Heart failure

Heart failure (HF) is a complex clinical syndrome caused by structural or functional impairment of ventricular filling and/or ejection of blood. The three main underlying causes of HF are coronary artery disease, diabetes mellitus, and hypertension; incidence increases with age. Typical clinical features include dyspnea and peripheral edema. The initial diagnostic workup includes measurement of natriuretic peptide levels, echocardiography, chest x-ray, and an ECG. Classification of patients based on left ventricular ejection fraction (LVEF), symptoms and functional capacity (NYHA class), and ACC/AHA stage helps guide management. Guideline-directed medical therapy for HF includes lifestyle modifications and treatment of associated conditions (e.g., hypertension) and comorbidities (e.g., anemia), along with a combination of pharmacological agents that reduce cardiac workload (e.g., SGLT2is, ARNIs, beta blockers, mineralocorticoid receptor antagonists). Treatment options for patients with advanced HF, a highly morbid condition, include device therapy for HF, mechanical circulatory support, and/or heart transplant. Acute heart failure (AHF) may occur as an exacerbation of HF (i.e., acute decompensated HF) or be caused by an acute cardiac condition such as myocardial infarction.

Preferred terminology ^[1][2][3]

• Heart failure (HF): a complex clinical syndrome in which there is structural or functional impairment of ventricular filling and/or ejection of blood ^[1]
• Congestive heart failure (CHF): HF with signs and/or symptoms of fluid overload, e.g., peripheral edema, jugular venous distention
• Left heart failure (LHF): HF caused by structural or functional impairment of the left heart circulatory system that results in tissue hypoperfusion and/or increased pulmonary capillary pressure
• Right heart failure (RHF): HF caused by structural or functional impairment of the right heart circulatory system that results in impaired blood flow to the pulmonary circulation and/or elevated venous pressures ^[4]
• Biventricular (global) heart failure: HF in which both the left and right ventricles are affected, resulting in the development of both RHF and LHF symptoms
• Chronic compensated heart failure: HF with stable symptoms
• Acute decompensated heart failure (ADHF): AHF due to decompensation of preexisting disease and/or cardiomyopathy (most common) ^[5]
• Systolic dysfunction: reduced ventricular contractility resulting in ventricular enlargement and reduced ejection fraction ^[6]
• Diastolic dysfunction: reduced ventricular compliance characterized by elevated filling pressures, abnormal relaxation, and increased ventricular stiffness ^[7]
• Guideline-directed medical therapy (GDMT): the stepwise use of evidence-based clinical evaluation, diagnostic studies, medication, and procedures to manage patients with HF

The term “heart failure” is preferred over “congestive heart failure” because not all patients present with symptoms of fluid overload. ^[8]

Historical terminology ^[1][2]

• Systolic HF has been used as a synonym for HF with reduced ejection fraction (HFrEF) but is no longer favored because individuals with HFrEF have both systolic and diastolic dysfunction.
• Diastolic HF has been used as a synonym for HF with preserved ejection fraction (HFpEF) but is no longer favored because individuals with HFpEF have both systolic and diastolic dysfunction.

• Approx. 1.9% of the US population (6.2 million individuals) has HF. ^[9]
• Incidence is higher among African American and Hispanic individuals. ^[10]
• Incidence increases with age: Approx. 20% of individuals aged > 75 years are affected. ^[11]
• An increasing proportion of patients with HF have HFpEF (≥ 50%). ^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Cardiovascular
  • Ischemic heart disease (50% of HFrEF cases): coronary artery disease (CAD), myocardial infarction ^[12]
  • Hypertension
  • Valvular heart disease
  • Arrhythmias and heart rhythm-related conditions, e.g., tachycardia, high PVC burden, RV pacing
  • Myocarditis, e.g., infectious, toxic, autoimmune
  • Cardiomyopathies
    • Dilated cardiomyopathy, e.g., hemochromatosis
    • Stress-induced cardiomyopathy
    • Peripartum cardiomyopathy
    • Hypertrophic cardiomyopathy
    • Infiltrative restrictive cardiomyopathy, e.g., amyloidosis, sarcoidosis
  • Constrictive pericarditis
• Endocrine/metabolic
  • Diabetes mellitus
  • Obesity
  • Thyroid disease
  • Kidney disease ^[13]
• Pulmonary
  • COPD
  • Pulmonary artery hypertension, cor pulmonale
• Toxic
  • Chemotherapy
  • Alcohol, tobacco
  • Cocaine, methamphetamines
• Other
  • Familial or genetic
  • Autoimmune, e.g., SLE, giant cell arteritis

The three major causes of HF are CAD, hypertension, and diabetes mellitus. Patients typically have multiple risk factors that contribute to the development of HF.

Classification of HF by LVEF ^[1]

• Heart failure with preserved ejection fraction (HFpEF): HF with reduced stroke volume, normal or reduced EDV, preserved LVEF : (≥ 50%), and evidence of increased LV filling pressures, e.g., increased natriuretic peptides, hemodynamic measurements ^[1][2]
• Heart failure with reduced ejection fraction (HFrEF): HF with reduced stroke volume and reduced LVEF (≤ 40%) ^[1][12]
• Heart failure with improved ejection fraction (HFimpEF): previous HFrEF, with a follow-up LVEF measurement > 40% ^[1]
• Heart failure with mildly reduced ejection fraction (HFmrEF): HF with an LVEF 41–49% and evidence of increased LV filling pressures, e.g., increased natriuretic peptides, hemodynamic measurements ^[1][2]

American College of Cardiology/American Heart Association (ACC/AHA) stages ^[1]

The ACC/AHA classification system categorizes patients based on an objective assessment of clinical features and diagnostic findings.

Patients with stage C HF will always remain categorized as such, even if they become asymptomatic (i.e., NYHA class I) with treatment. ^[1]

New York Heart Association NYHA functional classification ^[1]

The NYHA classification system is used to assess limitations in physical activity and symptoms of patients with symptomatic HF (i.e., ACC/AHA stages C and D); it helps determine treatment eligibility and prognosis.

Cardiac output, which is stroke volume times heart rate, is determined by three factors: preload, afterload, and ventricular contractility.

Underlying mechanism of reduced cardiac output

• Heart failure with reduced ejection fraction (HFrEF)
  • Reduced contractility → systolic ventricular dysfunction → decreased left ventricular ejection fraction (LVEF) → decreased cardiac output
  • Causes include:
    • Damage and loss of myocytes (e.g., following myocardial infarction, CAD, dilated cardiomyopathy)
    • Cardiac arrhythmias
    • High-output conditions (see “High-output heart failure” below)
• Heart failure with preserved ejection fraction (HFpEF)
  • Decreased ventricular compliance → diastolic ventricular dysfunction → reduced ventricular filling and increased diastolic pressure → decreased cardiac output (while the left ventricular ejection fraction remains normal)
  • Causes include:
    • Increased stiffness of the ventricle (e.g., long-standing arterial hypertension with ventricular wall hypertrophy, restrictive cardiomyopathy)
    • Impaired relaxation of the ventricle (e.g., constrictive pericarditis, pericardial tamponade)
• Left-sided heart failure (HFrEF and/or HFpEF)
  • Increased left ventricular afterload: increased mean aortic pressure; (e.g., arterial hypertension), outflow obstruction (e.g., aortic stenosis)
  • Increased left ventricular preload: left ventricular volume overload (e.g., backflow into the left ventricle caused by aortic insufficiency)
• Right-sided heart failure
  • Increased right ventricular afterload: increase in pulmonary artery pressure (e.g., pulmonary hypertension)
  • Increased right ventricular preload: right ventricular volume overload (e.g., tricuspid valve regurgitation, left-to-right shunt)

Consequences of decompensated heart failure

• Forward failure: reduced cardiac output → poor organ perfusion → organ dysfunction (e.g., hypotension, renal dysfunction)
• Backward failure
  • Left ventricle: increased left-ventricular volumes or pressures → backup of blood into lungs → increased pulmonary capillary pressure; → cardiogenic pulmonary edema (presenting with orthopnea) and increased pulmonary artery pressure
  • Right ventricle: increased pulmonary artery pressure → reduced right-sided cardiac output → systemic venous congestion → peripheral edema and progressive congestion of internal organs (e.g., liver, stomach)
  • Nutmeg liver: the macroscopic appearance of the liver which resembles a nutmeg seed due to ischemia and fatty degeneration from hepatic venous congestion

HF is characterized by reduced cardiac output that results in venous congestion and poor systemic perfusion.

Compensation mechanisms

The compensation mechanisms are meant to maintain the cardiac output when stroke volume is reduced.

• Increased adrenergic activity : increase in heart rate, blood pressure, and ventricular contractility
• Increase of renin-angiotensin-aldosterone system activity (RAAS): activated following decrease in renal perfusion secondary to reduction of stroke volume and cardiac output
  • ↑ Angiotensin II secretion results in:
    • Peripheral vasoconstriction → ↑ systemic blood pressure → ↑ afterload
    • Vasoconstriction of the efferent arterioles → ↓ net renal blood flow and ↑ intraglomerular pressure → maintained GFR
  • ↑ Aldosterone secretion → ↑ renal Na⁺ and H₂O resorption → ↑ preload
• Secretion of natriuretic peptides: ↑ intracellular smooth muscle cGMP → vasodilation → hypotension and decreased pulmonary capillary wedge pressure → cleavage of the prohormone proBNP into BNP and NT-proBNP
  • Brain natriuretic peptide (BNP): ventricular myocyte hormone released in response to increased ventricular filling and stretching
  • NT-proBNP: inert biomarker produced in cardiomyocytes from the cleavage of the prohormone proBNP

General features of heart failure

• Nocturia ^[14]
• Fatigue
• Tachycardia, various arrhythmias
• S₃/S₄ gallop on auscultation
• Pulsus alternans
• Cachexia ^[15]

Clinical features of left-sided heart failure

• Symptoms of pulmonary congestion
  • Dyspnea , orthopnea (a sensation of shortness of breath that occurs upon lying down and is relieved by sitting up)
  • Pulmonary edema
  • Paroxysmal nocturnal dyspnea
    • Nocturnal bouts of coughing and acute shortness of breath
    • Caused by reabsorption of peripheral edema at night → increased venous return
  • Cardiac asthma
    • Increased pressure in the bronchial arteries → airway compression and bronchospasm
    • Symptoms mimic asthma, with shortness of breath, wheezing, and coughing. ^[16]
• Physical examination findings ^[17]
  • Bilateral basilar rales may be audible on auscultation.
  • Laterally displaced apical heart beat (precordial palpation beyond the midclavicular line)
  • Coolness and pallor of lower extremities

Clinical features of right-sided heart failure

• Symptoms of fluid retention and increased CVP
  • Peripheral pitting edema: as a result of fluid transudation due to increased venous pressure
  • Hepatic venous congestion symptoms
    • Abdominal pain
    • Jaundice
  • Other symptoms of organ congestion (e.g., nausea, loss of appetite in congestive gastropathy)
• Physical examination findings
  • Jugular venous distention: visible swelling of the jugular veins due to an increase in CVP and venous congestion
  • Kussmaul sign
  • Hepatosplenomegaly: may result in cardiac cirrhosis and ascites
  • Hepatojugular reflux: jugular venous congestion induced by exerting manual pressure over the patient's liver → ↑ right heart volume overload → inability of the right heart to pump additional blood → visible jugular venous distention that persists for several seconds

High-output heart failure

• Definition: heart failure secondary to conditions associated with a high-output state, in which cardiac output is elevated to meet the peripheral tissue oxygen demands
• Etiology: conditions that lead to an increased cardiac demand (high-output state) ^[18]
  • Physiological causes
    • Pregnancy
    • Fever
    • Exercise
  • Other causes
    • Class III obesity
    • Advanced cirrhosis
    • Anemia
    • Systemic arteriovenous fistulas
    • Paget disease of bone
    • Hyperthyroidism; thyroid storm
    • Wet beriberi (vitamin B₁ deficiency)
    • Sepsis
    • Multiple myeloma
    • Glomerulonephritis
    • Polycythemia vera
    • Carcinoid heart disease ^[19]
• Pathophysiology: peripheral vasodilation or arteriovenous shunting → ↓ in systemic vascular resistance → ↑ heart rate and stroke volume → ↑ cardiac output
• Clinical features
  • Symptoms shared with low-output HF
    • Dyspnea, tachypnea
    • Tachycardia
    • Peripheral edema
    • Fatigue
    • Low blood pressure
  • Symptoms specific to high-output HF
    • Midsystolic murmur, S₃ gallop
    • Jugular distention with an audible hum over the internal jugular vein
    • Pulsatile tinnitus
    • Bounding peripheral pulses
    • Laterally displaced apex beat
• Diagnostics
  • Primarily a clinical diagnosis
  • X-ray and echocardiography: cardiomegaly
• Treatment
  • Heart failure management
    • Symptom relief
    • Hemodynamic stabilization
  • Treatment of the underlying condition

See “Diagnosis of AHF” for the evaluation of acute decompensated HF.

General principles

• Initial workup
  • Comprehensive clinical evaluation, focused on acuity and volume status
  • ECG, CXR, and TTE
  • BNP and additional laboratory studies, e.g., CBC, HbA1c
• HF is confirmed if a patient has clinical features of HF attributable to structural or functional cardiac abnormalities and either: ^[1][2]
  • Elevated natriuretic peptides
  • Evidence of cardiogenic pulmonary or systemic congestion
• If the diagnosis is uncertain, consider:
  • A validated clinical composite score, e.g., Framingham heart failure diagnostic criteria
  • Advanced studies, e.g., right heart catheterization
• Refer to a cardiologist or an HF specialist if advanced HF is suspected.

Multiple conditions can mimic HF and/or impact therapeutic decisions, e.g., anemia or kidney or liver failure. No single laboratory finding, imaging study, or clinical feature either excludes or is diagnostic for HF. ^[1][2]

Clinical evaluation

• Medical history
  • Family history of cardiac disease ^[1]
  • Lifestyle and behavioral factors
  • Social determinants of health
  • Systemic and comorbid conditions
• Physical examination
  • Vital signs and volume status assessment ^[1]
  • Findings suggestive of other underlying conditions, e.g.:
    • Clinical features of hemochromatosis
    • Hypertensive retinopathy on fundoscopic examination

Laboratory studies ^[1][20]

BNP or NT-proBNP

• Indication: all patients with suspected HF
• Uses: to help confirm the diagnosis and assess disease severity and prognosis ^[1][21]
• Interpretation
  • Elevated levels in patients with classic symptoms of HF support the diagnosis (high predictive index). ^[2][21]
  • HF is unlikely if:
    • BNP is < 35 pg/mL or NT-proBNP is < 125 pg/mL in chronic HF ^[2][12]
    • BNP is < 100 pg/mL or NT-proBNP is < 300 pg/mL in AHF ^[21]
  • Several conditions can affect levels of BNP and NT-proBNP. ^[1][21]
    • Increased levels: e.g., in advanced age, compromised kidney function, atrial fibrillation and other arrhythmias
    • Decreased levels: e.g., in obesity, flash pulmonary edema, pericardial constriction ^[12]

Normal BNP or NT-proBNP levels do not exclude HF. Always consider the complete clinical picture. ^[1][20]

Additional laboratory studies

Order the following studies to assess for causes of HF, comorbidities, and suitability for pharmacological treatment.

• CBC: screening for anemia and signs of infection
• BMP
  • Creatinine: normal or ↑
  • Na⁺: normal or ↓; hyponatremia may indicate a poor prognosis. ^[22]
• HbA1c or fasting glucose: diabetes mellitus screening
• Liver chemistries: Elevations, particularly of cholestatic enzymes, can indicate hepatic venous congestion.
• Fasting lipid panel: screening for lipid disorders
• TSH: to assess thyroid function
• Iron studies: to assess for iron deficiency in HF
  • Serum ferritin < 100 ng/mL ^[23]
  • Or serum ferritin < 300 ng/mL with transferrin saturation < 20% ^[23]
• Cardiac troponin T/I: may be useful for risk stratification ^[24]
  • Often elevated in patients with HF
  • In patients with significant elevations and a serial increase in value, ACS must be ruled out. ^[25][26]

Most patients with HF (> 85%) have two or more associated chronic conditions. ^[1]

Transthoracic echocardiogram (TTE) ^[1][20]

• Indications
  • All patients with suspected HF (preferred initial imaging modality) ^[1][20]
  • Patients receiving treatment with a change in clinical status
  • Patients undergoing evaluation for device therapy
• Findings
  • LV systolic dysfunction and/or diastolic dysfunction
  • Quantitative measurement of LVEF
  • Atrial and ventricular size and thickness
  • Evidence of complications, e.g.:
    • Cardiac dyssynchrony, functional mitral regurgitation, left atrial enlargement ^[27]
    • Pericardial and/or pleural effusion ^[28]
  • Underlying causes: e.g., LV hypertrophy in hypertension, regional wall motion abnormalities due to CAD

Chest x-ray ^[1]

• Indication: all patients with suspected HF; especially useful in AHF
• Findings
  • Changes to the cardiac silhouette
    • Cardiomegaly, i.e., cardiothoracic ratio > 0.5 ^[29]
    • Boot-shaped heart on PA view: RV enlargement
    • Signs of pericardial effusion (e.g., water bottle heart)
  • X-ray findings of pulmonary congestion
  • Signs of concomitant heart conditions, including:
    • Valvular calcifications in valvular disease
    • Pericardial calcification in constrictive pericarditis

12-lead ECG ^[1][30][31]

• Indications: all patients with suspected HF
• Findings
  • Some patients may have a normal ECG, especially those with HFpEF.
  • Changes associated with the etiology of HF and other cardiovascular comorbidities, e.g., ECG changes in STEMI, arrhythmias ^[1]
  • Abnormalities related to HF (common but mainly nonspecific), e.g.:
    • ECG signs of LV hypertrophy (e.g., positive Sokolow-Lyon index) ^[32]
    • ST-segment and T-wave abnormalities (e.g., ST depression)
    • P wave abnormalities (e.g., P mitrale)
    • Prolonged QTc interval ^[33]

Additional assessment ^[1][2]

Clinical composite scores

• Framingham heart failure diagnostic criteria may be used to rule in HF.
• H₂FPEF score
  • Use: estimates the likelihood of HF in symptomatic patients with preserved ejection fraction on echocardiogram
  • Variables
    • High BMI: > 30 kg/m² (2 points)
    • Hypertension treated with ≥ 2 medications (1 point)
    • Atrial fibrillation (paroxysmal or persistent) (3 points)
    • PA systolic pressure > 35 mm Hg on echocardiogram (1 point)
    • Elder age: > 60 years (1 point)
    • Filling pressure elevated on echocardiogram: E/e′ ratio > 9 (1 point)
  • Interpretation
    • Score 0–1: HFpEF is ruled out.
    • Score 2–5: Further diagnostic workup is needed.
    • Score 6–9: HFpEF is ruled in.

Advanced studies

The following studies may be ordered by a specialist if there is diagnostic uncertainty and/or to evaluate for underlying causes.

• Cardiac MRI: highly accurate assessment of ventricular volume, mass, and ejection fraction ^[1]
• Noninvasive stress imaging, i.e., echocardiography, nuclear scintigraphy: to assess for obstructive CAD and myocardial ischemia ^[1]
• Right heart catheterization (RHC)
  • Most sensitive and specific study for HFpEF confirmation, but expensive and invasive ^[20]
  • Used to assess right heart function and pulmonary vascular resistance in patients being considered for mechanical circulatory support or heart transplant
  • May be considered for monitoring and guiding management in certain patients with cardiogenic shock. SvO₂ is low in decompensated HF. ^[1]
• Endomyocardial biopsy
  • Ongoing diagnostic uncertainty and rapidly progressive disease
  • Suspected infiltrative heart disease ^[1]

Identifying the specific cause of HF is crucial because it allows for tailored treatment in addition to GDMT. ^[1]

Sputum analysis in patients with pulmonary edema may show heart failure cells (hemosiderin-containing cells).

See also “Differential diagnosis of dyspnea” and “Differential diagnosis of peripheral edema.”

• Cardiovascular
  • Cardiomyopathy
  • CAD
  • Valvular heart disease
  • Pericardial disease: e.g., constrictive pericarditis, pericardial effusion
  • Arrhythmia
  • Chronic venous insufficiency
• Pulmonary
  • Obstructive lung disease: e.g., COPD, asthma
  • Restrictive lung disease: e.g., ILD
  • Pleural disease: e.g., pneumothorax, pleural effusion
  • Pulmonary embolism
• Other causes of dyspnea and/or edema
  • Anemia
  • Obesity
  • Deconditioning
  • Anxiety
  • Cirrhosis
  • Kidney failure, nephrotic syndrome
  • Adverse effects of medications, e.g., calcium channel blockers, NSAIDs, glucocorticoids
  • Lymphedema
  • Neuromuscular disease: e.g., myasthenia gravis, amyotrophic lateral sclerosis

The differential diagnoses listed here are not exhaustive.

Management of AHF is detailed in “Acute HF.”

Approach ^[1][2][34]

• Counsel on nonpharmacological interventions and self-care.
• Manage comorbidities and precipitating factors.
• Start pharmacotherapy for HF based on HF staging and LVEF, and monitor at each patient visit to optimize GDMT.
• Consider indications for referral to a cardiologist, e.g.:
  • New-onset HF
  • Clinical suspicion for HFpEF mimics

Multidisciplinary management of HF that includes nurses, cardiologists, and clinical pharmacists is associated with lower hospitalization and mortality rates. ^[1][2]

Nonpharmacological interventions ^[1][20]

Encourage and/or provide the following in combination with pharmacotherapy for HF.

• Lifestyle modifications
  • Aerobic exercise, e.g., brisk walking for ≥ 150 minutes/week ^[1][2]
  • Weight loss
  • Nutrition and fluid management
    • Encourage healthy eating patterns, e.g., DASH diet, Mediterranean diet. ^[1]
    • Avoid excessive dietary sodium intake to reduce the risk of congestion. ^[1]
    • Fluid restriction does not reduce hospitalization or mortality rates in patients with HF. ^[1]
  • Smoking cessation, avoidance of alcohol and recreational drug use ^[1]
• Patient self-care
  • Daily self-monitoring
    • Weight: Patients with significant weight changes (e.g., > 2 kg in 3 days) should seek medical advice. ^[2][12]
    • Home blood pressure monitoring ^[2]
    • HF symptoms, e.g., persistent or increasing dyspnea and/or edema
  • Weight-based diuretic dose adjustment ^[1]
  • Monitoring of medication side effects
• Other interventions ^[1]
  • Vaccinations: pneumococcal vaccine, seasonal influenza vaccine, COVID-19 vaccine ^[1]
  • Identification of factors associated with poor self-care, e.g.: ^[1]
    • Frailty assessment
    • Screening for depression
    • Assessing for symptoms of cognitive impairment
    • Assessment of social situation for older adults
  • Cardiac rehabilitation ^[1]

Nonpharmacological interventions are associated with better patient outcomes, e.g., decreased rates of hospitalization and all-cause and cardiovascular mortality. ^[1]

Management of comorbidities ^[1][2][34]

The following recommendations are specific to comorbidities in HF. Treat other comorbidities (e.g., lipid disorders, ASCVD, atrial fibrillation) as recommended by guidelines.

• Hypertension: treatment target of < 130/80 mm Hg ^[1][2][35]
• Diabetes mellitus: SGLT2is are recommended for all patients.
• Iron deficiency: Parenteral iron therapy is recommended for patients with symptomatic HFrEF or HFmrEF. ^[1][36]
  • Initial dosing is based on hemoglobin levels:
    • Hgb ≤ 14 g/dL: ferric carboxymaltose
    • Hgb 14–14.9 g/dL: ferric carboxymaltose
  • Subsequent doses are based on patient weight and hemoglobin and ferritin levels.
• Obesity: Consider semaglutide (off-label) in patients with HFpEF. ^[37]
• Obstructive sleep apnea: Consider nocturnal continuous positive airway pressure (CPAP) therapy. ^[1]

Monitoring ^[1][2]

To optimize GDMT, the following factors should be assessed at each patient visit.

• Clinical status
  • Signs and symptoms of pulmonary congestion and/or leg edema
  • Tolerance of physical activity
  • Unexplained change in clinical status: Repeat TTE.
• Causes of clinical deterioration
  • Concurrent illness, e.g., infection, MI
  • Nonadherence to pharmacotherapy or nutritional recommendations
• Adverse effects and intolerance to pharmacotherapy, e.g.:
  • Hypotension, dizziness, and/or cough: ARNIs, ARBs, ISDN with hydralazine
  • Bradycardia: beta blockers, ivabradine
  • Mycotic genital infections: SGLT2is
• BMP to assess for:
  • Electrolyte derangements
    • Hyperkalemia in patients on RAAS inhibitors, SGLT2is, and/or aldosterone antagonists ^[1]
    • Hypokalemia in patients on diuretics
  • Kidney function in patients on RAAS inhibitors, SGLT2is, and/or digoxin

Indications for referral ^[34]

The following are guideline-based indications for referral to a cardiologist:

• New-onset HF
• ≥ 1 high-risk features of chronic HF
• LVEF ≤ 35% for ≥ 3 months despite treatment with GDMT ^[34]
• The patient or clinician would like a second opinion on the etiology of HF and possible targeted therapies, e.g., revascularization
• Consideration for enrollment in a clinical trial
• Advanced HF therapies, e.g., device therapy for HF ^[1]
• Clinical suspicion for HFpEF mimics, e.g.: ^[2]
  • Valvular disease
  • HCM
  • Familial amyloid cardiomyopathy
  • Pericardial disease
  • Cardiac sarcoidosis
  • Myocarditis

General principles ^[1][2][34]

• Titrate medications to the target dosage, even if symptoms improve at lower doses.
• Dosages may be adjusted as frequently as every 1–2 weeks. ^[1]
• Most patients with HFimpEF should continue treatment, even if asymptomatic, to prevent relapse and worsening LV dysfunction. ^[1]
• Patients with HFmrEF may benefit from the agents recommended for HFrEF, especially SGLT2i. ^[1][38]
• Diuretics are recommended for all patients with congestion regardless of LVEF.
• Avoid prescribing drugs that may worsen HF.
• See “Use of heart failure medications in pregnancy and lactation” for modifications.

Pharmacotherapy for HFrEF ^[1][3][34]

• ACC/AHA stage B: The goal of pharmacotherapy in these patients is to prevent symptomatic HF.
  • Beta blocker
  • PLUS either an ACEI or ARB
• ACC/AHA stages C and D: The goal of pharmacotherapy in these patients is to reduce morbidity, mortality, and hospitalizations.
  • One agent from each of the following drug classes, unless contraindicated (e.g., prior hypersensitivity reaction):
    • Diuretics
    • RAAS inhibitors
    • Beta blockers
    • SGLT2 inhibitors
    • Mineralocorticoid receptor antagonists
  • Consider additional pharmacotherapy for refractory symptoms.

Drugs that improve prognosis (i.e., reduce morbidity, mortality, and hospitalization rates) are beta blockers, ACEIs, ARNIs, MRAs, hydralazine with isosorbide dinitrate, and SGLT2is.

Diuretics and digoxin improve symptoms and significantly reduce the number of hospitalizations.

Pharmacotherapy for HFpEF ^[2][3][20]

• First-line agents
  • SGLT2i for all patients: e.g., dapagliflozin or empagliflozin ^[2][36]
  • Loop diuretic for patients with congestion: e.g., furosemide or torsemide
• Other agents may be considered, e.g.:
  • MRA, e.g., spironolactone (off-label) ^[2]
  • ARNI, i.e., sacubitril/valsartan or ARB, e.g., candesartan ^[2]

Drugs that may worsen HF ^[1]

The following drugs should be avoided or used with caution in patients with HF.

• Nondihydropyridine calcium channel blockers: associated with higher HF rate of recurrence
• NSAIDs: can worsen HF symptoms
• Thiazolidinediones (e.g., pioglitazone): increased risk of congestion and hospitalization
• Antidepressants (e.g., tricyclic antidepressants): Consider interactions with HF pharmacotherapy. ^[40]
• Inhalation anesthetics: may induce myocardial depression and peripheral vasodilation, and decrease sympathetic activity
• Class IC and class III antiarrhythmic drugs: increased mortality
• DPP-4 inhibitors (e.g., saxagliptin, alogliptin): increased risk of hospitalization for HF

Device therapy in HF

Automated implantable cardioverter defibrillators (AICDs) and cardiac resynchronization therapy devices (CRTs) are beneficial in select patients with HF who are at risk for sudden cardiac death from ventricular tachyarrhythmias and who have worsening HF from cardiac dyssynchrony. ^[1][41]

AICDs in heart failure ^[1]

For more information, see “AICDs.”

• Goal: prevention of sudden cardiac death from tachyarrhythmias caused by cardiomyopathy
• Indications
  • HFrEF patients with an expected survival of > 1 year and on GDMT with either:
    • Nonischemic dilated cardiomyopathy (DCM) or ischemic heart disease; at least 40 days post-MI with LVEF ≤ 35% and NYHA class II–III
    • Ischemic heart disease; at least 40 days post-MI with LVEF ≤ 30% and NYHA class I
  • Any other indication for AICDs

CRT in heart failure ^[1]

For more information, see “CRTs.”

• Goal consists of synchronizing contractions of the right and left ventricles, resulting in:
  • Improved ventricular function ^[42][43]
  • Reverse ventricular remodeling
  • Reduction in secondary mitral regurgitation
• Indications: The following criteria apply to patients with stage C HFrEF on optimized medical therapy and an expected survival of > 1 year.
  • LVEF ≤ 35% with NYHA class II–IV symptoms and sinus rhythm OR select patients with AFib PLUS:
    • QRS duration of > 150 ms with or without LBBB pattern
    • OR QRS duration of 120–149 ms with LBBB pattern
  • LVEF ≤ 35% requiring pacing for other purposes, e.g., replacement of existing PPM
  • LVEF 36–50% with high-risk AV block

Consider CRT-D in patients with indications for both CRT and AICD.

Advanced heart failure management (ACC/AHA stage D) ^[1][3]

Promptly refer all patients with advanced HF to an HF specialist for management.

• Mechanical circulatory support (MCS) ^[1]
  • May be short-term (days to weeks) or long-term (months to years)
  • Short-term devices include intra-aortic balloon pump and venoarterial extracorporeal membrane oxygenation.
  • Long-term devices include ventricular assist devices, e.g., LV assist device. ^[44]
• IV inotropic support: e.g., adrenergic agonists, PDE3 inhibitors, vasopressors ^[1]
  • May be used as a bridging measure for patients awaiting MCS or heart transplant
  • In rare cases, may be used for palliative symptom control
  • See also “Management of cardiogenic shock.”
• Heart transplant ^[1]
  • Heart transplant is the only cure for advanced HF.
  • Recommended for patients with advanced HF despite optimal pharmacological, device, and surgical therapy
  • Bridging measures, e.g., IV inotropic support and MCS, are usually required.
• Palliative care: Refer patients who are not candidates for transplant.

• Acute decompensated heart failure (see “Acute heart failure”)
• Cardiorenal syndrome
• Cardiac arrhythmias
• Central sleep apnea
• Cardiogenic shock
• Stroke: due to increased risk of arterial thromboembolisms (especially with concurrent atrial fibrillation)
• Chronic kidney disease
• Cardiac cirrhosis
  • A complication of right-sided heart failure characterized by cirrhosis due to chronic hepatic vein congestion.
  • Associated with "nutmeg liver" (diffuse mottling on imaging due to ischemia and fatty degeneration).
• Venous stasis, leg ulcers

We list the most important complications. The selection is not exhaustive.

• Definition: a complex syndrome in which renal function progressively declines as a result of severe cardiac dysfunction ^[45]
• Epidemiology: occurs in ∼ 30% of patients with acute decompensated heart failure
• AHA classification ^[46]
  • Type 1: acute cardiorenal syndrome (most common subtype)
    • Heart failure leading to acute kidney injury
    • Examples: acute coronary syndrome and/or acute heart failure resulting in acute kidney injury
  • Type 2: chronic cardiorenal syndrome
    • Chronic heart failure leading to chronic kidney disease
    • Example: chronic heart failure resulting in the new onset or progression of chronic kidney disease
  • Type 3: acute renocardiac syndrome
    • Acute kidney injury leading to acute heart failure
    • Example: heart failure resulting from acute kidney injury due to volume overload
  • Type 4: chronic renocardiac syndrome
    • Chronic kidney disease leading to chronic heart failure
    • Example: LV hypertrophy resulting from chronic kidney disease-associated cardiomyopathy
  • Type 5: secondary cardiorenal syndrome
    • Systemic disease leading to kidney and heart failure
    • Examples: cirrhosis, amyloidosis
• Pathophysiology
  • Systolic dysfunction → ↓ cardiac output → renal hypoperfusion → prerenal kidney failure
  • Diastolic dysfunction → systemic venous congestion → renal venous congestion → ↓ transglomerular pressure gradient → ↓ GFR → ↓ kidney function
  • RAAS activation → salt and fluid retention → hypertension → hypertensive nephropathy
• Diagnostics: ↓ GFR, ↑ creatinine that cannot be explained by underlying kidney disease
• Treatment: heart failure and renal failure management (see “Acute renal injury”)
• Prognosis: CHF with reduced GFR and high creatinine levels (> 3 mg/dL) is associated with a poor prognosis. ^[47]

The prognosis depends on the patient, type and severity of heart disease, and adherence to GDMT and nonpharmacological interventions. Risk stratification scales may be used to determine prognosis (e.g., CHARM and CORONA risk scores).

• Factors associated with worse prognosis
  • Signs of congestion, e.g., edema, S₃ heart sound, lung rales ^[12]
  • Persistently elevated BNP and/or NT-pro BNP ^[1][20][21]
  • Hyponatremia
  • Systolic BP < 120 mm Hg ^[1]
  • Chronic comorbidities, e.g., diabetes mellitus, anemia, obesity ^[2]
  • Unintentional weight loss or underweight
  • Implantable cardioverter-defibrillator use
• High-risk features of chronic HF ^[34]
  • Reliance on IV inotropic support, e.g., PDE3 inhibitors
  • Persistent NYHA class III-IV symptoms
  • Symptomatic hypotension or systolic BP ≤ 90 mm Hg
  • Creatinine ≥ 1.8 mg/dL or BUN ≥ 43 mg/dL
  • Ventricular arrhythmias, repetitive ICD shocks, atrial fibrillation
  • ≥ 2 ED visits or hospitalizations for HF exacerbation within the last 12 months
  • Intolerance of target dosing for beta-blockers, RAAS inhibitors, and/or mineralocorticoid antagonists
  • Clinical deterioration marked by any of the following:
    • Worsening symptoms, edema, and/or performance on exercise testing
    • Rising cardiac biomarkers, e.g., BNP
    • Acute decompensated HF
    • Imaging findings of progressive cardiac remodeling
  • High projected mortality risk using a validated risk model, e.g., Seattle Heart Failure Model
• 1-year survival according to NYHA stage
  • Stage I: ∼ 95%
  • Stage II: ∼ 85%
  • Stage III: ∼ 85%
  • Stage IV: ∼ 35%

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