Diagnosing and Treating Pulmonary Hypertension

During a presentation at the 14^th Annual Southern Hospital Medicine Conference, held November 7-9, 2013, in New Orleans, LA, Suma Jain, MD, a pulmonologist at the Ochsner Clinic Foundation, provided a clinical update on the diagnosis and treatment of pulmonary hypertension (PH).

Jain explained that untreated pulmonary arterial hypertension (PAH) has a median survival period of 2.8 years, characterized by a progressive increase in pulmonary vascular resistance (PVR) until the patient dies. Changes in pulmonary arterioles, such as vasoconstriction, obstructive remodeling of vessel walls, inflammation, and in-situ thrombosis, lead to increased PVR.

According to Jain, normal pulmonary artery systolic pressure (PASP) is 18 to 25 mm Hg at rest, while mean pulmonary artery pressure (MPAP) is 12 to 16 mm Hg. PAH is defined as mean PASP >25 mm Hg at rest or mean PASP >30 mm Hg with exercise. In 5% of people with a body mass index (BMI) >30 and 6% of people who are 50 years or older, PASP is above 40 mm Hg.

PAH, which occurs in 30 to 50 patient cases per million, is diagnosed at a mean age of 36 years. The condition is more common in those with sickle cell disease, HIV, systemic sclerosis, portal hypertension, congenital heart disease (CHD), and obstructive sleep apnea (OSA). Endothelial dysfunction of the pulmonary vessels can result in less production of vasodilators like prostacyclin and nitric oxide, more production of vasoconstrictors like endothelin, proliferation of endothelium and smooth muscle cells, remodeling of the pulmonary vascular bed, and increased vascular resistance, according to Jain.

Jain said collagen vascular disease, vasculitis, sarcoidosis, lymphangitic spread cancer, IV drug use, and hemoglobinopathies can obstruct the flow of blood through the lungs. Venous drainage can be obstructed by left ventricular dysfunction, mitral valve disease, mediastinal fibrosis, pulmonary veno-occlusive disease, and constrictive pericarditis. Chronic obstructive pulmonary disease (COPD), interstitial lung disease, OSA, kyphoscoliosis, and chronic mountain sickness cause alveolar hypoxia/acidosis that results in pulmonary vasoconstriction. According to Jain, all of those scenarios can lead to PAH.

The World Health Organization (WHO) has divided PH into different classifications that are important for determining treatment options. The classification 1 PAH contains idiopathic, heritable, and drug- or toxin-related cases, as well as those associated with other diseases. A 2 PH classification results from left heart disease, such as systolic or diastolic dysfunction and valvular disease, while a 3 PH is the result of lung diseases and/or hypoxia. Classification 4 PH comprises of chronic thromboembolic pulmonary hypertension, while 5 PH includes unclear and/or multifactorial mechanisms, as in hematological, systemic, and metabolic disorders.

Jain said early diagnosis and intervention is crucial in PAH because it’s a rare condition. The mean time from onset to diagnosis of PAH is about 2 years, and onset is insidious with nonspecific symptoms. Jain advised that electrocardiography (ECG), chest X-ray, echocardiography, and cardiac catheterization should be included in the initial valuation, and clinical history should detail dyspnea on exertion, chest pain, syncope/presyncope, hoarseness, and indications of contributing or underlying diseases. Patients should also be asked about past use of appetite suppressants dexfenfluramine, fenfluramine, and phentermine.

Physical exam may yield hepatomegaly, ascites, peripheral edema, cool extremities, and a louder P2 sound of the pulmonary valve, which may indicate leakage. Lab workup should include screening for connective tissue disease antibodies and thrombophilia, as well as checking liver enzymes and thyroid function and testing for viral hepatitis and HIV. Pulmonary function tests can characterize airway and/or parenchymal disease, indicate airflow obstruction, and detect decreased lung volumes. In addition, Jain said “X-rays are very useful in diagnosing PAH and causes of PH.”

PH patients have a prominent main pulmonary artery, right interlobar artery, and filling of the retrosternal airspace, though there may also be other findings, such as pleural effusions and fibrosis. Computed tomography angiography (CTA) can be used to diagnose PH if the diameter of the pulmonary artery is >29 mm the level of the bifurcation, and the main diameter is larger than the ascending aorta.

However, Jain said doppler echocardiography (DE) is “not very good” in assessing PASP, and she discussed several studies that revealed inaccuracies in DE estimations, especially at higher PASPs. In contrast, right heart catheterization (RHC) is required to confirm the diagnosis of PAH, so it may be more effective at monitoring severe PAH than DE.

The goals of therapy in PAH are to prevent clinical worsening and improve hemodynamics, exercise capacity, functional class, and, ultimately, chances of survival. Therapy includes anticoagulation, diuretics, oxygen therapy, and contraception to prevent pregnancy, which raises the risk of mortality in women with PAH, Jain said.

Treatment for PH must address left heart disease, OSA, and other underlying or contributing disorders. Weight loss may be required — though exercise should be included as part of therapy — and continuous positive airway pressure can keep airways open. Thromboembolism should be treated with anticoagulants and surgery, as necessary.

Concluding her presentation, Jain briefly summarized treatments that have been studied in PAH, including endothelin receptor antagonists, prostacyclin analogues, phosphodiesterase-5 inhibitors, and the novel guanylate cyclase nitric oxide receptor stimulant, riociguat.