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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.1" specific-use="sps-1.8" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">zWkKJ5fSYmvrWNmCYQ3hRND</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2018001300084</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20180114</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Carotid Sinus Massage in Syncope Evaluation: A Nonspecific and Dubious Diagnostic Method</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Wu</surname>
            <given-names>Tan Chen</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hachul</surname>
            <given-names>Denise T.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Darrieux</surname>
            <given-names>Francisco Carlos da Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Scanavacca</surname>
            <given-names>Maur&#237;cio I.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <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>
          <city>S&#227;o Paulo</city>
          <state>SP</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor) - Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Tan Chen Wu</bold>, Unidade de Arritmias Card&#237;acas do InCor-HC-FMUSP - Av. Dr En&#233;as de Carvalho Aguiar, 44. Postal Code 05403-000, S&#227;o Paulo, SP &#8211; Brazil. E-mail: tanchen.cardio@gmail.com, <email>tan.wu@cardiol.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research e Analysis and interpretation of the data: Wu TC, Hachul DT; Acquisition of data, Statistical analysis, Obtaining financing and Writing of the manuscript: Wu TC; Critical revision of the manuscript for intellectual content: Wu TC, Hachul DT, Darrieux FCC, Scanavacca MI.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <month>7</month>
        <year>2018</year>
      </pub-date>
      <volume>111</volume>
      <issue>1</issue>
      <fpage>84</fpage>
      <lpage>91</lpage>
      <history>
        <date date-type="received">
          <day>01</day>
          <month>09</month>
          <year>2017</year>
        </date>
        <date date-type="rev-recd">
          <day>20</day>
          <month>10</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>08</day>
          <month>12</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Carotid sinus hypersensitivity (CSH) is a frequent finding in the evaluation of syncope. However, its significance in the clinical setting is still dubious. A new criterion was proposed by Solari et al. with a symptomatic systolic blood pressure (SBP) cut-off value of &#8804; 85 mmHg to refine the vasodepressor (VD) response diagnosis.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To determine and compare the response to carotid sinus massage (CSM) in patients with and without syncope according to standard and proposed criteria.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>CSM was performed in 99 patients with and 66 patients without syncope. CSH was defined as cardioinhibitory (CI) for asystole &#8805; 3 seconds, or as VD for SBP decrease &#8805; 50 mmHg.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>No differences in the hemodynamic responses were observed during CSM between the groups, with 24.2% and 25.8% CI, and 8.1% and 13.6% VD in the symptomatic and asymptomatic groups, respectively (p = 0.466). A p value &lt; 0.050 was considered statistically significant. During the maneuvers, 45 (45.45%) and 34 (51.5%) patients in the symptomatic and asymptomatic groups achieved SBP below &#8804; 85 mmHg. Symptoms were reported especially in those patients in whom CSM caused a SBP decrease to below 90 mmHg and/or asystole &gt; 2.5 seconds, regardless of the pattern of response or the presence of previous syncope.</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>The response to CSM in patients with and without syncope was similar; therefore, CSH may be an unspecific condition. Clinical correlation and other methods of evaluation, such as long-lasting ECG monitoring, may be necessary to confirm CSH as the cause of syncope.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Syncope</kwd>
        <kwd>Carotid Sinus / physiopathology</kwd>
        <kwd>Accidental Falls</kwd>
        <kwd>Aged</kwd>
        <kwd>Hypotension</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Carotid sinus hypersensitivity (CSH), an age-related phenomenon, is rarely diagnosed in patients under the age of 50 years.<xref ref-type="bibr" rid="B1">1</xref> It has been accepted as a cause of syncope and unexplained falls in the elderly, with prevalence as high as 45% in some reports.<xref ref-type="bibr" rid="B2">2</xref>
			</p>
      <p>The clinical relevance of a positive response to carotid sinus massage (CSM) in patients with syncope is still controversial, in spite of the previous publications. Although the reported prevalence of CSH in patients with syncope is 23% to 41%,<xref ref-type="bibr" rid="B3">3</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref> it has been described in 17% of normal subjects, in 20% of patients with cardiovascular disease, and in 38% of patients with severe carotid artery disease.<xref ref-type="bibr" rid="B9">9</xref><sup>-</sup><xref ref-type="bibr" rid="B11">11</xref> Recently, some reports have proposed a modification of the diagnostic criterion according to hemodynamic findings during CSM,<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> with a cut-off value of symptomatic systolic blood pressure (SBP) of &#8804; 85 mmHg to determine a vasodepressor (VD) form, instead of the current definition of 50 mmHg SBP fall. To clarify the practical implications of CSM and CSH in syncope evaluation, this study was aimed at determining CSH prevalence and analyzing the patterns of the hemodynamic responses to CSM and symptoms in patients older than 50 years with and without symptoms of syncope or presyncope seen in a tertiary referral unit.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>The scientific and ethics committees of our institution approved this study. Written informed consent was obtained from each participant.</p>
      <p>Patients aged 50 years or older with at least two episodes of syncope or presyncope in the previous year, referred to the Arrhythmia and Syncope Unit of the Instituto do Cora&#231;&#227;o (InCor) &#8211; University of S&#227;o Paulo Medical School Hospital were selected as the symptomatic group. The number of patients was determined by convenience sampling. Patients presenting with structural heart disease, such as dilated cardiomyopathy with a left ventricular ejection fraction &#8804; 50%, moderate or significant valvular disease, myocardial infarction in the previous 6 months, unstable angina, stroke, carotid bruit or previously diagnosed carotid artery stenosis were excluded. Patients on chronic use of beta-blockers, digitalis, calcium channel blockers or alpha-methyldopa, who could not discontinue them, as well as patients with an artificial pacemaker, were also excluded.</p>
      <p>For the asymptomatic group, 66 patients with no history of syncope or presyncope were selected from the geriatric outpatient clinic of the same institution. The exclusion criteria for the group were the same as those applied to the symptomatic group.</p>
      <sec>
        <title>Carotid sinus massage</title>
        <p>Carotid sinus massage was performed from 1:00 pm to 5:00 pm. Cardiac medications, such as beta-blockers, calcium channel blockers (diltiazem and verapamil), digoxin and alpha-methyldopa, were discontinued 3 days before the procedure. All CSM were performed by the same physician. Continuous electrocardiogram and noninvasive, beat-to-beat blood pressure were recorded by digital photoplethysmography (Finapres Monitor&#174; Ohmeda, USA)<xref ref-type="bibr" rid="B14">14</xref> or a vascular unloading device (Task Force Monitor &#174; CNSystems Medizintechnik GmbH, Graz, Austria).<xref ref-type="bibr" rid="B15">15</xref><sup>-</sup><xref ref-type="bibr" rid="B17">17</xref>
				</p>
        <p>Blood pressure was monitored in the first 3 minutes with the patient in the 70&#176; upright position on a footplate-assisted tilt table to evaluate the presence of orthostatic hypotension (OH), which was defined as a postural drop in SBP of at least 20 mmHg or a drop in diastolic blood pressure (DBP) of at least 10 mmHg within the first 3 minutes of standing.<xref ref-type="bibr" rid="B18">18</xref>
				</p>
        <p>Carotid sinus massage was performed for 5 seconds, in the 70&#176; upright position after 5 minutes of standing, following the stabilization of blood pressure and heart rate, and at the point with the maximal carotid pulse on the anterior margin of the sternocleidomastoid muscle. Blood pressure and heart rate were monitored throughout. Right-sided CSM was followed by left-sided CSM (or vice versa) after at least 1 minute or as long as the heart rate and blood pressure values returned to baseline. The CSM was performed twice in each side to evaluate the reproducibility of the method. The sequence was completed even in the event of positivity of 1 massage. After each episode of CSM, patients were questioned about symptoms related to the maneuver. Cardioinhibitory (CI) CSH was defined as asystole of 3 seconds or more, and VD CSH was defined as a drop of 50 mmHg or more in SBP.<xref ref-type="bibr" rid="B19">19</xref>
				</p>
        <p>Blood pressure was recorded continuously immediately before each CSM until it reached the lowest value recorded during or shortly after the maneuver. The magnitude of the blood pressure response was obtained by the difference between the baseline SBP and the minimum SBP during CSM (&#916;SBP). Likewise, RR intervals were recorded, and the magnitude of heart rate response was given by the difference between the RR interval before CSM and the maximum RR interval during CSM (&#916;RR).</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>The data were analyzed by using Excel 2003 and SPSS software for Windows, version 15.0. The nominal measures are presented in absolute (n) and relative (%) frequencies, and numerical measurements are described as mean, standard deviation, median, minimum and maximum values. The clinical characteristics and responses to CSM (the order, result and symptoms associated with CSM) were compared between groups by using the chi-square test and the likelihood ratio test. The numerical measurements between the groups were summarized by descriptive statistics and compared by using Student <italic>t</italic> test, chi-square test for categorical data, and Mann-Whitney test for continuous data. Nonparametric tests were used in the absence of normally distributed data assumption (Kolmogorov-Smirnov test). The intraclass correlation coefficient was used to analyze the reproducibility of the CSM response. A p value of &lt; 0.050 was considered statistically significant.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>In the symptomatic group, almost all patients (93.9%) had syncope, with an average of 5.4 episodes (median - 3) in the year prior to evaluation. The baseline clinical characteristics of the 99 patients in the symptomatic group and the 66 patients in the asymptomatic group are shown in <xref ref-type="table" rid="t1">Table 1</xref>.</p>
      <table-wrap id="t1">
        <label>Table 1</label>
        <caption>
          <title>Clinical characteristics of the symptomatic and asymptomatic groups.</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">Variable</th>
              <th align="center">Symptomatic (n = 99)</th>
              <th align="center">Asymptomatic (n = 66)</th>
              <th align="center">p</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Age, mean &#177; sd (median) (minimum - maximum)</td>
              <td align="center">69.67 &#177; 10.26 (70) (50-93)</td>
              <td align="center">73.01 &#177; 9.68 (74) (52-92)</td>
              <td align="center">0.037</td>
            </tr>
            <tr>
              <td align="left">Male, n (%)</td>
              <td align="center">41 (41.4%)</td>
              <td align="center">23 (34.8)</td>
              <td align="center">0.396</td>
            </tr>
            <tr>
              <td align="left">Hypertension</td>
              <td align="center">73 (73.7%)</td>
              <td align="center">54 (81.8%)</td>
              <td align="center">0.227</td>
            </tr>
            <tr>
              <td align="left">Diabetes</td>
              <td align="center">13 (13.1)</td>
              <td align="center">20 (30.3)</td>
              <td align="center">0.007</td>
            </tr>
            <tr>
              <td align="left">Coronary artery disease</td>
              <td align="center">5 (5.1)</td>
              <td align="center">11(16.7)</td>
              <td align="center">0.014</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <p>chi-square test; sd: standard deviation.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Patients in the symptomatic group had the most significant decreases in blood pressure after being tilted to 70&#176;. The mean SBP and DBP changes after orthostatic stimulus are shown in <xref ref-type="fig" rid="f1">Figure 1</xref>. The symptomatic group had more occurrences of OH (29 patients, 29.2%), of whom, 19 patients met the diagnostic criterion of a SBP decrease &#8805; 20 mmHg, and 10 additional patients met the criterion of a DBP decrease &#8805; 10 mmHg. Only 8 patients (12.1%) in the asymptomatic group had a diagnosis of OH, which was due to decreased SBP in 7 of them (p = 0.014).</p>
      <p>
        <fig id="f1">
          <label>Figure 1</label>
          <caption>
            <title>Magnitudes of the responses of systolic and diastolic blood pressure to a 70&#176; tilt in the symptomatic and asymptomatic groups. Note there is significant fall in the systolic blood pressure (p &lt; 0,001) and diastolic blood pressure (p = 0,001) in the symptomatic group compared with asymptomatic group.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-111-01-0084-80114-gf01.jpg"/></fig>
      </p>
      <sec>
        <title>Carotid sinus massage</title>
        <p>There was no difference between the groups in the responses obtained during CSM (p = 0.466) (<xref ref-type="fig" rid="f2">Figure 2</xref>). The response to CSM was considered normal in 64.8% of patients in the entire sample, 67.7% in the symptomatic group and 60.6% in the asymptomatic group. Over 32% of the patients in both groups had an abnormal response to CSM, with predominance of CI responses.</p>
        <p>
          <fig id="f2">
            <label>Figure 2</label>
            <caption>
              <title>Results of carotid sinus massage according to the type of response obtained in the symptomatic and asymptomatic groups. CSH: carotid sinus hypersensitivity.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-111-01-0084-80114-gf02.jpg"/></fig>
        </p>
        <p>Men had more abnormal responses to CSM compared to women (53.8% vs. 23.0%, p &lt; 0.001). A predominance of CI response was also observed in men compared to women (43.1% vs. 13.0%). There was no significant difference in responses to CSM related to age. Likewise, no association was observed between CSH and underlying diseases, such as hypertension, diabetes and coronary artery disease (<xref ref-type="table" rid="t2">Table 2</xref>).</p>
        <table-wrap id="t2">
          <label>Table 2</label>
          <caption>
            <title>Distribution of responses to carotid sinus massage by age, sex, and underlying diseases, such as hypertension, diabetes and coronary artery disease.</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="3">Variable</th>
                <th align="center" colspan="6" style="border-bottom-width:thin;border-bottom-style:solid">Response to CSM</th>
                <th align="center" rowspan="2">TOTAL</th>
                <th align="center" rowspan="3">p</th>
              </tr>
              <tr>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">No CSH</th>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">Cardioinhibitory</th>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">Vasodepressor</th>
              </tr>
              <tr>
                <th align="center">n</th>
                <th align="center">%</th>
                <th align="center">n</th>
                <th align="center">%</th>
                <th align="center">n</th>
                <th align="center">%</th>
                <th align="center">n</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">
                  <bold>Age</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>0.356<sup><xref ref-type="table-fn" rid="TFN3">#</xref></sup></bold>
                </td>
              </tr>
              <tr>
                <td align="left">50-59</td>
                <td align="center">22</td>
                <td align="center">78.5</td>
                <td align="center">5</td>
                <td align="center">17.9</td>
                <td align="center">1</td>
                <td align="center">3.5</td>
                <td align="center">28</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">60-69</td>
                <td align="center">30</td>
                <td align="center">69.7</td>
                <td align="center">9</td>
                <td align="center">20.9</td>
                <td align="center">4</td>
                <td align="center">9.3</td>
                <td align="center">43</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">70-79</td>
                <td align="center">31</td>
                <td align="center">56.3</td>
                <td align="center">15</td>
                <td align="center">27.3</td>
                <td align="center">9</td>
                <td align="center">16.3</td>
                <td align="center">55</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">&#8805; 80</td>
                <td align="center">24</td>
                <td align="center">61.5</td>
                <td align="center">12</td>
                <td align="center">30.8</td>
                <td align="center">3</td>
                <td align="center">7.6</td>
                <td align="center">39</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Sex</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>&lt; 0.001<xref ref-type="table-fn" rid="TFN4">*</xref></bold>
                </td>
              </tr>
              <tr>
                <td align="left">Male</td>
                <td align="center">30</td>
                <td align="center">46.1</td>
                <td align="center">28</td>
                <td align="center">43.1</td>
                <td align="center">6</td>
                <td align="center">9.2</td>
                <td align="center">65</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Female</td>
                <td align="center">77</td>
                <td align="center">77.0</td>
                <td align="center">13</td>
                <td align="center">13.0</td>
                <td align="center">11</td>
                <td align="center">11.0</td>
                <td align="center">100</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Hypertension</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>0.849<sup><xref ref-type="table-fn" rid="TFN3">#</xref></sup></bold>
                </td>
              </tr>
              <tr>
                <td align="left">-</td>
                <td align="center">25</td>
                <td align="center">65.7</td>
                <td align="center">10</td>
                <td align="center">26.3</td>
                <td align="center">3</td>
                <td align="center">7.8</td>
                <td align="center">38</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">+</td>
                <td align="center">82</td>
                <td align="center">64.5</td>
                <td align="center">31</td>
                <td align="center">24.4</td>
                <td align="center">14</td>
                <td align="center">11.0</td>
                <td align="center">127</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Diabetes</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>0.095<sup><xref ref-type="table-fn" rid="TFN3">#</xref></sup></bold>
                </td>
              </tr>
              <tr>
                <td align="left">-</td>
                <td align="center">90</td>
                <td align="center">68.1</td>
                <td align="center">28</td>
                <td align="center">21.2</td>
                <td align="center">14</td>
                <td align="center">10.6</td>
                <td align="center">132</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">+</td>
                <td align="center">17</td>
                <td align="center">51.5</td>
                <td align="center">13</td>
                <td align="center">39.4</td>
                <td align="center">3</td>
                <td align="center">9.0</td>
                <td align="center">33</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Coronary artery disease</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>0.401<sup><xref ref-type="table-fn" rid="TFN3">#</xref></sup></bold>
                </td>
              </tr>
              <tr>
                <td align="left">-</td>
                <td align="center">99</td>
                <td align="center">66.4</td>
                <td align="center">35</td>
                <td align="center">23.5</td>
                <td align="center">15</td>
                <td align="center">10.0</td>
                <td align="center">149</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">+</td>
                <td align="center">8</td>
                <td align="center">50.0</td>
                <td align="center">6</td>
                <td align="center">37.5</td>
                <td align="center">2</td>
                <td align="center">12.5</td>
                <td align="center">16</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Total</td>
                <td align="center">103</td>
                <td align="center">62</td>
                <td align="center">41</td>
                <td align="center">25</td>
                <td align="center">21</td>
                <td align="center">13</td>
                <td align="center">165</td>
                <td align="center">
								</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>CSM: carotid sinus massage; CSH: carotid sinus hypersensitivity;</p>
            </fn>
            <fn id="TFN3">
              <label>#</label>
              <p>likelihood ratio test;</p>
            </fn>
            <fn id="TFN4">
              <label>*</label>
              <p>chi-square test</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>There was no difference (<xref ref-type="fig" rid="f3">Figure 3</xref>) in the response to CSM when comparing the decrease in SBP (&#916;SBP) and heart rate (&#916;RR) between the symptomatic and asymptomatic groups. All patients were in sinus rhythm except for 2 individuals from the symptomatic group, who had atrial fibrillation (AF). One patient had persistent AF, and the other had paroxysmal AF.</p>
        <p>
          <fig id="f3">
            <label>Figure 3</label>
            <caption>
              <title>Magnitudes of systolic blood pressure response (&#916;SBP) (above) and heart rate response (&#916;RR) (below) in the symptomatic and asymptomatic groups during carotid sinus massage.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-111-01-0084-80114-gf03.jpg"/></fig>
        </p>
        <p>During the maneuvers, 45 (45.45%) symptomatic patients and 34 (51.5%) asymptomatic patients dropped their SBP to values &#8804; 85 mmHg. The proportions of patients who achieved SBP &#8804; 85 mmHg in the series of CSM are shown in <xref ref-type="table" rid="t3">Table 3</xref>. The VD reflex increased from 8.0% to 31.3% in the symptomatic group and from 13.6% to 28.7% in the asymptomatic group, when applying the cut-off value of SBP &#8804; 85 mmHg for the diagnosis of CSH, compared to the classical blood pressure criteria with a fall in SBP &#8805; 50 mmHg. Therefore, the change in the cut-off value increased the diagnosis of CSH by 21.2% (or total 53.5%) and 15.2% (total 54.5%) in the symptomatic and asymptomatic groups, respectively.</p>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <title>Proportions of patients with systolic blood pressure (SBP) &#8804; 85 mmHg in the series of carotid sinus massage (CSM).</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="2">
								</th>
                <th align="center" colspan="5" style="border-bottom-width:thin;border-bottom-style:solid">Minimum SBP &#8804; 85 mmHg during CSM</th>
              </tr>
              <tr>
                <th align="center">Right CSM 1 n (%)</th>
                <th align="center">Right CSM 2 n (%)</th>
                <th align="center">Left CSM 1 n (%)</th>
                <th align="center">Left CSM 2 n (%)</th>
                <th align="center">Total n (%)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Asymptomatic</td>
                <td align="center">24 (36.3)</td>
                <td align="center">24 (36.3)</td>
                <td align="center">20 (30.3)</td>
                <td align="center">16 (30.3)</td>
                <td align="center">66 (100)</td>
              </tr>
              <tr>
                <td align="left">Symptomatic</td>
                <td align="center">33 (33.3)</td>
                <td align="center">34 (34.3)</td>
                <td align="center">26 (26.2)</td>
                <td align="center">29 (29.2)</td>
                <td align="center">99 (100)</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Although abnormal responses were similar in both groups, symptomatic patients reported more symptoms during CSM (41.4% vs. 27.3%, p = 0.063). The reported symptoms ranged from mild discomfort to syncope. In the symptomatic group, 20 patients reported presyncope, 16 patients reported dizziness, and 3 patients reported nonspecific symptoms. In the asymptomatic group, 5 patients reported presyncope, 10 patients, dizziness, and 2 patients, nonspecific symptoms. Only 2 patients in the symptomatic group had syncope, which occurred with ventricular pauses of 8.2 and 8.1 seconds. Symptoms reported with normal or abnormal responses made up 17.8% of normal, 78% of CI, and 47.1% of VD responders. Likewise, many asymptomatic patients showed a positive response without related symptoms, especially VD response (82.2% of normal, 22% of CI, and 52.9% of VD). Symptoms resulting from the CSM occurred mainly when the SBP dropped below 90 mmHg and/or the RR intervals extended longer than 2500 ms (<xref ref-type="table" rid="t4">Table 4</xref>).</p>
        <table-wrap id="t4">
          <label>Table 4</label>
          <caption>
            <title>Correlation between occurrence of symptoms during carotid sinus massage and the value of minimum systolic blood pressure (SBP) and maximum RR interval obtained during the massage</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="12%"/>
              <col width="12%"/>
              <col width="12%"/>
              <col width="12%"/>
              <col width="12%"/>
              <col width="12%"/>
              <col width="12%"/>
              <col width="12%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
								</th>
                <th align="center">Symptoms</th>
                <th align="center">Mean &#177; SD</th>
                <th align="center">Median</th>
                <th align="center">Minimum</th>
                <th align="center">Maximum</th>
                <th align="center">n</th>
                <th align="center">p</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" rowspan="3">Minimum right SBP (mmHg)</td>
                <td align="center">asymptomatic</td>
                <td align="center">102.5 &#177; 12.9</td>
                <td align="center">101</td>
                <td align="center">59</td>
                <td align="center">180</td>
                <td align="center">106</td>
                <td align="center">&lt; 0.001<xref ref-type="table-fn" rid="TFN6">*</xref>
								</td>
              </tr>
              <tr>
                <td align="center">symptomatic</td>
                <td align="center">86.4 &#177; 23.6</td>
                <td align="center">85</td>
                <td align="center">42</td>
                <td align="center">151</td>
                <td align="center">59</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="center">Total</td>
                <td align="center">96.7 &#177; 23.7</td>
                <td align="center">96</td>
                <td align="center">42</td>
                <td align="center">180</td>
                <td align="center">165</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">Minimum left SBP (mmHg)</td>
                <td align="center">asymptomatic</td>
                <td align="center">101.8 &#177; 20.7</td>
                <td align="center">98</td>
                <td align="center">64</td>
                <td align="center">185</td>
                <td align="center">106</td>
                <td align="center">&lt; 0.001<xref ref-type="table-fn" rid="TFN6">*</xref>
								</td>
              </tr>
              <tr>
                <td align="center">symptomatic</td>
                <td align="center">89.0 &#177; 20.3</td>
                <td align="center">87,5</td>
                <td align="center">51</td>
                <td align="center">178</td>
                <td align="center">58</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="center">Total</td>
                <td align="center">97.3 &#177; 21.4</td>
                <td align="center">95</td>
                <td align="center">51</td>
                <td align="center">185</td>
                <td align="center">164</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">Maximum right RR interval (ms)</td>
                <td align="center">asymptomatic</td>
                <td align="center">1326 &#177; 768</td>
                <td align="center">1154</td>
                <td align="center">625</td>
                <td align="center">5455</td>
                <td align="center">106</td>
                <td align="center">&lt; 0.000<xref ref-type="table-fn" rid="TFN7">#</xref>
								</td>
              </tr>
              <tr>
                <td align="center">symptomatic</td>
                <td align="center">2639 &#177; 1762</td>
                <td align="center">1800</td>
                <td align="center">880</td>
                <td align="center">7500</td>
                <td align="center">59</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="center">Total</td>
                <td align="center">1795 &#177; 1369</td>
                <td align="center">1225</td>
                <td align="center">625</td>
                <td align="center">7500</td>
                <td align="center">165</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">Maximum left RR interval (ms)</td>
                <td align="center">asymptomatic</td>
                <td align="center">1238 &#177; 564</td>
                <td align="center">1111</td>
                <td align="center">6326</td>
                <td align="center">4520</td>
                <td align="center">106</td>
                <td align="center">&lt; 0.000<xref ref-type="table-fn" rid="TFN7">#</xref>
								</td>
              </tr>
              <tr>
                <td align="center">symptomatic</td>
                <td align="center">2772 &#177; 1891</td>
                <td align="center">1840</td>
                <td align="center">811</td>
                <td align="center">8160</td>
                <td align="center">59</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="center">Total</td>
                <td align="center">1786 &#177; 1419</td>
                <td align="center">1200</td>
                <td align="center">632</td>
                <td align="center">8160</td>
                <td align="center">165</td>
                <td align="center">
								</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5">
              <p>SD:standard deviation;</p>
            </fn>
            <fn id="TFN6">
              <label>*</label>
              <p>Student's t Test;</p>
            </fn>
            <fn id="TFN7">
              <label>#</label>
              <p>Mann-Whitney test.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>The immediate reproducibility of the CSM response was evaluated by repeating the CSM during the same procedure. The heart rate response reproducibility was slightly superior as compared to the blood pressure response, with intraclass correlation coefficients of 0.68 for the right &#916;SBP, 0.71 for the left &#916;SBP, 0.83 for the right &#916;RR, and 0.81 for the left &#916;RR. The heart rate data demonstrate acceptable levels of conformity (above 0.75). Reproducibility of the abnormal blood pressure response (VD CSH) was observed in 40.8% (20/49 cases), and the abnormal heart rate response (CI CSH) in 48.5% (50/103 cases).</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>The diagnosis and management of syncope are still a challenging task in medical practice. In elderly patients, identifying the underlying diagnosis may be more complex due to multiple comorbidities, atypical presentations, amnesia from loss of consciousness, and difficulties in remembering and characterizing the episode.</p>
      <p>The occurrence of OH is an important risk factor for falls and syncope, especially in the elderly, with 18.2% of prevalence.<xref ref-type="bibr" rid="B20">20</xref><sup>-</sup><xref ref-type="bibr" rid="B23">23</xref> In this study, we observed more than twice the prevalence (29.2% vs. 12.1%) of OH in the symptomatic patients compared to the asymptomatic patients. This finding confirms the importance of investigating OH in aged patients with syncope, reinforcing OH as one of the most frequent causes of syncope in the elderly.</p>
      <p>Differently from the results observed in the search of OH, similar responses were obtained during CSM in symptomatic and asymptomatic groups. This finding perhaps reinforces the hypotheses that CSH is not a diagnostic marker of a clinical syndrome. With a similar proposal to assess the prevalence of CSH and the diagnostic value of CSM, Tan et al.<xref ref-type="bibr" rid="B24">24</xref> have found altered responses in 25% of the patients referred for evaluation of syncope and unexplained falls. This prevalence of CSH was lower when compared to the prevalence in another report<xref ref-type="bibr" rid="B25">25</xref> in individuals older than 65 years, randomly sampled from an unselected community. In that study, the authors observed CSH in 39% of the patients, and, in a subgroup of patients with no history of syncope or falling, 35% had a hypersensitive response to CSM, and 36% had CSM-related symptoms. Thus, a positive test for CSH may not necessarily determine the cause of fainting, leaving the clinician with the difficult decision whether to accept the test as a confirmation of the cause of syncope, which sometimes might induce an incorrect diagnosis.</p>
      <p>Solari et al.<xref ref-type="bibr" rid="B26">26</xref> have proposed a cut-off value of symptomatic SBP &#8804; 85 mmHg as more appropriate to identify the VD form of CSH in a study with 164 patients with CSM who produced spontaneous symptoms in the presence of hypotension or bradycardia (Method of Symptoms), or diagnosis of carotid sinus syndrome. The method does not require any cut-off value of asystolic pause or of the SBP fall induced by CSM, as positivity of the test is based on the reproduction of symptoms. They concluded that one third of patients with isolated VD form could not be identified by the classical blood pressure criteria for the diagnosis of CSH (a fall in SBP &#8805; 50 mmHg), as compared with the &#8804; 85 mmHg SBP cut-off value. Therefore, they offered this standardized objective methodology of classification of the VD reflex component to be used in clinical practice.<xref ref-type="bibr" rid="B26">26</xref> Few large-scale studies have evaluated the diagnostic value of CSM. When positive, it suggests a tendency or predisposition to carotid sinus syndrome; however, this does not establish it as the cause of the patient&#8217;s syncope, with no &#8220;ideal&#8221; protocol, given that there is an inexorable trade-off between sensitivity and specificity without a &#8220;gold standard&#8221; test to prospectively validate it in populations with rigorously defined carotid sinus syndrome. Likewise, the reproduction of spontaneous symptoms to confirm the diagnosis as recommended by the European Society of Cardiology with the Method of Symptoms may be imprecise in this population, since prodromal symptoms are absent in up to 93% of patients with carotid sinus syndrome, and most of all with frequent memory and cognitive deficit, confounding the correlation. Additionally, any etiology that causes hypotension might result in symptoms similar to those determined by CSH, with the first symptoms of retinal and cerebral hypoperfusion expected in the upright position when SBP drops below 80 mmHg. An association between impaired cerebral autoregulation and the symptomatic presentation of CSH was demonstrated by Tan et al.<xref ref-type="bibr" rid="B27">27</xref> in a study using transcranial Doppler ultrasonography during lower body negative pressure-induced systemic hypotension.<xref ref-type="bibr" rid="B27">27</xref> They have demonstrated that individuals with symptomatic CSH have lower cerebral blood flow than do asymptomatic individuals with CSH in response to comparable reductions in systemic blood pressure, and have suggested that symptomatic individuals have an increased susceptibility to syncope or falls compared with individuals with asymptomatic CSH due to a lower ability to maintain cerebral blood flow in the face of a hypotensive challenge.</p>
      <p>In our study, we observed that symptoms resulting from the CSM occurred mainly when the SBP dropped below 90 mmHg and/or the RR intervals extended longer than 2500 ms, regardless of the diagnosis associated with CSM. Associated with this factor, CSH is elicited by manual massage, which is a highly variable stimulus. This may be the reason for the low reproducibility of the positive response, as shown in this study.</p>
      <p>While CSH has been observed in patients with syncope, and the symptoms were reproduced during CSM, there are no reports demonstrating that the hemodynamic alterations seen in the laboratory occur in a spontaneous event. Trying to establish the relationship between CSH and falls or syncopes, Schoon et al. have tested the hypothesis that head turning triggers hypotensive episodes in elderly with CSH. They have concluded that head turning may cause hypotensive episodes in the elderly. Head turning led to hypotension in 39% (total of 96 patients) of patients, with a mean SBP drop of 36 mm Hg (SD &#177; 13; range 20-76) with similar occurrence compared to healthy elderly, with 44% (total of 25 patients) and a mean SBP drop of 35 mmHg (SD &#177; 19; range 20-85). A drawback of the observational design is that it does not allow for conclusions about the causal relationships among head turning-triggered hypotension and syncope, and falls. They have also found a discrepancy between the occurrence of that head turning-triggered hypotension and related symptoms.<xref ref-type="bibr" rid="B28">28</xref> Thus, the positive correlation between CSH and syncope and/or falls still needs to be redefined due to the accumulating evidence that CSM causes a similar positive response in the asymptomatic population with the current criteria to diagnose CSH. The cut-off value of symptomatic SBP &#8804; 85 mmHg to identify the VD form of CSH may cause overdiagnosis, sometimes leads to misdiagnosis, with no benefits in treatment plus potential side effects outweighing the benefits. Other options, such as long-lasting ECG monitoring with documentation of spontaneous events, are the only way to corroborate the diagnosis and its correlation with laboratorial findings.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>In conclusion, no differences in the response to CSM were demonstrated between patients with and without syncope or presyncope. Carotid sinus hypersensitivity may be an unspecific condition in the evaluation of syncope. The best cut-off values of the asystolic pause and SBP based or not on the reproduction of symptoms are still a challenging task in medical practice. Consequently, clinical correlation and other methods of evaluation, such as long-lasting ECG monitoring, may be necessary to confirm CSH as a cause of syncope.</p>
      <sec>
        <title>Study limitations</title>
        <p>The control group was composed of not completely healthy individuals, but with no significant heart disease and in stable clinical condition. It is already known that elderly people have an average of three comorbidities per person. Asymptomatic patients in this study were recruited from an outpatient geriatric unit. The institution is a referral tertiary cardiology center, and the patients usually have substantial clinical complexity. Even with the exclusion criteria, which led to the inclusion of only patients without significant heart disease and in stable clinical conditions at the time of selection, we observed that more patients with diabetes and coronary artery disease were in the asymptomatic group. On the other hand, patients in the asymptomatic group were a little older than those in the symptomatic group, with a mean age of 73.0 and 69.6 years, respectively. Despite this difference, patients in both groups are representative of the elderly population, in whom a positive vagal maneuver is believed to define the etiologic diagnosis of syncope. The presence of systemic underlying comorbidities in the asymptomatic group may be an important concern. The advanced age and the presence of simultaneous underlying diseases in these patients reinforce the hypothesis that CSH could be not much more than a laboratory finding related to aging and vascular diseases. We recognize that the difference in age and in comorbidities between groups could constitute a bias, but we are sure that both groups are representative of the elderly population in which unexplained syncope is a great challenge.</p>
        <p>In this study the CSM was performed with the patient in the 70&#176; upright position after 5 minutes in the orthostatic position different from other studies performed in the supine position. Thus, our findings may be different and, therefore, could not be applied to the CSM in supine position. We chose the orthostatic position because it is the most sensitive to detect CSH according to the study performed by Parry et al.,<xref ref-type="bibr" rid="B29">29</xref> who have demonstrated that the specificity and sensitivity of the initially supine positive test were thus 74% and 100%, respectively, while the upright positive test had 100% specificity and sensitivity. For this reason, we performed CSM only in the orthostatic position in this study.</p>
      </sec>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This article is part of the thesis of Doctoral submitted by Tan Chen Wu, from Faculdade de Medicina da Universidade de S&#227;o Paulo.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Ethical approval and informed consent</bold>
        </p>
        <p>This study was approved by the Ethics Committee of the Scientific and Ethics committees of clinical board of Hospital das Cl&#237;nicas and Faculdade de Medicina da Universidade de S&#227;o Paulo under the protocol number 424/01. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>References</title>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Massagem do Seio Carot&#237;deo na Avalia&#231;&#227;o da S&#237;ncope: Um M&#233;todo Diagn&#243;stico Inespec&#237;fico e Duvidoso</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Wu</surname>
            <given-names>Tan Chen</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hachul</surname>
            <given-names>Denise T.</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Darrieux</surname>
            <given-names>Francisco Carlos da Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Scanavacca</surname>
            <given-names>Maur&#237;cio I.</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
      </contrib-group>
      <aff id="aff2">
        <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor) - Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Tan Chen Wu</bold>, Unidade de Arritmias Card&#237;acas do InCor-HC-FMUSP - Av. Dr En&#233;as de Carvalho Aguiar, 44. CEP 05403-000, S&#227;o Paulo, SP - Brasil. E-mail: <email>tanchen.cardio@gmail.com</email>, <email>tan.wu@cardiol.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 e An&#225;lise e interpreta&#231;&#227;o dos dados: Wu TC, Hachul DT; Obten&#231;&#227;o de dados, An&#225;lise estat&#237;stica, Obten&#231;&#227;o de financiamento e Reda&#231;&#227;o do manuscrito: Wu TC; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Wu TC, Hachul DT, Darrieux FCC, Scanavacca MI.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>A hipersensibilidade do seio carot&#237;deo (HSC) &#233; um achado frequente na avalia&#231;&#227;o da s&#237;ncope. Entretanto, o valor da resposta positiva &#233; ainda incerto no contexto cl&#237;nico. Novo crit&#233;rio diagn&#243;stico para tentar refinar a resposta vasodepressora (VD) foi proposto por Solari et al. com determina&#231;&#227;o da queda sintom&#225;tica da press&#227;o arterial sist&#243;lica (PAS) a n&#237;veis &#8804; 85 mmHg como ponto de corte.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Determinar e comparar a resposta &#224; massagem do seio carot&#237;deo (MSC) em pacientes com e sem s&#237;ncope de acordo com os crit&#233;rios vigentes e propostos.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>A MSC foi realizada em 99 pacientes com s&#237;ncope e 66 pacientes sem s&#237;ncope. A HSC foi definida como cardioinibit&#243;ria (CI), se assistolia &#8805; 3 segundos, ou VD, se queda da PAS &#8805; 50 mmHg.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>N&#227;o foram observadas diferen&#231;as na resposta hemodin&#226;mica entre os grupos durante a MSC, com 24,2% e 25,8% de resposta CI, e 8,1% e 13,6% de resposta VD nos grupos sintom&#225;tico e assintom&#225;tico, respectivamente (p = 0,466). Considerou-se p &lt; 0,05 estatisticamente significativo. Durante as manobras, 45 (45,45%) e 34 (51,5%) pacientes nos grupos sintom&#225;tico e assintom&#225;tico atingiram PAS &#8804; 85 mmHg. Sintomas foram relatados principalmente por pacientes em que a MSC reduziu a PAS para menos de 90 mmHg e/ou causou assistolia &gt; 2,5 segundos, independentemente do padr&#227;o da resposta ou hist&#243;ria de s&#237;ncope pr&#233;via.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>As respostas &#224; MSC em pacientes com e sem s&#237;ncope foram semelhantes. Portanto, a HSC pode ser uma condi&#231;&#227;o inespec&#237;fica. A correla&#231;&#227;o cl&#237;nica mais precisa e outros m&#233;todos para avalia&#231;&#227;o, como monitoramento por ECG de longa dura&#231;&#227;o, podem ser necess&#225;rios para confirma&#231;&#227;o da HSC como causa da s&#237;ncope.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>S&#237;ncope</kwd>
        <kwd>Seio Carot&#237;deo / fisiopatologia</kwd>
        <kwd>Acidentes por Quedas</kwd>
        <kwd>Idoso</kwd>
        <kwd>Hipotens&#227;o</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A hipersensibilidade do seio carot&#237;deo (HSC), um fen&#244;meno ligado &#224; idade, &#233; raramente diagnosticado em pacientes com menos de 50 anos.<xref ref-type="bibr" rid="B1">1</xref> Foi aceita como causa de s&#237;ncope e quedas inexplicadas do idoso, com preval&#234;ncia chegando a 45% em alguns relatos.<xref ref-type="bibr" rid="B2">2</xref>
				</p>
        <p>A relev&#226;ncia cl&#237;nica de uma resposta positiva &#224; massagem do seio carot&#237;deo (MSC) em pacientes com s&#237;ncope ainda &#233; controversa, a despeito de publica&#231;&#245;es pr&#233;vias. Ainda que a preval&#234;ncia de HSC relatada em pacientes com s&#237;ncope varie de 23% a 41%,<xref ref-type="bibr" rid="B3">3</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref> foi descrita em 17% dos indiv&#237;duos normais, em 20% dos pacientes com doen&#231;a cardiovascular e em 38% dos pacientes com doen&#231;a arterial carot&#237;dea importante.<xref ref-type="bibr" rid="B9">9</xref><sup>-</sup><xref ref-type="bibr" rid="B11">11</xref> Recentemente, alguns estudos propuseram uma modifica&#231;&#227;o do crit&#233;rio diagn&#243;stico de acordo com os achados hemodin&#226;micos durante a MSC,<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> com um ponto de corte para a queda sintom&#225;tica da press&#227;o arterial sist&#243;lica (PAS) a n&#237;veis &#8804; 85 mmHg para defini&#231;&#227;o da forma vasodepressora (VD), em lugar da atual defini&#231;&#227;o que &#233; por queda da PAS &#8805; 50 mmHg. Para esclarecer as implica&#231;&#245;es pr&#225;ticas da MSC e da HSC na avalia&#231;&#227;o de s&#237;ncope, este estudo teve por objetivo determinar a preval&#234;ncia de HSC e analisar os padr&#245;es de resposta hemodin&#226;mica &#224; MSC e os sintomas em pacientes com mais de 50 anos com e sem s&#237;ncope ou pr&#233;-s&#237;ncope, atendidos em uma unidade de refer&#234;ncia terci&#225;ria.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Os comit&#234;s cient&#237;fico e de &#233;tica da nossa institui&#231;&#227;o aprovaram este estudo. Todos os participantes assinaram o termo de consentimento livre e esclarecido.</p>
        <p>Pacientes com idade &#8805; 50 anos e com pelo menos dois epis&#243;dios de s&#237;ncope ou pr&#233;-s&#237;ncope no ano anterior, encaminhados &#224; Unidade de Arritmia e S&#237;ncope do Instituto do Cora&#231;&#227;o (InCor) &#8211; Hospital da Faculdade de Medicina da Universidade de S&#227;o Paulo, foram selecionados como o grupo sintom&#225;tico. O n&#250;mero de pacientes foi determinado por amostragem por conveni&#234;ncia. Pacientes com as seguintes caracter&#237;sticas foram exclu&#237;dos: cardiopatia estrutural, como cardiomiopatia dilatada com fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda &#8804; 50%; valvulopatia moderada ou significativa; infarto do mioc&#225;rdio nos 6 meses anteriores; angina inst&#225;vel; acidente vascular encef&#225;lico; sopro carot&#237;deo; e diagn&#243;stico pr&#233;vio de estenose de car&#243;tida. Al&#233;m disso, pacientes em uso cr&#244;nico de betabloqueadores, digital, bloqueadores dos canais de c&#225;lcio ou alfa-metildopa, que n&#227;o pudessem descontinu&#225;-los, assim como aqueles com um marca-passo artificial, foram exclu&#237;dos.</p>
        <p>Para o grupo assintom&#225;tico, 66 pacientes sem hist&#243;ria de s&#237;ncope ou pr&#233;-s&#237;ncope foram selecionados do ambulat&#243;rio de geriatria da mesma institui&#231;&#227;o. Os crit&#233;rios de exclus&#227;o para esse grupo foram os mesmos aplicados ao grupo sintom&#225;tico.</p>
        <sec>
          <title>Massagem do seio carot&#237;deo</title>
          <p>A MSC foi realizada entre 13 e 17 horas. As medica&#231;&#245;es card&#237;acas, como betabloqueadores, bloqueadores dos canais de c&#225;lcio (diltiazem e verapamil), digoxina e alfa-metildopa, foram suspensas por 3 dias antes do procedimento. Todas as massagens foram realizadas pelo mesmo m&#233;dico. Registraram-se eletrocardiograma cont&#237;nuo e medida n&#227;o invasiva, batimento a batimento da press&#227;o arterial por fotopletismografia digital (Finapres Monitor&#174; Ohmeda, EUA)<xref ref-type="bibr" rid="B14">14</xref> ou dispositivo vascular (Task Force Monitor &#174; CNSystems Medizintechnik GmbH, Graz, &#193;ustria).<xref ref-type="bibr" rid="B15">15</xref><sup>-</sup><xref ref-type="bibr" rid="B17">17</xref>
					</p>
          <p>A press&#227;o arterial foi monitorada nos primeiros 3 minutos com o paciente submetido &#224; inclina&#231;&#227;o ortost&#225;tica a 70&#176; na mesa de inclina&#231;&#227;o com suporte para os p&#233;s para avaliar a presen&#231;a de hipotens&#227;o ortost&#225;tica (HO), definida por queda da PAS &#8805; 20 mmHg ou queda da press&#227;o arterial diast&#243;lica (PAD) &#8805; 10 mmHg nos primeiros 3 minutos em posi&#231;&#227;o ortost&#225;tica.<xref ref-type="bibr" rid="B18">18</xref>
					</p>
          <p>A MSC foi realizada por 5 segundos, com o paciente em posi&#231;&#227;o ortost&#225;tica a 70&#176; depois de 5 minutos em ortostase, ap&#243;s estabiliza&#231;&#227;o da press&#227;o arterial e da frequ&#234;ncia card&#237;aca, no ponto com maior impuls&#227;o carot&#237;dea na borda anterior do m&#250;sculo esternocleidomastoideo. A press&#227;o arterial e a frequ&#234;ncia card&#237;aca foram monitoradas durante todo o tempo. A MSC do lado direito foi seguida por MSC do lado esquerdo (ou vice-versa) ap&#243;s pelo menos 1 minuto ou at&#233; que os valores da frequ&#234;ncia card&#237;aca e da press&#227;o arterial retornassem ao basal. Realizou-se MSC duas vezes de cada lado para avaliar a reprodutibilidade do m&#233;todo. Completou-se a sequ&#234;ncia mesmo quando da positividade de uma massagem. Ap&#243;s cada epis&#243;dio de MSC, perguntava-se aos pacientes a respeito de sintomas relacionados &#224; manobra. A HSC foi classificada em aqueles com cardioinibit&#243;ria (CI) se presen&#231;a de assistolia &#8805; 3 segundos ou em HSC VD se redu&#231;&#227;o da PAS &#8805; 50mmHg.<xref ref-type="bibr" rid="B19">19</xref>
					</p>
          <p>A press&#227;o arterial foi registrada de maneira cont&#237;nua, imediatamente antes de cada MSC e at&#233; que atingir o valor mais baixo registrado durante ou logo ap&#243;s a manobra. A magnitude da resposta da press&#227;o arterial foi obtida pela diferen&#231;a entre a PAS basal e a PAS m&#237;nima durante a MSC (&#916;PAS). Da mesma forma, os intervalos RR foram registrados, e a magnitude da resposta da frequ&#234;ncia card&#237;aca foi obtida pela diferen&#231;a entre o intervalo RR antes da MSC e o intervalo RR m&#225;ximo durante a MSC (&#916;RR).</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>Os dados foram analisados usando Excel 2003 e o programa SPSS para Windows, vers&#227;o 15.0. As medidas nominais s&#227;o apresentadas como frequ&#234;ncias absoluta (n) e relativa (%), e as medidas num&#233;ricas como m&#233;dia, desvio-padr&#227;o, mediana e valores m&#237;nimo e m&#225;ximo. As caracter&#237;sticas cl&#237;nicas e as respostas &#224; MSC (ordem, resultados e sintomas associados &#224; MSC) foram comparadas entre os grupos usando-se o teste do qui-quadrado e o teste de verossimilhan&#231;a. As medidas num&#233;ricas entre os grupos foram resumidas por estat&#237;stica descritiva e comparadas usando o teste <italic>t</italic> de Student, o teste qui-quadrado para vari&#225;veis categ&#243;ricas e o teste de Mann-Whitney para vari&#225;veis cont&#237;nuas. Os testes n&#227;o param&#233;tricos foram usados para as vari&#225;veis sem distribui&#231;&#227;o normal (teste de Kolmogorov-Smirnov). O coeficiente de correla&#231;&#227;o intraclasse foi usado para analisar a reprodutibilidade da resposta &#224; MSC. Considerou-se estatisticamente significativo um valor de p &lt; 0,050.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>No grupo sintom&#225;tico, quase todos os pacientes (93,9%) tinham s&#237;ncope, com uma m&#233;dia de 5,4 epis&#243;dios (mediana &#8211; 3) no ano anterior &#224; avalia&#231;&#227;o. A <xref ref-type="table" rid="t5">Tabela 1</xref> mostra as caracter&#237;sticas cl&#237;nicas basais dos 99 pacientes sintom&#225;ticos e dos 66 assintom&#225;ticos.</p>
        <table-wrap id="t5">
          <label>Tabela 1</label>
          <caption>
            <title>Caracter&#237;sticas cl&#237;nicas dos grupos sintom&#225;tico e assintom&#225;tico</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Vari&#225;vel</th>
                <th align="center">Sintom&#225;tico (n = 99)</th>
                <th align="center">Assintom&#225;tico (n = 66)</th>
                <th align="center">p</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Idade, m&#233;dia &#177; dp (mediana) (m&#237;nimo - m&#225;ximo)</td>
                <td align="center">69,67 &#177; 10,26 (70) (50-93)</td>
                <td align="center">73,01 &#177; 9,68 (74) (52-92)</td>
                <td align="center">0,037</td>
              </tr>
              <tr>
                <td align="left">Homem, n (%)</td>
                <td align="center">41 (41,4%)</td>
                <td align="center">23 (34,8)</td>
                <td align="center">0,396</td>
              </tr>
              <tr>
                <td align="left">Hipertens&#227;o</td>
                <td align="center">73 (73,7%)</td>
                <td align="center">54 (81,8%)</td>
                <td align="center">0,227</td>
              </tr>
              <tr>
                <td align="left">Diabetes</td>
                <td align="center">13 (13,1)</td>
                <td align="center">20 (30,3)</td>
                <td align="center">0,007</td>
              </tr>
              <tr>
                <td align="left">Doen&#231;a arterial coronariana</td>
                <td align="center">5 (5,1)</td>
                <td align="center">11(16,7)</td>
                <td align="center">0,014</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN8">
              <p>Teste do qui-quadrado; dp: desvio-padr&#227;o.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Os pacientes do grupo sintom&#225;tico apresentaram as quedas mais significativas da press&#227;o arterial ap&#243;s inclina&#231;&#227;o a 70&#176;. A <xref ref-type="fig" rid="f4">Figura 1</xref> apresenta as altera&#231;&#245;es m&#233;dias de PAS e PAD ap&#243;s est&#237;mulo ortost&#225;tico. O grupo sintom&#225;tico teve maior ocorr&#234;ncia de HO, 29 pacientes (29,2%), dos quais 19 atingiram ao crit&#233;rio diagn&#243;stico de queda de PAS &#8805; 20 mmHg, e 10 outros pacientes atingiram ao crit&#233;rio diagn&#243;stico de queda de PAD &#8805; 10 mmHg. Apenas 8 pacientes (12,1%) do grupo assintom&#225;tico tiveram um diagn&#243;stico de HO, que resultou da queda da PAS em 7 deles (p = 0,014).</p>
        <p>
          <fig id="f4">
            <label>Figura 1</label>
            <caption>
              <title>Magnitudes das respostas das press&#245;es arteriais sist&#243;lica e diast&#243;lica (PAS e PAD, respectivamente) &#224; inclina&#231;&#227;o de 70&#176; nos grupos sintom&#225;tico e assintom&#225;tico. Note a significativa queda na PAS (p &lt; 0,001) e na PAD (p = 0,001) no grupo sintom&#225;tico em compara&#231;&#227;o ao grupo assintom&#225;tico.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-111-01-0084-80114-gf01-pt.jpg"/></fig>
        </p>
        <sec sec-type="results">
          <title>Massagem do seio carot&#237;deo</title>
          <p>Os grupos n&#227;o diferiram quanto &#224;s respostas obtidas durante a MSC (p = 0,466) (<xref ref-type="fig" rid="f5">Figura 2</xref>). A resposta &#224; MSC foi considerada normal em 64,8% dos pacientes de toda a amostra, 67,7% do grupo sintom&#225;tico e 60,6% do grupo assintom&#225;tico. Mais de 32% dos pacientes nos dois grupos apresentaram uma resposta anormal &#224; MSC, com predom&#237;nio de respostas CI.</p>
          <p>
            <fig id="f5">
              <label>Figura 2</label>
              <caption>
                <title>Resultados da massagem do seio carot&#237;deo de acordo com o tipo de resposta obtida nos grupos sintom&#225;tico e assintom&#225;tico. HSC: hipersensibilidade do seio carot&#237;deo.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-111-01-0084-80114-gf02-pt.jpg"/></fig>
          </p>
          <p>Os homens, se comparados &#224;s mulheres, apresentaram mais respostas anormais &#224; MSC (53,8% vs. 23,0%, respectivamente, p &lt; 0,001). Predom&#237;nio de resposta CI foi tamb&#233;m observado mais em homens do que em mulheres (43,1% vs. 13,0%, respectivamente). As respostas &#224; MSC n&#227;o diferiram significativamente quanto &#224; idade. Da mesma forma, n&#227;o houve associa&#231;&#227;o entre HSC e doen&#231;as subjacentes, como hipertens&#227;o, diabetes e doen&#231;a arterial coronariana (<xref ref-type="table" rid="t6">Tabela 2</xref>).</p>
          <table-wrap id="t6">
            <label>Tabela 2</label>
            <caption>
              <title>Distribui&#231;&#227;o das respostas &#224; massagem do seio carot&#237;deo (MSC) por idade, sexo e doen&#231;as subjacentes, como hipertens&#227;o, diabetes e doen&#231;a arterial coronariana</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" rowspan="3">Vari&#225;vel</th>
                  <th align="center" colspan="6" style="border-bottom-width:thin;border-bottom-style:solid">Resposta &#224; MSC</th>
                  <th align="center" rowspan="2">TOTAL</th>
                  <th align="center" rowspan="3">p</th>
                </tr>
                <tr>
                  <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">Sem HSC</th>
                  <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">Cardioinibidora</th>
                  <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">Vasodepressora</th>
                </tr>
                <tr>
                  <th align="center">n</th>
                  <th align="center">%</th>
                  <th align="center">n</th>
                  <th align="center">%</th>
                  <th align="center">n</th>
                  <th align="center">%</th>
                  <th align="center">n</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">
                    <bold>Idade</bold>
                  </td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
                    <bold>0,356<sup><xref ref-type="table-fn" rid="TFN10">#</xref></sup></bold>
                  </td>
                </tr>
                <tr>
                  <td align="left">50-59</td>
                  <td align="center">22</td>
                  <td align="center">78,5</td>
                  <td align="center">5</td>
                  <td align="center">17,9</td>
                  <td align="center">1</td>
                  <td align="center">3,5</td>
                  <td align="center">28</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">60-69</td>
                  <td align="center">30</td>
                  <td align="center">69,7</td>
                  <td align="center">9</td>
                  <td align="center">20,9</td>
                  <td align="center">4</td>
                  <td align="center">9,3</td>
                  <td align="center">43</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">70-79</td>
                  <td align="center">31</td>
                  <td align="center">56,3</td>
                  <td align="center">15</td>
                  <td align="center">27,3</td>
                  <td align="center">9</td>
                  <td align="center">16,3</td>
                  <td align="center">55</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">&#8805; 80</td>
                  <td align="center">24</td>
                  <td align="center">61,5</td>
                  <td align="center">12</td>
                  <td align="center">30,8</td>
                  <td align="center">3</td>
                  <td align="center">7,6</td>
                  <td align="center">39</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Sexo</bold>
                  </td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
                    <bold>&lt; 0,001<xref ref-type="table-fn" rid="TFN11">*</xref></bold>
                  </td>
                </tr>
                <tr>
                  <td align="left">Masculino</td>
                  <td align="center">30</td>
                  <td align="center">46,1</td>
                  <td align="center">28</td>
                  <td align="center">43,1</td>
                  <td align="center">6</td>
                  <td align="center">9,2</td>
                  <td align="center">65</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">Feminino</td>
                  <td align="center">77</td>
                  <td align="center">77,0</td>
                  <td align="center">13</td>
                  <td align="center">13,0</td>
                  <td align="center">11</td>
                  <td align="center">11,0</td>
                  <td align="center">100</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Hipertens&#227;o</bold>
                  </td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
                    <bold>0,849<sup><xref ref-type="table-fn" rid="TFN10">#</xref></sup></bold>
                  </td>
                </tr>
                <tr>
                  <td align="left">-</td>
                  <td align="center">25</td>
                  <td align="center">65,7</td>
                  <td align="center">10</td>
                  <td align="center">26,3</td>
                  <td align="center">3</td>
                  <td align="center">7,8</td>
                  <td align="center">38</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">+</td>
                  <td align="center">82</td>
                  <td align="center">64,5</td>
                  <td align="center">31</td>
                  <td align="center">24,4</td>
                  <td align="center">14</td>
                  <td align="center">11,0</td>
                  <td align="center">127</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Diabetes</bold>
                  </td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
                    <bold>0,095<sup><xref ref-type="table-fn" rid="TFN10">#</xref></sup></bold>
                  </td>
                </tr>
                <tr>
                  <td align="left">-</td>
                  <td align="center">90</td>
                  <td align="center">68,1</td>
                  <td align="center">28</td>
                  <td align="center">21,2</td>
                  <td align="center">14</td>
                  <td align="center">10,6</td>
                  <td align="center">132</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">+</td>
                  <td align="center">17</td>
                  <td align="center">51,5</td>
                  <td align="center">13</td>
                  <td align="center">39,4</td>
                  <td align="center">3</td>
                  <td align="center">9,0</td>
                  <td align="center">33</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Doen&#231;a arterial coronariana</bold>
                  </td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
                    <bold>0,401<sup><xref ref-type="table-fn" rid="TFN10">#</xref></sup></bold>
                  </td>
                </tr>
                <tr>
                  <td align="left">-</td>
                  <td align="center">99</td>
                  <td align="center">66,4</td>
                  <td align="center">35</td>
                  <td align="center">23,5</td>
                  <td align="center">15</td>
                  <td align="center">10,0</td>
                  <td align="center">149</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">+</td>
                  <td align="center">8</td>
                  <td align="center">50,0</td>
                  <td align="center">6</td>
                  <td align="center">37,5</td>
                  <td align="center">2</td>
                  <td align="center">12,5</td>
                  <td align="center">16</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">Total</td>
                  <td align="center">103</td>
                  <td align="center">62</td>
                  <td align="center">41</td>
                  <td align="center">25</td>
                  <td align="center">21</td>
                  <td align="center">13</td>
                  <td align="center">165</td>
                  <td align="center">
									</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN9">
                <p>HSC: hipersensibilidade do seio carot&#237;deo;</p>
              </fn>
              <fn id="TFN10">
                <label>#</label>
                <p>teste de verossimilhan&#231;a;</p>
              </fn>
              <fn id="TFN11">
                <label>*</label>
                <p>teste do qui-quadrado.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>As respostas &#224; MSC n&#227;o diferiram (<xref ref-type="fig" rid="f6">Figura 3</xref>) quando se comparou a queda da PAS (&#916;PAS) e da frequ&#234;ncia card&#237;aca (&#916;RR) entre os grupos sintom&#225;tico e assintom&#225;tico. Todos os pacientes estavam em ritmo sinusal, exceto dois do grupo sintom&#225;tico, que apresentaram fibrila&#231;&#227;o atrial, que foi persistente em um paciente e parox&#237;stica no outro.</p>
          <p>
            <fig id="f6">
              <label>Figura 3</label>
              <caption>
                <title>Magnitudes da resposta da press&#227;o arterial sist&#243;lica (&#916;PAS) (acima) e da resposta da frequ&#234;ncia card&#237;aca (&#916;RR) (abaixo) nos grupos sintom&#225;tico e assintom&#225;tico durante massagem do seio carot&#237;deo.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-111-01-0084-80114-gf03-pt.jpg"/></fig>
          </p>
          <p>Durante as manobras, 45 (45,45%) pacientes sintom&#225;ticos e 34 (51.5%) assintom&#225;ticos apresentaram redu&#231;&#227;o de PAS para n&#237;veis &#8804; 85 mmHg. A <xref ref-type="table" rid="t7">Tabela 3</xref> mostra as propor&#231;&#245;es de pacientes que alcan&#231;aram PAS &#8804; 85 mmHg na s&#233;rie de MSC. O reflexo VD aumentou de 8,0% para 31,3% no grupo sintom&#225;tico e de 13,6% para 28,7% no grupo assintom&#225;tico, ao se aplicar o ponto de corte da PAS &#8804; 85 mmHg para o diagn&#243;stico de HSC, quando comparado ao crit&#233;rio cl&#225;ssico de queda na PAS &#8805; 50 mmHg. Portanto, a mudan&#231;a no ponto de corte aumentou o diagn&#243;stico de HSC em 21,2% (total 53,5%) e 15,2% (total 54,5%) nos grupos sintom&#225;tico e assintom&#225;tico, respectivamente.</p>
          <table-wrap id="t7">
            <label>Tabela 3</label>
            <caption>
              <title>Propor&#231;&#227;o de pacientes com press&#227;o arterial sist&#243;lica (PAS) &#8804; 85 mmHg na s&#233;rie de massagem do seio carot&#237;deo (MSC)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" rowspan="2">
									</th>
                  <th align="center" colspan="5" style="border-bottom-width:thin;border-bottom-style:solid">PAS m&#237;nima &#8804; 85 mmHg durante MSC</th>
                </tr>
                <tr>
                  <th align="center">MSC direita 1 n (%)</th>
                  <th align="center">MSC direita 2 n (%)</th>
                  <th align="center">MSC esquerda 1 n (%)</th>
                  <th align="center">MSC esquerda 2 n (%)</th>
                  <th align="center">Total n (%)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Assintom&#225;tico</td>
                  <td align="center">24 (36,3)</td>
                  <td align="center">24 (36,3)</td>
                  <td align="center">20 (30,3)</td>
                  <td align="center">16 (30,3)</td>
                  <td align="center">66 (100)</td>
                </tr>
                <tr>
                  <td align="left">Sintom&#225;tico</td>
                  <td align="center">33 (33,3)</td>
                  <td align="center">34 (34,3)</td>
                  <td align="center">26 (26,2)</td>
                  <td align="center">29 (29,2)</td>
                  <td align="center">99 (100)</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <p>Embora as respostas anormais tenham sido similares nos dois grupos, os pacientes sintom&#225;ticos relataram mais sintomas durante a MSC (41,4% vs. 27,3%, p = 0,063). Os sintomas relatados variaram de leve desconforto a s&#237;ncope. No grupo sintom&#225;tico, 20 pacientes relataram pr&#233;-s&#237;ncope, 16 pacientes informaram tontura e 3 pacientes reportaram sintomas inespec&#237;ficos. No grupo assintom&#225;tico, 5 pacientes relataram pr&#233;-s&#237;ncope, 10 pacientes, tontura, e 2 pacientes, sintomas inespec&#237;ficos. Apenas 2 pacientes no grupo sintom&#225;tico tiveram s&#237;ncope, que ocorreu com pausas ventriculares de 8,2 e 8,1 segundos. Os sintomas foram relatados tanto em pacientes com respostas normal ou anormal, com relato de sintomas em a 17,8% dos casos com resposta fisiol&#243;gica, 78% nas respostas CI e 47,1% nas respostas VD. Da mesma forma, muitos pacientes apresentaram resposta positiva sem sintomas associados especialmente aqueles com resposta VD (82,2% do normal, 22% de CI e 52,9% de VD). Os sintomas resultantes de MSC ocorreram principalmente quando a PAS caiu abaixo de 90 mmHg e/ou os intervalos RR se estenderam por mais de 2500 ms (<xref ref-type="table" rid="t8">Tabela 4</xref>).</p>
          <table-wrap id="t8">
            <label>Tabela 4</label>
            <caption>
              <title>Correla&#231;&#227;o entre a ocorr&#234;ncia de sintomas durante a massagem do seio carot&#237;deo e a press&#227;o arterial sist&#243;lica (PAS) m&#237;nima e o intervalo RR m&#225;ximo obtidos durante a massagem</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="12%"/>
                <col width="12%"/>
                <col width="12%"/>
                <col width="12%"/>
                <col width="12%"/>
                <col width="12%"/>
                <col width="12%"/>
                <col width="12%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">Sintomas</th>
                  <th align="center">M&#233;dia &#177; DP</th>
                  <th align="center">Mediana</th>
                  <th align="center">M&#237;nimo</th>
                  <th align="center">M&#225;ximo</th>
                  <th align="center">n</th>
                  <th align="center">p</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left" rowspan="3">M&#237;nima PAS &#224; direita (mmHg)</td>
                  <td align="center">assintom&#225;tico</td>
                  <td align="center">102,5 &#177; 12,9</td>
                  <td align="center">101</td>
                  <td align="center">59</td>
                  <td align="center">180</td>
                  <td align="center">106</td>
                  <td align="center">&lt; 0,001<bold><xref ref-type="table-fn" rid="TFN13">*</xref></bold></td>
                </tr>
                <tr>
                  <td align="center">sintom&#225;tico</td>
                  <td align="center">86,4 &#177; 23,6</td>
                  <td align="center">85</td>
                  <td align="center">42</td>
                  <td align="center">151</td>
                  <td align="center">59</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="center">Total</td>
                  <td align="center">96,7 &#177; 23,7</td>
                  <td align="center">96</td>
                  <td align="center">42</td>
                  <td align="center">180</td>
                  <td align="center">165</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left" rowspan="3">M&#237;nima PAS &#224; esquerda (mmHg)</td>
                  <td align="center">assintom&#225;tico</td>
                  <td align="center">101,8 &#177; 20,7</td>
                  <td align="center">98</td>
                  <td align="center">64</td>
                  <td align="center">185</td>
                  <td align="center">106</td>
                  <td align="center">&lt; 0,001<xref ref-type="table-fn" rid="TFN13">*</xref>
									</td>
                </tr>
                <tr>
                  <td align="center">sintom&#225;tico</td>
                  <td align="center">89,0 &#177; 20,3</td>
                  <td align="center">87,5</td>
                  <td align="center">51</td>
                  <td align="center">178</td>
                  <td align="center">58</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="center">Total</td>
                  <td align="center">97,3 &#177; 21,4</td>
                  <td align="center">95</td>
                  <td align="center">51</td>
                  <td align="center">185</td>
                  <td align="center">164</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left" rowspan="3">M&#225;ximo intervalo RR &#224; direita (ms)</td>
                  <td align="center">assintom&#225;tico</td>
                  <td align="center">1326 &#177; 768</td>
                  <td align="center">1154</td>
                  <td align="center">625</td>
                  <td align="center">5455</td>
                  <td align="center">106</td>
                  <td align="center">&lt; 0,000<xref ref-type="table-fn" rid="TFN14">#</xref>
									</td>
                </tr>
                <tr>
                  <td align="center">sintom&#225;tico</td>
                  <td align="center">2639 &#177; 1762</td>
                  <td align="center">1800</td>
                  <td align="center">880</td>
                  <td align="center">7500</td>
                  <td align="center">59</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="center">Total</td>
                  <td align="center">1795 &#177; 1369</td>
                  <td align="center">1225</td>
                  <td align="center">625</td>
                  <td align="center">7500</td>
                  <td align="center">165</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left" rowspan="3">M&#225;ximo intervalo RR &#224; esquerda (ms)</td>
                  <td align="center">assintom&#225;tico</td>
                  <td align="center">1238 &#177; 564</td>
                  <td align="center">1111</td>
                  <td align="center">6326</td>
                  <td align="center">4520</td>
                  <td align="center">106</td>
                  <td align="center">&lt; 0,000<xref ref-type="table-fn" rid="TFN14">#</xref>
									</td>
                </tr>
                <tr>
                  <td align="center">sintom&#225;tico</td>
                  <td align="center">2772 &#177; 1891</td>
                  <td align="center">1840</td>
                  <td align="center">811</td>
                  <td align="center">8160</td>
                  <td align="center">59</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="center">Total</td>
                  <td align="center">1786 &#177; 1419</td>
                  <td align="center">1200</td>
                  <td align="center">632</td>
                  <td align="center">8160</td>
                  <td align="center">165</td>
                  <td align="center">
									</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN12">
                <p>DP: desvio-padr&#227;o;</p>
              </fn>
              <fn id="TFN13">
                <label>*</label>
                <p>teste t de Student;</p>
              </fn>
              <fn id="TFN14">
                <label>#</label>
                <p>teste de Mann-Whitney.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>A reprodutibilidade imediata da resposta &#224; MSC foi avaliada repetindo-se a MSC durante o mesmo procedimento. A reprodutibilidade da resposta de frequ&#234;ncia card&#237;aca foi discretamente superior se comparada &#224; resposta da press&#227;o arterial, com coeficientes de correla&#231;&#227;o intraclasse de 0,68 para a &#916;PAS &#224; direita, 0,71 para a &#916;PAS &#224; esquerda, 0,83 para a &#916;RR &#224; direita, e 0,81 para a &#916;RR &#224; esquerda. Os dados de frequ&#234;ncia card&#237;aca demonstram n&#237;veis aceit&#225;veis de conformidade (acima de 0,75). Observou-se reprodutibilidade da resposta anormal de press&#227;o arterial (HSC VD) em 40,8% (20/49 casos), e da resposta anormal de frequ&#234;ncia card&#237;aca (HSC CI) em 48,5% (50/103 casos).</p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>O diagn&#243;stico e o tratamento de s&#237;ncope ainda constituem um desafio na pr&#225;tica m&#233;dica. Nos pacientes idosos, a identifica&#231;&#227;o do diagn&#243;stico subjacente pode ser mais complexa devido &#224;s m&#250;ltiplas comorbidades, apresenta&#231;&#245;es at&#237;picas, amn&#233;sia por perda de consci&#234;ncia e dificuldades em lembrar do epis&#243;dio e caracteriz&#225;-lo.</p>
        <p>A ocorr&#234;ncia de HO &#233; um importante fator de risco para quedas e s&#237;ncope, especialmente em idosos, com 18,2% de preval&#234;ncia.<xref ref-type="bibr" rid="B20">20</xref><sup>-</sup><xref ref-type="bibr" rid="B23">23</xref> Neste estudo, observamos mais do que o dobro de preval&#234;ncia (29,2% vs. 12,1%) de HO nos pacientes sintom&#225;ticos em compara&#231;&#227;o aos assintom&#225;ticos. Tal achado confirma a import&#226;ncia de se investigar HO nos idosos com s&#237;ncope, refor&#231;ando a HO como uma das causas mais frequentes de s&#237;ncope naquela faixa et&#225;ria.</p>
        <p>Diferentemente dos resultados observados na investiga&#231;&#227;o de HO, respostas similares foram obtidas durante a MSC nos grupos sintom&#225;tico e assintom&#225;tico. Tal achado pode refor&#231;ar as hip&#243;teses de que a HSC n&#227;o seja um marcador diagn&#243;stico de uma s&#237;ndrome cl&#237;nica. Com proposta semelhante para avaliar a preval&#234;ncia de HSC e o valor diagn&#243;stico da MSC, Tan et al.,<xref ref-type="bibr" rid="B24">24</xref> relataram respostas alteradas em 25% dos pacientes encaminhados para avalia&#231;&#227;o de s&#237;ncope e quedas inexplicadas. Essa preval&#234;ncia de HSC foi menor quando comparada &#224; de outro estudo<xref ref-type="bibr" rid="B25">25</xref> em indiv&#237;duos acima dos 65 anos, provenientes de amostragem aleat&#243;ria de uma comunidade n&#227;o selecionada. Naquele estudo, os autores observaram HSC em 39% dos pacientes, e, num subgrupo sem hist&#243;ria de s&#237;ncope ou queda, 35% tinham hipersensibilidade &#224; MSC, enquanto 36% tinham sintomas relacionados &#224; MSC. Portanto, um teste positivo para HSC pode n&#227;o determinar necessariamente a causa da s&#237;ncope, deixando para o cl&#237;nico a dif&#237;cil decis&#227;o de aceitar o teste como confirma&#231;&#227;o da causa de s&#237;ncope, podendo induzir a um diagn&#243;stico incorreto.</p>
        <p>Solari et al.,<xref ref-type="bibr" rid="B26">26</xref> propuseram um ponto de corte com a queda sintom&#225;tica da PAS para valores &#8804; 85 mmHg como o mais adequado para identificar a forma VD da HSC em um estudo com 164 pacientes submetidos &#224; MSC que apresentaram sintomas na presen&#231;a de hipotens&#227;o ou bradicardia (M&#233;todo dos Sintomas), ou diagn&#243;stico de s&#237;ndrome do seio carot&#237;deo. O m&#233;todo n&#227;o requer qualquer ponto de corte para assistolia ou queda da PAS induzida por MSC, e a positividade do teste baseia-se na reprodu&#231;&#227;o dos sintomas. Os autores conclu&#237;ram que um ter&#231;o dos pacientes com a forma VD isolada n&#227;o p&#244;de ser diagnosticado com HSC atrav&#233;s do crit&#233;rio cl&#225;ssico de press&#227;o arterial (queda da PAS &#8805; 50 mmHg) em compara&#231;&#227;o com o crit&#233;rio do ponto de corte de PAS &#8804; 85 mmHg. Assim, propuseram essa metodologia objetiva e padronizada para classifica&#231;&#227;o do componente do reflexo VD para ser utilizada na pr&#225;tica cl&#237;nica.<xref ref-type="bibr" rid="B26">26</xref> Poucos estudos de larga escala avaliaram o valor diagn&#243;stico da MSC. Quando positiva, sugere uma tend&#234;ncia ou predisposi&#231;&#227;o para a s&#237;ndrome do seio carot&#237;deo; entretanto, n&#227;o estabelece tal positividade como a causa da s&#237;ncope, sem protocolo &#8220;ideal&#8221;, pois existe uma troca inexor&#225;vel entre sensibilidade e especificidade na aus&#234;ncia de um teste &#8220;padr&#227;o ouro&#8221; para valid&#225;-la prospectivamente em popula&#231;&#245;es com s&#237;ndrome do seio carot&#237;deo definida rigorosamente. Da mesma forma, a reprodu&#231;&#227;o de sintomas espont&#226;neos para confirmar o diagn&#243;stico como recomendado pela Sociedade Europeia de Cardiologia com o M&#233;todo dos Sintomas pode ser imprecisa nessa popula&#231;&#227;o, pois sintomas prodr&#244;micos est&#227;o ausentes em at&#233; 93% dos pacientes com s&#237;ndrome do seio carot&#237;deo, muitos com frequente d&#233;ficit de mem&#243;ria e cognitivo, confundindo a correla&#231;&#227;o. Al&#233;m disso, qualquer causa de hipotens&#227;o pode resultar em sintomas semelhantes &#224;queles determinados por HSC, com os primeiros sintomas de hipoperfus&#227;o retinal e cerebral esperados na posi&#231;&#227;o ortost&#225;tica quando a PAS cair para menos de 80 mmHg. Uma associa&#231;&#227;o entre comprometimento da autorregula&#231;&#227;o cerebral e apresenta&#231;&#227;o sintom&#225;tica de HSC foi demonstrada por Tan et al.,<xref ref-type="bibr" rid="B27">27</xref> em um estudo usando Doppler transcraniana durante hipotens&#227;o sist&#234;mica induzida por press&#227;o negativa nos membros inferiores. Os autores demonstraram menor fluxo sangu&#237;neo cerebral em indiv&#237;duos com HSC sintom&#225;ticos do que em indiv&#237;duos com HSC assintom&#225;ticos em resposta a redu&#231;&#245;es compar&#225;veis na press&#227;o arterial sist&#234;mica, e sugeriram que os sintom&#225;ticos t&#234;m uma maior suscetibilidade a s&#237;ncope ou quedas quando comparados aos assintom&#225;ticos, devido &#224; menor capacidade para manter o fluxo cerebral ante um desafio hipotensor.</p>
        <p>No nosso estudo, observamos que sintomas resultantes de MSC ocorreram principalmente quando a PAS caiu abaixo de 90 mmHg e/ou os intervalos RR estenderam-se por mais de 2500 ms, a despeito do diagn&#243;stico associado com a MSC. Al&#233;m disso, a HSC &#233; provocada por massagem manual, um est&#237;mulo altamente vari&#225;vel. Essa pode ser a raz&#227;o para a baixa reprodutibilidade da resposta positiva, como mostrado neste estudo.</p>
        <p>Embora a HSC tenha sido observada em pacientes com s&#237;ncope e os sintomas tenham sido reproduzidos durante a MSC, n&#227;o h&#225; relato demonstrando que as altera&#231;&#245;es hemodin&#226;micas vistas em laborat&#243;rio ocorram espontaneamente. Na tentativa de estabelecer a rela&#231;&#227;o entre HSC e quedas ou s&#237;ncopes, Schoon et al. testaram a hip&#243;tese de que a virada da cabe&#231;a desencadeia epis&#243;dios hipotensivos em idosos com HSC, tendo conclu&#237;do que a virada da cabe&#231;a pode causar epis&#243;dios hipotensivos em idosos. A virada da cabe&#231;a levou &#224; hipotens&#227;o em 39% do total de 96 pacientes, com queda m&#233;dia da PAS de 36 mmHg (varia&#231;&#227;o 20-76; DP &#177; 13), com ocorr&#234;ncia similar em idosos saud&#225;veis (44% de um total de 25 pacientes) e queda m&#233;dia da PAS de 35 mmHg (varia&#231;&#227;o 20-85; DP &#177; 19). O problema do desenho observacional &#233; n&#227;o permitir obter conclus&#245;es a respeito das rela&#231;&#245;es causais entre hipotens&#227;o por virada da cabe&#231;a e s&#237;ncope e quedas. Tamb&#233;m encontraram discrep&#226;ncia entre a ocorr&#234;ncia de hipotens&#227;o por virada da cabe&#231;a e os sintomas relacionados.<xref ref-type="bibr" rid="B28">28</xref> Da mesma forma a correla&#231;&#227;o positiva entre HSC e s&#237;ncope e/ou quedas precisa ser redefinida devido ao ac&#250;mulo de evid&#234;ncias de que a MSC causa resposta positiva similar na popula&#231;&#227;o assintom&#225;tica com o atual crit&#233;rio para diagn&#243;stico de HSC. O ponto de corte para queda sintom&#225;tica de PAS para n&#237;veis &#8804; 85 mmHg para identificar a forma VD de HSC pode levar a excesso de diagn&#243;stico e a erro diagn&#243;stico, sem conferir benef&#237;cios ao tratamento, podendo determinar efeitos adversos que superam os benef&#237;cios. Outras op&#231;&#245;es, como monitoramento por ECG de longa dura&#231;&#227;o com documenta&#231;&#227;o dos eventos espont&#226;neos, s&#227;o a &#250;nica maneira de confirmar o diagn&#243;stico e a sua correla&#231;&#227;o com os achados laboratoriais.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>N&#227;o foi demonstrada diferen&#231;a na resposta &#224; MSC entre pacientes com e sem s&#237;ncope ou pr&#233;-s&#237;ncope. A Hipersensibilidade do seio carot&#237;deo pode ser uma condi&#231;&#227;o inespec&#237;fica na avalia&#231;&#227;o de s&#237;ncope. Os melhores pontos de corte para assistolia e queda da PAS com base ou n&#227;o na reprodu&#231;&#227;o de sintomas ainda constituem um desafio na pr&#225;tica m&#233;dica. Consequentemente, a correla&#231;&#227;o cl&#237;nica e outros m&#233;todos de avalia&#231;&#227;o, como monitoramento por ECG de longa dura&#231;&#227;o, podem ser necess&#225;rios para confirmar a HSC como causa de s&#237;ncope.</p>
        <sec>
          <title>Limita&#231;&#245;es do estudo</title>
          <p>O grupo controle foi composto por indiv&#237;duos n&#227;o completamente saud&#225;veis, mas sem cardiopatia significativa e clinicamente est&#225;veis. Sabe-se que os idosos t&#234;m em m&#233;dia tr&#234;s comorbidades por pessoa. Os pacientes assintom&#225;ticos neste estudo foram recrutados em um ambulat&#243;rio de geriatria. A institui&#231;&#227;o &#233; um centro terci&#225;rio de cardiologia de refer&#234;ncia, apresentando os pacientes, em geral, uma substancial complexidade cl&#237;nica. Mesmo com os crit&#233;rios de exclus&#227;o, que levaram &#224; inclus&#227;o apenas de pacientes sem cardiopatia significativa e clinicamente est&#225;veis por ocasi&#227;o da sele&#231;&#227;o, observamos mais pacientes com diabetes e doen&#231;a arterial coronariana no grupo assintom&#225;tico. Por outro lado, os do grupo assintom&#225;tico foram discretamente mais velhos do que os do grupo sintom&#225;tico, com idade m&#233;dia de 73,0 e 69,6 anos, respectivamente. A despeito dessa diferen&#231;a, os pacientes dos dois grupos s&#227;o representativos da popula&#231;&#227;o idosa, na qual se acredita que a manobra vagal positiva defina o diagn&#243;stico etiol&#243;gico de s&#237;ncope. A presen&#231;a de comorbidades sist&#234;micas subjacentes no grupo assintom&#225;tico pode ser uma preocupa&#231;&#227;o importante. A idade avan&#231;ada e a presen&#231;a de doen&#231;as sist&#234;micas simult&#226;neas nesses pacientes refor&#231;am a hip&#243;tese de que a HSC possa ser n&#227;o muito mais do que um achado laboratorial relacionado ao envelhecimento e &#224;s doen&#231;as vasculares. Reconhecemos ainda que a diferen&#231;a de idade e de comorbidades entre os grupos possa constituir vi&#233;s, mas temos certeza de que os dois grupos s&#227;o representativos da popula&#231;&#227;o idosa, na qual a s&#237;ncope inexplicada &#233; um grande desafio.</p>
          <p>Neste estudo, a MSC foi realizada com os pacientes inclinados a 70&#176; ap&#243;s 5 minutos na posi&#231;&#227;o ortost&#225;tica, diferentemente de outros estudos em que a MSC foi realizada na posi&#231;&#227;o supina. Assim, nossos achados podem ser diferentes e, consequentemente, n&#227;o poderiam ser aplicados para a MSC na posi&#231;&#227;o supina. Escolhemos a posi&#231;&#227;o ortost&#225;tica, por ser a mais sens&#237;vel para detectar HSC de acordo com o estudo de Parry et al.,<xref ref-type="bibr" rid="B29">29</xref> que demonstraram especificidade e sensibilidade do teste positivo inicialmente na posi&#231;&#227;o supina de 74% e 100%, respectivamente, enquanto que o teste positivo na posi&#231;&#227;o ortost&#225;tica apresentou 100% de especificidade e de sensibilidade. Por tal raz&#227;o, realizamos a MSC apenas na posi&#231;&#227;o ortost&#225;tica neste estudo.</p>
        </sec>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>Este artigo &#233; parte de tese de Doutorado de Tan Chen Wu pela Faculdade de Medicina da Universidade de S&#227;o Paulo.</p>
        </fn>
        <fn>
          <p>
            <bold>Aprova&#231;&#227;o &#233;tica e consentimento informado</bold>
          </p>
          <p>Este estudo foi aprovado pelo Comit&#234; de &#201;tica do CAPPesq da Diretoria Cl&#237;nica do Hospital das Cl&#237;nicas e da Faculdade de Medicina da Universidade de S&#227;o Paulo sob o n&#250;mero de protocolo de pesquisa n&#186; 424/01. Todos os procedimentos envolvidos nesse estudo est&#227;o de acordo com a Declara&#231;&#227;o de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes inclu&#237;dos no estudo.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
