In a patient with severe mitral regurgitation, moderate tricuspid regurgitation, bipedal swelling, orthopnea, and a preserved ejection fraction of 70%, is it appropriate to start sacubitril/valsartan?

No, sacubitril/valsartan is NOT indicated in this patient with preserved ejection fraction (70%)

This patient has heart failure with preserved ejection fraction (HFpEF), not heart failure with reduced ejection fraction (HFrEF), and sacubitril/valsartan has not demonstrated clear mortality or hospitalization benefit in the HFpEF population. The FDA-approved indication for sacubitril/valsartan is specifically for heart failure with reduced ejection fraction 1.

Why This Patient Does Not Meet Criteria

Your patient presents with:

• EF 70% = HFpEF (preserved ejection fraction)
• Severe mitral regurgitation (MR) + moderate tricuspid regurgitation (TR)
• Volume overload symptoms (bipedal edema, orthopnea)

The primary issue here is valvular heart disease causing volume overload, not primary myocardial dysfunction with reduced EF.

Evidence Against Use in HFpEF

The PARAGON-HF trial in HFpEF patients (EF ≥45%) failed to meet its primary endpoint of reducing cardiovascular death or heart failure hospitalizations (rate ratio 0.87,95% CI 0.75-1.01, p=0.06) 2. While exploratory subgroup analyses suggested possible benefit in women and those with EF closer to 45-57%, these were not pre-specified primary findings and do not support routine use 2, 3.

The 2022 AHA/ACC Heart Failure Guidelines give sacubitril/valsartan only a Class 2b recommendation (may be considered) for HFpEF, and only in select patients—far weaker than the Class 1 recommendation for HFrEF 2.

What This Patient Actually Needs

Immediate Priorities:

1. Address the valvular pathology first: Severe MR with symptoms is a Class I indication for surgical intervention per ESC/EACTS guidelines 4. The patient needs:

   • Evaluation by a multidisciplinary Heart Team
   • Assessment for mitral valve repair/replacement
   • Consideration of tricuspid valve intervention given moderate TR and left-sided valve surgery indication 4, 5, 4

2. Optimize volume status with diuretics: The bipedal edema and orthopnea indicate congestion requiring aggressive diuretic therapy 2

3. Standard HFpEF medical therapy:

   • SGLT2 inhibitors (empagliflozin, dapagliflozin) have stronger evidence in HFpEF 6, 2
   • Mineralocorticoid receptor antagonists (spironolactone, eplerenone, or finerenone) 3
   • Blood pressure control if hypertensive
   • Rate control if atrial fibrillation present

Critical Pitfall to Avoid:

Do not use sacubitril/valsartan as a substitute for addressing the underlying severe valvular disease. The hemodynamic burden from severe MR and moderate TR is driving this patient's symptoms, not primary myocardial failure. Recent evidence suggests that optimizing guideline-directed medical therapy for HFpEF can actually reduce TR severity 7, but the severe MR requires definitive intervention.

When Might Sacubitril/Valsartan Be Considered in Valvular Disease?

Recent 2026 data suggests sacubitril/valsartan may improve secondary (functional) MR in patients with HFrEF by promoting left ventricular reverse remodeling 8, 9, 10. However, your patient has:

• Preserved EF (70%), not reduced
• Likely primary valvular pathology requiring structural intervention

If this patient had HFrEF (EF <40%) with secondary MR, then sacubitril/valsartan would be strongly indicated as it reduces MR severity through reverse remodeling 9, 10. But that is not this clinical scenario.

Bottom Line Algorithm:

For symptomatic severe MR + moderate TR with preserved EF:

1. Refer to Heart Team for valve intervention evaluation
2. Optimize diuretics for congestion
3. Start SGLT2 inhibitor
4. Consider MRA if tolerated
5. Do NOT start sacubitril/valsartan unless EF drops to <40% or post-valve intervention if EF becomes reduced