Case Presentation: A 72 year old male presented with worsening shortness of breath and increasing oxygen requirement for six weeks. The patient had been on supplemental oxygen for the past 2 years for hypoxia. As an outpatient, right heart catheterization revealed a pulmonary arterial pressure (PAP) of 76/24 mmHg, mean PAP of 41 mmHg, wedge pressure of 7mmHg, and cardiac index (CI) of 2.6. Workup for other etiologies of pulmonary hypertension was negative and patient was diagnosed with idiopathic pulmonary arterial hypertension (IPAH). During his hospitalization, patient underwent a vasodilator challenge with a post nitric oxide mean PAP of 31 mmHg. However despite a positive vasodilator response, the patient failed a trial of high dose diltiazem. Pulmonary arterial pressures remained elevated in the 70s without improvement in oxygenation. Patient’s course was complicated by development of right heart failure with worsening hemodynamic parameters which led to discontinuation of diltiazem. A trial of iloprost was initiated but with no improvement of filling pressures or hypoxemia as patient continued to saturate between 70-80% on minimal exertion. After management of his right heart failure, patient was placed on amlodipine and sildenafil for the remainder of his hospitalization. Repeat right heart catheterization revealed persistent elevations of PAP (50-60) with low wedge pressures. Deemed to be a World Health Organization (WHO) functional Class IV patient, he was transferred to a lung center for further management.
Discussion: Idiopathic pulmonary arterial hypertension is a complex disease state with evolving therapeutic options the oldest of which is the use of calcium channel blockers (CCB). Current recommendations suggest that prior to initiating CCB therapy, patients should undergo pulmonary vasodilator testing via right heart catheterization. It was believed that patients who have positive vasodilator responses have better prognoses from a trial of CCBs than non-responders. However, recent studies have found no difference in 10-year survival in PAH patients with a positive pulmonary vasodilator test with inhaled nitric oxide. By the current recommended criteria of a positive test approximately 10% of patients with IPAH will be vasoreactive, and of these, only about 50% will respond to a calcium-channel blocker. Of all the patients with idiopathic PAH, only 5% will actually benefit from a calcium channel blocker despite all of them going through a vasodilator test. The cost of the test is up to $8000 compared to the actual therapy itself which for most individuals is under $50. We believe that subjecting every IPAH patient to a test with such a low response rate does not seem cost effective. Currently, expert opinion discourages starting CCB therapy empirically in patients with IPAH due to concerns of systemic hypotension, worsening right heart failure, and death. However, these adverse events can also occur in patients with a positive vasodilator response as seen by our case. We believe that in IPAH patients of WHO functional class of 3 or 4, empiric therapy with CCB while foregoing vasodilator testing may be warranted.
Conclusions: In summary, clinicians managing IPAH should take into account the patients functional class when considering calcium channel blocker therapy and should consider initiating empiric therapy rather than vasodilator testing. Further studies into the cost-benefit analysis of pulmonary vasodilator testing in guiding management decisions for IPAH need to be done.