Definition and epidemiology
Heart failure (HF) is a clinical syndrome caused by structural or functional cardiac abnormality that results in elevated intracardiac pressures and/or inadequate cardiac output, producing symptoms such as dyspnea, fatigue, and fluid retention.
HF is classified by left ventricular ejection fraction (LVEF):
- HFrEF (reduced EF): LVEF ≤ 40%
- HFmrEF (mildly reduced EF): LVEF 41-49%
- HFpEF (preserved EF): LVEF ≥ 50%
Epidemiology
- Prevalence increases sharply with age; affects roughly 1-2% of adults overall and over 10% of people older than 70.
- Leading cause of hospitalization in adults over 65 in many high-income countries.
- HFpEF is increasingly common and now accounts for roughly half of new HF diagnoses, linked to the aging population and rising rates of obesity, diabetes, and hypertension.
- Ischemic heart disease and hypertension are the dominant underlying causes worldwide.
- BNP/NT-proBNP: elevated supports HF; normal level argues strongly against it
- S3 gallop is the classic exam finding of systolic HF
- Four pillars of HFrEF therapy: ARNI/ACEi, beta-blocker, MRA, SGLT2 inhibitor
- SGLT2 inhibitors benefit both HFrEF and HFpEF regardless of diabetes status
- ICD indicated for primary prevention when LVEF ≤ 35% despite optimal GDMT
- CRT indicated for LVEF ≤ 35% with LBBB and QRS ≥ 150 ms
- Loop diuretics relieve symptoms but do not reduce mortality
- Hydralazine-isosorbide dinitrate has added mortality benefit in Black patients with HFrEF
Etiology and risk factors
HF results from any condition that impairs systolic contraction, diastolic relaxation, or both.
Common causes of HFrEF
- Ischemic heart disease / prior myocardial infarction
- Dilated cardiomyopathy (idiopathic, genetic, alcoholic, peripartum, viral myocarditis)
- Chronic uncontrolled hypertension
- Valvular disease (aortic regurgitation, mitral regurgitation)
- Tachyarrhythmia-induced cardiomyopathy
- Cardiotoxic chemotherapy (e.g., anthracyclines, trastuzumab)
Common causes of HFpEF
- Chronic hypertension with concentric LV hypertrophy
- Diabetes mellitus and obesity
- Hypertrophic or restrictive cardiomyopathy (amyloidosis is an important mimic)
- Aging-related diastolic stiffness
Risk factors
- Coronary artery disease, hypertension, diabetes, obesity
- Chronic kidney disease
- Valvular heart disease
- Excess alcohol use, cocaine use
- Family history of cardiomyopathy
Pathophysiology
Regardless of the inciting insult, a fall in effective cardiac output (or elevated filling pressures) activates compensatory neurohormonal systems that are adaptive short-term but harmful when chronically engaged.
Key mechanisms
- Sympathetic nervous system activation: increases heart rate and contractility initially, but chronic activation promotes arrhythmia and myocyte toxicity.
- Renin-angiotensin-aldosterone system (RAAS) activation: causes vasoconstriction and sodium/water retention, worsening congestion over time.
- Natriuretic peptide release: BNP and ANP are released from stretched myocardium and promote natriuresis and vasodilation, counteracting RAAS; this is the basis of BNP testing.
- Ventricular remodeling: chronic pressure/volume overload leads to eccentric or concentric hypertrophy, fibrosis, and progressive chamber dilation or stiffening.
In HFrEF, the dominant problem is impaired contractility and reduced stroke volume. In HFpEF, the ventricle contracts normally but has impaired relaxation and increased stiffness, raising filling pressures despite normal or small chamber size.
Clinical features
Symptoms reflect a combination of pulmonary/systemic congestion and reduced forward flow.
Congestive symptoms
- Dyspnea on exertion, progressing to orthopnea and paroxysmal nocturnal dyspnea
- Peripheral edema, weight gain, abdominal bloating (right-sided congestion)
- Jugular venous distension, hepatomegaly, ascites in advanced disease
Low-output symptoms
- Fatigue, exercise intolerance
- Cool extremities, in severe cases hypotension and confusion (cardiogenic shock)
Exam findings
- S3 gallop (classic finding in systolic dysfunction/volume overload)
- Displaced apical impulse, pulmonary crackles
- Peripheral or sacral edema
- Signs specific to the underlying cause (e.g., murmurs in valvular disease)
NYHA functional class (I-IV) grades symptom severity relative to physical activity and guides prognosis and therapy intensity.
Diagnosis
Diagnosis combines clinical assessment, biomarkers, and imaging.
Initial workup
- BNP or NT-proBNP: elevated levels support the diagnosis; a normal level makes HF unlikely in an untreated patient (high negative predictive value). Values vary with age, renal function, and obesity.
- Chest X-ray: cardiomegaly, pulmonary venous congestion, Kerley B lines, pleural effusion
- ECG: may reveal prior MI, arrhythmia, or LVH; rarely normal in true HF
- Transthoracic echocardiogram: cornerstone test — determines EF, chamber size, wall motion, valve function, and diastolic parameters
Further evaluation
- Basic labs: electrolytes, renal function, liver function, TSH, iron studies
- Coronary evaluation (stress testing or angiography) if ischemia is suspected
- Cardiac MRI or biopsy if infiltrative disease (e.g., amyloidosis, sarcoidosis) is suspected
- Right heart catheterization in select advanced or diagnostically uncertain cases
Framingham criteria (classic, less used clinically now)
Requires 2 major or 1 major + 2 minor criteria (e.g., major: PND, S3, cardiomegaly; minor: bilateral edema, tachycardia, pleural effusion) — mainly of historical/exam interest.
Differential diagnosis
| Condition | Distinguishing feature |
|---|---|
| COPD exacerbation | Wheezing, prolonged expiration, normal/low BNP, hyperinflation on CXR |
| Pneumonia | Fever, focal infiltrate, productive cough, leukocytosis |
| Pulmonary embolism | Acute pleuritic pain, hypoxia, risk factors for VTE, normal cardiac silhouette |
| Nephrotic syndrome | Proteinuria, hypoalbuminemia, normal cardiac function |
| Liver cirrhosis | Ascites with normal JVP, stigmata of chronic liver disease |
| Constrictive pericarditis | Kussmaul sign, pericardial knock, pericardial calcification |
| Cardiac tamponade | Pulsus paradoxus, muffled heart sounds, electrical alternans |
Management
Management differs by phenotype (HFrEF vs HFpEF) and acuity (chronic vs acute decompensated HF). Guideline-directed medical therapy (GDMT) for HFrEF, per ACC/AHA/HFSA and ESC guidelines, rests on four pillars, generally started early and up-titrated together.
HFrEF — four pillars of GDMT
- ARNI (sacubitril-valsartan) preferred over ACE inhibitor/ARB when feasible; ACE inhibitors or ARBs are acceptable alternatives
- Beta-blockers (carvedilol, metoprolol succinate, or bisoprolol — the evidence-based agents)
- Mineralocorticoid receptor antagonists (MRA): spironolactone or eplerenone
- SGLT2 inhibitors (dapagliflozin, empagliflozin): now first-line regardless of diabetes status
Additional therapies
- Loop diuretics (furosemide, torsemide) for symptomatic volume control — do not improve mortality but reduce congestion
- Hydralazine plus isosorbide dinitrate: added benefit in Black patients with persistent symptoms
- Ivabradine: for persistent tachycardia despite beta-blockade
- Device therapy: ICD for primary prevention of sudden death (LVEF ≤ 35% despite GDMT); cardiac resynchronization therapy (CRT) if LVEF ≤ 35% with LBBB and QRS ≥ 150 ms
- Advanced therapies: LVAD or heart transplant in refractory end-stage disease
HFpEF
- SGLT2 inhibitors have the strongest evidence and are now recommended
- Diuretics for congestion
- Treat underlying contributors aggressively: hypertension, atrial fibrillation, obesity, diabetes
- MRAs may offer modest benefit, particularly in some patients
Acute decompensated HF
- IV loop diuretics as first-line for congestion
- Vasodilators (IV nitroglycerin) if hypertensive and congested
- Inotropes (dobutamine, milrinone) reserved for cardiogenic shock or low-output states
- Identify and treat precipitants (ischemia, arrhythmia, infection, medication nonadherence, dietary sodium indiscretion)
General measures (all patients)
- Sodium restriction, fluid restriction in select patients
- Daily weight monitoring
- Vaccination (influenza, pneumococcal), cardiac rehabilitation
- Avoid NSAIDs and non-dihydropyridine calcium channel blockers in HFrEF
Complications and prognosis
Complications
- Progressive pump failure and cardiogenic shock
- Arrhythmias, including atrial fibrillation and ventricular tachyarrhythmias (leading cause of sudden cardiac death in HF)
- Thromboembolism
- Renal dysfunction (cardiorenal syndrome)
- Hepatic congestion and cardiac cirrhosis in long-standing right-sided failure
Prognosis
- HF carries substantial morbidity and mortality; roughly half of patients die within 5 years of diagnosis, though outcomes have improved with GDMT.
- Higher NYHA class, lower EF, elevated BNP, and recurrent hospitalizations predict worse prognosis.
- Early initiation and up-titration of all four GDMT pillars meaningfully reduces mortality and hospitalization in HFrEF.
HFrEF therapy = "ABCD": ARNI/ACEi, Beta-blocker, mineralocorticoid-receptor antagonist (C for aldosterone/Cortico-), Dapagliflozin-class SGLT2 inhibitor.
Practice questions
1. A 68-year-old man with a history of myocardial infarction presents with progressive exertional dyspnea and bilateral leg swelling over 3 weeks. Exam reveals an S3 gallop, jugular venous distension, and bibasilar crackles. Echocardiogram shows LVEF of 30%. Which of the following medication classes should be initiated as part of his first-line regimen?
2. A 72-year-old woman with long-standing hypertension and type 2 diabetes presents with exertional dyspnea. Echocardiogram shows LVEF of 60% with left ventricular hypertrophy and impaired diastolic relaxation. Which therapy has the strongest evidence for improving outcomes in this condition?
3. A 55-year-old man with HFrEF (LVEF 25%) remains symptomatic (NYHA class II) despite being on optimal doses of an ARNI, beta-blocker, MRA, and SGLT2 inhibitor for over 3 months. ECG shows left bundle branch block with QRS duration of 160 ms. Which intervention is most appropriate next?
Frequently asked questions
What causes heart failure?
Heart failure is most commonly caused by coronary artery disease and prior myocardial infarction, followed by chronic hypertension, valvular disease, and cardiomyopathies. These conditions damage or overload the heart muscle, impairing its ability to contract (systolic dysfunction) or relax and fill (diastolic dysfunction). Diabetes, obesity, excessive alcohol use, and certain chemotherapy drugs are additional important contributors, especially for HFpEF and dilated cardiomyopathy.
What are the first symptoms of heart failure?
The earliest symptoms are usually shortness of breath with exertion and unusual fatigue. As the condition progresses, patients often develop orthopnea (breathlessness lying flat), paroxysmal nocturnal dyspnea, and swelling in the legs or abdomen. Many patients first notice reduced exercise tolerance or needing extra pillows to sleep comfortably before seeking medical attention.
How is heart failure diagnosed?
Heart failure is diagnosed using a combination of clinical symptoms, physical exam findings like an S3 gallop or edema, elevated BNP or NT-proBNP blood levels, and an echocardiogram that assesses ejection fraction and cardiac structure. Chest X-ray and ECG provide supportive information. The echocardiogram is essential because it determines whether the heart failure is due to reduced or preserved ejection fraction, which guides treatment.
Is heart failure curable?
Heart failure is generally a chronic, progressive condition rather than a curable one, though some causes, like a reversible arrhythmia-induced cardiomyopathy or alcohol-induced cardiomyopathy with abstinence, can substantially improve or normalize. Modern guideline-directed medical therapy can significantly slow progression, reduce hospitalizations, and improve survival and quality of life, but most patients require lifelong management.
HFrEF vs HFpEF — what is the difference?
HFrEF (heart failure with reduced ejection fraction) involves an EF of 40% or less due to impaired heart muscle contraction, usually from ischemic damage or dilated cardiomyopathy. HFpEF (preserved ejection fraction, EF 50% or more) involves normal contraction but impaired relaxation and a stiff ventricle, often related to hypertension, diabetes, and aging. Treatment overlaps but HFrEF has more proven mortality-reducing drug therapies than HFpEF.
Key drugs
Related conditions and differentials
Sources and further reading
StatPearls (NCBI Bookshelf)MedlinePlusWHO ICD-10: I50
Educational content for medical students, prepared by the WhiteCoat Pro editorial team with AI assistance; every page is reviewed by a second AI model for factual errors. It is not medical advice and does not replace the product label, local guidelines or a clinician.