Pulmonary arterial hypertension: newer treatments are improving outcomes

Journal of Family Practice, Dec, 2004 by Kasem Sirithanakul, Kamal K. Mubarak

Practice recommendations

* Echocardiography is useful for screening high-risk patients (SOR: A).

* The New York Heart Association classification of dyspnea has been modified by the World Health Organization to categorize pulmonary hypertension by the severity of symptoms, which, unlike pulmonary arterial pressure, correlates well with survival (SOR: A).

* Calcium channel blockers are useful only for patients who respond to vasodilator testing in a cardiac catheterization laboratory (SOR: A).

* Therapeutic modalities now include parenteral prostanoids, oral endothelin receptor antagonists, PDE5 inhibitors, and lung transplantation (SOR: A; for PDE5 inhibitors, SOR: B)

* Early referral to expert centers is crucial to patient survival (SOR: B).

Recent progress in understanding the pathobiology of pulmonary arterial hypertension (PAH) has been tremendous, and treatment options have multiplied to include prostanoids, endothelin antagonists, phosphodiesterase-5 inhibitors, anticoagulants, and surgical options such as lung transplantation and atrial septostomy.

Although idiopathic pulmonary arterial hypertension, formerly called "primary," is rare, other forms of PAH and associated cor pulmonale are more prevalent than conventionally believed. It is a life-threatening disease best managed within a diagnostic framework such as the one reviewed here with a treatment algorithm and recommendations from evidence-based guidelines.

* PATIENTS MOST LIKELY TO EXPERIENCE PULMONARY ARTERIAL HYPERTENSION

Pulmonary arterial hypertension may be idiopathic and sporadic (IPAH), familial (FPAH), or associated with (APAH) connective tissue diseases, congenital systemic to pulmonary shunts, portal hypertension, HIV, drugs including anorexigens or cocaine, and other disorders (Table 1). (1)

Annually, 1 to 2 cases of IPAH occur per million Population. (2) The mean age at diagnosis is 36 years, and women are affected more often than men by a ratio of 1.7-3.5:1. This female predominance has also been noted in PAH associated with scleroderma, (3) congenital heart disease, (4) and anorexigen-induced PAH. (5) The incidence among users of anorexigens such as fenfluramine, dexfenfluramine, and aminorex is estimated to be 25 to 50 per million per year. (2)

The prevalence of portopulmonary hypertension is about 0.73% in cirrhosis. (6) In scleroderma, the incidence is between 6% to 60%, (7,8) while in systemic lupus erythematosus (SLE) it is reported to be 4% to 14%. (9,10) In one study, 21% of rheumatoid arthritis patients without underlying cardiopulmonary disease had mild pulmonary hypertension (PH). (11) PAH occurs in about 0.5% of patients with HIV infection. (12)

Included in the "others" group are hemoglobinopathies such as sickle cell anemia. This classification does not include PH due to end-stage renal disease, a recently described entity in patients with arteriovenous fistulae that portends a poorer prognosis. (13) PH was present in a surprising 40% of hemodialysis patients.

* CLINICAL PRESENTATION

Pulmonary arterial hypertension manifests the following symptoms and signs:

Symptoms

* Progressive onset of exertional dyspnea (60%) (14)

* Chest pain or discomfort (17%)

* Palpitations (5%)

* Dizziness and light-headedness. There may be a history of near-syncope or syncope (13%)

* Fatigue (19%)

* Ortner's syndrome: hoarseness from compression of left recurrent laryngeal nerve by enlarged pulmonary artery (<1%) (See Ortner's syndrome)

* Raynaud's phenomenon (10%)

Signs

* Loud P2 (93%)

* Tricuspid regurgitation murmur (40%)

* Right ventricular heave

* Jugular venous distention with a prominent "a" wave

* Graham Steell's murmur: diastolic pulmonary regurgitation murmur best heard at upper left sternal border (13%)

* Signs of right heart failure including S3 gallop, "v" wave in central venous pressure tracing, hepatojugular reflux, peripheral edema, and ascites

* Cutaneous telangiectasia.

* AN EFFICIENT DIAGNOSTIC FRAMEWORK

Proceed with a stepwise assessment (Figure 1) of any patient exhibiting signs or symptoms suggestive of PH, particularly if there is an associated underlying condition or suggestive imaging study. Echocardiography (ECG) is usually the first test ordered, to detect thickening of the right ventricle or regurgitation of blood into the right atrium. ECG is neither sensitive nor specific for PAH. Not every patient will require the full work-up outlined in Figure 1. The sequence and extent of testing depend on the clinical scenario. Cardiac catheterization is sometimes the last procedure, given its risks of invasiveness. A surface echocardiogram has a sensitivity of 79% to 100% and specificity of 60% to 98% for detecting PAH. (15)

Functional assessment most important

Mean blood pressure above 25 mm Hg at rest or systolic pressure over 40 mm Hg in the pulmonary circulation constitutes pulmonary hypertension (see Pulmonary hypertension criteria). However, the correlation of mean pulmonary arterial pressure to disease severity is not straightforward. (16) Higher pulmonary artery pressure may portend better survival. The severity of pulmonary arterial hypertension is better determined by functional assessment. The New York Heart Association (NYHA) classification of dyspnea has been modified by the World Health Organization (WHO) to categorize PH by the severity of symptoms, which, unlike pulmonary arterial pressure, correlates well with survival. Even with epoprostenol treatment, functional class III patients have a survival of 60% at 7 years compared with less than 20% for class IV. (17)