What is the definition, epidemiology, stages, and classification of heart failure?

Heart Failure: Definition, Epidemiology, Stages, and Classification

Definition

Heart failure is a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality, corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. 1

• The syndrome results from the heart's inability to pump and/or fill with blood adequately, leading to inadequate cardiac output or requiring compensatory neurohormonal activation and increased left ventricular filling pressures. 1
• Most patients experience symptoms from impaired left ventricular myocardial function, manifesting as dyspnea and fatigue (limiting exercise tolerance) and fluid retention (causing pulmonary congestion and peripheral edema). 1
• The pathophysiology begins with myocardial injury that triggers maladaptive compensatory mechanisms including neurohormonal activation, ventricular remodeling, and hemodynamic alterations, perpetuating cardiac dysfunction and clinical deterioration. 2

Epidemiology

Heart failure affects more than 64 million people worldwide and represents a global pandemic with substantial geographical variations. 1, 3

Global Burden

• While incidence has stabilized and appears to be declining in industrialized countries, prevalence continues to increase due to population aging, improved survival following ischemic heart disease, and availability of effective evidence-based therapies prolonging life. 1
• The economic burden is staggering: in 2012, total costs in the USA were $30.7 billion, with projections suggesting an increase to $69.8 billion by 2030 (approximately $244 per US adult). 1

Regional Variations

• In Europe, prevalence ranges from 1-2.3% of the general population, with France reporting approximately 1 million affected individuals. 1
• South American data (primarily from Brazil) document a prevalence of approximately 1%. 1
• Low- and middle-income countries demonstrate starkly different patterns: patients present with more advanced heart failure at much younger ages, are more often women, and face substantial diagnostic and treatment barriers. 4
• Data from Africa and developing regions remain substantially lacking, though available evidence suggests different etiologies compared to Western populations (including rheumatic heart disease, HIV-associated heart disease, and endomyocardial fibrosis). 1, 4

Stages of Heart Failure

The ACC/AHA staging system (Stages A-D) reflects the progressive nature of heart failure, with patients typically advancing forward through stages without reversal, even when symptoms improve with treatment. 5

Stage A: At Risk for Heart Failure

• Patients have no structural heart disease, no symptoms, and no elevated biomarkers. 5
• Includes individuals with risk factors such as hypertension, diabetes, coronary artery disease, or family history of cardiomyopathy. 5
• Treatment should focus on reducing modifiable risk factors, including management of hypertension and hyperlipidemia. 1

Stage B: Pre-Heart Failure (Subclinical)

• Patients have structural heart disease but no current or previous symptoms. 5
• Evidence includes elevated natriuretic peptides, cardiac troponin, or increased filling pressures. 5
• Common findings include asymptomatic left ventricular systolic dysfunction with reduced ejection fraction, or diastolic dysfunction with LV hypertrophy or left atrial enlargement. 6
• To prevent symptomatic heart failure, ACE inhibitors and beta blockers should be used in all patients with stage B heart failure who have a reduced ejection fraction. 1
• The cardiac remodeling process typically precedes symptoms by months or years, emphasizing the importance of early detection and intervention. 6

Stage C: Symptomatic Heart Failure

• Patients have structural heart disease with current or previous symptoms. 5
• Patients remain Stage C even if symptoms resolve with treatment—they never revert to Stage B. 5, 6
• Patients with fluid retention should be treated with diuretics in addition to ACE inhibitors and beta blockers. 1
• All patients with reduced ejection fraction should receive guideline-directed medical therapy (ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists) regardless of NYHA class. 5

Stage D: Advanced Heart Failure

• Patients have marked symptoms that interfere with daily life and recurrent hospitalizations despite optimal guideline-directed medical therapy. 5
• Requires evaluation for advanced therapies including transplantation, mechanical circulatory support, or palliative care. 5

Key Clinical Pitfall: Do not wait for symptoms to develop before initiating evidence-based therapies in patients with documented structural heart disease or reduced ejection fraction. 6

Classification Systems

NYHA Functional Classification

The NYHA functional classification assesses current symptom severity and can change frequently in response to treatment or disease progression, unlike the ACC/AHA staging system. 5

• NYHA Class I: No limitation of physical activity; ordinary physical activity does not cause symptoms. 5
• NYHA Class II: Slight limitation of physical activity; comfortable at rest but ordinary physical activity results in symptoms. 5
• NYHA Class III: Marked limitation of physical activity; less than ordinary activity causes symptoms. 5
• NYHA Class IV: Symptoms at rest; inability to carry on any physical activity without symptoms. 5

The NYHA classification is subjective and determined by clinician assessment, and should be supplemented with objective measures (NT-proBNP, 6-minute walk distance, quality of life scores, cardiopulmonary exercise testing). 5

Classification by Left Ventricular Ejection Fraction

LVEF classification is critical because it determines prognosis and guides treatment selection, with most clinical trials enrolling patients based on ejection fraction. 5

• HFrEF (Heart Failure with Reduced Ejection Fraction): LVEF ≤40%. 1, 5
• HFmrEF (Heart Failure with Mildly Reduced Ejection Fraction): LVEF 41-49%. 1, 5
• HFpEF (Heart Failure with Preserved Ejection Fraction): LVEF ≥50%. 1, 5
• HFimpEF (Heart Failure with Improved Ejection Fraction): Baseline LVEF ≤40% with a ≥10-point increase from baseline and second measurement >40%. 1

Diagnostic Requirements

• Always measure ejection fraction to determine if symptoms are due to systolic dysfunction or another cause. 5
• For HFmrEF and HFpEF diagnosis, additional objective measures beyond symptoms and LVEF are required: elevated natriuretic peptides, evidence of elevated filling pressures, or structural abnormalities. 5
• Initial laboratory evaluation should include complete blood count, urinalysis, fasting lipid profile, liver function tests, serum electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, glucose, and thyroid-stimulating hormone. 1
• 12-lead electrocardiography should be obtained for all patients with heart failure. 1
• Measurement of BNP or NT-proBNP is useful to support clinical decision making in diagnosis, especially when there is clinical uncertainty, and for establishing prognosis or disease severity. 1

Integration of Classification Systems

• The ACC/AHA staging and NYHA functional classification are complementary: staging reflects disease progression while NYHA reflects current functional status. 5
• Progression from one ACC/AHA stage to the next is associated with reduced five-year survival and increased plasma natriuretic peptide concentrations. 1