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, MRA, and SGLT2 inhibitor—started as early as possible even at low doses, with rapid up-titration to target doses within 2 months. 1
Heart Failure Classification by Ejection Fraction
HFrEF (Heart Failure with Reduced Ejection Fraction):
HFmrEF (Heart Failure with Mildly Reduced Ejection Fraction):
HFpEF (Heart Failure with Preserved Ejection Fraction):
Management of HFrEF: The Four Pillars of GDMT
Foundational Quadruple Therapy (Start All Four Simultaneously)
1. ARNI (Angiotensin Receptor-Neprilysin Inhibitor) - PREFERRED FIRST-LINE
- Sacubitril/valsartan provides at least 20% mortality reduction, superior to ACE inhibitors 1, 3
- Preferred over ACEi/ARB for all symptomatic patients with NYHA class II-III 1
- Starting dose: 24/26 mg or 49/51 mg twice daily; target dose: 97/103 mg twice daily 4
- If already on ACEi/ARB and tolerating it, replace with ARNI 1
- Critical contraindication: Never combine ACEi with ARNI due to angioedema risk 3
- Wait 36 hours after stopping ACEi before starting ARNI 4
Alternative if ARNI not tolerated:
2. Evidence-Based Beta-Blockers
- Only three beta-blockers have proven mortality benefit: carvedilol, metoprolol succinate, or bisoprolol 1, 5
- Reduce mortality by at least 20% and decrease sudden cardiac death 3
- Start at low doses and up-titrate every 1-2 weeks 1
- Continue even during acute decompensation unless hemodynamically unstable 2
3. Mineralocorticoid Receptor Antagonists (MRAs)
- Spironolactone or eplerenone provide at least 20% mortality reduction and reduce sudden cardiac death 1, 3
- Minimal blood pressure effect, making them ideal for early initiation 1
- Use if eGFR >30 mL/min/1.73 m² and potassium <5.0 mEq/L 3
- Indicated for all symptomatic patients with LVEF ≤35% 6
- Monitor potassium and renal function closely; consider potassium binders (patiromer) rather than discontinuing if hyperkalemia develops 3
4. SGLT2 Inhibitors
- Dapagliflozin or empagliflozin reduce cardiovascular death and HF hospitalization regardless of diabetes status 1, 5
- Once-daily dosing with no up-titration required; benefits occur within weeks 3
- Minimal blood pressure effect (only -1.50 mmHg in patients with baseline SBP 95-110 mmHg) 3
- Can be used if eGFR ≥30 mL/min/1.73 m² for empagliflozin, or ≥20 mL/min/1.73 m² for dapagliflozin 3
Implementation Strategy: Simultaneous Initiation Approach
The modern approach is to start all four medication classes together at low doses rather than sequential step-by-step titration 1, 5
Practical Algorithm for Initiation:
Step 1: Start all four pillars simultaneously at low doses
- Begin SGLT2 inhibitor and MRA first (minimal BP effects) 1, 3
- Then add low-dose beta-blocker if heart rate >70 bpm 3
- Then initiate low-dose ARNI/ACEi/ARB 3
Step 2: Up-titrate one drug at a time every 1-2 weeks
- Increase doses using small increments until target or maximally tolerated dose achieved 1, 3
- Prioritize SGLT2 inhibitor and MRA first, then beta-blocker, then ARNI 3
- Goal: Achieve optimal treatment within 2 months 1, 5
Step 3: Add diuretics for volume management
- Loop diuretics (furosemide 20-40 mg, torsemide 10-20 mg, or bumetanide 0.5-1.0 mg) for congestion control 3
- Titrate to achieve euvolemia (no edema, no orthopnea, no jugular venous distension), then use lowest dose that maintains this state 3
- Diuretics do not reduce mortality—they are for symptom relief only 3
Managing Low Blood Pressure During GDMT Optimization
Critical Principle: Asymptomatic low BP (even <90 mmHg) without hypoperfusion is NOT a contraindication to GDMT 1, 5
Algorithm for Managing Hypotension:
If SBP <80 mmHg or symptomatic hypotension:
First, address reversible non-HF causes of hypotension 3
Do NOT down-titrate or stop GDMT for asymptomatic hypotension 3
Non-pharmacological interventions for symptomatic hypotension:
If GDMT adjustment is absolutely necessary:
Additional Therapies for Specific HFrEF Subgroups
Hydralazine/Isosorbide Dinitrate:
- Indicated for self-identified Black patients with NYHA class III-IV symptoms despite optimal GDMT 2, 3
- Starting dose: hydralazine 25 mg three times daily + isosorbide dinitrate 20 mg three times daily 3
- Can also be used in patients who cannot tolerate ACEi/ARB/ARNI 2
Ivabradine:
- Consider if heart rate ≥70 bpm in sinus rhythm despite maximally tolerated beta-blocker 3
- Starting dose: 2.5-5 mg twice daily 3
- Survival benefit is modest or negligible in broad HFrEF population 3
Digoxin:
- Can be beneficial for symptom control but does not reduce mortality 2
- Consider in patients with persistent symptoms despite GDMT 2
Anticoagulation:
- Indicated for patients with chronic HF who have permanent/persistent/paroxysmal atrial fibrillation and additional risk factors for cardioembolic stroke 2
- Not recommended in HFrEF without AF, prior thromboembolic event, or cardioembolic source 2
Device Therapy for HFrEF
Implantable Cardioverter-Defibrillator (ICD):
- Indicated for primary prevention if LVEF ≤35% despite ≥3 months of optimal GDMT and life expectancy >1 year 1, 3
- For NYHA class II-III symptoms 3
- Also indicated for secondary prevention in patients with prior ventricular arrhythmia causing hemodynamic instability 3
Cardiac Resynchronization Therapy (CRT):
- Indicated for patients with LVEF ≤35%, NYHA class II-IV, sinus rhythm, and LBBB with QRS ≥150 ms 1, 3
- Class I indication if QRS ≥130 ms and LBBB morphology 3
Management of HFpEF
The evidence base for HFpEF is much weaker than HFrEF, but recent trials have changed the landscape 2, 7
First-Line Therapy:
- SGLT2 inhibitors (empagliflozin or dapagliflozin) reduce HF hospitalizations and composite cardiovascular events 2, 7, 8
- This is now the only Class I recommendation with mortality/morbidity benefit in HFpEF 2
Diuretics:
Other Therapies with Weaker Evidence:
- MRAs (spironolactone) may reduce HF hospitalizations but do not reduce cardiovascular or all-cause death 2, 7
- ARNi (sacubitril/valsartan) results in smaller reductions in HF hospitalizations compared to HFrEF 2, 7
- ACEi/ARB have not demonstrated mortality benefit in HFpEF 7
Non-Pharmacological Management:
- Cardiac rehabilitation and exercise training are crucial 2, 8
- Treatment of comorbidities (hypertension, diabetes, obesity, atrial fibrillation, ischemic heart disease) 2, 8
- Risk factor modification 2, 8
Diagnostic Considerations:
- HFpEF diagnosis is challenging and requires excluding non-cardiac causes of dyspnea 2, 7
- May require exercise echocardiography or invasive hemodynamics 7
- Screen for "HFpEF mimickers" such as cardiac amyloidosis or hypertrophic cardiomyopathy, which have specific targeted therapies 9
Management of HFmrEF (EF 41-49%)
SGLT2 inhibitors are beneficial in decreasing HF hospitalizations and cardiovascular mortality 5
Evidence-based beta-blockers, ARNI, ACEi/ARB, and MRAs should be considered, particularly for patients with LVEF on the lower end of this spectrum 5
Acute Decompensated Heart Failure Management
Immediate Actions:
- Start IV loop diuretics immediately in the emergency department without delay 1
- Initial IV dose should equal or exceed the chronic oral daily dose 2
- Serial dose adjustments based on response 2
Continue GDMT:
- HFrEF patients on GDMT should continue these medications except in cases of hemodynamic instability or contraindications 2
- Beta-blocker therapy should be continued during hospitalization unless hemodynamically unstable 2
Diuretic Strategies:
- If diuresis inadequate, give higher doses of IV loop diuretics or add a second diuretic (thiazide) 2
- Low-dose dopamine infusion may be considered to improve diuresis 2
- Ultrafiltration may be considered for obvious volume overload 2
Reinitiation After Stabilization:
- Initiate beta-blocker therapy at low dose after optimization of volume status and discontinuation of IV inotropes 2
Thromboprophylaxis:
- Recommended for all patients hospitalized with HF 2
Advanced Heart Failure (Stage D) Management
Referral Criteria to HF Specialty Team:
- Persistent NYHA class III-IV symptoms despite optimal GDMT 1
- Recurrent hospitalizations for HF 1
- Need for continuous or intermittent inotropic support 1
- Consideration for advanced therapies (transplant, mechanical circulatory support) 1
Advanced Therapies:
- Cardiac transplantation evaluation is indicated for carefully selected patients with stage D HF despite GDMT, device, and surgical management 2
- Durable mechanical circulatory support (MCS) is reasonable to prolong survival for carefully selected patients with stage D HFrEF 2
- Nondurable MCS may be used as "bridge to recovery" or "bridge to decision" 2
Palliative Care:
- Should be addressed early in disease trajectory for stage D patients 2
- Referral to specialist palliative care if patient needs are unmet 2
- Consider ICD deactivation discussions 2
Medications to AVOID in HFrEF
Harmful or Not Beneficial:
- Calcium channel blockers (diltiazem, verapamil) increase risk of worsening HF and hospitalization 2, 3
- Non-evidence-based beta-blockers (atenolol, propranolol) do not reduce mortality 3
- Triple combination of ACEi + ARB + MRA increases risk of hyperkalemia and renal dysfunction 2, 3
- Statins are not beneficial as adjunctive therapy when prescribed solely for HF 2
- Long-term infusion of positive inotropic drugs is not recommended except as palliation 2
- Nutritional supplements and hormonal therapies (other than to correct deficiencies) are not recommended 2
Monitoring Requirements During GDMT Optimization
Frequency:
- Monitor blood pressure, renal function, and electrolytes at 1-2 weeks after each dose increment 3
- More frequent monitoring in elderly patients and those with chronic kidney disease 3
Acceptable Changes:
- Modest increases in creatinine (up to 30% above baseline) are acceptable and should not prompt discontinuation 3
- Worsening kidney function with successful decongestion is associated with lower mortality than failure to decongest with stable kidney function 3
Hyperkalemia Management:
- Potassium levels require close monitoring with MRAs 3
- If hyperkalemia develops, consider potassium binders (patiromer) rather than discontinuing life-saving medications 3
- Discontinuation of RAAS inhibitors after hyperkalemia is associated with two to fourfold higher risk of adverse events 3
Common Pitfalls to Avoid
- Delaying initiation of all four medication classes 3
- Accepting suboptimal doses without attempting up-titration 3
- Stopping medications for asymptomatic hypotension 3
- Inadequate monitoring of renal function and electrolytes 3
- Using non-evidence-based beta-blockers 3
- Sequential rather than simultaneous initiation of GDMT 1, 5
- Discontinuing GDMT during acute decompensation when patient is not hemodynamically unstable 2
- Not addressing reversible non-HF causes of hypotension before adjusting GDMT 3
Multidisciplinary Involvement
Cardiac Rehabilitation:
- Wealth of evidence for efficacy in HFrEF through improvement in quality of life and reduction in hospitalization 2
- Less data exists in HFpEF, but still recommended by five guidelines 2
Home Telemonitoring:
- Can be used for optimization of treatment or detection of deterioration 2
- Reduces mortality and HF hospitalizations according to Cochrane systematic review 2
- Increases accessibility for patients with poor mobility and in geographically underserved areas 2
Palliative Care: