History

• Common symptoms of heart failure include:
  • Dyspnea ^r2c1
    • Dyspnea on exertion; dyspnea at rest often occurs in advanced heart failure ^c2c3c4
    • Orthopnea ^c5
    • Paroxysmal nocturnal dyspnea ^c6
  • Fatigue ^r2c7
    • Exercise intolerance ^c8
    • Increased recovery time from activity
  • Peripheral edema ^r6c9
    • Ankle swelling ^c10
  • Ascites causing any of the following: ^r6c11
    • Anorexia ^c12
    • Early satiety ^c13
    • Gastrointestinal discomfort ^c14
    • Increased abdominal girth ^c15
    • Scrotal swelling ^c16
  • Change in weight ^r6c17
    • 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 ^r6c20
  • Confusion, especially in elderly people ^r7c21
  • Palpitations ^r8c22
  • Syncope ^r6c23
• 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: ^r2r6r8
  • 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): ^r2r6r8
  • 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 ^r6r7
  • Hypertension is the single most important modifiable cause of heart failure ^r2c38
  • Risk increases 8- to 10-fold after myocardial infarction ^r6c39
  • Patients with heart failure with preserved ejection fraction (usually older and female) more commonly have hypertension and less commonly have coronary artery disease ^c40c41
  • 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 ^c42
    • Predominantly mitral and aortic valve disease (eg, mitral regurgitation, aortic stenosis, aortic regurgitation) ^{r9c43c44c45c46c47}
  • Cardiomyopathies ^c48
    • Idiopathic dilated cardiomyopathy ^r2c49
      • 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) ^r2
    • Familial cardiomyopathy ^c50
      • 2 closely related family members must meet criteria for idiopathic cardiomyopathy ^r2
      • 20% to 35% of presumed idiopathic cardiomyopathies are now recognized as familial ^r2
    • Toxic cardiomyopathy ^c51
      • Heart failure may result from toxic effect on cardiac preload, cardiac afterload, or myocardial contractility ^r10
      • Heart failure may be reversible (eg, secondary to propofol), irreversible (eg, secondary to doxorubicin), or either (eg, secondary to cyclophosphamide) ^r10c52c53c54
      • Cardiotoxic cancer chemotherapies, particularly anthracyclines, can cause structural changes ^c55
        • 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 ^c56c57
      • Cardiomyopathy may be caused by other drugs, many with misuse potential (eg, ephedra, anabolic steroids, amphetamines, methylphenidate)
    • Inflammatory cardiomyopathy ^c58
      • Immune-mediated inflammatory myocarditis ^c59
        • Hypersensitivity to medication (eg, sulfonamides, penicillin, methyldopa, amphotericin B, streptomycin, phenytoin, isoniazid, tetanus toxoid, hydrochlorothiazide, dobutamine, chlorthalidone) ^{c60c61c62c63c64c65c66c67c68}
        • Autoimmune disorders (eg, systemic lupus erythematosus, scleroderma, sarcoidosis) ^c69c70c71c72
      • Infective inflammatory myocarditis ^c73
        • Most commonly of viral origin but also can be caused by other pathogens
        • Commonly occurs in patients with HIV infection
    • Metabolic/endocrine cardiomyopathy ^c74c75
      • 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 ^c76c77c78
    • Infiltration cardiomyopathy ^c79
      • Caused by malignancy or amyloidosis
    • Iron overload cardiomyopathy ^c80
      • 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 ^c81
      • Left ventricular dysfunction occurs typically in third trimester of pregnancy or in immediate postpartum period
      • Incidence varies from 0.2% to 3% of live births worldwide, depending on region ^r11
      • Prognosis is directly related to degree of recovery to near baseline left ventricular function; if cardiomegaly lasts for more than 6 months, the 6-year mortality rate is 50% ^r2
    • Tachycardia-related cardiomyopathy ^c82
      • Left ventricular myocardial dysfunction correlates with duration of tachycardia and magnitude of increased ventricular rate
      • Generally reversible with rate control
    • Stress cardiomyopathy (takotsubo cardiomyopathy) ^c83c84
      • 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 women

Risk factors and/or associations

Primary diagnostic tools

• Diagnosis is suspected based on thorough history and physical examination ^r2r6r8c107
• Obtain chest radiograph in acutely dyspneic patients to identify pulmonary edema. In nonacute diagnostic settings, chest radiograph is also recommended to detect or exclude alternative causes of symptoms ^r2r6r8
• Obtain ECG as part of initial evaluation in all patients ^r2r5r8c108
• Obtain laboratory testing
  • All patients ^r2r6r8
    • Electrolyte levels, BUN and creatinine levels, and urinalysis (important for treatment decisions) ^c109c110c111
    • Liver function tests
    • Fasting lipid levels and fasting glucose level to assess cardiovascular risk factors
    • CBC and TSH level to exclude anemia and thyroid disease (as a cause or exacerbating factor of heart failure) ^c112c113
    • B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide ^c114
      • 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) ^r6r16r17
      • When making an 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 an initial working diagnosis, identifying those who require further cardiac investigation. If values are below the cut point, echocardiography is not needed ^r3
      • During hospitalization for heart failure, measure predischarge natriuretic peptide level to help establish a postdischarge prognosis ^r17
  • 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 ^r17
• Obtain transthoracic 2-dimensional echocardiogram with Doppler flow studies for all patients with suspected heart failure, per 2013 American College of Cardiology Foundation/American Heart Association guideline for management of heart failure and the 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of heart failure ^r2r5
  • 2016 European Society of Cardiology guidelines recommend transthoracic echocardiogram as part of the initial diagnostic evaluation only if B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide are elevated ^r3
• Consider cardiac MRI if echocardiographic images are inadequate ^r3
• Noninvasive (myocardial perfusion/ischemia imaging) and/or invasive (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 ^r6r8r18
• 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

Laboratory

• Routine laboratory tests ^r2r6r8
  • Obtain on presentation to assist in determining causes of heart failure, identifying risk factors, and assessing baseline kidney function
    • Comprehensive metabolic panel ^c115
      • Electrolyte, magnesium, calcium, BUN, and creatinine levels ^{c116c117c118c119c120}
      • Elevated liver enzyme levels may be due to hepatic congestion or dysfunction ^c121
    • Fasting blood glucose level ^c122
      • Diabetes is a common comorbidity and risk factor for heart failure
    • Fasting lipid profile ^c123
      • To assess risk for coronary artery disease and metabolic syndrome
    • TSH level ^c124
      • Thyroid disease may mimic, aggravate, or cause heart failure
    • CBC ^c125
      • Anemia may cause or exacerbate heart failure
    • Urinalysis ^c126
• Cardiac biomarker tests ^r19
  • Natriuretic peptide levels ^c127c128
    • 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 ^r8r16
      • 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 ^r20
    • Note that obese patients may have falsely low natriuretic peptide levels
  • Cardiac troponin T or I levels ^{c129c130c131c132}
    • 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 ^r2r6r8c133
  • Indicated for suspected new-onset heart failure and acute decompensated heart failure
  • 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 a 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 ^r2r7r8c134
  • Perform 12-lead ECG initially on all patients presenting with symptoms of heart failure
  • Less than 2% of 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 primarily is performed to identify those patients and to detect other abnormalities that may need investigation or treatment ^r8
  • 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 ^r21r22c135
  • 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 the 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 ^r7r8
    • 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: ^r23
      • Normal or near normal ejection fraction (50% or higher)
      • Abnormal mitral inflow
      • Increased atrial volume
      • Increased left ventricular mass
• Cardiac MRI ^r2r7r8c136
  • Alternative to echocardiography for assessing left ventricular volume and ejection fraction; may be used if echocardiography is not diagnostic
  • Provides 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
  • Limitations include:
    • Lack of availability
    • Cost
    • Contraindications, including metal implants or severe kidney disease, which precludes use of contrast solution

Procedures

Most common

• Conditions that cause dyspnea ^r25
  • Chronic obstructive pulmonary disease ^r26c141d1
    • 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
    • Diagnosed by: spirometry shows decreased pulmonary function; chest radiography may show diaphragm flattening, increased retrosternal air space, and/or bronchovascular markings
    • Chronic obstructive pulmonary disease may coexist with heart failure
  • Asthma ^c142d2
    • 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
    • Diagnosed by: spirometry with postbronchodilator response; chest radiography may show hyperinflation
  • Pulmonary embolism ^r27c143d3
    • 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
    • Diagnosed by: CT angiography detects pulmonary emboli; D-dimer levels are elevated
  • Myocardial infarction ^r28c144d4
    • Myocardial necrosis resulting from occlusion of a coronary artery
    • Similar features: dyspnea and fatigue
    • Differing features: retrosternal chest pain and/or pressure (radiating to neck, jaw, shoulder, and/or arm) is typical; atypical presentation without chest pain may occur in women, elderly people, and those with diabetes
    • Diagnosed by: ECG shows ST elevation, ST depression, or T-wave inversion; cardiac troponin levels are elevated
  • Pneumonia ^c145
    • 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
    • Diagnosed by: chest radiography shows lobar or lobular consolidation; viral or atypical bacterial pneumonias often appear as interstitial infiltrates
  • Acute respiratory distress syndrome ^c146d5
    • 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
    • Diagnosed by: 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, and respiratory failure or pulmonary edema not fully explained by heart failure or fluid overload
• Conditions that cause edema ^r25
  • Cirrhosis ^c147d6
    • Irreversible liver disease caused by long-term excessive alcohol intake or viral hepatitis
    • 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
    • Diagnosed by: abdominal sonography or other abdominal imaging shows liver nodularity and features of portal hypertension; definitive diagnosis is by liver biopsy
  • Nephrotic syndrome ^c148
    • 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
    • Diagnosed by: 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 ^r2

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:

• Evidence or suspicion of acute myocardial ischemia or infarction
• Respiratory distress and/or pulmonary edema
• Significant arrhythmias
• Syncope or symptomatic hypotension
• Significant electrolyte abnormalities
• Anasarca
• Thromboembolic complications requiring inpatient treatment
• Severe comorbidities

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 elderly patients with multiple comorbidities
• Palliative care specialist for end-of-life decisions

Drug therapy ^c149c150

• ACE inhibitors ^r8c151
  • Enalapril ^c152
    • Enalapril Maleate Oral tablet; Adults: Initially, 2.5 mg PO twice daily. Reduce initial dose to 2.5 mg PO once daily in patients with hyponatremia. Increase dose as tolerated, adjusting to clinical response of patient up to Max: 10 to 20 mg PO twice daily.
  • Lisinopril ^c153
    • Lisinopril Oral tablet; Adults: Initially, 2.5 to 5 mg PO once daily. Increase dose as tolerated, adjusting to clinical response of patient up to Max: 20 to 40 mg/day.
  • Captopril ^c154
    • Captopril Oral tablet; Adults: Initially, 6.25 mg PO 3 times daily. Increase dose as tolerated, adjusting to clinical response of patient up to Max: 50 mg PO 3 times daily.
• Angiotensin receptor blockers ^r8c155
  • Candesartan ^c156
    • Candesartan Cilexetil Oral tablet; Adults: Initially, 4 to 8 mg PO once daily. Increase dose as tolerated, adjusting to clinical response of patient up to Max: 32 mg/day.
  • Losartan ^c157
    • Losartan Potassium Oral tablet; Adults: Initially, 25 to 50 mg PO once daily. Increase dose as tolerated, adjusting to clinical response of patient up to Max: 50 to 150 mg/day.
  • Valsartan ^c158c159
    • Valsartan Oral tablet; Adults: Initially, 20 to 40 mg PO twice daily. Increase dose as tolerated, adjusting to clinical response of patient up to up to Max: 160 mg PO twice daily.
• Angiotensin receptor–neprilysin inhibitor ^r8
  • Sacubitril-valsartan ^c160
    • Sacubitril, Valsartan Oral tablet; Adults: 24 mg sacubitril; 26 mg valsartan PO twice daily in patients not taking or on a low dose of an ACE inhibitor or ARB. 49 mg sacubitril; 51 mg valsartan PO twice daily in patients taking a high dose of an ACE inhibitor or ARB. Double the dose every 2 to 4 weeks as tolerated to a target dose of 97 mg sacubitril; 103 mg valsartan PO twice daily.
• β-blockers ^r8c161c162
  • Bisoprolol ^c163c164
    • Bisoprolol Fumarate Oral tablet; Adults: Initially, 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 ^c165c166
    • Carvedilol Oral tablet; Adults: Initially, 3.125 mg PO twice daily for 2 weeks. Increase dosage to 6.25, 12.5, and then 25 mg PO twice daily over intervals of at least 2 weeks as tolerated. Max: 50 mg PO twice daily. Reduce dose for bradycardia.
  • Metoprolol succinate ^c167c168
    • Metoprolol Succinate Oral tablet, extended-release; Adults: Initially, 25 mg PO once daily in patients with NYHA class II heart failure or 12.5 mg PO once daily in patients with more severe heart failure. Double the dose every 2 weeks as tolerated, up to target dosage of 200 mg PO once daily.
• Aldosterone receptor antagonists ^r8c169
  • Eplerenone ^c170
    • Eplerenone Oral tablet; Adults: Initially, 25 mg PO once daily. Increase dosage to 50 mg PO once daily as tolerated within 4 weeks. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Monitor serum potassium at baseline, within first week, and at 1 month after dosage initiation or adjustments; monitor more frequently in at-risk patients. If serum potassium 5.5 mEq/L or more, decrease dosage. Hold if serum potassium 6 mEq/L or more; may restart at 25 mg PO every other day once serum potassium less than 5.5 mEq/L.
  • Spironolactone ^c171
    • Spironolactone Oral tablet; Adults: Initially, 12.5 to 25 mg PO once daily. May reduce dosage to 25 mg PO every other day if hyperkalemia occurs with 25 mg PO once daily. May increase dosage to 50 mg/day, if clinically indicated and lower dose tolerated.
• Loop diuretics ^r8c172
  • Furosemide ^c173
    • Furosemide Oral tablet; Adults: Initially, 20 to 80 mg PO as a single dose; may repeat dose in 6 to 8 hours. Usual dose: 40 to 120 mg/day. Max: 600 mg/day.
    • Furosemide Solution for injection; Adults: Initially, 40 mg IV injected slowly. May give 80 mg injected slowly in 2 hours if needed.
  • Bumetanide ^c174c175
    • Bumetanide Oral tablet; Adults: 0.5 to 1 mg PO daily initially. Multiple daily doses may be given at 4 to 5 hour intervals if the initial diuretic response is not adequate. Max: 10 mg/day.
    • Bumetanide Solution for injection; Adults: 0.5 to 1 mg IV or IM initially. If the desired response is not achieved, administer a second or third dose at 2 to 3 hour intervals. Max: 10 mg/day.
  • Torsemide
    • Torsemide Oral tablet; Adults: Initially, 10 to 20 mg PO once daily. If needed, titrate by doubling the dose up to a maximum of 200 mg.
• Thiazide diuretics ^r8c176
  • Hydrochlorothiazide ^c177
    • Hydrochlorothiazide Oral tablet; Adults: 25 to 100 mg/day PO given in single or divided doses. Many patients respond to intermittent therapy (e.g., every other day or 3 to 5 days each week).
  • Indapamide ^c178c179
    • Indapamide Oral tablet; Adults: Initially, 2.5 mg PO once daily. May increase dosage up to 5 mg PO once daily after 1 week if response is inadequate. Doses greater than 5 mg have not appeared to provide additional benefits and are associated with greater degree of hypokalemia.
  • Metolazone ^c180
    • Metolazone Oral tablet; Adults: 5 to 20 mg PO once daily.
• Vasodilators ^r8c181
  • Hydralazine ^c182
    • Hydralazine Hydrochloride Oral tablet; Adults: Initially, 25 to 50 mg PO 3 to 4 times daily. Dosage may be increased weekly (e.g., by 25 mg/dose) to Max: 100 mg PO 3 times daily.
  • Isosorbide dinitrate ^c183
    • Isosorbide Dinitrate Oral tablet; Adults: Initially, 20 to 30 mg PO 3 to 4 times daily. Titrate dose at weekly intervals up to Max: 40 mg PO 3 times daily.
  • Nitroglycerin ^c184
    • Nitroglycerin Solution for injection; Adults: Initially, 5 mcg/minute continuous IV infusion. Titrate by 5 mcg/minute IV every 3 to 5 minutes until clinical response, or to a dose of 20 mcg/minute IV. May further increase dosage in increments of 10 mcg/minute, and if desired effect still not achieved, may increase in increments of 20 mcg/minute. Max titration: 20 mcg/minute every 3 to 5 minutes. Usual dose: 5 to 100 mcg/minute. Max: 200 mcg/minute.
  • Nitroprusside ^c185
    • 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.
  • Nesiritide ^c186
    • No longer routinely used for acute decompensated heart failure in the United States
    • Should not be used before traditional nitrates except by intensive care cardiologists familiar with potentially adverse hemodynamic effects
    • Nesiritide (E. coli) Solution for injection; Adults: 2 mcg/kg IV followed by 0.01 mcg/kg/minute continuous IV infusion. May titrate up no more frequently than every 3 hours. Max: 0.03 mcg/kg/minute. Loading dose may not be appropriate for patients with low systolic blood pressure or patients recently treated with afterload reducers. If hypotension occurs, reduce dose or discontinue nesiritide. May restart at a dose that is reduced by 30% (with no bolus administration) after stabilization of hemodynamics. Limited experience with use for longer than 96 hours.
• Hyperpolarization-activated cyclic nucleotide–gated channel blocker ^r8c187c188
  • Ivabradine ^c189
    • Ivabradine Oral tablet; Adults: 5 mg PO twice daily initially. Start at 2.5 mg PO twice daily in patients with conduction defects or in those whom bradycardia could lead to hemodynamic compromise. After 2 weeks, adjust dose to achieve resting heart rate of 50 to 60 bpm. For resting heart rate more than 60 bpm, increase dose by 2.5 mg PO twice daily. For resting heart rate of 50 to 60 bpm, maintain current dose. For a resting heart rate less than 50 bpm or symptomatic bradycardia, decrease dose by 2.5 mg PO twice daily; if current dose is 2.5 mg PO twice daily, discontinue therapy. After that, adjust dose as needed based on resting heart rate and tolerability. Max: 7.5 mg PO twice daily.
• Digitalis glycoside ^r8c190
  • Digoxin ^c191
    • Digoxin Oral tablet; Adults, Adolescents, and Children older than 10 years: Initially, 3.4 to 5.1 mcg/kg/day PO given once daily. Usual daily maintenance dose requirements for the treatment of congestive heart failure are based on corrected CrCl (mL/minute per 70 kg or mL/minute/1.73m2) and lean body weight (LBW). Doses are rounded to the nearest whole/half tablet. According to the Beers Criteria, digoxin should be avoided as first-line therapy for atrial fibrillation or heart failure; if use is necessary, the drug should not be prescribed in daily doses greater than 0.125 mg.
• Inotropic agents ^r8c192
  • Dopamine ^c193
    • 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 ^c194
    • Dobutamine Hydrochloride Solution for injection; Adults: 0.5 to 1 mcg/kg/minute continuous IV infusion; titrate to clinical response. Usual dosage range: 2 to 20 mcg/kg/minute. Max: 40 mcg/kg/minute.
  • Milrinone ^c195
    • Milrinone Lactate Solution for injection; Adults: 50 mcg/kg IV load, 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 ^r37
  • Ensure adequate intake of macro and micronutrients
  • Recommend DASH (dietary approaches to stop hypertension) or Mediterranean style diet of patients of normal weight ^r38
  • Recommend weight loss of 5% to 10% for patients with BMI 35 kg/m² or higher
  • Aim for protein intake of at least 1.1g/kg/day for patients with malnutrition or cachexia (develops in 10%-20% of patients with heart failure)
• American College of Cardiology Foundation/American Heart Association guideline recommends: ^r2c196c197
  • Restrict sodium to 1500 mg/day or less for patients with stage A and B 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 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 ^r39
  • 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 ^r40
  • High-dose marine omega-3 supplements are recommended for patients with congestive heart disease who are taking statins who and have elevated triglycerides ^r40

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 ^r38
• In adults with chronic heart failure with reduced ejection fraction, evidence suggests that exercise training (eg, cardiac rehabilitation) reduces all-cause hospitalizations, reduces hospitalizations due to heart failure in the short term, improves quality of life, and reduces long-term mortality. ^r17r41

General recommendations

• Order careful intake and output measurements in acute care setting ^c198
• 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 gain in 1 week of 2.3 kg or more ^c199
• Advise and assist with moderation or elimination of alcohol intake, owing to its negative effect on ventricular systolic function ^c200
• Advise and assist with smoking cessation ^c201d8
  • 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 ^c202c203

Provide patients and caregivers with comprehensive education about heart failure, medication regimens, and lifestyle modifications ^r2r8c204c205

Comorbidities

• Hypertension ^c211c212
  • In the Framingham study, 91% of patients with incident heart failure had underlying hypertension ^r46
  • 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 ^r47
    • In patients at increased risk for heart failure (stage A heart failure), optimal blood pressure in those with hypertension is lower than 130/80 mm Hg as a novel strategy to prevent progression to symptomatic heart failure ^r17
    • For patients who have heart failure with reduced ejection fraction and hypertension, prescribe guideline-directed management and titrate therapy to attain systolic blood pressure lower than 130 mm Hg ^r17
      • 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 lower than 130 mm Hg ^r17
  • 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 II receptor blockers or angiotensin receptor-neprilysin inhibitor, and a β-blocker is recommended based on high-quality, randomized controlled data ^r17r48
    • Second line agents (mineralocorticoid receptor antagonists or hydralazine) are added as required
    • Avoid nondihydropyridine calcium channel blockers and α-blockers ^r31
  • For patients who have heart failure with preserved ejection fraction, β-blockers, ACE inhibitor, angiotensin II receptor blockers, and possibly angiotensin receptor-neprilysin inhibitors are reasonable choices to manage blood pressure ^r17
• Diabetes mellitus ^r2r8c213c214
  • Risk factor for, and common comorbidity of, heart failure
    • Each condition independently increases risk for the other
    • Patients with diabetes mellitus without symptomatic heart failure often have subclinical abnormalities of cardiac structure and function and therefore may be American College of Cardiology/American Heart Association stage B
    • Among patients with heart failure, 46% of those aged 65 years or older have diabetes mellitus; this percentage is even higher in younger patients with heart failure ^r2
  • Having both conditions is associated with worse clinical outcomes
    • Health-related quality of life is worse than for patients with heart failure alone ^r49r50
    • Higher risk of hospitalization (up to 50% higher)^r51 and rehospitalization^r52 with diabetes mellitus
    • Diabetes mellitus increases mortality risk in both ambulatory and hospitalized patients with heart failure ^r53
      • 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 mellitus and heart failure with preserved ejection fraction as compared to heart failure with reduced ejection fraction ^r54r55
  • Management of heart failure in diabetes mellitus
    • Based on benefit in patients who have heart failure with reduced ejection fraction (regardless of diabetes mellitus status), these therapies should routinely be implemented in patients with diabetes mellitus and heart failure with reduced ejection fraction who meet guideline indications: ^r53
      • RAAS inhibitors
      • Angiotensin receptor-neprilysin inhibitors
      • β-blockers
      • Ivabradine
      • Implantable cardioverter-defibrillators and cardiac resynchronization therapy
  • Management of diabetes mellitus 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 mellitus 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%) ^r56
        • Recommend target hemoglobin A1C of 7% to 8% for most patients with heart failure and diabetes ^r53
        • Less stringent goals may be appropriate for patients with advanced, stage D heart failure not pursuing mechanical circulatory support or transplantation ^r53
      • ACE inhibitors, angiotensin II 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 ^r53
      • Spironolactone may modestly worsen glycemic control in patients with diabetes mellitus and heart failure with reduced ejection fraction ^r53
      • 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 ^r53
    • Management of type 1 diabetes mellitus in patients with heart failure is same as for patients without heart failure
    • In patients with type 2 diabetes mellitus, consider the effect of specific glucose-lowering pharmacotherapies on cardiovascular outcomes ^r57r58
      • In patients at high risk for heart failure and those with established heart failure, metformin and sodium glucose cotransporter type 2 inhibitors are preferable to use over sulfonylurea drugs ^r53
        • Metformin
          • First line treatment for most patients with type 2 diabetes mellitus ^r59r60
          • 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 type 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 mellitus, with and without established diagnosis of heart failure at baseline ^r61r62r63
          • 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 ^{r35r62r64r65r66r67}
            • 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 ^r35r62r68
          • Cardiovascular benefit must be balanced with potential risks, including genital candidiasis and other, rare potential complications (ie, euglycemic diabetic ketoacidosis; lower-limb amputation and fractures associated with canagliflozin)
      • Insulin may be considered; should be used with caution and close monitoring only if adequate glycemic control cannot be achieved with metformin and sodium glucose cotransporter type 2 inhibitors; associated with weight gain and increased risk of hypoglycemia ^r53r58
      • Glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase-4 inhibitors sitagliptin and linagliptin have a neutral effect on heart failure ^r58
        • 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 ^r53
      • Thiazolidinediones are not recommended for patients with established heart failure; both rosiglitazone and pioglitazone are associated with fluid retention and heart failure events ^r53r58
      • Do not use dipeptidyl peptidase-4 inhibitor saxagliptin in patients with established heart failure or those at high risk for heart failure ^r53r58
• Atrial fibrillation ^r2r8c215c216
  • 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. Women have worse outcomes than men ^r69
  • Best treatment strategies for patients with heart failure and atrial fibrillation are unclear ^r70
    • 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 ^r71
    • Rate control is typically accomplished with β-blockers in patients with heart failure
      • Non-dihydropyridine calcium-channel blockers are contraindicated in patients with left ventricle systolic dysfunction but are reasonable when systolic function is preserved ^r72
      • Digoxin has been associated with an increase mortality risk in patients with atrial fibrillation and patients with heart failure ^r73
    • The Atrial Fibrillation and Congestive Heart Failure Trial showed that pharmacological rhythm control is not superior to a rate control strategy for preventing cardiac death. Consider a rhythm control strategy for patients who remain symptomatic despite rate control alone ^r74
      • Pharmacologic rhythm control options are limited to amiodarone and dofetilide in heart failure with reduced ejection fraction ^r72
    • Catheter ablation (pulmonary vein isolation) may be superior to both pharmacological rate and rhythm control in patients with both heart failure and atrial fibrillation
      • CASTLE-AF trial 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 ^r75
      • Catheter ablation appears to be similarly effective for atrial fibrillation (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 ^r76
      • For the overall population, results from CABANA trial^r77r78 do not show improved survival with catheter ablation; detailed analysis of the heart failure subgroup in the trial is ongoing and will add additional information ^r70
    • 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 the CHA₂DS₂-VASc scoring system ^r31
• Coronary artery disease ^r2r8c217
  • Present in approximately two-thirds of patients with heart failure ^r2
  • 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 ^r79
  • Revascularization may be considered ^r31
• Anemia ^r2r8c218
  • Present in 25% to 40% of patients with heart failure ^r2
  • Often normocytic and accompanied by an abnormally low reticulocyte count ^r22
  • 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 patients with New York Heart Association class II and III heart failure 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 ^r17r80
  • 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 ^r81
    • 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 ^r17r81
• Chronic kidney disease ^{r2r8r59c219c220}
  • Complex interplay between heart and kidney whereby dysfunction in 1 organ can induce or worsen dysfunction in the other ^r59
    • 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 ^r31
• Chronic obstructive pulmonary disease ^r2r8c221
  • Present in approximately one-third of patients with heart failure ^r2
  • 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 ^r2c222c223
  • Prevalence of 24% to 42%
  • 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 ^r82
  • 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 ^r8
• Hyperlipidemia ^r2r8c224
  • Most patients with heart failure also have hyperlipidemia
  • Statin therapy has not been shown to improve symptoms of heart failure ^r83
  • Statin therapy is recommended according to current guidelines^r84 for prevention of atherosclerotic cardiovascular disease; not recommended routinely for heart failure in the absence of other indications ^r38
• Sleep disturbances ^r2r8c225
  • 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 ^r85
  • 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 a formal sleep assessment ^r17
  • In patients with cardiovascular disease and obstructive sleep apnea, consider CPAP to improve sleep quality and alleviate daytime sleepiness ^r17
    • However, it is important to differentiate central sleep apnea from obstructive sleep apnea as adaptive servo-ventilation for central sleep apnea may cause harm in patients with systolic heart failure ^r17

Special populations

• Women
  • In general, women with heart failure have a survival advantage compared with men ^r71
    • Women are more likely to have nonischemic heart failure than men
  • Digoxin is associated with increased risk for death in women compared with men, presumably owing to increased serum digoxin levels related to decreased lean body mass and renal function
  • Benefits of treatment with ACE inhibitors, angiotensin II receptor blockers and β-blockers are observed at lower dosages than required by men ^r86
• Black populations
  • Age of onset of heart failure is significantly younger in Black populations compared with White populations ^r6
  • Heart failure in Black populations is less likely due to ischemia and more likely due to hypertension compared with White populations ^r6
  • Morbidity and mortality are higher in Black populations than in White populations ^r2
  • ACE inhibitors are less effective and carry increased risk of angioedema^r2 in black patients with heart failure compared with white patients with heart failure
  • 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
• Elderly people
  • Heart failure is associated with increased morbidity and mortality in elderly people; median survival is 2.5 years after hospitalization for heart failure, with a 1-year mortality rate of 25% ^r6
  • During treatment with ACE inhibitors, β-blockers, and diuretics, it is imperative to monitor volume status, postural hypotension, and cerebrovascular symptoms