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Reversibility Testing

In recent years, reversibility testing has been increasingly performed in patients with known PAH. Previous practice offered reversibility testing only for patients with idiopathic PAH. The development of new medicaments and their spectrum of treatment options, however, have provided the framework to include in this testing also patients with PAH of other genesis. Some studies evaluating the treatment of these patients are still in progress. The aim of all measures, no matter whether idiopathic pulmonary arterial hypertension (PAH) or diseases associated with PAH are concerned, is to reduce the load on the right heart and thus relieve the symptoms and improve survival and the quality of life.
The initial aim should be to identify, by means of reversibility testing, those patients who will benefit from treatment with highly dosed calciumantagonists. Due to the fact that testing with highly dosed calciumantagonists would put the patients at high risk for severe hypertension, the testing is conducted using inhaled nitrogen monoxide (NO) or Iloprost. In recent years, however, acute testing of particular medicaments in order to investigate their therapeutic efficacy has become steadily established in some German centers. The test results are set forth in various test protocols developed by the several centers.
A frequently used criterion for a positive reversibility test is reduction in mean pulmonary arterial pressure by at least 10 mmHg to < 40 mmHg. These patients are then called “responders”.
Only in these patients it is justified to attempt a therapy with highly dosed
calciumantagonists. However, if these patients are in NYHA (New York Heart Association) class III or IV, this treatment has become obsolete particularly in the past two years.

Medicaments for reversibility testing
According to the recommendations given by the PAH World Conference in Evian in 1998, modified in Venice in 2003, medicaments with short-term efficacy are used for reversibility testing. The test substance is administered after the corresponding reproducible baseline measurements were performed. Medicaments with longer half-life require the use of multiple measurements which are normally performed at set intervals, e.g. every two hours. Once a new reproducible base line has been established, the next test substance is administered.
In order to foster the development of new therapies, some studies investigating test substances with longer so-called intermediary half-lives ranging from several hours up to 1 day have already been conducted. Another important factor, besides the substance´s efficacy, is duration of the effect, which may vary depending on the individual. So one is able to estimate the time intervals between
intakes. Today, such test substances with intermediary half-life include mainly
phosphodierase inhibitors (PDI).

Selective pulmonary vasodilatation with inhaled prostanoids
Selective pulmonary substances can be delivered directly to the pulmonary resistance vessels via the airways. The inhalative route of Iloprost application combines pulmonary selectivity with vasodilatatory action and antiproliferative and anti-inflammatory effects. Other remarkable features of Iloprost, apart from its pulmonary selectivity, include that pulmonary vasodilatation lasts longer than that achieved by the intravenous prostanoids used in earlier days. Treatment of PH with Iloprost aerosolized by specially developed ultrasonic nebulisers is an important and effective therapy. Numerous studies demonstrate the efficacy of Iloprost in patients with PH. First long-term studies also have reported prolonged survival. Because of its rapid activity, Iloprost is very suitable as test substance in reversibility testing.