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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">B4grftnTyDzKhxpKFDdQkGD</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2026000200605</article-id>
      <article-id pub-id-type="other">00605</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20250596</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Experi&#234;ncia Operat&#243;ria e Desfechos Cl&#237;nicos em Pacientes com Mixoma Card&#237;aco: Um Estudo Retrospectivo de Centro &#218;nico</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0007-5938-8053</contrib-id>
          <name>
            <surname>Madogolele</surname>
            <given-names>Heleut&#233;rio da Concei&#231;&#227;o Nicolau</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-7550-8912</contrib-id>
          <name>
            <surname>Barroso</surname>
            <given-names>Manuela Cristina Ribeiro Dias</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mej&#237;a</surname>
            <given-names>Hern&#225;n Patricio Garc&#237;a</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0191-7358</contrib-id>
          <name>
            <surname>Espinoza</surname>
            <given-names>Cristhian</given-names>
          </name>
          <role>An&#225;lise estat&#237;stica</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0003-7829-4408</contrib-id>
          <name>
            <surname>Correia</surname>
            <given-names>Vinicius Machado</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Madrini</surname>
            <given-names>Vagner</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Duncan</surname>
            <given-names>Jos&#233; Augusto</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Dias</surname>
            <given-names>Ricardo Ribeiro</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9323-8805</contrib-id>
          <name>
            <surname>Fernandes</surname>
            <given-names>F&#225;bio</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><label>Correspond&#234;ncia:</label> Heleut&#233;rio da Concei&#231;&#227;o Nicolau Madogolele Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo - Av. Dr. En&#233;as Carvalho de Aguiar, 44, CEP 05410-000, Cerqueira C&#233;sar, S&#227;o Paulo, SP &#8211; Brasil E-mail: <email>heleuteriodaconceicao@gmail.com</email> </corresp>
        <fn fn-type="edited-by">
          <label>Editor respons&#225;vel pela revis&#227;o:</label>
          <p> Henrique Ribeiro</p>
        </fn>
        <fn fn-type="coi-statement">
          <label>Potencial conflito de interesse:</label>
          <p> N&#227;o h&#225; conflito com o presente artigo.</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>23</day>
        <month>03</month>
        <year>2026</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>02</month>
        <year>2026</year>
      </pub-date>
      <volume>123</volume>
      <issue>2</issue>
      <elocation-id>e20250596</elocation-id>
      <history>
        <date date-type="received">
          <day>26</day>
          <month>08</month>
          <year>2025</year>
        </date>
        <date date-type="rev-recd">
          <day>09</day>
          <month>11</month>
          <year>2025</year>
        </date>
        <date date-type="accepted">
          <day>19</day>
          <month>12</month>
          <year>2025</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="pt">
          <license-p>Este &#233; um artigo de acesso aberto distribu&#237;do sob os termos da licen&#231;a de atribui&#231;&#227;o pelo Creative Commons</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento</title>
          <p> O mixoma card&#237;aco &#233; o segundo tumor card&#237;aco prim&#225;rio mais comum; no entanto, s&#233;ries contempor&#226;neas realizadas em centro &#250;nico que integrem estrat&#233;gia operat&#243;ria e desfechos cl&#237;nicos ainda s&#227;o limitadas.</p>
        </sec>
        <sec>
          <title>Objetivos</title>
          <p> Descrever as abordagens operat&#243;rias e os desfechos cl&#237;nicos de pacientes submetidos &#224; ressec&#231;&#227;o cir&#250;rgica de mixomas card&#237;acos em um &#250;nico centro.</p>
        </sec>
        <sec>
          <title>M&#233;todos</title>
          <p> Realizamos uma revis&#227;o retrospectiva de 74 pacientes consecutivos submetidos &#224; ressec&#231;&#227;o cir&#250;rgica de mixomas card&#237;acos com confirma&#231;&#227;o histol&#243;gica entre 2014 e 2024 em um centro terci&#225;rio de refer&#234;ncia no Brasil. Foram coletados dados cl&#237;nicos, de imagem, cir&#250;rgicos e de seguimento. O desfecho prim&#225;rio foi a incid&#234;ncia de eventos tromboemb&#243;licos. Foi adotado um n&#237;vel de signific&#226;ncia de 5% para todas as an&#225;lises estat&#237;sticas.</p>
        </sec>
        <sec>
          <title>Resultados</title>
          <p> A idade mediana foi de 60 anos (intervalo 52-66), e 68,9% dos pacientes eram do sexo feminino. O seguimento mediano foi de 60 meses (intervalo interquartil 40-79). Eventos tromboemb&#243;licos ocorreram em 14 pacientes (18,9%), incluindo acidente vascular encef&#225;lico (13,5%), infarto do mioc&#225;rdio emb&#243;lico (2,7%) e embolia pulmonar (2,7%). Na an&#225;lise multivariada de Cox, o diabetes foi independentemente associado a menor risco de eventos tromboemb&#243;licos (HR 0,11; intervalo de confian&#231;a de 95% [IC 95%] 0,006-0,740; p &lt; 0,05), enquanto a fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria foi associada a maior risco tromboemb&#243;lico (HR 6,74; IC 95% 1,490-30,510; p &lt; 0,05). Recorr&#234;ncia tumoral ocorreu em 2,7% dos casos. Apenas um &#243;bito foi registrado durante o seguimento.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o</title>
          <p> Os mixomas card&#237;acos est&#227;o associados a riscos tromboemb&#243;licos e hemodin&#226;micos significativos. A ressec&#231;&#227;o cir&#250;rgica precoce proporciona excelentes desfechos em longo prazo e deve ser considerada mesmo em pacientes assintom&#225;ticos. Em nossa coorte, a morfologia tumoral apresentou uma tend&#234;ncia n&#227;o significativa para maior risco de eventos tromboemb&#243;licos.</p>
        </sec>
      </abstract>
      <abstract abstract-type="graphical">
        <p>
          <fig id="f01">
            <label>Figura Central:</label>
            <caption>
              <title>Experi&#234;ncia Operat&#243;ria e Desfechos Cl&#237;nicos em Pacientes com Mixoma Card&#237;aco: Um Estudo Retrospectivo de Centro &#218;nico</title>
            </caption>
            <attrib>DM: diabetes melito; IC: intervalo de confian&#231;a; FA: fibrila&#231;&#227;o atrial; HR: raz&#227;o de risco; PSAP: press&#227;o sist&#243;lica da art&#233;ria pulmonar.</attrib>
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          </fig>
        </p>
      </abstract>
      <abstract abstract-type="key-points">
        <title>Destaques/Pontos-chave</title>
        <p>&#8226; Os mixomas card&#237;acos s&#227;o os segundos tumores card&#237;acos prim&#225;rios mais comuns, e a ressec&#231;&#227;o cir&#250;rgica permanece o tratamento de escolha.</p>
        <p>&#8226; Neste estudo de centro &#250;nico com 74 pacientes, os desfechos operat&#243;rios foram excelentes, com baixa taxa de recorr&#234;ncia (2,7%) e elevada sobrevida em longo prazo (98,6%).</p>
        <p>&#8226; Eventos tromboemb&#243;licos ocorreram em 18,9% dos pacientes, com o diabetes associado a menor risco desses eventos.</p>
        <p>&#8226; Esses achados sustentam a seguran&#231;a e a efic&#225;cia em longo prazo da ressec&#231;&#227;o cir&#250;rgica dos mixomas card&#237;acos, mesmo com uso conservador da reconstru&#231;&#227;o com <italic>patch</italic> interatrial.</p>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Mixoma</kwd>
        <kwd>Cardiovascular Disease</kwd>
        <kwd>Cirurgia</kwd>
        <kwd>Am&#233;rica Latina</kwd>
      </kwd-group>
      <funding-group>
        <funding-statement><bold>Fontes de financiamento:</bold> O presente estudo n&#227;o teve fontes de financiamento externas.</funding-statement>
      </funding-group>
      <counts>
        <fig-count count="20"/>
        <table-count count="12"/>
        <equation-count count="0"/>
        <ref-count count="28"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>Os mixomas card&#237;acos s&#227;o os segundos tumores card&#237;acos prim&#225;rios mais comuns, ap&#243;s os fibroelastomas papilares; no entanto, permanecem como as neoplasias card&#237;acas sintom&#225;ticas e tratadas cirurgicamente mais frequentes, correspondendo &#224; maioria dos tumores card&#237;acos benignos ressecados na pr&#225;tica cl&#237;nica.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Apesar de sua histologia benigna, sua localiza&#231;&#227;o intracard&#237;aca pode levar a morbidade significativa, incluindo obstru&#231;&#227;o, eventos emb&#243;licos e manifesta&#231;&#245;es sist&#234;micas.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Com uma incid&#234;ncia anual estimada de 0,5-1 caso por milh&#227;o, esses tumores raros ocorrem predominantemente em mulheres entre a terceira e a sexta d&#233;cadas de vida e est&#227;o mais comumente localizados no &#225;trio esquerdo (AE).<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> A ressec&#231;&#227;o cir&#250;rgica &#233; o tratamento de escolha e est&#225; associada a desfechos favor&#225;veis, embora a recorr&#234;ncia permane&#231;a uma preocupa&#231;&#227;o, particularmente em casos familiares.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>Na Am&#233;rica Latina, especialmente no Brasil, os mixomas card&#237;acos correspondem a aproximadamente 70%-75% dos tumores card&#237;acos benignos relatados em s&#233;ries cir&#250;rgicas. No entanto, sua incid&#234;ncia populacional global permanece baixa, em torno de 0,5-1 caso por milh&#227;o por ano. Portanto, embora raros na popula&#231;&#227;o geral, representam a neoplasia card&#237;aca tratada cirurgicamente mais comum na regi&#227;o.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
      <p>Este estudo apresenta dados cl&#237;nicos e cir&#250;rgicos sobre mixomas card&#237;acos a partir de uma perspectiva latino-americana, onde as evid&#234;ncias dispon&#237;veis ainda s&#227;o limitadas. Ao examinar padr&#245;es de recorr&#234;ncia e preditores de desfechos adversos, buscamos fornecer insights espec&#237;ficos da regi&#227;o que possam melhorar a avalia&#231;&#227;o de risco e orientar o manejo em longo prazo dos pacientes afetados.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <sec>
        <title>Desenho de estudo e aprova&#231;&#227;o &#233;tica</title>
        <p>Este estudo retrospectivo analisou os prontu&#225;rios m&#233;dicos de pacientes diagnosticados com mixomas card&#237;acos e tratados em um hospital terci&#225;rio no Brasil entre 2014 e 2024. O protocolo do estudo foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa da mesma institui&#231;&#227;o (Protocolo SDC-COP 26501, aprovado em 12 de janeiro de 2025). Todos os dados foram totalmente anonimizados para garantir a confidencialidade dos pacientes, de acordo com os padr&#245;es &#233;ticos.</p>
      </sec>
      <sec>
        <title>Popula&#231;&#227;o do estudo</title>
        <p>Os participantes eleg&#237;veis foram pacientes adultos (&#8805; 18 anos) com diagn&#243;stico confirmado de mixoma intracard&#237;aco com base em exames de imagem, que foram submetidos &#224; ressec&#231;&#227;o cir&#250;rgica seguida de confirma&#231;&#227;o histopatol&#243;gica e acompanhados nos ambulat&#243;rios da institui&#231;&#227;o por pelo menos 1 m&#234;s. Pacientes com idade &gt; 45 anos ou com fatores de risco cardiovascular foram submetidos &#224; avalia&#231;&#227;o pr&#233;-operat&#243;ria institucional padr&#227;o, incluindo avalia&#231;&#227;o da perviedade das art&#233;rias coron&#225;rias para minimizar o risco de infarto do mioc&#225;rdio perioperat&#243;rio. A inclus&#227;o exigiu documenta&#231;&#227;o m&#233;dica completa, incluindo anota&#231;&#245;es cl&#237;nicas e resultados de exames complementares, dispon&#237;veis no sistema institucional de prontu&#225;rio eletr&#244;nico.</p>
        <p>Os crit&#233;rios de exclus&#227;o inclu&#237;ram registros duplicados, documenta&#231;&#227;o m&#233;dica incompleta, cirurgia realizada em outra institui&#231;&#227;o, seguimento inferior a 30 dias e diagn&#243;stico n&#227;o confirmado de mixoma intracard&#237;aco.</p>
      </sec>
      <sec>
        <title>Coleta de dados e vari&#225;veis</title>
        <p>Os dados de seguimento foram obtidos exclusivamente do prontu&#225;rio eletr&#244;nico institucional, sem contato direto com os pacientes. As seguintes vari&#225;veis foram coletadas: i) caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas: idade, sexo, ra&#231;a e comorbidades, como diabetes mellitus, hipertens&#227;o, hist&#243;rico de tabagismo, dislipidemia e doen&#231;a arterial perif&#233;rica; ii) dados de apresenta&#231;&#227;o e diagn&#243;stico: sintomas iniciais e modalidade de imagem utilizada para o diagn&#243;stico; iii) dados cir&#250;rgicos: ano da interven&#231;&#227;o cir&#250;rgica, t&#233;cnica cir&#250;rgica e necessidade de procedimentos card&#237;acos adicionais; iv) par&#226;metros ecocardiogr&#225;ficos (registrados no pr&#233; e no p&#243;s-operat&#243;rio por meio de protocolos padronizados realizados por ecocardiografistas certificados): fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo (FEVE), di&#226;metro do AE, dimens&#245;es dos ventr&#237;culos esquerdo e direito (VD), fun&#231;&#227;o do VD e press&#227;o sist&#243;lica da art&#233;ria pulmonar (PSAP); v) caracter&#237;sticas tumorais: tamanho, morfologia, caracter&#237;sticas da superf&#237;cie, mobilidade, grau de obstru&#231;&#227;o e localiza&#231;&#227;o anat&#244;mica; vi) complica&#231;&#245;es e desfechos: eventos tromboemb&#243;licos, recorr&#234;ncia tumoral e eventos cardiovasculares adversos maiores.</p>
        <p>Eventos cardiovasculares maiores durante o seguimento foram identificados por meio de revis&#227;o abrangente dos registros cl&#237;nicos, resumos de alta hospitalar e, quando aplic&#225;vel, certid&#245;es oficiais de &#243;bito. Para garantir a precis&#227;o e consist&#234;ncia dos dados, todas as informa&#231;&#245;es coletadas foram revisadas de forma independente por dois pesquisadores. As discrep&#226;ncias foram resolvidas por consenso ou avaliadas por um terceiro pesquisador.</p>
        <p>Eventos tromboemb&#243;licos foram definidos como qualquer epis&#243;dio tromboemb&#243;lico clinicamente documentado confirmado por exames de imagem ou achados cir&#250;rgicos, incluindo acidente vascular encef&#225;lico isqu&#234;mico, ataque isqu&#234;mico transit&#243;rio, embolia sist&#234;mica ou oclus&#227;o arterial perif&#233;rica atribu&#237;vel a fragmentos tumorais ou trombos. Os eventos tamb&#233;m foram classificados de acordo com o momento de ocorr&#234;ncia em pr&#233;-operat&#243;rios, p&#243;s-operat&#243;rios precoces ou p&#243;s-operat&#243;rios tardios.</p>
      </sec>
      <sec>
        <title>An&#225;lise estat&#237;stica</title>
        <p>As vari&#225;veis cont&#237;nuas foram expressas como mediana e intervalo interquartil, uma vez que nenhuma apresentou distribui&#231;&#227;o normal de acordo com o teste de Kolmogorov&#8211;Smirnov. As vari&#225;veis categ&#243;ricas foram apresentadas como frequ&#234;ncias absolutas e porcentagens.</p>
        <p>As compara&#231;&#245;es entre grupos foram realizadas utilizando o teste de Mann&#8211;Whitney <italic>U</italic> para vari&#225;veis cont&#237;nuas e o teste do qui-quadrado ou o teste exato de Fisher para vari&#225;veis categ&#243;ricas, conforme apropriado. As compara&#231;&#245;es pareadas dos par&#226;metros ecocardiogr&#225;ficos pr&#233; e p&#243;s-operat&#243;rios foram avaliadas utilizando o teste de postos sinalizados de Wilcoxon. A sobrevida livre de eventos para desfechos tromboemb&#243;licos foi avaliada pelo m&#233;todo de Kaplan&#8211;Meier, com as curvas comparadas de forma descritiva.</p>
        <p>Para identificar preditores de eventos tromboemb&#243;licos, foi inicialmente realizada an&#225;lise de regress&#227;o de riscos proporcionais de Cox univariada. Vari&#225;veis com valor p &lt; 0,10 foram inclu&#237;das no modelo multivariado para determinar associa&#231;&#245;es independentes.</p>
        <p>Todas as an&#225;lises estat&#237;sticas foram realizadas utilizando o IBM SPSS Statistics for Windows, vers&#227;o 27.0 (IBM Corp., Armonk, N.Y., EUA). Um valor p bicaudal &lt; 0,05 foi considerado estatisticamente significativo.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <sec>
        <title>Popula&#231;&#227;o do estudo e caracter&#237;sticas basais</title>
        <p>A amostra do estudo foi composta por 74 pacientes diagnosticados com mixoma card&#237;aco de acordo com os crit&#233;rios de inclus&#227;o e exclus&#227;o predefinidos (<xref ref-type="fig" rid="f10">Diagrama 1</xref>). Os principais achados est&#227;o resumidos na <xref ref-type="fig" rid="f01">Figura Central</xref>.</p>
        <p>
          <fig id="f10">
            <caption>
              <title>Diagrama 1 &#8211; Fluxograma ilustrando o processo de sele&#231;&#227;o dos pacientes inclu&#237;dos no estudo. A maioria dos pacientes com seguimento inferior a 30 dias foi encaminhada de volta aos seus hospitais de origem ap&#243;s a primeira consulta p&#243;s-operat&#243;ria.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf01.tif"/></fig>
        </p>
        <p>As caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas basais est&#227;o apresentadas na <xref ref-type="table" rid="t1">Tabela 1</xref>. A coorte foi composta predominantemente por mulheres de meia-idade, com comorbidades cardiovasculares frequentes, particularmente hipertens&#227;o e dislipidemia. Entre os pacientes com neoplasias concomitantes, os tumores de tireoide e gastrointestinais foram os mais comuns. Dois pacientes apresentaram complexo de Carney confirmado, ambos com testes gen&#233;ticos positivos identificando muta&#231;&#245;es no gene <italic>PRKAR1A</italic>.</p>
        <p>
          <table-wrap id="t1">
            <label>Tabela 1</label>
            <caption>
              <title>&#8211; Caracter&#237;sticas basais por vari&#225;veis cl&#237;nicas e epidemiol&#243;gicas (n = 74)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Vari&#225;veis</th>
                  <th>Valor</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td colspan="2">
                    <bold>Dados cl&#237;nicos</bold>
                  </td>
                </tr>
                <tr>
                  <td>Idade (anos)</td>
                  <td align="center">60 (52-66)</td>
                </tr>
                <tr>
                  <td>HAS, n (%)</td>
                  <td align="center">56 (75,7)</td>
                </tr>
                <tr>
                  <td>Sexo feminino, n (%)</td>
                  <td align="center">51 (68,9)</td>
                </tr>
                <tr>
                  <td>Ra&#231;a branca, n (%)</td>
                  <td align="center">61 (82,4)</td>
                </tr>
                <tr>
                  <td>Ra&#231;a negra, n (%)</td>
                  <td align="center">6 (8,1)</td>
                </tr>
                <tr>
                  <td>Diabetes melito, n (%)</td>
                  <td align="center">24 (32,4)</td>
                </tr>
                <tr>
                  <td>Dislipidemia, n (%)</td>
                  <td align="center">42 (56,8)</td>
                </tr>
                <tr>
                  <td>Hist&#243;rico de tabagismo, n (%)</td>
                  <td align="center">32 (43,2)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Neoplasias concomitantes</bold>
                  </td>
                </tr>
                <tr>
                  <td>Tireoide, n (%)</td>
                  <td align="center">3 (4,1)</td>
                </tr>
                <tr>
                  <td>Mama, n (%)</td>
                  <td align="center">1 (1,4)</td>
                </tr>
                <tr>
                  <td>Outras, n (%)</td>
                  <td align="center">8 (10,8)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Manifesta&#231;&#245;es cl&#237;nicas</bold>
                  </td>
                </tr>
                <tr>
                  <td>Assintom&#225;tico, n (%)</td>
                  <td align="center">16 (21,8)</td>
                </tr>
                <tr>
                  <td>Dispneia, n (%)</td>
                  <td align="center">33 (44,6)</td>
                </tr>
                <tr>
                  <td>Sintomas constitucionais, n (%)</td>
                  <td align="center">13 (18,1)</td>
                </tr>
                <tr>
                  <td>Dor tor&#225;cica, n (%)</td>
                  <td align="center">6 (8,2)</td>
                </tr>
                <tr>
                  <td>Cardiopatia associada, n (%)</td>
                  <td align="center">15 (20,3)</td>
                </tr>
                <tr>
                  <td>Forma obstrutiva, n (%)</td>
                  <td align="center">27 (36,5)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Modalidade diagn&#243;stica pr&#233;-operat&#243;ria</bold>
                  </td>
                </tr>
                <tr>
                  <td>ETT, n (%)</td>
                  <td align="center">57 (77,0)</td>
                </tr>
                <tr>
                  <td>ETE, n (%)</td>
                  <td align="center">7 (9,5)</td>
                </tr>
                <tr>
                  <td>RMC, n (%)</td>
                  <td align="center">10 (13,5)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Diagn&#243;stico histopatol&#243;gico</bold>
                  </td>
                </tr>
                <tr>
                  <td>Mixoma isolado, n (%)</td>
                  <td align="center">69 (93,2)</td>
                </tr>
                <tr>
                  <td>M&#250;ltiplos mixomas, n (%)</td>
                  <td align="center">5 (6,8)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Procedimentos associados</bold>
                  </td>
                </tr>
                <tr>
                  <td>Cirurgia da valva mitral, n (%)</td>
                  <td align="center">14 (18,9)</td>
                </tr>
                <tr>
                  <td>Reconstru&#231;&#227;o com patch interatrial, n (%)</td>
                  <td align="center">11 (14,9)</td>
                </tr>
                <tr>
                  <td>Cirurgia da valva tric&#250;spide, n (%)</td>
                  <td align="center">2 (2,7)</td>
                </tr>
                <tr>
                  <td>Cirurgia da valva a&#243;rtica, n (%)</td>
                  <td align="center">1 (1,4)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Seguimento</bold>
                  </td>
                </tr>
                <tr>
                  <td>Dura&#231;&#227;o do seguimento (meses), mediana [IIQ]</td>
                  <td align="center">60 [40-79]</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN1">
                <p>ETE: ecocardiografia transesof&#225;gica; ETT: ecocardiografia transtor&#225;cica; HAS: hipertens&#227;o arterial sist&#234;mica; IIQ: intervalo interquartil; RMC: resson&#226;ncia magn&#233;tica card&#237;aca.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
      </sec>
      <sec>
        <title>Apresenta&#231;&#227;o cl&#237;nica</title>
        <p>Dispneia foi o sintoma inicial mais comum, refletindo a natureza obstrutiva dos mixomas card&#237;acos, particularmente daqueles localizados no AE. Notavelmente, 21,8% dos pacientes eram assintom&#225;ticos (<xref ref-type="fig" rid="f02">Figura 1</xref>), com tumores identificados incidentalmente em exames de imagem. Sintomas constitucionais, incluindo febre, perda de peso, anemia e astenia, foram documentados em 18,1% dos casos. Outros sintomas relatados inclu&#237;ram dor tor&#225;cica e palpita&#231;&#245;es, possivelmente relacionados a eventos tromboemb&#243;licos ou arritmias. Al&#233;m disso, 36,5% dos tumores apresentaram padr&#227;o obstrutivo, contribuindo para sintomas aos esfor&#231;os.</p>
        <p>
          <fig id="f02">
            <label>Figura 1</label>
            <caption>
              <title>&#8211; Sintomas de apresenta&#231;&#227;o em pacientes com mixoma card&#237;aco. Distribui&#231;&#227;o das principais manifesta&#231;&#245;es cl&#237;nicas na apresenta&#231;&#227;o inicial.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf02.tif"/></fig>
        </p>
      </sec>
      <sec>
        <title>Procedimentos cir&#250;rgicos e estrat&#233;gia operat&#243;ria</title>
        <p>Entre os 74 pacientes, a cirurgia da valva mitral foi o procedimento associado mais frequente (<xref ref-type="fig" rid="f03">Figura 2</xref>). Em 12 casos, a interven&#231;&#227;o foi necess&#225;ria devido ao envolvimento direto do mixoma nas c&#250;spides valvares, enquanto em dois pacientes o procedimento foi realizado de forma oportun&#237;stica. Outros procedimentos associados inclu&#237;ram corre&#231;&#227;o com <italic>patch</italic> interatrial, cirurgia da valva tric&#250;spide e cirurgia da valva a&#243;rtica.</p>
        <p>
          <fig id="f03">
            <label>Figura 2</label>
            <caption>
              <title>&#8211; Frequ&#234;ncia de procedimentos card&#237;acos concomitantes realizados durante a ressec&#231;&#227;o do mixoma.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf03.tif"/></fig>
        </p>
        <p>Todos os pacientes foram submetidos &#224; esternotomia mediana. Os mixomas do AE foram abordados por via transseptal atrav&#233;s do &#225;trio direito (AD), pela fossa oval quando havia suspeita de envolvimento septal ou implanta&#231;&#227;o de base ampla, permitindo ressec&#231;&#227;o em bloco com um segmento do septo interatrial seguido de fechamento com <italic>patch</italic>, ou por atriotomia esquerda direta nos casos de les&#245;es pediculadas ou localizadas na parede livre. Procedimentos valvares concomitantes foram realizados quando clinicamente indicados.</p>
      </sec>
      <sec>
        <title>Achados ecocardiogr&#225;ficos</title>
        <p>No pr&#233;-operat&#243;rio, a maioria dos pacientes apresentava fra&#231;&#227;o de eje&#231;&#227;o biventricular preservada e di&#226;metro diast&#243;lico do ventr&#237;culo esquerdo dentro da normalidade. Dilata&#231;&#227;o do AE foi observada em 41,9% dos casos, e PSAP elevada estava presente em 20,3% da coorte (<xref ref-type="table" rid="t2">Tabela 2</xref>).</p>
        <p>
          <table-wrap id="t2">
            <label>Tabela 2</label>
            <caption>
              <title>&#8211; Achados ecocardiogr&#225;ficos pr&#233; e p&#243;s-operat&#243;rios e caracter&#237;sticas dos mixomas</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Vari&#225;veis</th>
                  <th>n (%) ou mediana (IIQ)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td colspan="2">
                    <bold>Dados pr&#233;-operat&#243;rios</bold>
                  </td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>FEVE</bold>
                  </td>
                </tr>
                <tr>
                  <td><italic><bold> </bold></italic>Preservada</td>
                  <td align="center">69 (93,2)</td>
                </tr>
                <tr>
                  <td><italic><bold> </bold></italic>Levemente reduzida</td>
                  <td align="center">3 (4,1)</td>
                </tr>
                <tr>
                  <td><italic><bold> </bold></italic>Gravemente reduzida</td>
                  <td align="center">2 (2,7)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Di&#226;metro diast&#243;lico do VE</bold>
                  </td>
                </tr>
                <tr>
                  <td>Normal</td>
                  <td align="center">66 (89,2)</td>
                </tr>
                <tr>
                  <td>Dilatado</td>
                  <td align="center">8 (10,8)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>AE</bold>
                  </td>
                </tr>
                <tr>
                  <td>Normal</td>
                  <td align="center">43 (58,1)</td>
                </tr>
                <tr>
                  <td>Dilatado</td>
                  <td align="center">31 (41,9)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Fun&#231;&#227;o do VD</bold>
                  </td>
                </tr>
                <tr>
                  <td>Normal</td>
                  <td align="center">69 (93,2)</td>
                </tr>
                <tr>
                  <td>Disfun&#231;&#227;o leve</td>
                  <td align="center">3 (4,1)</td>
                </tr>
                <tr>
                  <td>Disfun&#231;&#227;o moderada</td>
                  <td align="center">2 (2,7)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>PSAP</bold>
                  </td>
                </tr>
                <tr>
                  <td>Normal</td>
                  <td align="center">59 (79,7)</td>
                </tr>
                <tr>
                  <td>Levemente aumentada</td>
                  <td align="center">6 (8,1)</td>
                </tr>
                <tr>
                  <td>Gravemente aumentada</td>
                  <td align="center">9 (12,2)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Caracter&#237;sticas do mixoma</bold>
                  </td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>FEVE</bold>
                  </td>
                </tr>
                <tr>
                  <td>Preservada</td>
                  <td align="center">56 (78,9)</td>
                </tr>
                <tr>
                  <td>Levemente reduzida</td>
                  <td align="center">4 (5,6)</td>
                </tr>
                <tr>
                  <td>Gravemente reduzida</td>
                  <td align="center">11 (15,5)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Di&#226;metro diast&#243;lico do VE</bold>
                  </td>
                </tr>
                <tr>
                  <td>Normal</td>
                  <td align="center">64 (86,5)</td>
                </tr>
                <tr>
                  <td>Dilatado</td>
                  <td align="center">6 (8,1)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>AE</bold>
                  </td>
                </tr>
                <tr>
                  <td>Normal</td>
                  <td align="center">47 (63,5)</td>
                </tr>
                <tr>
                  <td>Dilatado</td>
                  <td align="center">23 (31,1)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Fun&#231;&#227;o do VD</bold>
                  </td>
                </tr>
                <tr>
                  <td>Normal</td>
                  <td align="center">64 (86,5)</td>
                </tr>
                <tr>
                  <td>Disfun&#231;&#227;o leve</td>
                  <td align="center">6 (8,1)</td>
                </tr>
                <tr>
                  <td>Disfun&#231;&#227;o grave</td>
                  <td align="center">1 (1,4)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>PASP</bold>
                  </td>
                </tr>
                <tr>
                  <td>Normal</td>
                  <td align="center">57 (82,6)</td>
                </tr>
                <tr>
                  <td>Levemente aumentada</td>
                  <td align="center">9 (12,2)</td>
                </tr>
                <tr>
                  <td>Gravemente aumentada</td>
                  <td align="center">3 (4,1)</td>
                </tr>
                <tr>
                  <td>
                    <bold>Caracter&#237;sticas do mixoma</bold>
                  </td>
                  <td> </td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Localiza&#231;&#227;o</bold>
                  </td>
                </tr>
                <tr>
                  <td>AE</td>
                  <td align="center">65 (87,8)</td>
                </tr>
                <tr>
                  <td>AD</td>
                  <td align="center">4 (5,4)</td>
                </tr>
                <tr>
                  <td>Biatrial</td>
                  <td align="center">2 (2,7)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Morfologia</bold>
                  </td>
                </tr>
                <tr>
                  <td>Pediculado</td>
                  <td align="center">49 (68,1)</td>
                </tr>
                <tr>
                  <td>S&#233;ssil</td>
                  <td align="center">23 (31,9)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Superf&#237;cie da les&#227;o</bold>
                  </td>
                </tr>
                <tr>
                  <td>Lisa</td>
                  <td align="center">59 (79,7)</td>
                </tr>
                <tr>
                  <td>Vilosa</td>
                  <td align="center">15 (20,3)</td>
                </tr>
                <tr>
                  <td colspan="2">
                    <bold>Tamanho do tumor</bold>
                  </td>
                </tr>
                <tr>
                  <td>Comprimento (mm)</td>
                  <td align="center">45 (29-57)</td>
                </tr>
                <tr>
                  <td>Largura (mm)</td>
                  <td align="center">35 (22-42)</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN2">
                <p>AD: &#225;trio direito; AE: &#225;trio esquerdo; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo (VE); IIQ: intervalo interquartil; PSAP: press&#227;o sist&#243;lica da art&#233;ria pulmonar; VD: ventr&#237;culo direito.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>No p&#243;s-operat&#243;rio, a maioria dos pacientes manteve fra&#231;&#227;o de eje&#231;&#227;o biventricular preservada, embora a propor&#231;&#227;o com redu&#231;&#245;es graves da FEVE tenha aumentado em 12,8%. O tamanho normal do AE aumentou em 10,8%, e a normaliza&#231;&#227;o da PSAP foi observada em 6% dos pacientes (<xref ref-type="table" rid="t2">Tabela 2</xref>).</p>
        <p>Os mixomas estavam predominantemente localizados no AE (<xref ref-type="fig" rid="f04">Figura 3</xref>), geralmente com superf&#237;cie lisa, e apresentaram dimens&#245;es medianas de 45 &#215; 35 mm (<xref ref-type="table" rid="t2">Tabela 2</xref>). O teste de postos sinalizados de Wilcoxon (<xref ref-type="fig" rid="f05">Figura 4</xref>) demonstrou diferen&#231;as estatisticamente significativas entre as medidas pr&#233; e p&#243;s-operat&#243;rias tanto para a FEVE quanto para a PSAP. Especificamente, ambos os par&#226;metros apresentaram redu&#231;&#245;es significativas, com a PSAP diminuindo principalmente em pacientes com mixomas obstrutivos.</p>
        <p>
          <fig id="f04">
            <label>Figura 3</label>
            <caption>
              <title>&#8211; Morfologia tumoral e principais localiza&#231;&#245;es anat&#244;micas.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf04.tif"/></fig>
        </p>
        <p>
          <fig id="f05">
            <label>Figura 4</label>
            <caption>
              <title>&#8211; Compara&#231;&#227;o dos par&#226;metros ecocardiogr&#225;ficos pr&#233; e p&#243;s-operat&#243;rios. Compara&#231;&#227;o da FEVE e da PSAP demonstrando redu&#231;&#227;o significativa da PSAP no p&#243;s-operat&#243;rio e queda transit&#243;ria da FEVE. FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo; PSAP: press&#227;o sist&#243;lica da art&#233;ria pulmonar.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf05.tif"/></fig>
        </p>
      </sec>
      <sec>
        <title>Complica&#231;&#245;es e desfechos cl&#237;nicos</title>
        <p>Eventos tromboemb&#243;licos foram observados em 18,9% dos pacientes, sendo o acidente vascular encef&#225;lico isqu&#234;mico a manifesta&#231;&#227;o mais frequente. Todos os casos de AVC ocorreram em pacientes com fibrila&#231;&#227;o atrial pr&#233;-operat&#243;ria. Os eventos ocorreram em 8,1% no pr&#233;-operat&#243;rio e em 5,4% no p&#243;s-operat&#243;rio (<xref ref-type="table" rid="t3">Tabela 3</xref>). Complica&#231;&#245;es menos frequentes inclu&#237;ram fibrila&#231;&#227;o atrial, choque obstrutivo e s&#237;ndrome da veia cava superior (<xref ref-type="fig" rid="f06">Figura 5</xref>).</p>
        <p>
          <table-wrap id="t3">
            <label>Tabela 3</label>
            <caption>
              <title>&#8211; Desfechos de morbidade e mortalidade ap&#243;s ressec&#231;&#227;o de mixoma</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Desfecho</th>
                  <th>n (%)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>
                    <bold>Eventos tromboemb&#243;licos</bold>
                  </td>
                  <td align="center">14 (18,9)</td>
                </tr>
                <tr>
                  <td>Embolia pulmonar</td>
                  <td align="center">2 (2,7)</td>
                </tr>
                <tr>
                  <td>Acidente vascular encef&#225;lico</td>
                  <td align="center">10 (13,5)</td>
                </tr>
                <tr>
                  <td>Infarto do mioc&#225;rdio emb&#243;lico</td>
                  <td align="center">2 (2,7)</td>
                </tr>
                <tr>
                  <td>
                    <bold>Recorr&#234;ncia do mixoma</bold>
                  </td>
                  <td align="center">2 (2,7)</td>
                </tr>
                <tr>
                  <td>
                    <bold>Fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria</bold>
                  </td>
                  <td align="center">6 (8,1)</td>
                </tr>
                <tr>
                  <td>
                    <bold>Choque obstrutivo</bold>
                  </td>
                  <td align="center">2 (2,7)</td>
                </tr>
                <tr>
                  <td>
                    <bold>S&#237;ndrome da veia cava superior</bold>
                  </td>
                  <td align="center">1 (1,4)</td>
                </tr>
                <tr>
                  <td>
                    <bold>Mortalidade</bold>
                  </td>
                  <td align="center">1 (1,4)</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </p>
        <p>
          <fig id="f06">
            <label>Figura 5</label>
            <caption>
              <title>&#8211; Resumo dos eventos tromboemb&#243;licos e complica&#231;&#245;es p&#243;s-operat&#243;rias.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf06.tif"/></fig>
        </p>
        <p>A taxa de mortalidade foi baixa, com apenas um &#243;bito registrado durante um per&#237;odo mediano de seguimento de 60 meses. A sobrevida livre de eventos foi adicionalmente ilustrada por meio de uma curva de Kaplan&#8211;Meier, que demonstrou um decl&#237;nio progressivo na liberdade de eventos tromboemb&#243;licos ao longo do tempo (<xref ref-type="fig" rid="f07">Figura 6</xref>).</p>
        <p>
          <fig id="f07">
            <label>Figura 6</label>
            <caption>
              <title>&#8211; Curva de Kaplan&#8211;Meier para sobrevida livre de eventos tromboemb&#243;licos. Sobrevida livre de eventos at&#233; 60 meses, mostrando que a maioria dos pacientes permaneceu livre de eventos tromboemb&#243;licos durante o seguimento.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf07.tif"/></fig>
        </p>
      </sec>
      <sec>
        <title>Recorr&#234;ncia tumoral</title>
        <p>A recorr&#234;ncia do mixoma foi incomum. Ambos os casos recorrentes envolveram m&#250;ltiplos epis&#243;dios (tr&#234;s recorr&#234;ncias cada) e estavam associados ao complexo de Carney. Um caso envolveu uma paciente do sexo feminino de 18 anos com tr&#234;s recorr&#234;ncias ventriculares esquerdas, e o outro um paciente do sexo masculino de 44 anos com envolvimento sequencial do AE, AD e, por fim, recorr&#234;ncia biatrial.</p>
      </sec>
      <sec>
        <title>An&#225;lise comparativa de acordo com eventos tromboemb&#243;licos</title>
        <p>Pacientes que apresentaram eventos tromboemb&#243;licos (n = 14) foram comparados com aqueles que n&#227;o apresentaram (n = 60) utilizando os testes do qui-quadrado ou exato de Fisher para vari&#225;veis categ&#243;ricas e o teste de Mann&#8211;Whitney <italic>U</italic> para vari&#225;veis cont&#237;nuas devido &#224; distribui&#231;&#227;o n&#227;o normal (<xref ref-type="fig" rid="f08">Figuras 7</xref> e <xref ref-type="fig" rid="f09">8</xref>). A idade foi semelhante entre os grupos (mediana: 57,5 vs. 60,5 anos). Diabetes melito foi significativamente mais prevalente no grupo sem eventos (7,1% vs. 38,3%).</p>
        <p>
          <fig id="f08">
            <label>Figura 7</label>
            <caption>
              <title>&#8211; Boxplots das vari&#225;veis cl&#237;nicas de acordo com a ocorr&#234;ncia de eventos tromboemb&#243;licos. Distribui&#231;&#227;o da idade e do tamanho tumoral estratificada pela ocorr&#234;ncia de eventos tromboemb&#243;licos.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf08.tif"/></fig>
        </p>
        <p>
          <fig id="f09">
            <label>Figura 8</label>
            <caption>
              <title>&#8211; Compara&#231;&#227;o das caracter&#237;sticas cl&#237;nicas e tumorais de acordo com a ocorr&#234;ncia de eventos tromboemb&#243;licos. FA: fibrila&#231;&#227;o atrial.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf09.tif"/></fig>
        </p>
        <p>Outros fatores, incluindo tamanho tumoral, localiza&#231;&#227;o e par&#226;metros ecocardiogr&#225;ficos (FEVE, dilata&#231;&#227;o do AE e PSAP), n&#227;o apresentaram diferen&#231;as estatisticamente significativas entre os grupos (<xref ref-type="table" rid="t4">Tabela 4</xref>). Esses achados s&#227;o consistentes com os resultados do modelo de riscos proporcionais de Cox apresentados nas <xref ref-type="table" rid="t5">Tabelas 5</xref> e <xref ref-type="table" rid="t6">6</xref>, nos quais diabetes e fibrila&#231;&#227;o atrial emergiram como preditores independentes de eventos emb&#243;licos.</p>
        <p>
          <table-wrap id="t4">
            <label>Tabela 4</label>
            <caption>
              <title>&#8211; Compara&#231;&#227;o entre pacientes com e sem eventos tromboemb&#243;licos</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Vari&#225;vel</th>
                  <th>Evento (n = 14)</th>
                  <th>Sem evento (n = 60)</th>
                  <th>Valor p</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Idade, anos</td>
                  <td align="center">57,5 (44,2-62,0)</td>
                  <td align="center">60,5 (52,8-67,0)</td>
                  <td align="center">0,120</td>
                </tr>
                <tr>
                  <td>Sexo feminino</td>
                  <td align="center">11 (78,6%)</td>
                  <td align="center">40 (66,7%)</td>
                  <td align="center">0,520</td>
                </tr>
                <tr>
                  <td>Ra&#231;a branca</td>
                  <td align="center">13 (92,9%)</td>
                  <td align="center">48 (80,0%)</td>
                  <td align="center">0,440</td>
                </tr>
                <tr>
                  <td>Diabetes melito</td>
                  <td align="center">1 (7,1%)</td>
                  <td align="center">23 (38,3%)</td>
                  <td align="center">0,020</td>
                </tr>
                <tr>
                  <td>HAS</td>
                  <td align="center">9 (64,3%)</td>
                  <td align="center">47 (78,3%)</td>
                  <td align="center">0,300</td>
                </tr>
                <tr>
                  <td>Tumor pediculado</td>
                  <td align="center">12 (85,7%)</td>
                  <td align="center">37 (63,8%)</td>
                  <td align="center">0,200</td>
                </tr>
                <tr>
                  <td>Padr&#227;o obstrutivo</td>
                  <td align="center">8 (57,1%)</td>
                  <td align="center">19 (31,7%)</td>
                  <td align="center">0,120</td>
                </tr>
                <tr>
                  <td>FA p&#243;s-operat&#243;ria</td>
                  <td align="center">5 (35,7%)</td>
                  <td align="center">1 (1,6%)</td>
                  <td align="center">0,002</td>
                </tr>
                <tr>
                  <td>Comprimento tumoral (mm)</td>
                  <td align="center">42,5 (35,0-53,8)</td>
                  <td align="center">45,0 (27,0-57,8)</td>
                  <td align="center">0,910</td>
                </tr>
                <tr>
                  <td>Largura tumoral (mm)</td>
                  <td align="center">32,5 (26,2-43,8)</td>
                  <td align="center">35,0 (20,8-42,0)</td>
                  <td align="center">0,530</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN3">
                <p>Os valores s&#227;o apresentados como n (%) para vari&#225;veis categ&#243;ricas e mediana [IIQ] para vari&#225;veis cont&#237;nuas. Os valores de p foram calculados utilizando o teste exato de Fisher ou o teste de Mann&#8211;Whitney U, conforme apropriado. FA: fibrila&#231;&#227;o atrial; HAS: hipertens&#227;o arterial sist&#234;mica; IIQ: intervalo interquartil.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>
          <table-wrap id="t5">
            <label>Tabela 5</label>
            <caption>
              <title>&#8211; Regress&#227;o de riscos proporcionais de Cox univariada para eventos tromboemb&#243;licos</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Vari&#225;vel</th>
                  <th>HR</th>
                  <th>95% CI</th>
                  <th>Valor p</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Idade (por ano)</td>
                  <td align="center">0,96</td>
                  <td align="center">0,92-1,00</td>
                  <td align="center">0,06</td>
                </tr>
                <tr>
                  <td>Dislipidemia</td>
                  <td align="center">1,02</td>
                  <td align="center">0,31-3,30</td>
                  <td align="center">0,97</td>
                </tr>
                <tr>
                  <td>HAS</td>
                  <td align="center">2,00</td>
                  <td align="center">0,57-7,03</td>
                  <td align="center">0,27</td>
                </tr>
                <tr>
                  <td>FEVE reduzida no pr&#233;-operat&#243;rio</td>
                  <td align="center">2,22</td>
                  <td align="center">0,62-7,86</td>
                  <td align="center">0,21</td>
                </tr>
                <tr>
                  <td>Di&#226;metro diast&#243;lico do VE (dilatado)</td>
                  <td align="center">0,33</td>
                  <td align="center">0,06-1,60</td>
                  <td align="center">0,17</td>
                </tr>
                <tr>
                  <td>PSAP aumentada</td>
                  <td align="center">1,08</td>
                  <td align="center">0,47-2,49</td>
                  <td align="center">0,84</td>
                </tr>
                <tr>
                  <td>Mixoma m&#243;vel</td>
                  <td align="center">1,87</td>
                  <td align="center">0,52-6,71</td>
                  <td align="center">0,33</td>
                </tr>
                <tr>
                  <td>Comprimento tumoral (mm)</td>
                  <td align="center">0,99</td>
                  <td align="center">0,96-1,02</td>
                  <td align="center">0,67</td>
                </tr>
                <tr>
                  <td>Largura tumoral (mm)</td>
                  <td align="center">1,00</td>
                  <td align="center">0,96-1,03</td>
                  <td align="center">0,98</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN4">
                <p>IC: intervalo de confian&#231;a; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo (VE); HAS: hipertens&#227;o arterial sist&#234;mica; HR: raz&#227;o de risco; PSAP: press&#227;o sist&#243;lica da art&#233;ria pulmonar.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>
          <table-wrap id="t6">
            <label>Tabela 6</label>
            <caption>
              <title>&#8211; Regress&#227;o de riscos proporcionais de Cox multivariada para eventos tromboemb&#243;licos</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Vari&#225;vel</th>
                  <th>HR</th>
                  <th>95% CI</th>
                  <th>Valor p</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Diabetes melito</td>
                  <td align="center">0,11</td>
                  <td align="center">0,006-0,740</td>
                  <td align="center">&lt; 0,05</td>
                </tr>
                <tr>
                  <td>FA p&#243;s-operat&#243;ria</td>
                  <td align="center">6,74</td>
                  <td align="center">1,49-30,51</td>
                  <td align="center">&lt; 0,05</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN5">
                <p>IC: intervalo de confian&#231;a; FA: fibrila&#231;&#227;o atrial; HR: raz&#227;o de risco.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
      </sec>
      <sec>
        <title>Preditores de eventos tromboemb&#243;licos</title>
        <p>O modelo de regress&#227;o de Cox multivariado (<xref ref-type="table" rid="t6">Tabela 6</xref>) mostrou que a dilata&#231;&#227;o do AE esteve associada a um menor risco, embora n&#227;o significativo, de eventos tromboemb&#243;licos. Diabetes e fibrila&#231;&#227;o atrial estiveram significativamente associados ao risco de eventos tromboemb&#243;licos (HR = 0,11; IC 95%: 0,006-0,740; p &lt; 0,05). Tumores m&#243;veis apresentaram tend&#234;ncia a maior risco de tromboembolismo, embora esse aumento n&#227;o tenha sido estatisticamente significativo.</p>
        <p>An&#225;lises univariadas ou multivariadas de recorr&#234;ncia do mixoma e mortalidade n&#227;o foram realizadas devido ao pequeno n&#250;mero de eventos. Foi conduzida uma an&#225;lise direcionada para explorar vari&#225;veis associadas a maior risco de eventos tromboemb&#243;licos. A an&#225;lise univariada identificou o diabetes como um poss&#237;vel fator protetor, em contraste com seu papel estabelecido no aumento do risco tromboemb&#243;lico na popula&#231;&#227;o geral. Esse achado sugere que o pr&#243;prio mixoma pode ser o principal determinante do risco tromboemb&#243;lico nessa popula&#231;&#227;o, refor&#231;ando a justificativa para a remo&#231;&#227;o cir&#250;rgica precoce.</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>Este estudo refor&#231;a o papel cr&#237;tico da interven&#231;&#227;o cir&#250;rgica precoce no manejo dos mixomas card&#237;acos e destaca sua associa&#231;&#227;o com excelentes desfechos em longo prazo.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Nesta coorte de 74 pacientes, predominantemente com tumores espor&#225;dicos, o seguimento mediano foi de 60 meses, durante os quais a sobrevida atingiu 98,6% e a recorr&#234;ncia tumoral permaneceu baixa, em 2,7%. Esses achados s&#227;o consistentes com relatos pr&#233;vios que demonstram a efic&#225;cia da ressec&#231;&#227;o imediata na redu&#231;&#227;o da mortalidade e da recorr&#234;ncia, particularmente quando se alcan&#231;a a excis&#227;o completa do tumor e de sua base de implanta&#231;&#227;o.<sup><xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup></p>
      <p>A menor frequ&#234;ncia de sintomas constitucionais observada em nossa coorte contrasta com a maior preval&#234;ncia relatada em outras s&#233;ries. Essa diferen&#231;a pode ser explicada pelos padr&#245;es de encaminhamento, uma vez que muitos pacientes foram avaliados em nosso centro em est&#225;gios mais avan&#231;ados da doen&#231;a, quando manifesta&#231;&#245;es obstrutivas e emb&#243;licas podem predominar sobre sintomas sist&#234;micos.<sup><xref ref-type="bibr" rid="B10">10</xref>-<xref ref-type="bibr" rid="B12">12</xref></sup></p>
      <p>Todos os procedimentos em nossa coorte foram realizados por esternotomia mediana, que permanece a abordagem padr&#227;o em nossa institui&#231;&#227;o para garantir exposi&#231;&#227;o adequada e excis&#227;o tumoral completa. T&#233;cnicas minimamente invasivas e rob&#243;ticas, como aquelas que utilizam o sistema DaVinci Xi<sup>&#174;</sup>, n&#227;o estavam dispon&#237;veis durante o per&#237;odo do estudo. No entanto, essas abordagens t&#234;m sido associadas a tempos de recupera&#231;&#227;o mais curtos e melhor qualidade de vida p&#243;s-operat&#243;ria em centros selecionados.<sup><xref ref-type="bibr" rid="B13">13</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup></p>
      <p>O septo interatrial, particularmente a fossa oval, &#233; reconhecido como o local de origem mais comum dos mixomas card&#237;acos. A ressec&#231;&#227;o em bloco com remo&#231;&#227;o de uma por&#231;&#227;o do septo interatrial seguida de reconstru&#231;&#227;o com <italic>patch</italic> &#233; frequentemente recomendada para minimizar a recorr&#234;ncia. Em nossa coorte, apenas 14,9% dos pacientes foram submetidos &#224; reconstru&#231;&#227;o com <italic>patch</italic> interatrial. Essa taxa relativamente baixa reflete uma estrat&#233;gia cir&#250;rgica individualizada e baseada na pr&#225;tica real em nosso centro terci&#225;rio, onde as decis&#245;es operat&#243;rias foram guiadas pelo tamanho tumoral, morfologia da implanta&#231;&#227;o e achados intraoperat&#243;rios.<sup><xref ref-type="bibr" rid="B15">15</xref>-<xref ref-type="bibr" rid="B18">18</xref></sup></p>
      <p>Em muitos casos, tumores pequenos e pediculados permitiram excis&#227;o completa com margem estreita e fechamento septal prim&#225;rio, particularmente em pacientes idosos ou de alto risco.<sup><xref ref-type="bibr" rid="B18">18</xref>-<xref ref-type="bibr" rid="B20">20</xref></sup></p>
      <p>A incid&#234;ncia de eventos tromboemb&#243;licos em nossa coorte (18,9%), principalmente acidente vascular encef&#225;lico isqu&#234;mico (13,5%), &#233; compar&#225;vel &#224;s taxas relatadas em estudos anteriores. Stefanou et al. (2018) descreveram uma taxa de AVC de 11% entre pacientes com mixomas card&#237;acos, enquanto Pinede et al. (2001) relataram eventos tromboemb&#243;licos em aproximadamente 30% dos casos. Importante destacar que nossa an&#225;lise multivariada por regress&#227;o de Cox n&#227;o identificou a localiza&#231;&#227;o tumoral nem a idade como preditores significativos de risco tromboemb&#243;lico. A mobilidade tumoral apresentou tend&#234;ncia a aumento do risco, embora essa associa&#231;&#227;o n&#227;o tenha alcan&#231;ado signific&#226;ncia estat&#237;stica, provavelmente devido ao n&#250;mero limitado de eventos. Essa observa&#231;&#227;o &#233; consistente com a metan&#225;lise de Liu et al. (2020), que destacou a aus&#234;ncia de preditores morfol&#243;gicos consistentes entre os estudos.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B22">22</xref></sup></p>
      <p>A fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria emergiu como preditor independente de eventos tromboemb&#243;licos em nossa coorte, com aumento superior a seis vezes no risco. Esse achado refor&#231;a a associa&#231;&#227;o bem estabelecida entre fibrila&#231;&#227;o atrial de in&#237;cio recente e maior risco emb&#243;lico ap&#243;s cirurgia card&#237;aca e ressalta a import&#226;ncia do monitoramento rigoroso do ritmo e da anticoagula&#231;&#227;o oportuna nessa popula&#231;&#227;o.<sup><xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B24">24</xref></sup></p>
      <p>No modelo multivariado, o diabetes mellitus esteve associado a menor risco de eventos tromboemb&#243;licos. Essa observa&#231;&#227;o n&#227;o tem sido consistentemente relatada em estudos pr&#233;vios e deve ser interpretada com cautela. &#201; prov&#225;vel que tenha car&#225;ter explorat&#243;rio e potencialmente confuso, em vez de indicar um verdadeiro efeito biol&#243;gico protetor.<sup><xref ref-type="bibr" rid="B25">25</xref>-<xref ref-type="bibr" rid="B27">27</xref></sup> Poss&#237;veis explica&#231;&#245;es incluem monitoramento cl&#237;nico mais pr&#243;ximo, uso mais frequente de terapia antitromb&#243;tica ou estatinas, ou diferen&#231;as n&#227;o mensuradas no manejo do risco cardiovascular entre pacientes diab&#233;ticos. Devido ao pequeno n&#250;mero de eventos e ao delineamento retrospectivo, esse achado deve ser considerado gerador de hip&#243;teses e requer confirma&#231;&#227;o em estudos prospectivos maiores.</p>
      <p>A coorte demonstrou redu&#231;&#227;o significativa da PSAP no p&#243;s-operat&#243;rio (Wilcoxon Z = &#8722;2,070; p = 0,038), consistente com o al&#237;vio da obstru&#231;&#227;o ao fluxo de entrada no AE, particularmente em pacientes com mixomas obstrutivos.</p>
      <p>Por outro lado, a FEVE diminuiu no per&#237;odo p&#243;s-operat&#243;rio precoce (FEVE preservada 93,2% no pr&#233;-operat&#243;rio vs. 78,9% no p&#243;s-operat&#243;rio; redu&#231;&#227;o grave 2,7% vs. 15,5%; Wilcoxon Z = 3,052; p = 0,002). Esse padr&#227;o provavelmente reflete disfun&#231;&#227;o ventricular transit&#243;ria perioperat&#243;ria, e n&#227;o deteriora&#231;&#227;o sustentada da fun&#231;&#227;o sist&#243;lica, especialmente considerando que os ecocardiogramas p&#243;s-operat&#243;rios foram realizados dentro de 30 dias ap&#243;s a cirurgia. Esses achados sugerem que a cirurgia alivia prontamente a sobrecarga hemodin&#226;mica, enquanto a recupera&#231;&#227;o da fun&#231;&#227;o ventricular pode ocorrer de forma mais gradual e requer acompanhamento ecocardiogr&#225;fico longitudinal.</p>
      <p>Mikus et al. (2025) relataram FEVE preservada no per&#237;odo p&#243;s-operat&#243;rio, indicando que as altera&#231;&#245;es observadas em nossa coorte podem representar modifica&#231;&#245;es precoces e transit&#243;rias, e n&#227;o comprometimento em longo prazo.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
      <p>Por fim, a taxa de sobrevida observada em nosso estudo (98,6% ao longo de um seguimento mediano de 60 meses) &#233; favor&#225;vel quando comparada a s&#233;ries cir&#250;rgicas globais, incluindo a sobrevida em longo prazo de 93%&#8211;97% relatada por Jiang et al. (2019) e Perek et al. (2011). Esses resultados refor&#231;am a seguran&#231;a e a efic&#225;cia em longo prazo do tratamento cir&#250;rgico dos mixomas card&#237;acos quando realizado em centros especializados.<sup><xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B28">28</xref></sup></p>
      <sec>
        <title>Limita&#231;&#245;es do estudo</title>
        <p>O delineamento retrospectivo, de centro &#250;nico, e o tamanho relativamente pequeno da amostra podem limitar a generaliza&#231;&#227;o desses achados. Al&#233;m disso, devido ao longo per&#237;odo de coleta de dados inerente a estudos retrospectivos, algumas vari&#225;veis potencialmente relevantes, como morfologia tumoral e caracter&#237;sticas da superf&#237;cie, que podem estar associadas &#224; mobilidade e ao risco tromboemb&#243;lico, n&#227;o foram consistentemente documentadas.</p>
        <p>Al&#233;m disso, a redu&#231;&#227;o p&#243;s-operat&#243;ria observada na FEVE pode refletir parcialmente les&#227;o mioc&#225;rdica perioperat&#243;ria ou infarto, o que n&#227;o foi sistematicamente avaliado ou registrado em nossa coorte, limitando a interpreta&#231;&#227;o desse achado.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>Nosso estudo refor&#231;a que o mixoma card&#237;aco, quando tratado precocemente, est&#225; associado a excelente progn&#243;stico. Ao mesmo tempo, destaca o risco tromboemb&#243;lico significativo relacionado a essa condi&#231;&#227;o, que parece ser amplamente independente da morfologia tumoral. Esses achados apoiam a ressec&#231;&#227;o cir&#250;rgica precoce, mesmo em pacientes assintom&#225;ticos e naqueles com les&#245;es n&#227;o obstrutivas. O acompanhamento cont&#237;nuo permanece essencial para monitorar complica&#231;&#245;es tardias e poss&#237;vel recorr&#234;ncia.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>Refer&#234;ncias</title>
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  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20250596i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Operative Experience and Clinical Outcomes in Cardiac Myxoma Patients: A Retrospective Single-Center Study</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0007-5938-8053</contrib-id>
          <name>
            <surname>Madogolele</surname>
            <given-names>Heleut&#233;rio da Concei&#231;&#227;o Nicolau</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-7550-8912</contrib-id>
          <name>
            <surname>Barroso</surname>
            <given-names>Manuela Cristina Ribeiro Dias</given-names>
          </name>
          <role>Acquisition of data</role>
          <role>Writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mej&#237;a</surname>
            <given-names>Hern&#225;n Patricio Garc&#237;a</given-names>
          </name>
          <role>Acquisition of data</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0191-7358</contrib-id>
          <name>
            <surname>Espinoza</surname>
            <given-names>Cristhian</given-names>
          </name>
          <role>Statistical analysis</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0003-7829-4408</contrib-id>
          <name>
            <surname>Correia</surname>
            <given-names>Vinicius Machado</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Madrini</surname>
            <given-names>Vagner</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Duncan</surname>
            <given-names>Jos&#233; Augusto</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Dias</surname>
            <given-names>Ricardo Ribeiro</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9323-8805</contrib-id>
          <name>
            <surname>Fernandes</surname>
            <given-names>F&#225;bio</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001"><label>Mailing Address:</label> Heleut&#233;rio da Concei&#231;&#227;o Nicolau Madogolele Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo&#8211; Av. Dr. En&#233;as Carvalho de Aguiar, 44. Postal Code 05410-000, Cerqueira C&#233;sar, S&#227;o Paulo, SP &#8211; Brazil E-mail: heleuteriodaconceicao@gmail.com </corresp>
        <fn fn-type="coi-statement">
          <label>Potential conflict of interest:</label>
          <p> No potential conflict of interest relevant to this article was reported.</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor responsible for the review:</label>
          <p> Henrique Ribeiro</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background</title>
          <p> Cardiac myxoma is the second most common primary cardiac tumor; however, contemporary single-center series integrating operative strategy with clinical outcomes remain limited.</p>
        </sec>
        <sec>
          <title>Objectives</title>
          <p> To describe the operative approaches and clinical outcomes of patients undergoing surgical resection of cardiac myxomas at a single center.</p>
        </sec>
        <sec>
          <title>Methods</title>
          <p> We conducted a retrospective review of 74 consecutive patients who underwent surgical resection of histologically confirmed cardiac myxomas between 2014 and 2024 at a tertiary referral center in Brazil. Clinical, imaging, surgical, and follow-up data were collected. The primary outcome was the incidence of thromboembolic events. A significance level of 5% was adopted for all statistical analyses.</p>
        </sec>
        <sec>
          <title>Results</title>
          <p> The median age was 60 years (range 52-66), and 68.9% of patients were female. Median follow-up was 60 months (interquartile range 40-79). Thromboembolic events occurred in 14 patients (18.9%), including stroke (13.5%), embolic myocardial infarction (2.7%), and pulmonary embolism (2.7%). In multivariable Cox analysis, diabetes was independently associated with a lower hazard of thromboembolic events (HR 0.11; 95% CI 0.006-0.740; p &lt; 0.05), whereas postoperative atrial fibrillation was associated with a higher thromboembolic risk (HR 6.74; 95% CI 1.490-30.510; p &lt; 0.05). Tumor recurrence occurred in 2.7% of cases. Only one death was recorded during follow-up.</p>
        </sec>
        <sec>
          <title>Conclusion</title>
          <p> Cardiac myxomas are associated with significant thromboembolic and hemodynamic risks. Early surgical resection provides excellent long-term outcomes and should be considered even in asymptomatic patients. In our cohort, tumor morphology showed a non-significant trend toward a higher risk of thromboembolic events.</p>
        </sec>
      </abstract>
      <abstract abstract-type="graphical">
        <p>
          <fig id="f01001">
            <label>Central Illustration:</label>
            <caption>
              <title>Operative Experience and Clinical Outcomes in Cardiac Myxoma Patients: A Retrospective Single-Center Study</title>
            </caption>
            <attrib>AF: atrial fibrillation; DM: diabetes mellitus; HR: hazard ratio; PASP: pulmonary artery systolic pressure.</attrib>
            <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf01-en.tif"/></fig>
        </p>
      </abstract>
      <abstract abstract-type="key-points">
        <title>Highlights/Key points</title>
        <p>&#8226;Cardiac myxomas are the second most common primary cardiac tumors, and surgical resection remains the treatment of choice.</p>
        <p>&#8226;In this single-center study of 74 patients, operative outcomes were excellent, with a low recurrence rate (2.7%) and high long-term survival (98.6%).</p>
        <p>&#8226;Thromboembolic events occurred in 18.9% of patients, with diabetes associated with a lower hazard of these events.</p>
        <p>&#8226;These findings support the safety and long-term effectiveness of surgical resection for cardiac myxomas, even with conservative use of interatrial patch reconstruction.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Mixoma</kwd>
        <kwd>Doen&#231;as Cardiovasculares</kwd>
        <kwd>Surgery</kwd>
        <kwd>Latin America</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Cardiac myxomas are the second most common primary cardiac tumors, after papillary fibroelastomas; however, they remain the most frequent symptomatic and surgically treated cardiac neoplasms, accounting for the majority of resected benign cardiac tumors in clinical practice.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Despite their benign histology, their intracardiac location can lead to substantial morbidity, including obstruction, embolic events, and systemic manifestations.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> With an estimated annual incidence of 0.5-1 case per million, these rare tumors occur predominantly in women between the third and sixth decades of life and are most commonly located in the left atrium (LA).<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> Surgical resection is the treatment of choice and is associated with favorable outcomes, although recurrence remains a concern, particularly in familial cases.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup></p>
        <p>In Latin America, especially in Brazil, cardiac myxomas account for approximately 70%-75% of benign cardiac tumors reported in surgical series. However, their overall population incidence remains low, at approximately 0.5-1 case per million per year. Therefore, although rare in the general population, they represent the most common surgically treated cardiac neoplasm in the region.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
        <p>This study presents clinical and surgical data on cardiac myxomas from a Latin American perspective, where available evidence remains limited. By examining recurrence patterns and predictors of adverse outcomes, we aim to provide region-specific insights that may improve risk assessment and inform the long-term management of affected patients.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <sec>
          <title>Study design and ethical approval</title>
          <p>This retrospective study analyzed the medical records of patients diagnosed with cardiac myxomas and treated at a tertiary hospital in Brazil between 2014 and 2024. The study protocol was approved by the Institutional Review Board of the same institution (Protocol SDC-COP 26501, approved on January 12, 2025). All data were fully anonymized to ensure patient confidentiality in accordance with ethical standards.</p>
        </sec>
        <sec>
          <title>Study population</title>
          <p>Eligible participants were adult patients (&#8805; 18 years) with a confirmed diagnosis of intracardiac myxoma based on imaging studies, who underwent surgical resection followed by histopathological confirmation, and who were followed in the institution&#8217;s outpatient clinics for at least 1 month. Patients aged &gt; 45 years or those with cardiovascular risk factors underwent standard preoperative institutional evaluation, including assessment of coronary artery patency to minimize the risk of perioperative myocardial infarction. Inclusion required complete medical documentation, including clinical notes and complementary test results, available in the institutional electronic medical record system.</p>
          <p>Exclusion criteria comprised duplicate records, incomplete medical documentation, surgery performed at another institution, follow-up shorter than 30 days, and unconfirmed diagnosis of intracardiac myxoma.</p>
        </sec>
        <sec>
          <title>Data collection and variables</title>
          <p>Follow-up data were obtained exclusively from the institutional electronic medical record, with no direct patient contact. The following variables were collected: i) demographic and clinical characteristics: age, sex, race, and comorbidities, such as diabetes mellitus, hypertension, smoking history, dyslipidemia, and peripheral arterial disease; ii) presentation and diagnostic data: initial symptoms and the imaging modality used for diagnosis; iii) surgical data: year of surgical intervention, surgical technique, and the need for additional cardiac procedures; iv) echocardiographic parameters (recorded preoperatively and postoperatively using standardized protocols performed by certified echocardiographers): left ventricular ejection fraction (LVEF), LA diameter, left and right ventricular (RV) dimensions, RV function, and pulmonary artery systolic pressure (PASP); v) tumor characteristics: size, morphology, surface features, mobility, degree of obstruction, and anatomical location; vi) complications and outcomes: thromboembolic events, tumor recurrence, and major adverse cardiovascular events.</p>
          <p>Major cardiovascular events during follow-up were identified through a comprehensive review of clinical records, hospital discharge summaries, and, when applicable, official death certificates. To ensure data accuracy and consistency, all collected information was independently reviewed by two researchers. Discrepancies were resolved by consensus or adjudicated by a third researcher.</p>
          <p>Thromboembolic events were defined as any clinically documented thromboembolic episode confirmed by imaging or surgical findings, including ischemic stroke, transient ischemic attack, systemic embolism, or peripheral arterial occlusion attributable to tumor fragments or thrombus. Events were further classified according to timing as preoperative, early postoperative, or late postoperative.</p>
        </sec>
        <sec>
          <title>Statistical analysis</title>
          <p>Continuous variables were expressed as median and interquartile range, as none followed a normal distribution according to the Kolmogorov&#8211;Smirnov test. Categorical variables were summarized as absolute frequencies and percentages.</p>
          <p>Comparisons between groups were performed using the Mann&#8211;Whitney <italic>U</italic> test for continuous variables and the chi-square test or Fisher&#8217;s exact test for categorical variables, as appropriate. Paired comparisons of preoperative and postoperative echocardiographic parameters were evaluated using the Wilcoxon signed-rank test. Event-free survival for thromboembolic outcomes was assessed using the Kaplan&#8211;Meier method, with curves compared descriptively.</p>
          <p>To identify predictors of thromboembolic events, univariate Cox proportional hazards regression analysis was initially performed. Variables with a p-value &lt; 0.10 were entered into the multivariable model to determine independent associations.</p>
          <p>All statistical analyses were conducted using IBM SPSS Statistics for Windows, version 27.0 (IBM Corp., Armonk, N.Y., USA). A two-tailed p-value &lt; 0.05 was considered statistically significant.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <sec>
          <title>Study population and baseline characteristics</title>
          <p>The study sample consisted of 74 patients diagnosed with cardiac myxoma according to the predefined inclusion and exclusion criteria (<xref ref-type="fig" rid="f10001">Diagram 1</xref>). The main findings are summarized in <xref ref-type="fig" rid="f01001">Central Illustration</xref>.</p>
          <p>
            <fig id="f10001">
              <label>Diagram 1</label>
              <caption>
                <title>&#8211; Flowchart illustrating the selection process of patients included in the study. Most patients with follow-up shorter than 30 days were referred back to their originating hospitals after the first postoperative consultation.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf02-en.tif"/></fig>
          </p>
          <p>Baseline demographic and clinical characteristics are presented in <xref ref-type="table" rid="t1001">Table 1</xref>. The cohort was composed predominantly of middle-aged women, with frequent cardiovascular comorbidities, particularly hypertension and dyslipidemia. Among patients with concomitant neoplasms, thyroid and gastrointestinal tumors were the most common. Two patients had confirmed Carney complex, both with positive genetic testing identifying <italic>PRKAR1A</italic> gene mutations.</p>
          <p>
            <table-wrap id="t1001">
              <label>Table 1</label>
              <caption>
                <title>&#8211; Baseline characteristics by clinical and epidemiological variables (n = 74)</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Variables</th>
                    <th>Value</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td colspan="2">
                      <bold>Clinical data</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Age (years)</td>
                    <td align="center">60 (52-66)</td>
                  </tr>
                  <tr>
                    <td>Hypertension, n (%)</td>
                    <td align="center">56 (75.7)</td>
                  </tr>
                  <tr>
                    <td>Female sex, n (%)</td>
                    <td align="center">51 (68.9)</td>
                  </tr>
                  <tr>
                    <td>White race, n (%)</td>
                    <td align="center">61 (82.4)</td>
                  </tr>
                  <tr>
                    <td>Black race, n (%)</td>
                    <td align="center">6 (8.1)</td>
                  </tr>
                  <tr>
                    <td>Diabetes mellitus, n (%)</td>
                    <td align="center">24 (32.4)</td>
                  </tr>
                  <tr>
                    <td>Dyslipidemia, n (%)</td>
                    <td align="center">42 (56.8)</td>
                  </tr>
                  <tr>
                    <td>Smoking history, n (%)</td>
                    <td align="center">32 (43.2)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Concomitant neoplasms</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Thyroid, n (%)</td>
                    <td align="center">3 (4.1)</td>
                  </tr>
                  <tr>
                    <td>Breast, n (%)</td>
                    <td align="center">1 (1.4)</td>
                  </tr>
                  <tr>
                    <td>Other, n (%)</td>
                    <td align="center">8 (10.8)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Clinical manifestations</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Asymptomatic, n (%)</td>
                    <td align="center">16 (21.8)</td>
                  </tr>
                  <tr>
                    <td>Dyspnea, n (%)</td>
                    <td align="center">33 (44.6)</td>
                  </tr>
                  <tr>
                    <td>Constitutional symptoms, n (%)</td>
                    <td align="center">13 (18.1)</td>
                  </tr>
                  <tr>
                    <td>Chest pain, n (%)</td>
                    <td align="center">6 (8.2)</td>
                  </tr>
                  <tr>
                    <td>Associated heart disease, n (%)</td>
                    <td align="center">15 (20.3)</td>
                  </tr>
                  <tr>
                    <td>Obstructive form, n (%)</td>
                    <td align="center">27 (36.5)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Preoperative diagnostic modality</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>TTE, n (%)</td>
                    <td align="center">57 (77.0)</td>
                  </tr>
                  <tr>
                    <td>TEE, n (%)</td>
                    <td align="center">7 (9.5)</td>
                  </tr>
                  <tr>
                    <td>CMR, n (%)</td>
                    <td align="center">10 (13.5)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Histopathological diagnosis</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Isolated myxoma, n (%)</td>
                    <td align="center">69 (93.2)</td>
                  </tr>
                  <tr>
                    <td>Multiple myxomas, n (%)</td>
                    <td align="center">5 (6.8)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Associated procedures</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Mitral valve surgery, n (%)</td>
                    <td align="center">14 (18.9)</td>
                  </tr>
                  <tr>
                    <td>Interatrial patch reconstruction, n (%)</td>
                    <td align="center">11 (14.9)</td>
                  </tr>
                  <tr>
                    <td>Tricuspid valve surgery, n (%)</td>
                    <td align="center">2 (2.7)</td>
                  </tr>
                  <tr>
                    <td>Aortic valve surgery, n (%)</td>
                    <td align="center">1 (1.4)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Follow-up</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Follow-up duration (months), median [IQR]</td>
                    <td align="center">60 [40-79]</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN1001">
                  <p>CMR: cardiac magnetic resonance; IQR: interquartile range; TEE: transesophageal echocardiography; TTE: transthoracic echocardiography.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
        </sec>
        <sec>
          <title>Clinical presentation</title>
          <p>Dyspnea was the most common presenting symptom, reflecting the obstructive nature of cardiac myxomas, particularly those located in the LA. Notably, 21.8% of patients were asymptomatic (<xref ref-type="fig" rid="f02001">Figure 1</xref>), with tumors identified incidentally on imaging. Constitutional symptoms, including fever, weight loss, anemia, and asthenia, were documented in 18.1% of cases. Additional reported symptoms included chest pain and palpitations, possibly related to thromboembolic events or arrhythmias. Furthermore, 36.5% of tumors exhibited an obstructive pattern, contributing to exertional symptoms.</p>
          <p>
            <fig id="f02001">
              <label>Figure 1</label>
              <caption>
                <title>&#8211; Presenting symptoms in patients with cardiac myxoma. Distribution of the main clinical manifestations at initial presentation.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf03-en.tif"/></fig>
          </p>
        </sec>
        <sec>
          <title>Surgical procedures and operative strategy</title>
          <p>Among the 74 patients, mitral valve surgery was the most frequent associated procedure (<xref ref-type="fig" rid="f03001">Figure 2</xref>). In 12 cases, intervention was required due to direct myxoma involvement of the valve leaflets, while in two patients the procedure was performed opportunistically. Other associated procedures included interatrial patch repair, tricuspid valve surgery, and aortic valve surgery.</p>
          <p>
            <fig id="f03001">
              <label>Figure 2</label>
              <caption>
                <title>&#8211; Frequency of concomitant cardiac procedures performed during myxoma resection.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf04-en.tif"/></fig>
          </p>
          <p>All patients underwent median sternotomy. LA myxomas were approached either through a right atrial (RA) transseptal route via the fossa ovalis when septal involvement or broad-based implantation was suspected, allowing en bloc excision with a cuff of interatrial septum followed by patch closure, or through direct left atriotomy for pedunculated or free-wall lesions. Concomitant valve procedures were performed when clinically indicated.</p>
        </sec>
        <sec>
          <title>Echocardiographic findings</title>
          <p>Preoperatively, most patients had preserved biventricular ejection fraction and normal left ventricular diastolic diameter. LA dilation was observed in 41.9% of cases, and elevated PASP was present in 20.3% of the cohort (<xref ref-type="table" rid="t2001">Table 2</xref>).</p>
          <p>
            <table-wrap id="t2001">
              <label>Table 2</label>
              <caption>
                <title>&#8211; Preoperative and postoperative echocardiographic findings and myxoma characteristics</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Variables</th>
                    <th>(%) or median (IQR)</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td colspan="2">
                      <bold>Preoperative data</bold>
                    </td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>LVEF</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Preserved</td>
                    <td align="center">69 (93.2)</td>
                  </tr>
                  <tr>
                    <td>Mildly reduced</td>
                    <td align="center">3 (4.1)</td>
                  </tr>
                  <tr>
                    <td>Severely reduced</td>
                    <td align="center">2 (2.7)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>LV diastolic diameter</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Normal</td>
                    <td align="center">66 (89.2)</td>
                  </tr>
                  <tr>
                    <td>Dilated</td>
                    <td align="center">8 (10.8)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>LA</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Normal</td>
                    <td align="center">43 (58.1)</td>
                  </tr>
                  <tr>
                    <td>Dilated</td>
                    <td align="center">31 (41.9)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>RV function</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Normal</td>
                    <td align="center">69 (93.2)</td>
                  </tr>
                  <tr>
                    <td>Mild dysfunction</td>
                    <td align="center">3 (4.1)</td>
                  </tr>
                  <tr>
                    <td>Moderate dysfunction</td>
                    <td align="center">2 (2.7)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>PASP</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Normal</td>
                    <td align="center">59 (79.7)</td>
                  </tr>
                  <tr>
                    <td>Mildly increased</td>
                    <td align="center">6 (8.1)</td>
                  </tr>
                  <tr>
                    <td>Severely increased</td>
                    <td align="center">9 (12.2)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Postoperative data</bold>
                    </td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>LVEF</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Preserved</td>
                    <td align="center">56 (78.9)</td>
                  </tr>
                  <tr>
                    <td>Mildly reduced</td>
                    <td align="center">4 (5.6)</td>
                  </tr>
                  <tr>
                    <td>Severely reduced</td>
                    <td align="center">11 (15.5)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>LV diastolic diameter</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Normal</td>
                    <td align="center">64 (86.5)</td>
                  </tr>
                  <tr>
                    <td>Dilated</td>
                    <td align="center">6 (8.1)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>LA</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Normal</td>
                    <td align="center">47 (63.5)</td>
                  </tr>
                  <tr>
                    <td>Dilated</td>
                    <td align="center">23 (31.1)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>RV function</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Normal</td>
                    <td align="center">64 (86.5)</td>
                  </tr>
                  <tr>
                    <td>Mild dysfunction</td>
                    <td align="center">6 (8.1)</td>
                  </tr>
                  <tr>
                    <td>Severe dysfunction</td>
                    <td align="center">1 (1.4)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>PASP</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Normal</td>
                    <td align="center">57 (82.6)</td>
                  </tr>
                  <tr>
                    <td>Mildly increased</td>
                    <td align="center">9 (12.2)</td>
                  </tr>
                  <tr>
                    <td>Severely increased</td>
                    <td align="center">3 (4.1)</td>
                  </tr>
                  <tr>
                    <td>
                      <bold>Myxoma characteristics</bold>
                    </td>
                    <td> </td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Location</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>LA</td>
                    <td align="center">65 (87.8)</td>
                  </tr>
                  <tr>
                    <td>RA</td>
                    <td align="center">4 (5.4)</td>
                  </tr>
                  <tr>
                    <td>Biatrial</td>
                    <td align="center">2 (2.7)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Morphology</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Pedunculated</td>
                    <td align="center">49 (68.1)</td>
                  </tr>
                  <tr>
                    <td>Sessile</td>
                    <td align="center">23 (31.9)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Lesion surface</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Smooth</td>
                    <td align="center">59 (79.7)</td>
                  </tr>
                  <tr>
                    <td>Villous</td>
                    <td align="center">15 (20.3)</td>
                  </tr>
                  <tr>
                    <td colspan="2">
                      <bold>Tumor size</bold>
                    </td>
                  </tr>
                  <tr>
                    <td>Length (mm)</td>
                    <td align="center">45 (29-57)</td>
                  </tr>
                  <tr>
                    <td>Width (mm)</td>
                    <td align="center">35 (22-42)</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN2001">
                  <p>IQR: interquartile range; LA: left atrium; LV: left ventricle; LVEF: LV ejection fraction; PASP: pulmonary artery systolic pressure; RA: right atrium; RV: right ventricle<italic><bold>.</bold></italic></p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
          <p>Postoperatively, most patients maintained preserved biventricular ejection fraction, although the proportion with severe reductions in LVEF increased by 12.8%. Normal LA size increased by 10.8%, and normalization of PASP was observed in 6% of patients (<xref ref-type="table" rid="t2001">Table 2</xref>).</p>
          <p>Myxomas were predominantly located in the LA (<xref ref-type="fig" rid="f04001">Figure 3</xref>), generally with a smooth surface, and had median dimensions of 45 &#215; 35 mm (<xref ref-type="table" rid="t2001">Table 2</xref>). A Wilcoxon signed-rank test (<xref ref-type="fig" rid="f05001">Figure 4</xref>) demonstrated statistically significant differences between preoperative and postoperative measurements for both LVEF and PASP. Specifically, both parameters showed significant reductions, with PASP decreasing primarily in patients with obstructive myxomas.</p>
          <p>
            <fig id="f04001">
              <label>Figure 3</label>
              <caption>
                <title>&#8211; Tumor morphology and primary anatomical locations.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf05-en.tif"/></fig>
          </p>
          <p>
            <fig id="f05001">
              <label>Figure 4</label>
              <caption>
                <title>&#8211; Comparison of preoperative and postoperative echocardiographic parameters. Comparison of LVEF and PASP demonstrating a significant postoperative reduction in PASP and a transient decline in LVEF. LVEF: left ventricular ejection fraction. PASP: pulmonary artery systolic pressure.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf06-en.tif"/></fig>
          </p>
        </sec>
        <sec>
          <title>Complications and clinical outcomes</title>
          <p>Thromboembolic events were observed in 18.9% of patients, with ischemic stroke as the most frequent manifestation. All stroke cases occurred in patients with preoperative atrial fibrillation. Events occurred in 8.1% preoperatively and in 5.4% postoperatively (<xref ref-type="table" rid="t3001">Table 3</xref>). Less frequent complications included atrial fibrillation, obstructive shock, and superior vena cava syndrome (<xref ref-type="fig" rid="f06001">Figure 5</xref>).</p>
          <p>
            <table-wrap id="t3001">
              <label>Table 3</label>
              <caption>
                <title>&#8211; Morbidity and mortality outcomes after myxoma resection</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Outcome</th>
                    <th>n (%)</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>
                      <bold>Thromboembolic events</bold>
                    </td>
                    <td align="center">14 (18.9)</td>
                  </tr>
                  <tr>
                    <td>Pulmonary embolism</td>
                    <td align="center">2 (2.7)</td>
                  </tr>
                  <tr>
                    <td>Stroke</td>
                    <td align="center">10 (13.5)</td>
                  </tr>
                  <tr>
                    <td>Embolic myocardial infarction</td>
                    <td align="center">2 (2.7)</td>
                  </tr>
                  <tr>
                    <td>
                      <bold>Myxoma recurrence</bold>
                    </td>
                    <td align="center">2 (2.7)</td>
                  </tr>
                  <tr>
                    <td>
                      <bold>Postoperative atrial fibrillation</bold>
                    </td>
                    <td align="center">6 (8.1)</td>
                  </tr>
                  <tr>
                    <td>
                      <bold>Obstructive shock</bold>
                    </td>
                    <td align="center">2 (2.7)</td>
                  </tr>
                  <tr>
                    <td>
                      <bold>Superior vena cava syndrome</bold>
                    </td>
                    <td align="center">1 (1.4)</td>
                  </tr>
                  <tr>
                    <td>
                      <bold>Mortality</bold>
                    </td>
                    <td align="center">1 (1.4)</td>
                  </tr>
                </tbody>
              </table>
            </table-wrap>
          </p>
          <p>
            <fig id="f06001">
              <label>Figure 5</label>
              <caption>
                <title>&#8211; Summary of thromboembolic events and postoperative complications.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf07-en.tif"/></fig>
          </p>
          <p>The mortality rate was low, with only one death recorded during a median follow-up period of 60 months. Event-free survival was further illustrated using a Kaplan&#8211;Meier curve, which demonstrated a progressive decline in freedom from thromboembolic events over time (<xref ref-type="fig" rid="f07001">Figure 6</xref>).</p>
          <p>
            <fig id="f07001">
              <label>Figure 6</label>
              <caption>
                <title>&#8211; Kaplan&#8211;Meier curve for thromboembolic event-free survival. Event-free survival up to 60 months, showing that most patients remained free from thromboembolic events during follow-up.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf08-en.tif"/></fig>
          </p>
        </sec>
        <sec>
          <title>Tumor recurrence</title>
          <p>Myxoma recurrence was uncommon. Both recurrent cases involved multiple episodes (three recurrences each) and were associated with Carney complex. One case involved an 18-year-old female with three left ventricular recurrences, and the other a 44-year-old male with sequential involvement of the LA, RA, and eventually a biatrial recurrence.</p>
        </sec>
        <sec>
          <title>Comparative analysis according to thromboembolic events</title>
          <p>Patients who experienced thromboembolic events (n = 14) were compared with those who did not (n = 60) using chi-square or Fisher&#8217;s exact tests for categorical variables and the Mann&#8211;Whitney <italic>U</italic> test for continuous variables due to non-normal distribution (<xref ref-type="fig" rid="f08001">Figures 7</xref> and <xref ref-type="fig" rid="f09001">8</xref>). Age was similar between groups (median: 57.5 vs. 60.5 years). Diabetes mellitus was significantly more prevalent in the event-free group (7.1% vs. 38.3%).</p>
          <p>
            <fig id="f08001">
              <label>Figure 7</label>
              <caption>
                <title>&#8211; Boxplots of clinical variables according to thromboembolic event status. Distribution of age and tumor size stratified by the occurrence of thromboembolic events.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf09-en.tif"/></fig>
          </p>
          <p>
            <fig id="f09001">
              <label>Figure 8</label>
              <caption>
                <title>&#8211; Comparison of clinical and tumor characteristics by thromboembolic event status. AF: atrial fibrillation.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-123-02-e20250596-50596-gf10-en.tif"/></fig>
          </p>
          <p>Other factors, including tumor size, location, and echocardiographic parameters (LVEF, LA dilation, and PASP), showed no statistically significant differences between groups (<xref ref-type="table" rid="t4001">Table 4</xref>). These findings are consistent with the Cox proportional hazards model results presented in <xref ref-type="table" rid="t5001">Table 5</xref> and <xref ref-type="table" rid="t6001">Table 6</xref>, in which diabetes and atrial fibrillation emerged as independent predictors of embolic events.</p>
          <p>
            <table-wrap id="t4001">
              <label>Table 4</label>
              <caption>
                <title>&#8211; Comparison between patients with and without thromboembolic events</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Variable</th>
                    <th>Event (n = 14)</th>
                    <th>No event (n = 60)</th>
                    <th>p-value</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>Age, years</td>
                    <td align="center">57.5 (44.2-62.0)</td>
                    <td align="center">60.5 (52.8-67.0)</td>
                    <td align="center">0.120</td>
                  </tr>
                  <tr>
                    <td>Female sex</td>
                    <td align="center">11 (78.6%)</td>
                    <td align="center">40 (66.7%)</td>
                    <td align="center">0.520</td>
                  </tr>
                  <tr>
                    <td>White race</td>
                    <td align="center">13 (92.9%)</td>
                    <td align="center">48 (80.0%)</td>
                    <td align="center">0.440</td>
                  </tr>
                  <tr>
                    <td>Diabetes mellitus</td>
                    <td align="center">1 (7.1%)</td>
                    <td align="center">23 (38.3%)</td>
                    <td align="center">0.020</td>
                  </tr>
                  <tr>
                    <td>Hypertension</td>
                    <td align="center">9 (64.3%)</td>
                    <td align="center">47 (78.3%)</td>
                    <td align="center">0.300</td>
                  </tr>
                  <tr>
                    <td>Pedunculated tumor</td>
                    <td align="center">12 (85.7%)</td>
                    <td align="center">37 (63.8%)</td>
                    <td align="center">0.200</td>
                  </tr>
                  <tr>
                    <td>Obstructive pattern</td>
                    <td align="center">8 (57.1%)</td>
                    <td align="center">19 (31.7%)</td>
                    <td align="center">0.120</td>
                  </tr>
                  <tr>
                    <td>Postoperative AF</td>
                    <td align="center">5 (35.7%)</td>
                    <td align="center">1 (1.6%)</td>
                    <td align="center">0.002</td>
                  </tr>
                  <tr>
                    <td>Tumor length (mm)</td>
                    <td align="center">42.5 (35.0-53.8)</td>
                    <td align="center">45.0 (27.0-57.8)</td>
                    <td align="center">0.910</td>
                  </tr>
                  <tr>
                    <td>Tumor width (mm)</td>
                    <td align="center">32.5 (26.2-43.8)</td>
                    <td align="center">35.0 (20.8-42.0)</td>
                    <td align="center">0.530</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN3001">
                  <p>Values are presented as n (%) for categorical variables and median [IQR] for continuous variables. P-values were calculated using Fisher&#8217;s exact test or the Mann&#8211;Whitney U test, as appropriate. AF: atrial fibrillation; IQR: interquartile range.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
          <p>
            <table-wrap id="t5001">
              <label>Table 5</label>
              <caption>
                <title>&#8211; Univariate Cox proportional hazards regression for thromboembolic events</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Variable</th>
                    <th>HR</th>
                    <th>95% CI</th>
                    <th>p-value</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>Age (per year)</td>
                    <td align="center">0.96</td>
                    <td align="center">0.92-1.00</td>
                    <td align="center">0.06</td>
                  </tr>
                  <tr>
                    <td>Dyslipidemia</td>
                    <td align="center">1.02</td>
                    <td align="center">0.31-3.30</td>
                    <td align="center">0.97</td>
                  </tr>
                  <tr>
                    <td>Hypertension</td>
                    <td align="center">2.00</td>
                    <td align="center">0.57-7.03</td>
                    <td align="center">0.27</td>
                  </tr>
                  <tr>
                    <td>Preoperative reduced LVEF</td>
                    <td align="center">2.22</td>
                    <td align="center">0.62-7.86</td>
                    <td align="center">0.21</td>
                  </tr>
                  <tr>
                    <td>LV diastolic diameter (dilated)</td>
                    <td align="center">0.33</td>
                    <td align="center">0.06-1.60</td>
                    <td align="center">0.17</td>
                  </tr>
                  <tr>
                    <td>Increased PASP</td>
                    <td align="center">1.08</td>
                    <td align="center">0.47-2.49</td>
                    <td align="center">0.84</td>
                  </tr>
                  <tr>
                    <td>Mobile myxoma</td>
                    <td align="center">1.87</td>
                    <td align="center">0.52-6.71</td>
                    <td align="center">0.33</td>
                  </tr>
                  <tr>
                    <td>Tumor length (mm)</td>
                    <td align="center">0.99</td>
                    <td align="center">0.96-1.02</td>
                    <td align="center">0.67</td>
                  </tr>
                  <tr>
                    <td>Tumor width (mm)</td>
                    <td align="center">1.00</td>
                    <td align="center">0.96-1.03</td>
                    <td align="center">0.98</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN4001">
                  <p>HR: hazard ratio; LV: left ventricle; LVEF: LV ejection function; PASP: pulmonary artery systolic pressure.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
          <p>
            <table-wrap id="t6001">
              <label>Table 6</label>
              <caption>
                <title>&#8211; Multivariate Cox proportional hazards regression for thromboembolic events</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Variable</th>
                    <th>HR</th>
                    <th>95% CI</th>
                    <th>p-value</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>Diabetes mellitus</td>
                    <td align="center">0.11</td>
                    <td align="center">0.006-0.740</td>
                    <td align="center">&lt; 0.05</td>
                  </tr>
                  <tr>
                    <td>Postoperative AF</td>
                    <td align="center">6.74</td>
                    <td align="center">1.49-30.51</td>
                    <td align="center">&lt; 0.05</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN5001">
                  <p>AF: atrial fibrillation; HR: hazard ratio.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
        </sec>
        <sec>
          <title>Predictors of thromboembolic events</title>
          <p>The multivariable Cox regression model (<xref ref-type="table" rid="t6001">Table 6</xref>) showed that LA dilation was associated with a lower, although non-significant, risk of thromboembolic events. Diabetes and atrial fibrillation were significantly associated with the hazard of thromboembolic events (HR = 0.11; 95% CI: 0.006-0.740; p &lt; 0.05). Mobile tumors showed a trend toward a higher risk of thromboembolism, although this increase was not statistically significant.</p>
          <p>Univariate or multivariate analyses of myxoma recurrence and mortality were not performed due to the small number of events. A focused analysis was conducted to explore variables associated with an increased risk of thromboembolic events. Univariate analysis identified diabetes as a potential protective factor, contrasting with its established role in increasing thromboembolic risk in the general population. This finding suggests that the myxoma itself may be the primary driver of thromboembolic risk in this population, supporting the rationale for early surgical removal.</p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>This study reinforces the critical role of early surgical intervention in the management of cardiac myxomas and highlights its association with excellent long-term outcomes.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> In this cohort of 74 patients, predominantly with sporadic tumors, the median follow-up was 60 months, during which survival reached 98.6% and tumor recurrence remained low at 2.7%. These findings are consistent with previous reports demonstrating the effectiveness of prompt resection in reducing mortality and recurrence, particularly when complete excision of the tumor and its attachment is achieved.<sup><xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup></p>
        <p>The lower frequency of constitutional symptoms observed in our cohort contrasts with the higher prevalence reported in other series. This difference may be explained by referral patterns, as many patients were evaluated at our center at more advanced stages of disease, when obstructive and embolic manifestations may predominate over systemic symptoms.<sup><xref ref-type="bibr" rid="B10">10</xref>-<xref ref-type="bibr" rid="B12">12</xref></sup></p>
        <p>All procedures in our cohort were performed via median sternotomy, which remains the standard approach at our institution to ensure adequate exposure and complete tumor excision. Minimally invasive and robotic techniques, such as those using the DaVinci Xi<sup>&#174;</sup> system, were not available during the study period. However, these approaches have been associated with shorter recovery times and improved postoperative quality of life in selected centers.<sup><xref ref-type="bibr" rid="B13">13</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup></p>
        <p>The interatrial septum, particularly the fossa ovalis, is recognized as the most common site of origin for cardiac myxomas. En bloc resection with removal of a portion of the interatrial septum followed by patch reconstruction is often recommended to minimize recurrence. In our cohort, only 14.9% of patients underwent interatrial patch reconstruction. This relatively low rate reflects a tailored, real-world surgical strategy at our tertiary center, where operative decisions were guided by tumor size, attachment morphology, and intraoperative findings.<sup><xref ref-type="bibr" rid="B15">15</xref>-<xref ref-type="bibr" rid="B18">18</xref></sup></p>
        <p>In many cases, small pedunculated tumors allowed for complete excision with a narrow margin and primary septal closure, particularly in older or high-risk patients.<sup><xref ref-type="bibr" rid="B18">18</xref>-<xref ref-type="bibr" rid="B20">20</xref></sup></p>
        <p>The incidence of thromboembolic events in our cohort (18.9%), primarily ischemic stroke (13.5%), is comparable to rates reported in prior studies. Stefanou et al. (2018) described a stroke rate of 11% among patients with cardiac myxomas, while Pinede et al. (2001) reported thromboembolic events in approximately 30% of cases. Importantly, our multivariable Cox regression analysis did not identify tumor location or age as significant predictors of thromboembolic risk. Tumor mobility showed a trend toward increased risk, although this association did not reach statistical significance, likely due to the limited number of events. This observation is consistent with the meta-analysis by Liu et al. (2020), which highlighted the lack of consistent morphological predictors across studies.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B22">22</xref></sup></p>
        <p>Postoperative atrial fibrillation emerged as an independent predictor of thromboembolic events in our cohort, with more than a sixfold increase in hazard. This finding reinforces the well-established association between new-onset atrial fibrillation and heightened embolic risk following cardiac surgery and underscores the importance of close rhythm monitoring and timely anticoagulation in this population.<sup><xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B24">24</xref></sup></p>
        <p>In the multivariable model, diabetes mellitus was associated with a lower hazard of thromboembolic events. This observation has not been consistently reported in previous studies and should be interpreted cautiously. It is likely exploratory and potentially confounded, rather than indicative of a true protective biological effect.<sup><xref ref-type="bibr" rid="B25">25</xref>-<xref ref-type="bibr" rid="B27">27</xref></sup> Possible explanations include closer clinical monitoring, more frequent use of antithrombotic or statin therapy, or unmeasured differences in cardiovascular risk management among diabetic patients. Because of the small number of events and the retrospective design, this finding should be considered hypothesis-generating and requires confirmation in larger prospective studies.</p>
        <p>The cohort demonstrated a significant postoperative reduction in PASP (Wilcoxon Z = &#8722;2.070; p = 0.038), consistent with relief of LA inflow obstruction, particularly in patients with obstructive myxomas.</p>
        <p>Conversely, LVEF declined in the early postoperative period (preserved LVEF 93.2% preoperatively vs 78.9% postoperatively; severe reduction 2.7% vs 15.5%; Wilcoxon Z = 3.052; p = 0.002). This pattern likely reflects transient perioperative ventricular dysfunction rather than a sustained deterioration in systolic function, especially considering that postoperative echocardiograms were performed within 30 days of surgery. These findings suggest that surgery promptly alleviates hemodynamic burden, while recovery of ventricular function may occur more gradually and warrants longitudinal echocardiographic follow-up.</p>
        <p>Mikus et al. (2025) reported preserved LVEF in the postoperative period, indicating that the changes observed in our cohort may represent early, transient alterations rather than long-term impairment.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
        <p>Lastly, the survival rate observed in our study (98.6% over a median follow-up of 60 months) compares favorably with global surgical series, including the 93%-97% long-term survival reported by Jiang et al. (2019) and Perek et al. (2011). These results reinforce the long-term safety and effectiveness of surgical treatment for cardiac myxomas when performed in specialized centers.<sup><xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B28">28</xref></sup></p>
        <sec>
          <title>Study limitations</title>
          <p>The retrospective, single-center design and the relatively small sample size may limit the generalizability of these findings. Additionally, due to the long data collection period inherent to retrospective studies, certain potentially relevant variables, such as tumor morphology and surface characteristics, which may be associated with mobility and thromboembolic risk, were not consistently documented.</p>
          <p>Furthermore, the observed postoperative reduction in LVEF may partly reflect perioperative myocardial injury or infarction, which was not systematically assessed or recorded in our cohort, limiting the interpretation of this finding.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>Our study reinforces that cardiac myxoma, when treated promptly, is associated with an excellent prognosis. At the same time, it highlights the significant thromboembolic risk related to this condition, which appears to be largely independent of tumor morphology. These findings support early surgical resection, even in asymptomatic patients and those with non-obstructive lesions. Continuous follow-up remains essential to monitor for late complications and potential recurrence.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <label>Ethics statement:</label>
          <p> This study was conducted in accordance with the ethical standards of the Institutional Review Board (Protocol SDC-COP 26501). All data were anonymized to ensure patient confidentiality, and the requirement for informed consent was waived due to the retrospective design.</p>
        </fn>
        <fn fn-type="other">
          <label>Study association:</label>
          <p> This study is not associated with any thesis or dissertation work.</p>
        </fn>
        <fn fn-type="other">
          <label>Ethics approval and consent to participate:</label>
          <p> This study was approved by the Ethics Committee of the Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo (HCFM/USP) under the protocol number CAAE 86890725.3.0000.0068. PARECER NR 7.497.978. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013.</p>
        </fn>
        <fn fn-type="other">
          <label>Use of Artificial Intelligence:</label>
          <p> The authors did not use any artificial intelligence tools in the development of this work.</p>
        </fn>
        <fn fn-type="data-availability" specific-use="data-available-upon-request">
          <label>Data Availability Statement:</label>
          <p> All datasets supporting the results of this study are available upon request from the corresponding author.</p>
        </fn>
        <fn fn-type="financial-disclosure">
          <label>Sources of funding:</label>
          <p> There were no external funding sources for this study.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
