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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">HcLfgfxbwYmjDvFVqSWMbVN</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2021000500692</article-id>
      <article-id pub-id-type="publisher-id">abc.20210198</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20210198</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Abordagem ao Paciente com Endocardite Infecciosa e Complica&#231;&#227;o Neurol&#243;gica &#8211; O Grande Dilema que Persiste at&#233; Hoje</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0002-9700-9743</contrib-id>
          <name>
            <surname>Fortes</surname>
            <given-names>Claudio Querido</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Fortes</surname>
            <given-names>Nat&#225;lia Rodrigues Querido</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
          <institution content-type="orgdiv1">Hospital Universit&#225;rio Clementino Fraga Filho</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Universit&#225;rio Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ - Brasil.</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Universidade Est&#225;cio de S&#225;</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Faculdade de Medicina, Universidade Est&#225;cio de S&#225;, Rio de Janeiro, RJ - Brasil.</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution content-type="orgname">Universidade Federal Fluminense</institution>
          <institution content-type="orgdiv1">Hospital Universit&#225;rio Antonio Pedro</institution>
          <addr-line>
            <named-content content-type="city">Niter&#243;i</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Universit&#225;rio Antonio Pedro, Universidade Federal Fluminense, Niter&#243;i, RJ &#8211; Brasil.</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Claudio Querido Fortes</bold> &#8226; Universidade Federal do Rio de Janeiro - Servi&#231;o de Doen&#231;as Infecciosas e Parasit&#225;rias - 5o andar - Rua Rodolpho Paulo Rocco, 255 - Ilha do Fund&#227;o. CEP <postal-code>21941-590</postal-code>, Rio de Janeiro, RJ &#8211; Brasil. E-mail: <email>querido.fortes@gmail.com</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>16</day>
        <month>04</month>
        <year>2021</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <month>04</month>
        <year>2021</year>
      </pub-date>
      <volume>116</volume>
      <issue>4</issue>
      <fpage>692</fpage>
      <lpage>694</lpage>
      <permissions>
        <license license-type="open-access" xml:lang="en" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Endocardite Bacteriana/complica&#231;&#245;es</kwd>
        <kwd>Mortalidade</kwd>
        <kwd>Complica&#231;&#245;es Neurol&#243;gicas</kwd>
        <kwd>Insufici&#234;ncia Renal</kwd>
        <kwd>Pr&#243;teses Valvulares Card&#237;acas</kwd>
        <kwd>Pandemia/complica&#231;&#245;es</kwd>
        <kwd>Pr&#243;teses e Implantes</kwd>
        <kwd>Envelhecimento</kwd>
        <kwd>Emboliza&#231;&#227;o</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="14"/>
        <page-count count="3"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>A endocardite &#233; uma doen&#231;a extremamente desafiadora em seu diagn&#243;stico, pela diversidade de sua apresenta&#231;&#227;o e tamb&#233;m na conduta terap&#234;utica, o que torna necess&#225;ria a exist&#234;ncia de um time de endocardite, constitu&#237;do por profissionais de diversas especialidades. &#201; de fundamental import&#226;ncia a presen&#231;a de infectologista, microbiologista cl&#237;nico, cardiologista, cirurgi&#227;o card&#237;aco, neurologista e imagenologista e desej&#225;vel a assist&#234;ncia de outras especialidades que dependem de cada caso. Sua incid&#234;ncia tem aumentado nas &#250;ltimas d&#233;cadas, principalmente em decorr&#234;ncia do envelhecimento da popula&#231;&#227;o, pelo crescente n&#250;mero de indiv&#237;duos em tratamento renal substitutivo, pela maior frequ&#234;ncia de pacientes portadores de pr&#243;teses valvares e de dispositivos el&#233;tricos card&#237;acos implantados e, tamb&#233;m, devido aos avan&#231;os tecnol&#243;gicos incorporados nos m&#233;todos diagn&#243;sticos e terap&#234;uticos invasivos, al&#233;m da atual &#8220;epidemia&#8221; do uso de drogas recreativas intravenosas, o que constitui, em alguns pa&#237;ses, um grave problema de sa&#250;de p&#250;blica. Apesar de todo os avan&#231;os obtidos no diagn&#243;stico e na terap&#234;utica da endocardite, sua mortalidade permanece assustadoramente alta. A persist&#234;ncia dessa grande quantidade de &#243;bitos talvez possa, em parte, ser explicada pelo aumento do n&#250;mero de pacientes mais idosos, fr&#225;geis, com m&#250;ltiplas comorbidades e portadores de pr&#243;teses.</p>
    <p>O artigo &#8220;Complica&#231;&#245;es neurol&#243;gicas em pacientes com endocardite infecciosa: perspectivas de um centro terci&#225;rio&#8221;<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> tem como principais objetivos avaliar os preditores de complica&#231;&#245;es neurol&#243;gicas em pacientes com endocardite infecciosa e os preditores de mortalidade neste grupo, e comparar os resultados do tratamento cl&#237;nico com o cl&#237;nico-cir&#250;rgico, tanto na popula&#231;&#227;o de pacientes estudados quanto estratificar o grupo de pacientes com complica&#231;&#245;es neurol&#243;gicas.</p>
    <p>Na coorte de Alegria et al.,<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> os fatores predisponentes independentes para o desenvolvimento de complica&#231;&#245;es neurol&#243;gicas foram diabetes e aus&#234;ncia de febre na apresenta&#231;&#227;o, dado este interessante, pois o diabetes &#233; pouco citado como fator preditivo de emboliza&#231;&#227;o cerebral em pacientes com endocardite, embora tenha sido mencionado na European Society of Cardiology (ESC)<xref ref-type="bibr" rid="B2"><sup>2</sup></xref>e constitua uma das vari&#225;veis da calculadora desenvolvida por Hubert et al.,<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> para avaliar o risco de emboliza&#231;&#227;o nos pacientes com endocardite. A aus&#234;ncia de febre na admiss&#227;o n&#227;o &#233; relacionada na literatura a complica&#231;&#245;es neurol&#243;gicas, mas este achado &#233; curioso, j&#225; que pode demonstrar um atraso no diagn&#243;stico da endocardite e, por conseguinte, um tempo mais prolongado at&#233; o in&#237;cio da antibioticoterapia adequada, o que aumenta as chances de uma emboliza&#231;&#227;o para o sistema nervoso central (SNC), haja vista que a maior parte das complica&#231;&#245;es neurol&#243;gicas ocorre antes da interna&#231;&#227;o ou durante a primeira semana de antibioticoterapia. Tal complica&#231;&#227;o diminui, significativamente, ap&#243;s a segunda semana da terapia antimicrobiana. Outro fator preditor de emboliza&#231;&#227;o, citado pelos autores, foi a idade do paciente, ainda que este n&#227;o tenha apresentado signific&#226;ncia estat&#237;stica na an&#225;lise multivariada. &#201; importante observar que, na maior parte das coortes, inclusive na de Alegria et al.,<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> a idade mais avan&#231;ada se relaciona com um menor risco para emboliza&#231;&#227;o cerebral nos pacientes com endocardite.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref> No entanto, na calculadora de Hubert et al.,<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> a idade superior a 70 anos est&#225; associada a um maior risco de emboliza&#231;&#227;o.</p>
    <p>A endocardite que compromete a v&#225;lvula mitral e o microrganismo causador da infec&#231;&#227;o ser <italic>S. aureus</italic>, fatores predisponentes para o desenvolvimento de complica&#231;&#245;es neurol&#243;gicas classicamente descritos na maioria das publica&#231;&#245;es, curiosamente, n&#227;o foram observados nesta coorte.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B6"><sup>6</sup></xref> O tamanho da vegeta&#231;&#227;o, o principal fator predisponente para emboliza&#231;&#227;o, infelizmente n&#227;o foi avaliado nesta coorte, j&#225; que a mensura&#231;&#227;o das vegeta&#231;&#245;es n&#227;o foi feita em todos os pacientes.</p>
    <p>Alegria et al.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> abordam um dos dilemas mais angustiantes com que o time de endocardite pode se deparar: a tomada de decis&#227;o frente ao paciente que apresenta altera&#231;&#245;es neurol&#243;gicas consequentes da endocardite e que persiste com vegeta&#231;&#227;o de alto potencial embolig&#234;nico ou que desenvolve uma complica&#231;&#227;o potencialmente fatal, cuja cirurgia card&#237;aca constitui o &#250;nico tratamento poss&#237;vel. As tr&#234;s principais complica&#231;&#245;es que requerem o tratamento cir&#250;rgico s&#227;o a deteriora&#231;&#227;o hemodin&#226;mica, a preven&#231;&#227;o de emboliza&#231;&#227;o ou de sua recorr&#234;ncia e a infec&#231;&#227;o persistente. A quest&#227;o n&#227;o se restringe &#224; decis&#227;o de submeter ou n&#227;o o paciente a uma cirurgia, mas tamb&#233;m quanto ao momento ideal para o procedimento.</p>
    <p>Quando a indica&#231;&#227;o cir&#250;rgica se d&#225; pela deteriora&#231;&#227;o hemodin&#226;mica, mesmo com todo o risco da progress&#227;o da les&#227;o neurol&#243;gica, n&#227;o resta outra op&#231;&#227;o que n&#227;o seja faz&#234;-la o quanto antes, pois o desfecho fatal, sem a interven&#231;&#227;o cir&#250;rgica, &#233; bem conhecido. O mesmo ocorre quando a indica&#231;&#227;o cir&#250;rgica &#233; a persist&#234;ncia da infec&#231;&#227;o, por&#233;m, a maior preocupa&#231;&#227;o surge quando a indica&#231;&#227;o do tratamento cir&#250;rgico se d&#225; para prevenir a recorr&#234;ncia de emboliza&#231;&#227;o para o SNC. Nesta situa&#231;&#227;o, al&#233;m do risco inerente do procedimento cir&#250;rgico, que tamb&#233;m est&#225; presente quando as indica&#231;&#245;es do procedimento s&#227;o a deteriora&#231;&#227;o hemodin&#226;mica e a persist&#234;ncia da infec&#231;&#227;o, ainda existe o risco, potencialmente fatal, do agravamento do quadro neurol&#243;gico. N&#227;o operar e correr o risco de o paciente vir a apresentar um novo quadro de emboliza&#231;&#227;o que pode ser fatal, ou fazer o procedimento com o risco de a les&#227;o cerebral progredir e matar o paciente?</p>
    <p>Ainda que j&#225; se tenha decidido pela cirurgia, outro ponto muito controverso na literatura m&#233;dica &#233; o momento em que ela deve ser realizada. Os autores relatam que a m&#233;dia de tempo entre o diagn&#243;stico e a cirurgia foi de quatro semanas (36 dias). Eles comentam que este seria o intervalo necess&#225;rio para evitar o agravamento da complica&#231;&#227;o neurol&#243;gica causada pela hepariniza&#231;&#227;o necess&#225;ria para a extracorp&#243;rea, o que evidencia uma postura concordante com as diretrizes internacionais atuais.</p>
    <p>O &#250;ltimo guideline europeu publicado recomenda adiar a cirurgia card&#237;aca por ao menos quatro semanas na presen&#231;a de hemorragia intracraniana, a fim de evitar que, com a hepariniza&#231;&#227;o durante a CEC, haja um aumento da &#225;rea com sangramento ou a convers&#227;o de um infarto isqu&#234;mico em hemorr&#225;gico. Al&#233;m disto, o fluxo n&#227;o puls&#225;til da CEC e a hipotens&#227;o durante a cirurgia podem prejudicar a circula&#231;&#227;o cerebral, promovendo a extens&#227;o da &#225;rea de um infarto cerebral. Os autores desta diretriz consideram que os danos potenciais que a CEC pode causar sejam superiores ao benef&#237;cio que a cirurgia &#233; capaz de trazer; no entanto, essas recomenda&#231;&#245;es est&#227;o baseadas na opini&#227;o de especialistas.</p>
    <p>V&#225;rias publica&#231;&#245;es da &#250;ltima d&#233;cada referem que a presen&#231;a de complica&#231;&#245;es neurol&#243;gicas assintom&#225;ticas ou de ataques isqu&#234;micos transit&#243;rios n&#227;o aumentam o risco de complica&#231;&#245;es neurol&#243;gicas no p&#243;s-operat&#243;rio e que, portanto, a cirurgia card&#237;aca pode ser realizada a qualquer momento.<xref ref-type="bibr" rid="B7"><sup>7</sup></xref> No caso de um infarto cerebral de pequena extens&#227;o e com pouca repercuss&#227;o neurol&#243;gica, as recomenda&#231;&#245;es quanto ao momento da cirurgia card&#237;aca s&#227;o controversas: h&#225; quem recomende a cirurgia uma a duas semanas ap&#243;s o evento, h&#225; quem preconize que o intervalo poderia ser menor que 7 dias e os que consideram que a cirurgia deva ser realizada nas primeiras 72 horas e que a chance de complica&#231;&#245;es seria maior ap&#243;s este intervalo.<xref ref-type="bibr" rid="B8"><sup>8</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B9"><sup>9</sup></xref>O estudo de Garc&#237;a-Cabrera et al.,<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> em 2013, &#233; concordante com a revis&#227;o sistem&#225;tica da literatura de Tam et al.,<xref ref-type="bibr" rid="B10"><sup>10</sup></xref> que concluiu que os pacientes com acidente vascular encef&#225;lico (AVE) isqu&#234;mico podem se beneficiar de um atraso de 1 a 2 semanas na cirurgia e os com evento hemorr&#225;gico, mais de 21 dias.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B10"><sup>10</sup></xref> No entanto, as publica&#231;&#245;es mais recentes continuam a preconizar intervalos mais curtos.<xref ref-type="bibr" rid="B11"><sup>11</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B12"><sup>12</sup></xref></p>
    <p>O grande receio se d&#225; quando h&#225; um comprometimento neurol&#243;gico importante ou existe hemorragia intracraniana. Nessas situa&#231;&#245;es, alguns pesquisadores recomendam n&#227;o submeter o paciente ao procedimento cir&#250;rgico ou realizar a cirurgia card&#237;aca ap&#243;s um m&#234;s, em concord&#226;ncia com as diretrizes internacionais atuais. Por&#233;m, muitas publica&#231;&#245;es recentes n&#227;o encontraram associa&#231;&#227;o entre a presen&#231;a de hemorragias cerebrais ou de infarto extenso com uma chance significativamente maior de complica&#231;&#227;o neurol&#243;gica no p&#243;s-operat&#243;rio,<xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B12"><sup>12</sup></xref> mas, como j&#225; mencionado, h&#225; que se ter cautela na interpreta&#231;&#227;o destes resultados. Mesmo que a popula&#231;&#227;o total de pacientes avaliados por estes autores n&#227;o seja pequena, ap&#243;s as estratifica&#231;&#245;es, o n&#250;mero de participantes em cada grupo a ser analisado acaba sendo muito reduzido, al&#233;m da possibilidade de haver vi&#233;s de sele&#231;&#227;o. Atualmente, um n&#250;mero expressivo de autores continua recomendando um intervalo de pelo menos 21 dias entre o evento hemorr&#225;gico e a cirurgia, a n&#227;o ser que o atraso da cirurgia ponha em risco a vida do paciente.<xref ref-type="bibr" rid="B12"><sup>12</sup></xref></p>
    <p>Na coorte de Alegria et al.,<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> os pacientes que foram submetidos &#224; cirurgia apresentaram uma taxa menor de mortalidade quando comparados aos que foram tratados exclusivamente com antimicrobianos, o que &#233; concordante com a maior parte da literatura m&#233;dica atual.<xref ref-type="bibr" rid="B13"><sup>13</sup></xref> Tamb&#233;m n&#227;o foi encontrada diferen&#231;a na mortalidade dos pacientes com ou sem complica&#231;&#245;es neurol&#243;gicas, em contraste com a maior parte dos escritos, como os pr&#243;prios autores chamam a aten&#231;&#227;o.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B14"><sup>14</sup></xref></p>
    <p>Quando analisaram os dados ap&#243;s a estratifica&#231;&#227;o do grupo de pacientes com complica&#231;&#245;es neurol&#243;gicas e submetido ao procedimento cir&#250;rgico com o grupo que foi tratado apenas com antibioticoterapia, eles observaram uma taxa menor de mortalidade no grupo submetido ao procedimento cir&#250;rgico, o que &#233; concordante com a maioria das publica&#231;&#245;es mais recentes.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref> No entanto, os autores chamam a aten&#231;&#227;o para a possibilidade de um vi&#233;s de sele&#231;&#227;o.</p>
    <p>Quanto aos fatores independentes de mortalidade nos pacientes com endocardite e complica&#231;&#227;o neurol&#243;gica, os autores observaram que apenas a infec&#231;&#227;o pelo v&#237;rus HIV se mostrou estatisticamente significativa; por&#233;m, este resultado pode n&#227;o se repetir em outras coortes, haja vista que apenas dois pacientes eram portadores da s&#237;ndrome e apresentavam complica&#231;&#245;es neurol&#243;gicas da endocardite.</p>
    <p>Para concluir, a an&#225;lise da coorte de Alegria et al.,<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> apesar das limita&#231;&#245;es j&#225; citadas pelos autores, apresenta resultados extremamente interessantes, como apontar a diabetes como fator preditivo para a emboliza&#231;&#227;o e salientar a rela&#231;&#227;o da infec&#231;&#227;o pelo v&#237;rus HIV, de forma independente, &#224; mortalidade, al&#233;m de apresentar, de maneira bastante detalhada, aspectos ligados ao tratamento cir&#250;rgico em pacientes com endocardite e complica&#231;&#245;es neurol&#243;gicas.</p>
    <p>N&#227;o existem, at&#233; o momento, dados que permitam a cria&#231;&#227;o de recomenda&#231;&#245;es mais robustas quanto a abordagem dos pacientes com endocardite e que desenvolveram uma complica&#231;&#227;o neurol&#243;gica. As diretrizes podem ajudar, mas a tomada de decis&#227;o deve ser realizada pelo time de endocardite, ponderando as caracter&#237;sticas particulares de cada paciente.</p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo: Complica&#231;&#245;es Neurol&#243;gicas em Pacientes com Endocardite Infecciosa: Perspectivas de um Centro Terci&#225;rio</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Alegria</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Marques</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Cruz</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Broa</surname>
              <given-names>AL</given-names>
            </name>
            <name>
              <surname>Pereira</surname>
              <given-names>ARF</given-names>
            </name>
            <name>
              <surname>Jo&#227;o</surname>
              <given-names>I</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Complica&#231;&#245;es Neurol&#243;gicas em Pacientes com Endocardite Infecciosa: Perspectivas de um Centro Terci&#225;rio</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2021</year>
          <volume>116</volume>
          <issue>4</issue>
          <fpage>682</fpage>
          <lpage>691</lpage>
        </element-citation>
        <mixed-citation>1. Alegria A, Marques A, Cruz I, Broa AL, Pereira ARF, Jo&#227;o I, et al. Complica&#231;&#245;es Neurol&#243;gicas em Pacientes com Endocardite Infecciosa: Perspectivas de um Centro Terci&#225;rio. Arq Bras Cardiol. 2021; 116(4):682-691.</mixed-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
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  <sub-article article-type="translation" id="S01" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Managing Patients with Infectious Endocarditis and Neurological Complication &#8212; The Big Dilemma that Persists Until these Days</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0002-9700-9743</contrib-id>
          <name>
            <surname>Fortes</surname>
            <given-names>Claudio Querido</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Fortes</surname>
            <given-names>Nat&#225;lia Rodrigues Querido</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff6">
            <sup>3</sup>
          </xref>
        </contrib>
        <aff id="aff4">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Universit&#225;rio Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ - Brazil.</institution>
        </aff>
        <aff id="aff5">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Faculdade de Medicina, Universidade Est&#225;cio de S&#225;, Rio de Janeiro, RJ - Brazil.</institution>
        </aff>
        <aff id="aff6">
          <label>3</label>
          <addr-line>
            <named-content content-type="city">Niter&#243;i</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Universit&#225;rio Antonio Pedro, Universidade Federal Fluminense, Niter&#243;i, RJ &#8211; Brazil.</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Claudio Querido Fortes</bold> &#8226; Universidade Federal do Rio de Janeiro - Servi&#231;o de Doen&#231;as Infecciosas e Parasit&#225;rias - 5o andar - Rua Rodolpho Paulo Rocco, 255 - Ilha do Fund&#227;o. Postal Code <postal-code>21941-590</postal-code>, Rio de Janeiro, RJ &#8211; Brazil. E-mail: <email>querido.fortes@gmail.com</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Endocarditis</kwd>
        <kwd>Bacterial/complications</kwd>
        <kwd>Mortality</kwd>
        <kwd>Neurologic, Complications</kwd>
        <kwd>Renal Insufficiency</kwd>
        <kwd>Heart Valve Prosthesis</kwd>
        <kwd>Pandemics/complications</kwd>
        <kwd>Aging</kwd>
        <kwd>Embolization</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Endocarditis is an extremely challenging disease, both regarding diagnosis and due to the diversity of its presentation, as well as its management, which requires an endocarditis team including professionals from different specialties. An infectious disease specialist, clinical microbiologist, cardiologist, cardiac surgeon, neurologist and imaging specialist are of the essence, and assistance from other specialists is also desirable depending on each case. Its incidence has been increasing in recent decades, especially due to population aging, the growing number of individuals undergoing renal replacement therapy, the higher frequency of patients with prosthetic valves and cardiac electrical devices and also due to the technological advances in invasive diagnostic and therapeutic methods, in addition to the current &#8220;epidemic&#8221; of recreational intravenous drugs, which have become a serious public health problem in some countries. Despite all the progress made in the diagnosis and treatment of endocarditis, its mortality remains alarmingly high. The persistence of this high mortality may be partially explained by the increase in the number of older fragile patients with multiple comorbidities and patients with prostheses.</p>
      <p>The main objectives of the article &#8220; Neurological Complications in Patients with Infective Endocarditis: Insights from a Tertiary Centre&#8221;<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> are to evaluate the predictors of neurological complications in patients with infective endocarditis, the predictors of mortality in this group, and to compare the results of clinical treatment with a general practitioner and a surgeon, both among the study population, and stratifying the group of patients with neurological complications.</p>
      <p>In the Alegria et al.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> cohort, the independent predisposing factors for the development of neurological complications were diabetes and the absence of fever at presentation. This is an interesting information, as diabetes is little cited as a predictive factor for cerebral embolization in patients with endocarditis, although it has been mentioned in the European Society of Cardiology (ESC)<xref ref-type="bibr" rid="B2"><sup>2</sup></xref> and is one of the variables in the calculator developed by Hubert et al.,<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> to assess the risk of embolization in patients with endocarditis. The absence of fever on admission is not mentioned in the literature as being related to neurological complications. However, this is an intriguing finding, as it may be reflecting delayed diagnosis of endocarditis and, therefore, a longer time stretch until initiation of proper antibiotic therapy, increasing the chances of embolization to the central nervous system (CNS), since most neurological complications occur before hospitalization or during the first week of antibiotic therapy, significantly decreased after the second week of antimicrobial therapy. Another predictor of embolization mentioned by the authors was the patient&#8217;s age, although it did not present statistical significance in the multivariate analysis. It is important to note that in most cohorts, including that of Alegria et al.,<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> older age is related to lower risk for cerebral embolization in patients with endocarditis.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref> However, in the calculator by Hubert et al.,<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> age over 70 is considered to be associated with an increased risk of embolization.</p>
      <p>Interestingly, endocarditis involving the mitral valve and the infecting microorganism being S. aureus, predisposing factors for the development of neurological complications, classically described in most publications, were not found in this cohort.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B6"><sup>6</sup></xref> The size of the vegetation, which is the main predisposing factor for embolization, was unfortunately not evaluated in this cohort, as the vegetation was not measured in all patients.</p>
      <p>Alegria et al.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> address one of the most distressing dilemmas that the endocarditis team may face: decision-making for patients with neurological abnormalities resulting from endocarditis and persisting vegetation with high embolic potential or a potentially fatal complication, whose cardiac surgery is the only possible treatment. The three main complications that require surgical treatment are hemodynamic deterioration, prevention of embolization or its recurrence, and persistent infection. The issue is not restricted to the decision to submit the patient to surgery or not, but also as to the ideal moment for the intervention.</p>
      <p>When surgical indication is due to hemodynamic deterioration, even with all the risk of progression of neurological injury resulting from cardiopulmonary bypass (CPB), because a fatal outcome, without surgical intervention, is well known. The same occurs when surgical indication is persistence of infection. However, the greatest distress arises when indication for surgical treatment is to prevent the recurrence of embolization to the CNS, as, in this situation, in addition to the inherent risk of the surgical procedure (which is also present when the indications for the procedure are hemodynamic deterioration and persistence of infection), there is still a potentially fatal risk of worsening the neurological condition. In this situation, even if surgery has been chosen, another very controversial point in the literature is the moment when it should be performed.</p>
      <p>The authors report that the average time between diagnosis and surgery was 4 weeks (36 days) and that this would be the time interval required to avoid worsening the neurological complication as a result of the necessary heparinization for cardiopulmonary bypass, which is consistent with the current international guidelines.</p>
      <p>The latest European guideline recommends postponing cardiac surgery for at least 4 weeks in the presence of intracranial hemorrhage to prevent heparinization during cardiopulmonary bypass from increasing bleeding area or to prevent the conversion of ischemic infarction to hemorrhagic infarction. Besides, the non-pulsatile flow of cardiopulmonary bypass and hypotension during surgery may impair cerebral circulation and promote extension of cerebral infarction area. The authors of the guideline consider that the potential damage that cardiopulmonary bypass may cause is greater than the benefit that surgery can bring, but these recommendations are based on expert opinion.</p>
      <p>Over the last decade, several publications reported that the presence of asymptomatic neurological complications or transient ischemic attacks does not increase the risk of neurological complications in the postoperative period, and that, therefore, cardiac surgery can be performed at any time.<xref ref-type="bibr" rid="B7"><sup>7</sup></xref> When the patient has a small cerebral infarction with little neurological repercussion, they recommend that cardiac surgery be performed after 1 to 2 weeks after the neurological event, and other articles recommended that the interval could be less than 7 days. Others considered that surgery should be performed within the first 72 hours after the onset of the neurological condition and that after this interval the possibility of complications would be greater.<xref ref-type="bibr" rid="B8"><sup>8</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B9"><sup>9</sup></xref> However, the study by Garc&#237;a-Cabrera et al.,<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> in 2013, is consistent with the systematic literature review carried out by Tam et al.,10 where they concluded that patients with ischemic stroke can benefit from a delay of 1 to 2 weeks for surgery and those with a hemorrhagic event, more than 21 days.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B10"><sup>10</sup></xref> However, the most recent publications continue to recommend shorter intervals.<xref ref-type="bibr" rid="B11"><sup>11</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B12"><sup>12</sup></xref></p>
      <p>The greatest fears are severe neurological impairment or intracranial hemorrhage. In these situations, some researchers recommend not to operate the patient or to perform cardiac surgery after 1 month, in line with the current international guidelines. However, many recent publications have not found an association between the presence of cerebral hemorrhage or extensive infarction with significantly greater chances of neurological complications in the postoperative period,<xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B12"><sup>12</sup></xref> but, as mentioned before, care should be taken in the interpretation of these results, because, even if the total population of patients evaluated by these authors is not small, after stratifications, the number of participants in each group to be analyzed ends up being too small, in addition to the possibility of selection bias. Presently, a significant number of authors continue to recommend an interval of at least 21 days between the hemorrhagic event and the surgery, unless a surgery delay puts the patient&#8217;s life at risk.<xref ref-type="bibr" rid="B12"><sup>12</sup></xref></p>
      <p>In the cohort of Alegria et al.,<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> operated patients had lower mortality compared to those treated exclusively with antimicrobials, which is in line with most of the current literature.<xref ref-type="bibr" rid="B13"><sup>13</sup></xref> Alegria et al.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> found no difference in the mortality of patients with or without neurological complications, which was different from most of the literature, as the authors themselves argued.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B14"><sup>14</sup></xref></p>
      <p>When they compared the data after stratification of the group of patients with neurological complications who underwent the surgical procedure to the group of patients treated with antibiotic therapy only, they found lower mortality in the group undergoing the surgical procedure, which is in line with most of the latest publications,<xref ref-type="bibr" rid="B5"><sup>5</sup></xref> but the authors call attention to the possibility of a selection bias.</p>
      <p>Regarding the independent factors of mortality in patients with endocarditis with neurological complications, the authors found that only HIV infection was shown to be statistically significant, but this result may not be repeated in other cohorts, since only two patients had HIV infection and neurological complications from endocarditis.</p>
      <p>In conclusion, despite the limitations mentioned by the authors, the cohort of Alegria et al.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> presents extremely interesting results, such as diabetes as a predictive factor for embolization and HIV infection as independently related to mortality. It also presents, in a very detailed way, aspects related to surgical treatment in patients with endocarditis and neurological complications.</p>
      <p>Finally, there are, to date, no data that allow the creation of more robust recommendations regarding the approach of patients with endocarditis who have developed a neurological complication. The guidelines can help, but the decision must be made by the endocarditis team considering the particular characteristics of each patient and each case.</p>
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          <p>Short Editorial related to the article: Neurological Complications in Patients with Infective Endocarditis: Insights from a Tertiary Centre</p>
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