***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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    Input: BACKGROUND Cardiomyopathy following anthracycline chemotherapy may have ominous clinical implication s in cancer patients treated with this effective yet potentially toxic therapy . Early detection at sub clinical stage is pivotal to minimize the risk of overt cardiotoxicity . Liposomal anthracyclines have the potential for more selective uptake by cancer cells and reduced cardiac toxicity . OBJECTIVE We design ed a single-center r and omized clinical trial , the Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation ( LITE ) pilot study to compare the safety of liposomal doxorubicin vs st and ard epirubicin in terms of clinical and sub clinical cardiotoxicity . METHODS Whereas diagnostic and prognostic instruments effective at early recognition of cardiomyopathy are lacking , promising data have been reported for tissue Doppler imaging ( TDI ) echocardiography . The study will enroll 80 patients with breast cancer and indication to anthracycline chemotherapy  , r and omizing them in a 1:1 ratio to liposomal doxorubicin or st and ard epirubicin . The primary end-point will be the comparison of changes from baseline to 12-month follow-up of left ventricular TDI systolic function parameters , and the co- primary end-point will be based instead on changes in TDI diastolic function parameters . Among secondary end-points , we will adjudicate changes in st and ard 2-dimensional echocardiography parameters , including ejection fraction , peak values of biochemical markers of cardiac damage and heart failure , ie cardiac troponin T and BNP , overall survival , functional class , freedom from cancer recurrence , and adverse effects of chemotherapy . CONCLUSIONS Results of the LITE pilot study should provide important clinical and mechanistic insights on the promising role of liposomal anthracyclines in patients with breast cancer and indication to anthracycline chemotherapy ( Clinical Trials.gov identifier NCT00531973 ) 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 Anthracyclines are established cardiotoxic agents ; however , the exact extent and time course of such cardiotoxicity has not been appraised in detail . We aim ed to exploit serial measurements of st and ard and tissue Doppler imaging ( TDI ) echocardiographic parameters collected in a prospect i ve clinical trial to clarify the outlook of cardiac function during and long after anthracycline chemotherapy . Women enrolled in a r and omized trial focusing on liposomal doxorubicin-based chemotherapy for breast cancer and providing ≥4 separate echocardiographic assessment s were included . Repeat-measure nonparametric analyses were used to appraise changes over time in the st and ard and tissue Doppler imaging echocardiographic parameters . A total of 39 patients with serial imaging evaluations were enrolled . Significant temporal changes were found for the left ventricular ejection fraction and diastolic parameters , despite different temporal trends . Specifically , the left ventricular ejection fraction exhibited a V-shaped trend , decreasing initially from 63 % to 61 % but then recovering to 64 % ( p < 0.001 ) , with a similar trend in the TDI E/Em ratio ( p = 0.011 ) . In contrast , persistent impairments typical of an L-shaped trend were found for the E wave ( p = 0.006 ) , TDI lateral Em wave ( p = 0.001 ) , and TDI septal Em wave ( p = 0.001 ) . In conclusion , sub clinical temporal changes in the st and ard and TDI echocardiographic parameters after anthracycline chemotherapy showed a distinctive pattern of transient impairment followed by full recovery of the left ventricular ejection fraction versus a persistent impairment of the diastolic parameters , which must be taken into account in the everyday treatment of such patients Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug . A large‐scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7 % of patients developed doxorubicin‐related  congestive heart failure ( CHF ) after a cumulative dose of 550 mg/m2 . To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting , the authors evaluated data from three prospect i ve studies to determine both the incidence of  doxorubicin‐related CHF and the accumulated dose of doxorubicin at which CHF occurs OBJECTIVE --To assess the cardiac status of long-term survivors of pediatric malignancies who received chemotherapy , including anthracyclines .  DESIGN AND METHOD - Patients were evaluated by echocardiogram from 4 to 20 years ( median , 7 years ) after completion of anthracyclines  , with prospect i ve and retrospective analysis . PATIENTS --The consecutive sample of 201 patients had received a total anthracycline dose of 200 to 1275 mg/m2 ( median , 450 mg/m2 ) , and 51 patients had mediastinal radiotherapy .  MAIN OUTCOME MEASURES --The overall incidence and severity of abnormal systolic cardiac function were determined for the entire cohort . Risk factors of total anthracycline dose , mediastinal radiotherapy , age during treatment , and length of follow-up were examined . RESULTS --Twenty-three percent ( 47/201 ) of the cohort had abnormal cardiac function on noninvasive testing at long-term follow-up . Correlation between total cumulative dose , length of follow-up , and mediastinal irradiation with incidence of abnormalities was significant . Fifty-six patients were followed up for 10 years or more ( median , 12 years ) , with a median anthracycline dose of 495 mg/m2 . Thirty-eight percent ( 21/56 ) of these patients , compared with 18 % ( 26/145 ) of patients evaluated after less than 10 years , had abnormal findings . Sixty-three percent of patients followed up for 10 years or more after receiving 500 mg/m2 or more of anthracyclines had abnormal findings . Nine of 201 patients had late symptoms , including cardiac failure and dysrhythmia , and three patients died suddenly . Microscopic examination of the myocardium on biopsy and autopsy revealed fibrosis . CONCLUSION --The 23 % incidence of late cardiac abnormalities warrants continued evaluation of patients after anthracyclines  to guide patient care and the design of future chemotherapeutic protocol OBJECTIVES This study sought to evaluate the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction ( LVSD ) in patients with hematological malignancies . BACKGROUND Current chemotherapy may induce LVSD . Angiotensin-converting enzyme inhibitors and beta-blockers prevent LVSD in animal models of anthracycline-induced cardiomyopathy . METHODS In this r and omized , controlled study , 90 patients with recently diagnosed acute leukemia ( n = 36 ) or patients with malignant hemopathies undergoing autologous hematopoietic stem cell transplantation ( HSCT ) ( n = 54 ) and without LVSD were r and omly assigned to a group receiving enalapril and carvedilol ( n = 45 ) or to a control group ( n = 45 ) . Echocardiographic and cardiac magnetic resonance ( CMR ) imaging studies were performed before and at 6 months after r and omization . The primary efficacy endpoint was the absolute change from baseline in LV ejection fraction ( LVEF ) . RESULTS The mean age of patients was 50 ± 13 years old , and 43 % were women . At 6 months , LVEF did not change in the intervention group but significantly decreased in controls , result ing in a -3.1 % absolute difference by echocardiography ( p = 0.035 ) and -3.4 % ( p = 0.09 ) in the 59 patients who underwent CMR . The corresponding absolute difference ( 95 % confidence interval [ CI ] ) in LVEF was -6.38 % ( 95 % CI : -11.9 to -0.9 ) in patients with acute leukemia and -1.0 % ( 95 % CI : -4.5 to 2.5 ) in patients undergoing autologous HSCT ( p = 0.08 for interaction between treatment effect and disease category ) . Compared to controls , patients in the intervention group had a lower incidence of the combined event of death or heart failure ( 6.7 % vs. 22 % , p = 0.036 ) and of death , heart failure , or a final LVEF < 45 % ( 6.7 % vs. 24.4 % , p = 0.02 ) . CONCLUSIONS Combined treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with intensive chemotherapy . The clinical relevance of this strategy should be confirmed in larger studies . ( Prevention of Left Ventricular Dysfunction During Chemotherapy [ OVERCOME ] ; NCT01110824 ) 
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In conclusion , despite ongoing refinements in chemotherapy regimens , anthracyclines still pose a significant risk of cardiotoxicity , especially in those requiring a high cumulative dose or chest radiotherapy