Pulmonary Artery Hypertension

Transcription

1 Pulmonary Artery Hypertension Janet M. Pinson, RN, MSN, ACNP Maureen P. Flattery, RN, MS, ANP Virginia Commonwealth University Health System Richmond, VA Pulmonary artery hypertension (PAH) is defined as a mean pulmonary artery pressure of more than 25mmHg at rest or 30mmHg with exercise. 1 In 2004 the World Health Organization (WHO) classification defined PAH as idiopathic or associated with, based on the etiology of the disease. 2 Additionally, a system of functional classification was devised (Table 1). Idiopathic pulmonary artery hypertension (IPAH) is a disease affecting the pulmonary vascular bed for which there is no apparent cause. Associated Pulmonary Arterial Hypertension (APAH) is a composite of many other etiologies such as collagen vascular disease, congenital cardiac abnormalities, human immunodeficiency virus (HIV), as well as thromboembolic disease. The incidence of IPAH of 2-3:1,000, Initial symptoms of PAH are vague, leading to delayed diagnosis and a decline in functional status prior to diagnosis which may take up to two years. Dyspnea is the most commonly reported reason for seeking medical attention. Other symptoms include edema, fatigue, angina, and syncope. Without treatment this disease progresses to death within two to three years after diagnosis. 1 Investigation and diagnosis of PAH may be time consuming, requiring extensive testing to rule out other causes of symptoms (Table 2). For many years the treatment of PAH was limited to symptomatic treatment and, possibly,

2 lung transplantation. In cases of APAH, treatment of the underlying cause may improve symptoms and prognosis. This may include pulmonary thromboendarterectomy for chronic pulmonary embolic disease or repair of an atrial septal defect. In 1996 The Food and Drug Administration (FDA) approved prostacyclin (Flolan ) as the first treatment of PAH that improved survival. In the last several years new medications have been approved. Current treatment options are outlined in Table 3. In addition, oxygen and diuretic therapy can be used for symptomatic relief. Clinical trials are ongoing and more treatment options may become available in the U.S. in the next few years. Unfortunately, medical therapy for PAH is very expensive. Yearly costs for medications can exceed one hundred thousand dollars. Table 1. World Health Organization Functional Classification of Pulmonary Hypertension Class I Class II Class III Class IV Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may be present even at rest. Discomfort is increased by any physical activity.

3 Table 2. Evaluation for PAH Echocardiogram (diagnosis cannot be made on this alone) Pulmonary Function Testing Chest X-ray Ventilation/ perfusion scan High resolution Chest CT Screening for undiagnosed connective tissue disease Screening for undiagnosed HIV Screening for abnormal clotting syndromes Sleep study Cardiac angiogram if patient has cardiac risk factors or age >40years Right heart catheterization (considered the gold standard for diagnosis) Table 3. Treatment Options for PAH 4 Drug Class Drug Administration and Dosage Anticoagulants Warfarin Keep INR Calcium Channel Blockers Prostacyclin analogues Endothelin receptor antagonists Phosphodiasterase 5 inhibitors Diltiazem, nifedipine Prostacyclin (Flolan ) Iloprost (Ventavis ) Treprostinil (Remodulin ) Bosentan (Tracleer ) Ambrisentan (Letairis ) Sildenafil (Revatio ) Oral; high dose (diltiazem 900mg daily). Used only if reactive to vasodilator trial. Continuous intravenous infusion (very short halflife) 22-45ng/kg/min Inhaled; 5 mcg 6-9 times per day Continuous subcutaneous or intravenous; >10ng/kg/min Oral; initially 62.5mg BID; target 125mg BID Oral; 5 or 10mg daily Oral; 20 mg TID

4 Case Study This is a 56 yr old WW diagnosed with IPAH in Initial symptom: dyspnea on exertion 04/02: Echocardiogram: normal ejection fraction and left ventricular (LV) size mild left atrial (LA) dilatation Right ventricular (RV) moderately dilated with RV hypertrophy RV systolic pressure (RVSP): 100mmHg 09/02: Right heart catheterization: Right atrial pressure (RAP) 10mmHg Pulmonary artery pressure (PAP) 110/50mmHg, mean 65 Pulmonary capillary wedge (PCW) 11mmHg Minimal response to prostacyclin as trial in cath lab 2002: Bosentan initiated with improvement in symptomatology. Patients receiving bosentan must have their liv er enzymes checked monthly because of the high incidence of toxicity associated with this drug. Unfortunately, she quickly developed elevated transami nas es (AST, ALT) which persisted even at a lower dose of bosentan. Bosentan was discontinued with resolution of liver abnormality. Sildenafil started at 25mg TID, eventually increased 100mg TID with improvement in symptoms. 07/03: At this point the patient was referred to our center. Her only complaint was shortness of breath (SOB) climbing stairs. WHO Class II Medications: sildenafil 100 mg TID spironolactone 75 mg BID furosemide 60 mg BID warfarin (maintain INR ) Physical Exam: no jugular venous distension (JVD) lungs clear bilaterally prominent S2 on cardiac auscultation no peripheral edema 10/03: bosentan restarted at 62.5 mg BID, sildenifil continued at 100 mg TID 01/04: bosentan increased to 125 mg BID transaminases remain stable

5 03/04: Echocardiogram: enlarged & dilated RV PASP 55-65mmHg LA size upper limits normal LV normal size & function 04/04: 6 minute walk test (6MW): 1375 feet (considered the best measure of functional status in PAH patients) Medication therapy unchanged 03/05: Echocardiogram: RVSP mmHg 03/05: Patient complained of being more SOB and reported that she had been missing doses of her medications 6MW: 1536 feet 07/05: 6MW: 1480 feet B-type naturetic peptide (BNP): mildly elevated 11/05: doing well slight increase in transaminases 02/06: Transaminases remain stable 6MW: 1438 feet 08/06: Patient reported no change in symptoms, WHO class III 6MW: 1320 feet Echocardiogram: RV dilatation RVSP mmHg 12/06: Patient reported no change in symptoms however; new JVD 6MW: 1205 feet BNP: 119 ALT 3 times normal; bosentan decreased to 62.5 mg BID 02/07: Patient reported being very SOB Transaminases still elevated, but stable 6MW: 1090 feet BNP: 164 On the lower dose of bosentan she had significant worsening of her symptoms as well as a slow decline in functional capacity during the past year. Additional therapy was indicated. Two possibilities were discussed: iloprost (Ventavis ), or treprostinil (Remodulin ) both prostacyclin

6 analogues. Either treatment would require a significant commitment of both time and effort by the patient. Iloprost is an inhaled medication with a short half-life. It must be inhaled from 6 to 9 times a day through an I-neb. Treprostinil is delivered either subcutaneously or intravenously. The subcutaneous route, although easier to manage is associated with significant site pain. Intravenous therapy would require an indwelling catheter. Additionally, because of the short half-life of these medications she would need to be very compliant and avoid missing doses. She was given information on both iloprost and treprostinil in order to assist her to make an informed choice. 03/07: Patient has elected to initiate iloprost therapy. She will continue bosentan for the time being, but will eventually be maintained on iloprost and sildenifil. Pulmonary arterial hypertension is a complicated disease with equally complicated drug therapy. It is not uncommon for patients to have a delay in diagnosis and it may be necessary to attempt several therapeutic modalities before finding the optimum treatment for the individual patient. Frequent communication between the health care team and patient is essential. REFERENCES 1. Rubin LJ. (1997) Primary pulmonary hypertension. N Engl J Med; 336: Rich S. (2002) A new classification of pulmonary hypertension. Adv Pulm Hyper; 1: Pulmonary Hypertension. http/er.wikepedia.org/wiki/pulmonary_hypertension#epidemiology. Accessed October 31, Keogh AM, McNeil KD, Williams T, Gabbay E & Cleland LG. (2003) Pulmonary arterial hypertension: A new era in management emja; 178: