Pulmonary Arterial Hypertension: Early Recognition and Treatment Can Make a Lifetime Difference for Your Patient

Article Outline

• Abstract
• Clinical Manifestations
• Diagnostic Testing
• Treatment
• Combination Therapy
• Transplantation Guidelines
• Patient Teaching
• Psychosocial Issues
• Conclusion
• References
• Uncited reference
• Copyright

Abstract 

Pulmonary arterial hypertension (PAH) is a rare, life-threatening, progressive disease that is characterized by sustained elevations of pulmonary artery pressure with no apparent cause. Because it is often difficult to diagnose, the true incidence of PAH is unknown. The true number of cases has eluded researchers because accurate diagnosing of PAH is complex. The prevalence of PAH is estimated at 1 to 2 million people worldwide, with 500 to 1000 new cases diagnosed in the United States each year. It is important for nurse practitioners who work in both primary and acute care to be familiar with this devastating disease and to consider this condition as a differential diagnosis when caring for patients with dyspnea.

Keywords:  chronic illnesses , critical care , pulmonary artery pressure , pulmonary disease

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Pulmonary arterial hypertension (PAH) is a rare, life-threatening, progressive disease that is characterized by sustained elevations of pulmonary artery pressure with a variety of causes, ranging from familial to idiopathic causes. Although normal mean pulmonary artery pressure is approximately 12 to 14 mm Hg at rest, pressure in the patient with PAH is significantly higher: greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise.¹ This abnormally high pressure, or pulmonary hypertension (PH), results in restricted flow in the small blood vessels of the lungs, which places a strain on the right ventricle of the heart as it tries to pump into the thickening arteries. Over time, the right ventricle becomes overworked and enlarged, causing right-sided heart failure.

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Clinical Manifestations 

Patients with PAH may have nonspecific symptoms such as shortness of breath, lightheadedness, fatigue, and chest pain. As a result of these nonspecific symptoms, the diagnosis of PAH may be delayed. The first symptom is usually shortness of breath (dyspnea), which in the beginning may be exercise induced but eventually becomes chronic. As with many chronic respiratory diseases, symptoms of PAH progress from nonspecific symptoms to exercise-induced symptoms and to the chronic stage in which symptoms occur at rest (class IV).²

Other typical symptoms are tiredness or fatigue, cough, dizziness, and fainting spells (syncope). Swelling in the ankles (edema), bluish lips and skin (cyanosis), and chest pain (angina) are among other symptoms of the disease which are a result of right-sided heart failure. More specific findings of PAH that a clinician may identify are jugular venous pulsation, loud second cardiac sound such as a tricuspid regurgitation, clubbing, hepatojugular reflux, and ascites.³

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• The cause of PAH is still unknown, but factors such as cocaine use, portal hypertension, infection with the human immunodeficiency virus (HIV), and the use of certain appetite suppressants are thought to contribute to its onset.

Once PH is diagnosed, patients are assessed and classified by their functional level using the New York Heart Association (NYHA) functional classification system, which is based on patient reports of how comfortably he or she can undertake certain activities. The prognosis for a patient with PAH can be quite variable and will depend on many factors, such as the severity of the disease, and the patient's underlying medical condition. The survival rate can be longer for patients who do not develop heart failure and for those diagnosed younger than age 40 years.

The NYHA functional classification provides a simple way to classify the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity (Table 1).

Table 1. New York Heart Association Functional Classification²

The cause of PAH is still unknown, but factors such as cocaine use, portal hypertension, infection with the human immunodeficiency virus (HIV), and the use of certain appetite suppressants are thought to contribute to its onset. Other triggers have been identified such as pregnancy and methamphetamine use to name a few, which may act as the catalyst for “turning on” this deadly disease. In about 6% to 10% of cases, PAH is inherited.⁴

The biological triggers that initiate PAH remain unclear. However, we do know of three pathologic processes that occur in the lungs that lead to the presentation of clinical manifestations. The three processes are smooth muscle contraction that leads to vasoconstriction that increases pulmonary vascular resistance. In response to the increased blood pressure, new muscle begins to grow in the intimal layer of blood vessels, eventually forming scar tissue, which narrows the blood vessels and increases the blood pressure; this is known as vascular remodeling. As a result of these two biological events, intravascular thrombosis develops.⁵

In 2003, a group of experts associated with the World Health Organization met in Venice and developed the new clinical-based classification systems. This new clinical-based classification system of PAH is based on similar cause, response to, and candidacy for different therapeutic approaches. The following 5 classes were developed as a result of extensive discussion and represent a consensus of the present understanding of pathophysiology as well as of clinical-based differences or similarities within PH⁶:

PH must be diagnosed by eliminating all other possible causes of pulmonary hypertension, making it difficult to identify and making the diagnosis process long. Secondary PH is caused by an underlying diagnosis such as scleroderma, rheumatoid arthritis, or CREST (calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) syndrome, as well as other diseases. Patients with secondary PH experience the same physiologic deterioration of the blood vessels in the lungs and enlarging of the right side of the heart in addition to any other physiologic damage that occurs as a result of their underlying disease.

Because it is often difficult to diagnose, the true incidence of PAH is unknown. However, the disease is believed to affect 1 to 2 people per million (1-2:1,000,000) or 400 new cases per year in the United States. The greatest number of cases is reported in women between the ages of 21 and 40 years. However, men and women of all age ranges can develop the disease.⁷

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Diagnostic Testing 

If the clinician suspects PAH, the diagnostic tests used to work up the disease are usually chest x-ray, electrocardiogram, and echocardiogram. Other valuable tests include pulmonary function test, cardiopulmonary exercise test, blood tests, and lung ventilation perfusion scan. The final and most diagnostic test would be the right heart catheterization with acute vasodilation testing. The chest x-ray lacks sensitivity and specificity in diagnosing PAH; however, one should observe for enlarged main and hilar pulmonary artery shadows and a large right ventricle.⁸ Echocardiograms lack sensitivity and specificity, but right ventricular hypertrophy and right axis deviation may be suggestive of PAH. Both of these findings are detected 79% to 87% of the time in PAH. An echocardiogram may show increased tricuspid regurgitation. Electrocardiogram findings suggestive of PAH include a tall R wave and small S wave in lead V₁, a large S wave and small R wave in V₅ or V₆. Right atrial enlargement should be assessed, defined as a tall P wave greater than 2.5 mm in leads II, III, and aVF. These findings should prompt further investigation in patients with suspected PAH.⁸

A simple and practical substitute for full cardiopulmonary exercise testing is the 6-minute walk test (6MWT). The 6MWT is technically simple and inexpensive. It is predictive of survival in PAH and also correlates inversely with NYHA functional status severity. The 6MWT is usually combined with the Borg score that assesses the subjective level of dyspnea with the exercise. Reduction of arterial oxygen saturation greater than 10% during the 6MWT increases mortality risk 2.9 times during a median follow-up of 26 months. The distance ambulated and the arterial oxygen saturation by pulse oximetry obtained during a 6MWT shows strong correlation to the peak exercise oxygen consumption seen on cardiopulmonary exercise testing, as well as to total pulmonary vascular resistance, mean right arterial pressure, baseline cardiac output, and NYHA functional class. The 6MWT can also predict disease progression and the patient's response to therapy and is commonly used for this purpose clinically.⁸, ⁹, ¹⁰, ¹¹

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Treatment 

The treatment goals for patients with PAH include minimizing symptoms and hospitalizations, prolonging survival rate, and improving quality of life. Treatment is broken down into supportive and more aggressive therapies. Supportive therapies include the use of diuretics and oxygen therapy. Diuretics help facilitate output, thus preventing an increased return to the heart which can increase the heart failure associated with PAH. Oxygen therapy has proven to improve quality of life, increase exercise tolerance, decrease hematocrit levels, and cause vasodilation of pulmonary vessels leading to a decrease in PH. More aggressive therapies may include the use of anticoagulation therapy and calcium channel blockers. Many patients can be treated with calcium channel blockers, which relax the smooth muscle in the walls of the heart and blood vessels reducing blood pressure and easing strain on the heart. Anticoagulants are also used to decrease blood clotting. Although medications may not halt disease progression, they can help relieve symptoms and allow the patient to be more active. Patients with severe cases of PAH and who are not candidates for drug therapy may be eligible for a lung or heart-lung transplantation, the only definitive treatment for PAH.¹²

Currently, five therapies for PAH are approved by the Food and Drug Administration that fall into three therapeutic classes: prostacyclin derivatives, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors¹² (Table 2).

Table 2. Current Therapies for Pulmonary Artery Hypertension¹², ¹³

CCB, calcium channel blocker; INR, international normalized ratio; SaO₂, arterial oxygen saturation; PAH, pulmonary artery hypertension; IV, intravenous; SC, subcutaneous; PO, by mouth; BID, twice a day; TID, three times a day.

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Combination Therapy 

The data currently available pertaining to add-on or combination therapy are limited. Therapy should obviously be individualized, taking into account the patient's specific clinical situation. It is strongly recommended that patients be referred to centers of excellence and that long-term care be shared with the referring physician. Close follow-up, with frequent objective assessments of clinical status and therapeutic response, is essential to optimal long-term outcomes. Improvement of symptoms to World Health Organization (WHO) class II, longevity, and improvement in quality of life continue to be the hallmark for therapy selection.

Combination therapy is an additional option to address the multiple pathophysiologic mechanisms that are present in PAH. Many clinicians use the following strategies for combination therapy: the simultaneous initiation of two (or more) treatments or by the addition of a second (or third) treatment to a previous therapy that may be considered insufficient. Currently, data are insufficient to support which of these two strategies would be the best choice.¹⁵

A combination therapy of two drugs (inhaled iloprost [Ventavis] and bosentan [Tracleer]) appears to improve the condition of patients with PAH. McLaughlin et al¹⁵ studied 65 patients with PAH who were being treated with bosentan, an endothelin receptor antagonist that helps boost blood flow in the lungs. Of those patients, 32 were selected to receive inhaled iloprost (a prostacyclin analog) along with bosentan, and the remainder took a placebo and bosentan. By the end of the 12-week study, all the patients who received the bosentan and iloprost therapy were able to walk 98 feet further during a 6NWT, and 12 of them showed improvement in a measurement of how severely they were affected by PAH. In addition, none of the patients who received the bosentan and iloprost therapy experienced clinical deterioration during the course of the study.

In patients with PAH who were deteriorating despite chronic treatment with nonparenteral prostanoids, addition of bosentan or sildenafil (Revatio) to the ongoing treatment resulted in favorable improvements in pulmonary hemodynamics and exercise capacity in uncontrolled studies.

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Transplantation Guidelines 

Recent advances in medical and interventional approaches to the management of patients with PAH have had a marked effect on the policy toward referring such patients for transplantation, and there has been a reduction of 50% in the number of patients with primary PH undergoing transplantation during the past decade. In practice, patients are being referred at a later stage, often in decompensated right heart failure. The prognosis of patients with WHO class III and IV symptoms has been improved by both prostaglandin and endothelial antagonist therapies. But not all patients show a significant response, so the concept of assessing a patient with advanced disease, placing the patient on a candidate list for transplantation when appropriate, and removing the patient from the list if significant response to medical therapy such that the patient improved to WHO class II on symptoms, was supported. The literature supports that transplantation centers currently show wide variation in their approach to indications for and timing of candidate lists. It is clear that close communication between PAH centers and transplantation centers is appropriate.¹⁶, ¹⁷

Finally, brief guidelines about referral and candidate lists are as follows:

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Patient Teaching 

PAH therapies require an informed commitment from the patient. It is imperative that the nurse practitioner educate the patient on the unique characteristics of the drugs, the constant self-monitoring needed to maintain their effectiveness, and the responsibility that the patient or family will assume with this condition. PAH comes with intense, lifelong responsibilities. Patients must understand that this is a lifetime of therapy.

Because of the extensive management of this life-threatening condition, the nurse practitioner must provide patient teaching to prevent potential harmful situations. Teaching should include the following:

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Psychosocial Issues 

Patients with PAH have a potentially life-threatening condition, which causes them to live a life of anxiety. Support through support groups must be provided to help decrease their anxiety. These patients are faced with an intense financial burden because of the expense of their daily drugs, oxygen, and durable medical equipment that is required to maintain some quality of life. Psychosocial patient support should include:

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Conclusion 

When a patient regardless of age seeks treatment for nonspecific complaints such as shortness of breath, lightheadedness, fatigue, edema, and chest pain, these symptoms should not be ignored or attributed to a deconditioning state. The nurse practitioner must consider PAH as a differential diagnosis. After an adequate workup, the nurse practitioner can further identify the diagnosis of PAH and improve the survival time and quality of life for the patient.

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References 

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Uncited reference 

14. Badesch DB , Abman SH , Ahearn GS , et al.   Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines . Chest . 2004;126(suppl):35S–62S