Overview ã…¡ Heart failure typically classified by New York Heart Association (NYHA) I-IV functional classification or American College of Cardiology Foundation/American Heart Association (ACCF/AHA) A-D staging (see table 1). Heart failure with reduced ejection fraction (HFrEF) or systolic heart failure results in decreased heart pump function (left ventricular ejection fraction ≤ 40%) that may lead to insufficient amounts of oxygenated blood being delivered to meet the needs of tissues and organs.
Common causes of HFrEF include coronary artery disease, dilated cardiomyopathy, valvular heart disease (both related to pressure overload and volume overload), and hypertension. Selected blood and imaging studies may help identify asymptomatic individuals at risk for developing symptomatic HF, and lifestyle changes and medications may help prevent progression of asymptomatic to symptomatic HF.
EVALUATION
Suspect heart failure in patients with a history of dyspnea with exertion or at rest, or other symptoms of heart failure including fatigue, abdominal distention, lower extremity swelling, orthopnea, or paroxysmal nocturnal dyspnea. Signs may include evidence of volume overload (elevated jugular venous pressure, peripheral edema, or rales) or diminished perfusion (cold extremities). Differential diagnosis for heart failure includes other causes of dyspnea such as asthma, chronic obstructive pulmonary disease, sleep apnea, pulmonary embolism, and non-cardiogenic pulmonary edema.
Obtain the following initial tests in a patient with suspected heart failure: (1) 12-lead electrocardiogram (ECG). (2) Chest x-ray. (3) Blood tests including complete blood count, serum chemistries, fasting lipid profile, liver function tests, and thyroid-stimulating hormone. (4) B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP). (5) Transthoracic echocardiography (TTE) to assess systolic and diastolic function (including evaluation of left ventricular ejection fraction to confirm reduced ejection fraction), myocardial wall thickness, and valve function.
MANAGEMENT
For all patients with symptomatic heart failure and signs of volume overload, fluid retention or a history of fluid retention, to improve symptoms and exercise tolerance, and to manage beta-blocker associated fluid retention, prescribe loop diuretics. Loops preferred, but thiazides can be considered for patients with hypertension and mild fluid retention. Adjust dose to attain and maintain target (dry) weight. For further information, see notes on "Loop diuretic use in heart failure" AND "Steps to manage loop diuretics".
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Furosemide, initial 20 to 40 mg once or twice daily, max total daily dose 600 mg.
Bumetanide, initial 0.5 to 1 mg once or twice daily, max total daily dose 10 mg.
Torsemide, initial 10 to 20 mg once daily, max total daily dose 200 mg.
For all patients with HFrEF and without contraindications, prescribe the following medications: Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are used for patients with LVEF 40% or less (< 40%), with symptoms or prior symptoms, unless contraindicated, to reduce morbidity and mortality and asymptomatic patients with LVEF 35% or less. (ACE) inhibitors should be used with a beta-blocker. For further information, see note on "Angiotensin-Converting Enzyme (ACE) Inhibitors". Angiotensin receptor blockers (ARBs) are used for patients who are intolerant to ACEI due to cough or angioedema, and in whom an ACEI or ARNI is inappropriate. Patients with Class II to IV HF and LVEF 40% or less at high risk of HF events despite optimized ACEI plus beta-blocker (i.e., as an add-on to ACEI plus beta-blocker) (Canada). Patients who cannot take a beta-blocker, as an add-on to an ACEI (Canada). Do not combine with ACEI plus aldosterone antagonist. For further information, see note on "Angiotensin II Receptor Blockers (ARBs)".
Beta blockers are used for stable patients with LVEF 40% or less, with symptoms or prior symptoms, as soon as HF is diagnosed, unless contraindicated, to reduce morbidity and mortality. Beta blockers are used with an ACEI. you can start beta-blocker before ACEI is optimized and prescibe an evidence-based beta-blocker (carvedilol, bisoprolol, metoprolol, nibevolol). Consider dapagliflozin (Forxiga) for all patients, regardless of presence of diabetes. For further information, see note on "Consider heart failure when weighing medications for diabetes".
For selected patients with HFrEF requiring further management, prescribe hydralazine plus isosorbide dinitrate for patients of African ancestry with class III or IV HF and LVEF 40% or lower who are symptomatic despite optimized ACEI or ARB plus beta-blocker (i.e., as an add-on to ACEI [or ARB] plus beta-blocker), to reduce morbidity and mortality, unless contraindicated and patients who cannot take an ACEI or ARB (i.e., in place of ACEI or ARB with beta-blocker).
Aldosterone antagonist (eplerenone or spironolactone) is used for patients with Class II to IV HF and LVEF 35% or less, unless contraindicated, to reduce morbidity and mortality. (Patients with Class II HF should have a history of cardiovascular hospitalization or elevated BNP). Also can be used for patients
over 55 years of age with mild to moderate HF despite standard
treatment and a LVEF 30% or less (or 35% or less if QRS duration over
130 ms) and cardiovascular hospitalization within the previous six
months or elevated BNP or NT-proBNP levels an for post-MI
patients with LVEF 40% or less (30% or less, Canada) with symptoms or a
history of diabetes, unless contraindicated, to reduce morbidity and
mortality. Do
not start if baseline creatinine is over 2.5 mg/dL (221 umol/L) in men
or over 2 mg/dL (176.8 umol/L) in women, or eGFR is 30 mL/min or
lower, or potassium is 5 mEq (mmol)/L or higher. Used as an add-on to ACEI (or ARB) plus beta-blocker.
ARNI (sacubitril/valsartan [Entresto]) used for patients with chronic symptomatic Class II or III heart failure tolerating an adequate ACEI or ARB dose, as a substitute for ACEI or ARB. Do not use with an ACEI or ARB, or within 36 hours of the last dose of an ACEI. Do not start if patient has SBP < 100 mmHg, symptomatic hypotension, hyperkalemia, or a history of ACEI/ARB angioedema. Entresto prevents CV death or heart failure hospitalization in 1 in 21 patients treated for two years vs an ACEI, but also causes symptomatic hypotension in 1 in 21 patients.
Consider digoxin (Lanoxin) in patients with LVEF 40% or less, with persistent symptoms despite optimized treatments above, to decrease HF hospitalization, unless contraindicated. Used as add-on to the optimized regimen and patients with atrial fibrillation and poor rate control despite beta-blocker. No loading dose needed for HF. Consider target levels of 0.5 to 0.9 ng/mL (0.6 to 1.2 nmol/L). Consider starting with 0.125 mg every other day in patients with renal insufficiency, low lean body mass, or age over 70 years. Doses over 0.25 mg per day rarely needed.
Consider using ivabradine (Procoralan) for patients with symptomatic Class II or III stable chronic heart failure with LVEF of 35% or lower, in sinus rhythm with resting heart rate of 70 beats per minute or greater, in addition to guideline-directed therapy, including a beta-blocker at a maximally-tolerated dose, or who cannot take a beta-blocker. Procoralan reduces heart failure hospitalization in one in 25 patients vs placebo when added to standard therapy. It causes bradycardia in one in 13 patients and atrial fibrillation in one in 100 patients vs placebo.
Nondihydropyridine calcium channel blockers with negative inotropy should not be used in patients with heart failure with reduced ejection fraction. Consider anticoagulant therapy and statins as appropriate for associated comorbidities, but not as specific treatment for heart failure alone. For further information, see note on "Optimization of lipids in cardiovascular patients (focus on statin dose Instead of LDL levels)".
REFERENCES
Yancy, C.W., Jessup, M., and others (2013). ACCF/AHA Guideline for the Management of Heart Failure. Circulation, 128(16). Available at https://pubmed.ncbi.nlm.nih.gov/23741058
McKelvie, R.S., and others (2013). The 2012 Canadian Cardiovascular Society heart failure management guidelines update: focus on acute and chronic heart failure. The Canadian Journal of Cardiology, [online] 29(2), pp.168–181. Available at: https://pubmed.ncbi.nlm.nih.gov/23201056
Yancy, C.W., Jessup, M., and others (2017). ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation, 136(6). Available at: https://pubmed.ncbi.nlm.nih.gov/28455343
McMurray, J.J.V., and others (2014). Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure. New England Journal of Medicine, 371(11), pp.993–1004. Available at: https://pubmed.ncbi.nlm.nih.gov/25176015
Howlett, J.G., Chan, M., Ezekowitz, and others (2016). The Canadian Cardiovascular Society Heart Failure Companion: Bridging Guidelines to Your Practice. Canadian Journal of Cardiology, 32(3), pp.296–310. Available at: https://pubmed.ncbi.nlm.nih.gov/26391749