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Evaluation and Management of the Adult Patient With Pulmonary Hypertension
Evaluation and Management of the Adult Patient With Pulmonary Hypertension Todd Michael Tartavoulle, CNS-BC
ABSTRACT The prevalence of adult pulmonary hypertension (PH) in the United States has escalated in all races, gender, and ethnic populations. Nurse practitioners (NPs) are encountering adults with PH with increasing frequency. Through increased knowledge of the pathophysiological changes, diagnostic measures, and treatments for adults with PH, NPs collaborate with interdisciplinary teams to manage and improve client outcomes and quality of life. Keywords: endothelin receptor antagonists, mean pulmonary artery pressure, phosphodiesterase inhibitors, prostanoids, pulmonary hypertension, right heart catheterization © 2011 American College of Nurse Practitioners
P
ulmonary hypertension (PH) is a progressive and ultimately fatal disease that presents as an elevated blood pressure in the pulmonary arteries. PH evolves as a comorbidity of other diseases or conditions, such as connective tissue diseases, lung diseases, liver disease, pregnancy, HIV infection, left heart failure, and the usage of the diet medication Fen-Phen, a combination of the 2 drugs fenfluramine (Pondimin) and phentermine (Lonamin). Although triggered by other diseases or conditions, the specific etiology of PH is not known. PH and comorbidity conditions affect a diverse segment of the population. The demographic profile of adult PH patients includes men and women of all ages, racial, and ethnic groups. Between 2000 and 2002, the Centers for Disease Control and Prevention reported 807,000 adults were hospitalized with PH. Of these adults, 61% were women and 66% were 65 or older.1 During the time period of www.npjournal.org
1980-2002, the number of PH deaths increased from 10,922 to 15,668, respectively; however, the greatest increase was observed only among women.1 Among all racial populations, the number of adult PH deaths has increased mostly among the African American population.1 Death rates are higher among the elderly, especially men 85 or older, women 65 or older, whites 75 or older, and African Americans 65 or older.1 Regardless of gender, age, or race, PH patients require continuous evaluation and management by an interdisciplinary team to alter disease progression and the resultant impact on multiple organ systems. PH affects both the pulmonary and cardiovascular systems, with a potential negative impact on quality of life. PH patients have many acute and chronic health care needs that require meticulous evaluation, management, and care coordination. The nurse practitioner (NP) collaborates within an interdisciplinary team to effectively The Journal for Nurse Practitioners - JNP
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evaluate and manage the PH patient and their comorbid health conditions.
prostaglandin that promotes blood vessel vasodilatation and prevents the overgrowth of cells in the blood vessels. Prostacyclin prevents platelets from clumping together, PATHOPHYSIOLOGY which lowers the incidence of clogged blood vessels. NO The pulmonary vasculature contains arteries and arteriis a powerful vasodilator that prevents smooth muscle oles, which branch in the lungs to create a dense capilgrowth and inhibits platelets from sticking together. ET-1 lary bed to provide blood flow. is a messenger that causes vasoThe pulmonary capillary bed is constriction of the blood vesa high-volume, low-pressure, sels. In healthy adults, these low-resistance system that molecular messengers ensure Signs and symptoms of PH delivers blood to and from the appropriate compensatory are related to the severity lungs via the arterial and blood flow based on metabolic venous circulation systems, demands.4 of right heart failure. respectively. In a normal healthy In adults with PH, smooth adult, this system has a mean cells proliferate in the intima, pulmonary artery pressure thickening and clogging the (MPAP) that ranges from 12 to 16 mmHg.2 arteriole walls. This altered tissue inside the arterioles The dense capillary branching and the cumulative forms a plexiform lesion. The lesion clogs the inside of diameters of the capillaries provide a lower resistance the arterioles, causing scar formation of the intima and pressure while effectively facilitating gas exchange.3 The media arteriole layers. This narrows the vessel, with a pulmonary vasculature system is effective during times of resultant increase in MPAP. This scar tissue is fibrous and exercise as it can increase blood-carrying capacity by as prevents the arterioles from expanding and contracting, much as 5 times with little or no increase in pulmonary thereby decreasing the normal compensatory mechanism 3 pressure. In a healthy individual the arterioles are thinof the pulmonary circulatory system. This thickening or walled, distensible vessels that are able to dilate in times remodeling of the intima arteriole layer is irreversible and of increased metabolic need. The arterioles are composed leads to permanent vasoconstriction of the arterioles, of 3 layers: intima, media, and adventia.4 The intima is with a resultant increase in MPAP.4 the innermost layer and is responsible for tightening and In addition, adult PH clients experience an imbalance relaxing the blood vessel, blood clotting, forming new among the molecular messengers contributing to pulvessels, inflammation, and immune responses.4 The media monary vascular remodeling, systemic hypoxia, and pulis the middle layer that regulates the diameter and volmonary thrombosis, which leads to increased MPAP and ume of the vessels, thereby distributing blood to areas of the development of PH.2 The levels of the molecular the body in need. The adventitia is the outermost layer messengers prostacyclin and NO, which produce vasodi4 and comprises collagen, which gives the vessel stability. latation throughout the pulmonary circulation and preChemical messengers, which include tumor necrosis facvent platelet aggregation, are reduced, while concurrently tor and interleukin 1, serve as the mechanism of action there is an overabundance of the vasoconstricting properthat promotes the responsiveness of these arterial layers to ties of the molecular messenger ET-1. As a result of the increased metabolic needs.2 imbalance in the molecular messengers, pulmonary vasThe pulmonary vasculature generates chemical mescular resistance (PVR) and MPAP are increased and negsengers that produce, repair, and destroy cells in the vessel atively affect cardiac output. wall.2 The blood vessels of the pulmonary circulatory A patient with PH has a resting MPAP ⬎ 25 mmHg, system are controlled by a system of molecular messenwith a pulmonary capillary wedge pressure (PCWP) ⬍ gers that facilitate the metabolic compensation through 15 mmHg. As the disease progresses, right ventricular dilatation and constriction of these blood vessels. hypertrophy occurs as a result of the increased pulProstacyclin, nitric oxide (NO), and endothelin (ET-1) monary vascular resistance (PVR), which leads to right are the molecular messengers that control the flow of heart failure, activity intolerance, and eventually can lead blood in the pulmonary circulation. Prostacyclin is a to death.5 Signs and symptoms of PH are related to the 410
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severity of right heart failure. In the early stages of the disease, the patient may be asymptomatic. With progression of right heart failure, the patient may present with peripheral edema, ascites, hepatomegaly, anorexia, exercise intolerance, and progressive dyspnea from decreased cardiac output (CO).2
used to assess the severity of PH. The WHO, along with the American College of Chest Physicians, supports using this system to assess the functional status of PH patients. Functional status is delineated into 4 possible classes, with severity of symptoms determining class. Table 2 presents the WHO Functional Classes (WHO-FC) for PH.2
DIAGNOSIS INTERDISCIPLINARY TEAM MONITORING PH symptoms are similar to other pulmonary diseases Clinical presentation of the PH patient may reveal nonwhich increases the challenge of differential diagnosis. specific symptoms, such as dyspnea, fatigue, angina, synShortness of breath and exertional fatigue are the most cope, weakness, and abdominal distension. Symptoms at common subjective complaints. Many of the nonspecific rest only occur in the very advanced stages of PH (WHOsubjective and objective findings of PH resemble those of FC IV). Physical signs upon examination include a left heart failure thereby making a complete history and parasternal lift, an accentuated component of the second physical exam by the NP paramount.2 The NP must heart sound, a pansystolic murmur of tricuspid regurgitawork in unison with the other members of the healthtion, a diastolic murmur of pulmonary insufficiency, and a care team to accurately diagnose PH. right ventricular third sound. In advanced cases of PH, On average, patients with PH are not diagnosed until jugular vein distension, hepatomegaly, peripheral edema, the pulmonary vascular bed is significantly damaged, ascites, and cool extremities may be present. Bilateral resulting in shortness of breath. A series of diagnostic tests breath sounds are usually clear, unless an interstitial disease are used to confirm diagnosis, determine etiology and is involved, in which case crackles may be heard upon ausclinical classification, evaluate functional ability, and assess cultation. Rashes, skin tightening, or telangiectasias may be hemodynamic status. These tests present if a mixed connective can provide valuable informatissue disorder, such as sclerotion to the clinician and faciliderma, is present.7 tate diagnosis. As stated in the The NP works within an The NP should encourage introduction, PH is linked to interdisciplinary team to consupport groups and provide several comorbidities, making it tinually monitor and manage extensive teaching and important for the NP to the disease progression and reliable online services. develop a list of possible differquality of life of adult PH patients. An electrocardiogram ential diagnoses. Possible differential diagnoses include sleep (ECG) may reveal right ventricular hypertrophy and strain and right atrial enlargement. apnea, cor pulmonale, pulmonary embolism, hypothyFeatures of the ECG in right ventricular hypertrophy roidism, mixed connective tissue disease (scleroderma and include, right axis deviation, possibly a predominant R systemic lupus erythematosus), and portal hypertension. wave in lead V1, a deep S in V6, inverted T waves in right In addition to differentially diagnosing PH, the NP precordial leads V2 and V3, and peaked P waves.7 and interdisciplinary team must accurately classify the However, an ECG alone cannot diagnose PH. state of PH disease progression. The clinical classification Supraventricular arrhythmias, such as atrial flutter and of PH has undergone a series of revisions since first proatrial fibrillation, may be present in advanced stages of posed in 1978 by the World Health Organization PH and lead to further clinical deterioration.7 A chest (WHO). During 2008, at the 4th World Symposium on radiograph may reveal right atrium and ventricular PH, which convened in Dana Point, California, experts enlargement and pulmonary artery dilatation.4 proposed modifications to the previous classifications. While there is no known specific serological test to Currently, there are 5 clinical categories of PH. Table 1 6 diagnose and monitor PH progression, several serological summarizes the 2008 clinical classification of PH. A modified version of the New York Heart blood tests can be used to monitor thyroid, immune, and Associations’ system for classifying heart failure is also cardiac function, which are PH comorbidities. Thyroid www.npjournal.org
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Table 1. Updated Clinical Classification of Pulmonary Hypertension6 1. Pulmonary Arterial Hypertension 1.1 Idiopathic 1.2 Heritable 1.2.1 Bone morphogenic protein receptor, type 11 1.2.2 Activin receptor-like kinase 1, endoglin (with or without hereditary hemorrhagic telangiectasis) 1.2.3 Unknown 1.3 Drug- and toxin-induced 1.4 Associated with associated pulmonary arterial hypertension 1.4.1 Connective tissue disease 1.4.2 HIV infection 1.4.3 Portal hypertension 1.4.4 Congenital heart disease 1.4.5 Schistosomiasis 1.4.6 Chronic hemolytic anemia 1.5 Persistent pulmonary hypertension of the newborn 1’ Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatomasis 2. Pulmonary hypertension associated with left heart disease 2.1 Systolic dysfunction 2.2 Diastolic dysfunction 2.3 Valvular disease 3. Pulmonary hypertension as a result of lung diseases and/or hypoxemia 3.1 Chronic obstructive pulmonary disease 3.2 Interstitial lung disease 3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern 3.4 Sleep-disordered breathing 3.5 Alveolar hypoventilation disorders 3.6 Chronic exposure to high altitude 3.7 Developmental abnormalities 4. Chronic thromboembolic pulmonary hypertension 5. Pulmonary hypertension with unclear and/or multifactorial mechanisms 5.1 Hematalogical disorders: myeloproliferative disorders, spleenectomy 5.2 Systemic disorders: sarcoidosis, pulmonary Langerhan’s cell histiocytosis 5.3 Metabolic disorders: glycogen storage disease, Gaucher’s disease, thyroid disorders 5.4 Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis
diseases, such as thyrotoxicosis, may exacerbate PH and are common in idiopathic pulmonary arterial hypertension. Evaluation of thyroid function is necessary to assess as symptom improvement has occurred after thyroid function has been restored.8 Serological testing may also detect the presence of a mixed connective tissue disorder, such as scleroderma or systemic lupus erythematosus. A positive antinuclear antibody test may suggest a mixed connective tissue disorder.7 It is important to exclude the connective tissue disorder scleroderma as it has a high prevalence of pulmonary artery hypertension.7 Cardiac biomarkers are obtained to rule out myocardial ischemia. Brain-type natriuretic peptide (BNP) and Nterminal prohormone brain natriuretic peptide (NTproBNP) are indicators of right ventricular overload. Brain-type natriuretic peptide ⱖ 150 pg/mL and NT412
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proBNP ⬎ 1474 pg/mL correlate positively with an elevated MPAP and PVR.9 Serological testing can also detect HIV and hepatitis, which are also causes of PH.4 Pulmonary function tests are performed to identify underlying lung disease and assess severity of PH. The lungs of the PH patient are stiffer, smaller, and have a decreased lung diffusion capacity for carbon monoxide. The carbon monoxide diffusing test (DLCO) measures the efficiency of oxygen diffusion from the lungs to the alveoli. PH patients tend to have a decrease in oxygen diffusion across the capillary membrane.4 A chest computed tomography (CT) scan may be ordered to detect interstitial lung disease, along with possible emboli, and provide information on the heart. Recently an ultrafast CT scan called an electron-beam tomography has been used to monitor changes in the right atrium and Volume 7, Issue 5, May 2011
ventricle. Cardiac magnetic resonance imaging is useful in the assessment of the right heart as it provides a direct assessment of cardiac volume, muscle mass, and function. Ventilation/perfusion scans and pulmonary angiography may also be used to diagnose pulmonary embolism, which is a cause of chronic thromboembolic PH.4 Doppler echocardiography, which is more specific for diagnosing PH, measures pulmonary artery (PA) pressures noninvasively, provides information on pumping ability of both the right and left ventricles and valve function, and can detect congenital heart defects. Doppler findings indicative of advanced PH include right atrial enlargement and septal bowing into left ventricle, right ventricular enlargement and hypokinesis, and presence of a pericardial effusion.2 Other Doppler findings include a tricuspid jet velocity ⬎ 2.8 m/s, tricuspid insufficiency peak gradient ⱖ 31 mmHg, and tricuspid annular plane systolic excursion (TAPSE) ⬍ 1.8 cm. Tricuspid jet velocity measures the velocity of regurgitant blood flow through the tricuspid valve. Tricuspid peak insufficiency gradient evaluates the tricuspid valve for stenosis by measuring the peak gradient across the valve. Tricuspid annular plane systolic excursion is used as an index to evaluate right ventricular function. Decreases in TAPSE correlate with a progressive decrease in right ventricular function.10 Doppler echocardiography may also be performed on the PH patient while exercising as some PH patients’ MPAP may be elevated at this time. This exercise echo is performed while the patient is either exercising on a semi-erect or supine bicycle.4 MPAP ⬎ 30 mmHg while exercising is definitive for PH.9 An exercise tolerance test, more specifically a 6minute walk test (6MWT), is another diagnostic screen that may be used to assess and monitor PH. A healthy individual is able to walk a minimum of 500 meters in 6 minutes, whereas a patient with moderate PH may be able to walk only 300 meters.11 The 6MWT is simple to administer, inexpensive, reproducible, and well standardized. Finger oxygen saturation and dyspnea on exertion are recorded in addition to walk distance. Right-heart catheterization is the most accurate, useful, and definitive diagnostic test for PH. This invasive diagnostic test directly measures pulmonary artery pressures, PVR, CO, and PCWP. A normal MPAP at rest is between 12 to 16 mmHg. A patient with a resting MPAP ⱖ 25 mmHg is diagnosed with PH.9 www.npjournal.org
Table 2. World Health Organization Functional Classes Class I. No symptoms-induced limits on physical activity Class II. Slight symptoms-induced limits on physical activity Class III. Marked symptoms-induced limits on physical activity Class IV. Right-sided heart failure, with dyspnea and fatigue at rest and inability to perform any physical activity without symptoms
A vasodilator study is performed when the PH patient is undergoing a right heart catheterization. A vasodilator study evaluates the pulmonary arteries’ response to medications, such as adenosine, NO, or epoprostenol, that cause vasodilatation. While there is no definitive wording on what constitutes a positive vasoreactivity response, it is believed that MPAP ⬍ 40 mmHg while receiving a vasodilator is a positive response. The presence or absence of vasoreactivity of the pulmonary vasculature provides a diagnosis and guides treatment.4 PHARMACOLOGICAL TREATMENT Pharmacological treatment involves using medications to restore the vasodilator effects and prevent overgrowth of cells in an attempt to decrease PA pressures and increase CO. The vasodilator challenge performed during the right heart catheterization assesses the patient’s potential response to long-term vasodilator medications. When deciding on a plan of care and which medication to use, consideration must be given to medication effectiveness, side effects, lifestyle impact, and quality of life. Table 3 provides a summary of targeted therapy for treatment.4 Calcium Channel Blockers Calcium channel blockers, such as nifedipine (Procardia), amlodipine besylate (Norvasc), and diltiazem hydrochloride (Cardizem), are used initially if the patient had a positive response to the vasodilator challenge. Calcium channel blockers act on vascular smooth muscle to dilate the pulmonary vessels, causing a decrease in MPAP and PVR and increase in CO. Calcium channel blockers are administered orally and can be used long term to effectively manage PH. The dosage may vary from patient to patient.12 The Journal for Nurse Practitioners - JNP
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Table 3. Summary of Targeted Medication Therapy Used to Treat Pulmonary Hypertension6 Class of Medication
Name
Route of Administration
Prostanoids
Epoprostenol Iloprost Treprostinil
Intravenous Inhaled, intravenous Inhaled, intravenous, subcutaneous
Endothelin receptor antagonist
Bosentan Ambrisentan
Oral Oral
Revatio Tadalafil
Oral Oral
Phosphodiesterase type-5 inhibitors
Prostanoids Prostanoids, such as epoprostenol (Flolan), iloprost (Ventavis), and treprostinil (Remodulin, Tyvaso), may be used in the PH patient who had a positive response to the vasodilator challenge. Epoprostenol is an artificial prostacyclin that mimics prostaglandin, which is a naturally occurring substance in the human body. Acting like prostaglandin, epoprostenol dilates blood vessels, prevents platelets from clumping together, increases CO, and slows the growth of smooth muscle cells. Patients with PH in Classes III or IV will receive intravenous epoprostenol through a central line as it has a half life of only a few minutes. The drug is not stable at room temperature.12 Iloprost is a prostacyclin that is usually inhaled via a nebulizer but can also be administered intravenously. When inhaled, its effects are confined to the lungs, so side effects are minimal. Because the effects of the medication last approximately 30 to 90 minutes, the patient must inhale the 10-minute treatment many times throughout the day. It is approved for Classes III or IV.4 Treprostinil is a form of prostacyclin similar to epoprostenol, with a half life of approximately 4 hours. It can be administered intravenously, subcutaneously, or inhaled and is stable at room temperature. The mechanism of action produces vasodilatation in the pulmonary vasculature which reduces right and left ventricular afterload thereby increasing CO.4 Endothelin Receptor Antagonists Endothelin receptor antagonists include bosentan (Tracleer) and ambrisentan (Letairis). Endothelin receptor antagonists vasodilate and prevent cell growth in the 414
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arteries by preventing endothelin from activating receptors.12 Bosentan blocks the endothelin-A and endothelin-B receptors, thereby causing vasodilatation. It is administered orally and has been approved for Classes II, III, and IV. The drug can be toxic to the liver and cause birth defects. All patients on this medication must receive monthly liver function tests, and women must have a negative pregnancy test before initially starting the medication. A monthly pregnancy test should be obtained while the patient is on this medication.4 Ambrisentan is administered orally and only blocks the endothelin-A receptor. It has been approved for functional Class II and III. Pregnancy tests must also be collected monthly for women taking this medication.4 Phosphodiesterase Inhibitors Phosphodiesterase inhibitors, such as revatio (Sildenafil) and tadalafil (Adcirca), function by inhibiting cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type-5 (PDE-5). By inhibiting PDE-5, cGMP is not broken down and relaxes the pulmonary blood vessels. The phosphodiesterase inhibitors have been approved for Classes II, III, and IV.4 Combination Therapy Combination therapy may be used in patients who remain symptomatic on initial medication therapy. There are several potential advantages of combination therapy as current PH therapies act on 3 different yet potentially complementary mechanisms. The clinician may add a second or even a third medication to the regimen to improve exercise tolerance and symptoms. This type of therapy may be warranted if the patient has had a response to the initial therapy but it’s not satisfactory.4 Combination therapy has become the standard of care in most PH centers; numerous case series have suggested that various medication combinations have proven to be safe and effective.13-15 To date, clinical trials continue to be completed to gather evidence in support of combination therapy.4 Lung Transplantation Lung transplantation is an option when medications are not helping the patient to improve. This option may prolong survival and improve quality of life, but it is not recommended in the early stages of PH because life is not immediately threatened. However, lung transplantation Volume 7, Issue 5, May 2011
should be discussed before the patient becomes too ill. Approximately 150 lung transplants are done yearly on PH patients.4 THE ROLE OF THE NP PH is a chronic condition that requires an interdisciplinary team approach to continually monitor disease progression and manage care. The NP has a diagnostic and clinical management role in the care of the PH patient and must work collaboratively with the pulmonologist, cardiologist, respiratory therapist, physical therapist, nutritionist, and other practitioners who offer complementary therapies (eg, acupuncture, massage, and Reiki) to effectively meet the needs of this population. NPs provide follow-up and day-to-day care. Education is vital in order for the patient to return home and become functioning in society once again. Medication Medication adherence rates are approximately 50% in this population; deviations from prescribed therapy include skipping doses, not filling prescriptions, taking medications at wrong times of the day, or interrupting therapy.16 It is important to educate both patient and caregiver on medication mechanism of action and the importance of filling prescriptions and adhering to the scheduled doses, particularly epoprostenol and treprostinil, which have short half lives and should not be stopped abruptly. Education should be provided on signs and symptoms of infection, especially in patients who are receiving epoprostenol and treprostinil intravenously via a Hickman, Groshong, or Broviac catheter. These patients also need assistance to manage the complex medication regimens. A demonstration of sterile technique when caring for intravenous lines and pumps should be provided. The patient and caregiver should perform a return demonstration.16 Nutrition It is essential for the NP to collaborate with a nutritionist and to provide the PH patient with information on diet and weight. A low-sodium diet that is both low in calories and high in healthy carbohydrates is recommended. Information needs to be collected on herbs and supplements used by the patient because they may interfere with PH medications. Weight should be monitored daily, and a quick weight gain of 2 to 3 pounds should be www.npjournal.org
reported immediately to a physician—edema is a sign of heart failure, which can lead to progressive dyspnea.4 Exercise Physical activity should be encouraged, but the patient needs to listen to his or her body. The NP, physician, physical therapist, and patient should set reasonable goals on physical activity. Target values and treatment goals should be individualized. For PH patients a 6MWT ⬎ 400 meters is usually acceptable. Younger patients are capable of walking 500 meters or more. A possible referral to a pulmonary rehabilitation center may be needed. In previous PH cases, exercise has increased the 6MWT.17 Maintenance Suggested follow-up strategies for PH patients include performing a clinical assessment, WHO-FC determination, ECG, 6MWT, and BNP/NT-proBNP levels at baseline, every 3 to 6 months, and 3 to 4 months after changes in therapy or if clinical worsening occurs. An echocardiogram and right heart catheterization should be performed at baseline and 3 to 4 months after changes in therapy or if clinical worsening occurs.7 A quality of life assessment should be performed by administering the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire. This assessment tool contains 3 separate scales that measure symptoms, functioning, and quality of life and is specific for PH patients.18 A flu vaccine yearly in October should be recommended, along with information on means to prevent colds. NPs should instruct patients to wash hands before touching eyes, mouth, or nose. Patients with PH cannot take decongestants because of the vasoconstrictor effect.4 Mental Health Anxiety or depression affect approximately one-third of PH patients.19 It is important for the NP to screen for depression and make appropriate referrals to psychiatrists and psychotherapists.18 An interdisciplinary team approach is best as appropriate medications can be dispersed for distressing symptoms, and psychological, social, and spiritual support can be provided. NPs should also keep in mind that the caregiver faces stress, and both the patient and caregiver should be referred to a local PH support group. The Journal for Nurse Practitioners - JNP
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End of Life End-of-life and ethical issues need to be addressed because PH is a disease of progressive deterioration interspersed with episodes of acute decompensation. Death is difficult to predict; it may be sudden or slow. Communication with PH patients is essential to allow for advanced planning and discussion of their fears, concerns, and wishes. Prognosis should be discussed at the time of initial diagnosis, along with resuscitation status. Cardiopulmonary resuscitation tends to have poor outcomes in the PH patient.17
14. Ghofrani HA, Schemurly RF, Olschewski RT, et al. Oral sildenafil as longterm adjunct therapy to inhaled Iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol. 2003;42(1):158-164. 15. Mathai SC, Girgis RE, Fisher MR, et al. (2007). Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension. Eur Resp J. 2007;29:469-475. 16. Stewart T. Facilitating pulmonary arterial hypertension medication adherence: patient-centered management. Adv Pulm Hypertens. 2010;8(4):228-231. 17. Gin-Sing W. Pulmonary arterial hypertension: a multidisciplinary approach to care. Nurs Stand. 2010;24(38):40-47. 18. Coffin D, Duval K, Martel S, et al. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension. Eur J Clin Invest. 2006;36(Suppl 3):10-15. 19. Lowe B, Kerstin G, Ufer C, et al. Anxiety and depression in patients with pulmonary hypertension. Psychosom Med. 2004;66:831-836.
CONCLUSION PH is a progressive disease with no cure; however, the management of PH continues to evolve. There has been an increase in the number of medications in the past several years that lower MPAP, PVR, and improve CO and distance walked in 6 minutes. The NP must consider factors that affect quality of life. The NP should encourage support groups and provide extensive teaching and reliable online services. The NP and patient can establish realistic expectations for treatment, such as physical activity goals. By understanding PH and performing these actions, the NP is providing the best possible care while improving patient outlook and quality of life.
Todd Michael Tartavoulle, MN, RN, CNS-BC, is an instructor of nursing at the Louisiana State University Health Sciences Center, School of Nursing, in New Orleans. He can be reached at [email protected]. In compliance with national ethical guidelines, the author reports no relationships with business or industry that would pose a conflict of interest. 1555-4155/11/$ see front matter © 2011 American College of Nurse Practitioners doi:10.1016/j.nurpra.2010.11.002
References 1. Centers for Disease Control and Prevention. Pulmonary Hypertension Fact Sheet. 2009. www.cdc.gov/DHDSP/data_statistics/fact_sheets/docs/fs_ pulmonary_hypertension.pdf. Accessed March 16, 2011. 2. Vacca VM. On the alert for pulmonary arterial hypertension. Nursing2009. 2009;39(12):36-40. 3. Jacobs M, Meyer T. The push is on pulmonary hypertension. Nurs Made Incredibly Easy. 2006;4(3):42-52. 4. Hayes GB. Pulmonary hypertension: a patient’s survival guide. Silver Spring, MD: Pulmonary Hypertension Association; 2010. 5. Donahue D. Managing pulmonary arterial hypertension. Nursing2010. 2010;40(1):52-54. 6. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54(Suppl):S43-S54. 7. Nazzareno G, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2009;30:2493-2537. 8. Li JH, Safford RE, Aduen J, et al. Pulmonary hypertension and thyroid disease. Chest. 2007;132:793-797. 9. Badish DB, Hunter CC, Sanchez MG, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(Suppl):S55-S66. 10. Zeineh NS, Champion HC. Utility of tricuspid annular plane systolic excursion in the assessment of right ventricular function. Unpublished manuscript. Pittsburgh, PA: Department of Medicine and the Vascular Institute, University of Pittsburgh School of Medicine; 2010. 11. Villalba WO, Sampaio-Barros PD, Pereira MC, et al. Six-minute walk test for the evaluation of pulmonary disease severity in scleroderma patients. Chest. 2007;131:217-222. 12. Barst RJ, Gibbs JS, Ghofrani HA, et al. (2009). Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(Suppl):S78-S84. 13. Humbert M, Barst RJ, Robbins IM, et al. Combination of Bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Resp J. 2004;24:353-359.
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ABSTRACT The prevalence of adult pulmonary hypertension (PH) in the United States has escalated in all races, gender, and ethnic populations. Nurse practitioners (NPs) are encountering adults with PH with increasing frequency. Through increased knowledge of the pathophysiological changes, diagnostic measures, and treatments for adults with PH, NPs collaborate with interdisciplinary teams to manage and improve client outcomes and quality of life. Keywords: endothelin receptor antagonists, mean pulmonary artery pressure, phosphodiesterase inhibitors, prostanoids, pulmonary hypertension, right heart catheterization © 2011 American College of Nurse Practitioners
P
ulmonary hypertension (PH) is a progressive and ultimately fatal disease that presents as an elevated blood pressure in the pulmonary arteries. PH evolves as a comorbidity of other diseases or conditions, such as connective tissue diseases, lung diseases, liver disease, pregnancy, HIV infection, left heart failure, and the usage of the diet medication Fen-Phen, a combination of the 2 drugs fenfluramine (Pondimin) and phentermine (Lonamin). Although triggered by other diseases or conditions, the specific etiology of PH is not known. PH and comorbidity conditions affect a diverse segment of the population. The demographic profile of adult PH patients includes men and women of all ages, racial, and ethnic groups. Between 2000 and 2002, the Centers for Disease Control and Prevention reported 807,000 adults were hospitalized with PH. Of these adults, 61% were women and 66% were 65 or older.1 During the time period of www.npjournal.org
1980-2002, the number of PH deaths increased from 10,922 to 15,668, respectively; however, the greatest increase was observed only among women.1 Among all racial populations, the number of adult PH deaths has increased mostly among the African American population.1 Death rates are higher among the elderly, especially men 85 or older, women 65 or older, whites 75 or older, and African Americans 65 or older.1 Regardless of gender, age, or race, PH patients require continuous evaluation and management by an interdisciplinary team to alter disease progression and the resultant impact on multiple organ systems. PH affects both the pulmonary and cardiovascular systems, with a potential negative impact on quality of life. PH patients have many acute and chronic health care needs that require meticulous evaluation, management, and care coordination. The nurse practitioner (NP) collaborates within an interdisciplinary team to effectively The Journal for Nurse Practitioners - JNP
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evaluate and manage the PH patient and their comorbid health conditions.
prostaglandin that promotes blood vessel vasodilatation and prevents the overgrowth of cells in the blood vessels. Prostacyclin prevents platelets from clumping together, PATHOPHYSIOLOGY which lowers the incidence of clogged blood vessels. NO The pulmonary vasculature contains arteries and arteriis a powerful vasodilator that prevents smooth muscle oles, which branch in the lungs to create a dense capilgrowth and inhibits platelets from sticking together. ET-1 lary bed to provide blood flow. is a messenger that causes vasoThe pulmonary capillary bed is constriction of the blood vesa high-volume, low-pressure, sels. In healthy adults, these low-resistance system that molecular messengers ensure Signs and symptoms of PH delivers blood to and from the appropriate compensatory are related to the severity lungs via the arterial and blood flow based on metabolic venous circulation systems, demands.4 of right heart failure. respectively. In a normal healthy In adults with PH, smooth adult, this system has a mean cells proliferate in the intima, pulmonary artery pressure thickening and clogging the (MPAP) that ranges from 12 to 16 mmHg.2 arteriole walls. This altered tissue inside the arterioles The dense capillary branching and the cumulative forms a plexiform lesion. The lesion clogs the inside of diameters of the capillaries provide a lower resistance the arterioles, causing scar formation of the intima and pressure while effectively facilitating gas exchange.3 The media arteriole layers. This narrows the vessel, with a pulmonary vasculature system is effective during times of resultant increase in MPAP. This scar tissue is fibrous and exercise as it can increase blood-carrying capacity by as prevents the arterioles from expanding and contracting, much as 5 times with little or no increase in pulmonary thereby decreasing the normal compensatory mechanism 3 pressure. In a healthy individual the arterioles are thinof the pulmonary circulatory system. This thickening or walled, distensible vessels that are able to dilate in times remodeling of the intima arteriole layer is irreversible and of increased metabolic need. The arterioles are composed leads to permanent vasoconstriction of the arterioles, of 3 layers: intima, media, and adventia.4 The intima is with a resultant increase in MPAP.4 the innermost layer and is responsible for tightening and In addition, adult PH clients experience an imbalance relaxing the blood vessel, blood clotting, forming new among the molecular messengers contributing to pulvessels, inflammation, and immune responses.4 The media monary vascular remodeling, systemic hypoxia, and pulis the middle layer that regulates the diameter and volmonary thrombosis, which leads to increased MPAP and ume of the vessels, thereby distributing blood to areas of the development of PH.2 The levels of the molecular the body in need. The adventitia is the outermost layer messengers prostacyclin and NO, which produce vasodi4 and comprises collagen, which gives the vessel stability. latation throughout the pulmonary circulation and preChemical messengers, which include tumor necrosis facvent platelet aggregation, are reduced, while concurrently tor and interleukin 1, serve as the mechanism of action there is an overabundance of the vasoconstricting properthat promotes the responsiveness of these arterial layers to ties of the molecular messenger ET-1. As a result of the increased metabolic needs.2 imbalance in the molecular messengers, pulmonary vasThe pulmonary vasculature generates chemical mescular resistance (PVR) and MPAP are increased and negsengers that produce, repair, and destroy cells in the vessel atively affect cardiac output. wall.2 The blood vessels of the pulmonary circulatory A patient with PH has a resting MPAP ⬎ 25 mmHg, system are controlled by a system of molecular messenwith a pulmonary capillary wedge pressure (PCWP) ⬍ gers that facilitate the metabolic compensation through 15 mmHg. As the disease progresses, right ventricular dilatation and constriction of these blood vessels. hypertrophy occurs as a result of the increased pulProstacyclin, nitric oxide (NO), and endothelin (ET-1) monary vascular resistance (PVR), which leads to right are the molecular messengers that control the flow of heart failure, activity intolerance, and eventually can lead blood in the pulmonary circulation. Prostacyclin is a to death.5 Signs and symptoms of PH are related to the 410
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severity of right heart failure. In the early stages of the disease, the patient may be asymptomatic. With progression of right heart failure, the patient may present with peripheral edema, ascites, hepatomegaly, anorexia, exercise intolerance, and progressive dyspnea from decreased cardiac output (CO).2
used to assess the severity of PH. The WHO, along with the American College of Chest Physicians, supports using this system to assess the functional status of PH patients. Functional status is delineated into 4 possible classes, with severity of symptoms determining class. Table 2 presents the WHO Functional Classes (WHO-FC) for PH.2
DIAGNOSIS INTERDISCIPLINARY TEAM MONITORING PH symptoms are similar to other pulmonary diseases Clinical presentation of the PH patient may reveal nonwhich increases the challenge of differential diagnosis. specific symptoms, such as dyspnea, fatigue, angina, synShortness of breath and exertional fatigue are the most cope, weakness, and abdominal distension. Symptoms at common subjective complaints. Many of the nonspecific rest only occur in the very advanced stages of PH (WHOsubjective and objective findings of PH resemble those of FC IV). Physical signs upon examination include a left heart failure thereby making a complete history and parasternal lift, an accentuated component of the second physical exam by the NP paramount.2 The NP must heart sound, a pansystolic murmur of tricuspid regurgitawork in unison with the other members of the healthtion, a diastolic murmur of pulmonary insufficiency, and a care team to accurately diagnose PH. right ventricular third sound. In advanced cases of PH, On average, patients with PH are not diagnosed until jugular vein distension, hepatomegaly, peripheral edema, the pulmonary vascular bed is significantly damaged, ascites, and cool extremities may be present. Bilateral resulting in shortness of breath. A series of diagnostic tests breath sounds are usually clear, unless an interstitial disease are used to confirm diagnosis, determine etiology and is involved, in which case crackles may be heard upon ausclinical classification, evaluate functional ability, and assess cultation. Rashes, skin tightening, or telangiectasias may be hemodynamic status. These tests present if a mixed connective can provide valuable informatissue disorder, such as sclerotion to the clinician and faciliderma, is present.7 tate diagnosis. As stated in the The NP works within an The NP should encourage introduction, PH is linked to interdisciplinary team to consupport groups and provide several comorbidities, making it tinually monitor and manage extensive teaching and important for the NP to the disease progression and reliable online services. develop a list of possible differquality of life of adult PH patients. An electrocardiogram ential diagnoses. Possible differential diagnoses include sleep (ECG) may reveal right ventricular hypertrophy and strain and right atrial enlargement. apnea, cor pulmonale, pulmonary embolism, hypothyFeatures of the ECG in right ventricular hypertrophy roidism, mixed connective tissue disease (scleroderma and include, right axis deviation, possibly a predominant R systemic lupus erythematosus), and portal hypertension. wave in lead V1, a deep S in V6, inverted T waves in right In addition to differentially diagnosing PH, the NP precordial leads V2 and V3, and peaked P waves.7 and interdisciplinary team must accurately classify the However, an ECG alone cannot diagnose PH. state of PH disease progression. The clinical classification Supraventricular arrhythmias, such as atrial flutter and of PH has undergone a series of revisions since first proatrial fibrillation, may be present in advanced stages of posed in 1978 by the World Health Organization PH and lead to further clinical deterioration.7 A chest (WHO). During 2008, at the 4th World Symposium on radiograph may reveal right atrium and ventricular PH, which convened in Dana Point, California, experts enlargement and pulmonary artery dilatation.4 proposed modifications to the previous classifications. While there is no known specific serological test to Currently, there are 5 clinical categories of PH. Table 1 6 diagnose and monitor PH progression, several serological summarizes the 2008 clinical classification of PH. A modified version of the New York Heart blood tests can be used to monitor thyroid, immune, and Associations’ system for classifying heart failure is also cardiac function, which are PH comorbidities. Thyroid www.npjournal.org
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Table 1. Updated Clinical Classification of Pulmonary Hypertension6 1. Pulmonary Arterial Hypertension 1.1 Idiopathic 1.2 Heritable 1.2.1 Bone morphogenic protein receptor, type 11 1.2.2 Activin receptor-like kinase 1, endoglin (with or without hereditary hemorrhagic telangiectasis) 1.2.3 Unknown 1.3 Drug- and toxin-induced 1.4 Associated with associated pulmonary arterial hypertension 1.4.1 Connective tissue disease 1.4.2 HIV infection 1.4.3 Portal hypertension 1.4.4 Congenital heart disease 1.4.5 Schistosomiasis 1.4.6 Chronic hemolytic anemia 1.5 Persistent pulmonary hypertension of the newborn 1’ Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatomasis 2. Pulmonary hypertension associated with left heart disease 2.1 Systolic dysfunction 2.2 Diastolic dysfunction 2.3 Valvular disease 3. Pulmonary hypertension as a result of lung diseases and/or hypoxemia 3.1 Chronic obstructive pulmonary disease 3.2 Interstitial lung disease 3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern 3.4 Sleep-disordered breathing 3.5 Alveolar hypoventilation disorders 3.6 Chronic exposure to high altitude 3.7 Developmental abnormalities 4. Chronic thromboembolic pulmonary hypertension 5. Pulmonary hypertension with unclear and/or multifactorial mechanisms 5.1 Hematalogical disorders: myeloproliferative disorders, spleenectomy 5.2 Systemic disorders: sarcoidosis, pulmonary Langerhan’s cell histiocytosis 5.3 Metabolic disorders: glycogen storage disease, Gaucher’s disease, thyroid disorders 5.4 Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis
diseases, such as thyrotoxicosis, may exacerbate PH and are common in idiopathic pulmonary arterial hypertension. Evaluation of thyroid function is necessary to assess as symptom improvement has occurred after thyroid function has been restored.8 Serological testing may also detect the presence of a mixed connective tissue disorder, such as scleroderma or systemic lupus erythematosus. A positive antinuclear antibody test may suggest a mixed connective tissue disorder.7 It is important to exclude the connective tissue disorder scleroderma as it has a high prevalence of pulmonary artery hypertension.7 Cardiac biomarkers are obtained to rule out myocardial ischemia. Brain-type natriuretic peptide (BNP) and Nterminal prohormone brain natriuretic peptide (NTproBNP) are indicators of right ventricular overload. Brain-type natriuretic peptide ⱖ 150 pg/mL and NT412
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proBNP ⬎ 1474 pg/mL correlate positively with an elevated MPAP and PVR.9 Serological testing can also detect HIV and hepatitis, which are also causes of PH.4 Pulmonary function tests are performed to identify underlying lung disease and assess severity of PH. The lungs of the PH patient are stiffer, smaller, and have a decreased lung diffusion capacity for carbon monoxide. The carbon monoxide diffusing test (DLCO) measures the efficiency of oxygen diffusion from the lungs to the alveoli. PH patients tend to have a decrease in oxygen diffusion across the capillary membrane.4 A chest computed tomography (CT) scan may be ordered to detect interstitial lung disease, along with possible emboli, and provide information on the heart. Recently an ultrafast CT scan called an electron-beam tomography has been used to monitor changes in the right atrium and Volume 7, Issue 5, May 2011
ventricle. Cardiac magnetic resonance imaging is useful in the assessment of the right heart as it provides a direct assessment of cardiac volume, muscle mass, and function. Ventilation/perfusion scans and pulmonary angiography may also be used to diagnose pulmonary embolism, which is a cause of chronic thromboembolic PH.4 Doppler echocardiography, which is more specific for diagnosing PH, measures pulmonary artery (PA) pressures noninvasively, provides information on pumping ability of both the right and left ventricles and valve function, and can detect congenital heart defects. Doppler findings indicative of advanced PH include right atrial enlargement and septal bowing into left ventricle, right ventricular enlargement and hypokinesis, and presence of a pericardial effusion.2 Other Doppler findings include a tricuspid jet velocity ⬎ 2.8 m/s, tricuspid insufficiency peak gradient ⱖ 31 mmHg, and tricuspid annular plane systolic excursion (TAPSE) ⬍ 1.8 cm. Tricuspid jet velocity measures the velocity of regurgitant blood flow through the tricuspid valve. Tricuspid peak insufficiency gradient evaluates the tricuspid valve for stenosis by measuring the peak gradient across the valve. Tricuspid annular plane systolic excursion is used as an index to evaluate right ventricular function. Decreases in TAPSE correlate with a progressive decrease in right ventricular function.10 Doppler echocardiography may also be performed on the PH patient while exercising as some PH patients’ MPAP may be elevated at this time. This exercise echo is performed while the patient is either exercising on a semi-erect or supine bicycle.4 MPAP ⬎ 30 mmHg while exercising is definitive for PH.9 An exercise tolerance test, more specifically a 6minute walk test (6MWT), is another diagnostic screen that may be used to assess and monitor PH. A healthy individual is able to walk a minimum of 500 meters in 6 minutes, whereas a patient with moderate PH may be able to walk only 300 meters.11 The 6MWT is simple to administer, inexpensive, reproducible, and well standardized. Finger oxygen saturation and dyspnea on exertion are recorded in addition to walk distance. Right-heart catheterization is the most accurate, useful, and definitive diagnostic test for PH. This invasive diagnostic test directly measures pulmonary artery pressures, PVR, CO, and PCWP. A normal MPAP at rest is between 12 to 16 mmHg. A patient with a resting MPAP ⱖ 25 mmHg is diagnosed with PH.9 www.npjournal.org
Table 2. World Health Organization Functional Classes Class I. No symptoms-induced limits on physical activity Class II. Slight symptoms-induced limits on physical activity Class III. Marked symptoms-induced limits on physical activity Class IV. Right-sided heart failure, with dyspnea and fatigue at rest and inability to perform any physical activity without symptoms
A vasodilator study is performed when the PH patient is undergoing a right heart catheterization. A vasodilator study evaluates the pulmonary arteries’ response to medications, such as adenosine, NO, or epoprostenol, that cause vasodilatation. While there is no definitive wording on what constitutes a positive vasoreactivity response, it is believed that MPAP ⬍ 40 mmHg while receiving a vasodilator is a positive response. The presence or absence of vasoreactivity of the pulmonary vasculature provides a diagnosis and guides treatment.4 PHARMACOLOGICAL TREATMENT Pharmacological treatment involves using medications to restore the vasodilator effects and prevent overgrowth of cells in an attempt to decrease PA pressures and increase CO. The vasodilator challenge performed during the right heart catheterization assesses the patient’s potential response to long-term vasodilator medications. When deciding on a plan of care and which medication to use, consideration must be given to medication effectiveness, side effects, lifestyle impact, and quality of life. Table 3 provides a summary of targeted therapy for treatment.4 Calcium Channel Blockers Calcium channel blockers, such as nifedipine (Procardia), amlodipine besylate (Norvasc), and diltiazem hydrochloride (Cardizem), are used initially if the patient had a positive response to the vasodilator challenge. Calcium channel blockers act on vascular smooth muscle to dilate the pulmonary vessels, causing a decrease in MPAP and PVR and increase in CO. Calcium channel blockers are administered orally and can be used long term to effectively manage PH. The dosage may vary from patient to patient.12 The Journal for Nurse Practitioners - JNP
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Table 3. Summary of Targeted Medication Therapy Used to Treat Pulmonary Hypertension6 Class of Medication
Name
Route of Administration
Prostanoids
Epoprostenol Iloprost Treprostinil
Intravenous Inhaled, intravenous Inhaled, intravenous, subcutaneous
Endothelin receptor antagonist
Bosentan Ambrisentan
Oral Oral
Revatio Tadalafil
Oral Oral
Phosphodiesterase type-5 inhibitors
Prostanoids Prostanoids, such as epoprostenol (Flolan), iloprost (Ventavis), and treprostinil (Remodulin, Tyvaso), may be used in the PH patient who had a positive response to the vasodilator challenge. Epoprostenol is an artificial prostacyclin that mimics prostaglandin, which is a naturally occurring substance in the human body. Acting like prostaglandin, epoprostenol dilates blood vessels, prevents platelets from clumping together, increases CO, and slows the growth of smooth muscle cells. Patients with PH in Classes III or IV will receive intravenous epoprostenol through a central line as it has a half life of only a few minutes. The drug is not stable at room temperature.12 Iloprost is a prostacyclin that is usually inhaled via a nebulizer but can also be administered intravenously. When inhaled, its effects are confined to the lungs, so side effects are minimal. Because the effects of the medication last approximately 30 to 90 minutes, the patient must inhale the 10-minute treatment many times throughout the day. It is approved for Classes III or IV.4 Treprostinil is a form of prostacyclin similar to epoprostenol, with a half life of approximately 4 hours. It can be administered intravenously, subcutaneously, or inhaled and is stable at room temperature. The mechanism of action produces vasodilatation in the pulmonary vasculature which reduces right and left ventricular afterload thereby increasing CO.4 Endothelin Receptor Antagonists Endothelin receptor antagonists include bosentan (Tracleer) and ambrisentan (Letairis). Endothelin receptor antagonists vasodilate and prevent cell growth in the 414
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arteries by preventing endothelin from activating receptors.12 Bosentan blocks the endothelin-A and endothelin-B receptors, thereby causing vasodilatation. It is administered orally and has been approved for Classes II, III, and IV. The drug can be toxic to the liver and cause birth defects. All patients on this medication must receive monthly liver function tests, and women must have a negative pregnancy test before initially starting the medication. A monthly pregnancy test should be obtained while the patient is on this medication.4 Ambrisentan is administered orally and only blocks the endothelin-A receptor. It has been approved for functional Class II and III. Pregnancy tests must also be collected monthly for women taking this medication.4 Phosphodiesterase Inhibitors Phosphodiesterase inhibitors, such as revatio (Sildenafil) and tadalafil (Adcirca), function by inhibiting cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type-5 (PDE-5). By inhibiting PDE-5, cGMP is not broken down and relaxes the pulmonary blood vessels. The phosphodiesterase inhibitors have been approved for Classes II, III, and IV.4 Combination Therapy Combination therapy may be used in patients who remain symptomatic on initial medication therapy. There are several potential advantages of combination therapy as current PH therapies act on 3 different yet potentially complementary mechanisms. The clinician may add a second or even a third medication to the regimen to improve exercise tolerance and symptoms. This type of therapy may be warranted if the patient has had a response to the initial therapy but it’s not satisfactory.4 Combination therapy has become the standard of care in most PH centers; numerous case series have suggested that various medication combinations have proven to be safe and effective.13-15 To date, clinical trials continue to be completed to gather evidence in support of combination therapy.4 Lung Transplantation Lung transplantation is an option when medications are not helping the patient to improve. This option may prolong survival and improve quality of life, but it is not recommended in the early stages of PH because life is not immediately threatened. However, lung transplantation Volume 7, Issue 5, May 2011
should be discussed before the patient becomes too ill. Approximately 150 lung transplants are done yearly on PH patients.4 THE ROLE OF THE NP PH is a chronic condition that requires an interdisciplinary team approach to continually monitor disease progression and manage care. The NP has a diagnostic and clinical management role in the care of the PH patient and must work collaboratively with the pulmonologist, cardiologist, respiratory therapist, physical therapist, nutritionist, and other practitioners who offer complementary therapies (eg, acupuncture, massage, and Reiki) to effectively meet the needs of this population. NPs provide follow-up and day-to-day care. Education is vital in order for the patient to return home and become functioning in society once again. Medication Medication adherence rates are approximately 50% in this population; deviations from prescribed therapy include skipping doses, not filling prescriptions, taking medications at wrong times of the day, or interrupting therapy.16 It is important to educate both patient and caregiver on medication mechanism of action and the importance of filling prescriptions and adhering to the scheduled doses, particularly epoprostenol and treprostinil, which have short half lives and should not be stopped abruptly. Education should be provided on signs and symptoms of infection, especially in patients who are receiving epoprostenol and treprostinil intravenously via a Hickman, Groshong, or Broviac catheter. These patients also need assistance to manage the complex medication regimens. A demonstration of sterile technique when caring for intravenous lines and pumps should be provided. The patient and caregiver should perform a return demonstration.16 Nutrition It is essential for the NP to collaborate with a nutritionist and to provide the PH patient with information on diet and weight. A low-sodium diet that is both low in calories and high in healthy carbohydrates is recommended. Information needs to be collected on herbs and supplements used by the patient because they may interfere with PH medications. Weight should be monitored daily, and a quick weight gain of 2 to 3 pounds should be www.npjournal.org
reported immediately to a physician—edema is a sign of heart failure, which can lead to progressive dyspnea.4 Exercise Physical activity should be encouraged, but the patient needs to listen to his or her body. The NP, physician, physical therapist, and patient should set reasonable goals on physical activity. Target values and treatment goals should be individualized. For PH patients a 6MWT ⬎ 400 meters is usually acceptable. Younger patients are capable of walking 500 meters or more. A possible referral to a pulmonary rehabilitation center may be needed. In previous PH cases, exercise has increased the 6MWT.17 Maintenance Suggested follow-up strategies for PH patients include performing a clinical assessment, WHO-FC determination, ECG, 6MWT, and BNP/NT-proBNP levels at baseline, every 3 to 6 months, and 3 to 4 months after changes in therapy or if clinical worsening occurs. An echocardiogram and right heart catheterization should be performed at baseline and 3 to 4 months after changes in therapy or if clinical worsening occurs.7 A quality of life assessment should be performed by administering the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire. This assessment tool contains 3 separate scales that measure symptoms, functioning, and quality of life and is specific for PH patients.18 A flu vaccine yearly in October should be recommended, along with information on means to prevent colds. NPs should instruct patients to wash hands before touching eyes, mouth, or nose. Patients with PH cannot take decongestants because of the vasoconstrictor effect.4 Mental Health Anxiety or depression affect approximately one-third of PH patients.19 It is important for the NP to screen for depression and make appropriate referrals to psychiatrists and psychotherapists.18 An interdisciplinary team approach is best as appropriate medications can be dispersed for distressing symptoms, and psychological, social, and spiritual support can be provided. NPs should also keep in mind that the caregiver faces stress, and both the patient and caregiver should be referred to a local PH support group. The Journal for Nurse Practitioners - JNP
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End of Life End-of-life and ethical issues need to be addressed because PH is a disease of progressive deterioration interspersed with episodes of acute decompensation. Death is difficult to predict; it may be sudden or slow. Communication with PH patients is essential to allow for advanced planning and discussion of their fears, concerns, and wishes. Prognosis should be discussed at the time of initial diagnosis, along with resuscitation status. Cardiopulmonary resuscitation tends to have poor outcomes in the PH patient.17
14. Ghofrani HA, Schemurly RF, Olschewski RT, et al. Oral sildenafil as longterm adjunct therapy to inhaled Iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol. 2003;42(1):158-164. 15. Mathai SC, Girgis RE, Fisher MR, et al. (2007). Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension. Eur Resp J. 2007;29:469-475. 16. Stewart T. Facilitating pulmonary arterial hypertension medication adherence: patient-centered management. Adv Pulm Hypertens. 2010;8(4):228-231. 17. Gin-Sing W. Pulmonary arterial hypertension: a multidisciplinary approach to care. Nurs Stand. 2010;24(38):40-47. 18. Coffin D, Duval K, Martel S, et al. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension. Eur J Clin Invest. 2006;36(Suppl 3):10-15. 19. Lowe B, Kerstin G, Ufer C, et al. Anxiety and depression in patients with pulmonary hypertension. Psychosom Med. 2004;66:831-836.
CONCLUSION PH is a progressive disease with no cure; however, the management of PH continues to evolve. There has been an increase in the number of medications in the past several years that lower MPAP, PVR, and improve CO and distance walked in 6 minutes. The NP must consider factors that affect quality of life. The NP should encourage support groups and provide extensive teaching and reliable online services. The NP and patient can establish realistic expectations for treatment, such as physical activity goals. By understanding PH and performing these actions, the NP is providing the best possible care while improving patient outlook and quality of life.
Todd Michael Tartavoulle, MN, RN, CNS-BC, is an instructor of nursing at the Louisiana State University Health Sciences Center, School of Nursing, in New Orleans. He can be reached at [email protected]. In compliance with national ethical guidelines, the author reports no relationships with business or industry that would pose a conflict of interest. 1555-4155/11/$ see front matter © 2011 American College of Nurse Practitioners doi:10.1016/j.nurpra.2010.11.002
References 1. Centers for Disease Control and Prevention. Pulmonary Hypertension Fact Sheet. 2009. www.cdc.gov/DHDSP/data_statistics/fact_sheets/docs/fs_ pulmonary_hypertension.pdf. Accessed March 16, 2011. 2. Vacca VM. On the alert for pulmonary arterial hypertension. Nursing2009. 2009;39(12):36-40. 3. Jacobs M, Meyer T. The push is on pulmonary hypertension. Nurs Made Incredibly Easy. 2006;4(3):42-52. 4. Hayes GB. Pulmonary hypertension: a patient’s survival guide. Silver Spring, MD: Pulmonary Hypertension Association; 2010. 5. Donahue D. Managing pulmonary arterial hypertension. Nursing2010. 2010;40(1):52-54. 6. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54(Suppl):S43-S54. 7. Nazzareno G, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2009;30:2493-2537. 8. Li JH, Safford RE, Aduen J, et al. Pulmonary hypertension and thyroid disease. Chest. 2007;132:793-797. 9. Badish DB, Hunter CC, Sanchez MG, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(Suppl):S55-S66. 10. Zeineh NS, Champion HC. Utility of tricuspid annular plane systolic excursion in the assessment of right ventricular function. Unpublished manuscript. Pittsburgh, PA: Department of Medicine and the Vascular Institute, University of Pittsburgh School of Medicine; 2010. 11. Villalba WO, Sampaio-Barros PD, Pereira MC, et al. Six-minute walk test for the evaluation of pulmonary disease severity in scleroderma patients. Chest. 2007;131:217-222. 12. Barst RJ, Gibbs JS, Ghofrani HA, et al. (2009). Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(Suppl):S78-S84. 13. Humbert M, Barst RJ, Robbins IM, et al. Combination of Bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Resp J. 2004;24:353-359.
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