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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">8dpyk8CyCyhLv4QjZf3dPPM</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2012000100020</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(12)09800120</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2012000100020</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Atualiza&#231;&#227;o Cl&#237;nica</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Avalia&#231;&#227;o hemodin&#226;mica na insufici&#234;ncia card&#237;aca: papel do exame f&#237;sico e dos m&#233;todos n&#227;o invasivos</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Almeida Junior</surname>
            <given-names>Gustavo Luiz</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Xavier</surname>
            <given-names>S&#233;rgio Salles</given-names>
          </name>
          <xref ref-type="aff" rid="aff03"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Garcia</surname>
            <given-names>Marcelo Iorio</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Clausell</surname>
            <given-names>Nadine</given-names>
          </name>
          <xref ref-type="aff" rid="aff04"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="state"/>
        </addr-line>
        <institution content-type="orgname">Casa de Sa&#250;de S&#227;o Jos&#233;</institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff04">
        <addr-line>
          <named-content content-type="state">Rio Grande do Sul</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
        <institution content-type="orgdiv1">Hospital de Cl&#237;nicas </institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff03">
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">Rio de Janeiro</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="state"/>
        </addr-line>
        <institution content-type="orgname">Hospital Pr&#243;-Card&#237;aco</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>01</month>
        <year>2012</year>
      </pub-date>
      <volume>98</volume>
      <issue>1</issue>
      <fpage>e15</fpage>
      <lpage>e21</lpage>
      <history>
        <date date-type="received">
          <day>02</day>
          <month>05</month>
          <year>2011</year>
        </date>
        <date date-type="accepted">
          <day>22</day>
          <month>08</month>
          <year>2011</year>
        </date>
        <date date-type="rev-recd">
          <day>18</day>
          <month>08</month>
          <year>2011</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>Entre as doen&#231;as cardiovasculares, a insufici&#234;ncia card&#237;aca (IC) apresenta elevada taxa de interna&#231;&#227;o hospitalar, morbidade e mortalidade, consumindo grandes recursos financeiros do sistema de sa&#250;de no Brasil e em outros pa&#237;ses. A correta determina&#231;&#227;o das press&#245;es de enchimento do ventr&#237;culo esquerdo, por avalia&#231;&#227;o invasiva ou n&#227;o invasiva, &#233; fundamental para o adequado tratamento dos pacientes com IC cr&#244;nica descompensada, considerando que a congest&#227;o &#233; o principal fator determinante dos sintomas e da hospitaliza&#231;&#227;o. O exame f&#237;sico tem se mostrado inadequado para prever o padr&#227;o hemodin&#226;mico. V&#225;rios estudos sugerem que a concord&#226;ncia em achados de exame f&#237;sico por diferentes m&#233;dicos &#233; pequena e que, por fim, as pr&#243;prias altera&#231;&#245;es fisiol&#243;gicas adaptativas na IC cr&#244;nica mascaram importantes aspectos do exame f&#237;sico. Como a avalia&#231;&#227;o cl&#237;nica falha em prever a hemodin&#226;mica e pelo fato de a utiliza&#231;&#227;o do cateter de Swan-Ganz de rotina n&#227;o ser recomendada para esse fim em pacientes com IC, m&#233;todos de avalia&#231;&#227;o hemodin&#226;mica n&#227;o invasivos, como o BNP, o ecocardiograma e a bioimped&#226;ncia cardiogr&#225;fica, v&#234;m sendo crescentemente utilizados. O presente trabalho tem por objetivo realizar, para o cl&#237;nico, uma revis&#227;o da fun&#231;&#227;o de cada uma dessas ferramentas, na defini&#231;&#227;o da condi&#231;&#227;o hemodin&#226;mica em que se encontram os pacientes com IC descompensada, visando a um tratamento mais racional e individualizado.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Insufici&#234;ncia card&#237;aca</kwd>
        <kwd>hemodin&#226;mica</kwd>
        <kwd>cardiologia de imped&#226;ncia</kwd>
        <kwd>radiografia tor&#225;cica</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>08</day>
        <month>02</month>
        <year>2012</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ATUALIZA&#199;&#195;O CL&#205;NICA</bold>
    </p>
    <p>
      <bold>Avalia&#231;&#227;o hemodin&#226;mica na insufici&#234;ncia card&#237;aca: papel do exame f&#237;sico e dos m&#233;todos n&#227;o invasivos</bold>
    </p>
    <p>
      <bold>Gustavo Luiz Almeida Junior<sup>I</sup>; S&#233;rgio Salles Xavier<sup>III</sup>; Marcelo Iorio Garcia<sup>II</sup>; Nadine Clausell<sup>IV</sup></bold>
    </p>
    <p><sup>I</sup>Casa de Sa&#250;de S&#227;o Jos&#233;</p>
    <p><sup>II</sup>Hospital Pr&#243;-Card&#237;aco</p>
    <p><sup>III</sup>Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ</p>
    <p><sup>IV</sup>Hospital de Cl&#237;nicas da UFRGS, Rio Grande do Sul, RS, Brasil</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p>Entre as doen&#231;as cardiovasculares, a insufici&#234;ncia card&#237;aca (IC) apresenta elevada taxa de interna&#231;&#227;o hospitalar, morbidade e mortalidade, consumindo grandes recursos financeiros do sistema de sa&#250;de no Brasil e em outros pa&#237;ses. A correta determina&#231;&#227;o das press&#245;es de enchimento do ventr&#237;culo esquerdo, por avalia&#231;&#227;o invasiva ou n&#227;o invasiva, &#233; fundamental para o adequado tratamento dos pacientes com IC cr&#244;nica descompensada, considerando que a congest&#227;o &#233; o principal fator determinante dos sintomas e da hospitaliza&#231;&#227;o. O exame f&#237;sico tem se mostrado inadequado para prever o padr&#227;o hemodin&#226;mico. V&#225;rios estudos sugerem que a concord&#226;ncia em achados de exame f&#237;sico por diferentes m&#233;dicos &#233; pequena e que, por fim, as pr&#243;prias altera&#231;&#245;es fisiol&#243;gicas adaptativas na IC cr&#244;nica mascaram importantes aspectos do exame f&#237;sico. Como a avalia&#231;&#227;o cl&#237;nica falha em prever a hemodin&#226;mica e pelo fato de a utiliza&#231;&#227;o do cateter de Swan-Ganz de rotina n&#227;o ser recomendada para esse fim em pacientes com IC, m&#233;todos de avalia&#231;&#227;o hemodin&#226;mica n&#227;o invasivos, como o BNP, o ecocardiograma e a bioimped&#226;ncia cardiogr&#225;fica, v&#234;m sendo crescentemente utilizados. O presente trabalho tem por objetivo realizar, para o cl&#237;nico, uma revis&#227;o da fun&#231;&#227;o de cada uma dessas ferramentas, na defini&#231;&#227;o da condi&#231;&#227;o hemodin&#226;mica em que se encontram os pacientes com IC descompensada, visando a um tratamento mais racional e individualizado.</p>
    <p><bold>Palavras-chave:</bold> Insufici&#234;ncia card&#237;aca, hemodin&#226;mica, cardiologia de imped&#226;ncia, radiografia tor&#225;cica.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A insufici&#234;ncia card&#237;aca (IC) &#233; uma s&#237;ndrome cl&#237;nica cujos sinais e sintomas s&#227;o utilizados classicamente para definir o diagn&#243;stico, orientar o tratamento e avaliar o progn&#243;stico. A correta determina&#231;&#227;o das press&#245;es de enchimento do ventr&#237;culo esquerdo, por avalia&#231;&#227;o invasiva ou n&#227;o invasiva, &#233; fundamental para o adequado tratamento dos pacientes com IC cr&#244;nica, uma vez que a congest&#227;o &#233; o fator determinante dos sintomas e da hospitaliza&#231;&#227;o. A <xref ref-type="fig" rid="a20fig01m">Figura 1</xref> mostra os poss&#237;veis momentos para a identifica&#231;&#227;o e o tratamento da eleva&#231;&#227;o das press&#245;es de enchimento ventricular (PEV)<sup>1</sup>.</p>
    <p content-type="asset">
      <fig id="a20fig01m">
        <graphic xlink:href="1678-4170-abc-98-01-0e15-00020-gf01.jpg"/></fig>
    </p>
    <p>A avalia&#231;&#227;o hemodin&#226;mica invasiva tamb&#233;m possui grande import&#226;ncia no exame e no manejo desses pacientes, sendo h&#225; d&#233;cadas utilizada, inicialmente por pun&#231;&#227;o ventricular esquerda e direta<sup>2</sup> e, atualmente, por meio do cateter de Swan-Ganz<sup>3</sup>. No entanto, nos &#250;ltimos anos, o uso da monitoriza&#231;&#227;o hemodin&#226;mica invasiva vem diminuindo, especialmente pelas crescentes evid&#234;ncias de aus&#234;ncia de benef&#237;cio com esse m&#233;todo<sup>4</sup>.</p>
    <p>Com isso, a avalia&#231;&#227;o cl&#237;nica e hemodin&#226;mica n&#227;o invasiva ficou em evid&#234;ncia. Dessa forma, crit&#233;rios diagn&#243;sticos, como os de Boston ou de Framingham, t&#234;m sido amplamente utilizados nos ensaios cl&#237;nicos e nas diretrizes, para definir a IC, por serem de f&#225;cil realiza&#231;&#227;o, n&#227;o apresentarem custo e terem boa especificidade para o diagn&#243;stico. Ademais, a avalia&#231;&#227;o cl&#237;nica tamb&#233;m apresenta boa correla&#231;&#227;o progn&#243;stica. A classifica&#231;&#227;o funcional da <italic>New York Heart Association</italic> (NYHA) e, mais recentemente, a classifica&#231;&#227;o cl&#237;nico-hemodin&#226;mica de Stevenson, em quatro perfis hemodin&#226;micos de acordo com os achados do exame f&#237;sico de congest&#227;o e perfus&#227;o perif&#233;rica, constituem-se marcadores progn&#243;sticos bem documentados<sup>5</sup>. Os pept&#237;deos natriur&#233;ticos (BNP e NT-proBNP) mostram utilidade no diagn&#243;stico de IC descompensada na sala de emerg&#234;ncia, confirmando ou afastando o diagn&#243;stico em pacientes com dispneia e conferindo valor progn&#243;stico nessa popula&#231;&#227;o, especialmente na alta hospitalar, para prever eventos futuros.</p>
    <p>Observa-se, entretanto, que a hist&#243;ria, o exame f&#237;sico e os pept&#237;deos natriur&#233;ticos sofrem grande questionamento em rela&#231;&#227;o ao poder de avaliar a condi&#231;&#227;o hemodin&#226;mica, fundamentalmente de congest&#227;o ou baixo d&#233;bito, em pacientes com IC descompensada. Limita&#231;&#245;es do exame f&#237;sico come&#231;am pela, cada vez maior, falta de interesse dos m&#233;dicos em realizar um exame f&#237;sico de qualidade, apoiada na ampla disponibilidade de exames complementares que v&#234;m sendo utilizados, muitas vezes em substitui&#231;&#227;o ao exame f&#237;sico. Al&#233;m disso, o tempo reduzido de consultas m&#233;dicas e a forma&#231;&#227;o deficiente de muitos cursos de medicina podem ser fatores associados para a queda na qualidade do exame f&#237;sico. V&#225;rios estudos sugerem que a pr&#243;pria concord&#226;ncia em achados de exame f&#237;sico por diferentes m&#233;dicos &#233; pequena. O padr&#227;o ouro para a avalia&#231;&#227;o hemodin&#226;mica na IC &#233; o cateter de art&#233;ria pulmonar (Swan-Ganz), e v&#225;rios estudos compararam a avalia&#231;&#227;o hemodin&#226;mica invasiva ao exame f&#237;sico, mostrando a limita&#231;&#227;o dessa avalia&#231;&#227;o para definir a congest&#227;o ou o baixo d&#233;bito.</p>
    <p>Os pept&#237;deos natriur&#233;ticos come&#231;aram a ser utilizados na pr&#225;tica cl&#237;nica no in&#237;cio desta d&#233;cada, com a promessa de aumentar a acur&#225;cia diagn&#243;stica da IC e de diagnosticar a eleva&#231;&#227;o da PEV, definindo a congest&#227;o, uma vez que se elevam em resposta &#224; distens&#227;o ventricular. Todavia, com a progress&#227;o do conhecimento nessa &#225;rea, tamb&#233;m se observam v&#225;rias limita&#231;&#245;es dos pept&#237;deos natriur&#233;ticos na identifica&#231;&#227;o da congest&#227;o, n&#227;o havendo atualmente um ponto de coorte definido para isso.</p>
    <p>Assim como a avalia&#231;&#227;o cl&#237;nica, os pept&#237;deos natriur&#233;ticos tamb&#233;m falham em prever a hemodin&#226;mica, pelo fato de a utiliza&#231;&#227;o de cateter de Swan-Ganz de rotina n&#227;o ser recomendada para esse fim em pacientes com IC. Dessa forma, o uso de m&#233;todos n&#227;o invasivos de avalia&#231;&#227;o hemodin&#226;mica, como o ecocardiograma e a bioimped&#226;ncia cardiogr&#225;fica, v&#234;m crescendo.</p>
    <p>O presente trabalho tem por objetivo fazer, para o cl&#237;nico, uma revis&#227;o da fun&#231;&#227;o de cada uma dessas ferramentas, na defini&#231;&#227;o da condi&#231;&#227;o hemodin&#226;mica em que se encontram os pacientes com IC descompensada, visando a um tratamento mais racional e individualizado.</p>
    <p>
      <bold>Avalia&#231;&#227;o cl&#237;nica: hist&#243;ria, exame f&#237;sico, radiografia de t&#243;rax e monitoriza&#231;&#227;o do peso</bold>
    </p>
    <p>
      <bold>Hist&#243;ria e exame f&#237;sico</bold>
    </p>
    <p>Entre os v&#225;rios sintomas de IC, a ortopneia (dispneia que se inicia com a posi&#231;&#227;o ortost&#225;tica e se alivia com a eleva&#231;&#227;o do dec&#250;bito ou com a posi&#231;&#227;o sentada) destaca-se como o sintoma que mais se correlaciona com a eleva&#231;&#227;o das press&#245;es de enchimento ventricular.</p>
    <p>Em estudo com pacientes ambulatoriais de cl&#237;nica de IC no Brasil, a presen&#231;a da ortopneia foi o mais sens&#237;vel marcador de eleva&#231;&#227;o das press&#245;es de enchimento direita e esquerda<sup>6</sup>. Nesse estudo, a performance diagn&#243;stica dos diferentes achados do exame f&#237;sico individualmente foi sub&#243;tima para prever o padr&#227;o hemodin&#226;mico. Ap&#243;s avaliar um escore cl&#237;nico para a congest&#227;o (contendo as vari&#225;veis de crepita&#231;&#227;o pulmonar, turg&#234;ncia jugular patol&#243;gica, edema perif&#233;rico e terceira bulha), o melhor valor preditivo negativo para congest&#227;o foi a aus&#234;ncia desses sinais cl&#237;nicos agregados (95% de valor preditivo para press&#227;o atrial esquerda &lt; 20mmHg).</p>
    <p>A persist&#234;ncia de ortopneia com o tratamento tamb&#233;m apresenta rela&#231;&#227;o progn&#243;stica. Pacientes que mant&#234;m queixas de ortopneia durante um ano de tratamento para IC t&#234;m taxa de reinterna&#231;&#227;o quatro vezes maior em compara&#231;&#227;o &#224;queles que est&#227;o livres de ortopneia e, al&#233;m disso, n&#227;o melhoram a fun&#231;&#227;o ventricular esquerda ao final desse per&#237;odo (11&#177;13% <italic>vs.</italic> -1&#177;6%; p&lt;0,001)<sup>7</sup>.</p>
    <p>No subestudo de exame f&#237;sico do ESCAPE <italic>trial</italic>, a ortopneia foi o &#250;nico sintoma que se correlacionou com a eleva&#231;&#227;o da PEV. Quando os pacientes apresentavam ortopneia, apesar da utiliza&#231;&#227;o de dois ou mais travesseiros, a chance de terem uma press&#227;o de oclus&#227;o da art&#233;ria pulmonar (POAP) <underline>&gt;</underline> 30mmHg foi 3,6 vezes maior (OR 3,6; p&lt;0,05)<sup>8</sup>.</p>
    <p>Quanto ao exame f&#237;sico, diversos estudos avaliaram a capacidade em estimar a condi&#231;&#227;o hemodin&#226;mica de pacientes com IC. De todos os achados, a press&#227;o venosa jugular (PVJ) parece ser a mais acurada em detectar a eleva&#231;&#227;o das press&#245;es de enchimento do ventr&#237;culo esquerdo<sup>8</sup>. Desde a introdu&#231;&#227;o da avalia&#231;&#227;o da PVJ na pr&#225;tica cl&#237;nica, em 1930, por Lewis<sup>9</sup> e, posteriormente, da padroniza&#231;&#227;o de sua avalia&#231;&#227;o por Borst e Molhuysen, em 1952<sup>10</sup>, a PVJ vem sendo motivo de debate. A presen&#231;a de turg&#234;ncia jugular patol&#243;gica (TJP) reflete a eleva&#231;&#227;o das press&#245;es de enchimento das c&#226;maras direitas, o que, por sua vez, frequentemente se correlaciona com as press&#245;es de enchimento do ventr&#237;culo esquerdo. Uma an&#225;lise retrospectiva do estudo SOLVD mostrou que a presen&#231;a de TJP pode ser um marcador de pior progn&#243;stico, considerando que sua presen&#231;a foi um marcador de re-hospitaliza&#231;&#227;o, de hospitaliza&#231;&#227;o e morte por insufici&#234;ncia card&#237;aca e de morte por fal&#234;ncia card&#237;aca<sup>11</sup>.</p>
    <p>No entanto, os resultados da avalia&#231;&#227;o da TJP n&#227;o foram universalmente reprodut&#237;veis, e s&#227;o encontrados questionamentos acerca de seu real valor: a habilidade m&#233;dica em detectar eleva&#231;&#245;es da press&#227;o venosa jugular ao exame f&#237;sico, pois &#233; grande a evolu&#231;&#227;o tecnol&#243;gica e a disponibilidade de m&#233;todos complementares de diagn&#243;stico. A diversidade de metodologia em avaliar a PVJ tamb&#233;m &#233; um fator importante nos estudos, considerando que n&#227;o existe padroniza&#231;&#227;o universalmente aceita. No estudo cl&#225;ssico de Stevenson e Perloff<sup>12</sup>, a presen&#231;a de TJP foi definida como o aparecimento da veia jugular interna acima da clav&#237;cula, com o paciente elevado entre 30&#186; e 45&#186;. Apesar de amplamente utilizada, essa defini&#231;&#227;o pode deixar de detectar eleva&#231;&#245;es mais discretas das press&#245;es de enchimento. Os pacientes poderiam ter a acur&#225;cia diagn&#243;stica melhorada se avaliados quanto &#224; presen&#231;a do refluxo hepatojugular<sup>13,14</sup>.</p>
    <p>Os diversos estudos com pacientes portadores de IC, ainda que descompensados, mostram uma baixa preval&#234;ncia de TJP<sup>15-17</sup>, de 11% a 14%. Por fim, estima-se que a acur&#225;cia da PVJ em detectar eleva&#231;&#227;o da PAD &#233; inferior a 75% e que a concord&#226;ncia das press&#245;es direita e esquerda &#233; de, aproximadamente, 75% nos pacientes portadores de IC<sup>18</sup>.</p>
    <p>Outro importante achado ao exame f&#237;sico &#233; a presen&#231;a de terceira bulha (B3). Desde a primeira descri&#231;&#227;o do ritmo de galope por Potain<sup>19</sup>, em 1880, a B3 vem sendo estudada. Sua presen&#231;a &#233; altamente espec&#237;fica para a detec&#231;&#227;o de disfun&#231;&#227;o ventricular e eleva&#231;&#227;o das press&#245;es de enchimento, estimando-se em 93%<sup>20</sup>. Al&#233;m disso, &#233; apontada como marcador progn&#243;stico independente nos pacientes com IC<sup>11</sup>. Por outro lado, sua sensibilidade &#233; baixa (entre 13% e 52%) e exibe muita variabilidade interobservadores, dependendo da experi&#234;ncia deles<sup>21</sup>.</p>
    <p>Em estudo que avaliou especificamente os achados ao exame f&#237;sico na avalia&#231;&#227;o hemodin&#226;mica de pacientes com IC avan&#231;ada, a presen&#231;a de B3 n&#227;o acrescentou informa&#231;&#227;o relevante para a presen&#231;a de POAP &gt; 22mmHg<sup>8</sup>. No estudo de Stevenson e Perloff<sup>12</sup>, j&#225; mencionado anteriormente, 50 pacientes com IC avan&#231;ada &#224; espera de transplante card&#237;aco foram avaliados quanto ao exame f&#237;sico e &#224; hemodin&#226;mica invasiva. Do total, 48 apresentaram B3, n&#227;o sendo indicado, portanto, para discriminar pacientes com e sem eleva&#231;&#227;o das press&#245;es de enchimento.</p>
    <p>
      <bold>Radiografia de t&#243;rax</bold>
    </p>
    <p>A radiografia de t&#243;rax &#233; um exame complementar amplamente dispon&#237;vel e barato que, tradicionalmente, auxilia no diagn&#243;stico de insufici&#234;ncia card&#237;aca. Nos pacientes com IC, a presen&#231;a de sinais de congest&#227;o, como, por exemplo, cefaliza&#231;&#227;o da trama vascular pulmonar, edema intersticial e edema alveolar, tem alta especificidade para descompensa&#231;&#227;o (acima de 96%), mas possui baixa sensibilidade. Vinte por cento (20%) dos pacientes com cardiomegalia ao ecocardiograma n&#227;o apresentaram esse diagn&#243;stico na radiografia de t&#243;rax, e pacientes com eleva&#231;&#227;o das press&#245;es de enchimento ventricular podem n&#227;o apresentar qualquer sinal de congest&#227;o. Derrame pleural, quando presente, tem elevada especificidade para descompensa&#231;&#227;o (92%), mas baixa sensibilidade (25%). Estima-se, portanto, que um em cada cinco pacientes com sintomas de IC descompensada que procuram o setor de emerg&#234;ncia apresenta radiografia de t&#243;rax sem qualquer sinal de congest&#227;o, apesar de estar com eleva&#231;&#227;o das press&#245;es de enchimento ventricular<sup>22</sup>.</p>
    <p>
      <bold>Monitoriza&#231;&#227;o do peso</bold>
    </p>
    <p>A monitoriza&#231;&#227;o do peso de pacientes com IC &#233; recomendada segundo a III Diretriz Brasileira de Insufici&#234;ncia Card&#237;aca Cr&#244;nica, com o objetivo de verificar o estado vol&#234;mico<sup>23</sup>. Varia&#231;&#245;es de peso, especialmente em per&#237;odos curtos de tempo, podem ser bons indicativos de piora da volemia. Muitos estudos, entretanto, s&#227;o controversos nesse assunto, indicando que pouco ou nenhum ganho de peso &#233; observado antes de um epis&#243;dio de descompensa&#231;&#227;o ou que pequena redu&#231;&#227;o de peso &#233; observada ap&#243;s compensa&#231;&#227;o cl&#237;nica de epis&#243;dio de IC aguda. Em muitos casos, a descompensa&#231;&#227;o pode ocorrer n&#227;o por ac&#250;mulo real de l&#237;quido, mas por redistribui&#231;&#227;o h&#237;drica da periferia para os pulm&#245;es por ativa&#231;&#227;o aguda neuro-humoral e inflamat&#243;ria, levando a altera&#231;&#245;es card&#237;acas e vasculares que promovem redu&#231;&#227;o da capacit&#226;ncia venosa e aumento da resist&#234;ncia arterial perif&#233;rica<sup>24</sup>.</p>
    <p>
      <bold>Pept&#237;dios natriur&#233;ticos</bold>
    </p>
    <p>H&#225; tr&#234;s tipos de pept&#237;deos natriur&#233;ticos (PN): pept&#237;deo natriur&#233;tico atrial (ANP), pept&#237;deo natriur&#233;tico tipo B (BNP) e pept&#237;deo natriur&#233;tico tipo C (CNP). ANP e BNP s&#227;o produzidos fundamentalmente pelo cora&#231;&#227;o; e o CNP, pelas c&#233;lulas endoteliais.</p>
    <p>O BNP &#233; um horm&#244;nio produzido pelos cardiomi&#243;citos em resposta ao estiramento, secund&#225;rio ao aumento das press&#245;es de enchimento ventricular ou de sobrecarga de volume. Inicialmente, os cardiomi&#243;citos produzem o pr&#233;-proBNP, que &#233; convertido em proBNP e, finalmente, no metab&#243;lito ativo BNP, que promove vasodilata&#231;&#227;o e natriurese. O proBNP e o BNP t&#234;m sido muito utilizados na pr&#225;tica cl&#237;nica para diagn&#243;sticos, a fim de avaliar o estado vol&#234;mico e tra&#231;ar progn&#243;stico em pacientes com IC. V&#225;rios estudos demonstram a associa&#231;&#227;o positiva entre os n&#237;veis desses PN ao grau de disfun&#231;&#227;o ventricular e &#224; classe funcional. Outros ainda mostram que existe correla&#231;&#227;o positiva entre os n&#237;veis de BNP e os de POAP (r=0,72) em pacientes com IC aguda<sup>25</sup> e que o tratamento intensivo determina queda dos n&#237;veis de POAP e de PN.</p>
    <p>Apesar dessas evid&#234;ncias, alguns autores n&#227;o encontraram boa correla&#231;&#227;o entre os n&#237;veis de BNP e de proBNP com as PEV. Em estudo realizado com pacientes cr&#237;ticos, internados por diversas condi&#231;&#245;es cl&#237;nicas e que receberam cateter de Swan-Ganz como parte do tratamento, observou-se que os n&#237;veis de PN n&#227;o tiveram qualquer rela&#231;&#227;o com a medida da press&#227;o de oclus&#227;o da art&#233;ria pulmonar, n&#227;o sendo, portanto, um bom marcador n&#227;o invasivo da PEV para essa popula&#231;&#227;o<sup>26</sup>. Al&#233;m disso, ap&#243;s a normaliza&#231;&#227;o das press&#245;es de enchimento, medida de forma invasiva, com a terap&#234;utica para IC descompensada, percebeu-se que os n&#237;veis de BNP, apesar de tamb&#233;m se reduzirem, ainda permaneceram significativamente elevados<sup>27</sup>.</p>
    <p>Valores extremos de BNP, inferior a 100pg/ml ou superior a 400pg/ml, apresentam melhor correla&#231;&#227;o para press&#245;es de enchimento normais ou elevadas, respectivamente. Entretanto, a faixa situada entre esses valores &#233; chamada "zona cinzenta", caracterizada por n&#227;o apresentar boa correla&#231;&#227;o.</p>
    <p>Vale ressaltar que in&#250;meras condi&#231;&#245;es alteram a produ&#231;&#227;o e o <italic>clearence</italic> do BNP, tais como idade, peso, insufici&#234;ncia renal, doen&#231;as n&#227;o card&#237;acas, entre outras, o que tamb&#233;m limita sua utiliza&#231;&#227;o em uma parcela desses pacientes.</p>
    <p>
      <bold>Ecocardiograma</bold>
    </p>
    <p>O ecocardiograma &#233; o exame complementar de maior utilidade na avalia&#231;&#227;o dos pacientes com IC. Fornece informa&#231;&#245;es importantes em rela&#231;&#227;o &#224; morfologia card&#237;aca, quantifica a fun&#231;&#227;o sist&#243;lica e diast&#243;lica, e auxilia na defini&#231;&#227;o etiol&#243;gica, nos par&#226;metros progn&#243;sticos e na resposta &#224;s diversas interven&#231;&#245;es terap&#234;uticas.</p>
    <p>Nos &#250;ltimos anos, duas novas e fundamentais avalia&#231;&#245;es ecocardiogr&#225;ficas foram incorporadas na pr&#225;tica di&#225;ria: a avalia&#231;&#227;o de dissincronismo ventricular e a avalia&#231;&#227;o hemodin&#226;mica. Essa &#250;ltima tem sido muito importante no entendimento do perfil hemodin&#226;mico de pacientes com IC, especialmente aqueles descompensados ou de dif&#237;cil manejo. O chamado "ecocardiograma hemodin&#226;mico" refere-se &#224; avalia&#231;&#227;o ecocardiogr&#225;fica de par&#226;metros hemodin&#226;micos que espelham os dados hemodin&#226;micos obtidos pela monitoriza&#231;&#227;o invasiva. O <xref ref-type="fig" rid="a20qua01m">Quadro 1</xref> mostra os principais par&#226;metros ecocardiogr&#225;ficos que devem ser utilizados para estimar a condi&#231;&#227;o hemodin&#226;mica de pacientes com IC descompensada.</p>
    <p content-type="asset">
      <fig id="a20qua01m">
        <graphic xlink:href="1678-4170-abc-98-01-0e15-00020-gf02.jpg"/></fig>
    </p>
    <p>A utiliza&#231;&#227;o da t&#233;cnica de imagem de Doppler tissular (TDI) do movimento anular mitral foi incorporada &#224; avalia&#231;&#227;o de rotina ecocardiogr&#225;fica, permitindo estimar a press&#227;o atrial esquerda (PAE). Essa medida &#233; realizada por meio do corte apical 4 c&#226;maras na parede septal ou lateral do anel mitral, obtendo a velocidade precoce diast&#243;lica do Doppler tissular (E'). Com a medida de Doppler convencional do fluxo transmitral, &#233; obtida a velocidade de pico do fluxo diast&#243;lico (E). A rela&#231;&#227;o E/E' &#233; calculada, e seu valor tem boa correla&#231;&#227;o na literatura com a medida invasiva da press&#227;o diast&#243;lica final do ventr&#237;culo esquerdo (PDFVE). Utilizando-se a f&#243;rmula 1,24x(E/E')+1,9, calcula-se a PAE.</p>
    <p>Ommen e cols.<sup>28</sup> mostraram, no in&#237;cio da d&#233;cada passada, que uma rela&#231;&#227;o E/E' &gt; 15mmHg tem boa correla&#231;&#227;o com uma PDFVE superior a 12 mmHg (86% de especificidade). J&#225; quando a rela&#231;&#227;o E/E' &#233; inferior a 8 mmHg, a correla&#231;&#227;o &#233; boa para uma PDFVE normal (97% de valor preditivo negativo). Em compara&#231;&#227;o ao BNP, a rela&#231;&#227;o E/E' mostra melhor performance para detectar congest&#227;o, mesmo nos pacientes com fun&#231;&#227;o do VE preservada<sup>29</sup>.</p>
    <p>Assim como o BNP, a rela&#231;&#227;o E/E' tamb&#233;m possui uma "zona cinzenta". Valores de E/E' inferiores a 8 mmHg apresentam boa correla&#231;&#227;o com a PDFVE normal, ao passo que os superiores a 15 mmHg demonstram boa correla&#231;&#227;o com a eleva&#231;&#227;o das press&#245;es de enchimento. Entre esses valores, pode ocorrer muita varia&#231;&#227;o, portanto, outros par&#226;metros devem ser avaliados para tentar definir a presen&#231;a de congest&#227;o. Um esquema do ecocardiograma hemodin&#226;mico &#233; apresentado na <xref ref-type="fig" rid="a20fig02m">Figura 2</xref>.</p>
    <p content-type="asset">
      <fig id="a20fig02m">
        <graphic xlink:href="1678-4170-abc-98-01-0e15-00020-gf03.jpg"/></fig>
    </p>
    <p>
      <bold>Bioimped&#226;ncia transtor&#225;cica</bold>
    </p>
    <p>A bioimped&#226;ncia transtor&#225;cica (BIT) ou cardiografia por imped&#226;ncia tor&#225;cica &#233; um m&#233;todo diagn&#243;stico n&#227;o invasivo para avalia&#231;&#227;o hemodin&#226;mica, que fornece os seguintes par&#226;metros: d&#233;bito card&#237;aco e volume sist&#243;lico, resist&#234;ncia vascular sist&#234;mica, par&#226;metros de contratilidade ventricular e padr&#227;o de volemia (conte&#250;do de fluido tor&#225;cico). Altera&#231;&#245;es na voltagem e na imped&#226;ncia el&#233;trica tor&#225;cica, fundamentalmente pela varia&#231;&#227;o de fluxo sangu&#237;neo nos grandes vasos (o sangue &#233; excelente condutor de corrente), s&#227;o traduzidas em par&#226;metros hemodin&#226;micos.</p>
    <p>A medida de d&#233;bito card&#237;aco (DC) pela BIT apresenta boa correla&#231;&#227;o com a medida invasiva de DC, com coeficiente de correla&#231;&#227;o variando entre 0,76 e 0,89<sup>30-32</sup>. Em estudo que avaliou a causa de dispneia em pacientes idosos admitidos em emerg&#234;ncia, a avalia&#231;&#227;o pela bioimped&#226;ncia foi capaz de alterar o diagn&#243;stico cl&#237;nico inicial em 13% dos pacientes e teve impacto na mudan&#231;a do tratamento em 39%<sup>33</sup>. Esse m&#233;todo tem a vantagem de poder ser realizado &#224; beira do leito, em tempo real, monitorando a resposta &#224;s interven&#231;&#245;es terap&#234;uticas.</p>
    <p>A avalia&#231;&#227;o hemodin&#226;mica pela BIT, fundamentalmente na defini&#231;&#227;o da volemia, tem sido motivo de controv&#233;rsia. O estudo BIG<sup>34</sup>, o maior estudo randomizado de BIT em pacientes com IC, publicado recentemente, mostrou apenas modesta correla&#231;&#227;o entre os d&#233;bitos card&#237;acos medidos pela BIT e pela monitora&#231;&#227;o invasiva (r=0,4-0,6), mencionando que o conte&#250;do de fluido tor&#225;cico n&#227;o se correlacionou com a medida da POAP. Quando comparados os perfis hemodin&#226;micos de perfus&#227;o sist&#234;mica e de congest&#227;o, a BIT n&#227;o mostrou concord&#226;ncia com o padr&#227;o observado na monitora&#231;&#227;o invasiva, n&#227;o sendo capaz de dar informa&#231;&#227;o fiel sobre as press&#245;es de enchimento do ventr&#237;culo esquerdo. Al&#233;m disso, &#233; um m&#233;todo pouco dispon&#237;vel e com uma s&#233;rie de limita&#231;&#245;es a seu uso, como, por exemplo, derrame pleural, obesidade, insufici&#234;ncia a&#243;rtica, extremos de frequ&#234;ncia card&#237;aca, entre outro</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>A avalia&#231;&#227;o individualizada e integrada do exame f&#237;sico aos diversos m&#233;todos de avalia&#231;&#227;o hemodin&#226;mica n&#227;o invasiva para a presen&#231;a de congest&#227;o parece ser a forma ideal de estimar as press&#245;es de enchimento ventricular, tanto para ajuste terap&#234;utico nos pacientes descompensados quanto naqueles ambulatoriais, visando a identificar precocemente o aumento das press&#245;es de enchimento e prevenir a descompensa&#231;&#227;o cl&#237;nica.</p>
    <p>&#201; importante reconhecer a limita&#231;&#227;o dos sinais e dos sintomas tradicionais de insufici&#234;ncia card&#237;aca, especialmente do edema, dos estertores crepitantes e da terceira bulha, para guiar o tratamento e estimar a hemodin&#226;mica de pacientes com IC cr&#244;nica. Ortopneia e turg&#234;ncia jugular patol&#243;gica s&#227;o os melhores marcadores de eleva&#231;&#227;o das press&#245;es de enchimento nesse contexto. Em fun&#231;&#227;o disso, muitos m&#233;dicos utilizam o BNP para auxiliar na detec&#231;&#227;o de congest&#227;o. Valores muito baixos de BNP (&lt;100pg/ml) s&#227;o bons preditores de aus&#234;ncia de congest&#227;o, por&#233;m sua eleva&#231;&#227;o n&#227;o est&#225; associada, necessariamente, a press&#245;es de enchimento elevadas. A utiliza&#231;&#227;o do BNP para orientar o tratamento ainda precisa ser definida em ensaios cl&#237;nicos prospectivos.</p>
    <p>O ecocardiograma hemodin&#226;mico &#233; o melhor m&#233;todo complementar dispon&#237;vel para auxiliar o m&#233;dico na detec&#231;&#227;o de congest&#227;o. Diversos estudos mostraram que seus par&#226;metros se correlacionam de forma significativa com os mesmos par&#226;metros obtidos pela monitoriza&#231;&#227;o invasiva. Devem ser especialmente considerados valores de E/E' inferiores a 8mmHg, por apresentarem boa correla&#231;&#227;o com a PDFVE normal, e de E/E' superiores a 15mmHg, por se correlacionarem positivamente com aumento da PDFVE.</p>
    <p>A bioimped&#226;ncia transtor&#225;cica e outras novas tecnologias que v&#234;m sendo testadas ainda precisam demonstrar benef&#237;cios em futuros ensaios cl&#237;nicos para ser incorporadas &#224; pr&#225;tica de forma rotineira. Portanto, a utiliza&#231;&#227;o integrada do exame cl&#237;nico criterioso e desses m&#233;todos complementares permite uma abordagem mais completa e individualizada, visando a reduzir a morbidade e melhorar o progn&#243;stico dos pacientes com insufici&#234;ncia card&#237;aca descompensada.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>Este artigo &#233; parte de tese de Doutorado de Gustavo Luiz Almeia Junior pela Universidade Federal do Rio Grande do Sul.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Gustavo Luiz Almeida Junior </p>
        <p> Rua Alfredo Ceschiatti, 100 BL.01/ 1206, Barra da Tijuca </p>
        <p> 22775-045 - Rio de Janeiro, RJ, Brasil</p>
        <p> E-mail: </p>
        <p><email xlink:href="gustavogouvea@cardiol.br">gustavogouvea@cardiol.br</email>, </p>
        <p>
          <email xlink:href="gustavogouvea@globo.com">gustavogouvea@globo.com</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 02/05/11; revisado recebido em 18/08/11; aceito em 22/08/11.</p>
  </body>
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  <sub-article article-type="translation" id="TRes" xml:lang="es">
    <front-stub>
      <article-categories/>
      <title-group>
        <article-title xml:lang="es">Evaluaci&#243;n hemodin&#225;mica en la insuficiencia card&#237;aca: papel del examen f&#237;sico y de los m&#233;todos no invasivos</article-title>
      </title-group>
      <abstract xml:lang="es">
        <p>Entre las enfermedades cardiovasculares, la insuficiencia card&#237;aca (IC) presenta una elevada tasa de ingreso hospitalario, morbilidad y mortalidad, consumiendo enormes recursos financieros del sistema de sanidad en Brasil, y de otros pa&#237;ses. La correcta determinaci&#243;n de las presiones en el llenado del ventr&#237;culo izquierdo, por evaluaci&#243;n invasiva o no invasiva, es fundamental para el adecuado tratamiento de los pacientes con IC cr&#243;nica descompensada, considerando que la congesti&#243;n es el principal factor determinante de los s&#237;ntomas y del ingreso. El examen f&#237;sico ha sido inadecuado para prever el est&#225;ndar hemodin&#225;mico. Varios estudios sugieren que la concordancia en los hallazgos del examen f&#237;sico por diferentes m&#233;dicos es peque&#241;a y que, las propias alteraciones fisiol&#243;gicas adaptativas en la IC cr&#243;nica, disimulan los importantes aspectos del examen f&#237;sico. Como la evaluaci&#243;n cl&#237;nica falla a la hora de prevenir la hemodin&#225;mica, y tambi&#233;n por el hecho de que la utilizaci&#243;n del cat&#233;ter de Swan-Ganz de rutina no se recomiende con ese fin en los pacientes con IC, los m&#233;todos de evaluaci&#243;n hemodin&#225;mica no invasivos, como el PNB, el ecocardiograma y la bioimpedancia cardiogr&#225;fica, est&#225;n en aumento. Este trabajo pretende realizar, a favor del m&#233;dico, una revisi&#243;n de la funci&#243;n de cada una de esas herramientas, para definir la condici&#243;n hemodin&#225;mica en que est&#225;n los pacientes con IC descompensada, objetivando un tratamiento m&#225;s racional e individualizado.</p>
      </abstract>
    </front-stub>
    <body>
      <p>
        <bold>ACTUALIZACI&#211;N CL&#205;NICA</bold>
      </p>
      <p>
        <fn id="inicio-body2">
          <label>
            <bold>Evaluaci&#243;n hemodin&#225;mica en la insuficiencia card&#237;aca: papel del examen f&#237;sico y de los m&#233;todos no invasivos</bold>
          </label>
          <p>
            <bold>Gustavo Luiz Almeida Junior<sup>I</sup>; S&#233;rgio Salles Xavier<sup>III</sup>; Marcelo Iorio Garcia<sup>II</sup>; Nadine Clausell<sup>IV</sup></bold>
          </p>
        </fn>
      </p>
      <p><sup>I</sup>Casa de Sa&#250;de S&#227;o Jos&#233; </p>
      <p><sup>II</sup>Hospital Pr&#243;-Card&#237;aco </p>
      <p><sup>III</sup>Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ</p>
      <p><sup>IV</sup>Hospital de Cl&#237;nicas da UFRGS, Rio Grande do Sul, RS, Brasil </p>
      <p>Correspondencia</p>
      <p>
        <bold>RESUMEN</bold>
      </p>
      <p>Entre las enfermedades cardiovasculares, la insuficiencia card&#237;aca (IC) presenta una elevada tasa de ingreso hospitalario, morbilidad y mortalidad, consumiendo enormes recursos financieros del sistema de sanidad en Brasil, y de otros pa&#237;ses. La correcta determinaci&#243;n de las presiones en el llenado del ventr&#237;culo izquierdo, por evaluaci&#243;n invasiva o no invasiva, es fundamental para el adecuado tratamiento de los pacientes con IC cr&#243;nica descompensada, considerando que la congesti&#243;n es el principal factor determinante de los s&#237;ntomas y del ingreso. El examen f&#237;sico ha sido inadecuado para prever el est&#225;ndar hemodin&#225;mico. Varios estudios sugieren que la concordancia en los hallazgos del examen f&#237;sico por diferentes m&#233;dicos es peque&#241;a y que, las propias alteraciones fisiol&#243;gicas adaptativas en la IC cr&#243;nica, disimulan los importantes aspectos del examen f&#237;sico. Como la evaluaci&#243;n cl&#237;nica falla a la hora de prevenir la hemodin&#225;mica, y tambi&#233;n por el hecho de que la utilizaci&#243;n del cat&#233;ter de Swan-Ganz de rutina no se recomiende con ese fin en los pacientes con IC, los m&#233;todos de evaluaci&#243;n hemodin&#225;mica no invasivos, como el PNB, el ecocardiograma y la bioimpedancia cardiogr&#225;fica, est&#225;n en aumento. Este trabajo pretende realizar, a favor del m&#233;dico, una revisi&#243;n de la funci&#243;n de cada una de esas herramientas, para definir la condici&#243;n hemodin&#225;mica en que est&#225;n los pacientes con IC descompensada, objetivando un tratamiento m&#225;s racional e individualizado.</p>
      <p><bold>Palabras clave:</bold> Heart failure; hemodynamics; cardiography, impedance; radiography, thoracic.</p>
      <p>
        <bold>Introducci&#243;n</bold>
      </p>
      <p>La insuficiencia card&#237;aca (IC) es un s&#237;ndrome cl&#237;nico cuyos signos y s&#237;ntomas son utilizados cl&#225;sicamente para definir el diagn&#243;stico, orientar el tratamiento y evaluar el pron&#243;stico. La adecuada determinaci&#243;n de las presiones de llenado del ventr&#237;culo izquierdo, por evaluaci&#243;n invasiva o no invasiva, es fundamental para el correcto tratamiento de los pacientes con IC cr&#243;nica, una vez que la congesti&#243;n es el factor determinante de los s&#237;ntomas y del ingreso. La <xref ref-type="fig" rid="es_a20fig01-body2">Figura 1</xref> indica los posibles momentos para la identificaci&#243;n y para el tratamiento de la elevaci&#243;n de las presiones de llenado ventricular (PLLV)<sup>1</sup>.</p>
      <p content-type="asset">
        <fig id="es_a20fig01-body2">
          <graphic xlink:href="1678-4170-abc-98-01-0e15-00020-gf01-es.jpg"/></fig>
      </p>
      <p>La evaluaci&#243;n hemodin&#225;mica invasiva tambi&#233;n posee una gran importancia en el examen y en el manejo de esos pacientes, y hace d&#233;cadas se usa inicialmente por punci&#243;n ventricular izquierda y derecha<sup>2 </sup>y, actualmente, por medio del cat&#233;ter de Swan-Ganz<sup>3</sup>. Sin embargo, en los &#250;ltimos a&#241;os, el uso de la monitorizaci&#243;n hemodin&#225;mica invasiva ha venido disminuyendo, especialmente por las crecientes evidencias de la falta de beneficio con ese m&#233;todo<sup>4</sup>.</p>
      <p>As&#237;, la evaluaci&#243;n cl&#237;nica y hemodin&#225;mica no invasiva qued&#243; demostrada. Por tanto, criterios diagn&#243;sticos, como los de Boston o de Framingham, han sido ampliamente utilizados en los ensayos cl&#237;nicos y en las directrices para definir la IC, por ser de f&#225;cil realizaci&#243;n, no tener ning&#250;n coste y tener una buena especificidad para el diagn&#243;stico. Adem&#225;s, la evaluaci&#243;n cl&#237;nica tambi&#233;n presenta una buena correlaci&#243;n de pron&#243;stico. La clasificaci&#243;n funcional de la <italic>New York Heart Association</italic> (NYHA) y m&#225;s recientemente, la clasificaci&#243;n cl&#237;nico-hemodin&#225;mica de Stevenson en cuatro perfiles hemodin&#225;micos, a tono con los hallazgos del examen f&#237;sico de congesti&#243;n y perfusi&#243;n perif&#233;rica, son los marcadores de pron&#243;sticos mejor documentados<sup>5</sup>. Los p&#233;ptidos natriur&#233;ticos (PNB y NT-proPNB), tienen una utilidad en el diagn&#243;stico de IC descompensada en urgencias, confirmando o descartando el diagn&#243;stico en pacientes con disnea, y d&#225;ndole un valor de pron&#243;stico a esa poblaci&#243;n, especialmente en el alta hospitalaria, para prevenir los eventos futuros.</p>
      <p>Sin embargo, observamos que el historial, el examen f&#237;sico y los p&#233;ptidos natriur&#233;ticos, sufren un gran cuestionamento con relaci&#243;n a su poder de evaluar la condici&#243;n hemodin&#225;mica, fundamentalmente de congesti&#243;n o bajo d&#233;bito, en pacientes con IC descompensada. Las limitaciones del examen f&#237;sico empiezan por la cada vez m&#225;s intensa falta de inter&#233;s de los m&#233;dicos en realizar un examen f&#237;sico de calidad, lo que se sustenta en la amplia disponibilidad de ex&#225;menes complementarios que vienen siendo utilizados, muchas veces como reemplazo al examen f&#237;sico. Adem&#225;s, el tiempo reducido de consultas m&#233;dicas y la formaci&#243;n deficiente de muchos cursos de medicina, pueden ser factores asociados para la ca&#237;da de la calidad del examen f&#237;sico. Varios estudios sugieren que la propia concordancia en los hallazgos del examen f&#237;sico por diferentes m&#233;dicos es peque&#241;a. El est&#225;ndar oro para la evaluaci&#243;n hemodin&#225;mica en la IC es el cat&#233;ter de la arteria pulmonar (Swan-Ganz), y varios estudios compararon la evaluaci&#243;n hemodin&#225;mica invasiva con el examen f&#237;sico, demostrando la limitaci&#243;n de esa evaluaci&#243;n para definir la congesti&#243;n o el bajo d&#233;bito.</p>
      <p>Los p&#233;ptidos natriur&#233;ticos empezaron a ser utilizados en la pr&#225;ctica cl&#237;nica al inicio de esta d&#233;cada, con la promesa de aumentar la exactitud en el diagn&#243;stico de la IC y de diagnosticar la elevaci&#243;n de la PLLV definiendo la congesti&#243;n, una vez que se elevan como respuesta a la distensi&#243;n ventricular. Sin embargo, con el avance del conocimiento en esa &#225;rea, tambi&#233;n se observan varias limitaciones de los p&#233;ptidos natriur&#233;ticos en la identificaci&#243;n de la congesti&#243;n, no existiendo, hoy por hoy, un punto de cohorte definido para eso.</p>
      <p>De la misma forma en que se dio la evaluaci&#243;n cl&#237;nica, los p&#233;ptidos natriur&#233;ticos tambi&#233;n fallan en la previsi&#243;n de la hemodin&#225;mica, por el hecho de que la utilizaci&#243;n del cat&#233;ter de Swan-Ganz de rutina no est&#225; recomendada para ese fin en los pacientes con IC. Por tanto, el uso de m&#233;todos no invasivos de evaluaci&#243;n hemodin&#225;mica como el ecocardiograma y la bioimpedancia cardiogr&#225;fica, est&#225;n en aumento.</p>
      <p>El presente trabajo pretende proporcionarle al cl&#237;nico, una revisi&#243;n de la funci&#243;n de cada una de esas herramientas y la definici&#243;n de la condici&#243;n hemodin&#225;mica en que se encuentran los pacientes con IC descompensada, objetivando un tratamiento m&#225;s racional e individualizado.</p>
      <p>
        <bold>Evaluaci&#243;n cl&#237;nica: historial, examen f&#237;sico, radiograf&#237;a de t&#243;rax y monitorizaci&#243;n del peso</bold>
      </p>
      <p>
        <bold>Historial y examen f&#237;sico</bold>
      </p>
      <p>Entre los diversos s&#237;ntomas de la IC, la ortopnea (disnea que debuta con la posici&#243;n ortost&#225;tica y se alivia con la elevaci&#243;n del dec&#250;bito o con la posici&#243;n sentada), se destaca como el s&#237;ntoma que m &#225;s se correlaciona con la elevaci&#243;n de las presiones de llenado ventricular.</p>
      <p>En un estudio con pacientes ambulatoriales de cl&#237;nica de IC en Brasil, la presencia de la ortopnea fue el m&#225;s sensible marcador de elevaci&#243;n de las presiones de llenado de derecha e izquierda<sup>6</sup>. En ese estudio, el desempe&#241;o diagn&#243;stico de los diferentes hallazgos del examen f&#237;sico individualmente, fue sub&#243;ptimo para la prevenci&#243;n del est&#225;ndar hemodin&#225;mico. Despu&#233;s de evaluar una puntuaci&#243;n cl&#237;nica para la congesti&#243;n (conteniendo las variables de crepitaci&#243;n pulmonar, turgencia yugular patol&#243;gica, edema perif&#233;rico y tercer ruido), el mejor valor predictivo negativo para la congesti&#243;n fue la ausencia de esos signos cl&#237;nicos a&#241;adidos (95% de valor predictivo para la presi&#243;n atrial izquierda &lt; 20mmHg).</p>
      <p>La persistencia de la ortopnea con el tratamiento, tambi&#233;n presenta una relaci&#243;n de pron&#243;stico. Los pacientes que se siguen quejando de la ortopnea durante un a&#241;o de tratamiento para IC, poseen una tasa de reingreso cuatro veces mayor si los comparamos con los que no tienen ortopnea y adem&#225;s no mejoran la funci&#243;n ventricular izquierda al final de ese per&#237;odo (11&#177;13% <italic>vs.</italic> -1&#177;6%; p&lt;0,001)<sup>7</sup>.</p>
      <p>En el subestudio de examen f&#237;sico del ESCAPE <italic>trial</italic>, la ortopnea fue el &#250;nico s&#237;ntoma que se correlacion&#243; con la elevaci&#243;n de la PLLV. Cuando los pacientes ten&#237;an ortopnea, y pese a la utilizaci&#243;n de dos o m&#225;s almohadas, la chance de que tuviesen una presi&#243;n de oclusi&#243;n de la arteria pulmonar (POAP) <underline>&gt;</underline> 30mmHg fue 3,6 veces mayor (OR 3,6; p&lt;0,05)<sup>8</sup>.</p>
      <p>En cuanto al examen f&#237;sico, diversos estudios han evaluado la capacidad en estimar la condici&#243;n hemodin&#225;mica de pacientes con IC. De todos los hallazgos, la presi&#243;n venosa yugular (PVY), parece ser la m&#225;s exacta al detectar la elevaci&#243;n de las presiones de llenado del ventr&#237;culo izquierdo<sup>8</sup>. Desde la introducci&#243;n de la evaluaci&#243;n de la PVY en la pr&#225;ctica cl&#237;nica, en 1930, por Lewis<sup>9</sup> y posteriormente, de la estandarizaci&#243;n de su evaluaci&#243;n por Borst y Molhuysen en 1952<sup>10</sup>, la PVY ha venido siendo motivo de debate. La presencia de turgencia yugular patol&#243;gica (IYP) refleja la elevaci&#243;n de las presiones de llenado de las c&#225;maras derechas, lo que, a su vez, con frecuencia se correlaciona con las presiones de llenado del ventr&#237;culo izquierdo. Un an&#225;lisis retrospectivo del estudio SOLVD mostr&#243; que la presencia de IYP puede ser un marcador de un peor pron&#243;stico, considerando que su presencia fue un marcador de reingreso, de ingreso y deceso por insuficiencia card&#237;aca, y tambi&#233;n de muerte por fracaso card&#237;aco<sup>11</sup>.</p>
      <p> Sin embargo, los resultados de la evaluaci&#243;n de la IYP no fueron universalmente reproductibles, y encontramos cuestionamientos sobre su real valor: la habilidad m&#233;dica en detectar las elevaciones de la presi&#243;n venosa yugular al examen f&#237;sico, ya que es grande la evoluci&#243;n tecnol&#243;gica y la disponibilidad de m&#233;todos complementarios de diagn&#243;stico. La diversidad de la metodolog&#237;a en evaluar la PVY tambi&#233;n es un factor importante en los estudios, considerando que no existe una estandarizaci&#243;n aceptada universalmente. En el estudio cl&#225;sico de Stevenson y Perloff<sup>12</sup>, la presencia de IYP se defini&#243; como el aparecimiento de la vena yugular interna por encima de la clav&#237;cula, con el paciente elevado entre 30&#186; y 45&#186;. A pesar de ser ampliamente utilizada, esa definici&#243;n puede dejar de detectar elevaciones m&#225;s discretas de las presiones de llenado. Los pacientes podr&#237;an tener la exactitud diagn&#243;stica mejorada si los evaluamos en cuanto a la presencia del reflujo hepatoyugular<sup>13,14</sup>.</p>
      <p>Los diversos estudios realizados con pacientes portadores de IC, aunque sean descompensados, arrojan una baja prevalencia de IYP<sup>15-17</sup>, de 11% a 14%. Finalmente estimamos que la exactitud de la PVY en detectar la elevaci&#243;n de la PAD es inferior al 75% y que la concordancia de las presiones derecha e izquierda es de aproximadamente 75% en los pacientes portadores de IC<sup>18</sup>.</p>
      <p>Otro importante hallazgo al examen f&#237;sico es la presencia del tercer ruido (B3). Desde la primera descripci&#243;n del ritmo de galope por Potain<sup>19</sup> en 1880, el B3 ha venido siendo estudiado. Su presencia es altamente espec&#237;fica para la detecci&#243;n de la disfunci&#243;n ventricular y la elevaci&#243;n de las presiones de llenado, estim&#225;ndose en un 93%<sup>20</sup>. Adem&#225;s, se le indica como un marcador de pron&#243;stico independiente en los pacientes con IC<sup>11</sup>. Por otro lado, su sensibilidad es baja (entre 13% y 52%) y muestra una gran variabilidad interobservadores, dependiendo de la experiencia que ellos tengan<sup>21</sup>.</p>
      <p>En un estudio que evalu&#243; espec&#237;ficamente los hallazgos al examen f&#237;sico en la evaluaci&#243;n hemodin&#225;mica de pacientes con IC avanzada, la presencia del B3 no a&#241;adi&#243; ninguna informaci&#243;n relevante para la presencia de POAP &gt; 22mmHg<sup>8</sup>. En el estudio de Stevenson y Perloff<sup>12</sup> ya mencionado, 50 pacientes con IC avanzada a la espera de un transplante card&#237;aco, fueron evaluados en cuanto al examen f&#237;sico y a la hemodin&#225;mica invasiva. De ese total, 48 presentaron B3, no siendo indicado, por tanto, para desglosar a los pacientes con y sin elevaci&#243;n de las presiones de llenado.</p>
      <p>
        <bold>Radiograf&#237;a de t&#243;rax</bold>
      </p>
      <p>La Radiograf&#237;a de t&#243;rax es un examen complementario que est&#225; muy extendido y que es barato. Por tradici&#243;n, ayuda en el diagn&#243;stico de la insuficiencia card&#237;aca. En los pacientes con IC, la presencia de signos de congesti&#243;n como por ejemplo, cefalizaci&#243;n de la trama vascular pulmonar, edema intersticial y edema alveolar, tiene una alta especificidad para la descompensaci&#243;n (por encima del 96%), pero posee una baja sensibilidad. Veinte por ciento (20%) de los pacientes con cardiomegalia al ecocardiograma no ten&#237;an ese diagn&#243;stico en la radiograf&#237;a de t&#243;rax, y los pacientes con elevaci&#243;n de las presiones de llenado ventricular pueden no presentar ning&#250;n signo de congesti&#243;n. El derrame pleural, cuando est&#225; presente, tiene una elevada especificidad para la descompensaci&#243;n (92%), m&#225;s baja sensibilidad (25%). Se estima, por tanto, que uno de cada cinco pacientes con s&#237;ntomas de IC descompensada que acuden al servicio de urgencias, presenta una radiograf&#237;a de t&#243;rax sin ning&#250;n signo de congesti&#243;n, pese a estar con la elevaci&#243;n de las presiones de llenado ventricular<sup>22</sup>.</p>
      <p>
        <bold>Monitorizaci&#243;n del peso</bold>
      </p>
      <p>La monitorizaci&#243;n del peso de pacientes con IC se recomienda seg&#250;n la III Directriz Brasile&#241;a de Insuficiencia Card&#237;aca Cr&#243;nica, con el objetivo de verificar el estado vol&#233;mico<sup>23</sup>. Las variaciones de peso, especialmente en los cortos per&#237;odos de tiempo, pueden ser unos buenos indicadores del empeoramiento de la volemia. Muchos estudios sin embargo, son controversiales en ese asunto, indicando que poco o ninguna ganancia de peso se ha observado antes de un episodio de descompensaci&#243;n, o que una peque&#241;a reducci&#243;n de peso se observa despu&#233;s de la compensaci&#243;n cl&#237;nica del episodio de IC aguda. En muchos casos, la descompensaci&#243;n puede ocurrir no por la acumulaci&#243;n real de l&#237;quido, sino por la redistribuci&#243;n h&#237;drica de la periferia hacia los pulmones por la activaci&#243;n aguda neuro-humoral e inflamatoria, conllevando a alteraciones card&#237;acas y vasculares que generan una reducci&#243;n de la capacitancia venosa y del aumento de la resistencia arterial perif&#233;rica<sup>24</sup>.</p>
      <p>
        <bold>P&#233;ptidos natriur&#233;ticos</bold>
      </p>
      <p>Existen tres tipos de p&#233;ptidos natriur&#233;ticos (PN): p&#233;ptido natriur&#233;tico atrial (PNA), p&#233;ptido natriur&#233;tico tipo B (PNB) y p&#233;ptido natriur&#233;tico tipo C (PNC). El PNA y el PNB son producidos fundamentalmente por el coraz&#243;n; y el PNC, por las c&#233;lulas endoteliales.</p>
      <p>El PNB es una neurona producida por los cardiomiocitos como respuesta al estiramiento, secundario al aumento de las presiones de llenado ventricular o de sobrecarga de volumen.</p>
      <p> Inicialmente, los cardiomiocitos producen el pre-proPNB, que es convertido en proPNB y finalmente, en el metabolito activo PNB, que genera la vasodilataci&#243;n y la natriuresis. El proPNB y el PNB se han usado extensamente en la pr&#225;ctica cl&#237;nica para diagn&#243;sticos, con el fin de evaluar el estado vol&#233;mico y trazar el pron&#243;stico en los pacientes con IC. Varios estudios demuestran la asociaci&#243;n positiva entre los niveles de esos PN con el grado de disfunci&#243;n ventricular y con la clase funcional.</p>
      <p> Otros arrojan la existencia de una correlaci&#243;n positiva entre los niveles de PNB y los de POAP (r=0,72) en pacientes con IC aguda<sup>25</sup> y que el tratamiento intensivo determina la ca&#237;da de los niveles de POAP y de PN.</p>
      <p> A pesar de esas evidencias, algunos autores no encontraron una buena correlaci&#243;n entre los niveles de PNB y de proPNB con las PLLV. En un estudio realizado con pacientes cr&#237;ticos, ingresados por diversas condiciones cl&#237;nicas y que recibieron un cat&#233;ter de Swan-Ganz como parte del tratamiento, se observ&#243; que los niveles de PN no obtuvieron ninguna relaci&#243;n respecto de la medida de la presi&#243;n de oclusi&#243;n de la arteria pulmonar, y por tanto, no eran un buen marcador no invasivo de la PLLV para esa poblaci&#243;n<sup>26</sup>. Adem&#225;s, despu&#233;s de la normalizaci&#243;n de las presiones de llenado, la medida de forma invasiva, con la terap&#233;utica para la IC descompensada, nos dimos cuenta de que los niveles de PNB, pese a que tambi&#233;n se reduc&#237;an, todav&#237;a continuaban significativamente elevados<sup>27</sup>.</p>
      <p> Los valores extremos de PNB, inferior a 100pg/ml o superior a 400pg/ml, tienen una mejor correlaci&#243;n para las presiones de llenado normales o elevadas, respectivamente. Pero el rango situado entre esos valores se llama "zona gris", y se caracteriza por no presentar una buena correlaci&#243;n.</p>
      <p> Vale la pena destacar que innumerables condiciones alteran la producci&#243;n y el aclaramiento del PNB, tales como la edad, el peso, la insuficiencia renal, las enfermedades no card&#237;acas, entre otras, lo que tambi&#233;n limita su utilizaci&#243;n en una parte de esos pacientes.</p>
      <p>
        <bold>Ecocardiograma</bold>
      </p>
      <p> El ecocardiograma es el examen complementario de mayor utilidad en la evaluaci&#243;n de los pacientes con IC. Suministra informaciones importantes con relaci&#243;n a la morfolog&#237;a card&#237;aca, cuantifica la funci&#243;n sist&#243;lica y diast&#243;lica, y ayuda en la definici&#243;n etiol&#243;gica, en los par&#225;metros de pron&#243;sticos y en la respuesta a las diversas intervenciones terap&#233;uticas.</p>
      <p> En los &#250;ltimos a&#241;os, dos nuevas y fundamentales evaluaciones ecocardiogr&#225;ficas se incorporan a la pr&#225;ctica diaria: la evaluaci&#243;n del asincronismo ventricular y la evaluaci&#243;n hemodin&#225;mica.</p>
      <p> Esa &#250;ltima ha sido muy importante para comprender el perfil hemodin&#225;mico de los pacientes con IC, especialmente los descompensados o de dif&#237;cil manejo. El llamado "ecocardiograma hemodin&#225;mico" se refiere a la evaluaci&#243;n ecocardiogr&#225;fica de par&#225;metros hemodin&#225;micos que reflejan los datos hemodin&#225;micos obtenidos por la monitorizaci&#243;n invasiva. El <xref ref-type="fig" rid="es_a20tab01-body2">cuadro 1</xref> muestra los principales par&#225;metros ecocardiogr&#225;ficos que deben ser utilizados para estimar la condici&#243;n hemodin&#225;mica de pacientes con IC descompensada.</p>
      <p content-type="asset">
        <fig id="es_a20tab01-body2">
          <graphic xlink:href="1678-4170-abc-98-01-0e15-00020-gf02-es.jpg"/></fig>
      </p>
      <p>La utilizaci&#243;n de la t&#233;cnica de imagen de Doppler tisular (IDT) del movimiento anular mitral, se incorpor&#243; a la evaluaci&#243;n de rutina ecocardiogr&#225;fica, permitiendo estimar la presi&#243;n atrial izquierda (PAI). Esa medida se hace por medio del corte apical 4 c&#225;maras en la pared septal o lateral del anillo mitral, obteniendo la velocidad r&#225;pida diast&#243;lica del Doppler tisular (E'). Con la medida del Doppler convencional del flujo transmitral, se obtiene la velocidad de pico del flujo diast&#243;lico (E). La relaci&#243;n E/E' se calcula, y su valor tiene una buena correlaci&#243;n en la literatura con la medida invasiva de la presi&#243;n diast&#243;lica final del ventr&#237;culo izquierdo (PDFVI). Utilizando la f&#243;rmula 1,24x(E/E')+1,9, se calcula la PAI.</p>
      <p> Ommen et al<sup>28</sup> demostraron al comienzo de la d&#233;cada pasada, que una relaci&#243;n E/E' &gt; 15mmHg posee una buena correlaci&#243;n con una PDFVI superior a 12mmHg (86% de especificidad).</p>
      <p> Pero cuando la relaci&#243;n E/E' queda por debajo de 8mmHg, la correlaci&#243;n es buena para una PDFVI normal (97% de valor predictivo negativo). En comparaci&#243;n con el PNB, la relaci&#243;n E/E' muestra un mejor desempe&#241;o para detectar la congesti&#243;n, incluso en los pacientes con la funci&#243;n del VI preservada<sup>29</sup>.</p>
      <p> De la misma forma que el PNB, la relaci&#243;n E/E' tambi&#233;n tiene una "zona gris". Valores de E/E' inferiores a 8mmHg tienen una buena correlaci&#243;n con la PDFVI normal, en cambio los superiores a 15mmHg tienen una buena correlaci&#243;n con la elevaci&#243;n de las presiones de llenado. Entre esos valores, puede ocurrir mucha variaci&#243;n, por tanto, otros par&#225;metros deben ser evaluados para intentar definir la presencia de congesti&#243;n. Un esquema del ecocardiograma hemodin&#225;mico aparece en la <xref ref-type="fig" rid="es_a20fig02-body2">Figura 2</xref>.</p>
      <p content-type="asset">
        <fig id="es_a20fig02-body2">
          <graphic xlink:href="1678-4170-abc-98-01-0e15-00020-gf03-es.jpg"/></fig>
      </p>
      <p>
        <bold>Bioimpedancia transtor&#225;cica</bold>
      </p>
      <p>La bioimpedancia transtor&#225;cica (BIT) o cardiograf&#237;a por impedancia tor&#225;cica, es un m&#233;todo diagn&#243;stico no invasivo para la evaluaci&#243;n hemodin&#225;mica, que suministra los siguientes par&#225;metros: d&#233;bito card&#237;aco y volumen sist&#243;lico, resistencia vascular sist&#233;mica, par&#225;metros de contractilidad ventricular y est&#225;ndar de volemia (contenido de fluido tor&#225;cico). Las alteraciones en el voltaje y en la impedancia el&#233;ctrica tor&#225;cica, fundamentalmente por la variaci&#243;n del flujo sangu&#237;neo en los grandes vasos (la sangre es un excelente conductor de la corriente), se traducen en par&#225;metros hemodin&#225;micos.</p>
      <p> La medida de d&#233;bito card&#237;aco (DC) por la BIT presenta una buena correlaci&#243;n con la medida invasiva de DC, con un coeficiente de correlaci&#243;n variando entre 0,76 y 0,89<sup>30-32</sup>.</p>
      <p> En un estudio que evalu&#243; la causa de la disnea en pacientes ancianos que acudieron a urgencias, la evaluaci&#243;n por la bioimpedancia fue capaz de alterar el diagn&#243;stico cl&#237;nico inicial en un 13% de los pacientes, con un tiempo de impacto en el cambio del tratamiento en un 39%<sup>33</sup>. Ese m&#233;todo tiene la ventaja de poder ser realizado a pie de cama, en tiempo real, monitoreando la respuesta a las intervenciones terap&#233;uticaLa evaluaci&#243;n hemodin&#225;mica por la BIT, fundamentalmente en la definici&#243;n de la volemia, ha sido controversial. El estudio BIG<sup>34</sup>, el m&#225;s abarcador estudio randomizado de BIT en pacientes con IC publicado recientemente, solo arroj&#243; una modesta correlaci&#243;n entre los d&#233;bitos card&#237;acos medidos por la BIT y por la monitorizaci&#243;n invasiva (r=0,4-0,6), mencionando que el contenido de fluido tor&#225;cico no se correlacion&#243; con la medida de la POAP. Cuando se compararon los perfiles hemodin&#225;micos de perfusi&#243;n sist&#233;mica y de congesti&#243;n, la BIT no mostr&#243; una concordancia con el est&#225;ndar observado en la monitorizaci&#243;n invasiva, y no fue capaz de ofrecer una informaci&#243;n fiel sobre las presiones de llenado del ventr&#237;culo izquierdo. Adem&#225;s de eso, es un m&#233;todo que no est&#225; muy disponible y con una serie de limitaciones para su uso como, por ejemplo, el derrame pleural, la obesidad, la insuficiencia a&#243;rtica, los extremos de frecuencia card&#237;aca, entre otros.</p>
      <p>
        <bold>Conclusiones</bold>
      </p>
      <p>La evaluaci&#243;n individualizada e integrada del examen f&#237;sico a los diversos m&#233;todos de evaluaci&#243;n hemodin&#225;mica no invasiva para la presencia de congesti&#243;n, parece ser la forma ideal de estimar las presiones de llenado ventricular, tanto para el ajuste terap&#233;utico en los pacientes descompensados, como en los ambulatoriales, con el fin de identificar r&#225;pidamente el aumento de las presiones de llenado y prevenir la descompensaci&#243;n cl&#237;nica.</p>
      <p> Es importante reconocer la limitaci&#243;n de los signos y de los s&#237;ntomas tradicionales de la insuficiencia card&#237;aca, especialmente del edema, de los estertores crepitantes y del tercer ruido, para guiar el tratamiento y estimar la hemodin&#225;mica de los pacientes con IC cr&#243;nica. La ortopnea y la turgencia yugular patol&#243;gica, son los mejores marcadores de elevaci&#243;n de las presiones de llenado en ese contexto. Por ese motivo, muchos m&#233;dicos utilizan el PNB para ayudar en la detecci&#243;n de la congesti&#243;n. Los valores muy bajos de PNB (&lt;100pg/ml) son buenos predictores de ausencia de congesti&#243;n, sin embargo su elevaci&#243;n no est&#225; asociada, necesariamente, a presiones de llenado elevadas.</p>
      <p>La utilizaci&#243;n del PNB para orientar el tratamiento todav&#237;a necesita ser definida en los ensayos cl&#237;nicos prospectivos.</p>
      <p> El ecocardiograma hemodin&#225;mico es el mejor m&#233;todo complementario de que disponemos para ayudar al m&#233;dico a detectar la congesti&#243;n. Diversos estudios mostraron que sus par&#225;metros se correlacionan de forma significativa con los mismos par&#225;metros obtenidos por la monitorizaci&#243;n invasiva. Deben ser especialmente considerados valores de E/E' inferiores a 8mmHg, por presentar una buena correlaci&#243;n con la PDFVI normal, y de E/E' superiores a 15mmHg, por correlacionarse positivamente con el aumento de la PDFVI.</p>
      <p> La bioimpedancia transtor&#225;cica y otras nuevas tecnolog&#237;as que vienen siendo testadas, todav&#237;a necesitan demostrar los beneficios en futuros ensayos cl&#237;nicos para ser incorporadas a la pr&#225;ctica como rutina. Por tanto, la utilizaci&#243;n integrada de un examen cl&#237;nico juicioso y de esos m&#233;todos complementarios, permite un abordaje m&#225;s completo e individualizado, con el fin de reducir la morbilidad y mejorar el pron&#243;stico de los pacientes con insuficiencia card&#237;aca descompensada.</p>
      <p>
        <bold>Potencial Conflicto de Intereses</bold>
      </p>
      <p>Declaro no haber conflicto de intereses pertinentes.</p>
      <p>
        <bold>Fuentes de Financiaci&#243;n</bold>
      </p>
      <p>El presente estudio no tuve fuentes de financiaci&#243;n externas.</p>
      <p>
        <bold>Vinculaci&#243;n Acad&#233;mica</bold>
      </p>
      <p>Este art&#237;culo forma parte de tesis de Doctorado de Gustavo Luiz Almeia Junior, por Universidade Federal do Rio Grande do Sul.</p>
      <p>
        <bold>Referencias</bold>
      </p>
    </body>
  </sub-article>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Clinical Update</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Hemodynamic assessment in heart failure: role of physical examination and noninvasive methods</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>Among the cardiovascular diseases, heart failure (HF) has a high rate of hospitalization, morbidity and mortality, consuming vast resources of the public health system in Brazil and other countries. The correct determination of the filling pressures of the left ventricle by noninvasive or invasive assessment is critical to the proper treatment of patients with decompensated chronic HF, considering that congestion is the main determinant of symptoms and hospitalization. Physical examination has shown to be inadequate to predict the hemodynamic pattern. Several studies have suggested that agreement on physical findings by different physicians is small and that, ultimately, adaptive physiological alterations in chronic HF mask important aspects of the physical examination. As the clinical assessment fails to predict hemodynamic aspects and because the use of Swan-Ganz catheter is not routinely recommended for this purpose in patients with HF, noninvasive hemodynamic assessment methods, such as BNP, echocardiography and cardiographic bioimpedance, are being increasingly used. The present study intends to carry out, for the clinician, a review of the role of each of these tools when defining the hemodynamic status of patients with decompensated heart failure, aiming at a more rational and individualized treatment.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Heart failure</kwd>
        <kwd>hemodynamics</kwd>
        <kwd>cardiography, impedance</kwd>
        <kwd>radiography, thoracic</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>CLINICAL UPDATE</bold>
      </p>
      <p>
        <fn id="inicio-body3">
          <label>
            <bold>Hemodynamic assessment in heart failure: role of physical examination and noninvasive methods</bold>
          </label>
          <p>
            <bold>Gustavo Luiz Almeida Junior<sup>I</sup>; S&#233;rgio Salles Xavier<sup>III</sup>; Marcelo Iorio Garcia<sup>II</sup>; Nadine Clausell<sup>IV</sup></bold>
          </p>
        </fn>
      </p>
      <p><sup>I</sup>Casa de Sa&#250;de S&#227;o Jos&#233;</p>
      <p><sup>II</sup>Hospital Pr&#243;-Card&#237;aco</p>
      <p><sup>III</sup>Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ</p>
      <p><sup>IV</sup>Hospital de Cl&#237;nicas da UFRGS, Rio Grande do Sul, RS, Brazil</p>
      <p>Mailing Adress</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p>Among the cardiovascular diseases, heart failure (HF) has a high rate of hospitalization, morbidity and mortality, consuming vast resources of the public health system in Brazil and other countries. The correct determination of the filling pressures of the left ventricle by noninvasive or invasive assessment is critical to the proper treatment of patients with decompensated chronic HF, considering that congestion is the main determinant of symptoms and hospitalization. Physical examination has shown to be inadequate to predict the hemodynamic pattern. Several studies have suggested that agreement on physical findings by different physicians is small and that, ultimately, adaptive physiological alterations in chronic HF mask important aspects of the physical examination. As the clinical assessment fails to predict hemodynamic aspects and because the use of Swan-Ganz catheter is not routinely recommended for this purpose in patients with HF, noninvasive hemodynamic assessment methods, such as BNP, echocardiography and cardiographic bioimpedance, are being increasingly used. The present study intends to carry out, for the clinician, a review of the role of each of these tools when defining the hemodynamic status of patients with decompensated heart failure, aiming at a more rational and individualized treatment.</p>
      <p><bold>Keywords:</bold> Heart failure; hemodynamics; cardiography, impedance; radiography, thoracic.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Heart failure (HF) is a clinical syndrome of which signs and symptoms are classically used to define diagnosis, guide treatment and assess prognosis. The correct determination of the left ventricular filling pressures by noninvasive or invasive evaluation is crucial to the proper treatment of patients with chronic heart failure, as congestion is the determining factor of symptoms and hospitalization. <xref ref-type="fig" rid="en_a20fig01-body3">Figure 1</xref> shows the possible moments for the identification and treatment of elevated ventricular filling pressures (VFP)<sup>1</sup>.</p>
      <p content-type="asset">
        <fig id="en_a20fig01-body3">
          <graphic xlink:href="1678-4170-abc-98-01-0e15-00020-gf01-en.jpg"/></fig>
      </p>
      <p>Invasive hemodynamic assessment is also very important for the assessment and management of these patients, having been used for decades, initially by direct left ventricular puncture<sup>2</sup> and currently, by Swan-Ganz catheter<sup>3</sup>. However, in recent years, the use of invasive hemodynamic monitoring has been decreasing, especially due to the growing evidence of no benefit with this method<sup>4</sup>.</p>
      <p>Thus, clinical and noninvasive hemodynamic evaluation became prevalent. Hence, diagnostic criteria, such as Boston's or Framingham's criteria, have been widely used in clinical trials and guidelines to define HF, as they are easy to perform, are low-cost and have good specificity for the diagnosis. Furthermore, clinical evaluation also shows good prognostic correlation. The functional classification of the New York Heart Association (NYHA) and, more recently, Stevenson's clinical-hemodynamic classification in four hemodynamic profiles, according with the physical examination findings of congestion and peripheral perfusion, constitute well-documented prognostic markers<sup>5</sup>. Natriuretic peptides (BNP and NT-proBNP) have shown to be useful in the diagnosis of decompensated HF in the emergency room, by confirming or ruling out the diagnosis in patients with dyspnea and giving prognostic value in this population, especially at hospital discharge, to predict future events.</p>
      <p>It can be observed however, that the history, physical examination and natriuretic peptides are greatly questioned concerning the power to evaluate the hemodynamic condition, primarily of congestion or low cardiac output in patients with decompensated HF. Physical examination limitations increasingly start with physicians' lack of interest in performing a good-quality physical examination, supported by the wide availability of complementary examinations that have been used, often replacing the physical examination. Moreover, the reduced consultation time and poor training in many medical schools may be factors associated with the deterioration in the quality of the physical examination.</p>
      <p>Several studies have suggested that the agreement in physical findings by different physicians is small. The gold standard for hemodynamic evaluation in heart failure is the pulmonary artery catheter (Swan-Ganz), and several studies have compared the invasive hemodynamic assessment with the physical examination, showing the limitation of this assessment in defining congestion or low output.</p>
      <p>Natriuretic peptides were first used in clinical practice at the beginning of this decade, with the promise of increasing the diagnostic accuracy of HF and diagnose VFP elevation, defining congestion, as they increase in response to ventricular distension. However, with the advancement of knowledge in this area, several limitations were also observed regarding the use of natriuretic peptides in the identification of congestion, and there is no currently defined cutoff for that.</p>
      <p>As the clinical evaluation, the natriuretic peptides also fail to predict hemodynamics, as the routine use of the Swan-Ganz catheter is not recommended for this purpose in patients with HF. Thus, the use of noninvasive methods for hemodynamic assessment, such as echocardiography and bioimpedance cardiography, has been increasing.</p>
      <p>The present study aims to carry out for the clinician, a review of the role of each of these tools, when defining the hemodynamic condition of patients with decompensated heart failure, aiming at a more rational and individualized treatment.</p>
      <p>
        <bold>Clinical Evaluation: history, physical examination, chest x-ray and weight monitoring</bold>
      </p>
      <p>
        <bold>History and physical examination</bold>
      </p>
      <p>Among the several symptoms of HF, orthopnea (dyspnea that starts with the orthostatic position and is relieved by decubitus elevation or in the sitting position) stands out as the symptom that most correlates with the elevation of ventricular filling pressures.</p>
      <p>In a study with outpatients from a HF clinic in Brazil, the presence of orthopnea was the most sensitive marker of elevated filling pressures, both right and left<sup>6</sup>. In this study, the diagnostic performance of different physical examination findings alone was suboptimal in predicting the hemodynamic pattern. After evaluating a clinical score for congestion (containing the variables of pulmonary crackles, pathological jugular venous distention, peripheral edema and third heart sound), the best negative predictive value for congestion was the absence of these associated clinical signs (95% predictive value for left atrial pressure &lt;20 mmHg). </p>
      <p>Persistent orthopnea with treatment also has a prognostic association. Patients who maintain orthopnea complaints throughout one year of treatment for HF have a rehospitalization rate that is four times higher than those free of orthopnea and, moreover, do not show left ventricular function improvement at the end of this period (11 &#177; 13% vs. -1 &#177; 6%, p &lt;0.001)<sup>7</sup>.</p>
      <p>In the physical examination substudy of the ESCAPE trial, orthopnea was the only symptom that correlated with the elevation in the VFP. When patients had orthopnea, in spite of the use of two or more pillows, the chance of having a pulmonary artery occlusion pressure (PAOP) <underline>&gt;</underline> 30 mm Hg was 3.6 times higher (OR 3.6, p &lt;0.05)<sup>8</sup> .</p>
      <p>Regarding the physical examination, several studies have evaluated the capacity to estimate the hemodynamic status of patients with HF. Of all findings, the jugular venous pressure (JVP) seems to be more accurate in detecting the elevation of left ventricular filling pressures<sup>8</sup>. Since the introduction of JVP assessment in clinical practice in 1930 by Lewis<sup>9</sup> and later, the standardization of its assessment by Borst and Molhuysen, in 1952<sup>10</sup>, the JVP has been the object of discussion. The presence of pathological jugular distention (PJD) reflects the increase in filling pressure of the right chambers, which in turn frequently correlates with left ventricular filling pressures. A retrospective analysis of the SOLVD study showed that the presence of PJD may be a marker of poor prognosis, considering that its presence was a marker of re-hospitalization, hospitalization and death from heart failure<sup>11</sup>.</p>
      <p>However, the results of the PJD assessment have not been universally reproducible, and there are questions about its real significance: the capacity to detect medical elevations in the JVP at physical examination, considering the great technological evolution and the availability of complementary diagnostic methods. The diversity of the methodology in assessing the JVP is also an important factor in the studies, whereas there is no universally accepted standardization. In the classic study by Stevenson and Perloff<sup>12</sup>, the presence of PJD was defined as the appearance of the internal jugular vein above the clavicle, with the patient elevated between 30&#186; and 45&#186;. Although widely used, this definition may miss slighter filling pressure elevations. Patients could have improved diagnostic accuracy if they were assessed for the presence of hepatojugular reflux<sup>13,14</sup>.</p>
      <p>The several studies of patients with HF, even if decompensated, show a low prevalence of PJD<sup>15-17</sup>, from 11% to 14%. Finally, it is estimated that the accuracy of JVP to detect elevated RAP is less than 75% and the concordance of left and right pressures is approximately 75% in patients with HF<sup>18</sup>.</p>
      <p>Another important finding at the physical examination is the presence of third heart sound (S3). Since the first description of a gallop rhythm by Potain<sup>19</sup> in 1880, the S3 has been studied. Its presence is highly specific for the detection of ventricular dysfunction and elevated filling pressures, estimated at 93%<sup>20</sup>. Additionally, it is pointed out as an independent prognostic marker in patients with HF<sup>11</sup>. On the other hand, its sensitivity is low (between 13% and 52%) and it displays a lot of interobserver variability, depending on their experience<sup>21</sup>.</p>
      <p>In a study that specifically evaluated the physical examination findings at the hemodynamic evaluation of patients with advanced HF, the presence of S3 did not add any relevant information to the presence of PAOP &gt; 22 mmHg<sup>8</sup>. In the study by Stevenson and Perloff<sup>12</sup>, mentioned above, 50 patients with advanced HF awaiting cardiac transplantation were evaluated by physical examination and invasive hemodynamics. Of the total, 48 had S3, which is not indicated, therefore, to discriminate patients with and without elevated filling pressures.</p>
      <p>
        <bold>Chest X-ray</bold>
      </p>
      <p>The chest x-ray is a widely available and inexpensive complementary test, which traditionally helps in the diagnosis of heart failure. In patients with HF, the presence of signs of congestion, for instance, cephalization of the pulmonary vascular network, interstitial edema and alveolar edema, has high specificity for decompensation (above 96%), but has low sensitivity.</p>
      <p>Twenty percent (20%) of patients with cardiomegaly at the echocardiogram did not have that diagnosis in the chest x-ray, and patients with elevated ventricular filling pressures may not show any sign of congestion. Pleural effusion, if present, has a high specificity for decompensation (92%) but low sensitivity (25%). It is estimated, therefore, that one in five patients with symptoms of decompensated heart failure who seek the emergency room have a chest X-ray that shows no signs of congestion, in spite of having elevated ventricular filling pressures<sup>22</sup>.</p>
      <p>
        <bold>Weight monitoring</bold>
      </p>
      <p>Weight monitoring in patients with HF is recommended according to the III Brazilian Guidelines on Chronic Heart Failure, in order to check the volemic status<sup>23</sup>. Changes in weight, especially over short periods of time, can be good indicators of volemic worsening. Many studies, however, are controversial on this subject, indicating that little or no weight gain is observed before an episode of decompensation or that a modest weight loss is observed after clinical compensation of an acute HF episode. In many cases, decompensation may occur not due to the build up of fluid, but by water redistribution from the periphery to the lungs by neurohumoral and inflammatory acute activation, leading to cardiac and vascular alterations that promote reduced venous capacitance and increased peripheral arterial resistance<sup>24</sup>.</p>
      <p>
        <bold>Natriuretic peptides</bold>
      </p>
      <p>There are three types of natriuretic peptides (NP): atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). ANP and BNP are produced primarily by the heart, and CNP by endothelial cells.</p>
      <p>BNP is a hormone produced by cardiomyocytes in response to stretch, secondary to increased ventricular filling pressure or volume overload. Initially, cardiomyocytes produce pre-proBNP, which is converted to proBNP, and finally, in the active metabolite BNP, which promotes vasodilation and natriuresis. Both proBNP and BNP have been long used in clinical practice for diagnosis, to assess volemic status and define prognosis in patients with HF. Several studies have shown a positive association between levels of these NP and the degree of ventricular dysfunction and functional class. Others have shown that there is positive correlation between BNP levels and PAOP (r = 0.72) in patients with acute HF<sup>25</sup> and that intensive treatment determines a decrease in the levels of PAOP and NP.</p>
      <p>Despite this evidence, some authors have not found a good correlation between BNP and proBNP levels with the VFP. In a study of critically ill patients hospitalized for different medical conditions and who had received a Swan-Ganz catheter as part of treatment, it was observed that the NP levels showed no association with pulmonary artery occlusion pressure measurement, therefore, not being a good noninvasive marker of VFP for this population<sup>26</sup>. Furthermore, after normalization of the filling pressures, measured invasively, and with therapy for decompensated HF, it was observed that BNP levels, although decreased, still remained significantly elevated<sup>27</sup>.</p>
      <p>Extreme values of BNP, &lt; 100 pg/ml or &gt;400 pg/ml, have better correlation with normal or elevated filling pressures, respectively. However, the range between these values is called the "gray zone", characterized by not showing good correlation.</p>
      <p>It is noteworthy that many conditions affect the production and clearance of BNP, such as age, weight, renal failure, noncardiac disease, among others, which also limits its use in some of these patients</p>
      <p>
        <bold>Echocardiogram</bold>
      </p>
      <p>The echocardiography is the most useful complementary examination when evaluating patients with HF. It provides important information regarding heart morphology; quantifies the systolic and diastolic functions and helps define the etiology and prognostic parameters in response to different therapeutic interventions.</p>
      <p>In recent years, two new and fundamental echocardiographic evaluations were incorporated into daily practice: the evaluation of ventricular dyssynchrony and hemodynamic evaluation. The latter has been very important to understand the hemodynamic profile of patients with HF, especially decompensated ones or those difficult to manage. The so-called "hemodynamic echocardiogram" refers to the echocardiographic assessment of hemodynamic parameters that reflect the hemodynamic data obtained by invasive monitoring. <xref ref-type="fig" rid="en_a20chart01-body3">Chart 1</xref> shows the main echocardiographic parameters that must be used to estimate the hemodynamic status of patients with decompensated HF.</p>
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        <fig id="en_a20chart01-body3">
          <graphic xlink:href="1678-4170-abc-98-01-0e15-00020-gf02-en.jpg"/></fig>
      </p>
      <p>The use of tissue Doppler imaging (TDI) technique to assess the mitral annular motion was incorporated into the routine echocardiographic evaluation, enabling the estimation of left atrial pressure (LAP). This measurement is performed using the apical 4-chamber view of the septal wall or lateral of the mitral annulus, obtaining the early diastolic velocity of the tissue Doppler (E'). With the conventional Doppler measurement of transmitral flow, the peak diastolic flow velocity is obtained (E).</p>
      <p>The E / E ' ratio is calculated, and its value shows good correlation in the literature with the invasive measurement of left ventricular end-diastolic pressure (LVEDP). Using the formula 1.24 x (E / E ') +1.9, the LAP is calculated.</p>
      <p>Ommen et al<sup>28</sup> showed, in the beginning of the last decade, that an E / E ' &gt; 15 mmHg has a good correlation with LVEDP &gt; 12 mm Hg (86% specificity). But when the E/E 'is &lt; 8 mmHg, the correlation is good for a normal LVEDP (97% negative predictive value). In comparison with the BNP, the E/ E' ratio shows a better performance to detect congestion, even in patients with preserved LV function<sup>29</sup>.</p>
      <p>Similarly to the BNP, the E/E' ratio also has a "gray area". E / E ' values &lt; 8 mmHg correlate well with normal LVEDP, whereas values &gt; 15 mmHg showed a good correlation with the elevation in filling pressures. There can be great variation among these values, so other parameters must be evaluated to try to define the presence of congestion. A schematic hemodynamic echocardiogram is shown in <xref ref-type="fig" rid="en_a20fig02-body3">Figure 2</xref>.</p>
      <p content-type="asset">
        <fig id="en_a20fig02-body3">
          <graphic xlink:href="1678-4170-abc-98-01-0e15-00020-gf03-en.jpg"/></fig>
      </p>
      <p>
        <bold>Transthoracic bioimpedance</bold>
      </p>
      <p>The transthoracic bioimpedance (TTB) or by thoracic impedance cardiography is a noninvasive diagnostic method for hemodynamic assessment, which provides the following parameters: cardiac output and stroke volume, systemic vascular resistance, ventricular contractility parameters and volume standard (chest fluid content). Voltage and chest electrical impedance alterations, mainly due to the variation of blood flow in large vessels (the blood is an excellent current conductor), are translated into hemodynamic parameters.</p>
      <p>The cardiac output (CO) measurement by TTB correlates well with the invasive measurement of CO, with a correlation coefficient ranging between 0.76 and 0.89<sup>30-32</sup>. In a study evaluating the cause of dyspnea in elderly patients admitted to the emergency department, the assessment by bioimpedance was able to alter the initial clinical diagnosis in 13% of patients and had an impact in changing the treatment in 39%<sup>33</sup>. This method has the advantage of being performed at the bedside in real time by monitoring the response to therapeutic interventions.</p>
      <p>The hemodynamic evaluation by TTB, primarily in the definition of blood volume, has been controversial. The BIG study<sup>34</sup>, the largest randomized trial on TTB in patients with HF, published recently, showed only modest correlation between the cardiac outputs measured by the TTB and the invasive monitoring (r = 0.4-0.6), indicating that the thoracic fluid content did not correlate with the measurement of the PAOP. When comparing the hemodynamic profiles of systemic perfusion and congestion, the TTB did not show concordance with the pattern observed in invasive monitoring, not being able to give accurate information about the LV filling pressures. Moreover, this method is not widely available and has a number of limitations to its use, e.g., pleural effusion, obesity, aortic regurgitation, heart rate extremes, among others.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>The individualized physical examination integrated to the several methods of noninvasive hemodynamic evaluation for the presence of congestion appears to be the best way to estimate ventricular filling pressures, both to adjust therapy in outpatients and in those with decompensated HF, aiming to identify the early increased filling pressures and prevent clinical decompensation.</p>
      <p>It is important to recognize the limitations of traditional signs and symptoms of heart failure, especially edema, crackling rales and the third heart sound, to guide treatment and estimate the hemodynamics of patients with chronic heart failure. Orthopnea and pathological jugular distention are the best markers of elevated filling pressures in this context. As a result, many physicians use BNP to assist in detecting congestion. Very low values of BNP (&lt;100 pg/ml) are good predictors of the absence of congestion, but its elevation is not necessarily associated with elevated filling pressures. The use of BNP to guide treatment has yet to be defined in prospective clinical trials.</p>
      <p>The hemodynamic echocardiogram is the best method available to further assist the physician in detecting congestion. Several studies have shown that its parameters correlate significantly with the same parameters obtained by invasive monitoring. E/ E ' values &lt; 8 mmHg should be carefully considered, as they have good correlation with normal LVEDP and E/E' &gt; 15 mmHg, as they correlate positively with increased LVEDP.</p>
      <p>The transthoracic bioimpedance and other new technologies that have been tested have yet to demonstrate benefits in future clinical trials to be incorporated into practice on a routine basis. Therefore, the integrated use of careful clinical examination and these complementary methods allows a more comprehensive and individualized approach in order to reduce morbidity and improve the prognosis of patients with decompensated heart failure.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This article is part of the thesis of doctoral submitted by Gustavo Luiz Almeia Junior, from Universidade Federal do Rio Grande do Sul.</p>
      <p>
        <bold>References</bold>
      </p>
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