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 (EF ≤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

• HFrEF: EF ≤40% 1, 3
• HFmrEF: EF 41-49% 1, 3
• HFpEF: EF ≥50% 3, 4

Management of HFrEF (EF ≤40%)

Core Quadruple Therapy (The Four Pillars)

1. ARNI (Preferred) or ACEi/ARB

• Sacubitril/valsartan (ARNI) is the preferred first-line agent for NYHA class II-III symptoms, providing superior mortality reduction compared to ACE inhibitors 2, 3
• If already on ACEi/ARB and tolerating it, replace with ARNI to further reduce morbidity and mortality 2
• The mechanism involves neprilysin inhibition (increasing natriuretic peptides) combined with angiotensin II receptor blockade 5

2. Evidence-Based Beta-Blockers

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

3. Mineralocorticoid Receptor Antagonists (MRAs)

• Use spironolactone or eplerenone 1, 2, 3
• Indicated for NYHA Class III-IV heart failure to increase survival, manage edema, and reduce hospitalization 6
• Provide at least 20% mortality reduction and reduce sudden cardiac death 3

4. SGLT2 Inhibitors

• Use dapagliflozin or empagliflozin 1, 2, 3
• Recommended regardless of diabetes status 1, 2
• Benefits include once-daily dosing, minimal blood pressure effects, and early onset of benefits 2

Implementation Strategy

Start all four medication classes simultaneously at low doses rather than sequentially 1, 2, 3

Dose Titration Protocol:

• Increase doses every 1-2 weeks as tolerated 2
• Target evidence-based doses within 2 months 1, 2
• Do not wait to achieve target dose of one medication before starting the next 2
• Adjust based on blood pressure, heart rate, congestion, kidney function, and presence of atrial fibrillation 1

Monitoring:

• Check blood pressure, renal function, and electrolytes at 1-2 weeks after each dose increment 3
• Modest increases in creatinine (up to 30% above baseline) are acceptable and should not prompt discontinuation 3

Managing Low Blood Pressure During Optimization

Asymptomatic low BP (even <90 mmHg) without hypoperfusion is NOT a contraindication to guideline-directed medical therapy (GDMT) 1, 2

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
• Continue all four GDMT classes unless hemodynamic instability or cardiogenic shock is present 2

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 LVEF ≤35%, NYHA class II-IV, sinus rhythm, and 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

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

Advanced HF Referral Criteria

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

Cardiac transplantation evaluation is indicated for carefully selected patients with stage D HF despite GDMT, device, and surgical management 3

Management of HFmrEF (EF 41-49%)

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

Consider evidence-based beta-blockers, ARNI, ACEi/ARB, and MRAs, particularly for patients with LVEF on the lower end of this spectrum 1

Management of HFpEF (EF ≥50%)

SGLT2 inhibitors are the first-line treatment for HFpEF, reducing HF hospitalizations and composite cardiovascular events 3, 4

Diuretics are essential for symptomatic relief of congestion 3

Additional considerations:

• Renin-angiotensin-aldosterone blockers and angiotensin-neprilysin inhibitors result in smaller reductions in HF hospitalisations compared to their effects in HFrEF 4
• Treatment of risk factors and comorbidities is crucial 4
• Exercise training is beneficial 4
• Specific therapies are emerging for specific HFpEF etiologies, such as hypertrophic cardiomyopathy or cardiac amyloidosis 7

Multidisciplinary Management

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

Common Pitfalls to Avoid

• Do not delay initiation of all four pillars waiting for sequential up-titration of individual medications 1, 2
• Do not withhold GDMT for asymptomatic low blood pressure alone 1, 2
• Do not discontinue GDMT for modest creatinine increases (up to 30% above baseline) 3
• Do not forget SGLT2 inhibitors in non-diabetic patients—they are indicated regardless of diabetes status 1, 2