Principles of Therapy
Goals of Therapy
The
goals of therapy are: To reduce mortality, to prevent recurrent
hospitalizations caused by worsening heart failure, and to improve clinical
status, functional capacity, and quality of life.
Treatment Strategy
The use of foundational
medical therapy1 (eg angiotensin receptor-neprilysin inhibitor [ARNI],
angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor blocker [ARB],
beta-blocker, mineralocorticoid receptor agonist [MRA], and sodium-glucose co-transporter
2 [SGLT2] inhibitor) is important in
modifying the course of systolic heart failure. The use of the above drugs should
be considered in all symptomatic patients with heart failure NYHA Class II-IV because it decreases the risk
of heart failure hospitalization and premature death. Asymptomatic patients in NYHA Class I may be
given ACE inhibitors, beta-blockers, and SGLT2 inhibitors. These drugs are
continued in patients with heart failure with improved ejection fraction to prevent symptom relapse and left ventricular function
deterioration. They are commonly used in
conjunction with a diuretic to relieve the symptoms and signs of congestion. There
is no optimal order of treatment initiation and/or uptitration. Treatment
approach should be individualized. The four drug classes are generally initiated at
about the same time at low doses and up titrated to maximally tolerated or
target doses. Initiation of a beta-blocker is better
tolerated when the patient is less congested (dry), with adequate resting heart
rate, and an ARNI, ACE inhibitor, or ARB when the patient is congested (wet).
Uptitration
of foundational medical therapy at intervals of 1-2 weeks, as tolerated and
guided by symptoms, vital signs and lab findings, is recommended in patients
with heart failure to achieve the optimal target doses shown to be efficacious
in randomized controlled trials and reduce the risk of heart failure hospitalization
or death. Foundational medical therapy should then be continued at the highest
tolerated doses in all patients, including those who become asymptomatic or
experience improvement in left ventricular ejection fraction, to reduce the
risk of heart failure hospitalization and death.
Rapid initiation and titration
of therapy to maximally tolerated or target doses must be done in chronic heart
failure with reduced ejection fraction patients in order to achieve the maximal
benefits of guideline-directed medical therapy. Guideline-directed medical therapy
should be initiated, continued and further optimized
in hospitalized patients before discharge. To reduce the risk of heart failure readmission
or death, it is recommended that high-intensity evidence-based treatment be
started early and rapidly up-titrated pre-discharge and during follow-up visits
within the first 6 weeks after heart failure hospitalization. It is important
to reassess ventricular function 3-6 months after achieving maximally tolerated
or target doses of guideline-directed medical therapy to determine the need for
ICD and/or CRT.
Advance care planning
should be discussed in all patients with advanced heart failure regardless of
treatment strategy. Continuous IV inotropes should be considered in selected
patients with advanced heart failure with reduced ejection fraction, low
cardiac output and evidence of tissue hypoperfusion or end-organ dysfunction,
as a bridge to decision, bridge to transplantation or as a bridge to durable mechanical
circulatory support, to increase cardiac output and improve symptoms.
In COVID-19 infection, inhibition of
the renin-angiotensin-aldosterone system is not associated with infection risk
or disease severity and should be continued as long as hemodynamically
tolerated by the patient. Chronic heart failure patients should continue guideline-directed
medical therapy regardless of COVID-19 infection.
1Foundational
medical therapy refers to first-line therapies for the general heart failure
population that reduce morbidity and/or mortality. Additional medical therapy
refers to therapies for specific heart failure populations that improve
symptoms and/or quality of life. Both foundational medical therapy and additional
medical therapy are covered by guideline-directed medical therapy.
Pharmacological therapy
Please see the Heart Failure - Acute
disease management chart for information on intravenous drugs administered in
the hospital or healthcare facility for emergency cases of heart failure.
Heart Failure - Chronic_Management 1Angiotensin Converting Enzyme (ACE) Inhibitors
ACE inhibitors are recommended for the prevention of heart failure in patients at risk of this syndrome. They recommended in all patients with decreased left ventricular ejection fraction of <50% regardless of symptoms unless contraindicated or not tolerated. They may be considered for patients with symptomatic heart failure with preserved ejection fraction to decrease the risk of heart failure hospitalization. They are also recommended in patients with heart failure with reduced ejection fraction and CKD with an eGFR ≥30 mL/min/1.73 m² and may be considered with eGFR 15-29 mL/min/1.73 m² to reduce the risk of heart failure hospitalization and death. ACE inhibitors are also recommended in patients with CKD with eGFR ≥30 mL/min/1.73 m² and asymptomatic left ventricular dysfunction (≤35%) to reduce the risk of incident heart failure and heart failure-related hospitalizations.
It may be started as soon as a heart failure diagnosis is made because of its modest effect on left ventricular remodeling which delays the development of symptomatic chronic heart failure in patients with asymptomatic left ventricular dysfunction and those without ventricular dysfunction.
If a patient has a recent or current history of fluid retention, diuretics should be started prior to ACE inhibitors to ensure sodium balance, preventing peripheral and pulmonary edema.
An increase in creatinine and potassium levels is expected after treatment with an ACE inhibitor (or ARB) or ARNI. An increase in the creatinine level of up to 3 mg/dL (eGFR >25 mL/min/1.73 m2) or up to 50% above baseline (whichever is smaller) and a potassium level of ≤5.5 mmol/L is acceptable. Administration of potassium-lowering agents (eg patiromer and sodium zirconium cyclosilicate) may allow the renin-angiotensin-aldosterone system (RAAS) inhibitor initiation, continuation or uptitration in a large number of patients with hyperkalemia. Consider a specialist referral if with significant renal dysfunction or hyperkalemia.
Angiotensin Receptor Blockers (ARBs) or Angiotensin II Antagonists
ARBs are recommended as alternative drugs in patients who are intolerant of ARNI or ACE inhibitors due to cough or angioedema. They can also be used as alternatives to ACE inhibitors as first-line agents in those already on ARB for other indications. They may also be considered in patients with systolic chronic heart failure who remain symptomatic despite receiving an ACE inhibitor and a beta-blocker and are intolerant of MRA.
Candesartan may be considered the preferred RAAS inhibitor for ambulatory patients with symptomatic heart failure with non-reduced ejection fraction who are ineligible for or unable to receive ARNI therapy, to decrease the risk of heart failure hospitalization and cardiovascular death.
Avoid the use of ARBs in patients with recent acute myocardial infarction and decreased left ventricular ejection fraction who are on ACE inhibitors and beta-blockers. The triple combination of an ACE inhibitor, ARB, and MRA is not recommended due to the increased risk of hyperkalemia.
Angiotensin Receptor-Neprilysin Inhibitor (ARNI)
Example drug: Sacubitril/Valsartan
ARNI is recommended for appropriate patients with symptomatic heart failure and left ventricular ejection fraction <50%. It reduces the risk of cardiovascular death and heart failure hospitalization in adult patients with chronic heart failure with benefits most evident in those with left ventricular ejection fraction below normal.
ARNI may be considered for patients with symptomatic heart failure and left ventricular ejection fraction ≥50% with a systolic blood pressure of ≥100 mmHg and who are at low risk of symptomatic hypotension to decrease the risk of hospitalization. It is a recommended replacement for ACE inhibitor or ARB to further decrease morbidity and mortality in patients with chronic heart failure with reduced ejection fraction who remain symptomatic despite optimal medical therapy, provided the previous ACE inhibitor or ARB therapy was tolerated. One may consider starting Sacubitril/Valsartan rather than an ACE inhibitor or ARB for patients admitted with new-onset heart failure or decompensated chronic heart failure 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). In patients with heart failure with reduced ejection fraction and CKD with eGFR ≥30 mL/min/1.73 m², ARNI is recommended to reduce the risk of heart failure hospitalization and death and should be considered as an alternative to ACE inhibitor or ARB to reduce the risk of CKD progression. Continuation of an ARNI should be considered in patients with heart failure and CKD in whom the eGFR progresses to <30 mL/min/1.73 m² to avoid worsening of heart failure.
It 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 additional vasodilation, diuresis, natriuresis, and relaxation and anti-remodeling of the myocardium. It is important to interpret BNP values with caution as BNP levels may rise with ARNI therapy. Guideline-directed medical therapy optimization, including increased doses of RAAS inhibitors, may be done in patients in whom ARNI is not feasible. Treatment should not be combined with an ACE inhibitor or ARB or initiated within 36 hours from the last dose of an ACE inhibitor due to a higher risk of angioedema; patients on ARB can be transitioned directly to ARNI.
Beta-Blockers
Beta-blockers are recommended in all stable NYHA Class II-IV patients with symptomatic heart failure with reduced ejection fraction to relieve angina unless contraindicated or not tolerated, to reduce the risk of heart failure hospitalization and death. It is the recommended first-line therapy for short- and long-term ventricular rate control in stable patients with heart failure with reduced ejection fraction and atrial fibrillation, particularly those with NYHA Class I-III symptoms who are euvolemic. They may also be used to control the ventricular rate in heart failure patients with preserved ejection fraction and atrial fibrillation.
Beta-blockers are recommended in patients with heart failure with reduced ejection fraction and CKD with an eGFR ≥30 mL/min/1.73 m² and may be considered with eGFR 15-29 mL/min/1.73 m² to reduce the risk of heart failure hospitalization and death. Beta-blockers prevent ischemia and inhibit the adverse effects of the sympathetic nervous system in heart failure. It is recommended to use only evidence-based beta-blockers (eg Bisoprolol, Carvedilol, Metoprolol succinate, Nebivolol) in patients with heart failure with reduced ejection fraction and to initiate treatment using a “start low, go slow” approach. In selected patients with advanced heart failure with reduced ejection fraction who have persistent evidence of organ hypoperfusion despite initial treatment, reducing the dose or temporarily discontinuing beta-blockers or Ivabradine may be considered to improve cardiac output and symptoms.
Mineralocorticoid Receptor Antagonists (MRA) or Aldosterone Antagonists
Recommended for all patients with chronic symptomatic heart failure (NYHA Class II-IV), independent of left ventricular ejection fraction, to reduce morbidity, mortality and the risk of heart failure hospitalizations. Steroidal MRAs are recommended for heart failure with reduced ejection fraction while steroidal or non-steroidal MRA is recommended for heart failure with preserved ejection fraction. In heart failure and CKD, steroidal MRA is recommended in patients with eGFR ≥30 mL/min/1.73 m² and heart failure with reduced ejection fraction, while either steroidal or non-steroidal MRA should be considered in patients with left ventricular ejection fraction ≥40% and eGFR ≥25 mL/min/1.73 m².
Spironolactone is recommended for patients who remain severely symptomatic despite appropriate doses with ACE inhibitors, loop diuretics, and Digoxin. Eplerenone is recommended in patients after myocardial infarction with left ventricular ejection fraction of ≤40% with signs of heart failure or diabetes to reduce the risk of heart failure hospitalization or death. It is considered in patients with systolic heart failure who still have mild symptoms despite receiving standard therapy of ACE inhibitors and beta-blockers and has no antiandrogenic effects.
Finerenone is a non-steroidal MRA recommended in patients with type 2 diabetes mellitus and CKD to reduce the risk of heart failure. In addition to steroidal MRA therapy in patients with left ventricular ejection fraction <50%, Finerenone should be considered for the reduction of cardiovascular mortality and heart failure hospitalizations in patients with CKD associated with type 2 diabetes mellitus (diabetic nephropathy) or heart failure with left ventricular ejection fraction of ≥40%, and for the reduction of urgent heart failure visits in patients with heart failure with left ventricular ejection fraction of ≥40%. It may be considered the preferred MRA in patients with diabetic kidney disease given the high-quality evidence supporting its benefits on cardiovascular and kidney outcomes.
Renal dysfunction and hyperkalemia may lead to the underutilization of MRA. Administration of potassium-lowering agents may allow MRA initiation, continuation or uptitration in a large number of patients with hyperkalemia. Serial monitoring of serum electrolytes and renal function is therefore advised.
Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors
Example drugs: Dapagliflozin, Empagliflozin, Sotagliflozin
SGLT2 inhibitors are recommended for symptomatic heart failure patients across all ejection fraction subgroups, with or without diabetes, to decrease the risk of cardiovascular death, heart failure hospitalization and urgent heart failure visits; NYHA Class II-IV. They are recommended in patients with type 2 diabetes mellitus at risk of heart failure (ie multiple atherosclerotic cardiovascular disease risk factors or established atherosclerotic cardiovascular disease) and in patients with type 2 diabetes mellitus and CKD to reduce the risk of heart failure and cardiovascular death. They are also recommended in patients with heart failure and CKD with eGFR ≥20 mL/min/1.73 m², irrespective of left ventricular ejection fraction, to reduce the risk of (repeated) heart failure hospitalization and cardiovascular death. Continuation of an SGLT2 inhibitor should be considered in patients with heart failure and CKD in whom the eGFR progresses to <20 mL/min/1.73 m² to avoid worsening of heart failure. Sotagliflozin is an inhibitor of both SGLT1 and SGLT2; the inhibition of SGLT1 decreases intestinal absorption of sodium and glucose, which may cause diarrhea.
Diuretics
Diuretics are recommended as additional in NYHA Class II-IV patients with heart failure and those with clinical manifestations of congestion or fluid overload regardless of the left ventricular ejection fraction. Start with a low dose and titrate accordingly until clinical improvement is achieved. Diuretic dosing may need to be reduced with increasing doses of ARNI, ACE inhibitor, or ARB and/or initiation of an MRA or an SGLT2 inhibitor. Adjust the dose after the restoration of dry body weight to avoid the risk of dehydration, hypotension, and renal dysfunction. They may be discontinued if left ventricular ejection fraction has improved to >40-45% after treatment.
Patients with heart failure with preserved ejection fraction are given diuretics to control volume, manage high blood pressure, and relieve ischemia. If after the management of volume overload the patient with heart failure with preserved ejection fraction still has persistent hypertension, ACE inhibitors or ARBs and beta-blockers should be given to achieve a systolic blood pressure of <130 mmHg. Diuretics may be given to heart failure with mildly reduced ejection fraction who remain symptomatic with signs of congestion.
Diuretics may be considered to reduce the risk of heart failure hospitalization in patients in sinus rhythm with an ejection fraction of ≤45% who are unable to tolerate a beta-blocker.
They work synergistically when a different diuretic is used in combination with a loop diuretic for the treatment of resistant edema. Consider ultrafiltration in patients with refractory volume overload and congestive symptoms not responding to escalation of diuretic therapy to reduce the risk of rehospitalization.
Loop Diuretics
Loop diuretics are recommended in patients with heart failure and CKD with evidence of fluid retention to relieve signs and symptoms of congestion, including peripheral edema, to improve exercise capacity and reduce the risk of heart failure hospitalization. They are used in patients with more severe volume overload or if there is an inadequate response to thiazides. They produce a greater fractional excretion of filtered sodium and provide a more intense and shorter diuresis. They should be initiated at a dose based on renal function and prior diuretic exposure, with dynamic, individualized dose adjustments using the lowest dose needed to maintain euvolemia. If high doses of a loop diuretic are reached during treatment (ie equivalent of Furosemide 80 mg 12 hourly), one may consider switching to a different loop diuretic or adding a thiazide diuretic.
Heart Failure - Chronic_Management 2Potassium-Sparing Diuretics
Potassium-sparing diuretics are recommended in patients with excessive potassium losses secondary to the use of loop diuretics. They are also used in combination with thiazides for the treatment of hypertension. Caution is needed if a potassium-sparing diuretic is used in addition to an ACE inhibitor or ARB, and MRA.
Thiazide Diuretics
Thiazide diuretics may be effective as monotherapy in heart failure patients with mild congestion and normal renal function.
Combinations
Thiazides or Metolazone can be used in combination with loop diuretics for a synergistic effect in patients with persistent fluid retention despite a high-dose loop diuretic treatment. Chronic daily use of these agents, especially Metolazone, should be avoided because of the risk of electrolyte imbalance and dehydration.
Digoxin
Digoxin should be considered to decrease the risk of heart failure hospitalizations in NYHA Class II-IV patients with left ventricular ejection fraction ≤40% in sinus rhythm and persisting symptoms despite treatment with optimized guideline-directed medical therapy. It should be considered in patients with heart failure with reduced ejection fraction and CKD with eGFR >20 mL/min/1.73 m² to reduce the risk of heart failure hospitalization and death. In patients with symptomatic heart failure with reduced ejection fraction (left ventricular ejection fraction ≤40%) and concomitant atrial fibrillation, Digoxin may be considered to achieve acute ventricular rate control and stabilize hemodynamically unstable patients, and it may be initiated either prior to or in combination with a beta-blocker. Digoxin is recommended as the preferred second drug, in addition to a beta-blocker, to control the ventricular rate in patients with an inadequate response to a beta-blocker. It may replace a beta-blocker for rate control if systolic blood pressure <90 mmHg.
Hydralazine plus Isosorbide Dinitrate
Hydralazine plus Isosorbide dinitrate should be considered in self-identified black patients with heart failure with reduced ejection fraction with LVEF ≤40% who remain symptomatic despite optimal standard therapy with ARNI, ACE inhibitor or ARB, beta-blocker, aldosterone antagonist and SGLT2 inhibitor, to reduce the risk of HF hospitalization and mortality. They may be considered in symptomatic patients with heart failure with reduced ejection fraction with left ventricular ejection fraction of ≤40% who cannot tolerate ACE inhibitors, ARBs or ARNI or in whom these agents are contraindicated and if no other treatment options are available, to potentially reduce heart failure hospitalization and mortality. It should also be considered in self-identified black patients with heart failure with reduced ejection fraction and CKD with eGFR ≥30 mL/min/1.73 m² and dilated left ventricle in combination with a left ventricular ejection fraction of <45%, or left ventricular ejection fraction of ≤35%, when added to conventional heart failure with reduced ejection fraction therapy to reduce the risk of heart failure hospitalization and death.
Hydralazine and Isosorbide have complementary dilating actions. Hydralazine may interfere with the molecular mechanisms responsible for the progression of heart failure while Isosorbide may also inhibit abnormal myocardial and vascular growth, thus may reduce ventricular remodeling. The dose may be increased every 2 weeks to maximum tolerated or target dose.
Ivabradine
Ivabradine is a highly selective sinus node If channel inhibitor that is known for slowing the heart rate. It is approved for use in patients with a heart rate of ≥75 bpm.
Ivabradine should be considered to reduce mortality and the risk of heart failure hospitalization in patients in sinus rhythm with a left ventricular ejection fraction of ≤35%, heart rate of ≥70 bpm at rest, with persisting symptoms (NYHA Class II-III), and with:
- Inadequate response to guideline-directed medical therapy including maximally tolerated, evidence-based dose of beta-blocker
- Intolerance or contraindication to beta-blockers or when there is treatment failure after beta-blocker therapy; the patient should also be given an ACE inhibitor (or ARB/ARNI) and MRA
- Heart failure hospitalization within the last 12 months
Ivabradine
should be considered in patients with heart failure with reduced ejection
fraction and CKD with an eGFR ≥20 mL/min/1.73 m2 to reduce the risk
of cardiovascular and heart failure-related events.
Vericiguat
Vericiguat is an oral soluble guanylate cyclase
stimulator that may be considered to decrease the risk of heart failure
hospitalization and cardiovascular death in patients with symptomatic heart
failure with reduced ejection fraction and left ventricular ejection fraction
<45% despite maximally tolerated guideline-directed medical therapy. It may
be considered in patients with heart failure with reduced ejection fraction and
CKD with eGFR ≥30 mL/min/1.73 m² to reduce the risk of heart failure
hospitalization and cardiovascular death.
Calcium Channel
Blockers
Dihydropyridine
calcium channel blockers are not recommended for heart failure treatment in
patients with heart failure with reduced ejection fraction but may be used to
treat hypertension in patients with high blood pressure despite optimal
guideline-based medical treatment.
Non-dihydropyridine
calcium channel blockers that are negative inotropes are contraindicated in
patients with heart failure with reduced ejection fraction. However, Diltiazem
is sometimes used in patients with chronic heart failure and atrial fibrillation
to decrease excessive exercise-related heart rates.
Glucagon-like Peptide (GLP-1) Receptor Agonists
Example drugs: Semaglutide, Tirzepatide
GLP-1
receptor agonists should be considered for patients with symptomatic heart
failure NYHA Class II-IV, left ventricular ejection fraction of ≥45%, CKD with
eGFR ≥15 mL/min/1.73 m² and BMI ≥30 kg/m², regardless of diabetes status, to
reduce body weight and the risk of heart failure hospitalization and improve
quality of life. They should be considered in patients with type 2 diabetes
mellitus and at least one other additional cardiovascular risk factor to reduce
the risk of heart failure or cardiovascular death. Although the current
evidence suggests that GLP-1 receptor agonists may improve symptoms and
functional outcomes in patients with obesity and heart failure with non-reduced
ejection fraction, further research is needed to better define the patient subgroups
most likely to benefit with these agents.
Nitrates
A short-acting oral or
transcutaneous nitrate is an effective treatment for angina and is safe to use
in patients with heart failure.
Rivaroxaban
Rivaroxaban may be
considered, in addition to Aspirin therapy, for ambulatory patients with CAD,
and chronic heart failure in NYHA Class I/II with a left ventricular ejection
fraction of >30% to decrease the risk of stroke and cardiovascular death.
Tolvaptan
Tolvaptan
is a vasopressin V2 receptor antagonist that may be used for short-term
treatment of resistant hypervolemic hyponatremia despite water restriction and guideline-directed
medical therapy. It may be given during hospitalization to patients with heart
failure with reduced ejection fraction who have fluid retention unresponsive to
treatment with other diuretics including loop diuretics. Tolvaptan given during
hospitalization for acute heart failure may be used by patients with heart
failure with preserved ejection fraction after discharge to control congestion.
Adverse effects include thirst and dehydration.
Adjunctive Therapy
Coenzyme Q10 (CoQ10)
Coenzyme Q10 is 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.
The Q-SYMBIO trial, a double-blind
trial on Coenzyme Q10 as adjunctive therapy for chronic heart failure, found
that supplementation with Coenzyme Q10 was safe and has resulted in heart
failure symptom improvement and reduction in major adverse cardiovascular
events and mortality. As trials on Coenzyme Q10 have shown mixed results,
further evidence is needed to establish its beneficial effect.
Treatment of Comorbidity
Anticoagulation
Long-term anticoagulation should be given to
patients with chronic heart failure with permanent-persistent-paroxysmal atrial
fibrillation and a CHA2DS2-VASc score of ≥2 in men and ≥3
in women unless contraindicated. In eligible patients, direct oral anticoagulant (DOAC) is recommended
over Warfarin. A reasonable therapy for patients with chronic heart failure with
permanent-persistent-paroxysmal atrial fibrillation in the absence of
additional risk factors.
Intravenous Iron Replacement
Intravenous iron replacement
may be given in symptomatic patients with a left
ventricular ejection fraction <50%, and iron deficiency (serum
ferritin <100 ng/mL or 100-300 ng/mL if transferrin saturation is <20%) with
or without anemia for alleviation of heart failure symptoms and improvement of
exercise capacity and quality of life. Ferric carboxymaltose or Ferric
derisomaltose should be considered in above patients
as well as those with CKD to decrease the risk of heart failure
hospitalization.
Immunization
COVID-19, pneumococcal, and
annual influenza vaccinations are recommended in all patients with heart
failure independent of left ventricular ejection
fraction in the absence of known contraindications. Pulmonary congestion
and pulmonary hypertension increase the risk of respiratory infections (one of
the major causes of acute decompensation, especially in the elderly).
Nonpharmacological
Patient Education
General Counseling
Patient counseling tends to
improve patient compliance and outcomes. Educate the patient and caregivers
about chronic heart failure. Discuss the nature of heart failure, treatment
goals, drug regimens and side effects, dietary and activity restrictions, signs
and symptoms of worsening heart failure, what to do if these symptoms occur,
and prognosis. Counseling is also done regarding
coordination of care for concomitant comorbidities and regarding palliative and
end-of-life care. End-of-life care in advanced heart failure focuses on symptom
management (eg breathlessness, pain, and anxiety and depression), patient
comfort and maintaining quality of life while ensuring personalized,
compassionate care.
Advise the patient regarding
enrollment in a multidisciplinary heart failure management program,
self-management strategies, and either home-based and/or clinic-based programs
to decrease the risk of hospitalization and mortality. Provide discharge instructions with a transitional care plan and
programs for psychological and social support. Genetic counseling and screening
may be advised to patients with first-degree relatives with inherited or
genetic cardiomyopathies.
Medications
Inform patients about the drugs’
indications, dosage, side effects, and precautions. Emphasize the importance of
treatment adherence to the patients. Assist patients in dealing with
complicated drug regimens and in accessing affordable medications. Advise
patients to avoid non-steroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2
(COX-2) inhibitors since patients are at increased risk for fluid retention and
renal failure especially those with decreased renal function or who are on angiotensin-converting
enzyme (ACE) inhibitors. NSAIDs can cause sodium retention, peripheral
vasoconstriction, decrease the efficacy and increase the toxicity of ACE
inhibitors and diuretics. Patients are counseled
against the use of drugs such as anabolic steroids, cocaine, and amphetamines.
Weight Monitoring
An increase in body
weight is associated with deterioration of heart failure and fluid retention.
Patients should weigh themselves regularly to monitor their weight change. If a
patient has sudden unexpected weight gain of >2 kg in 3 days, the physician
should be informed, and diuretic dose may need to be adjusted.
Patients who are obese
need to lose weight to decrease symptoms, improve well-being, and prevent
progression of heart failure. Weight reduction should not routinely be done in
patients with moderate to severe heart failure since unintentional weight loss
and anorexia are common problems in these patients.
Please see Obesity disease management chart
for further information.
Cardiac
cachexia, defined as involuntary non-edematous weight loss ≥6% of total body
weight within the previous 6-12 months, is an important predictor of decreased
survival and should be prevented. Possible treatments are appetite stimulants,
exercise, anabolic agents, and nutritional supplements.
Diet Modification
Restrict sodium intake
to <2 g/day (~1/4 teaspoon of table salt). Advise patients regarding a low
potassium diet since hyperkalemia and/or abnormal renal function hinders the
ability to reach target medication doses.
Fluid
restriction should be individualized (ie guided by sense of thirst, more
liberal intake in excessive gastrointestinal losses and/or hot and humid
conditions), though generally patients may limit fluid intake to 1-1.5 L/day in
patients with normal renal function. Routine fluid restriction in all patients
with mild to moderate symptoms is probably not beneficial. Weight-based fluid
restriction (30 mL/kg body weight if body weight is ≤85 kg or 35 mL/kg if body
weight is >85 kg) may cause less thirst.
Excessive caffeine
intake may increase heart rate, increase blood pressure, and exacerbate
arrhythmia. Advise patients to limit caffeine beverages to 1-2 cups/day.
Limit saturated fat
intake in all patients with heart failure. Supplementation with omega-3
polyunsaturated fatty acids is a reasonable adjunctive therapy in chronic heart
failure NYHA Class II-IV. A trial showed
reduction in mortality or hospital admission for a cardiovascular event.
High
fiber diet is recommended to prevent constipation that is secondary to relative
gastrointestinal hypoperfusion. It helps avoid straining in stool which may
provoke angina, dyspnea, or arrhythmia. Frequent small meals may prevent
shunting of the cardiac output to the gastrointestinal tract, thus decreasing
the risk of angina, dyspnea, dizziness, or bloating.
Alcohol
Alcohol is a direct
myocardial toxin and may impair cardiac contractility, may have a negative
inotropic effect, may be associated with blood pressure elevation, and
increases the risk for arrhythmia.
Advise patients to
abstain from or avoid excessive alcohol consumption. Limit alcohol intake to
10-20 g/day (2 units/day in men or 1 unit/day in women). A standard drink of 14
g of pure alcohol is equal to 12 oz of beer (5% alcohol content), 8-9 oz of malt
liquor (7% alcohol content), 5 oz of table wine (12% alcohol content), or 1.5
oz of 80-proof distilled spirits or liquor such as gin, rum, vodka, whiskey
(40% alcohol content). 1 unit is equivalent to 10 mL (8 g) of pure alcohol (1/3
pint of beer [5.2% alcohol content], half a standard glass [175 mL] of wine
[12% alcohol content], or 1 measure [25 mL] of spirits [40% alcohol content]).
Smoking Cessation
The
primary goals in managing patients with heart failure are complete smoking
cessation and avoidance of passive smoking. Patients may be provided with
counseling, cessation programs, and pharmacotherapy (eg nicotine replacement,
Bupropion) to aid in smoking cessation.
Physical Activity
Regular
physical activity or aerobic exercise is strongly recommended in patients with
chronic heart failure (NYHA Class I-III). It should be individualized based on
the patient’s capacity. Physical activity improves exercise capacity and the
quality of life. Physicians should promote adherence to an exercise goal of 30
minutes of moderate activity or exercise, 5-7 days a week with warm up and cool
down exercise. When clinically stable, patients should be encouraged to carry
out daily physical activities and leisure activities that do not induce
symptoms.
Sexual Activity
Counsel
patients to defer sexual activities if they are in NYHA Class III-IV but may
resume when their cardiac condition is stabilized. Sexual activity is likely to
be safe in patients who are able to achieve approximately 5-6 metabolic
equivalents of exercise (ie can climb two flights of stairs without stopping
due to angina, dyspnea, or dizziness).
Advise
patients regarding the use of sublingual Nitroglycerin as prophylaxis against
dyspnea and chest pain during sexual activity. Drugs used in erectile
dysfunction (eg Avanafil, Sildenafil, Tadalafil) are contraindicated in
patients receiving nitrates or those who have hypotension, arrhythmias, or
angina pectoris.
Pregnancy and Contraception
Low-dose oral contraceptives have a
small risk of causing hypertension or thrombogenicity, but these risks need to
be weighed against the risk of pregnancy. Advise patients with left ventricular
ejection fraction of <30% and those in NYHA Class III-IV to not get
pregnant. If heart failure occurs during pregnancy, use beta-blockers, Digoxin,
diuretics, Hydralazine and/or nitrates judiciously. Women
with a history of heart failure or cardiomyopathy should be counseled prepregnancy regarding
contraception and the risks of cardiovascular status deterioration while being
pregnant.
Travel
Discuss travel plans with the
physician for patients with heart failure who are at increased risk of deep
venous thrombosis (DVT). Air travel is preferred to other means of
transportation, especially on long journeys. Long flights may predispose
patients to accidental omission of medicines, edema of the lower extremities,
dehydration, and deep vein thrombosis. Deep vein thrombosis prophylaxis with a
single injection of low-molecular-weight Heparin and/or graduated compression
stockings plus calf stretching during the flight are recommended.
Pharmacotherapy may be added if there is a significant risk of deep vein
thrombosis. Advise patients to avoid high altitude destinations of >1500
meters because of relative hypoxia.
Heart Failure - Chronic_Management 3Cardiac Rehabilitation
Cardiac rehabilitation is considered useful in patients who are clinically stable and able to participate in exercise programs. Following myocardial revascularization, patients should also be referred for cardiac rehabilitation. This may help with symptom monitoring, medication titration, and reducing patient anxiety and uncertainty.
The core components of a comprehensive program include the following:
- Patient assessment and risk stratification
- Optimization of cardiovascular pharmacotherapy
- Management of frailty and cardiovascular risk-related comorbidities
- Self-management, behavior change and education
- Physical activity and sedentary behavior counseling
- Exercise training
- Nutrition and body composition management
- Smoking cessation
- Psychosocial assessment and management
- Counselling on environmental cardiovascular risk factors
- Sexual counselling
- Interventions to support return to work
Long-term,
personalized exercise training, delivered either within a multidisciplinary
cardiac rehabilitation program or independently, is recommended for all stable heart
failure patients, unless contraindicated, to improve exercise capacity and
quality of life and to reduce all-cause hospitalizations. A supervised program is
considered in patients with frailty, more severe disease or comorbidities. It
is recommended in symptomatic patients with heart failure with reduced ejection
fraction who are stable to decrease the risk of hospitalization and in patients
with chronic heart failure with reduced ejection fraction to reduce all-cause
hospital admissions and improve physical functioning and health-related quality
of life. It is also recommended in patients with heart failure with preserved
ejection fraction to improve physical functioning and health-related quality of
life and should be considered in patients with chronic heart failure with
preserved ejection fraction to reduce all-cause hospitalizations. It is also
recommended in patients with advanced heart failure and left ventricular assist
device (LVAD) and in patients after heart transplantation to improve physical
functioning and quality of life.
Depression and Mood Disorder
Screening
for endogenous or prolonged reactive depression,
anxiety and frailty in patients with heart failure should be done
following its diagnosis and at periodic intervals as clinically
indicated to support the development of personalized care plans and to identify
factors that may contribute to adverse outcomes. Initiate appropriate
pharmacotherapy (eg selective serotonin receptor uptake inhibitors) and provide
psychosocial support
Sleep and Breathing Disorders
Patients with
symptomatic heart failure 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. Medical
therapy should be optimized in patients with central sleep apnea as adaptive servo-ventilation (ASV) is
contraindicated. ASV may be considered for patients
with heart failure with reduced ejection fraction and sleep-disordered
breathing characterized predominantly by obstructive sleep apnea, with
the aim of improving sleep quality, health-related quality of life and
symptoms. Continuous positive airway pressure (CPAP) should be
considered in polysomnograph-documented obstructive sleep apnea to improve
daily functional capacity and quality of life.
Interventional Therapy
Device-based Therapy
Cardiac Resynchronization Therapy (CRT)
CRT is indicated for
patients with ventricular dyssynchrony from conduction abnormalities. It is recommended
if NYHA Class II-IV symptomatic patient is in sinus rhythm with a QRS duration
of ≥150 msec, left bundle branch block, and left ventricular ejection fraction
of ≤35% despite optimal foundational medical
therapy for at least 3-6 months as it
improves symptoms and reduces morbidity and mortality. CRT provides high
economic value. Initiation of foundational medical
therapy and CRT implantation may be considered simultaneously in appropriate
patients with these characteristics; however, left ventricular ejection
fraction should be reassessed before CRT implantation to determine whether the
indication persists.
It should be considered in NYHA Class
II-IV symptomatic heart failure patients in sinus rhythm with a left
ventricular ejection fraction of ≤35% and QRS duration of ≥150 msec and non-left
bundle branch block pattern or QRS duration of 130-149
msec and left bundle branch block pattern despite optimal medical
therapy. It may be performed in patients more than 40 days post-myocardial
infarction and with a reasonably expected survival of more than 1 year.
CRT
should be considered (instead of right ventricular pacing) in patients with
heart failure with reduced ejection fraction regardless of NYHA class or QRS
width with an indication for ventricular pacing for high-degree atrioventricular
block in order to decrease the risk of heart
failure hospitalization and mortality. Review of the proportion of right
ventricular pacing should be considered in all patients with cardiac
implantable electronic device and de novo or worsening heart failure
with reduced ejection fraction.
Consider an upgrade to CRT
in patients with a left ventricular ejection fraction of ≤35% who have received
a conventional pacemaker or an implantable cardioverter-defibrillator (ICD) and
subsequently experience worsening heart failure despite optimal medical therapy
and who have a significant proportion of right ventricular pacing in order to reduce the risk of heart failure
hospitalization or death.
To improve symptoms and quality of life and to
reduce hospitalizations and total mortality, CRT may also be considered in the following patients:
- With high-degree or complete heart block and left ventricular ejection fraction of 36-50%
- In sinus rhythm NYHA Class III-IV with a QRS duration of 120-149 msec, non-left bundle branch block, and left ventricular ejection fraction of ≤35% on guideline-directed medical therapy
- With an ischemic cause of heart failure, in sinus rhythm NYHA Class I with a QRS duration of ≥150 msec, left bundle branch block, and left ventricular ejection fraction of ≤30% on guideline-directed medical therapy
- On guideline-directed medical therapy with left ventricular ejection fraction of ≤35% and undergoing placement of a new or replacement of a device implant with anticipated requirement for significant ventricular pacing
In patients with severely symptomatic permanent atrial
fibrillation, inadequate rate control despite medical therapy and at least one
prior heart failure hospitalization, atrioventricular-node ablation with CRT
should be considered to improve symptoms and physical limitations and reduce recurrent
heart failure hospitalization and mortality.
Implantable Cardioverter-Defibrillator (ICD)
Implantable
cardioverter-defibrillator is effective in preventing arrhythmic sudden cardiac
death and prolonging survival in patients with heart failure with reduced
ejection fraction who are at high risk of sudden cardiac death. It is also recommended
in selected patients with heart failure with reduced ejection fraction, left
ventricular ejection fraction ≤35% and an ischemic etiology, and should be
considered in those with a non-ischemic etiology. Primary prevention
or prophylactic implantable cardioverter-defibrillator implantation to decrease
the risk of sudden cardiac death may be done in an NYHA Class II-III
symptomatic patient with a left ventricular ejection fraction of ≤35% or NYHA
Class I symptomatic patient with a left ventricular ejection fraction of ≤30%
despite optimal guideline-directed medical therapy for at least 3-6 months and
without myocardial infarction in the prior 40 days, or with dilated ischemic
cardiomyopathy, or with a reasonable expected survival for more than 1 year with good functional status.
A transvenous implantable cardioverter-defibrillator
is of high economic value in the primary prevention
of sudden cardiac death.
Heart Failure - Chronic_ManagementImplantable cardioverter-defibrillator 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 arrhythmia or with hemodynamic instability caused by documented ventricular dysrhythmia, in the absence of reversible causes, or unless the ventricular arrhythmia has occurred <48 hours after a myocardial infarction
- Those with symptomatic chronic heart failure and left ventricular ejection fraction of ≤35% who experience syncope of unclear etiology
- Those with previous myocardial infarction (>40 days) and left ventricular ejection fraction of ≤40% with non-sustained ventricular tachycardia and ventricular tachycardia or ventricular fibrillation that is inducible and sustained during an electrophysiological study
- With previous myocardial infarction (>40 days) and 3 months after revascularization, left ventricular ejection fraction ≤35% and NYHA Class II-III
- No previous myocardial infarction, left ventricular ejection fraction ≤35%, on optimal medical treatment and NYHA Class II or III
Consider an implantable
cardioverter-defibrillator implantation in patients
with genetic arrhythmogenic cardiomyopathy with high-risk features of sudden
death and ejection fraction of ≤45% to decrease sudden death.
Left
Ventricular Assist Device (LVAD)
Mechanical circulatory support can improve
survival and symptoms of patients with advanced heart failure. Temporary mechanical
circulatory support aims to support cerebral and end-organ perfusion, reverse
acidosis and multiorgan failure, and provide support until the patient’s
condition moves towards myocardial recovery, transition to durable mechanical
circulatory support or heart transplantation, or a palliative pathway. Durable mechanical
circulatory support is indicated to prolong life and improve quality of life in
selected patients when medical and interventional therapies are insufficient or
when temporary mechanical circulatory support has not led to cardiac recovery
or clinical improvement. LVAD is by far the most common and reliable type of
durable mechanical circulatory support. LVAD is recommended in selected
patients with advanced heart failure with reduced ejection fraction despite
optimized foundational medical therapy and guideline-directed interventional
therapy, as a bridge to transplantation, bridge to candidacy, bridge to
recovery or destination therapy, to improve symptoms and reduce the risk of
death.
LVAD implantation should be considered in
patients with heart failure and severely reduced left ventricular ejection
fraction who meet ≥1 of the following criteria:
- Critical cardiogenic shock and progressive decline, including neurological and other end-organ dysfunction but no cardiac recovery on temporary mechanical circulatory support; or
- Patients who are progressively declining despite inotropic support, stable but dependent on continuous inotropes, or experiencing daily symptoms of congestion with fluctuating high diuretic needs; or
- Severe heart failure symptoms and signs (NYHA Class III-IV) despite
optimal medical and interventional treatment, and at least one of the following:
- Inability to exercise due to heart failure or, if able to perform CPET, pVO2 <12-14 mL/kg/min and/or <50% predicted value
- End-organ dysfunction (eg worsening kidney and/or liver function, group 2 pulmonary hypertension, cardiac cachexia) from reduced perfusion as indicated by a cardiac index ≤2 L/min/m² despite euvolemia or therapy-resistant hypervolemic status
- Repeated heart failure hospitalizations within the previous 12 months without an identifiable precipitating cause
Surgery
Coronary Revascularization
Coronary revascularization therapy includes
coronary artery bypass grafting (CABG) or percutaneous coronary intervention
(PCI). It is recommended for patients with heart
failure, obstructive CAD, and persistent angina to relieve persistent angina
symptoms despite optimal guideline-directed medical therapy for heart failure
and anti-anginal agents.
Valvular Surgery
Mitral valve repair or replacement
may be considered after optimization of guideline-directed medical
therapy in patients with left ventricular systolic dysfunction and moderate-severe
mitral regurgitation who will undergo surgical coronary revascularization.
Mitral
valve repair may be done in symptomatic patients with heart failure, severe
mitral regurgitation, and a left ventricular ejection fraction of <30%. A
MitraClip may be considered in select patients with heart failure with reduced
ejection fraction to decrease mitral regurgitation. Transcatheter mitral edge-to-edge
repair is recommended in hemodynamically stable, symptomatic patients with heart
failure with reduced ejection fraction and persistent severe secondary mitral
regurgitation despite optimized foundational medical therapy and CRT, when
indicated, provided they meet the specified clinical and echocardiographic
criteria, to reduce the risk of heart failure hospitalization and improve
quality of life.
Mitral valve replacement may be
considered in symptomatic patients with a left ventricular ejection fraction of
<30% and/or left ventricular end-systolic diameter of >55 mm unresponsive
to medical treatment, with comorbidities, and with a low likelihood for
successful surgical outcome.
Balloon mitral valvuloplasty (BMV) can
be considered in patients with mitral stenosis with suitable valve anatomy.
Percutaneous mitral commissurotomy
(PMC) may be considered in symptomatic patients with mitral stenosis with a
valve area of >1.5 cm2 with suitable valve anatomy at high risk
or with contraindications for surgery. It should be considered in asymptomatic
patients with high thromboembolic risk and/or high risk of hemodynamic decompensation
without contraindications to percutaneous mitral commissurotomy.
Aortic valve replacement
may be considered for patients with aortic regurgitation or aortic stenosis. Aortic valve intervention (eg surgical aortic valve
replacement [SAVR] or transcatheter aortic valve implantation [TAVI]) is
recommended in patients with severe aortic stenosis and heart failure to
improve symptoms and reduce the risk of death. It is recommended for
symptomatic patients irrespective of the left ventricular ejection fraction
value. It should also be considered in asymptomatic patients with a left
ventricular ejection fraction of ≤50%, left ventricular enlargement with a left
ventricular end-diastolic diameter of >70 mm, or left ventricular
end-systolic diameter of >50 mm. Transcatheter aortic valve replacement
(TAVR) or TAVI may be considered in patients
with high-risk aortic stenosis or patients who are not fit for surgery.
Aortic valve repair or valve-sparing
surgery should be considered in patients with pliable noncalcified tricuspid or
bicuspid valves with type I or type II aortic regurgitation.
Heart Failure - Chronic_Management 4Heart Transplantation
Heart transplantation remains the gold-standard treatment for advanced heart failure in the absence of contraindications and significantly improves survival and quality of life in appropriately selected patients. It is recommended in eligible patients with advanced or end-stage heart failure and severe symptoms who are refractory to optimal guideline-directed medical therapy or device therapy/surgery and have no other therapeutic options, except for durable mechanical circulatory support as a bridge to transplantation, provided no absolute contraindications exist. Early referral to an advanced heart failure center is recommended for motivated patients with advanced heart failure or those at risk of progression, without absolute contraindications to durable mechanical circulatory support or heart transplantation, to assess candidacy and determine the appropriate advanced therapy pathway. CPET and right heart catheterization are recommended in patients with advanced heart failure as part of the evaluation for durable mechanical circulatory support and heart transplantation. Evaluation by a specialized heart-kidney transplant team should be considered in patients with advanced heart failure who are heart-transplant candidates and have a baseline eGFR <30 mL/min/1.73 m² to determine whether combined heart-kidney transplantation is indicated. Pharmacological therapy and temporary mechanical circulatory support may be indicated in patients with advanced heart failure until durable mechanical circulatory support implantation or heart transplantation is available. LVAD should be considered as a destination therapy in patients who are ineligible for transplantation, or as a bridge to heart transplantation if a donor heart is not immediately available. Patients with contraindications to mechanical circulatory support or heart transplantation should receive palliative care.
Prevention
Control of Risk and Prevention of Cardiovascular Events
Hypertension and Dyslipidemia
The recommended optimal
blood pressure to reduce the risk of heart failure with hypertension or stage B
heart failure is <130/80 mmHg1. A healthy diet and statin therapy are potential preventive strategies for dyslipidemia.
1Recommendations for blood pressure target goals may vary between countries. Please refer to available guidelines from local health authorities.
Please see Hypertension and Dyslipidemia disease management charts for further information.
Diabetes Mellitus
SGLT2 inhibitors and glucagon-like
peptide 1 (GLP-1) receptor agonists with proven cardiovascular benefits significantly
decrease heart failure events in type 2 diabetes patients with heart failure, established
cardiovascular disease, or high risk for cardiovascular disease. Metformin may
be used in type 2 diabetes patients with stable heart failure, including heart failure with preserved ejection fraction.
Long-term treatment with ACE inhibitors or ARBs can prevent the development of end-organ disease, cardiovascular complications, and risk of heart failure in patients with diabetes and those without hypertension. Other agents that may also be given to patients with diabetes mellitus include a beta-blocker, MRA, an ARNI, and Ivabradine.
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 death, myocardial infarction, and stroke in patients with known vascular disease. ACE inhibitors prevent heart failure in patients who are at high risk of developing heart failure, have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors.
For the prevention of symptomatic heart failure in pre-heart failure patients, the following may be considered:
- ACE inhibitor (or ARB if intolerant to ACE inhibitor) is recommended in patients with left ventricular ejection fraction ≤40% to reduce the risk of heart failure hospitalization or death
- Beta-blocker is recommended in patients with left ventricular ejection fraction ≤50% to reduce the risk of heart failure hospitalization or death
- Eplerenone is recommended in patients with left ventricular ejection fraction ≤40% after myocardial infarction with signs of heart failure or diabetes to reduce the risk of heart failure hospitalization and death
- Statin therapy should be considered in people at high risk of, or with established atherosclerotic cardiovascular disease, to reduce the risk of heart failure
An implantable cardioverter-defibrillator may be placed in pre-heart failure patients who are at least 40 days post-myocardial infarction with a left ventricular ejection fraction of ≤30% and with more than 1 year expected survival.
Atrial Fibrillation
Patients with atrial fibrillation
should be treated according to guideline-directed medical therapy. Beta-blocker
or non-dihydropyridine calcium channel blocker plus Digoxin may be given if
needed for rate control. Rhythm control by pharmacotherapy or electrical therapy is recommended in
patients with recent-onset AF of <1 year duration or paroxysmal AF. Anticoagulation
may be done if without contraindications to reduce the risk of thromboembolic
events.
Chronic Kidney Disease (CKD)
ACE inhibitor, ARB, or ARNI, beta-blocker, MRA,
and SGLT2 inhibitors can be used in patients with eGFR >30 mL/min/1.73 m2. Finerenone reduced the risk of heart failure hospitalization in patients with type 2 diabetes mellitus and CKD.
Please see Chronic Kidney Disease disease management chart for further information.