Overview of the management of heart failure with reduced ejection fraction in adults

INTRODUCTION — Heart failure (HF) is a common clinical syndrome in which symptoms result from a structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. HF may be caused by disease of the myocardium, pericardium, endocardium, heart valves, vessels, or by metabolic disorders [1]. HF due to left ventricular (LV) dysfunction is categorized according to LV ejection fraction (LVEF) into HF with reduced ejection fraction (with LVEF ≤40 percent, known as HFrEF; also referred to as systolic HF), HF with preserved ejection fraction (with LVEF ≥50 percent; known as HFpEF; also referred to as diastolic HF), and HF with mid-range ejection fraction (with LVEF 41 to 49 percent; known as HFmrEF).

An overview of the management of chronic HFrEF in nonpregnant patients is presented here [1,2].

The management of acute HF, management of HF during pregnancy, and management of HFpEF and HFmrEF are discussed separately. (See "Treatment of acute decompensated heart failure: General considerations" and "Treatment of acute decompensated heart failure: Specific therapies" and "Management of heart failure during pregnancy" and "Treatment and prognosis of heart failure with preserved ejection fraction" and "Treatment and prognosis of heart failure with mildly reduced ejection fraction".) (Related Pathway(s): Heart failure: Primary pharmacologic therapy for compensated heart failure with reduced ejection fraction (HFrEF).)

GOALS AND OVERALL APPROACH — The goals of therapy of HFrEF are to reduce morbidity (ie, reduce symptoms, improve health-related quality of life and functional status, and decrease the rate of hospitalization), and to reduce mortality.

Management of HFrEF includes management of the cause of HF and associated conditions, monitoring, preventative care, care coordination, education and support for HF self-management (including lifestyle modification and daily monitoring), pharmacologic therapy, cardiac rehabilitation, palliative care, device therapy (including cardiac resynchronization therapy, implantable cardioverter defibrillator, and mechanical circulatory support [eg, LV assist device]) and cardiac transplantation.

Several major societies and organizations have published guidelines for the treatment of HF. These include the 2022 American Heart Association/American College of Cardiology (ACC)/Heart Failure Society of America guideline [1], the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment [3], and the 2016 European Society of Cardiology guidelines [2]. With few exceptions, these societies make similar recommendations regarding the treatment of HFrEF. Our approach is in broad agreement with these guidelines.

GENERAL MANAGEMENT

Management of causes and associated conditions — Treatment should address underlying causes (eg, intervention for coronary artery disease, intervention for symptomatic valve disease, therapy for treatable causes of cardiomyopathy) and associated conditions (eg, hypertension, diabetes mellitus, and thyroid dysfunction) (table 1) [1]. (See "Determining the etiology and severity of heart failure or cardiomyopathy".)

Ischemic heart disease — Coronary atherosclerosis is a dominant cause of HF in developed countries. Patients with ischemic heart disease may have HFrEF from either or both of two mechanisms: a prior myocardial infarction followed by LV dysfunction and remodeling; or hibernating myocardium due to chronic but potentially reversible ischemic dysfunction [4,5]. In addition, coronary artery disease may be present in patients with HF from other causes, and may sometimes be overlooked as a contributing factor [6]. Thus, patients with HFrEF should be evaluated for the presence of coronary artery disease and appropriate therapy instituted, including pharmacologic therapy for relief of angina and risk factor reduction (including lipid therapy) and coronary artery intervention as indicated. (See "Chronic coronary syndrome: Overview of care" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Surgical revascularization (in addition to medical therapy) is indicated for patients with ischemic cardiomyopathy with LVEF ≤35 percent and coronary artery disease amenable to surgical revascularization. The available evidence does not support routine concomitant surgical ventricular reconstruction. Patients with a history of repeated episodes of acute LV dysfunction and flash pulmonary edema should also undergo evaluation to evaluate the potential benefit of revascularization (percutaneous or surgical). (See "Treatment of ischemic cardiomyopathy" and "Evaluation of hibernating myocardium".)

Valvular disease — Valvular heart disease is a cause of HF and is also a secondary phenomenon in many individuals with HF. For example, some degree of secondary mitral and tricuspid regurgitation is frequently present in patients with severe dilated cardiomyopathy, regardless of etiology [7]. Valvular disease imposes a hemodynamic load on the ventricles, leading to further impairment in cardiac function, regardless of whether the valvular disease is primary or secondary. Clinically indicated valve intervention (eg, surgical replacement or transcatheter aortic valve implantation for severe aortic stenosis) can lead to improvement in symptoms and may also improve cardiac function.

Indications for valve intervention are discussed in specific valve disease topic reviews. Management of secondary mitral regurgitation, including indications for transcatheter or surgical mitral valve intervention, is discussed separately. (See "Chronic secondary mitral regurgitation: General management and prognosis".)

Cardiomyopathy — In patients in whom significant coronary artery disease has been excluded, the specific cause of nonischemic cardiomyopathy should be sought since disease-specific therapy is available for certain conditions (eg, alcoholic cardiomyopathy, arrhythmia-induced cardiomyopathy, cardiac sarcoidosis, cardiac amyloidosis, and abnormal thyroid function) and the diagnosis may alter the estimated risk of potential complications (eg, thromboembolism) and expected prognosis. (See "Determining the etiology and severity of heart failure or cardiomyopathy" and "Alcohol-induced cardiomyopathy" and "Arrhythmia-induced cardiomyopathy" and "Management and prognosis of cardiac sarcoidosis" and "Cardiac amyloidosis: Treatment and prognosis".)

Genetic causes of HFrEF should be considered, particularly if there is a suggestive family history, and may lead to genetic counseling for other family members. (See "Genetics of dilated cardiomyopathy" and "Familial dilated cardiomyopathy: Prevalence, diagnosis and treatment".)

Hypertension — Hypertension imposes an increased hemodynamic load on the failing ventricle in patients with established HF due to any etiology. The goals of therapy are to control blood pressure and to reduce LV afterload, thereby improving cardiac function and decreasing the progression of pathologic remodeling. (See "Treatment of hypertension in patients with heart failure".)

For patients with HFrEF and hypertension, the preferred antihypertensive therapy is standard combination therapy with primary pharmacologic agents for HFrEF including a diuretic (as needed for volume overload) and other agents, which are described separately (table 2). (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Regimen for patients with mild to moderate symptoms'.)

In patients with residual hypertension despite optimal use of the primary therapies for HFrEF, secondary agents may be indicated (table 3). (See "Secondary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Add isosorbide dinitrate plus hydralazine in select patients'.)

The presence of renovascular disease should be considered in patients with HF and hypertension, particularly in those with HF due to ischemic heart disease. Recurrent unexplained HF decompensation and/or flash (sudden-onset) pulmonary edema occur in some patients with renovascular hypertension, often with preserved (normal or near normal) LV systolic function. Treatment options include antihypertensive drug therapy and revascularization, as discussed separately. (See "Treatment of bilateral atherosclerotic renal artery stenosis or stenosis to a solitary functioning kidney" and "Treatment of unilateral atherosclerotic renal artery stenosis" and "Treatment of fibromuscular dysplasia of the renal arteries".)

Diabetes mellitus — HFrEF and diabetes mellitus (DM) are frequently associated. Management of HF in patients with DM is generally the same as management for nondiabetics. (See "Heart failure in patients with diabetes mellitus: Epidemiology, pathophysiology, and management", section on 'Management of HF in DM'.)

The management of blood glucose in adults with type 2 diabetes mellitus with HF is discussed separately. (See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Initial pharmacologic therapy' and "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Our approach'.)

The management blood glucose in adults with type 1 diabetes mellitus and HF is the same as for other adults with comorbidities, as described separately. (See "Management of blood glucose in adults with type 1 diabetes mellitus".)

Arrhythmias and conduction system disease — Management of supraventricular arrhythmias, ventricular arrhythmias, conduction system disease, and risk of sudden death in patients with HFrEF is discussed separately.

●Patients with HFrEF are at risk for supraventricular tachycardias, particularly atrial fibrillation. In patients with HFrEF and tachycardia, it is important to exclude arrhythmia-induced cardiomyopathy as a potential cause of ventricular systolic dysfunction. (See "The management of atrial fibrillation in patients with heart failure" and "Arrhythmia-induced cardiomyopathy".)

●Ventricular arrhythmias and risk for sudden cardiac death (SCD) are discussed separately. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)

●Standard bradycardic indications for a pacemaker apply. (See "Overview of pacemakers in heart failure" and "Cardiac resynchronization therapy in heart failure: Indications and choice of system".)

Other associated conditions — Management of the following commonly associated conditions is discussed separately.

●Anemia (see "Evaluation and management of anemia and iron deficiency in adults with heart failure")

●Sleep disordered breathing (see "Sleep-disordered breathing in heart failure")

Follow-up and preventive care — Patients with HF require serial follow-up to evaluate clinical status, support HF self-management including proper use of medications, evaluate response to therapy, and assess potential need for changes in management. Each visit should include assessment of ability to perform activities of daily living; volume status and weight; current use of alcohol, tobacco, illicit drugs, alternative therapies, and chemotherapy drugs; as well as diet and sodium intake.

For patients who have a change in clinical status, have experienced or recovered from a clinical event, or have received treatment that might significantly change these parameters, a follow-up echocardiogram is suggested if findings might change treatment to assess cardiac structure and function, including left and right ventricular size and function (including regional wall motion), atrial size, and valvular function. (See "Tests to evaluate left ventricular systolic function" and "Echocardiographic recognition of cardiomyopathies".)

The role of serial natriuretic peptide measurement as a guide to therapy of chronic HF is discussed separately. (See "Natriuretic peptide measurement in heart failure", section on 'Chronic HF'.)

Appropriate preventive care includes pneumococcal vaccination and annual influenza vaccination [8]. (See "Pneumococcal vaccination in adults" and "Seasonal influenza vaccination in adults".)

CARE COORDINATION AND REFERRALS — Provision of optimal care for patients with HFrEF is complex given the multiple components of management and the frequency of concurrent cardiac and noncardiac conditions, which may require management by multiple clinicians across many care settings and specialties [3]. Optimal care includes promotion of HF self-management, appropriate and timely referrals, and appropriate systems of care which may include an HF team, and close coordination of ambulatory care following admissions to the hospital.

HF self-management — Effective care includes patient education and support to promote HF self-management. HF-self management includes medication management, daily monitoring of signs and symptoms (including daily weight monitoring to detect fluid accumulation) and lifestyle modification. Lifestyle modification is largely based upon observational studies and physiologic rationale, as there have been scant randomized trials:

●Cessation of smoking. (See "Overview of smoking cessation management in adults".)

●Restriction of or abstinence from alcohol consumption, including the use of support groups such as Alcoholics Anonymous, and avoidance of illicit drug use (eg, cocaine). (See "Alcohol-induced cardiomyopathy" and "Alcohol use disorder: Treatment overview".)

●Based on expert opinion and limited evidence, we advise our patients with HF to restrict sodium intake to 3 g/day. This level of sodium restriction is likely sufficient for most patients with HF. A more restrictive sodium intake is not practical for many patients and there is limited evidence that a more restrictive intake can be harmful. The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America HF guidelines suggest some degree (eg, <3 g/day) of sodium restriction in patients with symptomatic HF [1]. The 2016 European Society of Cardiology HF guidelines suggest avoiding excessive salt intake (>6 g/day) [2]. (See "Heart failure self-management".)

●We advise restricted fluid intake (eg, 1.5 to 2 L/day) only in patients with refractory (stage D, class IV) HF or symptomatic or severe hyponatremia (serum sodium <120 meq/L) [9]. (See "Hyponatremia in patients with heart failure", section on 'Treatment' and "Overview of the treatment of hyponatremia in adults", section on 'Fluid restriction' and "Heart failure self-management".)

●Avoidance of obesity. (See "Obesity in adults: Overview of management".)

Strategies of HF self-management are discussed separately. (See "Heart failure self-management".)

When to refer — Prompt referral is indicated in patients with a trigger for referral, such as persistent or worsening symptoms of HF or symptomatic hypotension. Common indications for referral are included in the table (table 4).

System-based strategies — A team-based approach may aid complex HF management [10]. Patients with HF at high risk for hospitalization should be referred to a multidisciplinary disease management program, if available. HF disease management is a multidisciplinary framework for the care of HF patients, including discharge planning, patient education, and frequent outpatient assessment. Comprehensive outpatient and inpatient support programs may reduce hospitalization rates but less comprehensive approaches appear to be less effective. (See "Systems-based strategies to reduce hospitalizations in patients with heart failure".)

Palliative care — Palliative care is an interdisciplinary approach that focuses on improving the quality of life for patients and their caregivers through communication, clarification of goals of care, shared decision making, coordination of care, and advance care planning. The role of palliative care for HF is most intense for patients with advanced disease and includes care by palliative care specialists. In a broader sense, palliative care has a role across the stages of HF with palliative care for patients, with earlier stages of HF often provided by non-palliative care clinicians. (See "Palliative care for patients with advanced heart failure: Indications and systems of care" and "Palliative care for patients with advanced heart failure: Decision support and management of symptoms".)

PHARMACOLOGIC THERAPY — The goals of pharmacologic therapy of HFrEF are to improve symptoms (including risk of hospitalization), slow or reverse deterioration in myocardial function, and reduce mortality (table 5) [1,2]:

●Improvement in symptoms can be achieved by diuretic, beta blockers, renin-angiotensin system inhibitor (angiotensin converting enzyme [ACE] inhibitor, single-agent angiotensin II receptor blockers [ARB], or angiotensin receptor-neprilysin inhibitor [ARNI]), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, hydralazine plus nitrate, digoxin, and mineralocorticoid receptor antagonist (MRA).

●Prolongation of patient survival has been documented with beta blockers, ACE inhibitors (similar with single-agent ARB), ARNI, SGLT2 inhibitors, hydralazine plus nitrate, and MRA. Limited evidence of survival benefit is available for diuretic therapy.

In addition, all other drugs and supplements that the patient is taking should be reviewed, and those that may contribute to HF (eg, nonsteroidal anti-inflammatory drugs, antiarrhythmic drugs, calcium channel blockers, thiazolidinediones) should be avoided. (See "Drugs that should be avoided or used with caution in patients with heart failure".)

The treatment of HFrEF in pregnancy requires attention to specific concerns about the effects of medications on the fetus and the mother, which is discussed separately. (See "Management of heart failure during pregnancy".)

Primary therapy — The primary pharmacologic therapies for patients with HFrEF are described separately (table 2). (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction".) (Related Pathway(s): Heart failure: Primary pharmacologic therapy for compensated heart failure with reduced ejection fraction (HFrEF).)

Secondary therapy — In patients who cannot tolerate components of the primary regimen for the treatment of HFrEF or who have residual HF symptoms despite optimal therapy, additional therapies may be appropriate (table 3). (See "Secondary pharmacologic therapy for heart failure with reduced ejection fraction".)

Antithrombotic therapy — For patients in sinus rhythm with LV systolic dysfunction (with or without HF) without acute LV thrombus, coronary artery disease, or other indication for antithrombotic therapy, we recommend not administering antiplatelet or anticoagulant therapy. However, many patients with HFrEF have indications for antiplatelet or anticoagulant therapy. These issues are discussed separately. (See "Antithrombotic therapy in patients with heart failure".)

Statins — Use of statin therapy in patients with HF is discussed separately. (See "Statin therapy in patients with heart failure".)

Fish oil — We do not routinely use n-3 polyunsaturated fatty acid (PUFA) supplementation in patients with HFrEF as a randomized trial demonstrated minimal to no benefit [11]. While the adverse effects of n-3 PUFA are generally mild (eg, nausea or fishy taste after eructation), the additional pills increase the complexity of care. For patients with HFrEF who inquire about the use of fish oil, we discuss the potential limited benefit and risk. If n-3 PUFA is added to the regimen, we stress the importance of continued therapy with primary (table 2) and secondary (table 3) pharmacologic therapy for HFrEF (as described above).

The GISSI-HF trial enrolled 7046 patients with New York Heart Association (NYHA) class II to IV HF (91 percent with HFrEF) who were randomly assigned to receive 1 g/day n-3 PUFA (with 850 to 882 mg eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] as ethyl esters in a ratio of 1:1.2) or placebo [11]. There were small but not statistically significant benefits in unadjusted analysis which were borderline significant after adjustment for factors that were unbalanced at baseline. After a median follow-up of 3.9 years, the mortality rate in patients treated with n-3 PUFA was slightly lower (27 versus 29 percent; unadjusted hazard ratio [HR] 0.93, 95.5% CI 0.852-1.021; adjusted HR 0.91, 95.5% CI 0.833-0.998). The rate of hospitalization for cardiovascular disease or death was also slightly reduced in the PUFA group (57 versus 59 percent; unadjusted HR 0.94, 99% CI 0.869-1.022; adjusted HR 0.92, 99% CI 0.849-0.999).

The role of fish oil for hypertriglyceridemia and for prevention of coronary heart disease and other cardiovascular disease events is discussed separately. (See "Hypertriglyceridemia in adults: Management", section on 'Marine omega-3 fatty acids' and "Lipid management with diet or dietary supplements" and "Overview of primary prevention of cardiovascular disease", section on 'Omega-3 fatty acids' and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

CARDIAC REHABILITATION — For patients with stable New York Heart Association (NYHA) class II to III HF (table 6), we recommend referral to a cardiac rehabilitation program. The beneficial effects of exercise are seen with high or low levels of training and are apparent as early as three weeks after training. There are not enough data at present to recommend cardiac rehabilitation for patients with advanced HF. (See "Cardiac rehabilitation in patients with heart failure" and "Cardiac rehabilitation programs".)

CARDIAC ELECTRONIC IMPLANTABLE DEVICE THERAPIES — Cardiac electronic implantable device (CIED) therapies include devices that treat malignant arrythmias and interventricular dyssynchrony:

●Implantable cardioverter-defibrillator – An implantable cardioverter-defibrillator (ICD) can reduce the risk of SCD. Criteria for ICD implantation for primary and secondary prevention of SCD are discussed separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".)

●Cardiac resynchronization therapy – Cardiac resynchronization therapy (CRT) with biventricular pacing is indicated in selected patients with HFrEF with a prolonged QRS duration. Most patients who satisfy criteria for CRT implantation are also candidates for an ICD and receive a combined device. Criteria for CRT use are discussed separately. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system".)

In addition, CIEDs can measure parameters such as cardiac filling pressures and surrogates of total body water (eg, thoracic impedance) that may assist in the management of HFrEF. The role of these devices in the treatment of HFrEF and HFpEF are discussed separately. (See "Treatment and prognosis of heart failure with preserved ejection fraction", section on 'Device-based therapies'.)

ADVANCED HEART FAILURE CARE — Patients with refractory HF despite optimum therapy require advanced care which may include the following components. These patients often require repeated prolonged hospitalizations for intensive management. (See "Management of refractory heart failure with reduced ejection fraction".)

●For patients with refractory HF despite optimal primary (table 2) and secondary (table 3) pharmacologic therapies, the role of intravenous inotropes and other in-hospital therapies is discussed separately. (See "Management of refractory heart failure with reduced ejection fraction", section on 'Intravenous inotropes' and "Management of refractory heart failure with reduced ejection fraction", section on 'Intravenous vasodilator therapy'.)

●Palliative care is particularly important in patients with advanced HF to support discussion of treatment goals, shared-decision making (particularly for complex treatment options such as ICD, mechanical circulatory support, and cardiac transplantation), and to aid symptom management. (See "Palliative care for patients with advanced heart failure: Indications and systems of care" and "Palliative care for patients with advanced heart failure: Decision support and management of symptoms".)

●The role of intermediate to long-term mechanical circulatory support (including LV assist devices) is discussed separately. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device" and "Management of long-term mechanical circulatory support devices".)

●Indications for cardiac transplantation are discussed separately. (See "Heart transplantation in adults: Indications and contraindications".)

Management of refractory HF and potential treatment options are discussed separately. (See "Management of refractory heart failure with reduced ejection fraction" and "Heart transplantation in adults: Indications and contraindications" and "Treatment of advanced heart failure with a durable mechanical circulatory support device" and "Management of long-term mechanical circulatory support devices" and "Palliative care for patients with advanced heart failure: Indications and systems of care".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Heart failure (The Basics)" and "Patient education: Medicines for heart failure with reduced ejection fraction (The Basics)" and "Patient education: Coping with high drug prices (The Basics)" and "Patient education: Heart failure and atrial fibrillation (The Basics)" and "Patient education: Heart failure with reduced ejection fraction (The Basics)")

●Beyond the Basics topics (see "Patient education: Heart failure (Beyond the Basics)" and "Patient education: Coping with high prescription drug prices in the United States (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Goals and overall approach – The goals of management of heart failure with reduced ejection fraction (HFrEF) are to reduce morbidity (including reducing symptoms, improving health-related quality of life and functional status, and decreasing the risk of hospitalization), and to reduce mortality. (See 'Goals and overall approach' above.)

●Management of associated conditions – Management of HFrEF includes management of the cause of HF (eg, coronary artery disease) and the management of associated conditions (eg, diabetes) (table 1). (See 'Management of causes and associated conditions' above.)

●Follow-up and preventive care – Patients with HF require serial follow-up to evaluate clinical status, support HF self-management including proper use of medications, evaluate response to therapy, and assess potential need for changes in management. (See 'Follow-up and preventive care' above.)

●Care coordination and referrals

•HF self-management – HF self-management includes medication management, daily monitoring of signs and symptoms (including daily weight monitoring to detect fluid accumulation), and lifestyle modification. (See 'HF self-management' above.)

•When to refer – Prompt referral is indicated in patients with a trigger for referral, such as persistent or worsening symptoms of HF or symptomatic hypotension (table 4). (See 'When to refer' above.)

•Systems-based strategies – A team-based approach may aid complex HF management. Patients with HF at high risk for hospitalization should be referred to a multidisciplinary disease management program, if available. (See 'System-based strategies' above.)

•Palliative care – Palliative care is an interdisciplinary approach that focuses on improving the quality of life for patients and their caregivers through communication, clarification of goals of care, shared decision making, coordination of care, and advance care planning. (See 'Palliative care' above and "Palliative care for patients with advanced heart failure: Indications and systems of care" and "Palliative care for patients with advanced heart failure: Decision support and management of symptoms".)

●Pharmacologic therapy

•Primary therapy – The primary pharmacologic therapies for patients with HFrEF are described separately (table 2). (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction".) (Related Pathway(s): Heart failure: Primary pharmacologic therapy for compensated heart failure with reduced ejection fraction (HFrEF).)

•Secondary therapy – In patients who cannot tolerate components of the primary regimen for the treatment of HFrEF or who have residual HF symptoms despite optimal therapy, additional therapies may be appropriate (table 3). (See "Secondary pharmacologic therapy for heart failure with reduced ejection fraction".)

●Device therapy – Patients with HFrEF who meet specific criteria may benefit from placement of an implantable cardioverter-defibrillator (ICD) or a cardiac resynchronization pacemaker. (See 'Cardiac electronic implantable device therapies' above.)

●Advanced heart failure therapies – Patients with refractory HF despite optimum therapy require advanced care which may include intravenous vasodilator therapy and intravenous inotropes, palliative care, mechanical circulatory support (including left ventricular assist device), and cardiac transplantation. (See 'Advanced heart failure care' above.)