What are the guideline‑based treatment recommendations for a patient with heart failure (both reduced‑ejection‑fraction and preserved‑ejection‑fraction)?

Guideline-Based Treatment for Heart Failure

For HFrEF (EF ≤40%), initiate all four foundational medication classes simultaneously—SGLT2 inhibitors, ARNi/ACEi/ARB, beta-blockers, and mineralocorticoid receptor antagonists—to maximize mortality reduction and prevent hospitalizations. 1, 2

Heart Failure with Reduced Ejection Fraction (HFrEF, EF ≤40%)

Four-Pillar Medical Therapy (Start All Within Weeks 1-2)

SGLT2 Inhibitors - Start at full dose immediately:

• Dapagliflozin 10 mg daily OR empagliflozin 10 mg daily 1, 2
• Reduces cardiovascular mortality and HF hospitalizations independent of diabetes status 1
• Minimal blood pressure effects, making it safe to start early 1

Beta-Blockers - Initiate at low dose:

• Carvedilol 3.125 mg twice daily, metoprolol succinate 12.5-25 mg daily, OR bisoprolol 1.25 mg daily 1
• Target doses: carvedilol 25-50 mg twice daily, metoprolol succinate 200 mg daily, bisoprolol 10 mg daily 1
• Reduces mortality and sudden cardiac death across all HFrEF patients 1, 2

ARNi (Preferred) or ACEi/ARB:

• Sacubitril/valsartan 24/26 mg or 49/51 mg twice daily, titrate to 97/103 mg twice daily 1, 2
• ARNi provides superior mortality reduction compared to ACEi (enalapril) 2
• If ARNi not feasible, use enalapril 2.5-5 mg twice daily or lisinopril 2.5-5 mg daily 1
• ARBs are reserved only for ACEi/ARNi intolerance and have not consistently proven mortality benefit 2

Mineralocorticoid Receptor Antagonists (MRAs):

• Spironolactone 12.5-25 mg daily OR eplerenone 25 mg daily for LVEF ≤35% and NYHA class II-IV 1, 2
• Target doses: spironolactone 25-50 mg daily, eplerenone 50 mg daily 1
• Critical exclusions: baseline creatinine >2.5 mg/dL or potassium >5.0 mEq/L 2

Up-Titration Strategy (Weeks 2-12)

Increase one medication at a time every 1-2 weeks based on hemodynamics: 1

• If heart rate >70 bpm: Prioritize beta-blocker up-titration 1
• If systolic BP >100 mmHg: Up-titrate ARNi/ACEi/ARB 1
• If potassium <4.5 mmol/L with stable renal function: Up-titrate MRA 1
• Check blood pressure and heart rate before each increase; recheck potassium and creatinine 1-2 weeks after MRA or ARNi/ACEi increases 1

Managing Hemodynamic Barriers

Asymptomatic low BP (90-100 mmHg):

• Continue all four GDMT agents at current doses—low BP alone does not predict adverse outcomes 1
• Educate patients that transient orthostatic dizziness is expected and does not require dose reduction 1

Symptomatic hypotension (SBP <80 mmHg):

• Temporarily hold or reduce the most recently up-titrated drug 1
• Reduce non-GDMT antihypertensives first 1
• Never discontinue SGLT2 inhibitor or MRA for low BP alone 1

Bradycardia (HR <50 bpm):

• Reduce beta-blocker dose by ~50% 1
• If sinus rhythm with HR ≥70 bpm persists, add ivabradine 2.5-5 mg twice daily 1, 2
• Confirm absence of AV block with ECG before continuing beta-blocker 1

Additional Therapies for Specific Populations

African American patients with NYHA class III-IV:

• Add hydralazine 37.5 mg three times daily plus isosorbide dinitrate 20 mg three times daily 1, 2
• Up-titrate to hydralazine 75 mg TID and isosorbide dinitrate 40 mg TID for additional mortality benefit 1

Persistent symptoms despite optimal therapy:

• Ivabradine (starting 2.5-5 mg twice daily) for sinus rhythm with heart rate ≥70 bpm despite maximally tolerated beta-blocker 1, 2

Device Therapies

Implantable Cardioverter-Defibrillator (ICD):

• Indicated for LVEF ≤35% despite ≥3 months of optimal medical therapy, with expected survival >1 year 1

Cardiac Resynchronization Therapy (CRT):

• Indicated for LVEF ≤35%, sinus rhythm, left bundle branch block with QRS ≥150 ms, and NYHA class II-IV despite optimal therapy 1
• Consider CRT in permanent atrial fibrillation with NYHA class III-IV, EF ≤35%, QRS ≥120 ms if pacemaker dependent after AV nodal ablation 3

Critical Long-Term Management Points

Continue GDMT indefinitely, even if LVEF improves above 40% (HFimpEF)—withdrawal causes relapse of ventricular dysfunction 1, 2

Quantified survival benefit: Quadruple therapy (ARNi, beta-blocker, MRA, SGLT2i) provides approximately 5.3 additional life-years for a 70-year-old versus no treatment, reducing death risk by 73% over 2 years 2

Laboratory monitoring: Check potassium and creatinine every 3 months once stable on target doses 1

Heart Failure with Preserved Ejection Fraction (HFpEF, EF ≥50%)

Primary Medical Therapy

SGLT2 Inhibitors - First-line disease-modifying therapy:

• Dapagliflozin 10 mg daily OR empagliflozin 10 mg daily 3
• Reduces composite of cardiovascular death or HF hospitalizations 3
• Breakthrough therapy with proven benefit in HFpEF 3

Nonsteroidal Mineralocorticoid Receptor Antagonist (nsMRA):

• Finerenone has been shown to improve heart failure events in HFmrEF/HFpEF 4
• Combined SGLT2i and nsMRA therapy reduces cardiovascular death or first worsening HF event by 31% 4
• Projected to afford 3.6 additional years free from cardiovascular death or HF event in a 65-year-old patient 4

ARNi (Sacubitril/Valsartan) - For selected patients:

• Consider in patients with LVEF <60% (HFmrEF/lower range HFpEF) 4
• Combined SGLT2i, nsMRA, and ARNi therapy reduces risk by 39% in patients with LVEF <60% 4
• Results in smaller reductions in HF hospitalizations compared to HFrEF 5

Symptomatic Management

Diuretics for congestion:

• Loop diuretics for symptom relief and exercise capacity in patients with volume overload 3, 2
• No proven mortality benefit but essential for quality of life 2

Rate control in atrial fibrillation:

• Beta-blockers preferred over digoxin for rate control 3
• Rate-limiting calcium channel blockers (verapamil, diltiazem) may be used in HFpEF (unlike HFrEF where they are contraindicated) 3
• Combination of digoxin and beta-blocker more effective than beta-blocker alone for resting rate control 3

Comorbidity Management

Aggressive cardiovascular risk factor control through lifestyle modification and pharmacological therapy: 3

• Hypertension management
• Diabetes control
• Treatment of obesity
• Exercise programs 5

Key Differences from HFrEF Management

No consistent mortality benefit from ACEi, ARBs, or traditional MRAs in HFpEF, unlike HFrEF 5

Medication classes efficacious in HFrEF have been less effective at higher LVEF ranges, decreasing HF hospitalization risk but not cardiovascular or all-cause death 5

Burden of non-cardiac comorbidities increases as LVEF increases, requiring comprehensive non-cardiac management 5

Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF, EF 41-49%)

Treat similarly to HFrEF with the four-pillar approach: 6

• HFmrEF shares most important clinical features with HFrEF 6
• Evidence from post hoc analyses suggests drugs effective in HFrEF are also effective in HFmrEF 6
• Combined SGLT2i, nsMRA, and ARNi therapy particularly beneficial when LVEF <60% 4

Common Pitfalls to Avoid

Never use triple RAAS blockade (ACEi + ARB + MRA) due to renal dysfunction and hyperkalemia risk 2

Avoid diltiazem and verapamil in HFrEF due to increased risk of HF worsening and hospitalization 2

Do not delay initiation of all four foundational therapies—start simultaneously or in rapid sequence, not sequentially over months 2

Do not discontinue GDMT if LVEF improves above 40%—these patients (HFimpEF) should continue their HFrEF treatment regimen 1, 2