What is the best management plan for a 68-year-old female with heart failure with preserved ejection fraction (HFpEF), atrial fibrillation (A-fib), type 2 diabetes mellitus (DM 2), obstructive sleep apnea (OSA) on continuous positive airway pressure (CPAP) therapy, anxiety, fibromyalgia, and a history of post-COVID microvascular heart disease, presenting with increased shortness of breath, weight gain, and fatigue?

Management of HFpEF with Atrial Fibrillation and Multiple Comorbidities

Initiate SGLT2 inhibitors (dapagliflozin or empagliflozin) immediately as first-line disease-modifying therapy, as they reduce heart failure hospitalizations and cardiovascular death by approximately 20% in HFpEF patients, including those with atrial fibrillation. 1, 2, 3, 4

Immediate Pharmacological Priorities

Disease-Modifying Therapy (Start Now)

• Begin SGLT2 inhibitor (dapagliflozin 10mg daily or empagliflozin 10mg daily) as the cornerstone therapy, regardless of diabetes status, as this is the only Class 2a recommendation with mortality/morbidity benefit in HFpEF 1, 2, 3
• Add spironolactone 12.5-25mg daily (mineralocorticoid receptor antagonist), particularly given her LVEF is at the lower end of preserved range and she has severe left atrial dilation—monitor potassium and renal function closely 1, 2
• Consider sacubitril/valsartan 24/26mg twice daily (ARNI) as she is female and has LVEF in the lower preserved range, though this is a weaker recommendation (Class 2b) 1, 2

Congestion Management

• Optimize loop diuretic dosing aggressively given her 20-pound weight gain and elevated BNP—use the lowest effective dose to achieve euvolemia, but don't undertreat 2, 4
• Increase current diuretic dose before adding combination therapy if inadequate response 2
• Monitor daily weights with clear instructions to call if gain >2-3 pounds in 24 hours or >5 pounds in one week 1

Atrial Fibrillation Management

Rate Control Strategy:

• Use beta-blockers as first-line for rate control in HFpEF with compensated heart failure—this is Class I recommendation 1, 3
• Target resting heart rate <80 bpm and exercise heart rate <110 bpm 1
• Avoid non-dihydropyridine calcium channel blockers (diltiazem/verapamil) given her history of decompensated HF, despite being acceptable in stable HFpEF 1
• Digoxin can be added to beta-blocker if rate control inadequate (Class IIa) 1

Anticoagulation:

• Continue current anticoagulation—calculate CHA₂DS₂-VASc score (likely ≥4 with HF, age 68, DM, female = minimum 5 points) making anticoagulation mandatory 3, 5

Rhythm Control Consideration:

• Refer to electrophysiology for catheter ablation evaluation, as she has symptomatic paroxysmal/persistent AF with prior 2:1 flutter, severely dilated left atrium, and HFpEF—ablation-based rhythm control shows superior outcomes compared to rate control in this population 5, 6
• This is particularly important given her RVR episodes requiring hospitalization and troponin elevation from tachycardia 1, 5

Comorbidity Optimization

Diabetes Management

• Prioritize SGLT2 inhibitor for glycemic control as it provides dual benefit for both diabetes and HFpEF 2
• Continue metformin if renal function permits (eGFR >30) 1
• Avoid thiazolidinediones (pioglitazone) as they worsen fluid retention in HF 1

Hypertension Control

• Target blood pressure <130/80 mmHg as this is Class I recommendation in HFpEF 1, 2, 7
• Current beta-blocker for AF rate control will assist with BP management 1
• Add ACE inhibitor or ARB if BP remains elevated after optimizing above therapies (Class 2b in HFpEF) 1

OSA Management

• Ensure CPAP compliance is documented and optimized, as untreated OSA worsens HFpEF outcomes and contributes to AF burden 1
• Verify adequate CPAP pressure settings and mask fit 1

Anxiety/Fibromyalgia

• Avoid medications that elevate blood pressure (such as SNRIs like desvenlafaxine) as uncontrolled hypertension worsens HFpEF prognosis 7
• Consider SSRIs with more favorable cardiovascular profile if antidepressant needed 7

Non-Pharmacological Interventions

• Prescribe supervised cardiac rehabilitation with exercise training program—this provides clinically meaningful improvements in functional capacity and quality of life (Class I recommendation) 1, 2, 4
• Sodium restriction to <2-3 grams daily to reduce congestive symptoms 2, 4
• Weight loss program targeting 5-10% body weight reduction given obesity and recent 20-pound gain—diet-induced weight loss improves functional capacity in HFpEF 4
• Provide structured HF self-care education including medication adherence, dietary restrictions, symptom monitoring, and when to seek care 4

Diagnostic Workup Priorities

Immediate Testing

• Repeat echocardiogram to reassess:

  • Current LVEF and any interval change
  • Severity of pulmonary hypertension (previously mild)
  • Right ventricular function given pulmonary hypertension
  • Diastolic function parameters and filling pressures 1

• Nuclear stress test follow-up for the previously noted septal defect, though cardiac catheterization showed only mild CAD—this helps risk stratify and guide activity recommendations 1

• Labs to obtain:

  • NT-proBNP or BNP for baseline (already elevated per note)
  • Complete metabolic panel with eGFR and electrolytes
  • Thyroid function (TSH) given family history of thyroid cancer and unexplained symptoms
  • Hemoglobin A1c for diabetes control
  • Serum and urine protein electrophoresis with immunofixation to screen for cardiac amyloidosis given her age, HFpEF, and severe LA dilation 1

Consider Advanced Testing

• Technetium pyrophosphate (99mTc-PYP) scan if amyloidosis suspected based on clinical features (severe LA dilation, concentric LVH, HFpEF in elderly female) 1
• Cardiopulmonary exercise testing (CPET) to objectively quantify functional capacity and guide exercise prescription 1

Monitoring Strategy

• Follow-up in 2-4 weeks after initiating SGLT2 inhibitor and optimizing diuretics to assess:

  • Symptom improvement and weight trajectory
  • Renal function and electrolytes (especially with MRA)
  • Blood pressure control
  • Heart rate control at rest and with activity 2

• Monthly visits initially until stable on GDMT, then every 3 months 1

• Consider wireless pulmonary artery pressure monitoring if recurrent hospitalizations occur despite optimal medical therapy 2

Critical Pitfalls to Avoid

• Do not delay SGLT2 inhibitor initiation—this is the only therapy with proven mortality benefit and should be started immediately 2, 3
• Avoid excessive diuresis leading to hypotension and prerenal azotemia, which impairs tolerance of other HFpEF medications 2
• Do not use IV beta-blockers or calcium channel blockers if she presents with acute decompensated HF and overt congestion 1
• Do not assume traditional HFrEF medications work in HFpEF—only SGLT2 inhibitors have strong evidence; ACE inhibitors, ARBs, and beta-blockers have weak or no proven benefit for HFpEF specifically 2, 4
• Do not overlook cardiac amyloidosis as a mimic—her age, HFpEF phenotype, and severe LA dilation warrant screening 1, 2

Addressing Psychosocial Stressors

• Refer to social work for caregiver support resources given her burden caring for elderly father and relative with Down syndrome 1
• Integrate palliative care consultation to address goals of care, advance care planning, and symptom management given her complex medical issues and recent grief 1
• Screen for depression with validated tool and treat appropriately with cardiovascular-safe agents 1