***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension ( PAH ) in animal models . In the present study , we examined the clinical effects of mid-term oral treatment with an extended release formulation of AT-877 ( fasudil hydrochloride ) , a specific Rho-kinase inhibitor ( AT-877ER ) on PAH . METHODS AND RESULTS 23 PAH patients were treated with either placebo ( 10/2 females/males , 51 ± 16 years , idiopathic PAH ( IPAH ) in 6 , PAH associated with connective tissue disease ( CTD-PAH ) in 3 , PAH with congenital heart disease ( CHD-PAH ) in 2 , and portal PAH in 1 ) or AT-877ER ( 6/5 females/males , 47 ± 14 years , IPAH in 2 , CTD-PAH in 5 , and CHD-PAH in 4 ) ; 3 patients were excluded . We performed a 6-min walk test and right heart catheterization in the remaining 20 patients , before and 3 months after the treatment ( placebo n=11 , AT-877ER n=9 ) . Although there were no significant differences between the 2 groups for the 6-min walk distance , pulmonary hemodynamics tended to be improved in the AT-877ER group , especially the prevalence of improved cardiac index from baseline , which was significantly higher in the AT-877ER than in the placebo group . In the AT-877ER group , serum levels of hydroxyfasudil , an active metabolite of AT-877ER tended to correlate with improvements in the cardiac index and mean pulmonary artery pressure . CONCLUSIONS Mid-term treatment with oral AT-877ER showed additional improvement in pulmonary hemodynamics in patients with PAH OBJECTIVE To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival . DESIGN Registry with prospect i ve follow-up . SETTING Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart , Lung , and Blood Institute . PATIENTS Patients ( 194 ) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988 . MEASUREMENTS At diagnosis , measurements of hemodynamic variables , pulmonary function , and gas exchange variables were taken in addition to information on demographic variables , medical history , and life-style . Patients were followed for survival at 6-month intervals . MAIN RESULTS The estimated median survival of these patients was 2.8 years ( 95 % Cl , 1.9 to 3.7 years ) . Estimated single-year survival rates were as follows : at 1 year , 68 % ( Cl , 61 % to 75 % ) ; at 3 years , 48 % ( Cl , 41 % to 55 % ) ; and at 5 years , 34 % ( Cl , 24 % to 44 % ) . Variables associated with poor survival included a New York Heart Association ( NYHA ) functional class of III or IV , presence of Raynaud phenomenon , elevated mean right atrial pressure , elevated mean pulmonary artery pressure , decreased cardiac index , and decreased diffusing capacity for carbon monoxide ( DLCO ) . Drug therapy at entry or discharge was not associated with survival duration . CONCLUSIONS Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables : mean pulmonary artery pressure , mean right atrial pressure , and cardiac index . Such an equation , once vali date d prospect ively , could be used as an adjunct in planning treatment strategies and allocating medical re sources Recent studies have suggested that oxygen consumption ( VO2 ) may be dependent on systemic oxygen transport ( SOT ) in patients with the adult respiratory distress syndrome . To evaluate this relationship in patients with chronically impaired SOT , 2 groups underwent control right heart catheterization . Twenty-six patients with pulmonary hypertension ( Group I ) were then reevaluated after 48 h of treatment with a vasodilator , either hydralazine or nifedipine .  Nine patients with refractory left ventricular failure ( Group II ) were first studied using nitroprusside , and 24 h later were begun on a double-blind drug protocol using either minoxidil or hydralazine . A significant correlation existed between control SOT and VO2 in both groups ( r = 0.65 , p less than 0.001 ) . There were no changes in either group , however , in VO2 with vasodilator therapy , despite significant increases in cardiac output and SOT . We conclude that although resting oxygen consumption may be correlated with systemic oxygen transport when SOT is at low levels in stable patients with chronically impaired SOT , VO2 appears to be independent of SOT when oxygen delivery is increased by the administration of vasodilators BACKGROUND Primary pulmonary hypertension is a progressive , fatal disease of unknown cause . Vasodilator drugs have been used as a treatment , but their efficacy is uncertain . METHODS We treated 64 patients with primary pulmonary hypertension with high doses of calcium-channel blockers . Patients who responded to treatment ( defined as those whose pulmonary-artery pressure and pulmonary vascular resistance immediately fell by more than 20 percent after challenge ) were treated for up to five years . Their survival was compared with that of the patients who did not respond and with patients enrolled in the National Institutes of Health ( NIH ) Registry on Primary Pulmonary Hypertension . Warfarin was given to 55 percent of the patients as concurrent therapy , on the basis of a lung scan showing nonuniformity of pulmonary blood flow ( 47 percent of patients who responded and 57 percent of those who did not respond ) . RESULTS Seventeen patients ( 26 percent ) responded to treatment , as indicated by a 39 percent fall in pulmonary-artery pressure and a 53 percent fall in the pulmonary-vascular-resistance index ( P less than 0.001 ) . Nifedipine ( mean [ + /- SD ] daily dose , 172 + /- 41 mg ) was given to 13 patients , and diltiazem ( mean daily dose , 720 + /- 208 mg ) was given to 4 patients . After five years , 94 percent of the patients who responded ( 16 of 17 ) were alive , as compared with 55 percent of the patients who did not respond ( 26 of 47 , P = 0.003 ) . The survival of the patients who responded was also significantly better than that of the NIH registry cohort ( P = 0.002 ) and patients from the NIH registry who were treated at the University of Illinois ( P = 0.001 ) . The use of warfarin was associated with improved survival ( P = 0.025 ) , particularly in the patients who did not respond . CONCLUSIONS This study suggests that high doses of calcium-channel blockers in patients with primary pulmonary hypertension who respond with reductions in pulmonary-artery pressure and pulmonary vascular resistance may improve survival over a five-year period 
    Output:
    
Currently , as there is lack of valid evidence , the efficacy and safety of CCBs is unproven in the treatment of PAH .