What are the key investigations and management options for a patient with pulmonary hypertension, including medications and non-medical interventions?

Pulmonary Hypertension: Key Investigations and Management

Key Investigations

Initial Screening

• Transthoracic echocardiography is the first-line screening test to estimate pulmonary artery pressure using peak tricuspid regurgitant velocity (TRV), assess right ventricular function, right atrial/ventricular enlargement, pericardial effusion, and identify left-sided heart abnormalities 1, 2
• Electrocardiogram (ECG) at baseline and every 3-6 months to detect right ventricular strain patterns 1
• Chest radiography to evaluate cardiac silhouette and pulmonary vasculature 3

Essential Diagnostic Tests

• Right heart catheterization is mandatory to confirm diagnosis (mean PAP >20 mmHg defines PH), establish hemodynamic classification, determine severity, and guide all treatment decisions 1, 2
• Ventilation-perfusion (V/Q) lung scan must be performed in all patients with pulmonary arterial hypertension to rule out chronic thromboembolic pulmonary hypertension (CTEPH)—a normal scan effectively excludes CTEPH with 90-100% sensitivity 1, 2
• Do not rely on CT pulmonary angiography alone to exclude CTEPH as it has insufficient sensitivity and may miss the diagnosis 2

Laboratory Assessment

• Basic laboratory tests (every 3-6 months): complete blood count, serum creatinine, sodium, potassium, liver enzymes (AST/ALT), bilirubin, BNP/NT-proBNP 1
• Extended laboratory tests (every 6-12 months): TSH, troponin, uric acid, iron studies 1
• HIV and connective tissue disease screening in all patients with unexplained pulmonary arterial hypertension 1
• Arterial blood gas analysis to assess oxygenation 2

Functional Assessment

• 6-minute walk test (6MWT) with Borg dyspnea score at baseline and every 3-6 months for exercise capacity and prognostic stratification 1, 2
• Cardiopulmonary exercise testing (CPET) at baseline, every 6-12 months, and with clinical changes 1
• Pulmonary function tests (spirometry, lung volumes, DLCO) to evaluate for underlying lung disease 2

Specialized Testing

• Vasoreactivity testing is required in patients with idiopathic PAH, heritable PAH, and drug-induced PAH using short-acting agents (IV epoprostenol, adenosine, or inhaled nitric oxide) to identify candidates for calcium channel blocker therapy 1
• Abdominal ultrasound to screen for portal hypertension in unexplained cases 2
• Genetic testing and counseling for relatives of patients with familial/heritable PAH 2

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Management

Medical Therapies

Initial Treatment for PAH (Group 1)

• Initial monotherapy with approved drugs is recommended for treatment-naïve, low or intermediate risk patients 1
• Initial oral combination therapy is recommended for treatment-naïve, low or intermediate risk patients 1
• Approved medication classes include:
  • Endothelin receptor antagonists (bosentan) 1
  • Phosphodiesterase type 5 inhibitors 4
  • Soluble guanylate cyclase stimulators 4
  • Prostacyclin analogues (IV epoprostenol, subcutaneous treprostinil, inhaled iloprost, oral beraprost) 1, 5
  • Prostacyclin receptor agonists 4

Calcium Channel Blockers

• Only use calcium channel blockers in patients demonstrating acute vasoreactivity (defined as fall in mean PAP ≥10 mmHg to ≤40 mmHg with increased or unchanged cardiac output) 1
• Never use calcium channel blockers empirically without documented vasoreactivity testing, as this can be harmful 1, 2

Sequential Therapy

• Sequential combination therapy is recommended for patients with inadequate response to initial monotherapy or initial double combination therapy 1

IV Epoprostenol Specifics

• Initiate at 2 ng/kg/min and increase in 2 ng/kg/min increments every 15 minutes until dose-limiting effects occur 5
• Administer via continuous IV infusion through a central venous catheter using an ambulatory infusion pump 5
• Never abruptly discontinue or reduce dose due to risk of rebound pulmonary hypertension 5

Non-Medical Management

General Measures

• Pregnancy must be avoided in all patients with PAH due to high maternal and fetal mortality risk 1, 5
• Supervised physical activity and pulmonary rehabilitation to improve functional capacity 3
• Oxygen therapy for patients with hypoxemia 3
• Diuretics for volume management in right heart failure 3
• Anticoagulation should be considered, particularly in idiopathic PAH and heritable PAH 3

Surgical Interventions

• Pulmonary endarterectomy in deep hypothermia circulatory arrest is the treatment of choice for patients with CTEPH and must be performed at experienced centers 1
• Assessment of operability and treatment decisions (surgery, medical therapy, or balloon pulmonary angioplasty) must be made by a multidisciplinary expert team 1
• Lung or heart-lung transplantation should be considered for patients with WHO functional class III-IV symptoms refractory to medical therapy; bilateral lung transplant is the procedure of choice 1
• Balloon atrial septostomy may be considered in selected cases 1

Multidisciplinary Care

• Care must be provided by a multidisciplinary team including cardiology and respiratory medicine physicians, clinical nurse specialists, radiologists, and psychological/social work support with appropriate on-call expertise 1

Follow-Up Strategy

• Regular assessments every 3-6 months in stable patients using a comprehensive panel: functional class determination, ECG, 6MWT, basic labs, BNP/NT-proBNP 1
• Goal is achievement and maintenance of low-risk profile as defined by WHO functional class I-II, 6MWD >440m, BNP <50 ng/L, right atrial area <18 cm², cardiac index ≥2.5 L/min/m², and RAP <8 mmHg 1

Critical Contraindications

• PAH-approved therapies are NOT recommended for patients with pulmonary hypertension due to left heart disease (Group 2) or lung diseases (Group 3) 1

Key Pitfalls to Avoid

• Never perform lung biopsy routinely due to high risk; reserve only when tissue diagnosis is essential 2
• Always perform V/Q scanning before relying on CT alone to exclude CTEPH 2
• Closely monitor all dosing changes of PAH-specific therapies to avoid complications 5