and hospitalized patients with heart failure ^r57
      • Overall mortality risk is similar risk for both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction
      • Cardiovascular mortality risk is higher for patients with diabetes and heart failure with preserved ejection fraction as compared to heart failure with reduced ejection fraction ^r58r59
  • Management of heart failure in diabetes
    • Based on benefit in patients who have heart failure with reduced ejection fraction (regardless of diabetes status), these therapies should routinely be implemented in patients with diabetes and heart failure with reduced ejection fraction who meet guideline indications: ^r57
      • Renin-angiotensin-aldosterone system inhibitors
      • Angiotensin receptor–neprilysin inhibitors
      • β-Blockers
      • Ivabradine
      • Implantable cardioverter-defibrillators and cardiac resynchronization therapy
  • Management of diabetes in heart failure
    • Consider glycemic goals and the impact of heart failure medications on glycemic control
      • Moderate, rather than intensive, glycemic control may be optimal for patients with diabetes and heart failure
        • U-shaped relationship between mortality and hemoglobin A1C in patients with heart failure (lowest risk of death with modest glucose control and hemoglobin A1C of 7.1% to 7.8%) ^r60
        • Recommend target hemoglobin A1C of 7% to 8% for most patients with heart failure and diabetes ^r57
        • Less stringent goals may be appropriate for patients with advanced stage D heart failure not pursuing mechanical circulatory support or transplant ^r57
      • ACE inhibitors, angiotensin receptor blockers, and angiotensin receptor–neprilysin inhibitors have favorable effects on the development of diabetes mellitus and glycemic control in patients with heart failure with reduced ejection fraction ^r57
      • Spironolactone may modestly worsen glycemic control in patients with diabetes mellitus and heart failure with reduced ejection fraction ^r57
      • Carvedilol may be preferable to metoprolol succinate and bisoprolol for patients with heart failure with reduced ejection fraction and diabetes mellitus with poor glycemic control ^r57
    • Management of type 1 diabetes in patients with heart failure is same as for patients without heart failure
    • In patients with type 2 diabetes, consider the effect of specific glucose-lowering pharmacotherapies on cardiovascular outcomes ^r61r62
      • In patients at high risk for heart failure and those with established heart failure, metformin and sodium-glucose cotransporter-2 inhibitors are preferable to use over sulfonylurea drugs ^r57
        • Metformin
          • First line treatment for most patients with type 2 diabetes ^r63
          • Reduced mortality and a small reduction in all-cause hospitalization in patients with heart failure compared with control subjects
          • Lower risk of heart failure hospitalization than with sulfonylurea drugs
        • Sodium-glucose cotransporter-2 inhibitors
          • First class of glucose-lowering agents demonstrated to reduce heart failure symptoms, risk of heart failure hospitalization, and death in patients with diabetes, with and without established diagnosis of heart failure at baseline ^r64r65r66
          • Empagliflozin, canagliflozin, and dapagliflozin are recommended for treatment of type 2 diabetes in patients with known atherosclerotic cardiovascular disease, patients older than 50 years with additional risk factors for atherosclerotic heart disease, and those with mild-moderate heart failure with reduced ejection fraction ^{r38r65r67r68r69r70}
            • Also recommended in patients without type 2 diabetes who have mild to moderate heart failure with reduced ejection fraction as associated with reduced symptoms, hospitalizations, and cardiac mortality ^r38r71
          • Cardiovascular benefit must be balanced with potential risks, including genital candidiasis and other rare potential complications (ie, euglycemic diabetic ketoacidosis, lower-limb amputation, fractures associated with canagliflozin)
      • Insulin may be considered; use with caution and close monitoring only if adequate glycemic control cannot be achieved with metformin and sodium-glucose cotransporter-2 inhibitors; associated with weight gain and increased risk of hypoglycemia ^r57r62
      • Glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase-4 inhibitors sitagliptin and linagliptin have a neutral effect on heart failure. Do not use dipeptidyl peptidase-4 inhibitor saxagliptin in patients with established heart failure or those at high risk for heart failure ^r57r62
        • Use glucagon-like peptide 1 receptor agonists with caution in patients who have heart failure with reduced ejection fraction and recent decompensation. There are no data to guide use of these medications in heart failure with preserved ejection fraction ^r57
      • Thiazolidinediones are not recommended for patients with established heart failure; both rosiglitazone and pioglitazone are associated with fluid retention and heart failure events ^r57r62
• Atrial fibrillation ^r2c210c211
  • Heart failure and atrial fibrillation have a bidirectional association, share many of the same risk factors, and frequently complicate each other
  • Heart failure with atrial fibrillation is associated with worse outcomes, including increase in stroke severity and all-cause mortality. Female patients have worse outcomes than male patients ^r72
  • Best treatment strategies for patients with heart failure and atrial fibrillation are uncertain ^r73
    • Approach (rate control versus restoration of sinus rhythm) may be individualized depending on whether atrial fibrillation is resulting from or contributing to progression of underlying cardiac failure ^r74
      • Recent data suggest that early rhythm control (atrial fibrillation present for less than 1 year) in high-risk patients, including those with heart failure, may be beneficial in reducing composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome ^r75
    • Rate control is typically accomplished with β-blockers in patients with heart failure
      • Nondihydropyridine calcium channel blockers are contraindicated in patients with left ventricle systolic dysfunction but are reasonable when systolic function is preserved ^r76
      • Digoxin has been associated with increased mortality risk in patients with atrial fibrillation and patients with heart failure when used in high doses ^r77r78r79
    • Atrial Fibrillation and Congestive Heart Failure Trial showed that pharmacologic rhythm control is not superior to rate control strategy for preventing cardiac death. Consider rhythm control strategy for patients who remain symptomatic despite rate control alone ^r80
      • Pharmacologic rhythm control options are limited to amiodarone and dofetilide in heart failure with reduced ejection fraction ^r76
    • Catheter ablation (pulmonary vein isolation) may be superior to both pharmacologic rate and rhythm control in patients with both heart failure and atrial fibrillation
      • CASTLE-AF trial (Catheter Ablation versus Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation) results showed that, for patients with heart failure with reduced ejection fraction, atrial fibrillation catheter ablation was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure ^r81
      • Catheter ablation appears to be similarly effective for atrial fibrillation (eg, freedom from recurrent atrial arrhythmia, improvements in New York Heart Association functional class, symptom severity) in both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction ^r82
      • For the overall population, results from CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation)^r83r84 do not show improved survival with catheter ablation; detailed analysis of heart failure subgroup in the trial is ongoing and will add additional information ^r73
    • Atrioventricular nodal ablation and cardiac resynchronization device placement can be useful if other methods fail ^r2
  • Anticoagulation is typically indicated for the prevention of thromboembolic complications based on CHA₂DS₂-VASc scoring system ^r36
• Coronary artery disease ^c212
  • Present in approximately two-thirds of patients with heart failure
  • Evaluate patients with heart failure with reduced ejection fraction for coronary artery disease and treat accordingly
  • β-Blockers, nitrates, and ACE inhibitors are used to treat both heart failure and ischemic heart disease ^r85
  • Revascularization may be considered ^r36
• Anemia ^c213
  • Often normocytic and accompanied by an abnormally low reticulocyte count ^r86
  • Associated with an increased risk of hospitalization and mortality and decreased exercise capacity and quality of life
  • Correct any specific underlying cause (eg, iron, vitamin B₁₂, folate deficiency)
  • In symptomatic patients with ejection fraction 45% or less and iron deficiency (ferritin lower than 100 ng/mL or 100-300 ng/mL if transferrin saturation is less than 20%), consider IV iron replacement to improve functional status and quality of life ^r9r87r88
  • In symptomatic heart failure patients recently hospitalized for heart failure and with ejection fraction less than 50% and iron deficiency (serum ferritin less than 100 ng/mL or serum ferritin of 100-299 ng/mL with transferrin saturation less 20%), consider IV iron replacement to reduce risk of heart failure hospitalization ^r9r88
  • Patients with heart failure and symptomatic anemia may require RBC transfusion; in patients without symptoms due to anemia, a restrictive transfusion strategy (at hemoglobin levels of 7-8 g/dL) is recommended ^r89
    • Care must be taken to monitor volume status and avoid overload when transfusion is administered
  • Do not use erythropoietin-stimulating agents to improve morbidity and mortality in patients with anemia and heart failure ^r89
• Chronic kidney disease ^r90c214c215
  • Complex interplay between heart and kidney whereby dysfunction in 1 organ can induce or worsen dysfunction in the other ^r90
    • Chronic heart failure resulting in chronic kidney disease is described as chronic cardiorenal syndrome
    • Chronic kidney disease resulting in chronic heart failure is described as chronic renocardiac syndrome
  • GFR is reduced in most patients with advanced heart failure
  • Reduced renal function is strongly prognostic of poor outcome
  • Avoid treatment with nephrotoxic agents ^r36
• Chronic obstructive pulmonary disease ^c216
  • Present in approximately one-third of patients with heart failure
  • Associated with poorer functional status and prognosis
  • β-Blockers may exacerbate bronchospasm; oral corticosteroids can lead to sodium and fluid retention and thus worsen congestive symptoms
• Depression ^c217c218
  • Major depression is common in patients with heart failure during hospitalization and is often not recognized
  • Associated with nonadherence to heart failure therapy and worse prognosis ^r91
  • Avoid tricyclic antidepressants in patients with heart failure owing to association with cardiovascular adverse effects; selective serotonin reuptake inhibitors are a safer alternative for these patients
• Hyperlipidemia ^c219
  • Most patients with heart failure also have hyperlipidemia
  • Statin therapy has not been shown to improve symptoms of heart failure ^r92
  • Statin therapy is recommended according to current guidelines^r93 for prevention of atherosclerotic cardiovascular disease; not recommended routinely for heart failure in the absence of other indications ^r40
• Sleep disturbances ^c220
  • Common owing to orthopnea, paroxysmal nocturnal dyspnea, and nocturnal diuresis associated with diuretic use
  • In addition, obstructive sleep apnea has been noted in about one-third of patients with chronic heart failure ^r94
  • In patients with New York Heart Association class II through IV heart failure who are suspected to have sleep disordered breathing or excessive daytime sleepiness, consider formal sleep assessment ^r2
  • In patients with cardiovascular disease and obstructive sleep apnea, consider CPAP to improve sleep quality and alleviate daytime sleepiness ^r2

Special populations

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