What is the optimal management plan for an elderly male patient with heart failure with mid-range ejection fraction, atrial fibrillation, and moderate-severe mitral regurgitation?

Optimal Management of HFmrEF with Atrial Fibrillation and Moderate-Severe Mitral Regurgitation

This patient requires immediate initiation of comprehensive guideline-directed medical therapy (GDMT) for HFmrEF consisting of four foundational drug classes—SGLT2 inhibitor, beta-blocker (already started), ACE inhibitor/ARB/ARNI, and mineralocorticoid receptor antagonist—while continuing anticoagulation for atrial fibrillation and optimizing diuretic therapy for volume overload, with the moderate-severe mitral regurgitation managed medically first before considering any interventional procedures. 1, 2

Immediate Medication Optimization

Add SGLT2 Inhibitor Immediately

• Start dapagliflozin 10 mg daily or empagliflozin 10 mg daily now. SGLT2 inhibitors decrease heart failure hospitalizations and cardiovascular mortality in HFmrEF (LVEF 40-45% in this patient), with benefits extending across the entire HFmrEF spectrum. 1, 2
• SGLT2 inhibitors have minimal blood pressure effects, making them ideal for patients already on multiple medications, and should not be deferred to outpatient settings as this exposes patients to excess risk of early clinical worsening. 2
• Do not start if eGFR <30 mL/min/1.73m² (check current renal function given BNP 238 and potassium 4.5). 2

Optimize Beta-Blocker Therapy

• The switch from atenolol to metoprolol 50 mg daily is appropriate, but use metoprolol succinate (extended-release), carvedilol, or bisoprolol specifically—these are the evidence-based beta-blockers for heart failure, not all beta-blockers. 1, 3
• Target heart rate <70 bpm while monitoring for symptomatic bradycardia (<60 bpm). 1
• Titrate to target doses: metoprolol succinate 200 mg daily, carvedilol 25 mg twice daily, or bisoprolol 10 mg daily over 4-8 weeks as tolerated. 2, 4

Add ACE Inhibitor/ARB or Preferably ARNI

• Start sacubitril-valsartan (Entresto) 24/26 mg twice daily as first choice, or if cost-prohibitive, start lisinopril 5 mg daily or losartan 25 mg daily. 1, 2
• Sacubitril-valsartan specifically reduces mitral regurgitation effective regurgitant area compared to valsartan alone in patients with HFrEF and secondary MR. 1
• Monitor blood pressure, renal function, and potassium 1-2 weeks after initiation. 2
• Titrate gradually to target doses: sacubitril-valsartan 97/103 mg twice daily, lisinopril 20-40 mg daily, or losartan 150 mg daily. 2, 4

Add Mineralocorticoid Receptor Antagonist

• Start spironolactone 12.5-25 mg daily (preferred given cost) or eplerenone 25 mg daily. 2, 3
• Current potassium is 4.5 mEq/L, which is safe for initiation. Do not start if K+ >5.0 mEq/L or eGFR <30 mL/min/1.73m². 2
• Recheck potassium and renal function in 1 week, then 1-2 weeks after each dose increase. 2
• Target dose: spironolactone 25-50 mg daily or eplerenone 50 mg daily. 2

Diuretic Management for Volume Overload

• Continue loop diuretic therapy (dose not specified in case, but patient has lower extremity edema and shortness of breath). 2
• Adjust diuretic dose based on daily weights, symptoms, and physical exam findings—target euvolemia before aggressive GDMT uptitration. 1, 2
• Consider reducing diuretic dose as GDMT is optimized and volume status improves to avoid excessive preload reduction. 1

Anticoagulation for Atrial Fibrillation

• Continue Eliquis (apixaban) 5 mg twice daily—anticoagulation is mandatory in all patients with diabetes and atrial fibrillation given substantially higher risk of stroke. 1
• Verify dosing is appropriate: use 2.5 mg twice daily only if patient has 2 of 3 criteria (age ≥80 years, weight ≤60 kg, creatinine ≥1.5 mg/dL). 1

Management of Moderate-Severe Mitral Regurgitation

• Optimize GDMT first for at least 3-6 months before considering transcatheter edge-to-edge repair (TEER) or surgical intervention. GDMT, including RAAS inhibition, beta-blockers, and SGLT2 inhibitors, improves secondary MR and LV dimensions in patients with HFrEF/HFmrEF. 1, 2
• The patient's LVEF 40-45%, moderate-severe MR, and global hypokinesis suggest secondary (functional) MR related to LV dysfunction rather than primary valve pathology. 1
• TEER (transcatheter edge-to-edge repair) criteria from COAPT trial: Consider only if persistent NYHA class II-IV symptoms on optimal GDMT for adequate duration, LVEF 20-50%, LV end-systolic diameter ≤70 mm, and PA systolic pressure ≤70 mm Hg. 1
• The upcoming structural heart consultation is appropriate, but emphasize that medical optimization must precede any interventional decision. 1, 2

Addressing Comorbidities

Ischemic Evaluation

• Fixed apical defects on nuclear stress test suggest prior infarction rather than reversible ischemia. [@case presentation@]
• LDL 74 mg/dL is at goal; continue current statin therapy. [@case presentation@]
• No urgent revascularization indicated based on fixed defects and absence of active ischemic symptoms. 1

Other Medications to Review

• Avoid NSAIDs for rheumatoid arthritis and degenerative joint disease—these worsen heart failure, increase blood pressure, and reduce effectiveness of diuretics and ACE inhibitors. 1
• For RA, coordinate with rheumatology for NSAID alternatives (acetaminophen, topical agents, or disease-modifying agents if not already prescribed). 1
• Review all medications for potential heart failure exacerbation: calcium channel blockers (verapamil, diltiazem), antiarrhythmics other than amiodarone, and thiazolidinediones should be avoided. 1

Monitoring and Follow-Up Schedule

1-Week Follow-Up (Labs Only)

• Recheck potassium, creatinine, BUN, and eGFR after MRA initiation. 2
• Hold MRA if K+ >5.5 mEq/L; reduce dose if K+ 5.0-5.5 mEq/L. 2

4-Week In-Person Visit (As Planned)

• Assess symptoms (NYHA class), volume status (weight, edema, orthopnea), blood pressure, and heart rate. 2
• Recheck BNP, electrolytes, and renal function. 2
• Begin uptitration of beta-blocker, ACE inhibitor/ARB/ARNI, and MRA toward target doses if patient is stable. 2, 4

8-12 Week Follow-Up

• Continue medication titration every 2-4 weeks until target doses achieved or maximum tolerated doses reached. 2, 3
• Repeat echocardiogram at 3-6 months to assess response to GDMT, including changes in LVEF, LV dimensions, and MR severity. 1

Specialist Referral Considerations

• The planned structural heart consultation is appropriate but should occur after 3-6 months of optimized GDMT to accurately assess residual MR severity. 1, 2
• Consider heart failure specialist referral if: unable to tolerate GDMT uptitration, persistent NYHA class III-IV symptoms despite optimal therapy, worsening renal function, recurrent hospitalizations, or systolic blood pressure <90 mm Hg. 1
• Given LVEF 40-45% and persistent symptoms, reassess for ICD candidacy if LVEF remains ≤35% after 3 months of optimal GDMT. 1

Common Pitfalls to Avoid

• Do not defer SGLT2 inhibitor initiation—this is a Class 2a recommendation for HFmrEF and should be started immediately alongside other GDMT. 1, 2
• Do not use non-evidence-based beta-blockers (atenolol, propranolol)—only metoprolol succinate, carvedilol, or bisoprolol reduce mortality in heart failure. 1, 3
• Do not proceed with TEER or mitral valve surgery without first optimizing GDMT for adequate duration—medical therapy improves secondary MR and may eliminate need for intervention. 1, 2
• Do not withhold MRA due to "borderline" potassium—K+ 4.5 mEq/L is safe for initiation; only avoid if K+ >5.0 mEq/L or eGFR <30 mL/min/1.73m². 2
• Do not reduce or discontinue GDMT for asymptomatic or mildly symptomatic low blood pressure—this compromises long-term outcomes. 5
• Do not overlook medication interactions—review all medications for NSAIDs, calcium channel blockers, and other agents that worsen heart failure. 1

Medication Sequencing Strategy

Initiate simultaneously at low doses: SGLT2 inhibitor (full dose), MRA (low dose), continue beta-blocker (already started), and add ACE inhibitor/ARB/ARNI (low dose). 2, 3

This approach maximizes early benefit while minimizing risk of hypotension or electrolyte disturbances, with each medication class providing incremental mortality and morbidity reduction in HFmrEF. 1, 4, 6