What is the recommended diagnostic work‑up and management for a symptomatic patient with mild pulmonary hypertension (mean pulmonary artery pressure 21‑35 mmHg) without severe right‑ventricular dysfunction?

Management of Mild Pulmonary Hypertension (mPAP 21-35 mmHg)

For symptomatic patients with mild pulmonary hypertension (mean PAP 21-35 mmHg) without severe right ventricular dysfunction, proceed with a comprehensive diagnostic workup to identify the underlying cause and clinical group, but recognize that mean PAP between 21-24 mmHg is of uncertain clinical significance and warrants close follow-up rather than immediate treatment. 1

Initial Diagnostic Approach

Echocardiographic Assessment

• Transthoracic Doppler echocardiography should always be performed as the first-line screening test to estimate pulmonary artery pressure, assess right ventricular function, and evaluate for left heart disease or valvular abnormalities 1, 2
• Measure tricuspid regurgitation velocity (TRV), right ventricular size and function, interventricular septal position, right atrial size, and inferior vena cava diameter 1, 3
• Evaluate for left ventricular systolic/diastolic dysfunction, chamber enlargement, and valvular disease to identify Group 2 PH (left heart disease) 2
• Use contrast echocardiography to detect intracardiac shunting if clinically indicated 2

Important caveat: Detection of mild PH by echocardiography is limited, with sensitivity of 79-100% and specificity of 68-98% for moderate PH, but significantly lower accuracy for mild PH 1

Essential Baseline Testing

• Perform ventilation-perfusion (V/Q) scanning in all patients to exclude chronic thromboembolic pulmonary hypertension (CTEPH) - a normal V/Q scan effectively rules out CTEPH 2, 4
• Complete pulmonary function tests including spirometry, lung volumes, and DLCO measurement to evaluate for underlying lung disease (Group 3 PH) 2
• Obtain arterial blood gas analysis to assess oxygenation and acid-base status 2
• Perform chest radiography and high-resolution CT chest to identify parenchymal lung disease or signs of CTEPH 1

Critical pitfall: Do not rely on CT pulmonary angiography alone to exclude CTEPH, as it may miss the diagnosis - V/Q scanning must be performed 2

Right Heart Catheterization Indications

Right heart catheterization is required to confirm the diagnosis, establish specific hemodynamic classification, determine severity, and guide therapy 1, 2

For symptomatic patients with mild PH:

• RHC is necessary when echocardiography shows intermediate or high probability of PH before treatment initiation 1
• RHC should be performed to measure mean pulmonary artery pressure, pulmonary artery wedge pressure (PAWP), cardiac output, and calculate pulmonary vascular resistance 2
• This distinguishes precapillary PH (PAWP ≤15 mmHg, PVR >3 Wood units) from postcapillary PH (PAWP >15 mmHg) 1

RHC remains the gold standard for pulmonary hemodynamic measurement despite some limitations, including measurement variability and static resting conditions 1

Clinical Group Classification

After confirming PH by RHC, identify the specific clinical group:

Group 1: Pulmonary Arterial Hypertension (PAH)

• Perform detailed history for risk factors: family history, connective tissue disease, congenital heart disease, HIV infection, portal hypertension, drug/toxin exposure 1
• Obtain blood tests including complete blood count, metabolic panel, thyroid function, NT-proBNP, autoimmune serologies 1, 2
• Perform abdominal ultrasound to screen for portal hypertension in unexplained cases 2
• Consider genetic testing for familial/heritable PAH 2

Group 2: PH Due to Left Heart Disease

• Most common cause of PH in clinical practice 4
• Identified by elevated PAWP >15 mmHg on RHC and echocardiographic evidence of left heart dysfunction 1

Group 3: PH Due to Lung Disease

• Identified by pulmonary function testing showing obstructive or restrictive patterns and CT evidence of parenchymal disease 1

Group 4: Chronic Thromboembolic PH (CTEPH)

• Identified by multiple segmental perfusion defects on V/Q scan 1
• Requires CT pulmonary angiography, RHC, and selective pulmonary angiography for definitive diagnosis 1

Group 5: PH with Unclear/Multifactorial Mechanisms

• Diagnosis of exclusion after ruling out Groups 1-4 1

Functional Assessment

• Perform 6-minute walk test with Borg dyspnea score to establish baseline exercise capacity and provide prognostic information 2
• Assess WHO functional class, which correlates with prognosis 1
• Measure serum biomarkers such as BNP or NT-proBNP for diagnostic and prognostic purposes 1

Management Strategy for Mild PH

When mPAP is 21-24 mmHg:

• This range is of uncertain clinical significance and warrants close follow-up rather than specific PH therapy 1
• Treat underlying conditions (left heart disease, lung disease) appropriately 4
• Perform serial echocardiographic monitoring 3

When mPAP is 25-35 mmHg:

• Treatment depends entirely on the underlying clinical group identified 4
• For Group 2 (left heart disease): Management primarily involves treatment of the underlying cardiac condition 4
• For Group 3 (lung disease): Optimize treatment of underlying lung disease; targeted PAH therapies are generally not indicated 4
• For Group 4 (CTEPH): All patients must be referred to a specialist center - surgical pulmonary endarterectomy is the treatment of choice for eligible patients 4
• For Group 1 (PAH): All patients must be referred to a specialist PH center for consideration of targeted therapies 4

Critical warning: Never use calcium channel blockers empirically without documented acute vasoreactivity testing, as this can be harmful 2

Follow-Up and Monitoring

• Echocardiographic follow-up is recommended 3-4 months after initiation of or change in therapy 5
• Serial assessment of functional class, exercise capacity, and biomarkers guides ongoing management 1
• In symptomatic patients with risk factors who have "low probability" echocardiograms, echocardiographic follow-up should be considered, as a normal echocardiogram does not exclude PH 3

Key Pitfalls to Avoid

• Do not perform lung biopsy routinely due to high risk; reserve only for cases where tissue diagnosis is essential 2
• Avoid using exercise Doppler echocardiography for PH screening due to lack of validated criteria 3, 2
• Do not rely solely on TRV or estimated PA systolic pressure for diagnosis; consider the full clinical context and additional echocardiographic variables 3
• Recognize that echocardiographic estimation of pulmonary pressures may be inaccurate in individual patients, particularly with severe tricuspid regurgitation 3