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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">YW5dCQ3Rck3HGkLk7RtVwZm</article-id>
      <article-id pub-id-type="other">00017</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2005000400017</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(05)08400417</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2005000400017</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Atualiza&#231;&#227;o</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Determina&#231;&#227;o de par&#226;metros hemodin&#226;micos atrav&#233;s do ecocardiograma bidimensional com Doppler: ferramenta para busca de otimiza&#231;&#227;o terap&#234;utica em pacientes ambulatoriais com insufici&#234;ncia card&#237;aca congestiva</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Palombini</surname>
            <given-names>Dora V.</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rohde</surname>
            <given-names>Luis E.</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Crestana</surname>
            <given-names>Leticia</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Goldraich</surname>
            <given-names>L&#237;via</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lima</surname>
            <given-names>Marta Pereira</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Campos</surname>
            <given-names>Candice</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Clausell</surname>
            <given-names>Nadine</given-names>
          </name>
        </contrib>
      </contrib-group>
      <pub-date date-type="collection" publication-format="electronic">
        <month>04</month>
        <year>2005</year>
      </pub-date>
      <volume>84</volume>
      <issue>4</issue>
      <fpage>351</fpage>
      <lpage>356</lpage>
      <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>
      <pub-date publication-format="electronic" date-type="pub">
        <day>03</day>
        <month>05</month>
        <year>2005</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ATUALIZA&#199;&#195;O</bold>
    </p>
    <p>Determina&#231;&#227;o de par&#226;metros hemodin&#226;micos atrav&#233;s do ecocardiograma bidimensional com Doppler: ferramenta para busca de otimiza&#231;&#227;o terap&#234;utica em pacientes ambulatoriais com insufici&#234;ncia card&#237;aca congestiva</p>
    <p>
      <bold>Dora V. Palombini; Luis E. Rohde; Leticia Crestana; L&#237;via Goldraich; Marta Pereira Lima; Candice Campos; Nadine Clausell</bold>
    </p>
    <p> Porto Alegre, RS</p>
    <p>Hospital de Cl&#237;nicas de Porto Alegre </p>
    <p> Programa de P&#243;s-Gradua&#231;&#227;o em Ci&#234;ncias Cardiovasculares: Cardiologia </p>
    <p>
      <xref ref-type="corresp" rid="end">Endere&#231;o para correspond&#234;ncia</xref>
    </p>
    <p>Um dos principais problemas no manejo dos pacientes com insufici&#234;ncia card&#237;aca grave s&#227;o as freq&#252;entes hospitaliza&#231;&#245;es por descompensa&#231;&#227;o, que, al&#233;m de causar grande &#244;nus para o sistema de sa&#250;de previdenci&#225;rio, &#233; uma das principais causas da perda de qualidade de vida destes pacientes. Em m&#233;dia 30 a 50% dos pacientes reinternam ap&#243;s 3 a 6 meses da alta hospitalar<sup>1</sup>. Uma metan&#225;lise recente indicou que a freq&#252;&#234;ncia dessas rehospitaliza&#231;&#245;es pode ser reduzida atrav&#233;s de acompanhamento constante de uma equipe multidisciplinar de m&#233;dicos e enfermeiras em cl&#237;nica especializada em insufici&#234;ncia card&#237;aca<sup>2,3</sup>. Portanto, um acompanhamento meticuloso com tratamento individualizado e dirigido, para situa&#231;&#227;o espec&#237;fica e atual de cada paciente, poderia trazer benef&#237;cios a m&#233;dio e longo prazo no tratamento ambulatorial dos pacientes cr&#244;nicos com insufici&#234;ncia card&#237;aca congestiva moderada a grave. Neste artigo apontamos as potenciais aplica&#231;&#245;es de m&#233;todos como o ecocardiograma para o manejo otimizado de pacientes com insufici&#234;ncia card&#237;aca congestiva e apresentamos resultados iniciais da utiliza&#231;&#227;o deste instrumento para guiar sua terap&#234;utica. </p>
    <p><bold>Peculiaridades no desenvolvimento e nas manifesta&#231;&#245;es de congest&#227;o e baixo d&#233;bito na insufici&#234;ncia card&#237;aca congestiva - </bold>Em pacientes com insufici&#234;ncia card&#237;aca congestiva uma importante causa de rehospitaliza&#231;&#227;o e/ou visita &#224; sala de emerg&#234;ncia est&#225; associada a quadros congestivos<sup>4,5</sup>. Por outro lado, o diagn&#243;stico cl&#237;nico de estados congestivos pode ser, particularmente, dif&#237;cil em pacientes cr&#244;nicos, devido a uma s&#233;rie de adapta&#231;&#245;es fisiopatol&#243;gicas que fazem com que as manifesta&#231;&#245;es cl&#237;nicas de congest&#227;o sejam sutis nesses pacientes, freq&#252;entemente levando &#224; sub-utiliza&#231;&#227;o de diur&#233;ticos e vasodilatadores<sup>6</sup>, o que, por sua vez, contribui para risco de descompensa&#231;&#227;o. </p>
    <p>A identifica&#231;&#227;o de press&#245;es de enchimento ventricular elevadas na insufici&#234;ncia card&#237;aca congestiva n&#227;o segue o mesmo padr&#227;o dos achados cl&#237;nicos semi&#243;ticos encontrados nos quadros agudos, a ser considerada para tomada de decis&#245;es terap&#234;uticas. Um dos principais sinais e sintomas de congest&#227;o &#233; a eleva&#231;&#227;o da press&#227;o venosa jugular e a ortopn&#233;ia. A avalia&#231;&#227;o cl&#237;nica da press&#227;o venosa jugular requer t&#233;cnica cuidadosa, pois parece ser o sinal cl&#237;nico mais importante na avalia&#231;&#227;o do real estado congestivo dos portadores de insufici&#234;ncia card&#237;aca congestiva<sup>7</sup>. </p>
    <p>Sabe-se que na insufici&#234;ncia card&#237;aca congestiva, a concord&#226;ncia entre estimativas de press&#245;es &#224; direita e &#224; esquerda &#233; de 80%, pois Drazner e cols.<sup>8</sup> demonstraram que atrav&#233;s de uma press&#227;o atrial direita (PAD) &gt; ou &lt; 10mmHg &#233; poss&#237;vel estimar uma press&#227;o atrial esquerda (PAE) &gt; ou &lt; 22mmhg, respectivamente<sup>8,9</sup>. Outros fatores, como: compress&#227;o abdominal com refluxo hepato-jugular positivo, resposta press&#243;rica tipo "raiz quadrada" &#224; manobra de Valsalva e hiperfonese de 2&#186; bulha tamb&#233;m podem sinalizar eleva&#231;&#227;o das press&#245;es em cavidades direitas que, por sua vez, podem estimar press&#245;es altas &#224; esquerda<sup>9,10</sup>. </p>
    <p>Devido &#224; drenagem linf&#225;tica compensat&#243;ria existente cronicamente em portadores de insufici&#234;ncia card&#237;aca congestiva, estertores pulmonares est&#227;o ausentes em mais de 80% dos casos, mesmo existindo press&#245;es de enchimento elevadas. J&#225; os sintomas de dispn&#233;ia e cansa&#231;o se devem ao fato de que mesmo que o fluido intersticial residual n&#227;o comprometa a oxigena&#231;&#227;o, pode provocar uma restri&#231;&#227;o na inspira&#231;&#227;o e redu&#231;&#227;o da complac&#234;ncia pulmonar<sup>6</sup>. </p>
    <p>Edema de membros inferiores ocorre em apenas 25% dos pacientes com insufici&#234;ncia card&#237;aca congestiva abaixo dos 70 anos de idade, enquanto que nos mais velhos pode ser causado mais por fatores locais do que por eleva&#231;&#227;o da press&#227;o venosa central propriamente dita. Com estes dados &#233; poss&#237;vel sugerir que edema perif&#233;rico e press&#227;o venosa jugular elevada sejam mais espec&#237;ficos do que sens&#237;veis para detectar press&#245;es de enchimento esquerdas elevadas. </p>
    <p>A 3&#186; bulha est&#225; presente na maioria dos pacientes em insufici&#234;ncia card&#237;aca congestiva, e, em alguns pacientes, pelo contr&#225;rio, nunca &#233; identificada. Cumpre ressaltar que o grau de concord&#226;ncia, mesmo por m&#233;dicos experientes, &#233; moderado ou baixo sobre a presen&#231;a ou n&#227;o de 3&#186; bulha. Esse fato provavelmente est&#225; ligado &#224; perda de treinamento auscultat&#243;rio em tempos de m&#233;todos diagn&#243;sticos mais sofisticados e de f&#225;cil acessibilidade<sup>11-13</sup>. Alguns autores sugerem que a 3&#186; bulha n&#227;o se constitui em um par&#226;metro de avalia&#231;&#227;o confi&#225;vel do estado congestivo dos pacientes com insufici&#234;ncia card&#237;aca congestiva<sup>6</sup>. Ainda assim, a presen&#231;a de 3&#186; bulha e a eleva&#231;&#227;o da press&#227;o venosa jugular na insufici&#234;ncia card&#237;aca congestiva est&#227;o associados, independentemente, com maior incid&#234;ncia de hospitaliza&#231;&#245;es por insufici&#234;ncia card&#237;aca (RR=1,32, p &lt; 0,01), morte ou hospitaliza&#231;&#245;es por insufici&#234;ncia card&#237;aca (RR=1,30, p &lt; 0,005) e morte por insufici&#234;ncia card&#237;aca (RR=1,37, p &lt; 0,05)<sup>4</sup>. </p>
    <p>A raz&#227;o pela qual a eleva&#231;&#227;o da press&#227;o venosa jugular ou presen&#231;a de 3&#186; bulha est&#225; associada a um risco elevado de progress&#227;o da insufici&#234;ncia card&#237;aca congestiva n&#227;o &#233; clara. Press&#227;o venosa jugular elevada reflete aumento da press&#227;o atrial direita, que, por si s&#243;, se correlaciona com press&#245;es esquerdas elevadas nos pacientes com insufici&#234;ncia card&#237;aca congestiva. Estas, por sua vez, est&#227;o associadas com mau progn&#243;stico, possivelmente, pela apoptose desencadeada pela tens&#227;o parietal mioc&#225;rdica e pela ativa&#231;&#227;o do sistema nervoso simp&#225;tico<sup>14,15</sup>. A 3&#186; bulha, mais ligada &#224; baixa complac&#234;ncia do ventr&#237;culo esquerdo e a press&#245;es e velocidades de enchimento elevadas, tamb&#233;m tem sido associada a um mau progn&#243;stico por dist&#250;rbio na di&#225;stole em pacientes com disfun&#231;&#227;o sist&#243;lica<sup>4</sup>. </p>
    <p>Um dos poucos instrumentos cl&#237;nicos &#250;teis &#224; beira do leito na avalia&#231;&#227;o dos pacientes com insufici&#234;ncia card&#237;aca congestiva &#233; a press&#227;o de pulso (press&#227;o sist&#243;lica - press&#227;o diast&#243;lica / press&#227;o sist&#243;lica), que, quando &lt; que 25% estima um &#237;ndice card&#237;aco de 2,2 L/min/m<sup>2-6</sup>. Tamb&#233;m se pode utilizar com uma acur&#225;cia de 93%, a raz&#227;o entre a press&#227;o de pulso obtida com a respira&#231;&#227;o normal e a press&#227;o de pulso durante a manobra de Valsalva, para estimar a press&#227;o atrial esquerda<sup>16</sup>. </p>
    <p>Al&#233;m destas caracter&#237;sticas, em pacientes com insufici&#234;ncia card&#237;aca congestiva e di&#226;metros ventriculares aumentados, o grau de regurgita&#231;&#227;o mitral &#233;, via de regra, significativo, contribuindo de forma importante para o aparecimento de sinais e sintomas de congest&#227;o e baixo d&#233;bito. O mecanismo respons&#225;vel pela regurgita&#231;&#227;o mitral na insufici&#234;ncia card&#237;aca congestiva &#233; a n&#227;o coapta&#231;&#227;o adequada dos folhetos mitrais devido &#224; dilata&#231;&#227;o do anel mitral e comprometimento da geometria do aparato subvalvular<sup>17</sup>. Com a compensa&#231;&#227;o do quadro congestivo e redu&#231;&#227;o do volume ventricular e atrial esquerdo, a insufici&#234;ncia mitral e o orif&#237;cio regurgitante efetivo reduzem-se consideravelmente. Com isto, o "roubo" no volume sist&#243;lico de mais de 50%, que ocorre nos pacientes sintom&#225;ticos em repouso, &#233; redistribu&#237;do, e h&#225; um aumento do volume sist&#243;lico efetivo ventricular esquerdo<sup>18</sup>. Devido ao fato dos sintomas dominantes serem secund&#225;rios &#224; congest&#227;o, o conseq&#252;ente al&#237;vio dos sintomas em repouso se deve principalmente &#224; redu&#231;&#227;o de press&#245;es de enchimento elevadas. Outros fatores afetados positivamente pela redu&#231;&#227;o das press&#245;es de enchimento s&#227;o: a melhora da perfus&#227;o coronariana, a redu&#231;&#227;o da ativa&#231;&#227;o neurohormonal com redu&#231;&#227;o da libera&#231;&#227;o de norepinefrina e do estresse parietal<sup>14,19,20</sup>, melhora da capacidade funcional<sup>21</sup>, redu&#231;&#227;o de citocinas circulantes, dos pept&#237;deos natriur&#233;ticos, da congest&#227;o hep&#225;tica e mais adiante da desnutri&#231;&#227;o progressiva dos pacientes cr&#244;nicos<sup>22</sup>. </p>
    <p>Ao contr&#225;rio daqueles pacientes no p&#243;s-infarto agudo do mioc&#225;rdio, em que o mioc&#225;rdio enrijecido, ainda n&#227;o dilatado, se beneficia de press&#245;es de enchimento altas, pacientes com ventr&#237;culos cronicamente dilatados possuem sarc&#244;meros maximamente alongados, em que uma maior sobrecarga de press&#227;o ou volume n&#227;o ir&#225; along&#225;-lo ainda mais, mas sim, aumentar a tens&#227;o da parede e a incompet&#234;ncia valvular. Portanto, a redu&#231;&#227;o das press&#245;es de enchimento para n&#237;veis normais ou baixos com diur&#233;ticos e vasodilatadores, se reflete em aumento do volume sist&#243;lico. Este aumento se deve n&#227;o a uma melhora na fra&#231;&#227;o de eje&#231;&#227;o, que pouco se eleva, mas a grande redu&#231;&#227;o do volume sist&#243;lico perdido na regurgita&#231;&#227;o mitral<sup>23</sup>. </p>
    <p><bold>Otimiza&#231;&#227;o hemodin&#226;mica na insufici&#234;ncia card&#237;aca - </bold>Os objetivos b&#225;sicos que regem a terapia cl&#237;nica da insufici&#234;ncia card&#237;aca guiada por otimiza&#231;&#227;o hemodin&#226;mica s&#227;o aqueles definidos por Stevenson e cols.; especificamente - press&#227;o atrial esquerda de 15mmHg ou menos, press&#227;o de &#225;trio direito <underline>&lt;</underline> a 8mmHg, resist&#234;ncia vascular sist&#234;mica em torno de 1.200dinas/seg/cm-<sup>5</sup>, com press&#227;o arterial sist&#243;lica <underline>&gt;</underline> a 80mmHg<sup>24</sup>. Classicamente esta estrat&#233;gia requer ambiente de terapia intensiva com a utiliza&#231;&#227;o de cateter em art&#233;ria pulmonar. Redesenhando a terapia por 24 a 72h de acordo com a hemodin&#226;mica, utilizando essencialmente vasodilatador (nitroprussiato de s&#243;dio) e diur&#233;tico de al&#231;a (furosemide) intravenosos, pode-se otimizar o perfil hemodin&#226;mico e manter o paciente clinicamente est&#225;vel por v&#225;rios meses seguintes, com razo&#225;vel melhora dos sintomas, permitindo, inclusive, sua retirada, mesmo que provis&#243;ria, da lista de transplante card&#237;aco<sup>25-28</sup>. Embora a estrat&#233;gia de otimiza&#231;&#227;o hemodin&#226;mica, utilizando cateter em art&#233;ria pulmonar tenha repetidamente trazido resultados com melhora de desfechos funcionais e cl&#237;nicos, estes s&#227;o dados observacionais, n&#227;o testados em ensaio cl&#237;nico. Neste sentido, o estudo multic&#234;ntrico, randomizado, denominado ESCAPE est&#225; em andamento, comparando a estrat&#233;gia invasiva com manejo cl&#237;nico na insufici&#234;ncia card&#237;aca congestiva<sup>29</sup>. Estudos como esse devem responder se esta estrat&#233;gia de fato altera desfechos, criando sobreviventes, ou simplesmente identifica aqueles com mais chances de sobreviver, independentemente, da estrat&#233;gia terap&#234;utica utilizada. </p>
    <p>Al&#233;m de proporcionar adequa&#231;&#227;o do perfil hemodin&#226;mico com esta abordagem, estudo recente demonstrou que nos pacientes com s&#233;rio comprometimento hemodin&#226;mico, interven&#231;&#245;es com diur&#233;ticos e vasodilatadores, sem inotr&#243;picos, dirigidas para normalizar as condi&#231;&#245;es de sobrecarga e resist&#234;ncia sist&#234;mica reduzem marcadores de ativa&#231;&#227;o neurohumoral, como pept&#237;deo natriur&#233;tico atrial (ANP), pept&#237;deo natriur&#233;tico cerebral (BNP), e os vasoconstritores endotelina e norepinefrina<sup>30</sup>. Neste sentido, foi demonstrado que a intensifica&#231;&#227;o da terapia da insufici&#234;ncia card&#237;aca congestiva com diur&#233;ticos e inibidores da enzima de convers&#227;o da angiotensina (IECA) reduz os n&#237;veis s&#233;ricos do BNP, e, al&#233;m disso, pacientes tratados com terapia guiada por valores de BNP tiveram redu&#231;&#227;o de eventos cardiovasculares de 35% (p=0,02) em rela&#231;&#227;o ao grupo em acompanhamento cl&#237;nico apenas<sup>31</sup>. Por outro lado, dados recentes indicam que 54% dos pacientes com n&#237;veis basais de BNP de 480 pg/ml ou mais ter&#227;o um novo epis&#243;dio de congest&#227;o em 6 meses<sup>32</sup>. Este conjunto de dados indica que guiar o tratamento da insufici&#234;ncia card&#237;aca congestiva descompensada, objetivando redu&#231;&#245;es de press&#245;es de enchimento, seja atrav&#233;s de dados num&#233;ricos de hemodin&#226;mica, seja atrav&#233;s de redu&#231;&#227;o de n&#237;veis de BNP (marcador que se eleva indicando distens&#227;o dos sarc&#244;meros), traz benef&#237;cios cl&#237;nicos para estes pacientes. </p>
    <p><bold>Ferramentas alternativas para caracteriza&#231;&#227;o de par&#226;metros hemodin&#226;micos - </bold>A imensa maioria dos dados preconizando a busca de otimiza&#231;&#227;o hemodin&#226;mica adv&#233;m de estudos utilizando cateter em art&#233;ria pulmonar para avalia&#231;&#227;o invasiva dos par&#226;metros hemodin&#226;micos. Evidentemente, que esta estrat&#233;gia necessariamente se restringe a ambiente de terapia intensiva e se aplica &#224;queles pacientes em quadro de insufici&#234;ncia card&#237;aca congestiva descompensada que buscaram atendimento hospitalar. Considerando a import&#226;ncia de manter os pacientes com insufici&#234;ncia card&#237;aca congestiva euvol&#234;micos de forma a evitar ou proteg&#234;-los de descompensa&#231;&#245;es por congest&#227;o, ferramentas para utiliza&#231;&#227;o em ambiente ambulatorial seriam desej&#225;veis. Neste sentido, outros m&#233;todos n&#227;o invasivos para avaliar d&#233;bito card&#237;aco e press&#245;es de enchimento, como ecocardiografia com Doppler e dispositivo de bioimpend&#226;ncia, podem ser instrumentos &#250;teis para o acompanhamento e individualiza&#231;&#227;o da terapia da insufici&#234;ncia card&#237;aca congestiva<sup>33,9</sup>. </p>
    <p>Estudo recente utilizando um monitor hemodin&#226;mico de press&#245;es do ventr&#237;culo direito (<italic>Medtronic Incorporation</italic>) foi implantado como um marcapasso para guiar o manejo cl&#237;nico di&#225;rio em 32 pacientes com insufici&#234;ncia card&#237;aca congestiva, e resultou numa redu&#231;&#227;o de 57% das hospitaliza&#231;&#245;es (p &lt; 0,01)<sup>34</sup>. </p>
    <p><bold>Avalia&#231;&#227;o hemodin&#226;mica ecocardiogr&#225;fica - </bold>O ecocardiograma como ferramenta para avalia&#231;&#227;o hemodin&#226;mica pode ser uma alternativa atraente, pois pode fornecer, na grande maioria dos pacientes em insufici&#234;ncia card&#237;aca, dados hemodin&#226;micos com excelente correla&#231;&#227;o &#224;queles colhidos concomitantemente por cateterismo direito<sup>35,36</sup>. As press&#245;es do lado direito, por exemplo, podem ser obtidas em 97% das vezes ao se avaliar as press&#245;es diast&#243;lica (89%) e sist&#243;lica (73,5%) na art&#233;ria pulmonar<sup>37</sup>. </p>
    <p>Na insufici&#234;ncia card&#237;aca congestiva, estimativas de press&#245;es de enchimento &#224; direita podem ser feitas utilizando par&#226;metros ecocardiogr&#225;ficos, como por exemplo, o di&#226;metro da veia cava inferior associado ao seu &#237;ndice de colapsabilidade na inspira&#231;&#227;o. A tend&#234;ncia da veia cava inferior de colapsar total ou parcialmente ocorre porque durante a inspira&#231;&#227;o aumenta a press&#227;o negativa intrator&#225;cica, e desde que a veia cava inferior e as cavidades direitas n&#227;o estejam sobrecarregadas, o fluxo de sangue deve aumentar em dire&#231;&#227;o ao &#225;trio direito, causando o colabamento parcial ou total desse vaso. Nos casos em que, por motivos t&#233;cnicos, n&#227;o for poss&#237;vel avaliar a veia cava inferior e n&#227;o houver evid&#234;ncia de eleva&#231;&#227;o de press&#245;es em cavidades direitas, &#233; consenso geral a utiliza&#231;&#227;o simplesmente de um valor arbitr&#225;rio m&#233;dio de 10mmHg<sup>38</sup>. </p>
    <p>A press&#227;o em art&#233;ria pulmonar pode ser obtida atrav&#233;s da medida das velocidades das regurgita&#231;&#245;es entre cavidades direitas, basicamente regurgita&#231;&#227;o tric&#250;spide e pulmonar. Com uma avalia&#231;&#227;o completa de todas as "janelas" ecocardiogr&#225;ficas &#233; poss&#237;vel registrar o gradiente transvalvar trans-tricusp&#237;deo e a regurgita&#231;&#227;o pulmonar em 86% e 89% dos exames, respectivamente. Foi demonstrado que adicionando as duas possibilidades, em 97% de uma s&#233;rie de 200 pacientes detectou-se algum valor press&#243;rico em art&#233;ria pulmonar<sup>37,39</sup>. Em pacientes que n&#227;o apresentam regurgita&#231;&#227;o pulmonar em grau suficiente para estimar gradiente, utiliza-se a regurgita&#231;&#227;o tric&#250;spide no momento da abertura da v&#225;lvula pulmonar como estimativa da press&#227;o diast&#243;lica na art&#233;ria pulmonar. Esta t&#233;cnica simples mostrou uma correla&#231;&#227;o de r=0,92 com o cateterismo card&#237;aco, excluindo-se os pacientes com insufici&#234;ncia tric&#250;spide severa e aqueles em ventila&#231;&#227;o mec&#226;nica<sup>40,41</sup>. </p>
    <p>Outro importante dado hemodin&#226;mico, o d&#233;bito card&#237;aco, tamb&#233;m pode ser calculado por dados ecocardiogr&#225;ficos, apresentando um coeficiente de correla&#231;&#227;o com os dados obtidos pelo cateterismo direito de r=0,97<sup>35</sup>. Para tal, basta adquirir o produto da freq&#252;&#234;ncia card&#237;aca pelo tempo da integral de velocidade (TVI) e pela &#225;rea do trato da via de sa&#237;da do ventr&#237;culo esquerdo, corrigindo pela superf&#237;cie corporal para obter os valores de &#237;ndice card&#237;aco. </p>
    <p>A press&#227;o capilar pulmonar &#233; um par&#226;metro bem estabelecido na avalia&#231;&#227;o da fun&#231;&#227;o card&#237;aca e de enchimento ventricular esquerdo. Nos pacientes com insufici&#234;ncia card&#237;aca congestiva, a press&#227;o capilar pulmonar elevada est&#225; associada com um mau progn&#243;stico, descompensa&#231;&#245;es freq&#252;entes dos sintomas e baixa toler&#226;ncia ao exerc&#237;cio<sup>42-45</sup>. Redu&#231;&#227;o destes valores ap&#243;s tratamento adequado melhora a qualidade de vida dos pacientes<sup>46</sup>. A utiliza&#231;&#227;o de dados referentes a estes valores pode auxiliar no manejo terap&#234;utico rotineiro de pacientes com insufici&#234;ncia card&#237;aca congestiva. </p>
    <p>A press&#227;o capilar pulmonar ou atrial esquerda podem ser estimadas pela avalia&#231;&#227;o da velocidade do fluxo na art&#233;ria pulmonar, caso o paciente n&#227;o tenha doen&#231;a pulmonar, ou pelo fluxo transmitral e venoso pulmonar do lado esquerdo. A an&#225;lise do fluxo transmitral, tamb&#233;m, fornece informa&#231;&#245;es da press&#227;o atrial esquerda e progn&#243;sticas na insufici&#234;ncia card&#237;aca. No entanto, &#233; dependente de m&#250;ltiplas condi&#231;&#245;es, como freq&#252;&#234;ncia card&#237;aca, relaxamento e suc&#231;&#227;o ventricular, complac&#234;ncia atrial e ventricular esquerda e condi&#231;&#245;es da v&#225;lvula mitral. Para evitar a interfer&#234;ncia destes fatores, outros par&#226;metros como o fluxo venoso pulmonar, a resposta do fluxo transmitral para diferentes cargas de volume, o modo M colorido, e o Doppler tecidual do &#226;nulo mitral podem ser utilizados. A estimativa da press&#227;o atrial esquerda tamb&#233;m n&#227;o pode ser feita com regras isoladas, mas sim ap&#243;s avalia&#231;&#227;o de v&#225;rios par&#226;metros e respeitando as limita&#231;&#245;es de cada um. Para fins pr&#225;ticos considera-se que a press&#227;o capilar pulmonar e a press&#227;o de &#225;trio esquerdo s&#227;o equivalentes, porque os capilares pulmonares, as veias pulmonares e o &#225;trio esquerdo se comunicam livremente, formando na verdade uma grande c&#226;mara. Medidas simult&#226;neas de cateterismo direito e do &#225;trio esquerdo atrav&#233;s de cateteriza&#231;&#227;o transeptal j&#225; confirmaram a similaridade destas press&#245;es<sup>47-49</sup>. Os diversos c&#225;lculos utilizados para obter dados hemodin&#226;micos atrav&#233;s do ecocardiograma est&#227;o compilados na <xref ref-type="table" rid="tab01">tabela I</xref>. </p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-84-04-0351-00017-gt01.jpg"/></table-wrap>
    <p><bold>Outros m&#233;todos - </bold>O Doppler tecidual &#233; uma t&#233;cnica relativamente nova que registra as velocidades sist&#243;lica e diast&#243;lica do mioc&#225;rdio ao n&#237;vel do &#226;nulo mitral, preferencialmente, medial ou lateral. Devem-se usar filtros para eliminar as altas freq&#252;&#234;ncias e o limite de Nyquist deve ser mantido entre &#150;15 a 20 cm/s. Ao contr&#225;rio do fluxo transmitral (onda E), a velocidade registrada no &#226;nulo mitral pelo Doppler tecidual (E<sub>a</sub>) n&#227;o sofre a influ&#234;ncia da press&#227;o atrial esquerda e sim reflete o relaxamento ventricular esquerdo isoladamente. Assim sendo, &#233; um &#243;timo &#237;ndice para avaliar d&#233;ficit de relaxamento, mesmo nos casos pseudonormais, e quando acoplado ao fluxo transmitral n&#227;o tecidual pode estimar a press&#227;o atrial esquerda. Uma raz&#227;o E/ E<sub>a </sub>&gt; 10 pode prever uma PAE &gt; 12mmhg com uma sensibilidade de 91% e uma especificidade de 81%, ou uma rela&#231;&#227;o E/ E<sub>a </sub>&gt; 10 pode prever uma PAE &gt; 15mmhg com uma sensibilidade de 97% e especificidade de 78%. Ommen e cols.<sup>50</sup> demonstraram um n&#237;vel de correla&#231;&#227;o para a rela&#231;&#227;o E/ E<sub>a medial</sub> e a press&#227;o m&#233;dia diast&#243;lica do ventr&#237;culo esquerdo de r=0,64, maior nos pacientes com fra&#231;&#227;o de eje&#231;&#227;o menor do que 50%, comparativamente, &#224;queles sem disfun&#231;&#227;o ventricular. Esses autores tamb&#233;m demonstraram um valor preditivo positivo de 64% para uma press&#227;o diast&#243;lica final do ventr&#237;culo esquerdo &gt; de 12mmHg se E/ E<sub>a </sub>&gt; 15mmHg e um valor preditivo negativo de 97% para press&#245;es baixas no &#225;trio esquerdo se a rela&#231;&#227;o E/ E<sub>a </sub>for &lt; 8. Na presen&#231;a de infarto da parede lateral basal, fibrila&#231;&#227;o atrial e insufici&#234;ncia mitral severa h&#225; limita&#231;&#245;es t&#233;cnicas importantes que podem inviabilizar estas medidas<sup>51,52</sup>. </p>
    <p>Al&#233;m dos m&#233;todos citados, v&#225;rias outras f&#243;rmulas podem ser utilizadas na estimativa da press&#227;o atrial esquerda, utilizando os seguintes par&#226;metros ecocardiogr&#225;ficos: tempo de relaxamento isovolum&#233;trico, velocidade de propaga&#231;&#227;o do fluxo transmitral obtida pelo color modo M (VFTM)<sup>53-57</sup>, velocidade de desacelera&#231;&#227;o do fluxo transvalvar mitral precoce<sup>58-60</sup>, fra&#231;&#227;o sist&#243;lica do fluxo venoso pulmonar e tempo de desacelera&#231;&#227;o do fluxo pulmonar diast&#243;lico<sup>61</sup>, fra&#231;&#227;o sist&#243;lica da integral de velocidade do fluxo anter&#243;grado venoso pulmonar<sup>62</sup> e rela&#231;&#227;o entre o tempo de contra&#231;&#227;o atrial do fluxo retr&#243;grado venoso pulmonar e o anter&#243;grado transmitral<sup>63</sup>. A escolha da t&#233;cnica mais apropriada pode variar conforme caracter&#237;sticas individuais dos pacientes. </p>
    <p>Portanto, a avalia&#231;&#227;o hemodin&#226;mica n&#227;o invasiva, com as v&#225;rias informa&#231;&#245;es fornecidas pela ecocardiografia, pode ser obtida com boa acur&#225;cia utilizando-se mais de um par&#226;metro e conhecendo-se as vantagens e limita&#231;&#245;es de cada um dos m&#233;todos. Tecnicamente requer tempo e treinamento do ecocardiografista, e sua realiza&#231;&#227;o est&#225; ligada &#224; necessidade imposta pelo cardiologista cl&#237;nico no manejo de seus pacientes. </p>
    <p><bold>Aplica&#231;&#227;o cl&#237;nica do uso do ecocardiograma para buscar par&#226;metros hemodin&#226;micos otimizados - </bold>O nosso grupo est&#225; conduzindo um ensaio cl&#237;nico randomizado comparando tratamento ambulatorial guiado por ecocardiografia, objetivando adequa&#231;&#227;o do perfil hemodin&#226;mico (redu&#231;&#227;o de press&#245;es de enchimento e da resist&#234;ncia perif&#233;rica) <italic>versus</italic> manejo cl&#237;nico convencional objetivando melhora sintom&#225;tica, em que foram arrolados 99 pacientes com diagn&#243;stico de insufici&#234;ncia card&#237;aca congestiva de qualquer etiologia, em classe funcional II-IV, com fra&#231;&#227;o de eje&#231;&#227;o <underline>&lt;</underline> a 40% que tiveram interna&#231;&#227;o hospitalar ou visita a emerg&#234;ncia por insufici&#234;ncia card&#237;aca descompensada nos &#250;ltimos tr&#234;s meses. Dados preliminares de 70 pacientes com idade m&#233;dia de 60 &#177;15 anos, 60% do sexo masculino, fra&#231;&#227;o de eje&#231;&#227;o de 27&#177;7% e 31% de etiologia isqu&#234;mica, demonstraram que no grupo de tratamento guiado por ecocardiografia, houve redu&#231;&#227;o da press&#227;o atrial direita de 10,1&#177;5 para 7,8&#177;4 mmhg (p=0,004), da press&#227;o sist&#243;lica m&#225;xima da art&#233;ria pulmonar de 47&#177;12 para 39&#177;12 mmhg (p=0,003) e do &#237;ndice da resist&#234;ncia vascular sist&#234;mica de 3821&#177;1265 para 3390&#177;1142 dinas/s/cm<sup>-5 </sup>(p=0,048). N&#227;o houve diferen&#231;a significativa entre esses par&#226;metros no grupo com manejo cl&#237;nico convencional. Estes dados e a condu&#231;&#227;o deste estudo at&#233; o momento indicam que o emprego da ecocardiografia para guiar tratamento baseado em dados hemodin&#226;micos &#233; fact&#237;vel e mais eficaz do que o tratamento baseado em manejo cl&#237;nico tradicional para obten&#231;&#227;o de um perfil favor&#225;vel de redu&#231;&#227;o de press&#245;es de enchimento e da resist&#234;ncia perif&#233;rica em pacientes ambulatoriais com insufici&#234;ncia card&#237;aca. </p>
    <p><bold>Papel do perfil hemodin&#226;mico no progn&#243;stico na insufici&#234;ncia card&#237;aca cr&#244;nica e fatores preditivos - </bold>A import&#226;ncia do estado vol&#234;mico no progn&#243;stico dos pacientes com insufici&#234;ncia card&#237;aca congestiva pode ser tamb&#233;m observada nos dados que indicam que sobrevida destes pacientes varia entre 80% em dois anos para aqueles livres de congest&#227;o at&#233; menos do que 50% em 6 meses nos com sintomas refrat&#225;rios em repouso<sup>64</sup>. A manuten&#231;&#227;o de um estado cl&#237;nico livre de congest&#227;o, buscando n&#237;veis de press&#245;es de enchimento baixas ou normais dentro de 4 a 6 semanas ap&#243;s a alta hospitalar de pacientes em classe funcional IV se associou com melhor sobrevida nos 2 anos seguintes<sup>65</sup>. </p>
    <p>A monitoriza&#231;&#227;o hemodin&#226;mica tamb&#233;m pode ser &#250;til para estratificar risco, pois pacientes que apresentavam press&#245;es de enchimento iniciais normais tiveram uma sobrevida em um ano de 95%, enquanto nos com press&#245;es iniciais elevadas, foi sucesso a terapia em reduzir as press&#245;es que se correlacionaram com melhor progn&#243;stico e n&#227;o o n&#237;vel de congest&#227;o inicial<sup>66</sup>. </p>
    <p>Al&#233;m do estado congestivo dos pacientes, outros informa&#231;&#245;es progn&#243;sticas importantes na insufici&#234;ncia card&#237;aca congestiva podem ser obtidas por ecocardiograma, incluindo: grau de preserva&#231;&#227;o da fun&#231;&#227;o ventricular direita<sup>67,68</sup>, di&#226;metro diast&#243;lico final do ventr&#237;culo esquerdo<sup>69</sup>, press&#227;o atrial esquerda, padr&#227;o restritivo no fluxo diast&#243;lico transmitral<sup>70-72</sup> e graus de insufici&#234;ncia mitral e tric&#250;spide<sup>73,74</sup>. N&#237;veis de BNP, que est&#227;o elevados na insufici&#234;ncia card&#237;aca congestiva talvez indicando grau de congest&#227;o, tamb&#233;m se correlacionam com morte s&#250;bita<sup>75</sup>, classe funcional da NYHA<sup>76</sup> e eventos futuros<sup>77</sup>. </p>
    <p>Press&#245;es de enchimento, portanto, s&#227;o &#250;teis no manejo dos pacientes em insufici&#234;ncia card&#237;aca congestiva porque podem predizer desfechos mesmo ap&#243;s ajustes da terapia<sup>66</sup> e podem ser inferidas n&#227;o s&#243; pelos n&#237;veis de BNP, mas tamb&#233;m atrav&#233;s de par&#226;metros ecocardiogr&#225;ficos, como os j&#225; citados anteriormente. </p>
    <p><bold>Considera&#231;&#245;es finais - </bold>O tratamento da disfun&#231;&#227;o card&#237;aca sist&#243;lica tem avan&#231;ado consideravelmente nos &#250;ltimos 20 anos, devido, principalmente, &#224;s descobertas no campo patofisiol&#243;gico do papel dos fatores neurohormonais<sup>78</sup>; levando &#224; utiliza&#231;&#227;o de drogas comprovadamente redutoras de mortalidade como IECA<sup>79-81</sup>, beta-bloqueadores<sup>82,83</sup> e espironolactona<sup>84</sup>. A atua&#231;&#227;o de equipes multidisciplinares tem sido importante para especificamente atuar na redu&#231;&#227;o das readmiss&#245;es hospitalares<sup>85,86</sup>. </p>
    <p>Apesar destes avan&#231;os, ainda s&#227;o altas a mortalidade e os n&#237;veis de readmiss&#227;o hospitalar por descompensa&#231;&#227;o dos sintomas<sup>87,88</sup>, o que se deve, parcialmente, &#224; limita&#231;&#227;o do quadro cl&#237;nico para indicar adequa&#231;&#227;o do tratamento pr&#233;-alta, especialmente, na defini&#231;&#227;o do estado congestivo/vol&#234;mico desses pacientes. Testes convencionais, como a ecocardiografia, n&#227;o s&#227;o utilizados de rotina na sua potencialidade plena para fornecer informa&#231;&#245;es adicionais ao exame cl&#237;nico, em rela&#231;&#227;o &#224;s reais condi&#231;&#245;es hemodin&#226;micas do paciente. Por outro lado, a utiliza&#231;&#227;o frequente de cateteriza&#231;&#227;o card&#237;aca direita no manejo de pacientes com insufici&#234;ncia card&#237;aca descompensada &#233; inexeq&#252;&#237;vel, n&#227;o s&#243; pelos riscos e altos custos do procedimento, mas tamb&#233;m porque esta implica em utiliza&#231;&#227;o de leitos em terapia intensiva<sup>89-92</sup>. Neste sentido, m&#233;todos alternativos devem ser buscados para trazer informa&#231;&#245;es pertinentes ao estado vol&#234;mico dos pacientes com insufici&#234;ncia card&#237;aca congestiva. A dosagem do neurohorm&#244;nio BNP tem mostrado resultados iniciais positivos para monitorar o tratamento ambulatorial em longo prazo destes pacientes. A ampla disponibildade do ecocardiograma atualmente na cl&#237;nica cardiol&#243;gica poderia permitir um melhor controle ambulatorial de pacientes com insufici&#234;ncia card&#237;aca congestiva, fosse o potencial deste m&#233;todo para determinar perfil hemodin&#226;mico dominado de forma mais abrangente por cardiologistas/ecocardiografistas, que poderiam fornecer informa&#231;&#245;es preciosas ao cl&#237;nico permitindo um padr&#227;o de manejo diferenciado para este dif&#237;cil grupo de pacientes.</p>
    <p>
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    <p>50. Ommen SR, Nishimura RA, Appleton CP, Miller FZ, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures. Circulation 2000;102:1788-94. </p>
    <p>51. Nagheh SF, Middleton KJ, Kopelen H&#193;, Zoghbi WA, Qui&#241;ones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30:1527-33. </p>
    <p>52. Gorcsan III J. Tissue Doppler echocardiography. Lippincott Williams &amp; Wilkins, Inc. Cur Opin Cardiol 2000,15:323-9. </p>
    <p>53. Brun P, Tribouilloy C, Duval AM et al. Left ventricular flow propagation during early filling is related to wall relaxation: a color M-mode Doppler analysis. J Am Coll Cardiol 1992;20:420-32. </p>
    <p>54. Takasuji H, Mikami T, Urasawa K et al. A new approach for evaluation of left ventricular diastolic function: spatial and temporal analysis of left ventricular filling flow propagation by color M-mode Doppler echocardiography. J Am Coll Cardiol 1996;27:365-71. </p>
    <p>55. Duval-Moulin AM, Dupouy P, Brun P et al. Alteration of left ventricular diastolic function during coronary angioplasty-induced ischemia: a color M-mode Doppler study. J Am Coll Cardiol 1997;29:1246-55. </p>
    <p>56. Weiss JL, Ares MA, Asher C et al. An index of early left ventricular filling that combined with pulsed Doppler peak E velocity may estimate capillary wedge pressure. J Am Coll Cardiol 1997;29:448-54. </p>
    <p>57. Gon&#231;ales- Vilchez F, Ares M, Ayuela J, Alonso L. Combined use of pulsed and color M-mode Doppler echocardiography for the estimation of pulmonary capillary wedge pressure: an empirical approach based on an analytical relation. J Am Coll Cardiol 1999;34:515-23. </p>
    <p>58. Garcia MJ, Ares MA, Asher C et al. An index of Early left ventricular filling that combined with pulsed Doppler peak E velocity may estimate capillary wedge pressure. J Am Coll Cardiol 1997;29: 448-54. </p>
    <p>59. Pozzoli M, Capomolla S, Pinna G, Cobelli F, Tavazzi L. Doppler echocardiography reliably predicts pulmonary artery wedge pressure in patients with chronic heart failure with and without mitral regurgitation. J Am Coll Cardiol 1996; 27:883-93. </p>
    <p>60. Gianuzzi P, Imparato A, Temporelli PL et al. Doppler- derived mitral desaceleration time of early filling as a strong predictor of pulmonary capillary wedge pressure in post-infarction patients with left ventricular systolic dysfunction. J Am Coll Cardiol 1994;23:1630-7. </p>
    <p>61. Yamamuro A, Yoshida K, Hozumi T et al. Noninvasive evaluation of pulmonary capillary wedge pressure in patients with acute myocardial infarction by deceleration time of pulmonary venous flow velocity in diastole. J Am Coll Cardiol 1999; 34: 90-4. </p>
    <p>62. Brunazzi MC, Chirillo F, Pasqualini M et al. Estimation of left ventricular diastolic pressures from precordial pulsed-Doppler analysis of pulmonary venous and mitral flow. Am Heart J 1994;128:293-300. </p>
    <p>63. Rossvoll O, Hatle LK. Pulmonary venous flow velocities recorded by transthoracic Doppler ultrasound: relation to left ventricular diastolic pressures. J Am Coll Cardiol 1993;21:1687-96. </p>
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    <p>69. Gavazzi A, DeMaria R, Renosto G et al. The spectrum of left ventricular size in dilated cardiomiopathy: clinical correlates and prognostic implications. Am Heart J 1993;125:410-22. </p>
    <p>70. Xie GY, Martin RB, Smith MD et al. Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure. J Am Coll Cardiol 1994; 24:132-9. </p>
    <p>71. Pinamonti B, DiLenarda A, Sinagra G, Camerii F. Restrictive left ventricular filling pattern in dilated cardiomyopathy assessed by Doppler echocardiography: clinical, echocardiography and hemodynamic correlations and prognostic implications. Heart Muscle Disease Study Group. J Am Coll Cardiol 1993; 22:808-15. </p>
    <p>72. Lapu-Bula R, Robert A, De Kock M et al. Risk stratification in patients with dilated cardiomyopathy: Contribution of Doppler-derived left ventricular filling. Am J Cardiol 1998;82:779-85. </p>
    <p>73. Abrahmson SV, Burke JF, Kelly JJ et al. Pulmonary hypertension predicts mortality and morbidity in patients with dilated cardiomyopathy. Ann Intern Med 1992; 116:888-95. </p>
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    <p>75. Berger R, Hueslman M, Strecker K et al. B-type natriuretic predicts sudden death in patients with chronic heart failure. Circulation 2002;105:2392-7. </p>
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    <p>77. Cheng V, Kazanagra R, Garcia A et al. A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study. J Am Coll Cardiol 2001;37:386-91. </p>
    <p>78. Remme WJ. Therapeutic strategies and neurohormonal control in heart failure. Eur Heart F 1994;15 (suppl D):129-38. </p>
    <p>79. The SOLVD Investigators. The effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med 1991;325:293-302. </p>
    <p>80. Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on morbidity and mortality in patients with heart failure: Collaborative Group on ACE-Inhibitor Trials. JAMA 1995;273:1450-6. </p>
    <p>81. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987;316:1429-35. </p>
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    <p>84. Pitt B, Zannad F, Remme WJ et al. The effect of spironolactona on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709-717. </p>
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    <p>86. Rich MW, Beckham V, Wittnberg C et al. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995;333:1190-95. </p>
    <p>87. Philbin EF, DiSalvo TG. Prediction of hospital readmission for heart failure: Development of a simple risk score based on administrative data. J Am Coll Cardiol 1999;33:1560-6. </p>
    <p>88. Drumholtz HM, Chen YT, Wan Y et al. Predictors of readmission among elderly survivors of admission with heart failure. Am Heart J 2000;139:72-7. </p>
    <p>89. Adams KF: Post hoc subgroup analysis and the truth of a clinical trial. Am Heart J 1998;136:751-8. </p>
    <p>90. Stevenson LW, Massie BM, Francis GS. Optimizing therapy for complex or refractory heart failure: a management algorithm. Am Heart J 1998; 135(suppl): S293-309. </p>
    <p>91. Stevenson LW: Therapy tailored for symptomatic heart failure. Heart Failure 1995; 22:955-62 </p>
    <p>92. Connors AF Jr, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. JAMA 1996;276:889-97.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Endere&#231;o para correspond&#234;ncia</bold>
        </label>
        <p> Dra. Nadine Clausell </p>
        <p> Rua Hon&#243;rio Silveira Dias, 873/901 </p>
        <p> Cep 90550-150 - Porto Alegre - RS </p>
        <p> E-mail: </p>
        <p><email xlink:href="nclausell@cardiol.br">nclausell@cardiol.br</email> / </p>
        <p>
          <email xlink:href="clausell@portoweb.com.br">clausell@portoweb.com.br</email>
        </p>
      </fn>
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    <p>Enviado em 30/03/2004 - Aceito em 15/07/2004</p>
  </body>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Update</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Determination of hemodynamic parameters using Doppler two-dimensional echocardiography: a searching tool for therapeutic optimization in patients with congestive heart failure on an outpatient care follow-up</article-title>
      </title-group>
    </front-stub>
    <body>
      <p>
        <bold>UPDATE</bold>
      </p>
      <p>
        <bold>Determination of hemodynamic parameters using Doppler two-dimensional echocardiography: a searching tool for therapeutic optimization in patients with congestive heart failure on an outpatient care follow-up</bold>
      </p>
      <p>
        <bold>Dora V. Palombini; Luis E. Rohde; Leticia Crestana; L&#237;via Goldraich; Marta Pereira Lima; Candice Campos; Nadine Clausell</bold>
      </p>
      <p> Porto Alegre, RS - Brazil</p>
      <p>Hospital de Cl&#237;nicas de Porto Alegre</p>
      <p> Programa de P&#243;s-Gradua&#231;&#227;o em Ci&#234;ncias Cardiovasculares: Cardiologia </p>
      <p>
        <xref ref-type="corresp" rid="end-body2">Correspondence</xref>
      </p>
      <p>One of the major problems in the management of patients with severe heart failure is frequent hospital readmissions due to lack of compensation, which, in addition to causing a great burden to the public health system, is one of the major causes of loss in quality of life of those patients. On average, 30 to 50% of the patients are readmitted 3 to 6 months after hospital discharge <sup>1</sup>. A recent meta-analysis indicated that the frequency of hospital readmissions may be reduced through a constant follow-up by a multidisciplinary team of physicians and nurses in a specialized heart failure clinic<sup>2,3</sup>. Therefore, a careful follow-up with individualized treatment directed to the specific and current situation of each patient can have medium- and long-term benefits in the outpatient care of chronic patients with moderate to severe congestive heart failure. In this article, we report the potential applications of methods, such as echocardiography, for the optimized management of patients with congestive heart failure and present the initial results of the use of such an instrument for guiding the therapy. </p>
      <p><bold>Peculiarities of the development and manifestations of congestion and low cardiac output in congestive heart failure - </bold>In patients with congestive heart failure, an important cause of rehospitalization or visits to the emergency unit, or both, is related to congestive states <sup>4,5</sup>. On the other hand, the clinical diagnosis of congestive states may be particularly difficult in chronic patients, due to several pathophysiological adaptations that make the clinical manifestations of congestion subtle in those patients, frequently leading to underuse of diuretics and vasodilating agents <sup>6</sup>, which, in turn, contributes to increase the risk of decompensation. </p>
      <p>The identification of elevated ventricular filling pressures in congestive heart failure does not follow the same pattern of the semiotic clinical findings in the acute settings considered in therapeutic decision making processes. One of the major signs and symptoms of congestion is an elevation in jugular venous pressure and orthopnea. The clinical assessment of jugular venous pressure requires a careful technique, because it seems to be the most important clinical sign for assessing the real congestive status of patients with congestive heart failure <sup>7</sup>. </p>
      <p>In congestive heart failure, the concordance between the estimates of right- and left-sided pressures is known to be 80%, because Drazner et al <sup>8</sup> have shown that, through a right atrial pressure (RAP) &gt; or &lt; 10 mmHg, the left atrial pressure (LAP) may be estimated as &gt; or &lt; 22 mmHg, respectively <sup>8,9</sup>. Other factors, such as abdominal compression with positive hepatojugular reflux, a "square root"-type pressure response to the Valsalva maneuver, and increased intensity of the second cardiac sound may also indicate an elevation in the right-sided chamber cavities, which, in turn, may estimate high left-sided pressures <sup>9,10</sup>. </p>
      <p>Due to the compensatory lymphatic drainage chronically present in patients with congestive heart failure, pulmonary rales are lacking in more than 80% of cases, even in the presence of elevated filling pressures. The symptoms of dyspnea and fatigue are due to the fact that although the residual interstitial fluid does not hinder oxygenation it may restrict inspiration and reduce pulmonary compliance <sup>6</sup>. </p>
      <p>Lower limb edema occurs in only 25% of patients with congestive heart failure below the age of 70 years, while in older patients it may rather be caused by local factors than by an elevation in the central venous pressure itself. These data allow us to suggest that peripheral edema and elevated jugular venous pressure are more specific than sensitive for detecting elevated left-sided filling pressures. </p>
      <p>The third cardiac sound is present in most patients with congestive heart failure, although in some patients it may never be identified. It is worth emphasizing that the degree of concordance about the presence of the third cardiac sound, even within experienced physicians, is moderate or low. This fact may be related to the loss of auscultatory acuity in a time of more sophisticated and accessible diagnostic methods <sup>11-13</sup>. Some authors have suggested that the third cardiac sound is not a reliable parameter for assessing the congestive status of patients with congestive heart failure <sup>6</sup>. Nevertheless, the presence of the third cardiac sound and the elevation in jugular venous pressure in congestive heart failure are independently associated with a higher incidence of hospitalization due to heart failure (RR=1.32, P&lt;0.01), death, or hospitalizations due to heart failure (RR=1.30, P&lt;0.005) death due to heart failure (RR=1.37, P&lt;0.05) <sup>4</sup>. </p>
      <p>The reason why the elevation in jugular venous pressure or the presence of the third cardiac sound is associated with an elevated risk in congestive heart failure progression is not clear. The elevated jugular venous pressure reflects an increase in right atrial pressure, which, by itself, correlates with elevated left pressures in patients with congestive heart failure. The elevated left pressures, in turn, are associated with a poor prognosis perhaps because of the apoptosis triggered by the myocardial parietal tension and by the activation of the sympathetic nervous system<sup> 14,15</sup>. The third cardiac sound, which relates more to low left ventricular compliance and the elevated filling pressures and velocities, has also been associated with a poor prognosis due to a disorder in diastole in patients with systolic dysfunction <sup>4</sup>. </p>
      <p>One of the few useful clinical bedside instruments for patients with congestive heart failure is pulse pressure (systolic pressure - diastolic pressure/systolic pressure), which, when &lt; 25%, estimates a cardiac index of 2.2 L/min/m<sup>2-6</sup>. The ratio between the pulse pressure obtained with normal breathing and the pulse pressure during the Valsalva maneuver may also be used to estimate left atrial pressure with a 93% accuracy <sup>16</sup>. </p>
      <p>In addition to those characteristics, in patients with congestive heart failure and enlarged ventricular diameters, the degree of mitral regurgitation is usually significant, significantly contributing to the appearance of signs and symptoms of congestion and low cardiac output. The mechanism responsible for mitral regurgitation in congestive heart failure is the lack of appropriate coaptation of the mitral leaflets due to dilation of the mitral valve annulus and impairment of the geometry of the subvalvular apparatus <sup>17</sup>. With compensation of the congestive setting and the reduction in left ventricular and atrial volumes, mitral regurgitation and the effective regurgitant orifice decline significantly. Thus, the systolic volume "steal" greater than 50%, which occurs in symptomatic patients at rest, is redistributed and the effective left ventricular systolic volume increases <sup>18</sup>. Because the dominant symptoms are secondary to congestion, the consequent relief in symptoms at rest is mainly due to the reduction in the elevated filling pressures. Other factors positively affected by the reduction in filling pressures are as follows: the improvement in coronary percussion; the reduction in neurohormonal activation with a reduction in norepinephrine release and parietal stress <sup>14,19,20</sup>; the improvement in functional capacity <sup>21</sup>; a reduction in the circulating cytokines, in the natriuretic peptides, in liver congestion, and, later, in the progressive malnutrition of chronic patients <sup>22</sup>. </p>
      <p>Contrary to that which occurs in patients after acute myocardial infarction, whose stiff myocardium, not yet dilated, benefits from high filling pressures, patients with chronically dilated ventricles have maximally elongated sarcomeres, in which a greater pressure or volume overload will not elongate them any more, but increase the wall tension and valvular incompetence. Therefore, the decrease in the filling pressures to normal or low levels with diuretics and vasodilators reflects in systolic volume increase. This increase is due not to an improvement in the ejection fraction, which elevates just a little, but to a great reduction in the systolic volume lost during mitral regurgitation <sup>23</sup>. </p>
      <p><bold>Hemodynamic optimization in heart failure -</bold> The basic objectives of the clinical therapy of heart failure guided by hemodynamic optimization are those defined by Stevenson et al <sup>24</sup>, which are as follows: left atrial pressure of 15 mmHg or lower; right atrial pressure <underline>&lt;</underline> 8 mmHg; systemic vascular resistance around 1200 dynes/sec/cm<sup>5</sup>; and systolic blood pressure <underline>&gt;</underline> 80 mmHg. Classically this strategy requires an intensive care environment with the use of a catheter in the pulmonary artery. By redesigning therapy for 24 to 72 hours according to hemodynamics, essentially using a vasodilator (sodium nitroprusside) and intravenous loop diuretic (furosemide), the hemodynamic profile may be optimized and the patient may be maintained clinically stable for the following months, with a reasonable improvement in symptoms, which allows the patient's withdrawal, although temporarily, from the heart transplantation list <sup>25-28</sup>. Although the strategy of hemodynamic optimization using a catheter in the pulmonary artery has repeatedly resulted in an improvement in functional and clinical outcomes, these are observational data, which have not been tested in a clinical trial. Therefore, the multicentric randomized study called ESCAPE is being carried out, comparing the invasive strategy and clinical management in congestive heart failure <sup>29</sup>. Such studies should clarify whether that strategy in fact alters the outcomes, creating survivors, or whether it simply identifies those with greater chances to survive, regardless of the therapeutic strategy used. </p>
      <p>In addition to providing an adequate hemodynamic profile with that approach, a recent study <sup>30 </sup>has shown that in patients with severe hemodynamic impairment, interventions with diuretics and vasodilators, with no inotropic agents, directed to normalize the conditions of overload and systemic resistance reduce the markers of neurohumoral activation, such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and the vasoconstrictors endothelin and norepinephrine. Thus, intensification of the congestive heart failure therapy with diuretics and angiotensin-converting enzyme inhibitors (ACEI) has been shown to reduce BNP serum levels, and, in addition, patients treated with a therapy guided by BNP values had a 35% reduction in cardiovascular events (P=0.02) as compared with those undergoing clinical follow-up only <sup>31</sup>. On the other hand, recent data indicate that 54% of patients with baseline BNP levels of 480 pg/mL or greater will have a new congestive episode within 6 months <sup>32</sup>. These data indicate that the guidance of the treatment of decompensated congestive heart failure, aiming at reducing the filling pressures, either through numeric hemodynamic data, or through a reduction in BNP levels (a marker whose increase indicates distension of the sarcomeres), has clinical benefits to the patients. </p>
      <p><bold>Alternative tools for characterizing the hemodynamic parameters - </bold>Most data recommending the search for hemodynamic optimization result from studies using a pulmonary artery catheter for invasive assessment of the hemodynamic parameters. It is evident that that strategy is necessarily restricted to the intensive care therapy and applies to those patients with decompensated congestive heart failure who seek hospital care. Considering the importance of maintaining the patients with congestive heart failure euvolemic to avoid or protect them from decompensation due to congestion, tools to be used in the outpatient care environment are required. Therefore, other noninvasive methods for assessing cardiac output and filling pressures, such as Doppler echocardiography with a bioimpedance device, may be useful for the follow-up and individualization of the congestive heart failure therapy<sup>33,9</sup>. </p>
      <p>A recent study <sup>34 </sup>was carried out using a hemodynamic monitor of right ventricular pressure (Medtronic Incorporation) implanted as a pacemaker to guide daily clinical management of 32 patients with congestive heart failure, which resulted in a 57% reduction in hospitalizations (P&lt;0.01). </p>
      <p><bold>Echocardiographic hemodynamic assessment - </bold>Echocardiography may be an attractive alternative as a tool of hemodynamic assessment, because, in most patients with heart failure, it may provide hemodynamic data with an excellent correlation with those concomitantly collected by using right catheterization <sup>35,36</sup>. Right-sided pressures, for example, may be obtained 97% of the time when assessing the diastolic (89%) and systolic (73.5%) pressures in the pulmonary artery<sup> 37</sup>. </p>
      <p>In congestive heart failure, right-filling pressures may be estimated by using echocardiographic parameters, such as the inferior vena cava diameter associated with its collapse index during inspiration. The tendency of the inferior vena cava towards total or partial collapse occurs because, during inspiration, the negative intrathoracic pressure increases, and, as long as the inferior vena cava and the right cavities are not overloaded, blood flow should increase towards the right atrium, causing a partial or total collapse of that vessel. When, due to technical reasons, the assessment of the inferior vena cava is not possible and no evidence of elevation in the pressures of the right cavities exists, the simple use of an arbitrary mean value of 10 mmHg is the general consensus <sup>38</sup>. </p>
      <p>Pulmonary artery pressure may be obtained by measuring the velocities of regurgitation between the right cavities, basically tricuspid and pulmonary regurgitation. With the complete assessment of all echocardiographic "windows", the tricuspid transvalvular gradient and pulmonary regurgitation may be recorded in 86 and 89% of the tests, respectively. It has been shown that, by adding the 2 possibilities, a pressure value was detected in the pulmonary artery in 97% of a series of 200 patients <sup>37,39</sup>. In patients who do not have a sufficient degree of pulmonary regurgitation to estimate the gradient, tricuspid regurgitation is used at the moment of pulmonary valve opening to estimate the diastolic pressure in the pulmonary artery. This simple technique showed a correlation with cardiac catheterization (r=0.92), except for the patients with severe tricuspid regurgitation and those undergoing mechanical ventilation <sup>40,41</sup>. </p>
      <p>Another important hemodynamic parameter, cardiac output, can also be calculated by use of echocardiographic data and shows a correlation coefficient of r=0.97 with the data obtained through right catheterization <sup>35</sup>. For such, one should multiply heart rate by the time of the velocity integral (TVI) and the area of left ventricular outflow tract, corrected to body surface, for obtaining the cardiac index values. </p>
      <p>Pulmonary capillary pressure is a well-established parameter for assessing heart function and left ventricular filling. In patients with congestive heart failure, an elevated pulmonary capillary pressure is associated with a poor prognosis, frequent decompensations of symptoms and low exercise tolerance <sup>42-45</sup>. The reduction in those values after adequate treatment improves the patients' quality of life <sup>46</sup>. The use of data referring to those values may help in the routine therapeutic management of patients with congestive heart failure. </p>
      <p>Pulmonary capillary or left atrial pressure may be estimated by assessing blood flow velocity in the pulmonary artery, if the patient has no pulmonary disease, or by assessing the transmitral and pulmonary venous flow in the left side. Transmitral flow analysis also provides information on left atrial pressure and heart failure prognosis. However, it depends on multiple conditions, such as heart rate, ventricular relaxation and suction, left atrial and ventricular compliance, and mitral valve conditions. To avoid the interference of these factors, other parameters, such as pulmonary venous flow, the response of transmitral flow to different volume loads, color M mode, and Doppler tissue imaging of the mitral ring, may be used. Left atrial pressure cannot be estimated by using isolated rules, but after assessing several parameters and respecting the limitations of each one. For practical purposes, pulmonary capillary pressure and left atrial pressure are considered equivalent, because the pulmonary capillaries, the pulmonary veins, and the left atrium communicate freely, forming a large chamber. Simultaneous measurements of right catheterization and left atrium through transeptal catheterization have already confirmed the similarity of those pressures <sup>47-49</sup>. The several calculations used to obtain hemodynamic data through echocardiography are shown in <xref ref-type="table" rid="tab01-body2">table I</xref>. </p>
      <table-wrap id="tab01-body2">
        <graphic xlink:href="1678-4170-abc-84-04-0351-00017-gt01-en.jpg"/></table-wrap>
      <p><bold>Other methods -</bold> Doppler tissue imaging is a relatively new technique that records the systolic and diastolic myocardial velocities at the level of the mitral valve annulus, preferentially medial or lateral. Filters should be used to eliminate the high frequencies, and the Nyquist limit should be maintained between &#150;15 and 20 cm/s. Contrary to the transmitral flow (E wave), the velocity recorded at the mitral valve annulus by using Doppler tissue imaging (E<sub>a</sub>) does not undergo the influence of left atrial pressure and reflects isolated left ventricular relaxation. Thus, it is an excellent index for assessing the relaxation deficit, even in pseudo-normal cases, and, when coupled to nontissue transmitral valve flow, it may estimate left atrial pressure. An E/E<sub>a </sub>ratio &gt; 10 may foretell a LAP &gt; 12 mmHg with 91% sensitivity and 81% specificity, or an E/E<sub>a </sub>ratio &gt; 10 may foretell a LAP &gt; 15 mmHg with 97% sensitivity and 78% specificity. Ommen et al <sup>50</sup> have shown a correlation level between the E/E<sub>a medial</sub> ratio and the mean left ventricular diastolic pressure of r=0.64, greater in patients with ejection fraction lower than 50%, as compared with those without ventricular dysfunction. These authors have also shown a positive predictive value of 64% for a left ventricular end-diastolic pressure &gt; 12 mmHg, if E/E<sub>a </sub>is &gt; 15 mmHg, and a negative predictive value of 97% for low left atrial pressures, if the E/E<sub>a </sub>ratio is &lt; 8. In the presence of infarction in the laterobasal wall, atrial fibrillation, and severe mitral regurgitation, significant technical limitations exist and may render those measurements unfeasible <sup>51,52</sup>. </p>
      <p>In addition to the already cited methods, several other formulas may be used to estimate left atrial pressure, using the following echocardiographic parameters: time of isovolumetric relaxation; velocity of propagation of the transmitral valve flow obtained by using color M mode (TMVF) <sup>53-57</sup>; velocity of deceleration of the early transmitral valve flow <sup>58-60</sup>; systolic fraction of the pulmonary venous flow; time of deceleration of the diastolic pulmonary flow<sup>61</sup>; systolic fraction of the integral of velocity of the anterograde pulmonary venous flow <sup>62</sup>; and ratio between the time of atrial contraction of the retrograde pulmonary venous flow and the anterograde transmitral valve flow <sup>63</sup>. The choice of the most appropriate technique may vary according to the individual characteristics of the patients. </p>
      <p>Therefore, the noninvasive hemodynamic assessment with information provided by echocardiography may be obtained with a good accuracy by using more than one parameter and knowing the advantages and limitations of each method. Technically, it requires time and training of the echocardiographer, and its performance depends on the need of the clinical cardiologist in patients' management. </p>
      <p><bold>Clinical application of echocardiography in the search for optimum hemodynamic parameters -</bold> Our group is carrying out a randomized clinical trial comparing the echocardiography-guided outpatient care, which aims at tailoring the hemodynamic profile (a reduction in the filling pressures and peripheral resistance), with the conventional clinical management, which aims at improvement of symptoms. Our study comprised 99 patients diagnosed with congestive heart failure of any etiology, in functional class II-IV, with an ejection fraction <underline>&lt;</underline> 40%, who were hospitalized or visited the emergency unit due to decompensated heart failure in the prior 3 months. Our preliminary study comprised 70 patients, 31% of whom had congestive heart failure of ischemic etiology, a mean age of 60&#177;15 years, an ejection fraction of 27&#177;7%, and 60% were males. The preliminary data have shown that, in the group with the echocardiography-guided treatment, a reduction occurred in the right atrial pressure from 10.1&#177;5 to 7.8&#177;4 mmHg (P=0.004), in the maximum systolic pressure of the pulmonary artery from 47&#177;12 to 39&#177;12 mmHg (P=0.003), and in the systemic vascular resistance index from 3821&#177;1265 to 3390&#177; 1142 dynes/sec/cm<sup>5 </sup>(P=0.048). No significant difference was observed in those parameters in the conventional clinical management group. These data and the conduction of this study so far have indicated that the use of echocardiography-guided treatment based on hemodynamic data is feasible and more effective than the treatment based on traditional clinical management for obtaining a favorable profile of reduction in the filling pressures and peripheral resistance in patients with heart failure being followed up on an outpatient care basis. </p>
      <p><bold>Role of the hemodynamic profile for prognosis of chronic heart failure and predictive factors -</bold> The importance of the volemic status in the prognosis of patients with congestive heart failure may also be observed in data indicating that survival may range from 80% in 2 years in patients without congestion to less than 50% in 6 months in patients with refractory symptoms at rest <sup>64</sup>. The maintenance of a clinical status free from congestion, aiming at low or normal filling pressure levels within 4 to 6 weeks after hospital discharge in patients with functional class IV was associated with survival improvement in the following 2 years <sup>65</sup>. </p>
      <p>Hemodynamic monitoring may also be useful to stratify risk, because patients with normal initial filling pressures had a one-year survival of 95%, while in those with elevated initial pressures, a better prognosis was attributed to the therapy for reducing the pressures rather than to the level of initial congestion <sup>66</sup>. </p>
      <p>In addition to the congestive status of patients with congestive heart failure, the following important prognostic data may be obtained by use of echocardiography: degree of preservation of right ventricular function<sup>67,68</sup>; left ventricular end-diastolic diameter<sup>69</sup>; left atrial pressure; restrictive pattern in transmitral diastolic flow<sup>70-72</sup>; and degrees of mitral and tricuspid regurgitation<sup>73,74</sup>. The BNP levels, which are elevated in congestive heart failure perhaps indicating the degree of congestion, also correlate with sudden death<sup>75</sup>, NYHA functional class<sup>76</sup>, and future events<sup>77</sup>. </p>
      <p>Filling pressures, therefore, are useful in the management of patients with congestive heart failure, because they may foretell outcomes even after adjustments in therapy <sup>66</sup> and may be inferred not only through BNP levels, but also through echocardiographic parameters, such as those already cited. </p>
      <p><bold>Final considerations -</bold> The treatment of systolic heart dysfunction has advanced considerably in the past 20 years, mainly in the pathophysiological field due to the discoveries of the role of the neurohormonal factors<sup>78</sup>, which led to the use of drugs that proved to reduce mortality, such as ACEI<sup>79-81</sup>, beta-blockers<sup>82,83</sup>, and spironolactone<sup>84</sup>. The participation of multidisciplinary teams has been important for specifically reducing hospital readmissions<sup>85,86</sup>. </p>
      <p>Despite these advances, mortality and hospital readmission due to symptoms of decompensation are still high <sup>87,88</sup>, and this is partially due to the limitation in the clinical setting to indicate adequacy of the treatment before hospital discharge, especially in defining the congestive/volemic status of those patients. Conventional tests, such as echocardiography, have not been routinely used in their plain potential to provide additional information to clinical examination in regard to the real hemodynamic conditions of the patient. On the other hand, the frequent use of right cardiac catheterization in managing patients with decompensated heart failure is not feasible, not only due to the risks and high costs of the procedure, but also because it requires the use of intensive care unit beds <sup>89-92</sup>. Therefore, alternative methods should be sought to provide information about the volemic status of patients with congestive heart failure. The measurement of the BNP neurohormone has shown positive initial results for monitoring the long-term outpatient care treatment of those patients. The current ample availability of echocardiography in cardiology practice may allow better control of patients with congestive heart failure on an outpatient care basis, if the potential of that method for determining the hemodynamic profile is mastered in a more comprehensive form by cardiologists/echocardiographers, providing precious information to the clinician and allowing a pattern of differentiated management for that difficult group of patients. </p>
      <p>
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      <p>
        <fn id="end-body2" fn-type="corresp">
          <label>
            <bold>Correspondence to</bold>
          </label>
          <p> Nadine Clausell </p>
          <p> Rua Honorio Silveira Dias, 873/901</p>
          <p> Cep 90550-150 - Porto Alegre, RS, Brazil</p>
          <p> E-mail: </p>
          <p><email xlink:href="nclausell@cardiol.br">nclausell@cardiol.br</email>, </p>
          <p>
            <email xlink:href="clausell@portoweb.com.br">clausell@portoweb.com.br</email>
          </p>
        </fn>
      </p>
      <p>Received for publication: 03/30/2004 </p>
      <p> Accepted for publication: 07/15/2004 </p>
      <p>English version by Stela Maris Costalonga</p>
      <p>19. Johson W, Omland T, Collins CM et al. Neurohormonal activation rapidly decreases after intravenous vasodilator and diuretic therapy for class IV heart failure [abstract]. Circulation 1998; 98:I-780. </p>
    </body>
  </sub-article>
</article>
