Treatment of Pulmonary Hypertension
Critical First Step: Confirm Diagnosis and Classification Before Treatment
Do not initiate any PAH-specific therapy until right heart catheterization confirms the diagnosis and establishes the hemodynamic classification, as treatment differs fundamentally by PH group and empiric therapy can cause harm, particularly in Group 2 PH. 1, 2
All patients must be evaluated at an expert pulmonary hypertension center before starting treatment 1, 2. Early telephone consultation with PH specialists should occur immediately while arranging in-person evaluation 2.
Treatment Algorithm by PH Classification
Group 1: Pulmonary Arterial Hypertension (PAH)
Step 1: Vasoreactivity Testing
- Perform acute vasoreactivity testing during right heart catheterization in all patients with idiopathic, heritable, or drug-induced PAH 1
- For vasoreactive patients (positive responders): High-dose calcium channel blockers are first-line therapy 1, 3
Step 2: Risk Stratification for Non-Vasoreactive Patients
Treatment intensity depends on risk status 1, 3:
Low-Risk Patients:
- Monotherapy with approved PAH medications is acceptable 3
- Options include sildenafil (improves exercise ability and delays clinical worsening) 4 or other approved agents
Intermediate-Risk Patients:
- Initial oral combination therapy with ambrisentan plus tadalafil is recommended as it has proven superior to monotherapy in delaying clinical failure 1
- This approach is preferred over sequential monotherapy 3
High-Risk Patients:
- Initial combination therapy including intravenous prostacyclin analogs (such as epoprostenol) should be prioritized 1, 5
- These patients require aggressive upfront treatment 3
Step 3: Sequential Escalation
- Add additional therapies if inadequate response to initial treatment 3
- Target achieving low-risk status (WHO Functional Class I-II) 1
Group 2: PH Due to Left Heart Disease
PAH-specific therapies are NOT recommended and may be harmful in this population 1, 3, 2
- Focus treatment on optimizing the underlying cardiac disease 3
- Use diuretics for volume management 1
- Avoid vasodilators that could worsen pulmonary edema 1
Group 3: PH Due to Lung Disease
Long-term oxygen therapy is the primary treatment and has been shown to partially reduce PH progression 1, 3
- Maintain oxygen saturations >90% 1, 3
- Do not use conventional vasodilators like calcium channel blockers as they can worsen gas exchange 3
- PAH-specific drugs are not recommended in this group 3, 6
- Treat the underlying lung disease optimally 3
Group 4: Chronic Thromboembolic PH (CTEPH)
Surgical pulmonary endarterectomy in deep hypothermia with circulatory arrest is the treatment of choice 1, 3, 2
- Operability assessment must be performed by a multidisciplinary expert team 3
- Medical therapy is secondary to surgical intervention when feasible 2
- Anticoagulation targeting INR 2-3 is recommended 1
Essential Supportive Care for All PAH Patients
Volume Management
- Diuretics (such as furosemide) are recommended for all PAH patients with signs of right ventricular failure and fluid retention 1, 2
- Monitor electrolytes, renal function, and daily weights during active diuresis 2
Oxygenation
- Continuous long-term oxygen is recommended when arterial oxygen pressure is consistently <60 mmHg or to maintain saturations >90% 1, 3
Anticoagulation
- Consider anticoagulation in idiopathic PAH, heritable PAH, and anorexigen-induced PAH, targeting INR 1.5-2.5 1
- Higher INR target (2-3) for chronic thromboembolic PH 1
Exercise
- Supervised physical training should be considered for physically deconditioned patients under medical treatment 3
Monitoring and Treatment Goals
Regular Assessment Schedule
- Perform evaluations every 3-6 months in stable patients 1, 3
- Include WHO functional class, 6-minute walk distance, BNP/NT-proBNP, and echocardiography 1
Treatment Targets
- Primary goal: achieving and maintaining low-risk status (typically WHO FC I-II) 1, 3
- Target 6-minute walk distance >440 meters for most patients (lower values acceptable in elderly or those with significant comorbidities) 1, 3
Advanced Therapies and Rescue Options
Lung Transplantation
- Consider eligibility after inadequate response to initial monotherapy or combination therapy 1
- Refer for transplantation soon after inadequate response is confirmed on maximal combination therapy 1, 3
Palliative Procedures
- Balloon atrial septostomy may be considered as palliative or bridging procedure in patients deteriorating despite maximal medical therapy 1
Critical Care Management
ICU Indications
- Hospitalize in ICU for patients with high heart rate (>110 bpm), low blood pressure (systolic <90 mmHg), low urine output, or rising lactate 1, 2
Hemodynamic Support
- Inotropic support is recommended for hypotensive patients 1, 2
- Vasopressors and inotropes are preferred over fluid boluses in shock to avoid exacerbating right ventricular ischemia 7
- Avoid intubation if possible, though hypoxemia and hypercapnia also worsen right-sided heart function 7
Critical Pitfalls to Avoid
Never start PAH-specific drugs without right heart catheterization confirmation 1, 2. This delays appropriate treatment and causes harm, particularly in Group 2 PH where vasodilators can worsen outcomes 1, 2.
Avoid ACE inhibitors, ARBs, and beta-blockers in PAH unless specifically required for comorbidities 1, 3. These lack proven benefit in PAH 1.
Do not delay specialist referral 2. Attempting complete workup locally without specialist input results in incomplete phenotyping and inappropriate therapy 2.
Pregnancy must be avoided in PAH patients due to high mortality risk 3.
Patients on pulmonary vasodilators may rapidly develop right ventricular failure and death if these medications are interrupted 7. Never discontinue these therapies abruptly 7.