<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "http://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="editorial" 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">gZBYzFY8pfRDFk4V8MwsnPD</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2021001301028</article-id>
      <article-id pub-id-type="publisher-id">abc.20210809</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20210809</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>O Papel da Inflama&#231;&#227;o nos Desfechos P&#243;s-TAVI</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Melo</surname>
            <given-names>Pedro H. M. C. de</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0002-0047-7859</contrib-id>
          <name>
            <surname>Modolo</surname>
            <given-names>Rodrigo</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Hospital S&#237;rio Liban&#234;s</institution>
          <institution content-type="orgdiv1">Departamento de Cardiologia Intervencionista</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">Departamento de Cardiologia Intervencionista - Hospital S&#237;rio Liban&#234;s, S&#227;o Paulo, SP - Brasil</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Universidade Estadual de Campinas</institution>
          <institution content-type="orgdiv1">Faculdade de Ci&#234;ncias M&#233;dicas</institution>
          <institution content-type="orgdiv2">Departamento de Cl&#237;nica M&#233;dica</institution>
          <addr-line>
            <named-content content-type="city">Campinas</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Departamento de Cl&#237;nica M&#233;dica - Divis&#227;o de Cardiologia - Faculdade de Ci&#234;ncias M&#233;dicas - Universidade Estadual de Campinas (UNICAMP), Campinas, SP - Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Rodrigo Modolo &#8226;</bold> Departamento de Cl&#237;nica M&#233;dica - Divis&#227;o de Cardiologia, Faculdade de Ci&#234;ncias M&#233;dicas. Universidade Estadual de Campinas &#8211; UNICAMP, <postal-code>13084-971</postal-code>, Campinas, SP - Brasil, E-mail: <email>modolo.rodrigo@gmail.com</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>22</day>
        <month>11</month>
        <year>2021</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <month>11</month>
        <year>2021</year>
      </pub-date>
      <volume>117</volume>
      <issue>5</issue>
      <fpage>1028</fpage>
      <lpage>1029</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>Substitui&#231;&#227;o da Valva A&#243;rtica Transcateter/m&#233;todos</kwd>
        <kwd>Valva A&#243;rtica/cirurgia</kwd>
        <kwd>Mortalidade</kwd>
        <kwd>Comorbidade</kwd>
        <kwd>Biomarcadores</kwd>
        <kwd>Prote&#237;na C-Reativa</kwd>
        <kwd>Inflama&#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="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>Na experi&#234;ncia inicial de implanta&#231;&#227;o transcateter da v&#225;lvula a&#243;rtica (TAVI, do ingl&#234;s <italic>transcatheter aortic valve implantation</italic>) em pacientes com risco extremo ou alto para substitui&#231;&#227;o cir&#250;rgica da v&#225;lvula a&#243;rtica, a mortalidade global em um ano era de at&#233; 25%.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Desde ent&#227;o, o acesso &#224; TAVI foi estendido para pacientes de risco baixo e intermedi&#225;rio, e o volume anual de procedimentos aumentou significativamente. As taxas de mortalidade p&#243;s-alta diminu&#237;ram em paralelo com a introdu&#231;&#227;o de novos dispositivos e a ado&#231;&#227;o de indica&#231;&#245;es mais amplas. Entretanto, a mortalidade em um ano ap&#243;s a TAVI permanece relevante, superando 15% na pr&#225;tica contempor&#226;nea.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
    <p>Ao longo do tempo, regurgita&#231;&#227;o paravalvar significativa p&#243;s-procedimento, insufici&#234;ncia renal aguda e comorbidades como doen&#231;a pulmonar obstrutiva cr&#244;nica (DPOC), insufici&#234;ncia card&#237;aca, doen&#231;a renal cr&#244;nica (DRC) e acidente vascular cerebral (AVC) pr&#233;vio foram associados a taxas mais altas de mortalidade.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup> Os escores de risco originalmente validados para estimar a mortalidade ap&#243;s SAVR e biomarcadores s&#233;ricos relacionados &#224; insufici&#234;ncia card&#237;aca congestiva e a outras condi&#231;&#245;es tiveram seu desempenho testado em pacientes submetidos &#224; TAVI.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Entretanto, n&#227;o existe uma ferramenta espec&#237;fica e amplamente adotada para prever a mortalidade tardia de pacientes p&#243;s-TAVI.</p>
    <p>Em pacientes com estenose a&#243;rtica (EAo) degenerativa, a inflama&#231;&#227;o &#233; um est&#225;gio crucial no processo patogen&#233;tico que culmina em calcifica&#231;&#227;o e estenose,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> e faltam dados suficientes a respeito do impacto da inflama&#231;&#227;o cr&#244;nica nos desfechos de pacientes p&#243;s-TAVI. A prote&#237;na C-reativa (PCR) &#233; um preditor de longo prazo de eventos card&#237;acos na popula&#231;&#227;o em geral.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Este par&#226;metro bioqu&#237;mico, que est&#225; relacionado &#224; inflama&#231;&#227;o sist&#234;mica cr&#244;nica, tamb&#233;m foi extensivamente investigado em pacientes com doen&#231;a arterial coronariana, nos quais os n&#237;veis plasm&#225;ticos aumentados de PCR foram associados a piores desfechos cl&#237;nicos.<sup><xref ref-type="bibr" rid="B8">8</xref></sup><sup>,</sup> <sup><xref ref-type="bibr" rid="B9">9</xref></sup> Na presente edi&#231;&#227;o do Arquivos Brasileiros de Cardiologia, Sousa et al.,<sup><xref ref-type="bibr" rid="B10">10</xref></sup>, avaliaram o valor progn&#243;stico do biomarcador inflamat&#243;rio PCR em pacientes submetidos &#224; TAVI.</p>
    <p>Os autores avaliaram a PCR ultrassens&#237;vel (PCR-us) como marcador progn&#243;stico no primeiro ano p&#243;s-TAVI para estenose a&#243;rtica. O imunoensaio turbidim&#233;trico foi utilizado para medir os n&#237;veis s&#233;ricos de PCR-us antes da TAVI e ao longo da primeira semana ap&#243;s a interven&#231;&#227;o. Os pesquisadores analisaram retrospectivamente 137 pacientes com EAo grave sintom&#225;tica submetidos a TAVI de 2009 a 2015 em um &#250;nico centro. Pacientes em estado cr&#237;tico e procedimentos com complica&#231;&#245;es mec&#226;nicas foram exclu&#237;dos, totalizando uma popula&#231;&#227;o de 130 pacientes.</p>
    <p>No estudo, os pacientes eram em sua maioria octogen&#225;rios (mediana de idade de 83,0 anos), com alto risco cir&#250;rgico (mediana do escore da Society of Thoracic Surgeons - STS - de 8,6). A anestesia geral foi predominante (80,8% dos procedimentos), assim como a via transfemoral (94,6%). Quase todos os dispositivos implantados foram CoreValve (97%), com 3% de Edwards-Sapien XT.</p>
    <p>A mortalidade hospitalar foi de 6,2%. Os crit&#233;rios da s&#237;ndrome da resposta inflamat&#243;ria sist&#234;mica (SIRS, do ingl&#234;s <italic>systemic inflammatory response syndrome</italic>) estiveram presentes em 42,6% dos casos e 10% dos pacientes tiveram infec&#231;&#245;es tratadas com antibi&#243;ticos durante a hospitaliza&#231;&#227;o. O pico de PCR ultrassens&#237;vel (PCR-us) foi de 7,0 (5,3-12,1) mg/dL e ocorreu com maior frequ&#234;ncia 96h ap&#243;s a TAVI. Um n&#237;vel de PCR-us basal maior que 0,5 mg/dL, presente em um ter&#231;o dos pacientes, foi um preditor independente de mortalidade em 1 ano (raz&#227;o de risco de 4,1). Outros preditores independentes de mortalidade foram insufici&#234;ncia renal aguda e transfus&#227;o de sangue &#8805; 4 unidades de hem&#225;cias. O pico de PCR p&#243;s-TAVI foi um preditor de mortalidade em 1 ano apenas na an&#225;lise univariada.</p>
    <p>O estudo forneceu informa&#231;&#245;es detalhadas sobre a cin&#233;tica da PCR p&#243;s-TAVI. Os autores acrescentaram algumas informa&#231;&#245;es a respeito de quest&#245;es ainda n&#227;o totalmente respondidas: A inflama&#231;&#227;o cr&#244;nica em pacientes com EAo &#233; um reflexo do estado de sa&#250;de global e comorbidades ou uma consequ&#234;ncia do envelhecimento? Qual &#233; o mecanismo do pior progn&#243;stico em pacientes com EAo e n&#237;veis elevados de PCR pr&#233;-TAVI?</p>
    <p>O achado dos autores de PCR-us basal &#8805; 0,5 mg/dL como um preditor independente de mortalidade em 1 ano p&#243;s-TAVI &#233; apoiado por estudos retrospectivos anteriores utilizando PCR ou PCR-us e diferentes pontos de corte.<sup><xref ref-type="bibr" rid="B11">11</xref>-<xref ref-type="bibr" rid="B13">13</xref></sup> O impacto da PCR-us elevada na mortalidade em um ano pode indicar um pior estado basal de sa&#250;de (maior incid&#234;ncia de DPOC, maior STS escore e insufici&#234;ncia card&#237;aca mais avan&#231;ada). Curiosamente, mais da metade das mortes por todas as causas no estudo teve uma causa n&#227;o-cardiovascular. Isso pode estar relacionado ao pior progn&#243;stico de doen&#231;as infecciosas e neoplasias em pacientes com n&#237;veis elevados de PCR.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
    <p>Vale ressaltar, que esse estudo observacional e retrospectivo n&#227;o permitiu aos autores estabelecer uma rela&#231;&#227;o causal entre os n&#237;veis de PCR e os desfechos. Esta investiga&#231;&#227;o unic&#234;ntrica utilizou uma amostra pequena e os eventos cardiovasculares n&#227;o foram avaliados por um comit&#234; de avalia&#231;&#227;o de eventos.</p>
    <p>A PCR ultrassens&#237;vel pode melhorar a estratifica&#231;&#227;o de risco em pacientes submetidos &#224; implanta&#231;&#227;o transcateter de v&#225;lvula a&#243;rtica. Sousa et al.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> adicionaram informa&#231;&#245;es valiosas ao corpo de dados que apoiam os biomarcadores inflamat&#243;rios como um &#225;rbitro de progn&#243;stico p&#243;s-TAVI em pacientes com EAo. No entanto, mais estudos prospectivos s&#227;o necess&#225;rios para esclarecer o impacto dos n&#237;veis s&#233;ricos elevados de PCR na mortalidade em pacientes submetidos &#224; TAVI.</p>
    <p>A adi&#231;&#227;o dos n&#237;veis s&#233;ricos de biomarcadores inflamat&#243;rios a par&#226;metros como o escore de risco cir&#250;rgico, dados ecocardiogr&#225;ficos e fragilidade, pode ajudar na identifica&#231;&#227;o de pacientes que ter&#227;o desfechos negativos ap&#243;s a TAVI bem-sucedida e, em &#250;ltima an&#225;lise, melhorar o manejo p&#243;s-alta.</p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo Prote&#237;na C-reativa como Marcador Progn&#243;stico de Mortalidade no Primeiro Ano ap&#243;s Implante de V&#225;lvula A&#243;rtica Transcateter em Estenose A&#243;rtica</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>Grover</surname>
              <given-names>FL</given-names>
            </name>
            <name>
              <surname>Vemulapalli</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Carroll</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Edwards</surname>
              <given-names>FH</given-names>
            </name>
            <name>
              <surname>Mack</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Thourani</surname>
              <given-names>VH</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2016 Annual Report of The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2017</year>
          <volume>69</volume>
          <issue>10</issue>
          <fpage>1215</fpage>
          <lpage>1230</lpage>
        </element-citation>
        <mixed-citation>1 Grover FL, Vemulapalli S, Carroll JD, Edwards FH, Mack MJ, Thourani VH, et al. 2016 Annual Report of The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. J Am Coll Cardiol. 2017;69(10):1215-30.</mixed-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Carroll</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Mack</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Vemulapalli</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Herrmann</surname>
              <given-names>HC</given-names>
            </name>
            <name>
              <surname>Gleason</surname>
              <given-names>TG</given-names>
            </name>
            <name>
              <surname>Hanzel</surname>
              <given-names>G</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>STS-ACC TVT Registry of Transcatheter Aortic Valve Replacement</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2020</year>
          <volume>76</volume>
          <issue>21</issue>
          <fpage>2492</fpage>
          <lpage>2516</lpage>
        </element-citation>
        <mixed-citation>2 Carroll JD, Mack MJ, Vemulapalli S, Herrmann HC, Gleason TG, Hanzel G, et al. STS-ACC TVT Registry of Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2020;76(21):2492-516.</mixed-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tamburino</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Capodanno</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Ramondo</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Petronio</surname>
              <given-names>AS</given-names>
            </name>
            <name>
              <surname>Ettori</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Santoro</surname>
              <given-names>G</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Incidence and predictors of early and late mortality after transcatheter aortic valve implantation in 663 patients with severe aortic stenosis</article-title>
          <source>Circulation</source>
          <year>2011</year>
          <volume>123</volume>
          <issue>3</issue>
          <fpage>299</fpage>
          <lpage>308</lpage>
        </element-citation>
        <mixed-citation>3 Tamburino C, Capodanno D, Ramondo A, Petronio AS, Ettori F, Santoro G, et al. Incidence and predictors of early and late mortality after transcatheter aortic valve implantation in 663 patients with severe aortic stenosis. Circulation. 2011;123(3):299-308.</mixed-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>de Brito</surname>
              <given-names>FS</given-names>
              <suffix>Jr.</suffix>
            </name>
            <name>
              <surname>Carvalho</surname>
              <given-names>LA</given-names>
            </name>
            <name>
              <surname>Sarmento-Leite</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Mangione</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Lemos</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Siciliano</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Outcomes and predictors of mortality after transcatheter aortic valve implantation: results of the Brazilian registry</article-title>
          <source>Catheter Cardiovasc Interv</source>
          <year>2015</year>
          <volume>85</volume>
          <issue>5</issue>
          <fpage>E153</fpage>
          <lpage>E162</lpage>
        </element-citation>
        <mixed-citation>4 de Brito FS, Jr., Carvalho LA, Sarmento-Leite R, Mangione JA, Lemos P, Siciliano A, et al. Outcomes and predictors of mortality after transcatheter aortic valve implantation: results of the Brazilian registry. Catheter Cardiovasc Interv. 2015;85(5):E153-62.</mixed-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sinning</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Wollert</surname>
              <given-names>KC</given-names>
            </name>
            <name>
              <surname>Sedaghat</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Widera</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Radermacher</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Descoups</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Risk scores and biomarkers for the prediction of 1-year outcome after transcatheter aortic valve replacement</article-title>
          <source>Am Heart J</source>
          <year>2015</year>
          <volume>170</volume>
          <issue>4</issue>
          <fpage>821</fpage>
          <lpage>829</lpage>
        </element-citation>
        <mixed-citation>5 Sinning JM, Wollert KC, Sedaghat A, Widera C, Radermacher MC, Descoups C, et al. Risk scores and biomarkers for the prediction of 1-year outcome after transcatheter aortic valve replacement. Am Heart J. 2015;170(4):821-9.</mixed-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Otto</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Kuusisto</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Reichenbach</surname>
              <given-names>DD</given-names>
            </name>
            <name>
              <surname>Gown</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>O&#8217;Brien</surname>
              <given-names>KD</given-names>
            </name>
          </person-group>
          <article-title>Characterization of the early lesion of &#8216;degenerative&#8217; valvular aortic stenosis. Histological and immunohistochemical studies</article-title>
          <source>Circulation</source>
          <year>1994</year>
          <volume>90</volume>
          <issue>2</issue>
          <fpage>844</fpage>
          <lpage>853</lpage>
        </element-citation>
        <mixed-citation>6 Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O&#8217;Brien KD. Characterization of the early lesion of &#8216;degenerative&#8217; valvular aortic stenosis. Histological and immunohistochemical studies. Circulation 1994;90(2):844-53.</mixed-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ridker</surname>
              <given-names>PM</given-names>
            </name>
            <name>
              <surname>Cushman</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Stampfer</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Tracy</surname>
              <given-names>RP</given-names>
            </name>
            <name>
              <surname>Hennekens</surname>
              <given-names>CH</given-names>
            </name>
          </person-group>
          <article-title>Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men</article-title>
          <source>N Engl J Med</source>
          <year>1997</year>
          <volume>336</volume>
          <issue>14</issue>
          <fpage>973</fpage>
          <lpage>979</lpage>
        </element-citation>
        <mixed-citation>7 Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336(14):973-9.</mixed-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Liuzzo</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Biasucci</surname>
              <given-names>LM</given-names>
            </name>
            <name>
              <surname>Gallimore</surname>
              <given-names>JR</given-names>
            </name>
            <name>
              <surname>Grillo</surname>
              <given-names>RL</given-names>
            </name>
            <name>
              <surname>Rebuzzi</surname>
              <given-names>AG</given-names>
            </name>
            <name>
              <surname>Pepys</surname>
              <given-names>MB</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina</article-title>
          <source>N Engl J Med</source>
          <year>1994</year>
          <volume>331</volume>
          <issue>7</issue>
          <fpage>417</fpage>
          <lpage>424</lpage>
        </element-citation>
        <mixed-citation>8 Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med. 1994;331(7):417-24.</mixed-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Haverkate</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Thompson</surname>
              <given-names>SG</given-names>
            </name>
            <name>
              <surname>Pyke</surname>
              <given-names>SD</given-names>
            </name>
            <name>
              <surname>Gallimore</surname>
              <given-names>JR</given-names>
            </name>
            <name>
              <surname>Pepys</surname>
              <given-names>MB</given-names>
            </name>
          </person-group>
          <article-title>Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group</article-title>
          <source>Lancet</source>
          <year>1997</year>
          <volume>349</volume>
          <issue>9050</issue>
          <fpage>462</fpage>
          <lpage>466</lpage>
        </element-citation>
        <mixed-citation>9 Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 1997;349(9050):462-6</mixed-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sousa</surname>
              <given-names>ALS</given-names>
            </name>
            <name>
              <surname>Carvalho</surname>
              <given-names>LAF</given-names>
            </name>
            <name>
              <surname>Salgado</surname>
              <given-names>CG</given-names>
            </name>
            <name>
              <surname>Oliveira</surname>
              <given-names>RL</given-names>
            </name>
            <name>
              <surname>Lima</surname>
              <given-names>LCCL</given-names>
            </name>
            <name>
              <surname>Mattos</surname>
              <given-names>NDFG</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>C-reactive Protein as a Prognostic Marker of 1-Year Mortality after Transcatheter Aortic Valve Implantation in Aortic Stenosis</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2021</year>
          <volume>117</volume>
          <issue>5</issue>
          <fpage>1018</fpage>
          <lpage>1027</lpage>
        </element-citation>
        <mixed-citation>10 Sousa ALS, Carvalho LAF, Salgado CG, Oliveira RL, Lima LCCL, Mattos NDFG, et al. C-reactive Protein as a Prognostic Marker of 1-Year Mortality after Transcatheter Aortic Valve Implantation in Aortic Stenosis. Arq Bras Cardiol. 2021; 117(5):1018-1027.</mixed-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hioki</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Watanabe</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Kozuma</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Yamamoto</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Naganuma</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Araki</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Effect of Serum C-Reactive Protein Level on Admission to Predict Mortality After Transcatheter Aortic Valve Implantation</article-title>
          <source>Am J Cardiol</source>
          <year>2018</year>
          <volume>122</volume>
          <issue>2</issue>
          <fpage>294</fpage>
          <lpage>301</lpage>
        </element-citation>
        <mixed-citation>11 Hioki H, Watanabe Y, Kozuma K, Yamamoto M, Naganuma T, Araki M, et al. Effect of Serum C-Reactive Protein Level on Admission to Predict Mortality After Transcatheter Aortic Valve Implantation. Am J Cardiol. 2018;122(2):294-301.</mixed-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Zielinski</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Kalinczuk</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Chmielak</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Mintz</surname>
              <given-names>GS</given-names>
            </name>
            <name>
              <surname>Dabrowski</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Pregowski</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Additive Value of High-Density Lipoprotein Cholesterol and C-Reactive Protein Level Assessment for Prediction of 2-year Mortality After Transcatheter Aortic Valve Implantation</article-title>
          <source>Am J Cardiol</source>
          <year>2020</year>
          <volume>126</volume>
          <fpage>66</fpage>
          <lpage>72</lpage>
        </element-citation>
        <mixed-citation>12 Zielinski K, Kalinczuk L, Chmielak Z, Mintz GS, Dabrowski M, Pregowski J, et al. Additive Value of High-Density Lipoprotein Cholesterol and C-Reactive Protein Level Assessment for Prediction of 2-year Mortality After Transcatheter Aortic Valve Implantation. Am J Cardiol. 2020;126:66-72.</mixed-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Stundl</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Busse</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Leimkuhler</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Weber</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Zur</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Mellert</surname>
              <given-names>F</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Combination of high-sensitivity C-reactive protein with logistic EuroSCORE improves risk stratification in patients undergoing TAVI</article-title>
          <source>EuroIntervention</source>
          <year>2018</year>
          <volume>14</volume>
          <issue>6</issue>
          <fpage>629</fpage>
          <lpage>636</lpage>
        </element-citation>
        <mixed-citation>13 Stundl A, Busse L, Leimkuhler P, Weber M, Zur B, Mellert F, et al. Combination of high-sensitivity C-reactive protein with logistic EuroSCORE improves risk stratification in patients undergoing TAVI. EuroIntervention. 2018;14(6):629-636.</mixed-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Allin</surname>
              <given-names>KH</given-names>
            </name>
            <name>
              <surname>Nordestgaard</surname>
              <given-names>BG</given-names>
            </name>
          </person-group>
          <article-title>Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer</article-title>
          <source>Crit Rev Clin Lab Sci</source>
          <year>2011</year>
          <volume>48</volume>
          <issue>4</issue>
          <fpage>155</fpage>
          <lpage>170</lpage>
        </element-citation>
        <mixed-citation>14 Allin KH, Nordestgaard BG. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci, 2011;48(4):155-70.</mixed-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="S01" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>The Role of Inflammation in Post-TAVI Outcomes</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Melo</surname>
            <given-names>Pedro H. M. C. de</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0002-0047-7859</contrib-id>
          <name>
            <surname>Modolo</surname>
            <given-names>Rodrigo</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>2</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff3">
          <label>1</label>
          <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">Brazil</country>
          <institution content-type="original">Departamento de Cardiologia Intervencionista - Hospital S&#237;rio Liban&#234;s, S&#227;o Paulo, SP - Brazil</institution>
        </aff>
        <aff id="aff4">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">Campinas</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Departamento de Cl&#237;nica M&#233;dica - Divis&#227;o de Cardiologia - Faculdade de Ci&#234;ncias M&#233;dicas - Universidade Estadual de Campinas (UNICAMP), Campinas, SP - Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Rodrigo Modolo &#8226;</bold> Departamento de Cl&#237;nica M&#233;dica - Divis&#227;o de Cardiologia, Faculdade de Ci&#234;ncias M&#233;dicas. Universidade Estadual de Campinas &#8211; UNICAMP, <postal-code>13084-971</postal-code>, Campinas, SP - Brazil, E-mail: <email>modolo.rodrigo@gmail.com</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Implantation Transcatheter Aortic Valve/methods</kwd>
        <kwd>Aortic Valve/surgery</kwd>
        <kwd>Mortality</kwd>
        <kwd>Comorbidity</kwd>
        <kwd>Biomarkers</kwd>
        <kwd>C-Reactive Protein</kwd>
        <kwd>Inflammation</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>In the early transcatheter aortic valve implantation (TAVI) experience with extreme/high risk for surgical aortic valve replacement (SAVR) patients, global mortality in one year was as high as 25% <sup><xref ref-type="bibr" rid="B1">1</xref></sup>. Since then, access to TAVI has been extended to intermediate and low-risk patients, and the annual volume of procedures has markedly increased. Post-discharge mortality rates have declined in parallel with the introduction of new devices and the adoption of broader indications. However, the one-year mortality after TAVI remains relevant, exceeding 15% in contemporary practice <sup><xref ref-type="bibr" rid="B2">2</xref></sup>.</p>
      <p>Over time, significant postprocedural paravalvular leak, acute renal failure, and comorbidities such as chronic obstructive pulmonary disease (COPD), heart failure, chronic kidney disease (CKD) and prior stroke were linked to higher rates of mortality <sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup>. Risk scores originally validated to estimate mortality after SAVR, and serum biomarkers related to congestive heart failure and others had their performance tested in patients who underwent TAVI <sup><xref ref-type="bibr" rid="B5">5</xref></sup>. Nonetheless, there is no specific, widely adopted tool to predict late mortality of post-TAVI patients.</p>
      <p>In patients with degenerative aortic stenosis (AoS), inflammation is a crucial stage in the pathogenetic process that culminates with calcification and stenosis <sup><xref ref-type="bibr" rid="B6">6</xref></sup>, and sufficient data on the impact of chronic inflammation on outcomes of post-TAVI patients is lacking. C-reactive protein (CRP) is a long-term predictor of cardiac events in the general population <sup><xref ref-type="bibr" rid="B7">7</xref></sup>. This biochemical parameter, which is related to chronic systemic inflammation, has also been extensively investigated in patients with coronary artery disease, in which increased CRP plasma levels were associated with worse clinical outcomes <sup><xref ref-type="bibr" rid="B8">8</xref></sup><sup>,</sup> <sup><xref ref-type="bibr" rid="B9">9</xref></sup>. Thus, the prognostic value of this inflammatory biomarker, CRP, in TAVI patients was evaluated by Sousa et al. <sup><xref ref-type="bibr" rid="B10">10</xref></sup> in this issue of <italic>Arquivos Brasileiros de Cardiologia.</italic></p>
      <p>The authors have evaluated high-sensitive CRP as a prognostic marker in the first year after TAVI for aortic stenosis. Turbidimetric immunoassay was used to measure serum high-sensitive CRP concentrations before TAVI and along the first postoperative week. The investigators retrospectively analyzed 137 patients with symptomatic severe AoS who underwent TAVI from 2009 to 2015 in a single center. Critically-ill patients and procedures with mechanical complications were excluded, comprising a total population of 130 patients.</p>
      <p>In the study, patients were mostly octogenarians (median age of 83.0 years), with a high SAVR risk (median Society of Thoracic Surgeons - STS - score of 8.6). General anesthesia was predominant (80.8% of the procedures), as well as the transfemoral route (94.6%). Almost all implanted devices were CoreValve (97%), with 3% of Edwards-Sapien XT.</p>
      <p>The in-hospital mortality rate was 6.2%. Systemic inflammatory response syndrome (SIRS) criteria were met in 42.6% of the cases and 10% of the patients had infections treated with antibiotics during hospital stays. High-sensitive CRP (hs-CRP) peak was 7.0 (5.3-12.1) mg/dL and occurred more likely 96h after TAVI. A baseline hs-CRP level greater than 0.5 mg/dL, present in one-third of the patients, was an independent predictor of 1-year mortality (hazard ratio of 4.1). Other independent predictors of mortality were acute renal failure and blood transfusion &#8805; 4 red blood cell (RBC) units. Post-TAVI peak CRP was a predictor of 1-year mortality only in the univariate analysis.</p>
      <p>The study provided detailed information about CRP kinetics after TAVI. The authors have furnished some insight into questions not yet fully answered: Is chronic inflammation in AoS patients a reflection of the global health status and comorbidities or a consequence of aging? What is the mechanism for worse prognosis in patients with AoS and high pre-TAVI CRP levels?</p>
      <p>The authors&#8217; finding of baseline hs-CRP &#8805; 0.5 mg/dL as an independent predictor of 1-year mortality after TAVI is supported by previous retrospective studies using CRP or hs-CRP and different cutoffs <sup><xref ref-type="bibr" rid="B11">11</xref>-<xref ref-type="bibr" rid="B13">13</xref></sup>. The impact of high CRP on one one-year mortality could be due to more advanced disease at baseline (higher incidence of COPD, higher higher STS score and more advanced heart failure). Interestingly, more than half of all-cause deaths in the study had a non-cardiovascular cause. This could be related to the worse prognosis of infection and malignant disease in patients with elevated CRP levels <sup><xref ref-type="bibr" rid="B14">14</xref></sup>.</p>
      <p>It is worth mentioning that this observational and retrospective analysis could not allow the authors to establish a causal relationship between CRP levels and outcomes. This single-center investigation used a small sample size and cardiovascular events were not assessed by an event adjudication committee.</p>
      <p>High-sensitive CRP may improve risk stratification in patients undergoing transcatheter aortic valve implantation. Sousa et al. have added valuable information to the body of data that supports inflammatory biomarkers as an arbiter of prognosis after TAVI in AoS patients. Nonetheless, further prospective studies are warranted to enlighten the impact of elevated serum CRP levels on mortality in TAVI patients.</p>
      <p>Adding inflammatory serum biomarker levels to validated risk scores, echocardiographic parameters and frailty could support the identification of patients with poor outcomes after successful TAVI, and ultimately improve post-discharge management.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other" id="fn2">
          <p>Short Editorial related to the article: C-reactive Protein as a Prognostic Marker of 1-Year Mortality after Transcatheter Aortic Valve Implantation in Aortic Stenosis</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
