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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">P47bL8TBB9MDCkRPcCvMgRh</article-id>
      <article-id pub-id-type="other">00024</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2006001900024</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(06)08700624</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2006001900024</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Relato de Caso</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Vasoespasmo coronariano induzido pela ecocardiografia sob estresse pela dobutamina-atropina</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Bogaz</surname>
            <given-names>F&#225;bio A.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Saroute</surname>
            <given-names>Ally N. R.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tsutsui</surname>
            <given-names>Jeane Mike</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kowatsch</surname>
            <given-names>Ingrid</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>O. Neto</surname>
            <given-names>Francisco M.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nicolau</surname>
            <given-names>Jos&#233; C.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ramires</surname>
            <given-names>Jos&#233; A. F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mathias Junior</surname>
            <given-names>Wilson</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">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">FM </institution>
        <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>12</month>
        <year>2006</year>
      </pub-date>
      <volume>87</volume>
      <issue>6</issue>
      <fpage>e250</fpage>
      <lpage>e253</lpage>
      <history>
        <date date-type="accepted">
          <day>08</day>
          <month>12</month>
          <year>2005</year>
        </date>
        <date date-type="rev-recd">
          <day>08</day>
          <month>12</month>
          <year>2005</year>
        </date>
        <date date-type="received">
          <day>27</day>
          <month>11</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>Relatamos caso de mulher de 45 anos de idade, com antecedentes de hipertens&#227;o arterial sist&#234;mica e tabagismo, submetida a ecocardiografia sob estresse pela dobutamina-atropina para investiga&#231;&#227;o de doen&#231;a arterial coronariana. No pico do estresse, a paciente apresentou dor precordial s&#250;bita e de forte intensidade. O eletrocardiograma de doze deriva&#231;&#245;es revelou eleva&#231;&#227;o do segmento ST nas deriva&#231;&#245;es DII, DIII, aVF, V5 e V6 e depress&#227;o do segmento ST nas deriva&#231;&#245;es DI, aVL, V2 e V3. Pela monitora&#231;&#227;o das imagens ecocardiogr&#225;ficas foi observado aparecimento de discinesia do septo inferior e acinesia da parede inferior do ventr&#237;culo esquerdo. O exame foi interrompido imediatamente, a paciente foi medicada e evoluiu com melhora da dor precordial e das altera&#231;&#245;es de motilidade segmentar. A angiografia coronariana revelou les&#245;es coronarianas irregulares com menos de 50% de obstru&#231;&#227;o do di&#226;metro luminal. Trata-se de um caso de vasoespasmo coronariano induzido por estimula&#231;&#227;o alfa-adren&#233;rgica durante a ecocardiografia sob estresse pela dobutamina-atropina.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Ecocardiografia sob estresse</kwd>
        <kwd>vasoespasmo</kwd>
        <kwd>doen&#231;a arterial coronariana</kwd>
        <kwd>dobutamina</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>18</day>
        <month>01</month>
        <year>2007</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>RELATO DE CASO</bold>
    </p>
    <p>
      <bold>Vasoespasmo coronariano induzido pela ecocardiografia sob estresse pela dobutamina-atropina</bold>
    </p>
    <p>
      <bold>F&#225;bio A. Bogaz; Ally N. R. Saroute; Jeane Mike Tsutsui; Ingrid Kowatsch; Francisco M. O. Neto; Jos&#233; C. Nicolau; Jos&#233; A. F. Ramires; Wilson Mathias Junior</bold>
    </p>
    <p>Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas &#150; FMUSP - S&#227;o Paulo, SP</p>
    <p>
      <xref ref-type="corresp" rid="back">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p>Relatamos caso de mulher de 45 anos de idade, com antecedentes de hipertens&#227;o arterial sist&#234;mica e tabagismo, submetida a ecocardiografia sob estresse pela dobutamina-atropina para investiga&#231;&#227;o de doen&#231;a arterial coronariana. No pico do estresse, a paciente apresentou dor precordial s&#250;bita e de forte intensidade. O eletrocardiograma de doze deriva&#231;&#245;es revelou eleva&#231;&#227;o do segmento ST nas deriva&#231;&#245;es DII, DIII, aVF, V5 e V6 e depress&#227;o do segmento ST nas deriva&#231;&#245;es DI, aVL, V2 e V3. Pela monitora&#231;&#227;o das imagens ecocardiogr&#225;ficas foi observado aparecimento de discinesia do septo inferior e acinesia da parede inferior do ventr&#237;culo esquerdo. O exame foi interrompido imediatamente, a paciente foi medicada e evoluiu com melhora da dor precordial e das altera&#231;&#245;es de motilidade segmentar. A angiografia coronariana revelou les&#245;es coronarianas irregulares com menos de 50% de obstru&#231;&#227;o do di&#226;metro luminal. Trata-se de um caso de vasoespasmo coronariano induzido por estimula&#231;&#227;o alfa-adren&#233;rgica durante a ecocardiografia sob estresse pela dobutamina-atropina.</p>
    <p><bold>Palavras-chave:</bold> Ecocardiografia sob estresse, vasoespasmo, doen&#231;a arterial coronariana, dobutamina.</p>
    <p>A ecocardiografia sob estresse pela dobutamina (EED) &#233; um m&#233;todo amplamente empregado para avalia&#231;&#227;o de pacientes com doen&#231;a coronariana suspeita ou conhecida, tendo seu perfil de seguran&#231;a j&#225; estabelecido em estudos envolvendo grande n&#250;mero de pacientes<sup>1,2</sup>. A dobutamina &#233; uma catecolamina com meia-vida de dois a tr&#234;s minutos, que apresenta boa toler&#226;ncia e, pelo seu efeito inotr&#243;pico e cronotr&#243;pico positivo, causa aumento do consumo de oxig&#234;nio pelo mioc&#225;rdio. A avalia&#231;&#227;o de isquemia mioc&#225;rdica baseia-se na detec&#231;&#227;o de redu&#231;&#227;o do espessamento sist&#243;lico mioc&#225;rdico pela ecocardiografia bidimensional, induzida pelo desbalan&#231;o entre a demanda e a oferta de oxig&#234;nio, durante o estresse. A presen&#231;a de eleva&#231;&#227;o do segmento ST no eletrocardiograma de doze deriva&#231;&#245;es, associada a altera&#231;&#245;es transit&#243;rias da motilidade segmentar, quase sempre traduz obstru&#231;&#227;o coronariana grave, sendo um evento incomum durante a EED. Entretanto, o aumento da for&#231;a de cisalhamento pode levar a espasmo coronariano mesmo em pacientes sem obstru&#231;&#245;es coronarianas significativas.</p>
    <p>
      <bold>Relato do Caso</bold>
    </p>
    <p>Paciente do sexo feminino com 45 anos de idade, apresentando antecedentes de hipertens&#227;o arterial sist&#234;mica e tabagismo, foi submetida a EED para pesquisa de doen&#231;a arterial coronariana. A paciente relatava hist&#243;ria de um epis&#243;dio de angina inst&#225;vel h&#225; dois anos. Na &#233;poca, foi submetida a cintilografia de perfus&#227;o mioc&#225;rdica que demonstrou defeito de perfus&#227;o sugestivo de isquemia nas paredes inferior e lateral do ventr&#237;culo esquerdo. A angiografia coronariana, realizada h&#225; dois anos, revelou irregularidades nas art&#233;rias coron&#225;rias. A fun&#231;&#227;o ventricular esquerda era normal pela ventriculografia. Um ano ap&#243;s esse epis&#243;dio anginoso, a paciente foi submetida a uma nova cintilografia de perfus&#227;o mioc&#225;rdica que mostrou aus&#234;ncia de defeitos de perfus&#227;o.</p>
    <p>Vinte dias depois, a paciente voltou a apresentar dor precordial em aperto, de discreta intensidade, que se irradiava para membro superior direito, e n&#227;o apresentava rela&#231;&#227;o com esfor&#231;os f&#237;sicos. A dor precordial geralmente ocorria no per&#237;odo da manh&#227;, tinha curta dura&#231;&#227;o e melhorava com uso de nitrato sublingual. A paciente procurou atendimento ambulatorial, recebeu medica&#231;&#227;o para tratamento de insufici&#234;ncia coronariana (&#225;cido acetilsalic&#237;lico e betabloqueador), e foi encaminhada para realiza&#231;&#227;o de ecocardiografia sob estresse farmacol&#243;gico para investiga&#231;&#227;o do quadro anginoso. A paciente n&#227;o apresentava dor precordial nas 48 horas precedentes ao teste sob estresse.</p>
    <p>O eletrocardiograma em doze deriva&#231;&#245;es (ECG) realizado em estado basal n&#227;o apresentava altera&#231;&#245;es (<xref ref-type="fig" rid="figura1">fig. 1A</xref>) e o ecocardiograma em repouso evidenciou cavidades card&#237;acas de tamanho normal, fun&#231;&#227;o sist&#243;lica global e segmentar sem altera&#231;&#245;es, e presen&#231;a de valva a&#243;rtica espessada, com dupla disfun&#231;&#227;o de grau discreto. Foi realizada ecocardiografia sob estresse pela dobutamina-atropina, seguindo o protocolo da nossa institui&#231;&#227;o. A infus&#227;o endovenosa de dobutamina foi iniciada na dose de 5 &#181;g/kg/min, e aumentada para 10, 20 e 30 &#181;g/kg/min a cada tr&#234;s minutos. A administra&#231;&#227;o de atropina (0,25 mg a cada minuto) foi iniciada na dose de 20 &#181;g/kg/min. A paciente permaneceu assintom&#225;tica, sem altera&#231;&#245;es eletrocardiogr&#225;ficas ou da motilidade segmentar ventricular esquerda at&#233; a freq&#252;&#234;ncia card&#237;aca de 148 batimentos por minuto (85% da freq&#252;&#234;ncia card&#237;aca m&#225;xima, calculada como 220 menos a idade em anos). Ao atingir a freq&#252;&#234;ncia card&#237;aca de 159 batimentos por minuto (91% da freq&#252;&#234;ncia card&#237;aca m&#225;xima), com 30 &#181;g/kg/min de dobutamina e 1,25 mg de atropina, a paciente apresentou quadro de dor precordial s&#250;bita e de forte intensidade. O ECG demonstrou presen&#231;a de eleva&#231;&#227;o do segmento ST nas deriva&#231;&#245;es DII, DIII, aVF, V5 e V6, e depress&#227;o do segmento ST nas deriva&#231;&#245;es DI, aVL, V2 e V3 (<xref ref-type="fig" rid="figura1">fig. 1B</xref>). Nesse momento, a press&#227;o arterial, aferida no membro superior direito, era 120 x 70 mmHg. O ecocardiograma revelou acinesia da parede inferior e segmento basal do septo anterior e discinesia dos segmentos m&#233;dio e basal do septo inferior (<xref ref-type="fig" rid="figura2">fig. 2</xref>). A paciente apresentou extra-s&#237;stoles ventriculares, bigeminismo ventricular e per&#237;odos de taquicardia ventricular n&#227;o-sustentada. A infus&#227;o da dobutamina foi interrompida e iniciou-se a administra&#231;&#227;o endovenosa de 15 mg de metoprolol lentamente e 5 mg de nitrato sublingual.</p>
    <fig id="figura1">
      <graphic xlink:href="1678-4170-abc-87-06-e250-00024-gf01.jpg"/></fig>
    <fig id="figura2">
      <graphic xlink:href="1678-4170-abc-87-06-e250-00024-gf02.jpg"/></fig>
    <p>A paciente evoluiu com melhora da dor precordial, por&#233;m manteve padr&#227;o de eleva&#231;&#227;o do segmento ST no ECG por um per&#237;odo de dez minutos ap&#243;s a medica&#231;&#227;o. O segmento ST retornou para linha de base somente ap&#243;s vinte minutos da interrup&#231;&#227;o do estresse (<xref ref-type="fig" rid="figura1">fig. 1C</xref>). As altera&#231;&#245;es da motilidade segmentar do ventr&#237;culo esquerdo mantiveram-se por mais de trinta minutos, e a paciente foi ent&#227;o transferida para a Unidade Coronariana.</p>
    <p>Foi realizada curva enzim&#225;tica, que mostrou dosagem de troponina card&#237;aca I igual a 3,3 e menor que 0,7 ng/ml ap&#243;s oito e quatorze horas do quadro de dor precordial, respectivamente, e o valor normal de troponina card&#237;aca I na nossa institui&#231;&#227;o &#233; &lt; 2,0 ng/ml. Os respectivos valores de creatino-kinase fra&#231;&#227;o mB (massa) foram 2,4 e &lt; 0,7 ng/ml (valor normal &lt; 4,0 ng/ml). No dia seguinte, a paciente foi submetida a angiografia coronariana que revelou art&#233;rias interventricular anterior, coron&#225;ria direita, e art&#233;ria circunflexa com irregularidades. O primeiro ramo marginal da art&#233;ria circunflexa apresentava les&#227;o ostial menor que 50% (<xref ref-type="fig" rid="f3">fig. 3</xref>). Dois dias depois do teste sob estresse, foi realizado um ecocardiograma transtor&#225;cico que mostrou fun&#231;&#227;o global e segmentar do ventr&#237;culo normal. O uso de betabloqueador foi suspenso e foi introduzida terap&#234;utica com antagonistas dos canais de c&#225;lcio e nitrato via oral. A paciente apresentou boa evolu&#231;&#227;o cl&#237;nica e recebeu alta hospitalar sem outras intercorr&#234;ncias.</p>
    <p content-type="asset">
      <fig id="f3">
        <graphic xlink:href="1678-4170-abc-87-06-e250-00024-gf03.jpg"/></fig>
    </p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>As altera&#231;&#245;es da motilidade segmentar do ventr&#237;culo esquerdo durante a EED podem ocorrer na aus&#234;ncia de altera&#231;&#245;es eletrocardiogr&#225;ficas ou, ent&#227;o, ser acompanhadas mais comumente por depress&#227;o do segmento ST. A eleva&#231;&#227;o do segmento ST durante a EED &#233; uma altera&#231;&#227;o eletrocardiogr&#225;fica incomum, sendo explicada, na maioria das vezes, pelo fen&#244;meno de vasoespasmo. Essa &#233; uma causa importante de resultados falso-positivos da EED<sup>3</sup>. A interrup&#231;&#227;o do exame, associada &#224; utiliza&#231;&#227;o de f&#225;rmacos adequados, possibilita que o paciente n&#227;o evolua para infarto do mioc&#225;rdio, evento raro, mas que pode ocorrer ap&#243;s a EED<sup>4</sup>.</p>
    <p>No teste ergom&#233;trico convencional, a eleva&#231;&#227;o do segmento ST pode ocorrer em pacientes com infarto do mioc&#225;rdio pr&#233;vio, em raz&#227;o do movimento discin&#233;tico da parede infartada, ou ser secund&#225;rio &#224;s les&#245;es coronarianas cr&#237;ticas.</p>
    <p>O primeiro relato de indu&#231;&#227;o de espasmo coronariano durante a EED foi realizado por Cohen e cols.<sup>5</sup>, que descreveram o caso de um homem de 48 anos que cursou com eleva&#231;&#227;o dos segmento ST &#237;nfero-lateral e movimento discin&#233;tico da parede inferior na dose de 40 &#181;g/kg/min de dobutamina e 0,25mg de atropina. A angiografia coronariana subseq&#252;ente n&#227;o mostrou les&#245;es obstrutivas significativas. Da mesma forma, Deligonul e cols.<sup>6</sup> relataram o caso de um homem de 35 anos, sem infarto pr&#233;vio e com coronariopatia discreta &#224; angiografia, que apresentou dor retroesternal no final do est&#225;gio de 40 &#181;g/kg/min de dobutamina, associado a eletrocardiograma com eleva&#231;&#227;o do segmento ST. A an&#225;lise da motilidade mioc&#225;rdica no momento da dor tor&#225;cica ficou prejudicada pela inquieta&#231;&#227;o do paciente. Shaheen e cols.<sup>7</sup> descreveram um caso semelhante em um homem de 48 anos, que apresentou eleva&#231;&#227;o do segmento ST no ECG acompanhado de dor tor&#225;cica, seguido de fibrila&#231;&#227;o ventricular durante a EED. A presen&#231;a de espasmo coronariano induzido pela dobutamina tamb&#233;m foi confirmada por angiografia coronariana. Yamagishi e cols.<sup>8</sup> relataram o caso de uma paciente que apresentou eleva&#231;&#227;o do segmento ST durante infus&#227;o de 20 &#181;g/kg/min de dobutamina, acompanhada de dor tor&#225;cica. A angiografia confirmou aus&#234;ncia de les&#245;es obstrutivas e documentou oclus&#227;o total do ramo distal da art&#233;ria circunflexa, causada por vasoespasmo coronariano.</p>
    <p>A resposta vasoconstritora anormal em art&#233;rias de pequeno e m&#233;dio calibre ocorre na presen&#231;a de aterosclerose, e pode estar relacionada &#224; disfun&#231;&#227;o endotelial<sup>9</sup>. A a&#231;&#227;o farmacodin&#226;mica da dobutamina nas coron&#225;rias &#233; a vasodilata&#231;&#227;o, que ocorre por estimula&#231;&#227;o dos receptores 2-adren&#233;rgicos, na presen&#231;a de endot&#233;lio vascular normofuncionante. Gordon e cols.<sup>9</sup> demonstraram que os segmentos de art&#233;ria coron&#225;ria com irregularidades parietais respondem ao exerc&#237;cio e acetilcolina com espasmo, indicando disfun&#231;&#227;o do endot&#233;lio local.</p>
    <p>O caso aqui descrito &#233; um exemplo de paciente que apresentava irregularidades nas art&#233;rias coron&#225;rias pela angiografia coronariana, sugestivas de aterosclerose, que evoluiu com espasmo induzido pela estimula&#231;&#227;o alfa-adren&#233;rgica durante a EED. &#201; de grande valia ressaltar a caracter&#237;stica s&#250;bita da instala&#231;&#227;o do quadro anginoso, da eleva&#231;&#227;o do segmento ST e da altera&#231;&#227;o da motilidade segmentar como peculiaridades do fen&#244;meno de espasmo. Em pacientes com doen&#231;a arterial coronariana obstrutiva importante, as altera&#231;&#245;es eletrocardiogr&#225;ficas e ecocardiogr&#225;ficas s&#227;o decorrentes da diminui&#231;&#227;o da reserva coronariana. Essas altera&#231;&#245;es aparecem de forma progressiva, podendo ocorrer mesmo com baixas doses de dobutamina, e pioram com o aumento do consumo mioc&#225;rdico de oxig&#234;nio. No caso que descrevemos, a paciente n&#227;o apresentava estenose coronariana significativa e n&#227;o tinha antecedente de infarto do mioc&#225;rdio. Assim, o evento eletrocardiogr&#225;fico e as altera&#231;&#245;es de motilidade segmentar do ventr&#237;culo esquerdo podem ser explicados por um fen&#244;meno de espasmo coronariano.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Embora a EED seja um m&#233;todo seguro para avalia&#231;&#227;o de doen&#231;a arterial coronariana suspeita ou conhecida, pacientes com les&#245;es obstrutivas m&#237;nimas podem apresentar espasmo coronariano durante a EED em raz&#227;o da estimula&#231;&#227;o alfa adren&#233;rgica, resultando em quadro de dor precordial e altera&#231;&#245;es eletrocardiogr&#225;ficas significativas.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflitos de interesses pertinentes.</p>
    <p>
      <fn id="back" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Jeane Mike Tsutsui </p>
        <p> Rua Harmonia, 539/74B </p>
        <p> 05435-000 &#150; S&#227;o Paulo, SP </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="jeane.tsutsui@incor.usp.br">jeane.tsutsui@incor.usp.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 27/11/05; revisado recebido em 08/12/05; aceito em 08/12/05.</p>
  </body>
  <back>
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              <surname>Picano</surname>
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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>Case Report</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Coronary spasm induced by dobutamine-atropine stress echocardiography</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>This is the report on a 45-year-old female, with a history of systemic arterial hypertension and cigarette smoking, submitted to dobutamine-atropine stress echocardiography for the investigation of coronary artery disease. At stress peak, the patient reported sudden, highly intense precordial pain. The 12-lead electrocardiogram showed ST segment elevation in DII, DIII, aVF, V5 and V6, and depression in DI, aVL, V2 and V3. Echocardiographic imaging monitoring showed dyskinesia of inferior septum and akinesia of inferior wall. The test was interrupted immediately. The patient was medicated and improved her precordial pain condition as well as wall motion abnormalities. Coronary angiography showed irregular coronary lesions with &lt;50% luminal diameter obstruction. It is a case of coronary spasm induced by alpha-adrenergic stimulation during dobutamine-atropine stress echocardiography.</p>
      </abstract>
    </front-stub>
    <body>
      <p>
        <bold>CASE REPORT</bold>
      </p>
      <p>
        <bold>Coronary spasm induced by dobutamine-atropine stress echocardiography</bold>
      </p>
      <p>
        <bold>F&#225;bio A. Bogaz; Ally N. R. Saroute; Jeane Mike Tsutsui; Ingrid Kowatsch; Francisco M. O. Neto; Jos&#233; C. Nicolau; Jos&#233; A. F. Ramires; Wilson Mathias Junior</bold>
      </p>
      <p>Instituto do Cora&#231;&#227;o (InCor) - Hospital das Cl&#237;nicas da FMUSP - S&#227;o Paulo, SP, Brazil</p>
      <p>
        <xref ref-type="corresp" rid="back-body2">Mailing Address</xref>
      </p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p>This is the report on a 45-year-old female, with a history of systemic arterial hypertension and cigarette smoking, submitted to dobutamine-atropine stress echocardiography for the investigation of coronary artery disease. At stress peak, the patient reported sudden, highly intense precordial pain. The 12-lead electrocardiogram showed ST segment elevation in DII, DIII, aVF, V5 and V6, and depression in DI, aVL, V2 and V3. Echocardiographic imaging monitoring showed dyskinesia of inferior septum and akinesia of inferior wall. The test was interrupted immediately. The patient was medicated and improved her precordial pain condition as well as wall motion abnormalities. Coronary angiography showed irregular coronary lesions with &lt;50% luminal diameter obstruction. It is a case of coronary spasm induced by alpha-adrenergic stimulation during dobutamine-atropine stress echocardiography.</p>
      <p><bold>Key words:</bold> Stress echocardiography, coronary spasm, coronary artery disease, dobutamine.</p>
      <p>Dobutamine stress echocardiography (DSE) is a widely used method for the evaluation of patients with known or suspected coronary artery disease. DSE safety profile has been established by studies involving large numbers of patients<sup>1,2</sup>. Dobutamine is a well-tolerated catecholamine, with half-life of 2 to 3 minutes. Due to its positive inotropic and chronotropic effects, it increases myocardial oxygen consumption. The evaluation of myocardial ischemia is based on the detection of decreased myocardial systolic thickening by two-dimensional echocardiography. These wall motion abnormalities are induced by an unbalance between oxygen offer and demand during stress. The presence of ST segment elevation in 12-lead electrocardiogram (ECG), in association with transitory wall motion abnormalities, is an uncommon finding during DSE, and generally indicates severe coronary obstruction. However, it is already known that the increase in arterial shear stress during DSE may lead to coronary spasm even in patients with no significant coronary obstruction.</p>
      <p>
        <bold>Case Report</bold>
      </p>
      <p>This is the report on a 45-year-old female, with a history of systemic arterial hypertension and cigarette smoking, submitted to dobutamine-atropine DSE for the investigation of coronary artery disease. The patient reported one episode of unstable angina that had occurred two years before. At that time, the patient was submitted to myocardial perfusion scintigraphy which showed myocardial perfusion abnormalities in the inferior and lateral walls of the left ventricle, suggestive of ischemia. Coronary angiography showed coronary artery irregularities. Normal left ventricular systolic function was observed at ventriculography. A year after this initial episode of angina, the patient underwent a new myocardial perfusion scintigraphy that revealed normal perfusion.</p>
      <p>Twenty days later the patient reported new episodes of chest pain irradiating to right upper limb, not associated with physical strain. Chest pain occurred in the morning, and improved after the use of sublingual nitrate. The patient went to the outpatient unit for assistance. She was administered medication for coronary artery disease (acetylsalicilic acid and betablocker) and was referred for pharmacologic stress echocardiography to investigate the angina condition. The patient was free of chest pain in the 48 hours preceding the stress test.</p>
      <p>The baseline 12-lead ECG did not show any abnormality (<xref ref-type="fig" rid="figura1-body2">Fig. 1A</xref>) and the echocardiogram at rest showed normal sized cardiac cavities, normal global systolic function and no abnormalities in segmental wall motion. Aortic valve was thickened, with mild dysfunction. Dobutamine-atropine stress echocardiography was carried out following institutional protocol. Intravenous dobutamine infusion was started at 5 &#181;g/kg/min dose and increased to 10, 20 and 30 &#181;g/kg/min every three minutes. Atropine was started at 20 &#181;g/kg/min (0.25 mg every minute). At 30 &#181;g/kg/min of dobutamine and 1.25 mg de atropine, the patient presented sudden, highly intense chest pain. At this time, heart rate reached 159 beats per minute (91% of maximum heart rate, calculated as 220 &#150; age in years) and blood pressure was 120 x 70 mmHg. ST segment showed elevation in DII, DIII, aVF, V5 and V6, and depression in DI, aVL, V2 and V3 (<xref ref-type="fig" rid="figura1-body2">Fig. 1B</xref>). Echocardiogram showed akinesia of inferior wall and basal segment of the anterior septum; and diskynesia of mid and basal segments of inferior septum (<xref ref-type="fig" rid="figura2-body2">Fig. 2</xref>). The patient presented premature ventricular complexes, bigeminism, and periods of non-sustained ventricular tachycardia. The dobutamine infusion was interrupted. Intravenous metoprolol (15 mg) was administered slowly, as well as 5 mg of nitrate sublingually. After medication, the chest pain disappeared, but elevation of ST segment was maintained for ten minutes. There was return of ST segment to baseline levels only twenty minutes after stress interruption (<xref ref-type="fig" rid="figura1-body2">Fig. 1C</xref>). Left ventricular wall motion abnormalities were kept for another thirty minutes, and the patient was transferred to the intensive care coronary unit. Cardiac troponin I dosages were 3.3 ng/ml and &lt; 0.7 ng/ml, after eight and fourteen hours of chest pain, respectively (normal value at our institution is &lt; 2.0 ng/ml). Creatine-kinase mB fraction (mass) values were 2.4 ng/ml and &lt; 0.7 ng/ml, respectively (normal value &lt; 4.0 ng/ml).</p>
      <fig id="figura1-body2">
        <graphic xlink:href="1678-4170-abc-87-06-e250-00024-gf01-en.jpg"/></fig>
      <fig id="figura2-body2">
        <graphic xlink:href="1678-4170-abc-87-06-e250-00024-gf02-en.jpg"/></fig>
      <p>On the following day, the patient was submitted to coronary angiography that showed irregulatiries in left anterior descending coronary artery, right coronary artery, and left circumflex. The first marginal branch of the left circumflex showed &lt; 50% ostial lesion (<xref ref-type="fig" rid="e24f3-body2">Fig. 3</xref>). Two days after the stress test a transthoracic echocardiogram showed normal left ventricular global and segmental function. Betablocker therapy was interrupted, and calcium channel blocker and nitrate were introduced orally. The patient had satisfactory clinical course and was discharged from hospital with no other events.</p>
      <p content-type="asset">
        <fig id="e24f3-body2">
          <graphic xlink:href="1678-4170-abc-87-06-e250-00024-gf03-en.jpg"/></fig>
      </p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>Left ventricular wall motion abnormalities during DSE may occur with no electrocardiographic abnormalities. Or rather, and more commonly, may be associated with ST segment depression. ST segment elevation during DSE is an uncommon electrocardiographic abnormality, and most times is explained by a coronary spasm phenomenon. This is a major explanation for pseudo-positive DSE results<sup>3</sup>. Test interruption, associated to the use of proper drugs, helps preventing myocardial infarction, that is a rare complication that may occur after DSE<sup>4</sup>.</p>
      <p>In the conventional ergometric test, ST segment elevation may occur in patients with previous myocardial infarction, due to the diskynetic motion of infarcted wall, or in patients with severe coronary lesions.</p>
      <p>Cohen et al<sup>5</sup> were the first to report coronary spasm induction during DSE. The authors described the case of a 48-year-old male who showed ST segment elevation in the infero-lateral leads and dyskinetic motion in the inferior wall at 40 &#181;g/kg/min of dobutamine and 0.25mg of atropine. Subsequent coronary angiography revealed no significant obstructive lesions. Deligonul et al<sup>6</sup> have reported the case of a 35-year-old male with no previous history of infarction and mild coronary lesions at angiography. The patient presented chest pain at the end of the 40 &#181;g/kg/min of dobutamine, and ST segment elevation. Segmental wall motion analysis at the moment of chest pain was jeopardized by patient's unquietness.</p>
      <p>Shaheen et al<sup>7</sup> have described a similar case &#150; a 48-year-old male with ST segment elevation at ECG, associated to chest pain, and followed by ventricular fibrillation during DSE. Dobutamine-induced coronary spasm was also confirmed by coronary angiography. Yamagishi et al<sup>8</sup> have reported the case of a female patient with ST segment elevation during the stage of 20 &#181;g/kg/min of dobutamine infusion, associated to chest pain. Angiography confirmed the absence of obstructive lesions and documented total occlusion of distal branch of the left circumflex artery as a result of coronary spasm.</p>
      <p>Abnormal vasoconstricting response in small and mid-sized arteries occurs in the presence of atherosclerosis and may be related to endothelial dysfunction<sup>9</sup>. The dobutamine pharmacodynamic action in the coronary arteries is primarily vasodilation, which occurs because of b2-adrenergic receptors stimulation in the presence of normofunctioning vascular endothelium.</p>
      <p>Gordon et al<sup>9</sup> have demonstrated that coronary artery segments with parietal irregularities respond to exercise and to acetylcholine with spasm, thus indicating local endothelium dysfunction.</p>
      <p>The case described here is an example of a patient who had coronary arteries irregularities at coronary angiography. These abnormalities indicate atherosclerostic process which was complicated by spasm induced by the adrenergic stimulation during DSE. It is extremely relevant to point out the sudden onset of the angina, ST segment elevation, and of the wall motion abnormalities as peculiar to the spasm phenomenon. In patients with significant coronary artery disease, electrocardiographic and echocardiographic abnormalities result from reduced coronary reserve. These abnormalities arise gradually, and may even occur at low doses of dobutamine and worsen as myocardial oxygen consumption increases. In the case described the patient had no significant coronary artery stenosis; neither did she have previous history of myocardial infarction. Therefore, the electrocardiographic event as well as left ventricular wall motion abnormalities may be explained by a coronary spasm phenomenon.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>Although DSE is a safe method to evaluate patients with suspected or known coronary artery disease, patients with minimally obstructive lesions may present coronary spasm during DSE as a result of alpha-adrenergic stimulation, resulting in chest pain and significant electrocardiographic abnormalities.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>References</bold>
      </p>
      <p>
        <fn id="back-body2" fn-type="corresp">
          <label>
            <bold>Mailing Address:</bold>
          </label>
          <p> Jeane Mike Tsutsui</p>
          <p> Rua Harmonia, 539/74B</p>
          <p> 05435-000 &#150; S&#227;o Paulo, SP</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="jeane.tsutsui@incor.usp.br">jeane.tsutsui@incor.usp.br</email>
          </p>
        </fn>
      </p>
      <p>Manuscript received November 27, 2005; revised Manuscript received December 8, 2005; accepted on December 8, 2005.</p>
    </body>
  </sub-article>
</article>
