Primary pulmonary hypertension.

The use of pharmacologic agents in the treatment of pulmonary hypertension has not proved to be uniformly successful or predictable. One possible reason for the vagaries in response is that the pulmonary vascular lesions are not consistent. We examined the relation between the structure of the pulmonary resistance vessels in unexplained (primary) pulmonary hypertension and the response to pulmonary vasodilators. Our study involved 19 patients with clinically unexplained pulmonary hypertension (mean pressure, 59±14 mm Hg). After characterizing them clinically and performing control hemodynamic measurements, we determined the acute effects of a series of vasodilator agents that have different mechanisms of action. In 16 patients, lung biopsy material was related to the hemodynamic studies; in nine patients, including six who had undergone open lung biopsy, the hemodynamic studies were related to the pathologic changes found at autopsy. Histologic specimens from all 19 patients were evaluated qualitatively and sorted into three subsets of hypertensive pulmonary arteriopathy: medial hypertrophy (with minimal intimal proliferation), arteriopathy with plexiform lesions (associated predominantly with concentric laminar intimal proliferation and fibrosis), and arteriopathy with microthrombotic lesions (associated predominantly with eccentric intimal proliferation and fibrosis). The 16 lung biopsies were also quantitated by morphometric techniques. Using a decrease in calculated pulmonary vascular resistance of more than 30% accompanied by a decrease in mean pulmonary arterial pressure of at least 10% to define vasodilation, only four patients were responders. The patients varied considerably in their responses to different vasodilator agents. Patients with similar clinical and hemodynamic profiles differed considerably with respect to the nature of their pulmonary vascular obstructive lesions and their responses to vasodilator agents. Qualitative histologic examination of lung tissue did not provide a basis for predicting how individual patients would respond to vasodilator agents. However, quantitative morphologic analysis of the initial open lung biopsy specimens did prove helpful in predicting acute responsiveness to vasodilator agents and the subsequent clinical course of these patients with unexplained (primary) pulmonary hypertension. An intimal area of more than 18% of the vascular cross-sectional area had an 85% predictive value for identifying the patients who did poorly during the first 36 months of follow-up. (Circulation 1989;80:1207-1221)