INTRODUCTION: Practice guidelines recommend that patients with idiopathic pulmonary arterial hypertension (IPAH) undergo vasodilator testing to determine potential responders to calcium channel blockers (CCBs). Patients who fail adequate doses of CCBs may benefit from other therapies believed to have broader efficacy.
CASE PRESENTATION: KS is a 37 year-old athletic woman who was without medical problems until age 31 when she developed chest pain and pre-syncope during a 4th of July potato sack race. She was diagnosed with IPAH and treated empirically with diltiazem CR, 300 mg daily with slight improvement in symptoms. Two years later she underwent catheterization, was noted to have a markedly elevated pulmonary arterial (PA) pressure, was challenged with epoprostenol and found to be reactive. Her diltiazem was increased to 420 mg daily, but because there was no improvement in her symptoms, the endothelin-receptor blocker bosentan, 125 mg twice daily was added to the regimen. At age 36, with no improvement in her symptoms, she was referred to our center to evaluate her for intravenous epoprostenol therapy. Her assessment at that time included a treadmill test by Naughton-Balke protocol where she walked for 6 minutes and 14 seconds; (4.40 METS). Cardiac catheterization done on the diltiazem and bosentan demonstrated a PA pressure of 85/40 mmHg with a mean of 56mmHg and a pulmonary vascular resistance (PVR) of 9.78 Units. Upon administration of adenosine at 50 mcg/kg/min, the PA pressure decreased to 45/20 mmHg with a mean of 26 mmHg and the PVR to 2.71 Units. Based upon this vasodilator response, bosentan and diltiazem were discontinued and amlodipine 20 mg daily was begun. One year later, KS had a marked improvement in symptoms with a treadmill test response of 14 minutes and 16seconds, (8.40 METS). Cardiac catheterization now demonstrated: PA pressure of 38/15 with a mean of 25 mmHg and a PVR of 3.98 Units. She was maintained on her high dose CCBs and continues to do well.
DISCUSSIONS: This case re-illustrates the importance of vasodilator testing in patients with IPAH, and the fact that in patients who respond, effective therapy requires treatment with high-dose CCBs, as opposed to conventional dose CCBs. Moreover, this case refutes the notion that endothelin-receptor blockers have broader efficacy than the CCBs, and suggests their mechanism of action is distinctly different than the vasodilator actions of the CCBs or epoprostenol.
CONCLUSION: High-dose CCBs remain first-line therapy for vasoreactive patients with IPAH. Endothelin-receptor blockers are not an adequate substitute for the CCBs in these patients.
DISCLOSURE: William Borden, None.