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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <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>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">WPfjM9XZpCD7sKDtJ84pZkt</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2018000300270</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20180046</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
          <subj-group>
            <subject>Heart Failure</subject>
          </subj-group>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Natriuretic Peptide and Clinical Evaluation in the Diagnosis of Heart Failure Hemodynamic Profile: Comparison with Tissue Doppler Echocardiography</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Almeida</surname>
            <given-names>Gustavo Luiz Gouv&#234;a de</given-names>
            <suffix>Junior</suffix>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Clausell</surname>
            <given-names>Nadine</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Garcia</surname>
            <given-names>Marcelo Iorio</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Esporcatte</surname>
            <given-names>Roberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rangel</surname>
            <given-names>Fernando Oswaldo Dias</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rocha</surname>
            <given-names>Ricardo Mourilhe</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Beck-da-Silva</surname>
            <given-names>Luis</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Fabricio Braga da</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gorgulho</surname>
            <given-names>Paula de Castro Carvalho</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Xavier</surname>
            <given-names>Sergio Salles</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Casa de Sa&#250;de S&#227;o Jos&#233;</institution>
        <addr-line>
          <city>Rio de Janeiro</city>
          <state>RJ</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Casa de Sa&#250;de S&#227;o Jos&#233;, Rio de Janeiro, RJ - Brazil</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Hospital Pro-Card&#237;aco</institution>
        <addr-line>
          <city>Rio de Janeiro</city>
          <state>RJ</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital Pro-Card&#237;aco, Rio de Janeiro, RJ - Brazil</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
        <institution content-type="orgdiv1">Hospital Universit&#225;rio Clementino Fraga Filho</institution>
        <addr-line>
          <city>Rio de Janeiro</city>
          <state>RJ</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital Universit&#225;rio Clementino Fraga Filho - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ - Brazil</institution>
        <institution content-type="normalized">Universidade Federal do Rio de Janeiro</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
        <institution content-type="orgdiv1">Hospital de Cl&#237;nicas de Porto Alegre</institution>
        <addr-line>
          <city>Porto Alegre</city>
          <state>RS</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital de Cl&#237;nicas de Porto Alegre - Universidade Federal do Rio Grande do Sul, Porto Alegre, RS - Brazil</institution>
        <institution content-type="normalized">Universidade Federal do Rio Grande do Sul</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Gustavo Luiz Gouvea de Almeida Junior,</bold> Rua Macedo Sobrinho, 21. Unidade Coronariana. CEP 22271-080, Botafogo, RJ - Brazil. E-mail: <email>gustavogouvea@cardiol.br</email>, <email>gustavogouvea@globo.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research and Analysis and interpretation of the data: Almeida Junior GLG, Clausell N, Garcia MI, Esporcatte R, Rangel FOD, Rocha RM, Silva Neto LB, Silva FB, Gorgulho PCC, Xavier SS; Acquisition of data: Almeida Junior GLG, Garcia MI; Statistical analysis: Almeida Junior GLG, Clausell N, Silva FB, Xavier SS; Obtaining financing: Almeida Junior GLG; Writing of the manuscript: Almeida Junior GLG, Clausell N, Garcia MI, Xavier SS; Critical revision of the manuscript for intellectual content: Almeida Junior GLG, Clausell N, Garcia MI, Rangel FOD, Xavier SS.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <month>03</month>
        <year>2018</year>
      </pub-date>
      <volume>110</volume>
      <issue>3</issue>
      <fpage>270</fpage>
      <lpage>277</lpage>
      <history>
        <date date-type="received">
          <day>07</day>
          <month>08</month>
          <year>2017</year>
        </date>
        <date date-type="rev-recd">
          <day>09</day>
          <month>10</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>18</day>
          <month>10</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Physical examination and B-type natriuretic peptide (BNP) have been used to estimate hemodynamics and tailor therapy of acute decompensated heart failure (ADHF) patients. However, correlation between these parameters and left ventricular filling pressures is controversial.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>This study was designed to evaluate the diagnostic accuracy of physical examination, chest radiography (CR) and BNP in estimating left atrial pressure (LAP) as assessed by tissue Doppler echocardiogram.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>Patients admitted with ADHF were prospectively assessed. Diagnostic characteristics of physical signs of heart failure, CR and BNP in predicting elevation (&gt; 15 mm Hg) of LAP, alone or combined, were calculated. Spearman test was used to analyze the correlation between non-normal distribution variables. The level of significance was 5%.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>Forty-three patients were included, with mean age of 69.9 &#177; 11.1years, left ventricular ejection fraction of 25 &#177; 8.0%, and BNP of 1057 &#177; 1024.21 pg/mL. Individually, all clinical, CR or BNP parameters had a poor performance in predicting LAP &#8805; 15 mm Hg. A clinical score of congestion had the poorest performance [area under the receiver operating characteristic curve (AUC) 0.53], followed by clinical score + CR (AUC 0.60), clinical score + CR + BNP &gt; 400 pg/mL (AUC 0.62), and clinical score + CR + BNP &gt; 1000 pg/mL (AUC 0.66).</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>Physical examination, CR and BNP had a poor performance in predicting a LAP &#8805; 15 mm Hg. Using these parameters alone or in combination may lead to inaccurate estimation of hemodynamics.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Heart Failure</kwd>
        <kwd>Natriuretic Peptide, Brain</kwd>
        <kwd>Hemodynamics</kwd>
        <kwd>Ventricular Function, Left</kwd>
        <kwd>Echocardiography, Doppler</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Clinical evaluation of patients with acute decompensated heart failure (ADHF) based only on physical examination has proved to be inadequate for both assessment of left ventricular (LV) function (systolic versus diastolic dysfunction)<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref> and estimation of patient&#8217;s hemodynamic status.<xref ref-type="bibr" rid="B3">3</xref> Precise determination of LV filling pressures is critical to the proper treatment of patients with ADHF, since congestion is the main determinant of symptoms, hospitalization, and prognosis.<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref> Additional assessment using both invasive<xref ref-type="bibr" rid="B8">8</xref> and noninvasive tools may be useful, as it adds important information potentially contributing to tailored management.</p>
      <p>Echocardiography has proven its usefulness in assessing the hemodynamic status of patients with ADHF, especially after the advent of new techniques, such as tissue Doppler imaging.<xref ref-type="bibr" rid="B9">9</xref> The so-called &#8220;hemodynamic echocardiogram&#8221; may help physicians to detect congestion.<xref ref-type="bibr" rid="B10">10</xref> Several studies have shown that echocardiographic-derived hemodynamic parameters correlate significantly with those obtained by right heart catheterization.<xref ref-type="bibr" rid="B11">11</xref>
			</p>
      <p>Elevated levels of B-type natriuretic peptide (BNP) reflect increased LV filling pressures, secondary to myocyte stretch, due to volume or pressure overload.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> Whether the association of BNP values adds diagnostic accuracy to the standard clinical assessment in estimating patient&#8217;s hemodynamic status remains unknown. In this study we tested the hypothesis that BNP values add diagnostic accuracy to physical examination in detecting congestion in patients with ADHF, using echocardiogram-derived hemodynamic assessment as a reference method for comparison.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Sample studied</title>
        <p>A prospective convenience sample of patients admitted to the emergency department or coronary care unit of three hospitals (one university-affiliated and two tertiary hospitals) due to ADHF was studied. The study was conducted according to the Declaration of Helsinki standards for human research. Institutional review boards approved the research protocol, and all participants provided written informed consent before enrollment.</p>
      </sec>
      <sec>
        <title>Inclusion criteria</title>
        <p>Patients with ADHF due to LV systolic dysfunction, with LV ejection fraction (LVEF) &lt;40% by Simpson's method, New York Heart Association (NYHA) functional class III or IV on admission and sinus rhythm were included within 24 hours of emergency care.</p>
      </sec>
      <sec>
        <title>Exclusion criteria</title>
        <p>The exclusion criteria were as follows: ADHF due to acute coronary syndrome; echocardiographic window precluding adequate analysis of hemodynamic parameters; primary valve disease; mechanical prosthetic valve; single mitral flow pattern; and presence of cardiac pacing.</p>
      </sec>
      <sec>
        <title>Physical examination</title>
        <p>The following physical findings were evaluated: jugular venous distension; hepatojugular reflux; hepatomegaly; ascites; lower extremity edema; third heart sound (S3); pulmonary rales; arterial blood pressure; and proportional pulse pressure. Patients were examined in a quiet emergency or critical care room. The jugular venous distension was evaluated with the patient sitting upright and the presence of a visible internal jugular vein above the clavicle was considered elevated. The hepatojugular reflux was tested in patients with no visible jugular vein, applying a firm right abdominal pressure. The liver was examined with the patient in recumbent position. Hepatomegaly was considered when the liver had more than 10cm of length, considering percussion technique initiating on the third intercostal space, along the midclavicular line. Liver palpation was the method of choice to assess the lower margin of the liver if it was palpable in the abdomen.</p>
        <p>Patients with chest radiography showing any sign of congestion were considered to be congested. The radiological evaluation was done through the posterior-anterior and left lateral chest radiography. In cases of inability to take chest radiography in posterior-anterior and lateral positions, an anterior-posterior position with the patient sitting in bed was performed. The chest radiography was performed immediately prior to the echocardiogram.</p>
      </sec>
      <sec>
        <title>B-type natriuretic peptide assay</title>
        <p>Simultaneously to echocardiography, blood sample was drawn for measurement of BNP. Samples were drawn in EDTA tubes and BNP was measured in whole blood, by immunofluorescence technique, using a commercially available kit (Triage &#174; BNP test of Biosite Inc., San Diego, CA, USA). All measurements were performed within 30 minutes of blood sampling. Patients with levels of BNP &gt; 400 pg/mL were considered congested,<xref ref-type="bibr" rid="B14">14</xref> and with levels of BNP &lt; 200 pg/mL were considered &#8220;dry&#8221;.<xref ref-type="bibr" rid="B15">15</xref>
				</p>
      </sec>
      <sec>
        <title>Echocardiogram evaluation</title>
        <p>All patients were submitted to a transthoracic echocardiography with tissue Doppler imaging (GE Vivid 7, Wauwatosa, WI, USA) within a maximum of 30 minutes after completion of the physical exam. In each center, only one examiner (the most experienced) performed all echocardiographic evaluations. Echocardiographic measurements were performed in a blinded manner: the examiner was unaware of the physical findings. Images were obtained from patients in the left lateral and recumbent position, and measurements followed the recommendations of the American Society of Echocardiography.<xref ref-type="bibr" rid="B16">16</xref> All Doppler profiles were recorded in an apical 4-chamber view.</p>
        <p>The estimated left atrial pressure (LAP) was calculated as follows: calculation of the E/E' ratio by measuring the intra-myocardial flow velocity with tissue Doppler. The early diastolic mitral annular velocity (E') was obtained by tissue Doppler in the LV lateral wall and in case of technical impossibility of obtaining the velocity in this wall, as in ischemic involvement, it was measured in the interventricular septum. At least three consecutive cardiac cycles were used and an average was used as the final result. This measurement, when combined with the trans-mitral flow obtained with pulsed Doppler in early diastole (E) results in the relationship E/E'. The LAP was then estimated by the formula: LAP: 1.24 x (E/E&#8217;) + 1.9. Indication of increased LV filling pressure was defined as LAP &#8805; 15 mm Hg. Although patients with values below 15 mm Hg may have congestion, values &#8805; 15 mm Hg have high specificity for increased LV filling pressure. Ejection fraction was evaluated through the Simpson&#8217;s method.</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>Descriptive statistics were expressed as frequency (%) for categorical variables. For continuous variables data are presented as means &#177; standard deviation for normally distributed data or median and interquartile range (IQR) for non-normally distributed data. Measures of diagnostic performance (sensitivity, specificity, accuracy, positive and negative predictive values) were used to evaluate the diagnostic utility of physical exam signs of heart failure and/or BNP in predicting LAP &#8805; 15 mm Hg (defined as indication of increased LV filling pressure).</p>
        <p>The Spearman test was used to analyze the correlation between non-normal distribution variables. The level of significance was 5%.</p>
        <p>To determine the best cut-off value for BNP to estimate elevation in LAP, a receiver operating characteristic (ROC) curve was constructed. A clinical score (CS) was built by giving 1 point to each positive sign of decompensated heart failure (elevated jugular venous distension, hepatojugular reflux, hepatomegaly, pulmonary rales or edema). Patients with &#8805; 2 points were considered with a positive CS, according to analysis of ROC curve. To evaluate the capacity of physical exam and noninvasive diagnostic tests for the prediction of elevated LAP (LAP &#8805; 15 mm Hg), separate models were built using combination of CS, CS + chest radiography, CS + chest radiography + BNP &gt; 400 pg/mL, and finally CS + chest radiography + BNP &gt; 1000 pg/mL (based on optimal cut-off point of BNP). Each of these diagnostic tests was dichotomized and compared to determine the incremental predictive value. Statistical analyses were performed using SPSS&#210; (SPSS Inc, Chicago, IL, USA).</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Patients characteristics</title>
        <p>Forty-three patients were included in the study. Patients were predominantly male (75%), elderly (69.9 &#177; 11.1 years) and had ADHF of ischemic etiology (65%). The mean serum creatinine was 1.3 &#177; 0.4 mg/dL, and the mean BNP was 1057 pg/mL &#177; 1024 pg/mL. <xref ref-type="table" rid="t1">Table 1</xref> shows clinical and demographic characteristics of patients. All patients were in NYHA functional class III (10.7%) or IV (89.3%), with a mean LVEF of 25% &#177; 8.0%.</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Clinical and demographic characteristics of the patients</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="50%"/>
              <col width="50%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Characteristics</th>
                <th align="center">
								</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">n</td>
                <td align="center">43</td>
              </tr>
              <tr>
                <td align="left">Age (years)</td>
                <td align="center">69.9 &#177; 11.1</td>
              </tr>
              <tr>
                <td align="left">Gender (male %)</td>
                <td align="center">76</td>
              </tr>
              <tr>
                <td align="left">Weight</td>
                <td align="center">75.3 &#177; 17.1</td>
              </tr>
              <tr>
                <td align="left">Body mass index (kg/m<sup>2</sup>)</td>
                <td align="center">26.55.2</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Etiology</bold>
                </td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Ischemic</td>
                <td align="center">28 (65.1)</td>
              </tr>
              <tr>
                <td align="left">Idiopathic</td>
                <td align="center">7 (16.2)</td>
              </tr>
              <tr>
                <td align="left">Hypertensive</td>
                <td align="center">3 (6.9)</td>
              </tr>
              <tr>
                <td align="left">Valvular</td>
                <td align="center">4 (9.3)</td>
              </tr>
              <tr>
                <td align="left">Others</td>
                <td align="center">1 (2.3)</td>
              </tr>
              <tr>
                <td align="left">Left ventricular ejection fraction (%)</td>
                <td align="center">25.6 &#177; 8.0</td>
              </tr>
              <tr>
                <td align="left">B-type natriuretic peptide (pg/mL)</td>
                <td align="center">1057.39 &#177; 1024.21</td>
              </tr>
              <tr>
                <td align="left">Urea (mg/dL)</td>
                <td align="center">60.7 &#177; 23.4</td>
              </tr>
              <tr>
                <td align="left">Creatinine (mg/dL)</td>
                <td align="center">1.3 &#177; 0.4</td>
              </tr>
              <tr>
                <td align="left">Sodium (mEq/L)</td>
                <td align="center">135.9 &#177; 5.4</td>
              </tr>
              <tr>
                <td align="left">Potassium (mEq/L)</td>
                <td align="center">4.1 &#177; 0.5</td>
              </tr>
              <tr>
                <td align="left">Hemoglobin (g/dL)</td>
                <td align="center">11.8 &#177; 1.9</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Nine patients had LAP &lt; 15 mm Hg as assessed by echocardiogram. The most frequent sign of decompensation was the presence of rales (27 patients), followed by S3 (19 patients), edema, hepatomegaly and hepatojugular reflux (12 patients each). Prevalence of all clinical signs is show in <xref ref-type="table" rid="t2">Table 2</xref>.</p>
        <table-wrap id="t2">
          <label>Table 2</label>
          <caption>
            <title>Frequency of physical signs of heart failure decompensation</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="50%"/>
              <col width="50%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Physical Sign</th>
                <th align="center">Frequency (n&#176;)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">S3</td>
                <td align="center">19</td>
              </tr>
              <tr>
                <td align="left">PJVD</td>
                <td align="center">8</td>
              </tr>
              <tr>
                <td align="left">HJR</td>
                <td align="center">12</td>
              </tr>
              <tr>
                <td align="left">Rales</td>
                <td align="center">27</td>
              </tr>
              <tr>
                <td align="left">Edema</td>
                <td align="center">12</td>
              </tr>
              <tr>
                <td align="left">Ascites</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Hepatomegaly</td>
                <td align="center">12</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>S3: third heart sound; PJVD: pathologic jugular venous distension; HJR: hepatojugular reflux.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Accuracy of clinical signs to predict increased LV filling pressures</title>
        <p>Elevated jugular venous pressure was the most specific (88%) clinical sign to predict LAP &#8805; 15 mm Hg, and rales were the least specific (33%). Accuracy of each sign to predict LAP &#8805; 15 mm Hg is shown in <xref ref-type="table" rid="t3">Table 3</xref>. Combining any two signs of congestion has the best accuracy to predict elevation in LAP, according to the ROC curve.</p>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <title>Diagnostic characteristics of clinical signs to predict left atrial pressure &#8805; 15 mm Hg</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
								</th>
                <th align="left">Sensitivity</th>
                <th align="left">Specificity</th>
                <th align="left">PPV</th>
                <th align="left">NPV</th>
                <th align="left">Accuracy</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">S3</td>
                <td align="left">44</td>
                <td align="left">55</td>
                <td align="left">79</td>
                <td align="left">20</td>
                <td align="left">46</td>
              </tr>
              <tr>
                <td align="left">PJVD</td>
                <td align="left">20</td>
                <td align="left">88</td>
                <td align="left">87</td>
                <td align="left">22</td>
                <td align="left">34</td>
              </tr>
              <tr>
                <td align="left">HJR</td>
                <td align="left">29</td>
                <td align="left">77</td>
                <td align="left">83</td>
                <td align="left">22</td>
                <td align="left">39</td>
              </tr>
              <tr>
                <td align="left">Edema</td>
                <td align="left">29</td>
                <td align="left">77</td>
                <td align="left">83</td>
                <td align="left">22</td>
                <td align="left">39</td>
              </tr>
              <tr>
                <td align="left">Hepatomegaly</td>
                <td align="left">29</td>
                <td align="left">77</td>
                <td align="left">83</td>
                <td align="left">22</td>
                <td align="left">39</td>
              </tr>
              <tr>
                <td align="left">Rales</td>
                <td align="left">61</td>
                <td align="left">33</td>
                <td align="left">77</td>
                <td align="left">18</td>
                <td align="left">55</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>S3: third heart sound; PJVD: pathologic jugular venous distension; HJR: hepatojugular reflux, PPV: positive predictive value, NPV: negative predictive value.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Accuracy of chest radiography and BNP to predict increased LV filling pressures</title>
        <p>Levels of BNP &gt; 400 pg/mL had a suboptimal diagnostic capability to estimate congestion. <xref ref-type="fig" rid="f1">Figure 1</xref> illustrates the poor correlation between BNP and echocardiographically assessed LAP.</p>
        <p>
          <fig id="f1">
            <label>Figure 1</label>
            <caption>
              <title>Correlation between left atrial pressure (LAP) and B-type natriuretic peptide (BNP). r = 0.3 (p = 0.046).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-03-0270-80046-gf01.jpg"/></fig>
        </p>
        <p>In fact, chest radiography showed a slightly better accuracy than BNP levels to predict congestion. <xref ref-type="table" rid="t4">Table 4</xref> shows the performance of these variables to predict LAP &#8805; 15 mm Hg. We constructed a ROC curve to estimate the best cut-off point of BNP to predict elevation of LA filling pressure. Levels of BNP &gt; 1000 pg/mL showed a specificity of 88% and a positive predictive value of 93% to predict congestion, but this cut-off loses sensitivity (44% vs 73%) and accuracy (53% vs 67%) when compared with a value &gt; 400 pg/mL (<xref ref-type="table" rid="t4">Table 4</xref>).</p>
        <table-wrap id="t4">
          <label>Table 4</label>
          <caption>
            <title>Diagnostic characteristics of the B-type natriuretic peptide (BNP) and chest radiography to predict left atrial pressure &#8805; 15 mm Hg</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
								</th>
                <th align="center">Sensitivity</th>
                <th align="center">Specificity</th>
                <th align="center">PPV</th>
                <th align="center">NPV</th>
                <th align="center">Accuracy</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">BNP &gt; 400</td>
                <td align="center">73</td>
                <td align="center">44</td>
                <td align="center">83</td>
                <td align="center">30</td>
                <td align="center">67</td>
              </tr>
              <tr>
                <td align="left">BNP &gt;1000</td>
                <td align="center">44</td>
                <td align="center">88</td>
                <td align="center">93</td>
                <td align="center">29</td>
                <td align="center">53</td>
              </tr>
              <tr>
                <td align="left">Chest radiography</td>
                <td align="center">79</td>
                <td align="center">44</td>
                <td align="center">84</td>
                <td align="center">36</td>
                <td align="center">72</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3">
              <p>PPV: positive predictive value; NPV: negative predictive value.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Combinations of clinical signs, chest radiography and BNP to predict increased LV filling pressures</title>
        <p><xref ref-type="table" rid="t5">Table 5</xref> depicts the diagnostic characteristics of the CS alone, CS plus chest radiography and these two plus BNP &gt; 400 pg/mL to predict LAP &#8805;15 mm Hg. Incremental accuracy was observed when progressively combining these parameters. The three parameters combined achieved a sensitivity of 91% and a positive predictive value of 81% to detect a LAP &#8805; 15 mm Hg.</p>
        <table-wrap id="t5">
          <label>Table 5</label>
          <caption>
            <title>Diagnostic characteristics of clinical score, chest radiograph (CR), B-type natriuretic peptide (BNP) and all combined to predict left atrial pressure &#8805; 15 mm Hg</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
								</th>
                <th align="center">Sensitivity</th>
                <th align="center">Specificity</th>
                <th align="center">PPV</th>
                <th align="center">NPV</th>
                <th align="center">Accuracy</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">CS+</td>
                <td align="center">64</td>
                <td align="center">33</td>
                <td align="center">78</td>
                <td align="center">20</td>
                <td align="center">58</td>
              </tr>
              <tr>
                <td align="left">CS+ plus CR</td>
                <td align="center">82</td>
                <td align="center">33</td>
                <td align="center">82</td>
                <td align="center">33</td>
                <td align="center">72</td>
              </tr>
              <tr>
                <td align="left">CS+ plus CR plus BNP &gt; 400</td>
                <td align="center">91</td>
                <td align="center">22</td>
                <td align="center">81</td>
                <td align="center">40</td>
                <td align="center">76</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN4">
              <p>CS+: positive clinical score; PPV: positive predictive value; NPV: negative predictive value.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Diagnostic performances of combined clinical tools</title>
        <p>Accuracy of CS and its combinations with chest radiography and BNP with cut-off values of 400 pg/mL or 1000 pg/mL are illustrated in <xref ref-type="fig" rid="f2">Figure 2</xref>. Combinations of CS with chest radiography (AUC 0.60) and BNP &gt; 400 pg/mL (AUC 0.62) did not improve the ability to discriminate between low or high LAP. Combination with levels of BNP &gt; 1000 pg/mL improved only modestly (AUC 0.66).</p>
        <p>
          <fig id="f2">
            <label>Figure 2</label>
            <caption>
              <title>Receiver operator characteristics curves for estimating left atrial pressure &#8805; 15 mm Hg. Estimates were based on dichotomized variables. CS: clinical score; CR: chest radiography; BNP: B-type natriuretic peptide.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-03-0270-80046-gf02.jpg"/></fig>
        </p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>In this study, we have assessed the diagnostic accuracy of heart failure clinical signs to predict elevation of cardiac filling pressures as derived from echocardiogram-based parameters. Additionally, we have combined information from clinical signs and chest radiography regarding congestion and finally added the BNP value in order to augment the diagnostic accuracy in assessing congestion. This strategy reflects a &#8220;real world&#8221; practice to clinically evaluate the hemodynamics of ADHF patients, and we compared this clinical approach with objective measurements of hemodynamics derived from tissue Doppler echocardiogram. We have shown that a CS of congestion, chest radiography and BNP, alone or in combination do not accurately predict elevation of LAP.</p>
      <sec>
        <title>Clinical findings in ADHF</title>
        <sec>
          <title>Jugular venous pressure</title>
          <p>The jugular venous pressure is the most important and probably the only physical examination sign that is relatively accurate in estimating ventricular filling pressures.<xref ref-type="bibr" rid="B17">17</xref> In a study with 35 patients in a critical care unit, the jugular venous pressure was accurate in estimating low or high filling pressures.<xref ref-type="bibr" rid="B18">18</xref> In another study, after evaluating a thousand patients referred for cardiac transplantation, the authors observed that estimated right atrial pressure below or above 10 was concordant with a pulmonary capillary wedge pressure (PCWP) below or above 22 mm Hg in 79% of patients.<xref ref-type="bibr" rid="B19">19</xref> Other studies also have shown prognostic information about elevated jugular venous pressure in patients with heart failure. Its presence was associated with adverse outcome, including progression of heart failure, even after adjustment for other prognostic factors.<xref ref-type="bibr" rid="B20">20</xref> But several factors limit its power in predicting filling pressures. There is not a universal method to estimate the jugular venous pressure. Controversy exists regarding the position (sitting upright or semirecumbent position of 30-45&#186;), the jugular vein being used (internal x external), and the technique of measurement (vertically above clavicle, Louis angle or estimated right atrium position).<xref ref-type="bibr" rid="B21">21</xref><sup>,</sup><xref ref-type="bibr" rid="B22">22</xref> In patients with heart failure with preserved systolic function, the jugular vein pressure is far less studied.<xref ref-type="bibr" rid="B23">23</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref> In accordance with these observations, we have also found that elevated jugular venous pressure had the best specificity (88%) of all physical findings for elevated LAP. Additionally, in patients with no elevated jugular venous pressure, but with a positive hepatojugular reflux, we were able to identify an elevated LAP in 10 out of 12 patients. However, as expected, the absence of elevated jugular venous pressure was not able to exclude elevated LAP.</p>
        </sec>
        <sec>
          <title>Third heart sound</title>
          <p>Collins et al.<xref ref-type="bibr" rid="B25">25</xref> have studied patients with dyspnea in the emergency department and found that S3 did not improve diagnostic accuracy for ADHF, with a sensitivity of only 14.6%. Moreover, in that study, a low diagnostic accuracy (58%) for the diagnosis of ADHF when utilizing all signs together was observed. In our study, S3 was present in less than half of patients and, when present, showed a positive predictive value of 79% for LAP &gt; 15 mm Hg. When absent, an elevation of filling pressures could not be ruled out. In addition, S3 did not add any information regarding hemodynamic status. This is in accordance with other studies.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref> Of note, in our study, all physical examinations were done by a heart failure specialist. In the setting of a less experienced professional, the accuracy of physical exam (particularly S3) can be low, since studies suggest poor agreement between medical interns or residents and phonocardiographic findings.<xref ref-type="bibr" rid="B27">27</xref> On the other hand, reasonable agreement in S3 detection has been found among professionals of heart failure clinics.<xref ref-type="bibr" rid="B28">28</xref>
					</p>
        </sec>
        <sec>
          <title>Levels of BNP</title>
          <p>The strongest evidence for clinical use of BNP is to discriminate the cause of dyspnea in patients admitted in the emergency department<xref ref-type="bibr" rid="B29">29</xref> and to assess prognosis.<xref ref-type="bibr" rid="B30">30</xref><sup>,</sup><xref ref-type="bibr" rid="B31">31</xref> For other BNP purposes, data are less clear. In the Escape Trial,<xref ref-type="bibr" rid="B32">32</xref> the ROC curve for the performance of BNP in estimating an elevation in PCWP &gt; 22 mm Hg showed a poor performance (AUC = 0.55). Another study with 40 critically ill patients utilizing invasive hemodynamic monitoring has shown a weak correlation between BNP and PCWP (r = 0.58).<xref ref-type="bibr" rid="B33">33</xref> Our data were consistent with these studies, showing a weak correlation between BNP and LAP (r = 0.29). BNP was also tested for guiding treatment, because, theoretically, lowering BNP is a consequence of lowering filling pressures,<xref ref-type="bibr" rid="B34">34</xref> but this strategy failed to show clinical benefit.<xref ref-type="bibr" rid="B35">35</xref> In contrast, in the recent PROTECT trial,<xref ref-type="bibr" rid="B36">36</xref> a similar strategy of guiding treatment according to amino-terminal-Pro-BNP levels against standard of care resulted in decreased incidence of events, improvement in quality of life and in cardiac remodeling. However, that trial was conducted in an outpatient setting, involving very few heart failure patients in more advanced functional classes.</p>
          <p>In the present study, we used a cut-off point of 400 pg/mL for BNP as a marker of congestion, since this value was employed in previous studies.<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B35">35</xref> We have observed that BNP levels &gt; 400 pg/mL had a poor prediction performance to identify elevation in LAP, similar to other physical findings or chest radiography performances when taken individually. No valuable information on filling pressures was observed when BNP levels were below 400 pg/mL. Using the AUC, we found that BNP levels of 1000 pg/mL had the best specificity to predict LAP &#8805; 15 mm Hg. Therefore, we have also utilized this cut-off value in our subsequent combined analysis. Patients with moderate or severe renal impairment had higher BNP values, in our study the mean values of urea and creatinine were only slightly elevated and should not have influenced the results.</p>
          <p>Although there is a time difference between the change in ventricular filling pressures and the corresponding change in BNP levels, this time lapse does not seem to have clinical significance. The half-life of BNP is short, about 20 minutes, and, in addition, the treatment-induced decrease in pulmonary capillary pressure leads to a rapid reduction in BNP levels (30 to 50 pg/mL/hour).</p>
        </sec>
      </sec>
      <sec>
        <title>Combining tools to estimate congestion</title>
        <p>In patients with intermediate BNP levels (100-500 pg/mL), adding the information about the presence of S3 increases the positive predictive value from 54% to 80%.<xref ref-type="bibr" rid="B37">37</xref> A recent study with 50 patients utilized a very similar strategy to our study, comparing a CS, BNP and a hand carried ultrasound in estimating elevation of ventricular filling pressures, but the gold standard in that study was right heart catheterization.<xref ref-type="bibr" rid="B14">14</xref> As in ours, that study used a cut-off value for BNP &gt; 400 pg/mL and for PCWP &#8805;15 mm Hg as referencing parameters. The clinical symptom score had very little predictive utility for an elevated PCWP. Combining the information of jugular venous pressure, BNP and ultrasound, the best diagnostic characteristics for predicting elevated LV filling pressure was achieved (AUC 0.98). In our study, combining the findings of physical examination with chest radiography and BNP augmented progressively the sensitivity (64%, 82% and 91%, respectively) for detecting an elevated LAP, achieving a positive predictive value of 81%, although with a poor specificity. Still, combining these tools showed a modest power in predicting high filling pressures (AUC: 0.62). Thus, ours and the study by Goonewardena et al.<xref ref-type="bibr" rid="B14">14</xref> showed that clinical examination and BNP are not fully capable to precisely detect elevated filling pressures, and echocardiographically-derived hemodynamic assessment can reliably be incorporated into clinical practice of ADHF, avoiding the traditional invasive right heart catheterization method. The increasing utilization of hand carried ultrasound can be of great value in this area.</p>
      </sec>
      <sec>
        <title>Study limitations</title>
        <p>We have used the echocardiogram as the gold-standard method for defining filling pressures instead of right heart catheterization. Nonetheless, hemodynamic echocardiogram-derived parameters are well validated in the medical literature when correlated with invasive measurements.<xref ref-type="bibr" rid="B38">38</xref><sup>-</sup><xref ref-type="bibr" rid="B40">40</xref>
				</p>
        <p>We primarily use the lateral annulus to measure E/e' ratio. Although the most recent recommendations suggest using the mean of the lateral and septal annulus values, this was mainly validated in normal subjects. The most recent 2016 guideline of the American Society of Echocardiography and the European Association of Cardiovascular Imaging recognizes that at times only the lateral e&#8217; or septal e&#8217; velocity is available, and it is clinically valid.</p>
        <p>In addition, we did not follow patients during the hospitalization or in the post-discharge period to observe whether the initial hemodynamic profile was compatible with the clinical course.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusions</title>
      <p>In this study, we showed that in ADHF patients, clinical assessment alone or in conjunction with chest radiography and BNP may lead to inaccurate estimation of echocardiographically-derived hemodynamic profiling.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This article is part of the thesis of Doctoral submitted by Gustavo Luiz Gouv&#234;a de Almeida Junior, from Universidade Federal do Rio Grande do Sul.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Ethics approval and consent to participate</bold>
        </p>
        <p>This study was approved by the Ethics Committee of the Hospital Pr&#243;-Card&#237;aco under the protocol number 021/10 (CAAE:0021.1.346.001-10). All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
          <subj-group>
            <subject>Insufici&#234;ncia Card&#237;aca</subject>
          </subj-group>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Pept&#237;deo Natriur&#233;tico e Avalia&#231;&#227;o Cl&#237;nica no Diagn&#243;stico do Perfil Hemodin&#226;mico da Insufici&#234;ncia Card&#237;aca: Compara&#231;&#227;o com Ecodopplercardiograma Tecidual</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Almeida</surname>
            <given-names>Gustavo Luiz Gouv&#234;a de</given-names>
            <suffix>Junior</suffix>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Clausell</surname>
            <given-names>Nadine</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Garcia</surname>
            <given-names>Marcelo Iorio</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Esporcatte</surname>
            <given-names>Roberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rangel</surname>
            <given-names>Fernando Oswaldo Dias</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rocha</surname>
            <given-names>Ricardo Mourilhe</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Beck-da-Silva</surname>
            <given-names>Luis</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Fabricio Braga da</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gorgulho</surname>
            <given-names>Paula de Castro Carvalho</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Xavier</surname>
            <given-names>Sergio Salles</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">3</xref>
        </contrib>
      </contrib-group>
      <aff id="aff5">
        <label>1</label>
        <institution content-type="original">Casa de Sa&#250;de S&#227;o Jos&#233;, Rio de Janeiro, RJ - Brazil</institution>
      </aff>
      <aff id="aff6">
        <label>2</label>
        <institution content-type="original">Hospital Pro-Card&#237;aco, Rio de Janeiro, RJ - Brazil</institution>
      </aff>
      <aff id="aff7">
        <label>3</label>
        <institution content-type="original">Hospital Universit&#225;rio Clementino Fraga Filho - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ - Brazil</institution>
      </aff>
      <aff id="aff8">
        <label>4</label>
        <institution content-type="original">Hospital de Cl&#237;nicas de Porto Alegre - Universidade Federal do Rio Grande do Sul, Porto Alegre, RS - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Gustavo Luiz Gouvea de Almeida Junior,</bold> Rua Macedo Sobrinho, 21. Unidade Coronariana. CEP 22271-080, Botafogo, RJ - Brasil. E-mail: <email>gustavogouvea@cardiol.br</email>, <email>gustavogouvea@globo.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa e An&#225;lise e interpreta&#231;&#227;o dos dados: Almeida Junior GLG, Clausell N, Garcia MI, Esporcatte R, Rangel FOD, Rocha RM, Silva Neto LB, Silva FB, Gorgulho PCC, Xavier SS; Obten&#231;&#227;o de dados: Almeida Junior GLG, Garcia MI; An&#225;lise estat&#237;stica: Almeida Junior GLG, Clausell N, Silva FB, Xavier SS; Obten&#231;&#227;o de financiamento: Almeida Junior GLG; Reda&#231;&#227;o do manuscrito: Almeida Junior GLG, Clausell N, Garcia MI, Xavier SS; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Almeida Junior GLG, Clausell N, Garcia MI, Rangel FOD, Xavier SS.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>Exame f&#237;sico e pept&#237;deo natriur&#233;tico do tipo B (BNP) foram usados para estimar a hemodin&#226;mica e adequar a terapia de pacientes com insufici&#234;ncia card&#237;aca aguda descompensada (ICAD). Entretanto, correla&#231;&#227;o entre esses par&#226;metros e a press&#227;o de enchimento do ventr&#237;culo esquerdo &#233; controversa.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Avaliar a acur&#225;cia diagn&#243;stica do exame f&#237;sico, da radiografia de t&#243;rax (RT) e do BNP para estimar a press&#227;o atrial esquerda (PAE) avaliada pelo ecodopplercardiograma tecidual.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Pacientes admitidos com ICAD foram avaliados prospectivamente. As caracter&#237;sticas diagn&#243;sticas dos sinais f&#237;sicos de insufici&#234;ncia card&#237;aca, RT e BNP para predizer eleva&#231;&#227;o da PAE (&gt; 15 mmHg), isolados ou combinados, foram calculadas. Teste de Spearman foi usado para analisar a correla&#231;&#227;o entre vari&#225;veis de distribui&#231;&#227;o n&#227;o normal. O n&#237;vel de signific&#226;ncia foi 5%.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Este estudo incluiu 43 pacientes com idade m&#233;dia de 69,9 &#177; 11,1 anos, fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda de 25 &#177; 8.0%, e BNP de 1057 &#177; 1024,21 pg/mL. Individualmente, todos os par&#226;metros cl&#237;nicos, RT e BNP apresentaram fraco desempenho para predizer PAE &#8805; 15 mmHg. O escore cl&#237;nico de congest&#227;o teve o pior desempenho [&#225;rea sob a curva <italic>receiver operating characteristic</italic> (AUC) 0,53], seguindo-se escore cl&#237;nico + RT (AUC 0,60), escore cl&#237;nico + RT + BNP &gt; 400 pg/mL (AUC 0,62) e escore cl&#237;nico + RT + BNP &gt; 1000 pg/mL (AUC 0,66).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o: </title>
          <p>Exame f&#237;sico, RT e BNP tiveram desempenho fraco para predizer PAE &#8805;15 mmHg. O uso desses par&#226;metros isoladamente ou em combina&#231;&#227;o pode levar a estimativa imprecisa do perfil hemodin&#226;mico. (Arq Bras Cardiol. 2018; 110(3):270-277)</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Insufici&#234;ncia Card&#237;aca</kwd>
        <kwd>Pept&#237;deo Natriur&#233;tico Encef&#225;lico</kwd>
        <kwd>Hemodin&#226;mica</kwd>
        <kwd>Fun&#231;&#227;o Ventricular Esquerda</kwd>
        <kwd>Ecocardiografia Doppler</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A avalia&#231;&#227;o cl&#237;nica de pacientes com insufici&#234;ncia card&#237;aca aguda descompensada (ICAD) baseada apenas no exame f&#237;sico mostrou-se inadequada tanto para avaliar a fun&#231;&#227;o do ventr&#237;culo esquerdo (VE) (disfun&#231;&#227;o sist&#243;lica <italic>versus</italic> diast&#243;lica)<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref> quanto para estimar o <italic>status</italic> hemodin&#226;mico de pacientes.<xref ref-type="bibr" rid="B3">3</xref> A precisa determina&#231;&#227;o das press&#245;es de enchimento do VE &#233; cr&#237;tica para o tratamento adequado de pacientes com ICAD, pois a congest&#227;o &#233; o principal determinante dos sintomas, da hospitaliza&#231;&#227;o e do progn&#243;stico.<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref> Avalia&#231;&#227;o adicional usando ferramentas invasivas<xref ref-type="bibr" rid="B8">8</xref> e n&#227;o invasivas pode ser &#250;til, pois fornece importante informa&#231;&#227;o que pode contribuir para o tratamento adequado.</p>
        <p>A ecocardiografia mostrou-se &#250;til na avalia&#231;&#227;o do <italic>status</italic> hemodin&#226;mico de pacientes com ICAD, especialmente ap&#243;s o aparecimento de novas t&#233;cnicas, como a ecodopplercardiografia tecidual.<xref ref-type="bibr" rid="B9">9</xref> O &#8220;ecocardiograma hemodin&#226;mico&#8221; pode auxiliar os m&#233;dicos a detectar congest&#227;o.<xref ref-type="bibr" rid="B10">10</xref> V&#225;rios estudos mostraram que os par&#226;metros hemodin&#226;micos obtidos por ecocardiografia correlacionam-se significativamente com aqueles obtidos no cateterismo do lado direito do cora&#231;&#227;o.<xref ref-type="bibr" rid="B11">11</xref>
				</p>
        <p>N&#237;veis altos do pept&#237;deo natriur&#233;tico do tipo B (BNP) refletem eleva&#231;&#227;o da press&#227;o de enchimento do VE, secund&#225;ria ao estiramento do mi&#243;cito, devido &#224; sobrecarga de volume ou press&#227;o.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> Entretanto, n&#227;o est&#225; claro se a associa&#231;&#227;o dos n&#237;veis de BNP acrescenta acur&#225;cia diagn&#243;stica &#224; avalia&#231;&#227;o cl&#237;nica padr&#227;o para estimar o <italic>status</italic> hemodin&#226;mico dos pacientes. Neste estudo, testamos a hip&#243;tese de que os n&#237;veis de BNP acrescentam acur&#225;cia diagn&#243;stica ao exame f&#237;sico para a detec&#231;&#227;o de congest&#227;o em pacientes com ICAD, usando-se a avalia&#231;&#227;o hemodin&#226;mica obtida por ecocardiograma como m&#233;todo de refer&#234;ncia para compara&#231;&#227;o.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <sec>
          <title>Amostra do estudo</title>
          <p>Estudou-se uma amostra prospectiva de conveni&#234;ncia de pacientes admitidos no setor de emerg&#234;ncia ou na unidade coronariana de tr&#234;s hospitais (um universit&#225;rio e dois terci&#225;rios) devido a ICAD. O estudo foi conduzido de acordo com os padr&#245;es da Declara&#231;&#227;o de Helsinque para pesquisa humana. Os conselhos de revis&#227;o institucionais aprovaram o protocolo de pesquisa, tendo todos os participantes assinado o termo de consentimento livre e informado antes do arrolamento.</p>
        </sec>
        <sec>
          <title>Crit&#233;rios de inclus&#227;o</title>
          <p>Pacientes com ICAD devido a disfun&#231;&#227;o sist&#243;lica do VE, fra&#231;&#227;o de eje&#231;&#227;o do VE (FEVE) &lt; 40% pelo m&#233;todo de Simpson, classe funcional III ou IV de <italic>New York Heart Association</italic> (NYHA) na admiss&#227;o e ritmo sinusal foram inclu&#237;dos nas primeiras 24 horas de cuidados de emerg&#234;ncia. </p>
        </sec>
        <sec>
          <title>Crit&#233;rios de exclus&#227;o</title>
          <p>Os crit&#233;rios de exclus&#227;o foram: ICAD por s&#237;ndrome coronariana aguda; janela ecocardiogr&#225;fica impedindo a an&#225;lise adequada dos par&#226;metros hemodin&#226;micos; valvopatia prim&#225;ria; pr&#243;tese valvar mec&#226;nica; padr&#227;o de fluxo mitral &#250;nico; e presen&#231;a de marca-passo card&#237;aco.</p>
        </sec>
        <sec>
          <title>Exame f&#237;sico</title>
          <p>Os seguintes achados f&#237;sicos foram avaliados: turg&#234;ncia jugular; refluxo hepatojugular; hepatomegalia; ascite; edema de membros inferiores; terceira bulha (S3); estertores pulmonares; press&#227;o arterial; e press&#227;o de pulso proporcional. Os pacientes foram examinados em uma sala tranquila da emerg&#234;ncia ou da unidade coronariana. Avaliou-se turg&#234;ncia jugular com o paciente sentado, considerando-se presente quando a veia jugular interna estava vis&#237;vel acima da clav&#237;cula. O refluxo hepatojugular foi testado em pacientes sem veia jugular vis&#237;vel, aplicando-se firme press&#227;o abdominal &#224; direita. O f&#237;gado foi examinado com o paciente na posi&#231;&#227;o recumbente. Considerou-se hepatomegalia quando o f&#237;gado tinha mais de 10cm de comprimento, iniciando-se a percuss&#227;o no terceiro espa&#231;o intercostal, ao longo da linha hemiclavicular. Palpa&#231;&#227;o hep&#225;tica foi o m&#233;todo escolhido para avaliar a margem inferior do f&#237;gado se palp&#225;vel no abdome.</p>
          <p>Pacientes com qualquer sinal de congest&#227;o na radiografia de t&#243;rax eram considerados congestos. Realizou-se avalia&#231;&#227;o radiol&#243;gica com radiografia de t&#243;rax nas posi&#231;&#245;es p&#243;stero-anterior e lateral esquerda. Caso n&#227;o fosse poss&#237;vel realizar a radiografia de t&#243;rax nessas posi&#231;&#245;es, optava-se pela posi&#231;&#227;o &#226;ntero-posterior com o paciente sentado no leito. A radiografia de t&#243;rax foi obtida imediatamente antes da ecocardiografia.</p>
        </sec>
        <sec>
          <title>Ensaio do pept&#237;deo natriur&#233;tico do tipo B</title>
          <p>Simultaneamente &#224; ecocardiografia, colheu-se sangue para dosagem do BNP. As amostras foram colhidas em tubos com EDTA, sendo o BNP medido no sangue total por imunofluoresc&#234;ncia, usando-se <italic>kit</italic> comercial (Triidade &#174; BNP test of Biosite Inc., San Diego, CA, EUA). Todas as medidas foram realizadas em at&#233; 30 minutos ap&#243;s a coleta de sangue. Pacientes com n&#237;veis de BNP &gt; 400 pg/mL foram considerados congestos,<xref ref-type="bibr" rid="B14">14</xref> sendo aqueles com n&#237;veis de BNP &lt; 200 pg/mL considerados &#8220;secos&#8221;.<xref ref-type="bibr" rid="B15">15</xref>
					</p>
        </sec>
        <sec>
          <title>Avalia&#231;&#227;o do ecocardiograma</title>
          <p>Todos os pacientes foram submetidos a ecocardiografia transtor&#225;cica com Doppler tecidual (GE Vivid 7, Wauwatosa, WI, EUA) em no m&#225;ximo 30 minutos ap&#243;s completar o exame f&#237;sico. Em cada centro, apenas um examinador (o mais experiente) realizou todas as avalia&#231;&#245;es ecocardiogr&#225;ficas. As medidas ecocardiogr&#225;ficas foram tomadas de modo cego: o examinador n&#227;o conhecia os achados f&#237;sicos. As imagens foram obtidas dos pacientes nas posi&#231;&#245;es lateral esquerda e recumbente, tendo as medidas seguido as recomenda&#231;&#245;es da Sociedade Americana de Ecocardiografia.<xref ref-type="bibr" rid="B16">16</xref> Todos os perfis do Doppler foram registrados no corte apical de quatro c&#226;maras.</p>
          <p>A press&#227;o atrial esquerda (PAE) foi estimada como se segue: c&#225;lculo da raz&#227;o E/E' medindo-se a velocidade de fluxo intramioc&#225;rdico com Doppler tecidual. A velocidade diast&#243;lica inicial no anel mitral (E') foi obtida com Doppler tecidual na parede lateral do VE e, em caso de impossibilidade t&#233;cnica, como no comprometimento isqu&#234;mico, foi medida no septo interventricular. Pelo menos tr&#234;s ciclos card&#237;acos consecutivos foram avaliados, usando-se a m&#233;dia deles como resultado final. Essa medida, quando combinada com o fluxo trans-mitral obtido com Doppler pulsado no in&#237;cio da di&#225;stole (E), resultou na raz&#227;o E/E'. A PAE foi estimada pela f&#243;rmula: PAE: 1,24 x (E/E&#8217;) + 1,9. O aumento da press&#227;o de enchimento do VE foi definido como PAE &#8805; 15 mmHg. Ainda que pacientes com n&#237;veis inferiores a 15 mmHg possam ter congest&#227;o, n&#237;veis &#8805; 15 mmHg t&#234;m maior especificidade para press&#227;o de enchimento do VE aumentada. Avaliou-se a FEVE pelo m&#233;todo de Simpson.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>A estat&#237;stica descritiva foi expressa como frequ&#234;ncia (%) para as vari&#225;veis categ&#243;ricas. As vari&#225;veis cont&#237;nuas de distribui&#231;&#227;o normal foram apresentadas como m&#233;dia &#177; desvio-padr&#227;o, enquanto as vari&#225;veis cont&#237;nuas de distribui&#231;&#227;o n&#227;o normal foram apresentadas como mediana e intervalo interquartil (IIQ). As medidas de desempenho diagn&#243;stico (sensibilidade, especificidade, acur&#225;cia, valores preditivos positivo e negativo) foram usadas para avaliar a utilidade diagn&#243;stica dos sinais de exame f&#237;sico de insufici&#234;ncia card&#237;aca e/ou BNP para prever PAE &#8805; 15 mmHg (definida como indica&#231;&#227;o de eleva&#231;&#227;o da press&#227;o de enchimento do VE).</p>
          <p>Usou-se o teste de Spearman para analisar a correla&#231;&#227;o entre vari&#225;veis de distribui&#231;&#227;o n&#227;o normal. Adotou-se o n&#237;vel de signific&#226;ncia de 5%.</p>
          <p>Para determinar o melhor ponto de corte para o BNP para estimar a eleva&#231;&#227;o na PAE, construiu-se uma curva <italic>receiver operating characteristic</italic> (ROC). Elaborou-se o escore cl&#237;nico (EC) atribuindo-se 1 ponto a cada sinal positivo de insufici&#234;ncia card&#237;aca descompensada (elevada turg&#234;ncia jugular, refluxo hepatojugular, hepatomegalia, estertores pulmonares ou edema). Considerou-se positivo o EC &#8805; 2 pontos, de acordo com a an&#225;lise da curva ROC. Para avaliar a capacidade do exame f&#237;sico e dos testes diagn&#243;sticos n&#227;o invasivos para prever PAE elevada (&#8805; 15 mmHg), modelos separados foram constru&#237;dos usando combina&#231;&#227;o de EC, EC + radiografia de t&#243;rax, EC + radiografia de t&#243;rax + BNP &gt; 400 pg/mL, e finalmente EC + radiografia de t&#243;rax + BNP &gt; 1000 pg/mL (com base no ponto de corte &#243;timo do BNP). Cada um desses testes diagn&#243;sticos foi dicotomizado e comparado para determinar o valor preditivo incremental. As an&#225;lises estat&#237;sticas foram realizadas usando o programa SPSS&#210; (SPSS Inc, Chicago, IL, EUA).</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <sec>
          <title>Caracter&#237;sticas dos pacientes</title>
          <p>Este estudo incluiu 43 pacientes, a maioria do sexo masculino (75%), idosa (69,9 &#177; 11,1 anos) e com ICAD de etiologia isqu&#234;mica (65%). Os n&#237;veis m&#233;dios de creatinina s&#233;rica e de BNP eram 1,3 &#177; 0,4 mg/dL e 1057 &#177; 1024 pg/mL, respectivamente. A <xref ref-type="table" rid="t6">Tabela 1</xref> mostra as caracter&#237;sticas cl&#237;nicas e demogr&#225;ficas dos pacientes, que, em sua totalidade, apresentavam classe funcional NYHA III (10,7%) ou IV (89,3%), e m&#233;dia de FEVE de 25 &#177; 8,0%.</p>
          <table-wrap id="t6">
            <label>Tabela 1</label>
            <caption>
              <title>Caracter&#237;sticas cl&#237;nicas e demogr&#225;ficas dos pacientes</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="50%"/>
                <col width="50%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Caracter&#237;sticas</th>
                  <th align="center">
									</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">n</td>
                  <td align="center">43</td>
                </tr>
                <tr>
                  <td align="left">Idade (anos)</td>
                  <td align="center">69,9 &#177; 11,1</td>
                </tr>
                <tr>
                  <td align="left">Sexo (masculino %)</td>
                  <td align="center">76</td>
                </tr>
                <tr>
                  <td align="left">Peso</td>
                  <td align="center">75,3 &#177; 17,1</td>
                </tr>
                <tr>
                  <td align="left">&#205;ndice de massa corporal (kg/m<sup>2</sup>)</td>
                  <td align="center">26,5 &#177; 5,2</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Etiologia</bold>
                  </td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">Isqu&#234;mica</td>
                  <td align="center">28 (65,1)</td>
                </tr>
                <tr>
                  <td align="left">Idiop&#225;tica</td>
                  <td align="center">7 (16,2)</td>
                </tr>
                <tr>
                  <td align="left">Hipertensiva</td>
                  <td align="center">3 (6,9)</td>
                </tr>
                <tr>
                  <td align="left">Valvular</td>
                  <td align="center">4 (9,3)</td>
                </tr>
                <tr>
                  <td align="left">Outras</td>
                  <td align="center">1 (2,3)</td>
                </tr>
                <tr>
                  <td align="left">Fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo (%)</td>
                  <td align="center">25,6 &#177; 8,0</td>
                </tr>
                <tr>
                  <td align="left">Pept&#237;deo natriur&#233;tico do tipo B (pg/mL)</td>
                  <td align="center">1057,39 &#177; 1024,21</td>
                </tr>
                <tr>
                  <td align="left">Ureia (mg/dL)</td>
                  <td align="center">60,7 &#177; 23,4</td>
                </tr>
                <tr>
                  <td align="left">Creatinina (mg/dL)</td>
                  <td align="center">1,3 &#177; 0,4</td>
                </tr>
                <tr>
                  <td align="left">S&#243;dio (mEq/L)</td>
                  <td align="center">135,9 &#177; 5,4</td>
                </tr>
                <tr>
                  <td align="left">Pot&#225;ssio (mEq/L)</td>
                  <td align="center">4,1 &#177; 0,5</td>
                </tr>
                <tr>
                  <td align="left">Hemoglobina (g/dL)</td>
                  <td align="center">11,8 &#177; 1,9</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <p>Nove pacientes tinham PAE &lt; 15 mmHg na avalia&#231;&#227;o ecocardiogr&#225;fica. O sinal mais frequente de descompensa&#231;&#227;o foi a presen&#231;a de estertores (27 pacientes), seguindo-se S3 (19 pacientes), edema, hepatomegalia e refluxo hepatojugular (12 pacientes cada). A <xref ref-type="table" rid="t7">Tabela 2</xref> mostra a preval&#234;ncia de todos os sinais cl&#237;nicos.</p>
          <table-wrap id="t7">
            <label>Tabela 2</label>
            <caption>
              <title>Frequ&#234;ncia dos sinais f&#237;sicos de descompensa&#231;&#227;o da insufici&#234;ncia card&#237;aca</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="50%"/>
                <col width="50%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Sinal f&#237;sico </th>
                  <th align="center">Frequ&#234;ncia (n)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">S3</td>
                  <td align="center">19</td>
                </tr>
                <tr>
                  <td align="left">TJP</td>
                  <td align="center">8</td>
                </tr>
                <tr>
                  <td align="left">RHJ</td>
                  <td align="center">12</td>
                </tr>
                <tr>
                  <td align="left">Estertores</td>
                  <td align="center">27</td>
                </tr>
                <tr>
                  <td align="left">Edema</td>
                  <td align="center">12</td>
                </tr>
                <tr>
                  <td align="left">Ascite</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Hepatomegalia</td>
                  <td align="center">12</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN5">
                <p>S3: terceira bulha; TJP: turg&#234;ncia jugular patol&#243;gica; RHJ: refluxo hepatojugular.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Acur&#225;cia dos sinais cl&#237;nicos para predizer aumento da press&#227;o de enchimento do VE</title>
          <p>Eleva&#231;&#227;o da press&#227;o venosa jugular foi o sinal cl&#237;nico mais espec&#237;fico (88%) para predizer PAE &#8805; 15 mmHg, sendo a presen&#231;a de estertores o sinal cl&#237;nico menos espec&#237;fico (33%). A <xref ref-type="table" rid="t8">Tabela 3</xref> mostra a acur&#225;cia de cada sinal para predizer PAE &#8805; 15 mmHg. A combina&#231;&#227;o de quaisquer dois sinais de congest&#227;o tem a melhor acur&#225;cia para predizer eleva&#231;&#227;o da PAE, de acordo com a curva ROC.</p>
          <table-wrap id="t8">
            <label>Tabela 3</label>
            <caption>
              <title>Caracter&#237;sticas diagn&#243;sticas dos sinais cl&#237;nicos para predizer press&#227;o atrial esquerda &#8805; 15 mmHg</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">Sensibilidade</th>
                  <th align="center">Especificidade</th>
                  <th align="center">VPP</th>
                  <th align="center">VPN</th>
                  <th align="center">Acur&#225;cia</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">S3</td>
                  <td align="center">44</td>
                  <td align="center">55</td>
                  <td align="center">79</td>
                  <td align="center">20</td>
                  <td align="center">46</td>
                </tr>
                <tr>
                  <td align="left">TJP</td>
                  <td align="center">20</td>
                  <td align="center">88</td>
                  <td align="center">87</td>
                  <td align="center">22</td>
                  <td align="center">34</td>
                </tr>
                <tr>
                  <td align="left">RHJ</td>
                  <td align="center">29</td>
                  <td align="center">77</td>
                  <td align="center">83</td>
                  <td align="center">22</td>
                  <td align="center">39</td>
                </tr>
                <tr>
                  <td align="left">Edema</td>
                  <td align="center">29</td>
                  <td align="center">77</td>
                  <td align="center">83</td>
                  <td align="center">22</td>
                  <td align="center">39</td>
                </tr>
                <tr>
                  <td align="left">Hepatomegalia</td>
                  <td align="center">29</td>
                  <td align="center">77</td>
                  <td align="center">83</td>
                  <td align="center">22</td>
                  <td align="center">39</td>
                </tr>
                <tr>
                  <td align="left">Estertores</td>
                  <td align="center">61</td>
                  <td align="center">33</td>
                  <td align="center">77</td>
                  <td align="center">18</td>
                  <td align="center">55</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN6">
                <p>VPP: valor preditivo positivo; VPN: valor preditivo negativo; S3: terceira bulha; TJP: turg&#234;ncia jugular patol&#243;gica; RHJ: refluxo hepatojugular.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Acur&#225;cia da radiografia de t&#243;rax e do BNP para predizer eleva&#231;&#227;o da press&#227;o de enchimento do VE</title>
          <p>N&#237;veis de BNP &gt; 400 pg/mL apresentaram capacidade diagn&#243;stica sub&#243;tima para estimar congest&#227;o. A <xref ref-type="fig" rid="f3">Figura 1</xref> ilustra a fraca correla&#231;&#227;o entre BNP e PAE avaliada na ecocardiografia.</p>
          <p>
            <fig id="f3">
              <label>Figura 1</label>
              <caption>
                <title>Correla&#231;&#227;o entre press&#227;o atrial esquerda (PAE) e pept&#237;deo natriur&#233;tico do tipo B (BNP). r = 0,3 (p = 0,046).</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-110-03-0270-80046-gf01-pt.jpg"/></fig>
          </p>
          <p>A radiografia de t&#243;rax mostrou acur&#225;cia discretamente melhor do que os n&#237;veis de BNP para predizer congest&#227;o. A <xref ref-type="table" rid="t9">Tabela 4</xref> mostra o desempenho dessas vari&#225;veis para predizer PAE &#8805; 15 mmHg. Constru&#237;mos a curva ROC para estimar o melhor ponto de corte do BNP para predizer eleva&#231;&#227;o da press&#227;o de enchimento do &#225;trio esquerdo. N&#237;veis de BNP &gt; 1000 pg/mL apresentaram especificidade de 88% e valor preditivo positivo de 93% para predizer congest&#227;o, mas esse ponto de corte perde sensibilidade (44% vs 73%) e acur&#225;cia (53% vs 67%) quando comparado a um valor &gt; 400 pg/mL (<xref ref-type="table" rid="t9">Tabela 4</xref>).</p>
          <table-wrap id="t9">
            <label>Tabela 4</label>
            <caption>
              <title>Caracter&#237;sticas diagn&#243;sticas do pept&#237;deo natriur&#233;tico do tipo B (BNP) e da radiografia de t&#243;rax para predizer press&#227;o atrial esquerda &#8805; 15 mmHg</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">Sensibilidade</th>
                  <th align="center">Especificidade</th>
                  <th align="center">VPP</th>
                  <th align="center">VPN</th>
                  <th align="center">Acur&#225;cia</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">BNP &gt; 400</td>
                  <td align="center">73</td>
                  <td align="center">44</td>
                  <td align="center">83</td>
                  <td align="center">30</td>
                  <td align="center">67</td>
                </tr>
                <tr>
                  <td align="left">BNP &gt; 1000</td>
                  <td align="center">44</td>
                  <td align="center">88</td>
                  <td align="center">93</td>
                  <td align="center">29</td>
                  <td align="center">53</td>
                </tr>
                <tr>
                  <td align="left">Radiografia de t&#243;rax</td>
                  <td align="center">79</td>
                  <td align="center">44</td>
                  <td align="center">84</td>
                  <td align="center">36</td>
                  <td align="center">72</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN7">
                <p>VPP: valor preditivo positivo; VPN: valor preditivo negativo.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Combina&#231;&#245;es de sinais cl&#237;nicos, radiografia de t&#243;rax e BNP para predizer eleva&#231;&#227;o da press&#227;o de enchimento do VE</title>
          <p>A <xref ref-type="table" rid="t10">Tabela 5</xref> apresenta as caracter&#237;sticas diagn&#243;sticas do EC isolado, EC + radiografia de t&#243;rax e esses dois + BNP &gt; 400 pg/mL para predizer PAE &#8805; 15 mmHg. Observou-se acur&#225;cia incremental com a progressiva combina&#231;&#227;o desses par&#226;metros. A combina&#231;&#227;o dos tr&#234;s par&#226;metros alcan&#231;ou sensibilidade de 91% e valor preditivo positivo de 81% para detectar PAE &#8805; 15 mmHg.</p>
          <table-wrap id="t10">
            <label>Tabela 5</label>
            <caption>
              <title>Caracter&#237;sticas diagn&#243;sticas do escore cl&#237;nico (EC), da radiografia de t&#243;rax (RT), do pept&#237;deo natriur&#233;tico do tipo B (BNP) e dos tr&#234;s combinados para predizer press&#227;o atrial esquerda &#8805; 15 mmHg</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">Sensibilidade</th>
                  <th align="center">Especificidade</th>
                  <th align="center">VPP</th>
                  <th align="center">VPN</th>
                  <th align="center">Acur&#225;cia</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">ECP</td>
                  <td align="center">64</td>
                  <td align="center">33</td>
                  <td align="center">78</td>
                  <td align="center">20</td>
                  <td align="center">58</td>
                </tr>
                <tr>
                  <td align="left">ECP + RT</td>
                  <td align="center">82</td>
                  <td align="center">33</td>
                  <td align="center">82</td>
                  <td align="center">33</td>
                  <td align="center">72</td>
                </tr>
                <tr>
                  <td align="left">ECP + RT + BNP&gt;400</td>
                  <td align="center">91</td>
                  <td align="center">22</td>
                  <td align="center">81</td>
                  <td align="center">40</td>
                  <td align="center">76</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN8">
                <p>ECP: escore cl&#237;nico positivo; VPP: valor preditivo positivo; VPN: valor preditivo negativo.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Desempenhos diagn&#243;sticos das ferramentas cl&#237;nicas combinadas</title>
          <p>A <xref ref-type="fig" rid="f4">Figura 2</xref> ilustra a acur&#225;cia do EC e suas combina&#231;&#245;es com radiografia de t&#243;rax e BNP com pontos de corte de 400 pg/mL ou 1000 pg/mL. A combina&#231;&#227;o do EC com radiografia de t&#243;rax [&#225;rea sob a curva (AUC) 0,60] e BNP &gt; 400 pg/mL (AUC 0,62) n&#227;o melhorou a capacidade de discriminar entre PAE alta e baixa. A combina&#231;&#227;o com BNP &gt; 1000 pg/mL melhorou apenas discretamente (AUC 0,66).</p>
          <p>
            <fig id="f4">
              <label>Figura 2</label>
              <caption>
                <title>Curvas receiver operating characteristics para estimar a press&#227;o atrial esquerda &#8805; 15 mmHg. A estimativas foram baseadas nas vari&#225;veis dicot&#244;micas. EC: escore cl&#237;nico; RT: radiografia de t&#243;rax; BNP: pept&#237;deo natriur&#233;tico do tipo B.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-110-03-0270-80046-gf02-pt.jpg"/></fig>
          </p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Neste estudo, avaliamos a acur&#225;cia diagn&#243;stica dos sinais cl&#237;nicos de insufici&#234;ncia card&#237;aca para predizer eleva&#231;&#227;o das press&#245;es card&#237;acas de enchimento a partir de par&#226;metros ecocardiogr&#225;ficos. Al&#233;m disso, combinamos informa&#231;&#227;o dos sinais cl&#237;nicos e da radiografia de t&#243;rax referentes a congest&#227;o, tendo, por fim, acrescentado o valor do BNP para aumentar a acur&#225;cia diagn&#243;stica na avalia&#231;&#227;o de congest&#227;o. Tal estrat&#233;gia reflete a pr&#225;tica do &#8220;mundo real&#8221; para a avalia&#231;&#227;o cl&#237;nica da hemodin&#226;mica de pacientes com ICAD. Comparamos essa abordagem cl&#237;nica com as medidas hemodin&#226;micas objetivas obtidas no ecodopplercardiograma tecidual. Demonstramos que um EC de congest&#227;o, radiografia de t&#243;rax e BNP, isoladamente ou combinados, n&#227;o predizem com acur&#225;cia a eleva&#231;&#227;o da PAE.</p>
        <sec>
          <title>Achados cl&#237;nicos na ICAD</title>
          <sec>
            <title>Press&#227;o venosa jugular</title>
            <p>A press&#227;o venosa jugular &#233; o mais importante e provavelmente o &#250;nico sinal do exame f&#237;sico que apresenta relativa acur&#225;cia para estimar as press&#245;es de enchimento ventricular.<xref ref-type="bibr" rid="B17">17</xref> Em estudo com 35 pacientes em uma unidade de terapia intensiva, a press&#227;o venosa jugular apresentou acur&#225;cia para estimar press&#227;o de enchimento baixa ou alta.<xref ref-type="bibr" rid="B18">18</xref> Em outro estudo, avaliando mil pacientes encaminhados para transplante card&#237;aco, os autores observaram que uma press&#227;o atrial direita estimada abaixo ou acima de 10 mmHg acompanhava-se de uma press&#227;o capilar pulmonar em cunha (PCPC) abaixo ou acima de 22 mmHg em 79% dos pacientes.<xref ref-type="bibr" rid="B19">19</xref> Outros estudos relataram dados progn&#243;sticos sobre a eleva&#231;&#227;o da press&#227;o venosa jugular em pacientes com insufici&#234;ncia card&#237;aca. Sua presen&#231;a foi associada a desfecho adverso, como progress&#227;o da insufici&#234;ncia card&#237;aca, mesmo ap&#243;s ajuste para outros fatores progn&#243;sticos.<xref ref-type="bibr" rid="B20">20</xref> Entretanto, v&#225;rios fatores limitam seu poder de predizer press&#227;o de enchimento. N&#227;o existe um m&#233;todo universal para estimar a press&#227;o venosa jugular. H&#225; controv&#233;rsia quanto &#224; posi&#231;&#227;o (sentada ou semirrecumbente de 30-45&#186;), &#224; veia jugular usada (interna x externa) e &#224; t&#233;cnica de medida (verticalmente acima da clav&#237;cula, &#226;ngulo de Louis ou posi&#231;&#227;o estimada do &#225;trio direito).<xref ref-type="bibr" rid="B21">21</xref><sup>,</sup><xref ref-type="bibr" rid="B22">22</xref> Em pacientes com insufici&#234;ncia card&#237;aca e fun&#231;&#227;o sist&#243;lica preservada, a press&#227;o venosa jugular &#233; muito menos estudada.<xref ref-type="bibr" rid="B23">23</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref> Concordando com essas observa&#231;&#245;es, descobrimos que uma press&#227;o venosa jugular elevada apresentou a melhor especificidade (88%) entre todos os achados f&#237;sicos para PAE elevada. Al&#233;m disso, em pacientes sem press&#227;o venosa jugular elevada, mas com refluxo hepatojugular positivo, pudemos identificar PAE elevada em 10 de cada 12 pacientes. Entretanto, como esperado, a aus&#234;ncia de press&#227;o venosa jugular elevada n&#227;o conseguiu excluir PAE elevada.</p>
          </sec>
          <sec>
            <title>Terceira bulha</title>
            <p>Collins et al.,<xref ref-type="bibr" rid="B25">25</xref> estudaram pacientes com dispneia no setor de emerg&#234;ncia e descobriram que a presen&#231;a da S3 n&#227;o melhorava a acur&#225;cia diagn&#243;stica para ICAD, com uma sensibilidade de apenas 14,6%. Al&#233;m disso, naquele estudo, observou-se uma baixa acur&#225;cia diagn&#243;stica (58%) para ICAD ao se usarem todos os sinais juntos. No nosso estudo, a S3 esteve presente em menos da metade dos pacientes e, quando presente, apresentou valor preditivo positivo de 79% para PAE &gt;15 mmHg. Sua aus&#234;ncia n&#227;o permitiu descartar uma eleva&#231;&#227;o na press&#227;o de enchimento. Al&#233;m disso, a S3 n&#227;o acrescentou nenhuma informa&#231;&#227;o quanto ao <italic>status</italic> hemodin&#226;mico. Isso est&#225; de acordo com outros estudos.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref> Vale notar que, no nosso estudo, todos os exames f&#237;sicos foram realizados por especialista em insufici&#234;ncia card&#237;aca. Em um contexto profissional de menor experi&#234;ncia, a acur&#225;cia do exame f&#237;sico (em particular, S3) pode ser inferior, pois h&#225; estudos que sugerem baixa concord&#226;ncia entre internos de medicina ou residentes e achados fonocardiogr&#225;ficos.<xref ref-type="bibr" rid="B27">27</xref> Por outro lado, observou-se concord&#226;ncia razo&#225;vel quanto &#224; detec&#231;&#227;o de S3 entre profissionais de cl&#237;nicas de insufici&#234;ncia card&#237;aca.<xref ref-type="bibr" rid="B28">28</xref>
						</p>
          </sec>
          <sec>
            <title>N&#237;veis de BNP</title>
            <p>A mais forte evid&#234;ncia para o uso cl&#237;nico do BNP encontra-se na discrimina&#231;&#227;o da causa de dispneia em pacientes admitidos no setor de emerg&#234;ncia<xref ref-type="bibr" rid="B29">29</xref> e na avalia&#231;&#227;o de progn&#243;stico.<xref ref-type="bibr" rid="B30">30</xref><sup>,</sup><xref ref-type="bibr" rid="B31">31</xref> Quanto aos outros prop&#243;sitos de uso do BNP, os dados s&#227;o menos claros. No Estudo Escape,<xref ref-type="bibr" rid="B32">32</xref> a curva ROC do BNP para estimar uma eleva&#231;&#227;o na PCPC &gt; 22 mmHg mostrou um desempenho fraco (AUC = 0,55). Outro estudo com 40 pacientes cr&#237;ticos e usando monitoramento hemodin&#226;mico invasivo mostrou correla&#231;&#227;o fraca entre BNP e PCPC (r = 0,58).<xref ref-type="bibr" rid="B33">33</xref> Nossos achados foram consistentes com os desses estudos, mostrando fraca correla&#231;&#227;o entre BNP e PAE (r = 0,29). Testou-se ainda o BNP quanto &#224; orienta&#231;&#227;o do tratamento, pois, teoricamente, a redu&#231;&#227;o do BNP &#233; uma consequ&#234;ncia da diminui&#231;&#227;o das press&#245;es de enchimento,<xref ref-type="bibr" rid="B34">34</xref> mas essa estrat&#233;gia n&#227;o conseguiu mostrar benef&#237;cio cl&#237;nico.<xref ref-type="bibr" rid="B35">35</xref> Por outro lado, no recente Estudo PROTECT,<xref ref-type="bibr" rid="B36">36</xref> uma estrat&#233;gia similar para orientar o tratamento de acordo com os n&#237;veis de Pro-BNP <italic>versus</italic> o cuidado padr&#227;o resultou em diminui&#231;&#227;o de eventos, melhora na qualidade de vida e no remodelamento card&#237;aco. Entretanto, aquele estudo foi conduzido em ambiente ambulatorial, envolvendo poucos pacientes em classes funcionais mais avan&#231;adas de insufici&#234;ncia card&#237;aca.</p>
            <p>No presente estudo, usamos o ponto de corte de 400 pg/mL para o BNP como marcador de congest&#227;o, pois esse valor foi empregado em estudos pr&#233;vios.<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B35">35</xref> Observamos que n&#237;veis de BNP &gt; 400 pg/mL tinham um desempenho preditivo pobre para identificar eleva&#231;&#227;o na PAE, similar ao de outros achados f&#237;sicos ou da radiografia de t&#243;rax quando considerados individualmente. N&#227;o se observou informa&#231;&#227;o valiosa quanto &#224;s press&#245;es de enchimento para n&#237;veis de BNP abaixo de 400 pg/mL. Usando a AUC, descobrimos que n&#237;veis de BNP de 1000 pg/mL tinham melhor especificidade para predizer PAE &#8805;15 mmHg. Logo, usamos esse ponto de corte na nossa an&#225;lise combinada subsequente. Pacientes com comprometimento renal moderado ou grave apresentaram n&#237;veis de BNP mais altos; no nosso estudo, os n&#237;veis m&#233;dios de ureia e creatinina estavam apenas levemente elevados e n&#227;o devem ter influenciado os resultados.</p>
            <p>Embora haja uma diferen&#231;a temporal entre a altera&#231;&#227;o nas press&#245;es de enchimento ventricular e a correspondente mudan&#231;a nos n&#237;veis de BNP, tal diferen&#231;a parece n&#227;o ter significado cl&#237;nico. A vida-m&#233;dia do BNP &#233; curta, cerca de 20 minutos, e a redu&#231;&#227;o na press&#227;o capilar pulmonar induzida pelo tratamento leva a r&#225;pida redu&#231;&#227;o nos n&#237;veis de BNP (30 a 50 pg/ml/hora).</p>
          </sec>
        </sec>
        <sec>
          <title>Combina&#231;&#227;o de ferramentas para estimar congest&#227;o</title>
          <p>Em pacientes com n&#237;veis intermedi&#225;rios de BNP (100-500 pg/mL), acrescentar informa&#231;&#227;o sobre a presen&#231;a de S3 aumenta o valor preditivo positivo de 54% para 80%.<xref ref-type="bibr" rid="B37">37</xref> Um estudo recente com 50 pacientes usou estrat&#233;gia muito similar &#224; do nosso estudo, comparando um EC, BNP e um ultrassom port&#225;til para estimar a eleva&#231;&#227;o nas press&#245;es de enchimento ventricular, mas o padr&#227;o ouro naquele estudo foi o cateterismo do lado direito do cora&#231;&#227;o.<xref ref-type="bibr" rid="B14">14</xref> Como no nosso, aquele estudo usou um ponto de corte para BNP &gt; 400 pg/mL e para PCPC &#8805; 15 mmHg como par&#226;metros de refer&#234;ncia. O EC de sintomas apresentou pouca utilidade preditiva para uma PCPC elevada. A combina&#231;&#227;o das informa&#231;&#245;es de press&#227;o venosa jugular, BNP e ultrassom proporcionou as melhores caracter&#237;sticas diagn&#243;sticas para a predi&#231;&#227;o de press&#227;o de enchimento do VE elevada (AUC 0,98). No nosso estudo, a combina&#231;&#227;o dos achados de exame f&#237;sico com radiografia de t&#243;rax e BNP aumentou progressivamente a sensibilidade (64%, 82% e 91%, respectivamente) para detectar PAE elevada, alcan&#231;ando um valor preditivo positivo de 81%, embora com baixa especificidade. Ainda, a combina&#231;&#227;o dessas ferramentas mostrou modesto poder preditivo para altas press&#245;es de enchimento (AUC: 0,62). Portanto, nosso estudo e o de Goonewardena et al.,<xref ref-type="bibr" rid="B14">14</xref> mostraram que o exame cl&#237;nico e o BNP n&#227;o podem detectar com precis&#227;o a eleva&#231;&#227;o das press&#245;es de enchimento, podendo a avalia&#231;&#227;o ecocardiogr&#225;fica hemodin&#226;mica ser seguramente incorporada na pr&#225;tica cl&#237;nica de ICAD, evitando o tradicional e invasivo cateterismo do lado direito do cora&#231;&#227;o. A crescente utiliza&#231;&#227;o do ultrassom port&#225;til pode ser de grande valor nessa &#225;rea.</p>
        </sec>
        <sec>
          <title>Limita&#231;&#245;es do estudo</title>
          <p>Usamos o ecocardiograma como m&#233;todo padr&#227;o ouro para definir as press&#245;es de enchimento em lugar do cateterismo do lado direito do cora&#231;&#227;o. Os par&#226;metros hemodin&#226;micos derivados do ecocardiograma s&#227;o bem validados na literatura m&#233;dica quando correlacionados com medidas invasivas.<xref ref-type="bibr" rid="B38">38</xref><sup>-</sup><xref ref-type="bibr" rid="B40">40</xref>
					</p>
          <p>Usamos primeiro o anel lateral para medir a raz&#227;o E/e'. Embora as recomenda&#231;&#245;es mais recentes sugiram o uso dos n&#237;veis m&#233;dios dos an&#233;is lateral e septal, isso foi validado em indiv&#237;duos normais. A mais recente diretriz de 2016 da Sociedade Americana de Ecocardiografia e da Associa&#231;&#227;o Europeia de Imagem Cardiovascular reconhece que &#224;s vezes apenas a velocidade lateral e&#8217; ou septal e&#8217; est&#225; dispon&#237;vel, e isso &#233; clinicamente v&#225;lido.</p>
          <p>Al&#233;m disso, n&#227;o acompanhamos os pacientes durante a hospitaliza&#231;&#227;o nem ap&#243;s a alta para observar se o perfil hemodin&#226;mico inicial foi compat&#237;vel com o curso cl&#237;nico.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#245;es</title>
        <p>Neste estudo, mostramos que, em pacientes com ICAD, a avalia&#231;&#227;o cl&#237;nica isolada ou associada com radiografia de t&#243;rax e BNP pode levar a uma estimativa imprecisa do perfil hemodin&#226;mico derivado do ecocardiograma.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>Este artigo &#233; parte de tese de Doutorado de Gustavo Luiz Gouv&#234;a de Almeida Junior pela Universidade Federal do Rio Grande do Sul.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Aprova&#231;&#227;o &#233;tica e consentimento informado</bold>
          </p>
          <p>Este estudo foi aprovado pelo Comite&#770; de E&#769;tica do Hospital Pr&#243;-Card&#237;aco sob o nu&#769;mero de protocolo 021/10 (CAAE:0021.1.346.001-10). Todos os procedimentos envolvidos nesse estudo esta&#771;o de acordo com a Declarac&#807;a&#771;o de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes inclui&#769;dos no estudo.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
