What are the diagnostic and treatment options for a patient with suspected pulmonary hypertension?

Pulmonary Hypertension: Diagnostic and Treatment Approach

Diagnostic Evaluation

Right heart catheterization is essential to confirm the diagnosis of pulmonary hypertension, which is defined as a mean pulmonary arterial pressure ≥25 mmHg at rest. 1, 2

Initial Clinical Assessment

When suspecting pulmonary hypertension, look for:

• Exertional dyspnea (most common symptom), fatigue, weakness, angina, syncope, or abdominal distension 1
• Physical examination findings: left parasternal lift, accentuated pulmonary component of S2, pansystolic murmur of tricuspid regurgitation, jugular vein distension, hepatomegaly, peripheral edema, ascites, and cool extremities in advanced cases 1
• Lung sounds are typically normal, which helps distinguish PH from primary lung disease 1

Stepwise Diagnostic Algorithm

Phase 1 - Detection Studies:

• Electrocardiogram to assess for right ventricular hypertrophy 1
• Chest radiograph to exclude moderate-to-severe lung disease or pulmonary venous hypertension 1
• Transthoracic Doppler echocardiography as the primary screening tool to estimate pulmonary artery systolic pressure and assess right ventricular function 1

Phase 2 - Confirmation and Classification:

• Ventilation-perfusion (V/Q) lung scan is mandatory to exclude chronic thromboembolic pulmonary hypertension (CTEPH), as it may show segmental perfusion defects in CTEPH but only small peripheral non-segmental defects in pulmonary arterial hypertension 1, 3
• Right heart catheterization to definitively confirm diagnosis, measure hemodynamics (mean PAP, pulmonary wedge pressure, cardiac output), and classify PH type 1, 2
• Vasoreactivity testing during catheterization is mandatory for patients with idiopathic, heritable, or drug-induced PAH to identify calcium channel blocker responders 2, 4

Phase 3 - Etiology Identification:

• Blood tests: complete blood count, liver function tests, thyroid function, BNP/NT-proBNP, HIV serology, antinuclear antibodies, anticardiolipin antibodies for connective tissue disease and thrombophilia screening 1
• High-resolution CT chest to assess for interstitial lung disease, with contrast CT angiography if CTEPH is suspected 1
• Pulmonary function tests to exclude significant lung disease 1

Classification and Hemodynamic Definitions

PH is classified into five clinical groups based on hemodynamics measured at rest 1:

• Pre-capillary PH (Groups 1,3,4,5): Mean PAP ≥25 mmHg, pulmonary wedge pressure ≤15 mmHg 1
• Post-capillary PH (Group 2): Mean PAP ≥25 mmHg, pulmonary wedge pressure >15 mmHg 1

Risk Stratification

All patients must be risk-stratified into low, intermediate, or high-risk categories based on estimated 1-year mortality to guide treatment intensity. 1, 5

Low-risk criteria (1-year mortality <5%):

• WHO Functional Class I-II
• 6-minute walk distance >440 meters
• BNP <50 ng/L or NT-proBNP <300 ng/L
• Cardiac index ≥2.5 L/min/m²
• Right atrial pressure <8 mmHg 1, 5

Intermediate-risk criteria (1-year mortality 5-10%):

• WHO Functional Class III
• 6-minute walk distance 165-440 meters
• BNP 50-300 ng/L or NT-proBNP 300-1400 ng/L 1, 5

High-risk criteria (1-year mortality >10%):

• WHO Functional Class III-IV with progression
• 6-minute walk distance <165 meters
• BNP >300 ng/L or NT-proBNP >1400 ng/L
• Cardiac index <2.0 L/min/m²
• Right atrial pressure >14 mmHg 1, 5

Treatment Approach

Group 1: Pulmonary Arterial Hypertension (PAH)

For vasoreactive patients (positive acute vasodilator response), high-dose calcium channel blockers are first-line therapy. 2, 4

For non-vasoreactive low or intermediate-risk patients, initial oral combination therapy with ambrisentan plus tadalafil is the preferred approach, as it significantly delays clinical failure compared to monotherapy. 5

For high-risk patients, continuous intravenous epoprostenol must be initiated immediately, as it is the only therapy proven to reduce 3-month mortality. 2, 5, 6

Sequential combination therapy targeting multiple pathways is recommended for patients with inadequate response to initial therapy. 1, 4

Group 4: Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Surgical pulmonary endarterectomy in deep hypothermia circulatory arrest is the treatment of choice for operable patients. 4

Riociguat is recommended for inoperable CTEPH or persistent/recurrent PH after surgery. 4, 3

Lifelong anticoagulation is mandatory for all CTEPH patients. 4

Groups 2,3, and 5

Treatment primarily targets the underlying condition (left heart disease, lung disease, or multifactorial causes), as there are no approved targeted PAH therapies for these groups. 3, 7

Supportive Care Measures

Diuretics are indicated for all patients with signs of right ventricular failure and fluid retention, with careful monitoring of electrolytes and renal function. 2, 5

Continuous long-term oxygen therapy is recommended when arterial oxygen pressure is consistently <60 mmHg or to maintain saturations >90%. 2, 5

Supervised exercise training should be implemented for physically deconditioned PAH patients under medical therapy. 2, 5

Pregnancy must be avoided in PAH patients due to 30-50% mortality risk; effective contraception counseling is mandatory. 4

Monitoring and Treatment Goals

Regular follow-up assessments every 3-6 months in stable patients are required, including WHO functional class, 6-minute walk distance, BNP/NT-proBNP levels, and echocardiography. 1, 5

The primary treatment goal is achieving and maintaining low-risk status (WHO FC I-II, 6MWD >440m, preserved RV function). 1, 5

Achievement or maintenance of intermediate-risk profile should be considered inadequate treatment response for most PAH patients, prompting therapy escalation. 1

Advanced Therapies

Lung transplantation eligibility should be considered after inadequate response to initial monotherapy or combination therapy. 5

Balloon atrial septostomy may be considered as a palliative or bridging procedure in patients deteriorating despite maximal medical therapy. 5

Critical Pitfalls to Avoid

Patients with PAH must be managed at specialized centers with expertise in pulmonary hypertension. 2, 4

Never abruptly discontinue pulmonary vasodilators in patients already receiving them, as this may rapidly precipitate right ventricular failure and death. 8

Avoid aggressive fluid resuscitation in hypotensive patients with right ventricular failure; use vasopressors and inotropes instead to prevent exacerbating right ventricular ischemia. 8

Do not combine tadalafil with nitrates, guanylate cyclase stimulators (riociguat), or other PDE5 inhibitors due to risk of severe hypotension. 9

Intubation should be avoided if possible in patients with severe PH, as positive pressure ventilation can precipitate cardiovascular collapse. 8