<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" dtd-version="1.1" specific-use="sps-1.9" article-type="letter" xml:lang="pt">
  <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">HDF34nXX6W9j546MQqtVjPS</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2022000601141</article-id>
      <article-id pub-id-type="publisher-id">abc.20210581</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20210581</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Carta Cient&#237;fica</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Trombose Mec&#226;nica da V&#225;lvula Mitral em Paciente com Infec&#231;&#227;o por COVID-19</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7441-3367</contrib-id>
          <name>
            <surname>Aru&#287;aslan</surname>
            <given-names>Emre</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3828-7479</contrib-id>
          <name>
            <surname>&#199;alapkulu</surname>
            <given-names>Yunus</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5233-8658</contrib-id>
          <name>
            <surname>&#214;rnek</surname>
            <given-names>Ender</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5401-1149</contrib-id>
          <name>
            <surname>Karanfil</surname>
            <given-names>Mustafa</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-5634-7941</contrib-id>
          <name>
            <surname>Bayram</surname>
            <given-names>H&#252;seyin</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2462-3168</contrib-id>
          <name>
            <surname>K&#252;&#231;&#252;ker</surname>
            <given-names>Seref Alp</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Hospital da Cidade de Ancara</institution>
          <institution content-type="orgdiv1">Departamento de Cardiologia</institution>
          <addr-line>
            <named-content content-type="city">Ancara</named-content>
          </addr-line>
          <country country="TR">Turquia</country>
          <institution content-type="original">Departamento de Cardiologia, Hospital da Cidade de Ancara, Ancara &#8211; Turquia</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Hospital da Cidade de Ancara</institution>
          <institution content-type="orgdiv1">Departamento de Cirurgia Cardiovascular</institution>
          <addr-line>
            <named-content content-type="city">Ancara</named-content>
          </addr-line>
          <country country="TR">Turquia</country>
          <institution content-type="original">Departamento de Cirurgia Cardiovascular, Hospital da Cidade de Ancara, Ancara &#8211; Turquia</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Emre Arugaslan</bold> &#8226; Ankara &#350;ehir Hastanesi Kardiyoloji Klini&#287;i, &#220;niversiteler Mahallesi <postal-code>1604</postal-code>. Cadde No: 9 &#199;ankaya/ANKARA. E-mail: <email>dremrearugaslan@gmail.com</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Bayram H, K&#252;&#231;&#252;ker SA; Obten&#231;&#227;o de dados: Aru&#287;aslan E, &#199;alapkulu Y; An&#225;lise e interpreta&#231;&#227;o dos dados: Karanfil M; Reda&#231;&#227;o do manuscrito: Aru&#287;aslan E, Karanfil M, &#214;rnek E; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: &#214;rnek E, Bayram H, K&#252;&#231;&#252;ker SA.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesse</bold>
          </p>
          <p>N&#227;o h&#225; conflito com o presente artigo</p>
        </fn>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>10</day>
        <month>06</month>
        <year>2022</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <year>2022</year>
      </pub-date>
      <volume>118</volume>
      <issue>6</issue>
      <fpage>1141</fpage>
      <lpage>1143</lpage>
      <history>
        <date date-type="received">
          <day>08</day>
          <month>07</month>
          <year>2021</year>
        </date>
        <date date-type="rev-recd">
          <day>08</day>
          <month>10</month>
          <year>2021</year>
        </date>
        <date date-type="accepted">
          <day>08</day>
          <month>12</month>
          <year>2021</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xml:lang="en" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>COVID-19/complica&#231;&#245;es</kwd>
        <kwd>Valva Mitral/cirurgia</kwd>
        <kwd>Inflama&#231;&#227;o</kwd>
        <kwd>Trombose</kwd>
        <kwd>Transtornos da Coagula&#231;&#227;o Sangu&#237;nea/complica&#231;&#245;es</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="10"/>
        <page-count count="3"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>A nova doen&#231;a de coronav&#237;rus-2019 (COVID-19) causada pelo &#8220;<italic>Severe Acute Respiratory Syndrome Coronavirus-2</italic>&#8221; (SARS-CoV-2) tornou-se uma pandemia global. Embora o envolvimento respirat&#243;rio seja a apFontes de financiamentoresenta&#231;&#227;o predominante, as evid&#234;ncias atuais mostram que a COVID-19 &#233; uma doen&#231;a multissist&#234;mica com coagulopatia e complica&#231;&#245;es tromboemb&#243;licas. O aumento da produ&#231;&#227;o de fator tecidual e a redu&#231;&#227;o da fibrin&#243;lise da trombina devido &#224; hiperinflama&#231;&#227;o s&#227;o os mecanismos propostos da trombose induzida por COVID-19.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
      <p>Apresentamos um caso de um paciente infectado por COVID-19 com trombose da v&#225;lvula mitral mec&#226;nica.</p>
    </sec>
    <sec sec-type="cases">
      <title>Relato de caso</title>
      <p>Paciente do sexo masculino, 46 anos, submetido &#224; troca valvar mec&#226;nica mitral h&#225; 3 anos, foi admitido com hist&#243;ria de 1 semana de dispneia leve e mal-estar. O exame f&#237;sico revelou aus&#234;ncia de clique prot&#233;tico. N&#227;o havia distens&#227;o venosa jugular nem estertores &#224; ausculta pulmonar. O paciente estava hemodinamicamente est&#225;vel. O eletrocardiograma mostrou ritmo sinusal com altera&#231;&#245;es inespec&#237;ficas do segmento ST. As medica&#231;&#245;es regulares consistiam apenas em varfarina 5 mg/dia. Seu hist&#243;rico m&#233;dico recente foi not&#225;vel devido &#224; infec&#231;&#227;o por COVID-19 na sua casa. Decidiu-se testar o paciente para COVID-19 devido ao contato pr&#243;ximo e febre subfebril (37,5&#176;C). O teste de swab nasofar&#237;ngeo de rea&#231;&#227;o em cadeia da polimerase em tempo real foi positivo para SARS-CoV2. A tomografia computadorizada de t&#243;rax realizada no pronto-socorro revelou infiltra&#231;&#245;es centrolobulares bilaterais, que foram relatadas como at&#237;picas de COVID-19. O ecocardiograma transtor&#225;cico (ETT) detectou mobilidade dos folhetos severamente restrita, com gradiente transvalvar m&#233;dio de 23 mmHg (<xref ref-type="fig" rid="f1">Figura 1</xref>). Foi observado trombo obstrutivo com di&#226;metro de 2,2 x 0,8 cm estendendo-se at&#233; a via de sa&#237;da do ventr&#237;culo esquerdo (<xref ref-type="fig" rid="f1">Figura 1</xref>, <xref ref-type="app" rid="app1">V&#237;deo 1</xref>). A fluoroscopia tamb&#233;m mostrou mobilidade restrita dos folhetos. O INR de admiss&#227;o foi de 3,26. Os prontu&#225;rios m&#233;dicos revelaram medi&#231;&#245;es mensais do INR terap&#234;utico antes da interna&#231;&#227;o. N&#227;o houve outro epis&#243;dio tromb&#243;tico na hist&#243;ria m&#233;dica pregressa do paciente. Havia hipoxemia leve (PaO2:71 mmHg) na gasometria arterial. Os exames laboratoriais iniciais mostraram n&#237;veis de d&#237;mero D 1,0 mg/L (&lt; 0,55), prote&#237;na C-reativa 0,02708 g/L (0 - 0,005), IL-6 14,7 pg/mL (0 - 3,4), plaquetas 258 x 10^9 /L(150-400), e ferritina 58 &#181;g/L (22 &#8211; 322). Hemoculturas foram obtidas para descartar endocardite infecciosa. A cirurgia de emerg&#234;ncia foi recusada devido &#224; estabilidade hemodin&#226;mica e infec&#231;&#227;o ativa por COVID-19.</p>
      <fig id="f1">
        <label>Figura 1</label>
        <caption>
          <title>Imagens ecocardiogr&#225;ficas de v&#225;lvula mec&#226;nica obstru&#237;da.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-118-06-1141-10581-gf01.tif"/></fig>
      <p>O paciente foi internado na unidade de terapia intensiva para monitorar sintomas e hemodin&#226;mica. A varfarina foi interrompida e a heparina n&#227;o fracionada intravenosa foi administrada com dosagem guiada de aPTT. O paciente foi monitorado de perto quanto a sinais de insufici&#234;ncia card&#237;aca e instabilidade hemodin&#226;mica. No terceiro dia de tratamento, o ETT mostrou gradientes valvares mitrais diminu&#237;dos (m&#233;dia de 12 mmHg). O tratamento com heparina foi continuado. No entanto, o paciente piorou por causa de taquicardia supraventricular e edema pulmonar subsequente no dia 7. O ecocardiograma &#224; beira do leito foi realizado imediatamente e demonstrou reeleva&#231;&#227;o do gradiente press&#243;rico m&#233;dio para 28 mmHg. Foi administrado trombol&#237;tico emergente em bolus de 10 mg de tPA e infus&#227;o de 90 mg em 90 minutos; entretanto, nenhuma melhora foi observada nos par&#226;metros cl&#237;nicos e ecocardiogr&#225;ficos ap&#243;s a l&#237;tica. Foi necess&#225;ria a substitui&#231;&#227;o urgente da v&#225;lvula mitral. As ader&#234;ncias de cirurgia card&#237;aca pr&#233;via foram liberadas ap&#243;s refazer esternotomia mediana. A circula&#231;&#227;o extracorp&#243;rea foi estabelecida com canula&#231;&#227;o venosa. Trombose foi observada na valva mec&#226;nica pela abordagem da atriotomia esquerda. A v&#225;lvula mec&#226;nica trombosada foi excisada e uma nova v&#225;lvula mec&#226;nica (29 mm, Sorin) foi substitu&#237;da. Recebeu alta com um INR alvo de 3,5 ap&#243;s cuidados p&#243;s-operat&#243;rios sem intercorr&#234;ncias. Como a infec&#231;&#227;o por COVID-19 deveria ser o gatilho da trombose da v&#225;lvula mec&#226;nica, nenhuma investiga&#231;&#227;o hematol&#243;gica adicional foi feita. O paciente n&#227;o apresentou nenhum evento adverso ap&#243;s a alta.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>Descrevemos um caso de trombose mec&#226;nica da v&#225;lvula mitral em um paciente com COVID-19. As complica&#231;&#245;es tromb&#243;ticas do sistema cardiovascular s&#227;o evidentes na literatura. Houve relatos de casos de tromboembolismo venoso e trombose de art&#233;ria coron&#225;ria relacionados ao COVID-19.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> A trombose da valva mitral bioprot&#233;tica foi tratada com sucesso pelo in&#237;cio da anticoagula&#231;&#227;o em um paciente idoso com COVID-19.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> As diretrizes recomendam pelo menos dose profil&#225;tica de heparina de baixo peso molecular para todos os pacientes hospitalizados com COVID-19 na aus&#234;ncia de contraindica&#231;&#245;es absolutas.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
      <p>A trombose mec&#226;nica da v&#225;lvula card&#237;aca &#233; uma complica&#231;&#227;o com risco de vida que requer diagn&#243;stico e tratamento imediatos. Geralmente est&#225; associada &#224; anticoagula&#231;&#227;o inadequada. O ETT e a ecocardiografia transesof&#225;gica (ETE) s&#227;o essenciais para o diagn&#243;stico e determina&#231;&#227;o do grau e causa da disfun&#231;&#227;o valvar. O ETE n&#227;o foi realizado neste paciente com COVID-19 devido ao risco aumentado de dissemina&#231;&#227;o de SARS-Cov-2. A cinefluoroscopia fornece informa&#231;&#245;es adicionais sobre a mobilidade e abertura do folheto. A substitui&#231;&#227;o valvar de emerg&#234;ncia &#233; recomendada para trombose obstrutiva de pr&#243;tese valvar em pacientes cr&#237;ticos, mas a fibrin&#243;lise deve ser considerada se o risco cir&#250;rgico for alto.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Baixo risco de sangramento, envolvimento das valvas direitas, primeiro epis&#243;dio de trombose valvar e trombo menor que 1 cm&#178; s&#227;o outros fatores que tornam a fibrin&#243;lise mais favor&#225;vel.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> A equipe card&#237;aca decidiu administrar fibrinol&#237;tico devido a preocupa&#231;&#245;es com hiperinflama&#231;&#227;o perioperat&#243;ria e hipercoagulabilidade associada ao COVID-19,<sup><xref ref-type="bibr" rid="B7">7</xref></sup> mas a reopera&#231;&#227;o acabou sendo necess&#225;ria ap&#243;s a falha dos trombol&#237;ticos.</p>
      <p>A infec&#231;&#227;o por COVID-19 tem sido associada ao aumento da mortalidade em pacientes submetidos &#224; cirurgia card&#237;aca.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> A resposta inflamat&#243;ria exagerada ao v&#237;rus pode aumentar o risco de s&#237;ndrome do desconforto respirat&#243;rio agudo (SDRA) no p&#243;s-operat&#243;rio.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Um caso de trombose p&#243;s-operat&#243;ria aguda da v&#225;lvula a&#243;rtica e subsequente embolia coron&#225;ria foi relatada.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> O risco de transmiss&#227;o perioperat&#243;ria do v&#237;rus para os profissionais de sa&#250;de tamb&#233;m deve ser considerado. Entretanto, retardar a cirurgia em um paciente com trombose de pr&#243;tese valvar tamb&#233;m &#233; arriscado devido a complica&#231;&#245;es como choque cardiog&#234;nico, insufici&#234;ncia card&#237;aca e embolia sist&#234;mica. A decis&#227;o entre cirurgia e tromb&#243;lise para trombose valvar mec&#226;nica deve ser individualizada. Fatores cl&#237;nicos, experi&#234;ncia local e experi&#234;ncia cir&#250;rgica s&#227;o fatores cr&#237;ticos na via de decis&#227;o.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#245;es</title>
      <p>A literatura tem dados consistentes sobre a hipercoagulabilidade na infec&#231;&#227;o por COVID-19, ent&#227;o presumimos que a doen&#231;a por Coronav&#237;rus foi o fator predisponente no desenvolvimento de trombose de v&#225;lvula mec&#226;nica em um paciente com valores terap&#234;uticos de INR. No entanto, deve-se notar que a trombose se desenvolveu, embora os marcadores pr&#243;-inflamat&#243;rios estivessem moderadamente elevados. Da mesma forma, foi relatada trombose coronariana recorrente em um caso moderado de COVID-19,<sup><xref ref-type="bibr" rid="B2">2</xref></sup> portanto, a hiperinflama&#231;&#227;o pode n&#227;o ser a &#250;nica via que leva &#224; trombose em pacientes com COVID-19.</p>
      <p>Os m&#233;dicos devem estar cientes das complica&#231;&#245;es tromb&#243;ticas durante este surto. O uso preventivo e terap&#234;utico de drogas antitromb&#243;ticas deve ser feito em paralelo &#224;s recomenda&#231;&#245;es formais para mitigar a carga tromb&#243;tica em pacientes com COVID-19.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by" id="fn1">
        <p>
          <bold>Fontes de financiamento</bold>
        </p>
        <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
      </fn>
      <fn fn-type="other" id="fn2">
        <p>
          <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
        </p>
        <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
      </fn>
      <fn fn-type="other" id="fn3">
        <p>
          <bold>Aprova&#231;&#227;o &#233;tica e consentimento informado</bold>
        </p>
        <p>Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>Refer&#234;ncia</title>
      <ref id="B1">
        <label>1</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bikdeli</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Madhavan</surname>
              <given-names>MV</given-names>
            </name>
            <name>
              <surname>Jimenez</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Chuich</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Dreyfus</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Driggin</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>COVID-19 and Thrombotic or Thromboembolic Disease: implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2020</year>
          <volume>75</volume>
          <issue>25</issue>
          <fpage>2950</fpage>
          <lpage>2973</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2020.04.031</pub-id>
        </element-citation>
        <mixed-citation>1 Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al. COVID-19 and Thrombotic or Thromboembolic Disease: implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(25):2950&#8211;73. doi: 10.1016/j.jacc.2020.04.031.</mixed-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Muguerza</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Loizeau</surname>
              <given-names>PA</given-names>
            </name>
          </person-group>
          <article-title>Recurrent coronary thrombotic events in a moderate case of COVID-19</article-title>
          <source>BMJ Case Rep</source>
          <year>2021</year>
          <volume>14</volume>
          <issue>1</issue>
          <elocation-id>e237624</elocation-id>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2020.04.031</pub-id>
        </element-citation>
        <mixed-citation>2 Muguerza J, Loizeau PA. Recurrent coronary thrombotic events in a moderate case of COVID-19. BMJ Case Rep. 2021;14(1):e237624. doi: 10.1016/j.jacc.2020.04.031.</mixed-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Scudiero</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Pit&#236;</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Keim</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Parodi</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
          <article-title>Acute pulmonary embolism in COVID-19 patient: a case report of free-floating right heart thrombus successfully treated with fibrinolysis</article-title>
          <source>Eur Heart J Case Rep</source>
          <year>2020</year>
          <volume>5</volume>
          <issue>1</issue>
          <comment>ytaa388</comment>
          <pub-id pub-id-type="doi">10.1093/ehjcr/ytaa388</pub-id>
        </element-citation>
        <mixed-citation>3 Scudiero F, Pit&#236; A, Keim R, Parodi G. Acute pulmonary embolism in COVID-19 patient: a case report of free-floating right heart thrombus successfully treated with fibrinolysis. Eur Heart J Case Rep 2020;5(1):ytaa388. doi: 10.1093/ehjcr/ytaa388.</mixed-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Llopis Gisbert</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Vidal Urrutia</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Moruno Benita</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Pay&#225; Chaume</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Berenguer Jofresa</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Cubillos Arango</surname>
              <given-names>AM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Bioprosthetic Valve Thrombosis and Obstruction Secondary to COVID-19</article-title>
          <source>Can J Cardiol</source>
          <year>2021</year>
          <volume>37</volume>
          <issue>6</issue>
          <fpage>938.e3</fpage>
          <lpage>938.e6</lpage>
          <pub-id pub-id-type="doi">10.1016/j.cjca.2020.10.008</pub-id>
        </element-citation>
        <mixed-citation>4 Llopis Gisbert G, Vidal Urrutia V, Moruno Benita MA, Pay&#225; Chaume A, Berenguer Jofresa A, Cubillos Arango AM et al. Bioprosthetic Valve Thrombosis and Obstruction Secondary to COVID-19. Can J Cardiol. 2021;37(6):938.e3-938.e6. doi: 10.1016/j.cjca.2020.10.008.</mixed-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Baumgartner</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Falk</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Bax</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>De Bonis</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Hamm</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Holm</surname>
              <given-names>PJ</given-names>
            </name>
            <etal/>
            <collab>ESC Scientific Document Group</collab>
          </person-group>
          <article-title>2017 ESC/EACTS Guidelines for the management of valvular heart disease</article-title>
          <source>Eur Heart J</source>
          <year>2017</year>
          <volume>38</volume>
          <issue>36</issue>
          <fpage>2739</fpage>
          <lpage>2791</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehx391</pub-id>
        </element-citation>
        <mixed-citation>5 Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. ESC Scientific Document Group. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2017;38(36):2739-91. doi: 10.1093/eurheartj/ehx391.</mixed-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tarasoutchi</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Montera</surname>
              <given-names>MW</given-names>
            </name>
            <name>
              <surname>Ramos</surname>
              <given-names>AIO</given-names>
            </name>
            <name>
              <surname>Sampaio</surname>
              <given-names>RO</given-names>
            </name>
            <name>
              <surname>Rosa</surname>
              <given-names>VEE</given-names>
            </name>
            <name>
              <surname>Accorsi</surname>
              <given-names>TAD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Update of the Brazilian Guidelines for Valvular Heart Disease - 2020</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2020</year>
          <month>10</month>
          <volume>115</volume>
          <issue>4</issue>
          <fpage>720</fpage>
          <lpage>775</lpage>
          <pub-id pub-id-type="doi">10.36660/abc.20201047</pub-id>
        </element-citation>
        <mixed-citation>6 Tarasoutchi F, Montera MW, Ramos AIO, Sampaio RO, Rosa VEE, Accorsi TAD et al. Update of the Brazilian Guidelines for Valvular Heart Disease - 2020. Arq Bras Cardiol. 2020 Oct;115(4):720-75. doi: 10.36660/abc.20201047.</mixed-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>G&#252;naydin</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Stammers</surname>
              <given-names>AH</given-names>
            </name>
          </person-group>
          <article-title>Perioperative management of COVID-19 patients undergoing cardiac surgery with cardiopulmonary bypass</article-title>
          <source>Perfusion</source>
          <year>2020</year>
          <volume>3</volume>
          <issue>6</issue>
          <fpage>465</fpage>
          <lpage>473</lpage>
          <pub-id pub-id-type="doi">10.1177/0267659120941341</pub-id>
        </element-citation>
        <mixed-citation>7 G&#252;naydin S, Stammers AH. Perioperative management of COVID-19 patients undergoing cardiac surgery with cardiopulmonary bypass. Perfusion. 2020;3(6):465-73. doi: 10.1177/0267659120941341.</mixed-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sanders</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Akowuah</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Cooper</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Kirmani</surname>
              <given-names>BH</given-names>
            </name>
            <name>
              <surname>Kanani</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Acharya</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Cardiac surgery outcome during the COVID-19 pandemic: a retrospective review of the early experience in nine UK centers</article-title>
          <source>J Cardiothorac Surg</source>
          <year>2021</year>
          <volume>16</volume>
          <issue>1</issue>
          <fpage>43</fpage>
          <lpage>43</lpage>
        </element-citation>
        <mixed-citation>8 Sanders J, Akowuah E, Cooper J, Kirmani BH, Kanani M, Acharya M, et al. Cardiac surgery outcome during the COVID-19 pandemic: a retrospective review of the early experience in nine UK centers. J Cardiothorac Surg. 2021;16(1):43.</mixed-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mavio&#287;lu</surname>
              <given-names>HL</given-names>
            </name>
            <name>
              <surname>&#220;nal</surname>
              <given-names>EU</given-names>
            </name>
            <name>
              <surname>A&#351;k&#305;n</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>K&#252;&#231;&#252;ker</surname>
              <given-names>&#350;A</given-names>
            </name>
            <name>
              <surname>&#214;zatik</surname>
              <given-names>MA</given-names>
            </name>
          </person-group>
          <article-title>Perioperative planning for cardiovascular operations in the COVID-19 pandemic</article-title>
          <source>Turk Gogus Kalp Damar Cerrahisi Derg</source>
          <year>2020</year>
          <volume>28</volume>
          <issue>2</issue>
          <fpage>236</fpage>
          <lpage>243</lpage>
          <pub-id pub-id-type="doi">10.1186/s13019-021-01424-y</pub-id>
        </element-citation>
        <mixed-citation>9 Mavio&#287;lu HL, &#220;nal EU, A&#351;k&#305;n G, K&#252;&#231;&#252;ker &#350;A, &#214;zatik MA. Perioperative planning for cardiovascular operations in the COVID-19 pandemic. Turk Gogus Kalp Damar Cerrahisi Derg. 2020;28(2):236-43. doi: 10.1186/s13019-021-01424-y.</mixed-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Manghat</surname>
              <given-names>NE</given-names>
            </name>
            <name>
              <surname>Hamilton</surname>
              <given-names>MCK</given-names>
            </name>
            <name>
              <surname>Joshi</surname>
              <given-names>NV</given-names>
            </name>
            <name>
              <surname>Vohra</surname>
              <given-names>HA</given-names>
            </name>
          </person-group>
          <article-title>Acute postoperative thrombosis of an aortic valve prosthesis and embolic myocardial infarction in a coronavirus disease 2019 (COVID-19)-positive patient-an unrecognised complication</article-title>
          <source>JTCVS Tech</source>
          <year>2020</year>
          <volume>4</volume>
          <fpage>111</fpage>
          <lpage>113</lpage>
          <pub-id pub-id-type="doi">10.1016/j.xjtc.2020.09.020</pub-id>
        </element-citation>
        <mixed-citation>10 Manghat NE, Hamilton MCK, Joshi NV, Vohra HA. Acute postoperative thrombosis of an aortic valve prosthesis and embolic myocardial infarction in a coronavirus disease 2019 (COVID-19)-positive patient-an unrecognised complication. JTCVS Tech 2020: 4:111-3. doi: 10.1016/j.xjtc.2020.09.020.</mixed-citation>
      </ref>
    </ref-list>
    <app-group>
      <app id="app1">
        <label>*</label>
        <title>Material suplementar</title>
        <p>Para assistir ao v&#237;deo suplementar, por favor, <ext-link ext-link-type="uri" xlink:href=" http://abccardiol.org/supplementary-material/2022/11806/2021-0581-video.mp4">clique aqui</ext-link>.</p>
      </app>
    </app-group>
  </back>
  <sub-article article-type="translation" id="S01" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Research Letter</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Mechanical Mitral Valve Thrombosis in a Patient with COVID-19 Infection</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7441-3367</contrib-id>
          <name>
            <surname>Aru&#287;aslan</surname>
            <given-names>Emre</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3828-7479</contrib-id>
          <name>
            <surname>&#199;alapkulu</surname>
            <given-names>Yunus</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5233-8658</contrib-id>
          <name>
            <surname>&#214;rnek</surname>
            <given-names>Ender</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5401-1149</contrib-id>
          <name>
            <surname>Karanfil</surname>
            <given-names>Mustafa</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-5634-7941</contrib-id>
          <name>
            <surname>Bayram</surname>
            <given-names>H&#252;seyin</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2462-3168</contrib-id>
          <name>
            <surname>K&#252;&#231;&#252;ker</surname>
            <given-names>Seref Alp</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>2</sup>
          </xref>
        </contrib>
        <aff id="aff3">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Ancara</named-content>
          </addr-line>
          <country country="TR">Turkey</country>
          <institution content-type="original">Departamento de Cardiologia, Hospital da Cidade de Ancara, Ancara &#8211; Turkey</institution>
        </aff>
        <aff id="aff4">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">Ancara</named-content>
          </addr-line>
          <country country="TR">Turkey</country>
          <institution content-type="original">Departamento de Cirurgia Cardiovascular, Hospital da Cidade de Ancara, Ancara &#8211; Turkey</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Emre Arugaslan</bold> &#8226; Ankara &#350;ehir Hastanesi Kardiyoloji Klini&#287;i, &#220;niversiteler Mahallesi 1604. Cadde No: 9 &#199;ankaya/Ankara - Turkey. Email: <email>dremrearugaslan@gmail.com</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Author Contributions</bold>
          </p>
          <p>Conception and design of the research: Bayram H, K&#252;&#231;&#252;ker SA; Acquisition of data: Aru&#287;aslan E, &#199;alapkulu Y; Analysis and interpretation of the data: Karanfil M; Writing of the manuscript: Aru&#287;aslan E, Karanfil M, &#214;rnek E; Critical revision of the manuscript for intellectual contente: &#214;rnek E, Bayram H, K&#252;&#231;&#252;ker SA.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>COVID-19/complications</kwd>
        <kwd>Mitrakl Valvesurgery</kwd>
        <kwd>Infammation</kwd>
        <kwd>Thrombosis</kwd>
        <kwd>Blood Coagulation, Disorders/complications</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>The novel coronavirus disease-2019 (COVID-19) caused by &#8220;Severe Acute Respiratory Syndrome Coronavirus-2&#8221; (SARS-CoV-2) became a global pandemic. Although respiratory involvement is the predominant presentation, current evidence has shown that COVID-19 is a multisystemic disease with coagulopathy and thromboembolic complications. Increased production of tissue factor and thrombin reduced fibrinolysis due to hyperinflammation are the proposed mechanisms of COVID-19 induced thrombosis.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
        <p>We present a case of a COVID-19 infected patient with thrombosis of the mechanical mitral valve.</p>
      </sec>
      <sec sec-type="cases">
        <title>Case Report</title>
        <p>A 46-year-old male patient who underwent mitral mechanical valve replacement 3 years ago was admitted with a 1 week history of mild dyspnea and malaise. Physical examination revealed the absence of prosthetic click. There was neither jugular venous distension nor rales on lung auscultation. The patient was hemodynamically stable. Electrocardiography showed sinus rhythm with nonspecific ST-segment changes. Regular medications consisted of only warfarin 5 mg/day. His recent medical history was remarkable due to the COVID-19 infection in his household. It was decided to test the patient for COVID- 19 because of close contact and subfebrile fever (37.5 &#176;C). Real-time polymerase chain reaction nasopharyngeal swab test was positive for SARS-CoV2. Chest computed tomography scan performed in the emergency department revealed bilateral centrilobular infiltrations, which were reported as atypical COVID-19. Transthoracic echocardiography (TTE) detected severely restricted leaflet mobility, with a mean transvalvular gradient of 23 mmHg (<xref ref-type="fig" rid="f2">Figure 1</xref>). Obstructive thrombus with a 2.2 X 0.8 cm diameter extending to the left ventricular outflow tract was seen (<xref ref-type="fig" rid="f2">Figure 1</xref>, <xref ref-type="app" rid="app2">Video 1</xref>). Fluoroscopy also showed restricted mobility of leaflets. Admission INR was 3.26. Medical records revealed monthly therapeutic INR measurements before hospitalization. There was no other thrombotic episode in the patient&#8217;s past medical history. There was mild hypoxemia (PaO<sub>2</sub>:71 mmHg) on arterial blood gas analysis. Initial laboratory tests showed levels of D dimer 1.0 mg/L (&lt; 0.55), C- reactive protein 0.02708 g/L (0 - 0.005), IL-6 14.7 pg/mL (0 &#8211; 3.4), platelets 258 x 10^9/L(150-400), and ferritin 58 &#181;g/L (22 &#8211; 322). Blood cultures were obtained to rule out infective endocarditis. Emergent surgery was declined due to hemodynamic stability and active COVID-19 infection.</p>
        <fig id="f2">
          <label>Figure 1</label>
          <caption>
            <title>Echocardiographic images of obstructed mechanical valve.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-118-06-1141-10581-gf01-en.tif"/></fig>
        <p>The patient was admitted to the intensive care unit to monitor symptoms and hemodynamics. Warfarin was stopped, and intravenous unfractionated heparin was administered with aPTT guided dosing. The patient was closely monitored for signs of heart failure and hemodynamic instability. On the third day of treatment, TTE showed decreased mitral valve gradients (mean 12 mmHg). Heparin treatment was continued. However, the patient deteriorated because of supraventricular tachycardia and subsequent pulmonary edema on day 7. Bedside echocardiography was done immediately and demonstrated re-elevation of the mean pressure gradient to 28 mmHg. Emergent thrombolytic was administered 10 mg bolus of tPA and 90 mg infusion in 90 minutes; however, no amelioration was seen in neither clinical nor echocardiographic parameters after lytics. Urgent mitral valve replacement was needed. Adherences from previous cardiac surgery were released after redo median sternotomy. Cardiopulmonary bypass was established with venous cannulation. Thrombosis was observed on the mechanical valve by the left atriotomy approach. The thrombosed mechanical valve was excised, and a new mechanical valve (29 mm, Sorin) was replaced. He was discharged with a target INR of 3.5 after uneventful postoperative care. As COVID-19 infection was supposed to be the trigger of mechanical valve thrombosis, no further hematological investigation was done. The patient has not experienced any adverse event after discharge.</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>We described a case of mechanical mitral valve thrombosis in a COVID-19 patient. Thrombotic complications of the cardiovascular system are evident in the literature. There have been reports of venous thromboembolism and coronary artery thrombosis cases related to COVID-19.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> Bioprosthetic mitral valve thrombosis was successfully treated by the initiation of anticoagulation in an elderly patient with COVID-19.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Guidelines recommend at least prophylactic dose of low molecular weight heparin for all hospitalized COVID-19 patients in the absence of absolute contraindications.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
        <p>Mechanical heart valve thrombosis is a life-threatening complication necessitating prompt diagnosis and treatment. It is usually associated with inadequate anticoagulation. TTE and transesophageal echocardiography (TEE) are essential for diagnosis and determining the degree and cause of valve dysfunction. TEE was not performed in this COVID-19 patient due to the heightened risk for SARS-Cov-2 spread. Cinefluoroscopic provides additional information about leaflet mobility and opening. Emergency valve replacement is recommended for obstructive prosthetic valve thrombosis in critically ill patients, but fibrinolysis should be considered if the surgical risk is high.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Low risk of bleeding, involvement of the right valves, first episode of valve thrombosis, and thrombus smaller than 1 cm&#178; are other factors that make fibrinolysis more favorable.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> Heart team decided to administer fibrinolytic due to concerns about perioperative hyper inflammation and hypercoagulability associated with COVID-19 <sup><xref ref-type="bibr" rid="B7">7</xref></sup> but redo surgery was eventually needed after thrombolytics failed.</p>
        <p>COVID-19 infection has been associated with increased mortality in patients undergoing cardiac surgery.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Exaggerated inflammatory response to the virus may augment the risk of acute respiratory distress syndrome (ARDS) postoperatively.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> A case of acute postoperative thrombosis of the aortic valve and subsequent coronary embolism was reported.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> The risk of perioperative transmission of the virus to health care personnel should also be kept in mind. However, delaying the surgery in a patient with prosthetic valve thrombosis is also risky due to complications such as cardiogenic shock, heart failure and systemic embolism. The decision between surgery and thrombolysis for mechanical valve thrombosis should be individualized. Clinical factors, local experience and surgical expertise are critical factors in the decision pathway.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusions</title>
        <p>Literature has consistent data regarding hypercoagulability in COVID-19 infection, so we presumed that Coronavirus disease was the predisposing factor in the development of mechanical valve thrombosis in a patient with therapeutic INR values. However, it should be noted that thrombosis developed although proinflammatory markers were moderately elevated. Similarly, recurrent coronary thrombosis in a moderate case of COVID-19 was reported,<sup><xref ref-type="bibr" rid="B2">2</xref></sup> so hyper inflammation may not be the sole pathway leading to thrombosis in patients with COVID-19.</p>
        <p>Physicians should be aware of thrombotic complications during this outbreak. Preventive and therapeutic use of antithrombotic drugs should be done in parallel to formal recommendations to mitigate the thrombotic burden in COVID-19 patients.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by" id="fn4">
          <p>
            <bold>Sources of Funding</bold>
          </p>
          <p>There were no external funding sources for this study.</p>
        </fn>
        <fn fn-type="other" id="fn5">
          <p>
            <bold>Study Association</bold>
          </p>
          <p>This study is not associated with any thesis or dissertation work.</p>
        </fn>
        <fn fn-type="other" id="fn6">
          <p>
            <bold>Ethics approval and consent to participate</bold>
          </p>
          <p>This article does not contain any studies with human participants or animals performed by any of the authors.</p>
        </fn>
      </fn-group>
      <app-group>
        <app id="app2">
          <label>*</label>
          <title>Supplemental Materials</title>
          <p>See the Supplemental Video, please <ext-link ext-link-type="uri" xlink:href=" http://abccardiol.org/supplementary-material/2022/11806/2021-0581-video.mp4">click here</ext-link>.</p>
        </app>
      </app-group>
    </back>
  </sub-article>
</article>
