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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</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</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">Jc4M9SPmWsqvk7qvMcxbjbB</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2015002000028</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2015005050045</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20150045</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Left Atrial Function in Patients with Chronic Chagasic Cardiomyopathy</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Fragata</surname>
            <given-names>Claudia da Silva</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Matsumoto</surname>
            <given-names>Afonso Y.</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ramires</surname>
            <given-names>Felix J. A.</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>Fabio</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Buck</surname>
            <given-names>Paula de C&#225;ssia</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Salemi</surname>
            <given-names>Vera Maria C.</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nastari</surname>
            <given-names>Luciano</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mady</surname>
            <given-names>Charles</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ianni</surname>
            <given-names>Barbara Maria</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <label>1</label>
        <institution content-type="orgname">Instituto Dante Pazzanese de Cardiologia</institution>
        <institution content-type="orgdiv1">Se&#231;&#227;o M&#233;dica de Eletrofisiologia</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Se&#231;&#227;o M&#233;dica de Eletrofisiologia, Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo - Brazil</institution>
        <institution content-type="normalized">Instituto Dante Pazzanese de Cardiologia</institution>
      </aff>
      <aff id="aff02">
        <label>2</label>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Instituto do Cora&#231;&#227;o</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Unidade de Miocardiopatia, Instituto do Cora&#231;&#227;o (InCor), Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo - Brazil Mailing</institution>
        <institution content-type="normalized">Universidade de S&#227;o Paulo</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><bold>Mailing address: Claudia da Silva Fragata</bold>, Se&#231;&#227;o M&#233;dica de Eletrofisiologia, Instituto Dante Pazzanese de Cardiologia, Av. Dr. Dante Pazzanese, 500. Postal Code 04012-918. S&#227;o Paulo, SP - Brazil. email:   <email>claudiadasilvafragata@gmail.com</email>;   <email>claudia.fragata@dantepazzanese.org.br</email>
				</corresp>
        <fn fn-type="con">
          <label>Author contributions</label>
          <p>Conception and design of the research:Fragata CS, Matsumoto AY, Ramires FJA, Fernandes F, Buck PC, Salemi VMC, Mady C, Ianni BM. Acquisition of data:Fragata CS, Matsumoto AY, Ramires FJA, Fernandes F, Buck PC, Mady C, Ianni BM. Analysis and interpretation of the data: Fragata CS, Matsumoto AY, Ramires FJA, Fernandes F, Buck PC, Nastari L, Mady C, Ianni BM. Statistical analysis: Fragata CS, Mady C, Ianni BM. Obtaining financing: Fragata CS. Writing of the manuscript:Fragata CS, Matsumoto AY, Buck PC, Salemi VMC, Nastari L, Mady C, Ianni BM. Critical revision of the manuscript for intellectual content: Fragata CS, Matsumoto AY, Fernandes F, Buck PC, Salemi VMC, Nastari L, Mady C, Ianni BM.</p>
        </fn>
        <fn fn-type="conflict">
          <label>Potential Conflict of Interest</label>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="collection">
        <month>07</month>
        <year>2015</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>08</day>
        <month>05</month>
        <year>2015</year>
      </pub-date>
      <volume>105</volume>
      <issue>1</issue>
      <fpage>28</fpage>
      <lpage>36</lpage>
      <history>
        <date date-type="received">
          <day>22</day>
          <month>04</month>
          <year>2014</year>
        </date>
        <date date-type="rev-recd">
          <day>09</day>
          <month>12</month>
          <year>2014</year>
        </date>
        <date date-type="accepted">
          <day>23</day>
          <month>12</month>
          <year>2014</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution NonCommercial License which permits unrestricted noncommercial use, distribution, and reproduction in any medium provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <sec>
          <title>Background:</title>
          <p>Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>Reservoir function (Total Emptying Fraction: TEF): (p &lt;0.0001), lower in GIII as compared to CG (p = 0.003), GI (p &lt;0.001) and GII (p &lt;0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p&lt;0.0001) and GII (p = 0.002). There was a negative correlation of E/e&#8217;<italic><sub>average</sub></italic> with the reservoir and pump functions (TEF and AEF), and a positive correlation of e&#8217;<italic><sub>average</sub></italic> with s&#8217; wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions.</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>An impairment of LA functions in Chagas cardiomyopathy was observed.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Chagas Disease</kwd>
        <kwd>Chagas Cardiomyopathy</kwd>
        <kwd>Ventricular Dysfunction</kwd>
        <kwd>Atrial Function/physiopathology</kwd>
        <kwd>Echocardiography</kwd>
        <kwd>Doppler/methods</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="12"/>
        <equation-count count="0"/>
        <ref-count count="39"/>
        <page-count count="8"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Chagas disease, an infectious illness caused by the protozoan <italic>Trypanosoma cruzi</italic>, was described by Carlos Chagas in 1909, but its pathogenesis has yet to be completely elucidated<xref ref-type="bibr" rid="B01">1</xref>.</p>
      <p>Doppler echocardiography is the ideal method for cardiovascular research, especially anatomical and functional assessment, in patients with Chagas disease.</p>
      <p>Tissue Doppler provides important additional information on cardiac function. The s&#8217; wave is related to longitudinal left ventricular (LV) systolic function, while the e&#8217; wave is related to LV diastolic function. One of the advantages of using the e' wave to assess LV diastolic function is less dependence on hemodynamic loading conditions, contrary to what occurs with the E wave of the mitral flow<xref ref-type="bibr" rid="B02">2</xref>
				<sup>-</sup>
				<xref ref-type="bibr" rid="B08">8</xref>.</p>
      <p>The left atrial (LA) function is divided as follows:</p>
      <list list-type="order">
        <list-item>
          <p>Reservoir function: the left atrium stores pulmonary venous return during LV contraction and isovolumetric relaxation, getting 42% of the LV filling volume stored during these phases of the cardiac cycle<xref ref-type="bibr" rid="B09">9</xref>. Among the factors that influence it, the following must be highlighted: a) atrial contraction and relaxation, relaxation depending on contraction; b) LV contraction, which displaces the mitral annulus caudally; c) atrial stiffness and compliance; and d) right ventricular systole, which influences the flow in pulmonary veins.</p>
        </list-item>
        <list-item>
          <p>Conduit function: the left atrium passively transfers blood to the left ventricle. It depends fundamentally on LV diastolic properties.</p>
        </list-item>
        <list-item>
          <p>Pump function: the left atrium contracts actively during the final phase of ventricular diastole and contributes to 15%-30% of the LV end-diastolic volume. It depends on multiple factors, such as atrial contraction time, vagal stimulation, magnitude of the venous return (preload) and LV end-diastolic pressure (afterload).</p>
        </list-item>
      </list>
      <p>When LV relaxation is abnormal, the reservoir and propulsion pump functions occupy a high percentage of the cardiac cycle, while the conduit function decreases. However, with the progressive increase in LV filling pressure and worsening of diastolic dysfunction, the left atrium acts predominantly as a conduit<xref ref-type="bibr" rid="B10">10</xref>
				<sup>-</sup>
				<xref ref-type="bibr" rid="B14">14</xref>.</p>
      <p>The importance of assessing LA function has been highlighted in several clinical conditions, not only as part of pathophysiological mechanisms, but also as a prognostic factor<xref ref-type="bibr" rid="B15">15</xref>
				<sup>-</sup>
				<xref ref-type="bibr" rid="B24">24</xref>.</p>
      <p>This study aimed at finding elements for the better and earlier recognition of the following:</p>
      <list list-type="alpha-lower">
        <list-item>
          <p>changes in LA and LV functions in patients with Chagas disease;</p>
        </list-item>
        <list-item>
          <p>differences in LA function parameters;</p>
        </list-item>
        <list-item>
          <p>possible correlation between LA function data and Doppler echocardiographic parameters of LV systolic and diastolic function.</p>
        </list-item>
      </list>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>This study included patients selected consecutively at the Cardiomyopathy-Aortic Disease outpatient clinic of the Instituto do Cora&#231;&#227;o, of the University of S&#227;o Paulo Medical School, of both sexes, aged 18 to 55 years, who underwent clinical examination, electrocardiography, echocardiography, and laboratory tests (ELISA and immunofluorescence tests for Chagas disease, blood glucose and serum creatinine). Healthy age-matched volunteers were examined as a control group (CG).</p>
      <p>The usual medications were maintained during the tests (angiotensin-converting-enzyme inhibitors, beta-blockers, diuretics in patients with LV systolic dysfunction).</p>
      <p>The following exclusion criteria were considered: associated systemic diseases; ventricular arrhythmia or ventricular premature beats (&#8805; 10/hour on previous Holter, or frequent on physical examination); atrial fibrillation; moderate or severe mitral regurgitation; and implanted electronic cardiac devices.</p>
      <p>Patients with Chagas disease were divided into three groups as follows:</p>
      <list list-type="bullet">
        <list-item>
          <p>Group I (GI): with the indeterminate form (asymptomatic with normal findings on electrocardiography, chest radiography and esophageal and colonic contrast studies);</p>
        </list-item>
        <list-item>
          <p>Group II (GII): with electrocardiographic abnormalities and LV ejection fraction &#8805; 0.55;</p>
        </list-item>
        <list-item>
          <p>Group III (GIII): with electrocardiographic abnormalities and LV ejection fraction &lt; 0.55.</p>
        </list-item>
      </list>
      <sec>
        <title>Ethics Statement</title>
        <p>This study was registered with the approval of CAPPesq (Ethics Committee for Analysis of Research Projects of the Hospital das Cl&#237;nicas of the S&#227;o Paulo University - No. 0713/08). All subjects included in this study provided written informed consent in accordance with ethical regulations.</p>
      </sec>
      <sec>
        <title>Echocardiographic study</title>
        <p>All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and Tissue Doppler Imaging studies using a commercially available ultrasound system (Sequoia, Acuson-Siemens, Mountain View, California, USA).</p>
        <p>The quantitative measurements included LA e LV diameters on M-mode echocardiography, maximum, pre p-wave and minimum LA volumes (LAV<sub>max</sub>, LAV<sub>pre</sub> and LAV<sub>min</sub>, respectively) using the modified Simpson's method on two-dimensional echocardiography with 4-chamber view, in accordance with the American Society of Echocardiography (ASE) recommendations.</p>
        <p>The LV ejection fraction was calculated using the Teichholz method for uniformization<xref ref-type="bibr" rid="B25">25</xref>
					<sup>-</sup>
					<xref ref-type="bibr" rid="B27">27</xref>.</p>
        <p>Transmitral velocities were also obtained in accordance with the ASE. Measurements included E wave and A wave velocities, E/A ratio, and E wave deceleration time.</p>
        <p>Tissue Doppler imaging was performed with apical 4-chamber view. Measurements included systolic (s&#8217;), early diastolic (e&#8217;) and late diastolic (a&#8217;) waves, which were obtained from the lateral and septal margins of the mitral annulus, and the mean between the two sites (e&#8217;<sub>average</sub>) was used to calculate the E/e&#8217; ratio, which was also estimated from the LV filling pressure.</p>
        <p>All examinations and measurements were made by one observer, and the mean of three to five consecutive cardiac cycles was used in this study.</p>
        <p>Patients were positioned lying down on their left side, with 20&#176; to 30&#176; trunk inclination, and electrodes placed to obtain the electrocardiographic tracings.</p>
        <p>All echocardiographic measurements were performed in accordance with the ASE recommendations<xref ref-type="bibr" rid="B26">26</xref>
					<sup>-</sup>
					<xref ref-type="bibr" rid="B28">28</xref>.</p>
        <p>On two-dimensional echocardiography, the following parameters were calculated using the modified Simpson's method:</p>
        <list list-type="bullet">
          <list-item>
            <p>LAV<sub>max</sub> (in mL), measured at end-systole, just before the mitral valve opening;</p>
          </list-item>
          <list-item>
            <p>LAV<sub>min</sub> (in mL), measured at end-diastole, just before the mitral valve closing and after the P wave;</p>
          </list-item>
          <list-item>
            <p>LAV<sub>pre</sub> (in mL), measured immediately before the P wave (before atrial contraction).</p>
          </list-item>
        </list>
        <p>The volumes and LV diastolic diameter were corrected for body surface area (BSA), which was calculated by using the Dubois&#8217; method.</p>
      </sec>
      <sec>
        <title>Assessment of LA function</title>
        <p>The LA reservoir function was analyzed by use of total emptying fraction (TEF), calculated according to the following formula: TEF = (LAV<sub>max</sub> - LAV<sub>min</sub>) / LAV<sub>max</sub>.</p>
        <p>The LA conduit function was examined by use of passive emptying fraction (PEF), calculated according to the following formula: PEF = (LAV<sub>max</sub> &#8211; LAV<sub>pre</sub>) / LAV<sub>max</sub>.</p>
        <p>The LA pump function was analyzed by use of active emptying fraction (AEF), calculated according to the following formula: AEF = (LAV<sub>pre</sub> - LAV<sub>min</sub>) / LAV<sub>pre</sub>.</p>
      </sec>
      <sec>
        <title>Statistical Analysis</title>
        <p>The quantitative measures were described as means, medians, standard deviations and percentiles. Nonparametric Kruskal-Wallis test was applied to compare those measures among the four groups. When there were significant differences, the Bonferroni correction was used for multiple comparisons among the groups.</p>
        <p>The relation between measures was assessed by Spearman correlation coefficient. When it was significant, a positive correlation coefficient (<italic>r</italic>) indicated that higher values of the variable <italic>x</italic> correspond to higher values of the variable <italic>y</italic>. If<italic>r</italic>was negative, the relation was reverse and higher values of the variable <italic>x</italic> correspond to smaller values of the variable <italic>y</italic>. According to the absolute   <italic>r</italic> values, the correlations between variables were as follows:   <italic>r</italic> &lt; 0.3, weak correlation; <italic>r</italic> &#8805; 0.3 and &lt; 0.7, moderate correlation; and<italic> r</italic> &#8805; 0.7, strong correlation.</p>
        <p>The significance level adopted was "p" value &lt; 5%. The Statistical Package for the Social Sciences (SPSS) software, version 19, was applied<xref ref-type="bibr" rid="B29">29</xref>
					<sup>,</sup>
					<xref ref-type="bibr" rid="B30">30</xref>.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>This study included 85 individuals as follows: CG, 10 individuals; GI, 26; GII, 30; and GIII, 19. The groups did not differ regarding the following parameters: mean age (p = 0.107); weight (p = 0.815); height (p = 0.880); BSA (p = 0.791); heart rate (p = 0.164); and sex (p = 0.492) (<xref ref-type="table" rid="t01">Table 1</xref>).</p>
      <table-wrap id="t01">
        <label>Table 1</label>
        <caption>
          <title>Age, anthropometric characteristics, blood pressure and heart rate of the subjects Included In the study</title>
        </caption>
        <table frame="hsides" rules="groups">
          <thead>
            <tr>
              <th rowspan="2" align="left">
                <bold>Variables</bold>
              </th>
              <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                <bold>CG (n = 10)</bold>
              </th>
              <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                <bold>GI (n = 26)</bold>
              </th>
              <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                <bold>GII (n = 30)</bold>
              </th>
              <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                <bold>GIII (n = 19)</bold>
              </th>
              <th rowspan="2" align="center">
                <bold>p</bold>
              </th>
            </tr>
            <tr>
              <th>
                <bold>mean &#177; SD</bold>
              </th>
              <th>
                <bold>mean &#177; SD</bold>
              </th>
              <th>
                <bold>mean &#177; SD</bold>
              </th>
              <th>
                <bold>mean &#177; SD</bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td>Age (years)</td>
              <td align="center">40 &#177; 6</td>
              <td align="center">46 &#177; 6</td>
              <td align="center">43 &#177; 8</td>
              <td align="center">43 &#177; 7</td>
              <td align="center">0.11</td>
            </tr>
            <tr>
              <td>Weight (kg)</td>
              <td align="center">68 &#177; 13</td>
              <td align="center">68 &#177; 12</td>
              <td align="center">68 &#177; 11</td>
              <td align="center">71 &#177; 13</td>
              <td align="center">0.82</td>
            </tr>
            <tr>
              <td>Height (cm)</td>
              <td align="center">162 &#177; 8</td>
              <td align="center">163 &#177; 7</td>
              <td align="center">162 &#177; 9</td>
              <td align="center">164 &#177; 10</td>
              <td align="center">0.88</td>
            </tr>
            <tr>
              <td>BSA (m<sup>2</sup>)</td>
              <td align="center">1.70 &#177; 0.2</td>
              <td align="center">1.72 &#177; 0.2</td>
              <td align="center">1.70 &#177; 0.2</td>
              <td align="center">1.80 &#177; 0.2</td>
              <td align="center">0.79</td>
            </tr>
            <tr>
              <td>SBP (mm Hg)</td>
              <td align="center">109 &#177; 9</td>
              <td align="center">114 &#177; 10</td>
              <td align="center">118 &#177; 12</td>
              <td align="center">109 &#177; 10</td>
              <td align="center">0.05</td>
            </tr>
            <tr>
              <td>DBP (mm Hg)</td>
              <td align="center">70 &#177; 9</td>
              <td align="center">73 &#177; 8</td>
              <td align="center">72 &#177; 8</td>
              <td align="center">67 &#177; 8</td>
              <td align="center">0.14</td>
            </tr>
            <tr>
              <td>HR (bpm)</td>
              <td align="center">68 &#177; 10</td>
              <td align="center">70 &#177; 9</td>
              <td align="center">67 &#177; 9</td>
              <td align="center">64 &#177; 10</td>
              <td align="center">0.16</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn>
            <p>CG: control group; GI: indeterminate form; GII: electrocardiographic abnormalities and LV ejection fraction &#8805;0.55; GIII: electrocardiographic abnormalities and LV ejection fraction &lt; 0.55; SD: standard deviation; BSA: body surface area; SBP: systolic blood pressure; DBP: diastolic blood pressure; HR: heart rate.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <sec>
        <title>The baseline LA and LV echocardiographic parameters were as follows:</title>
        <sec>
          <title>&#8226; Left atrium</title>
          <p>There was a significant difference between groups in relation to LAV<sub>max</sub>(p &lt;0.0001). The mean value was higher in GIII as compared to CG (p = 0.001), GI (p = 0.0001) and GII (p = 0.012). Similarly, the mean values in GIII were higher when compared to GII and CG (p = 0.03). There was no significant difference between CG and GI.</p>
          <p>There was a significant difference between groups in relation to LAV<sub>pre</sub>(p &lt; 0.0001). The mean value was higher in GIII as compared to CG (p = 0.0004), GI (p = 0.0003) and GII (p = 0.012). Similarly, the mean values were higher when compared to GII and CG (p = 0.012). There was no significant difference between CG and GI.</p>
          <p>There was a significant difference between groups in relation to LAV<sub>min</sub>(p &lt; 0.0001). The mean value was higher in GIII as compared to CG (p = 0.0003), GI (p &lt; 0.0001) and GII (p = 0.0007). There was no significant difference in GI and GII as compared to CG, and between GI and GII (<xref ref-type="table" rid="t02">Table 2</xref>).</p>
          <table-wrap id="t02">
            <label>Table 2</label>
            <caption>
              <title>Baseline echocardiography parameters corrected for body surface, with respective means, standard deviations (SD) and p values (Kruskal-Wallis test)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th rowspan="2" align="left">
                    <bold>Variables</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>CG (n = 10)</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>GI (n = 26)</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>GII (n = 30)</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>GIII (n = 19)</bold>
                  </th>
                  <th rowspan="2" align="center">
                    <bold>p</bold>
                  </th>
                </tr>
                <tr>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>LVDD (mm/m<sup>2</sup>)</td>
                  <td align="center">25 &#177; 2.1</td>
                  <td align="center">25.9 &#177; 2.3</td>
                  <td align="center">28.4 &#177; 3.3<xref ref-type="table-fn" rid="TFN02">#</xref>
									</td>
                  <td align="center">37.1 &#177; 5.0<xref ref-type="table-fn" rid="TFN01">*</xref>
									</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
                <tr>
                  <td>LAV<sub>max</sub>(ml/m<sup>2</sup>)</td>
                  <td align="center">23 &#177; 4.5</td>
                  <td align="center">27 &#177; 6.4</td>
                  <td align="center">31 &#177; 8.7<xref ref-type="table-fn" rid="TFN02">#</xref>
									</td>
                  <td align="center">42 &#177; 12.1<xref ref-type="table-fn" rid="TFN01">*</xref>
									</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
                <tr>
                  <td>LAV<sub>pre P</sub>(ml/m<sup>2</sup>)</td>
                  <td align="center">14 &#177; 3</td>
                  <td align="center">17 &#177; 4.21</td>
                  <td align="center">21 &#177; 6.5<xref ref-type="table-fn" rid="TFN02">#</xref>
									</td>
                  <td align="center">32 &#177; 12<xref ref-type="table-fn" rid="TFN01">*</xref>
									</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
                <tr>
                  <td>LAV<sub>m&#237;n</sub>(ml/m<sup>2</sup>)</td>
                  <td align="center">8.5 &#177; 2</td>
                  <td align="center">9.8 &#177; 2.9</td>
                  <td align="center">12.3 &#177; 5.9</td>
                  <td align="center">24 &#177; 10.9<xref ref-type="table-fn" rid="TFN01">*</xref>
									</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN01">
                <label>*</label>
                <p>GIII values significantly different from those of other groups</p>
              </fn>
              <fn id="TFN02">
                <label>#</label>
                <p>GII values significantly different from CG values</p>
              </fn>
              <fn>
                <p>CG: control group; GI: indeterminate form; GII: electrocardiographic abnormalities and LV ejection fraction &#8805; 0.55; GIII: electrocardiographic abnormalities and LV ejection fraction &lt; 0.55; LVDD: left ventricular diastolic diameter; LAV<sub>max</sub>: maximum left atrial volume; LAV<sub>pre P</sub>: pre-P-wave left atrial volume; LAV<sub>min</sub>: minimum left atrial volume.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>&#8226; Left ventricle</title>
          <p>There was a significant difference between groups regarding LV diastolic diameter (p &lt;0.0001). The mean value was higher in GIII as compared to CG (p = 0.001), GI (p &lt; 0.0001) and GII (p &lt; 0.0001), and in GII as compared to CG (p = 0.05). There was no significant difference between CG and GI (<xref ref-type="table" rid="t02">Table 2</xref>).</p>
        </sec>
      </sec>
      <sec>
        <title>Parameter of LV systolic function</title>
        <sec>
          <title>&#8226; Ejection fraction</title>
          <p>There was a significant difference between groups regarding LV ejection fraction (p &lt; 0.0001). The mean value was lower in GIII as compared to CG (p = 0.001), GI (p &lt; 0.0001) and GII (p &lt; 0.0001). There was no significant difference between CG, GI and GII when compared to each other (<xref ref-type="table" rid="t03">Table 3</xref>).</p>
          <table-wrap id="t03">
            <label>Table 3</label>
            <caption>
              <title>Mitral flow variables used to assess LV diastolic function and LV ejection fraction, with respective means, standard deviations (SD) and p values (Kruskal-Wallis test)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th rowspan="2" align="left">
                    <bold>Variables</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>CG (n = 10)</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>GI (n = 26)</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>GII (n = 30)</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>GIII (n = 19)</bold>
                  </th>
                  <th rowspan="2" align="center">
                    <bold>p</bold>
                  </th>
                </tr>
                <tr>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>E wave (cm/s)</td>
                  <td align="center">74.2 &#177; 12.7</td>
                  <td align="center">71.9 &#177; 14.4</td>
                  <td align="center">71.2 &#177; 17.4</td>
                  <td align="center">68 &#177; 19.4</td>
                  <td align="center">0.7635</td>
                </tr>
                <tr>
                  <td>A wave (cm/s)</td>
                  <td align="center">54.1 &#177; 4.9</td>
                  <td align="center">62.5 &#177; 7.9</td>
                  <td align="center">59.7 &#177; 12.0</td>
                  <td align="center">58.9 &#177; 16.9</td>
                  <td align="center">0.0949</td>
                </tr>
                <tr>
                  <td>E/A</td>
                  <td align="center">1.4 &#177;0.2</td>
                  <td align="center">1.2 &#177; 0.3</td>
                  <td align="center">1.2 &#177; 0.4</td>
                  <td align="center">1.3 &#177; 0.6</td>
                  <td align="center">0.2279</td>
                </tr>
                <tr>
                  <td>DTE (ms)</td>
                  <td align="center">174.4 &#177; 18.1</td>
                  <td align="center">198.8 &#177; 30.7</td>
                  <td align="center">198.9 &#177; 33.1</td>
                  <td align="center">210 &#177; 64.6</td>
                  <td align="center">0.1836</td>
                </tr>
                <tr>
                  <td>LVEF</td>
                  <td align="center">0.67 &#177; 0.05</td>
                  <td align="center">0.66 &#177; 0.04</td>
                  <td align="center">0.67 &#177; 0.06</td>
                  <td align="center">0.41 &#177; 0.07<xref ref-type="table-fn" rid="TFN03">*</xref>
									</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN03">
                <label>*</label>
                <p>GIII values significantly different from those of other groups</p>
                <p>CG: control group; GI: indeterminate form; GII: electrocardiographic abnormalities and LV ejection fraction &#8805; 0.55; GIII: electrocardiographic abnormalities and LV ejection fraction &lt; 0.55; E wave: E wave in mitral flow; A wave: A wave in mitral flow; E/A: E wave/A wave ratio; DTE: E wave deceleration time; LVEF: left ventricular ejection fraction.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>Parameters of LV diastolic function:</title>
        <sec>
          <title>&#8226; Mitral flow</title>
          <p>There was no statistically significant difference between groups regarding E wave (p = 0.76), A wave (p = 0.09), E/A ratio (p = 0.22) and E wave deceleration time (p = 0.18) (<xref ref-type="table" rid="t03">Table 3</xref>).</p>
        </sec>
        <sec>
          <title>&#8226; Tissue Doppler</title>
          <p>There was a significant difference between groups (p = 0.0004) regarding e'<sub>lat</sub> evaluation on tissue Doppler. The mean value was lower in GIII as compared to CG (p = 0.0076), GI (p = 0.001) and GII (p = 0.036). There was no significant difference of mean values between CG, GI and GII.</p>
          <p>There was a significant difference between groups (p &lt;0.001) regarding e'<sub>sep</sub> evaluation on tissue Doppler. The mean value was lower in GIII as compared to CG (p = 0.0004), GI (p &lt; 0.001) and GII (p = 0.0001). There was no significant difference of mean values when comparing CG, GI and GII.</p>
          <p>A significant difference between groups was found (p &lt; 0.001) regarding e'<sub>average</sub> evaluation on tissue Doppler. The mean value was lower in GIII as compared to CG (p &lt; 0.001), GI (p &lt; 0.001) and GII (p &lt; 0.001). There was no significant difference of mean values between CG, GI and GII.</p>
          <p>Regarding E/e'<sub>average</sub>, there was a significant difference between groups (p &lt; 0.001). The mean value was significantly higher in GIII as compared to CG (p = 0.009), GI (p = 0.0001) and GII (p = 0.007). There was no significant difference of mean values between CG, GI and GII (<xref ref-type="table" rid="t04">Table 4</xref>).</p>
          <table-wrap id="t04">
            <label>Table 4</label>
            <caption>
              <title>Tissue Doppler variables used to assess LV diastolic function, with respective means, standard deviations (SD) and p values (Kruskal-Wallis test)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th rowspan="2" align="left">
                    <bold>Variables</bold>
                  </th>
                  <th align="center">
                    <bold>CG (n = 10)</bold>
                  </th>
                  <th align="center">
                    <bold>GI (n = 26)</bold>
                  </th>
                  <th align="center">
                    <bold>GII (n = 30)</bold>
                  </th>
                  <th align="center">
                    <bold>GIII (n = 19)</bold>
                  </th>
                  <th rowspan="2" align="center">
                    <bold>p</bold>
                  </th>
                </tr>
                <tr>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>S'<sub>lat</sub>
									</td>
                  <td align="center">11.4 &#177; 2.2</td>
                  <td align="center">13.2 &#177; 2.0</td>
                  <td align="center">13.5 &#177; 2.7</td>
                  <td align="center">8.0 &#177; 1.9<xref ref-type="table-fn" rid="TFN04">*</xref>
									</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
                <tr>
                  <td>e'<sub>lat</sub>
									</td>
                  <td align="center">15 &#177; 2.3</td>
                  <td align="center">15.1 &#177; 3.2</td>
                  <td align="center">13.3 &#177; 3.1</td>
                  <td align="center">9.8 &#177; 3.7<xref ref-type="table-fn" rid="TFN04">*</xref>
									</td>
                  <td align="center">0.0004</td>
                </tr>
                <tr>
                  <td>s'<sub>sep</sub>
									</td>
                  <td align="center">9.2 &#177; 2.8</td>
                  <td align="center">10.6 &#177; 1.5</td>
                  <td align="center">10.5 &#177; 2.0</td>
                  <td align="center">7.3 &#177; 1.8<xref ref-type="table-fn" rid="TFN04">*</xref>
									</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
                <tr>
                  <td>e'<sub>sep</sub>
									</td>
                  <td align="center">11.0 &#177; 2.1</td>
                  <td align="center">10.5 &#177; 2.3</td>
                  <td align="center">9.7 &#177; 1.8</td>
                  <td align="center">7 &#177; 1.5<xref ref-type="table-fn" rid="TFN04">*</xref>
									</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
                <tr>
                  <td>e'<sub>average</sub>
									</td>
                  <td align="center">13 &#177; 1.6</td>
                  <td align="center">12.8 &#177; 2.5</td>
                  <td align="center">11.3 &#177; 2.5</td>
                  <td align="center">8.1 &#177; 2.6<xref ref-type="table-fn" rid="TFN04">*</xref>
									</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
                <tr>
                  <td>E/e'<sub>average</sub>
									</td>
                  <td align="center">5.8 &#177; 1.5</td>
                  <td align="center">5.7 &#177; 0.8</td>
                  <td align="center">6.6 &#177; 2.3</td>
                  <td align="center">9.6 &#177; 3.4<xref ref-type="table-fn" rid="TFN04">*</xref>
									</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN04">
                <label>*</label>
                <p>GIII values significantly different from those of other groups</p>
              </fn>
              <fn>
                <p>CG: control group; GI: indeterminate form; GII: electrocardiographic abnormalities and LV ejection fraction &#8805; 0.55; GIII: electrocardiographic abnormalities and LV ejection fraction &lt; 0.55; s&#8217;<sub>lat</sub>: s wave in lateral wall (Tissue Doppler); e&#8217;<sub>lat</sub>: e wave in lateral wall (Tissue Doppler); s&#8217;<sub>sep</sub>: s wave in septal wall (Tissue Doppler); e&#8217;<sub>sep</sub>: e wave in septal wall (Tissue Doppler); e&#8217;<sub>average</sub>: the mean between e&#8217;<sub>lat</sub>and e&#8217;<sub>sep</sub>; E/e&#8217;<sub>average</sub>: E wave/e&#8217;<sub>average</sub>ratio</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>Parameters of LA function</title>
        <sec>
          <title>&#8226; Reservoir function</title>
          <p>The TEF significantly differed between groups (p &lt; 0.0001). The mean values were significantly lower in GIII as compared to CG (p = 0.003), GI (p &lt; 0.001) and GII (p &lt;0.001). The mean values did not significantly differ between CG, GI and GII (<xref ref-type="table" rid="t05">Table 5</xref>).</p>
          <table-wrap id="t05">
            <label>Table 5</label>
            <caption>
              <title>Assessment of left atrial function with respective means, standard deviations (SD) and p values (Kruskal-Wallis test)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th rowspan="2" align="left">
                    <bold>Variables</bold>
                  </th>
                  <th align="center">
                    <bold>CG (n = 10)</bold>
                  </th>
                  <th align="center">
                    <bold>GI (n = 26)</bold>
                  </th>
                  <th align="center">
                    <bold>GII (n = 30)</bold>
                  </th>
                  <th align="center">
                    <bold>GIII (n = 19)</bold>
                  </th>
                  <th rowspan="2" align="center">
                    <bold>P</bold>
                  </th>
                </tr>
                <tr>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                  <th>
                    <bold>mean &#177; SD</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>AEF (mL)</td>
                  <td align="center">0.38 &#177; 0.05</td>
                  <td align="center">0.44 &#177; 0.08</td>
                  <td align="center">0.42 &#177; 0.11</td>
                  <td align="center">0.27 &#177; 0.11*</td>
                  <td align="center">0.0001</td>
                </tr>
                <tr>
                  <td>TEF (mL)</td>
                  <td align="center">0.63 &#177; 0.09</td>
                  <td align="center">0.63 &#177; 0.08</td>
                  <td align="center">0.62 &#177; 0.10</td>
                  <td align="center">0.44 &#177; 0.13*</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
                <tr>
                  <td>PEF (mL)</td>
                  <td align="center">0.39 &#177; 0.12</td>
                  <td align="center">0.35 &#177; 0.10</td>
                  <td align="center">0.35 &#177; 0.10</td>
                  <td align="center">0.23 &#177; 0.12</td>
                  <td align="center">0.004</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN05">
                <label>*</label>
                <p>GIII values significantly different from those of other groups</p>
              </fn>
              <fn>
                <p>CG: control group; GI: indeterminate form; GII: electrocardiographic abnormalities and LV ejection fraction &gt; 0.55; GIII: electrocardiographic abnormalities and LV ejection fraction &lt; 0.55; AEF: active emptying fraction; TEF: total emptying fraction; PEF: passive emptying fraction.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>&#8226; Conduit function</title>
          <p>The PEF significantly differed between groups (p = 0.004). The mean value was lower in GIII, but with no statistical significance, when comparing GIII and CG (p = 0.06), GI and GII (p = 0.06), and GII and GIII (p = 0.07) (<xref ref-type="table" rid="t05">Table 5</xref>).</p>
        </sec>
        <sec>
          <title>&#8226; Pump function</title>
          <p>The AEF significantly differed between groups (p = 0.0001). The mean value was lower in GIII when compared to CG (p = 0.05), GI (p &lt; 0.0001) and GII (p = 0.002) (<xref ref-type="table" rid="t05">Table 5</xref>).</p>
        </sec>
      </sec>
      <sec>
        <title>Analysis of the correlations</title>
        <p>There was a negative correlation of E/e'<sub>average  </sub>with the reservoir and pump functions (TEF and AEF), and a positive correlation of e'<sub>average</sub> with s' (both septal and lateral walls) and the reservoir, conduit and pump functions.   <xref ref-type="table" rid="t06">Table 6</xref> describes the correlations among variables.</p>
        <table-wrap id="t06">
          <label>Table 6</label>
          <caption>
            <title>Correlations</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th>&#160;</th>
                <th align="center">
                  <bold>E/e'average</bold>
                </th>
                <th align="center">
                  <bold>e'average</bold>
                </th>
                <th align="center">
                  <bold>LVEF</bold>
                </th>
                <th align="center">
                  <bold>s'<sub>sep</sub>
									</bold>
                </th>
                <th align="center">
                  <bold>s'<sub>lat</sub>
									</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td rowspan="2">TEF</td>
                <td align="center">r = -0.26</td>
                <td align="center">r = 0.53</td>
                <td align="center">r = 0.35</td>
                <td align="center">r = 0.33</td>
                <td align="center">r= 0.28</td>
              </tr>
              <tr>
                <td align="center">p = 0.02</td>
                <td align="center">p &lt; 0.001</td>
                <td align="center">p = 0.003</td>
                <td align="center">p = 0.003</td>
                <td align="center">p = 0.003</td>
              </tr>
              <tr>
                <td rowspan="2">PEF</td>
                <td align="center">r = -0.09</td>
                <td align="center">r = 0.49</td>
                <td align="center">r = 0.42</td>
                <td align="center">r = 0.197</td>
                <td align="center">r = 0.118</td>
              </tr>
              <tr>
                <td align="center">p = 0.44</td>
                <td align="center">p &lt; 0.001</td>
                <td align="center">p &lt; 0.001</td>
                <td align="center">p = 0.135</td>
                <td align="center">p = 0.378</td>
              </tr>
              <tr>
                <td rowspan="2">AEF</td>
                <td align="center">r = -0.36</td>
                <td align="center">r = 0.39</td>
                <td align="center">r = 0.35</td>
                <td align="center">r = 0.37</td>
                <td align="center">r= 0.34</td>
              </tr>
              <tr>
                <td align="center">p = 0.002</td>
                <td align="center">p = 0.001</td>
                <td align="center">p = 0.003</td>
                <td align="center">p = 0.004</td>
                <td align="center">p = 0.01</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>AEF: active emptying fraction; TEF: total emptying fraction; PEF: passive emptying fraction; s&#8217;<sub>lat</sub>: s wave in lateral wall (Tissue Doppler); s&#8217;<sub>sep</sub>: s wave in septal wall (Tissue Doppler); e&#8217;<sub>average</sub>: the mean between e&#8217;<sub>lat</sub> and e&#8217;<sub>sep</sub>; E/e&#8217;<sub>average</sub>: E wave/e&#8217;<sub>average</sub>ratio; LVEF: left ventricular ejection fraction.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>This study reveals important features and details of the relationship and interdependency of the systolic and diastolic functions of the left ventricle and left atrium.</p>
      <p>The LA function has been extensively studied in recent decades, with great interest in the pathophysiological and prognostic implications and interrelation with LV systolic and diastolic functions. It has been investigated in several clinical situations and diseases. A hemodynamic study with simultaneous recording of pressure and volume curves is ideal to allow the assessment of LA relaxation and compliance, which directly influence LA filling. However, it is an invasive and costly exam, being reserved almost exclusively to experimental studies.</p>
      <p>Echocardiography is a good alternative, being currently the method of choice for non-invasive LA analysis. Alterations in diastolic function properties or in any of LA functions (reservoir, conduit or pump) may interfere in LV filling. In addition to some cardiovascular diseases, the aging process modifies the LA size and some functions, especially the passive and active emptying.<xref ref-type="bibr" rid="B31">31</xref>
			</p>
      <p>It is intuitive that all mechanisms involved in the process of LV filling and LA emptying are interdependent; therefore, the interpretation and importance of each of the influencing factors must be carefully analyzed.</p>
      <p>For these reasons, in this study, patients with moderate or severe mitral dysfunction were excluded, as were those older than 55 years, although this criterion finds no support in the literature.<xref ref-type="bibr" rid="B32">32</xref>
				<sup>,</sup>
				<xref ref-type="bibr" rid="B33">33</xref>
			</p>
      <p>Regarding Chagas cardiomyopathy, most published studies involve patients with LV systolic dysfunction, and use LA size as a prognostic marker, showing that individuals with higher volumes had more cardiovascular events. The LV diastolic dysfunction degree is also related to the LA volume, and most significant changes in this parameter occur when there is greater LV diastolic and systolic dysfunction.</p>
      <p>Some studies of patients with Chagas cardiomyopathy and preserved LV systolic function have suggested that there is a higher risk of atrial fibrillation when the atrial diameter is high. Other authors, studying various degrees of systolic impairment, including a group of patients with Chagas disease&#8217;s indeterminate form and others without Chagas disease, have analyzed LA size and volume, and reported no significant differences between those groups regarding diastolic function. However, atrial functional parameters have not been considered.</p>
      <p>In Brazil, Nunes et al.<xref ref-type="bibr" rid="B33">33</xref> have highlighted the importance of assessing LA function, relating it to LV systolic and diastolic functions. More recently, Mancuso et al.<xref ref-type="bibr" rid="B34">34</xref> have studied LA function, assessed by using LA total and active emptying fractions, and concluded that both decreased more in patients with Chagas cardiomyopathy than in those with idiopathic dilated cardiomyopathy<xref ref-type="bibr" rid="B34">34</xref>
				<sup>,</sup>
				<xref ref-type="bibr" rid="B35">35</xref>.</p>
      <p>The indeterminate form of Chagas disease has usually no symptoms, or only electrocardiographic alterations. The same occurs when there is a mild systolic dysfunction. Clinical manifestations could vary and depend on the degree and type of the predominant involvement.</p>
      <p>Functional capacity depends on cardiac output. Stroke volume results from the difference between LV systolic and end-diastolic volume. The LV end-diastolic volume depends on diastolic function and blood supply, being directly related to LA anatomical and functional properties<xref ref-type="bibr" rid="B36">36</xref>
				<sup>,</sup>
				<xref ref-type="bibr" rid="B37">37</xref>.</p>
      <p>According to the disease classification criteria, GIII patients had significantly lower LV ejection fraction values as compared to the other groups. The mean value of this parameter in GIII (0.41) suggests moderate systolic function impairment.</p>
      <p>Significantly lower values &#8203;&#8203;of the s wave in this group strengthen the evidence of myocardial damage, because this variable is related to longitudinal LV systolic function<xref ref-type="bibr" rid="B38">38</xref>.</p>
      <p>The positive correlations of those two variables with TEF and AEF shown in this study corroborate the decrease in the reservoir function in chagasic patients with LV systolic dysfunction probably by reducing the caudal displacement of the mitral annulus during ventricular systole and the effect of succion at the beginning of diastole. Moreover, the decrease in the propulsion pump function may be related to impaired myocardial function.</p>
      <p>The mitral flow variables, usually used to assess LV diastolic function, showed no significant difference between groups. However, when analyzed on tissue Doppler, some considerations should be highlighted.</p>
      <p>Patients with normal LV ejection fraction (CG, GI and GII) had normal values of e'<sub>sep</sub>, e'<sub>lat,  </sub>e'<sub>average</sub> and E/e'<sub>average</sub>&lt; 8, indicating normal LV filling pressure. In contrast, GIII patients showed signs of LV diastolic dysfunction, when analyzed regarding the same variables, with values of &#8203;&#8203;e'<sub>sep</sub> and e'<sub>lat</sub> lower than normal for age range according to the ASE criteria.</p>
      <p>The values &#8203;&#8203;of E/e'<sub>average</sub> were significantly higher in GIII (mean = 9.6). However, this result should be analyzed carefully. Values greater than 15 are indicative of increased LV filling pressure, while those lower than 8 are considered normal. When there are intermediary values, such as in GIII, the conclusion requires association with other data. In addition, E/e&#8217; is not adequate to assess LV filling pressure in individuals without significant heart disease.</p>
      <p>The LA volume, although significantly higher in GIII, can be interpreted in this study as a diastolic dysfunction parameter and there is chronic elevation of LV filling pressure<xref ref-type="bibr" rid="B39">39</xref>.</p>
      <p>The absence of other variables that point to significant diastolic dysfunction, such as mitral flow behavior, indicates that patients in GIII have mild diastolic dysfunction, with probably normal LA filling pressure, consistent with clinical features (all in NYHA functional class II when evaluated). Drug action should also be considered in these results, because all patients in this group were on optimized medical treatment.</p>
      <p>Reservoir, conduit and pump functions can be evaluated more consistently by analyzing the LA volume variation: the reservoir function, by using TEF; the conduit function, by using PEF; and the pump function, by using AEF.</p>
      <p>The results of this study demonstrate that patients with LV dysfunction (GIII) had decreased LA reservoir and pump functions, which does not occur in patients with the indeterminate form and those with electrocardiographic alterations only.</p>
      <p>The decrease in LA pump function is probably related to the LA involvement in chagasic myopathy, with consequent contractile injury and lower ejection during atrial systole, therefore, with larger atrial volume at the end of this phase of the cardiac cycle.</p>
      <p>According to the definition of the two functions and the way they are calculated, in this study, the reservoir function deterioration might be related only to the LA and LV contractile function impairment. Other factors analyzed in this study that significantly contribute to the reservoir function (relaxation, stiffness and compliance) showed no significant differences.</p>
      <p>Some facts regarding LA reservoir and pump functions should be considered. The negative correlations of E/e'<sub>average</sub> and these two parameters of atrial function demonstrate the influence of LV filling pressure (LA pressure or LV diastolic pressure) on LA filling and emptying.</p>
      <p>Another highlight is the positive correlation of these two roles (reservoir and pump) with LV diastolic function, specifically with myocardial relaxation evaluated by using e&#8217; wave.</p>
      <p>The parameter used to assess conduit function (PEF) was lower in GIII, with statistical significance. The positive correlation of the e&#8217; wave with the conduit function highlights the importance of diastolic dysfunction in LA passive emptying.</p>
      <p>Usually, the clinical and pathophysiological mechanisms involved in heart failure have their focus on higher LV systolic and diastolic dysfunction. The present study demonstrates that LA can play a critical role in this process. Determining the functional boundary of each structure in this context is still a big challenge.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>In patients with Chagas cardiomyopathy and LV systolic dysfunction, there was an impairment in LA reservoir, conduit and pump functions. Those with normal systolic function showed no alterations in these parameters. There was a correlation between LA function and LV systolic and diastolic functions assessed on tissue Doppler imaging.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>This study was funded by FAPESP.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This article is part of the thesis of Doctoral submitted by Claudia da Silva Fragata, from Faculdade de Medicina da Universidade de S&#227;o Paulo.</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="SA1" xml:lang="pt">
    <front-stub>
      <title-group>
        <article-title>Fun&#231;&#227;o Atrial Esquerda em Pacientes com Miocardiopatia Chag&#225;sica Cr&#244;nica</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Fragata</surname>
            <given-names>Claudia da Silva</given-names>
          </name>
          <xref ref-type="aff" rid="aff03">1</xref>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Matsumoto</surname>
            <given-names>Afonso Y.</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ramires</surname>
            <given-names>Felix J. A.</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>Fabio</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Buck</surname>
            <given-names>Paula de C&#225;ssia</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Salemi</surname>
            <given-names>Vera Maria C.</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nastari</surname>
            <given-names>Luciano</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mady</surname>
            <given-names>Charles</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ianni</surname>
            <given-names>Barbara Maria</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff03">
        <label>1</label>
        <institution content-type="orgname">Instituto Dante Pazzanese de Cardiologia</institution>
        <institution content-type="orgdiv1">Se&#231;&#227;o M&#233;dica de Eletrofisiologia</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Se&#231;&#227;o M&#233;dica de Eletrofisiologia, Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo - Brasil</institution>
        <institution content-type="normalized">Instituto Dante Pazzanese de Cardiologia</institution>
      </aff>
      <aff id="aff04">
        <label>2</label>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Instituto do Cora&#231;&#227;o</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Unidade de Miocardiopatia, Instituto do Cora&#231;&#227;o (InCor), Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo - Brasil</institution>
        <institution content-type="normalized">Universidade de S&#227;o Paulo</institution>
      </aff>
      <author-notes>
        <corresp id="c02"><bold>Correspond&#234;ncia: Claudia da Silva Fragata</bold>, Se&#231;&#227;o M&#233;dica de Eletrofisiologia, Instituto Dante Pazzanese de Cardiologia, Av. Dr. Dante Pazzanese, 500. CEP: 04012-918. S&#227;o Paulo, SP - Brasil. email:   <email>claudiadasilvafragata@gmail.com</email>;   <email>claudia.fragata@dantepazzanese.org.br</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: Fragata CS, Matsumoto AY, Ramires FJA, Fernandes F, Buck PC, Salemi VMC, Mady C, Ianni BM. Obten&#231;&#227;o de dados: Fragata CS, Matsumoto AY, Ramires FJA, Fernandes F, Buck PC, Mady C, Ianni BM. An&#225;lise e interpreta&#231;&#227;o dos dados: Fragata CS, Matsumoto AY, Ramires FJA, Fernandes F, Buck PC, Nastari L, Mady C, Ianni BM. An&#225;lise estat&#237;stica: Fragata CS, Mady C, Ianni BM. Obten&#231;&#227;o de financiamento: Fragata CS. Reda&#231;&#227;o do manuscrito: Fragata CS, Matsumoto AY, Buck PC, Salemi VMC, Nastari L, Mady C, Ianni BM. Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante:Fragata CS, Matsumoto AY, Fernandes F, Buck PC, Salemi VMC, Nastari L, Mady C, Ianni BM.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesse</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <sec>
          <title>Fundamento:</title>
          <p>A doen&#231;a de Chagas &#233; uma causa de miocardiopatia dilatada, sendo ainda pouco conhecida a fun&#231;&#227;o do &#225;trio esquerdo (AE) nessa doen&#231;a.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Avaliar as diferen&#231;as nas fun&#231;&#245;es do AE (reservat&#243;rio, conduto e bomba) e sua correla&#231;&#227;o com os par&#226;metros ecocardiogr&#225;ficos das fun&#231;&#245;es sist&#243;lica e diast&#243;lica do ventr&#237;culo esquerdo (VE).</p>
        </sec>
        <sec>
          <title>M&#233;todo:</title>
          <p>10 controles (GC) e os seguintes pacientes com doen&#231;a de Chagas: 26 com a forma indeterminada (GI); 30 com altera&#231;&#245;es eletrocardiogr&#225;ficas (GII); e 19 com disfun&#231;&#227;o de VE (GIII). Todos os pacientes foram submetidos a ecocardiografia bidimensional e em modo M, Doppler pulsado e Doppler tecidual.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Fun&#231;&#227;o de reservat&#243;rio (fra&#231;&#227;o de esvaziamento total: FET) (p &lt; 0,0001), mais baixa no GIII do que no GC (p = 0,003), GI (p &lt; 0,001) e GII (p &lt; 0,001). Fun&#231;&#227;o de conduto (fra&#231;&#227;o de esvaziamento passivo: FEP) (p = 0,004), mais baixa no GIII (GIII e GC, p = 0.06; GI e GII, p = 0.06; e GII e GIII, p = 0,07). Fun&#231;&#227;o de bomba (fra&#231;&#227;o de esvaziamento ativo: FEA) (p = 0,0001), mais baixa no GIII do que no CG (p = 0,05), GI (p&lt;0,0001) e GII (p = 0,002). Observou-se uma correla&#231;&#227;o negativa entre E/e&#8217;<sub>m&#233;dia</sub> e as fun&#231;&#245;es de reservat&#243;rio e de bomba (FET e FEA), e uma correla&#231;&#227;o positiva entre as ondas e&#8217;<sub>m&#233;dia</sub> e s&#8217; (paredes septal e lateral) e as fun&#231;&#245;es de reservat&#243;rio, conduto e bomba.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>Observou-se comprometimento das fun&#231;&#245;es do AE na miocardiopatia chag&#225;sica.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Doen&#231;a de Chagas</kwd>
        <kwd>Cardiomiopatia Chag&#225;sica</kwd>
        <kwd>Disfun&#231;&#227;o Ventricular</kwd>
        <kwd>Fun&#231;&#227;o Atrial/fisiopatologia</kwd>
        <kwd>Ecocardiografia Doppler/m&#233;todos</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A doen&#231;a de Chagas, enfermidade infecciosa descrita por Carlos Chagas em 1909, &#233; causada pelo protozo&#225;rio <italic>Trypanosoma cruzi</italic>, permanecendo sua patog&#234;nese parcialmente desconhecida<xref ref-type="bibr" rid="B01">1</xref>.</p>
        <p>A ecodopplercardiografia &#233; o m&#233;todo ideal para pesquisa cardiovascular em pacientes com doen&#231;a de Chagas, em especial para avalia&#231;&#227;o anat&#244;mica e funcional.</p>
        <p>O ecocardiograma com Doppler tecidual fornece importante informa&#231;&#227;o adicional sobre a fun&#231;&#227;o card&#237;aca. A onda s&#8217; est&#225; relacionada &#224; fun&#231;&#227;o sist&#243;lica longitudinal do ventr&#237;culo esquerdo (VE), enquanto a onda e&#8217; est&#225; relacionada &#224; fun&#231;&#227;o diast&#243;lica. Uma das vantagens de se utilizar a onda e' para avaliar a fun&#231;&#227;o diast&#243;lica do VE &#233; a menor depend&#234;ncia de condi&#231;&#245;es hemodin&#226;micas de enchimento, ao contr&#225;rio do que ocorre com a onda E do fluxo mitral<xref ref-type="bibr" rid="B02">2</xref>
					<sup>-</sup>
					<xref ref-type="bibr" rid="B08">8</xref>.</p>
        <p>A fun&#231;&#227;o do AE pode ser dividida como se segue:</p>
        <list list-type="order">
          <list-item>
            <p>Fun&#231;&#227;o de reservat&#243;rio: o &#225;trio esquerdo (AE) armazena o retorno venoso pulmonar durante a contra&#231;&#227;o do VE e relaxamento isovolum&#233;trico, o que corresponde a 42% do volume de enchimento do VE armazenado no AE durante essas fases do ciclo card&#237;aco<xref ref-type="bibr" rid="B09">9</xref>. Entre os fatores que influenciam essa fun&#231;&#227;o, destacam-se: a) contra&#231;&#227;o e relaxamento atrial, relaxamento dependente da contra&#231;&#227;o; b) contra&#231;&#227;o do VE, que desloca o anel mitral no sentido caudal; c) rigidez e complanc&#234;ncia da c&#226;mara atrial; e d) s&#237;stole ventricular direita, que influencia o fluxo nas veias pulmonares.</p>
          </list-item>
          <list-item>
            <p>Fun&#231;&#227;o de conduto: o AE transfere passivamente o sangue para o VE. Depende fundamentalmente das propriedades diast&#243;licas do VE.</p>
          </list-item>
          <list-item>
            <p>Fun&#231;&#227;o de bomba: o AE contrai ativamente durante a fase final da di&#225;stole ventricular, contribuindo com 15%-30% do volume do VE no final da di&#225;stole. Depende de m&#250;ltiplos fatores, como tempo de contra&#231;&#227;o atrial, est&#237;mulo vagal, magnitude do retorno venoso (pr&#233;-carga) e press&#227;o diast&#243;lica final do VE (p&#243;s-carga).</p>
          </list-item>
        </list>
        <p>Quando o relaxamento do VE &#233; anormal, a contribui&#231;&#227;o das fun&#231;&#245;es de reservat&#243;rio e de bomba aumenta, enquanto a da fun&#231;&#227;o de conduto diminui. No entanto, com o aumento progressivo da press&#227;o de enchimento do VE e piora da disfun&#231;&#227;o diast&#243;lica, o AE atua predominantemente como um conduto<xref ref-type="bibr" rid="B10">10</xref>
					<sup>-</sup>
					<xref ref-type="bibr" rid="B14">14</xref>.</p>
        <p>A import&#226;ncia da avalia&#231;&#227;o da fun&#231;&#227;o do AE tem sido enfatizada em v&#225;rias condi&#231;&#245;es cl&#237;nicas, n&#227;o apenas como parte dos mecanismos fisiopatol&#243;gicos, mas tamb&#233;m como um fator progn&#243;stico<xref ref-type="bibr" rid="B15">15</xref>
					<sup>-</sup>
					<xref ref-type="bibr" rid="B24">24</xref>.</p>
        <p>Este estudo teve por objetivo encontrar elementos para o melhor e mais precoce reconhecimento dos seguintes:</p>
        <list list-type="alpha-lower">
          <list-item>
            <p>altera&#231;&#245;es nas fun&#231;&#245;es de AE e VE em pacientes com doen&#231;a de Chagas;</p>
          </list-item>
          <list-item>
            <p>diferen&#231;as nos par&#226;metros funcionais do AE;</p>
          </list-item>
          <list-item>
            <p>poss&#237;vel correla&#231;&#227;o entre os dados de fun&#231;&#227;o do AE e os par&#226;metros ecodopplercardiogr&#225;ficos de fun&#231;&#245;es sist&#243;lica e diast&#243;lica do VE.</p>
          </list-item>
        </list>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Este estudo incluiu pacientes selecionados consecutivamente no ambulat&#243;rio de Miocardiopatia &#8211; Doen&#231;as da Aorta do Instituto do Cora&#231;&#227;o, da Faculdade de Medicina da Universidade de S&#227;o Paulo, de ambos os sexos, com idades variando de 18 a 55 anos. Esses pacientes foram submetidos a exame cl&#237;nico, eletrocardiografia, ecocardiografia e exames laboratoriais (ELISA e imunofluoresc&#234;ncia para doen&#231;a de Chagas, glicemia e creatinina s&#233;rica). Volunt&#225;rios saud&#225;veis e pareados para idade foram tamb&#233;m examinados, constituindo o grupo controle (GC).</p>
        <p>Os medicamentos usuais foram mantidos durante os exames [inibidores da enzima de convers&#227;o da angiotensina, betabloqueadores, diur&#233;ticos nos pacientes com disfun&#231;&#227;o sist&#243;lica do VE].</p>
        <p>Os crit&#233;rios de exclus&#227;o foram: doen&#231;as sist&#234;micas associadas; arritmia ventricular ou batimentos ventriculares prematuros (&#8805; 10/hora em Holter anterior ou frequente no exame f&#237;sico); fibrila&#231;&#227;o atrial; insufici&#234;ncia mitral moderada ou grave; e dispositivos card&#237;acos eletr&#244;nicos implantados.</p>
        <p>Os pacientes com doen&#231;a de Chagas foram classificados em tr&#234;s grupos:</p>
        <list list-type="bullet">
          <list-item>
            <p>Grupo I (GI): forma indeterminada (assintom&#225;ticos com achados normais de eletrocardiografia, radiografia de t&#243;rax e exames contrastados de es&#226;fago e c&#243;lon);</p>
          </list-item>
          <list-item>
            <p>Grupo II (GII): anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &#8805; 0,55;</p>
          </list-item>
          <list-item>
            <p>Grupo III (GIII): anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &lt; 0,55.</p>
          </list-item>
        </list>
        <sec>
          <title>Aspecto &#233;tico</title>
          <p>Este estudo foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa do Hospital das Cl&#237;nicas da Universidade de S&#227;o Paulo (CAPPesq - No. 0713/08). Todos os sujeitos inclu&#237;dos assinaram o termo de consentimento livre e esclarecido, conforme as regula&#231;&#245;es &#233;ticas.</p>
        </sec>
        <sec>
          <title>Estudo ecocardiogr&#225;fico</title>
          <p>Todos os pacientes foram submetidos a ecocardiografia bidimensional e em modo M, Doppler pulsado e Doppler tecidual, usando-se um sistema de ultrassom comercialmente dispon&#237;vel (Sequoia, Acuson-Siemens, Mountain View, Calif&#243;rnia, EUA).</p>
          <p>As medidas quantitativas inclu&#237;ram os di&#226;metros de AE e VE na ecocardiografia em modo M, e os volumes do AE m&#225;ximo, pr&#233;-onda-P, e m&#237;nimo (VAE<sub>m&#225;x</sub>, VAE<sub>pr&#233;</sub> e VAE<sub>m&#237;n</sub>, respectivamente) usando-se o m&#233;todo de Simpson modificado na ecocardiografia bidimensional com corte de quatro c&#226;maras, conforme recomenda&#231;&#227;o da Sociedade Americana de Ecocardiografia (<italic>American Society of Echocardiography</italic> - ASE).</p>
          <p>Calculou-se a fra&#231;&#227;o de eje&#231;&#227;o do VE usando-se o m&#233;todo de Teichholz para uniformiza&#231;&#227;o<xref ref-type="bibr" rid="B25">25</xref>
						<sup>-</sup>
						<xref ref-type="bibr" rid="B27">27</xref>.</p>
          <p>As velocidades transmitrais foram obtidas segundo as recomenda&#231;&#227;oes da ASE. As medidas inclu&#237;ram as velocidades da onda E e da onda A, a rela&#231;&#227;o E/A, e o tempo de desacelera&#231;&#227;o da onda E.</p>
          <p>O Doppler tecidual foi realizado com corte apical de quatro c&#226;maras. As medidas inclu&#237;ram as ondas sist&#243;lica (s&#8217;), diast&#243;lica inicial (e&#8217;) e diast&#243;lica tardia (a&#8217;), obtidas das margens lateral e septal do anel mitral, sendo a m&#233;dia dos dois locais (e&#8217;<sub>m&#233;dia</sub>) usada para calcular a rela&#231;&#227;o E/e&#8217;, que foi tamb&#233;m estimada a partir da press&#227;o de enchimento do VE.</p>
          <p>Todos os exames e as medidas foram realizados por um mesmo observador, e a m&#233;dia de tr&#234;s a cinco ciclos card&#237;acos consecutivos foi usada neste estudo.</p>
          <p>Os pacientes foram posicionados em dec&#250;bito lateral esquerdo, com inclina&#231;&#227;o do tronco de 20&#176; a 30&#176;, sendo os eletrodos posicionados para a obten&#231;&#227;o dos tra&#231;ados eletrocardiogr&#225;ficos.</p>
          <p>Todas as medidas ecocardiogr&#225;ficas foram realizadas conforme as recomenda&#231;&#245;es da ASE<xref ref-type="bibr" rid="B26">26</xref>
						<sup>-</sup>
						<xref ref-type="bibr" rid="B28">28</xref>.</p>
          <p>Na ecocardiografia bidimensional, os seguintes par&#226;metros foram calculados, usando-se o m&#233;todo de Simpson modificado:</p>
          <list list-type="bullet">
            <list-item>
              <p>VAE<sub>m&#225;x</sub> (em ml), medido no final da s&#237;stole, logo antes da abertura da valva mitral;</p>
            </list-item>
            <list-item>
              <p>VAE<sub>m&#237;n</sub> (em ml), medido no final da di&#225;stole, logo antes do fechamento da valva mitral e ap&#243;s a onda P;</p>
            </list-item>
            <list-item>
              <p>VAE<sub>pr&#233;</sub> (em ml), medido imediatamente antes da onda P (antes da contra&#231;&#227;o atrial).</p>
            </list-item>
          </list>
          <p>Os volumes e os di&#226;metros diast&#243;licos do VE foram corrigidos para a &#225;rea de superf&#237;cie corporal (ASC), calculada usando-se o m&#233;todo de Dubois.</p>
        </sec>
        <sec>
          <title>Avalia&#231;&#227;o da fun&#231;&#227;o atrial esquerda</title>
          <p>A fun&#231;&#227;o de reservat&#243;rio do AE foi analisada atrav&#233;s da fra&#231;&#227;o de esvaziamento total (FET), calculada conforme a seguinte f&#243;rmula: FET = (VAE<sub>m&#225;x</sub> - VAE<sub>m&#237;n</sub>) / VAE<sub>m&#225;x</sub>.</p>
          <p>A fun&#231;&#227;o de conduto do AE foi analisada atrav&#233;s da fra&#231;&#227;o de esvaziamento passivo (FEP), calculada conforme a seguinte f&#243;rmula: FEP = (VAE<sub>m&#225;x</sub> &#8211; VAE<sub>pr&#233;</sub>) / VAE<sub>m&#225;x</sub>.</p>
          <p>A fun&#231;&#227;o de bomba do AE foi analisada atrav&#233;s da fra&#231;&#227;o de esvaziamento ativo (FEA), calculada conforme a seguinte f&#243;rmula: FEA = (VAE<sub>pr&#233;</sub> - VAE<sub>m&#237;n</sub>) / VAE<sub>pr&#233;</sub>.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>As medidas quantitativas foram descritas como m&#233;dia, mediana, desvio padr&#227;o e percentil. O teste n&#227;o param&#233;trico de Kruskal-Wallis foi aplicado para comparar essas medidas entre os quatro grupos. Quando houve diferen&#231;as significativas entre os grupos, utilizou-se o ajuste de Bonferroni para m&#250;ltiplas compara&#231;&#245;es.</p>
          <p>A rela&#231;&#227;o entre as medidas foi avaliada usando-se o coeficiente de correla&#231;&#227;o de Spearman. Quando significativa, um coeficiente de correla&#231;&#227;o (<italic>r</italic>) positivo indicou que valores mais altos da vari&#225;vel <italic>x</italic>corresponderam a valores mais altos da vari&#225;vel <italic>y</italic>. Para um   <italic>r</italic> negativo, a rela&#231;&#227;o foi reversa, e valores mais altos da vari&#225;vel <italic>x</italic> corresponderam a valores mais baixos da vari&#225;vel   <italic>y</italic>. De acordo com os valores absolutos de<italic>r</italic>, as correla&#231;&#245;es entre as vari&#225;veis foram as seguintes: <italic>r</italic>&lt; 0,3, correla&#231;&#227;o fraca; <italic>r</italic> &#8805; 0,3 e &lt; 0,7, correla&#231;&#227;o moderada; e<italic>r</italic>&#8805; 0,7, correla&#231;&#227;o forte.</p>
          <p>Adotou-se o n&#237;vel de signific&#226;ncia de p &lt; 5%. Utilizou-se o programa Statistical Package for the Social Sciences (SPSS), vers&#227;o 19, para an&#225;lise estat&#237;stica<xref ref-type="bibr" rid="B29">29</xref>
						<sup>,</sup>
						<xref ref-type="bibr" rid="B30">30</xref>.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>Este estudo incluiu 85 indiv&#237;duos divididos nos seguintes grupos: GC, 10 indiv&#237;duos; GI, 26; GII, 30; e GIII, 19. Os grupos n&#227;o diferiam quanto aos seguintes par&#226;metros: idade m&#233;dia (p = 0,107); peso (p = 0,815); altura (p = 0,880); ASC (p = 0,791); frequ&#234;ncia card&#237;aca (p = 0,164); e sexo (p = 0,492) (<xref ref-type="table" rid="t07">Tabela 1</xref>).</p>
        <table-wrap id="t07">
          <label>Tabela 1</label>
          <caption>
            <title>Idade, caracter&#237;sticas antropom&#233;tricas, press&#227;o arterial e frequ&#234;ncia card&#237;aca dos participantes do estudo</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th rowspan="2" align="left">
                  <bold>Vari&#225;veis</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>GC (n =10)</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>GI (n =26)</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>GII (n =30)</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>GIII (n =19)</bold>
                </th>
                <th rowspan="2" align="center">
                  <bold>p</bold>
                </th>
              </tr>
              <tr>
                <th>
                  <bold>m&#233;dia &#177; DP</bold>
                </th>
                <th>
                  <bold>m&#233;dia &#177; DP</bold>
                </th>
                <th>
                  <bold>m&#233;dia &#177; DP</bold>
                </th>
                <th>
                  <bold>m&#233;dia &#177; DP</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>Idade (anos)</td>
                <td align="center">40 &#177; 6</td>
                <td align="center">46 &#177; 6</td>
                <td align="center">43 &#177; 8</td>
                <td align="center">43 &#177; 7</td>
                <td align="center">0,11</td>
              </tr>
              <tr>
                <td>Peso (kg)</td>
                <td align="center">68 &#177; 13</td>
                <td align="center">68 &#177; 12</td>
                <td align="center">68 &#177; 11</td>
                <td align="center">71 &#177; 13</td>
                <td align="center">0,82</td>
              </tr>
              <tr>
                <td>Altura (cm)</td>
                <td align="center">162 &#177; 8</td>
                <td align="center">163 &#177; 7</td>
                <td align="center">162 &#177; 9</td>
                <td align="center">164 &#177; 10</td>
                <td align="center">0,88</td>
              </tr>
              <tr>
                <td>ASC (m<sup>2</sup>)</td>
                <td align="center">1,70 &#177; 0,2</td>
                <td align="center">1,72 &#177; 0,2</td>
                <td align="center">1,70 &#177; 0,2</td>
                <td align="center">1,80 &#177; 0,2</td>
                <td align="center">0,79</td>
              </tr>
              <tr>
                <td>PAS (mm Hg)</td>
                <td align="center">109 &#177; 9</td>
                <td align="center">114 &#177; 10</td>
                <td align="center">118 &#177; 12</td>
                <td align="center">109 &#177; 10</td>
                <td align="center">0,05</td>
              </tr>
              <tr>
                <td>PAD (mm Hg)</td>
                <td align="center">70 &#177; 9</td>
                <td align="center">73 &#177; 8</td>
                <td align="center">72 &#177; 8</td>
                <td align="center">67 &#177; 8</td>
                <td align="center">0,14</td>
              </tr>
              <tr>
                <td>FC (bpm)</td>
                <td align="center">68 &#177; 10</td>
                <td align="center">70 &#177; 9</td>
                <td align="center">67 &#177; 9</td>
                <td align="center">64 &#177; 10</td>
                <td align="center">0,16</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>GC: grupo controle; GI: forma indeterminada; GII anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &#8805; 0,55; GIII: anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &lt; 0,55; DP: desvio padr&#227;o; ASC: &#225;rea de superf&#237;cie corporal; PAS: press&#227;o arterial sist&#243;lica; PAD: press&#227;o arterial diast&#243;lica; FC: freq&#252;&#234;ncia card&#237;aca.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <sec>
          <title>Os par&#226;metros ecocardiogr&#225;ficos basais de AE e VE foram:</title>
          <sec>
            <title>&#8226; &#193;trio esquerdo</title>
            <p>Houve significativa diferen&#231;a entre os grupos em rela&#231;&#227;o ao VAE<sub>m&#225;x</sub>(p &lt;0,0001). O valor m&#233;dio foi maior no GIII em compara&#231;&#227;o ao GC (p = 0,001), GI (p = 0,0001) e GII (p = 0,012). Da mesma forma, os valores m&#233;dios do GIII &#8203;&#8203;foram maiores quando comparados aos do GII e GC (p = 0,03). N&#227;o houve significativa diferen&#231;a entre GC e GI.</p>
            <p>Houve significativa diferen&#231;a entre os grupos em rela&#231;&#227;o ao VAE<sub>pr&#233;</sub>(p &lt;0,0001). O valor m&#233;dio foi maior no GIII em compara&#231;&#227;o ao GC (p = 0,0004), GI (p = 0,0003) e GII (p = 0,012). Da mesma forma, os valores m&#233;dios do GIII &#8203;&#8203;foram maiores quando comparados aos do GII e GC (p = 0,012). N&#227;o houve significativa diferen&#231;a entre GC e GI.</p>
            <p>Houve significativa diferen&#231;a entre os grupos em rela&#231;&#227;o ao VAE<sub>m&#237;n</sub>(p &lt; 0,0001). O valor m&#233;dio foi maior no GIII em compara&#231;&#227;o ao GC (p = 0,0003), GI (p &lt; 0,0001) e GII (p = 0,0007). N&#227;o houve diferen&#231;a significativa no GI e GII em compara&#231;&#227;o ao GC, e nem entre GI e GII (<xref ref-type="table" rid="t08">Tabela 2</xref>).</p>
            <table-wrap id="t08">
              <label>Tabela 2</label>
              <caption>
                <title>Par&#226;metros ecocardlogr&#225;flcos basais corrigidos para superf&#237;cie corporal, com respectivas m&#233;dias, desvios padr&#245;es (DP) e valores de p (teste de Kruskal-Wallis)</title>
              </caption>
              <table frame="hsides" rules="groups">
                <thead>
                  <tr>
                    <th rowspan="2" align="left">
                      <bold>Vari&#225;veis</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GC (n = 10)</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GI (n = 26)</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GII (n = 30)</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GIII (n = 19)</bold>
                    </th>
                    <th rowspan="2" align="center">
                      <bold>P</bold>
                    </th>
                  </tr>
                  <tr>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>DDVE (mm/m<sup>2</sup>)</td>
                    <td align="center">25 &#177; 2,1</td>
                    <td align="center">25,9 &#177; 2,3</td>
                    <td align="center">28,4 &#177; 3,3<xref ref-type="table-fn" rid="TFN07">#</xref>
										</td>
                    <td align="center">37,1 &#177; 5,0<xref ref-type="table-fn" rid="TFN06">*</xref>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                  <tr>
                    <td>VAE<sub>m&#225;x</sub> (ml/m<sup>2</sup>)</td>
                    <td align="center">23 &#177; 4,5</td>
                    <td align="center">27 &#177; 6,4</td>
                    <td align="center">31 &#177; 8,7<xref ref-type="table-fn" rid="TFN07">#</xref>
										</td>
                    <td align="center">42 &#177; 12,1<xref ref-type="table-fn" rid="TFN06">*</xref>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                  <tr>
                    <td>VAE<sub>p&#233;P</sub> p (ml/m<sup>2</sup>)</td>
                    <td align="center">14 &#177; 3</td>
                    <td align="center">17 &#177; 4,21</td>
                    <td align="center">21 &#177; 6,5<xref ref-type="table-fn" rid="TFN07">#</xref>
										</td>
                    <td align="center">32 &#177; 12<xref ref-type="table-fn" rid="TFN06">*</xref>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                  <tr>
                    <td>VAE<sub>m&#237;n</sub> (ml/m<sup>2</sup>)</td>
                    <td align="center">8,5 &#177; 2</td>
                    <td align="center">9,8 &#177; 2,9</td>
                    <td align="center">12,3 &#177; 5,9</td>
                    <td align="center">24 &#177; 10,9<xref ref-type="table-fn" rid="TFN06">*</xref>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN06">
                  <label>*</label>
                  <p>Valores de GIII significativamente diferentes daqueles dos outros grupos.</p>
                </fn>
                <fn id="TFN07">
                  <label>#</label>
                  <p>Valores de GII significativamente diferentes daqueles do GC.</p>
                  <p> GC: grupo controle; GI: forma indeterminada; GII anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &#8805; 0,55; GIII: anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &lt; 0,55; DDVE: di&#226;metro diast&#243;lico ventricular esquerdo; VAE<sub>m&#225;x</sub>: volume atrial esquerdo m&#225;ximo; VAE<sub>pr&#233; P</sub>: volume atrial esquerdo pr&#233;-onda-P; VAE<sub>m&#237;n</sub>: volume atrial esquerdo m&#237;nimo.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
          <sec>
            <title>&#8226; Ventr&#237;culo esquerdo</title>
            <p>Houve significativa diferen&#231;a entre os grupos quanto ao di&#226;metro diast&#243;lico do VE (p &lt;0,0001). O valor m&#233;dio foi maior no GIII em compara&#231;&#227;o ao GC (p = 0,001), GI (p &lt; 0,0001) e GII (p &lt; 0,0001), e no GII em compara&#231;&#227;o ao GC (p = 0,05). N&#227;o houve significativa diferen&#231;a entre GC e GI (<xref ref-type="table" rid="t08">Tabela 2</xref>).</p>
          </sec>
        </sec>
        <sec>
          <title>Par&#226;metro de fun&#231;&#227;o sist&#243;lica do VE</title>
          <sec>
            <title>&#8226; Fra&#231;&#227;o de eje&#231;&#227;o</title>
            <p>Houve significativa diferen&#231;a entre os grupos quanto &#224; fra&#231;&#227;o de eje&#231;&#227;o do VE (p &lt;0,0001). O valor m&#233;dio foi menor no GIII em compara&#231;&#227;o ao GC (p = 0,001), GI (p &lt;0,0001) e GII (p &lt;0,0001). N&#227;o houve significativa diferen&#231;a entre GC, GI e GII quando comparados entre si (<xref ref-type="table" rid="t09">Tabela 3</xref>).</p>
            <table-wrap id="t09">
              <label>Tabela 3</label>
              <caption>
                <title>Vari&#225;veis de fluxo mitral usadas para avaliar a fun&#231;&#227;o diast&#243;lica do ventr&#237;culo esquerdo e a fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo, com respectivas m&#233;dias, desvios padr&#245;es (DP) e valores de p (teste de Kruskal-Wallis)</title>
              </caption>
              <table frame="hsides" rules="groups">
                <thead>
                  <tr>
                    <th rowspan="2">
                      <bold>Vari&#225;veis</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GC (n = 10)</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GI (n = 26)</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GII (n = 30)</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GIII (n = 19)</bold>
                    </th>
                    <th rowspan="2" align="center">
                      <bold>P</bold>
                    </th>
                  </tr>
                  <tr>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>onda E (cm/s)</td>
                    <td align="center">74,2 &#177; 12,7</td>
                    <td align="center">71,9 &#177; 14,4</td>
                    <td align="center">71,2 &#177; 17,4</td>
                    <td align="center">68 &#177; 19,4</td>
                    <td align="center">0,7635</td>
                  </tr>
                  <tr>
                    <td>onda A (cm/s)</td>
                    <td align="center">54,1 &#177; 4,9</td>
                    <td align="center">62,5 &#177; 7,9</td>
                    <td align="center">59,7 &#177; 12,0</td>
                    <td align="center">58,9 &#177; 16,9</td>
                    <td align="center">0,0949</td>
                  </tr>
                  <tr>
                    <td>E/A</td>
                    <td align="center">1,4 &#177;0,2</td>
                    <td align="center">1,2 &#177; 0,3</td>
                    <td align="center">1,2 &#177; 0,4</td>
                    <td align="center">1,3 &#177; 0,6</td>
                    <td align="center">0,2279</td>
                  </tr>
                  <tr>
                    <td>TDE (ms)</td>
                    <td align="center">174,4 &#177; 18,1</td>
                    <td align="center">198,8 &#177; 30,7</td>
                    <td align="center">198,9 &#177; 33,1</td>
                    <td align="center">210 &#177; 64,6</td>
                    <td align="center">0,1836</td>
                  </tr>
                  <tr>
                    <td>FEVE</td>
                    <td align="center">0,67 &#177; 0,05</td>
                    <td align="center">0,66 &#177; 0,04</td>
                    <td align="center">0,67 &#177; 0,06</td>
                    <td align="center">0,41 &#177; 0,07<xref ref-type="table-fn" rid="TFN08">*</xref>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn>
                  <p>* Valores de GIII significativamente diferentes daqueles dos outros grupos.</p>
                </fn>
                <fn id="TFN08">
                  <label>#</label>
                  <p>Valores de GII significativamente diferentes daqueles do GC.</p>
                </fn>
                <fn>
                  <p>GC: grupo controle; GI: forma indeterminada; GII anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &#8805; 0,55; GIII: anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &lt; 0,55; DDVE: di&#226;metro diast&#243;lico ventricular esquerdo; VAE<sub>m&#225;x</sub>: volume atrial esquerdo m&#225;ximo; VAE<sub>pr&#233; P</sub>: volume atrial esquerdo pr&#233;-onda-P; VAE<sub>m&#237;n</sub>: volume atrial esquerdo m&#237;nimo.e atrial esquerdo m&#237;nimo.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
        </sec>
        <sec>
          <title>Par&#226;metros de fun&#231;&#227;o diast&#243;lica do VE:</title>
          <sec>
            <title>&#8226; Fluxo mitral</title>
            <p>N&#227;o houve significativa diferen&#231;a entre os grupos quanto &#224;s ondas E (p = 0,76) e A (p = 0,09), &#224; rela&#231;&#227;o E/A (p = 0,22) e ao tempo de desacelera&#231;&#227;o da onda E (p = 0,18) (<xref ref-type="table" rid="t09">Tabela 3</xref>).</p>
          </sec>
          <sec>
            <title>&#8226; Doppler tecidual</title>
            <p>Houve significativa diferen&#231;a entre os grupos quanto &#224; avalia&#231;&#227;o no Doppler tecidual da onda e'<sub>lat</sub> (p = 0,0004). O valor m&#233;dio foi menor no GIII em compara&#231;&#227;o ao GC (p = 0,0076), GI (p = 0,001) e GII (p = 0,036). N&#227;o houve diferen&#231;a significativa entre GC, GI e GII quanto aos valores m&#233;dios.</p>
            <p>Houve significativa diferen&#231;a entre os grupos quanto &#224; avalia&#231;&#227;o no Doppler tecidual da onda e'<sub>sep</sub> (p &lt; 0,001). O valor m&#233;dio foi menor no GIII em compara&#231;&#227;o ao GC (p = 0,0004), GI (p &lt; 0,001) e GII (p = 0,0001). N&#227;o houve diferen&#231;a significativa entre GC, GI e GII quanto aos valores m&#233;dios.</p>
            <p>Observou-se diferen&#231;a significativa entre os grupos com rela&#231;&#227;o &#224; avalia&#231;&#227;o da onda e'<sub>m&#233;dia</sub> no Doppler tecidual (p &lt; 0,001). O valor m&#233;dio foi menor no GIII em compara&#231;&#227;o ao GC (p &lt; 0,001), GI (p &lt; 0,001) e GII (p &lt; 0,001). N&#227;o houve diferen&#231;a significativa entre GC, GI e GII quanto aos valores m&#233;dios.</p>
            <p>Com rela&#231;&#227;o &#224; avalia&#231;&#227;o de E/e'<sub>m&#233;dia</sub>, observou-se diferen&#231;a significativa entre os grupos (p &lt; 0,001). O valor m&#233;dio foi significativamente maior no GIII em compara&#231;&#227;o ao GC (p = 0,009), GI (p = 0,0001) e GII (p = 0,007). N&#227;o houve diferen&#231;a significativa quanto aos valores m&#233;dios entre GC, GI e GII (<xref ref-type="table" rid="t10">Tabela 4</xref>).</p>
            <table-wrap id="t10">
              <label>Tabela 4</label>
              <caption>
                <title>Vari&#225;veis de Doppler tecidual usadas para avaliar a fun&#231;&#227;o diast&#243;lica do ventr&#237;culo esquerdo, com respectivas m&#233;dias, desvios padr&#245;es (DP) e valores de p (teste de Kruskal-Wallis)</title>
              </caption>
              <table frame="hsides" rules="groups">
                <thead>
                  <tr>
                    <th rowspan="2">
                      <bold>Vari&#225;veis</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GC (n = 10)</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GI (n = 26)</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GII (n = 30)</bold>
                    </th>
                    <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                      <bold>GIII (n = 19)</bold>
                    </th>
                    <th rowspan="2" align="center">
                      <bold>P</bold>
                    </th>
                  </tr>
                  <tr>
                    <th>
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th>
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th>
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th>
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>s' <sub>lat</sub>
										</td>
                    <td align="center">11,4 &#177; 2,2</td>
                    <td align="center">13,2 &#177; 2,0</td>
                    <td align="center">13,5 &#177; 2,7</td>
                    <td align="center">8,0 &#177; 1,9<sup>2</sup>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                  <tr>
                    <td>e' <sub>lat</sub>
										</td>
                    <td align="center">15 &#177; 2,3</td>
                    <td align="center">15,1 &#177; 3,2</td>
                    <td align="center">13,3 &#177; 3,1</td>
                    <td align="center">9,8 &#177; 3,7<xref ref-type="table-fn" rid="TFN09">*</xref>
										</td>
                    <td align="center">0,0004</td>
                  </tr>
                  <tr>
                    <td>s'<sub>sep</sub>
										</td>
                    <td align="center">9,2 &#177; 2,8</td>
                    <td align="center">10,6 &#177; 1,5</td>
                    <td align="center">10,5 &#177; 2,0</td>
                    <td align="center">7,3 &#177; 1,8<xref ref-type="table-fn" rid="TFN09">*</xref>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                  <tr>
                    <td>e'<sub>sep</sub>
										</td>
                    <td align="center">11,0 &#177; 2,1</td>
                    <td align="center">10,5 &#177; 2,3</td>
                    <td align="center">9,7 &#177; 1,8</td>
                    <td align="center">7 &#177; 1,5<xref ref-type="table-fn" rid="TFN09">*</xref>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                  <tr>
                    <td>e <sub>m&#233;dia</sub>
										</td>
                    <td align="center">13 &#177; 1,6</td>
                    <td align="center">12,8 &#177; 2,5</td>
                    <td align="center">11,3 &#177; 2,5</td>
                    <td align="center">8,1 &#177; 2,6<xref ref-type="table-fn" rid="TFN09">*</xref>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                  <tr>
                    <td>E/e' <sub>m&#233;dia</sub>
										</td>
                    <td align="center">5,8&#177;1,5</td>
                    <td align="center">5,7&#177;0,8</td>
                    <td align="center">6,6&#177;2,3</td>
                    <td align="center">9,6&#177;3,4<xref ref-type="table-fn" rid="TFN09">*</xref>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN09">
                  <label>*</label>
                  <p>Valores de GIII significativamente diferentes daqueles dos outros grupos.</p>
                  <p>GC: grupo controle; GI: forma indeterminada; GII anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &#8805; 0,55; GIII: anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &lt; 0,55; s&#8217;<sub>lat</sub>: onda s na parede lateral (Doppler tecidual); e&#8217;<sub>lat</sub>: onda e na parede lateral (Doppler tecidual); s&#8217;<sub>sep</sub>: onda s na parede septal (Doppler tecidual); e&#8217;<sub>sep</sub>: onda e na parede septal (Doppler tecidual); e&#8217;<sub>m&#233;dia</sub>: m&#233;dia entre e&#8217;<sub>lat</sub> e e&#8217;<sub>sep</sub>; E/e&#8217;<sub>m&#233;dia</sub>: rela&#231;&#227;o onda E /e&#8217;<sub>m&#233;dia</sub>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
        </sec>
        <sec>
          <title>Par&#226;metros de fun&#231;&#227;o do AE</title>
          <sec>
            <title>&#8226; Fun&#231;&#227;o de reservat&#243;rio</title>
            <p>A FET diferiu significativamente entre os grupos (p &lt; 0,0001). Os valores m&#233;dios foram significativamente mais baixos no GIII em compara&#231;&#227;o ao GC (p = 0,003), GI (p &lt; 0,001) e GII (p &lt; 0,001). Os valores m&#233;dios n&#227;o diferiram significativamente entre GC, GI e GII (<xref ref-type="table" rid="t11">Tabela 5</xref>).</p>
            <table-wrap id="t11">
              <label>Tabela 5</label>
              <caption>
                <title>Avalia&#231;&#227;o da fun&#231;&#227;o atrial esquerda com respectivas m&#233;dias, desvios padr&#245;es (DP) e valores de p (teste de Kruskal-Wallis)</title>
              </caption>
              <table frame="hsides" rules="groups">
                <thead>
                  <tr style="border-bottom-style:solid; border-bottom-width:thin">
                    <th>&#160;</th>
                    <th align="center">
                      <bold>GC (n = 10)</bold>
                    </th>
                    <th align="center">
                      <bold>GI (n = 26)</bold>
                    </th>
                    <th align="center">
                      <bold>GII (n = 30)</bold>
                    </th>
                    <th align="center">
                      <bold>GIII (n = 19)</bold>
                    </th>
                    <th align="center">&#160;</th>
                  </tr>
                  <tr>
                    <th>
                      <bold>Vari&#225;veis</bold>
                    </th>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th align="center">
                      <bold>m&#233;dia &#177; DP</bold>
                    </th>
                    <th align="center">
                      <bold>P</bold>
                    </th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>FEA (ml)</td>
                    <td align="center">0,38&#177;0,05</td>
                    <td align="center">0,44&#177;0,08</td>
                    <td align="center">0,42&#177;0,11</td>
                    <td align="center">0,27&#177;0,11<xref ref-type="table-fn" rid="TFN10">*</xref>
										</td>
                    <td align="center">0,0001</td>
                  </tr>
                  <tr>
                    <td>FET (ml)</td>
                    <td align="center">0,63&#177;0,09</td>
                    <td align="center">0,63&#177;0,08</td>
                    <td align="center">0,62&#177;0,10</td>
                    <td align="center">0,44&#177;0,13<xref ref-type="table-fn" rid="TFN10">*</xref>
										</td>
                    <td align="center">&lt; 0,0001</td>
                  </tr>
                  <tr>
                    <td>FEP (ml)</td>
                    <td align="center">0,39&#177;0,12</td>
                    <td align="center">0,35&#177;0,10</td>
                    <td align="center">0,35&#177;0,10</td>
                    <td align="center">0,23&#177;0,12</td>
                    <td align="center">0,004</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN10">
                  <label>*</label>
                  <p>Valores de GIII significativamente diferentes daqueles dos outros grupos.</p>
                </fn>
                <fn>
                  <p>GC: grupo controle; GI: forma indeterminada; GII anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &#8805; 0,55; GIII: anormalidades eletrocardiogr&#225;ficas e fra&#231;&#227;o de eje&#231;&#227;o de VE &lt; 0,55; FEA: fra&#231;&#227;o de esvaziamento ativo; FET: fra&#231;&#227;o de esvaziamento total; FEP: fra&#231;&#227;o de esvaziamento passivo.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
          <sec>
            <title>&#8226; Fun&#231;&#227;o de conduto</title>
            <p>A FEP diferiu significativamente entre os grupos (p = 0,004). O valor m&#233;dio foi menor no GIII, mas sem significado estat&#237;stico, quando comparado ao GIII e GC (p = 0,06), GI e GII (p = 0,06), e GII e GIII (p = 0,07) (<xref ref-type="table" rid="t11">Tabela 5</xref>).</p>
          </sec>
          <sec>
            <title>&#8226; Fun&#231;&#227;o de bomba</title>
            <p>A FEA diferiu significativamente entre os grupos (p = 0,0001). O valor m&#233;dio foi menor no GIII quando comparado ao GC (p = 0,05), GI (p &lt; 0,0001) e GII (p = 0,002) (<xref ref-type="table" rid="t11">Tabela 5</xref>).</p>
          </sec>
        </sec>
        <sec>
          <title>An&#225;lise das correla&#231;&#245;es</title>
          <p>Observou-se uma correla&#231;&#227;o negativa entre E/e'<sub>m&#233;dia  </sub>e as fun&#231;&#245;es de reservat&#243;rio e de bomba (FET e FEA), e uma correla&#231;&#227;o positiva da onda e'<sub>m&#233;dia</sub> com a onda s' (paredes septal e lateral) e as fun&#231;&#245;es de reservat&#243;rio, conduto e bomba. A<xref ref-type="table" rid="t12">Tabela 6</xref>apresenta as correla&#231;&#245;es entre as vari&#225;veis.</p>
          <table-wrap id="t12">
            <label>Tabela 6</label>
            <caption>
              <title>Correla&#231;&#245;es</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th>&#160;</th>
                  <th>
                    <bold>E/e&#8217;<sub>m&#233;dia</sub>
										</bold>
                  </th>
                  <th>
                    <bold>e&#8217;<sub>m&#233;dia</sub>
										</bold>
                  </th>
                  <th>
                    <bold>FEVE</bold>
                  </th>
                  <th>
                    <bold>s&#8217;<sub>sep</sub>
										</bold>
                  </th>
                  <th>
                    <bold>s&#8217;<sub>lat</sub>
										</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td rowspan="2">FET</td>
                  <td>r = -0,26</td>
                  <td>r= 0,53</td>
                  <td>r = 0,35</td>
                  <td>r = 0,33</td>
                  <td>r = 0,28</td>
                </tr>
                <tr>
                  <td>p = 0,02</td>
                  <td>p &lt; 0,001</td>
                  <td>p = 0,003</td>
                  <td>p = 0,003</td>
                  <td>p = 0,003</td>
                </tr>
                <tr>
                  <td rowspan="2">FEP</td>
                  <td>r = -0,09</td>
                  <td>r= 0,49</td>
                  <td>r = 0,42</td>
                  <td>r = 0,197</td>
                  <td>r = 0,118</td>
                </tr>
                <tr>
                  <td>p = 0,44</td>
                  <td>p &lt; 0,001</td>
                  <td>p &lt; 0,001</td>
                  <td>p = 0,135</td>
                  <td>p = 0,378</td>
                </tr>
                <tr>
                  <td rowspan="2">FEA</td>
                  <td>r = -0,36</td>
                  <td>r= 0,39</td>
                  <td>r = 0,35</td>
                  <td>r = 0,37</td>
                  <td>r = 0,34</td>
                </tr>
                <tr>
                  <td>p = 0,002</td>
                  <td>p = 0,001</td>
                  <td>p = 0,003</td>
                  <td>p = 0,004</td>
                  <td>p = 0,01</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn>
                <p>E/e&#8217;<sub>m&#233;dia</sub>: rela&#231;&#227;o onda E/e&#8217;<sub>m&#233;dia</sub>; s&#8217;<sub>lat</sub>: onda s na parede lateral (Doppler tecidual); s&#8217;<sub>sep</sub>: onda s na parede septal (Doppler tecidual); e&#8217;<sub>m&#233;dia</sub>: m&#233;dia entre e&#8217;<sub>lat</sub> e e&#8217;<sub>sep</sub>; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo FEA: fra&#231;&#227;o de esvaziamento ativo; FET: fra&#231;&#227;o de esvaziamento total; FEP: fra&#231;&#227;o de esvaziamento passivo.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Este estudo revela importantes caracter&#237;sticas e detalhes da rela&#231;&#227;o e da interdepend&#234;ncia das fun&#231;&#245;es sist&#243;lica e diast&#243;lica do VE e AE.</p>
        <p>A fun&#231;&#227;o do AE foi exaustivamente estudada em d&#233;cadas recentes, com especial interesse nas implica&#231;&#245;es fisiopatol&#243;gicas e progn&#243;sticas e na interrela&#231;&#227;o com as fun&#231;&#245;es sist&#243;lica e diast&#243;lica do VE. Foi investigada em v&#225;rias situa&#231;&#245;es cl&#237;nicas e doen&#231;as. Um estudo hemodin&#226;mico com registro simult&#226;neo das curvas de press&#227;o e volume &#233; o m&#233;todo de avalia&#231;&#227;o ideal, permitindo an&#225;lise do relaxamento e da complac&#234;ncia do AE, que influenciam diretamente o enchimento do AE. Trata-se, no entanto, de exame invasivo e dispendioso, sendo reservado quase exclusivamente para estudos experimentais.</p>
        <p>Uma boa alternativa &#233; a ecocardiografia, atualmente o m&#233;todo de escolha para a an&#225;lise n&#227;o invasiva do AE. Altera&#231;&#245;es nas propriedades da fun&#231;&#227;o diast&#243;lica ou em qualquer das fun&#231;&#245;es do AE (reservat&#243;rio, conduto ou bomba) podem interferir no enchimento do VE. Al&#233;m de algumas doen&#231;as cardiovasculares, o processo de envelhecimento modifica o tamanho do AE e algumas de suas fun&#231;&#245;es, em especial os esvaziamentos passivo e ativo<xref ref-type="bibr" rid="B31">31</xref>.</p>
        <p>&#201; intuitivo que todos os mecanismos envolvidos nos processos de enchimento do VE e esvaziamento do AE sejam interdependentes. Portanto, a interpreta&#231;&#227;o e a import&#226;ncia de cada fator que influencia tais processos devem ser consideradas com cuidado.</p>
        <p>Por essas raz&#245;es, este estudo excluiu pacientes com disfun&#231;&#227;o mitral moderada ou grave e aqueles com mais de 55 anos, embora tal crit&#233;rio n&#227;o tenha respaldo na literatura<xref ref-type="bibr" rid="B32">32</xref>
					<sup>,</sup>
					<xref ref-type="bibr" rid="B33">33</xref>.</p>
        <p>Quanto &#224; miocardiopatia chag&#225;sica, a maioria dos estudos publicados envolve pacientes com disfun&#231;&#227;o sist&#243;lica de VE, e utiliza o tamanho do AE como marcador progn&#243;stico, mostrando que indiv&#237;duos com maiores volumes apresentam mais eventos cardiovasculares. O grau de disfun&#231;&#227;o diast&#243;lica do VE tamb&#233;m se relaciona ao volume do AE, e as altera&#231;&#245;es mais significativas desse par&#226;metro ocorrem na presen&#231;a de maior disfun&#231;&#227;o diast&#243;lica e sist&#243;lica de VE.</p>
        <p>Alguns estudos de pacientes com miocardiopatia chag&#225;sica e preserva&#231;&#227;o da fun&#231;&#227;o sist&#243;lica de VE sugeriram maior risco de desenvolvimento de fibrila&#231;&#227;o atrial quando o di&#226;metro atrial &#233; grande. Outros autores, estudando v&#225;rios graus de comprometimento sist&#243;lico, inclusive um grupo de pacientes chag&#225;sicos com forma indeterminada e outros sem a doen&#231;a de Chagas, analisaram o tamanho e o volume do AE, e relataram a aus&#234;ncia de diferen&#231;as significativas entre os grupos quanto &#224; fun&#231;&#227;o diast&#243;lica. Entretanto, par&#226;metros de fun&#231;&#227;o atrial n&#227;o foram considerados.</p>
        <p>No Brasil, Nunes e cols.<xref ref-type="bibr" rid="B33">33</xref> ressaltaram a import&#226;ncia de se avaliar a fun&#231;&#227;o do AE, relacionando-a com as fun&#231;&#245;es sist&#243;lica e diast&#243;lica do VE. Mais recentemente, Mancuso e cols.<xref ref-type="bibr" rid="B34">34</xref> estudaram a fun&#231;&#227;o do AE, usando as fra&#231;&#245;es de esvaziamento total e ativo de AE, tendo conclu&#237;do que ambas diminuem mais em pacientes com miocardiopatia chag&#225;sica do que naqueles com miocardiopatia dilatada idiop&#225;tica<xref ref-type="bibr" rid="B34">34</xref>
					<sup>,</sup>
					<xref ref-type="bibr" rid="B35">35</xref>.</p>
        <p>Em geral, a forma indeterminada da doen&#231;a de Chagas n&#227;o apresenta sintomas, ou apenas altera&#231;&#245;es eletrocardiogr&#225;ficas. O mesmo ocorre quando h&#225; disfun&#231;&#227;o sist&#243;lica leve. As manifesta&#231;&#245;es cl&#237;nicas podem variar e dependem do grau e tipo de envolvimento predominante.</p>
        <p>A capacidade funcional depende do d&#233;bito card&#237;aco. O volume de eje&#231;&#227;o resulta da diferen&#231;a entre os volumes sist&#243;lico e diast&#243;lico final do VE. O volume final diast&#243;lico do VE depende da fun&#231;&#227;o diast&#243;lica e do suprimento sangu&#237;neo, relacionando-se diretamente com as propriedade anat&#244;micas e funcionais do AE<xref ref-type="bibr" rid="B36">36</xref>
					<sup>,</sup>
					<xref ref-type="bibr" rid="B37">37</xref>.</p>
        <p>De acordo com os crit&#233;rios de classifica&#231;&#227;o da doen&#231;a, os pacientes do GIII apresentaram valores de fra&#231;&#227;o de eje&#231;&#227;o do VE significativamente mais baixos do que aqueles dos outros grupos. O valor m&#233;dio desse par&#226;metro no GIII (0,41) sugere um moderado comprometimento da fun&#231;&#227;o sist&#243;lica.</p>
        <p>Valores significativamente mais baixos da onda s nesse grupo refor&#231;am a evid&#234;ncia de dano mioc&#225;dico, pois essa vari&#225;vel relaciona-se com a fun&#231;&#227;o sist&#243;lica longitudinal do VE<xref ref-type="bibr" rid="B38">38</xref>.</p>
        <p>As correla&#231;&#245;es positivas dessas duas vari&#225;veis com FET e FEA demonstradas neste estudo refor&#231;am a redu&#231;&#227;o da fun&#231;&#227;o de reservat&#243;rio nos pacientes chag&#225;sicos com disfun&#231;&#227;o sist&#243;lica de VE provavelmente devido &#224; diminui&#231;&#227;o do deslocamento caudal do anel mitral durante a s&#237;stole ventricular e do efeito de suc&#231;&#227;o no in&#237;cio da di&#225;stole. Al&#233;m disso, a redu&#231;&#227;o da fun&#231;&#227;o propulsora de bomba pode estar relacionada ao comprometimento da fun&#231;&#227;o mioc&#225;rdica.</p>
        <p>As vari&#225;veis do fluxo mitral, em geral usadas para avaliar a fun&#231;&#227;o diast&#243;lica do VE, diferiram significativamente entre os grupos. No entanto, quando analizadas no Doppler tecidual, algumas considera&#231;&#245;es se fazem necess&#225;rias.</p>
        <p>Pacientes com fra&#231;&#227;o de eje&#231;&#227;o do VE normal (GC, GI e GII) apresentaram valores normais de e'<sub>sep</sub>, e'<sub>lat,  </sub>e'<sub>m&#233;dia</sub> e E/e'<sub>m&#233;dia</sub> &lt; 8, indicando press&#227;o de enchimento do VE normal. Ao contr&#225;rio, os pacientes do GIII apresentaram sinais de disfun&#231;&#227;o diast&#243;lica de VE, quando as mesmas vari&#225;veis foram analisadas, com valores de e'<sub>sep</sub> e e'<sub>lat</sub> mais baixos do que o normal para a faixa et&#225;ria de acordo com os crit&#233;rios da ASE.</p>
        <p>Os valores &#8203;&#8203;de E/e'<sub>m&#233;dia</sub> foram significativamente maiores no GIII (m&#233;dia = 9,6). No entanto, esse resultado deve ser avaliado com cuidado. Valores superiores a 15 indicam aumento da press&#227;o de enchimento do VE, enquanto que inferiores a 8 s&#227;o considerados normais. Quando os valores s&#227;o intermedi&#225;rios, como no GIII, a conclus&#227;o requer a associa&#231;&#227;o com outros dados. Al&#233;m disso, a vari&#225;vel E/e&#8217; n&#227;o &#233; apropriada para a avalia&#231;&#227;o da press&#227;o de enchimento do VE em indiv&#237;duos sem cardiopatia significativa.</p>
        <p>O volume do AE, embora significativamente maior no GIII, pode ser interpretado neste estudo como um par&#226;metro de disfun&#231;&#227;o diast&#243;lica, havendo eleva&#231;&#227;o cr&#244;nica da press&#227;o de enchimento do VE<xref ref-type="bibr" rid="B39">39</xref>.</p>
        <p>A aus&#234;ncia de outras vari&#225;veis indicadoras de significativa disfun&#231;&#227;o diast&#243;lica, como comportamento do fluxo mitral, indica que os pacientes no GIII t&#234;m leve disfun&#231;&#227;o diast&#243;lica, com press&#227;o de enchimento do AE provavelmente normal, consistente com as caracter&#237;sticas cl&#237;nicas (todos em classe funcional II da NYHA). A a&#231;&#227;o de medicamentos tamb&#233;m deve ser considerada nesses resultados, pois todos os pacientes nesse grupo estavam em tratamento otimizado.</p>
        <p>As fun&#231;&#245;es de reservat&#243;rio, conduto e bomba podem ser avaliadas mais consistentemente atrav&#233;s da an&#225;lise da varia&#231;&#227;o do volume do AE: a fun&#231;&#227;o de reservat&#243;rio, usando-se FET; a fun&#231;&#227;o de conduto, usando-se FEP; e a fun&#231;&#227;o de bomba, usando-se FEA.</p>
        <p>Os resultados deste estudo demonstram que os pacientes com disfun&#231;&#227;o de VE (GIII) apresentaram redu&#231;&#227;o das fun&#231;&#245;es de reservat&#243;rio e de bomba do AE, o que n&#227;o ocorre em pacientes com a forma indeterminada e aqueles com apenas altera&#231;&#245;es eletrocardiogr&#225;ficas.</p>
        <p>A redu&#231;&#227;o da fun&#231;&#227;o de bomba do AE acha-se provavelmente relacionada ao envolvimento dessa estrutura na miopatia chag&#225;sica, com consequente dano contr&#225;til e menor eje&#231;&#227;o durante a s&#237;stole atrial, o que resulta em maior volume atrial ao final dessa fase do ciclo card&#237;aco.</p>
        <p>Pela defini&#231;&#227;o das duas fun&#231;&#245;es e a maneira como s&#227;o calculadas, neste estudo, a deteriora&#231;&#227;o da fun&#231;&#227;o de reservat&#243;rio deve estar relacionada apenas ao comprometimento da fun&#231;&#227;o contr&#225;til de AE e VE. Outros fatores que contribuem significativamente para a fun&#231;&#227;o de reservat&#243;rio (relaxamento, rigidez e complac&#234;ncia) analisados neste estudo n&#227;o apresentaram diferen&#231;as significativas.</p>
        <p>Alguns fatos concernentes &#224;s fun&#231;&#245;es de reservat&#243;rio e de bomba do AE devem ser considerados. As correla&#231;&#245;es negativas desses dois par&#226;metros de fun&#231;&#227;o atrial com a E/e'<sub>m&#233;dia</sub> demonstram a influ&#234;ncia da press&#227;o de enchimento do VE (press&#227;o de AE ou press&#227;o diast&#243;lica do VE) no enchimento e no esvaziamento do AE.</p>
        <p>Outra considera&#231;&#227;o importante &#233; a correla&#231;&#227;o positiva dessas duas fun&#231;&#245;es (reservat&#243;rio e bomba) com a fun&#231;&#227;o diast&#243;lica do VE, especificamente com o relaxamento mioc&#225;rdico avaliado usando-se a onda e&#8217;.</p>
        <p>O par&#226;metro usado para avaliar a fun&#231;&#227;o de conduto (FEP) foi mais baixo no GIII, com significado estat&#237;stico. A correla&#231;&#227;o positiva da onda e&#8217; com a fun&#231;&#227;o de conduto ressalta a import&#226;ncia da disfun&#231;&#227;o diast&#243;lica no esvaziamento passivo do AE.</p>
        <p>Em geral, os mecanismos cl&#237;nicos e fisiopatol&#243;gicos envolvidos na insufici&#234;ncia card&#237;aca est&#227;o centrados em maior disfun&#231;&#227;o sist&#243;lica e diast&#243;lica do VE. Este estudo demonstra que o AE pode desempenhar papel cr&#237;tico neste processo. A determina&#231;&#227;o do limite funcional de cada estrutura nesse contexto ainda permaneceum grande desafio.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Os pacientes com miocardiopatia chag&#225;sica e disfun&#231;&#227;o sist&#243;lica do VE apresentaram comprometimento das fun&#231;&#245;es de reservat&#243;rio, conduto e bomba do AE. Os pacientes com fun&#231;&#227;o sist&#243;lica normal n&#227;o apresentaram altera&#231;&#245;es desses par&#226;metros. Observou-se correla&#231;&#227;o entre a fun&#231;&#227;o do AE e as fun&#231;&#245;es sist&#243;lica e diast&#243;lica do VE avaliadas no Doppler tecidual.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo foi financiado por FAPESP.</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 Claudia da Silva Fragata pela Faculdade de Medicina da Universidade de S&#227;o Paulo.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
