Pharmacotherapy Case: Pulmonary Arterial Hypertension (PAH) by Dr. Nehad Ahmed

Age: 45 years

Gender: Female

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Subjective Data

• Chief Complaint: "I’ve been increasingly short of breath over the past year, even when resting. My ankles started swelling last month."

• History of Present Illness:

  • Progressive dyspnea on exertion (now NYHA/WHO Functional Class III).

  • Fatigue and intermittent substernal chest pain with exertion.

  • Recent onset of bilateral lower extremity edema.

  • Denies syncope, cough, or hemoptysis.

• Past Medical History: Raynaud’s phenomenon (no formal diagnosis of connective tissue disease).

• Medications: NSAIDs PRN for Raynaud’s-related pain.

• Social History: Non-smoker, works as an office manager, no illicit drug use.

• Family History: No known PAH or cardiovascular diseases.

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Objective Data

• Vital Signs:

  • BP: 110/70 mmHg | HR: 98 bpm | RR: 20 breaths/min | SpO2: 92% (RA).

• Physical Exam:

  • Cardiovascular: Loud P2 heart sound, right ventricular heave, jugular venous distension.

  • Respiratory: Clear lung fields bilaterally.

  • Extremities: 2+ pitting edema to mid-calf.

• Diagnostic Testing:

  • Echocardiogram: Right ventricular hypertrophy, estimated RVSP 65 mmHg, normal LV function.

  • Right Heart Catheterization (RHC):

    • Mean pulmonary arterial pressure (mPAP): 48 mmHg.

    • Pulmonary capillary wedge pressure (PCWP): 10 mmHg.

    • Pulmonary vascular resistance (PVR): 12 Wood units.

  • Labs: BNP 450 pg/mL (elevated), normal LFTs, negative HIV/hepatitis serology.

  • 6-Minute Walk Distance (6MWD): 320 meters.

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Assessment

• Diagnosis: Idiopathic Pulmonary Arterial Hypertension (WHO Group 1), Intermediate-Risk (ESC/ERS 2022 Guidelines).

  • Supporting Evidence:

    • mPAP >25 mmHg, PCWP ≤15 mmHg, elevated PVR.

    • WHO Functional Class III, 6MWD <400 meters, elevated BNP.

    • Exclusion of secondary causes (no CTD, thromboembolism, or lung disease).

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Pharmacotherapy Plan

1. Dual Oral Therapy (Initial Combination):

   • Ambrisentan (Endothelin Receptor Antagonist): 10 mg PO daily.
     Rationale: Targets endothelin pathway to reduce vasoconstriction.

   • Tadalafil (Phosphodiesterase-5 Inhibitor): 40 mg PO daily.
     Rationale: Enhances NO-mediated vasodilation.

2. Adjunctive Therapies:

   • Furosemide: 20 mg PO daily PRN edema.

   • Anticoagulation: Apixaban 5 mg PO BID (if no contraindications after bleeding risk assessment).

3. Non-Pharmacologic Interventions:

   • Oxygen Therapy: Titrate to maintain SpO2 ≥92%.

   • Pulmonary Rehabilitation: Referral for supervised exercise program.

   • Dietary Counseling: Low-sodium diet for volume management.

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Follow-Up/Monitoring

• 1 Month:

  • Assess dyspnea, edema, and functional status (repeat 6MWD).

  • Monitor BNP, renal function, and LFTs (ambrisentan requires monthly LFTs initially).

• 3 Months:

  • Repeat RHC if no clinical improvement.

  • Consider adding prostacyclin analog (e.g., treprostinil) if high-risk features emerge.

• Ongoing:

  • Annual echocardiogram and 6MWD.

  • Screen for connective tissue disease (ANA, anti-centromere antibodies).

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Education

• Medication Adherence: Stress importance of daily therapy to delay progression.

• Symptom Recognition: Report syncope, worsening edema, or chest pain immediately.

• Lifestyle Modifications: Avoid pregnancy (teratogenic medications), high altitudes, and heavy exertion.

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Outcome Goals

• Short-Term: Improve 6MWD to >380 meters, reduce BNP to <300 pg/mL.

• Long-Term: Maintain WHO Functional Class II, prevent right heart failure.