What are the treatment recommendations for a patient with newly diagnosed heart failure with reduced ejection fraction (HFrEF) and severe pulmonary hypertension who is already on guideline-directed medical therapy (GDMT)?

Management of Pulmonary Hypertension in HFrEF

For a patient with newly diagnosed HFrEF and severe pulmonary hypertension who is already on guideline-directed medical therapy (GDMT), the primary recommendation is to optimize the existing GDMT regimen to target doses, as this is the most effective approach for treating pulmonary hypertension secondary to left heart disease.

Understanding Pulmonary Hypertension in HFrEF

• Pulmonary hypertension in HFrEF is typically classified as WHO Group 2 (due to left heart disease) and primarily results from backward transmission of elevated left ventricular filling pressures 1
• Optimization of GDMT for HFrEF is the cornerstone of management for pulmonary hypertension in this setting 2
• Specific pulmonary vasodilators approved for pulmonary arterial hypertension (WHO Group 1) are contraindicated in HFrEF 3

Optimizing GDMT for HFrEF with Pulmonary Hypertension

First-Line Approach:

• Ensure all four pillars of GDMT are optimized to target doses or highest tolerated doses 2, 1:

  1. Renin-angiotensin system inhibitors (ACEi/ARB or preferably ARNI)
  2. Evidence-based beta-blockers (carvedilol, metoprolol succinate, or bisoprolol)
  3. Mineralocorticoid receptor antagonists (spironolactone or eplerenone)
  4. SGLT2 inhibitors (dapagliflozin or empagliflozin)

• Titration to target doses is crucial - only 1% of patients receive all medications at target doses, but this approach provides the greatest mortality benefit 2, 1

Special Considerations for Low Blood Pressure:

• If systolic BP is low (<90 mmHg), prioritize medications in this order 2:

  1. SGLT2 inhibitors and MRAs (minimal effect on BP)
  2. Selective β₁ receptor blockers (less BP-lowering effect than non-selective)
  3. Low-dose ACEi/ARB or very low-dose ARNI (25-50 mg twice daily)

• For patients with low BP but adequate perfusion, use small incremental dose increases with close monitoring 2

• If beta-blockers are not hemodynamically tolerated, consider ivabradine as an alternative for heart rate control 2

Volume Management

• Optimize diuretic therapy to reduce pulmonary congestion and right ventricular afterload 2
• For diuretic resistance, consider combination diuretic therapy (loop + thiazide) 2
• Avoid excessive diuresis which may worsen hypotension 2

Important Cautions

• Epoprostenol (prostacyclin) is contraindicated in HFrEF due to increased mortality demonstrated in clinical trials 3
• Other pulmonary vasodilators approved for PAH (sildenafil, bosentan, etc.) have not shown consistent benefit in HFrEF with pulmonary hypertension and may worsen outcomes 1
• Avoid non-HF medications that can exacerbate hypotension, such as calcium channel blockers or alpha-blockers 2

Follow-up and Monitoring

• Schedule early follow-up (within 7-14 days) after medication adjustments 2
• Monitor for:
  • Changes in volume status and blood pressure 2
  • Renal function and electrolytes 2
  • Symptoms of worsening heart failure 2

Multidisciplinary Approach

• Consider referral to a dedicated HF clinic, which has been shown to improve GDMT optimization and outcomes 4
• Multidisciplinary HF disease-management programs are recommended for high-risk patients 2

When to Consider Advanced Therapies

• If pulmonary hypertension persists despite optimal GDMT, consider evaluation for advanced HF therapies 2
• Persistent severe pulmonary hypertension despite optimal medical therapy may indicate progression to advanced HF requiring specialized interventions 2