How should I evaluate and manage an adult presenting with dyspnea, fatigue, or syncope who is suspected of having pulmonary hypertension?

Evaluation and Management of Suspected Pulmonary Hypertension

In an adult presenting with dyspnea, fatigue, or syncope suspected of having pulmonary hypertension, immediately obtain transthoracic echocardiography as the screening test, followed by mandatory right heart catheterization for definitive diagnosis before initiating any PH-specific therapy. 1, 2

Initial Clinical Assessment

Key Symptoms to Elicit

• Dyspnea on exertion is the most common presenting symptom (present in >90% of cases) 1
• Syncope, particularly with exertion, suggests severe disease and warrants urgent evaluation 1, 3
• Fatigue and weakness from decreased cardiac output 1
• Angina may occur from right ventricular ischemia or left main coronary artery compression by dilated pulmonary artery 1, 4
• Dry cough and exercise-induced nausea/vomiting are less common but supportive 1
• Abdominal distension and peripheral edema indicate advanced right ventricular failure 1, 4

Critical Physical Examination Findings

• Left parasternal lift (right ventricular heave) 1
• Accentuated pulmonary component of S2 1
• Pansystolic murmur of tricuspid regurgitation 1
• Elevated jugular venous pressure with prominent V waves 4
• Hepatomegaly with pulsatile liver, ascites, and cool extremities in advanced disease 1, 4
• Digital clubbing should raise suspicion for pulmonary veno-occlusive disease, congenital heart disease, interstitial lung disease, or liver disease—NOT idiopathic PAH 1, 4

Diagnostic Algorithm

Step 1: Initial Screening Tests (Perform Simultaneously)

Transthoracic Echocardiography (Most Critical Initial Test)

• This is the screening test of choice for detecting elevated pulmonary pressures 1, 2
• Estimates right ventricular systolic pressure based on tricuspid regurgitation jet velocity 1
• Assesses right atrial and ventricular enlargement, interventricular septal abnormalities, and pericardial effusion 1
• Critical caveat: Normal echocardiogram does NOT exclude PH; false negatives can occur 1
• Evaluates for left ventricular systolic/diastolic dysfunction and valvular disease to identify Group 2 PH (left heart disease) 1

Electrocardiogram

• Right axis deviation, right ventricular hypertrophy, right ventricular strain pattern, P pulmonale 1
• Important limitation: Sensitivity only 55%, specificity 70%—normal ECG does NOT exclude severe PH 1, 2
• Right ventricular strain is more sensitive than isolated right ventricular hypertrophy 1

Chest Radiograph

• Central pulmonary arterial dilatation with peripheral vessel "pruning" 1, 2
• Right atrial and ventricular enlargement 1
• 90% of idiopathic PAH patients have abnormal findings at diagnosis, but normal chest X-ray does NOT exclude PH 1, 2

Step 2: Determine PH Group and Exclude Common Causes

Pulmonary Function Tests with DLCO

• Identifies Group 3 PH (lung disease and/or hypoxia) 1, 2
• PAH patients typically show decreased DLCO with mild-to-moderate reduction in lung volumes 1
• Arterial blood gases assess for hypoxemia 1

Ventilation-Perfusion (V/Q) Scan (MANDATORY)

• Must be performed in all patients with suspected PH to exclude chronic thromboembolic pulmonary hypertension (CTEPH) 1, 2, 5
• Sensitivity >90%, specificity >94% for CTEPH 2
• Normal V/Q scan effectively excludes CTEPH 1
• V/Q scanning is superior to CT pulmonary angiography for CTEPH screening 1

Laboratory Testing

• HIV testing in all patients with unexplained PAH 1, 2
• Antinuclear antibodies and connective tissue disease serologies (especially in women) 1, 2
• Liver function tests to assess for portopulmonary hypertension 1
• BNP or NT-proBNP for prognostic assessment 1

High-Resolution CT Chest

• Evaluates for interstitial lung disease (Group 3 PH) 1
• May identify pulmonary veno-occlusive disease (ground-glass opacities, septal lines, lymphadenopathy) 1, 6

Step 3: Definitive Diagnosis with Right Heart Catheterization

Right heart catheterization is MANDATORY before initiating any PH-specific therapy 1, 2

Hemodynamic Criteria for PH Diagnosis:

• Mean pulmonary artery pressure (mPAP) ≥25 mmHg at rest defines pulmonary hypertension 1
• Pulmonary capillary wedge pressure (PCWP) ≤15 mmHg defines pre-capillary PH and excludes left heart disease 1, 2
• Pulmonary vascular resistance (PVR) >3 Wood units confirms true pulmonary vascular disease 1, 2

Additional Measurements Required:

• Right atrial pressure, right ventricular pressure, systolic/diastolic/mean pulmonary artery pressure 1
• Cardiac output measured in triplicate (preferably by thermodilution or Fick method) 1
• Calculate cardiac index and PVR 1

Vasoreactivity Testing (Performed During Catheterization)

• Only perform in idiopathic PAH, heritable PAH, or drug-induced PAH 1
• Use short-acting agents: IV epoprostenol, adenosine, or inhaled nitric oxide 1
• Positive response: Fall in mPAP ≥10 mmHg to ≤40 mmHg with increased or unchanged cardiac output 1
• Only vasoreactivity-positive patients should receive calcium channel blocker trial 1, 2
• Never use calcium channel blockers empirically without documented acute vasoreactivity 1, 2

Management Based on Etiology

Group 1: Pulmonary Arterial Hypertension

• Immediate referral to pulmonary hypertension specialist center is mandatory 2, 5
• Vasoreactivity-positive patients: Trial of high-dose calcium channel blockers (diltiazem, nifedipine, amlodipine) 1
• Vasoreactivity-negative or functional class III patients: Targeted PAH therapies (phosphodiesterase-5 inhibitors, endothelin receptor antagonists, prostacyclin analogues) 5

Group 2: PH Due to Left Heart Disease

• Optimize treatment of underlying hypertension and left ventricular dysfunction 2
• Do NOT use PAH-specific vasodilators—these are contraindicated 2, 3

Group 3: PH Due to Lung Disease

• Treat underlying lung disease 5
• PAH-specific therapies generally not indicated 5

Group 4: Chronic Thromboembolic Pulmonary Hypertension

• Referral to center experienced in pulmonary thromboendarterectomy 2, 5
• Surgical pulmonary endarterectomy is the treatment of choice for eligible patients 2, 5
• Riociguat for inoperable or persistent/recurrent CTEPH 5

Group 5: Unclear/Multifactorial Mechanisms

• Individualized management based on contributing factors 5

Functional Assessment and Follow-Up

Six-Minute Walk Test

• Provides baseline exercise capacity and prognostic information 1
• Serial measurements track disease progression and treatment response 1

WHO Functional Class Assessment

• Class I: No limitation of physical activity 1
• Class II: Slight limitation; comfortable at rest 1
• Class III: Marked limitation; less than ordinary activity causes symptoms 1
• Class IV: Unable to perform any activity without symptoms; right heart failure present 1

Critical Pitfalls to Avoid

• Never diagnose PH based on echocardiography alone—right heart catheterization is mandatory 1, 2
• Never start PAH-specific therapies without hemodynamic confirmation 1, 2
• Never use calcium channel blockers without documented acute vasoreactivity 1, 2
• Never miss CTEPH—always perform V/Q scanning, as this is the only potentially curable form of PH 1, 2
• Do not use PAH-specific vasodilators in Group 2 PH (left heart disease)—they may worsen outcomes 2, 3
• Urgent referral required for syncope, rapidly progressing symptoms, or heart failure 3