What is the optimal management plan for an elderly female smoker with a history of hypercholesterolemia, newly diagnosed A-fib, and HFmrEF, currently on Xarelto and recently started on metoprolol succinate, with elevated BNP and LDL levels?

Optimal Management Plan for Elderly Female with New-Onset A-fib and HFmrEF

Continue metoprolol succinate as currently prescribed, add an ACE inhibitor or ARB (or preferentially switch to sacubitril/valsartan), add an SGLT2 inhibitor (empagliflozin or dapagliflozin), and intensify statin therapy to achieve LDL <70 mg/dL, while maintaining Xarelto for stroke prophylaxis. 1

Beta-Blocker Optimization

Metoprolol succinate is appropriate and should be continued as it is one of only three beta-blockers proven to reduce mortality in heart failure with reduced ejection fraction (HFrEF), along with bisoprolol and carvedilol. 1 The 2022 ACC/AHA/HFSA guidelines specifically recommend these three agents with Class 1, Level A evidence for patients with current or prior HFrEF symptoms (LVEF ≤40%). 1

• Your patient has HFmrEF (LVEF 45-50%), which falls into a treatment zone where beta-blockers provide benefit for both heart failure and atrial fibrillation rate control. 1
• The current metoprolol succinate dose should be uptitrated to target doses (200 mg daily) as tolerated, monitoring for heart rate, blood pressure, and symptoms. 1
• Consider switching to carvedilol if blood pressure remains elevated, as carvedilol has superior antihypertensive effects due to combined α1-β1-β2-blocking properties compared to metoprolol succinate or bisoprolol. 1

RAAS Inhibition - Critical Missing Component

This patient urgently needs initiation of RAAS inhibition therapy, which is conspicuously absent from the current regimen. 1

• First-line recommendation: Start sacubitril/valsartan (ARNI) at 24/26 mg twice daily, uptitrating to target dose of 97/103 mg twice daily. 1 The 2022 ACC/AHA/HFSA guidelines give sacubitril/valsartan a Class 1A recommendation for HFrEF/HFmrEF to reduce mortality and hospitalization. 1
• Alternative if ARNI not feasible: Start an ACE inhibitor (e.g., lisinopril 2.5-5 mg daily, target 20-40 mg daily) or ARB (e.g., losartan 25 mg daily, target 50-100 mg daily). 1
• Critical safety consideration: Screen for history of angioedema before initiating any RAAS inhibitor, as this is an absolute contraindication. 1 If starting ARNI, ensure 36-hour washout period if patient was previously on ACE inhibitor. 1

SGLT2 Inhibitor - Disease-Modifying Therapy

Add an SGLT2 inhibitor immediately - this represents the most recent breakthrough in HFmrEF management. 1

• Recommended agents: Empagliflozin 10 mg daily or dapagliflozin 10 mg daily. 1
• SGLT2 inhibitors have Class 1A evidence for reducing heart failure hospitalizations and cardiovascular death in HFmrEF, independent of diabetes status. 1
• These agents provide modest blood pressure lowering (additional benefit given her hypercholesterolemia risk profile) and are well-tolerated. 1
• No dose adjustment needed for her renal function based on the clinical scenario presented. 1

Mineralocorticoid Receptor Antagonist Consideration

Consider adding spironolactone 12.5-25 mg daily, particularly given her LVEF is in the lower range of HFmrEF (45-50%). 1

• MRAs have proven mortality benefit in HFrEF and show benefit in HFmrEF patients with LVEF closer to 45%. 1, 2
• Monitor potassium closely - check baseline potassium and renal function before initiation, then recheck at 1 week and 1 month. 1
• Discontinue if potassium rises above 5.5 mEq/L despite dietary modification. 1
• Given her history of hypokalemia (K+ 2.2 at presentation), close monitoring is essential but MRA may actually help prevent recurrent hypokalemia. 1

Lipid Management Intensification

Intensify statin therapy to achieve LDL <70 mg/dL (current LDL 110 mg/dL is above target for a patient with heart failure and cardiovascular risk factors). 1

• Start high-intensity statin therapy (e.g., atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily). 1
• Recheck lipid panel in 4-6 weeks and consider adding ezetimibe 10 mg daily if LDL remains >70 mg/dL. 1

Anticoagulation Management

Continue Xarelto (rivaroxaban) for stroke prophylaxis - this is appropriate for atrial fibrillation. 3, 4

• Standard dosing for non-valvular atrial fibrillation is 20 mg once daily with evening meal. 3, 4
• Dose adjustment required if CrCl 15-50 mL/min: reduce to 15 mg once daily. 3 Check renal function at next visit to confirm appropriate dosing.
• Monitor for bleeding complications, particularly given her age and multiple medications. 3
• No routine coagulation monitoring required with rivaroxaban, unlike warfarin. 4

Smoking Cessation - Critical Intervention

Aggressive smoking cessation counseling and pharmacotherapy must be prioritized as smoking dramatically increases cardiovascular risk and heart failure progression. 1

• Offer combination nicotine replacement therapy plus varenicline or bupropion. 1
• Smoking increases angioedema risk with RAAS inhibitors, making cessation even more critical. 1

Monitoring Strategy

Structured follow-up schedule:

• 2 weeks: Check BMP (potassium, creatinine), blood pressure, heart rate, symptoms after initiating RAAS inhibitor and SGLT2 inhibitor. 1
• 4-6 weeks: Recheck BMP, uptitrate medications toward target doses, check lipid panel. 1
• 3 months: Repeat echocardiogram to assess response to guideline-directed medical therapy (GDMT), check BNP, BMP. 1
• Every 3-6 months: Monitor BNP trends, renal function, electrolytes, and clinical status. 1

BNP Interpretation

The mildly elevated BNP of 111 pg/mL is consistent with HFmrEF and atrial fibrillation. 5, 6

• BNP levels are elevated in both heart failure and atrial fibrillation, making interpretation complex in patients with both conditions. 6
• Use BNP for trend monitoring rather than absolute values - decreasing BNP suggests treatment response. 1, 5
• Interestingly, patients with lower baseline natriuretic peptides may show greater response to spironolactone therapy. 5

Critical Pitfalls to Avoid

• Do not delay RAAS inhibition - this is the most significant gap in current management and delays increase mortality risk. 1
• Do not use non-evidence-based beta-blockers (e.g., metoprolol tartrate, atenolol) - only bisoprolol, carvedilol, and metoprolol succinate have mortality benefit. 1, 7
• Avoid calcium channel blockers (except dihydropyridines for refractory hypertension after optimizing GDMT) as they can worsen heart failure. 1
• Do not withhold beta-blockers due to atrial fibrillation - they provide dual benefit for rate control and heart failure mortality reduction. 1, 8
• Monitor for hyperkalemia closely when combining RAAS inhibitor with MRA, especially in elderly patients. 1