What are the core pillars in heart failure management?

Core Pillars of Heart Failure Management

The modern management of heart failure with reduced ejection fraction (HFrEF) is built on four foundational medication classes—SGLT2 inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and angiotensin receptor-neprilysin inhibitors (ARNi) or ACE inhibitors/ARBs—which should be initiated simultaneously at low doses and rapidly titrated to target, as these medications work synergistically to reduce mortality and hospitalizations. 1

The Four Pillars of GDMT for HFrEF

1. SGLT2 Inhibitors (Sodium-Glucose Cotransporter-2 Inhibitors)

• SGLT2 inhibitors are recommended for all symptomatic chronic HFrEF patients to reduce hospitalization and cardiovascular mortality, regardless of diabetes status (Class I recommendation). 1
• These agents should be initiated early in the treatment algorithm, as they provide benefit independent of other therapies. 2, 3
• SGLT2 inhibitors also have a Class 2a recommendation for heart failure with mildly reduced ejection fraction (HFmrEF, LVEF 41-49%). 1

2. Beta-Blockers (Evidence-Based)

• Evidence-based beta-blockers are Class I recommended for all HFrEF patients unless contraindicated. 1
• The specific beta-blockers with proven mortality benefit in HFrEF include carvedilol, metoprolol succinate, and bisoprolol. 3, 4
• Beta-blockers reduce mortality through neurohormonal modulation and prevention of adverse cardiac remodeling. 5

3. Mineralocorticoid Receptor Antagonists (MRAs)

• MRAs (spironolactone or eplerenone) are Class I recommended for symptomatic HFrEF patients with LVEF ≤35%. 1
• These agents block aldosterone-mediated myocardial fibrosis and adverse remodeling. 5
• Monitor potassium and renal function closely, particularly when combined with ACE inhibitors or ARNi. 1, 4

4. Renin-Angiotensin System Inhibition

• Angiotensin receptor-neprilysin inhibitors (ARNi, specifically sacubitril-valsartan) are preferred over ACE inhibitors for NYHA class II-III HFrEF patients. 1, 6
• ARNi demonstrated superior reduction in cardiovascular death and HF hospitalization compared to enalapril in the PARADIGM-HF trial. 6
• If ARNi is not tolerated, ACE inhibitors are Class I recommended for all patients with significantly reduced LVEF unless contraindicated. 1
• ARBs serve as an alternative when ACE inhibitors cannot be used. 1

Critical Implementation Strategy

Simultaneous Initiation Approach

• All four pillars should be started simultaneously at initial low doses, rather than sequentially waiting for target dosing of each medication. 1
• This approach maximizes early benefit through synergistic mechanisms targeting multiple pathophysiological pathways. 3, 5
• Doses should then be uptitrated to target as tolerated with serial reassessment. 1

Diuretics for Symptom Management

• Diuretics are essential for managing fluid overload and congestion but do not reduce mortality. 1
• Loop diuretics (furosemide) are first-line for volume management. 7
• Consider doubling the loop diuretic dose up to furosemide 500 mg equivalent if no initial response. 7
• Thiazide-type diuretics may be added to loop diuretics to improve diuresis in resistant cases. 1

Additional Therapies Beyond the Four Pillars

Hydralazine-Isosorbide Dinitrate

• This combination is Class I recommended for African American patients with NYHA class III-IV HFrEF as add-on therapy to standard GDMT. 1
• It serves as an alternative in patients who cannot tolerate ACE inhibitors or ARNi. 1

Ivabradine

• Consider for patients in sinus rhythm with heart rate ≥70 bpm despite beta-blocker therapy. 2

Vericiguat (Emerging Fifth Pillar)

• Vericiguat, a soluble guanylate cyclase stimulator, reduces hospitalizations and deaths in patients with worsening HF, particularly beneficial in older and frail patients. 8
• This represents a potential fifth pillar for patients with recent decompensation. 8

Device Therapies

Implantable Cardioverter-Defibrillator (ICD)

• ICD is recommended for patients with LVEF ≤35% and NYHA class II-III for primary prevention of sudden cardiac death. 1

Cardiac Resynchronization Therapy (CRT)

• CRT is Class I recommended for patients with LVEF ≤35%, sinus rhythm, left bundle branch block (LBBB), and QRS duration ≥150 ms with NYHA class II-IV symptoms. 1
• The benefit is greatest with LBBB morphology and QRS ≥150 ms. 1
• Patients with non-LBBB and QRS 120-149 ms derive less benefit. 1

Management of Challenging Clinical Scenarios

Hypotension

• Do not automatically discontinue GDMT for asymptomatic hypotension if the patient is otherwise stable. 4
• Reassess volume status and consider reducing or temporarily holding diuretics before stopping disease-modifying therapies. 4

Worsening Renal Function

• Transient increases in creatinine (up to 30% above baseline) during GDMT initiation are acceptable if not accompanied by hyperkalemia or severe symptoms. 4
• Continue GDMT unless creatinine rises >50% or eGFR falls below 20 mL/min/1.73m². 4

Hyperkalemia

• Optimize diuretic therapy and consider potassium binders (patiromer, sodium zirconium cyclosilicate) rather than discontinuing MRAs or ARNi. 4
• Reduce or temporarily hold MRA if potassium >5.5 mEq/L, but attempt reinitiation once normalized. 4

Atrial Fibrillation

• Digoxin is Class I recommended for rate control in HF patients with atrial fibrillation and rapid ventricular rates. 1
• Anticoagulation is Class I recommended for HF patients with atrial fibrillation. 1

Common Pitfalls to Avoid

• Never delay initiation of all four pillars waiting for "stability"—early simultaneous initiation is key. 1, 3
• Avoid calcium channel blockers (except for amlodipine/felodipine) in HFrEF as they increase mortality. 1
• Do not routinely treat asymptomatic ventricular arrhythmias with antiarrhythmic drugs (Class III recommendation). 1
• Avoid excessive reliance on inotropes (dobutamine, milrinone) for chronic management, as long-term use increases mortality. 1
• Do not withhold GDMT in elderly or frail patients—these populations also benefit, though may require more gradual titration. 8

Monitoring and Follow-Up

Hospital Discharge Criteria

• Before discharge, ensure acute HF episode has resolved, congestion is absent, stable oral diuretic regimen established for ≥48 hours, and GDMT optimized. 1, 7
• Schedule follow-up within 7-14 days of discharge and telephone contact within 3 days. 1

Serial Reassessment

• Continuously reassess symptoms, volume status, blood pressure, renal function, electrolytes, and LVEF with each visit. 1
• Uptitrate medications to target doses as tolerated, as higher doses provide greater mortality benefit. 1, 3

Multidisciplinary Disease Management

• Multidisciplinary HF disease-management programs are Class I recommended for high-risk patients to reduce readmissions. 1

Advanced Therapies for Refractory HF

Mechanical Circulatory Support

• Consider durable mechanical circulatory support (MCS) or cardiac transplantation for Stage D refractory HF despite optimal GDMT. 1
• Intra-aortic balloon pump or other temporary MCS may be considered in acute decompensation. 7

Hemodynamic Monitoring

• Wireless pulmonary artery pressure monitoring may be considered (Class 2b) for NYHA class III patients with history of HF hospitalization or elevated natriuretic peptides. 1
• Pulmonary artery catheterization should be reserved for patients refractory to pharmacological treatment or with uncertain hemodynamics. 7