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  <front>
    <journal-meta>
      <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-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">VyCCFDsB3SwW5R5dMNNxVHv</article-id>
      <article-id pub-id-type="other">00019</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2010000200019</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(10)09400219</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2010000200019</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Experi&#234;ncia com transplante card&#237;aco heterot&#243;pico em pacientes com resist&#234;ncia pulmonar elevada: seguimento tardio</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Vila</surname>
            <given-names>Jose Henrique Andrade</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Jos&#233; Pedro da</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fonseca</surname>
            <given-names>Luciana da</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Baumgratz</surname>
            <given-names>Jos&#233; Francisco</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tangari Jr</surname>
            <given-names>Am&#233;rico</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Leite</surname>
            <given-names>Weverton Ferreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Guilhen</surname>
            <given-names>Claudia Jesus</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Armelin</surname>
            <given-names>Egas</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Benem&#233;rita Sociedade de Benefic&#234;ncia Portuguesa de S&#227;o Paulo</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>02</month>
        <year>2010</year>
      </pub-date>
      <volume>94</volume>
      <issue>2</issue>
      <fpage>261</fpage>
      <lpage>267</lpage>
      <history>
        <date date-type="accepted">
          <day>11</day>
          <month>11</month>
          <year>2008</year>
        </date>
        <date date-type="rev-recd">
          <day>31</day>
          <month>10</month>
          <year>2008</year>
        </date>
        <date date-type="received">
          <day>22</day>
          <month>08</month>
          <year>2008</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>FUNDAMENTO: Nos &#250;ltimos anos o numero de artigos sobre transplante card&#237;aco heterot&#243;pico tem sido escasso na literatura, inclusive internacional, e em particular do seguimento de longo prazo destes pacientes, o que levou ao presente relato. OBJETIVO: Relatar a experi&#234;ncia cl&#237;nica inicial e evolu&#231;&#227;o tardia de quatro pacientes submetidos a transplante card&#237;aco heterot&#243;pico, sua indica&#231;&#227;o e principais complica&#231;&#245;es. M&#201;TODOS: As cirurgias ocorreram entre 1992 e 2001, sendo que a indica&#231;&#227;o de transplante heterot&#243;pico, em todas, foi pela RVP, vari&#225;vel de 4,8UW a 6.5UW, com gradiente transpulmonar acima de 15mmHg. No 3&#186; paciente, foi realizada uma anastomose direta entre as art&#233;rias pulmonares sem emprego de tubo prot&#233;tico e, no cora&#231;&#227;o nativo, foi realizada uma valvoplastia mitral e aneurismectomia de ventr&#237;culo esquerdo (VE). O esquema imunossupressor imediato foi duplo com ciclosporina e azatioprina nos tr&#234;s primeiros pacientes e ciclosporina e micofenolato mofetil no 4&#186; paciente. RESULTADOS: Um &#243;bito imediato por fal&#234;ncia do enxerto, um &#243;bito ap&#243;s dois anos e meio por endocardite em trombo intraventricular no cora&#231;&#227;o nativo, e um terceiro &#243;bito seis anos ap&#243;s o transplante, por complica&#231;&#245;es p&#243;s-operat&#243;rias de cirurgia na valva a&#243;rtica do cora&#231;&#227;o nativo. O remanescente, 15 anos ap&#243;s o transplante, encontra-se bem, em classe funcional II (NYHA), seis anos ap&#243;s a oclus&#227;o cir&#250;rgica da valva a&#243;rtica do cora&#231;&#227;o nativo. CONCLUS&#195;O: O transplante card&#237;aco heterot&#243;pico &#233; um procedimento com resultado inferior ao transplante card&#237;aco ortot&#243;pico, por apresentarem maior RVP. Os trombos intraventriculares no cora&#231;&#227;o nativo, que exigem anticoagula&#231;&#227;o prolongada, bem como as complica&#231;&#245;es de v&#225;lvula a&#243;rtica, tamb&#233;m no cora&#231;&#227;o nativo, podem exigir tratamento cir&#250;rgico. Entretanto, em um paciente, a sobrevida de 15 anos mostrou a efic&#225;cia de longo prazo desse tipo de alternativa, para pacientes selecionados.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>transplante card&#237;aco</kwd>
        <kwd>hipertens&#227;o pulmonar</kwd>
        <kwd>seguimentos</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>05</day>
        <month>05</month>
        <year>2010</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>ARTIGO ORIGINAL </p>
    <p> TRANSPLANTE CARD&#205;ACO</p>
    <p>
      <bold>Experi&#234;ncia com transplante card&#237;aco heterot&#243;pico em pacientes com resist&#234;ncia pulmonar elevada. Seguimento tardio</bold>
    </p>
    <p>
      <bold>Jose Henrique Andrade Vila; Jos&#233; Pedro da Silva; Luciana da Fonseca; Jos&#233; Francisco Baumgratz; Am&#233;rico Tangari Jr; Weverton Ferreira Leite; Claudia Jesus Guilhen; Egas Armelin</bold>
    </p>
    <p>Hospital Benefic&#234;ncia Portuguesa de S&#227;o Paulo, S&#227;o Paulo, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="back">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO: </bold> Nos &#250;ltimos anos o numero de artigos sobre transplante card&#237;aco heterot&#243;pico tem sido escasso na literatura, inclusive internacional, e em particular do seguimento de longo prazo destes pacientes, o que levou ao presente relato. </p>
    <p><bold>OBJETIVO:</bold> Relatar a experi&#234;ncia cl&#237;nica inicial e evolu&#231;&#227;o tardia de quatro pacientes submetidos a transplante card&#237;aco heterot&#243;pico, sua indica&#231;&#227;o e principais complica&#231;&#245;es. </p>
    <p><bold>M&#201;TODOS:</bold> As cirurgias ocorreram entre 1992 e 2001, sendo que a indica&#231;&#227;o de transplante heterot&#243;pico, em todas, foi pela RVP, vari&#225;vel de 4,8UW a 6.5UW, com gradiente transpulmonar acima de 15mmHg. No 3&#186; paciente, foi realizada uma anastomose direta entre as art&#233;rias pulmonares sem emprego de tubo prot&#233;tico e, no cora&#231;&#227;o nativo, foi realizada uma valvoplastia mitral e aneurismectomia de ventr&#237;culo esquerdo (VE). O esquema imunossupressor imediato foi duplo com ciclosporina e azatioprina nos tr&#234;s primeiros pacientes e ciclosporina e micofenolato mofetil no 4&#186; paciente. </p>
    <p><bold>RESULTADOS:</bold> Um &#243;bito imediato por fal&#234;ncia do enxerto, um &#243;bito ap&#243;s dois anos e meio por endocardite em trombo intraventricular no cora&#231;&#227;o nativo, e um terceiro &#243;bito seis anos ap&#243;s o transplante, por complica&#231;&#245;es p&#243;s-operat&#243;rias de cirurgia na valva a&#243;rtica do cora&#231;&#227;o nativo. O remanescente, 15 anos ap&#243;s o transplante, encontra-se bem, em classe funcional II (NYHA), seis anos ap&#243;s a oclus&#227;o cir&#250;rgica da valva a&#243;rtica do cora&#231;&#227;o nativo. </p>
    <p><bold>CONCLUS&#195;O:</bold> O transplante card&#237;aco heterot&#243;pico &#233; um procedimento com resultado inferior ao transplante card&#237;aco ortot&#243;pico, por apresentarem maior RVP. Os trombos intraventriculares no cora&#231;&#227;o nativo, que exigem anticoagula&#231;&#227;o prolongada, bem como as complica&#231;&#245;es de v&#225;lvula a&#243;rtica, tamb&#233;m no cora&#231;&#227;o nativo, podem exigir tratamento cir&#250;rgico. Entretanto, em um paciente, a sobrevida de 15 anos mostrou a efic&#225;cia de longo prazo desse tipo de alternativa, para pacientes selecionados.</p>
    <p><bold>Palavras-chave: </bold> transplante card&#237;aco, hipertens&#227;o pulmonar/complica&#231;&#245;es, seguimentos.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A resist&#234;ncia vascular pulmonar (RVP) elevada, que ocorre na fase final das miocardiopatias, tem sido um dos maiores obst&#225;culos para a realiza&#231;&#227;o do transplante card&#237;aco ortot&#243;pico. Isso ocorre pelo risco de fal&#234;ncia precoce do ventr&#237;culo direito (VD) do &#243;rg&#227;o transplantado, limitando o seu emprego para pacientes com RVP inferior a 5 unidades Wood (UW)<sup>1,2</sup>, ou preferencialmente 4 unidades Wood em dias atuais.</p>
    <p>A aplica&#231;&#227;o cl&#237;nica do transplante card&#237;aco heterot&#243;pico (TxHet), por Barnard em 1974, ampliou a possibilidade dos transplantes card&#237;acos para pacientes com RVP acima de 4 UW<sup>3,4</sup>, e foi muito utilizada pelo grupo da &#193;frica do Sul, principalmente com o argumento adicional de que, em caso de fal&#234;ncia do enxerto, naquele cen&#225;rio sem a disponibilidade da ciclosporina, o paciente sobreviveria gra&#231;as ao &#243;rg&#227;o nativo. Entre outras indica&#231;&#245;es desse procedimento, podemos citar a sua utiliza&#231;&#227;o nas disfun&#231;&#245;es ventriculares, potencialmente revers&#237;veis, e em casos de despropor&#231;&#227;o de tamanho entre doador e receptor. Esta &#250;ltima condi&#231;&#227;o &#233; particularmente poss&#237;vel em pacientes portadores de miocardiopatia isqu&#234;mica, ainda com possibilidade de tratamento cir&#250;rgico convencional, quando o enxerto heterot&#243;pico poderia ser implantado para maior seguran&#231;a na evolu&#231;&#227;o precoce desses pacientes<sup>3-5</sup>.</p>
    <p>O objetivo deste trabalho &#233; relatar a experi&#234;ncia com quatro procedimentos, realizados em nosso servi&#231;o, enfatizando as indica&#231;&#245;es do procedimento, uma modifica&#231;&#227;o original na t&#233;cnica operat&#243;ria, bem como o seguimento tardio de at&#233; 15 anos dos pacientes operados.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>Entre agosto de 1988 e dezembro de 2007, foram realizados 222 transplantes card&#237;acos em nosso grupo no Hospital da Benefic&#234;ncia Portuguesa de S&#227;o Paulo, incluindo seis retransplantes. Dessa experi&#234;ncia, em quatro pacientes optou-se pela posi&#231;&#227;o heterot&#243;pica, em fun&#231;&#227;o da acentuada eleva&#231;&#227;o dos n&#237;veis de RVP. As caracter&#237;sticas cl&#237;nicas desses quatro pacientes est&#227;o descritas na <xref ref-type="table" rid="t01">tabela 1</xref>, que enfatiza os n&#237;veis de RVP significativamente elevados.</p>
    <p content-type="asset">
      <table-wrap id="t01">
        <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gt01.jpg"/></table-wrap>
    </p>
    <p>Do ponto de vista cl&#237;nico, os pacientes apresentavam quadro de grave miocardiopatia isqu&#234;mica, todos com extenso infarto do mioc&#225;rdio e art&#233;rias coron&#225;rias n&#227;o pass&#237;veis de tratamento cir&#250;rgico. Encontravam-se em UTI, recebendo drogas vasodilatadoras e inotr&#243;picas, em lista de espera de transplante card&#237;aco. O primeiro paciente tinha sido submetido &#224; cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica pr&#233;via, com oclus&#227;o dos enxertos empregados, e o &#250;ltimo paciente sofrera por duas vezes angioplastia coronariana anterior ao transplante. Neste &#250;ltimo paciente, operado em novembro de 2001, al&#233;m do implante do enxerto em posi&#231;&#227;o heterot&#243;pica, procedeu-se a corre&#231;&#227;o do aneurisma de ventr&#237;culo esquerdo, bem como a realiza&#231;&#227;o de valvoplastia cir&#250;rgica da valva mitral. Os outros dois pacientes tamb&#233;m se encontravam em classe funcional IV <italic>New York Heart Association</italic> (NYHA), com frequentes interna&#231;&#245;es em UTI para receber drogas inotr&#243;picas e vasodilatadoras por via venosa.</p>
    <p>O procedimento cir&#250;rgico foi realizado utilizando-se cora&#231;&#245;es obtidos de doadores &#224; dist&#226;ncia no 1&#186;, 3&#186; e 4&#186; pacientes, e de doador em sala cont&#237;gua no 2&#186; paciente. Os &#243;rg&#227;os foram retirados dos doadores, seccionada a aorta acima do tronco branquiocef&#225;lico e a art&#233;ria pulmonar (AP), na parte inicial dos ramos pulmonares. Para prote&#231;&#227;o mioc&#225;rdica, foi utilizada solu&#231;&#227;o cardiopl&#233;gica de St. Thomas, com infus&#227;o anter&#243;grada via a&#243;rtica no cora&#231;&#227;o nativo do receptor, exceto no ultimo caso, em que utilizamos a infus&#227;o retr&#243;grada no seio coronariano. No cora&#231;&#227;o do doador, tamb&#233;m utilizamos a infus&#227;o da cardioplegia anter&#243;grada por via a&#243;rtica. Associamos hipotermia t&#243;pica, atrav&#233;s da imers&#227;o do &#243;rg&#227;o em solu&#231;&#227;o gelada de Ringer, e acondicionados para transporte local ou &#224; dist&#226;ncia. No cora&#231;&#227;o do receptor, a prote&#231;&#227;o mioc&#225;rdica foi realizada com solu&#231;&#227;o cardiopl&#233;gica sangu&#237;nea gelada.</p>
    <p>As t&#233;cnicas cir&#250;rgicas de implante foram similares nos dois primeiros casos, onde a art&#233;ria pulmonar do cora&#231;&#227;o doado foi conectada ao tronco da AP nativa utilizando-se enxerto de peric&#225;rdio bovino para facilitar essas anastomoses. J&#225; no 3&#186; e 4&#186; pacientes, foi utilizada a t&#233;cnica original com anastomose direta da AP do doador ao ramo direito da AP do receptor, sem interposi&#231;&#227;o de qualquer enxerto, j&#225; que a dist&#226;ncia entre as duas &#233; bem mais curta<sup>5</sup>. Esse procedimento foi poss&#237;vel com a transec&#231;&#227;o da veia cava superior do recipiente, pr&#243;ximo ao &#225;trio direito (AD), sendo suturada sua extremidade inferior e mobilizada sua extremidade superior, expondo amplamente o ramo direito da AP. Para que isso seja poss&#237;vel, &#233; necess&#225;ria a ampla dissec&#231;&#227;o da art&#233;ria pulmonar e do ramo esquerdo da mesma, no doador, quando da retirada do &#243;rg&#227;o. Ap&#243;s a anastomose dos &#225;trios esquerdos e das AP, foi realizada a anastomose da extremidade superior da veia cava superior do receptor &#224; veia cava superior do doador. Outra conex&#227;o atrial direita foi feita na por&#231;&#227;o inferior do AD do receptor, pr&#243;ximo ao septo interatrial, permitindo que o retorno venoso do receptor pudesse atingir o AD do doador. A aorta ascendente longa do doador foi anastomosada o mais distante poss&#237;vel da aorta ascendente do receptor, para facilitar o acesso &#224; AP, em caso de sangramento.</p>
    <p>Eletrodos tempor&#225;rios para marcapasso externo foram colocados nos AD de ambos os cora&#231;&#245;es e no VD do cora&#231;&#227;o transplantado, possibilitando a estimula&#231;&#227;o card&#237;aca sincronizada atrav&#233;s de um marcapasso sequencial, conectando-se os p&#243;los atriais aos eletrodos atriais do cora&#231;&#227;o nativo (de frequ&#234;ncia maior) e os eletrodos atriais do cora&#231;&#227;o transplantado aos p&#243;los ventriculares do marcapasso. Dessa forma, o marcapasso sente a onda P do cora&#231;&#227;o nativo e, ap&#243;s pausa regul&#225;vel, estimula o &#225;trio do cora&#231;&#227;o transplantado, conseguindo-se batimentos sincronizados dos dois cora&#231;&#245;es, na mesma l&#243;gica sequencial do bal&#227;o intra-a&#243;rtico, o que tem import&#226;ncia na otimiza&#231;&#227;o do d&#233;bito card&#237;aco nos primeiros dias de p&#243;s-operat&#243;rio<sup>6-8</sup>. Entretanto, ap&#243;s a alta da UTI, e com a retirada dos fios epic&#225;rdicos do marcapasso, n&#227;o houve mais a sincroniza&#231;&#227;o el&#233;trica entre os dois cora&#231;&#245;es, ocorrendo, no entanto, espontaneamente, uma tend&#234;ncia de equaliza&#231;&#227;o das frequ&#234;ncias card&#237;acas, que poderia ser atribu&#237;da &#224; menor estimula&#231;&#227;o adren&#233;rgica propiciada pela melhora do d&#233;bito card&#237;aco, devido principalmente ao cora&#231;&#227;o implantado (<xref ref-type="fig" rid="f01">figura 1</xref>).</p>
    <p content-type="asset">
      <fig id="f01">
        <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gf01.jpg"/></fig>
    </p>
    <p>O esquema imunossupressor utilizado inicialmente foi duplo com ciclosporina e azatioprina, nos tr&#234;s primeiros pacientes, e ciclosporina e micofenolato mofetil no 4&#186; paciente. Realizamos bi&#243;psias controle semanais no primeiro m&#234;s e quinzenais nos dois meses seguintes, ap&#243;s mapeamento mioc&#225;rdico com G&#225;lio e ecocardiograma para o controle de rejei&#231;&#227;o. No primeiro paciente, tivemos dois epis&#243;dios de rejei&#231;&#227;o mioc&#225;rdica importante, que foram respons&#225;veis por uma piora da fun&#231;&#227;o mioc&#225;rdica, e, ap&#243;s o primeiro epis&#243;dio, passamos para esquema tr&#237;plice de imunossupress&#227;o com predinisona 0,5mg/kg/dia, que foi reduzido gradualmente para 0,1mg/kg/dia, ap&#243;s a pulsoterapia intravenosa por tr&#234;s dias.</p>
    <p>No 3&#186; e 4&#186; pacientes, tivemos um &#250;nico epis&#243;dio de rejei&#231;&#227;o grau II, controladas por dois meses de esquema via oral de predinisona. Mantivemos tamb&#233;m o anticoagulante oral nos pacientes tr&#234;s e quatro que sobreviveram tardiamente, bem como diur&#233;ticos, antagonistas enzim&#225;ticos e, posteriormente, o betabloqueador carvedilol, no intuito de prevenir ou retardar a disfun&#231;&#227;o mioc&#225;rdica progressiva do cora&#231;&#227;o nativo.</p>
    <p>Essa pr&#225;tica, entretanto, n&#227;o demonstrou sucesso e, pelo contr&#225;rio, a deteriora&#231;&#227;o da fun&#231;&#227;o ventricular esquerda do cora&#231;&#227;o nativo foi inexor&#225;vel, surgindo inclusive em ambos os pacientes sobreviventes tardios, com insufici&#234;ncia a&#243;rtica progressiva e piora clinica acentuada, que demandou corre&#231;&#227;o cir&#250;rgica, fato esse j&#225; referido na literatura<sup>9</sup>.</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>Os resultados precoces e tardios das cirurgias est&#227;o sintetizados na <xref ref-type="table" rid="t2">tabela 2</xref>. Tivemos um &#243;bito hospitalar, do 2&#186; paciente, 12 horas ap&#243;s o transplante, por fal&#234;ncia do enxerto e do cora&#231;&#227;o nativo.</p>
    <table-wrap id="t2">
      <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gt02.jpg"/></table-wrap>
    <p>O 1&#186; paciente teve boa evolu&#231;&#227;o no primeiro ano, e a seguir passou a ter insufici&#234;ncia card&#237;aca progressiva ap&#243;s dois epis&#243;dios de rejei&#231;&#227;o card&#237;aca aguda e coronariopatia no enxerto. Foi retransplantado dois anos ap&#243;s o transplante, evoluindo para &#243;bito por baixo d&#233;bito card&#237;aco e septicemia aguda no 7&#186; dia de p&#243;s-operat&#243;rio.</p>
    <p>O 3&#186; paciente teve evolu&#231;&#227;o inicial adequada com boa capacidade f&#237;sica, classe funcional II (NYHA), praticando esportes, como nata&#231;&#227;o, regularmente. A <xref ref-type="fig" rid="f2">figura 2</xref> mostra os aspectos das radiografias de t&#243;rax com a t&#233;cnica cir&#250;rgica convencional e com a nova t&#233;cnica desenvolvida pelo grupo<sup>5</sup>. A angiografia pulmonar nesse paciente, que foi submetido &#224; nova t&#233;cnica cir&#250;rgica, mostra um bom resultado anat&#244;mico e funcional (<xref ref-type="fig" rid="f3">figura 3</xref>).</p>
    <fig id="f2">
      <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gf02.jpg"/></fig>
    <fig id="f3">
      <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gf03.jpg"/></fig>
    <p>O controle ecocardiogr&#225;fico sequencial demonstrou queda progressiva e r&#225;pida da fun&#231;&#227;o ventricular do cora&#231;&#227;o nativo, com forma&#231;&#227;o de trombo ao final do primeiro ano, que desapareceu com o incremento da anticoagula&#231;&#227;o oral. Houve, a partir do 6&#186; ano de evolu&#231;&#227;o, uma progressiva insufici&#234;ncia a&#243;rtica por ectasia anulo-a&#243;rtica, com deteriora&#231;&#227;o da condi&#231;&#227;o cl&#237;nica, apesar do incremento da terap&#234;utica cl&#237;nica com antagonistas enzim&#225;ticos (captopril), espironolactona, carvedilol e diur&#233;ticos. Optamos pela corre&#231;&#227;o cir&#250;rgica da insufici&#234;ncia valvar a&#243;rtica, que foi preferida por raz&#245;es t&#233;cnicas ao explante do &#243;rg&#227;o nativo, tendo levado a uma significativa melhora funcional do paciente, que retornou ao tipo funcional II (NYHA). A fun&#231;&#227;o ventricular do enxerto em posi&#231;&#227;o heterot&#243;pica nesse paciente permaneceu sempre normal, n&#227;o tendo havido rejei&#231;&#245;es significativas aos exames n&#227;o invasivos de mapeamento mioc&#225;rdico com G&#225;lio e ecocardiograma</p>
    <p>O 4&#186; paciente, de forma muito semelhante, apresentou tamb&#233;m progressiva piora funcional do ventr&#237;culo esquerdo nativo e recebeu anticoagulantes orais desde o in&#237;cio do p&#243;s-operat&#243;rio. Da mesma maneira, houve o surgimento da insufici&#234;ncia valvar a&#243;rtica do cora&#231;&#227;o nativo, o que o obrigou tamb&#233;m a uma cirurgia para a corre&#231;&#227;o desse defeito. Quando foi realizado o explante do cora&#231;&#227;o nativo, o paciente infelizmente teve grave quadro de acidente vascular cerebral, possivelmente tromboemb&#243;lico, vindo a falecer por complica&#231;&#245;es infecciosas na unidade de terapia intensiva, com uma sobrevida total de sete anos e quatro meses da cirurgia de transplante.</p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>Ao analisarmos nossos resultados com o transplante ortot&#243;pico, notamos que a hiper-resist&#234;ncia pulmonar foi uma importante causa, direta ou indireta, de mortalidade hospitalar. Isso est&#225; de acordo com a experi&#234;ncia da <italic>Stanford University,</italic> que relata mortalidade de 42% nos primeiros tr&#234;s meses, quando a RVP dos receptores era superior a 2,5 UW, apesar do uso de nitroprussiato de s&#243;dio <italic>(Nipride<sup>&#174;</sup>);</italic> e mortalidade de 25% para aqueles cuja RVP foi reduzida a menos de 2,5 UW com <italic>Nipride<sup>&#174;</sup></italic>, mas &#224;s custas de hipotens&#227;o sist&#234;mica<sup>10</sup>.</p>
    <p>As indica&#231;&#245;es de TxHet ainda apresentam controv&#233;rsias, mas os pacientes de RVP entre 4,5 e 7 UW se beneficiam com essa t&#233;cnica, de acordo com a maioria dos centros de transplante<sup>10,11</sup>. Entretanto, nos casos de RVP de 7 ou mais unidades fixas, o TxHet cederia lugar para o transplante cardiopulmonar, porque, al&#233;m do risco cir&#250;rgico ser mais alto, esse n&#237;vel de RVP estaria associado com altera&#231;&#245;es anat&#244;micas irrevers&#237;veis e, provavelmente, progressivas da vasculatura pulmonar<sup>1</sup>. Nesse &#250;ltimo grupo, &#233; poss&#237;vel tamb&#233;m a utiliza&#231;&#227;o de transplante card&#237;aco e pulmonar unilateral em bloco, com perspectiva de revers&#227;o das altera&#231;&#245;es anat&#244;micas e funcionais da vasculatura pulmonar, devido &#224; queda imediata da press&#227;o pulmonar e, portanto, do est&#237;mulo para rea&#231;&#227;o vascular pulmonar<sup>12</sup>.</p>
    <p>Um crit&#233;rio mais simples, pr&#225;tico e acurado foi proposto pelo grupo de Pittsburg<sup>13</sup> e se baseia no gradiente transpulmonar (GTp), que &#233; a diferen&#231;a entre a press&#227;o m&#233;dia da art&#233;ria pulmonar e a press&#227;o m&#233;dia capilar pulmonar. Esse estudo demonstrou que pacientes com GTp superior a 15 mmHg apresentam maior mortalidade do que os GTp entre 10 a 15 mmHg, e mortalidade ainda menor quando esse gradiente era inferior a 10 mmHg. Por outro lado, esse estudo n&#227;o define qual o limite m&#225;ximo do gradiente em que o transplante cardiopulmonar se faz necess&#225;rio.</p>
    <p>Nem sempre &#233; f&#225;cil trabalhar baseado em dados hemodin&#226;micos como proposto pela maioria dos autores, principalmente em nosso meio, no qual existe uma grande demora entre o estudo hemodin&#226;mico pr&#233;-operat&#243;rio e o dia da realiza&#231;&#227;o do transplante, o que implica, muitas vezes, na progress&#227;o da doen&#231;a vascular pulmonar. Por isso, temos usado, como rotina, a monitoriza&#231;&#227;o hemodin&#226;mica com drogas vasodilatadoras no dia da realiza&#231;&#227;o do transplante, seja na UTI ou no centro cir&#250;rgico (antes da indu&#231;&#227;o anest&#233;sica), com car&#225;ter de Swan-Ganz, enquanto aguardamos a chegada do doador. Isso pode surpreender (<xref ref-type="table" rid="t01">tab. 1</xref>), onde o 2&#186; paciente apresentava 1 UW maior que a medida do pr&#233;-operat&#243;rio inicial. Essa avalia&#231;&#227;o permite que empreguemos preventivamente, nos casos de RVP mais elevada, drogas vasodilatadoras pulmonares, inclusive inalat&#243;rias e, ap&#243;s a alta de UTI, por via oral.</p>
    <p>No 1&#186; paciente, notamos que a RVP encontrava-se um pouco inferior a 5 UW, por&#233;m se observamos o GTp, ele era superior a 10. A grave evolu&#231;&#227;o cl&#237;nica desse paciente nos &#250;ltimos tr&#234;s meses de espera, teve a indica&#231;&#227;o do TxHet refor&#231;ada pelo encontro de um doador de tamanho n&#227;o adequados (peso 15% inferior).</p>
    <p>Quanto &#224; nova t&#233;cnica, que foi utilizada no 3&#186; paciente e que evita o uso de enxerto de <italic>Dacron</italic> entre as art&#233;rias pulmonares, ela representa a primeira inova&#231;&#227;o importante nos &#250;ltimos 20 anos. Tem as vantagens de prevenir as complica&#231;&#245;es teoricamente poss&#237;veis com esse enxerto artificial (infec&#231;&#227;o, trombose, embolias pulmonares e obstru&#231;&#227;o por <italic>panus</italic> fibroso), e ainda facilita a bi&#243;psia endomioc&#225;rdica, porque a anastomose das cavas superiores conduz a pin&#231;a de bi&#243;psia facilmente ao VD do cora&#231;&#227;o transplantado<sup>5</sup>.</p>
    <p>Quanto aos resultados tardios, os TxHet que apresentam sobrevida inferior ao transplante ortot&#243;pico (sobrevida actuarial de um ano de 61,4% e de dois anos de 56%), por&#233;m, essa compara&#231;&#227;o &#233; valida apenas como fonte de informa&#231;&#227;o, uma vez que os pacientes submetidos ao TxHet apresentam caracter&#237;sticas cl&#237;nicas distintas dos submetidos ao transplante card&#237;aco ortot&#243;pico<sup>14</sup>.</p>
    <p>Nessa pequena experi&#234;ncia, foi poss&#237;vel notar que pacientes com miocardiopatia global, envolvendo tamb&#233;m o VD, como nosso 2&#186; paciente, t&#234;m risco maior durante a cirurgia, porque o VD doente do receptor teria que manter a circula&#231;&#227;o pulmonar depois do pin&#231;amento a&#243;rtico, geralmente longo, durante o transplante. Al&#233;m desse risco imediato maior, h&#225; o problema da progress&#227;o da miocardiopatia, que tornou a presen&#231;a desse cora&#231;&#227;o desvantajoso pelas potenciais complica&#231;&#245;es. Entretanto, pacientes que tenham miocardiopatias isqu&#234;micas restritas ao VE, com o VD apenas hipertr&#243;fico, como ocorreu no 1&#186;, 3&#186; e 4&#186; pacientes de nossa experi&#234;ncia, s&#227;o candidatos ideais, porque ter&#227;o melhor desempenho inicial com o VD cumprindo bem o seu papel de vencer a RVP elevada.</p>
    <p>No entanto, o seguimento de longo prazo demonstrou, no 3&#186; e 4&#186; pacientes, as complica&#231;&#245;es j&#225; referidas em literatura<sup>15,16</sup>, fundamentalmente: progressiva deteriora&#231;&#227;o da fun&#231;&#227;o ventricular esquerda e insufici&#234;ncia a&#243;rtica por ectasia &#226;nulo-valvar grave no cora&#231;&#227;o nativo. Esta &#250;ltima complica&#231;&#227;o demandou cirurgia corretiva no 3&#186; paciente h&#225; seis anos, o que possibilitou melhor compensa&#231;&#227;o cl&#237;nica, com a exclus&#227;o do cora&#231;&#227;o nativo da circula&#231;&#227;o, que foi mantida satisfatoriamente pelo cora&#231;&#227;o implantado, estando o paciente em boas condi&#231;&#245;es cl&#237;nicas, 15 anos ap&#243;s a cirurgia. No 4&#186; paciente, a tentativa durante essa cirurgia de corre&#231;&#227;o da insufici&#234;ncia valvar a&#243;rtica de explante total do cora&#231;&#227;o nativo, foi complicada por epis&#243;dio de acidente vascular cerebral grave, que evoluiu para &#243;bito no per&#237;odo hospitalar.</p>
    <p>As causas da disfun&#231;&#227;o ventricular progressiva no cora&#231;&#227;o nativo poderiam ser resumidas em: progress&#227;o da doen&#231;a mioc&#225;rdica, por arritmias e progress&#227;o da doen&#231;a coronariana no cora&#231;&#227;o nativo; eleva&#231;&#227;o da p&#243;s-carga em fun&#231;&#227;o do d&#234;s-sincronismo do cora&#231;&#227;o implantado com o nativo, podendo levar &#224; ocorr&#234;ncia de batimentos simult&#226;neos e determinando importante eleva&#231;&#227;o da imped&#226;ncia durante a s&#237;stole do cora&#231;&#227;o doente; e dilata&#231;&#227;o anulo-valvar a&#243;rtica pelos mecanismos supra mencionados, determinando insufici&#234;ncia a&#243;rtica progressiva<sup>9</sup>.</p>
    <p>Cowell e cols.<sup>17</sup> e Morris-Thurgood e cols.<sup>18</sup> demonstraram que a sincronia atrav&#233;s de marcapasso dos batimentos entre ambos cora&#231;&#245;es, utilizando o principio cl&#225;ssico do bal&#227;o intra-a&#243;rtico, ou seja, a contra&#231;&#227;o do cora&#231;&#227;o nativo comandando atrav&#233;s de sua frequ&#234;ncia atrial a contra&#231;&#227;o atrial e ventricular do cora&#231;&#227;o implantado, ap&#243;s o fechamento da valva a&#243;rtica do cora&#231;&#227;o nativo, poderia impedir as complica&#231;&#245;es derivadas da maior imped&#226;ncia &#224; eje&#231;&#227;o ventricular do cora&#231;&#227;o nativo. Em decorr&#234;ncia, nesse cen&#225;rio, seria de se esperar a melhor preserva&#231;&#227;o funcional do ventr&#237;culo esquerdo do cora&#231;&#227;o nativo e talvez a preven&#231;&#227;o das disfun&#231;&#245;es valvares desse &#243;rg&#227;o.</p>
    <p>Em conclus&#227;o, a presente experi&#234;ncia com o transplante card&#237;aco heterot&#243;pico foi ilustrativa, pois apesar de uma sobreviv&#234;ncia tardia de 15 anos, com o paciente em boas condi&#231;&#245;es, um procedimento cir&#250;rgico para exclus&#227;o funcional do cora&#231;&#227;o nativo foi necess&#225;rio. Os outros pacientes faleceram, um no per&#237;odo hospitalar, outro dois anos ap&#243;s a cirurgia, e o remanescente sete anos ap&#243;s a cirurgia. Entendemos, entretanto, que a disfun&#231;&#227;o ventricular progressiva do cora&#231;&#227;o nativo, bem como, a ectasia anulo-a&#243;rtica deste e a insufici&#234;ncia a&#243;rtica decorrente, poderiam ser postergadas com o emprego de sincroniza&#231;&#227;o permanente atrav&#233;s de marcapasso, que n&#227;o foi utilizado na &#233;poca em nossos pacientes. Com isso, esse procedimento poderia comparar-se favoravelmente, por exemplo, ao transplante cardio-pulmonar, outra op&#231;&#227;o para o tratamento de pacientes com RVP elevada, em que sobreviv&#234;ncias de 15 anos s&#227;o peculiarmente raras<sup>19-20</sup>.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
    <p>
      <fn id="back" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p> Jose Henrique Andrade Vila </p>
        <p> Rua Gaivota, 222/81, Indian&#243;polis </p>
        <p> 0422-030, S&#227;o Paulo, SP - Brasil </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="jhavila@cardiol.br">jhavila@cardiol.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 22/08/08; revisado recebido em 31/10/08; aceito em 11/11/08.</p>
  </body>
  <back>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <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">Experience with heterotopic heart transplantation in patients with elevated pulmonary vascular resistance: late follow-up</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Along the past few years the number of papers on heterotopic cardiac transplant has been very scarce in the medical literature, including at the international level; this is particularly true in reference to the long term follow-up of these patients and the reason which led to the presentation of our report. OBJECTIVE: To report the initial clinical experience and late evolution of 4 patients undergoing heterotopic heart transplantation, indications for this procedure and its major complications. METHODS: The surgeries were performed between 1992 and 2001, and all had as indication for heterotopic transplantation the PVR, which ranged from 4.8 WU to 6.5WU, with a transpulmonary gradient above 15mmHg. In the 3rd patient, a direct anastomosis between the pulmonary arteries was performed without the use of a prostetic tube, and a mitral valvuloplasty and a LV aneurysmectomy were performed in the native heart. The immediate immunosuppressive regimens were double, with cyclosporine and azathioprine in the first 3 patients, and cyclosporine and mycophenolate mofetil in the 4th patient. RESULTS: One immediate death occurred from graft failure, one death occurred after 2 &#189; years, from endocarditis in an intraventricular thrombus in the native heart, and a third death occurred 6 years after transplantation, from post-operative complications of the aortic valve surgery in the native heart. The remaining patient is well, 15 years after the transplantation. This patient is in functional class II (NYHA), 6 years after a surgical occlusion of the native heart aortic valve. CONCLUSION: Heterotopic heart transplantation results are inferior to those of orthotopic heart transplantation because they present higher RVP. The intraventricular thrombi, in the native heart, which require prolonged anticoagulation, and aortic valve complications, also in the native heart, may require surgical treatment. However, a patient's 15-year survival has demonstrated a long-term effectiveness of this option for selected patients.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>heart transplantation</kwd>
        <kwd>hypertension</kwd>
        <kwd>pulmonary</kwd>
        <kwd>follow-up studies</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>
        <fn id="top-body2">
          <label>
            <bold>Experience with heterotopic heart transplantation in patients with elevated pulmonary vascular resistance. Late follow-up</bold>
          </label>
          <p>
            <bold>Jose Henrique Andrade Vila; Jos&#233; Pedro da Silva; Luciana da Fonseca; Jos&#233; Francisco Baumgratz; Am&#233;rico Tangari Jr; Weverton Ferreira Leite; Claudia Jesus Guilhen; Egas Armelin</bold>
          </p>
        </fn>
      </p>
      <p>Hospital Benefic&#234;ncia Portuguesa de S&#227;o Paulo, S&#227;o Paulo, SP - Brazil</p>
      <p>Mailing address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>BACKGROUND: </bold> Along the past few years the number of papers on heterotopic cardiac transplant has been very scarce in the medical literature, including at the international level; this is particularly true in reference to the long term follow-up of these patients and the reason which led to the presentation of our report.</p>
      <p><bold>OBJECTIVE:</bold> To report the initial clinical experience and late evolution of 4 patients undergoing heterotopic heart transplantation, indications for this procedure and its major complications.</p>
      <p><bold>METHODS:</bold> The surgeries were performed between 1992 and 2001, and all had as indication for heterotopic transplantation the PVR, which ranged from 4.8 WU to 6.5WU, with a transpulmonary gradient above 15mmHg. In the 3rd patient, a direct anastomosis between the pulmonary arteries was performed without the use of a prostetic tube, and a mitral valvuloplasty and a LV aneurysmectomy were performed in the native heart.</p>
      <p> The immediate immunosuppressive regimens were double, with cyclosporine and azathioprine in the first 3 patients, and cyclosporine and mycophenolate mofetil in the 4th patient.</p>
      <p><bold>RESULTS:</bold> One immediate death occurred from graft failure, one death occurred after 2 &#189; years, from endocarditis in an intraventricular thrombus in the native heart, and a third death occurred 6 years after transplantation, from post-operative complications of the aortic valve surgery in the native heart. The remaining patient is well, 15 years after the transplantation. This patient is in functional class II (NYHA), 6 years after a surgical occlusion of the native heart aortic valve.</p>
      <p><bold>CONCLUSION:</bold> Heterotopic heart transplantation results are inferior to those of orthotopic heart transplantation because they present higher RVP. The intraventricular thrombi, in the native heart, which require prolonged anticoagulation, and aortic valve complications, also in the native heart, may require surgical treatment. However, a patient's 15-year survival has demonstrated a long-term effectiveness of this option for selected patients.</p>
      <p><bold>Key Words:</bold> Heart transplantation; hypertension, pulmonary / complications; follow-up studies.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>The high pulmonary vascular resistance (PVR) which occurs in the final stage of cardiomyopathies has been a major obstacle to the performance of orthotopic heart transplantation, due to the risk of early failure of the right ventricle (RV) of the transplanted organ, limiting its use in patients with PVR below 5 Wood units (WU)<sup>1,2</sup>, or 4 Wood units, currently in preference.</p>
      <p>The clinical application of the heterotopic heart transplantation (HetTrx) by Barnard, in 1974, increased the possibility of performing cardiac transplantation in patients with a PVR above 4 WU<sup>3,4</sup>, and it was widely used by the South African Group, especially with the additional argument that in case of graft failure, in a scenario when cyclosporine was not yet available, the patients would survive thanks to the native organ. Among other indications of this procedure, we can mention its use in potentially reversible ventricular dysfunctions, and in cases of size disproportion between donor and recipient. This last condition is a possibility, particularly in patients with ischemic cardiomyopathy, even with the possibility of conventional surgical treatment, when the heterotopic graft could be implanted for greater security in the early evolution of these patients<sup>3-5</sup>.</p>
      <p>The aim of this article is to report the experience of four procedures performed in our department, emphasizing the details of the procedures, a modification in the original operative technique, and the later follow-up of the patients, up to 15 years.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>Between August 1988 and December 2007, 222 heart transplants were performed in our group in the Hospital Benefic&#234;ncia Portuguesa of S&#227;o Paulo, including 6 re-transplants. In this experiment, in 4 patients, we opted for the heterotopic transplantation, according to the marked increase of PVR. The clinical characteristics of these 4 patients are described in <xref ref-type="table" rid="t1-body2">Table 1</xref>, which emphasizes the significantly high levels of PVR.</p>
      <table-wrap id="t1-body2">
        <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gt01-en.jpg"/></table-wrap>
      <p>From a clinical perspective, the patients had severe ischemic cardiomyopathy. All of them had extensive myocardial infarction, and their coronary arteries were not suitable to surgical treatment. They were in the ICU, receiving inotropic and vasodilator drugs, and were on the waiting list for heart transplantation. The first patient had undergone a previous myocardial revascularization surgery, with occlusion of the grafts, and the last patient had undergone coronary angioplasty on two occasions prior to the transplantion. In the latter patient, who underwent surgery in November 2001, in addition to a graft implant in a heterotopic position, the correction of a left ventricle aneurysm and a valvuloplasty of the mitral valve were performed. The other two patients were also in functional class IV (NYHA), and they had been frequently admitted to the ICU to receive vasodilator and inotropic drugs intravenously.</p>
      <p>The surgical procedure was carried out with distant donor hearts in patients 1, 3 and 4, and with the heart from a donor in the adjacent room in patient 2. The donor organs were removed by sectioning the aorta above the brachiocephalic trunk and the pulmonary artery (PA) in the proximal part of the pulmonary branches. For myocardial protection, we used the St. Thomas cardioplegic solution, with antegrade infusion via native aortic valve in the heart of the receiver, except in the last case, in which we used retrograde coronary sinus infusion. In the donor heart we also used the antegrade cardioplegia administered via aortic infusion. We associated topical hypothermia by the immersion of the organs in cold Ringer's solution, and by packaging them for local or distant transportation. In the heart of the receiver, myocardial protection was performed with a cold blood cardioplegic solution.</p>
      <p>The implantation surgical techniques were similar in the first two cases - the pulmonary artery of the donor heart was connected to the trunk of the native PA, using a bovine pericardium graft to facilitate the anastomosis. In patients 3 and 4 the original technique was used, with a direct anastomosis of the donor's PA to the right branch of the receiver's PA, without any interposition graft, because the distance between them was much shorter<sup>5</sup>. To make this procedure feasible, the superior vena cava of the receiver was transected near the right atrium (RA), its lower end was sutured and its upper end was mobilized, fully exposing the right branch of the PA. To make this possible, we needed a wide dissection of the donor's pulmonary artery and its left branch, when the organ was removed. After the anastomoses of the left atria and the PAs were performed, the upper end of the superior vena cava of the receiver was anastomosed to the superior vena cava of the donor. Another right atrial connection was made in the lower portion of the receiver RA, near the interatrial septum, allowing the venous return of the receiver to reach the donor RA. The long ascending aorta of the donor was anastomosed as far as possible from the ascending aorta of the recipient, so as to facilitate the access to the PA in case of bleeding.</p>
      <p>As an external pacemaker, temporary electrodes were placed in the RA of both hearts and in the RV of the transplanted heart, enabling a synchronized cardiac pacing through a sequential pacemaker, connecting the atrial poles to the atrial electrodes of the native heart (of higher frequency) and the atrial electrodes of the transplanted heart to the ventricular poles of the pacemaker. Thus, the pacemaker feels the P-wave of the native heart and, after an adjustable pause, stimulates the atrium of the transplanted heart, producing synchronized beats of both hearts, in the same logical sequence of the intra-aortic balloon which is important in optimizing the cardiac output in the first postoperative days<sup>6-8</sup>. After discharge from the ICU and the removal of epicardial wires of the pacemaker, there was no more electrical synchronization between the two hearts; however, a spontaneous tendency to an equalization of the heart beats occurred, which could be attributed to the lower adrenergic stimulation provided by an improved cardiac output, due to the implanted heart. (<xref ref-type="fig" rid="en_19f01-body2">Figure 1</xref>)</p>
      <p content-type="asset">
        <fig id="en_19f01-body2">
          <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gf01-en.jpg"/></fig>
      </p>
      <p>Initialy the immunosuppressive regimen was double, with cyclosporine and azathioprine in the first 3 patients, and cyclosporine and mycophenolate mofetil in the 4th patient. We conducted weekly biopsy controls in the first month, then fortnightly over the following 2 months, and after that, we conducted myocardial mapping with Gallium and echocardiogram to control rejection. The first patient had two episodes of significant myocardial rejection, which was responsible for the worsening of the myocardial function. After the first episode, we started triple immunosuppression with prednisone 0.5 mg/kg/d, which was gradually reduced to 0.1 mg/kg/d after an intravenous pulse for three days.</p>
      <p>The third and fourth patients had a single grade II rejection episode each, which was controlled by an oral regimen of prednisone for two months. We also maintained oral anticoagulant in patients 3 and 4, who had late survival, and diuretics, enzyme antagonists and, then, the beta-blocker carvedilol, in order to prevent or delay the progressive myocardial dysfunction of the native heart.</p>
      <p>This practice, however, was not successful; on the contrary, the deterioration of the left ventricular function of the native heart was relentless, and even both patients with late survival showed progressive aortic insufficiency with marked clinical worsening, which required surgical correction, as mentioned in the literature<sup>9</sup>.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>The early and late results of the surgeries are summarized in <xref ref-type="table" rid="t2-body2">Table 2</xref>. Patient 2 died at the hospital, 12 hours after transplantation, from graft and native heart failure.</p>
      <table-wrap id="t2-body2">
        <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gt02-en.jpg"/></table-wrap>
      <p>Patient 1 had good evolution in the first year and then showed progressive heart failure, after two episodes of acute rejection and coronary artery disease in the graft. A retransplantation was performed two years after the transplantation, which resulted in death from low cardiac output and acute sepsis on the seventh postoperative day.</p>
      <p>Initially the 3<sup>rd</sup> patient had an adequate evolution, with good physical capacity-functional class II (NYHA)-practicing sports, such as swimming, regularly. <xref ref-type="fig" rid="en_19f02-body2">Figure 2</xref> shows chest X-rays features, with the conventional surgical technique and the new technique developed by the group<sup>5</sup>. In this patient, who underwent the new surgical technique, the pulmonary angiography showed good anatomical and functional results (<xref ref-type="fig" rid="f3-body2">Figure 3</xref>).</p>
      <p content-type="asset">
        <fig id="en_19f02-body2">
          <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gf02-en.jpg"/></fig>
      </p>
      <fig id="f3-body2">
        <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gf03-en.jpg"/></fig>
      <p>The sequential echocardiographic control showed rapid and progressive decline of the ventricular function of the native heart, with a thrombus formation at the end of the first year, which disappeared with the increase in oral anti-coagulation. After the sixth year of evolution, there was progressive aortic insufficiency due to anuloaortic ectasia, with a deterioration of the clinical conditions, despite the increase in the clinical treatment with enzyme antagonists (captopril), spironolactone, carvedilol and diuretics. We opted for the surgical correction of the aortic valve insufficiency, which was preferred for technical reasons to the native organ explantation, and this resulted in a significant functional improvement of the patient, who returned to functional class II (NYHA). The ventricular function of the graft in heterotopic position in this patient had always been normal, and there was no significant rejections detected by non-invasive tests, such as myocardial mapping with Gallium and echocardiogram.</p>
      <p>The fourth patient, in a very similar manner, also presented a progressive worsening of the left ventricular function of the native heart and received oral anticoagulants from the beginning of the postoperative period. Similarly, aortic valve insufficiency of the native heart occurred, which also required surgery to correct this defect. When the explantation of the native heart was performed, the patient unfortunately had a severe cerebral vascular accident, possibly from thromboembolic origin, and died from infectious complications in the intensive care unit, with a total survival of 7 years and 4 months after the transplant surgery.</p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>In reviewing our results with orthotopic heart transplantation, we observed that the pulmonary hyperresistance was an important direct or indirect cause of hospital mortality. This is in line with the experience of the Stanford University, which reported a mortality rate of 42% in the first three months, when the receivers' PVR was more than 2.5 WU, despite the use of sodium nitroprusside (Nipride R), and a mortality rate of 25 % for those whose PVR was reduced to less than 2.5 WU with Nipride R, though at the expense of systemic hypotension<sup>10</sup>.</p>
      <p>The indications for HetTrx are still controversial, but the patients with PVR between 4.5 and 7 WU benefit from this technique, according to the majority of transplant centers<sup>10,11</sup>. However, in cases of PVR of 7 or more fixed units, a cardiopulmonary transplantation is preferred to the HetTrx because, besides the higher surgical risk, this level of PVR is associated with irreversible and probably progressive anatomical changes in the pulmonary vasculature<sup>1</sup>. In the latter group, a unilateral heart and lung block transplantation is also possible, with the possibility of reverting the anatomical and functional changes in the pulmonary vasculature due to the immediate reduction in the pulmonary pressure and the consequent stimulus for pulmonary vascular reaction<sup>12</sup>.</p>
      <p>A more simple, practical and accurate criterium was proposed by the group of Pittsburg<sup>13</sup>, based on the transpulmonary gradient (TPG), which is the difference between the mean pulmonary artery pressure and the mean pulmonary capillary pressure. This study demonstrated that patients with TPG greater than 15 mmHg had higher mortality rates than those with TPG from 10 to 15; the mortality was even lower when the gradient was less than 10 mmHg. Furthermore, this study does not define what is the gradient that renders the cardiopulmonary transplant necessary.</p>
      <p>It is not always easy to work based on hemodynamic data as proposed by most authors, especially in Brazil where there is a long delay between the preoperative hemodynamic study and the day when the transplant is performed, which often results in the progression of the vascular lung disease. Therefore, we have routinely used a hemodynamic monitoring with vasodilator drugs on the day of the transplant, in the ICU or in the operating room (before anesthetic induction), using a Swan-Ganz catheter, while we awaited the arrival of the donor. It may be surprising (<xref ref-type="table" rid="t1-body2">Table 1</xref>) to observe that the 2<sup>nd</sup> patient had 1 WU above the initial preoperative measure. This assessment allows us, in cases of higher PVR, to use pulmonary vasodilator drugs preventively, including via inhalation, and orally, after discharge from the ICU.</p>
      <p>In patient 1, we noticed that the PVR was a little less than 5 WU, but the TPG was above 10. The severe clinical evolution of this patient in the last 3 months of waiting stressed the indication for a HetTrx, which was reinforced by the finding of a donor of inappropriate size (weight 15% lower).</p>
      <p>As to the new technique, which was used in 3 patients and avoids the use of the Dacron graft between the pulmonary arteries, it represents the first major innovation in the last 20 years and has the advantages of preventing the theoretically possible complications with the artificial graft (infection, thrombosis, pulmonary embolism and obstruction by fibrous panus), and it also facilitates the endomyocardial biopsy, because the anastomosis of the cava superior easily leads the biopsy forceps to the RV of the transplanted heart<sup>5</sup>.</p>
      <p>As to the late results, the HetTrx showed lower survival than the orthotopic transplantation (one-year actuarial survival of 61.4%, and 56% for 2 years), but this comparison is valid only as an information source, since the HetTrx patients have different clinical characteristics in comparison to the orthotopic heart transplantation patients<sup>14</sup>.</p>
      <p>In this small experiment, we observed that the patients with global cardiomyopathy, involving also the RV, as our patient 2, suffer higher risk during surgery, because the receiver's diseased RV would have to maintain the pulmonary circulation after the aortic clamping, which is usually long, during the transplantation. Beyond this more immediate risk, there is the problem of progression of the cardiomyopathy, which made the presence of this heart disadvantageous due to potential complications. However, the patients who have ischemic cardiomyopathies that are restricted to the LV, with only RV hypertrophy, as in cases 1, 3 and 4 of our experience, are ideal candidates, because they will have a better initial performance, and their RV will perform well its role of overcoming the high PVR.</p>
      <p>However, in patients 3 and 4, the long-term follow up demonstrated the complications mentioned in the literature<sup>15,16</sup>, mainly progressive deterioration of the left ventricular function and aortic insufficiency due to severe anuloaortic ectasia, in the native heart. This latter complication required corrective surgery in the third patient 6 years ago, resulting in better clinical conditions, with the exclusion of the native heart from circulation, which was maintained satisfactorily by the implanted heart, and the patient was in good clinical conditions, 15 years after surgery. In the fourth patient, during the surgical correction of the aortic valve insufficiency, an attempt of total explantation of the native heart was complicated by an episode of severe stroke, and the patient died at the hospital.</p>
      <p>The causes of progressive ventricular dysfunction in the native heart could be summarized as follows: 1) Progression of myocardial disease, due to arrhythmias and progression of coronary disease in the native heart; 2) elevation of the post-load due to dyssynchrony of the implanted heart with the native heart, which may lead to the simultaneous occurrence of heart beats, determining an important elevation of the impedance during the systole of the diseased heart; 3) anullo-aortic dilatation by the mechanisms mentioned above, determining progressive aortic insufficiency<sup>9</sup>.</p>
      <p>Cowell et al<sup>17</sup> and Morris-Thurgood et al<sup>18</sup> demonstrated that the synchronization of the beats of both hearts by pacemaker, using the classical principle of the intra aortic balloon, or else, the contraction of the native heart by its atrial frequency, leading the atrial and ventricular contraction of the implanted heart, after the closing of the aortic valve of the native heart, could prevent the complications arising from the increased impedance to the ventricular output of the native heart. As a result, this could lead to a better functional preservation of the left ventricle of the native heart and perhaps the prevention of valve dysfunctions of the organ.</p>
      <p>In conclusion, this experience with heterotopic heart transplantation was illustrative, because despite a late survival of 15 years, with the patient in good condition, even in this case, a surgical procedure for functional exclusion of the native heart was necessary. The other patients died, one at hospital, other two years after surgery, and the remaining 7 years after surgery. We believe, however, that the progressive ventricular dysfunction in the native heart, and the annulo-aortic ectasia and its consequent aortic insufficiency could be postponed by the employment of permanent synchronization by pacemaker, which was not used at the time in our patients. With it, this procedure could compare itself favorably with, for instance, cardio-pulmonary transplantation, another option for the treatment of patients with high PVR, in which a survival of 15 years is peculiarly rare<sup>19-20</sup>.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This study is not associated with any post-graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
  <sub-article article-type="translation" id="TRes" xml:lang="es">
    <front-stub>
      <article-categories/>
      <title-group>
        <article-title xml:lang="es">Experiencia con trasplante card&#237;aco heterot&#243;pico en pacientes con resistencia pulmonar elevada: seguimiento tard&#237;o</article-title>
      </title-group>
      <abstract xml:lang="es">
        <p>FUNDAMENTO: En los &#250;ltimos a&#241;os el n&#250;mero de art&#237;culos sobre trasplante card&#237;aco heterot&#243;pico y, en particular, del seguimiento a largo plazo de estos pacientes, ha sido escaso en la literatura, inclusive internacional, lo que llev&#243; al presente relato. OBJETIVO: Relatar la experiencia cl&#237;nica inicial y la evoluci&#243;n tard&#237;a de cuatro pacientes sometidos a trasplante card&#237;aco heterot&#243;pico, su indicaci&#243;n y principales complicaciones. M&#201;TODOS: Las cirug&#237;as se realizaron entre 1992 y 2001, y la indicaci&#243;n de trasplante heterot&#243;pico, en todas, fue mediante RVP, variable de 4,8 UW; a 6.5 UW, con gradiente transpulmonar superior a 15 mmHg. En el tercer paciente, se realiz&#243; una anastomosis directa entre las arterias pulmonares sin empleo de tubo prost&#233;tico, y, en el coraz&#243;n nativo, se realiz&#243; una valvuloplastia mitral y aneurismectom&#237;a de VI. El esquema inmunosupresor inmediato fue doble, con ciclosporina y azatioprina en los tres primeros pacientes y ciclosporina y micofenolato mofetil en el cuarto paciente. RESULTADOS: Un &#243;bito inmediato por falla del injerto, un &#243;bito luego de dos a&#241;os y medio por endocarditis en trombo intraventricular en el coraz&#243;n nativo, y un tercer &#243;bito seis a&#241;os despu&#233;s del trasplante, por complicaciones postoperatorias de una cirug&#237;a en la v&#225;lvula a&#243;rtica del coraz&#243;n nativo. El restante, 15 a&#241;os despu&#233;s del trasplante, se encuentra bien, en clase funcional II (NYHA), seis a&#241;os despu&#233;s de una oclusi&#243;n quir&#250;rgica de la v&#225;lvula a&#243;rtica del coraz&#243;n nativo. CONCLUSI&#211;N: El trasplante card&#237;aco heterot&#243;pico es un procedimiento con resultado inferior al trasplante card&#237;aco ortot&#243;pico, por presentar mayor RVP. Los trombos intraventriculares en el coraz&#243;n nativo, que exige anticoagulaci&#243;n prolongada, as&#237; como las complicaciones de v&#225;lvula a&#243;rtica, tambi&#233;n en el coraz&#243;n nativo, pueden exigir tratamiento quir&#250;rgico. Sin embargo, en un paciente, la sobrevida de 15 a&#241;os mostr&#243; la eficacia a largo plazo de este tipo de alternativa, para pacientes seleccionados.</p>
      </abstract>
      <kwd-group xml:lang="es">
        <kwd>Trasplante card&#237;aco</kwd>
        <kwd>hipertensi&#243;n pulmonar</kwd>
        <kwd>seguimiento</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ART&#205;CULO ORIGINAL</bold>
      </p>
      <p>
        <fn id="top-body3">
          <label>
            <bold>Experiencia con trasplante card&#237;aco heterot&#243;pico en pacientes con resistencia pulmonar elevada. Seguimiento tard&#237;o</bold>
          </label>
          <p>
            <bold>Jose Henrique Andrade Vila; Jos&#233; Pedro da Silva; Luciana da Fonseca; Jos&#233; Francisco Baumgratz; Am&#233;rico Tangari Jr; Weverton Ferreira Leite; Claudia Jesus Guilhen; Egas Armelin</bold>
          </p>
        </fn>
      </p>
      <p>Hospital Benefic&#234;ncia Portuguesa de S&#227;o Paulo, S&#227;o Paulo, SP - Brasil</p>
      <p>Correspondencia</p>
      <p>
        <bold>RESUMEN</bold>
      </p>
      <p><bold>FUNDAMENTO: </bold> En los &#250;ltimos a&#241;os el n&#250;mero de art&#237;culos sobre trasplante card&#237;aco heterot&#243;pico y, en particular, del seguimiento a largo plazo de estos pacientes, ha sido escaso en la literatura, inclusive internacional, lo que llev&#243; al presente relato.</p>
      <p><bold>OBJETIVO: </bold> Relatar la experiencia cl&#237;nica inicial y la evoluci&#243;n tard&#237;a de cuatro pacientes sometidos a trasplante card&#237;aco heterot&#243;pico, su indicaci&#243;n y principales complicaciones.</p>
      <p><bold>M&#201;TODOS: </bold> Las cirug&#237;as se realizaron entre 1992 y 2001, y la indicaci&#243;n de trasplante heterot&#243;pico, en todas, fue mediante RVP, variable de 4,8 UW; a 6.5 UW, con gradiente transpulmonar superior a 15 mmHg. En el tercer paciente, se realiz&#243; una anastomosis directa entre las arterias pulmonares sin empleo de tubo prost&#233;tico, y, en el coraz&#243;n nativo, se realiz&#243; una valvuloplastia mitral y aneurismectom&#237;a de VI. El esquema inmunosupresor inmediato fue doble, con ciclosporina y azatioprina en los tres primeros pacientes y ciclosporina y micofenolato mofetil en el cuarto paciente.</p>
      <p><bold>RESULTADOS: </bold> Un &#243;bito inmediato por falla del injerto, un &#243;bito luego de dos a&#241;os y medio por endocarditis en trombo intraventricular en el coraz&#243;n nativo, y un tercer &#243;bito seis a&#241;os despu&#233;s del trasplante, por complicaciones postoperatorias de una cirug&#237;a en la v&#225;lvula a&#243;rtica del coraz&#243;n nativo. El restante, 15 a&#241;os despu&#233;s del trasplante, se encuentra bien, en clase funcional II (NYHA), seis a&#241;os despu&#233;s de una oclusi&#243;n quir&#250;rgica de la v&#225;lvula a&#243;rtica del coraz&#243;n nativo.</p>
      <p><bold>CONCLUSI&#211;N: </bold> El trasplante card&#237;aco heterot&#243;pico es un procedimiento con resultado inferior al trasplante card&#237;aco ortot&#243;pico, por presentar mayor RVP. Los trombos intraventriculares en el coraz&#243;n nativo, que exige anticoagulaci&#243;n prolongada, as&#237; como las complicaciones de v&#225;lvula a&#243;rtica, tambi&#233;n en el coraz&#243;n nativo, pueden exigir tratamiento quir&#250;rgico. Sin embargo, en un paciente, la sobrevida de 15 a&#241;os mostr&#243; la eficacia a largo plazo de este tipo de alternativa, para pacientes seleccionados.</p>
      <p><bold>Palabras clave: </bold> Trasplante card&#237;aco, hipertensi&#243;n pulmonar/complicaciones, seguimiento.</p>
      <p>
        <bold>Introducci&#243;n</bold>
      </p>
      <p>La resistencia vascular pulmonar (RVP) elevada, que aparece en la fase final de las miocardiopat&#237;as, ha sido uno de los mayores obst&#225;culos para la realizaci&#243;n del trasplante card&#237;aco ortot&#243;pico. Esto ocurre por el riesgo de falla precoz del ventr&#237;culo derecho (VD) del &#243;rgano trasplantado, limitando su empleo para pacientes con RVP inferior a 5 unidades Wood (UW)<sup>1,2</sup>, o preferencialmente 4 unidades Wood en nuestros d&#237;as.</p>
      <p>La aplicaci&#243;n cl&#237;nica del trasplante card&#237;aco heterot&#243;pico (TxHet), por Barnard en 1974, ampli&#243; la posibilidad de los trasplantes card&#237;acos para pacientes con RVP superior a 4 UW<sup>3,4</sup>, y fue muy utilizada por el grupo de Sud&#225;frica, principalmente con el argumento adicional de que, en caso de falla del injerto, en aquel escenario sin la disponibilidad de la ciclosporina, el paciente sobrevivir&#237;a gracias al &#243;rgano nativo. Entre otras indicaciones de este procedimiento, podemos citar su utilizaci&#243;n en las disfunciones ventriculares, potencialmente reversibles, y en casos de desproporci&#243;n de tama&#241;o entre donante y receptor. Esta &#250;ltima condici&#243;n es particularmente posible en pacientes portadores de miocardiopat&#237;a isqu&#233;mica, a&#250;n con posibilidad de tratamiento quir&#250;rgico convencional, cuando el injerto heterot&#243;pico podr&#237;a ser implantado para mayor seguridad en la evoluci&#243;n precoz de estos pacientes<sup>3-5</sup>.</p>
      <p>El objetivo de este trabajo es relatar la experiencia con cuatro procedimientos, realizados en nuestro servicio, enfatizando las indicaciones del procedimiento, una modificaci&#243;n original en la t&#233;cnica operatoria, as&#237; como el seguimiento tard&#237;o, de hasta 15 a&#241;os, de los pacientes operados.</p>
      <p>
        <bold>M&#233;todos</bold>
      </p>
      <p>Entre agosto de 1988 y diciembre de 2007, se realizaron 222 trasplantes card&#237;acos en nuestro grupo en el Hospital da Benefic&#234;ncia Portuguesa de S&#227;o Paulo, incluyendo seis retrasplantes. De esa experiencia, en cuatro pacientes se opt&#243; por la posici&#243;n heterot&#243;pica, en funci&#243;n de la acentuada elevaci&#243;n de los niveles de RVP. Las caracter&#237;sticas cl&#237;nicas de esos cuatro pacientes est&#225;n descritas en la <xref ref-type="table" rid="es_19t01-body3">tabla 1</xref>, que destaca los niveles de RVP significativamente elevados.</p>
      <p content-type="asset">
        <table-wrap id="es_19t01-body3">
          <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gt01-es.jpg"/></table-wrap>
      </p>
      <p>Desde el punto de vista cl&#237;nico, los pacientes presentaban un cuadro grave de miocardiopat&#237;a isqu&#233;mica, todos con extenso infarto de miocardio y arterias coronarias no pasibles de tratamiento quir&#250;rgico. Se encontraban en UCI, recibiendo drogas vasodilatadoras e inotr&#243;picas, en lista de espera de trasplante card&#237;aco. El primer paciente hab&#237;a sido sometido a cirug&#237;a de revascularizaci&#243;n mioc&#225;rdica previa, con obstrucci&#243;n de los injertos empleados, y el &#250;ltimo paciente hab&#237;a sido sometido dos veces a angioplastia coronaria previo al trasplante. En este &#250;ltimo paciente, operado en noviembre de 2001, adem&#225;s del implante del injerto en posici&#243;n heterot&#243;pica, se procedi&#243; a la correcci&#243;n del aneurisma de ventr&#237;culo izquierdo, as&#237; como a la realizaci&#243;n de una valvuloplastia quir&#250;rgica de la v&#225;lvula mitral. Los otros dos pacientes tambi&#233;n se encontraban en clase funcional IV New York Heart Association (NYHA), con frecuentes internaciones en UCI para recibir drogas inotr&#243;picas y vasodilatadoras por v&#237;a endovenosa.</p>
      <p>El procedimiento quir&#250;rgico fue realizado utilizando corazones obtenidos de donantes a distancia en el primero, tercero y cuarto pacientes, y de donante en sala contigua en el segundo paciente. Los &#243;rganos fueron retirados de los donantes, seccionada la aorta por encima del tronco braquiocef&#225;lico y la arteria pulmonar (AP), en el inicio de las ramas pulmonares. Para protecci&#243;n mioc&#225;rdica, se utiliz&#243; soluci&#243;n cardiopl&#233;jica de St. Thomas, con infusi&#243;n anter&#243;grada v&#237;a a&#243;rtica en el coraz&#243;n nativo del receptor, excepto en el &#250;ltimo caso, en que utilizamos la infusi&#243;n retr&#243;grada en el seno coronario. En el coraz&#243;n del donante, tambi&#233;n utilizamos la infusi&#243;n de soluci&#243;n cardiopl&#233;jica anter&#243;grada por v&#237;a a&#243;rtica. Asociamos hipotermia t&#243;pica, a trav&#233;s de la inmersi&#243;n del &#243;rgano en soluci&#243;n helada de Ringer, y lo acondicionamos para transporte local o a distancia. En el coraz&#243;n del receptor, la protecci&#243;n mioc&#225;rdica fue realizada con soluci&#243;n cardiopl&#233;jica sangu&#237;nea helada.</p>
      <p>Las t&#233;cnicas quir&#250;rgicas de implante fueron similares en los dos primeros casos, donde la arteria pulmonar del coraz&#243;n donado fue conectada al tronco de la AP nativa utilizando injerto de pericardio bovino para facilitar esas anastomosis. En el tercero y cuarto pacientes, se utiliz&#243; la t&#233;cnica original con anastomosis directa de la AP del donante a la rama derecha de la AP del receptor, sin interposici&#243;n de injerto alguno, ya que la distancia entre las dos es bastante m&#225;s corta<sup>5</sup>. Ese procedimiento fue posible con la transecci&#243;n de la vena cava superior del receptor, pr&#243;ximo a la aur&#237;cula derecha (AD), siendo suturada su extremidad inferior y movilizada su extremidad superior, exponiendo ampliamente la rama derecha de la AP. Para que esto sea posible, se requiere la amplia disecci&#243;n de la arteria pulmonar y de la rama izquierda de la misma, en el donante, al retirar el &#243;rgano. Despu&#233;s de la anastomosis de las aur&#237;culas izquierdas y de las AP, se realiz&#243; la anastomosis de la extremidad superior de la vena cava superior del receptor a la vena cava superior del donante. Otra conexi&#243;n auricular directa se hizo en la porci&#243;n inferior de la AD del receptor, pr&#243;ximo al septum interauricular, permitiendo que el retorno venoso del receptor pueda alcanzar la AD del donante. La aorta ascendente larga del donante fue anastomosada lo m&#225;s distante posible de la aorta ascendente del receptor, para facilitar el acceso a la AP, en caso de sangrado.</p>
      <p>En las AD de ambos corazones y en el VD del coraz&#243;n trasplantado se colocaron electrodos temporarios para marcapasos externo, posibilitando la estimulaci&#243;n cardiaca sincronizada a trav&#233;s de un marcapasos secuencial, conectando los polos auriculares a los electrodos auriculares del coraz&#243;n nativo (de frecuencia mayor) y los electrodos auriculares del coraz&#243;n trasplantado a los polos ventriculares del marcapasos. De esta forma, el marcapasos siente la onda P del coraz&#243;n nativo y, despu&#233;s de una pausa regulable, estimula la aur&#237;cula del coraz&#243;n trasplantado, obteniendo as&#237; latidos sincronizados de los dos corazones, en la misma l&#243;gica secuencial del bal&#243;n intraa&#243;rtico, lo que es importante para la optimizaci&#243;n del d&#233;bito card&#237;aco en los primeros d&#237;as del posquir&#250;rgico<sup>6-8</sup>. Sin embargo, luego del alta de la UCI, y al retirar los hilos epic&#225;rdicos del marcapasos, dej&#243; de existir la sincronizaci&#243;n el&#233;ctrica entre los dos corazones, apareciendo, no obstante, espont&#225;neamente, una tendencia de ecualizaci&#243;n de las frecuencias card&#237;acas, que podr&#237;a ser atribuida a la menor estimulaci&#243;n adren&#233;rgica propiciada por la mejora del d&#233;bito card&#237;aco, debido principalmente al coraz&#243;n implantado (<xref ref-type="fig" rid="es_19f01-body3">figura 1</xref>).</p>
      <p content-type="asset">
        <fig id="es_19f01-body3">
          <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gf01-es.jpg"/></fig>
      </p>
      <p>El esquema inmunosupresor utilizado inicialmente fue doble, con ciclosporina y azatioprina, en los tres primeros pacientes, y ciclosporina y micofenolato mofetil en el cuarto paciente. Realizamos biopsias de control semanales en el primer mes y quincenales en los dos meses siguientes, luego del mapeo mioc&#225;rdico con Galio y ecocardiograma para control del rechazo. En el primer paciente, tuvimos dos episodios de rechazo mioc&#225;rdico importante, que provocaron un deterioro de la funci&#243;n mioc&#225;rdica, y, tras el primer episodio, pasamos a un esquema triple de inmunosupresi&#243;n, con predinisona 0,5 mg/k/d, que fue reducido gradualmente hasta 0,1 mg/k/d, luego de la pulsoterapia intravenosa durante tres d&#237;as.</p>
      <p>En el tercero y cuarto pacientes, tuvimos un &#250;nico episodio de rechazo grado II, que fue controlado con un esquema de predinisona por v&#237;a oral durante dos meses. Mantuvimos tambi&#233;n el anticoagulante oral en los pacientes tres y cuatro que sobrevivieron tard&#237;amente, as&#237; como los diur&#233;ticos, antagonistas enzim&#225;ticos y, posteriormente, el betabloqueante carvedilol, con el objetivo de prevenir o retardar la disfunci&#243;n mioc&#225;rdica progresiva del coraz&#243;n nativo.</p>
      <p>Esta pr&#225;ctica, sin embargo, no demostr&#243; tener &#233;xito y, por el contrario, el deterioro de la funci&#243;n ventricular izquierda del coraz&#243;n nativo fue inexorable, surgiendo inclusive en ambos pacientes una insuficiencia a&#243;rtica progresiva y un deterioro cl&#237;nico acentuado, que demand&#243; correcci&#243;n quir&#250;rgica, hecho &#233;ste ya referido en la literatura<sup>9</sup>.</p>
      <p>
        <bold>Resultados</bold>
      </p>
      <p>Los resultados precoces y tard&#237;os de las cirug&#237;as est&#225;n sintetizados en la <xref ref-type="table" rid="t2-body3">tabla 2</xref>. Tuvimos un &#243;bito hospitalario, del segundo paciente, 12 horas despu&#233;s del trasplante, por falla del injerto y del coraz&#243;n nativo.</p>
      <table-wrap id="t2-body3">
        <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gt02-es.jpg"/></table-wrap>
      <p>El primer paciente tuvo buena evoluci&#243;n en el primer a&#241;o, y posteriormente desarroll&#243; una insuficiencia cardiaca progresiva tras dos episodios de rechazo cardiaco agudo y coronariopat&#237;a en el injerto. Fue retrasplantado dos a&#241;os despu&#233;s del trasplante, con mala evoluci&#243;n que culmin&#243; en &#243;bito por bajo d&#233;bito card&#237;aco y septicemia aguda en el 7&#186; d&#237;a del postoperatorio.</p>
      <p>El tercer paciente tuvo una evoluci&#243;n inicial adecuada con buena capacidad f&#237;sica, clase funcional II (NYHA), practicando deportes, como nataci&#243;n, regularmente. La <xref ref-type="fig" rid="f2-body3">figura 2</xref> muestra el aspecto de las radiograf&#237;as de t&#243;rax con la t&#233;cnica quir&#250;rgica convencional y con la nueva t&#233;cnica desarrollada por el grupo<sup>5</sup>. La angiograf&#237;a pulmonar en este paciente, que fue sometido a la nueva t&#233;cnica quir&#250;rgica, muestra un buen resultado anat&#243;mico y funcional (<xref ref-type="fig" rid="f3-body3">figura 3</xref>).</p>
      <fig id="f2-body3">
        <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gf02-es.jpg"/></fig>
      <fig id="f3-body3">
        <graphic xlink:href="1678-4170-abc-94-02-0261-00019-gf03-es.jpg"/></fig>
      <p>El control ecocardiogr&#225;fico secuencial demostr&#243; ca&#237;da progresiva y r&#225;pida de la funci&#243;n ventricular del coraz&#243;n nativo, con formaci&#243;n de trombo al final del primer a&#241;o, que desapareci&#243; con el incremento de la anticoagulaci&#243;n oral. Hubo, a partir del 6&#186; a&#241;o de evoluci&#243;n, una progresiva insuficiencia a&#243;rtica por ectasia anuloa&#243;rtica, con deterioro de la condici&#243;n cl&#237;nica, a pesar del incremento de la medicaci&#243;n, con antagonistas enzim&#225;ticos (captopril), espironolactona, carvedilol y diur&#233;ticos. Optamos por la correcci&#243;n quir&#250;rgica de la insuficiencia valvular a&#243;rtica, que se prefiri&#243;, por razones t&#233;cnicas, al explante del &#243;rgano nativo, lo que condujo a una significativa mejora funcional del paciente, que retorn&#243; a clase funcional II (NYHA). La funci&#243;n ventricular del injerto en posici&#243;n heterot&#243;pica en este paciente permaneci&#243; siempre normal, sin rechazos significativos detectados en los ex&#225;menes no invasivos de mapeo mioc&#225;rdico con Galio y ecocardiograma.</p>
      <p>El cuarto paciente, de forma muy semejante, present&#243; tambi&#233;n progresivo deterioro funcional del ventr&#237;culo izquierdo nativo y recibi&#243; anticoagulantes orales desde el inicio del postoperatorio. De la misma manera, surgi&#243; una insuficiencia valvular a&#243;rtica en el coraz&#243;n nativo, lo que oblig&#243; tambi&#233;n a la correcci&#243;n quir&#250;rgica de ese defecto. Al realizarse el explante del coraz&#243;n nativo, el paciente infelizmente sufri&#243; un grave accidente cerebrovascular, posiblemente tromboemb&#243;lico, falleciendo por complicaciones infecciosas en la unidad de terapia intensiva, con una sobrevida total de siete a&#241;os y cuatro meses tras la cirug&#237;a de trasplante.</p>
      <p>
        <bold>Discusi&#243;n</bold>
      </p>
      <p>Al analizar nuestros resultados con el trasplante ortot&#243;pico, notamos que la hiperresistencia pulmonar fue una importante causa, directa o indirecta, de mortalidad hospitalaria. Ello concuerda con la experiencia da <italic>Stanford University,</italic> que relata una mortalidad del 42% en los primeros tres meses, cuando la RVP de los receptores era superior a 2,5 UW, a pesar del uso de nitroprusiato de sodio <italic>(Nipride R);</italic> y una mortalidad del 25% para aquellos cuya RVP se redujo a menos de 2,5 UW con <italic>Nipride R</italic> m&#225;s la hipotensi&#243;n sist&#233;mica<sup>10</sup>.</p>
      <p>Las indicaciones de TxHet presentan a&#250;n controversias, pero los pacientes con RVP entre 4,5 y 7 UW se benefician con esa t&#233;cnica, de acuerdo con la mayor&#237;a de los centros de transplante<sup>10,11</sup>. No obstante, en los casos de RVP de 7 o m&#225;s unidades fijas, el TxHet ceder&#237;a lugar al trasplante cardiopulmonar, porque, adem&#225;s de ser m&#225;s elevado el riesgo quir&#250;rgico, ese nivel de RVP estar&#237;a asociado a alteraciones anat&#243;micas irreversibles y, probablemente, progresivas de la vasculatura pulmonar<sup>1</sup>. En este &#250;ltimo grupo, es posible tambi&#233;n el trasplante card&#237;aco y pulmonar unilateral en bloque, con perspectiva de reversi&#243;n de las alteraciones anat&#243;micas y funcionales de la vasculatura pulmonar, debido a la ca&#237;da inmediata de la presi&#243;n pulmonar y, por lo tanto, del est&#237;mulo para la reacci&#243;n vascular pulmonar<sup>12</sup>.</p>
      <p>Un criterio m&#225;s simple, pr&#225;ctico y seguro fue propuesto por el grupo de Pittsburg<sup>13</sup> y se basa en el gradiente transpulmonar (GTp), que es la diferencia entre la presi&#243;n media de la arteria pulmonar y la presi&#243;n media capilar pulmonar. Este estudio demostr&#243; que pacientes con GTp superior a 15 mmHg presentan mayor mortalidad que la de aquellos con GTp entre 10 y 15 mmHg, y mortalidad a&#250;n menor cuando ese gradiente es inferior a 10 mmHg. Por otro lado, este estudio no define cu&#225;l es el l&#237;mite m&#225;ximo del gradiente en que el trasplante cardiopulmonar se hace necesario.</p>
      <p>No siempre es f&#225;cil trabajar bas&#225;ndose en datos hemodin&#225;micos como lo propone la mayor&#237;a de los autores, principalmente en nuestro medio, en el cual existe una gran demora entre el estudio hemodin&#225;mico preoperatorio y el d&#237;a de la realizaci&#243;n del trasplante, lo que implica, muchas veces, la progresi&#243;n de la enfermedad vascular pulmonar. Por eso, hemos utilizado, como rutina, el monitoreo hemodin&#225;mico con drogas vasodilatadoras en el d&#237;a de la realizaci&#243;n del trasplante, sea en la UCI o en el centro quir&#250;rgico (previo a la inducci&#243;n anest&#233;sica), con cat&#233;ter de Swan-Ganz, mientras aguardamos la llegada del donante. Esto puede sorprender (<xref ref-type="table" rid="es_19t01-body3">tab. 1</xref>), donde el segundo paciente presentaba 1 UW mayor que la medida del preoperatorio inicial. Esta evaluaci&#243;n permite que empleemos preventivamente, en los casos de RVP m&#225;s elevada, drogas vasodilatadoras pulmonares, inclusive inhalatorias y, luego del alta de UCI, por v&#237;a oral.</p>
      <p>En el primer paciente, notamos que la RVP era un poco inferior a 5 UW, aunque si observamos el GTp, era superior a 10. La grave evoluci&#243;n cl&#237;nica de este paciente en los &#250;ltimos tres meses de espera, impuls&#243; a la indicaci&#243;n del TxHet reforzada por la aparici&#243;n de un donante de tama&#241;o no adecuado (peso 15% inferior).</p>
      <p>En cuanto a la nueva t&#233;cnica, que fue utilizada en el tercer paciente y que evita el uso de injerto de <italic>Dacron</italic> entre las arterias pulmonares, representa la primera innovaci&#243;n importante en los &#250;ltimos 20 a&#241;os. Tiene la ventaja de prevenir las complicaciones te&#243;ricamente posibles con este injerto artificial (infecci&#243;n, trombosis, embolias pulmonares y obstrucci&#243;n por pannus fibroso), y facilita adem&#225;s la biopsia endomioc&#225;rdica, porque la anastomosis de las cavas superiores conduce la pinza de biopsia f&#225;cilmente al VD del coraz&#243;n transplantado<sup>5</sup>.</p>
      <p>En cuanto a los resultados tard&#237;os, los TxHet que presentan sobrevida inferior al trasplante ortot&#243;pico (sobrevida actuarial de un a&#241;o del 61,4% y de dos a&#241;os del 56%), pero esa comparaci&#243;n es v&#225;lida s&#243;lo como fuente de informaci&#243;n, toda vez que los pacientes sometidos al TxHet presentan caracter&#237;sticas cl&#237;nicas distintas a las de los sometidos a trasplante card&#237;aco ortot&#243;pico<sup>14</sup>.</p>
      <p>En esta peque&#241;a experiencia, fue posible observar que pacientes con miocardiopat&#237;a global, que involucra tambi&#233;n al VD, como nuestro segundo paciente, tienen un riesgo mayor durante la cirug&#237;a, porque el VD enfermo del receptor tendr&#237;a que mantener la circulaci&#243;n pulmonar despu&#233;s del pinzamiento a&#243;rtico, generalmente largo, durante el trasplante. Adem&#225;s de ese riesgo mayor inmediato, existe el problema de la progresi&#243;n de la miocardiopat&#237;a, que torna desventajosa la presencia de ese coraz&#243;n, debido a las potenciales complicaciones. No obstante, los pacientes con miocardiopat&#237;as isqu&#233;micas que se circunscriben al VI, con el VD apenas hipertr&#243;fico, como ocurri&#243; en el primero, tercero y cuarto pacientes de nuestra experiencia, son candidatos ideales, porque tendr&#225;n mejor desempe&#241;o inicial, con el VD cumpliendo bien su papel de vencer la RVP elevada.</p>
      <p>No obstante, el seguimiento a largo plazo demostr&#243;, en el tercero y cuarto pacientes, las complicaciones ya referidas en la literatura<sup>15,16</sup>, fundamentalmente: el deterioro progresivo de la funci&#243;n ventricular izquierda y la insuficiencia a&#243;rtica por ectasia anulovalvular grave en el coraz&#243;n nativo. Esta &#250;ltima complicaci&#243;n demand&#243; cirug&#237;a correctiva en el tercer paciente hace seis a&#241;os, lo que posibilit&#243; mejor compensaci&#243;n cl&#237;nica, con la exclusi&#243;n del coraz&#243;n nativo de la circulaci&#243;n, que fue mantenida satisfactoriamente por el coraz&#243;n implantado, estando el paciente en buena condici&#243;n cl&#237;nica, 15 a&#241;os tras la cirug&#237;a. En el cuarto paciente, el intento durante la cirug&#237;a correctora de la insuficiencia valvular a&#243;rtica de explantar totalmente el coraz&#243;n nativo, se complic&#243; con el episodio del accidente cerebrovascular grave, que lo condujo al &#243;bito en el per&#237;odo hospitalario.</p>
      <p>Las causas de la disfunci&#243;n ventricular progresiva en el coraz&#243;n nativo podr&#237;an resumirse en: Progresi&#243;n de la patolog&#237;a mioc&#225;rdica, por arritmias y progreso de la enfermedad coronaria en el coraz&#243;n nativo; aumento de la postcarga en funci&#243;n de la disincron&#237;a del coraz&#243;n implantado con el nativo, pudiendo llevar a la aparici&#243;n de latidos simult&#225;neos y determinando importante aumento de la impedancia durante la s&#237;stole del coraz&#243;n enfermo; y dilataci&#243;n anulovalvular a&#243;rtica por los mecanismos antes mencionados, determinando insuficiencia a&#243;rtica progresiva<sup>9</sup>.</p>
      <p>Cowell et al<sup>17</sup> y Morris-Thurgood et al<sup>18</sup> demostraron que, utilizando el principio cl&#225;sico del bal&#243;n intraa&#243;rtico, o sea, la contracci&#243;n del coraz&#243;n nativo comandando mediante su frecuencia auricular la contracci&#243;n de aur&#237;cula y ventr&#237;culo del coraz&#243;n implantado, tras el cierre de la v&#225;lvula a&#243;rtica del coraz&#243;n nativo, la sincron&#237;a de los latidos entre ambos corazones, lograda por el marcapasos, podr&#237;a impedir las complicaciones derivadas de la mayor impedancia a la eyecci&#243;n ventricular del coraz&#243;n nativo. En consecuencia, en ese escenario, ser&#237;a de esperar una mejor preservaci&#243;n funcional del ventr&#237;culo izquierdo del coraz&#243;n nativo y quiz&#225;s la prevenci&#243;n de las disfunciones valvulares de ese &#243;rgano.</p>
      <p>En conclusi&#243;n, la presente experiencia con el trasplante card&#237;aco heterot&#243;pico fue ilustrativa, pues a pesar de una supervivencia tard&#237;a de 15 a&#241;os, con el paciente en buenas condiciones, fue necesario un procedimiento quir&#250;rgico para la exclusi&#243;n funcional del coraz&#243;n nativo. Los otros pacientes fallecieron, uno en el per&#237;odo hospitalario, otro, dos a&#241;os despu&#233;s de la cirug&#237;a, y el restante, siete a&#241;os despu&#233;s de la cirug&#237;a. Entendemos, no obstante, que la disfunci&#243;n ventricular progresiva del coraz&#243;n nativo, as&#237; como la ectasia anuloa&#243;rtica de &#233;ste y la insuficiencia a&#243;rtica derivada, podr&#237;an ser demoradas con el empleo de sincronizaci&#243;n permanente mediante el marcapasos, que no fue utilizado entonces en nuestros pacientes. Con ello este procedimiento podr&#237;a compararse favorablemente, por ejemplo, al trasplante cardiopulmonar, otra opci&#243;n para el tratamiento de pacientes con RVP elevada, en que es particularmente rara son las supervivencia de 15 a&#241;os<sup>19-20</sup>.</p>
      <p>
        <bold>Potencial Conflicto de Intereses</bold>
      </p>
      <p>Declaro no haber conflicto de intereses pertinentes.</p>
      <p>
        <bold>Fuentes de Financiaci&#243;n</bold>
      </p>
      <p>El presente estudio no tuvo fuentes de financiaci&#243;n externas.</p>
      <p>
        <bold>Vinculaci&#243;n Acad&#233;mica</bold>
      </p>
      <p>No hay vinculaci&#243;n de este estudio a programas de postgrado.</p>
      <p>
        <bold>Referencias</bold>
      </p>
    </body>
  </sub-article>
</article>
