***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 — Heart failure has an annual mortality rate ranging from 5 % to 75 % . The purpose of the study was to develop and vali date a multivariate risk model to predict 1- , 2- , and 3-year survival in heart failure patients with the use of easily obtainable characteristics relating to clinical status , therapy ( pharmacological as well as devices ) , and laboratory parameters . Methods and Results — The Seattle Heart Failure Model was derived in a cohort of 1125 heart failure patients with the use of a multivariate Cox model . For medications and devices not available in the derivation data base , hazard ratios were estimated from published literature . The model was prospect ively vali date d in 5 additional cohorts totaling 9942 heart failure patients and 17 307 person-years of follow-up . The accuracy of the model was excellent , with predicted versus actual 1-year survival rates of 73.4 % versus 74.3 % in the derivation cohort and 90.5 % versus 88.5 % , 86.5 % versus 86.5 % , 83.8 % versus 83.3 % , 90.9 % versus 91.0 % , and 89.6 % versus 86.7 % in the 5 validation cohorts . For the lowest score , the 2-year survival was 92.8 % compared with 88.7 % , 77.8 % , 58.1 % , 29.5 % , and 10.8 % for scores of 0 , 1 , 2 , 3 , and 4 , respectively . The overall receiver operating characteristic area under the curve was 0.729 ( 95 % CI , 0.714 to 0.744 ) . The model also allowed estimation of the benefit of adding medications or devices to an individual patient 's therapeutic regimen . Conclusions — The Seattle Heart Failure Model provides an accurate estimate of 1- , 2- , and 3-year survival with the use of easily obtained clinical , pharmacological , device , and laboratory characteristics Background — An increase in troponin I soon after high-dose chemotherapy ( HDC ) is a strong predictor of poor cardiological outcome in cancer patients . This finding has important clinical implication s and provides a rationale for the development of prophylactic strategies for preventing cardiotoxicity . Angiotensin-converting enzyme inhibitors slow the progression of left ventricular dysfunction in different clinical setting s , but their role in the prevention of cardiotoxicity has never been investigated . Methods and Results — Of the 473 cancer patients evaluated , 114 ( 72 women ; mean age , 45±12 years ) who showed a troponin I increase soon after HDC were r and omized to receive ( angiotensin-converting enzyme inhibitor group ; 20 mg/d ; n=56 ) or not to receive ( control subjects ; n=58 ) enalapril . Treatment was started 1 month after HDC and continued for 1 year . Cardiological evaluation was performed at baseline and at 1 , 3 , 6 , and 12 months after HDC . The primary end point was an absolute decrease > 10 percent units in left ventricular ejection fraction , with a decline below the normal limit value . A significant reduction in left ventricular ejection fraction and an increase in end-diastolic and end-systolic volumes were observed only in untreated patients . According to the Kaplan-Meier analysis , the incidence of the primary end point was significantly higher in control subjects than in the angiotensin-converting enzyme inhibitor group ( 43 % versus 0 % ; P<0.001 ) . Conclusions — In high-risk , HDC-treated patients , defined by an increased troponin I value , early treatment with enalapril seems to prevent the development of late cardiotoxicity PURPOSE We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant ( HERA ) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy . PATIENTS AND METHODS The HERA trial is a three-group , r and omized trial that compared 1 year or 2 years of trastuzumab with observation in women with human epidermal growth factor receptor-2 ( HER2 ) -positive early breast cancer . Eligible patients had normal left ventricular ejection fraction ( LVEF ; > or= 55 % ) after completion of (neo)adjuvant chemotherapy with or without radiotherapy .  Cardiac function was monitored throughout the trial . This analysis considers patients r and omly assigned to 1 year of trastuzumab treatment or observation . RESULTS There were 1,698 patients r and omly assigned to observation and 1,703 r and omly assigned to 1 year of trastuzumab treatment ; 94.1 % of patients had been treated with anthracyclines . The incidence of discontinuation of trastuzumab because of cardiac disorders was low ( 5.1 % ) . At a median follow-up of 3.6 years , the incidence of cardiac end points remained low , though it was higher in the trastuzumab group than in the observation group ( severe CHF , 0.8 % v 0.0 % ; confirmed significant LVEF decreases , 3.6 % v 0.6 % ) In the trastuzumab group , 59 of 73 patients with a cardiac end point reached acute recovery ; of these 59 patients , 52 were considered by the cardiac advisory board ( CAB ) to have a favorable outcome from the cardiac end point . CONCLUSION The incidence of cardiac end points remains low even after longer-term follow-up . The cumulative incidence of any type of cardiac end point increases during the scheduled treatment period of 1 year , but it remains relatively constant thereafter BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . PURPOSE The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy .  PATIENTS AND METHODS The Herceptin Adjuvant ( HERA ) trial is a three-group , multicenter , open-label r and omized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer . Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction ( LVEF > or = 55 % ) were eligible . A repeat LVEF assessment was performed in case of cardiac dysfunction . RESULTS Data were available for 1,693 patients r and omly assigned to 1 year trastuzumab and 1,693 patients r and omly assigned to observation . The incidence of  trastuzumab discontinuation due to cardiac disorders was low ( 4.3 % ) . The incidence of cardiac end points was higher in the trastuzumab group compared with observation ( severe congestive heart failure [ CHF ] , 0.60 % v 0.00 % ; symptomatic CHF , 2.15 % v 0.12 % ; confirmed significant LVEF drops , 3.04 % v 0.53 % ) . Most patients with cardiac dysfunction recovered in fewer than 6 months . Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin ( 287 mg/m(2 ) v 257 mg/m(2 ) ) or epirubicin ( 480 mg/m(2 ) v 422 mg/m(2 ) ) and had a lower screening LVEF and a higher body mass index . CONCLUSION Given the clear benefit in disease-free survival , the low incidence of cardiac adverse events , and the suggestion that cardiac dysfunction might be reversible , adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy .  RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation .  We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P<0.0001 by the log-rank test , crossing the interim analysis boundary ) , representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points . Overall survival in the two groups was not significantly different ( 29 deaths with trastuzumab vs. 37 with observation ) . Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab . CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer . ( Clinical Trials.gov number , NCT00045032 . OBJECTIVES The aim of this study was to determine the protective effect of carvedilol in anthracycline (ANT)-induced cardiomyopathy ( CMP ) . BACKGROUND Despite its broad effectiveness , ANT therapy is associated with ANT-induced CMP . Recent animal studies and experimental observations showed that carvedilol prevented development of CMP due to chemotherapeutics . However , there is no placebo-controlled clinical trial concerning prophylactic carvedilol use in preventing ANT-induced CMP . METHODS Patients in whom ANT therapy was planned were r and omized to administration of carvedilol or placebo .  We enrolled 25 patients in carvedilol and control groups . In the carvedilol group , 12.5 mg once-daily oral carvedilol was given during 6 months . The patients were evaluated with echocardiography before and after chemotherapy .  Left ventricular ejection fraction ( EF ) and systolic and diastolic diameters were calculated . RESULTS At the end of 6 months of follow-up , 1 patient in the carvedilol group and 4 in the control group had died . Control EF was below 50 % in 1 patient in the carvedilol group and in 5 in the control group . The mean EF of the carvedilol group was similar at baseline and control echocardiography ( 70.5 vs. 69.7 , respectively ; p = 0.3 ) , but in the control group the mean EF at control ech 
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By following these recommendations the incidence of heart failure is reduced to approximately five per cent of treated patients .
CONCLUSION In summary , the favourable effects of trastuzumab are convincing , but cardiotoxicity is a significant challenge in treatment .