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Many people throughout the world are living with a severe pulmonary disease, known as pulmonary arterial hypertension. This disease has various etiologies and is often not diagnosed appropriately or early in the disease process, leading to limited, long-term survival. Fortunately in the past 20 years, medications and other options have been developed that provide patients with life-prolonging treatments that also increase their quality of life. Pathophysiology, disease identification and classification, and treatment options, focusing on current pharmacological treatments, are discussed in this article.
PULMONARY ARTERIAL hypertension (pah) is a relatively rare disease causing pulmonary vascular dysfunction that leads to right ventricular failure and death. It is estimated that 5 to 286 people per 1 million cases will be diagnosed with some form of PAH.1 This devastatingly progressive and fatal disease has various etiologies that make early diagnosis difficult and as a result this leads to poorer outcomes. Once diagnosed, even with treatment, the average 3-year survival rate was noted to be around 67%.1 That being said, the fact is that with all of the new treatment options available for patients, many patients are doubling and tripling that noted survival rate. Many patients are living more than 10 years past their diagnosis date, which in the early days of being diagnosed with PAH was rare. Although the incidence of PAH is less common, it is important for all nurses to have a basic understanding about the disease process and the life-prolonging treatments that will need to be administered while a patient with PAH is receiving nursing care. This article provides a brief overview of the pathophysiology of the disease process, identify the various types and causes of PAH, and review the diagnosis and staging. The main focus is on current treatment options that are used for PAH and include endothelin receptor antagonists (ERAs), phospodiesterase type 5 (PDE5) inhibitors, and prostacyclins. Their doses and delivery systems (oral, subcutaneous, intravenous, or inhaled) are detailed in this article along with a brief summary of therapies under clinical trial and surgical options.
Although the exact pathophysiologic process remains uncertain, PAH is known to originate from a complex combination of vasoconstriction, inflammation, fibrosis, thrombosis, vascular wall hypertrophy, and abnormal cell proliferation that leads to pulmonary vascular dysfunction.1,2 It is believed that endothelial dysfunction seen in PAH causes an overproduction of vasoconstricting agents with proliferative properties such as endothelin-1 and thromboxane A2. In addition, endothelial dysfunction is associated with a decreased production in vasodilating and antiproliferative agents such as nitric oxide (NO) and prostacyclin. The imbalances caused by this endothelial dysfunction leads to an increase in vascular tone, inflammation, fibrosis, and vascular remodeling of the small pulmonary arteries.3 These pathologic changes lead to an increase in pulmonary vascular resistance and elevated pulmonary arterial pressures (PAPs) that eventually cause right-sided heart failure and death.1
In 1998, The World Health Organization4 (WHO) formulated a classification system for the causes of pulmonary hypertension, with revisions in 2003 and 2008. In all, 5 subgroups were established on the basis of their similar pathology, clinical features, and treatment options (Table 1). The WHO pulmonary hypertension classifications are as follows: group 1, pulmonary arterial hypertension; group 2, pulmonary hypertension with left-sided heart disease; group 3, pulmonary hypertension associated with lung disease and/or hypoxia; group 4, pulmonary hypertension due to chronic thromboembolic disease; and group 5, a miscellaneous category (sarcoidosis, histiocytosis X, lymphangiomatosis, adenopathy, tumors, and fibrosing mediastinitis).1 For the purposes of this article, WHO group 1: PAH is the primary focus.
In addition to classifying the causes of pulmonary hypertension, the WHO also outlined the different etiologies that comprise each group. Group 1: PAH has 5 recognized etiologies. When PAH develops without any evidence of familial disease or predisposition, it is called idiopathic pulmonary arterial hypertension (IPAH).3 Familial disease, now termed heritable PAH, is associated with 3 known predisposing genetic mutations: bone morphogenetic protein receptor type II (BMPR2), activin-like kinase type 1, and 5-hydroxytryptamine (serotonin) transporter gene.5
Having one of these mutations does not guarantee a diagnosis of PAH; rather, it increases the odds of developing it. Carriers of the BMPR2 mutation, for example, have a 15% to 20% lifetime risk of developing PAH.1 Genetic mutations are not the only risk factors associated with PAH; in fact, there are several associated conditions and even drugs that have been linked to PAH, and when they are present at diagnosis, it is termed associated with pulmonary arterial hypertension. Some of the medications for associated with pulmonary arterial hypertension are appetite suppressants from the 1960s, and now there is even some question of whether medications used to treat attention-deficit disorder can be implicated.3 The associated conditions recognized by the WHO are connective tissue disorders (CTDs) such as systemic sclerosis, HIV, portal hypertension, congenital heart disease, schistosomiasis, and hemolytic anemias such as sickle cell disease. Information from US and European registries shows that systemic sclerosis-related PAH has the poorest survival outcomes. The fourth etiology is PAH associated with significant involvement of the venous or capillary vessels. This category includes pulmonary capillary hemangiomatosis and pulmonary veno-occlusive disease. One of the final subgroups of PAH is called persistent pulmonary hypertension of the newborn,1 which occurs when pulmonary vascular resistance remains high after birth, resulting in abnormal circulation and hypoxia.6
With its many etiologies and nonspecific symptoms, PAH is often difficult to diagnose and is commonly a diagnosis of exclusion. In the early stages of the disease, symptoms present similarly to those of other cardiopulmonary illnesses. The symptoms of early PAH include dyspnea on exertion, syncope, weakness, abdominal distention, chest pain, and fatigue. As the disease progresses, symptoms worsen to the point that dyspnea is reported at rest.3,7 Upon physical examination, PAH may present with the following signs: a left parasternal lift, a pansystolic murmur of tricuspid regurgitation, the diastolic murmur of pulmonary regurgitation, and an S3 heart sound. With advanced disease, the physical examination may reveal jugular venous distention, peripheral edema, ascites, hepatomegaly, and cool extremities.3
There are several diagnostic tests that can be done to support the clinical suspicion of PAH. Although electrocardiography has unsatisfactory selectivity and specificity to be considered a screening tool, it can provide supportive evidence of PAH by indicating right axis deviation or right ventricular hypertrophy with stain. A chest radiograph is another helpful tool used for making the diagnosis of PAH. Chest radiographs have been shown to be abnormal for IPAH, at the time of diagnosis, in 90% of cases. The abnormal radiographic findings seen include enlargement of the right atria and/or right ventricle and dilation of the central pulmonary arteries. They are also helpful in differentiating some of the other causes of pulmonary hypertension such as WHO group 2 associated with left-sided heart disease and group 3 associated with lung disease and/or hypoxia. Another widely used test is transthoracic echocardiography. Transthoracic echocardiographs are useful in determining the cause of suspected pulmonary hypertension, and they provide variables such as PAP that are associated with hemodynamics.3
When physical examination findings and preliminary diagnostic tests point to PAH, clinical suspicion can be confirmed with a right heart catheterization, which is considered the gold standard in the diagnosis of PAH because it can directly assess hemodynamic impairment and its severity.3 The findings of right heart catheterization are confirmatory of PAH when the mean PAP is greater than 25 mm Hg, the pulmonary capillary wedge pressure is 15 mm Hg or less, and the pulmonary vascular resistance (PVR) is greater than 3 Wood units.1
Once a diagnosis is made, patients are classified into 1 of 4 groups, using subjective assessment of their abilities and severity of symptoms.1 Through an adaptation of the New York Heart Association's classification system, the WHO was able to create this classification system for PAH based on functional capacity (Table 2). It is used in everyday practice to describe patents and has been shown to be a strong predictor of disease mortality.3 Even the Food and Drug Administration (FDA), with the introduction of PAH-specific therapies, uses the WHO functional classes to specify for whom approved therapies are indicated.
Prior to 1995, when the FDA approved the first PAH-specific medication, epoprostenol sodium, conventional therapies were the only treatment options available. These conventional therapies, still used today, are individually tailored depending on the form of PAH, patient lifestyle, and comorbidities. For example, evidence shows that anticoagulation is a favorable treatment option for idiopathic, heritable, and drug-induced PAH. In these subgroups, there are associated coagulation abnormalities and a higher rate of thrombotic lesions. Also, for patients who are receiving intravenous prostacyclin therapy, some providers may choose to use anticoagulation to avoid catheter-related thrombosis: however, it may not be an appropriate treatment option for all PAH patients, especially those with portal hypertension and esophageal varices. Diuretics are another class of medications often used to alleviate the symptoms of right ventricular decompensation in advanced PAH. Although there is little researchable evidence to support their use, clinically they have been shown to provide benefit by reducing peripheral edema, ascities, and other symptoms of fluid overload. Research has shown that acutely ill patients with IPAH can benefit from digoxin therapy. In the short term, digoxin has been shown to increase cardiac output, but it has not been tested for long-term benefit in this population.3 The systemic vasodilatory effects of calcium channel blockers have also proven to be beneficial for some patients with IPAH, but before starting this therapy, an acute vasodilator test should be performed. This test is normally done during a diagnostic right heart catheterization. A acute vasodilator such as NO, adenosine, or epoprostenol is used to assess the patient's reaction. Only those who score positively on the test should be given a calcium channel blocker; otherwise, severe adverse effects, such as syncope, hypotension, and right ventricular failure, can result.8 In addition, oxygen therapy has been shown to reduce pulmonary vascular resistance in all patients with PAH, but there have been no randomized control studies to prove its benefit in the long term. It is currently indicated for a PaO2 that is steadily less than 60 mm Hg, those who desaturate with activity, and when there is proof of symptomatic benefit.3
Fortunately, from the time epoprostenol sodium (Flolan) was released in 1995 until now, 11 additional medications have been approved by the FDA for the treatment of PAH. For the purposes of this article, approved medications are categorized by their routes of administration (oral, intravenous, subcutaneous, and inhaled) (Table 3).
Currently, there are 6 oral medications available in the United States. Bosentan (Tracleer), an endothelin receptor antagonist (ERA), was the first FDA-approved oral agent in November 2001 for patients with WHO functional class III or IV and then was later approved for WHO functional class II in August 2009.8 At the present time, it is only indicated for idiopathic, heritable, and associated PAH. Bosentan works by blocking both endothelin receptors (ETA and ETB) that are believed to play a significant role in the pathogenesis of PAH. Through research, it has been correlated with a significant reduction in PAPs and an increase in cardiac index (CI).9 In addition to its favorable impact on hemodynamics, bosentan has been shown to significantly improve the 6-Minute Walk Test (6MWT) and delay clinical worsening.10
A 6MWT is performed to determine a patient's cardiopulmonary functional capacity and his or her ability to perform activities of daily living. The patient's vital signs and pulse oximetry are taken before, during, and 5 minutes at the end to the test. The test measures the distance a patient can walk quickly over a flat surface for 6 minutes. During the test, the patient's vital signs and pulse oximetry are monitored. The test is stopped if the patient has chest pain, hypertension, desaturation, and/or intolerable dyspnea. The distance that the patient walks is then calculated, along with patient's perception of breathlessness, and the vital signs and pulse oximetry reading to determine the overall score and patient's level of function.
Like many other medications, however, there are serious side effects associated with bosentan use; therefore, it is important to monitor for signs and symptoms of hepatotoxicity, fluid retention, and anemia. In addition, female users need to be educated about the importance of birth control to prevent serious birth defects and male users about the potential for low sperm counts. More common adverse reactions include headache, flushing, syncope, hypotension, sinusitis, arthralgias, arrhythmias, and respiratory tract infections.11 The initiating dose of bosentan is 62.5 mg twice a day for 4 weeks and is then increased to the maintenance dose of 125 mg twice a day.
Ambrisentan (Letairis), approved in June 2007, is the only other FDA-approved ERA currently on the market. It is indicated for those who have WHO functional class II-III symptoms with idiopathic, heritable, or associated PAH.12 It works in a manner similar to bosentan by working at the level of the endothelin receptors, but unlike other medications, ambrisentan has a greater selectivity for ETA. This allows for a decrease in vascular smooth muscle vasoconstriction without hindering the vasodilatory effects of ETB.8 It has hemodynamic benefits very similar to that of bosentan, showing the ability to lower PAP and PVR while increasing CI.13 Research has also shown an improvement in the 6MWT and a low risk of clinical worsening while taking ambrisentan therapy.14 Similarly, the serious side effect profile includes fluid retention, anemia, and birth defects, but instead of hepatotoxicity, there is a risk of pulmonary veno-occlusive disease. Adverse reactions are similar. Patients are given a daily 5-mg dose and, and if well tolerated, it can be increased to 10 mg daily.12
Phosphodiesterase type 5 (PDE5) inhibitors are the second class of oral treatment options and include the medications sildenafil citrate (Revatio) and tadalafil (Adcirca). These inhibitors help enhance vasodilation mediated by NO. Nitric oxide plays an important role in adjusting vascular tone systemically as well as in the pulmonary vessels. PDE5 inhibitors have been shown to promote smooth muscle relaxation and inhibit cellular proliferation.8
Sildenafil citrate was the first PDE5 inhibitor to be approved in June 2005 for functional class II-III symptoms with either idiopathic PAH or associated with connective tissue disease PAH. Studies have shown that it, too, significantly improves hemodynamics by reducing PAP and PVR while increasing CI. During clinical trials, it proved effective in significantly increasing the 6MWT and functional class at all tested doses; therefore, because there was a lack of difference among the treatment groups, the FDA chose the smallest tested dose of 20 mg three times a day for approval.8 Research shows sildenafil is generally well-tolerated. Common adverse reactions include epistaxis, headache, diarrhea, blurry vision, flushing, insomnia, and dyspepsia.15 More serious adverse reactions reported include grand mal seizures, drug hypersensitivity, gastroesophageal reflux disease, hypotension, and angioedema.16 All patients taking PDE5 inhibitors should be cautioned about the risk of using organic nitrates because when these drugs combine they cause severe hypotension that may be irreversible.
Tadalafil (Adcirca) gained its approval in 2009 as the second PDE5 inhibitor for the treatment of idiopathic, heritable, and associated PAH with functional class II-III symptoms.8 Similar to sildenafil, during clinical trials, tadalafil produced significant hemodynamic improvements in PAP, PVR, and CI. It also significantly improved exercise capacity, as measured by the 6MWT. What makes tadalafil different is that although it does not have an effect on WHO functional class, it has been shown to significantly improve the time to clinical worsening.17 Another difference is that tadalafil has a convenient once-a-day dosing of 40 mg. Its common adverse reactions are similar to those of sildenafil, but it has its own serious adverse reactions of hypotension, priapism, hearing loss, and vision loss.18
Two other new medications to be discussed belonged to investigational drug clinical trials, but as of October 15, 2013, both of the medications were released from trial by the FDA and are now approved therapies. The first one is Adempas (riociguat) from Bayer Healthcare LLC. This is a member of a new class of compounds, soluble guanylate cyclase stimulators. Adempas is indicated for the treatment of persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) (WHO group 4) after surgical treatment, or inoperable CTEPH, to improve exercise capacity and WHO functional class. Adempas is also indicated for the treatment of PAH (WHO group 1) to improve exercise capacity, WHO functional class, and delay clinical worsening. This medication is initiated at 1 mg 3 times a day and titrated up to 2.5 mg 3 times a day, depending on patient tolerance.19 The second medication recently approved by the FDA is Opsumit (macitentan) from Actelion Pharmaceuticals. Opsumit is an ERA indicated for the treatment of PAH (WHO group 1) to delay disease progression. Disease progression included death, initiation of intravenous or subcutaneous prostanoids, or clinical worsening of PAH or worsened PAH symptoms. This medication is dosed at 10 mg once daily.20 Both of these new medications have a embryo-fetal toxicity safety warning and should not be administered to a pregnant female, and females of reproductive potential need to be counseled accordingly.
Currently, there are 3 FDA-approved intravenous prostacyclins available for treatment of PAH. In healthy individuals, endothelial cells release prostacyclin to cause vasodilation and inhibit platelet aggregation and are believed to have antiproliferative effects. Unfortunately, for patients with PAH, their associated endothelial dysfunction leads to a reduction in the level of prostacyclin that is synthesized and therefore they do not get its benefits.1
The first intravenous prostacyclin approved by the FDA in 1995 was epoprostenol (Flolan). It is presently indicated for patients of WHO functional class III-IV with idiopathic, heritable, and connective tissue disease-associated PAH. Research has shown that epoprostenol can significantly improve hemodynamics, the 6MWT, and WHO functional class, but it is not without serious risks.8 The half-life of epoprostenol is only 2 to 3 minutes; therefore, any infusion interruption, whether from catheter occlusion or pump malfunction, can lead to severe rebound pulmonary hypertension (dyspnea, dizziness, and weakness) and death. Similarly, overdosage of epoprostenol can result in fatal hypotension, hypoxemia, and respiratory arrest.21 Once reconstituted and ready for infusion, the pump cartridge containing the medication must be kept on ice, because the solution has a pH of 10.2 to 10.8 and is unstable at room temperature.21 Patients are trained to reconstitute and administer the medication on their own every 24 hours through the only approved pump, the CADD-Legacy 1. The pump, the size of a videocassette tape, is set to deliver the medication in nanograms per kilogram per minute. Doses start at 1 to 3 ng/kg/min and are individually titrated depending on the therapeutic response and adverse effects.7 Commonly reported adverse effects include flushing, headache, jaw pain, nausea, vomiting, and diarrhea. Generally, patients do very well with epoprostenol infusions, but they are susceptible to errors, and even death, when hospitalized if the staff is not familiar with the drug therapy.8
In 2010, the FDA approved a stable form of epoprostenol AM under the brand name Veletri. It is approved for the same etiologies and functional classes as Flolan but differs because it is stable after reconstitution at therapeutic doses; therefore, patients who switch to Veletri are no longer required to keep their pumps on ice. It has the same half-life, risk profile, and common adverse effects as Flolan, and both are contraindicated for congestive heart failure due to severe left ventricular systolic dysfunction, pulmonary edema during initiation, and hypersensitivity reactions. Veletri dosing starts at 2 ng/kg/min via the CADD-Legacy 1 pump and is titrated according to therapeutic response and adverse effects.20
Treprostinil sodium (Remodulin) received FDA approval as an intravenous prostacyclin in 2004 for WHO functional classes II-IV with idiopathic, heritable, and congenital heart disease/CTD-associated PAH.
Treprostinil is "a stable tricyclic benzindene analogue of epoprostenol" that has been shown to improve the 6MWT, WHO functional class, and dyspnea.1,7 It is indicated to help lessen the exercise-associated symptoms of PAH and used as a transitional drug if patients develop clinical worsening while taking epoprostenol. The advantages of treprostinil are that it has a longer half-life of approximately 4.5 hours; it has no contraindications; a cartridge of medication can last 48 hours; and it can be infused using much smaller pumps, such as CRONO Five and CADD-MS 3.7 A disadvantage is that intravenous treprostinil has shown a greater rate of gram-negative infections than do other prostacyclins.1 It is initially dosed at 1 to 3 ng/kg/min and is gradually increased to standard long-term doses of 80 to 120 ng/kg/min or more. As with all other prostacyclins, an individual's goal dose is determined by his or her therapeutic response and adverse effects.7 The most common adverse effects reported are jaw pain, nausea, diarrhea, widening of the blood vessels, hypotension, and edema of the feet, ankles, and legs.1
Usually, intravenous prostacyclin therapies are started when oral therapies fail to be effective, when functional class worsens, or when the disease is diagnosed in later stages; however, before starting one of these medications, is it important that the patient is fully aware of the lifelong commitment to therapy and that he or she is competent to take on this type of treatment. All of the intravenous prostacyclins require comprehensive patient education to make certain of user safety and compliance with sterile medication preparation, pump management, and aseptic care of the central venous catheter.7
To date, there is only one subcutaneous option for PAH approved by the FDA and that is treprostinil sodium (Remodulin). Treprostinil was actually first approved in 2002 as a subcutaneous infusion agent, but a treatment-limiting factor for some patients became infusion site pain, so it was tested as an intravenous formulation. The subcutaneous preparation is bioequivalent to the intravenous preparation and is actually the preferred route of administration because it requires no dilution and is not associated with bloodstream infections. Subcutaneous treprostinil is administered via the MiniMed 407C pump but may require anticoagulation therapy to maintain its catheter patency. In addition to the possible need for anticoagulation, the MiniMed 407C pump was associated with a large number of pump malfunctions and adverse events; therefore, for patients receiving subcutaneous treprostinil, it has been recommended to use the CADD-MS 3 pump for infusions.7
At this time, there are 2 inhalation medications that are FDA approved for the treatment of PAH. Both medications cause direct vasodilation of the pulmonary and systemic arterial vasculature while also inhibiting platelet aggregation. They also have very similar side effect profiles and contraindications. Treprostinil (Tyvaso), a prostacyclin analogue, was the first inhalation preparation made available in 2002. It is approved for patients with idiopathic, heritable, and CTD-associated PAH with functional class III symptoms.22 It was first evaluated as an additional therapy for patients who were already taking bosentan or sildenafil and then later as a transitional option for intravenous or subcutaneous prostacyclins. As an additional therapy, Tyvaso was reported to improve the 6MWT but did not improve functional class, time to clinical worsening, or symptoms. In addition, when used to transition patients off intravenous or subcutaneous prostacyclins, Tyvaso was shown to maintain the results of the 6MWT and hemodynamics, but some patients experienced a worsening in their functional class.1 With a half-life of 4.5 hours, patients receive the medication via the Tyvaso Inhalation System at 4 separate equally spaced treatment times while awake.23 Initial dosing consists of 3 breaths (18 [mu]g) per treatment time, equaling 12 breaths per day. Doses are increased every week by 3 breaths, until the target dose of 9 breaths per session (54 [mu]g) is reached, equaling 36 breaths per day. Tyvaso has shown to be safe and well tolerated. Common adverse effects reported include headache, flushing, cough, sore throat, syncope, and nausea.22
Iloprost (Ventavis) was the second inhalation therapy approved in 2004 for idiopathic, heritable, and CTD-associated PAH with WHO functional class III-IV symptoms. Its mechanism of action is very similar to Tyvaso, but it has a much shorter half-life of 30 minutes, requiring more frequent dosing. Patients are required to administer 6 to 9 inhalations per day (5 [mu]g per dose) using the I-neb AAD System, with doses spaced at least 2 hours apart. Research has shown that the preparation and administration of iloprost are more time consuming than Tyvaso's, which has led more patients to report compliance difficulties.23 A decrease in compliance leads to a decrease in therapeutic effects. For this reason, iloprost may not be a good choice for everyone.
It is feasible to think that a combination of the 3 different PAH-approved drug classes (ERAs, PDE5 inhibitors, and prostacyclins) would provide a greater benefit, since they work through different pathways, but there are currently no formal recommendations developed to address combination therapy. Although there are no formal guidelines or recommendations, combination therapy is routinely used in clinical practice. Studies have shown that using a combination therapy significantly improves exercise capacity, and hemodynamics, while decreasing the time to clinical worsening. This practice has shown to be well tolerated, with no increase in adverse effects. The only disadvantage of combination therapy thus far is that it has not shown to make any significant improvements in functional class or mortality.1
Researchers continue to search for additional treatment options to improve symptom management, slow disease progression, and eventually cure PAH. Currently under investigation are 2 oral therapies that work though the prostacyclin pathway. The first investigational drug is oral treprostinil. It is undergoing clinical trials as a monotherapy and as an add-on therapy. In trials assessing treprostinil as a monotherapy, positive outcomes have been reported; however, in the initial add-on therapy trial, which assessed twice-daily dosing of sustained-release treprostinil in combination with ERAs or PDE -5 inhibitors, significant results were not obtained. Despite these negative results, future studies of oral treprostinil are planned.1
The second investigational drug under clinical trial is selexipag, which is different from current prostacyclins and prostacyclin analogues because it is a prostacyclin IP receptor agonist. This means that it does not activate other prostacyclin receptors in the body, but it is highly selective to the prostacyclin IP receptor.1 This has been associated with a greater vasodilatory effect than iloprost because it does not activate any vasoconstricting pathways. Research thus far shows that it has a half-life of approximately 8 hours and that with twice-daily dosing, it is generally well-tolerated. It has also shown a significant reduction in pulmonary vascular resistance.24
Despite the ability of recent medical therapies to improve symptoms and delay time to clinical worsening, there is still no cure for PAH. There are, however, surgical treatments available for disease management. Atrial septosotomy is a procedure often used as a palliative treatment option for patients who do not respond to medical therapy and for those with advanced disease. Clinically, it has been shown that patients with IPAH who have a patent foramen ovale tend to have a survival advantage when compared with those without; therefore, surgically, a right-to-left shunt is created between the atria. Creating this shunt helps relieve right ventricular pressure, improve left ventricular preload, increase systemic blood flow, and increase oxygen transport. The procedure is, however, associated with a high rate of mortality and therefore should be performed only in an experienced treatment facility.25
Another surgical option available is pulmonary thromboendarterectomy. This is a surgical procedure that removes chronic blood clots from the arteries of the lungs. Chronic blood clots can cause partial or complete occlusion of the pulmonary arteries, resulting in elevated pulmonary pressures. This is known as CTEPH. This is a very specialized surgical procedure, first developed at the University of California, San Diego, and is performed in a very limited number of facilities in the United States. Patients who develop CTEPH and undergo pulmonary thromboendarterectomy, which removes the blood clots from the pulmonary arteries and vasculature, can possibly be cured of their pulmonary hypertension.
Although atrial septosotomy and/or pulmonary thromboendarterectomy are surgical options, the mainstay of surgical treatment since the 1980s has been organ transplantation. Transplant referral is generally reserved for patients with WHO functional class III or IV symptoms whose response to treatment is either suboptimal or under evaluation. Patients can be listed for a single-lung, a double-lung, or a heart-lung transplant.25 According to the International Society for Heart and Lung Transplantation's 23rd report, patients with IPAH who receive a lung transplant have the highest rate of perioperative mortality and have the lowest rates of survival, at 1 year posttransplant, when compared with other types of recipients. Despite this, recent advancements in surgical technique, organ preservation, infection prophylaxis, and immunosuppression have been shown to increase the survival rates reported by the International Society for Heart and Lung Transplantation by upwards of 40%.26
Although PAH remains a challenging disease to diagnose and manage, a better understandings of its pathophysiology has led to advancements in medical treatment options, such as ERAs, PDE-5 inhibitors, and prostacylcins, which have been shown to significantly improve patient outcomes. Also, when indicated, surgical treatments can be beneficial for a select group of patients; however, despite these recent advancements, right ventricular failure remains a frequent complication of PAH that is potentially fatal. Statistics have shown that even with treatment, the mean survival rate at 1, 2, and 3 years is 87%, 76%, and 67%, respectively.1 The good news is that with the increase in the level of research being done to find appropriate and stable treatment options for the disease, as well as the number of new medications available, there is much hope for the future. Many patients are doubling and tripling their live expectancy over what the statistical data state. With that said, further research is necessary for closer examination of the pathophysiologic process, develop new pathways for drug therapy that increase patients' life, decrease symptoms associated with the disease, and increase patients' quality of life.
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cardiac index (CI); connective tissue disorders (CTD); endothelin receptor agonists (ERA); 6-Minute Walk Test (6MWT); phosphodiesterase type 5 inhibitors (PDE5); prostacyclins; pulmonary artery pressures (PAP); pulmonary vascular resistance (PVR); right heart catheterization (RHC)
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