What are the management strategies for a patient with heart failure, including those with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)?

Management of Heart Failure

All patients with HFrEF (LVEF ≤40%) should receive simultaneous initiation of four foundational medication classes—ARNI (or ACEi/ARB), beta-blocker, mineralocorticoid receptor antagonist (MRA), and SGLT2 inhibitor—started together at low doses with rapid up-titration to target doses within 2 months. 1, 2, 3

Heart Failure Classification

Heart failure is categorized by left ventricular ejection fraction (LVEF):

• HFrEF: LVEF ≤40% 1, 3
• HFmrEF: LVEF 41-49% 3
• HFpEF: LVEF ≥50% 3

Management of HFrEF

Core Quadruple Therapy (All Four Classes Mandatory)

1. ARNI (Preferred) or ACEi/ARB

• Sacubitril/valsartan (ARNI) is the preferred first-line agent over ACE inhibitors, providing superior mortality reduction of at least 20% 2, 3
• If already on ACEi or ARB and tolerating it, replace with ARNI to further reduce morbidity and mortality 2
• ARNI works by inhibiting neprilysin (increasing natriuretic peptides) and blocking angiotensin II type-1 receptors simultaneously 4

2. Evidence-Based Beta-Blockers

• Use carvedilol, metoprolol succinate, or bisoprolol 1, 2
• These reduce mortality by at least 20% and decrease sudden cardiac death 3

3. Mineralocorticoid Receptor Antagonists (MRAs)

• Use spironolactone or eplerenone 1, 2
• Provide at least 20% mortality reduction and reduce sudden cardiac death 3
• Spironolactone is indicated for NYHA Class III-IV heart failure to increase survival, manage edema, and reduce hospitalization 5

4. SGLT2 Inhibitors

• Use dapagliflozin or empagliflozin regardless of diabetes status 1, 2
• Class 1 recommendation with benefits including once-daily dosing, minimal blood pressure effects, and early onset of benefits 2
• Reduce cardiovascular death and HF hospitalization 3

Implementation Strategy

Start all four medication classes simultaneously at low doses rather than sequentially 1, 2, 3. This represents a paradigm shift from the traditional step-by-step approach.

Rapid up-titration protocol:

• Increase doses every 1-2 weeks as tolerated 2
• Target evidence-based doses within 2 months 2, 3
• Do not wait to achieve target dose of one medication before starting the next 2
• Monitor blood pressure, renal function, and electrolytes at 1-2 weeks after each dose increment 3

Managing Low Blood Pressure During Optimization

Critical pitfall to avoid: Low blood pressure alone (even <90 mmHg systolic) without symptoms or hypoperfusion is NOT a contraindication to guideline-directed medical therapy (GDMT) 2.

For asymptomatic low BP:

• Continue all four GDMT classes 1
• Do not use as a barrier to GDMT initiation or maintenance 1

For symptomatic low BP:

• Address reversible non-HF causes of hypotension 1
• Consider temporary discontinuation of non-HF medications that lower BP 1
• Re-optimize GDMT with careful dose adjustments 1
• Only discontinue GDMT if hemodynamic instability or cardiogenic shock is present 2

Acceptable changes during optimization:

• Modest increases in creatinine (up to 30% above baseline) are acceptable and should not prompt discontinuation of GDMT 3

Device Therapies

Implantable Cardioverter-Defibrillator (ICD):

• Indicated for primary prevention if LVEF ≤35% despite ≥3 months of optimal GDMT and life expectancy >1 year 2, 3

Cardiac Resynchronization Therapy (CRT):

• Indicated for patients with LVEF ≤35%, NYHA class II-IV, sinus rhythm, and left bundle branch block (LBBB) with QRS ≥150 ms 2, 3
• Recommended for patients with prolonged QRS duration 1

Transcatheter Mitral Valve Repair:

• Recommended for selected patients with significant secondary mitral regurgitation 1

Advanced Heart Failure Referral

Refer to HF specialty team if:

• Persistent NYHA class III-IV symptoms despite optimal GDMT 2, 3
• Recurrent hospitalizations for HF 2, 3
• Need for continuous or intermittent inotropic support 2, 3
• Consideration for advanced therapies (transplant, mechanical circulatory support) 2

Acute Decompensated HFrEF

Start IV loop diuretics immediately in the emergency department without delay, with an initial IV dose equal to or exceeding the chronic oral daily dose 2.

Management of HFmrEF (LVEF 41-49%)

SGLT2 inhibitors are beneficial in decreasing HF hospitalizations and cardiovascular mortality 1.

Evidence-based beta-blockers, ARNI, ACEi/ARB, and MRAs should be considered, particularly for patients with LVEF on the lower end of this spectrum (closer to 40%) 1.

Management of HFpEF (LVEF ≥50%)

SGLT2 inhibitors are the first-line treatment for HFpEF, reducing HF hospitalizations and composite cardiovascular events 3, 6.

Diuretics are essential for symptomatic relief of congestion 1, 3.

Additional considerations:

• Treatment with SGLT2 inhibitors reduces the risk of composite cardiovascular events, driven by a reduction in HF hospitalization 6
• Renin-angiotensin-aldosterone blockers and angiotensin-neprilysin inhibitors result in smaller reductions in HF hospitalization among patients with HFpEF compared to HFrEF 6
• Rigorous management of comorbidities (obesity, arterial hypertension, diabetes) is crucial 7
• Exercise and lifestyle modification are important components of comprehensive management 6

Important distinction: Medication classes efficacious in HFrEF have been less effective at higher LVEF ranges, decreasing the risk of HF hospitalization but not cardiovascular or all-cause death in HFpEF 6. This reflects the burden of non-cardiac comorbidities and complex pathophysiological mechanisms in HFpEF.

Multidisciplinary Support

Cardiac rehabilitation is recommended for patients with HFrEF, improving quality of life and reducing hospitalization 3.

Home telemonitoring can be used for optimization of treatment or detection of deterioration, reducing mortality and HF hospitalizations 3.

Palliative care should start early in disease trajectory, with referral to specialist palliative care if patient needs are unmet 3.