THREE COMMON MISTAKES IN PAH MANAGEMENT
VALLERIE V. MCLAUGHLIN, MD

Pulmonary arterial hypertension (PAH) is a disease of the small pulmonary arterioles which results in increased pulmonary vascular resistance and often progresses to right ventricular failure. The prototype form of PAH is idiopathic PAH, but PAH may also be heritable, drug or toxin induced, or associated with other diseases such as scleroderma. The prevalence of PAH is approximately 15-30/million. Due to this low prevalence, the diagnosis of PAH is often delayed and often times, a patient experiences symptoms for years before the diagnosis is made. There are many other more common forms of pulmonary hypertension (PH) including any heart disease that results in elevated left heart filling pressures. PH can also be caused by parenchymal lung disease and chronic thromboembolic disease. The diagnosis of PAH requires a series of tests, and ultimately a right heart catheterization. Precise measurement of hemodynamics is critical in the diagnostic evaluation of these patients. Herein lies one of the most common mistakes of PAH management, delayed and inaccurate diagnosis. Having a high index of suspicion, and methodically following the published diagnostic evaluation algorithms will help minimize this very common mistake that can lead to delayed and sometimes inappropriate therapy.

Calcium channel blockers have historically been considered a treatment for PAH. However, for the majority of the patients, calcium channel blockers will not be effective, and may even be harmful. Acute vasodilator testing at the time of right heart catheterization is important to delineate the very small group of patients with idiopathic PAH who might respond to calcium channel blockers. Appropriate agents for acute vasodilator testing included inhaled nitric oxide, intravenous epoprostenol, and intravenous adenosine. The definition of a positive acute vasodilator response is a fall in mean pulmonary artery pressure by at least 10 mmHg, to a mean pulmonary artery pressure of less than 40 mmHg, in the setting of a normal cardiac output. Patients who meet these criteria at the time of acute vasodilator challenge are appropriate to treat with calcium channel blockers. However, these patients should be followed for a clinical response. Patients who improve to functional class I or II symptoms are likely to do well on calcium channel blocker therapy. Those who do not improve to functional class I or II symptoms should proceed to PAH specific therapy. Only about 6% of idiopathic PAH patients will fall into this category. The inappropriate use of calcium channel blockers is a common mistake in PAH management.

Previously thought to be a progressive and almost uniformly fatal disease, the prognosis of patients with PAH has improved as specific medical therapies for PAH have been studied and approved over the recent years. Current therapies can be divided into three broad categories: the prostacylins (epoprostenol, treprostinil, iloprost), the endothelin receptor antagonists (bosentan, ambrisentan) and the phosphodiesterase inhibitors (sildenafil, tadalafil). It is important to follow patients closely after initiation of therapy, as some may have an inadequate response to monotherapy and may need escalation of therapy. Such suboptimal treatment of patients is another common mistake in the management of PAH. Setting appropriate “goals of therapy” may improve long term outcomes. Recent registries have demonstrated important prognostic indicators including functional class, 6 minute walk distance, and right ventricular function. Optimizing treatments to achieve these specific goals may improve long term prognosis. This may require combination therapy or more aggressive treatment with prostacylin therapy for some patients. Lung transplantation is a consideration for some patients who have an inadequate response to medical therapy.

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