***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 —Chemotherapy with trastuzumab and anthracycline is associated with incident heart failure ( HF ) in patients with breast cancer . We hypothesized that continuous incidental use of & bgr;-blocker agents ( BB ) was protective against HF in patients without established structural heart disease who were receiving trastuzumab and anthracycline .  Methods and Results —We identified 920 consecutive patients with breast cancer ( age 52.3±11.0 years ) with normal ejection fraction before receiving trastuzumab and anthracycline therapy at our institution between 2005 and 2010 . Using a propensity score and a greedy 5 to 1 digit-matching algorithm , 106 of these patients on continuous BB during cancer treatment were matched with 212 patients from the same pool with similar characteristics but not on continuous BB . During a median follow-up of 3.2±2.0 years , 32 incident HF admissions were identified in these 318 patients with breast cancer , whereas 28 cancer-related ( noncardiac ) deaths occurred before any incident HF . Cumulative incidence regression models and cause-specific hazards of new HF events were estimated from competing risk Cox models of time-dependent covariates . Although trastuzumab therapy showed significant association with incident HF , independent of anthracycline-related cardiotoxicity ( hazard ratio , 9.0 ; 95 % confidence interval , 3.0–27.0 ; P<0.0001 ) , continuous use of BB was associated with lower risk of new HF events ( hazard ratio , 0.2 ; 95 % confidence interval , 0.1–0.5 ; P=0.003 ) . Conclusions —Coincidental , continuous use of BB is associated with lower incidence of HF in patients with breast cancer and normal baseline ejection fraction in a competing risk framework , and after matching for demographics , clinical , and cancer-related treatment characteristics . Prospect i ve r and omized clinical trials to vali date these findings are warranted 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 BACKGROUND The current treatment of hematologic malignancies includes diverse potentially cardiotoxic chemotherapy agents , including high-dose myeloablative regimens used in autologous hematopoietic stem cell transplantation ( HSCT ) . Many of these treatments could induce left ventricular dysfunction ( LVD ) , and limit their efficacy . Angiotensin-converting enzime inhibitors and beta-blockers prevent LVD and prolong survival after infa rct ion , and recent animal and pilot clinical studies suggest that they can prevent the development of chemotherapy-induced cardiac toxicity . METHODS This is a prevention , parallel-assignment , r and omized , controlled , clinical efficacy study . Ninety patients recently diagnosed of acute leukemia or undergoing autologous HSCT and with normal LV ejection fraction will be r and omized to enalapril and carvedilol or to the control group . Echocardiogram and a cardiac magnetic resonance imaging studies will be performed at baseline and 6 - 9 months after r and omization . The primary efficacy endpoint is the change from baseline in LV ejection fraction . Secondary endpoints include the assessment of LV volumes and diastolic function , and the incidence of death , heart failure , or LVD . CONCLUSIONS The OVERCOME study will be the first clinical trial to test the preventive efficacy on LVD of combined treatment with enalapril and carvedilol administered to patients with hematologic malignancies su bmi tted to current treatment with intensive chemotherapy BACKGROUND Oxidative stress and RAAS play an important role in the occurrence of anthracyclines-induced cardiotoxicity . Telmisartan , an angiotensin II type 1 receptor blocker , inhibits activation of superoxide sources and induces anti-inflammatory effects . METHODS The possible role of telmisartan in preventing myocardial damage induced by epirubicin ( EPI ) was investigated . Forty-nine patients free from cardiovascular diseases affected by a variety of solid cancers were examined . Eligible patients were r and omized to receive telmisartan ( 40 mg/d ; TEL , n = 25 ) or placebo ( PLA , n = 24 ) starting 1 week before chemotherapy . Patients were studied by means of echocardiography , tissue Doppler , and strain and strain rate ( SR ) imaging . We also measured plasma levels of inflammatory and oxidative stress markers . All parameters were assessed at baseline and 7 days after every new EPI dose of 100 mg/m(2 ) . RESULTS An impairment of the SR peak was observed at the EPI dose of 200 mg/m(2 ) , with no significant differences between TEL and PLA ( 1.41 + /- 0.31 vs 1.59 + /- 0.36/s ) . At growing cumulative doses of EPI , SR normalized only in TEL , showing a significant difference in comparison to PLA at EPI doses of 300 mg/m(2 ) ( 1.69 + /- 0.42 vs 1.34 + /- 0.18/s , P < .001 ) and 400 mg/m(2 ) ( 1.74 + /- 0.27 vs 1.38 + /- 0.24/s , P < .001 ) . Moreover , a significant increase in reactive oxygen species and interleukin-6 was found in PLA ; but these remained unchanged in TEL . CONCLUSIONS We confirmed that EPI-induced cardiotoxicity is primarily related to the inactivation of the cardiac antioxidant defenses . In addition , we showed that telmisartan can reduce EPI-induced radical species , antagonize the inflammation , and reverse the early myocardial impairment PURPOSE To determine whether an angiotensin-converting enzyme ( ACE ) inhibitor , enalapril , prevents cardiac function deterioration ( defined using maximal cardiac index [ MCI ] on exercise testing or increase in left ventricular end-systolic wall stress [ LVESWS ] ) in long-term survivors of pediatric cancer . PATIENTS AND METHODS This was a r and omized , double-blind , controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure . RESULTS There was no difference in the rate of change in MCI per year between enalapril and placebo groups ( 0.30 v 0.18 L/min/m(2 ) ; P = .55 ) . However , during the first year of treatment , the rate of change in LVESWS was greater in the enalapril group than in the placebo group ( -8.59 v 1.85 g/cm(2 ) ; P = .033 ) and this difference was maintained over the study period , result ing in a 9 % reduction in estimated LVESWS by year 5 in the enalapril group . Six of seven patients removed from r and om assignment to treatment because of cardiac deterioration were initially treated with placebo ( P = .11 ) , and one has died as a result of heart failure . Side effects from enalapril included dizziness or hypotension ( 22 % v 3 % in the placebo group ; P = .0003 ) and fatigue ( 10 % v 0 % ; P = .013 ) . CONCLUSION Enalapril treatment did not influence exercise performance , but did reduce LVESWS in the first year ; this reduction was maintained over the study period . Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions OBJECTIVE To investigate the effect of low-dose carvedilol combined with c and esartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer . METHODS Forty patients were r and omly divided into two groups : the experimental group with chemotherapy plus low-dose carvedilol combined with c and esartan ( 20 cases ) and control group with chemotherapy alone ( 20 cases ) . The same chemotherapy was given to the two groups . All the 40 patients had no contraindication for carvedilol and c and esartan .  Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions , and c and esartan 2.5 mg orally once a day . Electrocardiogram , ultrasonic cardiogram , arrhythmia , troponin and non-hematologic toxicity were recorded and compared after the second , forth and sixth cycle of chemotherapy . Each cycle included 21 days . RESULTS LVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group . LVEDD and LVESD showed no significant changes in the experimental group , but gradually increased in the control group . After four and six cycles of chemotherapy , LVEF were ( 57.00 ± 5.13)% and ( 45.95 ± 3.68)% , respectively , in the control group , significantly lower than that of ( 67.00 ± 5.13)% and ( 57.50 ± 2.57)% , respectively , in the experimental group ( P < 0.05 ) . After six cycles of chemotherapy , LVEDD and LVESD were ( 50.00 ± 10.48 ) mm and ( 35.01 ± 2.99 ) mm , respectively , in the control group , significantly higher than those before chemotherapy ( P < 0.05 ) and experimental group ( P < 0.001 ) . The rate of ST segment and T wave abnormalities was 80.0 % in the control group after six cycles of chemotherapy , significantly higher than that of 25.0 % after four cycles of chemotherapy ( P = 0.001 ) and 10.0 % after two cycles of chemotherapy ( P < 0.001 ) . The reduction of QRS voltage , arrhythmia and abnormal troponin were 55.0 % , 45.0 % and 45.0 % , respectively , in the control group , significantly higher than those in the experimental group ( 20.0 % , P < 0.05 ) , ( 10.0 % , P = 0.010 ) and ( 10.0 % , P < 0.05 ) , respectively . The rate of abnormal expression of troponin was 45.0 % in the control group , significantly higher than the 10.0 % in the experimental group ( P < 0.05 ) . CONCLUSIONS The use of low-dose carvedilol combined with c and esartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs , and with tolerable toxicities . This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer BACKGROUND We aim ed to evaluate the effect of prophylactic nebivolol use on prevention of antracycline-induced cardiotoxicity in breast cancer patients . METHODS In this small , prospect i ve , double-blind study , we r and omly assigned 45 consecutive patients with breast cancer and planned chemotheraphy to receive  nebivolol 5 mg daily ( n=27 ) or placebo ( n=18 ) . Echocardiographic measurements and N-terminal pro-brain natriuretic peptide ( NT-pro-BNP ) levels were obtained at baseline and at 6-month of chemotherapy . RESULTS Both studied groups had comparable echocardiographic variables and NT-pro-BNP levels at baseline . At 6-month , the left ventricular ( LV ) end-systolic and end-diastolic diameters increased in the placebo group ( LVESD : 29.7 ± 3.4 to 33.4 ± 4. 
    Output:
    
Though the point estimate for the relative rate of cardiac events was lower in the experimental arm , the difference was not statistically significant .
In an exploratory subgroup analysis , the benefit of experimental agents on LVEF preservation was prominent in patients treated with higher accumulative dose of anthracyclines , but not in the lower dose group .
CONCLUSIONS β-Blockers and angiotensin antagonists treatments were associated with better LVEF preservation , and the benefit was prominent in patients treated with higher anthracyclines accumulative dose .
This analysis provides some support for the routine use of β-blockers or angiotensin antagonists in patients undergoing anthracyclines treatment , especially when higher accumulative dose is expected