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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">WgqFv4SnJqmTcnqHh7yCdBB</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2012000600010</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(12)09800610</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2012005000049</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Colapsibilidade da Veia Cava Inferior e sinais e sintomas de insufici&#234;ncia card&#237;aca: novos insights e poss&#237;veis associa&#231;&#245;es</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>De Vecchis</surname>
            <given-names>Renato</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ciccarelli</surname>
            <given-names>Antonio</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ariano</surname>
            <given-names>Carmelina</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <institution content-type="orgname">Presidio Sanitario Intermedio Elena d Aosta</institution>
        <institution content-type="orgdiv1">Cardiology Unit </institution>
      </aff>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="city">Somma Vesuviana</named-content>
          <named-content content-type="state">Napoli</named-content>
        </addr-line>
        <institution content-type="orgname">Clinica S. Maria del Pozzo</institution>
        <institution content-type="orgdiv1">Neurorehabilitation Unit </institution>
        <country country="IT">Italy</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>06</month>
        <year>2012</year>
      </pub-date>
      <volume>98</volume>
      <issue>6</issue>
      <fpage>544</fpage>
      <lpage>552</lpage>
      <history>
        <date date-type="received">
          <day>28</day>
          <month>08</month>
          <year>2011</year>
        </date>
        <date date-type="accepted">
          <day>06</day>
          <month>02</month>
          <year>2012</year>
        </date>
        <date date-type="rev-recd">
          <day>30</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>FUNDAMENTO: Nos pacientes com Insufici&#234;ncia Card&#237;aca Cr&#244;nica (ICC) foram propostas medidas ultrassonogr&#225;ficas do &#205;ndice de Colapsibilidade da Veia Cava Inferior (ICVCI) para obter uma avalia&#231;&#227;o e classifica&#231;&#227;o minuciosa da congest&#227;o hemodin&#226;mica. OBJETIVO: A finalidade deste estudo era correlacionar os achados no exame f&#237;sico com o ICVCI em pacientes com ICC. M&#201;TODOS: De acordo com um projeto de coorte retrospectivo, analisamos 54 pacientes com ICC, direita ou biventricular, classe NYHA III. O plano era determinar se alguma faixa de ICVCI basal poderia predizer uma persist&#234;ncia ou agravamento da congest&#227;o cl&#237;nica achada no final do acompanhamento subsequente (isto &#233;, ap&#243;s 1-2 meses do tratamento oral otimizado). Para essa finalidade, os pacientes foram subdivididos em tr&#234;s grupos de acordo com o valor de ICVCI basal: &#8804; 15% (13 pts), 16 - 40% (21 pts) e &gt; 40% (20 pts). Diversos crit&#233;rios cl&#237;nicos de congest&#227;o foram comparados por meio dos tr&#234;s grupos e incorporados subsequentemente ao modelo multivariado de Cox. RESULTADOS: Preditores multivariados de alto escore de congest&#227;o foram distens&#227;o da veia jugular (FC: 13,38 95% IC: 2,13 - 84 p = 0,0059) e estertores (FC: 11 95% C.I : 1,45 - 83,8 p = 0,0213). O ICVCI &#8804; 15% esteve sempre associado com um alto escore de congest&#227;o na segunda visita; todavia, o ICVCI o &#8804; 15% n&#227;o predisse um alto escore de congest&#227;o na segunda visita. CONCLUS&#195;O: No &#226;mbito da ICC, um baixo ICVCI n&#227;o predisse, em forma confi&#225;vel, um elevado escore de congest&#227;o. N&#227;o obstante, o conjunto com ICVCI &#8804; 15% sempre se achou associado com sinais e sintomas de uma ICC descompensada, tanto do lado direito como do esquerdo. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Baixo d&#233;bito card&#237;aco</kwd>
        <kwd>insufici&#234;ncia card&#237;aca</kwd>
        <kwd>veia cava inferior</kwd>
        <kwd>disfun&#231;&#227;o ventricular esquerda</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>29</day>
        <month>05</month>
        <year>2012</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>Colapsibilidade da Veia Cava Inferior e sinais e sintomas de insufici&#234;ncia card&#237;aca. Novos insights e poss&#237;veis associa&#231;&#245;es</p>
    <p>
      <bold>Renato De Vecchis<sup>I</sup>; Antonio Ciccarelli<sup>II</sup>; Carmelina Ariano<sup>II</sup></bold>
    </p>
    <p><sup>I</sup>Cardiology Unit, Presidio Sanitario Intermedio Elena d Aosta </p>
    <p><sup>II</sup>Napoli; Neurorehabilitation Unit, Clinica S. Maria del Pozzo, Somma Vesuviana, Italy</p>
    <p>
      <xref ref-type="corresp" rid="nota">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> Nos pacientes com Insufici&#234;ncia Card&#237;aca Cr&#244;nica (ICC) foram propostas medidas ultrassonogr&#225;ficas do &#205;ndice de Colapsibilidade da Veia Cava Inferior (ICVCI) para obter uma avalia&#231;&#227;o e classifica&#231;&#227;o minuciosa da congest&#227;o hemodin&#226;mica. </p>
    <p><bold>OBJETIVO:</bold> A finalidade deste estudo era correlacionar os achados no exame f&#237;sico com o ICVCI em pacientes com ICC. </p>
    <p><bold>M&#201;TODOS:</bold> De acordo com um projeto de coorte retrospectivo, analisamos 54 pacientes com ICC, direita ou biventricular, classe NYHA III. O plano era determinar se alguma faixa de ICVCI basal poderia predizer uma persist&#234;ncia ou agravamento da congest&#227;o cl&#237;nica achada no final do acompanhamento subsequente (isto &#233;, ap&#243;s 1-2 meses do tratamento oral otimizado). Para essa finalidade, os pacientes foram subdivididos em tr&#234;s grupos de acordo com o valor de ICVCI basal: &#8804; 15% (13 pts), 16 - 40% (21 pts) e &gt; 40% (20 pts). Diversos crit&#233;rios cl&#237;nicos de congest&#227;o foram comparados por meio dos tr&#234;s grupos e incorporados subsequentemente ao modelo multivariado de Cox. </p>
    <p><bold>RESULTADOS:</bold> Preditores multivariados de alto escore de congest&#227;o foram distens&#227;o da veia jugular (FC: 13,38 95% IC: 2,13 - 84 p = 0,0059) e estertores (FC: 11 95% C.I : 1,45 - 83,8 p = 0,0213). O ICVCI &#8804; 15% esteve sempre associado com um alto escore de congest&#227;o na segunda visita; todavia, o ICVCI o &#8804; 15% n&#227;o predisse um alto escore de congest&#227;o na segunda visita. </p>
    <p><bold>CONCLUS&#195;O:</bold> No &#226;mbito da ICC, um baixo ICVCI n&#227;o predisse, em forma confi&#225;vel, um elevado escore de congest&#227;o. N&#227;o obstante, o conjunto com ICVCI &#8804; 15% sempre se achou associado com sinais e sintomas de uma ICC descompensada, tanto do lado direito como do esquerdo. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)</p>
    <p><bold>Palavras-chave:</bold> Baixo d&#233;bito card&#237;aco, insufici&#234;ncia card&#237;aca, veia cava inferior/anormalidades, disfun&#231;&#227;o ventricular esquerda.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>Acredita-se que a congest&#227;o hemodin&#226;mica<sup>1</sup> se deriva especialmente de &#237;ndice card&#237;aco diminu&#237;do &#8211; com ou sem redu&#231;&#227;o na fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda. Isso gera, por sua vez, uma eleva&#231;&#227;o na Press&#227;o de Oclus&#227;o da Art&#233;ria Pulmonar (Poap)<sup>2</sup>, no caso de descompensa&#231;&#227;o isolada das c&#226;maras esquerdas, ou de aumento combinado na press&#227;o atrial direita e Poap, no caso de insufici&#234;ncia card&#237;aca biventricular<sup>3</sup>. O &#237;ndice card&#237;aco diminu&#237;do, somente para insufici&#234;ncia card&#237;aca ventricular esquerda, ou a combina&#231;&#227;o do &#237;ndice card&#237;aco diminu&#237;do mais a press&#227;o venosa central elevada, no caso de insufici&#234;ncia card&#237;aca direita ou biventricular, com ou sem diminui&#231;&#227;o evidente da press&#227;o arterial, reduz substancialmente o fluxo renal de sangue, a vari&#225;vel mais importante na capacidade de filtra&#231;&#227;o do rim em pacientes que apresentam insufici&#234;ncia card&#237;aca congestiva, gerando assim um est&#237;mulo neuro-hormonal e o desenvolvimento de reten&#231;&#227;o hidrossalina<sup>4-8</sup>. O agravamento hidrodin&#226;mico consistente em um &#237;ndice card&#237;aco comprometido e press&#245;es de enchimento aumentadas, que ativar&#227;o posteriormente o sistema renina-angiotensina e o sistema nervoso simp&#225;tico, reduzir&#227;o o &#243;xido n&#237;trico no endot&#233;lio e induzir&#227;o mediadores inflamat&#243;rios, de forma de agravar o estado de hipoperfus&#227;o dos glom&#233;rulos, para posteriormente danificar a fun&#231;&#227;o renal<sup>9</sup>. A redu&#231;&#227;o na depura&#231;&#227;o de &#225;gua e sal, por sua vez, propicia a persist&#234;ncia da congest&#227;o hemodin&#226;mica de forma a criar e manter por maior tempo a condi&#231;&#227;o de sobrecarga card&#237;aca. A congest&#227;o hemodin&#226;mica contribui &#224; progress&#227;o da IC pela ativa&#231;&#227;o adicional de neuro-horm&#244;nios e por causar isquemia subendoc&#225;rdica, que resulta em necrose/apoptose mioc&#225;rdica e/ou insufici&#234;ncia mitral secund&#225;ria pelos seus efeitos na geometria do VE (que muda de elipsoide a esfera)<sup>10</sup>. Al&#233;m disso, uma elevada press&#227;o atrial direita pode contribuir para a s&#237;ndrome cardiorrenal mediante a redu&#231;&#227;o do gradiente de perfus&#227;o nos rins<sup>11-12</sup>. Entre os m&#233;todos propostos para estimar e classificar a congest&#227;o hemodin&#226;mica na insufici&#234;ncia card&#237;aca direita ou biventricular, a avalia&#231;&#227;o ultrassonogr&#225;fica do Di&#226;metro da Veia Cava Inferior (DVCI) e seu &#205;ndice de Colapsibilidade (ICVCI) t&#234;m um papel importante<sup>13</sup>. Essa t&#233;cnica visa identificar quaisquer mudan&#231;as no padr&#227;o respirat&#243;rio da VCI que indiquem presen&#231;a de anormalidades no estado volum&#233;trico (ou seja, congest&#227;o hemodin&#226;mica ou deple&#231;&#227;o intravascular). Com base no conhecimento consagrado, amplas flutua&#231;&#245;es do ICVCI indicariam que a deple&#231;&#227;o intravascular &#233; prov&#225;vel, visto que os valores baixos desse par&#226;metro significariam uma elevada probabilidade de congest&#227;o hemodin&#226;mica. Essas infer&#234;ncias t&#234;m confirma&#231;&#227;o exaustiva de muitos estudos reconhecidos<sup>13-20</sup>. </p>
    <p>
      <bold>Objetivos</bold>
    </p>
    <p>Em uma s&#233;rie de pacientes com ICC direita ou biventricular, testamos as poss&#237;veis rela&#231;&#245;es entre ICVCI e alguns sinais e sintomas da ICC. Adicionalmente, tentamos estabelecer se nesses pacientes com ICC um valor baixo de ICVCI, encontrado na primeira visita, pode ser considerado preditor confi&#225;vel de congest&#227;o cl&#237;nica subsequente &#8211; ap&#243;s um acompanhamento de um a dois meses. </p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>Foi realizado um estudo retrospectivo observacional incluindo pacientes de dois Centros (C.U. E. d&#8217; A. e N.R. S.M.d P.). Para a inclus&#227;o no estudo, foram necess&#225;rias evid&#234;ncias documentadas da insufici&#234;ncia card&#237;aca cr&#244;nica direita ou biventricular classe de NYHA II - III. Os crit&#233;rios de exclus&#227;o foram: pacientes com marca-passos ou submetidos a terapia de ressincroniza&#231;&#227;o card&#237;aca; infarto do mioc&#225;rdio nos &#250;ltimos 30 dias; sincope relacionado com arritmia; cirurgia card&#237;aca de grande porte; angina inst&#225;vel; hipertens&#227;o n&#227;o controlada; <italic>cor pulmonale</italic>; doen&#231;a pulmonar avan&#231;ada; doen&#231;a neurol&#243;gica importante ou doen&#231;a vascular cerebral; suspeita de estenose arterial renal; insufici&#234;ncia renal avan&#231;ada (isto &#233;, creatinina s&#233;rica &gt; 2,5 mg/dL em valores basais); ou outra doen&#231;a potencialmente fatal. </p>
    <p>Foi realizado um exame retrospectivo de prontu&#225;rios para analisar as caracter&#237;sticasde todos os pacientes eleg&#237;veis. Para cada paciente foram registrados: data de nascimento; sexo; ra&#231;a; peso e altura.Tamb&#233;m foram extra&#237;das de cada paciente as comorbidades; diabetes; dislipidemia; abuso de nicotina; hipertens&#227;o arterial; insufici&#234;ncia card&#237;aca isqu&#234;mica; nefropatia diab&#233;tica preexistente ou outra doen&#231;a renal cr&#244;nica al&#233;m do tratamento m&#233;dico na interna&#231;&#227;o. O ICVCI foi definido como a diferen&#231;a entre o di&#226;metro expirat&#243;rio m&#225;ximo e o di&#226;metro inspirat&#243;rio m&#237;nimo dividido pelo di&#226;metro expirat&#243;rio m&#225;ximo. As medidas do ICVCI foram obtidas de 1 a 2 cm abaixo do n&#237;vel das veias hep&#225;ticas, usando ultrassonografia bidimensional (aparelho de ultrassom Vivid 7, GE Healthcare Systems, Milwaukee, WI). O registro do di&#226;metro VCI foi realizado no modo M, a aproximadamente 3 cm do &#225;trio direito com o paciente deitado a 45&#186;. Foram utilizadas janelas subxifoide ou subcostal segundo as vistas dispon&#237;veis, h&#225;bitos do paciente, presen&#231;a de impedimentos externos (por exemplo, drenos, curativos cir&#250;rgicos), e prefer&#234;ncia do ultrassonografista. </p>
    <p>Os pacientes foram divididos em tr&#234;s grupos de acordo com os valores de ICVCI: ICVCI &#8804; 15% (13 pts), ICVCI 16-40% (21 pts), ICVCI &gt; 40% (20 pts). Entre esses, o primeiro e o terceiro intervalos foram considerados como indica&#231;&#227;o da presen&#231;a de condi&#231;&#227;o congestiva venosa sist&#234;mica ou prov&#225;vel deple&#231;&#227;o intravascular, respectivamente; enquanto um ICVCI no intervalo intermedi&#225;rio (0,16 a 0,40) foi considerado &#250;til na discrimina&#231;&#227;o da PVC. </p>
    <p>Nos tr&#234;s grupos foram comparados os seguintes crit&#233;rios cl&#237;nicos de congest&#227;o: dispneia/ortopneia; dispneia de esfor&#231;o; distens&#227;o da veia jugular; edema perif&#233;rico; hepatomegalia congestiva; estertores pulmonares; ganho m&#233;dio de peso &#8805; 1 kg por semana de acompanhamento. </p>
    <p>Esses sinais e sintomas foram escolhidos pela comprovada rela&#231;&#227;o com a s&#237;ndrome de ICC. Particularmente, dispneia de repouso com ortopneia foi selecionada como sendo um sintoma geralmente associado com o comprometimento severo da fun&#231;&#227;o de bombeio do ventr&#237;culo esquerdo (em nosso caso, a ser ajustado no contexto da descompensa&#231;&#227;o card&#237;aca biventricular, uma vez que a insufici&#234;ncia card&#237;aca direita estava presente em todos os casos pelo crit&#233;rio definitivo de inclus&#227;o). A ortopneia foi definida como qualquer dificuldade respirat&#243;ria associada ao fato de deitar-se ou a necessidade percebida de usar mais um travesseiro para evitar a dificuldade respirat&#243;ria. Os estertores foram considerados em raz&#227;o de sua conhecida associa&#231;&#227;o com a capilaridade pulmonar e a degenera&#231;&#227;o hem&#225;tica venosa, geralmente relacionados com altos n&#237;veis de Press&#227;o de Oclus&#227;o Pulmonar capilar (POAP). A dispneia de esfor&#231;o foi inclu&#237;da na an&#225;lise como sendo um sintoma que normalmente indica um menor comprometimento card&#237;aco quando comparado com a ortopneia, gerada pela insufici&#234;ncia card&#237;aca esquerda, bem como a biventricular combinada. Al&#233;m disso, os outros quatro sinais (distens&#227;o da veia jugular, edema perif&#233;rico, hepatomegalia congestiva e ganho de peso &#8805; 1 kg por semana) foram avaliados no estudo como marcadores de reten&#231;&#227;o hidrossalina, normalmente encontrados em congest&#227;o sist&#234;mica decorrente de ICC direita ou biventricular avan&#231;ada. Particularmente, a distens&#227;o da veia jugular foi considerada presente quando visualizada pelo menos 10 cm verticalmente acima do &#225;trio direito. O ganho de peso foi definido como o aumento &#8805; 1 kg por semana. </p>
    <p>Al&#233;m disso, o escore de congest&#227;o foi criado e definido retrospectivamente para esta an&#225;lise como a soma dos sete crit&#233;rios para congest&#227;o, com um intervalo poss&#237;vel de 0 a 7.Um escore &#8805; 4 foi denominado "alto escore de congest&#227;o" e usado como vari&#225;vel de desfecho ("<italic>end-point</italic>") na an&#225;lise estat&#237;stica posterior. De acordo com a abordagem habitual aplicada nos dois Centros, cada paciente em cada um dos hospitais-dia passou por um cuidado exame cl&#237;nico, juntamente com uma avalia&#231;&#227;o ecocardiogr&#225;fica completa, incluindo uma avalia&#231;&#227;o completa da VCI com c&#225;lculo do ICVCI. Posteriormente, era realizada uma segunda consulta agendada em um ou dois meses, a fim de estabelecer oportunamente qualquer mudan&#231;a na farmacologia e na dosagem a ser realizada segundo a evolu&#231;&#227;o do quadro cl&#237;nico. Havendo qualquer queixa ou intercorr&#234;ncia, os pacientes eram aconselhados a antecipar a data da consulta. </p>
    <p>Nosso estudo retrospectivo visava determinar se poderia existir qualquer associa&#231;&#227;o entre os valores do ICVCI, detectados na primeira visita e um ou mais dos sinais e sintomas de congest&#227;o referidos, observados ap&#243;s 1-2 meses de acompanhamento. Pesquisamos essa hip&#243;tese usando a categoriza&#231;&#227;o preliminar dos valores do ICVCI em tr&#234;s faixas (ICVCI &#8804; 15%, ICVCI 16%-40%, ICVCI &gt;40%) e levando em conta o quadro cl&#237;nico ap&#243;s o tratamento oral adequado mantido por um a dois meses. Tamb&#233;m verificamos a poss&#237;vel exist&#234;ncia de qualquer associa&#231;&#227;o significativa entre o grupo caracterizado pelo ICVCI mais baixo (&#8804; 15%) no momento basal e o achado de "alto escore de congest&#227;o", encontrado na segunda visita ap&#243;s um a dois meses. O tratamento oral prescrito normalmente inclui inibidores de ECA, betabloqueadores e diur&#233;ticos; al&#233;m disso, de acordo com o crit&#233;rio do m&#233;dico, tamb&#233;m foram administrados antagonistas do receptor de aldosterona, nitrato oral ou transd&#233;rmico, agentes antiagregantes, warfarina, amiodarona e digoxina. Foi ainda determinado que cada paciente que requeresse diur&#233;ticos ou inotr&#243;picos intravenosos pelo agravamento da IC durante o acompanhamento fosse exclu&#237;do da an&#225;lise estat&#237;stica, por ser considerado demonstra&#231;&#227;o da falha do tratamento. </p>
    <p>
      <bold>An&#225;lise estat&#237;stica</bold>
    </p>
    <p>Foi utilizado o Pacote Estat&#237;stico para Ci&#234;ncias Sociais (SPSS vers&#227;o 14) e Excel para realizar a an&#225;lise. Foram comparados os dados demogr&#225;ficos iniciais, exames f&#237;sicos e achados laboratoriais, entre os pacientes nas tr&#234;s faixas de ICVCI. O teste &#967;<sup>2</sup> (qui-quadrado) e o teste <italic>t</italic> n&#227;o pareado foram aplicados respectivamente para compara&#231;&#227;o das vari&#225;veis cont&#237;nuas e categ&#243;ricas. A an&#225;lise de vari&#226;ncia unidirecional (Anova) e o teste de Student-Newman-Keuls foram utilizados para todas as compara&#231;&#245;es em pares (an&#225;lise <italic>post hoc</italic>) nas compara&#231;&#245;es m&#250;ltiplas. O teste de Kruskal Wallis tamb&#233;m foi empregado na compara&#231;&#227;o dos dados com distribui&#231;&#227;o assim&#233;trica.</p>
    <p>Para identificar os preditores de congest&#227;o hemodin&#226;mica, foram utilizadas as an&#225;lises de regress&#227;o de Cox de riscos proporcionais, univariado e multivariado. As seguintes vari&#225;veis foram inseridas no modelo como vari&#225;veis da exposi&#231;&#227;o:</p>
    <p>ICVCI 15% </p>
    <p> ganho de peso m&#233;dia &#8805; 1 kg por semana </p>
    <p> edema </p>
    <p> ortopneia </p>
    <p> estertores </p>
    <p> distens&#227;o da veia jugular </p>
    <p> dispneia de esfor&#231;o durante o tratamento otimizado </p>
    <p> hepatomegalia congestiva</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>Um total de 54 pacientes foi inclu&#237;do retrospectivamente, por extra&#231;&#227;o dos prontu&#225;rios de todos os pacientes com ICC admitidos no hospital-dia entre junho de 2009 e junho de 2010 nos dois Centros. Esse grupo consistiu em 28 mulheres e 26 homens, com idade m&#233;dia de 78 &#177; 5,5 anos. Suas caracter&#237;sticas cl&#237;nicas e hematoqu&#237;micas basais s&#227;o descritas na <xref ref-type="table" rid="aop04512_port_t1">tabela 1</xref>. Na <xref ref-type="table" rid="aop04512_port_t2">tabela 2</xref> s&#227;o alistadas as respectivas percentagens de todos os sinais e sintomas cl&#237;nicos investigados.</p>
    <p content-type="asset">
      <table-wrap id="aop04512_port_t1">
        <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gt01.jpg"/></table-wrap>
    </p>
    <p content-type="asset">
      <table-wrap id="aop04512_port_t2">
        <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gt02.jpg"/></table-wrap>
    </p>
    <p>A <xref ref-type="table" rid="aop04512_port_t3">tabela 3</xref> mostra os resultados das an&#225;lises de regress&#227;o de Cox de riscos proporcionais incluindo oito covari&#225;veis inseridas no modelo, utilizando como vari&#225;vel de desfecho o alto escore de congest&#227;o.</p>
    <p content-type="asset">
      <table-wrap id="aop04512_port_t3">
        <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gt03.jpg"/></table-wrap>
    </p>
    <p>Preditores multivariados de alto escore de congest&#227;o foram a distens&#227;o da veia jugular (rela&#231;&#227;o de risco: 13,38 95% IC: 2,13 a 84 <italic>p</italic> = 0,0059) e estertores (rela&#231;&#227;o de risco: 11 95% C.I : 1,45 a 83,8 <italic>p</italic> = 0,0213).</p>
    <p>A <xref ref-type="fig" rid="aop04512_port_f1">figura 1</xref> mostra a distribui&#231;&#227;o (%) de casos (17 ao todo) da distens&#227;o da veia jugular (DVJ) por meio dos tr&#234;s grupos ICVCI, encontrada na segunda visita. Ele documenta que no grupo com ICVCI &#8804;15%, a ocorr&#234;ncia de distens&#227;o da veia jugular era mais elevada que nos grupos de ICVCI=16%-40% e ICVCI&gt;40%: p (Kruskal Wallis) &lt; 0,05 para ambas as compara&#231;&#245;es. </p>
    <p content-type="asset">
      <fig id="aop04512_port_f1">
        <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gf01.jpg"/></fig>
    </p>
    <p>Al&#233;m disso, considerando a rela&#231;&#227;o entre cada categoria de ICVCI e a probabilidade de desenvolvimento de ortopneia (<xref ref-type="fig" rid="aop04512_port_f2">fig. 2</xref>), surge uma diferen&#231;a importante: realmente, os pacientes com ICVCI &#8804; 15% foram sobrecarregados com um risco muito mais elevado de apresentarem ortopneia no acompanhamento posterior. Al&#233;m disso, foi achada uma baixa colapsibilidade venosa implicada na alta taxa de encaminhamento precoce &#224; unidade de insufici&#234;ncia card&#237;aca, em raz&#227;o da readmiss&#227;o n&#227;o programada por agravamento dos sintomas e sinas de congest&#227;o pulmonar e sist&#234;mica. Comparando as tr&#234;s classes de colapsibilidade da veia cava, o comprometimento mais severo do quadro cl&#237;nico foi apresentado por pacientes pertencentes &#224; classe de valores mais baixos de ICVCI (<xref ref-type="fig" rid="aop04512_port_f3">fig. 3</xref>-<xref ref-type="fig" rid="aop04512_port_f4">4</xref>). Todavia, o modelo de riscos proporcionais multivariado de Cox n&#227;o conseguiu identificar ICVCI &#8804; 15% como um preditor multivariado significativo de agravamento da congest&#227;o cl&#237;nica (<xref ref-type="table" rid="aop04512_port_t3">tab. 3</xref>). Al&#233;m disso, havia sido observado que esse padr&#227;o foi acompanhado em todos os casos pela participa&#231;&#227;o simult&#226;nea de sinais e sintomas de insufici&#234;ncia card&#237;aca, tanto esquerda como direita; e pelo contr&#225;rio, pacientes pertencentes ao intervalo intermedi&#225;rio de colapsibilidade da veia cava (ICVCI 16-40%) apresentaram a maior taxa de congest&#227;o sist&#234;mica isolada, mas n&#227;o pulmonar, no final do acompanhamento prescrito (30 a 60 dias ap&#243;s a primeira visita) (<xref ref-type="fig" rid="aop04512_port_f5">fig. 5</xref>). </p>
    <p content-type="asset">
      <fig id="aop04512_port_f2">
        <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gf02.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop04512_port_f3">
        <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gf03.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop04512_port_f4">
        <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gf04.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop04512_port_f5">
        <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gf05.jpg"/></fig>
    </p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>Com base nos conceitos fisiopatol&#243;gicos acima, espera-se una import&#226;ncia progn&#243;stica da congest&#227;o cl&#237;nica em pacientes com IC. No entanto, a congest&#227;o cl&#237;nica pode ser a "ponta do iceberg" de les&#245;es hemodin&#226;micas que precedem os sintomas<sup>21-22</sup>. Por exemplo, na IC biventricular cr&#244;nica, mesmo a congest&#227;o hemodin&#226;mica severa raramente provoca estertores e/ou edema pulmonar radiogr&#225;fico. Isso pode estar relacionado com v&#225;rias mudan&#231;as fisiopatol&#243;gicas adaptativas, como aumentos na espessura da membrana capilar alveolar, drenagem linf&#225;tica aumentada e/ou hipertens&#227;o pulmonar<sup>3,21</sup>. Assim, na opini&#227;o de diversos autores<sup>13,22</sup>, seria muito interessante e &#250;til explorar n&#227;o somente a congest&#227;o cl&#237;nica, mas tamb&#233;m a hemodin&#226;mica, para realizar uma avalia&#231;&#227;o realmente criteriosa dos pacientes. Na verdade, isso seria oportuno considerando que pacientes com congest&#227;o hemodin&#226;mica somente apresentaram pobres resultados<sup>23-25</sup>.</p>
    <p>A avalia&#231;&#227;o por ultrassonografia das flutua&#231;&#245;es respirat&#243;rias da VCI tem sido proposta h&#225; muito tempo como poss&#237;vel ferramenta diagn&#243;stica para a obten&#231;&#227;o, n&#227;o invasiva, de uma estimativa confi&#225;vel do estado volum&#233;trico e/ou press&#227;o atrial direita em pacientes com ICC. Momentaneamente, em indiv&#237;duos respirando espontaneamente, a press&#227;o intrator&#225;cica diminui durante a inspira&#231;&#227;o, aumentando assim o retorno venoso e induzindo ao colapso da VCI; ao contr&#225;rio, durante a expira&#231;&#227;o, o retorno venoso diminui, ocasionando um aumento no di&#226;metro da VCI<sup>26</sup>. Press&#245;es atriais direitas elevadas dilatam a VCI e agravam a colapsibilidade normal da VCI. De acordo com essas observa&#231;&#245;es, a congest&#227;o seria indicada por valores relativamente baixos de ICVCI, enquanto a deple&#231;&#227;o intravascular seria revelada por grandes flutua&#231;&#245;es no di&#226;metro da VCI, gerando valores relativamente elevados de ICVCI. Portanto, VCI pequenas e colaps&#225;veis, conforme visualizado por ecocardiograma, representam baixas press&#245;es atriais direitas baixas, enquanto VCI grandes e n&#227;o colaps&#225;veis refletem altas press&#245;es atriais direitas<sup>13</sup>. Na presen&#231;a de marcada sobrecarregada de volume, o ciclo respirat&#243;rio conduz a uma m&#237;nima mudan&#231;a no di&#226;metro da VCI, independentemente do seu di&#226;metro absoluto<sup>27</sup>. Isso depende do relacionamento n&#227;o linear peculiar entre press&#227;o e di&#226;metro da VCI de modo que, acima de uma press&#227;o limiar (isto &#233;, PVC &gt; 20 mmHg), n&#227;o &#233; observado aumento posterior no di&#226;metro da VCI<sup>28</sup>. Isso foi confirmado por um estudo recente em que um ICVCI &#8804; 15% era altamente sens&#237;vel e espec&#237;fico para o diagn&#243;stico de insufici&#234;ncia card&#237;aca aguda descompensada, uma vez que o di&#226;metro absoluto da VCI, por si mesmo, era n&#227;o diagn&#243;stico<sup>19</sup>. </p>
    <p>Em nosso estudo, decidimos classificar os valores de ICVCI em tr&#234;s classes: &#8804; 15%, 16%- 40% e &gt; 40%. Esses valores de corte do ICVCI foram determinados arbitrariamente, visando &#224; sele&#231;&#227;o de grupos com &#237;ndices de colapsibilidade baixo, intermedi&#225;rio e alto.</p>
    <p>Com base nas nossas an&#225;lises, estertores e distens&#227;o da veia jugular foram preditores de escore de congest&#227;o elevado, medido ap&#243;s um acompanhamento de 60 dias. </p>
    <p>Al&#233;m disso, um baixo valor de ICVCI (&#8804; 15%) indicou uma probabilidade mais elevada de apresentar-se com escore de congest&#227;o elevado, ou seja &#8805; 4 sintomas e/ou sinais de congest&#227;o dentro de uma escala entre 0 e 7, comparado a outros dois grupos de ICVCI; mas quando avaliada pela an&#225;lise de regress&#227;o de Cox de riscos proporcionais, incluindo oito covari&#225;veis, a categoria de ICVCI mais baixo n&#227;o demonstrou ser um preditor multivariado significativo de congest&#227;o cl&#237;nica no acompanhamento de 60 dias do tratamento oral otimizado. </p>
    <p>Al&#233;m disso, todos os pacientes que apresentavam ICVCI &#8804; 15% apresentaram um quadro cl&#237;nico de insufici&#234;ncia card&#237;aca direita e esquerda, essa constata&#231;&#227;o provavelmente estava associada a valores elevados de press&#227;o atrial direita e Poap.</p>
    <p>
      <bold>Limita&#231;&#245;es do estudo</bold>
    </p>
    <p>O presente estudo &#233; limitado por sua natureza retrospectiva, bem como pelo tamanho relativamente pequeno da amostra. As medidas VCI n&#227;o foram feitas por um &#250;nico operador, ent&#227;o um vi&#233;s interobservador n&#227;o pode ser exclu&#237;do. Al&#233;m disso, n&#227;o podemos excluir o fato de que a insufici&#234;ncia tric&#250;spide afetou o di&#226;metro da veia cava inferior, embora essa influ&#234;ncia seja menos pronunciada no ICVCI. Adicionalmente, a medi&#231;&#227;o da press&#227;o venosa jugular continua sendo dif&#237;cil de determinar exatamente e tamb&#233;m exp&#245;e ao risco consider&#225;vel de vi&#233;s, relativo &#224; alta variabilidade esperada entre observadores.</p>
    <p>Em conclus&#227;o, no &#226;mbito da ICC a distens&#227;o venosa jugular e os estertores foram preditores &#250;teis de resulta quando avaliados ap&#243;s quatro a oito semanas de tratamento para elimin&#225;-los. Valores baixos de ICVCI (&#8804; 15%) n&#227;o predizem de modo confi&#225;vel o alto escore de congest&#227;o, bem como as classes de ICVCI n&#227;o separam de forma confi&#225;vel pacientes com ICC com diferentes escores de congest&#227;o. Todavia, o grupo com ICVCI &#8804; 15% sempre se achou associado com a presen&#231;a simult&#226;nea de sinais e sintomas de ICC descompensada, tanto do lado direito como do esquerdo.</p>
    <p>
      <fn id="nota" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Renato De Vecchis </p>
        <p> P. Gaurico 21 &#8211; 80125 - Napoli, Italy </p>
        <p> E-mail: </p>
        <p><email xlink:href="r.de.vecchis@alice.it">r.de.vecchis@alice.it</email>, </p>
        <p>
          <email xlink:href="carmelariano@tiscali.it">carmelariano@tiscali.it</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 28/08/11 </p>
    <p> Revisado recebido em 30/08/11 </p>
    <p> Aprovado em 06/02/12.</p>
  </body>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Inferior Vena Cava collapsibility and heart failure signs and symptoms: new insights about possible links</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: In chronic heart failure patients (CHF), ultrasound measurement of inferior vena cava collapsibility index (IVCCI) has been proposed to yield careful assessment and grading of the hemodynamic congestion. OBJECTIVE: The purpose of this study was to correlate the findings of physical examination with IVCCI in CHF patients. METHODS: According to a retrospective cohort design, we analyzed 54 CHF patients with right or biventricular CHF, belonging to III NYHA class. We planned to determine whether any basal IVCCI range would be able to predict persistent or worsening clinical congestion found at the end of subsequent follow up (i.e. after 1-2 months of oral optimized therapy). For this purpose, the patients were subdivided by three groups according to the basal IVCCI value: &#8804; 15% (13 pts), 16 - 40% (21 pts) and &gt; 40% (20 pts).Several clinical criteria of congestion were compared across the three groups and subsequently entered in the Cox multivariate model. RESULTS: Multivariate predictors of high congestion score were jugular venous distension (HR: 13,38 95% C.I.: 2,13 - 84 p = 0,0059) and rales (HR: 11 95% C.I : 1,45 - 83,8 p = 0,0213). IVCCI &#8804; 15% was always associated with high congestion score at the second visit; but IVCCI &#8804; 15% failed to predict high congestion score at the second visit. CONCLUSION: In CHF setting, low IVCCI did not reliably predict high congestion score. Nevertheless, the cluster with IVCCI &#8804; 15% was always found associated with signs and symptoms from both right and left-sided decompensated CHF. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Cardiac output, low</kwd>
        <kwd>heart failure</kwd>
        <kwd>vena cava, inferior</kwd>
        <kwd>ventricular dysfunction</kwd>
        <kwd>left</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p><undefined id="topo-body2"/>Inferior Vena Cava collapsibility and heart failure signs and symptoms. New insights about possible links</p>
      <p>
        <bold>Renato De Vecchis<sup>I</sup>; Antonio Ciccarelli<sup>II</sup>; Carmelina Ariano<sup>II</sup></bold>
      </p>
      <p><sup>I</sup>Cardiology Unit, Presidio Sanitario Intermedio Elena d Aosta</p>
      <p><sup>II</sup>Napoli; Neurorehabilitation Unit, Clinica S. Maria del Pozzo, Somma Vesuviana, Italy</p>
      <p>Correspond&#234;ncia</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>BACKGROUND:</bold> In chronic heart failure patients (CHF), ultrasound measurement of inferior vena cava collapsibility index (IVCCI) has been proposed to yield careful assessment and grading of the hemodynamic congestion.</p>
      <p><bold>OBJECTIVE:</bold> The purpose of this study was to correlate the findings of physical examination with IVCCI in CHF patients.</p>
      <p><bold>METHODS:</bold> According to a retrospective cohort design, we analyzed 54 CHF patients with right or biventricular CHF, belonging to III NYHA class. We planned to determine whether any basal IVCCI range would be able to predict persistent or worsening clinical congestion found at the end of subsequent follow up (i.e. after 1-2 months of oral optimized therapy). For this purpose, the patients were subdivided by three groups according to the basal IVCCI value: &#8804; 15% (13 pts), 16 - 40% (21 pts) and &gt; 40% (20 pts).Several clinical criteria of congestion were compared across the three groups and subsequently entered in the Cox multivariate model.</p>
      <p><bold>RESULTS:</bold> Multivariate predictors of high congestion score were jugular venous distension (HR: 13,38 95% C.I.: 2,13 - 84 p = 0,0059) and rales (HR: 11 95% C.I : 1,45 - 83,8 p = 0,0213). IVCCI &#8804; 15% was always associated with high congestion score at the second visit; but IVCCI &#8804; 15% failed to predict high congestion score at the second visit.</p>
      <p><bold>CONCLUSIONS: </bold>In CHF setting, low IVCCI did not reliably predict high congestion score. Nevertheless, the cluster with IVCCI &#8804; 15% was always found associated with signs and symptoms from both right and left-sided decompensated CHF. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)</p>
      <p><bold>Keywords</bold>: Cardiac output, low; heart failure; vena cava,inferior/abnormalities; ventricular dysfunction, left.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Hemodynamic congestion<sup>1</sup> is thought to derive primarily from impaired cardiac index - with or without reduction in left ventricular ejection fraction- .This in turn generates elevation in pulmonary capillary wedge pressure (PCWP)<sup>2</sup>, in the case of left chambers isolated decompensation, or combined increase in both PCWP and right atrial pressure, in the case of biventricular heart failure<sup>1</sup>. Impaired cardiac index, for left only ventricular heart failure, or the combination of impaired cardiac index plus elevated central venous pressure, in the case of right or biventricular heart failure, with or without patent fall in blood pressure, substantially reduce renal blood flow, the most important variable of kidney filtration gradient in patients presenting with congestive heart failure, thus generating neuro-hormonal stimulation and development of hydrosaline retention<sup>4-8</sup>. Hemodynamic worsening consisting in impaired cardiac index and increased filling pressures will further activate the renin-angiotensin and sympathetic nervous system, reduce nitric oxide in the endothelium, and induce inflammatory mediators, to aggravate the hypoperfusion state of the glomeruli and so to further harm the renal function<sup>9</sup>. Reduction in water and salt clearance in turn propitiates persistence of hemodynamic congestion to create and maintain over time a condition of cardiac overload. Hemodynamic congestion contributes to the progression of HF by further activating neurohormones and by causing subendocardial ischaemia, resulting in myocardial necrosis/apoptosis and/or secondary mitral insufficiency by its effects on LV geometry (changing it from an ellipsoid to a sphere)<sup>10</sup>. In addition, elevated right atrial pressure may contribute to the cardio-renal syndrome through reduction of the perfusion gradient across the kidneys<sup>11-12</sup>.</p>
      <p>Among the proposed methods for estimating and grading hemodynamic congestion in right or biventricular heart failure, a remarkable role is played by ultrasound evaluation of the inferior vena cava diameter (IVCD) and its collapsibility index (IVCCI)<sup>13</sup>. This technique is aimed to identify any changes in respiratory pattern of IVC indicating the presence of abnormalities in volume status (that is hemodynamic congestion or intravascular depletion). Based on well-established knowledge, wide respiratory fluctuations of IVCCI would indicate that intravascular depletion is likely, whereas low values of this parameter would mean high probability of hemodynamic congestion. These inferences have received exhaustive confirmation by many large well-conducted studies<sup>13-20</sup>. </p>
      <p>
        <bold>Objectives</bold>
      </p>
      <p>In a number of patients with right or biventricular CHF, we have tested the possible relationships between IVCCI and some signs and symptoms of CHF. Besides, we have tried to establish whether in these CHF patients a low IVCCI value, as found at the first visit, can be assumed as a reliable predictor of subsequent clinical congestion &#8211; after a clinical follow up of one-two months - . </p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>An observational retrospective study was carried out by enrolling patients from two Centers (C.U. E. d&#8217;A. and N.R. S.M.d P.). For enrollment in the study , documented evidence of right or bi-ventricular chronic heart failure in II- III NYHA class was required. Exclusion criteria were: patients with pace-maker or treated by cardiac resynchronization therapy; myocardial infarction within 30 days, arrhythmia-related syncope, major cardiac surgery, unstable angina, uncontrollable hypertension, cor pulmonale, advanced pulmonary disease, major neurologic disease or cerebrovascular disease, suspected renal artery stenosis, advanced renal failure (i.e. serum creatinine &gt;2,5 mg/dl at baseline), other life-threatening disease. </p>
      <p>Retrospective chart review was performed to analyze characteristicsof all eligible patients. For each patient, date of birth, sex, race, and weight and heightwere noted. Comorbidities, including diabetes, dyslipidemia, nicotine abuse, hypertension , ischemic heart disease, preexisting diabetic nephropathy or other chronic renal disease in addition to medical treatment at the time of hospital stayalso were extracted for each patient. IVCCI was defined as the difference between maximum expiratory diameter and minimum inspiratory diameter divided by the maximum expiratory diameter . IVCCI measurements were obtained 1 to 2 cm below the level of the hepatic veins, using a two-dimensional echographic sector (Vivid 7 ultrasound machine, GE Healthcare Systems, Milwaukee, WI).The IVC diameter recording was made on M-mode approximately 3 cm from the right atrium with patients in a 45&#186; recumbent position. Subcostal or subxiphoid windows were used based on available views, patient habits, presence of external impediments (e.g., drains, surgical dressings), and preference of the sonologist. </p>
      <p>The patients were divided into three groups according to IVCCI values: IVCCI &#8804; 15%(13 pts), IVCC I 16-40%(21 pts), IVCC I &gt;40% (20 pts). Among these, first and third layers were assumed to indicate the presence of systemic venous congestive status or of likely intravascular depletion , respectively; whereas an IVCCI in the intermediate range(0,16 to 0,40) was considered not helpful in discriminating CVP. </p>
      <p>The following clinical criteria of congestion were compared across the three groups: dyspnea/orthopnea, dyspnea on exertion, jugular venous distension, peripheral edema, congestive hepatomegaly, pulmonary rales, mean weight gain &#8805; 1 kg per week through the follow up. </p>
      <p>These signs and symptoms were chosen due to their proven relationship with CHF syndrome. Particularly, dyspnea at rest with orthopnea was selected as being a symptom usually associated with severe impairment in left ventricle pump function (in our case to be set in the context of biventricular cardiac decompensation, as right heart failure was present in all recruited cases by definite enrollment criterion ). Orthopnea was defined as any respiratory distress associated with lying down or the perceived need to use more than one pillow to avoid respiratory distress. Rales were considered owing to their well-known association with pulmonary capillary and venous hematic stagnation usually related to relatively high levels of capillary pulmonary wedge pressure (CPWP). Dyspnea on exertion was included in analysis as being a symptom that usually indicates lesser cardiac impairment compared to orthopnea, generated by right-sided as well as by combined biventricular heart failure. Besides, the other four signs (jugular venous distension, peripheral edema, congestive hepatomegaly and weight gain &#8805; 1 kg per week) were evaluated in the study as markers of hydrosaline retention as usually found in systemic congestion from right or biventricular advanced CHF. Particularly, jugular venous distension was considered present if visualized at least 10 cm vertically above the right atrium. Weight gain was defined as &#8805; 1kg mean increase per week. </p>
      <p>In addition, a congestion score was set up and defined retrospectively for this analysis as the sum of the seven criteria for congestion, with a possible range from 0 to 7.A score &#8805; 4 was termed "high congestion score" and used as outcome variable ("end &#8211; point") in the subsequent statistical analysis. According to the customary approach applied at the two Centers, every patient in each of the day hospitals underwent a careful clinical examination along with a complete echocardiography including a thorough assessment of IVC with IVCCI calculation. Subsequently, a second scheduled visit was usually accomplished within one-two months in order to timely establish any appropriate pharmacologic and dosing change to be done based on the evolving clinical picture. Should any complaint or unexpected complication arise, the patients were recommended to bring forward the date of the visit . </p>
      <p>In our retrospective study, we tried to ascertain whether any association could exist between IVCCI values, as detected at the first visit, and one or more of the abovementioned signs and symptoms of congestion, as noticed after 1-2 months of clinical follow up. We investigated this hypothesis by using the preliminary categorization of IVCCI values by three layers (IVCCI &#8804; 15% , IVCC I 16-40%, IVCC I &gt;40%) and by considering the clinical picture after adequate oral therapy kept for one-two months. We also verified the possible existence of any significant association between the cluster characterized by the lowest IVCCI (&#8804; 15%) at baseline and the finding of "high congestion score", as found at the second visit after one-two months. The prescribed oral therapy usually included ACE-inhibitors, beta-blockers and diuretics; in addition, according to the physician&#8217;s judgment, aldosterone receptor antagonists, oral or transdermal nitrates, antiaggregant drugs, warfarin, amiodarone and digoxin were also administered if necessary. It was also established that every patient requiring intravenous diuretics or inotropes for worsening HF during follow up would have been excluded from the statistical analysis, as being considered to demonstrate treatment failure. </p>
      <p>
        <bold>Statistical analysis</bold>
      </p>
      <p>We used the Statistical Package of Social Sciences (SPSS Version 14 ) and Excel to perform the analysis. Baseline demographics, physical examination, and laboratory findings were compared between patients across the three IVCCI layers. The <italic>&#967;</italic><sup>2</sup> (chi square) test and the unpaired t-test were respectively applied for comparison of dichotomous or continuous variables. One-way analysis of variance (ANOVA) and Student-Newman-Keuls test for all peer comparisons ("post hoc" analysis) were used for multiple comparisons . Kruskal Wallis test was also employed for comparison of data with asymmetric distribution.</p>
      <p>For identifying the predictors of hemodynamic congestion, univariate and multivariate Cox proportional hazards regression analyses were used . The following variables were entered into the model as exposure variables:</p>
      <p>IVCCI 15%</p>
      <p> mean weight gain &#8805; 1 Kg per week </p>
      <p> edema </p>
      <p> orthopnea </p>
      <p> rales </p>
      <p> jugular venous distension </p>
      <p> dyspnea on exertion during optimized therapy </p>
      <p> congestive hepatomegaly</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>A total of 54 patients were retrospectively enrolled, by drawing them from the charts of all CHF patients admitted for day-hospital stay between June 2009 and June 2010 at the two Centers. This group consisted of 28 women and 26 men, with mean age of 78 &#177;5,5 years. Their basal clinical and hematochemical characteristics are described in <xref ref-type="table" rid="aop04512_ing_t1-body2">Table 1</xref>. In <xref ref-type="table" rid="aop04512_ing_t2-body2">Table 2</xref>, the respective percentages of all of the investigated clinical signs and symptoms are listed.</p>
      <p content-type="asset">
        <table-wrap id="aop04512_ing_t1-body2">
          <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gt01-en.jpg"/></table-wrap>
      </p>
      <p content-type="asset">
        <table-wrap id="aop04512_ing_t2-body2">
          <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gt02-en.jpg"/></table-wrap>
      </p>
      <p><xref ref-type="table" rid="aop04512_ing_t3-body2">Table 3</xref> shows the results of the multivariate Cox proportional hazards regression analysis including 8 covariates entered in the model, with high congestion score being used as outcome variable.</p>
      <p content-type="asset">
        <table-wrap id="aop04512_ing_t3-body2">
          <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gt03-en.jpg"/></table-wrap>
      </p>
      <p>Multivariate predictors of high congestion score were jugular venous distension (hazard ratio: 13,38 95% C.I.: 2,13 to 84 <italic>p</italic> = 0,0059) and rales (hazard ratio: 11 95% C.I : 1,45 to 83,8 <italic>p</italic> = 0,0213).</p>
      <p><xref ref-type="fig" rid="aop04512_ing_f1-body2">Figure 1</xref> shows the distribution (%) of the cases (17 on the whole) of jugular venous distension (jvd) across the 3 IVCCI groups, as found at the second visit. It documents that in the IVCCI &#8804;15% group, occurrence of jugular venous distension was higher than in IVCCI=16-40% and IVCCI&gt;40% groups: p (Kruskal Wallis ) &lt;0.05 for both comparisons. </p>
      <p content-type="asset">
        <fig id="aop04512_ing_f1-body2">
          <graphic xlink:href="1678-4170-abc-98-06-0544-00049-gf01-en.jpg"/></fig>
      </p>
      <p>Furthermore, by considering the relation between every category of IVCCI and the probability of developing orthopnea (<xref ref-type="fig" rid="aop04512_ing_f2-body2">figure 2</xref>), a remarkable difference emerges: actually, the patients with IVCCI &#8804; 15% were burdened with a much higher risk of being involved by orthopnea during the subsequent follow up. In addition, low venous collapsibility was found to entail high rate of early referral to heart failure unit, due to unscheduled re-admission for worsening symptoms and signs of systemic and pulmonary congestion. By comparing the three classes of caval collapsibility, the most severe impairment of the clinical picture was exhibited by patients belonging to the lowest class of IVCCI values (<xref ref-type="fig" rid="aop04512_ing_f3-body2">figures 3</xref>-<xref ref-type="fn" rid="aop04512_ing_f5-body2">5</xref>) . Nevertheless, Cox multivariate proportional hazard model failed to identify IVCCI &#8804; 15% as a significant multivariate predictor of worsening clinical congestion (<xref ref-type="table" rid="aop04512_ing_t3-body2">Tab 3</xref>). In addition, it would be noted that this pattern was accompanied in any case by simultaneous involvement of signs and symptoms from both left-sided and right-sided cardiac failure; on the contrary, the patients belonging to the intermediate range of caval collapsibility(IVCCI 16-40%) exhibited the highest rate of isolated systemic - but not pulmonary - congestion at the end of the prescribed follow up (30-60 days after the first visit)(<xref ref-type="fn" rid="aop04512_ing_f5-body2">figure 5</xref>).</p>
      <p content-type="asset">
        <fig id="aop04512_ing_f2-body2">
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            <graphic xlink:href="1678-4170-abc-98-06-0544-00049-e01-en.jpg"/></p>
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      <p>
        <bold>Discussion</bold>
      </p>
      <p>Based on the pathophysiological concepts represented above, prognostic importance of clinical congestion in HF patients is expected. However, clinical congestion may be the &#8216;tip of the iceberg&#8217; of the hemodynamic derangements that precede symptoms<sup>21-22</sup>. For instance, in chronic biventricular HF, even severe hemodynamic congestion rarely causes rales and/or radiographic pulmonary edema. This may be related to several adaptive pathophysiological changes such as increases in alveolar capillary membrane thickness, increased lymphatic drainage, and/or pulmonary hypertension<sup>3,21</sup> (3,21). Thus, in the opinion of several Authors<sup>13,22</sup>, it would be very interesting and useful to explore not only clinical but also hemodynamic congestion in order to achieve a really careful patient assessment. In truth, this would be opportune considering that patients with even only hemodynamic congestion were shown to have poor outcomes<sup>23-25</sup>.</p>
      <p>Ultrasound assessment of IVC respiratory fluctuations has been proposed from a long while as a possible diagnostic tool for obtaining noninvasive reliable estimation of volume status and/or right atrial pressure in CHF patients. Briefly, in spontaneously breathing subjects, intrathoracic pressure decreases during inspiration, thereby increasing venous return and inducing collapse of the IVC; inversely, during expiration, venous return decreases, so causing an increase in the diameter of the IVC<sup>26</sup>. High right atrial pressures dilate the IVC and worsen this normal IVC collapsibility. According to these observations, congestion would be indicated by relatively small IVCCI values, while intravascular depletion would be revealed by wide fluctuations of IVC diameter, generating relatively high values of IVCCI. Therefore, small, collapsible IVCs as visualized by echocardiography represent low right atrial pressures, whereas large, non-collapsible IVCs reflect high right atrial pressures<sup>13</sup>. In the presence of marked volume overload, the respiratory cycle leads to minimal change in diameter of IVC, regardless of its absolute diameter<sup>27</sup>. This depend on the peculiar non-linear pressure-diameter relationship of the IVC so that, above a threshold pressure (i.e., CVP &gt;20 mmHg), no further increase in IVC diameter can be observed<sup>28</sup>.This has been confirmed by a recent study in which a IVCCI &#8804; 15% was highly sensitive and specific for the diagnosis of acute decompensated heart failure, whereas the absolute diameter of the IVC in itself was non diagnostic<sup>19</sup>. </p>
      <p>In our study, we decided to categorize IVCCI values by grouping them in three classes: &#8804; 15%, 16-40 % and &gt; 40 %.These IVCCI cut-off values were determined arbitrarily, with the intention of selecting groups with low, intermediate and high collapsibility indices.</p>
      <p>Based on our analysis, rales and jugular venous distension were predictors of elevated score of congestion as measured after a follow up period of 60 days. </p>
      <p>Moreover, a low (&#8804; 15%) IVCCI value indicated higher probability of presenting with elevated congestion score - that is &#8805; 4 symptoms and/or signs of congestion within a range extending from 0 to 7 - compared to the other two IVCCI clusters; but , when evaluated by Cox proportional hazards regression analysis including 8 covariates, the lowest IVCCI category was not demonstrated to be a significant multivariate predictor of clinical congestion kept over a 60 day follow-up on optimized oral therapy. </p>
      <p>Furthermore, all of the patients presenting with IVCCI &#8804; 15% were found to have a clinical picture of combined right and left heart failure, this finding being presumably associated with both high CPWP and right atrial pressure.</p>
      <p>
        <bold>Study limitations</bold>
      </p>
      <p>This study is limited by its retrospective nature as well as by relatively small sample size. IVC measurements were not done by a single operator, so inter-observer bias cannot be excluded. Moreover, we cannot exclude that tricuspid regurgitation affected inferior vena cava diameter, although this influence is less pronounced on IVCCI. Besides, measurement of the jugular venous pressure remains hard to be exactly performed and it also exposes to considerable risk of bias, related to high inter-observer variability expected.</p>
      <p>In conclusion, in CHF setting both jugular venous distension and rales were useful predictors of outcome when assessed after 4 to 8 weeks of therapy to eliminate them. Low (&#8804; 15%) IVCCI did not reliably predict high congestion score as well as IVCCI classes did not reliably separate CHF patients with different congestion scores. Nevertheless, the cluster with IVCCI &#8804; 15% was always found associated with simultaneous presence of signs and symptoms from both right and left-sided decompensated CHF.</p>
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        <xref ref-type="undefined" rid="aop04512_ing_f4-body2">Click to enlarge</xref>
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      <p>
        <bold>References</bold>
      </p>
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