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      Strategies to prevent anthracycline-induced cardiotoxicity in cancer survivors

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          Abstract

          Cancer diagnostics and therapies have improved steadily over the last few decades, markedly increasing life expectancy for patients at all ages. However, conventional and newer anti-neoplastic therapies can cause short- and long-term cardiotoxicity. The clinical implications of this cardiotoxicity become more important with the increasing use of cardiotoxic drugs. The implications are especially serious among patients predisposed to adverse cardiac effects, such as youth, the elderly, those with cardiovascular comorbidities, and those receiving additional chemotherapies or thoracic radiation. However, the optimal strategy for preventing and managing chemotherapy-induced cardiotoxicity remains unknown. The routine use of neurohormonal antagonists for cardioprotection is not currently justified, given the marginal benefits and associated adverse events, particularly with long-term use. The only United States Food and Drug Administration and European Medicines Agency approved treatment for preventing anthracycline-related cardiomyopathy is dexrazoxane. We advocate administering dexrazoxane during cancer treatment to limit the cardiotoxic effects of anthracycline chemotherapy.

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          The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.

          Aldosterone is important in the pathophysiology of heart failure. In a doubleblind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes. The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001). This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes. The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group (relative risk of hospitalization, 0.65; 95 percent confidence interval, 0.54 to 0.77; P<0.001). In addition, patients who received spironolactone had a significant improvement in the symptoms of heart failure, as assessed on the basis of the New York Heart Association functional class (P<0.001). Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone, as compared with 1 percent of men in the placebo group (P<0.001). The incidence of serious hyperkalemia was minimal in both groups of patients. Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure.
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            Prevalence of childhood and adult obesity in the United States, 2011-2012.

            More than one-third of adults and 17% of youth in the United States are obese, although the prevalence remained stable between 2003-2004 and 2009-2010. To provide the most recent national estimates of childhood obesity, analyze trends in childhood obesity between 2003 and 2012, and provide detailed obesity trend analyses among adults. Weight and height or recumbent length were measured in 9120 participants in the 2011-2012 nationally representative National Health and Nutrition Examination Survey. In infants and toddlers from birth to 2 years, high weight for recumbent length was defined as weight for length at or above the 95th percentile of the sex-specific Centers for Disease Control and Prevention (CDC) growth charts. In children and adolescents aged 2 to 19 years, obesity was defined as a body mass index (BMI) at or above the 95th percentile of the sex-specific CDC BMI-for-age growth charts. In adults, obesity was defined as a BMI greater than or equal to 30. Analyses of trends in high weight for recumbent length or obesity prevalence were conducted overall and separately by age across 5 periods (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012). In 2011-2012, 8.1% (95% CI, 5.8%-11.1%) of infants and toddlers had high weight for recumbent length, and 16.9% (95% CI, 14.9%-19.2%) of 2- to 19-year-olds and 34.9% (95% CI, 32.0%-37.9%) of adults (age-adjusted) aged 20 years or older were obese. Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults. Tests for an interaction between survey period and age found an interaction in children (P = .03) and women (P = .02). There was a significant decrease in obesity among 2- to 5-year-old children (from 13.9% to 8.4%; P = .03) and a significant increase in obesity among women aged 60 years and older (from 31.5% to 38.1%; P = .006). Overall, there have been no significant changes in obesity prevalence in youth or adults between 2003-2004 and 2011-2012. Obesity prevalence remains high and thus it is important to continue surveillance.
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              Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline.

              Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.
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                Author and article information

                Contributors
                nbansal@montefiore.org
                Adamsmj14@yahoo.com
                sarju.ganatra@lahey.org
                steven.colan@cardio.chboston.org
                ssanjeev@dmc.org
                rsteiner@siux.ch
                amdanis@ccf.org
                elipshultz@gmail.com
                716-323-0000 , slipshultz@upa.chob.edu , slipshultz@buffalo.edu
                Journal
                Cardiooncology
                Cardiooncology
                Cardio-oncology
                BioMed Central (London )
                2057-3804
                2 December 2019
                2 December 2019
                2019
                : 5
                : 18
                Affiliations
                [1 ]ISNI 0000 0004 0566 7955, GRID grid.414114.5, Division of Pediatric Cardiology, , Children’s Hospital at Montefiore, ; Bronx, NY USA
                [2 ]ISNI 0000 0004 1936 9166, GRID grid.412750.5, Department of Public Health Sciences, , University of Rochester School of Medicine and Dentistry, ; Rochester, NY USA
                [3 ]ISNI 0000 0001 0725 1353, GRID grid.415731.5, Cardio-Oncology Program, Division of Cardiovascular Medicine, Department of Medicine, , Lahey Hospital and Medical Center, ; Burlington, MA USA
                [4 ]ISNI 0000 0004 0378 8294, GRID grid.62560.37, Cardio-Oncology Program, Dana-Farber Cancer Institute / Brigham and Women’s Hospital, ; Boston, MA USA
                [5 ]ISNI 0000 0004 0378 8438, GRID grid.2515.3, Department of Pediatric Cardiology, , Boston Children’s Hospital, ; Boston, MA USA
                [6 ]ISNI 0000 0000 9144 1055, GRID grid.414154.1, Division of Pediatric Cardiology, Department of Pediatrics, , Children’s Hospital of Michigan, ; Detroit, MI USA
                [7 ]ISNI 0000 0004 1937 0650, GRID grid.7400.3, University of Zurich, ; Zurich, Switzerland
                [8 ]ISNI 0000 0001 0675 4725, GRID grid.239578.2, Division of Pediatric Cardiology, , Cleveland Clinic Children’s Hospital, ; Cleveland, OH USA
                [9 ]ISNI 0000 0001 2106 9910, GRID grid.65499.37, Dana-Farber Cancer Institute, ; Boston, MA USA
                [10 ]ISNI 0000 0004 1936 8606, GRID grid.26790.3a, University of Miami Miller School of Medicine, ; Miami, FL USA
                [11 ]ISNI 0000 0004 1936 9887, GRID grid.273335.3, Department of Pediatrics, , University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Oishei Children’s Hospital, ; 1001 Main Street, Buffalo, NY 14203 USA
                [12 ]ISNI 0000 0000 9958 7286, GRID grid.413993.5, Oishei Children’s Hospital, ; Buffalo, NY USA
                [13 ]Roswell Park Comprehensive Cancer Center, Buffalo, NY USA
                Article
                54
                10.1186/s40959-019-0054-5
                7048046
                32154024
                b7757ba2-97fa-4c0c-b9f9-2ba37d96c4e0
                © The Author(s). 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 May 2019
                : 16 October 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: HL072705
                Award ID: HL078522
                Award ID: HL053392
                Award ID: CA127642
                Award ID: CA068484
                Award ID: HD052104
                Award ID: AI50274
                Award ID: HD052102
                Award ID: HL087708
                Award ID: HL079233
                Award ID: HL004537
                Award ID: HL087000
                Award ID: HL007188
                Award ID: HL094100
                Award ID: HL095127
                Award ID: HD80002
                Award ID: HD028820
                Funded by: FundRef http://dx.doi.org/10.13039/100004319, Pfizer;
                Award ID: n/a
                Funded by: Roche Diagnostics
                Award ID: n/a
                Funded by: FundRef http://dx.doi.org/10.13039/100009714, Children's Cardiomyopathy Foundation;
                Award ID: n/a
                Funded by: Sofia’s Hope, Inc
                Award ID: n/a
                Funded by: the Kyle John Rymiszewski Foundation
                Award ID: n/a
                Funded by: the Children’s Hospital of Michigan Foundation
                Award ID: n/a
                Funded by: the Scott Howard Fund
                Award ID: n/a
                Funded by: the Michael Garil Fund
                Award ID: n/a
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                cardiotoxicity,cardio-oncology,pediatrics,beta-blockers,ace inhibitors,anthracyclines,cancer

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