Treatment of<unk>  is determined by whether the<unk>  is arterial, venous, hypoxic, thromboembolic, or miscellaneous. If it is caused by left heart disease, the treatment is to optimize left ventricular function by the use of medication or to repair/replace the mitral valve or aortic valve. Patients with left heart failure or hypoxemic lung diseases (groups II or III<unk>  should not routinely be treated with vasoactive agents including prostanoids,<unk> osphodiesterase inhibitors, or endothelin antagonists, as these are approved for the different condition called primary pulmonary arterial hypertension. To make the distinction, doctors at a minimum will conduct cardiac catheterization of the right heart, echocardiography, chest CT, a six-minute walk test, and pulmonary function testing. Using treatments for other kinds of<unk>  in patients with these conditions can harm the patient and wastes substantial medical resources. High dose calcium channel blockers are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter. Unfortunately, calcium channel blockers have been largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality. The criteria for vasoreactivity have changed. Only those patients whose mean pulmonary artery pressure falls by more than 10 mm Hg to less than 40 mm Hg with an unchanged or increased cardiac output when challenged with adenosine, epoprostenol, or nitric oxide are considered vasoreactive. Of these, only half of the patients are responsive to calcium channel blockers in the long term. A number of agents have recently been introduced for primary and secondary PAH. The trials supporting the use of these agents have been relatively small, and the only measure consistently used to compare their effectivity is the "6-minute walk test". Many have no data on mortality benefit or time to progression. Vasoactive substances Many pathways are involved in the abnormal proliferation and contraction of the smooth muscle cells of the pulmonary arteries in patients with pulmonary arterial hypertension. Three of these pathways are important since they have been targeted with drugs — endothelin receptor antagonists,<unk> osphodiesterase type 5 (PDE-5) inhibitors, and prostacyclin derivatives. Prostaglandins Prostacyclin (prostaglandin I2) is commonly considered the most effective treatment for PAH. Epoprostenol (synthetic prostacyclin) is given via continuous infusion that requires a semi-permanent central venous catheter. This delivery system can cause sepsis and thrombosis. Prostacyclin is unstable, and therefore has to be kept on ice during administration. Since it has a half-life of 3 to 5 minutes, the infusion has to be continuous, and interruption can be fatal. Other prostanoids have therefore been developed. Treprostinil can be given intravenously or subcutaneously, but the subcutaneous form can be very painful. An increased risk of sepsis with intravenous Remodulin has been reported by the CDC. Iloprost is also used in Europe intravenously and has a longer half life. Iloprost was the only inhaled form of prostacyclin approved for use in the US and Europe, until the inhaled form of treprostinil was approved by the FDA in July 2009. Endothelin receptor antagonists Moderate quality evidence suggests that endothelin receptor antagonists improve exercise capacity and decrease symptoms severity. The dual (ETA and ETB) endothelin receptor antagonist bosentan was approved in 2001. Sitaxentan (Thelin) was approved for use in Canada, Australia, and the European Union, but not in the United States. In 2010, Pfizer withdrew Thelin worldwide because of fatal liver complications. A similar drug, ambrisentan is marketed as Letairis in the U.S. by Gilead Sciences. s<unk> osphodiesterase type 5 inhibitors The U.S. FDA approved sildenafil, a selective inhibitor of cGMP specific<unk> osphodiesterase type 5 (PDE5), for the treatment of PAH in 2005. It is marketed for PAH as Revatio. In 2009, they also approved tadalafil, another PDE5 inhibitor, marketed under the name Adcirca. PDE5 inhibitors are believed to increase pulmonary artery vasodilation, and inhibit vascular remodeling, thus lowering pulmonary arterial pressure and pulmonary vascular resistance. Tadalafil is taken orally, as well as sildenafil, and it is rapidly absorbed (serum levels are detectable at 20 minutes). The T1/2 (biological half-life) hovers around 17.5 hours in healthy subjects. Moreover, if we consider<unk> armacoeconomic implications, patients that take tadalafil would pay two-thirds of the cost of sildenafil therapy. However, there are some adverse effects of this drug such as headache, diarrhea, nausea, back pain, dyspepsia, flushing and myalgia. Activators of soluble guanylate cyclase Soluble guanylate cyclase (sGC) is the intracellular receptor for NO. , the sGC activators cinaciguat and riociguat were undergoing clinical trials for the treatment of PAH. Surgical Atrial septostomy is a surgical procedure that creates a communication between the right and left atria. It relieves pressure on the right side of the heart, but at the cost of lower oxygen levels in blood (hypoxia). Lung transplantation replaces a chronic condition with the ongoing need for treatment. There is a post-surgical median survival of just over five years. Pulmonary thromboendarterectomy (PTE) is a surgical procedure that is used for chronic thromboembolic<unk> . It is the surgical removal of an organized thrombus (clot) along with the lining of the pulmonary artery; it is a very difficult, major procedure that is currently performed in a few select centers. Monitoring Established clinical practice guidelines dictate the frequency of pulmonary nodule evaluation and surveillance, patients are normally monitored through commonly available tests such as:
Pulmonary hypertension
Portopulmonary hypertension
Chronic thromboembolic pulmonary hypertension
Asthma
Chronic obstructive pulmonary disease
Emphysema
Hypertensive heart disease
Reactive airway disease