***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 — A treatment gap exists between heart failure ( HF ) guidelines and the clinical care of patients . The Registry to Improve the Use of Evidence -Based Heart Failure Therapies in the Outpatient Setting ( IMPROVE HF ) prospect ively tested a multidimensional practice -specific performance improvement intervention on the use of guideline -recommended therapies for HF in outpatient cardiology practice s. Methods and Results — Performance data were collected in a r and om sample of HF patients from 167 US outpatient cardiology practice s at baseline , longitudinally after intervention at 12 and 24 months , and in single-point-in-time patient cohorts at 6 and 18 months . Participants included 34 810 patients with reduced left ventricular ejection fraction ( ≤35 % ) and chronic HF or previous myocardial infa rct ion . To quantify guideline adherence , 7 quality measures were assessed . Interventions included clinical decision support tools , structured improvement strategies , and chart audits with feedback . The performance improvement intervention result ed in significant improvements in 5 of 7 quality measures at the 24-month assessment compared with baseline : & bgr;-blocker ( 92.2 % versus 86.0 % , + 6.2 % ) , aldosterone antagonist ( 60.3 % versus 34.5 % , + 25.1 % ) , cardiac resynchronization therapy ( 66.3 % versus 37.2 % , + 29.9 % ) , implantable cardioverter-defibrillator ( 77.5 % versus 50.1 % , + 27.4 % ) , and HF education ( 72.1 % versus 59.5 % , + 12.6 % ) ( each P<0.001 ) . There were no statistically significant improvements in angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use or anticoagulation for atrial fibrillation . Sensitivity analyses at the patient level and limited to patients with both baseline and 24-month quality measure data yielded similar results . Improvements in the single-point-in-time cohorts were smaller , and there were no concurrent control practice s. Conclusions — The Registry to Improve the Use of Evidence -Based Heart Failure Therapies in the Outpatient Setting , a defined and scalable practice -specific performance improvement intervention , was associated with substantial improvements in the use of guideline -recommended therapies in eligible patients with HF in outpatient cardiology practice s. Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00303979 BACKGROUND Patients with heart failure ( HF ) are at high risk for mortality and rehospitalization in the early period after hospital discharge . We developed clinical models predictive of short-term clinical outcomes in a broad patient population discharged after hospitalization for HF . METHODS The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure ( OPTIMIZE-HF ) registry is a comprehensive hospital-based registry and performance-improvement program for patients hospitalized with HF . Follow-up data were scheduled to be prospect ively collected at 60 to 90 days postdischarge in a prespecified 10 % sample . For the 4,402 patients included in this analysis , 19 prespecified potential predictor variables were used in a stepwise Cox proportional hazards model for all-cause mortality . Logistic regression including 45 potential variables was used to model mortality or rehospitalization . RESULTS The 60- to 90-day postdischarge mortality rate was 8.6 % ( n = 481 ) , and 29.6 % ( n = 1,715 ) were rehospitalized . Factors predicting early postdischarge mortality include age , serum creatinine , reactive airway disease , liver disease , lower systolic blood pressure , lower serum sodium , lower admission weight , and depression . Use of statins and beta-blockers at discharge was associated with significantly decreased mortality . The C-index of the model was 0.74 . The most important predictors for the combined end point of death or rehospitalization were admission serum creatinine , systolic blood pressure , admission hemoglobin , discharge use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker , and pulmonary disease . From this analysis , 8 factors identified to carry significant risk were selected for use in a point scoring system to predict the risk of mortality within 60 days after discharge , with a C-index of 0.72 . CONCLUSIONS A substantial risk of mortality and mortality or rehospitalization is present in the first 60 to 90 days after discharge from a hospitalization for HF . Several factors were identified that signal high-risk patients . Application of these findings with a simple algorithm can distinguish patients who are low risk from those at high risk who may benefit from closer monitoring and aggressive evidence -based treatment OBJECTIVES We wished to examine the effects of age and gender on plasma brain natriuretic peptide ( BNP ) concentration in a population -based study . BACKGROUND Measurement of BNP concentration is approved for use in the diagnosis of heart failure and may aid in the detection of left ventricular dysfunction . Although BNP is approved for clinical use , there are few data regarding the range of BNP observed in persons without cardiovascular disease or cardiac dysfunction . These data are essential for the interpretation of BNP . METHODS In 2,042 r and omly selected residents of Olmsted County , Minnesota , > 44 years old , BNP ( Shionogi and Biosite assays ) , Doppler echocardiography , and medical record review were performed . A normal subset of subjects ( n = 767 ) in sinus rhythm without cardiovascular , renal , or pulmonary disease or diabetes ; on no cardiovascular medications ; and with normal systolic , diastolic , and valvular function was identified . RESULTS Within the normal subset , the distribution of BNP differed by age , gender , and assay system . With both assays , BNP increased significantly with age and was significantly higher in women than men , leading to age- , gender- , and assay-specific reference ranges . Receiver operating characteristic analysis for the ability of BNP to detect an ejection fraction < or = 40 % was performed in each age/gender stratum in the entire cohort ( n = 2,042 ) and confirmed that discriminatory values for BNP for detection of reduced ejection fraction were higher in women and older persons and were different between the two assays . CONCLUSIONS Interpretation of BNP should include consideration of age- , gender- , and assay-specific partition values AIMS To assess physicians ' adherence to guideline -recommended medications for the treatment of chronic heart failure ( CHF ) with reduced ejection fraction . METHODS AND RESULTS QUALIFY is an international prospect i ve observational longitudinal survey of 7092 CHF out patients recruited 1 - 15 months after hospitalization for heart failure from September 2013 to December 2014 in 547 centres in 36 countries . We constructed a five-class guideline adherence score for angiotensin converting enzyme inhibitors ( ACEIs ) , beta-blockers , angiotensin receptor blockers ( ARBs ) , mineralocorticoid receptor antagonists , and ivabradine . The adherence score was good in 67 % , moderate in 25 % , and poor in 8 % of patients . Adherence was lower in women than men but there were differences in age ( 65.7 ± 12.5 years women vs. 62.2 ± 12.4 years men , P < 0.001 ) and the proportion of women at ≥50 % target dose of beta-blockers was lower in those > 67 years ( median ) ( 11 % vs. 16.2 % , P = 0.005 ) . Geographic variations were observed with lower adherence scores in Central /Eastern European countries . The proportion of patients at target dose and ≥50 % of target dose was low ( 27.9 % and 63.3 % for ACEIs , 14.8 % and 51.8 % for beta-blockers , 6.9 % and 39.5 % for ARBs , and 6.9 % and 39.5 % for ivabradine , respectively ) . It was also lower in patients most recently hospitalized ( < 6 vs. ≥6 months ) except for beta-blockers . CONCLUSION This international survey shows that adherence to guideline -recommended medications is relatively satisfactory but the dosage of recommended CHF medications is usually suboptimal . Action plans aim ed at improving adherence to guidelines are required Background : To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial ( Prospect i ve Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF ) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality . Methods and Results : We report key demographic , clinical , and laboratory findings , and baseline therapies , of 4822 patients r and omized in PARAGON-HF , grouped by factors that influence criteria for study inclusion . We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction ( HFpEF ) . Among patients enrolled from various regions ( 16 % Asia-Pacific , 37 % Central Europe , 7 % Latin America , 12 % North America , 28 % Western Europe ) , the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years , 52 % of patients were female , and mean left ventricular ejection fraction was 57.5 % , similar to other trials of HFpEF . Most patients were in New York Heart Association class II , and 38 % had ≥1 hospitalizations for heart failure within the previous 9 months . Diabetes mellitus ( 43 % ) and chronic kidney disease ( 47 % ) were more prevalent than in previous trials of HFpEF . Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers ( 85 % ) , & bgr;-blockers ( 80 % ) , calcium channel blockers ( 36 % ) , and mineralocorticoid receptor antagonists ( 24 % ) . As specified in the protocol , virtually all patients were on diuretics , had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide ( median , 911 pg/mL ; interquartile range , 464–1610 ) , and structural heart disease . Conclusions : PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities . These findings provide insights into the impact of inclusion criteria on , and regional variation in , HFpEF patient characteristics . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT01920711 AIMS The impact of frailty on outcomes in r and omized heart failure with preserved ejection fraction ( HFpEF ) trials has not been previously reported . This analysis sought to characterize frailty in a large contemporary HFpEF clinical trial cohort and to evaluate its impact on patient relevant outcomes . METHODS AND RESULTS Using data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist ( TOPCAT ) trial , a frailty index ( FI ) was constructed at baseline using 39 clinical , laboratory , and self-reported variables . The relationship between frailty and outcomes and the role of frailty in modulating the benefits of spironolactone were examined in a subset of 1767 TOPCAT patients . For the cohort as a whole ( mean age 71.5 years , 49 % female ) , the mean FI at baseline was 0.37 ± 0.11 . Four frailty classes were defined ranging from FI < 0.3 to FI ≥ 0.5 . Overall , 94 % of subjects were considered frail ( defined as a FI > 0.21 ) . Mean age was lowest for the most frail class ( 69 ± 9 years for Class 4 ; 73 ± 10 years for Class 1 ; P < 0.001 ) . Body mass index , systolic blood pressure , and pulse pressure all increased as FI increased . Both primary and secondary outcomes increased as frailty severity increased . There was no interaction between frailty class and treatment effect of spironolactone . CONCLUSIONS Frailty was very common in TOPCAT HFpEF participants . Greater frailty was associated with a higher risk of cardiovascular outcomes and mortality . The benefit of spironolactone on outcomes in TOPCAT was not attenuated by frailty class 
    Output:
    
Many HF trials do not report baseline comorbidities .