What is the recommended management for a patient with heart failure with reduced ejection fraction (HFrEF), pulmonary sarcoidosis, and hypertension, currently taking Entresto (sacubitril and valsartan)?

Management of HFrEF Patient on Entresto with Pulmonary Sarcoidosis and Hypertension

Continue Entresto as the cornerstone of guideline-directed medical therapy (GDMT) and ensure the patient is on complete quadruple therapy including an SGLT2 inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA), as this combination reduces all-cause mortality by 61% and provides approximately 5.3 additional life-years compared to no treatment. 1, 2

Optimize Current Entresto Therapy

• Target dose: Titrate Entresto to 97/103 mg twice daily if not already achieved, doubling the dose every 2-4 weeks as tolerated. 1, 3
• Current dose assessment: If the patient is on a lower dose, aggressive uptitration should be pursued unless contraindicated by symptomatic hypotension (SBP <80 mmHg with symptoms) or severe renal impairment (eGFR <30 mL/min/1.73 m²). 4, 3
• Do not reduce or discontinue Entresto for asymptomatic hypotension with adequate perfusion, as efficacy is maintained even with baseline SBP <110 mmHg. 4, 2

Complete Quadruple Therapy for HFrEF

Add SGLT2 Inhibitor (if not already prescribed)

• Initiate dapagliflozin 10 mg once daily or empagliflozin 10 mg once daily regardless of diabetes status, as these reduce cardiovascular death and HF hospitalization with minimal blood pressure effects. 1, 2
• Requirement: eGFR ≥30 mL/min/1.73 m² for empagliflozin or ≥20 mL/min/1.73 m² for dapagliflozin. 2
• Advantage: No uptitration required; benefits occur within weeks of initiation. 4, 2

Ensure Beta-Blocker Therapy

• Use evidence-based beta-blockers only: carvedilol, metoprolol succinate, or bisoprolol, which reduce mortality by at least 20%. 1, 2
• Starting doses: Carvedilol 3.125 mg twice daily, metoprolol succinate 12.5-25 mg once daily, or bisoprolol 1.25 mg once daily. 1
• Target doses: Carvedilol 25 mg twice daily (50 mg twice daily if >85 kg), metoprolol succinate 200 mg once daily, or bisoprolol 10 mg once daily. 1
• Titrate every 2 weeks as tolerated by heart rate and blood pressure. 1

Ensure Mineralocorticoid Receptor Antagonist (MRA)

• Initiate spironolactone 12.5-25 mg once daily or eplerenone 25 mg once daily if eGFR >30 mL/min/1.73 m² and potassium <5.0 mEq/L. 1, 2
• Target doses: Spironolactone 25-50 mg once daily or eplerenone 50 mg once daily. 1
• Monitor potassium and renal function at 2-3 days after initiation, then monthly for 3 months, then every 3 months. 1, 4
• Important: Entresto actually reduces hyperkalemia risk compared to ACE inhibitors when combined with MRAs. 2

Manage Hypertension in Context of HFrEF

• GDMT medications are the primary antihypertensive therapy for HFrEF patients with hypertension. 1
• If blood pressure remains elevated despite optimal GDMT doses, consider adding amlodipine or long-acting nitrates rather than non-evidence-based agents. 2
• Avoid diltiazem or verapamil as they increase risk of HF worsening and hospitalization. 1
• Target blood pressure: Aim for SBP <130 mmHg, but prioritize GDMT optimization over strict BP targets. 1

Address Pulmonary Sarcoidosis Considerations

• Corticosteroid effects: If the patient requires systemic corticosteroids for sarcoidosis, monitor closely for fluid retention and adjust diuretic doses accordingly. 1
• Cardiac sarcoidosis screening: Ensure cardiac involvement has been excluded or is being monitored, as this may affect prognosis and device therapy decisions. 1
• Drug interactions: Corticosteroids may worsen hyperglycemia and hypertension, requiring closer monitoring of GDMT tolerability. 2

Diuretic Management for Volume Status

• Titrate loop diuretics to achieve euvolemia: no edema, no orthopnea, no jugular venous distension. 1, 2
• Starting doses: Furosemide 20-40 mg once or twice daily, torsemide 10-20 mg once daily, or bumetanide 0.5-1.0 mg once or twice daily. 2
• Reduce diuretic doses as GDMT is optimized due to enhanced natriuresis from Entresto. 4
• If high doses required (furosemide ≥80 mg twice daily), consider switching loop diuretics or adding thiazide diuretics. 1

Monitoring Parameters

• Blood pressure: Check at every visit and during dose titrations; address symptomatic hypotension by reducing non-essential BP medications first (not GDMT). 4, 2
• Renal function and electrolytes: Monitor at 1-2 weeks after each GDMT dose change, then every 3 months once stable. 1, 4
• Acceptable creatinine increase: Up to 30% above baseline is acceptable and should not prompt GDMT discontinuation. 2
• Potassium management: If hyperkalemia develops (K+ >5.5 mEq/L), consider potassium binders like patiromer rather than stopping MRA or Entresto. 2

Device Therapy Evaluation

• ICD consideration: If LVEF ≤35% despite ≥3 months of optimal GDMT and NYHA class II-III symptoms, refer for ICD evaluation. 1, 2
• CRT consideration: If QRS ≥150 msec with LBBB morphology, LVEF ≤35%, and sinus rhythm, refer for CRT evaluation. 1, 2

Common Pitfalls to Avoid

• Never discontinue GDMT for asymptomatic hypotension with adequate perfusion (warm extremities, normal mentation, adequate urine output). 4, 2
• Never accept suboptimal GDMT doses without attempting uptitration; target doses provide maximum mortality benefit. 4, 2
• Never stop Entresto and MRA simultaneously for hyperkalemia; use potassium binders first. 2
• Never use non-evidence-based beta-blockers (atenolol, metoprolol tartrate) as they lack mortality benefit. 2
• Never delay SGLT2 inhibitor initiation waiting for "optimization" of other medications; start all four classes simultaneously. 2