Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure in the arteries of the lungs. Symptoms include shortness of breath, fainting, tiredness, chest pain, swelling of the legs, and a fast heartbeat. The condition may make it difficult to exercise. Onset is typically gradual. According to the definition at the 6th World Symposium of Pulmonary Hypertension in 2018, a patient is deemed to have pulmonary hypertension if the pulmonary mean arterial pressure is greater than 20mmHg at rest, revised down from a purely arbitrary 25mmHg, and pulmonary vascular resistance (PVR) greater than 3 Wood units. The cause is often unknown. Risk factors include a family history, prior pulmonary embolism (blood clots in the lungs), HIV/AIDS, sickle cell disease, cocaine use, chronic obstructive pulmonary disease, sleep apnea, living at high altitudes, and problems with the mitral valve. The underlying mechanism typically involves inflammation and subsequent remodeling of the arteries in the lungs. Diagnosis involves first ruling out other potential causes. High cardiac output states, such as advanced liver disease or the presence of large arteriovenous fistulas, may lead to an elevated mean pulmonary artery pressure (mPAP) greater than 20 mm Hg despite a pulmonary vascular resistance (PVR) less than 2 Wood units, which does not necessarily indicate pulmonary vascular disease. As of 2022 there was no cure for pulmonary hypertension, although research to find a cure is ongoing. Treatment depends on the type of disease. A number of supportive measures such as oxygen therapy, diuretics, and medications to inhibit blood clotting may be used. Medications specifically used to treat pulmonary hypertension include epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, macitentan, and sildenafil, tadalafil, selexipag, riociguat. Lung transplantation may be an option in severe cases.
The frequency of occurrence is estimated at 1,000 new cases per year in the United States. Females are more often affected than males. Onset is typically between 20 and 60 years of age. Pulmonary hypertension was identified by Ernst von Romberg in 1891.
Classification According to the WHO classification, there are 5 groups of PH. Group I (pulmonary arterial hypertension) is further subdivided into Group I' and Group I'' classes. The WHO classification system in 2022 (with adaptations from the more recent ESC/ERS guidelines shown in italics) can be summarized as follows: WHO Group I – Pulmonary arterial hypertension (PAH)
Caused by narrowing and thickening of tiny arteries of the lung Idiopathic in most cases (heritable in some cases) Heritable (BMPR2, ALK1, SMAD9, caveolin 1, KCNK3 mutations) Drug- and toxin-induced (e.g., methamphetamine, amphetamine, or cocaine use ) Associated conditions:Connective tissue disease, HIV infection, Portal hypertension, Congenital heart diseases, Schistosomiasis WHO Group I' – Pulmonary veno-occlusive disease (PVOD), pulmonary capillary hemangiomatosis (PCH)
Idiopathic Heritable (EIF2AK4 mutations) Drugs, toxins, and radiation-induced Associated conditions: connective tissue disease, HIV infection WHO Group I" – Persistent pulmonary hypertension of the newborn WHO Group II – Pulmonary hypertension secondary to left heart disease
Left ventricular systolic dysfunction Left ventricular diastolic dysfunction Valvular heart disease Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathy Congenital/acquired pulmonary venous stenosis WHO Group III – Pulmonary hypertension due to lung disease, chronic hypoxia
Chronic obstructive pulmonary disease (COPD) Interstitial lung disease Mixed restrictive and obstructive pattern pulmonary diseases Sleep-disordered breathing Alveolar hypoventilation disorders Chronic exposure to high altitude Developmental abnormalities WHO Group IV – Chronic arterial obstruction
Chronic thromboembolic pulmonary hypertension (CTEPH) Other pulmonary artery obstructions Angiosarcoma or other tumor within the blood vessels Arteritis Congenital pulmonary artery stenosis Parasitic infection (hydatidosis) WHO Group V – Pulmonary hypertension with unclear or multifactorial mechanisms
Hematologic diseases: chronic hemolytic anemia (including sickle cell disease) Systemic diseases: sarcoidosis, pulmonary Langerhans cell histiocytosis: lymphangioleiomyomatosis, neurofibromatosis, vasculitis Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid diseases Others: pulmonary tumoral thrombotic microangiopathy, fibrosing mediastinitis, chronic kidney failure, segmental pulmonary hypertension (pulmonary hypertension restricted to one or more lobes of the lungs)
Signs and symptoms The symptoms of pulmonary hypertension include the following:
Less common signs/symptoms include a non-productive cough and exercise-induced nausea and vomiting. Coughing up of blood may occur in some patients, particularly those with specific subtypes of pulmonary hypertension such as heritable pulmonary arterial hypertension, Eisenmenger syndrome, and chronic thromboembolic pulmonary hypertension. Pulmonary venous hypertension typically presents with shortness of breath while lying flat or sleeping (orthopnea or paroxysmal nocturnal dyspnea), while pulmonary arterial hypertension (PAH) typically does not. Other typical signs of pulmonary hypertension include an accentuated pulmonary component of the second heart sound, a right ventricular third heart sound, and parasternal heave indicating a hypertrophied right ventricle. Signs of systemic congestion resulting from right-sided heart failure include jugular venous distension, ascites, and hepatojugular reflux. Evidence of tricuspid insufficiency and pulmonic regurgitation is also sought and, if present, is consistent with the presence of pulmonary hypertension.
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