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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">f5R5VSPFFmZBjDvjWPWMskg</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2026000104202</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20250648</article-id>
      <article-id pub-id-type="other">04202</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Carta ao Editor</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Rela&#231;&#227;o Troponina/Linf&#243;cito na Miocardite Associada a Inibidores de Checkpoint Imunol&#243;gico: Um Marcador &#218;til com Limita&#231;&#245;es</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6965-5713</contrib-id>
          <name>
            <surname>Ceyhun</surname>
            <given-names>G&#246;khan</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">Ataturk University Faculty of Medicine</institution>
          <institution content-type="orgdiv1">Department of Cardiology</institution>
          <addr-line>
            <named-content content-type="city">Erzurum</named-content>
          </addr-line>
          <country country="TR">Turquia</country>
          <institution content-type="original">Ataturk University Faculty of Medicine &#8211; Department of Cardiology, Erzurum &#8211; Turquia</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><label>Correspond&#234;ncia:</label><bold>G&#246;khan Ceyhun</bold> &#8226; Department of Cardiology, Atat&#252;rk University School of Medicine, Erzurum, 25240 &#8211; Turquia E-mail: <email>gokhanceyhun@gmail.com</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>02</day>
        <month>03</month>
        <year>2026</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <year>2026</year>
      </pub-date>
      <volume>123</volume>
      <issue>1</issue>
      <elocation-id>e20250648</elocation-id>
      <history>
        <date date-type="received">
          <day>21</day>
          <month>09</month>
          <year>2025</year>
        </date>
        <date date-type="rev-recd">
          <day>10</day>
          <month>10</month>
          <year>2025</year>
        </date>
        <date date-type="accepted">
          <day>10</day>
          <month>10</month>
          <year>2025</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>
      <related-article related-article-type="letter" id="r1" xlink:href="10.36660/abc.20250047" ext-link-type="doi"/>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Troponina</kwd>
        <kwd>Linf&#243;citos T</kwd>
        <kwd>Miocardite</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="6"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>Prezado Editor,</bold>
    </p>
    <p>Lemos com grande interesse o artigo de Chen et al. sobre o papel progn&#243;stico da raz&#227;o troponina-linf&#243;cito (cTn/ALC) em pacientes com miocardite associada a inibidores de checkpoint imunol&#243;gico (ICI).<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Essa complica&#231;&#227;o, embora infrequente, acarreta um risco desproporcionalmente alto de morbidade e mortalidade entre pacientes com c&#226;ncer submetidos &#224; imunoterapia. Os autores devem ser elogiados por explorarem um marcador simples e amplamente dispon&#237;vel que reflete tanto a les&#227;o mioc&#225;rdica quanto o estado imunol&#243;gico. Tal abordagem &#233; clinicamente atraente porque tanto a troponina quanto a contagem de linf&#243;citos s&#227;o medidas rotineiramente, s&#227;o de baixo custo e facilmente padronizadas. Relat&#243;rios anteriores j&#225; destacaram o papel progn&#243;stico da eleva&#231;&#227;o da troponina e da din&#226;mica dos linf&#243;citos na miocardite associada a ICI,<sup><xref ref-type="bibr" rid="B2">2</xref>&#8211;<xref ref-type="bibr" rid="B5">5</xref></sup> e a integra&#231;&#227;o desses dois marcadores em um &#237;ndice composto &#233; um passo l&#243;gico e potencialmente valioso.</p>
    <p>Contudo, diversas quest&#245;es metodol&#243;gicas merecem considera&#231;&#227;o. O desenho retrospectivo e unic&#234;ntrico inevitavelmente introduz vi&#233;s de sele&#231;&#227;o e limita a validade externa dos achados. O tamanho relativamente pequeno da amostra, embora compreens&#237;vel dada a raridade da miocardite induzida por ICI, reduz o poder estat&#237;stico e resulta em amplos intervalos de confian&#231;a, o que enfraquece a robustez das associa&#231;&#245;es relatadas. Al&#233;m disso, o curto per&#237;odo de acompanhamento (mediana de 69 dias) pode n&#227;o captar adequadamente eventos cardiovasculares tardios ou mortalidade a longo prazo. Outra limita&#231;&#227;o importante &#233; que a confirma&#231;&#227;o histol&#243;gica da miocardite estava dispon&#237;vel em apenas um caso, o que pode levar a um vi&#233;s de classifica&#231;&#227;o err&#244;nea, visto que o diagn&#243;stico cl&#237;nico isolado pode, por vezes, sobrepor-se a outras causas de eleva&#231;&#227;o da troponina. Ademais, embora a raz&#227;o cTn/ALC tenha apresentado melhor desempenho do que qualquer um dos par&#226;metros isoladamente na an&#225;lise ROC, a aus&#234;ncia de diferen&#231;as estatisticamente significativas entre os valores da &#225;rea sob a curva (AUC) questiona o verdadeiro valor progn&#243;stico incremental dessa raz&#227;o em compara&#231;&#227;o com marcadores j&#225; estabelecidos.</p>
    <p>Apesar dessas limita&#231;&#245;es, o estudo enriquece o conhecimento atual ao propor uma abordagem combinada de biomarcadores. A troponina j&#225; &#233; fundamental na detec&#231;&#227;o de les&#227;o mioc&#225;rdica, enquanto a linfopenia tem sido associada a piores desfechos de toxicidade imunomediada. Ao combinar esses par&#226;metros, a raz&#227;o cTn/ALC pode refletir melhor a intera&#231;&#227;o entre o dano card&#237;aco e a imunossupress&#227;o sist&#234;mica. Esse conceito est&#225; alinhado com evid&#234;ncias recentes sobre o papel progn&#243;stico da troponina de alta sensibilidade em pacientes tratados com ICI<sup><xref ref-type="bibr" rid="B6">6</xref></sup> e sugere que &#237;ndices compostos poderiam refinar os modelos atuais de estratifica&#231;&#227;o de risco. Pesquisas futuras devem buscar validar esses achados em coortes multic&#234;ntricas maiores, com acompanhamento mais longo e, idealmente, incorporar modalidades de imagem ou dados de bi&#243;psia para fortalecer a precis&#227;o diagn&#243;stica. Tamb&#233;m seria interessante avaliar se as altera&#231;&#245;es din&#226;micas na raz&#227;o cTn/ALC ao longo do tempo, em vez de uma &#250;nica medida basal, fornecem informa&#231;&#245;es progn&#243;sticas superiores.</p>
    <p>Em resumo, Chen et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> fornecem dados oportunos e instigantes sobre o valor progn&#243;stico da raz&#227;o cTn/ALC na miocardite associada a ICI. Embora os resultados sejam promissores e clinicamente relevantes, devem ser interpretados com cautela, dadas as limita&#231;&#245;es metodol&#243;gicas. N&#227;o obstante, este trabalho abre uma importante linha de investiga&#231;&#227;o e ressalta a necessidade de ferramentas simples e confi&#225;veis para identificar precocemente pacientes de alto risco. A valida&#231;&#227;o por meio de estudos prospectivos multic&#234;ntricos ser&#225; essencial antes da implementa&#231;&#227;o rotineira da raz&#227;o cTn/ALC na tomada de decis&#245;es cl&#237;nicas. Parabenizamos os autores por sua contribui&#231;&#227;o e aguardamos ansiosamente mais pesquisas nesta &#225;rea.</p>
  </body>
  <back>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chen</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Zhang</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Luo</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Cai</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Lin</surname>
              <given-names>X</given-names>
            </name>
            <name>
              <surname>Zhou</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prognostic Value of Troponin to Lymphocyte Ratio in Patients with Immune Checkpoint Inhibitor-Associated Myocarditis</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2025</year>
          <volume>122</volume>
          <issue>8</issue>
          <elocation-id>e20250047</elocation-id>
          <pub-id pub-id-type="doi">10.36660/abc.20250047</pub-id>
        </element-citation>
        <mixed-citation>1 Chen W, Zhang W, Luo C, Cai J, Lin X, Zhou C, et al. Prognostic Value of Troponin to Lymphocyte Ratio in Patients with Immune Checkpoint Inhibitor-Associated Myocarditis. Arq Bras Cardiol. 2025;122(8):e20250047. doi: 10.36660/abc.20250047.</mixed-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mahmood</surname>
              <given-names>SS</given-names>
            </name>
            <name>
              <surname>Fradley</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Cohen</surname>
              <given-names>JV</given-names>
            </name>
            <name>
              <surname>Nohria</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Reynolds</surname>
              <given-names>KL</given-names>
            </name>
            <name>
              <surname>Heinzerling</surname>
              <given-names>LM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Myocarditis in Patients Treated with Immune Checkpoint Inhibitors</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2018</year>
          <volume>71</volume>
          <issue>16</issue>
          <fpage>1755</fpage>
          <lpage>1764</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2018.02.037</pub-id>
        </element-citation>
        <mixed-citation>2 Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, et al. Myocarditis in Patients Treated with Immune Checkpoint Inhibitors. J Am Coll Cardiol. 2018;71(16):1755-64. doi: 10.1016/j.jacc.2018.02.037.</mixed-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Drobni</surname>
              <given-names>ZD</given-names>
            </name>
            <name>
              <surname>Zafar</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Zubiri</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Zlotoff</surname>
              <given-names>DA</given-names>
            </name>
            <name>
              <surname>Alvi</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Lee</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio with Immune Checkpoint Inhibitor-Associated Myocarditis</article-title>
          <source>J Am Heart Assoc</source>
          <year>2020</year>
          <volume>9</volume>
          <issue>23</issue>
          <elocation-id>e018306</elocation-id>
          <pub-id pub-id-type="doi">10.1161/JAHA.120.018306</pub-id>
        </element-citation>
        <mixed-citation>3 Drobni ZD, Zafar A, Zubiri L, Zlotoff DA, Alvi RM, Lee C, et al. Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio with Immune Checkpoint Inhibitor-Associated Myocarditis. J Am Heart Assoc. 2020;9(23):e018306. doi: 10.1161/JAHA.120.018306.</mixed-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Puzanov</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Subramanian</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Yatsynovich</surname>
              <given-names>YV</given-names>
            </name>
            <name>
              <surname>Jacobs</surname>
              <given-names>DM</given-names>
            </name>
            <name>
              <surname>Chilbert</surname>
              <given-names>MR</given-names>
            </name>
            <name>
              <surname>Sharma</surname>
              <given-names>UC</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Clinical Characteristics, Time Course, Treatment and Outcomes of Patients with Immune Checkpoint Inhibitor-Associated Myocarditis</article-title>
          <source>J Immunother Cancer</source>
          <year>2021</year>
          <volume>9</volume>
          <issue>6</issue>
          <elocation-id>e002553</elocation-id>
          <pub-id pub-id-type="doi">10.1136/jitc-2021-002553</pub-id>
        </element-citation>
        <mixed-citation>4 Puzanov I, Subramanian P, Yatsynovich YV, Jacobs DM, Chilbert MR, Sharma UC, et al. Clinical Characteristics, Time Course, Treatment and Outcomes of Patients with Immune Checkpoint Inhibitor-Associated Myocarditis. J Immunother Cancer. 2021;9(6):e002553. doi: 10.1136/jitc-2021-002553.</mixed-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Thuny</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Naidoo</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Neilan</surname>
              <given-names>TG</given-names>
            </name>
          </person-group>
          <article-title>Cardiovascular Complications of Immune Checkpoint Inhibitors for Cancer</article-title>
          <source>Eur Heart J</source>
          <year>2022</year>
          <volume>43</volume>
          <issue>42</issue>
          <fpage>4458</fpage>
          <lpage>4468</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehac456</pub-id>
        </element-citation>
        <mixed-citation>5 Thuny F, Naidoo J, Neilan TG. Cardiovascular Complications of Immune Checkpoint Inhibitors for Cancer. Eur Heart J. 2022;43(42):4458-68. doi: 10.1093/eurheartj/ehac456.</mixed-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Waissengein</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Abu Ata</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Merimsky</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Shamai</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Wolf</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Arnold</surname>
              <given-names>JH</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>The Predictive Value of High Sensitivity Troponin Measurements in Patients Treated with Immune Checkpoint Inhibitors</article-title>
          <source>Clin Res Cardiol</source>
          <year>2023</year>
          <volume>112</volume>
          <issue>3</issue>
          <fpage>409</fpage>
          <lpage>418</lpage>
          <pub-id pub-id-type="doi">10.1007/s00392-022-02118-8</pub-id>
        </element-citation>
        <mixed-citation>6 Waissengein B, Abu Ata B, Merimsky O, Shamai S, Wolf I, Arnold JH, et al. The Predictive Value of High Sensitivity Troponin Measurements in Patients Treated with Immune Checkpoint Inhibitors. Clin Res Cardiol. 2023;112(3):409-18. doi: 10.1007/s00392-022-02118-8.</mixed-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="S1" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20250648i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Letter to the Editor</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Troponin-to-Lymphocyte Ratio in ICI Associated Myocarditis: A Useful Marker with Limitations</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6965-5713</contrib-id>
          <name>
            <surname>Ceyhun</surname>
            <given-names>G&#246;khan</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">Erzurum</named-content>
          </addr-line>
          <country country="TR">T&#252;rkiye</country>
          <institution content-type="original">Ataturk University Faculty of Medicine &#8211; Department of Cardiology, Erzurum &#8211; T&#252;rkiye</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><label>Mailing Address:</label><bold>G&#246;khan Ceyhun</bold> &#8226; Department of Cardiology, Atat&#252;rk University School of Medicine, Erzurum, 25240 &#8211; T&#252;rkiye E-mail: <email>gokhanceyhun@gmail.com</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Troponin</kwd>
        <kwd>T-Lymphocytes</kwd>
        <kwd>Myocarditis</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>Dear Editor,</bold>
      </p>
      <p>We read with great interest the article by Chen et al. on the prognostic role of the troponin-to-lymphocyte ratio (cTn/ALC) in patients with immune checkpoint inhibitor (ICI) associated myocarditis.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> This complication, although infrequent, carries a disproportionately high risk of morbidity and mortality among cancer patients receiving immunotherapy. The authors should be commended for exploring a simple and widely available marker that reflects both myocardial injury and immune status. Such an approach is clinically attractive because both troponin and lymphocyte count are routinely measured, inexpensive, and easily standardized. Previous reports have already highlighted the prognostic role of troponin elevation and lymphocyte dynamics in ICI associated myocarditis,<sup><xref ref-type="bibr" rid="B2">2</xref>&#8211;<xref ref-type="bibr" rid="B5">5</xref></sup> and the integration of these two markers into a composite index is a logical and potentially valuable step forward.</p>
      <p>Nevertheless, several methodological issues deserve consideration. The retrospective and single-center design inevitably introduces selection bias and limits the external validity of the findings. The relatively small sample size, while understandable given the rarity of ICI myocarditis, reduces statistical power and results in wide confidence intervals, which weakens the robustness of the associations reported. In addition, the short follow-up period (median 69 days) may not adequately capture late cardiovascular events or long-term mortality. Another important limitation is that histological confirmation of myocarditis was available in only one case, which may lead to misclassification bias, as clinical diagnosis alone can sometimes overlap with other causes of troponin elevation. Furthermore, while the cTn/ALC ratio performed better than either parameter alone in ROC analysis, the lack of statistically significant differences between the AUC values calls into question the true incremental prognostic value of this ratio compared to established markers.</p>
      <p>Despite these limitations, the study enriches current knowledge by proposing a combined biomarker approach. Troponin is already a cornerstone in the detection of myocardial injury, while lymphopenia has been linked to worse immune-mediated toxicity outcomes. By combining these parameters, the cTn/ALC ratio may better reflect the interplay between cardiac damage and systemic immune suppression. This concept aligns with recent evidence on the prognostic role of high-sensitivity troponin in ICI treated patients<sup><xref ref-type="bibr" rid="B6">6</xref></sup> and suggests that composite indices could refine current risk stratification models. Future research should aim to validate these findings in larger, multicenter cohorts with longer follow-up and ideally incorporate imaging modalities or biopsy data to strengthen diagnostic accuracy. It would also be of interest to assess whether dynamic changes in cTn/ALC ratio over time, rather than a single baseline measurement, provide superior prognostic information.</p>
      <p>In summary, Chen et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> provide timely and thought-provoking data on the prognostic value of the cTn/ALC ratio in ICI associated myocarditis. While the results are promising and clinically relevant, they should be interpreted with caution, given the methodological constraints. Nonetheless, this work opens an important line of investigation and underscores the need for simple, reliable tools to identify high-risk patients early. Validation through prospective, multicenter studies will be essential before the routine implementation of the cTn/ALC ratio in clinical decision-making. We congratulate the authors for their contribution and look forward to further research in this field.</p>
    </body>
  </sub-article>
</article>
