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HEART FAILURE - CHRONIC
Heart failure is a clinical syndrome due to a structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood in order to deliver oxygen at a rate commensurate with the requirements of the metabolizing tissues.
Symptoms are caused by ventricular dysfunction secondary to abnormalities of the myocardium, pericardium, endocardium, valves, heart rhythm and conduction.
Chronic heart failure is a state where patient's signs and symptoms have been unchanged (stable) for at least a month but may decompensate suddenly or slowly when stable chronic heart failure deteriorates leading to hospitalization.

Pharmacotherapy

Please see the Heart Failure - Acute disease management chart for information on intravenous (IV) drugs administered in the hospital/healthcare facility for emergency cases of heart failure

Control of Risk and Prevention of Cardiovascular Events

Hypertension and Dyslipidemia

  • Please see Hypertension and Dyslipidemia disease management charts for further information
  • Recommended optimal BP for HF patients with hypertension is <130/80 mmHg1

1Recommendations for BP target goals may vary between countries. Please refer to available guidelines from local health authorities

Diabetes Mellitus (DM)

  • Long-term treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)
    • ACE inhibitors and ARBs can prevent the development of end-organ disease, cardiovascular complications and risk of HF in patients with diabetes and those without hypertension
  • Other agents that may also be given to patients with DM include a beta-blocker, MRA, an ARNI and Ivabradine
  • Metformin may be used in type 2 diabetes patients with stable HF; sodium-glucose co-transporter 2 (SGLT-2) inhibitors may be considered in type 2 diabetes patients with established HF to decrease risk of HF hospitalization
  • Please see Diabetes Mellitus disease management chart for further information

Atherosclerotic Disease

  • One large-scale trial showed that long-term therapy with an ACE inhibitor decreased the risk of cardiovascular (CV) death, myocardial infarction (MI) and stroke in patients with known vascular disease
  • ACE inhibitors prevent HF in patients who are at high risk of developing HF, have a history of atherosclerotic vascular disease, DM or hypertension with associated CV risk factors

Treatment Strategy

  • The use of ACE inhibitor or ARB, beta-blocker and mineralocorticoid receptor antagonist (MRA) is important in modifying the course of systolic HF
    • Should be considered in all patients with HF because it decreases the risk of HF hospitalization and premature death
    • They are commonly used in conjunction with a diuretic to relieve the symptoms and signs of congestion
  • A study showed that the initial HF drug therapy exerts a possible synergistic effect from the add-on drug therapy and the baseline drug therapy

ACE Inhibitors

  • Recommended for the prevention of HF in patients at risk of this syndrome
  • ACE inhibitors should be prescribed to all patients with decreased left ventricular ejection fraction (LVEF) of ≤40% regardless of symptoms unless contraindicated or not tolerated
  • Started as soon as HF diagnosis is made because of its modest effect on left ventricular (LV) remodelling which delays the development of symptomatic CHF in patients with asymptomatic LV dysfunction and those without ventricular dysfunction
  • Should only be used in patients with adequate renal function and normal serum potassium
  • If a patient has recent or current history of fluid retention, diuretics should be started prior to ACE inhibitors to ensure sodium balance, preventing peripheral and pulmonary edema

Angiotensin II Antagonists/Angiotensin Receptor Blockers (ARBs)

  • Recommended as an alternative in patients who are intolerant of ACE inhibitors due to cough or angioedema; patients should also be given a beta-blocker and an MRA
  • May also be considered in patients with systolic CHF who remain symptomatic despite receiving ACE inhibitor and a beta-blocker and are intolerant of MRA
  • Candesartan may be considered for ambulatory patients with symptomatic HF with mid-range EF to decrease the risk of HF hospitalization and CV death 
  • Avoid use in patients with recent acute MI and decreased LVEF who are on ACE inhibitor and beta-blocker
  • Triple combination of ACE inhibitor, ARB and MRA is not recommended due to increased risk of hyperkalemia

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

  • Eg Sacubitril/valsartan
  • Acts by inhibiting neprilysin which slows down the degradation of natriuretic peptides, bradykinin and other peptides leading to high amounts of circulating A-type natriuretic peptide and BNP resulting in diuresis, natriuresis and relaxation and anti-remodelling of the myocardium
  • Recommended as a replacement for an ACE inhibitor or ARB to further decrease morbidity and mortality in ambulatory patients with HF with reduced ejection fraction (EF) who are still symptomatic despite optimal therapy with an ACE inhibitor or ARB, a beta-blocker and an MRA
  • May consider starting Sacubitril/valsartan rather than an ACE inhibitor or ARB for patients admitted with new-onset HF or decompensated CHF for reduction of short-term risk of adverse events and for simplification of management (ie the need to initially titrate ACE inhibitor then switch to Sacubitril/valsartan is avoided)
  • Treatment should not be combined with ACE inhibitor or ARB or within 36 hours from the last dose of ACE inhibitor due to a higher risk of angioedema

Beta-Blockers

  • Recommended in all stable class II-IV HF patients with decreased LVEF to relieve angina, unless contraindicated or not tolerated 
  • Preferred 1st-line treatment to control ventricular rate for patients in New York Heart Association (NYHA) Class I-III provided they are euvolemic
    • May also be used to control the ventricular rate in HF patients with preserved EF and AF
  • Also used in patients with prior MI to reduce mortality, recurrent MI and development of HF
    • Slow down symptom onset and decrease cardiac morbidity in post-MI patients with asymptomatic LV dysfunction
  • May be considered for ambulatory patients with symptomatic HF with mid-range EF to decrease the risk of all-cause and CV death
  • Prevent ischemia and inhibit the adverse effects of the sympathetic nervous system in HF

Calcium Channel Blockers

  • Dihydropyridine calcium channel blockers may be used to treat hypertension and coronary heart disease in patients with systolic CHF
    • Have not shown survival benefits but no adverse outcomes were observed
  • Non-dihydropyridine calcium channel blockers that are negative inotropes are contraindicated in patients with systolic HF
    • However, Diltiazem is sometimes used in patients with CHF and AF to decrease excessive exercise-related heart rates

Digoxin

  • May be used to slow a rapid ventricular rate in patients with symptomatic HF, LVEF ≤40% and AF in addition to or prior to a beta-blocker
    • Recommended as the preferred second drug, in addition to a beta-blocker, to control the ventricular rate in patients with inadequate response to beta-blocker
  • May be considered to reduce the risk of HF hospitalization in patients in sinus rhythm with an EF ≤45% who are unable to tolerate a beta-blocker
    • Patient should also receive an ACE inhibitor (or ARB) and MRA (or ARB)
  • May also be used be in patients with EF ≤ 45% in sinus rhythm and persisting symptoms despite treatment with a beta-blocker, ACE inhibitor (or ARB) and MRA (or ARB)

Diuretics

  • Recommended in patients with HF and those with clinical manifestations of congestion or fluid overload regardless of EF
  • Start with a low dose and titrate accordingly until clinical improvement is achieved
  • Adjust dose after restoration of dry body weight to avoid risk of dehydration, hypotension and renal dysfunction
  • Patients with preserved ejection fraction are given diuretics to control volume, manage high BP and relieve ischemia
    • If after management of volume overload patient with preserved ejection fraction still has persistent hypertension, ACE inhibitors or ARBs and beta-blockers should be given to achieve SBP <130 mmHg
  • Work synergistically when a different diuretic is used in combination with a loop diuretic for the treatment of resistant edema

Loop Diuretics

  • Preferred diuretic for the treatment of HF
  • Used in patients with more severe volume overload or if there is inadequate response to thiazide
    • Produce a greater fractional excretion of filtered sodium and more intense, shorter diuresis

Thiazide Diuretics

  • May be effective as a monotherapy in HF patients with mild congestion and normal renal function

Potassium-Sparing Diuretics

  • Recommended in patients with excessive potassium losses secondary to the use of loop diuretics
  • Also used in combination with thiazides for the treatment of hypertension
  • Caution is needed if a potassium-sparing diuretic is used in addition to ACE inhibitor or ARB and MRA

Combinations

  • Thiazides or Metolazone can be used in combination with loop diuretics for a synergistic effect in patients with persistent fluid retention despite high-dose loop diuretic treatment
  • Chronic daily use of these agents, especially of Metolazone, should be avoided because of the risk of electrolyte imbalance and dehydration

Hydralazine + Isosorbide Dinitrate

  • This combination is reserved in patients who cannot tolerate ACE inhibitors and ARBs, in whom these agents are contraindicated and if no other treatment options are available
  • May be considered in patients with HF and decreased LVEF who remain symptomatic despite optimal standard therapy
  • Hydralazine and Isosorbide have complementary dilating actions
    • Isosorbide may also inhibit abnormal myocardial and vascular growth and therefore may reduce ventricular remodeling
    • Hydralazine may interfere with the molecular mechanisms responsible for the progression of HF

Ivabradine

  • A selective sinus node I(f) channel inhibitor that is known for slowing the heart rate
  • Considered in patients in sinus rhythm suffering from angina who cannot tolerate or have contraindication to beta-blockers or when there is treatment failure after beta-blocker therapy
  • Approved for use in patients with a heart rate of ≥75 bpm
  • May be considered to reduce mortality and the risk of HF hospitalization in patients in sinus rhythm with an LVEF ≤35%, heart rate of ≥70 bpm at rest, with persisting symptoms (NYHA Class II-III) and with inadequate response to evidence-based dose of beta-blockers, ACE inhibitors (or ARB) and MRA (or ARB)

Mineralocorticoid Receptor Antagonists (MRA)/Aldosterone Antagonists

  • Recommended for patients who remain symptomatic despite treatment with ACE inhibitor and beta-blocker
    • Recommended in patients following an acute MI, with clinical heart failure manifestations or history of DM and LVEF <40%, while receiving standard therapy
    • Treatment option for patients with HF with preserved ejection fraction (EF ≥45%, increased BNP, estimated GFR >30 mL/min, creatinine <2.5 mg/dL, potassium <5 mEq/L) to reduce hospitalizations
  • Recommended also for NYHA Class II symptomatic patients with a history of previous CV hospitalization or an elevated level of natriuretic peptide 
  • Spironolactone and Eplerenone block receptors that bind aldosterone and other corticosteroids and are best characterized as MRAs 
  • Spironolactone is recommended for patients who remain severely symptomatic despite appropriate doses with ACE inhibitors, loop diuretics and Digoxin
    • May be considered for ambulatory patients with symptomatic HF with mid-range EF without contraindications to decrease the risk of HF hospitalization and CV death
  • Eplerenone is considered in patients with systolic HF who still have mild symptoms despite receiving standard therapy of ACE inhibitors and beta-blockers
  • Should only be used in patients with adequate renal function and normal serum potassium
    • Serial monitoring of serum electrolytes and renal enzymes are mandatory

Nitrates 

  • A short-acting oral or transcutaneous nitrate is an effective treatment for angina and is safe in patients with HF

Tolvaptan

  • A vasopressin V2-receptor antagonist that may be used in the short term for the treatment of resistant hypervolemic hyponatremia despite water restriction and guideline-directed medical therapy
  • Adverse effects may include thirst and dehydration

Rivaroxaban

  • May be considered, in addition to Aspirin therapy, for ambulatory patients with CAD and CHF in NYHA Class I/II with an LVEF >30% to decrease the risk of stroke and CV death

Adjunctive Therapy

Coenzyme Q10 (CoQ10) 

  • A lipid-soluble cofactor found in the mitochondrial inner membrane that has antioxidant properties and a bioenergetic role; it is predominantly located in the myocardium
  • Q-SYMBIO trial, a double-blind trial on CoQ10 as adjunctive therapy of chronic heart failure, found that supplementation with CoQ10 was safe and resulted in heart failure symptom improvement and reduction in major adverse cardiovascular events and mortality
  • As trials on CoQ10 have shown mixed results, further evidence is needed to establish beneficial effect

Treatment of Comorbidity

Intravenous Iron

  • Consider giving in symptomatic HF patients with reduced EF (NYHA Class II and III) and iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL if transferrin saturation is <20%) for alleviation of HF symptoms and improvement of exercise capacity and quality of life

Non-Pharmacological Therapy

Cardiac Rehabilitation

  • Useful in patients who are clinically stable
  • Several meta-analyses demonstrated cardiac rehabilitation improves functional capacity, exercise duration and health-related quality of life and decreases hospitalizations and mortality in HF patients
    • An exercise-based cardiac rehabilitation is recommended in HF patients with reduced EF to decrease risk of hospitalization 
  • Following revascularization, patients may also be referred for cardiac rehabilitation

Sleep and Breathing Disorders

  • Patients with symptomatic HF usually have sleep-related breathing disorders (eg central or obstructive sleep apnea)
  • Weight loss in obese patients, smoking cessation and abstinence from alcohol are recommended to decrease the risks
  • Continuous positive airway pressure (CPAP) should be considered in polysomnograph-documented obstructive sleep apnea to improve daily functional capacity and quality of life

Depression and Mood Disorder

  • Screening for endogenous or prolonged reactive depression in patients with HF should be done following diagnosis and at periodic intervals as clinically indicated
  • Initiate appropriate pharmacotherapy and provide psychosocial support

Interventional Therapy

Device-based Therapy

Cardiac Resynchronization Therapy (CRT)

  • Recommended if symptomatic patient is in sinus rhythm with a QRS duration of ≥130 msec, left bundle branch block and LVEF ≤35% despite optimal medical therapy    
  • CRT with a pacemaker is recommended (instead of a right ventricular pacing) in patients with HF, bradycardia and high-degree atrioventricular block  

Implantable Cardioverter-Defibrillator (ICD)

  • Primary prevention or prophylactic ICD implantation to decrease the risk of sudden cardiac death may be done in a NYHA Class II-III symptomatic patient with an LVEF ≤35% and:
    • Without an MI in the prior 40 days 
    • With dilated cardiomyopathy 
  • ICD may be done for secondary prevention in the following patients to improve survival:
    • Cardiac arrest survivors (expected survival rate of >1 year with good functional status) from ventricular fibrillation or with hemodynamic instability caused by documented ventricular dysrhythmia
    • Those with symptomatic CHF and LVEF ≤35% who experience syncope of unclear etiology  
    • With previous MI and LVEF ≤40% with non-sustained ventricular tachycardia and ventricular tachycardia or ventricular fibrillation that is inducible and sustained during an electrophysiological study   

Left Ventricular Assist Device (LVAD)

  • A mechanical circulatory support used as a bridge to transplantation or to recovery  
  • May be used long-term as a transplantation alternative in patients with end-stage HF not eligible for transplantation or long-term waiting for heart transplantation  

Surgery

Coronary Revascularization

  • Eg coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)  
  • Considered in patients with HF and suitable coronary anatomy  

Valvular Surgery

  • Mitral valve repair may be done in patients with HF, severe mitral regurgitation and LVEF <30%  
    • A MitraClip may be considered in select HF patients with reduced EF to decrease mitral regurgitation 
  • Mitral valve repair or replacement may be considered in patients with LV systolic dysfunction and severe mitral regurgitation who will undergo surgical coronary revascularization  
  • Surgical or transcatheter approach to aortic valve replacement may be considered in patients with critical aortic stenosis  

Heart Transplantation

  • Considered in patients with poor prognosis, end-stage HF and severe symptoms  
  • Significantly increases patient’s survival and quality of life
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