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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">whTjKLJM47vyczx4FmGGmTv</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2022000700109</article-id>
      <article-id pub-id-type="publisher-id">abc.20220393</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20220393</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Medicina de Precis&#227;o: A Tomografia por Emiss&#227;o de P&#243;sitrons com 18F-FDG pode Identificar Fen&#243;tipos de Cardiotoxicidade?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0002-1466-9413</contrib-id>
          <name>
            <surname>Mesquita</surname>
            <given-names>Claudio Tinoco</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Rezende</surname>
            <given-names>Maria Fernanda</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade Federal Fluminense</institution>
          <addr-line>
            <named-content content-type="city">Niter&#243;i</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal Fluminense, Niter&#243;i, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Hospital Pr&#243;-Card&#237;aco</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">Hospital Pr&#243;-Card&#237;aco, Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution content-type="orgname">Hospital Vit&#243;ria e Samaritano da Barra</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">Hospital Vit&#243;ria e Samaritano da Barra, Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Claudio Tinoco Mesquita</bold> &#8226; Faculdade de Medicina &#8211; Universidade Federal Fluminense &#8211; Rua Marqu&#234;s do Paran&#225;, 303 CEP <postal-code>24033-900</postal-code>, Centro, Niter&#243;i, RJ &#8211; Brasil, E-mail: <email>claudiotinocomesquita@id.uff.br</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>11</day>
        <month>07</month>
        <year>2022</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <month>07</month>
        <year>2022</year>
      </pub-date>
      <volume>119</volume>
      <issue>1</issue>
      <fpage>109</fpage>
      <lpage>110</lpage>
      <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>Cintilografia</kwd>
        <kwd>Tomografia por Emiss&#227;o de P&#243;sitrons</kwd>
        <kwd>Toxicidade</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="7"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>A publica&#231;&#227;o nos Arquivos Brasileiros de Cardiologia do artigo de Dourado et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> deve ser vista com bastante interesse por cardiologistas que buscam a Medicina de Precis&#227;o. Neste estudo, os autores, em setenta pacientes com linfoma, a intensidade de capta&#231;&#227;o de 2-[18F]-fluoro-2-desoxi-D-glicose (18F-FDG) pelo mioc&#225;rdio por tomografia por emiss&#227;o de p&#243;sitrons associada a tomografia computadorizada (PET/CT) antes, durante e ap&#243;s quimioterapia. Os autores observaram progressivo aumento do metabolismo de glicose no ventr&#237;culo esquerdo do PET/CT basal para o PET/CT intermedi&#225;rio, e desse para o PET/CT p&#243;s-terapia. Mais da metade dos pacientes analisados demonstraram um aumento &#8805; 30% na intensidade de capta&#231;&#227;o de glicose, conforme medida pelo SUV m&#225;xima no ventr&#237;culo esquerdo. Os autores inferem que o PET/CT &#233; capaz de avaliar de modo confi&#225;vel a intensidade de capta&#231;&#227;o de 18F-FDG em pacientes com linfoma durante e ap&#243;s quimioterapia. Mais do que isto, os autores conseguiram identificar um grupo de pacientes em que a quimioterapia causou maior repercuss&#227;o metab&#243;lica no ventr&#237;culo esquerdo.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Esses achados podem contribuir para uma estrat&#233;gia de identifica&#231;&#227;o precoce de pacientes com maior sensibilidade &#224; toxicidade card&#237;aca das drogas empregadas e de defini&#231;&#227;o, de modo mais personalizada, de medidas de preven&#231;&#227;o dos danos irrevers&#237;veis ao cora&#231;&#227;o.</p>
    <p>A Medicina de Precis&#227;o &#233; comumente definida como uma abordagem para tratamento e preven&#231;&#227;o de doen&#231;as que leva em considera&#231;&#227;o a variabilidade individual e a manifesta&#231;&#227;o da doen&#231;a em cada indiv&#237;duo. Para que isso ocorra de modo adequado, &#233; necess&#225;rio que se identifiquem mecanismos espec&#237;ficos de desenvolvimento das doen&#231;as e pontos chaves para implementa&#231;&#227;o de abordagens eficazes.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Esse processo, &#233; conhecido como fenotipagem profunda, onde se identificam fen&#243;tipos subjacentes (end&#243;tipos) ao fen&#243;tipo comum inicial, permitindo um melhor direcionamento de abordagens terap&#234;uticas.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
    <p>O 18F-FDG &#233; uma sonda molecular sens&#237;vel, capaz de avaliar tanto a express&#227;o aumentada da capta&#231;&#227;o de glicose em c&#233;lulas tumorais vi&#225;veis como monitorar a efetividade da resposta terap&#234;utica ao tratamento do c&#226;ncer. Borde et al.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> foram um dos primeiros a demonstrar o impacto da toxicidade das antraciclinas na capta&#231;&#227;o de FDG em um grupo de pacientes com aumento consider&#225;vel da concentra&#231;&#227;o do tra&#231;ador ap&#243;s o tratamento. Os autores especularam que a dose de adriamicina administrada tenha atingido o limite individual e levou &#224; ativa&#231;&#227;o da via NRG-erb com aumento da utiliza&#231;&#227;o de glicose pelos mi&#243;citos. Estudos experimentais com uso de radioterapia na &#225;rea card&#237;aca mostraram que a alta capta&#231;&#227;o de FDG em um campo irradiado parece estar associada ao dano na microcircula&#231;&#227;o relacionada &#224; les&#227;o mitocondrial.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
    <p>No recente Posicionamento Brasileiro sobre o Uso da Multimodalidade de Imagens na Cardio-Oncologia da Sociedade Brasileira de Cardiologia,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> a t&#233;cnica do PET-CT com 18F-FDG &#233; mencionada no diagn&#243;stico da cardiotoxicidade induzida pelos inibidores dos checkpoints imunol&#243;gicos, visto que permite detectar e avaliar a extens&#227;o e at&#233; mesmo quantificar o processo inflamat&#243;rio de diversas afec&#231;&#245;es cardiovasculares, tais como miocardite, pericardite e vasculites.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> Al&#233;m do PET CT com 18F-FDG, existem muitas outras aplica&#231;&#245;es da medicina nuclear na avalia&#231;&#227;o da toxicidade do c&#226;ncer ao cora&#231;&#227;o. Na <xref ref-type="fig" rid="f1">figura 1</xref> podemos observar que a lista de aplica&#231;&#245;es da medicina nuclear est&#225; progressivamente aumentando, incluindo n&#227;o somente exames para avalia&#231;&#227;o da fun&#231;&#227;o sist&#243;lica e diast&#243;lica ventricular (que s&#243; ficam anormais em fases mais avan&#231;adas do dano card&#237;aco), como tamb&#233;m exames que avaliam processos mais sens&#237;veis do cora&#231;&#227;o como a perfus&#227;o, a inerva&#231;&#227;o e o metabolismo da c&#233;lula card&#237;aca.</p>
    <fig id="f1">
      <label>Figura 1</label>
      <caption>
        <title>Principais aplica&#231;&#245;es da Medicina Nuclear na Detec&#231;&#227;o e Acompanhamento da Toxicidade Card&#237;aca do Tratamento do C&#226;ncer. MIBI: sestamibi; Rb: Rub&#237;dio; PET-CT: Tomografia por emiss&#227;o de p&#243;sitrons acoplada com tomografia computadorizada; SPECT: Tomografia computadorizada de emiss&#227;o de f&#243;ton &#250;nico; NH3: am&#244;nia; Tc: Tecn&#233;cio.</title>
      </caption>
      <graphic xlink:href="1678-4170-abc-119-01-0109-20393-gf01.tif"/></fig>
    <p>Em suma, a medicina de precis&#227;o &#233; um caminho de grande import&#226;ncia para a medicina atual. Como no exemplo do estudo de Dourado et al.,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> em que se encontrou um perfil molecular de resposta ao tratamento quimioter&#225;pico para um grupo de pacientes, acreditamos que tamb&#233;m ser&#225; individualizada, futuramente, a abordagem preventiva e terap&#234;utica na cardio-oncologia. Alguns estudos experimentais t&#234;m sugerido que abordagens n&#227;o-farmacol&#243;gicas, como atividade f&#237;sica regular, podem ser &#250;teis na preven&#231;&#227;o da cardiotoxicidade induzida por quimioterapia, e que poderiam ser orientadas de modo mais preciso com a correta identifica&#231;&#227;o dos pacientes em maior risco.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Desta forma, a estratifica&#231;&#227;o de pacientes e a compreens&#227;o das suas respostas celulares e bioqu&#237;micas aos diversos tratamentos permitir&#225; uma abordagem personalizada, reduzindo a morbidade e aumentando as chances de bons desfechos do tratamento.</p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo: Aumento de Capta&#231;&#227;o Card&#237;aca de 18F-FDG Induzida por Quimioterapia em Pacientes com Linfoma: Um Marcador Precoce de Cardiotoxicidade?</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="S01" 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>Precision Medicine: Can 18F-FDG PET Detect Cardiotoxicity Phenotypes?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0002-1466-9413</contrib-id>
          <name>
            <surname>Mesquita</surname>
            <given-names>Claudio Tinoco</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="aff6">
            <sup>3</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Rezende</surname>
            <given-names>Maria Fernanda</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">
            <sup>3</sup>
          </xref>
        </contrib>
        <aff id="aff4">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Niter&#243;i</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal Fluminense, Niter&#243;i, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff5">
          <label>2</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">Hospital Pr&#243;-Card&#237;aco, Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff6">
          <label>3</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">Hospital Vit&#243;ria e Samaritano da Barra, Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Claudio Tinoco Mesquita</bold> &#8226; Faculdade de Medicina &#8211; Universidade Federal Fluminense &#8211; Rua Marqu&#234;s do Paran&#225;, 303 Postal Code <postal-code>24033-900</postal-code>, Centro, Niter&#243;i, RJ &#8211; Brazil, E-mail: <email>claudiotinocomesquita@id.uff.br</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Radionuclide Imaging</kwd>
        <kwd>Positron-Emission Tomography</kwd>
        <kwd>Toxicity</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>The publication of the article by Dourado et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> in the <italic>Arquivos Brasileiros de Cardiologia</italic> should be carefully considered by cardiologists engaged in Precision Medicine. In this study,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> the authors investigated the intensity of 2-deoxy-2[18F] fluoro-D-glucose (18F-FDG) myocardial uptake in 70 patients with lymphoma by positron emission tomography associated with computed tomography (PET/CT) scans before, during and after chemotherapy. They observed a progressive increase in glucose metabolism in the left ventricle from baseline PET/CT to interim PET/CT, and from interim PET/CT to post-therapy PET/CT. More than half of patients showed an increase of &#8805; 30% in cardiac 18F-FDG uptake measured by left ventricular SUV max. The authors inferred that PET/CT is a reliable method to assess the intensity of 18F-FDG uptake in patients with lymphoma during and after chemotherapy. More importantly, the authors could identify a group of patients in which the metabolic effects of chemotherapy on the left ventricle were the greatest.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> These findings can contribute to a strategy for the early identification of patients who are more sensitive to cardiotoxicity of chemotherapeutic agents and for the definition of individualized preventive measures of irreversible myocardial damage.</p>
      <p>Precision Medicine is commonly defined as an approach for disease treatment and prevention that takes into account individual variability and disease manifestation for each person. For this purpose, it is fundamental to clarify specific mechanisms of disease and key points for the implementation of effective interventions.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> This process is known as deep phenotyping, where endotypes, <italic>i.e</italic>., phenotypes underlying the common phenotype are identified, allowing a more effective guidance of therapeutic approaches.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>18F-FDG is a sensitive molecular probe that can evaluate not only an increased expression of glucose uptake by viable tumor cells but also monitor the effectiveness of therapeutic response to cancer treatment. Borde et al.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> were one of the first to demonstrate the impact of anthracycline toxicity on FGD uptake in a group of patients who showed a considerable increase in the tracer uptake after treatment. The authors speculated that the dose of adriamycin may have reached the individual limit, leading to activation of the NRG-erbB pathway and increased glucose utilization by the myocytes. Experimental studies with cardiac radiotherapy have shown that the increased FDG uptake in an irradiated field may be associated with microvascular damage related to the direct injury of the mitochondria by radiation.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>In the recent Brazilian position statement on the use of multimodality imaging in cardio-oncology,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> 18F-FDG PET/CT is mentioned in the diagnosis of cardiotoxicity induced by immune checkpoint inhibitors, as the method allows to detect, assess and even quantify the extent of inflammation in several cardiovascular disorders, including myocarditis, pericarditis and vasculitis.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> In addition to 18F-FDG PET/CT, other nuclear medicine techniques can be used to assess cardiac toxicity induced by cancer. <xref ref-type="fig" rid="f2">Figure 1</xref> illustrates that the list of the nuclear medicine applications has been progressively increasing, including not only tests for evaluation of systolic and diastolic functions (which become abnormal in advanced stages of cardiac damage only), but also tests that evaluate more sensitive processes in the heart, such as perfusion, innervation, and cell metabolism.</p>
      <fig id="f2">
        <label>Figure 1</label>
        <caption>
          <title>Main applications of nuclear medicine for detection and monitoring of cardiotoxicity in cancer treatment. MIBI: sestamibi; Rb: Rubidium; PET CT: positron emission tomography-computed tomography; SPECT: single-photon emission computed tomography; NH3: ammonia; Tc: Technetium.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-119-01-0109-20393-gf01-en.tif"/></fig>
      <p>In summary, Precision Medicine is very important for current medicine. As in the study by Dourado et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> who found a profile of molecular response to chemotherapy treatment in a group of patients, we believe that, in the future, preventive and therapeutic approach in cardio-oncology will also be individualized. Some experimental studies have suggested that non-pharmacological approaches, like regular exercise, can be useful to prevent chemotherapy-induced cardiotoxicity, and are more precisely prescribed with the identification of patients at higher risk.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Therefore, the stratification of patients and the understanding of their cellular and biochemical responses to treatments will allow a tailored approach, reducing morbidity and increasing the chances of successful treatment outcomes.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other" id="fn2">
          <p>Short Editorial related to the article: Chemotherapy-induced Cardiac 18F-FDG Uptake in Patients with Lymphoma: An Early Metabolic Index of Cardiotoxicity?</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
