What are the symptoms and treatment options for pulmonary hypertension?

Pulmonary Hypertension: Symptoms and Treatment

Clinical Symptoms

The symptoms of pulmonary hypertension are non-specific and primarily reflect progressive right ventricular dysfunction, with exertional dyspnea being the most common presenting complaint. 1

Primary Symptoms (Exertion-Induced)

• Shortness of breath - the cardinal symptom, initially occurring only with exertion 1
• Fatigue and weakness - related to decreased cardiac output 1
• Angina - may occur due to right ventricular ischemia or compression of the left main coronary artery by dilated pulmonary arteries 1
• Syncope - particularly with exertion, indicating severe disease 1

Less Common Symptoms

• Dry cough - occurs in some patients 1
• Exercise-induced nausea and vomiting 1
• Hemoptysis - from rupture of hypertrophied bronchial arteries 1
• Hoarseness - caused by compression of the left recurrent laryngeal nerve by dilated pulmonary arteries 1

Advanced Disease Manifestations

• Symptoms at rest - occur only in advanced cases 1
• Abdominal distension - from hepatic congestion and ascites 1, 2
• Ankle edema - indicating right ventricular failure 1, 2

Physical Examination Findings

• Left parasternal lift - indicating right ventricular hypertrophy 1
• Accentuated pulmonary component of S2 1
• Right ventricular S3 gallop 1, 2
• Pansystolic murmur of tricuspid regurgitation 1
• Elevated jugular venous pressure with prominent V waves 1, 2
• Hepatomegaly with pulsatile liver 1, 2
• Peripheral edema and cool extremities 1, 2
• Wheeze and crackles are usually absent - their presence suggests alternative diagnoses 1

Treatment Algorithm

Step 1: General Measures and Supportive Therapy

All patients with pulmonary arterial hypertension require comprehensive general measures including pregnancy avoidance, immunizations, and psychosocial support. 1

Mandatory Recommendations

• Avoid pregnancy - remains associated with substantial mortality (Class I recommendation) 1
• Immunization against influenza and pneumococcal infection (Class I recommendation) 1
• Psychosocial support - including patient support groups (Class I recommendation) 1

Strongly Recommended Measures

• Supervised exercise training - for physically deconditioned patients already on medical therapy (Class IIa recommendation) 1
• In-flight oxygen - for WHO Functional Class III-IV patients or those with arterial oxygen pressure <60 mmHg (Class IIa recommendation) 1
• Epidural over general anesthesia - for elective surgery when possible (Class IIa recommendation) 1

Contraindicated Activities

• Excessive physical activity leading to distressing symptoms (Class III recommendation) 1

Step 2: Initial Pharmacologic Therapy

Treatment selection depends on acute vasoreactivity testing results and prognostic risk stratification. 1

For Vasoreactive Patients (Positive Acute Vasoreactivity Test)

• High-dose calcium channel blockers (CCBs) - for the minority of patients demonstrating acute vasoreactivity 1
• Long-term responders to CCBs have improved outcomes, including during pregnancy 1

For Non-Vasoreactive Patients (Majority)

Initiate PAH-specific therapy based on disease severity:

• Prostacyclin pathway agents:

  • Epoprostenol (intravenous) - treatment of choice for WHO Functional Class III-IV disease 3
  • Initial dose: 2 ng/kg/min, increased in 2 ng/kg/min increments every 15 minutes until dose-limiting effects occur 3
  • Administered via continuous IV infusion through central venous catheter 3
  • Demonstrated improvements in symptoms, hemodynamics, and survival 4

• Phosphodiesterase-5 (PDE5) inhibitors - for appropriate patients 5

• Endothelin receptor antagonists - for appropriate patients 5

Step 3: Response Assessment and Escalation

If inadequate response to initial therapy, escalate to combination therapy with approved drugs from different pathways. 1

• Reassess at regular intervals using functional class, exercise capacity, and hemodynamics 1
• Consider combination therapy with drugs targeting different pathways 1
• Evaluate for lung transplantation in patients not responding to maximal medical therapy 1, 4

Step 4: Advanced Interventions

For refractory disease despite maximal medical therapy:

• Lung transplantation - single lung, double lung, or heart-lung transplant (single lung currently preferred) 4
• Atrial septostomy - in select cases 5
• Balloon pulmonary angioplasty - for chronic thromboembolic pulmonary hypertension only, performed exclusively in high-volume expert centers 1

Critical Management Pitfalls

Emergency Department Considerations

• Avoid fluid boluses in hypotensive patients - use vasopressors and inotropes instead to prevent right ventricular ischemia 6
• Avoid intubation when possible - hypoxemia and hypercapnia worsen right ventricular function 6
• Never abruptly discontinue pulmonary vasodilators - can cause rapid right ventricular failure and death 3, 6
• Early consultation with pulmonary hypertension specialist - patients may require pulmonary artery catheter, inhaled vasodilators, or mechanical support 6

Diagnostic Considerations

• Digital clubbing suggests alternative diagnoses - consider pulmonary veno-occlusive disease, congenital heart disease, interstitial lung disease, or liver disease rather than idiopathic PAH 1, 2
• Normal ECG does not exclude severe disease - ECG has inadequate sensitivity (55%) and specificity (70%) for screening 1
• Right heart catheterization is mandatory - for definitive diagnosis showing mean pulmonary arterial pressure ≥25 mmHg at rest 1

Treatment-Specific Warnings

• Epoprostenol requires continuous infusion - do not mix with other parenteral medications 3
• Careful volume management is imperative - patients are often volume overloaded but require cautious diuresis 6
• Group 5 pulmonary hypertension requires disease-specific therapy - treat the underlying condition, not just the pressure; PAH-approved drugs lack evidence and may worsen venous component 1, 7