Pulmonary arterial hypertension (PAH) is a progressive and potentially life-threatening disease that affects the pulmonary vasculature.

PAH is characterized by increased pulmonary arterial pressure that causes significant hemodynamic compromise to the right heart leading to right heart failure and ultimately death if not managed properly.

Diagnosis

Early diagnosis of PAH is critical for successful management of the disease. Unfortunately, diagnosis is often delayed due to the nonspecific symptoms such as fatigue, shortness of breath, dizziness and chest pain. Physicians may not consider PAH in the differential diagnosis until the disease has progressed significantly.

Thus, it is essential to suspect the disease early based on the patient’s clinical clues, medical history, and examination.

Medical History and Evaluation

Patient history evaluation is the first step towards diagnosing PAH. A proper clinical interview can provide important indicators of PAH. Patients often report symptoms for many months or even years before a diagnosis is established.

Information about symptoms, past medical history, and family history are essential for the diagnosis. The medical history and evaluation may include:.

Childhood heart disease
Autoimmune disease such as lupus, scleroderma, and rheumatoid arthritis
Current medication profile
Pulmonary embolism
Obstructive sleep apnoea
Exposure to toxins such as cocaine or methamphetamines

Physical Examination

Physical examination is equally important in diagnosing PAH. The following findings may suggest PAH:.

Heart rate greater than 100 bpm
Systolic murmur
Narrow splitting of S2 heart sound
Presence of jugular vein distention
Abdominal examination may show ascites and hepatomegaly

Diagnostics

PAH can only be confirmed through a combination of diagnostic testing. The diagnostic workup for PAH should include:.

Transthoracic echocardiogram (TTE)
High-resolution computed tomography (HRCT)
Pulmonary function testing (PFT)
Ventilation/perfusion (V/Q) scan
Right heart catheterization (RHC)

Transthoracic Echocardiogram (TTE)

A TTE is the first imaging study to detect PAH and should be ordered in any patient with suspected PAH. The examination assesses pulmonary artery pressure by measuring the velocity of tricuspid valve regurgitant jet.

Moreover, TTE will also evaluate heart function and structure as part of the workup.

High-Resolution Computed Tomography (HRCT)

HRCT imaging of the pulmonary arteries can help identify underlying causes of PAH such as pulmonary embolism or lung disease.

HRCT is not a definitive test for PAH, but it can help in identifying or ruling out other potential causes before performing more invasive testing.

Pulmonary Function Testing (PFT)

PFT is important to rule out pulmonary disease and can help identify potential candidates for lung transplant.

Patients who have severe pulmonary hypertension may have reduced diffusion capacity for carbon monoxide (DLCO) due to reduced lung surface area for gas exchange.

Ventilation/Perfusion (V/Q) Scan

A ventilation-perfusion scan is not a diagnostic test for PAH but can identify or rule out the presence of a pulmonary embolus that can cause PAH.

A perfusion defect may suggest a chronic thromboembolic pulmonary hypertension (CTEPH) or acute pulmonary embolism (PE).

Right Heart Catheterization (RHC)

Right heart catheterization is considered the gold standard for diagnosing PAH. A specialized catheter is inserted through a small incision in the groin and passed up into the pulmonary artery.

RHC can measure pulmonary artery pressure, cardiac output, and pulmonary vascular resistance (PVR). A PVR greater than 3 Woods units is considered diagnostic for pulmonary hypertension.

Treatment

The goals of PAH treatment are to improve symptoms and quality of life, slow disease progression, prevent hospital admissions and increase survival.

Treatment should be tailored to the individual patient based on the severity of the disease, the underlying cause, and the patient’s comorbidities. Treatment options for PAH may include:.

Vasodilator therapy
Anticoagulation therapy
Diuretics
Oxygen therapy
Phosphodiesterase inhibitors
Prostacyclin analogs
Endothelin receptor antagonists

Vasodilator Therapy

Vasodilator therapy is effective for patients with idiopathic PAH or connective tissue disease. These drugs work by decreasing pulmonary artery pressure by dilating the pulmonary artery and improving blood flow to the lungs.

Calcium channel blockers are used as a first-line therapy for patients who have a positive acute response to vasodilator testing. Responders have an increase in cardiac output and a reduction in pulmonary vascular resistance after administration of intravenous epoprostenol or adenosine.

Anticoagulation Therapy

Anticoagulation therapy is used to prevent blood clots from forming in the pulmonary arteries and lung vessels. Warfarin therapy is commonly used in patients with idiopathic or hereditary pulmonary hypertension in the absence of contraindications.

Diuretics

Diuretics are used to remove excess fluid buildup in the body, including the lungs, and to decrease the overall blood volume. Fluid accumulation in the lungs can lead to hypoxemia and impair right ventricular function in PAH patients.

Oxygen Therapy

Oxygen therapy may be prescribed for patients with PAH who have hypoxemia or require the treatment for alternative conditions. Oxygen therapy helps improve oxygen saturation, thereby reducing pulmonary hypertension and improving symptoms in patients.

Phosphodiesterase Inhibitors

Phosphodiesterase inhibitors (PDE5 inhibitors) are the first oral medications approved for the treatment of PAH.

They work by increasing the level of cGMP (a vasodilator) in pulmonary arteries, promoting vasodilation, and lowering pulmonary artery pressure. Sildenafil and Tadalafil are the two PDE5 inhibitors available in the market.

Prostacyclin Analogues

Prostacyclin analogues are a potent vasodilator that relaxes smooth muscle and dilates pulmonary blood vessels. They are used primarily for patients with severe PAH who respond to treatment.

Prostacyclin analog long-term effects can maintain the improvement in hemodynamics and improve quality of life.

Endothelin Receptor Antagonists

Endothelin receptor antagonists (ERAs) act by blocking the action of the potent vasoconstrictor peptides.

ERAs are used for long-term treatment of PAH to improve functional capacity, reduce hospitalizations, and improve clinical outcomes in patients with PAH. Some of the commonly used ERAs are Ambrisentan and Bosentan.

Surgical Intervention

Surgical intervention may be required in a minority of patients with PAH to alleviate disease burden. PTE is an effective therapy in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Lung Transplantation

Lung transplantation is reserved for patients with advanced PAH who have severe symptoms and poor quality of life despite optimal medical therapy. Lung transplantation improves morbidity and mortality in these patients.

Conclusion

PAH is a rare and progressive disease that is challenging to diagnose and manage. Early diagnosis and treatment are essential to prevent disease progression, which can ultimately lead to right heart failure or death.

The use of diagnostic tests, physician experience in recognizing signs and symptoms of PAH, treatment options, and ongoing patient evaluation are all essential components of successful PAH management.