***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 
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    ***EXAMPLES*** 
    Input: BACKGROUND The effect of treatment with β-blockers on the prognosis of patients newly diagnosed with heart failure with preserved ejection fraction ( HFpEF ) is unknown . OBJECTIVE To analyze the relationship of commencing treatment with the β-blockers bisoprolol or carvedilol ( CT-βB ) with the prognosis of newly diagnosed HFpEF . METHODS Prospect i ve study over 10years on 2704 patients with HFpEF . Main outcomes were mortality ( all-cause and cardiovascular ) , hospitalizations for HF worsening , and visits . The independent relationship between CT-βB and the prognosis , stratifying patients for cardiovascular co-morbidity after propensity score-matching ( 985 patients CT-βB vs. another 985 patients non-CT-βB ) , was analyzed . RESULTS During a median follow-up of 1877.4days ( interquartile range , 1 - 3651.2 ) 1600 died ( 81.2 % ) , and 1702 were hospitalized ( 86.4 % ) . CT-βB was associated with a lower risk of mortality ( all-cause : HR [ CI 95 % ] 0.78 [ 0.71 to 0.85 ] , and cardiovascular : 0.75 [ 0.69 to 0.82 ] ) , a lower hospitalization rate ( per 100 persons-year ) , 15.8 vs. 19.2 , and a lower 30-day readmission rate ( per 100 persons-year ) , 4.0 vs. 5.8 , ( P<0.001 in all cases ) , even after adjustment for the propensity to take β-blockers or other medications , comorbidities , and other potential confounders . These effects of CT-βB were independent of gender , and were observed in both patients taking high dose βB ( over the median dose ) and lower dose βB ( under or equal to the median dose ) . CONCLUSIONS In this propensity matched study , commencing treatment with bisoprolol or carvedilol , both at high and at lower doses , is associated with an improved prognosis of patients newly diagnosed with HFpEF Fifteen elderly patients with normal left ventricular ( LV ) systolic function and New York Heart Association functional class II-III were studied . The effect of verapamil on LV diastolic function was assessed by congestive heart failure ( CHF ) score , treadmill exercise test , and Doppler echocardiography at baseline , and after each three-month treatment period ( placebo or verapamil 120 mg once daily ) , separated by a one-week washout period before crossover . Blood pressure , heart rate , LV ejection fraction , LV mass , and cardiac output were unaltered by placebo or verapamil . Verapamil treatment significantly improved CHF score at 3 months ( 3.5 + /- 0.5 , p<0.05 ) compared with baseline ( 5.6 + /- 0.5 ) or placebo ( 5.5 + /- 0.5 ) . The exercise time was similar at baseline ( 7.4 + /- 1.2 min ) and after placebo ( 7.4 + /- 1.3 min ) treatment but significantly ( p<0.05 ) increased after verapamil ( 8.3 + /- 1.2 min ) treatment . The ratio of mitral A wave duration /pulmonary venous atrial systolic reversal duration increased after verapamil ( 1.11 + /- 0.08 ) treatment compared with placebo ( 0.91 + /- 0.07 , p<0.05 ) and baseline ( 0.89 + /- 0.08 ) which had similar duration s. The isovolumic relaxation time was significantly ( p<0.05 ) decreased from 84 + /- 12 ms at baseline and 86 + /- 13 ms with placebo to 73 + /- 9 ms with verapamil . The results of this study suggest that in elderly patients with Doppler evidence of diastolic dysfunction as the cause of CHF , three months treatment with verapamil can improve CHF , increase exercise tolerance and improve LV diastolic function Background — Heart failure ( HF ) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction ( PEF [ ≥50 % ] or REF [ < 50 % ] ) . In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , 42 418 high-risk hypertensive patients were r and omized to chlorthalidone , amlodipine , lisinopril , or doxazosin , providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF . Methods and Results — HF diagnostic criteria were prespecified in the ALLHAT protocol . EF estimated by contrast ventriculography , echocardiography , or radionuclide study was available in 910 of 1367 patients ( 66.6 % ) with hospitalized events meeting ALLHAT criteria . Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF ( overall and by PEF and REF ) . HF case fatality rates were examined . Of those with EF data , 44.4 % had HFPEF and 55.6 % had HFREF . Chlorthalidone reduced the risk of HFPEF compared with amlodipine , lisinopril , or doxazosin ; the hazard ratios were 0.69 ( 95 % confidence interval [ CI ] , 0.53 to 0.91 ; P=0.009 ) , 0.74 ( 95 % CI , 0.56 to 0.97 ; P=0.032 ) , and 0.53 ( 95 % CI , 0.38 to 0.73 ; P<0.001 ) , respectively . Chlorthalidone  reduced the risk of HFREF compared with amlodipine or doxazosin ; the hazard ratios were 0.74 ( 95 % CI , 0.59 to 0.94 ; P=0.013 ) and 0.61 ( 95 % CI , 0.47 to 0.79 ; P<0.001 ) , respectively . Chlorthalidone was similar to lisinopril with regard to incidence of HFREF ( hazard ratio , 1.07 ; 95 % CI , 0.82 to 1.40 ; P=0.596 ) . After HF onset , death occurred in 29.2 % of participants ( chlorthalidone/amlodipine/lisinopril ) with new-onset HFPEF versus 41.9 % in those with HFREF ( P<0.001 ; median follow-up , 1.74 years ) ; and in the chlorthalidone/doxazosin comparison that was terminated early , 20.0 % of HFPEF and 26.0 % of HFREF patients died ( P=0.185 ; median follow-up , 1.55 years ) . Conclusions — In ALLHAT , with adjudicated outcomes , chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin . Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril . Among high-risk hypertensive men and women , HFPEF has a better prognosis than HFREF Background — Patients with heart failure are at increased risk of sudden death and death attributed to progressive pump failure . We assessed the effect of c and esartan on cause-specific mortality in patients enrolled in the C and esartan in Heart failure Assessment of Reduction in Mortality and morbidity ( CHARM ) program . Methods and Results —The CHARM program consisted of 3 component trials that enrolled patients with symptomatic heart failure : CHARM-Alternative ( n=2028 ; LVEF=40 % and ACE intolerant ) , CHARM-Added ( n=2548 ; LVEF=40 % , already on ACE inhibitors ) , and CHARM-Preserved ( n=3023 ; LVEF > 40 % ) . Patients were r and omized to c and esartan , titrated to 32 mg QD , or placebo and were followed up for a median of 37.7 months . All deaths were review ed by a blinded adjudication committee and categorized according to prespecified definitions on the basis of a narrative and source documentation . The number and rate of deaths by cause were calculated for each of the component trials and the overall program . Of all the patients , 8.5 % died suddenly , and 6.2 % died of progressive heart failure .  C and esartan reduced both sudden death ( HR 0.85 [ 0.73 to 0.99 ] , P=0.036 ) and death from worsening heart failure ( HR 0.78 [ 0.65 to 0.94 ] , P=0.008 ) . These reductions were most apparent in the patients with LVEF=40 % . Conclusions —C and esartan reduced sudden death and death from worsening heart failure in patients with symptomatic heart failure , although this reduction was most apparent in patients with systolic dysfunction AIMS To determine the effects of digoxin on all-cause mortality and heart failure ( HF ) hospitalizations , regardless of ejection fraction , accounting for serum digoxin concentration ( SDC ) . METHODS AND RESULTS This comprehensive post-hoc analysis of the r and omized controlled Digitalis Investigation Group trial ( n=7788 ) focuses on 5548 patients : 1687 with SDC , drawn r and omly at 1 month , and 3861 placebo patients , alive at 1 month . Overall , 33 % died and 31 % had HF hospitalizations during a 40-month median follow-up . Compared with placebo , SDC 0.5 - 0.9 ng/mL was associated with lower mortality [ 29 vs. 33 % placebo ; adjusted hazard ratio ( AHR ) , 0.77 ; 95 % confidence interval ( CI ) , 0.67 - 0.89 ] , all-cause hospitalizations ( 64 vs. 67 % placebo ; AHR , 0.85 ; 95 % CI , 0.78 - 0.92 ) and HF hospitalizations ( 23 vs. 33 % placebo ; AHR , 0.62 ; 95 % CI , 0.54 - 0.72 ) . SDC > or = 1.0 ng/mL was associated with lower HF hospitalizations ( 29 vs. 33 % placebo ; AHR , 0.68 ; 95 % CI , 0.59 - 0.79 ) , without any effect on mortality . SDC 0.5 - 0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction > 45 % ( P=0.834 ) or sex ( P=0.917 ) . CONCLUSIONS Digoxin at SDC 0.5 - 0.9 ng/mL reduces mortality and hospitalizations in all HF patients , including those with preserved systolic function . At higher SDC , digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations Background —Exercise intolerance is the primary symptom in older patients with heart failure and preserved ejection fraction ( HFPEF ) ; however , little is known regarding its mechanisms and therapy . Methods and Results —Seventy-one stable elderly ( 70±1 years ) patients ( 80 % women ) with compensated HFPEF and controlled blood pressure were r and omized into a 12-month follow-up double-blind trial of enalapril 20 mg/d versus placebo . Assessment s were peak exercise oxygen consumption ; 6-minute walk test ; Minnesota Living with HF Question naire ; MRI ; Doppler echocardiography ; and vascular ultrasound . Compliance by pill count was excellent ( 94 % ) . Twenty-five patients in the enalapril group versus 34 in the placebo group completed the 12-month follow-up . During follow-up , there was no difference in the primary outcome of peak exercise oxygen consumption  ( enalapril , 14.5±3.2 mL/kg/min ; placebo , 14.3±3.4 mL/kg/min ; P=0.99 ) , or in 6-minute walk distance , aortic distensibility ( the primary mechanistic outcome ) , left ventricle mass , or neurohormonal profile . The effect size of enalapril  on peak exercise oxygen consumption was small ( 0.7 % ; 95 % CI , 4.2 % to 5.6 % ) . There was a trend toward improved Minnesota Living with HF Question naire total score ( P=0.07 ) , a modest reduction in systolic blood pressure at peak exercise ( P=0.02 ) , and a marginal improvement in carotid arterial distensibility ( P=0.04 ) . Conclusions —In stable , older patients with compensated HFPEF and controlled blood pressure , 12 months of enalapril did not improve exercise capacity or aortic distensibility . These data , combined with those from large clinical event trials , suggest that angiotensin inhibition does not substantially improve key long-term clinical outcomes in this group of patients . This finding contrasts sharply with observations in HF with reduced EF and highlights our incomplete underst and ing of this important and common disorder Background —The Minnesota Living with Heart Failure Question naire ( MLHFQ ) was used in a large 
    Output:
    
There was no effect seen with ACE inhibitors , aldosterone receptor blockers , mineralocorticoid receptor antagonists and other drug classes , compared with placebo .
Similar results were observed for cardiovascular mortality .
No single drug class reduced heart failure hospitalisation compared with placebo .
Conclusion The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40 % differ depending on the type of therapy , with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality .