***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 — Cardiac resynchronization therapy ( CRT ) alone or combined with an implantable defibrillator ( CRT-D ) has been shown to improve exercise capacity and quality of life and to reduce heart failure ( HF ) hospitalizations and mortality in patients with New York Heart Association ( NYHA ) class III and IV HF . There is concern that the device procedure may destabilize these very ill class IV patients . We sought to examine the outcomes of NYHA class IV patients enrolled in the Comparison of Medical Therapy , Pacing , and Defibrillation in Heart Failure ( COMPANION ) trial to assess the potential benefits of CRT and CRT-D. Methods and Results — The COMPANION trial r and omized 1520 patients with NYHA class III and IV HF to optimal medical therapy , CRT , or CRT-D. In the class IV patients ( n=217 ) , the primary end point of time to death or hospitalization for any cause was significantly improved by both CRT ( hazard ratio [ HR ] , 0.64 ; 95 % CI , 0.43 to 0.94 ; P=0.02 ) and CRT-D ( HR , 0.62 ; 95 % CI , 0.42 to 0.90 ; P=0.01 ) . Time to all-cause death and HF hospitalization was also significantly improved in both CRT ( HR , 0.57 ; 95 % CI , 0.37 to 0.87 ; P=0.01 ) and CRT-D ( HR , 0.49 ; 95 % CI , 0.32 to 0.75 ; P=0.001 ) Time to all-cause death trended to an improvement in both CRT ( HR , 0.67 ; 95 % CI , 0.41 to 1.10 ; P=0.11 ) and CRT-D ( HR , 0.63 ; 95 % CI , 0.39 to 1.03 ; P=0.06 ) . Time to sudden death appeared to be significantly reduced in the CRT-D group ( HR , 0.27 ; 95 % CI , 0.08 to 0.90 ; P=0.03 ) . There was a nonsignificant reduction in time to HF deaths for both CRT ( HR , 0.68 ; 95 % CI , 0.34 to 1.37 ; P=0.28 ) and CRT-D ( HR , 0.79 ; 95 % CI , 0.41 to 1.52 ; P=0.48 ) . Conclusions — CRT and CRT-D significantly improve time to all-cause mortality and hospitalizations in NYHA class IV patients , with a trend for improved mortality . These devices should be considered in ambulatory NYHA class IV HF patients similar to those enrolled in COMPANION Background — The factors that determine the risk for sudden death or implantable cardioverter defibrillator therapy in patients receiving cardiac resynchronization therapy ( CRT ) therapies  are largely unknown . Methods and Results — We hypothesized that clinical measures of heart failure severity and the presence of comorbid conditions would predict the risk of malignant arrhythmias in the 1520 patients enrolled in the Comparison of Medical Therapy , Pacing , and Defibrillation in Heart Failure ( COMPANION ) Trial . Outcomes in the CRT group after implantable cardioverter defibrillator therapy were also evaluated . The CRT-defibrillator device reduced the risk of sudden death by 56 % compared with drug therapy ( 17 of 595 [ 2.9 % ] versus 18 of 308 [ 5.8 % ] , P<0.02 ) . CRT therapy was not associated with sudden death risk reduction ( 48 of 617 [ 7.8 % ] ) . Other factors associated with reduced sudden death risk were left ventricular ejection fraction > 20 % ( HR , 0.55 [ 95 % CI , 0.35 to 0.87 ] ; P=0.01 ) , QRS duration > 160 ms ( HR , 0.63 [ 95 % CI , 0.40 to 0.997 ] ; P=0.05 ) , and female gender ( HR , 0.56 [ 95 % CI , 0.34 to 0.94 ] ; P=0.003 ) . The risk for sudden death was increased by advanced New York Heart Association class IV heart failure ( HR , 2.62 [ 95 % CI , 1.61 to 4.26 ] ; P<0.011 ) and renal dysfunction ( HR , 1.69 [ 95 % CI , 1.06 to 2.69 ] ; P=0.03 ) . An appropriate shock was experienced in 88 ( 15 % ) of the 595 CTR-D patients . In the CRT-defibrillator patients , female gender ( HR , 0.54 [ 95 % CI , 0.31 to 0.94 ] ; P=0.03 ) and use of neurohormonal antagonists were associated with reduced risk . Class IV heart failure status increased risk . Appropriate implantable cardioverter defibrillator therapy was positively associated with risk of death or all-cause hospitalization ( HR , 1.57 ; P<0.002 ) , pump failure death or hospitalization ( HR , 2.35 ; P<0.001 ) , and sudden death ( HR , 2.99 ; P=0.03 ) , but not total mortality ( HR , 1.3 ; P=0.28 ) . Conclusions — In CRT c and i date s , sudden cardiac death risk is associated with higher New York Heart Association class and renal dysfunction . In CRT-defibrillator recipients , reduction in the risk of an appropriate shock is associated with medical therapy with neurohormonal antagonists , female gender , and New York Heart Association functional class III versus IV clinical status . Shock therapy was associated with worse outcome INTRODUCTION Biventricular cardiac pacemakers provide important hemodynamic benefit in selected patients with heart failure and severe left ventricular ( LV ) dysfunction . Nevertheless , these patients remain at high mortality risk . To address this issue , we examined mortality outcome in patients with heart failure treated with biventricular pacemakers alone and those treated with biventricular implantable cardioverter defibrillators ( ICDs ) .  METHODS AND RESULTS The study population consisted of 126 consecutive patients with LV dysfunction and heart failure who received either a biventricular ICD ( n = 62 ) or a biventricular pacemaker ( n = 64 ) between January 1998 and December 2002 . A minimum 12 months of follow-up was obtained in all survivors . ICD indications were conventional in all patients . Kaplan-Meier actuarial method and log rank statistics were used to calculate and compare survival rates in both groups . Comparison of mortality rates utilized Chi-square test . The two groups had similar clinical and demographic features , LV ejection fraction , and medication use . Average follow-up times were 13 + /- 11.8 months ( range 4 - 60 ) and 18 + /- 13.2 months ( range 0.5 - 53 ) for biventricular ICD and pacemaker groups , respectively . Overall mortality rate was significantly lower in the biventricular ICD group ( 13 % , 8 deaths ) compared to the pacemaker group ( 41 % , 26 deaths ) ( P = 0.01 ) . Further , the predominant survival benefit for ICD-treated patients becomes evident after the first 12 months of follow-up . CONCLUSION The findings in this study , although necessarily limited in their interpretation by the absence of treatment r and omization , suggest that biventricular ICDs offer a survival benefit compared to biventricular pacing alone . Furthermore , this benefit may be most apparent if other clinical factors do not preclude patient survival > 1 year postimplant This multicenter longitudinal observational trial was design ed to analyze the long-term outcome of patients with heart failure ( HF ) treated with cardiac resynchronization therapy ( CRT ) alone or with implantable cardioverter-defibrillator ( ICD ) backup  in a daily practice scenario . It is unknown whether the magnitude of survival benefits conferred by CRT in a daily practice scenario is comparable to what has been observed in r and omized controlled trials and whether this benefit is sustained over the long term . The outcome of 1,303 consecutive patients with ischemic or nonischemic cardiomyopathy on optimal pharmacologic therapy treated from August 1 , 1995 to August 1 , 2004 at 4 European centers with CRT alone ( 44 % ) or with ICD backup for symptomatic HF and prolonged QRS duration was assessed . Cumulative event-free survival was evaluated for a combined end point , defined as death from any cause , urgent transplantation , or implantation of a left ventricular assist device . The cumulative incidence of competing events , HF , sudden cardiac death , and noncardiac death , was also assessed . Event-free survival was similar across the different centers . At 1 and 5 years , cumulative event-free survivals were 92 % ( 95 % confidence interval [ CI ] 91 to 94 ) and 56 % ( 95 % CI 48 to 64 ) , respectively . The cumulative incidence of HF deaths was 25.1 % ( 95 % CI 19 to 31.7 ) , whereas that of sudden death was 9.5 % ( 95 % CI 5.1 to 15.7 ) . Using multivariate analysis , CRT with an ICD backup was associated with a nonsignificant decrease in mortality by 20 % ( hazard ratio 0.83 , 95 % CI 0.58 to 1.17 , p = 0.284 ) , with a highly significant protective effect against sudden cardiac death ( hazard ratio 0.04 , 95 % CI 0.04 to 0.28 , p < 0.002 ) . In conclusion , patients with advanced HF and a wide QRS complex routinely treated with CRT have a favorable long-term outcome that was reproducible at different centers . The leading cause of death in these patients remained HF , and this mode of death was competing with other causes in determining outcome . Total mortality was 20 % lower with ICD backup ( 95 % CI 42 % lower to 17 % higher ) due to a protective effect against sudden cardiac death OBJECTIVE To compare the rates of all-cause mortality in recipients of cardiac resynchronization therapy devices without ( CRT-PM ) versus with defibrillator ( CRT-D ) .  METHODS Between February 1999 and July 2004 , 233 patients ( mean age = 69 + /- 8 years , 180 men ) underwent implantation of CRT-PM or CRT-D devices .  New York Heart Association ( NYHA ) heart failure functional class II was present in 11 % , class III in 69 % , and class IV in 20 % of patients ; mean left ventricle ejection fraction ( LVEF ) was 26.5 + /- 6.5 % , 48 % presented with idiopathic dilated cardiomyopathy and 49 % with ischemic heart disease . Cox multiple variable regression analysis was performed in search of predictors of death . RESULTS The clinical characteristics of the 117 CRT-PM and 116 CRT-D recipients were similar , except for LVEF ( 28.2 + /- 6.2 % vs 25.0 + /- 6.5 % , respectively ; P < 0.001 ) , and ischemic versus nonischemic etiology of heart failure ( 41 % vs 56 % , respectively P = 0.02 ) . Over a mean follow-up of 58 + /- 15 months , no significance difference in overall mortality rate was observed between the two study groups . Male sex , NYHA functional class IV , and atrial fibrillation at implant were significant predictors of death . CONCLUSIONS There was no difference in long-term survival rate among patients with CRT-D versus CRT-PM  , although CRT-D more effectively lowered the sudden death rate . Male sex , NYHA functional class IV , and atrial fibrillation predicted the worst prognosis Background — In the Comparison of Medical Therapy , Pacing and Defibrillation in Heart Failure ( COMPANION ) trial , 1520 patients with advanced heart failure were assigned in a 1:2:2 ratio to optimal pharmacological therapy or optimal pharmacological therapy plus cardiac resynchronization therapy ( CRT-P ) or CRT with defibrillator ( CRT-D ) . Use of CRT-P and CRT-D was associated with a significant reduction in combined risk of death or all-cause hospitalizations . Because mortality also was significantly reduced ( optimal pharmacological therapy versus CRT-D only ) , an assessment of the true reduction in hospitalization rates must consider the competing risk of death and varying follow-up times . Methods and Results — To overcome the challenges of comparing treatment groups , we used a nonparametric test of right-censored recurrent events that accounts for multiple hospital admissions , differential follow-up time between treatment groups , and death as a competing risk . An end-point committee adjudicated and classified all hospitalizations . Compared with optimal pharmacological therapy , CRT-P and CRT-D were associated with a 21 % and 25 % reduction in all-cause , 34 % and 37 % reduction in cardiac , and 44 % and 41 % reduction in heart failure hospital admissions per patient-year of follow-up , respectively . Similar reductions were seen in hospitalization days per patient-year . The reduction in hospitalization rate for heart failure in the CRT groups appeared within days of r and omization and remained sustained . Noncardiac hospitalization rates were not 
    Output:
    
Evidence from current r and omised and non-r and omised trials demonstrates some superiorities of CRT-D over CRT , such as all-cause death rate after one-year follow-up and cardiac death , in patients with LV impairment .