Respiratory · Year 1 · from Respiratory

Case 2: Pulmonary Arterial Hypertension - Progressive Dyspnea

Clinical Image

Source: Wikimedia Commons - Pulmonary hypertension - CC BY-SA 3.0

Patient Presentation

A 35-year-old woman presents with progressive exertional dyspnea over the past year. She initially noticed breathlessness when climbing stairs, but now she becomes short of breath walking short distances. She also reports occasional chest discomfort with exertion and has had two episodes of near-syncope during physical activity in the past month. She denies any prior lung or heart disease.

Demographics

  • Age: 35 years
  • Sex: Female
  • Past Medical History: Raynaud phenomenon, positive ANA (followed but no definitive diagnosis)
  • Medications: None
  • Family History: Sister with "lupus"

Chief Complaint

Progressive exertional dyspnea, near-syncope with exertion

Physical Examination

  • Blood pressure: 108/72 mmHg
  • Heart rate: 92 bpm at rest
  • Respiratory rate: 18/min at rest
  • Oxygen saturation: 94% on room air (drops to 86% with ambulation)
  • General: Thin, appears fatigued
  • Neck: Elevated JVP with prominent a-wave
  • Cardiovascular: RV heave, loud P2 (palpable), grade 3/6 holosystolic murmur at left lower sternal border (TR), right-sided S4
  • Respiratory: Clear
  • Extremities: Mild peripheral edema, nail fold capillary changes consistent with scleroderma spectrum

Workup

  • ECG: Right axis deviation, RV hypertrophy, R > S in V1
  • Chest X-ray: Enlarged main and hilar pulmonary arteries, clear lung fields, RV enlargement
  • BNP: 420 pg/mL
  • ANA: Positive (1:640, nucleolar pattern)
  • Anti-Scl-70: Positive
  • PFTs: Mildly reduced DLCO (52% predicted), normal spirometry
  • V/Q scan: Normal (excludes CTEPH)
  • Echocardiography: Estimated RVSP 75 mmHg, RV dilation and hypertrophy, flattened interventricular septum
  • Right heart catheterization:
  • Mean PAP: 52 mmHg (PH confirmed)
  • PCWP: 10 mmHg (pre-capillary PH)
  • PVR: 12 Wood units (elevated)
  • Cardiac output: 3.8 L/min (reduced)
  • Acute vasodilator challenge: Negative (no acute responders)

Diagnosis

WHO Group 1 Pulmonary Arterial Hypertension associated with Systemic Sclerosis

Treatment

  1. Risk stratification: Intermediate-high risk (WHO FC III, elevated BNP, near-syncope)
  2. Combination PAH therapy (initial triple therapy considered for high-risk):
  • Endothelin receptor antagonist (ambrisentan or macitentan)
  • PDE-5 inhibitor (tadalafil) or sGC stimulator (riociguat)
  • Consider prostacyclin analog if needed
  1. Diuretics for fluid management
  2. Supplemental oxygen with exercise
  3. Anticoagulation (controversial; often used in IPAH, less clear in CTD-PAH)
  4. Contraception counseling (pregnancy contraindicated - 30-50% mortality)
  5. Referral to expert PAH center
  6. Lung transplant evaluation if disease progression

Physiological Principles Demonstrated

  • PAH pathophysiology: Pulmonary vascular remodeling (intimal proliferation, medial hypertrophy, in situ thrombosis) increases pulmonary vascular resistance, leading to RV pressure overload and eventual RV failure.
  • CTD-PAH association: Systemic sclerosis has the highest prevalence of PAH among connective tissue diseases (~15%), particularly in those with limited cutaneous disease.
  • Exertional syncope significance: Indicates inability to augment cardiac output with exercise due to fixed pulmonary vascular resistance - a poor prognostic sign.
  • Right heart catheterization importance: Gold standard for diagnosis; distinguishes pre-capillary (PAH) from post-capillary (left heart disease) PH based on PCWP.

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