- ACRONYMS AND DEFINITIONS
- AHA - American Heart Association
- BNP - B-type natriuretic peptide
- CABG - Coronary artery bypass grafting
- CAD - Coronary artery disease
- CRT - Cardiac resynchronization therapy
- DCM - Dilated cardiomyopathy
- DOAC - Direct-acting oral anticoagulant
- ECG - Electrocardiogram
- ECHO - Echocardiography
- EF - Ejection fraction
- GDMT - Guideline-directed medical therapy
- HF - Heart failure
- HFimpEF - Heart failure with improved ejection fraction (past LVEF ≤ 40%, now > 40%)
- HFmrEF - Heart failure with mildly reduced ejection fraction (LVEF 41 - 49%)
- HFpEF - Heart failure with preserved ejection fraction (LVEF ≥ 50%)
- HFrEF - Heart failure with reduced ejection fraction (LVEF ≤ 40%)
- ICD - Implantable cardiac defibrillator
- ISDN - Isosorbide dinitrate
- LBBB - Left bundle branch block
- LV - Left ventricular
- NT-proBNP - N-terminal of the prohormone brain natriuretic peptide
- NYHA - New York Heart Association
- PAP - Pulmonary artery pressure
- SBP - Systolic blood pressure
- The lifetime risk of developing heart failure for Americans who live to be ≥ 40 years of age is 20%. Heart failure accounts for > 1 million hospital admissions each year, and the 1-month readmission rate is 25%. Five-year survival rates for AHA heart failure stages A, B, C, and D are 97%, 96%, 75%, and 20%, respectively.
- HFrEF makes up about 50% of heart failure cases, and HFpEF accounts for the other half [1,4]
- RISK FACTORS
- Risk factors for heart failure include the following:
- Hypertension - most important modifiable risk factor
- Atherosclerosis - including coronary, cerebral, and peripheral vascular disease
- Advanced age - heart failure affects 2% of those 65 - 69 years and > 8% of those ≥ 85 years
- Sex - males are at higher risk for HFrEF while females are at higher risk for HFpEF
- Black race
- Metabolic syndrome - defined as having any 3 of the following: abdominal adiposity, hypertriglyceridemia, low HDL, hypertension, fasting hyperglycemia
- Cardiotoxic agents (e.g. alcohol, amphetamines, cancer chemotherapy and radiation)
- Obesity - associated with both types of heart failure, but may be an independent risk factor for HFpEF
- Atrial fibrillation - associated with both types of heart failure, may be an independent risk factor for HFpEF
- Valvular heart disease [1,4,5,6]
- SIGNS AND SYMPTOMS
- Symptoms of heart failure include the following:
- Shortness of breath
- Reduced exercise tolerance
- Orthopnea - shortness of breath when lying supine. Occurs from increased venous return that leads to pulmonary congestion.
- Paroxysmal nocturnal dyspnea
- Abdominal bloating / early satiety - may occur in advanced disease. Secondary to increased right atrial pressure that increases intestinal venous congestion.
- Signs of heart failure include the following:
- Lung rales / crackles - if pulmonary congestion is present
- Lower extremity edema
- Elevated jugular venous pressure - occurs from increased right atrial pressure
- Lateral displacement of apex beat - enlarged left ventricle causes the apex beat to move laterally
- Third heart sound (S3 gallop) - third heart sound heard when blood from atria hits an enlarged, noncompliant ventricle
- Ascites - may be seen in advanced disease
- The underlying pathology in all cases of heart failure is a left ventricle that cannot eject enough blood to support normal circulation. Impaired circulation causes inadequate perfusion of tissues and organs that leads to fluid retention and volume overload.
- Heart failure has traditionally been divided into two subtypes: (1) heart failure with reduced ejection fraction (HFrEF), also called systolic heart failure, (2) heart failure with preserved ejection fraction (HFpEF), also called diastolic dysfunction. The structural and functional abnormalities of HFrEF are well defined, while the pathology behind HFpEF is not completely understood. A review of each type of heart failure is provided below.
- Heart failure with reduced ejection fraction (HFrEF)
- In HFrEF, a weakened left ventricle has a reduced capacity to eject its blood volume during systole (reduced ejection fraction). The weakness may result from ischemic injury, intrinsic structural abnormalities (e.g. cardiomyopathies, valve disease), or years of increased workload (e.g. long-standing hypertension). In order to compensate for the weakness, the muscular wall of the ventricle hypertrophies and dilates. As the disease progresses, fibrosis develops, and the shape of the left ventricle becomes more spherical than elliptical. The abnormal shape can stretch the mitral valve and cause it to regurgitate.
- The kidneys, sensing reduced perfusion from the failing ventricle, stimulate processes that promote fluid retention. The added volume increases strain on the heart, and signs of fluid overload (e.g. edema, pulmonary congestion) develop.
- Ischemic heart disease is the root cause of ventricular wall damage in half of HFrEF patients. Other causes of HFrEF that involve a dilated, dysfunctional heart are collectively referred to as dilated cardiomyopathies. Dilated cardiomyopathy can occur in isolation (non-ischemic cardiomyopathy), or it may be accompanied by ischemic heart disease. See dilated cardiomyopathies below.
- Heart failure with preserved ejection fraction (HFpEF)
- In HFpEF, the left ventricle does not relax appropriately during diastole, and this impairs its ability to fill with blood. Inadequate filling reduces the amount of blood that is ejected during systole, and circulation is compromised. The reason for the loss of compliance is not completely understood, but the predominant theory is that inflammatory mediators released in response to comorbidities (e.g. diabetes, obesity, COPD) have a detrimental effect on the processes that promote ventricular wall relaxation.
- Dilated cardiomyopathies (DCM)
- Dilated cardiomyopathies are a group of conditions that lead to HFrEF. Unlike other causes of HFrEF that have an extrinsic etiology (e.g. ischemia, hypertension), DCM are caused by intrinsic myocardial disorders that cause the heart to dilate and fail. Patients with DCM and heart failure have a worse prognosis than heart failure patients without DCM. Some causes of DCM are listed below.
- Familial cardiomyopathies - familial cardiomyopathies are caused by inherited genetic defects that alter the myocardium's structure and function. A number of genes have now been identified that are associated with cardiomyopathies, and genetic testing is available for many of them. First-degree family members of people who are diagnosed with idiopathic or familial cardiomyopathy should undergo periodic echocardiographic screening.
- Endocrine and metabolic cardiomyopathies - a number of endocrine and metabolic disorders have been independently associated with the development of cardiomyopathy. Some examples are listed below.
- Hyperthyroidism - possibly because of tachycardia and/or atrial fibrillation
- Growth hormone excess and deficiency - growth hormone is involved in cardiac development
- Toxic cardiomyopathies - a number of drugs and toxins have been independently associated with the development of cardiomyopathy
- Alcohol - can occur with 7 - 8 drinks per day for > 5 years
- Cocaine - toxicity occurs independently of CAD and infarctions
- Chemotherapeutic agents - anthracyclines (e.g. doxorubicin), trastuzumab (Herceptin®), high-dose cyclophosphamide, taxoids, mitomycin-C, 5-fluorouracil, interferons
- Anabolic steroids
- Tachycardia-induced cardiomyopathy - chronic ventricular tachycardia can cause cardiomyopathy through an unknown mechanism. Any supraventricular tachycardia with a rapid ventricular response (e.g. A fib, SVT) can induce cardiomyopathy as can chronic and frequent premature ventricular complexes. Treatment involves correcting the underlying arrhythmia before cardiomyopathy develops.
- Inflammatory cardiomyopathies - myocardial inflammation from infections, autoimmune disorders, and hypersensitivity reactions can lead to cardiomyopathy.
- Viral infections - coxsackie B virus (most common), HIV, adenovirus, echoviruses, COVID-19, etc.
- Drug reactions - sulfonamides, penicillins, methyldopa, amphotericin B, streptomycin, phenytoin, isoniazid, tetanus toxoid, hydrochlorothiazide, dobutamine, chlorthalidone
- Chagas disease - Trypanosoma cruzi infection
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Giant cell arteritis
- Peripartum cardiomyopathy - peripartum cardiomyopathy is a rare condition that affects women in the last trimester of pregnancy. Risk factors include advanced maternal age, multiparity, African descent, and long-term tocolysis. After delivery, 30 - 50% of women have an improvement in their left ventricular function within 6 months, while the remaining women go on to develop chronic cardiomyopathy. The cause of peripartum cardiomyopathy is unknown.
- Iron overload cardiomyopathy - chronic iron overload causes iron deposition in the myocardium that can lead to cardiomyopathy. Iron overload can develop in hemochromatosis and conditions that require regular transfusion therapy (e.g. alpha and beta thalassemia, sickle cell disease). Iron-chelating agents, and in the case of hemochromatosis, therapeutic phlebotomy, can help to prevent iron overload.
- Amyloidosis-induced cardiomyopathy - amyloids are abnormal proteins that can deposit in organs and cause toxicity. Most amyloids originate from abnormal antibodies produced by plasma cells in the bone marrow. Other forms of amyloidosis are hereditary and involve defects in transthyretin, a transport protein for thyroid hormone and retinol. Amyloid buildup in the heart can lead to cardiomyopathy.
- Stress (Takotsubo) cardiomyopathy - stress cardiomyopathy is a reversible cardiomyopathy triggered by extreme emotional or physical stress. A characteristic feature of the condition is "apical ballooning" of the left ventricle during systole, which gives the appearance of a takotsubo (Japanese octopus pot) on imaging. The condition is believed to be caused by a sudden, overwhelming release of catecholamines. It typically affects postmenopausal women, and a transient rise in cardiac enzymes is common. 
- Heart failure subtypes
- The ejection fraction (EF) is used to divide heart failure into subtypes. Traditionally, heart failure was viewed as a syndrome of volume overload secondary to a reduction in ejection fraction. Over time, though, it has become evident that many patients with signs and symptoms of heart failure have normal or near-normal ejection fractions. This led to the realization that diastolic relaxation/compliance also plays an important role in cardiac output, and the syndrome of HFpEF was created to describe these individuals.
- The table below shows the different subtypes of HF based on the EF as defined by the AHA 2022 HF guidelines
|AHA Heart Failure Subtypes Based on EF|
HFrEF (HF with reduced EF)
HFimpEF (HF with improved EF)
HFmrEF (HF with mildly reduced EF)
HFpEF (HF with preserved EF)
- New York Heart Association heart failure classification (NYHA)
- The NYHA heart failure classification system is a widely used method for classifying heart failure patients based on the severity of their symptoms. Most clinical trials and professional recommendations use the NYHA classification system to subdivide heart failure patients.
|I||No limitation of physical activity. Ordinary physical activity does not result in symptoms.|
|II||Slight limitation of physical activity. Comfortable at rest, but ordinary activity results in fatigue, palpitations, or shortness of breath.|
|III||Marked limitation of activity. Comfortable at rest, but less than ordinary activity results in fatigue, palpitations, or shortness of breath.|
|IV||Symptoms at rest. Unable to carry on any physical activity without discomfort. Any physical activity results in discomfort.|
|AHA Stages of Heart Failure|
Stage A - At risk for HF
Stage B - Pre-HF
Stage C - Symptomatic HF
Stage D - Advanced HF
- Heart failure is a clinical diagnosis based on symptoms, physical exam findings, and diagnostic test results. No universally accepted diagnostic criteria exist for either type of heart failure, and there is no single lab or imaging study that is considered diagnostic.
- Heart failure should be considered in anyone who presents with signs and symptoms of the disease (see above). Initial testing should include an ECG, chest X-ray, CBC, CMP, and BNP/NT-proBNP. If testing is consistent with heart failure and/or no alternative etiology is identified, echocardiography should be performed. Diagnostic tests for heart failure are discussed below.
- Chest X-ray
- The chest X-ray is important in evaluating heart failure because certain findings are very specific for the condition; it also helps to identify other causes of shortness of breath (e.g. pneumonia, COPD). That being said, it is not a highly sensitive test as studies have shown that up to 20% of patients with acute heart failure have no signs of pulmonary congestion on chest X-ray. Even among advanced heart failure patients, pulmonary congestion on chest X-ray is absent in over a quarter.
- The table below gives the sensitivity and specificity of different chest X-ray findings in heart failure. The information is from a study that included 202 patients who presented to the ER with shortness of breath. Consistent with the fact that a negative chest X-ray does not rule out heart failure, only cardiomegaly and overall radiographic interpretation of heart failure had a sensitivity above 50%.
|Chest X-ray findings in heart failure|
|Overall radiographic interpretation of HF||53.3%||86.3%|
|Kerley B lines||23.4%||95.8%|
|Bilateral pleural effusion||19.6%||94.7%|
- A 12-lead ECG should be performed in all patients with suspected heart failure. ECG findings suggestive of heart failure are listed below; although, it is important to note that no single ECG finding is highly sensitive or specific for heart failure. Other significant ECG findings associated with an increased risk of heart failure include evidence of acute or prior myocardial infarction, evidence of ischemia, and arrhythmias such as atrial fibrillation.
- ECG findings that may be seen in heart failure
- Left ventricular hypertrophy
- Left atrial enlargement
- Sinus tachycardia
- Left axis deviation 
- BNP / NT-proBNP
- Natriuretic peptides include atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). BNP is sometimes referred to as "brain natriuretic peptide" because it was originally identified in pig brain extracts.
- Myocardial distension causes the release of ANP from the atria and BNP from the ventricles. CNP is released by vascular endothelial cells in response to inflammatory mediators. Natriuretic peptides have the following physiologic effects: (1) stimulation of fluid and sodium excretion in the kidneys, (2) promotion of myocardial relaxation while inhibiting hypertrophy and fibrosis, (3) suppression of sympathetic outflow in the brain, (4) stimulation of vasodilation.
- NT-proBNP stands for "N-terminal of the prohormone brain natriuretic peptide." It is an inactive amino acid fragment that is released when proBNP is cleaved to BNP. Levels of NT-proBNP are directly proportional to BNP, and therefore, it is an indirect marker of BNP activity. BNP and NT-proBNP perform equally well in studies, so either test is recommended with one exception - NT-proBNP is preferred in patients taking the heart failure drug Entresto® because it can raise BNP levels but does not affect NT-proBNP levels. 
- BNP/NT-proBNP and heart failure
- BNP/NT-proBNP levels are elevated in both types of heart failure; although, patients with HFpEF tend to have lower values on average. In HFrEF, BNP is released in response to ventricular wall distension. In HFpEF, ventricular wall distress during diastole is believed to stimulate BNP release. Other conditions can cause BNP/NT-proBNP levels to rise (see factors affecting BNP below), so elevated BNP/NT-proBNP levels are not diagnostic for heart failure. They are, however, very sensitive for heart failure, and normal levels can generally be used to rule out heart failure.
- BNP/NT-proBNP levels have been studied in determining prognosis and guiding heart failure therapy. In general, lower levels are associated with better outcomes, but studies comparing BNP/NT-proBNP-guided therapy to standard of care have had mixed results. [4,5,9,10,13]
|BNP / NT-proBNP Levels in Heart Failure|
|Condition||BNP level||NT-proBNP level|
|Rule in acute heart failure||> 100 pg/ml||
|Rule out acute heart failure||< 100 pg/ml||< 300 pg/ml|
|Rule out chronic heart failure||< 35 pg/ml||< 125 pg/ml|
|Factors that may affect BNP and NT-proBNP values|
|High output states||
- Echocardiography (echo)
- While echocardiography is not independently diagnostic for heart failure, it is essential in qualifying and quantifying the disease. It also provides important information about possible etiologies (e.g. cardiomyopathy, infarctions, heart valve disease) and contributing factors. Findings in both types of heart failure are discussed below along with the ejection fraction.
- Ejection fraction (EF)
- The ejection fraction is used to determine the type of heart failure that is present (HFrEF vs HFpEF), and in the case of HFrEF, the severity of the condition.
- EF can be thought of in the following manner:
- At the end of diastole, the left ventricle is filled with blood and at its "end-diastolic volume"
- During systole, the ventricle contracts and forces a portion of that blood into the circulation (stroke volume)
- The volume of blood forced into the bloodstream divided by the volume of blood in a full ventricle is the ejection fraction
- In short, it's the percent of blood in a full ventricle that the ventricle can pump (eject) into the circulation. A normal EF is ≥ 50%.
- EF is defined by the following formula:
- EF = Change in LV volume / Initial LV volume = Stroke volume / End-diastolic volume
|41 - 49%||
- ECHO findings in HFrEF
- In HFrEF, the ejection fraction is < 40%, and this reduction in the ability of the left ventricle to force blood into the circulation causes signs and symptoms of heart failure. Other findings on echocardiography that may be seen in HFrEF are listed below.
- Echocardiographic findings in HFrEF
- EF ≤ 40%. EF may also be 41 - 49% in patients with HFrEF that has improved
- Increased LV end-systolic volume
- Increased LV end-diastolic volume
- Relative or absolute decrease in LV wall thickness
- Hypokinesis or akinesis of ventricular wall - suggests coronary artery disease
- Mitral valve regurgitation - occurs from LV dilation stretching the mitral valve [1,4,5]
- ECHO findings in HFpEF
- In HFpEF, the left ventricle does not relax appropriately during diastole, and this impairs its ability to fill with blood. Inadequate filling reduces the amount of blood that is ejected during systole, and circulation is compromised. The EF in HFpEF is ≥ 41%.
- To understand how ventricular relaxation is measured on echocardiography, it's important to review what happens during diastole
- Early diastole - in early diastole, the left ventricle relaxes, and this creates negative pressure in the ventricle that pulls the mitral leaflets down. Blood from the atria then flows into the ventricle. Under normal conditions, the majority of ventricular filling (80%) occurs during this phase. Echocardiographic measurements during this phase include the following:
- E wave - the E wave (E is for early) represents the peak velocity at which blood flows from the atria into the ventricle during early diastole
- Deceleration time - the deceleration time is the amount of time it takes for E wave flow to go from its peak velocity to zero
- Mitral annulus tissue velocity (e') - the mitral annulus is the tissue surrounding the mitral valve leaflets. During systole, the mitral annulus is displaced in the direction of the left ventricular apex. As diastole starts, it moves back to its original position. The peak velocity at which it moves back is called the mitral annulus tissue velocity (e').
- Isovolumetric relaxation time (IVRT) - the IVRT is the amount of time between the end of systole and the beginning of ventricular filling
- Late diastole (atrial phase) - after early diastole, a small amount of blood remains in the left atrium. In order to eject this blood, the atrium contracts, and the blood is forced into the ventricle.
- A wave - the A wave (A is for atrial) represents the peak velocity at which blood flows into the ventricle during the atrial phase
- Diastolic function is assessed using the measures above and their ratios, specifically the E/A ratio and the E/e' ratio. The table below describes how these values change in different types of diastolic function. It's important to note that definitions of diastolic dysfunction and its severity differ across the medical literature, so the criteria listed below may not coincide with other sources.
|Echocardiographic measures of diastolic function|
|Grade 1 diastolic dysfunction
|Grade 2 diastolic dysfunction
|Grade 3 diastolic dysfunction
|Grade 4 diastolic dysfunction
- Other testing
- Other testing in heart failure should be individualized. Half of HFrEF cases are of ischemic etiology, so coronary angiography is appropriate in many patients. If non-ischemic dilated cardiomyopathy is a consideration, an endomyocardial biopsy may be indicated.
|AHA 2022 HFrEF Treatment Recommendations|
STEP 1 - All patients with Stage C HF and LVEF ≤ 40%
STEP 2 - After optimizing therapy, reevaluate patient
Aldosterone antagonist therapy (spironolactone, eplerenone)
- Heart failure with mildly reduced EF (LVEF 41 - 49%)
- AHA 2022 recommendations
- In patients with HFmrEF, SGLT2 inhibitors can be beneficial in decreasing HF hospitalizations and cardiovascular mortality
- Among patients with current or previous symptomatic HFmrEF (LVEF, 41%–49%), use of evidence-based beta blockers for HFrEF, sacubitril-valsartan (Entresto®), ACE inhibitors, or ARB, and aldosterone antagonists may be considered to reduce the risk of HF hospitalization and cardiovascular mortality, particularly among patients with LVEF on the lower end of this spectrum
- Heart failure with improved EF (past LVEF ≤ 40%, now > 40%)
- AHA 2022 recommendations
- In patients with HFimpEF after treatment, GDMT should be continued to prevent relapse of HF and LV dysfunction, even in patients who may become asymptomatic. 
- Heart failure with preserved EF (LVEF ≥ 50%)
- Drug classes that have proven beneficial in HFrEF (e.g. RAAS inhibitors, beta blockers, aldosterone antagonists) have not performed as well in HFpEF. No drug had been FDA-approved to treat HFpEF until 2021 when the SGLT2 inhibitor empagliflozin was granted Breakthrough Therapy Designation after a successful trial was published (see empagliflozin in HFpEF). Current HFpEF treatment is primarily focused on managing blood pressure and relieving congestive symptoms with diuretics. AHA recommendations for treating HpEF are presented below, along with a review of HFpEF trials (HFpEF drug studies).
- AHA 2022 recommendations
- Patients with HFpEF and hypertension should have medication titrated to attain blood pressure targets in accordance with published clinical practice guidelines to prevent morbidity
- In patients with HFpEF, SGLT2 inhibitors (empagliflozin) can be beneficial in decreasing HF hospitalizations and cardiovascular mortality
- In patients with HFpEF, management of A fib can be useful to improve symptoms
- In selected patients with HFpEF, aldosterone antagonists may be considered to decrease hospitalizations, particularly among patients with LVEF on the lower end of this spectrum
- In selected patients with HFpEF, the use of ARB may be considered to decrease hospitalizations, particularly among patients with LVEF on the lower end of this spectrum
- In selected patients with HFpEF, sacubitril-valsartan (Entresto®) may be considered to decrease hospitalizations, particularly among patients with LVEF on the lower end of this spectrum
- In patients with HFpEF, routine use of nitrates or phosphodiesterase-5 inhibitors to increase activity or quality of life is ineffective 
- Drug studies in HFpEF
- Empagliflozin (Jardiance®) - in 2021, the EMPEROR-Preserved trial was published that showed empagliflozin improved outcomes in patients with HFpEF. The benefit was primarily driven by reduced hospitalizations, and there was no significant effect on mortality or cardiovascular death.
- ACE inhibitors - a trial that compared perindopril to placebo found that it did not improve the primary outcome. [PMID 16963472]
- ARBs - two trials have compared ARBs to placebo in HFpEF. In one trial, candesartan did not improve the primary outcome [PMID 13678871], and in another study, irbesartan was not found to be beneficial. [PMID 19001508]
- Sacubitril-valsartan (Entresto®) - Entresto was compared to valsartan in the PARAGON-HF trial, where it did not achieve its primary outcome, but there was a trend toward a significant decrease in heart failure hospitalizations. Another study (N=2572) that looked at the effect of Entresto on surrogate endpoints in HFpEF found that Entresto lowered NT-proBNP levels but did not improve 6-minute walk distance. [PMID 34783839]
- Beta blockers - well-done studies of beta blockers in HFpEF are lacking. In one small study, carvedilol did not improve outcomes. [PMID 22983988]
- Aldosterone antagonists - spironolactone was compared to placebo in the TOPCAT study, and while it did not improve the primary outcome, it did reduce heart failure hospitalizations. A secondary analysis of the study found an unusually large difference in the number of outcome events between geographic regions. In Russia/Georgia (N=1678), the incidence of the primary outcome was 4-fold lower than in the Americas (N=1767); this led researchers to suspect that a number of patients without heart failure were enrolled in the Russia/Georgia regions. A post hoc analysis that excluded the Russia/Georgia data found that spironolactone significantly improved the primary outcome. [PMID 25406305]
- Cardiac resynchronization therapy (CRT)
- CRT involves the implantation of a device that synchronizes ventricular contractions. Some patients with heart failure have a condition called left bundle branch block (LBBB), where the nerves that stimulate the left ventricle to contract (left bundle) are damaged, and conduction through the left ventricle is delayed in relation to the right; this can impair cardiac pumping efficiency. A CRT device has lead wires that run along the ventricles. When it senses asynchronous contractions, it sends electrical impulses along the wires that induce simultaneous contractions. CRT recommendations from the AHA and links to CRT trials are provided below.
- AHA 2022 CRT recommendations
- For patients who have LVEF ≤ 35%, sinus rhythm, left bundle branch block (LBBB) with a QRS duration ≥ 150 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT, CRT is indicated to reduce total mortality, reduce hospitalizations, and improve symptoms and quality of life.
- For patients who have LVEF ≤ 35%, sinus rhythm, a non-LBBB pattern with a QRS duration ≥ 150 ms, and NYHA class II, III, or ambulatory class IV symptoms on GDMT, CRT can be useful to reduce total mortality, reduce hospitalizations, and improve symptoms and quality of life.
- In patients with high-degree or complete heart block and LVEF of 36% to 50%, CRT is reasonable to reduce total mortality, reduce hospitalizations, and improve symptoms and quality of life.
- For patients who have LVEF ≤ 35%, sinus rhythm, LBBB with a QRS duration of 120 to 149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT, CRT can be useful to reduce total mortality, reduce hospitalizations, and improve symptoms and quality of life.
- In patients with A fib and LVEF ≤ 35% on GDMT, CRT can be useful to reduce total mortality, improve symptoms and QOL, and increase LVEF, if: a) the patient requires ventricular pacing or otherwise meets CRT criteria and b) atrioventricular nodal ablation or pharmacological rate control will allow near 100% ventricular pacing with CRT.
- For patients on GDMT who have LVEF ≤ 35% and are undergoing placement of a new or replacement device implantation with anticipated requirement for significant (> 40%) ventricular pacing, CRT can be useful to reduce total mortality, reduce hospitalizations, and improve symptoms and quality of life.
- For patients who have LVEF ≤ 35%, sinus rhythm, a non-LBBB pattern with QRS duration of 120 to 149 ms, and NYHA class III or ambulatory class IV on GDMT, CRT may be considered to reduce total mortality, reduce hospitalizations, and improve symptoms and quality of life.
- For patients who have LVEF ≤ 30%, ischemic cause of HF, sinus rhythm, LBBB with a QRS duration ≥ 150 ms, and NYHA class I symptoms on GDMT, CRT may be considered to reduce hospitalizations and improve symptoms and quality of life. 
- CRT trials
- Implantable cardiac defibrillator (ICD)
- An ICD senses life-threatening arrhythmias (e.g. ventricular fibrillation), and it shocks the heart in an attempt to restore a normal rhythm. Dilated, enlarged ventricles, as seen in HFrEF, are more susceptible to arrhythmias, and patients with HFrEF are at an increased risk of sudden cardiac death. ICDs have been shown to reduce sudden cardiac death in HFrEF patients who meet certain criteria. ICD recommendations from the AHA and links to ICD trials are provided below.
- AHA 2022 ICD recommendations
- In patients with nonischemic DCM or ischemic heart disease at least 40 days post-MI with LVEF ≤ 35% and NYHA class II or III symptoms on chronic GDMT, who have reasonable expectation of meaningful survival for > 1 year, ICD therapy is recommended for primary prevention of SCD to reduce total mortality.
- In patients at least 40 days post-MI with LVEF ≤ 30% and NYHA class I symptoms while receiving GDMT, who have reasonable expectation of meaningful survival for > 1 year, ICD therapy is recommended for primary prevention of sudden cardiac death to reduce total mortality.
- In patients with genetic arrhythmogenic cardiomyopathy with high-risk features of sudden death, with EF ≤ 45%, implantation of ICD is reasonable to decrease sudden death. 
- ICD trials
- ICD vs Amiodarone vs Placebo in Heart Failure with Reduced EF, NEJM (2005) [PubMed abstract]
- ICD + Medical Therapy vs Medical Therapy Alone in Nonischemic Dilated Cardiomyopathy, NEJM (2004) [PubMed abstract]
- ICD + Medical Therapy vs Medical Therapy Alone in HFrEF with Prior MI, NEJM (2002) [PubMed abstract]
- Mitral valve repair
- As the left ventricle dilates, it can stretch and distort the mitral leaflets and their supporting structures. This can cause blood to regurgitate across the mitral valve during systole, a condition referred to as secondary mitral regurgitation (MR). Recommendations for the treatment of secondary MR are available here - secondary MR treatment.
- AHA 2022 recommendations
- In patients with chronic severe secondary mitral regurgitation and HFrEF, optimization of GDMT is recommended before any intervention for secondary mitral regurgitation related to LV dysfunction. 
- Cardiac rehabilitation
- Cardiac rehabilitation programs are structured exercise programs that focus on improving overall strength and endurance. A large trial that randomized stable heart failure patients (NYHA II - IV | median EF 25%) to cardiac rehabilitation or usual care found that cardiac rehabilitation had a nonsignificant trend towards improved outcomes. When the analysis was adjusted for baseline CVD risk factors, cardiac rehabilitation significantly improved mortality and hospitalization outcomes. [PMID 19351941]. Another study found that cardiac rehabilitation was safe and beneficial in older hospitalized patients with acute heart failure. [PMID 33999544]
- AHA 2022 recommendations
- For patients with HF who are able to participate, exercise training (or regular physical activity) is recommended to improve functional status, exercise performance, and quality of life
- In patients with HF, a cardiac rehabilitation program can be useful to improve functional capacity, exercise tolerance, and health-related quality of life. 
- Pulmonary artery pressure (PAP) monitoring
- Studies have shown that increases in intracardiac and pulmonary artery pressure occur days to weeks before overt signs of volume overload appear. Implantable devices that monitor pulmonary artery pressures have been developed for use in ambulatory patients to detect early signs of congestion so that therapy can be adjusted more acutely. A study (N=550) lasting 6 months in patients with NYHA class III symptoms found that PAP-monitored patients had a lower rate of hospitalization when compared to usual care. [PMID 21315441] Another study (N=1022) that included patients with NYHA class II - IV symptoms found no benefit of PAP monitoring. [PMID 34461042]
- Dietary sodium restriction
- Heart failure stimulates renal processes that lead to sodium and fluid retention. In theory, limiting dietary sodium could abate these counterproductive reactions. Studies that have looked at the effects of dietary sodium restriction on heart failure have been mixed. A study published in 2022 that compared dietary sodium restriction (< 1500 mg/day) to usual care in 806 patients with NYHA II-III heart failure found that sodium restriction had no effect on a composite outcome of CV-related hospital admission, CV-related emergency department visit, or all-cause death. [PMID 35381194]
- AHA 2022 recommendations
- For patients with stage C HF, avoiding excessive sodium intake is reasonable to reduce congestive symptoms 
- Patients with atrial fibrillation
- Patients with heart failure are at increased risk of developing atrial fibrillation, with up to 40% of patients with NYHA class IV heart failure having concomitant A fib. Arrhythmia-induced heart failure can also occur in the setting of A fib with a rapid ventricular rate (RVR). Any patient who presents with new-onset heart failure while in A fib with RVR should be assumed to have arrhythmia-induced heart failure until proven otherwise.
- A fib in heart failure can be treated with a rhythm or rate control strategy, and neither approach has been proven to be superior to the other. A small study (N=363) that compared rhythm control with catheter ablation to medical therapy (rate or rhythm control) in patients with NYHA class II - IV heart failure found that catheter ablation was superior to medical therapy for a number of outcomes (see CASTLE-AF study). Larger studies with a broader range of patients are needed to confirm these results.
- For patients receiving rate control medications, beta blockers are preferred and nondihydropyridine calcium channel blockers (diltiazem, verapamil) should be avoided because of their potential negative inotropic effects. Digoxin can be used in patients who cannot take beta blockers or as adjunctive therapy in patients who require further slowing.
- AHA 2022 recommendations
- Patients with chronic HF with permanent-persistent-paroxysmal A fib and a CHA2DS2-VASc score of ≥ 2 (for men) and ≥ 3 (for women) should receive chronic anticoagulant therapy
- For patients with chronic HF with permanent-persistent-paroxysmal A fib, DOAC is recommended over warfarin in eligible patients
- For patients with HF and symptoms caused by A fib, A fib ablation is reasonable to improve symptoms and quality of life
- For patients with A fib and LVEF ≤ 50%, if a rhythm control strategy fails or is not desired, and ventricular rates remain rapid despite medical therapy, atrioventricular nodal ablation with implantation of a CRT device is reasonable
- For patients with chronic HF and permanent-persistent-paroxysmal A fib, chronic anticoagulant therapy is reasonable for men and women without additional risk factors 
- Patients with coronary artery disease
- Patients with CAD and heart failure should be treated according to standard CAD and heart failure guidelines. The STICH trial compared medical therapy to CABG in patients with HFrEF and stable CAD. CABG was not superior to medical therapy for the primary outcome of overall mortality at 5 years, but at 10 years, it did show a significant benefit. STICH was performed before newer heart failure drugs like Entresto were available, so it is unknown how the treatments would compare with current medical therapy.
- AHA 2022 recommendations
- In selected patients with HF, reduced EF (EF ≤ 35%), and suitable coronary anatomy, surgical revascularization plus GDMT is beneficial to improve symptoms, cardiovascular hospitalizations, and long-term all-cause mortality 
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