How should I manage a 57‑year‑old woman with heart failure with preserved ejection fraction, moderate mitral stenosis, paroxysmal atrial fibrillation, poorly controlled type 2 diabetes, hypertension, hyperlipidemia with statin intolerance, COPD, recent sepsis, currently on dapagliflozin (Farxiga), bumetanide 1 mg twice daily, and rivaroxaban (Xarelto) to be switched to warfarin, who now has recent weight gain, peripheral edema, moderately elevated BNP, normal potassium and mild renal impairment, and a negative nuclear stress test?

Management of HFpEF with Multiple Comorbidities and Recent Decompensation

Continue dapagliflozin (Farxiga) and bumetanide 1 mg twice daily, switch rivaroxaban to warfarin, initiate semaglutide (Ozempic) as planned, start PCSK9 inhibitor (Repatha) for statin-intolerant hyperlipidemia, and closely monitor volume status with daily weights and BNP trending.

Guideline-Directed Medical Therapy for HFpEF

SGLT2 Inhibitor Continuation (Dapagliflozin)

• Dapagliflozin is the cornerstone therapy and must be continued as it is one of the few evidence-based treatments for HFpEF that reduces heart failure events and improves symptoms 1.
• SGLT2 inhibitors are unique in that they do not affect blood pressure, heart rate, or potassium levels, and require no dose adjustment or up-titration 1.
• Dapagliflozin has proven beneficial in patients with moderate kidney dysfunction (eGFR ≥20 mL/min/1.73 m²) and demonstrates long-term kidney protection despite mild and transient drops in eGFR after initiation 1.
• The effectiveness of dapagliflozin is maintained in vulnerable populations including those with signs of congestion, recent HF hospitalization, and the elderly 1.
• In HFpEF specifically, dapagliflozin significantly improved Kansas City Cardiomyopathy Questionnaire scores (5.8 points improvement), 6-minute walk distance (20.1 m improvement), and reduced weight after 12 weeks 2.
• The mild elevation in creatinine (1.5 mg/dL from 1.2 mg/dL) with declining BNP (from 1400 to 900 pg/mL, now 177 pg/mL) suggests successful decongestion rather than true tubular injury, and worsening kidney function in the setting of successful decongestion is associated with better outcomes than failure to decongest 1.

Diuretic Management for Congestion

• Continue bumetanide 1 mg twice daily given the recent 8-pound weight gain over 10 days and recurrent lower extremity edema 1.
• The current BNP of 177 pg/mL (down from 2 days ago at 150 pg/mL) indicates improved but still present congestion requiring ongoing diuretic therapy 1.
• Aggressive decongestion is appropriate even if it causes transient worsening of kidney function, as long as the patient maintains adequate organ perfusion 1.
• Monitor daily weights and instruct the patient to increase bumetanide to 2 mg twice daily for 3 days if weight increases by more than 2-3 pounds over 2 days 1.

Anticoagulation Strategy for Atrial Fibrillation

Switch from Rivaroxaban to Warfarin

• Proceed with the planned switch from rivaroxaban (Xarelto) to warfarin given the moderate mitral stenosis 1.
• Patients with chronic HF with paroxysmal atrial fibrillation and additional risk factors (this patient has hypertension, diabetes, and age >75 years) require chronic anticoagulation 1.
• While the 2013 ACC/AHA guidelines state that anticoagulant selection should be individualized, warfarin is traditionally preferred in moderate-to-severe mitral stenosis due to limited data on DOACs in valvular heart disease 1.
• Target INR should be 2.0-3.0 with close monitoring during the transition period 1.

GLP-1 Receptor Agonist Therapy

Initiate Semaglutide (Ozempic)

• Start semaglutide as planned by the endocrinologist given the combination of poorly controlled type 2 diabetes, heart failure, and paroxysmal atrial fibrillation 1.
• GLP-1 receptor agonists provide cardiovascular benefits in patients with diabetes and heart failure, including weight reduction which will help with volume management 1.
• Begin with semaglutide 0.25 mg subcutaneously once weekly for 4 weeks, then increase to 0.5 mg weekly, with potential further titration to 1 mg weekly based on glycemic control and tolerability 1.

Lipid Management with Statin Intolerance

PCSK9 Inhibitor (Repatha/Evolocumab)

• Initiate evolocumab (Repatha) 140 mg subcutaneously every 2 weeks or 420 mg monthly for the statin-intolerant patient with elevated LDL and triglycerides 1.
• PCSK9 inhibitors are the preferred alternative for patients with statin intolerance and established cardiovascular disease 1.
• The elevated triglycerides should also be addressed with optimization of diabetes control through semaglutide, which will provide additional triglyceride-lowering effects 1.

Monitoring Strategy and Follow-Up

Short-Term Monitoring (1 Month)

• Recheck comprehensive metabolic panel, lipid profile, BNP, and INR (once on warfarin) in 1 month as planned 1.
• Monitor for hyperkalemia given the peaked T waves noted on previous EKG, though current potassium is within normal limits 1.
• Assess volume status with daily weights and clinical examination for peripheral edema 1.
• Review INR weekly until therapeutic range is achieved and stable on warfarin 1.

Medium-Term Monitoring (4-6 Months)

• Repeat echocardiogram in 4-6 months to reassess the moderate mitral stenosis and left ventricular function 1.
• The nuclear stress test showed no evidence of ischemia or prior infarct, so no further cardiac catheterization is needed unless symptoms change 1.
• Reassess need for diuretic adjustment based on BNP trends, weight stability, and symptom burden 1.

Critical Pitfalls to Avoid

Do Not Discontinue SGLT2 Inhibitor

• Never stop dapagliflozin due to mild creatinine elevation in the setting of successful decongestion, as this represents hemodynamic changes rather than tubular injury 1.
• The mild decline in eGFR after SGLT2 inhibitor initiation is expected and transient, with long-term kidney protective effects 1, 3.

Avoid Calcium Channel Blockers

• Do not use diltiazem or verapamil for rate control in this patient with HFpEF, as they increase the risk of heart failure worsening and hospitalization 4.
• If additional rate control is needed for atrial fibrillation, optimize beta-blocker dosing (metoprolol) or consider digoxin or amiodarone 5, 4.

Monitor for Hypotension

• Given the multiple medications that can affect blood pressure, assess for orthostatic hypotension at each visit by measuring blood pressure both supine and standing 1.
• Hypotension associated with minor symptoms is not a reason to withhold or reduce heart failure medications 1.

Warfarin-Drug Interactions

• Be vigilant for drug interactions with warfarin, particularly if antibiotics or antifungals are prescribed for future infections 1.
• Ensure consistent vitamin K intake and avoid significant dietary changes that could affect INR stability 1.

Addressing the Moderate Mitral Stenosis

Surveillance and Intervention Thresholds

• The moderate mitral stenosis requires serial echocardiographic monitoring every 6-12 months to assess for progression 1.
• If the patient develops worsening dyspnea, declining functional capacity, or evidence of pulmonary hypertension on future echocardiograms, consider referral to a structural heart disease specialist for evaluation of percutaneous mitral balloon valvuloplasty or surgical intervention 1.
• Maintain strict rate control of atrial fibrillation to optimize diastolic filling time across the stenotic mitral valve 5, 4.