***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 —No treatment strategies have been demonstrated to be beneficial for the population for patients with heart failure ( HF ) and preserved ejection fraction ( EF ) . Methods and Results —The CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients ( CHAMPION ) trial was a prospect i ve , single-blinded , r and omized controlled clinical trial testing the hypothesis that hemodynamically guided HF management decreases decompensation leading to hospitalization . Of the 550 patients enrolled in the study , 119 had left ventricular EF ≥40 % ( average , 50.6 % ) , 430 patients had low left ventricular EF ( < 40 % ; average , 23.3 % ) , and 1 patient had no documented left ventricular EF .  A microelectromechanical system pressure sensor was permanently implanted in all participants during right heart catheterization . After implant , subjects were r and omly assigned in single-blind fashion to a treatment group in whom daily uploaded pressures were used in a treatment strategy for HF management or to a control group in whom st and ard HF management included weight-monitoring , and pressures were uploaded but not available for investigator use . The primary efficacy end point of HF hospitalization rate > 6 months for preserved EF patients was 46 % lower in the treatment group compared with control ( incidence rate ratio , 0.54 ; 95 % confidence interval , 0.38–0.70 ; P<0.0001 ) . After an average of 17.6 months of blinded follow-up , the hospitalization rate was 50 % lower ( incidence rate ratio , 0.50 ; 95 % confidence interval , 0.35–0.70 ; P<0.0001 ) . In response to pulmonary artery pressure information , more changes in diuretic and vasodilator therapies were made in the treatment group . Conclusions —Hemodynamically guided management of patients with HF with preserved EF reduced decompensation leading to hospitalization compared with st and ard HF management strategies . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00531661 Background — Heart failure with preserved ejection fraction ( HFpEF ) is a heterogeneous syndrome associated with multiple pathophysiologic abnormalities , including left ventricular ( LV ) diastolic dysfunction , longitudinal LV systolic dysfunction , abnormal ventricular-arterial coupling , pulmonary hypertension , and right ventricular ( RV ) remodeling/dysfunction . However , the relative prognostic significance of each of these pathophysiologic abnormalities in HFpEF is unknown . Methods and Results — We prospect ively studied 419 patients with HFpEF using echocardiography and sphygmomanometry to assess HFpEF pathophysiologic markers . Cox proportional hazards analyses were used to determine the associations between pathophysiologic markers and outcomes . Mean age was 65±12 years ; 62 % were women ; 39 % were black ; comorbidities were common ; and study participants met published criteria for HFpEF .  RV abnormalities were frequent : 28 % had abnormal tricuspid annular plane systolic excursion , 15 % had reduced RV fractional area change , and 34 % had RV hypertrophy . During a median follow-up time of 18 months , 102 ( 24 % ) were hospitalized for HF and 175 ( 42 % ) experienced the composite end point of cardiovascular hospitalization or death . Decreased LV compliance , measured as reduced LV end-diastolic volume at an idealized LV end-diastolic pressure of 20 mm Hg ( EDV20 ) , and RV remodeling , as indicated by increased RV wall thickness , were the 2 pathophysiologic markers most predictive of worse outcomes : adjusted hazard ratio per 1 SD decrease in EDV20=1.39 ( 95 % confidence interval [ CI ] , 1.10–1.75 ; P=0.006 ) , and hazard ratio per 1 SD increase in RV wall thickness=1.37 ( 95 % CI , 1.16–1.61 ; P<0.001 ) . These associations persisted after additional adjustment for markers of HF severity . By contrast , markers of LV relaxation , longitudinal LV systolic dysfunction , and ventricular-arterial coupling were not significantly associated with adverse outcomes . Conclusions — In patients with HFpEF  , reduced LV compliance and RV remodeling are the strongest pathophysiologic predictors of adverse outcomes BACKGROUND Exercise intolerance is common in people with heart failure and preserved ejection fraction ( HFpEF ) . Right ventricular ( RV ) dysfunction has been shown at rest in HFpEF but little data are available regarding dynamic RV-pulmonary artery ( PA ) coupling during exercise . METHODS AND RESULTS Subjects with HFpEF ( n = 50 ) and controls ( n = 24 ) prospect ively underwent invasive cardiopulmonary exercise testing using high-fidelity micromanometer catheters along with simultaneous assessment of RV and left ventricular ( LV ) mechanics by echocardiography . Compared with controls at rest , subjects with HFpEF displayed preserved RV systolic and diastolic mechanics ( RV s ' and e ' ) , impaired LV s ' and e ' , higher biventricular filling pressures , and higher pulmonary artery pressures . On exercise , subjects with HFpEF displayed less increase in stroke volume , heart rate , and cardiac output ( CO ) , with blunted increase in CO relative to O2 consumption ( VO2 ) . Enhancement in RV systolic and diastolic function on exercise was impaired in HFpEF compared with controls . Exercise-induced PA vasodilation was reduced in HFpEF in correlation with greater venous hypoxia . Elevations in biventricular filling pressures and limitations in CO reserve were strongly correlated with abnormal enhancement in ventricular mechanics in the RV and LV during stress . CONCLUSIONS In addition to limited LV reserve , patients with HFpEF display impaired RV reserve during exercise that is associated with high filling pressures and inadequate CO responses . These findings highlight the importance of biventricular dysfunction in HFpEF and suggest that novel therapies targeting myocardial reserve in both the left and right heart may be effective to improve clinical status Background — Heart failure with preserved ejection fraction ( HFpEF ) is associated with substantial morbidity and mortality . Existing data on cardiac structure and function in HFpEF suggest significant heterogeneity in this population . Methods and Results — Echocardiograms were obtained from 935 patients with HFpEF ( left ventricular ejection fraction ≥45 % ) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist ( TOPCAT ) trial before initiation of r and omized therapy . Average age was 70±10 years , 49 % were women , 14 % were of African descent , and comorbidities were highly prevalent . Central ized quantitative analysis in a blinded core laboratory demonstrated a mean left ventricular ejection fraction of 59.3±7.9 % , with prevalent concentric left ventricular remodeling ( 34 % ) and hypertrophy ( 43 % ) , and left atrial enlargement ( 53 % ) . Diastolic dysfunction was present in 66 % of gradable participants and was significantly associated with greater left ventricular hypertrophy and a higher prevalence of left atrial enlargement . Doppler evidence of pulmonary hypertension was present in 36 % . At least 1 measure of structural heart disease was present in 93 % of patients . Conclusions — Patients enrolled in TOPCAT demonstrated heterogeneous patterns of ventricular remodeling , with high prevalence of structural heart disease , including left ventricular hypertrophy and left atrial enlargement , in addition to pulmonary hypertension , each of which has been associated with adverse outcomes in HFpEF . Diastolic function was normal in approximately one third of gradable participants , highlighting the heterogeneity of the cardiac phenotype in this syndrome . These findings deepen our underst and ing of the TOPCAT trial population and exp and our knowledge of the diversity of the cardiac phenotype in HFpEF . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00094302 Background — The prevalence of heart failure with preserved ejection fraction is increasing . The prognosis worsens with pulmonary hypertension and right ventricular ( RV ) failure development . We targeted pulmonary hypertension and RV burden with the phosphodiesterase-5 inhibitor sildenafil . Methods and Results — Forty-four patients with heart failure with preserved ejection fraction ( heart failure signs and symptoms , diastolic dysfunction , ejection fraction ≥50 % , and pulmonary artery systolic pressure > 40 mm Hg ) were r and omly assigned to placebo or sildenafil  ( 50 mg thrice per day ) . At 6 months , there was no improvement with placebo , but sildenafil mediated significant improvements in mean pulmonary artery pressure ( −42.0±13.0 % ) and RV function , as suggested by leftward shift of the RV Frank-Starling relationship , increased tricuspid annular systolic excursion ( + 69.0±19.0 % ) and ejection rate ( + 17.0±8.3 % ) , and reduced right atrial pressure ( −54.0±7.2 % ) . These effects may have result ed from changes within the lung ( reduced lung water content and improved alveolar-capillary gas conductance , + 15.8±4.5 % ) , the pulmonary vasculature ( arteriolar resistance , −71.0±8.2 % ) , and left-sided cardiac function ( wedge pulmonary pressure , −15.7±3.1 % ; cardiac index , + 6.0±0.9 % ; deceleration time , −13.0±1.9 % ; isovolumic relaxation time , −14.0±1.7 % ; septal mitral annulus velocity , −76.4±9.2 % ) . Results were similar at 12 months . Conclusions — The multifaceted response to phosphodiesterase-5 inhibition in heart failure with preserved ejection fraction includes improvement in pulmonary pressure and vasomotility , RV function and dimension , left ventricular relaxation and distensibility ( structural changes and /or ventricular interdependence ) , and lung interstitial water metabolism ( wedge pulmonary pressure decrease improving hydrostatic balance and right atrial pressure reduction facilitating lung lymphatic drainage ) . These results enhance our underst and ing of heart failure with preserved ejection fraction and offer new directions for therapy . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01156636 Background —Right ventricular ( RV ) dysfunction ( RVD ) is a poor prognostic factor in heart failure with preserved ejection fraction ( HFpEF ) . The physiological perturbations associated with RVD or RV function indexed to load ( RV – pulmonary arterial [ PA ] coupling ) in HFpEF have not been defined . HFpEF patients with marked impairment in RV – PA coupling may be uniquely sensitive to sildenafil . Methods and Results —In a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure ( RELAX ) trial , physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD ( tricuspid annular plane systolic excursion [ TAPSE ] ) and according to impairment in RV – PA coupling ( TAPSE/pulmonary artery systolic pressure ) ratio . The prevalence of atrial fibrillation and diuretic use , n-terminal probrain natriuretic peptide levels , renal dysfunction , neurohumoral activation , myocardial necrosis and fibrosis biomarkers , and the severity of diastolic dysfunction all increased with severity of RVD . Peak oxygen consumption decreased and ventilatory inefficiency ( VE/VCO2 slope ) increased with increasing severity of RVD . Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio . Compared with placebo , at 24 weeks , TAPSE decreased , and peak oxygen consumption and VE/CO2 slope were unchanged with sildenafil . There was no interaction between RV – PA coupling and treatment effect , and sildenafil did not improve TAPSE , peak oxygen consumption , or VE/VCO2 in patients with pulmonary hypertension and RVD . Conclusions —HFpEF patients with RVD and impaired RV – PA coupling have more advanced heart failure . In RELAX patients with RVD and impaired RV – PA coupling , sildenafil did not improve RV function , exercise capacity , or ventilatory efficiency . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00763867 PURPOSE Pulmonary hypertension ( PHT ) is a predictor of mortality and morbidity in patients with chronic heart failure ( HF ) . However , the prevalence , determinants , and prognostic significance of PHT in elderly patients admitted with acute decompensated HF are unclear . METHODS We prospect ively evaluated 401 patients aged ≥ 75 years ( mean age 83 ± 5 years , 50 % women 
    Output:
    
RV dysfunction and PH are highly prevalent and are both associated with poor outcome in patients with HFpEF