<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.0" specific-use="sps-1.3" 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">zq8NCxzkftMd5XdmvmXxJ4L</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2016000500382</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20160056</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2016005010104</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Lifetime Prevalence of Transient Loss of Consciousness in an Urban Russian Population</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Gudkova</surname>
            <given-names>S</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cherepanova</surname>
            <given-names>N</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Duplyakov</surname>
            <given-names>D</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Golovina</surname>
            <given-names>G</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Khokhlunov</surname>
            <given-names>S</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Surkova</surname>
            <given-names>E</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rotar</surname>
            <given-names>O</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Konradi</surname>
            <given-names>A</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Shlyakhto</surname>
            <given-names>E</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Samara Regional Cardiology Dispensary</institution>
        <addr-line>
          <named-content content-type="city">Samara</named-content>
        </addr-line>
        <country country="RU">Russiam</country>
        <institution content-type="original">Samara Regional Cardiology Dispensary, Samara - Russiam</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Samara State Medical University</institution>
        <addr-line>
          <named-content content-type="city">Samara</named-content>
        </addr-line>
        <country country="RU">Russiam</country>
        <institution content-type="original">Samara State Medical University, Samara - Russiam</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Samara Medical Clinical Centre</institution>
        <addr-line>
          <named-content content-type="city">Togliatti</named-content>
        </addr-line>
        <country country="RU">Russiam</country>
        <institution content-type="original">Samara Medical Clinical Centre, Togliatti - Russiam</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Federal North-West Medical Research Centre</institution>
        <addr-line>
          <named-content content-type="city">Saint-Petersburg</named-content>
        </addr-line>
        <country country="RU">Russiam</country>
        <institution content-type="original">Federal North-West Medical Research Centre, Saint-Petersburg - Russiam</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Dmitry Duplyakov</bold>, Samara Regional Cardiology Dispensary - Aerodromnaya Str. 43. Postal Code 443070, Samara - Russian e-mail: <email>duplyakov@yahoo.com</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Gudkova S, Cherepanova N, Duplyakov D, Khokhlunov S, Rotar O; Acquisition of data: Gudkova S, Cherepanova N; Analysis and interpretation of the data: Gudkova S, Cherepanova N, Golovina G, Khokhlunov S, Rotar O; Statistical analysis: Golovina G; Writing of the manuscript: Gudkova S, Cherepanova N, Duplyakov D, Surkova E; Critical revision of the manuscript for intellectual content: Duplyakov D, Surkova E, Rotar O, Konradi A; Supervision: Shlyakhto E.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potential Conflict of Interest</p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>15</day>
        <month>4</month>
        <year>2016</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>05</month>
        <year>2016</year>
      </pub-date>
      <volume>106</volume>
      <issue>05</issue>
      <fpage>382</fpage>
      <lpage>388</lpage>
      <history>
        <date date-type="received">
          <day>20</day>
          <month>07</month>
          <year>2015</year>
        </date>
        <date date-type="rev-recd">
          <day>12</day>
          <month>11</month>
          <year>2015</year>
        </date>
        <date date-type="accepted">
          <day>05</day>
          <month>02</month>
          <year>2016</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0">
          <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>Most international studies on epidemiology of transient loss of consciousness (TLC) were performed many years ago. There are no data about the lifetime prevalence of TLC in Russia.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To identify the lifetime prevalence and presumed mechanisms of TLC in an urban Russian population.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>1796 individuals (540 males [30.1%] and 1256 females [69.9%]) aged 20 to 69 years (mean age 45.8 &#177; 11.9 years) were randomly selected and interviewed within the framework of multicentre randomised observational trial.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>The overall prevalence of TLC in the studied population was 23.3% (418/1796), with the highest proportion (28%) seen in 40-49 year age group. TLC was significantly more common in women than in men (27.5% vs 13.5%). The mean age of patients at the time of the first event was 16 (11; 23) years, with 333 (85%) individuals experiencing the first episode of TLC under 30 years. The average time after the first episode of TLC was 27 (12; 47) years. The following mechanisms of TLC were determined using the questionnaire: neurally-mediated syncope (56.5%), arrhythmogenic onset of syncope (6.0%), nonsyncopal origin of TLC (1.4%), single episode during lifetime (2.1%). Reasons for TLC remained unidentified in 34% cases. 27 persons (6.5%) reported a family history of sudden death, mainly patients with presumably arrhythmogenic origin (24%).</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>Our findings suggest that the overall prevalence of TLC in individuals aged 20-69 years is high. The most common cause of TLC is neurally-mediated syncope. These data about the epidemiology can help to develop cost-effective management approaches to TLC.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Unconsciousness / epidemiology</kwd>
        <kwd>Syncope, Vasovagal</kwd>
        <kwd>Cross-Sectional Studies</kwd>
        <kwd>Urban Population</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Even after publication of Framingham study in 2002 we still have to say that data about epidemiology and prognosis of transient loss of consciousness (TLC) in the community are lacking.<xref ref-type="bibr" rid="B1">1</xref> The prevalence of TLC, often described as a "blackout" or a "collapse", in population has a bimodal distribution with peaks in teenagers (13-15 years) and in the elderly (after 70 years). In the young, almost all cases of TLC have neurally-mediated origin, while in the elderly, cardiac causes and orthostatic hypotension predominate. However, the lifetime prevalence of TLC is difficult to obtain due to recollection bias of fainting episodes which occurred many years ago.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref> Available evidence as well as limitations of multiple cohort and population-based studies on epidemiology of TLC are summarized in European Guidelines for the diagnosis and management of syncope and recent reviews.<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B6">6</xref>
			</p>
      <p>The objectives of this study were to identify the lifetime prevalence and presumed mechanisms of TLC in an urban Russian population.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>The data analysed in this paper were collected as part of a multicentre cross-sectional study of the epidemiology of Cardiovascular Disorders in Regions of the Russian Federation (ESSE-RF). Participants were from a random population sample of the residents of the city of Samara (1.1 million residents). Multi-stage random sampling was used to select people:<xref ref-type="bibr" rid="B7">7</xref>
			</p>
      <list list-type="simple">
        <list-item>
          <p>-four outpatient clinics were randomly selected from a total of 17 clinics in Samara City;</p>
        </list-item>
        <list-item>
          <p>-within these clinics, 10 residential catchment areas were randomly selected;</p>
        </list-item>
        <list-item>
          <p>-within catchment areas, 50 households per area were randomly selected.</p>
        </list-item>
      </list>
      <p>A survey was conducted by specially trained medical staff. Initially, people were invited to participate in the study by postcards and/or by phone calls. If we did not receive any response, than researchers went to the selected homes, explained the goals of the study, and invited them directly. The results were recorded using structured questionnaires and then entered into a database. Initially individuals from 25 to 64 years were recruited, while patients from 20 to 24 years of age and from 65 to 69 years of age were added later, using the same selection principles. Of the 2200 individuals approached, we were successful in recruiting 1796, resulting in a response rate 81.6%.</p>
      <p>Twelve data collection modules used in ESSE-RF Trial were supplemented by the additional module specifically designed for the purposes of our study.<xref ref-type="bibr" rid="B8">8</xref> The following self-reported information was collected in this module: 1) family history of sudden death (SD) related to cardiac pathology in first-degree relatives (parents and siblings) under the age of 45 years; 2) one or more episodes of having had a sensation of pulsation or movement in the chest; 3) a history of TLC: age at the time of the first event, as well as 14 questions that allowed to suspect neurally-mediated mechanism of TLC. This questionnaire (<xref ref-type="table" rid="t01">Table 1</xref>) was used in previous work to diagnose the neurally-mediated syncope (NMS) with a sensitivity of 95% and a specificity of 57%.<xref ref-type="bibr" rid="B9">9</xref> In addition, information was obtained from medical records concerning doctor-diagnosed episodes of paroxysmal palpitations and their main characteristics, such as duration of the attack, type of heart rhythm, its association with TLC, suddenness of the onset and offset, ECG recording during the attack, and its interpretation. Blood pressure measurement, rest ECG and cholesterol levels were obtained for all recruited patients according to the protocol of ESSE-RF study.</p>
      <table-wrap id="t01">
        <label>Table 1</label>
        <caption>
          <title>Questionnaire to diagnose the neurally-mediated origin of transient loss of consciousness<xref ref-type="bibr" rid="B9">9</xref>
					</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="50%"/>
            <col width="50%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">
                <bold>Questions</bold>
              </th>
              <th align="center">
                <bold>Points (if, yes)</bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Do you have a faint without obvious reasons?</td>
              <td align="center">-3</td>
            </tr>
            <tr>
              <td align="left">Do you have a faint with head rotation?</td>
              <td align="center">-3</td>
            </tr>
            <tr>
              <td align="left">Have you ever had spells or faint lying in bed?</td>
              <td align="center">-2</td>
            </tr>
            <tr>
              <td align="left">Have you ever had spells or faint while walking?</td>
              <td align="center">-2</td>
            </tr>
            <tr>
              <td align="left">Do you experience aura (strange light, unpleasant smell, confusing thoughts) before a faint?</td>
              <td align="center">-2</td>
            </tr>
            <tr>
              <td align="left">Do you need more than 30 minutes to recover after a faint?</td>
              <td align="center">-1</td>
            </tr>
            <tr>
              <td align="left">Do you feel drowsiness during recovery period?</td>
              <td align="center">-1</td>
            </tr>
            <tr>
              <td align="left">Do you faint in hot places?</td>
              <td align="center">1</td>
            </tr>
            <tr>
              <td align="left">Have you ever had spells or faint during medical procedures?</td>
              <td align="center">1</td>
            </tr>
            <tr>
              <td align="left">Do you have blurred vision before a faint?</td>
              <td align="center">1</td>
            </tr>
            <tr>
              <td align="left">Do you feel warm before a faint?</td>
              <td align="center">1</td>
            </tr>
            <tr>
              <td align="left">Do you have warning symptoms more than 30 seconds before your faint?</td>
              <td align="center">2</td>
            </tr>
            <tr>
              <td align="left">Do you faint with prolonged standing?</td>
              <td align="center">2</td>
            </tr>
            <tr>
              <td align="left">Have bystander noted you to be pale during your faints?</td>
              <td align="center">3</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <p>Neurally-mediated syncope may be considered if the point score is &#8805; 1</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>We defined TLC as an episode of spontaneous loss of consciousness not associated with brain injury, and followed by spontaneous recovery of consciousness regardless of the underlying mechanism. Syncope was defined as TLC related to temporary total brain hypoperfusion.<xref ref-type="bibr" rid="B3">3</xref> The tentative mechanism of TLC was determined on the basis of criteria proposed by the European Society of Cardiology.<xref ref-type="bibr" rid="B5">5</xref>
			</p>
      <p>Statistical analysis was performed using Statistica software 7.0. Data were presented as mean values and standard deviations (M &#177; s) in case of normal distribution, and as medians (Me) and 25 and 75 percentile values if the distribution was non-normal. Statistical analysis for normally distributed data was made using two-sided unpaired <italic>t-</italic> test for continuous variables and X<sup>2</sup>-test for categorical ones. Otherwise, Wilcoxon-Mann-Whitney test was used for comparison between groups. A two-tailed p value &lt; 0.05 was considered statistically significant.</p>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>General characteristics of the patients with TLC</title>
        <p>This study enrolled 1796 individuals (mean age was 45.8 &#177; 11.9 years; 1256 women and 540 men), 418 of whom reported a history of TLC during lifetime, resulting in an overall lifetime prevalence of TLC of 23.3%, with the highest level of 28% in those aged 40-49 years (<xref ref-type="fig" rid="f01">Figure 1</xref>). In men, TLC prevalence (13.5%; mean age 45.3 &#177; 11.2) was significantly lower than in women (27.5%; mean age 47.6 &#177; 11.2), p &lt; 0.01.</p>
        <p>
          <fig id="f01">
            <label>Figure 1</label>
            <caption>
              <title>Lifetime prevalence of transient loss of consciousness (TLC) by age at survey.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-106-05-0382-60056-gf01.jpg"/></fig>
        </p>
        <p>The vast majority of interviewed individuals (79.9%) had no concomitant heart condition. One-fifth reported arterial hypertension, and 15 patients (3.5%) suffered from coronary artery disease (CAD). On ECG, premature ventricular complexes were recorded in 20 subjects (4.8%), atrial fibrillation in 5 subjects (1.2%), and WPW syndrome in 3 (0.7%). Other 23 patients (5.5%) reported recent episodes of arrhythmias on ECG, but did not know their exact type. Twenty-seven individuals (6.5%) reported SD among first degree relatives under age of 45 years.</p>
        <p>The mean age of patients at the time of the first TLC episode was 16 (11; 23) years, with 333 (85.0%) individuals (both men and women) experiencing their first episode of TLC before 30 years of age (<xref ref-type="table" rid="t02">Table 2</xref>). Almost half of the patients (55% men and 47% women) experienced the first TLC aged 10-19 years (<xref ref-type="fig" rid="f02">Figure 2</xref>). The prevalence of the first episode of TLC in the population declined with age, being as low as 1% in women aged 60-69 years. The average time between first reported episode of TLC and the survey was 27 (12; 47) years.</p>
        <table-wrap id="t02">
          <label>Table 2</label>
          <caption>
            <title>Clinical characteristics of patients with transient loss of consciousness (TLC)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
								</th>
                <th align="center">
                  <bold>NMS</bold>
                </th>
                <th align="center">
                  <bold>Arrhythmogenic TLC</bold>
                </th>
                <th align="center">
                  <bold>Nonsyncopal</bold>
                </th>
                <th align="center">
                  <bold>Single episode</bold>
                </th>
                <th align="center">
                  <bold>Unidentified reason</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left"># (%) of patients</td>
                <td align="center">236 (56.5%)</td>
                <td align="center">25 (6%)</td>
                <td align="center">6 (1.4%)</td>
                <td align="center">9 (2.1%)</td>
                <td align="center">142 (34%)</td>
              </tr>
              <tr>
                <td align="left">Score by questionnaire</td>
                <td align="center">2.33 &#177; 1.77</td>
                <td align="center">0.91 &#177; 0.05</td>
                <td align="center">-4.17 &#177; 1.72</td>
                <td align="center">0.38 &#177; 0.11</td>
                <td align="center">-1.69 &#177; 1.37</td>
              </tr>
              <tr>
                <td align="left">Mean age, years</td>
                <td align="center">46.5 &#177; 11.1</td>
                <td align="center">55.4 &#177; 7.9</td>
                <td align="center">52.2 &#177; 8.5</td>
                <td align="center">49.3 &#177; 9.6</td>
                <td align="center">46.5 &#177; 11.8</td>
              </tr>
              <tr>
                <td align="left">Male</td>
                <td align="center">18.6%</td>
                <td align="center">12%</td>
                <td align="center">0%</td>
                <td align="center">0%</td>
                <td align="center">14.8%</td>
              </tr>
              <tr>
                <td align="left">Mean age at the debut of TLC, years</td>
                <td align="center">15.6 &#177; 11.0</td>
                <td align="center">17.4 &#177; 9.9</td>
                <td align="center">19.3 &#177; 8.7</td>
                <td align="center">NA</td>
                <td align="center">16 (11;22)</td>
              </tr>
              <tr>
                <td align="left">The length of clinical history of TLC, years</td>
                <td align="center">26.8 &#177; 14.5</td>
                <td align="center">28.7 &#177; 12.1</td>
                <td align="center">32.0 &#177; 14.9</td>
                <td align="center">NA</td>
                <td align="center">25 (13;36)</td>
              </tr>
              <tr>
                <td align="left">Family history of sudden cardiac death</td>
                <td align="center">5.1%</td>
                <td align="center">24.0%<xref ref-type="table-fn" rid="TFN3">*</xref>
								</td>
                <td align="center">0%</td>
                <td align="center">0%</td>
                <td align="center">6.3%</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>NMS: neurally-mediated syncope ; NA: not applicable;</p>
            </fn>
            <fn id="TFN3">
              <label>*</label>
              <p>p &lt; 0.01. TLC: transient loss of consciousness.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>
          <fig id="f02">
            <label>Figure 2</label>
            <caption>
              <title>The age of patients at the first episode of transient loss of consciousness (years).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-106-05-0382-60056-gf02.jpg"/></fig>
        </p>
        <p>Based on the data obtained from the questionnaire, we classified the likely underlying mechanisms of first reported episode of TLC in the study population (<xref ref-type="table" rid="t03">Table 3</xref>). In all age groups, NMS predominated, being observed in 50% to 66% of individuals (<xref ref-type="fig" rid="f03">Figure 3</xref>). TLC of presumably arrhythmogenic origin first appeared in patients &gt; 40 years of age, and its frequency increased in older patients, reaching 14% in 60 69 year age category (p &lt; 0.01). TLC due to nonsyncopal reasons or a single episode of TLC was also seen in older patients only (&gt; 40 years). The prevalence of cases with unidentified reason varied from 46% in the youngest age group to 28%-36% in other age groups.</p>
        <table-wrap id="t03">
          <label>Table 3</label>
          <caption>
            <title>Prevalence of presumed mechanisms of transient loss of consciousness (TLC)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="50%"/>
              <col width="50%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
                  <bold>Presumed mechanisms</bold>
                </th>
                <th align="center">
                  <bold>Prevalence</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">NMS</td>
                <td align="center">56.5%</td>
              </tr>
              <tr>
                <td align="left">Arrhythmogenic onset of syncope</td>
                <td align="center">6.0%</td>
              </tr>
              <tr>
                <td align="left">Nonsyncopal origin of TLC</td>
                <td align="center">1.4%</td>
              </tr>
              <tr>
                <td align="left">Single episode of TLC</td>
                <td align="center">2.1%</td>
              </tr>
              <tr>
                <td align="left">Unidentified genesis of TLC</td>
                <td align="center">34.0%</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN4">
              <p>NMS: Neurally-mediated syncope; TLC: transient loss of consciousness.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>
          <fig id="f03">
            <label>Figure 3</label>
            <caption>
              <title>Prevalence of different classes of transient loss of consciousness by age (* p &lt; 0.01). NMS: neurally-mediated syncope.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-106-05-0382-60056-gf03.jpg"/></fig>
        </p>
      </sec>
      <sec>
        <title>Presumed NMS</title>
        <p>Based on the data collected using the questionnaire, NMS as a tentative mechanism of TLC was identified in 236 (56.5%) individuals. Mean questionnaire score within this group was 2.33 &#177; 1.77.</p>
        <p>One or more typical NMS triggers identified through the questionnaire included: syncope occurring in crowded and hot places, 172 (72.9%) individuals; syncope associated with prolonged time in standing position, 38 (16.1%) individuals; syncope associated with intravenous injections, medical procedures, 57 (24.2%) individuals; syncope associated with neck movement, 8 (3.4%) individuals; syncope associated with severe pain or emotional stress, 3 (1.3%) individuals.</p>
        <p>Less than half of the individuals (106; 44.9%) with presumably NMS had overt and typical prodromal symptoms, mostly "blurred vision" in 101 (95.3%) patients, and feeling of warmth in 31 (29.2%) patients. Other patients (130; 55.1%) experienced little (100 patients; 42.4%) or no symptoms at all (30 patients; 12.7%).</p>
        <p>In most cases, the recovery was quick, and consciousness restored rapidly. However, in 43 (18.2%) individuals, complete recovery took 30 minutes or more, and 15 (6.4%) individuals experienced drowsiness after TLC.</p>
      </sec>
      <sec>
        <title>Presumed arrhythmogenic origin of TLC</title>
        <p>Twenty-five (6%) individuals reported palpitation sensations before TLC. Thirteen (52%) patients described their episodes of palpitation as having sudden onset and a regular pulse, whereas 9 (36%) patients experienced irregular heartbeats during palpitation. Only 16 patients (64%) sought medical help, the following cardiovascular disorders being diagnosed in 7: CAD (n = 3); arterial hypertension (n = 2); atrioventricular reciprocating tachycardia (n = 1); and atrial fibrillation (n = 1).</p>
        <p>Using the questionnaire, we failed to identify risk factors potentially associated with life-threatening ventricular arrhythmias. Only 2 (8%) individuals experienced TLC while walking, and none of them complained of loss of consciousness in horizontal position.</p>
        <p>In 11 (44%) individuals from this group, symptoms of arrhythmia were combined with typical NMS triggers. Episodes associated with crowded and hot environments were observed in 10 individuals, syncopes associated with prolonged time in standing position in 4 individuals, and syncopes associated with intravenous injections in 2 individuals. Six of those 11 patients experienced blurred vision and/or had warm sensation at the debut of TLC. Eight patients required more than 30 minutes to recover, and 5 individuals reported drowsiness after an episode. Thus, in a proportion of patients in this group, NMS may also have contributed to the development of TLC.</p>
      </sec>
      <sec>
        <title>Presumed nonsyncopal origin of TLC</title>
        <p>In 6 (1.4%) women, loss of consciousness was not associated with any obvious cardiovascular symptom, but they experienced visual or auditory hallucinations during prodromal period. None of them had any comorbidity. In 2 women, hallucinations were combined with impaired vision during prodromal period and one "hot flash", and collapse was sudden in 3 of them. Recovering phase lasted more than 30 minutes in 2 women, and 4 of them slept after the episode suggesting epilepsy as a contributing factor.</p>
      </sec>
      <sec>
        <title>Single episode of TLC</title>
        <p>Nine (2.1%) women reported only one episode of TLC during lifetime. These occurred during pregnancy (n = 5), were associated with specific medical conditions (pneumonia, hepatitis, toxic shock, one each), or stress related (take-off of an aircraft - 1 patient). They earned 0.38 &#177; 0.11 points by questionnaire.</p>
      </sec>
      <sec>
        <title>Unidentified reason for TLC</title>
        <p>Absence of any reported triggers and development of TLC "for no obvious reason" was the basis for including such individuals in the group with unidentified genesis of TLC. This group consisted of 142 (34%) individuals, and almost 78% of them (110 individuals) had no symptom of any cardiovascular disease. Hypertension had been diagnosed in 31 (21.8%) patients previously, CAD in 8 patients, and atrial fibrillation in 2 patients.</p>
        <p>Sixty-five (45%) patients with TLC of unknown origin did not have any prodromal symptoms. "Blurred vision" during prodromal period was observed in 62 (43%) individuals, feeling of warmth in 17 (12%). Syncope with "sudden" fall was reported by 42 (29%) patients. Rapid and full recovery was seen in the vast majority of cases; however, in 21 (15%) patients, full recovery took over 30 minutes, and some of them (12 patients) slept for a while after TLC.</p>
      </sec>
      <sec>
        <title>Sudden cardiac death</title>
        <p>Twenty-seven individuals (6.5%) reported family history of SD. The highest prevalence of SD in close relatives (n = 6, 24%) was recorded in patients with presumed arrhythmogenic origin of TLC, which was significantly higher compared to patients with presumably NMS (5.1%) and unidentified reasons (6.3%). There was no SD among relatives of persons from the nonsyncopal and single episode groups.</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>Despite numerous publications, data about the incidence and prevalence of TLC in general population and different clinical settings are lacking, because some of them were published decades ago.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref> To our knowledge, this is the first report of lifetime prevalence of TLC in urban Russian population. The overall lifetime prevalence of one or more episodes of TLC in our population was 23%, with the highest prevalence of 28% observed in individuals aged 40-49 years. In women, TLC prevalence was twice as high compared to men (27.5% and 13.5%, respectively, p &lt; 0.01).</p>
      <p>The first episode of TLC is known to commonly occur in people aged 10-30 years, with overall frequency peaking at 13-15 years and after 70 years of age.<xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B15">15</xref> These data were confirmed in our study: the mean age at the time of first TLC in Samara city population was 16 (11; 23) years, with 85% of all TLC developing in patients under 30 years of age. However, contrary to the Framingham study results,<xref ref-type="bibr" rid="B1">1</xref> in our population the risk of TLC decreased with age. This fact may be partially explained by the absence of individuals older than 70 years in our study, since the second peak of TLC occurrence in the Framingham study was observed at the age of 70 years, for both men and women.</p>
      <p>The prevalence of TLC varies with age and its epidemiological characteristics could be significantly affected by diagnostic criteria and methods used in a particular study. The value of standardized questionnaires for screening has been demonstrated in multiple studies.<xref ref-type="bibr" rid="B16">16</xref><sup>-</sup><xref ref-type="bibr" rid="B20">20</xref> In our study, we also used specialized questionnaire, but no further diagnostic procedures, and medical examination was conducted according to the protocol of ESSE-RF study.</p>
      <p>The most commonly presumed cause of TLC in our population was NMS, which predominated in all age and gender groups. Therefore, our results were generally in agreement with the previously reported TLC scenarios, NMS being the most common cause of TLC, while cardiogenic syncope is usually less frequent, mostly having an arrhythmic origin. In approximately one-third of cases, the syncope genesis remains unidentified.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B25">25</xref>
			</p>
      <p>Information about the prevalence of various types of TLC is of utmost importance for clinical practice. Careful medical examination allows confirming the neurally-mediated mechanism in most patients with presumed NMS.<xref ref-type="bibr" rid="B5">5</xref> Tilt-table test, carotid sinus massage, and implantation of event recorders may be recommended in approximately half of patients with suspected neurally-mediated TLC without typical symptoms in prodromal period. Importantly, in 15-30% of patients with NMS, the differential diagnosis may be complicated due to symptoms overlapping other types of TLC.<xref ref-type="bibr" rid="B19">19</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref><sup>-</sup><xref ref-type="bibr" rid="B28">28</xref>
			</p>
      <p>In patients with suspected arrhythmic syncope, further diagnostic tests should be performed to exclude overt heart disease, mainly due to a high prevalence (24%) of SD among first-degree relatives. This is especially true for patients with syncope onset during physical exertion and short medical history of TLC. However, for patients having typical NMS triggers and prodromal symptoms, it is also important to examine the autonomous nervous system function, because, in some of those episodes, palpitation may be a sign of NMS, which is difficult to differentiate only on the basis of medical history.</p>
      <p>Detailed neurological examination, including video-EEG monitoring, is recommended for patients with suspected epilepsy. At the same time, 3 out of 6 patients with nonsyncopal TLC had a long history of falls, "hot flash" as a prodromal symptom, paleness of the skin during loss of consciousness and a short recovery period. We therefore recommend that all diagnostic tests recommended for patients with NMS should be considered in this group.</p>
      <p>In patients with unidentified origin of TLC, examination should start with an autonomous nervous system function assessment, due to a potentially high (40%) prevalence of NMS with atypical clinical presentations in this group.<xref ref-type="bibr" rid="B29">29</xref><sup>,</sup><xref ref-type="bibr" rid="B30">30</xref> Heart diseases and arrhythmias have to be excluded as well, as they often constitute the main risk factors for SD in this category of patients.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B31">31</xref>
			</p>
      <sec>
        <title>Limitations</title>
        <p>Our study has several limitations. First, despite a lot of methods used in clinical practice, there is no gold standard in syncope evaluation. We collected self-reported information and data from medical records, accompanied by ECG and blood pressure measurement, which are currently considered enough by European Society of Cardiology guidelines<xref ref-type="bibr" rid="B5">5</xref> for the initial evaluation of the vast majority of patients with syncope.</p>
        <p>Second, syncope with different underlying mechanisms might have common predisposing factors and prodromal symptoms. Thus, it can be sometimes challenging to distinguish them. However, NMS is considered the most common cause of TLC in population. We used a specialized questionnaire with proven accuracy to diagnose NMS in our study.</p>
        <p>Third, the results obtained in our study may not be applicable to patients with TLC admitted to tertiary centers, where TLC prevalence and mechanisms will be different.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>Our findings suggest that the lifetime prevalence of TLC in individuals aged 20-69 years is high. The most common cause of TLC is NMS. History of SD in close relatives was recorded in 24% of patients with presumably arrhythmogenic TLC origin. These epidemiological data can help to develop cost-effective management approaches to TLC.</p>
    </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 study is not associated with any thesis or dissertation work.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>References</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1 Soteriades ES, Evans JC, Larson MG, Chen MH, Chen L, Benjamin EJ, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12):878-85.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Soteriades</surname>
              <given-names>ES</given-names>
            </name>
            <name>
              <surname>Evans</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Larson</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>MH</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Benjamin</surname>
              <given-names>EJ</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Incidence and prognosis of syncope</article-title>
          <source>N Engl J Med</source>
          <year>2002</year>
          <volume>347</volume>
          <issue>12</issue>
          <fpage>878</fpage>
          <lpage>885</lpage>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2 Ganzeboom KS, Mairuhu G, Reitsma J, Linzer M, Wieling W, van Dijk N. Lifetime cumulative incidence of syncope in the general population: a study of 549 Dutch subjects aged 35-60 years. J Cardiovasc Electrophysiol. 2006;17(11):1172-6.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ganzeboom</surname>
              <given-names>KS</given-names>
            </name>
            <name>
              <surname>Mairuhu</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Reitsma</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Linzer</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Wieling</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>van Dijk</surname>
              <given-names>N</given-names>
            </name>
          </person-group>
          <article-title>Lifetime cumulative incidence of syncope in the general population: a study of 549 Dutch subjects aged 35-60 years</article-title>
          <source>J Cardiovasc Electrophysiol</source>
          <year>2006</year>
          <volume>17</volume>
          <issue>11</issue>
          <fpage>1172</fpage>
          <lpage>1176</lpage>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3 Olde Nordkamp LA, van Dijk N, Ganzeboom KS, Reitsma JB, Luitse JS, Dekker LR, et al. Syncope prevalence in the ED compared to that in the general practice and population: a strong selection process. Am J Emerg Med 2009;27(3):271-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Olde Nordkamp</surname>
              <given-names>LA</given-names>
            </name>
            <name>
              <surname>van Dijk</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Ganzeboom</surname>
              <given-names>KS</given-names>
            </name>
            <name>
              <surname>Reitsma</surname>
              <given-names>JB</given-names>
            </name>
            <name>
              <surname>Luitse</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Dekker</surname>
              <given-names>LR</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Syncope prevalence in the ED compared to that in the general practice and population: a strong selection process</article-title>
          <source>Am J Emerg Med</source>
          <year>2009</year>
          <volume>27</volume>
          <issue>3</issue>
          <fpage>271</fpage>
          <lpage>279</lpage>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4 Brignole M, Alboni P, Benditt DG, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, et al; Task Force on Syncope, European Society of Cardiology. Guidelines on management (diagnosis and treatment) of syncope--update 2004. Europace. 2004;6(6):467-537.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Brignole</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Alboni</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Benditt</surname>
              <given-names>DG</given-names>
            </name>
            <name>
              <surname>Bergfeldt</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Blanc</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Bloch Thomsen</surname>
              <given-names>PE</given-names>
            </name>
            <etal/>
            <collab>Task Force on Syncope, European Society of Cardiology</collab>
          </person-group>
          <article-title>Guidelines on management (diagnosis and treatment) of syncope--update 2004</article-title>
          <source>Europace</source>
          <year>2004</year>
          <volume>6</volume>
          <issue>6</issue>
          <fpage>467</fpage>
          <lpage>537</lpage>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5 Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB, et al; Task Force for the Diagnosis and Management of Syncope; European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA); Heart Failure Association (HFA); Heart Rhythm Society (HRS). Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J. 2009;30(21):2631-71.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Moya</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Sutton</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Ammirati</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Blanc</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Brignole</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Dahm</surname>
              <given-names>JB</given-names>
            </name>
            <etal/>
            <collab>Task Force for the Diagnosis and Management of Syncope</collab>
            <collab>European Society of Cardiology</collab>
            <collab>European Heart Rhythm Association</collab>
            <collab>Heart Failure Association</collab>
            <collab>Heart Rhythm Society</collab>
          </person-group>
          <article-title>Guidelines for the diagnosis and management of syncope (version 2009)</article-title>
          <source>Eur Heart J.</source>
          <year>2009</year>
          <volume>30</volume>
          <issue>21</issue>
          <fpage>2631</fpage>
          <lpage>2671</lpage>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6 Colman N, Nahm K, Ganzeboom KS, Shen WK, Reitsma J, Linzer M, et al. Epidemiology of reflex syncope. Clin Auton Res. 2004;14 Suppl 1:9-17.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Colman</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Nahm</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Ganzeboom</surname>
              <given-names>KS</given-names>
            </name>
            <name>
              <surname>Shen</surname>
              <given-names>WK</given-names>
            </name>
            <name>
              <surname>Reitsma</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Linzer</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Epidemiology of reflex syncope</article-title>
          <source>Clin Auton Res</source>
          <year>2004</year>
          <volume>14</volume>
          <supplement>Suppl 1</supplement>
          <fpage>9</fpage>
          <lpage>17</lpage>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7 Kish L. A procedure for objective respondent selection within the household. J Am Stat Assoc. 1949;44(247):380-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kish</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>A procedure for objective respondent selection within the household</article-title>
          <source>J Am Stat Assoc</source>
          <year>1949</year>
          <volume>44</volume>
          <issue>247</issue>
          <fpage>380</fpage>
          <lpage>387</lpage>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8 Scientific Organizing Committee of the RF-ESSAY. Epidemiology of cardiovascular disease in different regions of Russia (ESSAY-RF). Rationale and study design. Preventive Medicine. 2013;6:25-34.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <collab>Scientific Organizing Committee of the RF-ESSAY</collab>
          </person-group>
          <article-title>Epidemiology of cardiovascular disease in different regions of Russia (ESSAY-RF). Rationale and study design</article-title>
          <source>Preventive Medicine</source>
          <year>2013</year>
          <volume>6</volume>
          <fpage>25</fpage>
          <lpage>34</lpage>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9 Dupliakov DV, Golovina GA, Sysuenkova EV, Gluchova VL. [Assessment of vasovagal origin of syncope based on history features]. Kardiologiia. 2012;52(6):55-60.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dupliakov</surname>
              <given-names>DV</given-names>
            </name>
            <name>
              <surname>Golovina</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Sysuenkova</surname>
              <given-names>EV</given-names>
            </name>
            <name>
              <surname>Gluchova</surname>
              <given-names>VL</given-names>
            </name>
          </person-group>
          <article-title>Assessment of vasovagal origin of syncope based on history features</article-title>
          <source>Kardiologiia</source>
          <year>2012</year>
          <volume>52</volume>
          <issue>6</issue>
          <fpage>55</fpage>
          <lpage>60</lpage>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10 Murdoch BD. Loss of consciousness in healthy South African men: incidence, causes and relationship to EEG abnormality. S Afr Med J. 1980;57(19):771-4.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Murdoch</surname>
              <given-names>BD</given-names>
            </name>
          </person-group>
          <article-title>Loss of consciousness in healthy South African men: incidence, causes and relationship to EEG abnormality</article-title>
          <source>S Afr Med J</source>
          <year>1980</year>
          <volume>57</volume>
          <issue>19</issue>
          <fpage>771</fpage>
          <lpage>774</lpage>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11 Lamb LE, Green HC, Combs JJ, Cheeseman SA, Hammond J, et al. Incidence of loss of consciousness in Air Force personnel. Aerosp Med. 1960;31:973-88.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lamb</surname>
              <given-names>LE</given-names>
            </name>
            <name>
              <surname>Green</surname>
              <given-names>HC</given-names>
            </name>
            <name>
              <surname>Combs</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Cheeseman</surname>
              <given-names>SA</given-names>
            </name>
            <name>
              <surname>Hammond</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Incidence of loss of consciousness in Air Force personnel</article-title>
          <source>Aerosp Med</source>
          <year>1960</year>
          <volume>31</volume>
          <fpage>973</fpage>
          <lpage>988</lpage>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12 Ganzeboom KS, Colman N, Reitsma JB, Shen WK, Wieling W. Prevalence and triggers of syncope in medical students. Am J Cardiol. 2003;91(8):1006-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ganzeboom</surname>
              <given-names>KS</given-names>
            </name>
            <name>
              <surname>Colman</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Reitsma</surname>
              <given-names>JB</given-names>
            </name>
            <name>
              <surname>Shen</surname>
              <given-names>WK</given-names>
            </name>
            <name>
              <surname>Wieling</surname>
              <given-names>W</given-names>
            </name>
          </person-group>
          <article-title>Prevalence and triggers of syncope in medical students</article-title>
          <source>Am J Cardiol</source>
          <year>2003</year>
          <volume>91</volume>
          <issue>8</issue>
          <fpage>1006</fpage>
          <lpage>1008</lpage>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13 Serletis A, Rose S, Sheldon AG, Sheldon RS. Vasovagal syncope in medical students and their first-degree relatives. Eur Heart J. 2006;27(16):1965-70.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Serletis</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Rose</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Sheldon</surname>
              <given-names>AG</given-names>
            </name>
            <name>
              <surname>Sheldon</surname>
              <given-names>RS</given-names>
            </name>
          </person-group>
          <article-title>Vasovagal syncope in medical students and their first-degree relatives</article-title>
          <source>Eur Heart J</source>
          <year>2006</year>
          <volume>27</volume>
          <issue>16</issue>
          <fpage>1965</fpage>
          <lpage>1970</lpage>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14 Wieling W, Ganzeboom KS, Saul JP. Reflex syncope in children and adolescents. Heart. 2004;90(9):1094-100.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wieling</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Ganzeboom</surname>
              <given-names>KS</given-names>
            </name>
            <name>
              <surname>Saul</surname>
              <given-names>JP</given-names>
            </name>
          </person-group>
          <article-title>Reflex syncope in children and adolescents</article-title>
          <source>Heart</source>
          <year>2004</year>
          <volume>90</volume>
          <issue>9</issue>
          <fpage>1094</fpage>
          <lpage>1100</lpage>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15 Brignole M, Menozzi C, Bartoletti A, Giada F, Lagi A, Ungar A, et al. A new management of syncope: prospective systematic guideline-based evaluation of patients referred urgently to general hospitals. Eur Heart J. 2006;27(1):76-82.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Brignole</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Menozzi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Bartoletti</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Giada</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Lagi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Ungar</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>A new management of syncope: prospective systematic guideline-based evaluation of patients referred urgently to general hospitals</article-title>
          <source>Eur Heart J</source>
          <year>2006</year>
          <volume>27</volume>
          <issue>1</issue>
          <fpage>76</fpage>
          <lpage>82</lpage>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16 Accurso V, Winnicki M, Shamsuzzaman AS, Wenzel A, Johnson AK, Somers VK. Predisposition to vasovagal syncope in subjects with blood/injury phobia. Circulation. 2001;104(8):903-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Accurso</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Winnicki</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Shamsuzzaman</surname>
              <given-names>AS</given-names>
            </name>
            <name>
              <surname>Wenzel</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Johnson</surname>
              <given-names>AK</given-names>
            </name>
            <name>
              <surname>Somers</surname>
              <given-names>VK</given-names>
            </name>
          </person-group>
          <article-title>Predisposition to vasovagal syncope in subjects with blood/injury phobia</article-title>
          <source>Circulation</source>
          <year>2001</year>
          <volume>104</volume>
          <issue>8</issue>
          <fpage>903</fpage>
          <lpage>907</lpage>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>17 Calkins H, Shyr Y, Frumin H, Schork A, Morady F. The value of clinical history in the differentiation of syncope due to ventricular tachycardia, atrioventricular block and neurocardiogenic syncope. Am J Med. 1995;98(4):365-73.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Calkins</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Shyr</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Frumin</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Schork</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Morady</surname>
              <given-names>F</given-names>
            </name>
          </person-group>
          <article-title>The value of clinical history in the differentiation of syncope due to ventricular tachycardia, atrioventricular block and neurocardiogenic syncope</article-title>
          <source>Am J Med</source>
          <year>1995</year>
          <volume>98</volume>
          <issue>4</issue>
          <fpage>365</fpage>
          <lpage>373</lpage>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>18 Del Rosso A, Ungar A, Maggi R, Giada F, Petix NR, De Santo T, et al. Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score. Heart. 2008;94(12):1620-6.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Del Rosso</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Ungar</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Maggi</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Giada</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Petix</surname>
              <given-names>NR</given-names>
            </name>
            <name>
              <surname>De Santo</surname>
              <given-names>T</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score</article-title>
          <source>Heart</source>
          <year>2008</year>
          <volume>94</volume>
          <issue>12</issue>
          <fpage>1620</fpage>
          <lpage>1626</lpage>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>19 Sheldon R, Rose S, Ritchie D, Connolly SJ, Koshman ML, Lee MA, et al. Historical criteria that distinguish syncope from seizures. J Am Coll Cardiol. 2002;40(1):142-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sheldon</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Rose</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Ritchie</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Connolly</surname>
              <given-names>SJ</given-names>
            </name>
            <name>
              <surname>Koshman</surname>
              <given-names>ML</given-names>
            </name>
            <name>
              <surname>Lee</surname>
              <given-names>MA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Historical criteria that distinguish syncope from seizures</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2002</year>
          <volume>40</volume>
          <issue>1</issue>
          <fpage>142</fpage>
          <lpage>148</lpage>
        </element-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <mixed-citation>20 Van Dijk N, Boer KR, Colman N, Bakker A, Stam J, van Grieken JJ, et al. High diagnostic yield and accuracy of history, physical examination, and ECG in patients with transient loss of consciousness in FAST: The Fainting Assessment Study. J Cardiovasc Electrophysiol. 2008;19(1):48-55.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Van Dijk</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Boer</surname>
              <given-names>KR</given-names>
            </name>
            <name>
              <surname>Colman</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Bakker</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Stam</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>van Grieken</surname>
              <given-names>JJ</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>High diagnostic yield and accuracy of history, physical examination, and ECG in patients with transient loss of consciousness in FAST: The Fainting Assessment Study</article-title>
          <source>J Cardiovasc Electrophysiol</source>
          <year>2008</year>
          <volume>19</volume>
          <issue>1</issue>
          <fpage>48</fpage>
          <lpage>55</lpage>
        </element-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <mixed-citation>21 Ammirati F, Colivicchi F, Santini M. Diagnosing syncope in clinical practice. Implementation of a simplified diagnostic algorithm in a multicentre prospective trial-the OESIL 2 study (Osservatorio Epidemiologico della Sincope nel Lazio). Eur Heart J. 2000;21(11):935-40.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ammirati</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Colivicchi</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Santini</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Diagnosing syncope in clinical practice. Implementation of a simplified diagnostic algorithm in a multicentre prospective trial-the OESIL 2 study (Osservatorio Epidemiologico della Sincope nel Lazio)</article-title>
          <source>Eur Heart J</source>
          <year>2000</year>
          <volume>21</volume>
          <issue>11</issue>
          <fpage>935</fpage>
          <lpage>940</lpage>
        </element-citation>
      </ref>
      <ref id="B22">
        <label>22</label>
        <mixed-citation>22 Sarasin FP, Louis-Simonet M, Carballo D, Slama S, Rajeswaran A, Metzger JT, et al. Prospective evaluation of patients with syncope: a population-based study. Am J Med. 2001;111(3):177-84.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sarasin</surname>
              <given-names>FP</given-names>
            </name>
            <name>
              <surname>Louis-Simonet</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Carballo</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Slama</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Rajeswaran</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Metzger</surname>
              <given-names>JT</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prospective evaluation of patients with syncope: a population-based study</article-title>
          <source>Am J Med</source>
          <year>2001</year>
          <volume>111</volume>
          <issue>3</issue>
          <fpage>177</fpage>
          <lpage>184</lpage>
        </element-citation>
      </ref>
      <ref id="B23">
        <label>23</label>
        <mixed-citation>23 Blanc JJ, L'her C, Touiza A, Garo B, L'Her E, Mansourati J. Prospective evaluation and outcome of patients admitted for syncope over a 1 year period. Eur Heart J. 2002;23(10):815-20.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Blanc</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>L'her</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Touiza</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Garo</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>L'Her</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Mansourati</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Prospective evaluation and outcome of patients admitted for syncope over a 1 year period</article-title>
          <source>Eur Heart J</source>
          <year>2002</year>
          <volume>23</volume>
          <issue>10</issue>
          <fpage>815</fpage>
          <lpage>820</lpage>
        </element-citation>
      </ref>
      <ref id="B24">
        <label>24</label>
        <mixed-citation>24 Farwell D, Sulke N. How do we diagnose syncope? J Cardiovasc Electrophysiol. 2002;13(1 Suppl):S9-13.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Farwell</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Sulke</surname>
              <given-names>N</given-names>
            </name>
          </person-group>
          <article-title>How do we diagnose syncope?</article-title>
          <source>J Cardiovasc Electrophysiol</source>
          <year>2002</year>
          <volume>13</volume>
          <issue>1</issue>
          <supplement>Suppl</supplement>
          <fpage>S9</fpage>
          <lpage>S13</lpage>
        </element-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <mixed-citation>25 Disertori M, Brignole M, Menozzi C, Raviele A, Rizzon P, Santini M, et al; Evaluation of Guidelines in Syncope Study. Management of patients with syncope referred urgently to general hospitals. Europace. 2003;5(3):283-91.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Disertori</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Brignole</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Menozzi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Raviele</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Rizzon</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Santini</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
            <collab>Evaluation of Guidelines in Syncope Study</collab>
          </person-group>
          <article-title>Management of patients with syncope referred urgently to general hospitals</article-title>
          <source>Europace</source>
          <year>2003</year>
          <volume>5</volume>
          <issue>3</issue>
          <fpage>283</fpage>
          <lpage>291</lpage>
        </element-citation>
      </ref>
      <ref id="B26">
        <label>26</label>
        <mixed-citation>26 Colman N, Bakker A, Linzer M, Reitsma JB, Wieling W, Wilde AA. Value of history-taking in syncope patients: in whom to suspect long QT syndrome? Europace. 2009;11(7):937-43.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Colman</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Bakker</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Linzer</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Reitsma</surname>
              <given-names>JB</given-names>
            </name>
            <name>
              <surname>Wieling</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Wilde</surname>
              <given-names>AA</given-names>
            </name>
          </person-group>
          <article-title>Value of history-taking in syncope patients: in whom to suspect long QT syndrome?</article-title>
          <source>Europace</source>
          <year>2009</year>
          <volume>11</volume>
          <issue>7</issue>
          <fpage>937</fpage>
          <lpage>943</lpage>
        </element-citation>
      </ref>
      <ref id="B27">
        <label>27</label>
        <mixed-citation>27 Romme JJCM, Van Dijk N, Boer KR, Bossuyt PM, Wieling W, Reitsma JB. Diagnosing vasovagal syncope based on quantitative history-taking: validation of the Calgary Syncope Symptom Score. Eur Heart J. 2009;30(3):2888-96.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Romme</surname>
              <given-names>JJCM</given-names>
            </name>
            <name>
              <surname>Van Dijk</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Boer</surname>
              <given-names>KR</given-names>
            </name>
            <name>
              <surname>Bossuyt</surname>
              <given-names>PM</given-names>
            </name>
            <name>
              <surname>Wieling</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Reitsma</surname>
              <given-names>JB</given-names>
            </name>
          </person-group>
          <article-title>Diagnosing vasovagal syncope based on quantitative history-taking: validation of the Calgary Syncope Symptom Score</article-title>
          <source>Eur Heart J</source>
          <year>2009</year>
          <volume>30</volume>
          <issue>3</issue>
          <fpage>2888</fpage>
          <lpage>2896</lpage>
        </element-citation>
      </ref>
      <ref id="B28">
        <label>28</label>
        <mixed-citation>28 Duplyakov D, Golovina G, Garkina S, Lyukshina N. Is it possible to accurately differentiate neurocardiogenic syncope and epilepsy? Cardiol J. 2010;17(4):420-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Duplyakov</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Golovina</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Garkina</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Lyukshina</surname>
              <given-names>N</given-names>
            </name>
          </person-group>
          <article-title>Is it possible to accurately differentiate neurocardiogenic syncope and epilepsy?</article-title>
          <source>Cardiol J</source>
          <year>2010</year>
          <volume>17</volume>
          <issue>4</issue>
          <fpage>420</fpage>
          <lpage>427</lpage>
        </element-citation>
      </ref>
      <ref id="B29">
        <label>29</label>
        <mixed-citation>29 Kapoor WN. Current evaluation and management of syncope. Circulation. 2002;106(13):1606-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kapoor</surname>
              <given-names>WN</given-names>
            </name>
          </person-group>
          <article-title>Current evaluation and management of syncope</article-title>
          <source>Circulation</source>
          <year>2002</year>
          <volume>106</volume>
          <issue>13</issue>
          <fpage>1606</fpage>
          <lpage>1609</lpage>
        </element-citation>
      </ref>
      <ref id="B30">
        <label>30</label>
        <mixed-citation>30 Merlos P, Rumiz E, Ruiz-Granell R, Mart&#237;nez &#193;, Izquierdo MT, Ferrero &#193;, et al. Outcome of patients with syncope beyond the implantable loop recorder. Europace. 2013;15(1):122-6.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Merlos</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Rumiz</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Ruiz-Granell</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Mart&#237;nez</surname>
              <given-names>&#193;</given-names>
            </name>
            <name>
              <surname>Izquierdo</surname>
              <given-names>MT</given-names>
            </name>
            <name>
              <surname>Ferrero</surname>
              <given-names>&#193;</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Outcome of patients with syncope beyond the implantable loop recorder</article-title>
          <source>Europace</source>
          <year>2013</year>
          <volume>15</volume>
          <issue>1</issue>
          <fpage>122</fpage>
          <lpage>126</lpage>
        </element-citation>
      </ref>
      <ref id="B31">
        <label>31</label>
        <mixed-citation>31 Strickberger SA, Benson DW, Biaggioni I, Callans DJ, Cohen MI, Ellenbogen KA, et al; American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke; Quality of Care and Outcomes Research Interdisciplinary Working Group; American College of Cardiology Foundation; Heart Rhythm Society. AHA/ACCF scientific statement on the evaluation of syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation In Collaboration With the Heart Rhythm Society. J Am Coll Cardiol. 2006;47(2):473-84.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Strickberger</surname>
              <given-names>SA</given-names>
            </name>
            <name>
              <surname>Benson</surname>
              <given-names>DW</given-names>
            </name>
            <name>
              <surname>Biaggioni</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Callans</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Cohen</surname>
              <given-names>MI</given-names>
            </name>
            <name>
              <surname>Ellenbogen</surname>
              <given-names>KA</given-names>
            </name>
            <etal/>
            <collab>American Heart Association Councils on Clinical Cardiology</collab>
            <collab>Cardiovascular Nursing</collab>
            <collab>Cardiovascular Disease in the Young, and Stroke</collab>
            <collab>Quality of Care and Outcomes Research Interdisciplinary Working Group</collab>
            <collab>American College of Cardiology Foundation</collab>
            <collab>Heart Rhythm Society</collab>
          </person-group>
          <article-title>AHA/ACCF scientific statement on the evaluation of syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation In Collaboration With the Heart Rhythm Society</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2006</year>
          <volume>47</volume>
          <issue>2</issue>
          <fpage>473</fpage>
          <lpage>484</lpage>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="SA1" xml:lang="pt">
    <front-stub>
      <title-group>
        <article-title>Preval&#234;ncia de Perda de Consci&#234;ncia Tempor&#225;ria em Popula&#231;&#227;o Russa Urbana</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Gudkova</surname>
            <given-names>S</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cherepanova</surname>
            <given-names>N</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Duplyakov</surname>
            <given-names>D</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Golovina</surname>
            <given-names>G</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Khokhlunov</surname>
            <given-names>S</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Surkova</surname>
            <given-names>E</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rotar</surname>
            <given-names>O</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Konradi</surname>
            <given-names>A</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Shlyakhto</surname>
            <given-names>E</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
      </contrib-group>
      <aff id="aff5">
        <label>1</label>
        <institution content-type="orgname">Samara Regional Cardiology Dispensary</institution>
        <addr-line>
          <named-content content-type="city">Samara</named-content>
        </addr-line>
        <country country="RU">Russia</country>
        <institution content-type="original">Samara Regional Cardiology Dispensary, Samara, - Russia</institution>
      </aff>
      <aff id="aff6">
        <label>2</label>
        <institution content-type="orgname">Samara State Medical University</institution>
        <addr-line>
          <named-content content-type="city">Samara</named-content>
        </addr-line>
        <country country="RU">Russia</country>
        <institution content-type="original">Samara State Medical University, Samara - Russia</institution>
      </aff>
      <aff id="aff7">
        <label>3</label>
        <institution content-type="orgname">Samara Medical Clinical Centre</institution>
        <addr-line>
          <named-content content-type="city">Togliatti</named-content>
        </addr-line>
        <country country="RU">Russia</country>
        <institution content-type="original">Samara Medical Clinical Centre, Togliatti, - Russia</institution>
      </aff>
      <aff id="aff8">
        <label>4</label>
        <institution content-type="orgname">Federal North-West Medical Research Centre</institution>
        <addr-line>
          <named-content content-type="city">Saint-Petersburg</named-content>
        </addr-line>
        <country country="RU">Russia</country>
        <institution content-type="original">Federal North-West Medical Research Centre, Saint-Petersburg - Russia</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Dmitry Duplyakov</bold>, Samara Regional Cardiology Dispensary - Aerodromnaya Str. 43. CEP 443070, Samara - Russia e-mail: <email>duplyakov@yahoo.com</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Gudkova S, Cherepanova N, Duplyakov D, Khokhlunov S, Rotar O; Obten&#231;&#227;o de dados: Gudkova S, Cherepanova N; An&#225;lise e interpreta&#231;&#227;o dos dados: Gudkova S, Cherepanova N, Golovina G, Khokhlunov S, Rotar O; An&#225;lise estat&#237;stica: Golovina G; Reda&#231;&#227;o do manuscrito: Gudkova S, Cherepanova N, Duplyakov D, Surkova E; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Duplyakov D, Surkova E, Rotar O, Konradi A; Supervis&#227;o: Shlyakhto E.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesse</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>A maioria dos estudos internacionais sobre epidemiologia da perda de consci&#234;ncia tempor&#225;ria (PCT) foi realizada h&#225; muitos anos. N&#227;o h&#225; dados sobre sua preval&#234;ncia ao longo da vida na R&#250;ssia.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Identificar a preval&#234;ncia ao longo da vida e os supostos mecanismos da PCT em uma popula&#231;&#227;o russa urbana.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>1.796 indiv&#237;duos (540 homens 30,1% e 1.256 mulheres 69,9%) com idade entre 20 e 69 anos (idade m&#233;dia, 45,8 &#177; 11,9 anos) foram selecionados aleatoriamente e entrevistados no contexto de um estudo multic&#234;ntrico randomizado observacional.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>A preval&#234;ncia global de PCT na popula&#231;&#227;o estudada foi 23,3% (418/1.796), sendo a mais alta propor&#231;&#227;o (28%) observada na faixa et&#225;ria de 40-49 anos. PCT foi significativamente mais comum nas mulheres (27,5% vs 13,5%). A idade m&#233;dia dos pacientes por ocasi&#227;o do primeiro evento foi 16 (11; 23) anos, com 333 (85%) indiv&#237;duos experienciando o primeiro epis&#243;dio de PCT antes dos 30 anos. O tempo m&#233;dio ap&#243;s o primeiro epis&#243;dio de PCT foi 27 (12; 47) anos. Os seguintes mecanismos de PCT foram determinados usando-se um question&#225;rio: s&#237;ncope neuromediada (56,5%), s&#237;ncope de origem arritmog&#234;nica (6,0%), PCT de origem n&#227;o sincopal (1,4%), epis&#243;dio &#250;nico durante a vida (2,1%). A causa de PCT n&#227;o foi identificada em 34% dos casos, sendo que 27 pacientes (6,5%) relataram hist&#243;ria familiar de morte s&#250;bita, principalmente aqueles com PCT de suposta origem arritmog&#234;nica (24%).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>Nossos achados sugerem uma alta preval&#234;ncia global de PCT em indiv&#237;duos com idade entre 20 e 69 anos. A causa mais comum de PCT &#233; a s&#237;ncope neuromediada. Esse dado sobre a epidemiologia pode contribuir para o desenvolvimento de abordagem custo-efetiva para PCT.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Inconsci&#234;ncia / epidemiologia</kwd>
        <kwd>Sincope Vasovagal</kwd>
        <kwd>Estudos Transversais</kwd>
        <kwd>Popula&#231;&#227;o Urbana</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>Mesmo ap&#243;s a publica&#231;&#227;o do estudo Framingham em 2002, informa&#231;&#227;o sobre a epidemiologia e o progn&#243;stico da perda de consci&#234;ncia tempor&#225;ria (PCT) na comunidade ainda &#233; escassa.<xref ref-type="bibr" rid="B1">1</xref> A preval&#234;ncia da PCT, com frequ&#234;ncia descrita como "apag&#227;o" ou "colapso", na popula&#231;&#227;o tem distribui&#231;&#227;o bimodal com picos nos adolescentes (13-15 anos) e nos idosos (ap&#243;s os 70 anos). Nos jovens, quase todos os casos de PCT t&#234;m origem neuromediada, enquanto que, nos idosos, as causas card&#237;acas e hipotens&#227;o ortost&#225;tica predominam. A preval&#234;ncia da PCT ao longo da vida, entretanto, &#233; dif&#237;cil de ser obtida, devido ao vi&#233;s de mem&#243;ria dos epis&#243;dios de desmaio ocorridos h&#225; muitos anos.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref> As evid&#234;ncias e as limita&#231;&#245;es de m&#250;ltiplas coortes e estudos de base populacional sobre a epidemiologia da PCT acham-se resumidas nas Diretrizes Europeias para o diagn&#243;stico e tratamento de s&#237;ncope e em recentes revis&#245;es.<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B6">6</xref>
				</p>
        <p>Este estudo teve por objetivo identificar a preval&#234;ncia ao longo da vida e poss&#237;veis mecanismos da PCT em uma popula&#231;&#227;o russa urbana.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Os dados analisados neste estudo foram obtidos de um estudo multic&#234;ntrico transversal sobre epidemiologia de doen&#231;as cardiovasculares em regi&#245;es da R&#250;ssia (ESSE-RF). Os participantes eram de uma amostra populacional aleat&#243;ria de residentes da cidade de Samara (1,1 milh&#227;o de habitantes). Utilizou-se amostragem aleat&#243;ria em m&#250;ltiplos est&#225;gios:<xref ref-type="bibr" rid="B7">7</xref>
				</p>
        <list list-type="simple">
          <list-item>
            <p>- quatro ambulat&#243;rios foram selecionados aleatoriamente de um total de 17 na cidade de Samara;</p>
          </list-item>
          <list-item>
            <p>- nesses ambulat&#243;rios, 10 &#225;reas residenciais foram selecionadas aleatoriamente;</p>
          </list-item>
          <list-item>
            <p>- nessas &#225;reas, 50 domic&#237;lios por &#225;rea foram selecionados aleatoriamente.</p>
          </list-item>
        </list>
        <p>A pesquisa foi realizada por um grupo de m&#233;dicos especialmente treinados. No in&#237;cio, o convite para participar do estudo foi feito atrav&#233;s de comunica&#231;&#227;o postal e/ou telefonema. Caso n&#227;o recebessem nenhuma resposta, os pesquisadores se dirigiam &#224;s resid&#234;ncias selecionadas, explicavam os objetivos do estudo e faziam o convite diretamente. Os resultados foram registrados sob a forma de question&#225;rios estruturados e, depois, armazenados em um banco de dados. No in&#237;cio, indiv&#237;duos entre 25 e 64 anos foram recrutados, adicionando-se mais tarde outros entre 20 e 24 anos e entre 65 e 69 anos, usando-se os mesmos princ&#237;pios de sele&#231;&#227;o. Dos 2.200 indiv&#237;duos abordados, 1.796 foram recrutados, resultando em uma taxa de resposta de 81,6%.</p>
        <p>Doze m&#243;dulos de coleta de dados usados no estudo ESSE-RF foram suplementados com o m&#243;dulo adicional especificamente projetado para este.<xref ref-type="bibr" rid="B8">8</xref> Nesse m&#243;dulo, as seguintes informa&#231;&#245;es autorrelatadas foram coletadas: 1) hist&#243;ria familiar de morte s&#250;bita (MS) relacionada a patologia card&#237;aca em parentes de primeiro grau (pais e irm&#227;os) com menos de 45 anos de idade; 2) um ou mais epis&#243;dios de sensa&#231;&#227;o de pulsa&#231;&#227;o ou movimento no peito; 3) uma hist&#243;ria de PCT: idade na &#233;poca do primeiro evento, assim como 14 perguntas que permitiam suspeitar de mecanismo neuromediado de PCT. Esse question&#225;rio (<xref ref-type="table" rid="t04">Tabela 1</xref>) foi usado em estudo anterior para diagnosticar s&#237;ncope neuromediada (SNM) com sensibilidade de 95% e especificidade de 57%.<xref ref-type="bibr" rid="B9">9</xref> Al&#233;m disso, obteve-se informa&#231;&#227;o dos prontu&#225;rios m&#233;dicos relacionada a epis&#243;dios de palpita&#231;&#245;es parox&#237;sticas diagnosticadas pelo m&#233;dico e suas principais caracter&#237;sticas, como dura&#231;&#227;o do ataque, tipo de ritmo card&#237;aco, sua associa&#231;&#227;o com PCT, in&#237;cio e fim s&#250;bitos, ECG registrado durante o ataque e sua interpreta&#231;&#227;o. Medida da press&#227;o arterial, ECG de repouso e n&#237;veis de colesterol foram obtidos em todos os pacientes recrutados segundo o protocolo do estudo ESSE-RF.</p>
        <table-wrap id="t04">
          <label>Tabela 1</label>
          <caption>
            <title>Question&#225;rio para diagn&#243;stico de origem neuromediada da perda de consci&#234;ncia tempor&#225;ria<xref ref-type="bibr" rid="B9">9</xref>
						</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="50%"/>
              <col width="50%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
                  <bold>Perguntas</bold>
                </th>
                <th align="center">
                  <bold>Pontos (se, sim)</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Voc&#234; desmaia sem motivo &#243;bvio?</td>
                <td align="center">-3</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; desmaia com a rota&#231;&#227;o da cabe&#231;a?</td>
                <td align="center">-3</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; j&#225; desmaiou na cama?</td>
                <td align="center">-2</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; j&#225; desmaiou enquanto caminhava?</td>
                <td align="center">-2</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; experiencia aura (luz estranha, cheiro desagrad&#225;vel, pensamentos confusos) antes de desmaiar?</td>
                <td align="center">-2</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; precisa de mais de 30 minutos para se recuperar ap&#243;s um desmaio?</td>
                <td align="center">-1</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; tem sonol&#234;ncia durante a recupera&#231;&#227;o?</td>
                <td align="center">-1</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; desmaia em locais quentes?</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; j&#225; desmaiou durante procedimentos m&#233;dicos?</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Sua vis&#227;o fica emba&#231;ada antes de voc&#234; desmaiar?</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; sente calor antes de desmaiar?</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; tem sintomas de alerta por mais de 30 segundos antes de desmaiar?</td>
                <td align="center">2</td>
              </tr>
              <tr>
                <td align="left">Voc&#234; desmaia ao ficar em p&#233; por muito tempo?</td>
                <td align="center">2</td>
              </tr>
              <tr>
                <td align="left">As pessoas &#224; sua volta percebem palidez cut&#226;nea durante seus desmaios?</td>
                <td align="center">3</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5">
              <p>S&#237;ncope neuromediada pode ser considerada para um escore &#8805; 1</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Definiu-se PCT como um epis&#243;dio de perda espont&#226;nea de consci&#234;ncia n&#227;o associado com les&#227;o cerebral, seguido por recupera&#231;&#227;o espont&#226;nea da consci&#234;ncia independentemente do mecanismo subjacente. Definiu-se s&#237;ncope como PCT relacionada a hipoperfus&#227;o cerebral total tempor&#225;ria.<xref ref-type="bibr" rid="B3">3</xref> O prov&#225;vel mecanismo de PCT foi determinado com base nos crit&#233;rios propostos pela Sociedade Europeia de Cardiologia.<xref ref-type="bibr" rid="B5">5</xref>
				</p>
        <p>A an&#225;lise estat&#237;stica foi realizada usando-se o programa Statistica, vers&#227;o 7.0. Os dados foram apresentados como m&#233;dia e desvio-padr&#227;o para as vari&#225;veis de distribui&#231;&#227;o normal, e como mediana e percentis 25 e 75 para as vari&#225;veis de distribui&#231;&#227;o n&#227;o normal. A an&#225;lise estat&#237;stica dos dados com distribui&#231;&#227;o normal foi realizada com o teste <italic>t</italic> n&#227;o pareado bicaudal para as vari&#225;veis cont&#237;nuas, e com o teste do qui-quadrado para as vari&#225;veis categ&#243;ricas. Utilizou-se o teste de Wilcoxon-Mann-Whitney para compara&#231;&#227;o entre os grupos. Considerou-se estatisticamente significativo um valor de p bicaudal &lt; 0,05.</p>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <sec>
          <title>Caracter&#237;sticas gerais dos pacientes com PCT</title>
          <p>Este estudo arrolou 1.796 indiv&#237;duos (idade m&#233;dia de 45,8 &#177; 11,9 anos; 1.256 mulheres e 540 homens), 418 dos quais relataram hist&#243;ria de PCT, resultando em uma preval&#234;ncia de PCT ao longo da vida de 23,3%, observando se o mais alto n&#237;vel de 28% na faixa et&#225;ria de 40-49 anos (<xref ref-type="fig" rid="f04">Figura 1</xref>). Nos homens, a preval&#234;ncia de PCT (13,5%; idade m&#233;dia de 45,3 &#177; 11,2) foi significativamente mais baixa do que nas mulheres (27,5%; idade m&#233;dia de 47,6 &#177; 11,2), p &lt; 0,01.</p>
          <p>
            <fig id="f04">
              <label>Figura 1</label>
              <caption>
                <title>Preval&#234;ncia de perda de consci&#234;ncia tempor&#225;ria (PCT) ao longo da vida de acordo com a idade no momento da pesquisa.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-106-05-0382-60056-gf01-pt.jpg"/></fig>
          </p>
          <p>A grande maioria dos entrevistados (79,9%) n&#227;o tinha doen&#231;a card&#237;aca concomitante. Um quinto dos entrevistados relatou hipertens&#227;o arterial, e 15 pacientes (3,5%) tinham doen&#231;a arterial coronariana (DAC). No ECG, complexos ventriculares prematuros foram registrados em 20 indiv&#237;duos (4,8%), fibrila&#231;&#227;o atrial em 5 indiv&#237;duos (1,2%), e s&#237;ndrome de Wolf-Parkinson-White em 3 (0,7%). Outros 23 pacientes (5,5%) relataram recentes epis&#243;dios de arritmias no ECG, mas n&#227;o souberam informar o tipo exato. Vinte e sete indiv&#237;duos (6,5%) relataram MS entre os parentes de primeiro grau com menos de 45 anos.</p>
          <p>A idade m&#233;dia dos pacientes na ocasi&#227;o do primeiro epis&#243;dio de PCT foi 16 (11; 23) anos, tendo 333 (85,0%) indiv&#237;duos (homens e mulheres) experienciado seu primeiro epis&#243;dio de PCT antes dos 30 anos (<xref ref-type="table" rid="t05">Tabela 2</xref>). Quase metade dos pacientes (55% dos homens e 47% das mulheres) apresentou o primeiro epis&#243;dio de PCT entre 10 e 19 anos (<xref ref-type="fig" rid="f05">Figura 2</xref>). A preval&#234;ncia do primeiro epis&#243;dio de PCT na popula&#231;&#227;o declinou com a idade, chegando a 1% em mulheres com idade entre 60 e 69 anos. O tempo m&#233;dio entre o primeiro epis&#243;dio de PCT relatado e a pesquisa foi de 27 (12; 47) anos.</p>
          <table-wrap id="t05">
            <label>Tabela 2</label>
            <caption>
              <title>Caracter&#237;sticas cl&#237;nicas dos pacientes com perda de consci&#234;ncia tempor&#225;ria</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">
                    <bold>SNM</bold>
                  </th>
                  <th align="center">
                    <bold>PCT arritmog&#234;nica</bold>
                  </th>
                  <th align="center">
                    <bold>N&#227;o sincopal</bold>
                  </th>
                  <th align="center">
                    <bold>Epis&#243;dio &#250;nico</bold>
                  </th>
                  <th align="center">
                    <bold>Causa n&#227;o identificada</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">n (%) de pacientes</td>
                  <td align="center">236 (56,5%)</td>
                  <td align="center">25 (6%)</td>
                  <td align="center">6 (1,4%)</td>
                  <td align="center">9 (2,1%)</td>
                  <td align="center">142 (34%)</td>
                </tr>
                <tr>
                  <td align="left">Escore do question&#225;rio</td>
                  <td align="center">2,33 &#177; 1,77</td>
                  <td align="center">0,91 &#177; 0,05</td>
                  <td align="center">-4,17 &#177; 1,72</td>
                  <td align="center">0,38 &#177; 0,11</td>
                  <td align="center">-1,69 &#177; 1,37</td>
                </tr>
                <tr>
                  <td align="left">Idade m&#233;dia, anos</td>
                  <td align="center">46,5 &#177; 11,1</td>
                  <td align="center">55,4 &#177; 7,9</td>
                  <td align="center">52,2 &#177; 8,5</td>
                  <td align="center">49,3 &#177; 9,6</td>
                  <td align="center">46,5 &#177; 11,8</td>
                </tr>
                <tr>
                  <td align="left">Homem</td>
                  <td align="center">18,6%</td>
                  <td align="center">12%</td>
                  <td align="center">0%</td>
                  <td align="center">0%</td>
                  <td align="center">14,8%</td>
                </tr>
                <tr>
                  <td align="left">Idade m&#233;dia no in&#237;cio da PCT, anos</td>
                  <td align="center">15,6 &#177; 11,0</td>
                  <td align="center">17,4 &#177; 9,9</td>
                  <td align="center">19,3 &#177; 8,7</td>
                  <td align="center">NA</td>
                  <td align="center">16 (11;22)</td>
                </tr>
                <tr>
                  <td align="left">Dura&#231;&#227;o da hist&#243;ria cl&#237;nica de PCT, anos</td>
                  <td align="center">26,8 &#177; 14,5</td>
                  <td align="center">28,7 &#177; 12,1</td>
                  <td align="center">32,0 &#177; 14,9</td>
                  <td align="center">NA</td>
                  <td align="center">25 (13;36)</td>
                </tr>
                <tr>
                  <td align="left">Hist&#243;ria familiar de morte s&#250;bita card&#237;aca</td>
                  <td align="center">5,1%</td>
                  <td align="center">24,0%<xref ref-type="table-fn" rid="TFN7">*</xref>
									</td>
                  <td align="center">0%</td>
                  <td align="center">0%</td>
                  <td align="center">6,3%</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN6">
                <p>SNM: s&#237;ncope neuromediada; NA: n&#227;o aplic&#225;vel;</p>
              </fn>
              <fn id="TFN7">
                <label>*</label>
                <p>p &lt; 0,01. PCT perda de consci&#234;ncia tempor&#225;ria.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>
            <fig id="f05">
              <label>Figura 2</label>
              <caption>
                <title>Idade dos pacientes (anos) por ocasi&#227;o do primeiro epis&#243;dio de perda de consci&#234;ncia tempor&#225;ria.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-106-05-0382-60056-gf02-pt.jpg"/></fig>
          </p>
          <p>Com base nos dados obtidos a partir do question&#225;rio, classificamos os prov&#225;veis mecanismos do primeiro epis&#243;dio relatado de PCT na popula&#231;&#227;o do estudo (<xref ref-type="table" rid="t06">Tabela 3</xref>). Em todas as faixas et&#225;rias, a SNM predominou, sendo observada em 50% a 66% dos indiv&#237;duos (<xref ref-type="fig" rid="f06">Figura 3</xref>). A PCT de suposta origem arritmog&#234;nica apareceu pela primeira vez em pacientes com idade superior a 40 anos, tendo sua frequ&#234;ncia aumentado nos mais idosos, chegando a 14% na faixa et&#225;ria de 60 a 69 anos (p &lt; 0,01). A PCT de origem n&#227;o sincopal ou um &#250;nico epis&#243;dio de PCT tamb&#233;m s&#243; foi observada em pacientes mais idosos (&gt; 40 anos). A preval&#234;ncia de casos com origem n&#227;o identificada variou de 46% nos mais jovens a 28%-36% nas demais faixas et&#225;rias.</p>
          <table-wrap id="t06">
            <label>Tabela 3</label>
            <caption>
              <title>Preval&#234;ncia do suposto mecanismo da perda de consci&#234;ncia tempor&#225;ria</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="50%"/>
                <col width="50%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
                    <bold>Mecanismo suposto</bold>
                  </th>
                  <th align="center">
                    <bold>Preval&#234;ncia</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">SNM</td>
                  <td align="center">56,5%</td>
                </tr>
                <tr>
                  <td align="left">Origem arritmog&#234;nica da s&#237;ncope</td>
                  <td align="center">6,0%</td>
                </tr>
                <tr>
                  <td align="left">Origem n&#227;o sincopal da PCT</td>
                  <td align="center">1,4%</td>
                </tr>
                <tr>
                  <td align="left">Epis&#243;dio &#250;nico de PCT</td>
                  <td align="center">2,1%</td>
                </tr>
                <tr>
                  <td align="left">Origem n&#227;o identificada de PCT</td>
                  <td align="center">34,0%</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN8">
                <p>SNM: S&#237;ncope neuromediada; POT: perda de consci&#234;ncia tempor&#225;ria.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>
            <fig id="f06">
              <label>Figura 3</label>
              <caption>
                <title>Preval&#234;ncia de diferentes tipos de perda de consci&#234;ncia tempor&#225;ria por idade (*p &lt; 0,01). SNM: s&#237;ncope neuromediada.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-106-05-0382-60056-gf03-pt.jpg"/></fig>
          </p>
        </sec>
        <sec>
          <title>Suposta SNM</title>
          <p>Com base nos dados obtidos a partir do question&#225;rio, identificou-se a SNM como o poss&#237;vel mecanismo de PCT em 236 (56,5%) indiv&#237;duos. O escore m&#233;dio do question&#225;rio nesse grupo foi 2,33 &#177; 1,77.</p>
          <p>Atrav&#233;s do question&#225;rio, identificaram-se os seguintes desencadeantes t&#237;picos de SNM: s&#237;ncope que ocorre em locais cheios de gente e quentes, 172 (72,9%) indiv&#237;duos; s&#237;ncope associada com tempo prolongado na posi&#231;&#227;o ereta, 38 (16,1%) indiv&#237;duos; s&#237;ncope associada com inje&#231;&#245;es intravenosas, procedimentos cl&#237;nicos, 57 (24,2%) indiv&#237;duos; s&#237;ncope associada com movimento do pesco&#231;o, 8 (3,4%) indiv&#237;duos; s&#237;ncope associada com dor intensa ou estresse emocional, 3 (1,3%) indiv&#237;duos.</p>
          <p>Menos da metade dos indiv&#237;duos (106; 44,9%) com suposta SNM apresentou sintomas prodr&#244;micos t&#237;picos e claros, em especial "vis&#227;o emba&#231;ada" (101 pacientes -95,3%), e sensa&#231;&#227;o de calor (31 pacientes - 29,2%). Outros pacientes (130; 55,1%) apresentaram poucos (100 pacientes; 42,4%) ou nenhum sintoma (30 pacientes; 12,7%).</p>
          <p>Na maioria dos casos, a recupera&#231;&#227;o deu-se logo, sendo a consci&#234;ncia recobrada rapidamente. Em 43 (18,2%) indiv&#237;duos, entretanto, a recupera&#231;&#227;o completa levou 30 minutos ou mais, e 15 (6,4%) indiv&#237;duos apresentaram sonol&#234;ncia ap&#243;s a PCT.</p>
        </sec>
        <sec>
          <title>Suposta origem arritmog&#234;nica da PCT</title>
          <p>Sensa&#231;&#227;o de palpita&#231;&#227;o precedeu a PCT segundo o relato de 25 (6%) indiv&#237;duos. Treze (52%) pacientes descreveram seus epis&#243;dios de palpita&#231;&#227;o como tendo in&#237;cio s&#250;bito e pulso regular, enquanto 9 (36%) pacientes apresentaram batimentos irregulares durante a palpita&#231;&#227;o. Apenas 16 pacientes (64%) buscaram assist&#234;ncia m&#233;dica, tendo-se diagnosticado os seguintes dist&#250;rbios cardiovasculares em 7: DAC (n = 3); hipertens&#227;o arterial (n = 2); taquicardia reentrante atrioventricular (n = 1); e fibrila&#231;&#227;o atrial (n = 1).</p>
          <p>A utiliza&#231;&#227;o do question&#225;rio n&#227;o permitiu identificar fatores de risco potencialmente associados com arritmias ventriculares que representem amea&#231;a &#224; vida. Apenas 2 (8%) indiv&#237;duos apresentaram PCT enquanto caminhavam e nenhum deles se queixou de perda de consci&#234;ncia na posi&#231;&#227;o horizontal.</p>
          <p>Em 11 (44%) indiv&#237;duos desse grupo, sintomas de arritmia combinaram-se com desencadeantes t&#237;picos de SNM. Epis&#243;dios associados a ambientes cheios de gente e quentes foram observados em 10 indiv&#237;duos, s&#237;ncopes associadas com tempo prolongado na posi&#231;&#227;o ereta, em 4 indiv&#237;duos, e s&#237;ncopes associadas com inje&#231;&#245;es intravenosas, em 2 indiv&#237;duos. Seis desses 11 pacientes apresentaram emba&#231;amento de vis&#227;o e/ou sensa&#231;&#227;o de calor no in&#237;cio da PCT. Oito pacientes precisaram de mais de 30 minutos para se recuperar, e 5 indiv&#237;duos relataram sonol&#234;ncia ap&#243;s um epis&#243;dio. Portanto, em alguns pacientes desse grupo, a SNM parece ter contribu&#237;do para o desenvolvimento da PCT.</p>
        </sec>
        <sec>
          <title>Suposta origem n&#227;o sincopal da PCT</title>
          <p>Em 6 (1,4%) mulheres, a perda de consci&#234;ncia n&#227;o se associou a sintoma cardiovascular &#243;bvio, mas elas apresentaram alucina&#231;&#245;es visuais ou auditivas durante o per&#237;odo prodr&#244;mico. Nenhuma apresentou qualquer comorbidade. Em 2 mulheres, as alucina&#231;&#245;es se combinaram com comprometimento da vis&#227;o durante o per&#237;odo prodr&#244;mico e, em uma, houve "fogacho". Colapso foi s&#250;bito em 3 mulheres. A fase de recupera&#231;&#227;o durou mais de 30 minutos em 2 mulheres, e 4 dormiram depois do epis&#243;dio, sugerindo que a epilepsia seja um fator contribuinte.</p>
        </sec>
        <sec>
          <title>Epis&#243;dio &#250;nico de PCT</title>
          <p>Nove (2,1%) mulheres relataram apenas um epis&#243;dio de PCT ao longo da vida. Tais epis&#243;dios ocorreram durante a gravidez (n = 5), estavam associados com condi&#231;&#245;es m&#233;dicas espec&#237;ficas (pneumonia, hepatite, choque t&#243;xico, um de cada) ou relacionados ao estresse (decolagem de aeronave - 1 paciente). Corresponderam a 0,38 &#177; 0,11 pontos por question&#225;rio.</p>
        </sec>
        <sec>
          <title>Origem n&#227;o identificada de PCT</title>
          <p>Aus&#234;ncia de desencadeantes relatados e desenvolvimento de PCT "por causa n&#227;o &#243;bvia" foi a base para a inclus&#227;o de tais indiv&#237;duos no grupo 'origem n&#227;o identificada de PCT'. Esse grupo consistiu de 142 (34%) indiv&#237;duos, e quase 78% deles (110 indiv&#237;duos) n&#227;o tinham sintoma de doen&#231;a cardiovascular. Hipertens&#227;o havia sido diagnosticada em 31 (21,8%) pacientes antes, DAC, em 8 pacientes e fibrila&#231;&#227;o atrial, em 2 pacientes.</p>
          <p>Sessenta e cinco (45%) pacientes com PCT de origem desconhecida n&#227;o apresentaram sintomas prodr&#244;micos. "Vis&#227;o emba&#231;ada" durante o per&#237;odo prodr&#244;mico foi relatada por 62 (43%) indiv&#237;duos, e sensa&#231;&#227;o de calor, por 17 (12%). S&#237;ncope com queda "s&#250;bita" foi relatada por 42 (29%) pacientes. Observou-se recupera&#231;&#227;o r&#225;pida e total na grande maioria dos casos; entretanto, em 21 (15%) pacientes, a recupera&#231;&#227;o total levou mais de 30 minutos, tendo 12 pacientes dormido ap&#243;s a PCT.</p>
        </sec>
        <sec>
          <title>Morte s&#250;bita card&#237;aca</title>
          <p>Hist&#243;ria familiar de MS foi informada por 27 indiv&#237;duos (6,5%). A mais alta preval&#234;ncia de MS em parentes pr&#243;ximos (n = 6, 24%) foi observada nos pacientes com suposta origem arritmog&#234;nica de PCT, que foi significativamente mais alta do que a observada nos pacientes com suposta SNM (5,1%) e origem n&#227;o identificada (6,3%). N&#227;o houve MS entre os parentes dos pacientes dos grupos de origem n&#227;o sincopal e epis&#243;dio &#250;nico.</p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>A despeito das in&#250;meras publica&#231;&#245;es, faltam dados sobre a incid&#234;ncia e a preval&#234;ncia de PCT na popula&#231;&#227;o geral e em diferentes cen&#225;rios cl&#237;nicos, pois alguns foram publicados d&#233;cadas atr&#225;s.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref> At&#233; onde se sabe, este &#233; o primeiro relato de preval&#234;ncia de PCT ao longo da vida em uma popula&#231;&#227;o urbana russa. A preval&#234;ncia global ao longo da vida de um ou mais epis&#243;dios de PCT na nossa popula&#231;&#227;o foi 23%, sendo a mais alta (28%) observada na faixa et&#225;ria de 40-49 anos. Nas mulheres, a preval&#234;ncia de PCT foi duas vezes maior do que nos homens (27,5% e 13,5%, respectivamente, p &lt; 0,01).</p>
        <p>Sabe-se que o primeiro epis&#243;dio de PCT &#233; mais comum na faixa et&#225;ria de 10-30 anos, com frequ&#234;ncia geral alcan&#231;ando um pico entre 13 e 15 anos e depois dos 70 anos.<xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B15">15</xref> Tais dados foram confirmados no nosso estudo: a idade m&#233;dia na ocasi&#227;o da primeira PCT na popula&#231;&#227;o da cidade de Samara foi 16 (11; 23) anos, sendo que 85% de todas as PCT ocorreram antes dos 30 anos de idade. Entretanto, em contraste com os resultados do estudo Framingham,<xref ref-type="bibr" rid="B1">1</xref> na nossa popula&#231;&#227;o, o risco de PCT diminuiu com a idade. Isso pode ser explicado em parte pela aus&#234;ncia de indiv&#237;duos com mais de 70 anos no nosso estudo, pois, no estudo Framingham, observou-se o segundo pico de PCT aos 70 anos de idade, tanto para homens quanto para mulheres.</p>
        <p>A preval&#234;ncia de PCT varia com a idade, e suas caracter&#237;sticas epidemiol&#243;gicas podem ser significativamente afetadas pelos crit&#233;rios diagn&#243;sticos e m&#233;todos usados em cada estudo. O valor de question&#225;rios padronizados para a triagem foi demonstrado em v&#225;rias publica&#231;&#245;es.<xref ref-type="bibr" rid="B16">16</xref><sup>-</sup><xref ref-type="bibr" rid="B20">20</xref> No nosso estudo, tamb&#233;m usamos question&#225;rio padronizado, mas sem nenhum outro procedimento diagn&#243;stico adicional, sendo os exames cl&#237;nicos conduzidos de acordo com o protocolo do estudo ESSE-RF.</p>
        <p>A suposta causa de PCT mais comum na nossa popula&#231;&#227;o foi SNM, que predominou em todas as faixas et&#225;rias e sexos. Nossos resultados, portanto, estavam alinhados com outros relatos de PCT, SNM sendo a causa mais comum de PCT, enquanto s&#237;ncope cardiog&#234;nica foi a menos frequente, sendo a maioria de origem arr&#237;tmica. Em cerca de um ter&#231;o dos casos, a origem da s&#237;ncope permanece n&#227;o identificada.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B25">25</xref>
				</p>
        <p>A informa&#231;&#227;o sobre a preval&#234;ncia dos v&#225;rios tipos de PCT &#233; da maior import&#226;ncia para a pr&#225;tica cl&#237;nica. Cuidadoso exame cl&#237;nico permite confirmar o mecanismo neuromediado na maioria dos pacientes com suposta SNM.<xref ref-type="bibr" rid="B5">5</xref> Teste de inclina&#231;&#227;o postural, massagem do seio carot&#237;deo e implanta&#231;&#227;o de gravadores de eventos podem ser recomendados em cerca de metade dos pacientes com suspeita de PCT neuromediada sem sintomas t&#237;picos no per&#237;odo prodr&#244;mico. Importante notar que, em 15-30% dos pacientes com SNM, o diagn&#243;stico diferencial pode ser complicado por sobreposi&#231;&#227;o de sintomas de outros tipos de PCT.<xref ref-type="bibr" rid="B19">19</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref><sup>-</sup><xref ref-type="bibr" rid="B28">28</xref>
				</p>
        <p>Em pacientes com s&#237;ncope de origem arritmog&#234;nica, exames diagn&#243;sticos adicionais devem ser realizados para excluir doen&#231;a card&#237;aca manifesta, em especial devido &#224; alta preval&#234;ncia (24%) de MS entre os parentes de primeiro grau. Isso &#233; especialmente verdadeiro para pacientes com in&#237;cio de s&#237;ncope durante esfor&#231;o f&#237;sico e breve hist&#243;ria cl&#237;nica de PCT. Para pacientes com desencadeantes t&#237;picos de SNM e pr&#243;dromos, entretanto, tamb&#233;m &#233; importante examinar a fun&#231;&#227;o do sistema nervoso aut&#244;nomo, pois, em alguns epis&#243;dios, a palpita&#231;&#227;o pode ser um sinal de SNM, que &#233; dif&#237;cil diferenciar apenas com base na hist&#243;ria cl&#237;nica.</p>
        <p>Recomenda-se exame neurol&#243;gico detalhado, incluindo monitora&#231;&#227;o com v&#237;deo-EEG, para pacientes com suspeita de epilepsia. Ao mesmo tempo, 3 de 6 pacientes com PCT n&#227;o sincopal tinham uma longa hist&#243;ria de quedas, "fogachos" como pr&#243;dromos, palidez cut&#226;nea durante a perda de consci&#234;ncia e um curto per&#237;odo de recupera&#231;&#227;o. Recomendamos, portanto, que sejam considerados todos os exames diagn&#243;sticos para pacientes com SNM nesse grupo.</p>
        <p>Para os pacientes com PCT de origem n&#227;o identificada, deve-se iniciar o exame com avalia&#231;&#227;o da fun&#231;&#227;o do sistema nervoso aut&#244;nomo, devido &#224; alta (40%) preval&#234;ncia de SNM de apresenta&#231;&#227;o cl&#237;nica at&#237;pica nesse grupo.<xref ref-type="bibr" rid="B29">29</xref><sup>,</sup><xref ref-type="bibr" rid="B30">30</xref> Devem ainda ser exclu&#237;das as doen&#231;as e arritmias card&#237;acas, pois com frequ&#234;ncia constituem os principais fatores de risco para MS nesses pacientes.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B31">31</xref>
				</p>
        <sec>
          <title>Limita&#231;&#245;es</title>
          <p>Nosso estudo apresenta v&#225;rias limita&#231;&#245;es. Primeiro, a despeito dos v&#225;rios m&#233;todos usados na pr&#225;tica cl&#237;nica, n&#227;o h&#225; um padr&#227;o-ouro para a avalia&#231;&#227;o de s&#237;ncope. Coletamos informa&#231;&#227;o autorrelatada e dados dos prontu&#225;rios m&#233;dicos, acompanhados de ECG e medida da press&#227;o arterial, atualmente considerados suficientes pelas diretrizes da Sociedade Europeia de Cardiologia<xref ref-type="bibr" rid="B5">5</xref> para avalia&#231;&#227;o inicial da grande maioria dos pacientes com s&#237;ncope.</p>
          <p>Segundo, s&#237;ncope com diferentes mecanismos subjacentes pode ter fatores predisponentes e pr&#243;dromos comuns, o que, por vezes, pode tornar sua distin&#231;&#227;o um desafio. No entanto, a SNM &#233; considerada a causa mais comum de PCT na popula&#231;&#227;o. Usamos question&#225;rio especializado com comprovada acur&#225;cia para diagnosticar SNM no nosso estudo.</p>
          <p>Terceiro, os resultados obtidos no nosso estudo podem n&#227;o ser aplic&#225;veis a pacientes com PCT admitidos em centros terci&#225;rios, onde a preval&#234;ncia e os mecanismos de PCT s&#227;o diferentes.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Nossos achados sugerem uma alta preval&#234;ncia de PCT ao longo da vida em indiv&#237;duos com idade entre 20 e 69 anos. A causa mais comum de PCT &#233; SNM. Uma hist&#243;ria de MS em parentes pr&#243;ximos foi obtida em 24% dos pacientes com PCT de suposta origem arritmog&#234;nica. Tais dados epidemiol&#243;gicos podem contribuir para o desenvolvimento de abordagens custo-efetivas para PCT.</p>
      </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>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
