Does a patient with heart failure with reduced ejection fraction (HFrEF), pulmonary sarcoidosis, and hypertension, currently taking Entresto (sacubitril/valsartan), require therapeutic phlebotomy?

Therapeutic Phlebotomy is NOT Indicated for This Patient

This patient with HFrEF, pulmonary sarcoidosis, and hypertension on Entresto does not require therapeutic phlebotomy. Therapeutic phlebotomy has no role in the management of heart failure with reduced ejection fraction, and none of the established guidelines for HFrEF treatment mention phlebotomy as a therapeutic intervention 1.

Why Phlebotomy is Not Indicated

No Evidence Base in Heart Failure Guidelines

• Guideline-directed medical therapy (GDMT) for HFrEF consists of four foundational medication classes: ARNI (like Entresto), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors 1, 2
• Therapeutic phlebotomy is not mentioned in any Class I, II, or III recommendations for HFrEF management in major international guidelines 1
• The focus of HFrEF treatment is neurohormonal blockade and decongestion through diuretics, not blood volume reduction via phlebotomy 1

Current Optimal Management Strategy

Since this patient is already on Entresto (sacubitril/valsartan), the appropriate next steps are:

Ensure complete quadruple therapy:

• Add an SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) to reduce cardiovascular death and HF hospitalization 1, 2
• Add a mineralocorticoid receptor antagonist (spironolactone 12.5-25 mg daily, target 25-50 mg daily) if not already prescribed, as this provides at least 20% mortality reduction 1, 2
• Ensure beta-blocker therapy (bisoprolol, carvedilol, or metoprolol succinate) is optimized to target doses 1

Optimize Entresto dosing:

• Target dose is 97/103 mg twice daily, starting from 24/26-49/51 mg twice daily 1
• Entresto provides superior mortality reduction compared to ACE inhibitors and is appropriately prescribed 1, 3

Management of Hypertension in This Context

• Blood pressure should be targeted to <130/80 mmHg in patients with HFrEF 1
• The current HFrEF medications (Entresto, beta-blockers, MRAs) will provide blood pressure control as part of their mechanism 1
• If additional BP control is needed, add diuretics or consider calcium channel blockers (avoiding diltiazem/verapamil which are contraindicated in HFrEF) 1

Addressing Pulmonary Sarcoidosis Considerations

• Entresto may actually improve pulmonary pressures in patients with pulmonary hypertension secondary to left heart disease 4, 5
• Sacubitril/valsartan has been shown to reduce pulmonary artery pressures through increased natriuretic peptides causing vasodilation 4, 5
• There is no indication that sarcoidosis changes the approach to HFrEF management or creates a need for phlebotomy 1

When Phlebotomy IS Indicated (Not This Case)

Therapeutic phlebotomy is only appropriate for:

• Polycythemia vera or secondary polycythemia with hematocrit >45% causing hyperviscosity
• Hemochromatosis with iron overload
• Severe erythrocytosis in cyanotic heart disease

None of these conditions are mentioned in this patient's presentation, and HFrEF itself is not an indication for phlebotomy 1.

Critical Next Steps for This Patient

Immediate priorities:

1. Verify the patient is on all four pillars of GDMT (ARNI/ACE-I, beta-blocker, MRA, SGLT2 inhibitor) 1, 2
2. Titrate medications to target doses as tolerated, monitoring blood pressure, potassium, and renal function 1
3. Use diuretics for congestion management if signs/symptoms of volume overload are present 1
4. Assess for device therapy (ICD/CRT) if LVEF ≤35% despite ≥3 months of optimal medical therapy 1

Monitoring requirements:

• Check potassium and renal function 1-2 weeks after starting/titrating MRA 2
• Ensure eGFR >30 mL/min/1.73 m² and potassium <5.0 mEq/L before starting spironolactone 2
• Monitor blood pressure during medication titration 1