***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 Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospect i ve , r and omized trial to improve survival . METHODS We conducted a 12-week prospect i ve , r and omized , multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol ( formerly called prostacyclin ) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension ( New York Heart Association functional class III or IV ) . RESULTS Exercise capacity was improved in the 41 patients treated with epoprostenol ( median distance walked in six minutes , 362 m at 12 weeks vs. 315 m at base line ) , but it decreased in the 40 patients treated with conventional therapy alone ( 204 m at 12 weeks vs. 270 m at base line ; P < 0.002 for the comparison of the treatment groups ) . Indexes of the quality of life were improved only in the epoprostenol group ( P < 0.01 ) . Hemodynamics improved at 12 weeks in the epoprostenol-treated patients . The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and + 3 percent , respectively ( difference in mean change , -6.7 mm Hg ; 95 percent confidence interval , -10.7 to -2.6 mm Hg ; P < 0.002 ) , and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and + 9 percent , respectively ( difference in mean change , -4.9 mm Hg/liter/min ; 95 percent confidence interval , -7.6 to -2.3 mm Hg/liter/min ; P < 0.001 ) . Eight patients died during the study , all of whom had been r and omly assigned to conventional therapy ( P = 0.003 ) . Serious complications included four episodes of catheter-related sepsis and one thrombotic event . CONCLUSIONS As compared with conventional therapy , the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement , as well as improved survival in patients with severe primary pulmonary hypertension BACKGROUND Pulmonary arterial hypertension with systemic dysfunctions , including metabolic disorders and renal dysfunction , has a poor prognosis . However , it remains to be eluci date d whether chronic thromboembolic pulmonary hypertension ( CTEPH ) is also associated with systemic dysfunctions , and if so , whether balloon pulmonary angioplasty ( BPA ) improves them . METHODS AND RESULTS Fifty-five consecutive patients who underwent BPA from March 2012 to December 2014 for systemic dysfunctions , including glycemic control , lipid profiles , renal and vascular function , and nutritional status were examined . The analyses were performed before and after BPA ( mean , 3.5 sessions/patient ) and changes in hemodynamic parameters were compared . The average follow-up period was 474±245 days . Baseline prevalence of hypertension , diabetes mellitus , dyslipidemia and advanced chronic kidney disease was 58 , 7 , 33 and 36 % , respectively . BPA caused marked hemodynamic improvements in the CTEPH patients . Importantly , BPA also significantly improved dysglycemia ( fasting blood sugar , hemoglobin A1c and homeostatic assessment model of insulin resistance ) , renal ( creatinine and estimated glomerular filtration rate ) and vascular ( cardio-ankle vascular index ) functions and nutritional status ( albumin , cholesterols , and body mass index ) . Importantly , there were positive correlations between the degrees of the hemodynamic improvements and those of other improvements . CONCLUSIONS These results indicate that BPA may exert multiple beneficial effects in CTEPH patients , not only in terms of hemodynamics but also in other systemic functions , with positive correlations among them Background — Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality ; however , no treatment is approved for this indication . We hypothesized that riociguat , a novel soluble guanylate cyclase stimulator , would have beneficial hemodynamic effects in patients with pulmonary hypertension caused by systolic left ventricular dysfunction . Methods and Results — Overall , 201 patients with heart failure result ing from pulmonary hypertension caused by systolic left ventricular dysfunction were r and omized to double-blind treatment with oral placebo or riociguat ( 0.5 , 1 , or 2 mg 3 times daily ) for 16 weeks in 4 parallel arms . The primary outcome was the placebo-corrected change from baseline at week 16 in mean pulmonary artery pressure . Although the decrease in mean pulmonary artery pressure in the riociguat 2 mg group ( −6.1±1.3 mm Hg ; P<0.0001 versus baseline ) was not significantly different from placebo ( P=0.10 ) , cardiac index ( 0.4 L·min−1·m−2 ; 95 % confidence interval , 0.2–0.5 ; P=0.0001 ) and stroke volume index ( 5.2 mL·m−2 ; 95 % confidence interval , 2.0–8.4 ; P=0.0018 ) were significantly increased without changes in heart rate or systemic blood pressure compared with placebo . Both pulmonary ( −46.6 dynes·s−1·cm−5 ; 95 % confidence interval , –89.4 to –3.8 ; P=0.03 ) and systemic vascular resistance ( −239.3 dynes·s−1·cm−5 ; 95 % confidence interval , –363.4 to –115.3 ; P=0.0002 ) were significantly reduced with riociguat 2 mg . Riociguat  reduced the Minnesota Living With Heart Failure score ( P=0.0002 ) . Discontinuation of treatment was similar between treatment groups . Conclusions — Although the primary end point of the study was not met , riociguat was well tolerated in patients with pulmonary hypertension caused by systolic left ventricular dysfunction and improved cardiac index and pulmonary and systemic vascular resistance . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01065454 The aim of the present study was to determine contemporary survival in pulmonary arterial hypertension ( PAH ) , and to investigate whether or not the National Institutes of Health ( NIH ) equation remains an accurate predictor of survival . In 576 patients with PAH referred during 1991–2007 , observed survival was described using the Kaplan – Meier method . In patients with idiopathic , familial and anorexigen-associated PAH ( n = 247 ) , observed versus NIH equation predicted survival was compared . A new survival prediction equation was developed using exponential regression analysis . The observed 1- , 3- and 5-yr survival in the total cohort were 86 , 69 and 61 % , respectively . In patients with idiopathic , familial and anorexigen-associated PAH , the observed 1- , 3- and 5-yr survival ( 92 , 75 and 66 % , respectively ) were significantly higher than the predicted survival ( 65 , 43 and 32 % , respectively ) . The new equation ( P(t ) = e-A(x , y , z)t , where P(t ) is probability of survival , t the time interval in years , A(x , y , z ) = e(−1.270–0.0148x+0.0402y–0.361z ) , x the mean pulmonary artery pressure , y the mean right atrial pressure and z the cardiac index ) performed well when applied to published contemporary studies of survival in PAH . Contemporary survival in the PAH cohort was better than that predicted by the NIH registry equation . The NIH equation underestimated survival in idiopathic , familial and anorexigen-associated PAH . Once prospect ively vali date d , the new equation may be used to determine prognosis We assessed the therapeutic potential of riociguat , a novel soluble guanylate cyclase stimulator , in adults with chronic thromboembolic pulmonary hypertension ( CTEPH ; n = 42 ) or pulmonary arterial hypertension ( PAH ; n = 33 ) in World Health Organization ( WHO ) functional class II/III . In this 12-week , multicentre , open-label , uncontrolled phase II study , patients received oral riociguat 1.0–2.5 mg t.i.d . titrated according to systemic systolic blood pressure ( SBP ) . Primary end-points were safety and tolerability ; pharmacodynamic changes were secondary end-points . Riociguat was generally well tolerated . Asymptomatic hypotension ( SBP < 90 mmHg ) occurred in 11 patients , but blood pressure normalised without dose alteration in nine and after dose reduction in two . Median 6-min walking distance increased in patients with CTEPH ( 55.0 m from baseline ( 390 m ) ; p<0.0001 ) and PAH ( 57.0 m from baseline ( 337 m ) ; p<0.0001 ) ; patients in functional class II or III and bosentan pre-treated patients showed similar improvements . Pulmonary vascular resistance was significantly reduced by 215 dyn·s·cm−5 from baseline ( 709 dyn·s·cm−5 ; p<0.0001 ) . 42 ( 56 % ) patients were considered to have experienced drug-related adverse events ( AEs ; 96 % mild or moderate ) . Dyspepsia , headache and hypotension were the most frequent AEs . Study discontinuation because of AEs was 4 % . These preliminary data show that riociguat has a favourable safety profile and improves exercise capacity , symptoms and pulmonary haemodynamics in CTEPH and PAH . R and omised controlled trials are underway PATENT PLUS evaluated the safety and efficacy of riociguat in combination with sildenafil in pulmonary arterial hypertension patients . Patients receiving sildenafil ( 20 mg three times daily ) were r and omised to placebo or riociguat ( up to 2.5 mg three times daily ) for 12 weeks . The primary outcome was maximum change in supine systolic blood pressure ( SBP ) from baseline within 4 h of dosing . Secondary objectives comprised additional blood pressure , heart rate and exploratory efficacy variables , and safety .  Patients could enter a long-term extension ( LTE ) , where all patients received riociguat plus sildenafil . There was no difference in maximum change in supine SBP from baseline within 4 h between the riociguat ( n=12 ) ( mean±sd baseline : –20.2±15.3 mmHg ; week 12 : –20.7±18.0 mmHg ) and placebo groups ( n=6 ) ( –7.6±3.9 and –20.2±12.9 mmHg , respectively ) . Changes in st and ing SBP and supine or st and ing diastolic blood pressure were also not different . Combination therapy showed no favourable effects on exploratory clinical parameters , including haemodynamics and exercise capacity . In the LTE , there were high rates of discontinuation due to hypotension and three ( 18 % ) deaths ( not considered study drug-related by the investigator ) . There were potentially unfavourable safety signals  with sildenafil plus riociguat and no evidence of a positive benefit/risk ratio . Concomitant use of riociguat with phosphodiesterase-5 inhibitors is therefore contraindicated . Sildenafil+riociguat in PAH : no evidence of a positive benefit/risk ratio and potentially unfavourable safety signals We assessed the safety , tolerability and preliminary efficacy of riociguat , a soluble guanylate cyclase stimulator , in patients with pulmonary hypertension associated with interstitial lung disease ( PH-ILD ) . In this open-label , uncontrolled pilot trial , patients received oral riociguat  ( 1.0–2.5 mg three times daily ) for 12 weeks ( n=22 ) , followed by an ongoing long-term extension ( interim analysis at 12 months ) in those eligible ( n=15 ) . Primary end-points were safety and tolerability . Secondary end-points included haemodynamic changes and 6-min walk distance ( 6MWD ) . Overall , 104 adverse events were reported , of which 25 were serious ; eight of the latter were considered drug-related . After 12 weeks of therapy , mean cardiac output increased ( 4.4±1.5 L·min−1 to 5.5±1.8 L·min−1 ) , pulmonary vascular resistance ( PVR ) decreased ( 648±207 dyn·s−1·cm−5 to 528±181 dyn·s−1·cm−5 ) and mean pulmonary artery pressure ( mPAP ) remained unchanged compared with baseline . Arterial oxygen saturation decreased but mixed-venous oxygen saturation slightly increased . The 6MWD increased from 325±96 m at baseline to 351±111 m after 12 weeks . Riociguat was well tolerated by most patients and improved cardiac output and PVR , but not mPAP . Further studies are necessary to evaluate the safety and efficacy  of riociguat in patients with PH-ILD Riociguat ( BAY 63 - 2521 ) and war 
    Output:
    
sGC stimulators improve pulmonary artery pressures in people with PAH ( who are treatment naive or receiving a prostanoid or endothelin antagonist ) or those with recurrent or inoperable CTEPH .
In these setting s this can be achieved without notable complication .
However , sGC stimulators should not be taken by people also receiving phosphodiestase-V inhibitors or nitrates due to the risks of hypotension , and there is currently no evidence supporting their use in pulmonary hypertension associated with left heart disease .
There is no evidence supporting their use in children .