Heart Failure Guidelines 

Updated: Feb 04, 2016
  • Author: Henry H Ooi, MD, MRCPI; more...
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Heart Failure Criteria, Classification, and Staging

In the Framingham classification, the diagnosis of heart failure is based on the concurrent presence of either two major criteria or one major and two minor criteria. [1]

Major criteria comprise the following:

  • Paroxysmal nocturnal dyspnea
  • Weight loss of 4.5 kg in 5 days in response to treatment
  • Neck vein distention
  • Rales
  • Acute pulmonary edema
  • Hepatojugular reflux
  • S 3 gallop
  • Central venous pressure >16 cm water
  • Circulation time of ≥25 seconds
  • Radiographic cardiomegaly
  • Pulmonary edema, visceral congestion, or cardiomegaly at autopsy

Minor criteria (accepted only if they cannot be attributed to another medical condition) are as follows:

  • Nocturnal cough
  • Dyspnea on ordinary exertion
  • A decrease in vital capacity by one third the maximal value recorded
  • Pleural effusion
  • Tachycardia (rate of 120 bpm)
  • Hepatomegaly
  • Bilateral ankle edema

The New York Heart Association (NYHA) classification of heart failure is widely used in practice and in clinical studies. It is based on symptom severity and the amount of exertion needed to provoke symptoms. NYHA heart failure classes are as follows [2] :

  • Class I: No limitation of physical activity
  • Class II: Slight limitation of physical activity in which ordinary physical activity leads to fatigue, palpitation, dyspnea, or anginal pain; the person is comfortable at rest
  • Class III: Marked limitation of physical activity in which less-than-ordinary activity results in fatigue, palpitation, dyspnea, or anginal pain; the person is comfortable at rest
  • Class IV: Inability to carry on any physical activity without discomfort but also symptoms of heart failure or the anginal syndrome even at rest, with increased discomfort if any physical activity is undertaken

The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) staging system complements the NYHA classification to reflect the progression of disease and comprises four stages, as shown in Table1. below. [3]

Table 1. American College of Cardiology Foundation/American Heart Association (ACCF/AHA) heart failure staging system (Open Table in a new window)

Level Description Examples Notes
A At high risk for heart failure but without structural heart disease or symptoms of heart failure Patients with coronary artery disease, hypertension, or diabetes mellitus without impaired left ventricular (LV) function, LV hypertrophy (LVH), or geometric chamber distortion Patients with predisposing risk factors for developing heart failure



No corresponding NYHA Functional Classification



B Structural heart disease but without signs/symptoms of heart failure Patients who are asymptomatic but who have LVH and/or impaired LV function Corresponds with patients with NYHA class I
C Structural heart disease with current or past symptoms of heart failure Patients with known structural heart disease and shortness of breath and fatigue, reduced exercise tolerance The majority of patients with heart failure are in this stage



Corresponds with NYHA classes I, II, III and IV



D Refractory heart failure requiring specialized interventions Patients who have marked symptoms at rest despite maximal medical therapy Patients in this stage may be eligible to receive mechanical circulatory support, receive continuous inotropic infusions, undergo procedures to facilitate fluid removal, or undergo heart transplantation or other procedures



Corresponds with patients with NYHA class IV



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Screening and Genetic Testing

An expert consensus statement issued jointly in 2011 by the Heart Rhythm Society and the European Heart Rhythm Association (HRS/EHRA) included recommendations for genetic testing for the following channelopathies and cardiomyopathies [4] :

  • Long QT syndrome (LQTS)
  • Catecholaminergic polymorphic ventricular tachycardia (CPVT)
  • Brugada syndrome (BrS)
  • Cardiac conduction disease (CCD)
  • Short QT syndrome (SQTS)
  • Hypertrophic cardiomyopathy (HCM)
  • Left ventricular noncompaction (LVNC)
  • Restrictive cardiomyopathy (RCM)
  • Dilated cardiomyopathy (DCM)

Long QT syndrome

The HRS/EHRA recommend comprehensive genetic testing for LQTS or targeted testing of LQT1-3 (KCNQ1, KCNH2, and SCN5A) in the following individuals:

  • Individuals with strong clinical index of suspicion for LQTS based on clinical history, family history, and expressed electrocardiographic (ECG) phenotype (on resting 12-lead ECGs and/or provocative stress testing with exercise or catecholamine infusion)
  • Asymptomatic individuals with idiopathic QT prolongation on serial 12-lead ECGs; QT prolongation is defined as corrected QT (QTc) >480 ms in prepubertal patients or >500 ms in adults; testing may be considered for QTc values >460 ms (prepuberty) or >480 ms (adult)

Mutation-specific genetic testing is recommended for family members following identification of an LQTS mutation in an index case.

Catecholaminergic polymorphic ventricular tachycardia (CPVT)

The HRS/EHRA recommend comprehensive CPVT genetic testing or targeted CPVT1 and CVPT2 (RYR2 and CASQ2) CPVT genetic testing for any individual with a clinical index of suspicion for CPVT based on clinical history, family history, and expressed ECG phenotype during provocative stress testing with cycle, treadmill, or catecholamine infusion. Mutation-specific genetic testing is recommended for family members following identification of CPVT mutation in an index case

Brugada syndrome (BrS)

The HRS/EHRA recommend considering comprehensive or BrS1 (SCN5A)-targeted BrS genetic testing for individuals with a clinical index of suspicion for BrS based on clinical history, family history, and expressed ECG (resting 12-lead ECGs and/or provocative drug challenge testing) phenotype. Mutation-specific genetic testing is recommended for family members following identification of BrS mutation in an index case

Cardiac conduction disease (CCD)

The HRS/EHRA recommend considering genetic testing as part of the diagnostic evaluation for individuals with either isolated CCD or CCD with concomitant congenital heart disease, especially those with a documented family history of CCD. Mutation-specific genetic testing is recommended for family members following identification of CCD mutation in an index case.

Short QT syndrome (SQTS)

The HRS/EHRA recommend considering comprehensive or SQT1-3 (KCNH2, KCNQ1, and KCNJ2)–targeted SQTS genetic testing for individuals with a clinical index of suspicion for SQTS based on clinical history, family history, and expressed electrocardiographic (resting 12-lead ECGs and/or provocative drug challenge testing) phenotype. Mutation-specific genetic testing is recommended for family members following identification of SQTS mutation in an index case.

Hypertrophic cardiomyopathy (HCM)

The HRS/EHRA recommendations for HCM genetic testing are as follows:

  • Comprehensive or targeted ( MYBPC3, MYH7, TNNI3, TNNT2, TPM1) HCM genetic testing for individuals with a clinical diagnosis of HCM
  • Mutation-specific genetic testing for family members following identification of HCM mutation in an index case

Left ventricular noncompaction (LVNC)

Genetic testing for individuals with a clinical diagnosis of LVNC may be useful. Mutation-specific genetic testing is recommended for family members following identification of LVNC mutation in an index case

Restrictive cardiomyopathy (RCM)

Consider genetic testing for individuals with a clinical diagnosis of RCM. Mutation-specific genetic testing is recommended for family members following identification of RCM mutation in an index case

Dilated cardiomyopathy (DCM)

HRS/EHRA recommend comprehensive or targeted (LMNA and SCN5A) DCM genetic testing for individuals with DCM and significant cardiac conduction disease (ie, first-, second-, or third-degree heart block) and/or a family history of premature unexpected sudden death. Mutation-specific genetic testing is recommended for family members following identification of DCM mutation in an index case

The 2013 ACCF/AHA guidelines for management of heart failure include the following recommendations for screening and genetic testing for familial DCM (DCM with two close relatives who meet the criteria for idiopathic DCM) [3] :

  • First-degree relatives not known to be affected should undergo periodic, serial echocardiographic screening with assessment of LV function and size.
  • Frequency of screening is uncertain; every 3–5 years is reasonable.
  • Consider genetic testing in conjunction with genetic counseling.

The ACCF/AHA guidelines include the following recommendations for screening and genetic testing for idiopathic DCM [3] :

  • Inform first-degree relatives of diagnosis
  • Relatives should discuss with their clinicians whether they should undergo screening with echocardiography
  • Value of genetic testing is unclear but potentially valuable in patients with significant cardiac conduction disease and/or a family history of premature sudden cardiac death

In its 2010 comprehensive clinical guidelines, the Heart Failure Society of America (HFSA) offers the following recommendations for screening and genetic evaluation of cardiomyopathy [5] :

  • For all patients with cardiomyopathy, take a detailed family history for at least three generations
  • For patients with the following phenotypes: hypertrophic cardiomyopathy [HCM], dilated cardiomyopathy [DCM], arrhythmic right ventricular dysplasia [ARVD], left ventricular noncompaction [LVNC], restrictive cardiomyopathy [RCM], and cardiomyopathies associated with extra-cardiac manifestations, clinical screening for cardiomyopathy in asymptomatic first-degree relatives is recommended
  • Carefully assess the patient's medical history as well as that of asymptomatic first-degree relatives, with special focus on heart failure symptoms, arrhythmias, presyncope, and syncope
  • Screen for cardiomyopathy at intervals in asymptomatic at-risk relatives who are known to carry the disease-causing mutation(s)
  • Screen for cardiomyopathy in asymptomatic at-risk first-degree relatives who have not undergone genetic testing or in whom a disease-causing mutation has not been identified
  • At-risk first degree relatives with any abnormal screening tests should be considered for repeat clinical screening at 1 year
  • Consider genetic screening for the one most clearly affected person in a family to facilitate family screening and management (HCM, DCM, ARVD, LVNC, RCM, and cardiomyopathies associated with extracardiac manifestations)
  • Screening for Fabry disease is recommended in all men with sporadic or non–autosomal dominant (male-to-male) transmission of unexplained cardiac hypertrophy.

Due to the complexity of genetic evaluation, testing, and counseling of patients with cardiomyopathy, HFSA further recommends that patients be referred to centers with expertise in these matters and in family-based management. [5]

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Diagnostic Procedures

The American College of Cardiology Foundation/American Heart Association (ACCF/AHA), the Heart Failure Society of America (HFSA) and the European Society of Cardiology (ESC) [3] {ref 5} [6] recommend the following basic laboratory tests and studies in the initial evaluation of patients with suspected heart failure:

  • Complete blood count (CBC), which may indicate anemia or infection as potential causes of heart failure
  • Urinalysis (UA), which may reveal proteinuria, which is associated with cardiovascular disease
  • Serum electrolyte levels, which may be abnormal owing to causes such as fluid retention or renal dysfunction
  • Blood urea nitrogen (BUN) and creatinine levels, which may indicate decreased renal blood flow
  • Fasting blood glucose levels, because elevated levels indicate a significantly increased risk for heart failure (in both diabetic and nondiabetic patients)
  • Liver function tests (LFTs), which may show elevated liver enzyme levels and indicate liver dysfunction due to heart failure
  • B-type natriuretic peptide (BNP) and N-terminal pro-B-type (NT-proBNP) natriuretic peptide levels, which are increased in heart failure; these measurements correlate closely with the NYHA heart failure classification
  • Electrocardiogram (ECG) (12-lead), which may reveal arrhythmias, ischemia/infarction, and coronary artery disease (CAD) as possible causes of heart failure

The ACCF/AHA recommendations also include obtaining a lipid profile and thyroid-stimulating hormone (TSH) level. [3] These tests may reveal cardiovascular or thyroid disease as potential causes of heart failure. If the clinical presentation also suggests an acute coronary syndrome, the ESC recommends obtaining levels of troponin I or T [6] ; elevated troponin levels indicate injury to the myocytes and the severity of heart failure.

The ACCF/AHA, HFSA, and ESC recommend the following imaging studies and procedures [3, 5, 6] :

  • Chest radiography (posterior-anterior, lateral), which may show pulmonary congestion, an enlarged cardiac silhouette, or other potential causes of the patient's symptoms
  • Two-dimensional echocardiographic and Doppler flow ultrasonographic studies, which may reveal ventricular dysfunction and/or valvular abnormalities
  • Coronary arteriography in patients with a history of exertional angina or suspected ischemic LV dysfunction, which may reveal coronary artery disease
  • In certain cases, maximal exercise testing with or without respiratory gas exchange and/or blood oxygen saturation, assesses cardiac and pulmonary function with activity;, the inability to walk more than short distances, and a decreased peak oxygen consumption reflect more severe disease

Other studies may be indicated in selected patients, [3] such as the following:

  • Screening for hemochromatosis, in which iron overload affects cardiac function
  • Screening for sleep-disturbed breathing, which affects neurohormonal activation
  • Screening for human immunodeficiency virus (HIV) infection, which may result in heart failure from possible direct infectious effects, from disease treatment effects causing CAD, or from other causes
  • Testing for rheumatologic diseases, amyloidosis, or pheochromocytoma, all of which may cause cardiomyopathy
  • Serum and urine electrophoresis for light-chain disease
  • Holter monitoring, which may reveal arrhythmias or abnormal electrical activity (eg, in patients with heart failure and a history of myocardial infarction who are being considered for electrophysiologic study to document ventricular tachycardia inducibility) [5, 6]

The ESC indicates that pulmonary function testing is generally not helpful in the diagnosis of heart failure. However, such testing may demonstrate or exclude respiratory causes of dyspnea and help in the assessment of any pulmonary causes of dyspnea. [6]

Catheterization and angiography

According to the ACCF/AHA, HFSA, and ESC, cardiac catheterization and coronary angiography should be considered for patients with heart failure in the following situations [3, 5, 6] :

  • Coronary angiography should be considered in patients with an initial diagnosis of HF, no angina, unknown coronary artery disease (CAD) status who are at high risk for CAD.  Coronary angiography may also be considered in patients with unknown CAD status and are at low risk for CAD.
  •  When symptoms worsen without a clear cause in patients with heart failure and known coronary artery disease but no angina
  • In heart failure caused by systolic dysfunction in association with angina or regional wall-motion abnormalities and/or scintigraphic evidence of reversible myocardial ischemia, when revascularization is being considered
  • When pretest probability of underlying ischemic cardiomyopathy is high and surgical coronary procedures are being considered
  • Before cardiac transplantation or left ventricular assist device placement

Endomyocardial biopsy

The ACCF/AHA updated guidelines do not recommend routine endomyocardial biopsy in all cases of heart failure, given the risk of complications. However, it may be considered in the following situations [3] :

  • Rapidly progressive heart failure or worsening ventricular dysfunction that persists despite appropriate medical therapy
  • Suspected cases of acute cardiac rejection status after heart transplantation or myocardial infiltrative processes
  • Rapidly progressive and unexplained cardiomyopathy, when active myocarditis, especially giant cell myocarditis, is being considered.

The HFSA suggests that endomyocardial biopsy be considered in patients with rapidly progressive clinical heart failure or ventricular dysfunction, despite appropriate medical therapy, as well as in patients suspected of having myocardial infiltrative processes (eg, sarcoidosis, amyloidosis) or in patients with malignant arrhythmias out of proportion to their left ventricular dysfunction (eg, sarcoidosis, giant cell myocarditis). [5]

Assessment of functional capacity

The ESC considers the 6-minute walk test a good indicator of functional status in patients with heart failure. [6] It evaluates distance walked, dyspnea index on a Borg scale from 0 to 10, oxygen saturation, and heart rate response to exercise. The ESC considers patients with a 6-minute walk distance of ≤300 m to have severe impairment of functional capacity.

The ACCF/AHA and HFSA do not recommend routine maximal exercise stress testing. [3, 5] HFSA guidelines indicate it may be useful in situations such as the following, with measurement of gas exchange [5] :

  • To assess the disparity between symptomatic limitation and objective indicators of disease severity
  • To distinguish causes of functional limitation that are unrelated to heart failure, specifically cardiac versus pulmonary
  • To help determine whether patients are candidates for cardiac transplantation or mechanical circulatory support
  • To determine the prescription for cardiac rehabilitation
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Nonpharmacologic Therapy

By definition, patients in American College of Cardiology Foundation/American Heart Association (ACCF/AHA) stage A are at high risk for heart failure but do not have structural heart disease or symptoms of heart failure. For these individuals, ACCF/AHA and Heart Failure Society of America (HFSA)  guidelines recommend nonpharmacologic management focused on prevention through reduction of risk factors. Measures include the following [3, 5] :

  • Treat hypertension and lipid disorders
  • Encourage smoking cessation
  • Discourage heavy alcohol intake and illicit drug use
  • Prevent or control prevent diabetes mellitus, insulin resistance, and vascular risk
  • Encourage physical activity
  • Encourage weight reduction if obese or overweight

For patients with chronic heart failure, the ACCF/AHA, HFSA, and the European Society of Cardiology (ESC) recommend regular aerobic exercise to improve functional capacity and symptoms. [3, 5, 6] However, ACCF/AHA cautions that limitation of activity is appropriate during acute heart failure exacerbations and in patients with suspected myocarditis. Most patients should not participate in heavy labor or exhaustive sports. [3]

ACCF/AHA and ESC recommend specific patient education to facilitate heart failure self-care but because nonadherence to diet and medication can have rapid and profound adverse effects on patients’ clinical status, close observation and follow-up are important aspects of care. Close supervision, including surveillance by the patient and family, home-based visits, telephone support or remote monitoring should be provided to improve adherence. [3, 6]

Dietary sodium should generally be restricted to 2-3 g/day according to the ACCF/AHA, ESC, and HFSA.  The ACCF/AHA recommends restriction of sodium to 1500 mg/d in most patients with stage A and B HF [3, 5, 6] However, both the ACCF/AHA and ESC note that evidence to support this recommendation is inconclusive. [5, 6]

Fluid restriction to 2 L/day is recommended for patients with evidence of hyponatremia (serum sodium level <130 mEq/dL) and for those whose fluid status is difficult to control despite sodium restriction and the use of high-dose diuretics. [3, 5, 6]

ACCF/AHA and HFSA guidelines recommend caloric supplementation for patients with evidence of cardiac cachexia. [3, 5] HFSA recommends against the use of anabolic steroids for these patients [5] and ESC recommends palliative care be considered. [6]

HFSA recommends against naturoceutical use for relief of symptomatic heart failure or for the secondary prevention of cardiovascular events. Natural or synthetic products containing ephedra (ma huang), ephedrine, or its metabolites should be avoided, as well as products that have significant drug interactions with digoxin, vasodilators, beta blockers, antiarrhythmic drugs, and anticoagulants. [5]

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Pharmacologic Therapy

The 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) updated guidelines, [3] 2010 Heart Failure Society of America (HFSA) guidelines, [5] and the 2012 European Society of Cardiology (ESC) [6] guidelines, with varying levels of evidence, recommend the following:

  • Diuretics (to reduce edema by reduction of blood volume and venous pressures) and salt restriction (to reduce fluid retention) in patients with current or previous heart failure symptoms and reduced left ventricular ejection fraction (LVEF), for symptomatic relief
  • Angiotensin-converting enzyme inhibitors (ACEIs), for neurohormonal modification, vasodilatation, improvement in LVEF, and survival benefit
  • Angiotensin receptor blockers (ARBs), for neurohormonal modification, vasodilatation, improvement in LVEF, and survival benefit
  • Hydralazine and nitrates to improve symptoms, ventricular function, exercise capacity, and survival in patients who cannot tolerate an ACEI/ARB or as an add-on therapy to ACEI/ARB and beta-blockers in the black population for survival benefit
  • Beta-adrenergic blockers for neurohormonal modification, improvement in symptoms and LVEF, survival benefit, arrhythmia prevention, and control of ventricular rate
  • Aldosterone antagonists, as an adjunct to other drugs for additive diuresis, heart failure symptom control, improved heart rate variability, decreased ventricular arrhythmias, reduction in cardiac workload, improved LVEF, and increase in survival
  • Digoxin, which can lead to a small increase in cardiac output, improvement in heart failure symptoms, and decreased rate of heart failure hospitalizations
  • Anticoagulants to decrease the risk of thromboembolism
  • Inotropic agents to restore organ perfusion and reduce congestion

2016 Updated recommendations for stage C heart failure.

In May 2016, a focused update on new pharmacological therapy for heart failure was published. In this publication, both Class (Strength) of Recommendation and Level (Quality) of evidence is applied to the various pharmacological therapies. [15]  This focused update incorporates new study results and medications and is designed primarily for management of those patients with Stage C Heart Failure with reduced ejection fraction. The remainder of the “2016 ACC/AHA/HSFA Focused Update on the Management of Heart Failure: An Update of the 2013 ACCF/AHA Guidelines for the Management of Heart Failure” will be forthcoming.

These current updated recommendations for patients with Stage C Heart Failure with reduced ejection fraction differ from the previous guidelines in the following ways:

ACE inhibitors, angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs)

Class I recommendation: The clinical strategy of inhibition of the renin-angiotensin aldosterone system with ACE Inhibitors (Level of Evidence A) or ARBs (Level of Evidence A) or ARNI (Level of Evidence B-R) in conjunction with evidence-based beta-blockers, and aldosterone antagonists in selected patients, is recommended for patients with chronic Heart Failure with reduced ejection fraction(HFrEF) to reduce morbidity and mortality

Class IA recommendation: The use of ARBs to reduce morbidity and mortality is recommended in patients with prior or current symptoms of chronic HFrEF who are intolerant to ACE inhibitors because of cough or angioedema

Class I B-R: In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACE Inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality

Class III: Harm. ARNI should not be administered concomitantly with ACE Inhibitors or within 36 hours of the last dose of an ACE Inhibitor

Class III: Harm. ARNI should not be administered to patients with a history of angioedema

Ivabradine recommendations

Class IIa B-R: Ivabradine can be beneficial to reduce HF hospitalizations for patients with symptomatic (NYHA Class II-III) stable chronic HFrEF (LVEF less than or equal to 35%), who are receiving guideline-directed evaluation and management(GDEM), including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest.

The specific recommendations for pharmacological therapy for heart failure are summarized in Tables 2 and 3, below. [3, 5, 6]

Table 2. Recommended pharmacologic therapy for heart failure (Open Table in a new window)

Drug Class Recommendation 2013 ACCF/AHA 2010 HFSA 2012 ESC
ACE inhibitors and ARBs ACE inhibitors, or ARBs for patients intolerant of ACE inhibitors, for prevention of HF in patients with MI and reduced EF Class I Recommended Class I
ACE inhibitors for all patients with a reduced EF to prevent HF, even if they do not have a history of MI Class I   Class I
ARBs are reasonable as alternatives to ACE inhibitors as first-line therapy for patients with HF and reduced EF Class IIa May be considered  
Addition of ARB may be considered in persistently symptomatic patients with HF and reduced EF on guideline-determined medical therapy (GDMT) in whom an aldosterone receptor antagonist cannot be used Class IIb Should consider Class I
Beta-blockers Evidence-supported beta-blockers (eg, bisoprolol, carvedilol, and sustained-release metoprolol succinate) for all patients with current or prior symptoms of HF and reduced EF Class I Recommended  
Evidence-supported beta-blockers for prevention of HF in patients with MI and reduced EF Class I   Class I
Beta-blockers should be initiated at low doses and up-titrated gradually in patients with reduced LVEF following newly diagnosed MI   Recommend  
Beta-blockers for all patients with a reduced EF to prevent HF, even if they do not have a history of MI Class I Recommend Class I
Aldosterone receptor antagonists Routine combined use of an ACE inhibitor, ARB, and aldosterone receptor antagonist is potentially harmful Class III    
Aldosterone receptor antagonists in patients with NYHA class II–IV HF who have LVEF of ≤35%. Class I Recommend (NYHA Class III-IV) Class I
Aldosterone receptor antagonists following an acute MI in patients with LVEF of ≤40% and symptomatic HF or diabetes mellitus Class I Should consider  
Inappropriate use of aldosterone receptor antagonists is potentially harmful Class III Not recommended  
Other agents The combination of hydralazine and isosorbide dinitrate for African Americans with NYHA class III–IV HF and reduced EF on GDMT Class I Recommended  
A combination of hydralazine and isosorbide dinitrate may be useful in patients with HF and reduced EF who cannot be given an ACE inhibitor or ARB Class IIa May consider Class IIb
Digoxin can be beneficial in patients with HF and reduced EF, to decrease HF-related hospitalizations Class IIa May consider Class IIb
Diuretics for patients with HF and reduced EF who have evidence of fluid retention Class I Recommended  
Statins are not beneficial as adjunctive therapy for HF Class III   Not recommended
  Omega-3 fatty acid supplementation as adjunctive therapy Class IIa   Class IIb
ACCF/AHA=American College of Cardiology Foundation/American Heart Association; ACE=angiotensin-converting enzyme; ARB=angiotensin receptor blocker; EF=ejection fraction; ESC=European Society of Cardiology; HF=heart failure; HFSA=Heart Failure Society of America; LVEF=left ventricular ejection fraction; MI=myocardial infarction; NYHA=New York Heart Association

 

Table 3. Anticoagulation recommendations for patients with heart failure (Open Table in a new window)

Recommendation



 



2013 ACCF/AHA 2010 HFSA 2012 ESC 



 



The selection of an anticoagulant agent should be individualized Class I    
Patients with chronic HF with permanent, persistent, or paroxysmal AF and an additional risk factor for cardioembolic stroke, or ≥75 years of age, should receive long-term anticoagulant therapy Class I   Class I
Warfarin therapy (goal INR 2.0-3.0) for all patients with chronic HF with permanent, persistent, or paroxysmal AF or a history of systemic or pulmonary embolism (PE), including stroke or TIA   Recommended  
Long-term anticoagulation is reasonable for patients with chronic HF who have permanent/persistent/paroxysmal AF but no additional risk factor for cardioembolic stroke Class IIa    
Anticoagulation is not recommended in patients with chronic HF and reduced EF without AF, a prior thromboembolic event, or a cardioembolic source Class III Not recommended  
Long-term treatment with aspirin, 75-81 mg, for patients with HF due to ischemic cardiomyopathy, whether or not they are receiving ACE inhibitors   Recommended  
Warfarin (goal INR 2.0-3.0) and clopidogrel (75 mg) in post MI patients as alternatives to aspirin.   May consider  
Routine use of aspirin in patients with HF without atherosclerotic vascular disease is not recommended Not recommended Not recommended  
ACCF/AHA= American College of Cardiology Foundation/American Heart Association; AF=atrial fibrillation; EF=ejection fraction; ESC=European Society of Cardiology; HF=heart failure; HFSA=Heart Failure Society of America; INR=international normalized ratio; MI=myocardial infarction; TIA=transient ischemic attack

Newer agents

Ivabradine was approved by the European Medicines Agency in 2012 and the updated ESC guidelines recommend its use to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with an LVEF of 35% or lower, who are in sinus rhythm with a resting heart rate of 70 bpm or higher, and who are either on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use. [6] In April 2015, the US Food and Drug Administration (FDA) approved ivabradine (Corlanor) for those same indications, based on the results of the SHIFT placebo-controlled trial. [7, 8]

In the May 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure, Ivabradine carries a Class IIa B-R recommendation. Ivabradine can be beneficial to reduce HF hospitalizations for patients with symptomatic (NYHA class II-III) stable chronic HFrEF (LVEF less than or equal to 35%) who are receiving Guideline-Directed Evaluation and Management(GDEM), including a beta-blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest.

The combination of the angiotensin receptor blocker valsartan and the neprilysin inhibitor sacubitril (Entresto, )also known as an Angiotensin-Receptor-Blocker-Neprilysin-Inhibitor(ARNI), was approved US Food and Drug Administration in 2015 to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with NYHA class II-IV heart failure and reduced ejection fraction. FDA approval was based on the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. [13, 14]  

In the 2016 ACC/AHA/HFSA Focused Udate on New Pharmacological Therapy for Heart Failure, ARNIs carry The following COR (Class of Recommendation) and LOE (Level of Evidence) recommendations:

Class I A recommendation. For use to reduce morbidity and mortality in patients with prior or current symptoms of chronic HFrEF who are intolerant to ACE Inhibitors because of cough or angioedema,

Class I A recommendation. For use in patients with chronic HFrEF inconjunction with evidence-based beta-blockers, and aldosterone antagonists in selected patients to reduce morbidity and mortality.

Class I B-R recommendation.  In patients with chronic symptomatic HFrEF NYHA Class II or III who tolerate an ACE Inhibitor or ARB, replacement by an ARNI is recommended to further reduction in morbidity and mortality

Agents not recommended

The ACCF/AHA and ESC guidelines advise that nonsteroidal anti-inflammatory drugs (NSAIDs) with the exception of low-dose aspirin, calcium channel blockers, and most antiarrhythmic agents may exacerbate heart failure and should be avoided in most patients. [3, 6]

Antiarrhythmic agents can have cardiodepressant effects and may promote arrhythmia. Only amiodarone and dofetilide have been shown not to adversely affect survival.

Calcium channel blockers can worsen heart failure and may increase the risk of cardiovascular events. Only amlodipine may be considered for the management hypertension or ischemic heart disease because it has been shown not to adversely affect survival. [3, 6] Thiazolidinediones (eg, rosiglitazone) should not be used to treat diabetes mellitus in heart failure patients, as they are associated with fluid retention and worsening heart failure and increase the risk of hospitalization. [3, 6]

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Electrophysiologic Intervention

The 2010 Heart Failure Society of America (HFSA) guidelines indicate that device therapy is an integral part of the treatment of heart failure and that considerations such as the nature and severity of the condition and any patient comorbidities are essential in optimizing the use of this therapy. [5] The Committee for Practice Guidelines (CPG) of the European Society of Cardiology (ESC) and the ACC/AHA/Heart Rhythm Society (HRS) emphasized the importance of medical devices in heart failure in their respective 2010 and 2012 focused updates on these interventions. [9, 10]

Pacemakers

Because right ventricular pacing may worsen heart failure due to an increase in ventricular dyssynchrony, the current 2010 HFSA Practice Guidelines recommend against placement of a dual-chamber pacemaker in heart failure patients in the absence of symptomatic bradycardia or high-degree atrioventricular (AV) block. [5]

Implantable cardioverter-defibrillators (ICDs)

Current ACCF/AHA guidelines recommend an ICD in most patients with an LVEF of less than 35%. The ACCF/AHA and ESC recommend ICD placement for the following categories of heart failure patients [3, 6, 10] :

  • Patients with LV dysfunction (LVEF ≤35%) from a previous myocardial infarction (MI) who are at least 40 days post-Ml
  • Patients with nonischemic cardiomyopathy; with an LVEF of 35% or less; in NYHA class II or III; receiving optimal medical therapy; and expected to survive longer than 1 year with good functional status
  • Patients with ischemic cardiomyopathy who are at least 40 days post-MI; have an LVEF of 30% or less; are in NYHA functional class I; are on long-term optimal medical therapy; and are expected to survive longer than 1 year with good functional status
  • Patients who have had ventricular fibrillation (VF)
  • Patients with documented hemodynamically unstable ventricular tachycardia (VT) and/or VT with syncope; on optimal medical therapy; and expected to survive longer than 1 year with good functional status

Cardiac resynchronization therapy/biventricular pacing

The ACCF/AHA guidelines recommend cardiac resynchronization therapy (CRT)for patients in sinus rhythm or atrial fibrillation with a QRS duration of 120 ms or longer (the greatest benefit is in patients with a QRS >150 ms) and reduced LVEF (LVEF of 35% or less) with persistent, moderate-to-severe heart failure (NYHA class III and functional NYHA class IV) despite optimal medical therapy. [3] A 2012 update of ACC/AHA/HRS guidelines on CRT expanded class I indications to patients with NYHA class II symptoms and left bundle branch block (LBBB) of ≥150 ms. [10] CRT recommendations are listed below. [3, 10]

Class I

CRT is recommended in patients who have all of the following:

  • Reduced LVEF
  • Sinus rhythm
  • LBBB and a QRS complex of 150 ms or longer
  • NYHA II, III, or ambulatory IV symptoms on optimal medical therapy

Class IIa

CRT can be useful in patients with any of the following:

  • Reduced LVEF, sinus rhythm, a LBBB pattern with a QRSD 120-149 msec who have NYHA II, III, or ambulatory IV symptoms on optimal medical therapy
  • Reduced LVEF, sinus rhythm, a non-LBBB pattern with a QRSD ≥150 msec who have NYHA III or ambulatory IV symptoms on optimal medical therapy
  • Atrial fibrillation with reduced LVEF who require chronic pacing and in whom near 100% ventricular pacing is expected, on optimal medical therapy
  • Reduced LVEF who are undergoing new or replacement device placement with anticipated requirement for significant (>40%) ventricular pacing

Class IIb

CRT may be considered in patients with any of the following:

  • LVEF ≤30%, ischemic etiology of HF, sinus rhythm LBBB with QRSD ≥150 msec and NYHA class I symptoms on optimal medical therapy
  • Reduced LVEF, sinus rhythm, a non-LBBB pattern with QRSD 120-149 sec, and NYHA class III/ambulatory class IV symptoms on optimal medical therapy
  • Reduced LVEF, sinus rhythm, a non-LBBB pattern with QRSD ≥150 sec, and NYHA class II on optimal medical therapy

Class III (no benefit)

CRT is not recommended in patients with NYHA class I/II symptoms, non-LBBB morphology, and QRSD ≤150 msec, or whose expected life expectancy ≤ 1 year.

ESC guidelines

The ESC guidelines find strong evidence to support the use of CRT in the following groups, who are expected to survive for >1 year with good functional status [6] :

  • Patients in sinus rhythm with a QRS duration of 120 ms or longer, LBBB QRS morphology, and an LVEF of 35% or less with NYHA functional class III and ambulatory class IV symptoms despite optimal medical therapy.
  • Patients in sinus rhythm with a QRS duration of 150 ms or longer, irrespective of QRS morphology and an LVEF of 35% or less with NYHA functional class III and ambulatory class IV symptoms despite optimal medical therapy.
  • Patients in sinus rhythm with a QRS duration of 130 ms or longer, LBBB QRS morphology, and an LVEF of 30% or less with NYHA functional class II despite optimal medical therapy.
  • Patients in sinus rhythm with a QRS duration of 150 ms or longer, irrespective of QRS morphology, and an LVEF of 30% or less with NYHA functional class II symptoms despite optimal medical therapy.

The ESC guidelines find uncertain evidence supporting the use of CRT in patients in permanent atrial fibrillation with QRS duration of 120 ms or longer and an LVEF of 35% or less with NYHA functional class III or ambulatory class IV symptoms who meet the following criteria [6] :

  • Pacing is required because of intrinsically slow ventricular rate
  • Patient is pacemaker dependent as a result of AV nodal ablation
  • Ventricular rate is ≤60 bpm at rest and ≤90 bpm with exercise

Evidence is uncertain but CRT should also be considered in patients with NYHA functional class III-IV symptoms and LVEF ≤35%, irrespective of QRS duration, and may be considered in those with NYHA functional class II with an LVEF ≤35% who have an indication for conventional pacing and no other indication for CRT. 

In April 2014, the FDA approved 10 Medtronic biventricular pacemakers, some with defibrillators and some without, for use in patients with less severe systolic heart failure and atrioventricular (AV) block. The approvals expand the labeling on the defibrillating and pacing-only cardiac resynchronization therapy devices (CRT-D and CRT-P, respectively), which until now had been approved only for heart failure patients with LVEF <35% and prolonged QRS intervals. [11]

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Revascularization Procedures

ACCF/AHA, HFSA, and ESC guidelines recommend coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) revascularization procedures in selected patients with heart failure and CAD to improve symptoms and survival. In patients who are at low risk for CAD, findings from noninvasive tests such as exercise ECG, stress echocardiography, and stress nuclear perfusion imaging should determine whether subsequent angiography is indicated. [3, 5, 6]

ACCF/AHA guidelines recommend revascularization procedures for the following heart failure patients [5] :

  • CABG or PCI for individuals on medical therapy with angina and suitable coronary anatomy, especially significant left main stenosis or left main equivalent
  • CABG to improve survival in patients with mild to moderate LV systolic dysfunction and significant multivessel CAD or proximal left anterior descending (LAD) artery stenosis when viable myocardium is present
  • CABG to improve survival for patients with LVEF of 35% or less and significant multivessel CAD
  • CABG may also be considered in patients with ischemic heart disease, severe LV systolic dysfunction, and operable coronary anatomy whether or not viable myocardium is present

ESC guidelines are in general agreement with ACCF/AHA, with the choice between CABG and PCI individualized for each patient. In addition, the ESC points out that the benefit-risk balance of revascularization in patients without angina and without viable myocardium remains uncertain. [6]

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Valvular Surgery

The ACC/AHA recommends aortic valve replacement for patients with critical aortic stenosis and predicted surgical mortality of 10% or less, and transcatheter aortic valve replacement for selected patients who are deemed inoperable. Transcatheter mitral valve repair or mitral valve surgery for functional mitral insufficiency is of uncertain benefit and should only be considered after careful candidate selection. [3]

The HFSA indicates that isolated mitral valve repair or replacement for severe mitral regurgitation secondary to ventricular dilatation in the presence of severe LV systolic dysfunction is not generally recommended. [5]

Although the ESC recommends that medical treatment be optimized for aortic stenosis, it also cautions that vasodilators may cause hypotension and should be used with caution. Surgical decision making should not be delayed. For patients unfit for surgery, transcatheter aortic valve replacement should be considered. Additional valvular surgery recommendations include the following [6] :

  • Aortic valve repair or replacement in all symptomatic patients and in asymptomatic patients with severe aortic regurgitation and LVEF less than 50% who are fit for surgery
  • Consider surgery for severe aortic regurgitation and LV end-diastolic diameter greater than 70 mm or end-systolic diameter greater than 50 mm
  • Isolated mitral valve surgery is questionable in patients with severe functional mitral regurgitation and severe LV systolic dysfunction who cannot be revascularized or have non-ischemic cardiomyopathy; conventional medical and device therapy are preferred. In selected cases, repair may be considered in order to avoid or postpone transplantation.
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Mechanical Circulatory Support Devices

The AHA has published guidelines on heart device strategies, patient selection, and postoperative care. The guidance focuses on risk stratification and early referral of high-risk patients with heart failure to centers that can implant mechanical circulatory support (MCS) devices. The specific recommendations for MCS include the following [12] :

  • Consider MCS as a bridge to transplantation (BTT) for eligible patients with end-stage heart failure who are failing optimal medical, surgical, and or device therapies and are at high risk for dying before receiving a transplantation
  • Early referral for MCS, before development of advanced heart failure, is preferred
  • Durable, implantable MCS devices are recommended as permanent therapy for patients with advanced heart failure, prognosis for high 1-year mortality resulting from heart failure, and the absence of other life-limiting organ dysfunction; who are failing medical, surgical, and/or device therapies; and who are ineligible for heart transplantation
  • Patients who are ineligible for heart transplantation because of pulmonary hypertension related to heart failure alone should be considered for bridge to potential transplant eligibility with durable, long-term MCS
  • Consider urgent nondurable MCS in hemodynamically compromised patients with end-organ dysfunction and/or relative contraindications to heart transplantation/durable MCS that are expected to improve with restoration of an improved hemodynamic profile
  • Long-term MCS is not recommended in patients with advanced kidney disease in whom renal function is unlikely to recover despite improved hemodynamics
  • Long-term MCS as a bridge to heart–kidney transplantation may be considered on the basis of availability of outpatient hemodialysis
  • Patients with obesity (body mass index [BMI] 30-40 kg/m 2) may benefit from long-term MCS
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Heart Transplantation

According to the HFSA and ACCF/AHA guidelines, selected patients with refractory end-stage heart failure, debilitating refractory angina, ventricular arrhythmia, or congenital heart disease that cannot be controlled despite pharmacologic, medical device, or alternative surgical therapy should be evaluated for heart transplantation. [3, 5]

The ESC guidelines recommend heart transplantation be considered for patients with progressive end-stage heart failure despite maximal medical therapy who have a poor prognosis and no viable alternative form of treatment; patient must be well informed, motivated, and emotionally stable; and be capable of complying with intensive medical treatment. [6]

The ESC considers heart transplantation contraindicated in patients with the following conditions [6] :

  • Active infection, except for left ventricular assist device (LVAD) infection
  • Severe peripheral arterial or cerebrovascular disease
  • Current alcohol and/or drug abuse
  • Treated cancer in the past 5 years
  • Unhealed peptic ulcer
  • Recent thromboembolism
  • Significant renal failure (creatinine clearance <50 mL/min)
  • Significant liver disease
  • Irreversible high pulmonary vascular resistance (>4-5 Wood units and mean transpulmonary gradient >15 mm Hg)
  • Multiorgan systemic disease
  • Other serious comorbidity with a poor prognosis
  • Emotional instability or untreated mental illness

Note that the HFSA and ESC indicate that cardiomyoplasty and partial left ventriculectomy (Batista operation) is not recommended to treat heart failure, nor should it be used as an alternative to heart transplantation. [5, 6]

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Management of Acute Decompensated Heart Failure (ADHF)

The HFSA guidelines recommend the following treatment goals for patients with acute decompensated heart failure (ADHF) [5] :

  • Symptom improvement (ie, congestion, low output)
  • Restoration of normal oxygenation
  • Optimization of volume status
  • Identification of etiology and addressing of precipitating factors
  • Optimization of long-term oral therapy
  • Minimization of side effects
  • Identification of patients who may benefit from revascularization or device therapy
  • Prevention of venous thromboembolism
  • Patient education concerning medications and self-management
  • Initiation of a disease management program, where possible

HFSA indications for hospital admission in patients with ADHF are as follows [5] :

  • Evidence of severely decompensated HF, including hypotension, worsening renal function, and altered mentation
  • Dyspnea at rest
  • Hemodynamically significant arrhythmia, including new onset of rapid atrial fibrillation
  • Acute coronary syndromes

ACCF/AHA recommendations regarding adjustment of maintenance heart failure medications in patients admitted with ADHF are as follows:

  • Oral therapy should be continued, or even uptitrated, in most patients with reduced ejection fraction heart failure
  • Continuation of ACE inhibitors or ARBs and beta-blockers is well tolerated and results in better outcomes for most patients
  • Withholding of beta-blockers or reduction in dosage should be considered only in patients hospitalized after recent beta-blocker initiation or dosage increase, or those with marked volume overload or marginal/low cardiac output
  • In patients with significant worsening of renal function, dose reduction or temporary discontinuation of ACE inhibitors, ARBs, and/or aldosterone antagonists should be considered until renal function improves

Pharmacologic therapy

ACCF/AHA, HFSA, and ESC agree that diuretics remain the cornerstone of standard therapy. IV administration of a loop diuretic (eg, furosemide, bumetanide, torsemide) is preferred initially. [3, 5, 6] In patients with hypertensive heart failure who have mild fluid retention, thiazide diuretics may be preferred because of their more persistent antihypertensive effects. [5]

When diuresis is inadequate, ACCF/AHA, HFSA and ESC guidelines recommend higher doses or the addition of a second diuretic (eg, a thiazide). [3, 5, 6] Careful monitoring to avoid hypokalemia, renal dysfunction, and hypovolemia is required. The ACC/AHA and ESC suggest the use of ultrafiltration for fluid reduction when diuretic therapies are unsuccessful. [3, 6]

Vasodilators (eg, nitroprusside, nitroglycerin, or nesiritide) are recommended as an adjuvant to diuretics for relief of symptoms. [3, 5, 6] The ESC cautions against their use in patients with systolic blood pressure <100 mm Hg or with significant mitral or aortic stenosis. [6]

ACCF/AHA and ESC guidelines recommend that in hospitalized patients, beta-blocker therapy should be initiated after optimization of volume status and successful discontinuation of intravenous diuretics, vasodilators, and inotropic agents. Beta-blockers should be started at a low dose and only in stable patients, and should be used cautiously in patients who have required inotropes during their hospital course. [3, 6]

Additional recommendations from the 2013 ACC/AHA and 2010 HSFA guidelines include the following [3, 5] :

  • If symptomatic hypotension is absent, intravenous nitroglycerin, nitroprusside, or nesiritide may be considered an adjuvant to diuretic therapy for relief of dyspnea in hospitalized patients
  • Venous thromboembolism prophylaxis with an anticoagulant medication for patients admitted to the hospital, if the risk-benefit ratio is favorable

Invasive hemodynamic monitoring

The 2013 ACC/AHA and 2010 HSFA guidelines found no benefit found for the routine use of invasive hemodynamic monitoring in normotensive patients with acute decompensated HF and congestion with symptomatic response to diuretics and vasodilators. [3, 5] The HSFA guidelines include a recommendation for consideration of invasive hemodynamic monitoring for patients with any of the following [5] :

  • Disease refractory to initial therapy
  • Unclear volume status and cardiac filling pressures
  • Clinically significant hypotension or worsening renal function during therapy
  • Need for assessment of degree and reversibility of pulmonary hypertension, as part of the evaluation for possible cardiac transplantation
  • Need for documentation of an adequate hemodynamic response to inotropic therapy, when long-term outpatient infusion is being considered.

Ventilation

The HFSA recommends routine administration of supplemental oxygen in the presence of hypoxia only; noninvasive positive pressure ventilation (NIPPV) should be considered for severe dyspnea. [5] ESC recommends noninvasive ventilation as an adjunctive therapy to relieve symptoms in patients with pulmonary edema and severe respiratory distress or in those who fail to improve with medical therapy. Contraindications are hypotension, vomiting, pneumothorax, and depressed consciousness. [6]

ESC reserves endotracheal intubation for respiratory failure leading to hypoxemia, hypercapnia, and acidosis. Intubation may also be considered in cases of physical exhaustion, diminished consciousness, and an inability to maintain or protect the airway. [6]

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