use endothelin antagonist to treat pulmonary hypertension in sickle cell patients

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This patient has the subacute onset of dyspnea on exertion, and his evaluation, including right heart catheterization, shows pulmonary arterial hypertension (PAH; World Health Organization [WHO] group 1 pulmonary hypertension) by virtue of his mean pulmonary arterial pressure >20 mm Hg, pulmonary capillary wedge pressure <15 mm Hg, and pulmonary vascular resistance >3 Wood units. Of note, the presence of pulmonary hypertension of any type correlates with worsened mortality in patients with sickle cell disease. In patients such as this one with sickle cell disease, PAH, and mild to moderate symptoms (WHO functional class II or III), endothelin-1 receptor antagonists such as ambrisentan are considered the treatment of choice (choice A is correct).

Because of the complexities of its continuous IV administration and the potential for complications such as infection of indwelling central catheters, treatment with epoprostenol would not be appropriate in this patient (choice B is incorrect). However, if the patient progresses to more advanced disease, with the inability to carry out any physical activity without symptoms, develops signs of right heart failure and dyspnea and/or fatigue at rest (WHO functional class IV), then therapy with an IV prostanoid would be appropriate.

While sildenafil and other phosphodiesterase 5 inhibitors play an important therapeutic role in the treatment of PAH of other etiologies, they should be avoided in patients with PAH related to sickle cell disease because increased hospitalizations for pain crisis were seen in the largest clinical trial of sildenafil in this population (choice C is incorrect).

Calcium channel antagonists have limited utility in the treatment of PAH and are reserved for patients who demonstrate vasoreactivity in response to a short-acting pulmonary vasodilator, defined as a reduction in the mean pulmonary artery pressure by ≥10 mm Hg and reaching an absolute mean pulmonary arterial pressure of ≤40 mm Hg. Because this patient does not exhibit pulmonary vasoreactivity, treatment with the calcium channel antagonist nifedipine would not be of utility (choice D is incorrect).

Of note, diastolic dysfunction is a very common cause of pulmonary hypertension in patients with sickle cell disease, and cardiac catheterization of such patients will show a pulmonary capillary wedge pressure or left ventricular end diastolic pressure ≥15 mm Hg, unlike in this patient. Patients with pulmonary hypertension and an elevated left atrial pressure should not be treated with endothelin-1 receptor antagonists or other advanced therapies for PAH.1

Footnotes

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