Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

symptomatic HF: LVEF ≤40%

1st line – renin-angiotensin system inhibitor

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ONGOING
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symptomatic HF: LVEF ≤40%
1st line – 

renin-angiotensin system inhibitor

Renin-angiotensin system inhibitors include: sacubitril/valsartan (an angiotensin receptor-neprilysin inhibitor [ARNi]; ACE inhibitors; and angiotensin-II receptor antagonists.

The American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) guidelines recommend sacubitril/valsartan for all patients with HF with reduced ejection fraction (HFrEF) and New York Heart Association (NYHA) class II to III symptoms, in preference to an ACE inhibitor or angiotensin-II receptor antagonist, because of improvement in morbidity and mortality.[7] An ACE inhibitor is recommended when use of ARNi is not feasible.[7]  

European and UK guidelines recommend ACE inhibitors in all patients unless contraindicated or not tolerated.[9][122]​​​​​ European guidelines recommend sacubitril/valsartan as a replacement for an ACE inhibitor in patients with HFrEF who remain symptomatic despite optimal treatment, to reduce the risk of hospitalisation and death.[9]  

Concomitant administration of an ARNi with an ACE inhibitor, or within 36 hours of the last dose of an ACE inhibitor, is not recommended.[7]

Angiotensin-II receptor antagonists are considered a reasonable alternative to an ARNi or ACE inhibitor in patients who are intolerant of ACE inhibitors and when use of ARNi is not feasible.​[7][9][122]​​​[147]

Primary options

sacubitril/valsartan: treatment-naive or treatment-experienced on a low dose: 24 mg (sacubitril)/26 mg (valsartan) orally twice daily initially, increase gradually according to response, maximum 97 mg (sacubitril)/103 mg (valsartan) twice daily; treatment-experienced on a usual dose: 49 mg (sacubitril)/51 mg (valsartan) orally twice daily initially, increase gradually according to response, maximum 97 mg (sacubitril)/103 mg (valsartan) twice daily

More

OR

captopril: 6.25 to 50 mg orally three times daily

OR

enalapril: 2.5 to 20 mg orally twice daily

OR

fosinopril: 5-40 mg orally once daily

OR

lisinopril: 2.5 to 40 mg orally once daily

OR

perindopril: 2-16 mg orally once daily

OR

quinapril: 5-20 mg orally twice daily

OR

ramipril: 1.25 to 10 mg orally once daily

OR

trandolapril: 1-4 mg orally once daily

Secondary options

candesartan: 4-32 mg orally once daily

OR

losartan: 25-150 mg orally once daily

OR

valsartan: 40-160 mg orally twice daily

Plus – beta-blocker

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ONGOING
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symptomatic HF: LVEF ≤40%
Plus – 

beta-blocker

Treatment recommended for ALL patients in selected patient group

All patients with chronic HF should receive a beta-blocker, unless there is a contraindication based on bradycardia, reactive airway disease, and unstable or low-output HF.​[7][9][122]​​

AHA/ACC/HFSA guidelines recommend either bisoprolol, carvedilol, or sustained-release metoprolol succinate; European Society of Cardiology (ESC) guidelines also recommend nebivolol.[7][9]

Carvedilol seems superior to metoprolol, although there is no evidence of superiority to other beta-blockers.[249] In the SENIORS study, nebivolol, a cardioselective beta-blocker with nitric oxide-mediated vasodilating properties, was found to be an effective and well-tolerated treatment for HF in patients aged 70 years or more.[250] Data suggest that initiation with moderate doses of nebivolol is not associated with the adverse haemodynamic effects usually observed with other beta-blockers in patients with HF; therefore, a long up-titration period may not be necessary with nebivolol.[251]

Beta-blockers have been shown to decrease the morbidity and mortality associated with HF.​[7][9][122]​​​​​​​ They are initiated at low doses and titrated to target dosages.​[7][9][122][144]​​​​​ [ Cochrane Clinical Answers logo ] ​​​​​​ One meta-analysis found that irrespective of pre-treatment heart rate, beta-blockers reduced mortality in patients with HF with reduced ejection fraction (HFrEF) in sinus rhythm.[145]

Primary options

carvedilol: 3.125 mg orally (immediate-release) twice daily initially, increase according to response, maximum 50 mg/day (body weight ≤85 kg) or 100 mg/day (body weight >85 kg)

Secondary options

metoprolol: 12.5 to 200 mg orally (extended-release) once daily

OR

bisoprolol: 1.25 mg orally once daily initially, increase according to response, maximum 10 mg/day

OR

nebivolol: 1.25 mg orally once daily initially, increase according to response, maximum 10 mg/day

Plus – aldosterone antagonist

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ONGOING
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symptomatic HF: LVEF ≤40%
Plus – 

aldosterone antagonist

Treatment recommended for ALL patients in selected patient group

Aldosterone antagonists (e.g., spironolactone, eplerenone) are recommended in patients with HF with reduced ejection fraction (HFrEF) to reduce mortality and morbidity.[7][9]

Spironolactone and eplerenone can both cause hyperkalaemia, and precautions should be taken to minimise the risk; regular monitoring of serum potassium and renal function is recommended.[7][9]​​​ In the EPHESUS trial, the addition of eplerenone to standard care did not increase the risk of hyperkalaemia when potassium was regularly monitored.[149]​ US guidelines advise that if serum potassium cannot be maintained below 5.5 mEq/L, the aldosterone antagonist should be discontinued.[7]

Primary options

spironolactone: 12.5 to 50 mg orally once daily

OR

eplerenone: 25-50 mg orally once daily

Plus – sodium-glucose cotransporter-2 (SGLT2) inhibitor

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ONGOING
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symptomatic HF: LVEF ≤40%
Plus – 

sodium-glucose cotransporter-2 (SGLT2) inhibitor

Treatment recommended for ALL patients in selected patient group

An SGLT2 inhibitor (e.g., dapagliflozin, empagliflozin) is recommended, in addition to optimal medical therapy with a renin-angiotensin system inhibitor, a beta-blocker, and an aldosterone antagonist, for patients with HF with reduced ejection fraction (HFrEF) regardless of diabetes status.[7][9][150][151][152]

Primary options

dapagliflozin: 10 mg orally once daily

OR

empagliflozin: 10 mg orally once daily

Plus – lifestyle changes

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ONGOING
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symptomatic HF: LVEF ≤40%
Plus – 

lifestyle changes

Treatment recommended for ALL patients in selected patient group

The success of pharmacological therapy is strongly related to, and greatly enhanced by, encouraging the patient and his/her family to participate in various complementary non-pharmacological management strategies. These mainly include lifestyle changes, dietary and nutritional modifications, exercise training, and health maintenance.[123]

In patients with HF, cardiac rehabilitation and exercise training improves functional status, exercise tolerance, and quality of life, with decreased morbidity and mortality.[124][125][126]​​​​[127][128][129][130][131][132]​​​ [ Cochrane Clinical Answers logo ] ​​​​ Patients with stable HF who are able to participate are therefore encouraged to do regular exercise and enrol in a cardiac rehabilitation programme.​[7][9]​​​​ [ Cochrane Clinical Answers logo ] ​​​​ There is developing evidence to support home-based cardiac rehabilitation alternatives to centre-based programmes.[133][134][135]

Dietary sodium intake is an easily modifiable factor that complements pharmacological therapy for HF. There is limited evidence for sodium restriction in patients with HF; however, guidelines recommend that excessive sodium intake should be avoided.​[7][9][122]​​​​[136]

Patients with HF need continuous and close monitoring of their health. A variety of programmes have been shown to decrease morbidity and re-hospitalisation in this context, including home nursing, telephone advice/triage, telemedicine services, and specialised HF clinic-based care.[252] [ Cochrane Clinical Answers logo ] ​

Consider – diuretic

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ONGOING
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symptomatic HF: LVEF ≤40%
Consider – 

diuretic

Additional treatment recommended for SOME patients in selected patient group

All patients with symptoms and signs of congestion should receive a diuretic, irrespective of the left ventricular ejection fraction (LVEF). In patients with reduced LVEF, diuretics should be used in combination with other guideline-directed medical therapy (e.g., a renin-angiotensin system inhibitor, beta-blocker, and aldosterone antagonist).[7][9]

Loop diuretics used for the treatment of HF and congestion include furosemide, bumetanide, and torasemide. The most commonly used agent appears to be furosemide, but some patients may respond more favourably to another loop diuretic. In resistant cases, loop diuretics should be combined with a thiazide diuretic (e.g., hydrochlorothiazide) or a thiazide-like diuretic (e.g., metolazone, indapamide). Careful monitoring of renal function and electrolytes is essential in these patients.

The minimum dose of diuretic should be used to relieve congestion, keep the patient asymptomatic, and maintain a dry weight. In patients with stable congestive HF, loop diuretics are the preferred agent. In patients with comorbid hypertension and only mild fluid retention, a thiazide diuretic may be considered.

Diuretics produce symptomatic benefits more rapidly than any other drug for HF. They can relieve pulmonary and peripheral oedema within hours or days. Few patients with HF and fluid retention can maintain sodium balance without the use of diuretic drugs.[253]

In intermediate-term studies, diuretics have been shown to improve cardiac function, symptoms, and exercise tolerance in patients with HF.[253][254]​​​ There have been no long-term studies of diuretic therapy in HF, and thus their effects on morbidity and mortality are not known.

Primary options

furosemide: 20-80 mg/dose orally initially, increase by 20-40 mg/dose increments every 6-8 hours according to response, maximum 600 mg/day

OR

bumetanide: 0.5 to 2 mg orally once daily initially, may repeat every 4-5 hours until response, maximum 10 mg/day given in 1-2 divided doses

OR

torasemide: 5-20 mg orally once daily initially, increase according to response, maximum 40 mg/day

OR

hydrochlorothiazide: 25 mg orally once daily, increase according to response, maximum 200 mg/day

OR

indapamide: 2.5 to 5 mg orally once daily

OR

metolazone: 5-20 mg orally once daily

Consider – isosorbide dinitrate/hydralazine

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ONGOING
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symptomatic HF: LVEF ≤40%
Consider – 

isosorbide dinitrate/hydralazine

Additional treatment recommended for SOME patients in selected patient group

The addition of a combination of hydralazine and a nitrate is reasonable for patients with reduced left ventricular ejection fraction (LVEF) who have persistent symptoms despite receiving optimal medical therapy and has demonstrated benefit in black patients with HF.[199][200]

Guidelines recommend the combination of hydralazine and isosorbide dinitrate for black patients with New York Heart Association (NYHA) class III to IV HF with reduced ejection fraction (HFrEF) receiving optimal medical therapy, to improve symptoms and reduce morbidity and mortality.​[7][9][122]​​

The combined use of hydralazine and isosorbide dinitrate may also be considered as a therapeutic option in symptomatic patients who cannot receive renin-angiotensin system inhibitors because of intolerance or contraindications; consultation with a specialist is advised.[7][9]

A combination formulation containing hydralazine and isosorbide dinitrate is available in some countries, and is approved specifically for self-identified black patients with chronic HF.

Primary options

isosorbide dinitrate: 20-40 mg orally (immediate-release) three times daily

and

hydralazine: 25-100 mg orally three times daily

OR

isosorbide dinitrate/hydralazine: 20 mg (isosorbide dinitrate)/37.5 mg (hydralazine) orally three times daily initially, increase according to response, maximum 40 mg (isosorbide dinitrate)/75 mg (hydralazine) three times daily

Consider – ivabradine

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ONGOING
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symptomatic HF: LVEF ≤40%
Consider – 

ivabradine

Additional treatment recommended for SOME patients in selected patient group

Ivabradine can be considered for patients with stable, symptomatic chronic HF with left ventricular ejection fraction (LVEF) ≤35%, who are in sinus rhythm with a resting heart rate ≥70 beats per minute (UK National Institute for Health and Care Excellence [NICE] guidelines advise ≥75 beats per minute) and are either on a maximum dose of beta-blockers or have a contraindication to beta-blockers.​[7][9][122]​​​

Its use should be initiated by a specialist cardiologist and only after a stabilisation period of 4 weeks on optimised standard therapy.[255]​ Patients should be on a maximally tolerated dose of a beta-blocker prior to initiation.

Primary options

ivabradine: 2.5 to 5 mg orally twice daily for 2 weeks initially, adjust dose according to response and heart rate, maximum 15 mg/day

Consider – digoxin

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ONGOING
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symptomatic HF: LVEF ≤40%
Consider – 

digoxin

Additional treatment recommended for SOME patients in selected patient group

Digoxin can be beneficial in patients with reduced left ventricular ejection fraction (LVEF), especially those with atrial fibrillation.

When added to ACE inhibitors, beta-blockers, and diuretics, digoxin can reduce symptoms, prevent hospitalisation, control rhythm, and enhance exercise tolerance.[203]

Digoxin reduces the composite end point of mortality or hospitalisations in ambulatory patients with chronic HF with New York Heart Association (NYHA) class III or IV symptoms, LVEF <25%, or cardiothoracic ratio of >55% and should be considered in these patients.[204]

Digoxin reduces the composite end point of mortality or hospitalisations, but does not reduce all-cause mortality.[204] Digoxin should be used cautiously with plasma level monitoring; one meta-analysis suggests that digoxin use in patients with HF is associated with a higher risk of all-cause mortality.[205]

Overt digitalis toxicity is commonly associated with serum digoxin levels >2.6 nanomols/L (2 nanograms/mL). However, toxicity may occur with lower levels, especially if hypokalaemia, hypomagnesaemia, or hypothyroidism co-exists.[256][257]

Lower doses should be used initially if the patient is over 70 years old, has impaired renal function, or has a low lean body mass.[258]​ Higher doses are rarely used or needed. There is no reason to use loading doses of digoxin to initiate therapy.

Primary options

digoxin: 62.5 to 250 micrograms orally once daily

Consider – vericiguat

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ONGOING
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symptomatic HF: LVEF ≤40%
Consider – 

vericiguat

Additional treatment recommended for SOME patients in selected patient group

Vericiguat, an oral soluble guanylate cyclase stimulator, may be considered in selected high-risk patients with HF with reduced ejection fraction (HFrEF) and New York Heart Association (NYHA) class II to IV symptoms, who have had worsening HF despite treatment with an ACE inhibitor or angiotensin-receptor neprilysin inhibitor, a beta-blocker, and an aldosterone antagonist to reduce the risk of cardiovascular mortality or HF hospitalisation.[7][9]

Primary options

vericiguat: 2.5 mg orally once daily initially, increase according to response, maximum 10 mg/day

Consider – omega-3 polyunsaturated fatty acid supplementation

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ONGOING
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symptomatic HF: LVEF ≤40%
Consider – 

omega-3 polyunsaturated fatty acid supplementation

Additional treatment recommended for SOME patients in selected patient group

In patients with New York Heart Association (NYHA) class II to IV symptoms and HF who are already on guideline-directed medical therapy (GDMT) and other evidence-based therapies, omega-3 polyunsaturated fatty acid supplementation may be reasonable to use as adjunctive therapy to reduce mortality and cardiovascular hospitalisations.[7]

Consider – vasopressin antagonist

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ONGOING
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symptomatic HF: LVEF ≤40%
Consider – 

vasopressin antagonist

Additional treatment recommended for SOME patients in selected patient group

Considered for patients with symptomatic or severe hyponatraemia (<130 mmol/L) and persistent congestion despite standard therapy, to correct hyponatraemia and related symptoms.​​[7][9]

Primary options

tolvaptan: 15 mg orally once daily initially, increase gradually according to response, maximum 60 mg/day for up to 30 days

Consider – implantable device therapy

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ONGOING
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symptomatic HF: LVEF ≤40%
Consider – 

implantable device therapy

Additional treatment recommended for SOME patients in selected patient group

Device therapy with implantable cardioverter-defibrillator (ICD) or cardiac re-synchronisation therapy (CRT) should be considered in selected patients to reduce mortality and morbidity.

ICDs are recommended to reduce sudden cardiac death and mortality in selected patients when there is a reasonable expectation of meaningful survival for at least 1 year, left ventricular ejection fraction (LVEF) is ≤35% (New York Heart Association [NYHA] class II-III) or ≤30% (NYHA class I) despite guideline-directed medical therapy (GDMT), and the patient is at least 40 days post-myocardial infarction.[7][9] Specific indications vary in different countries, and guidelines should be consulted for full details.

CRT is recommended in selected patients to reduce morbidity and mortality and improve symptoms. It can be used as a pacemaker alone (CRT-P) or combined with an ICD (CRT-D). Broadly, CRT is recommended in patients with LVEF ≤35% despite GDMT, who are in sinus rhythm, with a left bundle branch block (LBBB) and QRS ≥150 ms.[7][9][233]​​ CRT should also be considered in those with LBBB and QRS ≥120-149 ms or those with a non-LBBB pattern and QRS ≥150 ms. Again, specific indications vary in different countries, and guidelines should be consulted for full details.

Consider – supportive measures +/- nephrology referral

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with chronic kidney disease
Consider – 

supportive measures +/- nephrology referral

Additional treatment recommended for SOME patients in selected patient group

Some drugs used in the management of heart failure should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information. Initiation of GDMT for HF with an ACE inhibitor, angiotensin-II receptor antagonist, ARNi, or SGLT2 inhibitor may result in an initial rise in serum creatinine and a drop in estimated glomerular filtration rate (eGFR), but this change is generally transient and should not necessarily be a reason for discontinuation.[9][246]

An increase in serum creatinine of <50% above baseline, up to 265 micromols/L, or a decrease in eGFR of <10% from baseline, as long as eGFR is >25 mL/minute/1.73 m², may be considered as acceptable. If the serum creatinine increases to >265 micromols/L, the renal insufficiency can severely limit the efficacy and enhance the toxicity of established treatments.[247][248]​​​

Aldosterone antagonists should be used with caution in patients with CKD and hyperkalaemia. US guidelines advise that they are only initiated in patients with eGFR >30 mL/minute/1.73 m² and serum potassium <5.0 mEq/L.[7]

Consultation with a nephrology specialist should be considered.

See Chronic kidney disease (Treatment algorithm).

Consider – intravenous iron supplementation

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with anaemia/ iron-deficiency
Consider – 

intravenous iron supplementation

Additional treatment recommended for SOME patients in selected patient group

Patients with iron deficiency anaemia and transferrin saturation <20% should receive intravenous iron supplementation.[7][9][143]​​​

For more details on management, see Iron-deficiency anaemia (Treatment algorithm).

Consider – surgical revascularisation

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with chronic coronary disease
Consider – 

surgical revascularisation

Additional treatment recommended for SOME patients in selected patient group

In selected patients with CAD and HF with LVEF ≤35% and suitable coronary anatomy, surgical revascularisation in addition to GDMT may improve symptoms, cardiovascular hospitalisations, and long-term all-cause mortality.[7][9]​​

For more details, see Chronic coronary disease (Treatment algorithm).

Consider – multidisciplinary team management

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ONGOING
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symptomatic HF: LVEF ≤40%
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with valvular heart disease
Consider – 

multidisciplinary team management

Additional treatment recommended for SOME patients in selected patient group

Aortic stenosis, aortic regurgitation, mitral regurgitation, and tricuspid regurgitation are associated with adverse outcomes in patients with HF and timely management (by a multidisciplinary team with expertise in HF and VHD) is important to prevent worsening of HF.[7][9]​​

For more details, see Aortic stenosis (Treatment algorithm), Aortic regurgitation (Treatment algorithm), Mitral regurgitation (Treatment algorithm), Tricuspid regurgitation (Treatment algorithm).

Consider – rate and rhythm control + anticoagulation

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ONGOING
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symptomatic HF: LVEF ≤40%
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with atrial fibrillation
Consider – 

rate and rhythm control + anticoagulation

Additional treatment recommended for SOME patients in selected patient group

AF and HF may cause or exacerbate each other and the relationship is complex.

HF therapies should be optimised. Beta-blockers may be used in HFrEF whether or not the patient has associated AF.[145][146]​​

Treatment of AF involves correction of the abnormal rate/rhythm, along with anticoagulation. Options for rate and rhythm control are determined by the presence of HF and extent of LV dysfunction.[7][9]

For details of management of patients with AF and HF, see Established atrial fibrillation (Treatment algorithm).

Plus – treatment of hyperglycaemia

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with diabetes
Plus – 

treatment of hyperglycaemia

Treatment recommended for ALL patients in selected patient group

Treatment of HFrEF is similar in patients with and without diabetes.

SGLT2 inhibitors are recommended as first-line treatment of hyperglycaemia in patients with type 2 diabetes and HF to reduce HF-related morbidity and mortality.[7][9]

See Overview of diabetes.​​

Consider – finerenone

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with diabetes
Consider – 

finerenone

Additional treatment recommended for SOME patients in selected patient group

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, is recommended for the prevention of HF hospitalisation in patients with CKD and type 2 diabetes.[143]

Primary options

finerenone: 20 mg orally once daily

More

Consider – weight loss programme

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with obesity
Consider – 

weight loss programme

Additional treatment recommended for SOME patients in selected patient group

Treatment of obesity in patients with HFrEF may improve symptoms, functional status, quality of life, and comorbidities.[38] In advanced HF, weight loss in patients with obesity may allow the option of heart transplantation (obesity may be a contraindication).​

See Obesity in adults (Treatment algorithm).

Consider – lipid-lowering therapy

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with hyperlipidaemia
Consider – 

lipid-lowering therapy

Additional treatment recommended for SOME patients in selected patient group

All patients with HFrEF and hyperlipidaemia will need lifestyle modifications and most will also require treatment with a statin possibly with additional non-statin lipid-lowering therapy.

For details of management of HF with hypercholesterolaemia, see Hypercholesterolaemia (Treatment algorithm).

Consider – referral to endocrinologist

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with thyroid disorders
Consider – 

referral to endocrinologist

Additional treatment recommended for SOME patients in selected patient group

Both hypo- and hyperthyroidism are associated with HF and assessment of thyroid function is recommended. Thyroid disorders are treated as per endocrinology guidelines; referral to endocrinologist should be considered.

See Overview of thyroid dysfunction.

Consider – assessment and treatment of sleep apnoea

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with daytime sleepiness
Consider – 

assessment and treatment of sleep apnoea

Additional treatment recommended for SOME patients in selected patient group

Patients with HF and daytime sleepiness may have sleep studies to assess for obstructive sleep apnoea and central sleep apnoea.[7][9]

In patients with HF and obstructive sleep apnoea, continuous positive airway pressure is recommended to improve sleep quality and reduce daytime sleepiness; however, it does not seem to reduce mortality.[7][9]​​

Adaptive servo-ventilation has been associated with increased mortality and is not recommended for the treatment of central sleep apnoea in patients with HFrEF.[7][9]

See Obstructive sleep apnoea in adults (Treatment algorithm) and Central sleep apnoea (Treatment algorithm).

Plus – interventions to improve HF self-care

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with depression
Plus – 

interventions to improve HF self-care

Treatment recommended for ALL patients in selected patient group

Depression is common in patients with HF and is associated with a reduced quality of life and increased mortality.

Treatment with conventional therapies (e.g., antidepressants) does not seem to directly improve these outcomes. However, interventions that focus on improving HF self-care (e.g., psychotherapy, nurse-led support) may reduce hospitalisation and mortality in patients with moderate or severe depression.[7][9]​​​

See Depression in adults (Treatment algorithm).

Plus – multidisciplinary team management

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ONGOING
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symptomatic HF: LVEF ≤40%
|
with cancer
Plus – 

multidisciplinary team management

Treatment recommended for ALL patients in selected patient group

Patients who develop HF and/or depressed LV systolic function secondary to cancer therapy should be treated with guideline directed-medical therapy (GDMT). Generally, GDMT should not be discontinued unless there are specific and compelling reasons to hold these medicines and this should be managed by a multidisciplinary team.

Before starting any cardiotoxic cancer therapy baseline cardiac function should be measured and ongoing monitoring after completion of a course of chemotherapy may be helpful for risk stratification.[7][9]

symptomatic HF: LVEF 41% to 49%

1st line – sodium-glucose cotransporter-2 (SGLT2) inhibitor

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ONGOING
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symptomatic HF: LVEF 41% to 49%
1st line – 

sodium-glucose cotransporter-2 (SGLT2) inhibitor

SGLT2 inhibitors are now recommended for patients with HFmrEF, to reduce HF hospitalisations and cardiovascular mortality.[7][143][153][154]

Primary options

dapagliflozin: 10 mg orally once daily

OR

empagliflozin: 10 mg orally once daily

Plus – lifestyle changes

Back
ONGOING
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symptomatic HF: LVEF 41% to 49%
Plus – 

lifestyle changes

Treatment recommended for ALL patients in selected patient group

The success of pharmacological therapy is strongly related to, and greatly enhanced by, encouraging the patient and his/her family to participate in various complementary non-pharmacological management strategies. These mainly include lifestyle changes, dietary and nutritional modifications, exercise training, and health maintenance.[123]

In patients with HF, cardiac rehabilitation and exercise training improves functional status, exercise tolerance, and quality of life, with decreased morbidity and mortality.[124][125][126]​​​​[127][128][129][130][131][132]​​​ [ Cochrane Clinical Answers logo ] ​​​​ Patients with stable HF who are able to participate are therefore encouraged to do regular exercise and enrol in a cardiac rehabilitation programme.​[7][9]​​​​ [ Cochrane Clinical Answers logo ] ​​​​ There is developing evidence to support home-based cardiac rehabilitation alternatives to centre-based programmes.[133][134][135]

Dietary sodium intake is an easily modifiable factor that complements pharmacological therapy for HF. There is limited evidence for sodium restriction in patients with HF; however, guidelines recommend that excessive sodium intake should be avoided.​[7][9][122]​​​​[136]

Patients with HF need continuous and close monitoring of their health. A variety of programmes have been shown to decrease morbidity and re-hospitalisation in this context, including home nursing, telephone advice/triage, telemedicine services, and specialised HF clinic-based care.[252] [ Cochrane Clinical Answers logo ]

Consider – diuretic

Back
ONGOING
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symptomatic HF: LVEF 41% to 49%
Consider – 

diuretic

Additional treatment recommended for SOME patients in selected patient group

All patients with symptoms and signs of congestion should receive a diuretic, irrespective of the left ventricular ejection fraction (LVEF).

Loop diuretics used for the treatment of HF and congestion include furosemide, bumetanide, and torasemide. The most commonly used agent appears to be furosemide, but some patients may respond more favourably to another loop diuretic. In resistant cases, loop diuretics should be combined with a thiazide diuretic (e.g., hydrochlorothiazide) or a thiazide-like diuretic (e.g., metolazone, indapamide). Careful monitoring of renal function and electrolytes is essential in these patients.

The minimum dose of diuretic should be used to relieve congestion, keep the patient asymptomatic, and maintain a dry weight. In patients with stable congestive HF, loop diuretics are the preferred agent. In patients with comorbid hypertension and only mild fluid retention, a thiazide diuretic may be considered.

Diuretics produce symptomatic benefits more rapidly than any other drug for HF. They can relieve pulmonary and peripheral oedema within hours or days. Few patients with HF and fluid retention can maintain sodium balance without the use of diuretic drugs.[253]

In intermediate-term studies, diuretics have been shown to improve cardiac function, symptoms, and exercise tolerance in patients with HF.[253][254]​​​​ There have been no long-term studies of diuretic therapy in HF, and thus their effects on morbidity and mortality are not known.

Primary options

furosemide: 20-80 mg/dose orally initially, increase by 20-40 mg/dose increments every 6-8 hours according to response, maximum 600 mg/day

OR

bumetanide: 0.5 to 2 mg orally once daily initially, may repeat every 4-5 hours until response, maximum 10 mg/day given in 1-2 divided doses

OR

torasemide: 5-20 mg orally once daily initially, increase according to response, maximum 40 mg/day

OR

hydrochlorothiazide: 25 mg orally once daily, increase according to response, maximum 200 mg/day

OR

indapamide: 2.5 to 5 mg orally once daily

OR

metolazone: 5-20 mg orally once daily

Consider – renin-angiotensin system inhibitor

Back
ONGOING
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symptomatic HF: LVEF 41% to 49%
Consider – 

renin-angiotensin system inhibitor

Additional treatment recommended for SOME patients in selected patient group

Guidelines advise that use of renin-angiotensin system inhibitors may be considered in patients with HFmrEF to reduce risk of HF hospitalisation and cardiovascular mortality.[7][9][143]

Primary options

sacubitril/valsartan: treatment-naive or treatment-experienced on a low dose: 24 mg (sacubitril)/26 mg (valsartan) orally twice daily initially, increase gradually according to response, maximum 97 mg (sacubitril)/103 mg (valsartan) twice daily; treatment-experienced on a usual dose: 49 mg (sacubitril)/51 mg (valsartan) orally twice daily initially, increase gradually according to response, maximum 97 mg (sacubitril)/103 mg (valsartan) twice daily

More

OR

captopril: 6.25 to 50 mg orally three times daily

OR

enalapril: 2.5 to 20 mg orally twice daily

OR

fosinopril: 5-40 mg orally once daily

OR

lisinopril: 2.5 to 40 mg orally once daily

OR

perindopril: 2-16 mg orally once daily

OR

quinapril: 5-20 mg orally twice daily

OR

ramipril: 1.25 to 10 mg orally once daily

OR

trandolapril: 1-4 mg orally once daily

Secondary options

candesartan: 4-32 mg orally once daily

OR

losartan: 25-150 mg orally once daily

OR

valsartan: 40-160 mg orally twice daily

Consider – aldosterone antagonist

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symptomatic HF: LVEF 41% to 49%
Consider – 

aldosterone antagonist

Additional treatment recommended for SOME patients in selected patient group

Guidelines advise that use of an aldosterone antagonist may be considered in patients with HFmrEF to reduce risk of HF hospitalisation and cardiovascular mortality.[7][9][143]

Primary options

spironolactone: 12.5 to 50 mg orally once daily

OR

eplerenone: 25-50 mg orally once daily

Consider – beta-blocker

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symptomatic HF: LVEF 41% to 49%
Consider – 

beta-blocker

Additional treatment recommended for SOME patients in selected patient group

Guidelines advise that use of a beta-blocker may be considered in patients with HFmrEF to reduce risk of HF hospitalisation and cardiovascular mortality.[7][9][143]​​​

Primary options

carvedilol: 3.125 mg orally (immediate-release) twice daily initially, increase according to response, maximum 50 mg/day (body weight ≤85 kg) or 100 mg/day (body weight >85 kg)

Secondary options

metoprolol: 12.5 to 200 mg orally (extended-release) once daily

OR

bisoprolol: 1.25 mg orally once daily initially, increase according to response, maximum 10 mg/day

OR

nebivolol: 1.25 mg orally once daily initially, increase according to response, maximum 10 mg/day

Consider – supportive measures +/- nephrology referral

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symptomatic HF: LVEF 41% to 49%
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with chronic kidney disease
Consider – 

supportive measures +/- nephrology referral

Additional treatment recommended for SOME patients in selected patient group

Some drugs used in the management of HF should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information.

Consultation with a nephrology specialist should be considered.

See Chronic kidney disease (Treatment algorithm).

Consider – intravenous iron supplementation

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symptomatic HF: LVEF 41% to 49%
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with anaemia/ iron-deficiency
Consider – 

intravenous iron supplementation

Additional treatment recommended for SOME patients in selected patient group

Patients with iron deficiency anaemia and transferrin saturation <20% should receive intravenous iron supplementation.[7][9]​​[143]

For more details on management, see Iron-deficiency anaemia (Treatment algorithm).

Consider – surgical revascularisation

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symptomatic HF: LVEF 41% to 49%
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with chronic coronary disease
Consider – 

surgical revascularisation

Additional treatment recommended for SOME patients in selected patient group

In selected patients with CAD and HF with LVEF ≤35% and suitable coronary anatomy, surgical revascularisation in addition to GDMT may improve symptoms, cardiovascular hospitalisations, and long-term all-cause mortality.[7][9]​​

For more details, see Chronic coronary disease (Treatment algorithm).

Consider – multidisciplinary management

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symptomatic HF: LVEF 41% to 49%
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with valvular heart disease
Consider – 

multidisciplinary management

Additional treatment recommended for SOME patients in selected patient group

Aortic stenosis, aortic regurgitation, mitral regurgitation, and tricuspid regurgitation are associated with adverse outcomes in patients with HF and timely management (by a multidisciplinary team with expertise in HF and VHD) is important to prevent worsening of HF.[7][9]​​

For more details, see Aortic stenosis (Treatment algorithm), Aortic regurgitation (Treatment algorithm), Mitral regurgitation (Treatment algorithm), Tricuspid regurgitation (Treatment algorithm).

Consider – rate and rhythm control + anticoagulation

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symptomatic HF: LVEF 41% to 49%
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with atrial fibrillation
Consider – 

rate and rhythm control + anticoagulation

Additional treatment recommended for SOME patients in selected patient group

AF and HF may cause or exacerbate each other and the relationship is complex.

HF therapies should be optimised. Beta-blockers may be used in HFrEF whether or not the patient has associated AF.[145][146]

Treatment of AF involves correction of the abnormal rate/rhythm, along with anticoagulation. Options for rate and rhythm control are determined by the presence of HF and extent of LV dysfunction.[7][9]

For details of management of patients with AF and HF, see Established atrial fibrillation (Treatment algorithm).

Plus – treatment of hyperglycaemia

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symptomatic HF: LVEF 41% to 49%
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with diabetes
Plus – 

treatment of hyperglycaemia

Treatment recommended for ALL patients in selected patient group

Treatment of HFrEF is similar in patients with and without diabetes.

SGLT2 inhibitors are recommended as first-line treatment of hyperglycaemia in patients with type 2 diabetes and HF to reduce HF-related morbidity and mortality.[7][9] See also information above on SGLT2 inhibitors.​​

See Overview of diabetes.

Consider – finerenone

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symptomatic HF: LVEF 41% to 49%
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with diabetes
Consider – 

finerenone

Additional treatment recommended for SOME patients in selected patient group

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, is recommended for the prevention of HF hospitalisation in patients with CKD and type 2 diabetes.[143]

Primary options

finerenone: 20 mg orally once daily

More

Consider – weight loss programme

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symptomatic HF: LVEF 41% to 49%
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with obesity
Consider – 

weight loss programme

Additional treatment recommended for SOME patients in selected patient group

Treatment of obesity in patients with HFrEF may improve symptoms, functional status, quality of life, and comorbidities.[38]​ In advanced HF, weight loss in patients with obesity may allow the option of heart transplantation (obesity may be a contraindication).

See Obesity in adults (Treatment algorithm).

Consider – lipid-lowering therapy

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symptomatic HF: LVEF 41% to 49%
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with hyperlipidaemia
Consider – 

lipid-lowering therapy

Additional treatment recommended for SOME patients in selected patient group

All patients with HFrEF and hyperlipidaemia will need lifestyle modifications and most will also require treatment with a statin possibly with additional non-statin lipid-lowering therapy.

For details of management of HF with hypercholesterolaemia, see Hypercholesterolaemia (Treatment algorithm).

Consider – referral to endocrinologist

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symptomatic HF: LVEF 41% to 49%
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with thyroid disorders
Consider – 

referral to endocrinologist

Additional treatment recommended for SOME patients in selected patient group

Both hypo- and hyperthyroidism are associated with HF and assessment of thyroid function is recommended. Thyroid disorders are treated as per endocrinology guidelines; referral to endocrinologist should be considered.

See Overview of thyroid disorders.

Consider – assessment and treatment of sleep apnoea

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symptomatic HF: LVEF 41% to 49%
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with daytime sleepiness
Consider – 

assessment and treatment of sleep apnoea

Additional treatment recommended for SOME patients in selected patient group

Patients with HF and daytime sleepiness may have sleep studies to assess for obstructive sleep apnoea and central sleep apnoea.[7][9]​​

In patients with HF and obstructive sleep apnoea, continuous positive airway pressure is recommended to improve sleep quality and reduce daytime sleepiness; however, it does not seem to reduce mortality.[7][9]​​

Adaptive servo-ventilation has been associated with increased mortality and is not recommended for the treatment of central sleep apnoea in patients with HFrEF.[7][9]​​

See Obstructive sleep apnoea in adults (Treatment algorithm) and Central sleep apnoea (Treatment algorithm).

Plus – interventions to improve HF self-care

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symptomatic HF: LVEF 41% to 49%
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with depression
Plus – 

interventions to improve HF self-care

Treatment recommended for ALL patients in selected patient group

Depression is common in patients with HF and is associated with a reduced quality of life and increased mortality.

Treatment with conventional therapies (e.g., antidepressants) does not seem to directly improve these outcomes. However, interventions that focus on improving HF self-care (e.g., psychotherapy, nurse-led support) may reduce hospitalisation and mortality in patients with moderate or severe depression.[7][9]

See Depression in adults.

Plus – multidisciplinary team management

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symptomatic HF: LVEF 41% to 49%
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with cancer
Plus – 

multidisciplinary team management

Treatment recommended for ALL patients in selected patient group

Patients who develop HF and/or depressed LV systolic function secondary to cancer therapy should be treated with guideline directed-medical therapy (GDMT). Generally, GDMT should not be discontinued unless there are specific and compelling reasons to hold these medicines and this should be managed by a multidisciplinary team.

Before starting any cardiotoxic cancer therapy baseline cardiac function should be measured and ongoing monitoring after completion of a course of chemotherapy may be helpful for risk stratification.[7][9]

advanced HF

1st line – referral to specialist care for advanced HF therapies

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advanced HF
1st line – 

referral to specialist care for advanced HF therapies

Patients with indicators of advanced HF require timely referral to specialist care to assess suitability for management options that may include inotropic support, mechanical circulatory support (MCS), cardiac transplantation, and palliative care.[7][9]

Inotropic support: in patients with advanced HF refractory to optimal medical and device therapy, prolonged intravenous inotropic support may be used as a bridge to long-term mechanical circulatory support or cardiac transplant.[7] Continuous intravenous inotropic support may also be considered as palliative therapy for the relief of symptoms in patients without other treatment options.[7][9]

MCS: helps to maintain sufficient end organ perfusion by unloading the heart. Temporary MCS, such as percutaneous and extracorporeal ventricular assist devices, may be used in patients with advanced HF and haemodynamic compromise or shock as a bridge to recovery or bridge to decision about future care.[7][9] Long-term MCS, such as a durable left ventricular assist device (LVAD), is considered in carefully selected patients who have end-stage HF despite optimal medical and device therapy, or dependence on intravenous inotropes or temporary MCS, either as a bridge to transplantation or as destination therapy (permanent pump implantation in patients not eligible for cardiac transplantation).[7][9]​​[236][237]

Cardiac transplantation: significantly improves quality of life and functional status and is the established treatment for eligible patients with advanced HF refractory to optimal medical and device therapy.[7][9]

Palliative and supportive care: should be provided to all patients with HF to improve quality of life, and this care intensifies as disease progresses to advanced and end-of-life stages.[7][9] Palliative and supportive care is a multidisciplinary approach that includes high-quality communication, discussion of prognosis, shared decision-making, advance care planning, relief from pain and other distressing symptoms, attention to emotional, psychological, and spiritual aspects of care, and support for families and carers during illness and bereavement.[7][9]

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