Treatment of Pulmonary Hypertension
Initial Diagnostic Confirmation and Risk Stratification
Right heart catheterization must be performed to confirm the diagnosis of pulmonary arterial hypertension (PAH) and guide all treatment decisions 1, 2. This is non-negotiable as it establishes hemodynamic severity and differentiates between PAH groups that require fundamentally different management approaches.
Vasoreactivity Testing
- Perform acute vasoreactivity testing during right heart catheterization in all patients with idiopathic, heritable, or drug-induced PAH to identify the approximately 10% who may respond to calcium channel blockers 1, 3, 2.
- This testing determines eligibility for high-dose calcium channel blocker therapy, which is first-line for vasoreactive patients 3, 2.
Risk Assessment Parameters
- Systematically evaluate severity using WHO functional class, 6-minute walk distance, BNP/NT-proBNP levels, and echocardiographic parameters to classify patients as low, intermediate, or high risk 1, 3, 2.
- Perform regular follow-up assessments every 3-6 months in stable patients 1, 2.
- The primary treatment goal is achieving and maintaining low-risk status (WHO functional class I-II, 6-minute walk distance >440 meters) 2.
Treatment Algorithm for Pulmonary Arterial Hypertension (WHO Group 1)
For Vasoreactive Patients
- High-dose calcium channel blockers (amlodipine, diltiazem, or nifedipine) are first-line therapy for patients demonstrating acute vasoreactivity 3, 2.
For Non-Vasoreactive Patients at Low or Intermediate Risk
Initial oral combination therapy with ambrisentan plus tadalafil is the preferred first-line approach for treatment-naïve patients, as it significantly delays clinical failure compared to monotherapy 2. This represents the most current evidence-based strategy from the European Society of Cardiology guidelines.
Alternative initial monotherapy options include:
- Phosphodiesterase-5 inhibitors (sildenafil) 3
- Endothelin receptor antagonists 1
- Oral prostacyclin receptor agonist (selexipag) 4
- Soluble guanylate cyclase stimulator (riociguat) 4, 5
For High-Risk PAH Patients
Continuous intravenous epoprostenol must be prioritized as it is the only therapy proven to reduce 3-month mortality 2, 6. This is critical for patients presenting with WHO functional class IV symptoms or evidence of right ventricular failure.
- Treprostinil injection (IV or subcutaneous) is an alternative prostacyclin analogue indicated for PAH to diminish symptoms associated with exercise 7.
- Initial dosing for treprostinil is 1.25 ng/kg/min, reduced to 0.625 ng/kg/min if not tolerated 7.
Sequential Combination Therapy
For patients with inadequate response to initial monotherapy or double combination therapy, add a third agent from a different drug class 1, 2.
- For WHO functional class III-IV patients on endothelin receptor antagonist or PDE5 inhibitor monotherapy, add inhaled treprostinil to improve 6-minute walk distance 4.
- Optimal inhaled treprostinil dosing may require titration up to 9 inhalations (54 mcg) every 6 hours 4.
Treatment for Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Surgical pulmonary endarterectomy in deep hypothermia circulatory arrest is the treatment of choice and potentially curative 1, 5, 8, 9.
- Assessment of operability and decisions regarding alternative treatments (drug therapy or balloon pulmonary angioplasty) must be made by a multidisciplinary team of experts 1.
- For inoperable CTEPH patients, riociguat (soluble guanylate cyclase stimulator) has proven efficacy 5, 9.
Treatment for PH Due to Left Heart Disease or Lung Disease
Do NOT use PAH-approved therapies in patients with pulmonary hypertension due to left heart disease or lung diseases 1, 5, 9. These medications have not been proven safe or effective in these populations and may cause harm.
Essential Supportive Care Measures
Diuretics and Oxygen
- Administer diuretics for all PAH patients with signs of right ventricular failure and fluid retention, monitoring electrolytes and renal function carefully 3, 2.
- Provide continuous long-term oxygen therapy when arterial blood oxygen pressure is consistently <60 mmHg or to maintain saturations >90-91% 3, 2.
Anticoagulation
- Consider oral anticoagulation in idiopathic PAH, heritable PAH, and anorexigen-induced PAH, though evidence is based on observational data 3, 2.
- Anticoagulation should be considered for patients with indwelling catheters for IV prostanoid administration 3.
Pregnancy and Immunizations
- Pregnancy must be avoided in all PAH patients 1, 3.
- Immunization against influenza and pneumococcal pneumonia is recommended 3.
- Patients should avoid high altitude exposure or use supplemental oxygen during air travel to maintain oxygen saturations >91% 3.
Advanced Interventions and Surgical Options
Lung Transplantation
- Consider eligibility for lung transplantation after inadequate response to initial monotherapy or combination therapy 2.
- Referral should occur soon after inadequate response is confirmed on maximal combination therapy 2.
- Lung transplantation and heart-lung transplantation remain important options when medical therapy is unavailable or unsuccessful 1.
Atrial Septostomy
- Balloon atrial septostomy may be considered as a palliative or bridging procedure in patients deteriorating despite maximal medical therapy 1, 2.
Critical Pitfalls to Avoid
- Never combine riociguat with PDE5 inhibitors—this is contraindicated 2.
- Avoid abrupt cessation of prostacyclin infusion, as this can lead to rapid clinical deterioration 7.
- Do not use conventional vasodilators (ACE inhibitors, ARBs, beta-blockers) in PAH unless specifically required for comorbidities, as they lack proven benefit 2.
- All PAH-approved therapies maintain pregnancy category X contraindications 4.
- All PAH patients should be managed at or in consultation with specialized pulmonary hypertension centers with multidisciplinary teams including cardiology and respiratory medicine physicians, clinical nurse specialists, radiologists, and psychological/social work support 1, 2.