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<article xmlns:xlink="http://www.w3.org/1999/xlink" specific-use="sps-1.9" dtd-version="1.1" xml:lang="pt" article-type="case-report">
  <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">3tDKCnVfzVsvSYvFV7vLksv</article-id>
      <article-id pub-id-type="other">00012</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2005001500012</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(05)08500212</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2005001500012</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Relato de Caso</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Doen&#231;a ateroscler&#243;tica difusa desmascarada pela avalia&#231;&#227;o fisiol&#243;gica invasiva da circula&#231;&#227;o coron&#225;ria</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Sant'Anna</surname>
            <given-names>Fernando Mendes</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Expedito E. Ribeiro da</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Batista</surname>
            <given-names>Leonardo Alves</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ventura</surname>
            <given-names>F&#225;bio Machado</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Barrozo</surname>
            <given-names>Carlos Alberto Mussel</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pijls</surname>
            <given-names>Nico H.J.</given-names>
          </name>
        </contrib>
      </contrib-group>
      <pub-date date-type="collection" publication-format="electronic">
        <month>08</month>
        <year>2005</year>
      </pub-date>
      <volume>85</volume>
      <issue>2</issue>
      <fpage>135</fpage>
      <lpage>137</lpage>
      <history>
        <date date-type="received">
          <day>07</day>
          <month>11</month>
          <year>2004</year>
        </date>
        <date date-type="accepted">
          <day>04</day>
          <month>03</month>
          <year>2005</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>Sabe-se que a aterosclerose coron&#225;ria &#233; um processo difuso, pouco vis&#237;vel &#224; angiografia. Este artigo descreve um paciente com angina est&#225;vel, tr&#234;s meses ap&#243;s infarto agudo do mioc&#225;rdio (IAM), e uma les&#227;o severa na art&#233;ria descendente anterior (ADA), evidenciada pela cinecoronariografia. A reserva de fluxo fracionada do mioc&#225;rdio (FFR), obtida atrav&#233;s de medidas press&#243;ricas intracoron&#225;rias, foi 0,37 durante a hiperemia m&#225;xima, demonstrando claramente a exist&#234;ncia de isquemia. Um stent foi implantado na ADA e, a despeito do excelente resultado angiogr&#225;fico, a FFR p&#243;s-stent foi apenas 0,75, o limite m&#237;nimo abaixo do qual existe isquemia. Quando a corda guia press&#243;rica (pressure wire - PW) foi lentamente recuada da por&#231;&#227;o distal da ADA para sua por&#231;&#227;o proximal, notou-se um aumento cont&#237;nuo e gradativo na press&#227;o intracoron&#225;ria, o que indica claramente aterosclerose difusa e n&#227;o estenose focal. N&#227;o se notava gradiente no local do stent. O paciente foi mantido em tratamento m&#233;dico e permanece assintom&#225;tico at&#233; o momento.</p>
      </abstract>
      <pub-date publication-format="electronic" date-type="pub">
        <day>29</day>
        <month>09</month>
        <year>2005</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>RELATO DE CASO</bold>
    </p>
    <p>Doen&#231;a ateroscler&#243;tica difusa desmascarada pela avalia&#231;&#227;o fisiol&#243;gica invasiva da circula&#231;&#227;o coron&#225;ria</p>
    <p>
      <bold>Diffuse atherosclerotic disease unmasked by invasive physiologic assessment of coronary flow</bold>
    </p>
    <p>
      <bold>Fernando Mendes Sant'Anna; Expedito E. Ribeiro da Silva; Leonardo Alves Batista; F&#225;bio Machado Ventura; Carlos Alberto Mussel Barrozo; Nico H.J. Pijls</bold>
    </p>
    <p>Santa Helena Hospital do Cora&#231;&#227;o - Cabo Frio, RJ - Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas (FMUSP) - S&#227;o Paulo, SP e Catharina Hospital - Eindhoven, Holanda</p>
    <p>
      <xref ref-type="corresp" rid="back10">Endere&#231;o para correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p>Sabe-se que a aterosclerose coron&#225;ria &#233; um processo difuso, pouco vis&#237;vel &#224; angiografia. Este artigo descreve um paciente com angina est&#225;vel, tr&#234;s meses ap&#243;s infarto agudo do mioc&#225;rdio (IAM), e uma les&#227;o severa na art&#233;ria descendente anterior (ADA), evidenciada pela cinecoronariografia. A reserva de fluxo fracionada do mioc&#225;rdio (FFR), obtida atrav&#233;s de medidas press&#243;ricas intracoron&#225;rias, foi 0,37 durante a hiperemia m&#225;xima, demonstrando claramente a exist&#234;ncia de isquemia. Um <italic>stent</italic> foi implantado na ADA e, a despeito do excelente resultado angiogr&#225;fico, a FFR p&#243;s-<italic>stent</italic> foi apenas 0,75, o limite m&#237;nimo abaixo do qual existe isquemia. Quando a corda guia press&#243;rica (<italic>pressure wire</italic> &#150; PW) foi lentamente recuada da por&#231;&#227;o distal da ADA para sua por&#231;&#227;o proximal, notou-se um aumento cont&#237;nuo e gradativo na press&#227;o intracoron&#225;ria, o que indica claramente aterosclerose difusa e n&#227;o estenose focal. N&#227;o se notava gradiente no local do <italic>stent</italic>. O paciente foi mantido em tratamento m&#233;dico e permanece assintom&#225;tico at&#233; o momento.</p>
    <p>
      <bold>ABSTRACT</bold>
    </p>
    <p>It is known that coronary atherosclerosis is a diffuse process, very little visible at angiography. This article describes a stable angina patient, three months after acute myocardial infarction (AMI), and a severe lesion in anterior descending artery (ADA), evinced by coronariography. Myocardial fractional flow reserve (FFR), obtained through intracoronary pressure measurements, was 0.37 during maximum hyperemia, clearly showing the presence of ischemia. A stent was implanted in ADA and, despite the excellent angiographic result, post-stent FFR was only 0.75, the minimum limit, below which there is ischemia. When the pressure wire (PW) was slowly drawn back from the distal portion of ADA to its proximal portion, a continuous and gradual increase in intracoronary pressure was noted, which clearly indicates diffuse atherosclerosis and not focal stenosis. A gradient was not observed at the stent place. The patient was kept under medical treatment and has been asymptomatic so far.</p>
    <p>Estudos anatomopatol&#243;gicos e com ultra-som intravascular demonstraram que, quando uma estenose &#233; vis&#237;vel &#224; angiografia, o restante da circula&#231;&#227;o coron&#225;ria est&#225; freq&#252;entemente acometido por aterosclerose difusa, embora tal fato possa muitas vezes n&#227;o ser identificado pela coronariografia<sup>1-4</sup>.</p>
    <p>De Bruyne e cols. mostraram que art&#233;rias coron&#225;rias epic&#225;rdicas com aterosclerose difusa, ao contr&#225;rio das coron&#225;rias normais, mostram, freq&#252;entemente, uma queda press&#243;rica cont&#237;nua ao longo de seus trajetos, reduzindo a reserva de fluxo fracionada do mioc&#225;rdio (FFR) e contribuindo para causar isquemia mioc&#225;rdica e perfus&#227;o anormal, durante o exerc&#237;cio e/ou vasodilata&#231;&#227;o farmacol&#243;gica. Tal fato pode ser identificado pelas medidas de press&#227;o intracoron&#225;rias<sup>5</sup>.</p>
    <p>A FFR pode ser definida como o produto da divis&#227;o entre o fluxo coronariano hiper&#234;mico m&#225;ximo na presen&#231;a de uma estenose e este mesmo fluxo na aus&#234;ncia de estenose, e &#233; calculada dividindo-se a press&#227;o m&#233;dia no leito distal da art&#233;ria coron&#225;ria (Pd) pela press&#227;o m&#233;dia em aorta (Pa) durante hiperemia m&#225;xima (FFR=Pd/Pa)<sup>6</sup>. Quanto maior a resist&#234;ncia ao fluxo, maior o decl&#237;nio na press&#227;o distal e, logo, menor a FFR. A FFR &#233; um &#237;ndice de resist&#234;ncia ao fluxo ao longo do vaso epic&#225;rdico e n&#227;o &#233; afetada por mudan&#231;as na press&#227;o arterial, freq&#252;&#234;ncia card&#237;aca e outras patologias. Mesmo na presen&#231;a de doen&#231;a de microcircula&#231;&#227;o, a FFR ainda fornece informa&#231;&#227;o sobre a resist&#234;ncia (anormal) ao fluxo ao longo da art&#233;ria, dado aquele estado de disfun&#231;&#227;o da microcircula&#231;&#227;o. A FFR e suas caracter&#237;sticas foram muito bem estudadas e validadas nos &#250;ltimos anos<sup>7-9</sup>. O mais importante &#233; saber que uma FFR menor que 0,75 est&#225; associada a les&#245;es capazes de provocar isquemia e possui uma acur&#225;cia de quase 100%<sup>8,9</sup>.</p>
    <p>O presente relato descreve um paciente com angina est&#225;vel que apresentava uma estenose importante na art&#233;ria descendente anterior (ADA). A FFR medida foi 0,37, sendo indicativa de isquemia importante. Um gradiente press&#243;rico focal acentuado estava presente no local da estenose. Ap&#243;s tratamento dessa les&#227;o por angioplastia com implante de <italic>stent</italic>, a FFR melhorou significativamente, por&#233;m seu valor continuou dentro da &#225;rea onde se pode provocar isquemia. No entanto, o tra&#231;ado press&#243;rico coronariano obtido com a <italic>pressure wire</italic>, durante hiperemia m&#225;xima (curva de retra&#231;&#227;o), n&#227;o mostrou gradiente na &#225;rea onde o <italic>stent</italic> foi implantado, mas sim um aumento cont&#237;nuo e gradual da press&#227;o m&#233;dia intracoron&#225;ria do leito distal para o ter&#231;o proximal da ADA, t&#237;pico de doen&#231;a ateroscler&#243;tica difusa. Este artigo pretende demonstrar como a FFR pode desmascarar a doen&#231;a ateroscler&#243;tica difusa ap&#243;s tratamento de uma les&#227;o focal.</p>
    <p>
      <bold>Relato do Caso</bold>
    </p>
    <p>Paciente do sexo masculino, 58 anos, com hist&#243;ria de infarto agudo do mioc&#225;rdio (IAM) em 25 de janeiro de 2004, evoluindo com dor precordial t&#237;pica aos esfor&#231;os moderados (angina est&#225;vel CCS 2). Fatores de risco: hipercolesterolemia e hipertens&#227;o arterial sist&#234;mica. Exame f&#237;sico normal. O eletrocardiograma (ECG) de repouso mostrava ondas Q com aus&#234;ncia de ondas R de V1 a V4.</p>
    <p>Ecocardiograma evidenciava apenas discreta hipocinesia de parede anterior e fun&#231;&#227;o ventricular levemente deprimida.</p>
    <p>Na cinecoronariografia, pod&#237;amos observar importante estenose no ter&#231;o proximal da ADA, quantificada em 90% pela estimativa visual (<xref ref-type="fig" rid="fig1">fig. 1</xref>). Como o paciente estava sintom&#225;tico e a fun&#231;&#227;o ventricular esquerda era praticamente normal, foi indicada angioplastia coron&#225;ria com implante de <italic>stent</italic> na ADA.</p>
    <fig id="fig1">
      <graphic xlink:href="1678-4170-abc-85-02-0135-00012-gf01.jpg"/></fig>
    <p>A avalia&#231;&#227;o fisiol&#243;gica invasiva da circula&#231;&#227;o coron&#225;ria, atrav&#233;s da utiliza&#231;&#227;o da <italic>pressure wire</italic> (PW), &#233; realizada de rotina em nosso Servi&#231;o de Hemodin&#226;mica, como uma ferramenta adicional e extremamente importante para confirmar a presen&#231;a de isquemia coron&#225;ria e checar o implante adequado (&#243;timo) do <italic>stent</italic>. Uma corda guia de 0,014 polegadas, desconect&#225;vel, equipada com um sensor de press&#227;o de alta fidelidade (<italic>Pressure Wire</italic><sup>4</sup>, <italic>Radi Medical Systems</italic>, <italic>Upsala, Su&#233;cia</italic>) foi introduzida na ADA e, ap&#243;s administra&#231;&#227;o intravenosa de adenosina na dosagem de 140 &#181;g/kg/minuto, foi obtido o tra&#231;ado press&#243;rico apresentado na <xref ref-type="fig" rid="fig2">figura 2</xref>. Durante a hiperemia m&#225;xima, a FFR da ADA foi 0,37 e a curva de retra&#231;&#227;o mostrou claramente, dentro da ADA, exatamente no local da estenose, a ocorr&#234;ncia de uma queda s&#250;bita de press&#227;o registrada pela <italic>pressure wire</italic> (<xref ref-type="fig" rid="fig2">fig. 2</xref>).</p>
    <fig id="fig2">
      <graphic xlink:href="1678-4170-abc-85-02-0135-00012-gf02.jpg"/></fig>
    <p>A les&#227;o foi pr&#233;-dilatada com um bal&#227;o de 2.5 mm de di&#226;metro e dois <italic>stents</italic> (di&#226;metros 3.0 mm e 2.5 mm) foram implantados na ADA, de modo a cobrir todo o segmento doente. Ap&#243;s excelente resultado angiogr&#225;fico (<xref ref-type="fig" rid="fig3">fig. 3</xref>), a FFR foi medida de novo e seu valor subira para 0,75, justamente no limiar m&#237;nimo abaixo do qual se pode provocar isquemia. No entanto, quando a <italic>pressure wire</italic> foi recuada do ter&#231;o distal para o proximal da ADA, durante hiperemia m&#225;xima, n&#227;o mais se observava um gradiente focal dentro da art&#233;ria ou atrav&#233;s do <italic>stent</italic>, mas apenas uma subida cont&#237;nua e progressiva da press&#227;o intracoron&#225;ria (<xref ref-type="fig" rid="fig4">fig. 4</xref>), o que &#233; t&#237;pico de doen&#231;a ateroscler&#243;tica difusa (e n&#227;o de les&#227;o focal) e, conseq&#252;entemente, n&#227;o mais trat&#225;vel atrav&#233;s de angioplastia coron&#225;ria. O paciente foi, ent&#227;o, mantido em tratamento cl&#237;nico e est&#225; evoluindo bem, assintom&#225;tico, at&#233; o momento.</p>
    <fig id="fig3">
      <graphic xlink:href="1678-4170-abc-85-02-0135-00012-gf03.jpg"/></fig>
    <fig id="fig4">
      <graphic xlink:href="1678-4170-abc-85-02-0135-00012-gf04.jpg"/></fig>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>As art&#233;rias coron&#225;rias normais s&#227;o caracterizadas pela aus&#234;ncia de qualquer decl&#237;nio de press&#227;o ao longo de seus trajetos, mesmo sob hiperemia m&#225;xima<sup>8,9</sup>. Na doen&#231;a ateroscler&#243;tica difusa, pode-se observar uma queda press&#243;rica progressiva durante a hiperemia que pode, inclusive, ser respons&#225;vel por isquemia<sup>5</sup>.</p>
    <p>No paciente do presente caso, uma estenose muito importante (tanto anat&#244;mica, quanto funcional) estava presente na ADA, o que foi confirmado pela s&#250;bita queda na press&#227;o intracoron&#225;ria durante hiperemia, quando o sensor da <italic>pressure wire</italic> cruzava a les&#227;o (<xref ref-type="fig" rid="fig2">fig. 2</xref>). Ap&#243;s o implante de <italic>stent</italic> nesta les&#227;o focal, o fluxo sang&#252;&#237;neo, atrav&#233;s da mesma, aumentou em mais de 100% (0,37 &#174; 0,75) e, devido a este aumento, a doen&#231;a ateroscler&#243;tica difusa (antes n&#227;o observada) foi ent&#227;o desmascarada.</p>
    <p>&#201; importante mencionar que a ocorr&#234;ncia de emboliza&#231;&#227;o distal da microcircula&#231;&#227;o coron&#225;ria, devido ao implante de <italic>stent</italic>, poderia causar um falso aumento (e n&#227;o diminui&#231;&#227;o) no valor final da FFR<sup>10</sup>, n&#227;o tendo tido, assim, qualquer participa&#231;&#227;o no resultado alcan&#231;ado.</p>
    <p>Esse caso ensina duas importantes li&#231;&#245;es &#150; 1) A avalia&#231;&#227;o fisiol&#243;gica (ou funcional) da ADA confirmou que os <italic>stents</italic> foram implantados adequadamente (n&#227;o havia gradientes atrav&#233;s dos mesmos). Sem esta observa&#231;&#227;o fundamental, queixas residuais, porventura apresentadas, seriam certamente atribu&#237;das a implante inadequado dos <italic>stents</italic> e poderiam provocar outras interven&#231;&#245;es nos locais onde estes foram implantados (como, por exemplo: dilata&#231;&#227;o com bal&#245;es de di&#226;metro maior e/ou com altas press&#245;es); 2) Doen&#231;a ateroscler&#243;tica difusa na ADA foi desmascarada por tratamento adequado de uma les&#227;o focal, o que foi provado pela curva de retra&#231;&#227;o durante hiperemia m&#225;xima.</p>
    <p>Esses achados t&#234;m importantes implica&#231;&#245;es na avalia&#231;&#227;o do implante adequado do <italic>stent</italic>. J&#225; foi demonstrado, tanto por ultra-som intravascular, quanto por medidas press&#243;ricas intravasculares, que a presen&#231;a de uma estenose focal est&#225; quase sempre associada com algum grau de doen&#231;a ateroscler&#243;tica difusa da circula&#231;&#227;o coron&#225;ria<sup>2-5</sup>. Mesmo ap&#243;s tratamento bem sucedido de uma estenose focal, um gradiente residual ao longo da art&#233;ria pode permanecer e a FFR medida na por&#231;&#227;o distal da coron&#225;ria pode ser anormal (&lt;0,75). Logo, para avaliar se o <italic>stent</italic> restabeleceu totalmente a condut&#226;ncia de um segmento previamente esten&#243;tico, a FFR desse segmento deve ser calculada dividindo-se a press&#227;o logo ap&#243;s o <italic>stent</italic> pela press&#227;o imediatamente antes do mesmo, durante uma manobra de retra&#231;&#227;o da corda guia sob hiperemia m&#225;xima. O gradiente press&#243;rico entre as duas bordas do <italic>stent</italic> indica o estado do <italic>stent</italic> propriamente dito, enquanto a curva de retra&#231;&#227;o registrada ao longo do vaso indica a condut&#226;ncia de todo o segmento epic&#225;rdico da art&#233;ria coron&#225;ria em quest&#227;o, incluindo o segmento aonde foi implantado o <italic>stent</italic><sup>5</sup>. Esta &#250;ltima informa&#231;&#227;o &#233; importante para sabermos se esta art&#233;ria poder&#225; induzir isquemia.</p>
    <p>Embora esteja bem estabelecido por estudos recentemente publicados<sup>11</sup> que a FFR p&#243;s-<italic>stent</italic> tem importantes implica&#231;&#245;es progn&#243;sticas, temos que estar conscientes que, especialmente em pacientes com doen&#231;a multiarterial e alguns tipos de patologias associadas (diabetes, por exemplo), &#233; imposs&#237;vel, algumas vezes, obtermos resultados fisiol&#243;gicos ideais (FFR&gt;0,94) ap&#243;s implante de <italic>stent</italic> e tal fato deve-se &#224; presen&#231;a de aterosclerose difusa ao longo do vaso e n&#227;o ao implante inadequado da endopr&#243;tese.</p>
    <p>
      <fn id="back10" fn-type="corresp">
        <label>
          <bold>Endere&#231;o para correspond&#234;ncia</bold>
        </label>
        <p> Fernando Mendes Sant'Anna </p>
        <p> Rua Safira 20, Portinho, Cabo Frio </p>
        <p> 28915-400 - Cabo Frio, RJ </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="fernandomendes@cardiol.br">fernandomendes@cardiol.br</email>
        </p>
      </fn>
    </p>
    <p>Enviado em 07/11/2004 </p>
    <p> Aceito em 04/03/2005</p>
  </body>
  <back>
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  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Case Report</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Diffuse atherosclerotic disease unmasked by invasive physiologic assessment of coronary flow</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>It is known that coronary atherosclerosis is a diffuse process, very little visible at angiography. This article describes a stable angina patient, three months after acute myocardial infarction (AMI), and a severe lesion in anterior descending artery (ADA), evinced by coronariography. Myocardial fractional flow reserve (FFR), obtained through intracoronary pressure measurements, was 0.37 during maximum hyperemia, clearly showing the presence of ischemia. A stent was implanted in ADA and, despite the excellent angiographic result, post-stent FFR was only 0.75, the minimum limit, below which there is ischemia. When the pressure wire (PW) was slowly drawn back from the distal portion of ADA to its proximal portion, a continuous and gradual increase in intracoronary pressure was noted, which clearly indicates diffuse atherosclerosis and not focal stenosis. A gradient was not observed at the stent place. The patient was kept under medical treatment and has been asymptomatic so far.</p>
      </abstract>
    </front-stub>
    <body>
      <p>
        <bold>CASE REPORT</bold>
      </p>
      <p>
        <bold>Diffuse atherosclerotic disease unmasked by invasive physiologic assessment of coronary flow</bold>
      </p>
      <p>
        <bold>Fernando Mendes Sant'Anna; Expedito E. Ribeiro da Silva; Leonardo Alves Batista; F&#225;bio Machado Ventura; Carlos Alberto Mussel Barrozo; Nico H.J. Pijls</bold>
      </p>
      <p>Santa Helena Hospital do Cora&#231;&#227;o - Cabo Frio, RJ - Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas (FMUSP) - S&#227;o Paulo, SP e Catharina Hospital - Eindhoven, The Netherlands</p>
      <p>
        <xref ref-type="corresp" rid="back10-body2">Correspondence</xref>
      </p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p>It is well known that coronary atherosclerosis is often a diffuse process poorly visible at angiography. This paper describes a patient with persisting stable angina after acute myocardial infarction (AMI) 3 months earlier and a severe lesion in the left anterior descending artery (LAD) at coronary angiography. Fractional flow reserve (FFR), measured by coronary pressure measurements, was 0.37 during hyperemia, unequivocally demonstrating the presence of ischemia. A stent was placed in the LAD and despite excellent angiographic result, post FFR was only 0.75, the lower limit for ischemia. When the pressure sensor was slowly pulled back from distal to proximal LAD there was a graded, continuous increase in coronary pressure, which clearly indicates diffuse atherosclerosis, not focal stenosis. Across the stent no hyperemic gradient was present. The patient was treated medically and remained event free thereafter.</p>
      <p>Coronary circulation is generally considered a two compartment model, which consists of epicardial vessels, also referred as "conductance vessels" and microcirculation, arteries &lt;400 mm or "resistive vessels"<sup>1</sup>. When there is no stenosis, myocardial flow is primarily controlled by resistive vessels.</p>
      <p>Pathological and intravascular ultrasound studies have shown that when a stenosis is visible at angiography, the remainder of the coronary tree is often diffusely involved by atherosclerosis, although this may not be identified by coronary angiography<sup>2-5</sup>.</p>
      <p>De Bruyne et al. showed that diffusely atherosclerotic epicardial coronary arteries in contrast to truly normal coronary arteries often cause a continuous pressure decline along their length, reduce fractional flow reserve, contribute to myocardial ischemia and abnormal perfusion during exercise and pharmacological vasodilatation, and are identifiable by intracoronary pressure measurements<sup>6</sup>.</p>
      <p>Fractional flow reserve (FFR) is defined as the ratio of maximal hyperemic blood flow in the presence of a stenosis divided by normal hyperemic blood flow without stenosis and is calculated as the ratio of distal coronary pressure (Pd) divided by aortic pressure (Pa) at maximum hyperemia (FFR=Pd/Pa)<sup>7</sup>. The larger the resistance to blood flow, the larger the decline in pressure and, thus, the smaller FFR. Therefore, FFR is an index of resistance to flow along the epicardial vessel and is not affected by changes in blood pressure, heart rate and other pathologic conditions. Even if microcirculatory disease is present, FFR still gives the (abnormal) resistance to flow along the epicardial artery, given that state of microcirculatory disease. FFR and its properties have been well validated over recent years<sup>8-10</sup>. Importantly, FFR below 0.75-0.80 discriminate lesions which are associated with inducible ischemia with a diagnostic accuracy of almost 100%<sup>9,10</sup>.</p>
      <p>The present report describes a patient with stable angina who had a severe stenosis in the left anterior descending (LAD) coronary artery. Measured FFR was 0.37 and thus indicative of important ischemia. A major, focal gradient was present across the stenosis itself. After treating this lesion by stent implantation, FFR improved significantly but still remained inside the area for inducible ischemia. However, coronary pressure tracings obtained by the pullback curve under maximal hyperemia showed no gradient across the stent individually deployed well, but a continuous increase from distal to proximal LAD typical of diffuse atherosclerotic disease. This report might demonstrate how FFR can unmask diffuse atherosclerotic disease after treatment of a focal lesion.</p>
      <p>
        <bold>Case Report</bold>
      </p>
      <p>A 58-year-old male, suffering from AMI 3 months earlier, presented at outpatient clinic with typical recurrent chest pain at moderate exercise. Known risk factors were hypercholesterolemia and arterial hypertension. Physical examination was normal. Resting ECG showed Q-waves with absent R waves from V1 to V4. Echocardiography showed a mild anterior hypokinesia of the left ventricle with a slightly depressed left ventricular function.</p>
      <p>At cardiac catheterization, there was a very tight stenosis in the LAD, approximately 90% by visual assessment (<xref ref-type="fig" rid="fig1-body2">Figure 1</xref>). As the patient was symptomatic and left ventricular function was almost normal, coronary angioplasty followed by stent implantation was chosen as the best treatment option.</p>
      <fig id="fig1-body2">
        <graphic xlink:href="1678-4170-abc-85-02-0135-00012-gf01-en.jpg"/></fig>
      <p>Pressure measurements are routinely performed before and after PCI in our cath lab as an additional tool to confirm the presence of ischemia by determining the FFR, and to check adequate stent deployment. A 0.014-inch disconnectable sensor-mounted high-fidelity pressure wire (Pressure Wire, Radi Medical Systems, Upsala, Sweden) was introduced into the LAD and, after intravenous administration of adenosine 140 mg/kg per minute, the recordings were made as presented in <xref ref-type="fig" rid="fig2-body2">Figure 2</xref>. At maximal hyperemia, FFR of the LAD equaled 0.37 and the pressure pullback curve showed a clear spot inside the LAD at the place of the stenosis where a sudden drop of the pressure was recorded by the pressure wire (<xref ref-type="fig" rid="fig2-body2">Figure 2</xref>).</p>
      <fig id="fig2-body2">
        <graphic xlink:href="1678-4170-abc-85-02-0135-00012-gf02-en.jpg"/></fig>
      <p>The lesion was then predilated with a 2.5 mm balloon and two stents (3.0 and 2.5 mm diameters) were implanted in order to cover the entire diseased segment. After excellent angiographic result (<xref ref-type="fig" rid="fig3-body2">Figure 3</xref>), FFR was measured again and its value was 0.75, around the threshold for inducible ischemia. When the pressure wire was slowly pulled back from distal to proximal LAD, there was no residual gradient across the stent itself but a graded, continuous increase in coronary pressure (<xref ref-type="fig" rid="fig4-body2">Figure 4</xref>), which clearly indicates diffuse atherosclerosis, not focal stenosis, and thus not amenable for further stenting. The patient was kept in medical treatment and remained event free thereafter.</p>
      <fig id="fig3-body2">
        <graphic xlink:href="1678-4170-abc-85-02-0135-00012-gf03-en.jpg"/></fig>
      <fig id="fig4-body2">
        <graphic xlink:href="1678-4170-abc-85-02-0135-00012-gf04-en.jpg"/></fig>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>Normal coronary arteries are characterized by the absence of any decline of pressure along its course, not even at maximal hyperemia<sup>9</sup>. In diffuse disease, hyperemic decline is often observed and can even be responsible for inducible ischemia<sup>6</sup>.</p>
      <p>In this patient, a very tight (anatomic and physiologic) stenosis was present in the LAD with large focal hyperemic pressure drop and little further decline (<xref ref-type="fig" rid="fig2-body2">Figure 2</xref>).</p>
      <p>After stenting the focal spot, blood flow increased by more than 100% (0.37 &#174; 0.75) and due to this increase in flow the diffuse disease (not observable before) was unmasked.</p>
      <p>It is also important to mention that distal embolization due to stent implantation could not have been responsible for the low FFR; it would make the FFR higher than expected yielding a false result.</p>
      <p>This case teaches two important lessons:</p>
      <p>1. Pressure measurements proved that stents were placed well (there were no gradients across them). Without that observation, residual ischemic complaints could be attributed to insufficient stent deployment and might have provoked further action in the stents.</p>
      <p>2. The diffuse disease was unmasked by successful stenting of a focal stenosis, as proven by the hyperemic pullback curve.</p>
      <p>These findings have important implications for evaluation of coronary stenting. It has already been demonstrated by intravascular ultrasound and also by pressure measurements, that the presence of a focal stenosis is almost always associated with diffuse atherosclerosis of coronary vasculature<sup>3-6</sup>. Even after successful stenting of a focal stenosis, a residual gradient may remain with an abnormal FFR if pressure is measured in the distal part of the artery. Therefore, to evaluate whether the stent has fully re-established the conductance of a previously stenotic stented segment, FFR should be calculated from the ratio of the pressure just distal to just proximal to the stented segment during a pullback maneuver under maximal hyperemia. The pressure gradient between the two edges of the stent indicates the status of the stented segment alone, whereas the pullback pressure recording along the length of the artery indicates the conductance of the entire epicardial artery, including the stented segment<sup>6</sup>, and also indicates if ischemia will be inducible at exercise.</p>
      <p>Although it is well known, by recently published studies<sup>11</sup>, that post stent FFR has important prognostic implications, we have to be aware that, specially in patients with multivessel disease and certain types of associated diseases (like diabetes), sometimes it is impossible to reach optimal physiologic results and this is due to diffuse atherosclerosis not to inadequate stent deployment.</p>
      <p>
        <bold>References</bold>
      </p>
      <p>
        <fn id="back10-body2" fn-type="corresp">
          <label>
            <bold>Correspondence to</bold>
          </label>
          <p> Fernando Mendes Sant'Anna</p>
          <p> Rua Safira 20, Portinho, Cabo Frio</p>
          <p> 28915-400 - Cabo Frio, RJ - Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="fernandomendes@cardiol.br">fernandomendes@cardiol.br</email>
          </p>
        </fn>
      </p>
      <p>Sent for publishing on 11/07/2004</p>
      <p> Accepted on 03/04/2005</p>
    </body>
  </sub-article>
</article>
