What is the next management step for a 56-year-old female with a history of intravenous (IV) drug abuse, presenting with shortness of breath, an ejection fraction (EF) of 25-30%, hypotension, and currently on diuretics and levophed (norepinephrine)?

Management of Heart Failure with Reduced Ejection Fraction and Hypotension

The next management step for this patient should be initiation of very low-dose ARNI (sacubitril/valsartan) starting at 24/26 mg twice daily with careful uptitration while maintaining SGLT2 inhibitor therapy. 1

Patient Assessment and Clinical Context

This 56-year-old female presents with:

• History of IV drug abuse
• Shortness of breath
• Normal coronary arteries on catheterization
• Severely reduced EF (25-30%)
• Hypotension (systolic BP in the 90s)
• Currently on diuretics and levophed (norepinephrine)
• Asymptomatic at present

Management Algorithm

Step 1: Optimize Volume Status

• Reassess volume status and carefully titrate diuretics
• Consider spacing diuretic administration to minimize synergistic hypotensive effects with other medications 1
• If patient is euvolemic, consider reducing diuretic dose to help improve blood pressure

Step 2: Initiate Guideline-Directed Medical Therapy (GDMT)

• Start with medications having minimal BP-lowering effects:

  • SGLT2 inhibitor (dapagliflozin 10mg daily or empagliflozin 10mg daily) 2
  • Consider low-dose MRA (spironolactone 12.5-25mg daily) if potassium <5.0 and eGFR >30 ml/min/1.73m² 1

• Add very low-dose ARNI:

  • Initiate sacubitril/valsartan at 24/26mg twice daily 1, 2
  • If not tolerated, shift to low-dose ACE inhibitor or ARB 1

Step 3: Gradual Uptitration

• Uptitrate one medication at a time every 2 weeks as blood pressure allows 2
• Target at least 50% of target doses for each medication class 2
• Monitor blood pressure, renal function, and electrolytes closely during titration

Step 4: Consider Beta-Blocker Therapy

• Once blood pressure stabilizes, initiate very low-dose beta-blocker (e.g., carvedilol 3.125mg BID) 1, 2
• Uptitrate gradually based on heart rate and blood pressure tolerance

Evidence-Based Rationale

The 2021 ACC Expert Consensus recommends ARNI therapy for patients with HFrEF, as it demonstrated a 20% reduction in cardiovascular death or HF hospitalization compared to ACE inhibitors in the PARADIGM-HF trial 1. Even in patients with hypotension, starting with very low doses and careful uptitration can allow patients to benefit from this life-saving therapy.

The 2025 HFA Clinical Consensus Statement specifically addresses management of HFrEF with low blood pressure, recommending initiation of very low-dose ARNI (25mg twice daily) with careful uptitration 1. This approach prioritizes medications with the greatest mortality benefit while managing hypotension.

SGLT2 inhibitors have minimal impact on blood pressure while providing significant mortality benefit and should be maintained if possible 2. MRAs also have relatively modest effects on blood pressure while providing substantial clinical benefit 1.

Special Considerations for This Patient

• Hypotension management: Space out medications to reduce synergistic hypotensive effects; consider compression stockings to minimize orthostatic drops in BP 1
• IV drug abuse history: Monitor closely for adherence issues and consider social support needs
• Norepinephrine dependence: Work toward gradual weaning of vasopressors as GDMT is established
• Monitoring: Schedule frequent follow-up (every 1-2 weeks initially) to assess vital signs, volume status, renal function, and electrolytes 2

Common Pitfalls to Avoid

• Undertreatment: Avoiding GDMT entirely due to hypotension concerns, when low-dose therapy can often be tolerated and provide benefit
• Inappropriate discontinuation: Consider dose reduction rather than discontinuation if side effects occur 2
• Clinical inertia: Delaying uptitration due to apparent clinical stability; outcomes improve with higher doses even in stable patients 2
• Neglecting non-pharmacological interventions: Physical training can improve orthostatic hypotension and low BP 1

By following this approach, the patient has the best chance of improved survival and quality of life while managing the challenge of hypotension.