What is the functional classification of heart failure and the corresponding drug therapy for each New York Heart Association (NYHA) class?

From the Guidelines

Heart failure is classified into four functional classes according to the New York Heart Association (NYHA) classification system, with specific drug therapies recommended for each class to reduce morbidity, mortality, and improve quality of life. The classification system is based on the severity of symptoms and limitations on physical activity, with Class I being asymptomatic and Class IV being severely symptomatic.

Classification and Treatment

• Class I patients have no limitation of physical activity and are typically treated with ACE inhibitors (like enalapril 2.5-20 mg twice daily or lisinopril 10-40 mg daily) or ARBs (such as losartan 25-100 mg daily) to prevent disease progression, as recommended by the American College of Cardiology Foundation (ACCF) and American Heart Association (AHA) guidelines 1.
• Class II patients have slight limitation of physical activity and require beta-blockers (carvedilol 3.125-25 mg twice daily, metoprolol succinate 25-200 mg daily, or bisoprolol 1.25-10 mg daily) in addition to ACE inhibitors/ARBs, to reduce sympathetic stimulation and heart rate.
• Class III patients experience marked limitation of activity and benefit from adding mineralocorticoid receptor antagonists (spironolactone 25-50 mg daily or eplerenone 25-50 mg daily) and possibly diuretics (furosemide 20-80 mg daily or as needed) to manage fluid overload, as recommended for patients with stage C heart failure and fluid retention 1.
• Class IV patients are unable to carry out physical activity without discomfort and require intensive therapy including all previous medications plus loop diuretics at higher doses, possible inotropic support, and consideration for advanced therapies like cardiac resynchronization therapy, ventricular assist devices, or heart transplantation.

Additional Therapies

For patients with heart failure with reduced ejection fraction (HFrEF), SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) are now recommended across all classes, as they provide cardiorenal protection through multiple pathways. These medications work through different mechanisms: ACE inhibitors/ARBs block the renin-angiotensin system to reduce cardiac remodeling, beta-blockers reduce sympathetic stimulation and heart rate, aldosterone antagonists prevent sodium retention and fibrosis, and SGLT2 inhibitors provide cardiorenal protection through multiple pathways.

Guideline-Based Recommendations

The ACCF and AHA guidelines recommend treating stage A heart failure by reducing modifiable risk factors, including management of hypertension and hyperlipidemia, and using ACE inhibitors and beta blockers in all patients with stage B or C heart failure who have a reduced ejection fraction 1. The goal of treatment is to reduce morbidity, mortality, and improve quality of life, and the choice of therapy should be guided by the patient's functional class and underlying condition.

From the FDA Drug Label

The Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial (SHIFT) was a randomized, double-blind trial comparing ivabradine and placebo in 6,558 adult patients with stable New York Heart Association (NYHA) class II to IV heart failure, left ventricular ejection fraction ≤ 35%, and resting heart rate ≥ 70 bpm Patients had to have been clinically stable for at least 4 weeks on an optimized and stable clinical regimen, which included maximally tolerated doses of beta-blockers and, in most cases, ACE inhibitors or ARBs, spironolactone, and diuretics, with fluid retention and symptoms of congestion minimized. At baseline, approximately 49% of randomized patients were NYHA class II, 50% were NYHA class III, and 2% were NYHA class IV.

The functional classification of heart failure is based on the New York Heart Association (NYHA) classification, which includes:

• Class II: Patients with cardiac disease resulting in slight, occasional limitation of physical activity. They are comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea.
• Class III: Patients with marked limitation of physical activity. They are comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea.
• Class IV: Patients with severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.

Drug therapy for each class includes:

• Beta-blockers: Used in all classes to reduce mortality and morbidity.
• ACE inhibitors or ARBs: Used in all classes to reduce mortality and morbidity.
• Diuretics: Used in all classes to manage fluid retention and symptoms of congestion.
• Spironolactone: Used in Class III and IV to reduce mortality and morbidity.
• Ivabradine: Used in Class II-IV with a heart rate ≥ 70 bpm, to reduce the risk of hospitalization for worsening heart failure 2.

From the Research

Functional Classification of Heart Failure

The New York Heart Association (NYHA) classification is a fundamental tool for risk stratification of heart failure (HF) and determines clinical trial eligibility and candidacy for drugs and devices 3. The NYHA classification has four classes:

• Class I: No symptoms with ordinary physical activity
• Class II: Mild symptoms with ordinary physical activity
• Class III: Marked limitation in physical activity due to symptoms
• Class IV: Severe limitations, experiences symptoms even while at rest

Drug Therapy for Each Class

The following medications are used to treat heart failure, depending on the NYHA class:

• Beta-blockers: Used in all classes to reduce mortality and hospitalization rates 4
• Angiotensin-converting enzyme (ACE) inhibitors: Used in all classes to reduce mortality and hospitalization rates 5, 4
• Angiotensin II receptor antagonists: Used as an alternative to ACE inhibitors in patients who cannot tolerate them 5
• Diuretics: Used in classes II-IV to reduce symptoms of fluid overload 4
• Aldosterone antagonists: Used in classes III-IV to reduce mortality and hospitalization rates 4
• Ivabradine: Used in classes II-IV to reduce hospitalization rates 4
• Devices: Such as automatic implantable cardioverter defibrillators and cardiac resynchronization therapy, used in classes III-IV to reduce mortality and hospitalization rates 4
• Digoxin: Used in classes III-IV to reduce symptoms and hospitalization rates 4

Key Findings

• The NYHA classification poorly discriminates HF patients across the spectrum of functional impairment 3
• Patient- and provider-determined NYHA class are poorly correlated, with patients consistently reporting better NYHA class than providers 6
• The benefits of MitraClip implantation were consistent in patients with better or worse functional status as assessed by NYHA functional class 7
• ACE inhibitors and angiotensin II receptor antagonists have similar effects on mortality and hospitalization rates, but differ in their mechanism of action and adverse effects 5