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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">8vJggLXhPbdGx9mBdNYhgJM</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2023001200205</article-id>
      <article-id pub-id-type="other">00205</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20230821</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Biomarcadores na Avalia&#231;&#227;o de Pacientes Submetidos &#224; Quimioterapia com Antraciclinas</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0002-4894-6116</contrib-id>
          <name>
            <surname>Issa</surname>
            <given-names>Aurora Felice Castro</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Instituto Nacional de Cardiologia</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto Nacional de Cardiologia, Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Aurora Felice Castro Issa &#8226;</bold> Instituto Nacional de Cardiologia &#8211; Rua das Laranjeiras, 374. CEP <postal-code>22240-006</postal-code>, Rio de Janeiro, RJ &#8211; Brasil E-mail: <email>auroraissa@gmail.com</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>04</day>
        <month>03</month>
        <year>2024</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <year>2023</year>
      </pub-date>
      <volume>120</volume>
      <issue>12</issue>
      <elocation-id>e20230821</elocation-id>
      <history>
        <date date-type="received">
          <day>27</day>
          <month>11</month>
          <year>2023</year>
        </date>
        <date date-type="rev-recd">
          <day>06</day>
          <month>12</month>
          <year>2023</year>
        </date>
        <date date-type="accepted">
          <day>06</day>
          <month>12</month>
          <year>2023</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xml:lang="en" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Biomarcadores Farmacol&#243;gicos/dosagem</kwd>
        <kwd>Neoplasias</kwd>
        <kwd>Tratamento Farmacol&#243;gico/efeitos adversos</kwd>
        <kwd>Antraciclinas/uso terap&#234;utico</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="10"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>As antraciclinas s&#227;o componentes importantes de muitos regimes de quimioterapia para v&#225;rias malignidades s&#243;lidas e hematol&#243;gicas, incluindo c&#226;ncer de mama, ginecol&#243;gico e de bexiga, bem como leucemia e linfoma. Infelizmente, est&#227;o associadas a um risco reconhecido de cardiotoxicidade.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Os medicamentos desta classe incluem doxorrubicina, daunorrubicina, epirrubicina, mitoxantrona e idarrubicina. As evid&#234;ncias dispon&#237;veis sugerem que a les&#227;o card&#237;aca induzida pela antraciclina ocorre durante a exposi&#231;&#227;o e evolui ao longo do tempo.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
    <p>A disfun&#231;&#227;o card&#237;aca relacionada &#224; terapia do c&#226;ncer (DCRTC), a cardiotoxicidade cl&#225;ssica associada &#224;s antraciclinas, &#233; um evento adverso grave que leva &#224; interrup&#231;&#227;o do tratamento do c&#226;ncer, &#224; insufici&#234;ncia card&#237;aca (IC) potencialmente grave e at&#233; &#224; morte. A identifica&#231;&#227;o precoce da disfun&#231;&#227;o card&#237;aca relacionada &#224; terapia do c&#226;ncer &#233; essencial, pois permite a implementa&#231;&#227;o precoce da terapia m&#233;dica para IC.</p>
    <p>Atualmente, n&#227;o existe uma defini&#231;&#227;o universal para toxicidade card&#237;aca induzida por antraciclina (TCIA). O diagn&#243;stico &#233; feito devido a IC de in&#237;cio recente ou evid&#234;ncia de imagem de disfun&#231;&#227;o ventricular esquerda (VE), que &#233; comumente caracterizada por uma diminui&#231;&#227;o de &#8805; 10% na fra&#231;&#227;o de eje&#231;&#227;o do VE para um valor menor que o limite inferior do normal.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Uma redu&#231;&#227;o relativa de &gt; 15% na deforma&#231;&#227;o longitudinal global do VE &#233; um par&#226;metro &#250;til para prever a TCIA, uma vez que o comprometimento da deforma&#231;&#227;o mioc&#225;rdica precede a disfun&#231;&#227;o contr&#225;til.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> A abordagem diagn&#243;stica dispon&#237;vel carece de sensibilidade para detectar disfun&#231;&#227;o card&#237;aca subcl&#237;nica precoce e n&#227;o pode prever com seguran&#231;a resultados futuros. Um modelo preditivo melhorado seria capaz de detectar TCIA antes da diminui&#231;&#227;o da FEVE e do in&#237;cio dos sintomas.</p>
    <p>Michelettie et al.,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> demonstraram a exist&#234;ncia de uma rede pr&#243;-inflamat&#243;ria desencadeada pela quimioterapia do c&#226;ncer de mama que poderia aumentar a permeabilidade dos cardiomi&#243;citos, permitir o extravasamento de prote&#237;nas circulantes e induzir a produ&#231;&#227;o de um marcador inflamat&#243;rio como a Prote&#237;na C Reativa altamente sens&#237;vel, o que evidencia o papel potencial dos biomarcadores na identifica&#231;&#227;o do TCIA.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
    <p>A literatura sobre o uso de biomarcadores para estratifica&#231;&#227;o de risco de DCRTC antes da terapia oncol&#243;gica &#233; limitada e as recomenda&#231;&#245;es baseiam-se principalmente na opini&#227;o de especialistas. Neste momento, considera-se que a troponina e os pept&#237;deos natriur&#233;ticos apresentam benef&#237;cios potenciais se forem dosados durante o tratamento, apesar dos achados controversos.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> Mas, na verdade, os pontos de corte geralmente aceitos e os valores de refer&#234;ncia dos biomarcadores CV n&#227;o foram estabelecidos para pacientes com c&#226;ncer ou para aqueles que recebem terapias contra o c&#226;ncer. Al&#233;m disso, os n&#237;veis de NP e cTn podem diferir de acordo com os laborat&#243;rios locais e podem ser alterados por muitos fatores, incluindo idade, sexo, fun&#231;&#227;o renal, obesidade, infec&#231;&#245;es e comorbidades.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> A literatura tamb&#233;m &#233; limitada, especialmente em outros novos biomarcadores.</p>
    <p>Recentemente, Dean et al. examinaram os n&#237;veis de biomarcadores card&#237;acos e n&#227;o card&#237;acos antes, ap&#243;s a &#250;ltima dose e 3&#8211;6 meses ap&#243;s o t&#233;rmino da quimioterapia com doxorrubicina e identificaram biomarcadores com altera&#231;&#245;es significativas de intervalo em resposta &#224; terapia com antraciclina.<sup><xref ref-type="bibr" rid="B8">8</xref></sup></p>
    <p>Nesta edi&#231;&#227;o foram apresentados os resultados de um estudo caso-controle que comparou os valores de diferentes biomarcadores cardiovasculares que foram medidos em pacientes com c&#226;ncer de mama ap&#243;s o &#250;ltimo ciclo de tratamento com doxorrubicina e em pacientes sem c&#226;ncer de mama ou doen&#231;a cardiovascular. Foram encontradas algumas diferen&#231;as nos resultados, mas n&#227;o s&#227;o definitivas sobre o uso dos estudos de biomarcadores.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Apesar disso, esses resultados preliminares podem ser importantes para estudos futuros.</p>
    <p>A procura de testes que melhorem a avalia&#231;&#227;o e o tratamento dos pacientes em cardio-oncologia est&#225; ligada ao objetivo global desta disciplina, que &#233; permitir que os pacientes com c&#226;ncer recebam os melhores tratamentos oncol&#243;gicos poss&#237;veis com seguran&#231;a, minimizando a toxicidade cardiovascular relacionada com a terapia oncol&#243;gica.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Estudos de valida&#231;&#227;o em diferentes cen&#225;rios cl&#237;nicos e de custos sobre os biomarcadores s&#227;o essenciais.</p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo: Novos Biomarcadores Cardiovasculares em Pacientes com C&#226;ncer de Mama Submetidas a Quimioterapia &#224; Base de Doxorrubicina</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="S1" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Biomarkers in the Evaluation of Patients Undergoing Chemotherapy with Anthracyclines</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0002-4894-6116</contrib-id>
          <name>
            <surname>Issa</surname>
            <given-names>Aurora Felice Castro</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff2">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto Nacional de Cardiologia, Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Aurora Felice Castro Issa &#8226;</bold> Instituto Nacional de Cardiologia &#8211; Rua das Laranjeiras, 374. Postal Code <postal-code>22240-006</postal-code>, Rio de Janeiro, RJ &#8211; Brazil E-mail: <email>auroraissa@gmail.com</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Biomarkers Pharmacological/dosage</kwd>
        <kwd>Neoplasms</kwd>
        <kwd>Drug Therapy/adverse effects</kwd>
        <kwd>Anthracyclines/therapeutic use</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Anthracyclines are important components of many chemotherapy regimens for various solid and hematologic malignancies, including breast, gynecologic, and bladder cancers, as well as leukemia and lymphoma. Unfortunately, they are associated with a recognized risk of cardiotoxicity.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Drugs in this class include doxorubicin, daunorubicin, epirubicin, mitoxantrone and idarubicin. The available evidence suggests that anthracycline-induced injury to the heart occurs during exposure and evolves over time.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
      <p>Cancer therapy-related cardiac dysfunction (CTRCD), the classic cardiotoxicity associated with anthracyclines, is a serious adverse event that leads to interruption of cancer treatment, potentially severe heart failure (HF), and even death. Early identification of cancer therapy-related cardiac dysfunction is essential as it allows for early implementation of medical HF therapy.</p>
      <p>Currently, there is no universal definition for anthracycline-induced cardiac toxicity (AICT). Diagnosis is made due to new-onset HF or imaging evidence of left ventricular (LV) dysfunction, which is commonly characterized by a &#8805; 10% decrease in LV ejection fraction to a value less than the lower limit of normal.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> A relative reduction of &gt; 15% in LV global longitudinal strain is a useful parameter to predict AICT as impairment in myocardial deformation precedes contractile dysfunction.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> The available diagnostic approach lacks the sensitivity to detect early subclinical cardiac dysfunction and cannot reliably predict future outcomes. An improved predictive model would be able to detect AICT prior to decreases in LVEF and symptom onset.</p>
      <p>Micheletti et al.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> demonstrated the existence of a proinflammatory net triggered by breast cancer chemotherapy that could increase cardiomyocyte permeability, allow the leakage of circulating proteins, and induce the production of an inflammatory marker as highly sensitive C Reactive Protein, which evidences the potential role of biomarkers in the identification of AICT.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
      <p>The literature on the use of biomarkers for CTRCD risk stratification before cancer therapy is limited, and recommendations are mostly based on expert opinion. At this moment, troponin and natriuretic peptides are considered to have potential benefits if they are going to be measured during the treatment, despite controversial findings.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> But, in fact, generally accepted cut-offs and reference values of CV biomarkers have not been established for patients with cancer or for those who receive cancer therapies. In addition, levels of NP and cTn may differ according to local laboratories and may be altered by many factors, including age, sex, renal function, obesity, infections, and comorbidities.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> The literature is also limited specially in other novel biomarkers.</p>
      <p>Recently, Dean et al. examined the levels of cardiac and noncardiac biomarkers before, after the last dose of, and 3&#8211;6 months after completion of doxorubicin chemotherapy and identified biomarkers with significant interval changes in response to anthracycline therapy.<sup><xref ref-type="bibr" rid="B8">8</xref></sup></p>
      <p>In this issue was presented the results of a case-control study that compared the results of different cardiovascular biomarkers that were measured in patients with breast cancer after the last cycle of treatment with doxorubicin and in patients without breast cancer or cardiovascular disease. Some differences in the results were found, but they are not definitive about the use of the biomarkers studies.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Despite that, these preliminary results can be important for future studies.</p>
      <p>The search for tests that improve the evaluation and treatment of patients in cardio-oncology is linked to the overarching goal of this discipline, which is to allow patients with cancer to receive the best possible cancer treatments safely, minimizing cancer therapy-related cardiovascular toxicity during cancer care.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Validation studies in different clinical scenarios and studies about the costs of the biomarkers will be essential.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other" id="fn2">
          <p>Short Editorial related to the article: New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
