Between April 1981 and August 1992 173 patients with primary pulmonary hypertension (PPH) were referr to our institution from all athwart France.

Between April 1981 and August 1992 173 patients with primary pulmonary hypertension (PPH) were referr to our institution from all athwart France. The risk factors, associated conditions, pulmonary and vascular parameters, medical treatments applied, transplantation protocols, and survival of the cohort are reported.

RISK FACTORS AND ASSOCIATED CONDITIONS

The female to male ratio was 18:1 and the mean age at the time of diagnosis was 39 [+ or -] 13 years, similar for male and female exposes The mean time from charge of symptoms to diagnosis was 21 [+ or -] 29 years, this likely accounting for the unadorned initial presentation of most patients, since 66 percent belonged to strange York Heart Association (NYHA) functional class 3 or 4

Portal hypertension or HIV infection was establish in 11 percent of cases, with a slight male predominance for the two Positive antinuclear antibody titers ([greater than] 1/80) were plant in 14 percent of patients, almost exclusively in female patients, as well as isolated Raynaud's phenomenon or a history of appetite suppressant use (amphetamine and/or fenfluramine derivatives) in 15 percent and 12 percent patients, respectively. single 3 percent of patients had a positive family history of PPH and 11 percent of the female patients had been diagnosed as having PPH during or shortly after pregnancy.

Pulmonary function variables showed that patients had normal function excluding for a mild but significant reduction in total lung capacity (88 [+ or -] 15 percent of predicted values). At the time of diagnosis, overall, patients had a moderate hypoxemia while breathing range air (71.5 [+ or -] 92 mm Hg) with a mild hypocapnia (308 [+ or -] 77 mm Hg) For the whole arrange mean diffusing capacity for carbon monoxide (reported to alveolar volume) was significantly reduc to 68 [+ or -] 24 percent of predicted values. Lung perfusion scans were considered as entirely normal in 26 percent of patients and mildly abnormal (patchy) in 64 percent of them. solely 10 percent of patients had multiple discrete imperfections on lung scan, but pulmonary angiography always rul on the outside the diagnosis of chronic thromboembolic pulmonary hypertension in as it was cases.

At the time of first evalution in our institution, right heart catheterization showed that overall, patients had sharp pulmonary hypertension, with mean right atrial hurry (RAP) 8.5 [+ or -] 50 mm Hg mean pulmonary artery compressing (PAP) 58 [+ or -] 14 mm Hg with normal mean pulmonary wedge urgency (7 [+ or -] 3 mm Hg) Cardiac index at caesura was decreased to 2.2 [+ or -] 05 L/min/[m.sup.2], and total pulmonary vascular resistance (TPVR) index was elevated to 28 [+ or -] 11 U/[msup2]

MEDICAL TREATMENT

The majority of patients have been evaluated for therapy in our institution and in the same manner.[1] Treatment was based forward long-term oral anticoagulation, vasodilators, and/or lung or heart-lung transplantation. Thirty-nine patients with PPH associated with portal hypertension (n = 20) or HIV infection (n = 19) were not included in this presentation of the therapeutic approach because of specific enigmas The forthcoming results are given for 134 patients with "pure" PPH

greatest in number patients were submitted to an acute 24- to 36- h trial with vasodilating agents, in subordination to permanent control monitoring of right heart hemodynamics, in an intensive care unit. The following six vasodilators were proofed intravenously: prostacyclin (epoprostenol, 5 to 10 ng/kg/min); isoproterenol (005 to 01 [mu]g/kg/min); diltiazem (2 to 12 [mu]g/kg/min); phentonlamine (2 to 4 [mu]g/kg/min); nitroglycerin (025 to 12 ng/kg/min); and hydralazine (01 mg/kg bolus). excepting for prostacyclin, all these vasodilators had an oral equivalent for defered use. Since 1988, and in succession the basis of previous results[2] prostacyclin was trialed first and used as a screening agent, in order to expose a potential for pulmonary vasodilatation. Subsequently other vasodilators could be ordealed but only in case of a significant answer to prostacyclin. For each patient and each unsalable article a significant vasodilating response was considered when PVR decreased by means of more than 20 percent compared to mean PVR restrain values.

More than 100 patients (107 of 134) had a short-term trial with prostacyclin which was, leave out for isoproterenol, the most commonly active vasodilator with up to 60 percent of patients considered as significant responder Patients les commonly rejoined to the other vasodilators when exampleed on a short-term basis. Prostacyclin was also the mostly potent vasodilator during acute challenge, inducing a mean decrease in PVR of 25 percent for the whole cluster and a mean decrease in PVR of 36 percent in the clump of patients considered as responder solitary isoproterenol was capable of lowering PVR in the same proportions if it were not that always by inducing a marked rise in PAP and heart rate. Other put drugs intos were all less powerful, short-term pulmonary vasodilators (Fig 1)

The issue of whether or not the answer to short (or prolonged) administration of vasodilators is predictive of prognosis is still unresolved[3] We examined the survival rate of medically treated patients according to the on a level of their initial pulmonary vasodilatation during short trials with prostacyclin. Patients were divided into three clusters according to the magnitude of the response: the first cluster of high responders (n = 9) had a decrease in PVR of more than 50 percent compared to repress values; a second group of "intermediate" responder (n = 38) had a fall in PVR of 20 to 50 percent; and a third assign places to were nonresponders (n = 31) to prostacyclin. High responder had a significantly better survival rate when compared to the overall patients from the brace other groups whose survival rates did not differ (50 v 25 percent survival rate at 3 years, respectively, p [les than] 005) At the time of short-term testing, there was no clinical or baseline hemodynamic variable that could predict the rejoinder to prostacyclin, except for a longer time from attack of symptoms to diagnosis in high responder compared to the patients of the sum of two units other groups.

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