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<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" dtd-version="3.0" article-type="research-article" xml:lang="pt">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</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</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">YxfpjnySvwn7QMk9vP8TBhc</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2014000500012</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2014005040039</article-id>
      <article-id pub-id-type="other">00012</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20140039</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="pt">NHETS - Estudo de Necr&#243;psias de Pacientes Submetidos a
               Transplante Card&#237;aco</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Valette</surname>
            <given-names>Thiago Ninck</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ayub-Ferreira</surname>
            <given-names>Silvia Moreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Benvenuti</surname>
            <given-names>Luiz Alberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Issa</surname>
            <given-names>Victor Sarli</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bacal</surname>
            <given-names>Fernando</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chizzola</surname>
            <given-names>Paulo Roberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Souza</surname>
            <given-names>Germano Emilio Concei&#231;&#227;o</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fiorelli</surname>
            <given-names>Alfredo In&#225;cio</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Ronaldo Honorato Barros dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bocchi</surname>
            <given-names>Edimar Alcides</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <aff id="aff1">
          <institution content-type="orgdiv3">Instituto do Cora&#231;&#227;o</institution>
          <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina</institution>
          <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country>Brasil</country>
          <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da
                  Faculdade de Medicina da Universidade de S&#227;o Paulo (USP), S&#227;o Paulo, SP -
                  Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c01"><bold>Correspond&#234;ncia: Thiago Ninck Valette,</bold> Avenida Interlagos, 871, bloco 7,
               apto. 43, Jardim Marajoara. CEP 04661-100, S&#227;o Paulo, SP - Brasil. E-mail:
                  <email>thiago.valette@gmail.com</email>, <email>t_valette@hotmail.com</email>
				</corresp>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial Conflito de Interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>17</day>
        <month>04</month>
        <year>2014</year>
      </pub-date>
      <pub-date pub-type="collection">
        <day>10</day>
        <month>06</month>
        <year>2014</year>
      </pub-date>
      <volume>102</volume>
      <issue>05</issue>
      <fpage>505</fpage>
      <lpage>509</lpage>
      <history>
        <date date-type="received">
          <day>20</day>
          <month>08</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>17</day>
          <month>11</month>
          <year>2013</year>
        </date>
        <date date-type="accepted">
          <day>18</day>
          <month>11</month>
          <year>2013</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">
          <license-p>This is an Open Access article distributed under the terms of the Creative
                  Commons Attribution Non-Commercial License which permits unrestricted
                  non-commercial use, distribution, and reproduction in any medium, provided the
                  original work is properly cited. </license-p>
        </license>
      </permissions>
      <abstract xml:lang="pt">
        <sec>
          <title>Fundamento:</title>
          <p>Discord&#226;ncias entre diagn&#243;stico pre e post-mortem s&#227;o relatadas na literatura,
                  podendo variar de 4,1 a 49,8% dentre os casos encaminhados para exame
                  necrosc&#243;pico, com importante repercuss&#227;o no tratamento dos pacientes.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Analisar pacientes com &#243;bito ap&#243;s o transplante card&#237;aco e confrontar os
                  diagn&#243;sticos pre e post-mortem.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Por meio da revis&#227;o de prontu&#225;rios, foram analisados dados cl&#237;nicos, presen&#231;a de
                  comorbidades, esquema de imunossupress&#227;o, exames laboratoriais, causa cl&#237;nica do
                  &#243;bito e causa do &#243;bito &#224; necr&#243;psia. Foram confrontadas, ent&#227;o, a causa cl&#237;nica e a
                  causa necrosc&#243;pica do &#243;bito de cada paciente.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Foram analisados 48 &#243;bitos submetidos &#224; necr&#243;psia no per&#237;odo de 2000 a 2010; 29
                  (60,4%) tiveram diagn&#243;sticos cl&#237;nico e necrosc&#243;pico concordantes, 16 (33,3%)
                  tiveram diagn&#243;sticos discordantes e tr&#234;s (6,3%) tiveram diagn&#243;stico n&#227;o
                  esclarecido. Entre os discordantes, 15 (31,3%) apresentaram poss&#237;vel impacto na
                  sobrevida e um (2,1%) n&#227;o apresentou impacto na sobrevida. O principal diagn&#243;stico
                  cl&#237;nico feito equivocadamente foi o de infec&#231;&#227;o, com cinco casos (26,7% dos
                  discordantes), seguido por rejei&#231;&#227;o hiperaguda, com quatro casos (20% dos
                  discordantes), e tromboembolismo pulmonar, com tr&#234;s casos (13,3% dos
                  discordantes).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>Discord&#226;ncias entre o diagn&#243;stico cl&#237;nico e achados da necr&#243;psia s&#227;o comumente
                  encontradas no transplante card&#237;aco. Novas estrat&#233;gias no aperfei&#231;oamento do
                  diagn&#243;stico cl&#237;nico devem ser introduzidas, considerando-se os resultados da
                  necr&#243;psia para melhoria do tratamento da insufici&#234;ncia card&#237;aca por meio do
                  transplante card&#237;aco.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Transplante de Cora&#231;&#227;o</kwd>
        <kwd>Autopsia</kwd>
      </kwd-group>
      <counts>
        <fig-count count="3"/>
        <table-count count="2"/>
        <equation-count count="0"/>
        <ref-count count="12"/>
        <page-count count="1"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>O exame necrosc&#243;pico tem contribu&#237;do para a evolu&#231;&#227;o do conhecimento m&#233;dico. Entretanto,
            a frequ&#234;ncia com que os centros m&#233;dicos realizam necr&#243;psias vem se reduzindo nas &#250;ltimas
            d&#233;cadas, em diferentes casu&#237;sticas. As raz&#245;es aventadas para esse fen&#244;meno s&#227;o diversas
            e incluem aspectos culturais, negativa das fam&#237;lias, aus&#234;ncia de fontes financiadoras do
            procedimento, envelhecimento da popula&#231;&#227;o e menor interesse em achados necrosc&#243;picos em
            idosos, redu&#231;&#227;o do interesse cient&#237;fico nos achados necrosc&#243;picos e hesita&#231;&#227;o frente &#224;
            possibilidade de detec&#231;&#227;o de erros m&#233;dicos. Em que pese essa tend&#234;ncia hist&#243;rica,
            discord&#226;ncias entre diagn&#243;stico <italic>pre</italic> e <italic>post-mortem</italic>
            continuam a ser relatadas, podendo variar de 4,1 a 49,8% dos casos encaminhados para
            exame necrosc&#243;pico<xref ref-type="bibr" rid="B01">1</xref>. N&#227;o se avaliaram, em
            casu&#237;stica recente, os diagn&#243;sticos obtidos com dados cl&#237;nicos
               <italic>pre-mortem</italic> e diagn&#243;sticos necrosc&#243;picos de pacientes submetidos a
            transplante card&#237;aco.</p>
      <p>Este estudo se prop&#244;s a analisar pacientes com &#243;bito ap&#243;s o transplante card&#237;aco e que
            tenham sido submetidos &#224; necr&#243;psia, analisando as causas de morte e confrontando os
            diagn&#243;sticos <italic>pre</italic> e <italic>post-mortem.</italic>
			</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <p>An&#225;lise retrospectiva por meio de consulta ao prontu&#225;rio m&#233;dico dos &#243;bitos de
            transplante card&#237;aco submetidos &#224; necr&#243;psia no per&#237;odo de 2000 a 2010. Foram coletados
            os dados cl&#237;nicos para an&#225;lise de presen&#231;a de comorbidades, esquema de imunossupress&#227;o,
            resultado de exames laboratoriais, causa cl&#237;nica do &#243;bito e causa do &#243;bito &#224;
            necr&#243;psia.</p>
      <p>O diagn&#243;stico <italic>pre-mortem</italic> de &#243;bito foi confrontado com o
               <italic>post-mortem</italic>, sendo, ent&#227;o, classificadas as discord&#226;ncias entre os
            dois diagn&#243;sticos de acordo com os crit&#233;rios de Goldman e cols.<xref ref-type="bibr" rid="B02">2</xref> adaptados por Battle e cols.<xref ref-type="bibr" rid="B03">3</xref>, havendo ainda os casos n&#227;o classificados<xref ref-type="bibr" rid="B04">4</xref>. A classifica&#231;&#227;o ficou do seguinte modo:</p>
      <list list-type="bullet">
        <list-item>
          <p>Discord&#226;ncias maiores</p>
        </list-item>
      </list>
      <list list-type="simple">
        <list-item>
          <p>- classe I: discord&#226;ncias em diagn&#243;stico principal, com impacto na sobrevida;</p>
        </list-item>
        <list-item>
          <p>- classe II: discord&#226;ncias no diagn&#243;stico principal, sem impacto na sobrevida;</p>
        </list-item>
      </list>
      <list list-type="bullet">
        <list-item>
          <p>Discord&#226;ncias menores:</p>
        </list-item>
      </list>
      <list list-type="simple">
        <list-item>
          <p>- classe III: discord&#226;ncias em diagn&#243;sticos secund&#225;rios n&#227;o diretamente
                  relacionados ao &#243;bito;</p>
        </list-item>
        <list-item>
          <p>- classe IV: discord&#226;ncias em diagn&#243;sticos menores n&#227;o diagnostic&#225;veis, mas com
                  poss&#237;vel import&#226;ncia epidemiol&#243;gica ou gen&#233;tica;</p>
        </list-item>
      </list>
      <list list-type="bullet">
        <list-item>
          <p>Concordantes:</p>
        </list-item>
      </list>
      <list list-type="simple">
        <list-item>
          <p>- classe V: diagn&#243;sticos concordantes;</p>
        </list-item>
      </list>
      <list list-type="bullet">
        <list-item>
          <p>Casos n&#227;o classificados:</p>
        </list-item>
      </list>
      <list list-type="simple">
        <list-item>
          <p>- classe VI: pacientes cujo diagn&#243;stico cl&#237;nico ou necrosc&#243;pico n&#227;o pode ser
                  realizado de forma adequada.</p>
        </list-item>
      </list>
      <p>Os &#243;bitos foram tamb&#233;m diferenciados como precoces ou tardios, sendo precoces os que
            ocorreram at&#233; 1 ano ap&#243;s o transplante e tardios aqueles que ocorreram ap&#243;s 12 meses. As
            discord&#226;ncias foram avaliadas nesses dois grupos, verificando-se as causas de &#243;bito.</p>
      <p>O trabalho foi aprovado pelo Comit&#234; de &#201;tica e Pesquisa. N&#227;o foi necess&#225;ria a assinatura
            de termo de consentimento livre e esclarecido, por se tratar de um estudo retrospectivo
            baseado na consulta de prontu&#225;rios.</p>
      <p>O estudo foi apoiado pela Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo, processo
            2010/12278-5.</p>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>Entre 2000 a 2010, 124 pacientes submetidos a transplante card&#237;aco evolu&#237;ram a &#243;bito. O
            transplante card&#237;aco dos 124 pacientes datava de fevereiro de 1987 a mar&#231;o de 2010.
            Destes 124 pacientes, 48 foram submetidos &#224; necr&#243;psia, os quais caracterizam a amostra
            estudada. Na <xref ref-type="fig" rid="f01">Figura 1</xref>, &#233; apresentado o fluxograma
            da sele&#231;&#227;o dos casos do estudo.</p>
      <fig id="f01" fig-type="other">
        <label>Figura 1</label>
        <caption>
          <title>Fluxograma de sele&#231;&#227;o dos casos.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-102-05-0505-40039-gf01.jpg"/></fig>
      <p>A m&#233;dia de idade foi de 41 anos, e 67% dos pacientes eram homens. O tempo de seguimento
            m&#233;dio p&#243;s-transplante foi de 991 &#177; 1.728 dias. A etiologia da cardiopatia (pr&#233;via ao
            transplante) mais frequente foi cardiopatia chag&#225;sica. Quanto &#224;s comorbidades, 44% dos
            pacientes apresentavam hipertens&#227;o arterial sist&#234;mica; 31%, dislipidemia; e 18%,
            diabetes melito. Na <xref ref-type="table" rid="t01">Tabela 1</xref> s&#227;o apresentadas as
            caracter&#237;sticas gerais dos pacientes.</p>
      <table-wrap id="t01">
        <label>Tabela 1</label>
        <caption>
          <title>Caracter&#237;sticas cl&#237;nicas dos pacientes estudados</title>
        </caption>
        <table frame="hsides" rules="rows">
          <thead>
            <tr>
              <th colspan="2" align="left">
                <bold>Caracter&#237;sticas</bold>
              </th>
              <th>
                <bold>n = 48 </bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td colspan="2">Idade (anos)</td>
              <td align="center">41 &#177; 16</td>
            </tr>
            <tr>
              <td colspan="2">Sexo masculino (%)</td>
              <td align="center">67</td>
            </tr>
            <tr>
              <td colspan="2">Seguimento ap&#243;s transplante (dias)</td>
              <td align="center">991 &#177; 1.728</td>
            </tr>
            <tr>
              <td colspan="3">Etiologia (%)</td>
            </tr>
            <tr>
              <td>&#160;</td>
              <td>Isqu&#234;mica </td>
              <td align="center">14,6</td>
            </tr>
            <tr>
              <td>&#160;</td>
              <td>Idiop&#225;tica</td>
              <td align="center">29,2</td>
            </tr>
            <tr>
              <td>&#160;</td>
              <td>Hipertensiva </td>
              <td align="center">2,1</td>
            </tr>
            <tr>
              <td>&#160;</td>
              <td>Doen&#231;a de Chagas</td>
              <td align="center">31,3</td>
            </tr>
            <tr>
              <td colspan="2">Outras</td>
              <td align="center">13</td>
            </tr>
            <tr>
              <td colspan="2">Hipertens&#227;o arterial sist&#234;mica (%)</td>
              <td align="center">44</td>
            </tr>
            <tr>
              <td colspan="2">Diabetes melito (%)</td>
              <td align="center">18</td>
            </tr>
            <tr>
              <td colspan="2">Dislipidemia (%)</td>
              <td align="center">31</td>
            </tr>
            <tr>
              <td colspan="2">Leuc&#243;citos</td>
              <td align="center">8.590 &#177; 4.972</td>
            </tr>
            <tr>
              <td colspan="2">S&#243;dio (mEq/L)</td>
              <td align="center">136 &#177; 4</td>
            </tr>
            <tr>
              <td colspan="2">Creatinina (mg/dL)</td>
              <td align="center">1,9 &#177; 0,6</td>
            </tr>
            <tr>
              <td colspan="2">Ureia (mg/dL)</td>
              <td align="center">79 &#177; 56</td>
            </tr>
            <tr>
              <td colspan="2">Pot&#225;ssio (mEq/L)</td>
              <td align="center">4,5 &#177; 0,6</td>
            </tr>
            <tr>
              <td colspan="2">Hemoglobina (g/dL)</td>
              <td align="center">12,5 &#177; 2,17</td>
            </tr>
            <tr>
              <td colspan="3">Medica&#231;&#245;es (%)</td>
            </tr>
            <tr>
              <td>&#160;</td>
              <td>Ciclosporina</td>
              <td align="center">50</td>
            </tr>
            <tr>
              <td>&#160;</td>
              <td>Tacrolimus</td>
              <td align="center">14,6</td>
            </tr>
            <tr>
              <td>&#160;</td>
              <td>Micofenolato mofetil</td>
              <td align="center">54</td>
            </tr>
            <tr>
              <td>&#160;</td>
              <td>Corticosteroides</td>
              <td align="center">77</td>
            </tr>
            <tr>
              <td>&#160;</td>
              <td>Azatioprina</td>
              <td align="center">29,2</td>
            </tr>
            <tr>
              <td>&#160;</td>
              <td>Sirolimus</td>
              <td align="center">14,6</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p>Dos 48 casos analisados, 29 (60,4%) tiveram diagn&#243;sticos cl&#237;nico e necrosc&#243;pico
            concordantes (classe V), 16 (33,3%) tiveram diagn&#243;sticos discordantes e tr&#234;s (6,3%)
            tiveram diagn&#243;stico n&#227;o esclarecido (classe VI). Entre os discordantes, 15 (31,3%)
            apresentaram poss&#237;vel impacto na sobrevida (classe I) e um (2,1%) n&#227;o apresentou impacto
            na sobrevida (classe II). O principal diagn&#243;stico cl&#237;nico feito equivocadamente foi o de
            infec&#231;&#227;o, com cinco casos (26,7% dos discordantes), seguido por rejei&#231;&#227;o hiperaguda, com
            quatro casos (20% dos discordantes), e por tromboembolismo pulmonar, com tr&#234;s casos
            (13,3% dos discordantes). Na <xref ref-type="fig" rid="f02">Figura 2</xref>, &#233;
            apresentado o gr&#225;fico de distribui&#231;&#227;o das necropsias, com base na classifica&#231;&#227;o de
            discord&#226;ncias. Na <xref ref-type="fig" rid="f03">Figura 3 </xref>e na <xref ref-type="table" rid="t02">Tabela 2</xref> s&#227;o confrontados os diagn&#243;sticos cl&#237;nico e
            necrosc&#243;pico dos casos discordantes classe I.</p>
      <fig id="f02" fig-type="other">
        <label>Figura 2</label>
        <caption>
          <title>Distribui&#231;&#227;o das discord&#226;ncias entre diagn&#243;stico cl&#237;nico e
                  necrosc&#243;pico.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-102-05-0505-40039-gf02.jpg"/></fig>
      <fig id="f03" fig-type="other">
        <label>Figura 3</label>
        <caption>
          <title>Confrontamento entre os diagn&#243;sticos cl&#237;nico e necrosc&#243;pico dos casos
                  discordantes classe I.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-102-05-0505-40039-gf03.jpg"/></fig>
      <table-wrap id="t02">
        <label>Tabela 2</label>
        <caption>
          <title>Confrontamento entre os diagn&#243;sticos cl&#237;nico e necrosc&#243;pico dos casos
                  discordantes classe I</title>
        </caption>
        <table frame="hsides" rules="rows">
          <thead>
            <tr>
              <th colspan="10">
                <bold>Diagn&#243;stico Cl&#237;nico</bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td rowspan="7">
                <alternatives>
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              <td>&#160;</td>
              <td align="center">RH</td>
              <td align="center">RAC</td>
              <td align="center">RAH</td>
              <td align="center">CS</td>
              <td align="center">CC</td>
              <td align="center">TEP</td>
              <td align="center">CH</td>
              <td align="center">IIMOS</td>
            </tr>
            <tr>
              <td align="center">DVE</td>
              <td>&#160;</td>
              <td align="center">2</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td align="center">1</td>
              <td>&#160;</td>
              <td>&#160;</td>
            </tr>
            <tr>
              <td align="center" style="border-bottom:hidden">TEP</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td align="center">1</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
            </tr>
            <tr>
              <td align="center" style="border-bottom:hidden">CM</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td align="center">1</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
            </tr>
            <tr>
              <td align="center" style="border-bottom:hidden">CIVD</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td align="center">1</td>
              <td>&#160;</td>
              <td>&#160;</td>
            </tr>
            <tr>
              <td align="center">DAE</td>
              <td align="center">3</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td align="center">1</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td align="center">1</td>
              <td align="center">1</td>
            </tr>
            <tr>
              <td align="center">RAH</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td align="center">2</td>
              <td align="center">1</td>
              <td>&#160;</td>
              <td>&#160;</td>
              <td>&#160;</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn>
            <p>RH: rejei&#231;&#227;o hiperaguda; RAC: rejei&#231;&#227;o aguda celular; RAH: rejei&#231;&#227;o aguda
                     humoral; CS: choque s&#233;ptico; CC: choque cardiog&#234;nico; TEP: tromboembolismo
                     pulmonar; CH: choque hemorr&#225;gico; IMOS: insufici&#234;ncia de m&#250;ltiplos &#243;rg&#227;os e
                     sistemas; DVE: doen&#231;a vascular do enxerto; CM: choque misto; CIVD: coagula&#231;&#227;o
                     intravascular disseminada; DAE: disfun&#231;&#227;o aguda do enxerto.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Foram classificados como precoces 62,5% dos &#243;bitos (30 casos) e como tardios 37,5% (18
            casos). Dentre os precoces, 56% foram concordantes (classe V), 33% discordantes com
            impacto na sobrevida (classe I), 3% discordantes sem impacto na sobrevida (classe II) e
            6% apresentaram diagn&#243;stico n&#227;o esclarecido (classe VI). Dentre os tardios, 67% foram
            concordantes (classe V), 28% discordantes com impacto na sobrevida (classe I) e 5,6%
            apresentaram diagn&#243;stico n&#227;o esclarecido (classe VI).</p>
      <p>As causas de &#243;bito encontradas nas necr&#243;psias foram: disfun&#231;&#227;o aguda do enxerto (22,9%),
            rejei&#231;&#227;o aguda (20,8%), infec&#231;&#227;o (18,8%), Doen&#231;a Vascular do Enxerto (DVE - 16,7%),
            outras causas (14,6%) e n&#227;o esclarecida (6,3%).</p>
      <p>No grupo dos &#243;bitos classificados como precoces, 37% das causas de &#243;bito foram por
            disfun&#231;&#227;o aguda do enxerto, 20% por rejei&#231;&#227;o aguda humoral, 16,7% por choque s&#233;ptico,
            16,7% de outras causas e 6% de causa n&#227;o esclarecida.</p>
      <p>No grupo dos tardios, 45% das causas de &#243;bito foram por DVE, 17% de rejei&#231;&#227;o aguda
            celular, 11% de choque s&#233;ptico, 22% de outras causas e 5% de causa n&#227;o esclarecida.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>Nosso trabalho mostrou uma frequ&#234;ncia significativa de discord&#226;ncia entre os
            diagn&#243;sticos cl&#237;nico e necrosc&#243;pico da causa de &#243;bito, na maioria das vezes com poss&#237;vel
            impacto na sobrevida.</p>
      <p>Na literatura, n&#227;o foram encontrados trabalhos recentes que comparassem as causas
            cl&#237;nicas e necrosc&#243;picas de &#243;bitos em pacientes submetidos a transplante card&#237;aco,
            tornando este trabalho uma ferramenta atual para an&#225;lise dessas informa&#231;&#245;es.</p>
      <p>Por outro lado, a taxa de discord&#226;ncia da presente casu&#237;stica, em m&#233;dia, foi superior
            &#224;quela observada em outras s&#233;ries de pacientes n&#227;o relacionados ao transplante card&#237;aco.
            Em pacientes internados em unidade de cuidados intensivos encontraram-se valores de 7,5
            a 23% para discord&#226;ncias classificadas como maiores e de 11 a 13% para menores<xref ref-type="bibr" rid="B05">5</xref>
				<sup>,</sup>
				<xref ref-type="bibr" rid="B06">6</xref>. No caso de pacientes internados em hospital geral, houve 6 a 37% de
            discord&#226;ncias maiores e 25 a 28% de menores<xref ref-type="bibr" rid="B07">7</xref>
				<sup>-</sup>
				<xref ref-type="bibr" rid="B09">9</xref>.</p>
      <p>O diagn&#243;stico necrosc&#243;pico mais dif&#237;cil de ser aventado clinicamente foi a disfun&#231;&#227;o
            aguda do enxerto. Na presente casu&#237;stica, este foi confundido com rejei&#231;&#227;o hiperaguda,
            choque hemorr&#225;gico e choque s&#233;ptico. Esses dados evidenciam a dificuldade da confirma&#231;&#227;o
            desse diagn&#243;stico na pr&#225;tica cl&#237;nica, j&#225; que ele depende das situa&#231;&#245;es relacionadas ao
            perioperat&#243;rio (condi&#231;&#245;es do doador, tempo de isquemia, prote&#231;&#227;o mioc&#225;rdica e
            hipertens&#227;o pulmonar pr&#233;via do receptor) e do grau de suspei&#231;&#227;o do m&#233;dico respons&#225;vel,
            j&#225; que n&#227;o existe nenhum marcador espec&#237;fico para esse diagn&#243;stico.</p>
      <p>Outro diagn&#243;stico necrosc&#243;pico n&#227;o suspeitado <italic>pre-mortem</italic> foi a DVE.
            Este foi confundido com outras situa&#231;&#245;es que levam &#224; disfun&#231;&#227;o ventricular com rejei&#231;&#227;o
            celular e tromboembolismo pulmonar. Apesar da DVE ser uma das principais causas tardias
            de &#243;bito p&#243;s-transplante<xref ref-type="bibr" rid="B10">10</xref>, tamb&#233;m &#233; necess&#225;ria
            uma dose de suspei&#231;&#227;o do cl&#237;nico para se proceder ao m&#233;todo diagn&#243;stico adequado.</p>
      <p>Finalmente, outro frequente erro diagn&#243;stico foi a rejei&#231;&#227;o aguda humoral, da qual se
            conhece a dificuldade diagn&#243;stica, necessitando-se de m&#233;todos imuno-histol&#243;gicos
            avan&#231;ados como imunofluoresc&#234;ncia e imunoperoxidase, al&#233;m do paciente ter condi&#231;&#245;es
            cl&#237;nicas de ser submetido ao procedimento de bi&#243;psia endomioc&#225;rdica.</p>
      <p>Levando-se em conta apenas a causa necrosc&#243;pica de &#243;bito, os dados do presente estudo
            s&#227;o semelhantes aos da literatura<xref ref-type="bibr" rid="B11">11</xref>
				<sup>,</sup>
				<xref ref-type="bibr" rid="B12">12</xref>, com destaque para
            disfun&#231;&#227;o aguda do enxerto, infec&#231;&#227;o, rejei&#231;&#227;o e DVE. Separando-se os &#243;bitos em precoces
            e tardios, destacaram-se a disfun&#231;&#227;o aguda do enxerto e a DVE, respectivamente.</p>
      <p>Quanto &#224; causa da miocardiopatia que levou ao transplante, esta casu&#237;stica difere da
            encontrada no relat&#243;rio anual da <italic>International Society of Heart and Lung
               Transplantation</italic>, de 2012. Enquanto a etiologia prevalente neste estudo foi
            cardiopatia chag&#225;sica seguida por miocardiopatia dilatada idiop&#225;tica, nos dados mundiais
            a etiologia mais prevalente foi a miocardiopatia dilatada idiop&#225;tica (54%), seguida por
            cardiopatia isqu&#234;mica (37%)<xref ref-type="bibr" rid="B10">10</xref>. Essa diferen&#231;a se
            d&#225; pela preval&#234;ncia da doen&#231;a de Chagas em nosso meio, diferentemente do que acontece na
            Europa e Am&#233;rica do Norte.</p>
      <p>Dentre as limita&#231;&#245;es deste trabalho, deve-se ressaltar o tamanho da amostra, que reflete
            a diminui&#231;&#227;o do n&#250;mero de necr&#243;psias nas &#250;ltimas d&#233;cadas, como j&#225; mencionado. Por
            conseguinte, apenas 38,7% dos &#243;bitos, entre 2000 e 2010, foram submetidos a necr&#243;psias e
            foram inclu&#237;dos no trabalho, o que pode interferir nos resultados.</p>
      <p>Ainda pode-se acrescentar que a an&#225;lise de prontu&#225;rios pode n&#227;o revelar precisamente a
            causa cl&#237;nica do &#243;bito, j&#225; que fatores como preenchimento incompleto dos prontu&#225;rios e
            dificuldade de entendimento dos prontu&#225;rios mais antigos, que ainda n&#227;o eram
            eletr&#244;nicos, podem interferir na impress&#227;o sobre a causa cl&#237;nica de &#243;bito aventada.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>Discord&#226;ncias entre o diagn&#243;stico cl&#237;nico e achados da necr&#243;psia s&#227;o comumente
            encontradas no transplante card&#237;aco. Novas estrat&#233;gias no aperfei&#231;oamento do diagn&#243;stico
            cl&#237;nico devem ser introduzidas, considerando-se os resultados da necr&#243;psia para melhoria
            do tratamento da insufici&#234;ncia card&#237;aca por meio do transplante card&#237;aco.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="con">
        <p>
          <bold>Contribui&#231;&#227;o dos autores</bold>
        </p>
        <p>Concep&#231;&#227;o e desenho da pesquisa: Ayub-Ferreira SM, Bocchi EA; Obten&#231;&#227;o de dados:
               Valette TN, Ayub-Ferreira SM, Benvenuti LA, Bacal F, Chizzola PR, Souza GEC, Fiorelli
               AI, Santos RHB; An&#225;lise e interpreta&#231;&#227;o dos dados: Valette TN, Ayub-Ferreira SM,
               Benvenuti LA, Issa VS, Bacal F, Chizzola PR, Souza GEC, Fiorelli AI, Santos RHB;
               An&#225;lise estat&#237;stica: Ayub-Ferreira SM, Issa VS; Reda&#231;&#227;o do manuscrito: Valette TN;
               Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante:
               Ayub-Ferreira SM, Benvenuti LA, Issa VS, Bocchi EA; Supervis&#227;o/ como investigador
               principal: Bocchi EA.</p>
      </fn>
      <fn fn-type="financial-disclosure">
        <p>
          <bold>Fontes de Financiamento</bold>
        </p>
        <p>O presente estudo foi financiado parcialmente por FAPESP.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
        </p>
        <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo com disserta&#231;&#245;es e teses de p&#243;s-gradua&#231;&#227;o.</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" xml:lang="en" id="SA1">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">NHETS &#8722; Necropsy Heart Transplantation
               Study</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Valette</surname>
            <given-names>Thiago Ninck</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ayub-Ferreira</surname>
            <given-names>Silvia Moreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Benvenuti</surname>
            <given-names>Luiz Alberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Issa</surname>
            <given-names>Victor Sarli</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bacal</surname>
            <given-names>Fernando</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chizzola</surname>
            <given-names>Paulo Roberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Souza</surname>
            <given-names>Germano Emilio Concei&#231;&#227;o</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fiorelli</surname>
            <given-names>Alfredo In&#225;cio</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Ronaldo Honorato Barros dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bocchi</surname>
            <given-names>Edimar Alcides</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <aff id="aff2">
          <institution content-type="orgdiv3">Instituto do Cora&#231;&#227;o</institution>
          <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina</institution>
          <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country>Brazil</country>
          <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da
                  Faculdade de Medicina da Universidade de S&#227;o Paulo (USP), S&#227;o Paulo, SP -
                  Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c02"><bold>Mailing Address: Thiago Ninck Valette,</bold> Avenida Interlagos, 871, bloco 7,
               apto. 43, Jardim Marajoara. Postal Code 04661-100, S&#227;o Paulo, SP - Brazil. E-mail:
                  <email>thiago.valette@gmail.com</email>, <email>t_valette@hotmail.com</email>
				</corresp>
        <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>
      <abstract xml:lang="en">
        <sec>
          <title>Background:</title>
          <p>Discrepancies between pre and post-mortem diagnoses are reported in the
                  literature, ranging from 4.1 to 49.8 % in cases referred for necropsy, with
                  important impact on patient treatment.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To analyze patients who died after cardiac transplantation and to compare the pre-
                  and post-mortem diagnoses.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>Perform a review of medical records and analyze clinical data, comorbidities,
                  immunosuppression regimen, laboratory tests, clinical cause of death and cause of
                  death at the necropsy. Then, the clinical and necroscopic causes of death of each
                  patient were compared.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>48 deaths undergoing necropsy were analyzed during 2000-2010; 29 (60.4 %) had
                  concordant clinical and necroscopic diagnoses, 16 (33.3%) had discordant diagnoses
                  and three (6.3%) had unclear diagnoses. Among the discordant ones, 15 (31.3%) had
                  possible impact on survival and one (2.1%) had no impact on survival. The main
                  clinical misdiagnosis was infection, with five cases (26.7 % of discordant),
                  followed by hyperacute rejection, with four cases (20 % of the discordant ones),
                  and pulmonary thromboembolism, with three cases (13.3% of discordant ones).</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>Discrepancies between clinical diagnosis and necroscopic findings are commonly
                  found in cardiac transplantation. New strategies to improve clinical diagnosis
                  should be made, considering the results of the necropsy, to improve the treatment
                  of heart failure by heart transplantation.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Heart Transplantation</kwd>
        <kwd>Autopsy</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>The necroscopic examination has contributed to the evolution of medical knowledge.
               However, the frequency at which medical centers perform necropsies has been declining
               in recent decades, in different series. The assumed reasons for this phenomenon are
               diverse and include cultural aspects, lack of authorization by families, lack of
               financial resources for the procedure, an aging population and less interest in
               necropsy findings in the elderly, a decrease in the scientific interest in the
               necroscopic findings and hesitation facing the possibility of medical error
               detection. Considering this historical trend, discrepancies between pre and
               post-mortem diagnoses continue to be reported, ranging from 4.1 to 49.8% of cases
               referred for necroscopic examination<xref ref-type="bibr" rid="B01">1</xref>. A
               recent study did not evaluate the diagnoses obtained through pre-mortem clinical data
               with the necroscopic diagnoses of patients undergoing cardiac transplantation.</p>
        <p>This study aimed to assess patients who died after cardiac transplantation and were
               submitted to necropsy, analyzing the causes of death and comparing the pre- and
               post-mortem diagnoses.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <p>Retrospective study was carried out by analysis of medical records of deaths from
               heart transplantation that were submitted necropsy in the period 2000-2010. Clinical
               data for analysis of comorbidities, immunosuppression regimen, laboratory test
               results, clinical cause of death and cause of death at the necropsy were
               collected.</p>
        <p>The pre-mortem death diagnosis was compared with the post-mortem one and then the
               discrepancies between the two diagnoses were classified according to Goldman et
                  al<xref ref-type="bibr" rid="B02">2</xref> criteria adapted by Battle et al<xref ref-type="bibr" rid="B03">3</xref>, while some cases were not classified<xref ref-type="bibr" rid="B04">4</xref>. The classification was as follows:</p>
        <list list-type="bullet">
          <list-item>
            <p>Major discrepancies:</p>
          </list-item>
        </list>
        <list list-type="simple">
          <list-item>
            <p>- class I: discrepancies in major diagnosis, with impact on survival;</p>
          </list-item>
          <list-item>
            <p>- class II: discrepancies in major diagnosis, with no impact on survival;</p>
          </list-item>
        </list>
        <list list-type="bullet">
          <list-item>
            <p>Minor discrepancies:</p>
          </list-item>
        </list>
        <list list-type="simple">
          <list-item>
            <p>- class III: discrepancies in minor diagnoses not directly related to cause of
                     death;</p>
          </list-item>
          <list-item>
            <p>- class IV: discrepancies in minor occult diagnoses (non-diagnosable), but with
                     possible epidemiological or genetic importance;</p>
          </list-item>
        </list>
        <list list-type="bullet">
          <list-item>
            <p>Non-discrepancy:</p>
          </list-item>
        </list>
        <list list-type="simple">
          <list-item>
            <p>- class V: non-discrepant diagnoses;</p>
          </list-item>
        </list>
        <list list-type="bullet">
          <list-item>
            <p>Non-classifiable cases:</p>
          </list-item>
        </list>
        <list list-type="simple">
          <list-item>
            <p>- class VI: patients whose clinical or necroscopic diagnoses cannot be
                     performed adequately.</p>
          </list-item>
        </list>
        <p>Deaths were also differentiated as early or late, with early being those that
               occurred up to 1 year after transplantation and late the ones that occurred after 12
               months. Discrepancies were evaluated in these two groups, verifying the causes of
               death.</p>
        <p>This study was approved by the Research Ethics Committee. It was not necessary to
               obtain the signed free and informed consent, as this was a retrospective study based
               on the analysis of medical records.</p>
        <p>The study received financial support from Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de
               S&#227;o Paulo, process #2010/12278-5.</p>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>From 2000 to 2010, 124 patients submitted to cardiac transplantation died. Cardiac
               transplantation of the 124 patients occurred from February 1987 to March 2010. Of
               these 124 patients, 48 were submitted to necropsy, which comprise the study sample.
                  <xref ref-type="fig" rid="f04">Figure 1</xref> shows the case selection flowchart
               of the study.</p>
        <fig id="f04" fig-type="other">
          <label>Figure 1</label>
          <caption>
            <title>Flowchart of case selection.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-102-05-0505-40039-gf01-en.jpg"/></fig>
        <p>The mean age was 41 years and 67% were men. The mean post-transplantation follow-up
               duration was 991 &#177; 1,728 days. The most frequent etiology of the disease (before
               transplantation) was chagasic heart disease. Regarding comorbidities, 44% of the
               patients had hypertension, 31% dyslipidemia, and 18% diabetes mellitus. <xref ref-type="table" rid="t03">Table 1</xref> shows the general characteristics of the
               patients.</p>
        <table-wrap id="t03">
          <label>Table 1</label>
          <caption>
            <title>Clinical characteristics of studied patients</title>
          </caption>
          <table frame="hsides" rules="rows">
            <thead>
              <tr>
                <th colspan="2" align="left">
                  <bold>Characteristics</bold>
                </th>
                <th>
                  <bold>n = 48 </bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td colspan="2">Age (years )</td>
                <td align="center">41 &#177; 16</td>
              </tr>
              <tr>
                <td colspan="2">Male gender (%)</td>
                <td align="center">67</td>
              </tr>
              <tr>
                <td colspan="2">Follow-up after transplantation (days)</td>
                <td align="center">991 &#177; 1,728</td>
              </tr>
              <tr>
                <td colspan="3">Etiology (%)</td>
              </tr>
              <tr>
                <td>&#160;</td>
                <td>Ischemic</td>
                <td align="center">14.6</td>
              </tr>
              <tr>
                <td>&#160;</td>
                <td>Idiopathic</td>
                <td align="center">29.2</td>
              </tr>
              <tr>
                <td>&#160;</td>
                <td>Hypertensive</td>
                <td align="center">2.1</td>
              </tr>
              <tr>
                <td>&#160;</td>
                <td>Chagas disease</td>
                <td align="center">31.3</td>
              </tr>
              <tr>
                <td colspan="2">Others</td>
                <td align="center">13</td>
              </tr>
              <tr>
                <td colspan="2">Systemic Arterial Hypertension (%)</td>
                <td align="center">44</td>
              </tr>
              <tr>
                <td colspan="2">Diabetes mellitus (%)</td>
                <td align="center">18</td>
              </tr>
              <tr>
                <td colspan="2">Dyslipidemia (%)</td>
                <td align="center">31</td>
              </tr>
              <tr>
                <td colspan="2">Leukocytes</td>
                <td align="center">8,590 &#177; 4,972</td>
              </tr>
              <tr>
                <td colspan="2">Sodium (mEq/L)</td>
                <td align="center">136 &#177; 4</td>
              </tr>
              <tr>
                <td colspan="2">Creatinine (mg/dL)</td>
                <td align="center">1.9 &#177; 0.6</td>
              </tr>
              <tr>
                <td colspan="2">Urea (mg/dL)</td>
                <td align="center">79 &#177; 56</td>
              </tr>
              <tr>
                <td colspan="2">Potassium (mEq/L)</td>
                <td align="center">4.5 &#177; 0.6</td>
              </tr>
              <tr>
                <td colspan="2">Hemoglobin (g/dL)</td>
                <td align="center">12.5 &#177; 2.17</td>
              </tr>
              <tr>
                <td colspan="3">Medications (%)</td>
              </tr>
              <tr>
                <td>&#160;</td>
                <td>Cyclosporine</td>
                <td align="center">50</td>
              </tr>
              <tr>
                <td>&#160;</td>
                <td>Tacrolimus</td>
                <td align="center">14.6</td>
              </tr>
              <tr>
                <td>&#160;</td>
                <td>Mycophenolate mofetil</td>
                <td align="center">54</td>
              </tr>
              <tr>
                <td>&#160;</td>
                <td>Corticosteroids</td>
                <td align="center">77</td>
              </tr>
              <tr>
                <td>&#160;</td>
                <td>Azathioprine</td>
                <td align="center">29.2</td>
              </tr>
              <tr>
                <td>&#160;</td>
                <td>Sirolimus</td>
                <td align="center">14.6</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Of the 48 analyzed cases, 29 (60.4 %) had concordant clinical and necroscopic
               diagnoses (class V), 16 (33.3 %) had discordant diagnoses and three (6.3%) had an
               unclear diagnosis (class VI). Among the discordant ones, 15 (31.3%) had possible
               impact on survival (class I) and one (2.1%) had no impact on survival (class II). The
               main clinical misdiagnosis was infection, with five cases (26.7% of discordant ones),
               followed by hyperacute rejection, with four cases (20% of discordant ones) and
               pulmonary thromboembolism with three cases (13.3% of discordant ones). <xref ref-type="fig" rid="f05">Figure 2</xref> shows the chart distribution of
               necropsies, based on the classification of discrepancies. <xref ref-type="fig" rid="f06">Figure 3</xref> and <xref ref-type="table" rid="t04">Table 2</xref>
               compare the clinical and necroscopic diagnoses of class I discordant cases.</p>
        <fig id="f05" fig-type="other">
          <label>Figure 2</label>
          <caption>
            <title>Distribution of discrepancies between clinical and necroscopic
                     diagnoses.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-102-05-0505-40039-gf02-en.jpg"/></fig>
        <fig id="f06" fig-type="other">
          <label>Figure 3</label>
          <caption>
            <title>Comparison between clinical and necroscopic diagnoses of class I discordant
                     cases.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-102-05-0505-40039-gf03-en.jpg"/></fig>
        <table-wrap id="t04">
          <label>Table 2</label>
          <caption>
            <title>Comparison between clinical and necroscopic diagnoses of class I discordant
                     cases</title>
          </caption>
          <table frame="hsides" rules="rows">
            <thead>
              <tr>
                <th colspan="10">
                  <bold>Clinical Diagnosis</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td rowspan="7">
                  <alternatives>
                    <inline-graphic xlink:href="https://minio.scielo.br/documentstore/1678-4170/YxfpjnySvwn7QMk9vP8TBhc/d269d1a9cfc4f59cd1486e321ddd1d4e30b5a2c9.jpg"/>
                    <inline-graphic xlink:href="https://minio.scielo.br/documentstore/1678-4170/YxfpjnySvwn7QMk9vP8TBhc/d269d1a9cfc4f59cd1486e321ddd1d4e30b5a2c9.jpg"/>
                  </alternatives>
                </td>
                <td>&#160;</td>
                <td align="center">HR</td>
                <td align="center">ACR</td>
                <td align="center">AHR</td>
                <td align="center">SS</td>
                <td align="center">CS</td>
                <td align="center">PTE</td>
                <td align="center">HS</td>
                <td align="center">MOSF</td>
              </tr>
              <tr>
                <td align="center">GVD</td>
                <td>&#160;</td>
                <td align="center">2</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td align="center">1</td>
                <td>&#160;</td>
                <td>&#160;</td>
              </tr>
              <tr>
                <td align="center" style="border-bottom:hidden">PTE</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td align="center">1</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
              </tr>
              <tr>
                <td align="center" style="border-bottom:hidden">MS</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td align="center">1</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
              </tr>
              <tr>
                <td align="center" style="border-bottom:hidden">DIC</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td align="center">1</td>
                <td>&#160;</td>
                <td>&#160;</td>
              </tr>
              <tr>
                <td align="center">AGD</td>
                <td align="center">3</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td align="center">1</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td align="center">1</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="center">AHR</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td align="center">2</td>
                <td align="center">1</td>
                <td>&#160;</td>
                <td>&#160;</td>
                <td>&#160;</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>HR: hyperacute rejection; ACR: acute cellular rejection; AHR: acute humoral
                        rejection, SS: septic shock, CS: cardiogenic shock; PTE: pulmonary
                        thromboembolism, HS: Hemorrhagic shock; MOSF: multiple organ and system
                        failure; GVD: graft vascular disease, MS: mixed shock, DIC: disseminated
                        intravascular coagulation; AGD: acute graft dysfunction.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>A total of 62.5 % (30 cases) were classified as early deaths and 37.5 % as late ones
               (18 cases). Among the early cases, 56% were concordant with impact on survival (class
               V), 33% discordant with impact on survival (class I), 3% discordant with no impact on
               survival (class II) and 6 % had unclear diagnoses (Class VI). Among the late, 67%
               were concordant with impact on survival (class V), 28% discordant with impact on
               survival (class I) and 5.6% had unclear diagnoses (Class VI).</p>
        <p>The causes of death verified at the necropsies were acute graft dysfunction (22.9%),
               acute rejection (20.8 %), infection (18.8%), Graft Vascular Disease (GVD-16.7%),
               other causes (14.6%) and unknown causes (6.3%).</p>
        <p>In the group classified as early death, 37 % of deaths were due to acute graft
               dysfunction, 20% acute humoral rejection, 16.7% septic shock, 16.7% from other
               causes, and 6% of unknown causes.</p>
        <p>In the late group, 45% of deaths were due to GVD, 17% to acute cellular rejection,
               11% to septic shock, 22% from other causes and 5% of unknown causes.</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>Our study showed a significant frequency of discrepancies between clinical and
               necroscopic diagnoses of the cause of death, most often with a possible impact on
               survival.</p>
        <p>In the literature, no recent studies were found comparing the clinical and
               necroscopic causes of death in patients undergoing cardiac transplantation, making
               this work a current tool for information analysis.</p>
        <p>On the other hand, the rate of discordance in the present sample, on average, was
               higher than that observed in other series of patients unrelated to heart
               transplantation. Discrepancies values of 7.5 to 23 %, classified as major, were found
               in patients admitted to the intensive care unit, with 11-13% for minor
                  discrepancies<xref ref-type="bibr" rid="B05">5</xref>
					<sup>,</sup>
					<xref ref-type="bibr" rid="B06">6</xref>. For patients admitted to general hospitals,
               there were 6-37 % of major discrepancies and 25-28 % of minor ones<xref ref-type="bibr" rid="B07">7</xref>
					<sup>-</sup>
					<xref ref-type="bibr" rid="B09">9</xref>.</p>
        <p>The most difficult necroscopic diagnosis to be clinically hypothesized was acute
               graft dysfunction. In this series, it was misdiagnosed as hyperacute rejection,
               hemorrhagic shock and septic shock. These data show the difficulty to confirm this
               diagnosis in clinical practice, as it depends on situations related to the
               perioperative period (the donor's conditions, time of ischemia, myocardial protection
               and the recipient's prior pulmonary hypertension) and the degree of suspicion of the
               attending physician, as there is no specific marker for the diagnosis.</p>
        <p>Another premortem unsuspected necroscopic diagnosis was GVD. This was confused with
               other conditions that lead to ventricular dysfunction with cellular rejection and
               pulmonary thromboembolism. Although GVD is one of the main late causes of
               post-transplantation death<xref ref-type="bibr" rid="B10">10</xref>a dose of clinical
               suspicion is also needed to initiate the appropriate diagnostic method.</p>
        <p>Finally, another common diagnostic error was acute humoral rejection, which is known
               by its diagnostic difficulties, requiring advanced immunohistological methods, such
               as immunofluorescence and immunoperoxidase, in addition to the fact that the patient
               needs to be capable of being submitted to endomyocardial biopsy procedure.</p>
        <p>Taking into account only the necroscopic cause of death, the data from this study are
               similar to those in the literature<xref ref-type="bibr" rid="B11">11</xref>
					<sup>,</sup>
					<xref ref-type="bibr" rid="B12">12</xref>, with emphasis on
               acute graft dysfunction, infection, rejection and GVD. Separating the deaths in early
               and late cases, acute graft dysfunction and GVD stood out, respectively.</p>
        <p>Regarding the cause of cardiomyopathy that led to transplantation, this sample
               differs from that found in the International Society of Heart and Lung
               Transplantation Annual Report, 2012. While the most prevalent etiology in this study
               was Chagas' disease, followed by idiopathic dilated cardiomyopathy, the global data
               showed the most prevalent etiology was idiopathic dilated cardiomyopathy (54 %),
               followed by ischemic heart disease (37 %)<xref ref-type="bibr" rid="B10">10</xref>.
               This difference is due to the prevalence of Chagas disease in our country, unlike
               what occurs in Europe and North America.</p>
        <p>Among the limitations of this study is sample size, which reflects the decrease in
               the number of necropsies in recent decades, as mentioned before. Consequently, only
               38.7 % of deaths between 2000 and 2010 were submitted to necropsy and were included
               in the study, which may interfere with the results.</p>
        <p>Moreover, the analysis of records may not accurately reveal the clinical cause of
               death, as factors such as incomplete filling out of medical records and difficulties
               in understanding older records, which were not yet electronic, can interfere with the
               impression of the presumed clinical cause of death.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>Discrepancies between clinical diagnosis and necroscopic findings are commonly found
               in cardiac transplantation. New strategies to improve clinical diagnosis should be
               made, considering necroscopic results to improve the treatment of heart failure by
               heart transplantation.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Ayub-Ferreira SM, Bocchi EA; Acquisition of
                  data: Valette TN, Ayub-Ferreira SM, Benvenuti LA, Issa VS, Bacal F, Chizzola PR,
                  Souza GEC, Fiorelli AI, Santos RHB; Analysis and interpretation of the data:
                  Valette TN, Ayub-Ferreira SM, Benvenuti LA, Issa VS, Bacal F, Chizzola PR, Souza
                  GEC, Fiorelli AI, Santos RHB; Statistical analysis: Ayub-Ferreira SM; Writing of
                  the manuscript: Valette TN; Critical revision of the manuscript for intellectual
                  content: Ayub-Ferreira SM, Benvenuti LA, Bocchi EA; Supervision / as principal
                  investigator: Bocchi EA.</p>
        </fn>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Sources of Funding</bold>
          </p>
          <p>This study was partially funded by FAPESP.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Study Association </bold>
          </p>
          <p>This study is not associated with any thesis or dissertation work.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
