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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.0" specific-use="sps-1.6" 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">FZxgNSKdcSz8VMLBm4h38fH</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2017001300299</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20170131</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2017005017105</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Pre-Frailty Increases the Risk of Adverse Events in Older Patients Undergoing Cardiovascular Surgery</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Rodrigues</surname>
            <given-names>Miguel K.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Marques</surname>
            <given-names>Artur</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lobo</surname>
            <given-names>Denise M. L.</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Umeda</surname>
            <given-names>Iracema I. K.</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Oliveira</surname>
            <given-names>Mayron F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
          <xref ref-type="aff" rid="aff4">4</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Hospital S&#237;rio Liban&#234;s</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital S&#237;rio Liban&#234;s, S&#227;o Paulo, SP - Brasil</institution>
        <institution content-type="normalized">Hospital S&#237;rio-Liban&#234;s</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Instituto Dante Pazzanese de Cardiologia</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brasil</institution>
        <institution content-type="normalized">Instituto Dante Pazzanese de Cardiologia</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Faculdade Metropolitana da Grande Fortaleza</institution>
        <addr-line>
          <named-content content-type="city">Fortaleza</named-content>
          <named-content content-type="state">CE</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Faculdade Metropolitana da Grande Fortaleza (FAMETRO), Fortaleza, CE - Brasil</institution>
        <institution content-type="normalized">Faculdade Metropolitana da Grande Fortaleza</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Universidade Fortaleza</institution>
        <institution content-type="orgdiv1">Centro de Ci&#234;ncias da Sa&#250;de</institution>
        <addr-line>
          <named-content content-type="city">Fortaleza</named-content>
          <named-content content-type="state">CE</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Fortaleza (UNIFOR), Centro de Ci&#234;ncias da Sa&#250;de, Fortaleza, CE - Brasil</institution>
        <institution content-type="normalized">Universidade de Fortaleza</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Mayron Faria Oliveira.</bold> Av. Dr. Dante Pazzanese, 500. Postal Code 04012-180, Vila Mariana, S&#227;o Paulo, SP - Brazil. E-mail: <email>mayronfaria@hotmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Rodrigues MK, Oliveira MF; acquisition of data: Marques A, Umeda IIK, Oliveira MF; analysis and interpretation of the data: Rodrigues MK, Marques A, Lobo DML, Umeda IIK, Oliveira MF; statistical analysis: Rodrigues MK, Lobo DML; writing of the manuscript: Rodrigues MK, Marques A, Lobo DML; critical revision of the manuscript for intellectual content: Umeda IIK, Oliveira MF.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>04</day>
        <month>09</month>
        <year>2017</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>10</month>
        <year>2017</year>
      </pub-date>
      <volume>109</volume>
      <issue>4</issue>
      <fpage>299</fpage>
      <lpage>306</lpage>
      <history>
        <date date-type="received">
          <day>31</day>
          <month>03</month>
          <year>2017</year>
        </date>
        <date date-type="rev-recd">
          <day>06</day>
          <month>06</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>19</day>
          <month>06</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Frailty is identified as a major predictor of adverse outcomes in older surgical patients. However, the outcomes in pre-frail patients after cardiovascular surgery remain unknown.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To investigate the main outcomes (length of stay, mechanical ventilation time, stroke and in-hospital death) in pre-frail patients in comparison with no-frail patients after cardiovascular surgery.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>221 patients over 65 years old, with established diagnosis of myocardial infarction or valve disease were enrolled. Patients were evaluated by Clinical Frailty Score (CFS) before surgery and allocated into 2 groups: no-frailty (CFS 1~3) vs. pre-frailty (CFS 4) and followed up for main outcomes. For all analysis, the statistical significance was set at 5% (p &lt; 0.05).</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>No differences were found in anthropometric and demographic data between groups (p &gt; 0.05). Pre-frail patients showed a longer mechanical ventilation time (193 &#177; 37 vs. 29 &#177; 7 hours; p&lt;0.05) than no-frail patients; similar results were observed for length of stay at the intensive care unit (5 &#177; 1 vs. 3 &#177; 1 days; p &lt; 0.05) and total time of hospitalization (12 &#177; 5 vs. 9 &#177; 3 days; p &lt; 0.05). In addition, the pre-frail group had a higher number of adverse events (stroke 8.3% vs. 3.9%; in-hospital death 21.5% vs. 7.8%; p &lt; 0.05) with an increased risk for development stroke (OR: 2.139, 95% CI: 0.622-7.351, p = 0.001; HR: 2.763, 95%CI: 1.206-6.331, p = 0.0001) and in-hospital death (OR: 1.809, 95% CI: 1.286-2.546, p = 0.001; HR: 1.830, 95% CI: 1.476-2.269, p = 0.0001). Moreover, higher number of pre-frail patients required homecare services than no-frail patients (46.5% vs. 0%; p &lt; 0.05).</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>Patients with pre-frailty showed longer mechanical ventilation time and hospital stay with an increased risk for cardiovascular events compared with no-frail patients.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Aging</kwd>
        <kwd>Cardiovascular Surgery</kwd>
        <kwd>Adverse Events</kwd>
        <kwd>Fragility</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Frailty is characterized as a multidimensional syndrome with decline in physiologic and cognitive status.<xref ref-type="bibr" rid="B1">1</xref> In addition, pre-frailty and frailty have been described as biological syndromes resulting from the dysregulation of multiple metabolic pathways.<xref ref-type="bibr" rid="B1">1</xref><sup>-</sup><xref ref-type="bibr" rid="B3">3</xref>
			</p>
      <p>Recent data have revealed a significant association between pre-frailty and the risk of cardiovascular disease - with 25-50% more cardiovascular events in frail older individuals than in healthy elderly subjects<xref ref-type="bibr" rid="B2">2</xref> - irrespective of any classical cardiometabolic risk factors, suggesting that pre-frailty should be targeted as a potentially reversible risk factor for cardiovascular diseases in the older population.<xref ref-type="bibr" rid="B1">1</xref>
			</p>
      <p>In recent years, the number of older patients undergoing cardiovascular surgery has increased, and the number of complications from cardiovascular surgery in this population is higher compared with younger patients.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref> A comprehensive preoperative assessment is essential in order to determine the risks and benefits of surgical intervention in this population; however, current methods of risk stratification have some limitations.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref>
			</p>
      <p>Frailty has also been consistently identified as a major predictor of adverse outcomes in older surgical patients.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref> Higher levels of frailty lead to increased risk during the postoperative period, with more time on mechanical ventilation, longer hospital stay, and more postoperative complications (stroke and death) compared with patients with low frailty levels.<xref ref-type="bibr" rid="B3">3</xref> However, most studies have focused exclusively on demonstrating that patients with frailty are more susceptible to adverse events than patients without frailty after cardiovascular surgery,<xref ref-type="bibr" rid="B8">8</xref> while the outcomes for patients in early stages of frailty (pre-frailty) are still unknown.</p>
      <p>Therefore, we aimed to investigate the main outcomes after cardiovascular surgery in pre-frail patients compared with non-frail patients. We hypothesized that pre-frail patients have a higher incidence of cardiovascular events compared with non-frail patients. Early detection of pre-frailty enables a more careful preoperative classification of these individuals and encourages the development of prevention programs in this population.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>The present investigation was conducted as a prospective observational study. A convenience sample of 283 patients over 65 years of age were enrolled in this study. All patients had an established diagnosis of cardiovascular disease (myocardial infarction, valve regurgitation or stenosis), determined by previous electrocardiogram and/or Doppler echocardiography, and all had surgical indications (coronary artery bypass [CAB], valve replacement or valve repair, or combined surgery). Patients with prior neurological disease (previous stroke or muscular dystrophies), cognitive impairment resulting from previous injury, frailty score &#8805; 5, non-elective/emergency surgery procedures and patients who refused to participate in the study were excluded.</p>
      <p>Twenty-four hours before elective surgery, frailty of all patients was assessed by Clinical Frailty Score (CFS) (<xref ref-type="table" rid="t4">Chart 1</xref>), which was performed by a single physiotherapist, previously trained. All patients were able to participate in the assessment in an active way. Then, the patients were allocated into two groups: no-frailty (CFS 1~3) and pre-frailty (CFS 4).<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref> The CFS is a practical, efficient and validated scale that measures frailty. It was developed to provide clinicians with an easily applicable tool to stratify older adults according to level of vulnerability.<xref ref-type="bibr" rid="B11">11</xref>
			</p>
      <table-wrap id="t4">
        <label>Chart 1</label>
        <caption>
          <title>Clinical Frailty Scale. Adapted from Rockwood9 and McDermid.10</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="50%"/>
            <col width="50%"/>
          </colgroup>
          <tbody>
            <tr>
              <td align="left">1 Very Fit - People who are robust, active, energetic and motivated. These people commonly exercise regularly. They are among the fittest for their age.</td>
              <td align="left">6 Moderately Frail - People need help with all outside activities and with keeping house. Inside, they often have problems with stairs and need help with bathing and might need minimal assistance (cuing, standby) with dressing.</td>
            </tr>
            <tr>
              <td align="left"><bold>2 Well</bold> - People who have no active disease symptoms but are less fit than category 1. Often, they exercise or are very active occasionally, e.g. seasonally.</td>
              <td align="left"><bold>7 Severely Frail</bold> - Completely dependent for personal care, from whatever cause (physical or cognitive). Even so, they seem stable and not at high risk of dying (within ~ 6 months).</td>
            </tr>
            <tr>
              <td align="left"><bold>3 Managing Well</bold> - People whose medical problems are well controlled, but are not regularly active beyond routine walking.</td>
              <td align="left"><bold>8 Very Severely Frail</bold> - Completely dependent, approaching the end of life. Typically, they could not recover even from a minor illness.</td>
            </tr>
            <tr>
              <td align="left"><bold>4 Vulnerable</bold> - While not dependent on others for daily help, often symptoms limit activities. A common complaint is being &#8220;slowed up&#8221;, and/or being tired during the day.</td>
              <td align="left"><bold>9 Terminally iII</bold> - Approaching the end of life. This category applies to people with a life expectancy &lt;6 months, who are not otherwise evidently frail.</td>
            </tr>
            <tr>
              <td align="left"><bold>5 Mildly Frail</bold> - These people often have more evident slowing, and need help in high order IADLs (finances, transportation, heavy housework, medications). Typically, mild frailty progressively impairs shopping and walking outside alone, meal preparation and housework.</td>
              <td align="left">
							</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p>All patients were admitted to the intensive care unit (ICU) after undergoing cardiovascular surgery. Heart rate, mean arterial pressure, and oxyhemoglobin saturation by pulse oximetry (SpO<sub>2</sub>) were measured with a Dixtal monitor (DX 2010&#226;), and all of them were followed up (60 days) for hospital discharge or major adverse cardiovascular events: stroke, infection and in-hospital death. In addition, length of stay, duration of mechanical ventilation, use of vasopressor agents, and the need for home-based physiotherapy services after hospital discharge were also evaluated.</p>
      <p>The study was approved by the Institutional Ethics Committee (registration number - 1048554). Written informed consent was obtained from all participants.</p>
      <sec>
        <title>Statistical analysis</title>
        <p>Statistical analysis was carried out using the SPSS program (version 20; SPSS Inc.). Data are expressed as mean &#177; standard deviation and percentage, as appropriate. The Kolmogorov-Smirnov test was used to determine normality of the data distribution; the non-paired t test and the c <xref ref-type="bibr" rid="B2">2</xref> test were used to assess differences in categorical data.</p>
        <p>The survival variables were compared using the log rank test, and Kaplan-Meier survival curves were constructed. Subsequently, Cox regression models were used to assess the relationship between baseline (surgery data) frailty and mortality. Follow-up time was calculated in days from the date of the baseline measurement to the date of a major adverse cardiovascular event. The odds ratio (OR), hazard ratio (HR), and 95% confidence intervals (95% CIs) were calculated. For all of the analysis, the statistical significance was set at 5% (p &lt; 0.05).</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>A total of 283 patients who underwent elective cardiovascular surgery were enrolled in this study, and of these 62 patients were excluded: 11 patients refused to participate, 17 patients had a CFS &gt; 5, 22 patients had their post-surgery data lost, and 12 patients underwent non-elective/emergency surgical procedures. Thus, 221 patients were included in the study: 144 with pre-frailty and 77 without frailty.</p>
      <p>Baseline characteristics are shown in <xref ref-type="table" rid="t1">Table 1</xref>. There were a higher percentage of male patients in both groups, and body mass index was slightly increased in the pre-frail group than in patients without frailty. None of the patients had heart failure or renal insufficiency prior to surgery. Moreover, there were no differences in CAB or valve replacement surgery between groups (<xref ref-type="table" rid="t1">Table 1</xref>). In addition, cardiopulmonary bypass time and cross-clamping time during procedures (extracorporeal circulation) were similar between pre-frailty and no-frailty groups (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
      <table-wrap id="t1">
        <label>Table 1</label>
        <caption>
          <title>Patients' characteristics</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left" rowspan="2">
							</th>
              <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">No-frailty</th>
              <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Pre-frailty</th>
              <th align="center" rowspan="2">p value</th>
            </tr>
            <tr>
              <th align="center">(n = 77)</th>
              <th align="center">(n = 144)</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">
                <bold>Anthropometrics/Demographics</bold>
              </td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">Male, n (%)</td>
              <td align="center">52 (67.5%)</td>
              <td align="center">93 (64.5%)</td>
              <td align="center">0.26</td>
            </tr>
            <tr>
              <td align="left">Age, years</td>
              <td align="center">70 &#177; 2</td>
              <td align="center">72 &#177; 4</td>
              <td align="center">0.42</td>
            </tr>
            <tr>
              <td align="left">Weight, kg</td>
              <td align="center">69.3 &#177; 9.8</td>
              <td align="center">73.4 &#177; 14.3</td>
              <td align="center">0.02</td>
            </tr>
            <tr>
              <td align="left">Height, m</td>
              <td align="center">1.64 &#177; 0.09</td>
              <td align="center">1.63 &#177; 0.10</td>
              <td align="center">0.76</td>
            </tr>
            <tr>
              <td align="left">BMI, kg/m<sup>2</sup></td>
              <td align="center">25.4 &#177; 2.6</td>
              <td align="center">27.1 &#177; 3.9</td>
              <td align="center">0.001</td>
            </tr>
            <tr>
              <td align="left">LVEF, %</td>
              <td align="center">54 &#177; 12</td>
              <td align="center">55 &#177; 11</td>
              <td align="center">0.52</td>
            </tr>
            <tr>
              <td align="left">Euro Score</td>
              <td align="center">2 &#177; 0.5</td>
              <td align="center">6 &#177; 0.4</td>
              <td align="center">&lt; 0.001</td>
            </tr>
            <tr>
              <td align="left">ASA</td>
              <td align="center">2 &#177; 0.3</td>
              <td align="center">3 &#177; 0.6</td>
              <td align="center">&lt; 0.001</td>
            </tr>
            <tr>
              <td align="left">
                <bold>Main comorbidities</bold>
              </td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">Hypertension, n (%)</td>
              <td align="center">58 (75.3%)</td>
              <td align="center">120 (83.3%)</td>
              <td align="center">0.01</td>
            </tr>
            <tr>
              <td align="left">Type II Diabetes, n (%)</td>
              <td align="center">27 (35%)</td>
              <td align="center">56 (38.8%)</td>
              <td align="center">0.12</td>
            </tr>
            <tr>
              <td align="left">Dyslipidemia, n (%)</td>
              <td align="center">33 (42.8%)</td>
              <td align="center">66 (45.8%)</td>
              <td align="center">0.38</td>
            </tr>
            <tr>
              <td align="left">Smoker, n (%)</td>
              <td align="center">14 (18.2%)</td>
              <td align="center">16 (11.1%)</td>
              <td align="center">0.09</td>
            </tr>
            <tr>
              <td align="left">
                <bold>Surgical data</bold>
              </td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">Coronary artery bypass, n (%)</td>
              <td align="center">41 (53.2%)</td>
              <td align="center">83 (57.6%)</td>
              <td align="center">0.65</td>
            </tr>
            <tr>
              <td align="left">Valve replacement, n (%)</td>
              <td align="center">25 (32.4%)</td>
              <td align="center">42 (29.2%)</td>
              <td align="center">0.42</td>
            </tr>
            <tr>
              <td align="left">Coronary artery bypass + valve replacement, n (%)</td>
              <td align="center">11 (14.2%)</td>
              <td align="center">19 (13.2%)</td>
              <td align="center">0.71</td>
            </tr>
            <tr>
              <td align="left">Activated partial thromboplastin time, s</td>
              <td align="center">27 &#177; 6</td>
              <td align="center">25 &#177; 7</td>
              <td align="center">0.19</td>
            </tr>
            <tr>
              <td align="left">Cardiopulmonary bypass time, min</td>
              <td align="center">100 &#177; 40</td>
              <td align="center">90 &#177; 39</td>
              <td align="center">0.17</td>
            </tr>
            <tr>
              <td align="left">Cross-clamp time, min</td>
              <td align="center">73 &#177; 26</td>
              <td align="center">63 &#177; 31</td>
              <td align="center">0.12</td>
            </tr>
            <tr>
              <td align="left">
                <bold>Baseline hemodynamic and blood measurements</bold>
              </td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">HR, bpm</td>
              <td align="center">97 &#177; 22</td>
              <td align="center">93 &#177; 19</td>
              <td align="center">0.21</td>
            </tr>
            <tr>
              <td align="left">MAP, mmHg</td>
              <td align="center">98 &#177; 11</td>
              <td align="center">101 &#177; 14</td>
              <td align="center">0.43</td>
            </tr>
            <tr>
              <td align="left">Hemoglobin, g/dL</td>
              <td align="center">10.7 &#177; 2.1</td>
              <td align="center">10.8 &#177; 1.7</td>
              <td align="center">0.68</td>
            </tr>
            <tr>
              <td align="left">Hematocrit, %</td>
              <td align="center">33.2 &#177; 6.0</td>
              <td align="center">33.9 &#177; 8.7</td>
              <td align="center">0.49</td>
            </tr>
            <tr>
              <td align="left">Platelets, mm<sup>3</sup></td>
              <td align="center">143,126 &#177; 60,725</td>
              <td align="center">146,726 &#177; 53,742</td>
              <td align="center">0.64</td>
            </tr>
            <tr>
              <td align="left">Creatinine, mg/dL</td>
              <td align="center">1.16 &#177; 0.50</td>
              <td align="center">1.27 &#177; 0.54</td>
              <td align="center">0.54</td>
            </tr>
            <tr>
              <td align="left">hs-CRP, mg/L</td>
              <td align="center">8.8 &#177; 0.8</td>
              <td align="center">9.0 &#177; 0.8</td>
              <td align="center">0.86</td>
            </tr>
            <tr>
              <td align="left">PaO<sub>2</sub>, mmHg</td>
              <td align="center">118 &#177; 5</td>
              <td align="center">117 &#177; 9</td>
              <td align="center">0.90</td>
            </tr>
            <tr>
              <td align="left">PaCO<sub>2</sub>, mmHg</td>
              <td align="center">42 &#177; 11</td>
              <td align="center">39 &#177; 8</td>
              <td align="center">0.06</td>
            </tr>
            <tr>
              <td align="left">HCO<sub>3</sub><sup>-</sup>, mmol/L</td>
              <td align="center">22 &#177; 2</td>
              <td align="center">21 &#177; 3</td>
              <td align="center">0.53</td>
            </tr>
            <tr>
              <td align="left">SpO<sub>2</sub>, %</td>
              <td align="center">96 &#177; 4</td>
              <td align="center">97 &#177; 3</td>
              <td align="center">0.37</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <p>Definition of abbreviations: BMI: body mass index; LVEF: left ventricular ejection fraction; ASA: American society of anesthesiologists; HR: heart rate; MAP: mean arterial pressure; hs-CPR: high sensitive c-reactive protein; PaO<sub>2</sub>: arterial oxygen pressure; PaCO<sub>2</sub>: arterial carbon dioxide pressure; HCO<sub>3</sub>-: bicarbonate; SpO<sub>2</sub>: oxyhemoglobin saturation by pulse oximetry. Values are expressed in mean &#177; standard deviation or frequency. Non-paired t student test was applied to variables described as mean &#177; standard deviation and the &#967;<sup>2</sup> test was used to assess differences of frequencies in categorical variables.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>No differences in hemodynamic values or blood samples were observed between the groups after admission to the ICU (<xref ref-type="table" rid="t1">Table 1</xref>). However, pre-frailty group had a higher number of patients using vasopressor medications compared with no-frailty group (<xref ref-type="table" rid="t2">Table 2</xref>). A longer time in mechanical ventilation, with more patients in prolonged ventilation, as well as longer ICU and total hospital length of stay was observed in the pre-frailty group compared with the group without frailty. In addition, in the pre-frailty group, there was a higher incidence of cardiovascular events and a greater number of patients with stroke and in-hospital deaths than in the no-frailty group (<xref ref-type="table" rid="t2">Table 2</xref>).</p>
      <table-wrap id="t2">
        <label>Table 2</label>
        <caption>
          <title>Prospective data observed at the intensive care unit and until hospital discharge in no frail and pre-frail groups</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">
							</th>
              <th align="center">No-frailty (n = 77)</th>
              <th align="center">Pre-frailty (n = 144)</th>
              <th align="center">p value</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">
                <bold>Length of stay</bold>
              </td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">Intensive care unit, days</td>
              <td align="center">3 &#177; 1</td>
              <td align="center">5 &#177; 1</td>
              <td align="center">0.03</td>
            </tr>
            <tr>
              <td align="left">Total time hospitalization, days</td>
              <td align="center">9 &#177; 3</td>
              <td align="center">12 &#177; 5</td>
              <td align="center">&lt; 0.001</td>
            </tr>
            <tr>
              <td align="left">
                <bold>Mechanical ventilation</bold>
              </td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">Time in Mechanical ventilation, hours</td>
              <td align="center">29 &#177; 7</td>
              <td align="center">193 &#177; 37</td>
              <td align="center">0.001</td>
            </tr>
            <tr>
              <td align="left">Prolonged time in mechanical ventilation, n (%)</td>
              <td align="center">0</td>
              <td align="center">21 (14.5%)</td>
              <td align="center">0.001</td>
            </tr>
            <tr>
              <td align="left">
                <bold>Vasopressor</bold>
              </td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">Noradrenaline, n (%)</td>
              <td align="center">26 (33.8%)</td>
              <td align="center">46 (31.9%)</td>
              <td align="center">0.87</td>
            </tr>
            <tr>
              <td align="left">Dobutamine, n (%)</td>
              <td align="center">8 (10.4%)</td>
              <td align="center">29 (20.1%)</td>
              <td align="center">0.03</td>
            </tr>
            <tr>
              <td align="left">Dopamine, n (%)</td>
              <td align="center">14 (18.2%)</td>
              <td align="center">15 (10.4%)</td>
              <td align="center">0.08</td>
            </tr>
            <tr>
              <td align="left">Nitroglicerine, n (%)</td>
              <td align="center">8 (10.4%)</td>
              <td align="center">20 (13.8%)</td>
              <td align="center">0.24</td>
            </tr>
            <tr>
              <td align="left">
                <bold>Adverse events</bold>
              </td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">Infection, n (%)</td>
              <td align="center">4 (5.2%)</td>
              <td align="center">7 (4,8%)</td>
              <td align="center">0.69</td>
            </tr>
            <tr>
              <td align="left">Stroke, n (%)</td>
              <td align="center">3 (3.9%)</td>
              <td align="center">12 (8.3%)</td>
              <td align="center">0.02</td>
            </tr>
            <tr>
              <td align="left">In-hospital deaths, n (%)</td>
              <td align="center">6 (7.8%)</td>
              <td align="center">31 (21.5%)</td>
              <td align="center">0.001</td>
            </tr>
            <tr>
              <td align="left">
                <bold>Home care facility</bold>
              </td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">Physiotherapy, n (%)</td>
              <td align="center">0</td>
              <td align="center">67 (46.5%)</td>
              <td align="center">&lt; 0.001</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN2">
            <p>Values are expressed in mean &#177; standard deviation or frequency. Non-paired t student test was applied to variables described as mean &#177; standard deviation and the &#967;<sup>2</sup> test was used to assess categorical data differences in frequency variables.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Kaplan-Meier analysis showed that cumulative events were significantly higher in patients with pre-frailty, both in stroke (<xref ref-type="fig" rid="f1">Figure 1</xref>) and in-hospital deaths (<xref ref-type="fig" rid="f2">Figure 2</xref>). Moreover, the OR and HR indicated an increased risk for stroke and in-hospital deaths in patients with higher frailty scores (pre-frailty group; <xref ref-type="table" rid="t3">Table 3</xref>).</p>
      <p>
        <fig id="f1">
          <label>Figure 1</label>
          <caption>
            <title>Cumulative survival of stroke events between no-frail and pre-frail groups.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-109-04-0299-70131-gf01.jpg"/></fig>
      </p>
      <p>
        <fig id="f2">
          <label>Figure 2</label>
          <caption>
            <title>Cumulative survival of in-hospital deaths events between no-frail and pre-frail groups.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-109-04-0299-70131-gf02.jpg"/></fig>
      </p>
      <table-wrap id="t3">
        <label>Table 3</label>
        <caption>
          <title>Odds ratio and hazard ratio for stroke and in-hospital deaths in the pre-frail group</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
          </colgroup>
          <tbody>
            <tr style="border-bottom-width:thin;border-bottom-style:solid">
              <td align="left">
                <bold>&#160;</bold>
              </td>
              <td align="center">
                <bold>OR</bold>
              </td>
              <td align="center">
                <bold>95%CI</bold>
              </td>
              <td align="center">
                <bold>p value</bold>
              </td>
            </tr>
            <tr>
              <td align="left">Stroke</td>
              <td align="center">2.139</td>
              <td align="center">0.622 - 7.351</td>
              <td align="center">0.001</td>
            </tr>
            <tr style="border-bottom-width:thin;border-bottom-style:solid">
              <td align="left">In-hospital deaths</td>
              <td align="center">2.763</td>
              <td align="center">1.206 - 6.331</td>
              <td align="center">0.0001</td>
            </tr>
            <tr style="border-bottom-width:thin;border-bottom-style:solid">
              <td align="left">
                <bold>&#160;</bold>
              </td>
              <td align="center">
                <bold>HR</bold>
              </td>
              <td align="center">
                <bold>95%CI</bold>
              </td>
              <td align="center">
                <bold>p value</bold>
              </td>
            </tr>
            <tr>
              <td align="left">Stroke</td>
              <td align="center">1.809</td>
              <td align="center">1.286 - 2.546</td>
              <td align="center">0.001</td>
            </tr>
            <tr>
              <td align="left">In-hospital deaths</td>
              <td align="center">1.830</td>
              <td align="center">1.476 - 2.269</td>
              <td align="center">0.0001</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN3">
            <p>OR: odds ratio; HR: hazard ratio; IC: interval of confidence.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>In the present study, we investigated the relationship between pre-frailty and adverse postoperative outcomes following cardiovascular surgery. The main and new findings of the present study were: 1) Pre-frailty patients have more cumulative events than no-frailty patients, both in stroke and in-hospital deaths, and 2) Pre-frailty patients have longer mechanical ventilation time and hospital stay compared with the no-frailty patients. These findings are strongly relevant, as there are no previous studies that have demonstrated a relationship between pre-frailty and adverse postoperative outcomes in cardiovascular surgery.</p>
      <p>Our results contribute to understanding whether the extent of premorbid deficit accumulation adds prognostic value in patients after cardiovascular surgery. Currently, more than half of all cardiovascular surgeries are performed on patients over 75 years<xref ref-type="bibr" rid="B12">12</xref>. A recent systematic review<xref ref-type="bibr" rid="B13">13</xref> showed that the incidence of frailty increased steadily with age (65-69 years: 4%; 70-74 years: 7%; 75-79 years: 9%; 80-84 years: 16%; and older than 85 years: 26%), as a consequence of age-related decline in many physiological systems, which collectively results in vulnerability to sudden changes in health status triggered by minor stressor events.<xref ref-type="bibr" rid="B2">2</xref> It also has been demonstrated that these patients have an increased risk of falls, prolonged hospitalization and mortality after surgery.<xref ref-type="bibr" rid="B14">14</xref> Moreover, previous data have shown that each one-point increase in frailty score is associated with increased incidence of functional limitation and higher mortality risk in six months.<xref ref-type="bibr" rid="B15">15</xref> A prospective study showed that 47% of a total cohort of 5,210 patients over 65 years of age were classified as pre-frailty (phenotype model), with an increased mortality rate (23%) during seven years of follow-up.<xref ref-type="bibr" rid="B16">16</xref> Sundermann et al.<xref ref-type="bibr" rid="B17">17</xref> reported that pre-frailty patients have an intermediate outcome between frailty and no-frailty patients. In addition, pre-frailty has been associated with a four-fold higher risk of becoming frail over a four-year follow-up period<xref ref-type="bibr" rid="B16">16</xref>. Sergi et al.<xref ref-type="bibr" rid="B1">1</xref> found that patients with pre-frailty have more cardiovascular diseases compared with no-frailty patients. However, most of frailty studies on postoperative outcomes have only compared frailty versus no-frailty patients.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref> In this context, the present study extends the knowledge regarding pre-frailty patients. Over a short follow-up period, pre-frailty patients who underwent cardiovascular surgery had more major adverse cardiovascular events and in-hospital deaths than no-frailty patients. Thus, our study presents new evidence suggesting that pre-frailty patients should be better evaluated and rehabilitated prior to cardiovascular surgery.</p>
      <p>In our study, pre-frailty patients undergoing cardiovascular surgery had a higher incidence of stroke. In fact, this is a common finding in the scientific literature, and has been related to aging<xref ref-type="bibr" rid="B20">20</xref> and intraoperative period, although previous studies have not evaluated frailty or pre-frailty.<xref ref-type="bibr" rid="B21">21</xref> Actually, frailty patients undergoing non-cardiovascular surgery had more intraoperative cerebral desaturation compared with no-frailty patients,<xref ref-type="bibr" rid="B22">22</xref> and older patients with comorbidities such as hypertension and diabetes might be at increased risk due to changes in autoregulation of cerebral blood flow.<xref ref-type="bibr" rid="B23">23</xref> Our data are in line with current literature that suggests that pre-frailty patients undergoing a valve replacement present a higher incidence of stroke compared to patients submitted to CAB, this fact can be explained due to the higher cardiopulmonary bypass and anoxia time during surgery. Interestingly, 25% of pre-frailty patients with stroke progressed to death during the hospitalization period, demonstrating that patient's pre-morbid health status is an important point to be evaluated and may influence the prognosis after a critical event. Furthermore, they were more likely to experience cerebrovascular events and prolonged mechanical ventilation. In this context, it is highly likely that these findings explain the high incidence of stroke in the pre-frailty group in our study. Also, the higher percentage of hypertension and diabetes observed in this group might be related to an increased incidence of cerebrovascular events in these patients.</p>
      <p>It is well established that prolonged mechanical ventilation has been related to new deficits or worsening of pre-existing deficits associated with the frailty syndrome in critically ill patients, that persist even after resolution of the critical condition,<xref ref-type="bibr" rid="B24">24</xref> regardless of the use of invasive or non-invasive ventilation.<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref> Our patients with pre-frailty had higher mechanical ventilation time. In fact, increased mechanical ventilation time might be a consequence of the main complications found in our study.</p>
      <p>Moreover, prolonged mechanical ventilation is associated with impaired functionality, longer hospitalization period and higher incidence of in-hospital deaths.<xref ref-type="bibr" rid="B26">26</xref> It has been demonstrated that more than 80% of these patients require a second hospitalization within 12 months of discharge from the ICU<xref ref-type="bibr" rid="B26">26</xref> with high incidence of six-month mortality.<xref ref-type="bibr" rid="B27">27</xref><sup>,</sup><xref ref-type="bibr" rid="B28">28</xref> Furthermore, those patients who survive may have worsened functional capacity for almost five years after hospital discharge.<xref ref-type="bibr" rid="B29">29</xref> Although it is out of scope of our study to follow up patients after hospital discharge, the pre-frailty group had longer hospital length of stay, required treatment in skilled or assisted-living facility, including physiotherapy and rehabilitation after discharge. Together, these findings suggest that this group is on increased risk of re-hospitalization and/or death in a short period of time.</p>
      <sec>
        <title>Clinical implications</title>
        <p>Frailty is recognized as a multi-dimensional syndrome characterized by the loss of reserves (physical and cognitive) that result in vulnerability. The CFS is an easy-to-use frailty scale for risk stratification of older adults that enables the assessment of frailty-related outcomes even in the preoperative period, and may improve treatments and interventions, prevent possible complications, and reduce the length of stay.</p>
        <p>Our study presents important clinical findings, as frailty is a reversible condition when treated in the early stages with interventions such as exercise. These interventions are effective and might delay the transition from pre-frailty to frailty.<xref ref-type="bibr" rid="B30">30</xref> Exercise prior to cardiovascular surgery may also contribute to better recovery in ICU.</p>
        <p>In addition, our study emphasizes the need to incorporate a frailty evaluation before cardiovascular surgery, in order to better understand the risks to these older patients and to guide specific interventions in the preoperative period to minimize the risk of adverse events, even in patients in the early stages of frailty.</p>
      </sec>
      <sec>
        <title>Study limitations</title>
        <p>This study has some limitations that should be addressed. There is a blank in the recent literature regarding the best evaluation criteria for frailty. There is significant heterogeneity among frailty criteria in clinical trials, thus making it more difficult to recognize and identify frailty in post-surgical patients.<xref ref-type="bibr" rid="B31">31</xref>
				</p>
        <p>Pre-frailty group had a larger number of patients than no-frailty group. To rule out the possibility that this issue might affect our findings, statistical power for the main outcomes was calculated and revealed a power of 99.98% for total time hospitalization and 74.22% for in-hospital death.</p>
        <p>A recent study showed that widely used scores (Acute Physiology Score and Acute Physiology and Chronic Health Evaluation) failed to predict higher death risk.<xref ref-type="bibr" rid="B32">32</xref> However, frailty, when associated to traditional risk scales (ASA, Eagle and Lee), is an independently predictor of postoperative complications, length of stay, and requirement of skilled or assisted-living care after hospital discharge in older surgical patients.<xref ref-type="bibr" rid="B8">8</xref> Our study took care to evaluate some types of risk scale: CFS, ASA and EuroScore, and all of them were increased in patients that had worse outcomes. Furthermore, frailty was able to predict major cardiovascular events in post-cardiac surgery, even in patients with early stages of frailty.</p>
        <p>There are two frailty models: phenotype and cumulative deficit models. We decided to use just the CFS because it is readily available at the bedside and is easier to understand and use than other frailty assessment tools. Moreover, the CFS has been considered an optimal tool for use on admission to the ICU.<xref ref-type="bibr" rid="B10">10</xref>
				</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>Patients with pre-frailty showed longer mechanical ventilation time, longer ICU and hospital length of stay, and higher requirement for home-based physiotherapy services than no-frailty patients after cardiovascular surgery. Moreover, the presence of pre-frailty on pre-operative period predicts more cumulative events (stroke or in-hospital death). However, it remains unknown whether pre-frailty treatment before cardiovascular surgery is effective to prevent cumulative outcomes.</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>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Pr&#233;-Fragilidade Aumenta o Risco de Eventos Adversos em Idosos Submetidos &#224; Cirurgia Cardiovascular</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Rodrigues</surname>
            <given-names>Miguel K.</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Marques</surname>
            <given-names>Artur</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lobo</surname>
            <given-names>Denise M. L.</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Umeda</surname>
            <given-names>Iracema I. K.</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Oliveira</surname>
            <given-names>Mayron F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
          <xref ref-type="aff" rid="aff8">4</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
      </contrib-group>
      <aff id="aff5">
        <label>1</label>
        <institution content-type="original">Hospital S&#237;rio Liban&#234;s, S&#227;o Paulo, SP - Brasil</institution>
      </aff>
      <aff id="aff6">
        <label>2</label>
        <institution content-type="original">Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brasil</institution>
      </aff>
      <aff id="aff7">
        <label>3</label>
        <institution content-type="original">Faculdade Metropolitana da Grande Fortaleza (FAMETRO), Fortaleza, CE - Brasil</institution>
      </aff>
      <aff id="aff8">
        <label>4</label>
        <institution content-type="original">Universidade Fortaleza (UNIFOR), Centro de Ci&#234;ncias da Sa&#250;de, Fortaleza, CE - Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Mayron Faria Oliveira.</bold> Av. Dr. Dante Pazzanese, 500. CEP 04012-180, Vila Mariana, S&#227;o Paulo, SP - Brasil. E-mail: <email>mayronfaria@hotmail.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: Rodrigues MK, Oliveira MF; obten&#231;&#227;o de dados: Marques A, Umeda IIK, Oliveira MF; an&#225;lise e interpreta&#231;&#227;o dos dados: Rodrigues MK, Marques A, Lobo DML, Umeda IIK, Oliveira MF; an&#225;lise estat&#237;stica: Rodrigues MK, Lobo DML; reda&#231;&#227;o do manuscrito: Rodrigues MK, Marques A, Lobo DML; revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Umeda IIK, Oliveira MF.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamentos:</title>
          <p>A fragilidade &#233; reconhecida como um importante preditor de eventos adversos em pacientes cir&#250;rgicos idosos. Entretanto, os desfechos em pacientes com pr&#233;-fragilidade ap&#243;s a cirurgia cardiovascular ainda permanecem desconhecidos.</p>
        </sec>
        <sec>
          <title>Objetivos:</title>
          <p>Investigar os principais desfechos (tempo de interna&#231;&#227;o, tempo de ventila&#231;&#227;o mec&#226;nica, incid&#234;ncia de acidente vascular cerebral e &#243;bito intra-hospitalar) ap&#243;s cirurgia cardiovascular em pacientes com pr&#233;-fragilidade em compara&#231;&#227;o a pacientes sem fragilidade.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>221 pacientes acima de 65 anos de idade, com diagn&#243;stico de infarto do mioc&#225;rdio ou doen&#231;a valvar foram recrutados no estudo. Os pacientes foram avaliados pela escala de fragilidade cl&#237;nica (<italic>CFS, Clinical Frailty Score</italic>) antes da cirurgia e separados em 2 grupos: sem-fragilidade (CFS 1~3) <italic>vs.</italic> pr&#233;-fragilidade (CFS 4). Para todas as an&#225;lises, foi considerada diferen&#231;a significativa quando p &lt; 0,05.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>N&#227;o foram observadas diferen&#231;as nos dados antropom&#233;tricos e demogr&#225;ficos entre os grupos. Os pacientes com pr&#233;-fragilidade apresentaram maior tempo de ventila&#231;&#227;o mec&#226;nica em compara&#231;&#227;o a pacientes sem fragilidade (193 &#177; 37 vs. 29 &#177; 7 horas; p &lt; 0,05); resultados similares foram observados para tempo de perman&#234;ncia na unidade de terapia intensiva (5 &#177; 1 vs. 3 &#177; 1 days; p &lt; 0,05) e tempo total de interna&#231;&#227;o hospitalar (12 &#177; 5 vs. 9 &#177; 3 dias; p &lt; 0,05). Al&#233;m disso, os pacientes com pr&#233;-fragilidade apresentaram maior n&#250;mero de eventos adversos (acidente vascular cerebral-AVC 8,3% vs. 3,9%; &#243;bito intra-hospitalar 21,5% vs. 7,8%; p&lt;0,05) com risco aumentado para AVC (OR: 2,139, IC 95%: 0,622-7,351, p = 0,001; HR: 2,763, IC 95%: 1,206-6,331, p = 0,0001) e morte intra-hospitalar (OR: 1,809, IC 95%: 1,286-2,546, p = 0,001; HR: 1,830, IC 95%: 1,476-2,269, p = 0,0001). Al&#233;m disso, um maior n&#250;mero de pacientes com pr&#233;-fragilidade necessitaram de fisioterapia domiciliar que pacientes sem fragilidade (46,5% vs. 0%; p&lt; 0,05).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>Pacientes com pr&#233;-fragilidade apresentaram maior tempo de ventila&#231;&#227;o mec&#226;nica e maior tempo de interna&#231;&#227;o hospitalar, com maior risco de desenvolverem eventos cardiovasculares adversos em compara&#231;&#227;o a pacientes sem fragilidade.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Envelhecimento</kwd>
        <kwd>Cirurgia Cardiovascular</kwd>
        <kwd>Eventos Adversos</kwd>
        <kwd>Fragilidade</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A fragilidade &#233; caracterizada por uma s&#237;ndrome multidimensional com diminui&#231;&#227;o no status fisiol&#243;gico e cognitivo,<xref ref-type="bibr" rid="B1">1</xref> e tanto a pr&#233;-fragilidade como a fragilidade foram descritas como s&#237;ndromes biol&#243;gicas resultantes da desregula&#231;&#227;o de v&#225;rias vias metab&#243;licas.<xref ref-type="bibr" rid="B1">1</xref><sup>-</sup><xref ref-type="bibr" rid="B3">3</xref>
				</p>
        <p>Dados recentes revelaram uma associa&#231;&#227;o significativa entre pr&#233;-fragilidade e o risco de doen&#231;a cardiovascular - com 25-50% mais eventos cardiovasculares em idosos fr&#225;geis que em idosos saud&#225;veis<xref ref-type="bibr" rid="B2">2</xref> - independentemente de quaisquer fatores de risco cardiometab&#243;licos. Tal fato sugere que a pr&#233;-fragilidade deve ser considerada como um potencial fator de risco modific&#225;vel para doen&#231;a cardiovascular na popula&#231;&#227;o idosa.</p>
        <p>Nos &#250;ltimos anos, tem aumentado o n&#250;mero de pacientes idosos submetidos &#224; cirurgia cardiovascular, e o n&#250;mero de complica&#231;&#245;es decorrentes de cirurgia cardiovascular nessa popula&#231;&#227;o &#233; maior que em pacientes mais jovens.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref> &#201; necess&#225;rio uma avalia&#231;&#227;o pr&#233;-operat&#243;ria abrangente para determinar os riscos e os benef&#237;cios da interven&#231;&#227;o cir&#250;rgica nessa popula&#231;&#227;o. No entanto, os m&#233;todos atuais de estratifica&#231;&#227;o de risco possuem algumas limita&#231;&#245;es.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref>
				</p>
        <p>A fragilidade tamb&#233;m tem sido reconhecida como um importante preditor de eventos adversos em pacientes idosos submetidos &#224; cirurgias.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref> Maiores escores de fragilidade elevam o risco durante o per&#237;odo p&#243;s-operat&#243;rio, com maior tempo em ventila&#231;&#227;o mec&#226;nica, maior tempo de interna&#231;&#227;o hospitalar, e maior ocorr&#234;ncia de complica&#231;&#245;es - acidente vascular cerebral (AVC) e morte em compara&#231;&#227;o a pacientes com menores escores de fragilidade.<xref ref-type="bibr" rid="B3">3</xref> No entanto, a maioria dos estudos focaram exclusivamente em mostrar que pacientes com fragilidade s&#227;o mais suscept&#237;veis a eventos adversos que pacientes sem fragilidade ap&#243;s cirurgia cardiovascular,<xref ref-type="bibr" rid="B8">8</xref> enquanto que os desfechos cl&#237;nicos em pacientes em est&#225;gios precoces de fragilidade (pr&#233;-fragilidade) ainda s&#227;o desconhecidos.</p>
        <p>Portanto, nosso objetivo foi investigar os principais desfechos ap&#243;s cirurgia cardiovascular em pacientes pr&#233;-fr&#225;geis em compara&#231;&#227;o a pacientes n&#227;o fr&#225;geis. A detec&#231;&#227;o precoce de pr&#233;-fragilidade permite uma classifica&#231;&#227;o pr&#233;-operat&#243;ria mais cuidadosa desses indiv&#237;duos e estimula o desenvolvimento de programas de preven&#231;&#227;o nessa popula&#231;&#227;o.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>O presente estudo &#233; do tipo prospectivo observacional. Foram recrutados, atrav&#233;s de uma amostra de conveni&#234;ncia, 283 pacientes acima de 65 anos. Todos os pacientes tinham diagn&#243;stico estabelecido de doen&#231;a cardiovascular (infarto do mioc&#225;rdio, insufici&#234;ncia ou estenose valvar), determinado por eletrocardiograma pr&#233;vio e/ou ecocardiografia, e todos tinham indica&#231;&#227;o cir&#250;rgica revasculariza&#231;&#227;o do mioc&#225;rdio, troca ou plastia valvar, ou cirurgia combinada). Foram exclu&#237;dos pacientes com doen&#231;a neurol&#243;gica pr&#233;via (AVC ou distrofia muscular), disfun&#231;&#227;o cognitiva resultante de les&#227;o pr&#233;via, escore de fragilidade &#8805; 5, procedimentos cir&#250;rgicos n&#227;o-eletivos/de emerg&#234;ncia e pacientes que se recusaram a participar do estudo.</p>
        <p>Vinte e quatro horas antes da cirurgia eletiva, a fragilidade de todos os pacientes foi avaliada pela escala <italic>Clinical Frailty Score</italic> (CFS) (<xref ref-type="table" rid="t8">Quadro 1</xref>), a qual foi aplicada por um &#250;nico fisioterapeuta previamente treinado. Todos os pacientes foram capazes de ser avaliados de forma ativa, ou seja, sem aux&#237;lio de familiares/amigos. Os pacientes foram ent&#227;o alocados em dois grupos: sem fragilidade (CFS 1 a 3) e pr&#233;-fragilidade (CFS 4).<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref> O CFS &#233; uma escala pr&#225;tica, eficiente e validada que quantifica a fragilidade; foi desenvolvida como um instrumento de f&#225;cil aplica&#231;&#227;o para estratificar idosos de acordo com o grau de vulnerabilidade.<xref ref-type="bibr" rid="B11">11</xref>
				</p>
        <table-wrap id="t8">
          <label>Quadro 1</label>
          <caption>
            <title>Escala de fragilidade cl&#237;nica (CFS, Clinical Frailty Scale). Adaptado de Rockwood9 e McDermid.10</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="50%"/>
              <col width="50%"/>
            </colgroup>
            <tbody>
              <tr>
                <td align="left">1 Em excelente forma f&#237;sica- Pessoas fortes, ativas, energ&#233;ticas e motivadas. Estas pessoas normalmente se exercitam regularmente; est&#227;o entre os indiv&#237;duos mais em forma entre aqueles da mesma idade.</td>
                <td align="left">6 Com fragilidade moderada - As pessoas necessitam de ajuda para todas as atividades ao ar livre e dom&#233;sticas. Geralmente apresentam dificuldade em subir e descer escadas, necessitam de ajuda para tomar banho e podem necessitar de alguma ajuda (orienta&#231;&#227;o ou algu&#233;m em prontid&#227;o) no momento de se vestir.</td>
              </tr>
              <tr>
                <td align="left"><bold>2 Bem</bold> - Pessoas sem sintomas de doen&#231;a ativa, mas menos em forma que os indiv&#237;duos da categoria 1. Geralmente se exercitam ou s&#227;o muito ativos ocasionalmente, p.ex. sazonalmente.</td>
                <td align="left"><bold>7 Com fragilidade grave</bold> - Completamente dependentes para o cuidado pessoal, seja por causa f&#237;sica ou cognitiva. Mesmo assim, estas pessoas parecem est&#225;veis e sem alto risco de morte (dentro de ~6 meses).</td>
              </tr>
              <tr>
                <td align="left"><bold>3 Bem controlados</bold>- Pessoas cujos problemas m&#233;dicos est&#227;o bem controlados, mas cuja atividade f&#237;sica regular n&#227;o vai al&#233;m da caminhada de rotina.</td>
                <td align="left"><bold>8 Com fragilidade muito grave</bold>- Completamente dependentes, aproximando-se do fim da vida. Tipicamente, n&#227;o conseguem se recuperar nem de uma doen&#231;a simples.</td>
              </tr>
              <tr>
                <td align="left"><bold>4 Vulner&#225;veis</bold> - Apesar de n&#227;o dependerem de outros na rotina di&#225;ria, geralmente suas atividades s&#227;o limitadas por sintomas. Uma queixa comum &#233; de se sentirem &#8220;lentos&#8221; e/ou cansados durante o dia.</td>
                <td align="left"><bold>9 Doentes terminais</bold> - Pr&#243;ximos do fim da vida. Esta categoria aplica-se para pessoas com uma expectativa de vida &lt; 6 meses, sem outra evid&#234;ncia de fragilidade.</td>
              </tr>
              <tr>
                <td align="left"><bold>5 Levemente fr&#225;geis</bold> - Estas pessoas t&#234;m uma lentid&#227;o mais evidente, e necessitam de ajudam para atividades da vida di&#225;ria (finan&#231;as, transporte, atividades dom&#233;sticas pesadas, uso de medicamentos). Tipicamente, a fragilidade leve progressivamente prejudica a realiza&#231;&#227;o de atividades sozinhos, como fazer compras, caminhar ao ar livre, preparar as refei&#231;&#245;es e tarefas dom&#233;sticas.</td>
                <td align="left">
								</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Ap&#243;s a cirurgia cardiovascular, todos os pacientes foram admitidos na unidade de terapia intensiva (UTI). Frequ&#234;ncia card&#237;aca, press&#227;o arterial m&#233;dia e satura&#231;&#227;o da oxihemoglobina por oximetria de pulso (SpO<sub>2</sub>) foram mensuradas por meio do monitor Dixtal (DX2010&#174;). O seguimento de todos os pacientes ocorreu por 60 dias, onde foram observados quanto &#224; alta hospitalar e &#224; ocorr&#234;ncia de eventos cardiovasculares adversos importantes: AVC, infec&#231;&#227;o e &#243;bito durante interna&#231;&#227;o hospitalar, assim como o tempo de interna&#231;&#227;o, tempo em ventila&#231;&#227;o mec&#226;nica, uso de vasopressores e necessidade de fisioterapia domiciliar ap&#243;s a alta hospitalar.</p>
        <p>O estudo foi aprovado pelo comit&#234; de &#233;tica da institui&#231;&#227;o (n&#250;mero 1.048.554). Todos os pacientes assinaram o termo de consentimento livre e esclarecido.</p>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>A an&#225;lise estat&#237;stica foi realizada pelo programa SPSS (vers&#227;o 20; SPSS Inc.). Os dados foram expressos em m&#233;dia &#177; desvio padr&#227;o e porcentagem, conforme apropriado. O teste Kolmogorov-Smirnov foi utilizado para determinar a normalidade dos dados; o teste t n&#227;o pareado e o teste c <xref ref-type="bibr" rid="B2">2</xref> foi aplicado para avaliar diferen&#231;as nos dados categ&#243;ricos.</p>
          <p>As vari&#225;veis de sobrevida foram comparadas utilizando o teste log rank, e as curvas de sobrevida de Kaplan-Meier foram constru&#237;das. Em seguida, modelos de regress&#227;o de Cox foram usados para avaliar a rela&#231;&#227;o entre fragilidade basal (dados da cirurgia) e mortalidade. O tempo de acompanhamento foi calculado em dias a partir da data da medida basal &#224; data de ocorr&#234;ncia de um evento cardiovascular adverso. Foram calculados a raz&#227;o de chances (<italic>odds ratio</italic>, OR), a raz&#227;o de risco (<italic>hazard ratio</italic>, HR), e intervalos de confian&#231;a de 95% (IC95%). Para todas as an&#225;lises, a signific&#226;ncia estat&#237;stica foi estabelecida em 5% (p &lt; 0,05).</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>Um total de 283 pacientes que se submeteram &#224; cirurgia cardiovascular eletiva foram recrutados e, desses, 62 pacientes foram exclu&#237;dos: 11 pacientes se recusaram a participar, 17 pacientes apresentaram CFS &gt; 5, 22 pacientes tiveram seus dados p&#243;s-cir&#250;rgicos perdidos, e 12 pacientes submeteram-se a procedimentos cir&#250;rgicos n&#227;o eletivos/emerg&#234;ncia. Assim, 221 pacientes foram inclu&#237;dos no estudo - 144 com pr&#233;-fragilidade e 77 sem fragilidade.</p>
        <p>As caracter&#237;sticas basais est&#227;o apresentadas na <xref ref-type="table" rid="t5">Tabela 1</xref>. Houve uma porcentagem maior de pacientes do sexo masculino em ambos os grupos, e o &#237;ndice de massa corporal foi ligeiramente maior no grupo pr&#233;-fragilidade que no grupo sem fragilidade. Nenhum paciente apresentou insufici&#234;ncia card&#237;aca ou insufici&#234;ncia renal antes da cirurgia. Al&#233;m disso, n&#227;o houve diferen&#231;a no n&#250;mero de <italic>cirurgias de</italic> revasculariza&#231;&#227;o do mioc&#225;rdio ou de troca ou plastia valvar entre os grupos (<xref ref-type="table" rid="t5">Tabela 1</xref>). Adicionalmente, o tempo de circula&#231;&#227;o extracorp&#243;rea e o tempo de an&#243;xia durante as cirurgias foram similares entre os grupos pr&#233;-fragilidade e sem fragilidade (<xref ref-type="table" rid="t5">Tabela 1</xref>).</p>
        <table-wrap id="t5">
          <label>Tabela 1</label>
          <caption>
            <title>Caracter&#237;sticas dos pacientes</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="2">
								</th>
                <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Sem fragilidade</th>
                <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Pr&#233;-fragilidade</th>
                <th align="center" rowspan="2">p</th>
              </tr>
              <tr>
                <th align="center">(n = 77)</th>
                <th align="center">(n = 144)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">
                  <bold>Antropom&#233;tricas/Demogr&#225;ficas</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Homens, n (%)</td>
                <td align="center">52 (67,5%)</td>
                <td align="center">93 (64,5%)</td>
                <td align="center">0,26</td>
              </tr>
              <tr>
                <td align="left">Idade, anos</td>
                <td align="center">70 &#177; 2</td>
                <td align="center">72 &#177; 4</td>
                <td align="center">0,42</td>
              </tr>
              <tr>
                <td align="left">Peso, kg</td>
                <td align="center">69,3 &#177; 9,8</td>
                <td align="center">73,4 &#177; 14,3</td>
                <td align="center">0,02</td>
              </tr>
              <tr>
                <td align="left">Altura, m</td>
                <td align="center">1,64 &#177; 0,09</td>
                <td align="center">1,63 &#177; 0,10</td>
                <td align="center">0,76</td>
              </tr>
              <tr>
                <td align="left">IMC, kg/m<sup>2</sup></td>
                <td align="center">25,4 &#177; 2,6</td>
                <td align="center">27,1 &#177; 3,9</td>
                <td align="center">0,001</td>
              </tr>
              <tr>
                <td align="left">FEVE, %</td>
                <td align="center">54 &#177; 12</td>
                <td align="center">55 &#177; 11</td>
                <td align="center">0,52</td>
              </tr>
              <tr>
                <td align="left">Euro Score</td>
                <td align="center">2 &#177; 0,5</td>
                <td align="center">6 &#177; 0,4</td>
                <td align="center">&lt; 0,001</td>
              </tr>
              <tr>
                <td align="left">ASA</td>
                <td align="center">2 &#177; 0,3</td>
                <td align="center">3 &#177; 0,6</td>
                <td align="center">&lt; 0,001</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Principais comorbidades</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Hipertens&#227;o arterial sist&#234;mica, n (%)</td>
                <td align="center">58 (75,3%)</td>
                <td align="center">120 (83,3%)</td>
                <td align="center">0,01</td>
              </tr>
              <tr>
                <td align="left">Diabetes mellitus tipo 2, n (%)</td>
                <td align="center">27 (35%)</td>
                <td align="center">56 (38,8%)</td>
                <td align="center">0,12</td>
              </tr>
              <tr>
                <td align="left">Dislipidemia, n (%)</td>
                <td align="center">33 (42,8%)</td>
                <td align="center">66 (45,8%)</td>
                <td align="center">0,38</td>
              </tr>
              <tr>
                <td align="left">Tabagismo, n (%)</td>
                <td align="center">14 (18,2%)</td>
                <td align="center">16 (11,1%)</td>
                <td align="center">0,09</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Dados cir&#250;rgicos</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Revasculariza&#231;&#227;o do mioc&#225;rdio, n (%)</td>
                <td align="center">41 (53,2%)</td>
                <td align="center">83 (57,6%)</td>
                <td align="center">0,65</td>
              </tr>
              <tr>
                <td align="left">Troca ou plastia valvar, n (%)</td>
                <td align="center">25 (32,4%)</td>
                <td align="center">42 (29,2%)</td>
                <td align="center">0,42</td>
              </tr>
              <tr>
                <td align="left">Revascularia&#231;&#227;o do mioc&#225;rdio + troca ou plastia valvar, n (%)</td>
                <td align="center">11 (14,2%)</td>
                <td align="center">19 (13,2%)</td>
                <td align="center">0,71</td>
              </tr>
              <tr>
                <td align="left">Tempo de tromboplastina parcialmente ativada, s</td>
                <td align="center">27 &#177; 6</td>
                <td align="center">25 &#177; 7</td>
                <td align="center">0,19</td>
              </tr>
              <tr>
                <td align="left">Tempo de circula&#231;&#227;o extracorp&#243;rea, min</td>
                <td align="center">100 &#177; 40</td>
                <td align="center">90 &#177; 39</td>
                <td align="center">0,17</td>
              </tr>
              <tr>
                <td align="left">Tempo de an&#243;xia, min</td>
                <td align="center">73 &#177; 26</td>
                <td align="center">63 &#177; 31</td>
                <td align="center">0,12</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Par&#226;metros basais hemodin&#226;micos e sangu&#237;neos</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">FC, bpm</td>
                <td align="center">97 &#177; 22</td>
                <td align="center">93 &#177; 19</td>
                <td align="center">0,21</td>
              </tr>
              <tr>
                <td align="left">PAM, mmHg</td>
                <td align="center">98 &#177; 11</td>
                <td align="center">101 &#177; 14</td>
                <td align="center">0,43</td>
              </tr>
              <tr>
                <td align="left">Hemoglobina, g/dL</td>
                <td align="center">10,7 &#177; 2,1</td>
                <td align="center">10,8 &#177; 1,7</td>
                <td align="center">0,68</td>
              </tr>
              <tr>
                <td align="left">Hemat&#243;crito, %</td>
                <td align="center">33,2 &#177; 6,0</td>
                <td align="center">33,9 &#177; 8,7</td>
                <td align="center">0,49</td>
              </tr>
              <tr>
                <td align="left">Plaquetas, mm<sup>3</sup></td>
                <td align="center">143.126 &#177; 60.725</td>
                <td align="center">146.726 &#177; 53.742</td>
                <td align="center">0,64</td>
              </tr>
              <tr>
                <td align="left">Creatinina, mg/dL</td>
                <td align="center">1,16 &#177; 0,50</td>
                <td align="center">1,27 &#177; 0,54</td>
                <td align="center">0,54</td>
              </tr>
              <tr>
                <td align="left">PCR-us, mg/L</td>
                <td align="center">8,8 &#177; 0,8</td>
                <td align="center">9,0 &#177; 0,8</td>
                <td align="center">0,86</td>
              </tr>
              <tr>
                <td align="left">PaO<sub>2</sub>, mmHg</td>
                <td align="center">118 &#177; 5</td>
                <td align="center">117 &#177; 9</td>
                <td align="center">0,90</td>
              </tr>
              <tr>
                <td align="left">PaCO<sub>2</sub>, mmHg</td>
                <td align="center">42 &#177; 11</td>
                <td align="center">39 &#177; 8</td>
                <td align="center">0,06</td>
              </tr>
              <tr>
                <td align="left">HCO<sub>3</sub><sup>-</sup>, mmol/L</td>
                <td align="center">22 &#177; 2</td>
                <td align="center">21 &#177; 3</td>
                <td align="center">0,53</td>
              </tr>
              <tr>
                <td align="left">SpO<sub>2</sub>, %</td>
                <td align="center">96 &#177; 4</td>
                <td align="center">97 &#177; 3</td>
                <td align="center">0,37</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN4">
              <p>IMC: &#237;ndice de massa corporal; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo; ASA: Sociedade Americana de Anestesistas (American Society of Anesthesiologists); FC: frequ&#234;ncia card&#237;aca; PAM: press&#227;o arterial m&#233;dia; PCR-us: prote&#237;na C reativa ultrassens&#237;vel; PaO2: press&#227;o arterial de oxig&#234;nio; HCO3-: bicarbonato; SpO2: satura&#231;&#227;o da oxihemoglobina por oximetria de pulso. Valores expressos em m&#233;dia &#177; desvio padr&#227;o ou frequ&#234;ncia. Teste t de Student n&#227;o pareado foi utilizado para vari&#225;veis descritas em m&#233;dia &#177; desvio padr&#227;o; teste de &#967;<sup>2</sup> foi utilizado para avaliar diferen&#231;as de frequ&#234;ncias nas vari&#225;veis categ&#243;ricas.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>N&#227;o foram observadas diferen&#231;as nos valores hemodin&#226;micos ou nas amostras sangu&#237;neas entre os grupos ap&#243;s admiss&#227;o na UTI (<xref ref-type="table" rid="t5">Tabela 1</xref>). No entanto, o grupo pr&#233;-fragilidade apresentou maior n&#250;mero de pacientes em uso de drogas vasoativas em compara&#231;&#227;o ao grupo sem fragilidade ((<xref ref-type="table" rid="t6">Tabela 2</xref>). Maior tempo em ventila&#231;&#227;o mec&#226;nica, com n&#250;mero maior de pacientes em ventila&#231;&#227;o prolongada, e maior tempo de perman&#234;ncia na UTI e de interna&#231;&#227;o hospitalar foram observados no grupo pr&#233;-fragilidade em compara&#231;&#227;o ao grupo sem fragilidade. Al&#233;m disso, no grupo pr&#233;-fragilidade, houve maior incid&#234;ncia de eventos cardiovasculares e maior n&#250;mero de pacientes com AVC e &#243;bito intra-hospitalar que no grupo sem fragilidade (<xref ref-type="table" rid="t6">Tabela 2</xref>).</p>
        <table-wrap id="t6">
          <label>Tabela 2</label>
          <caption>
            <title>Dados prospectivos observados na unidade de terapia intensiva e at&#233; a alta hospitalar no grupo sem fragilidade e no grupo pr&#233;-fragilidade</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
								</th>
                <th align="center">Sem fragilidade (n = 77)</th>
                <th align="center">Pr&#233;-fragilidade (n = 144)</th>
                <th align="center">p</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">
                  <bold>Tempo de perman&#234;ncia</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Unidade de terapia intensiva, dias</td>
                <td align="center">3 &#177; 1</td>
                <td align="center">5 &#177; 1</td>
                <td align="center">0,03</td>
              </tr>
              <tr>
                <td align="left">Tempo total de hospitaliza&#231;&#227;o, dias</td>
                <td align="center">9 &#177; 3</td>
                <td align="center">12 &#177; 5</td>
                <td align="center">&lt;0,001</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Ventila&#231;&#227;o mec&#226;nica</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Tempo em ventila&#231;&#227;o mec&#226;nica, horas</td>
                <td align="center">29 &#177; 7</td>
                <td align="center">193 &#177; 37</td>
                <td align="center">0,001</td>
              </tr>
              <tr>
                <td align="left">Tempo prolongado em ventila&#231;&#227;o mec&#226;nica, n (%)</td>
                <td align="center">0</td>
                <td align="center">21 (14,5%)</td>
                <td align="center">0,001</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Vasopressor</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Noradrenalina, n (%)</td>
                <td align="center">26 (33,8%)</td>
                <td align="center">46 (31,9%)</td>
                <td align="center">0,87</td>
              </tr>
              <tr>
                <td align="left">Dobutamina, n (%)</td>
                <td align="center">8 (10,4%)</td>
                <td align="center">29 (20,1%)</td>
                <td align="center">0,03</td>
              </tr>
              <tr>
                <td align="left">Dopamina, n (%)</td>
                <td align="center">14 (18,2%)</td>
                <td align="center">15 (10,4%)</td>
                <td align="center">0,08</td>
              </tr>
              <tr>
                <td align="left">Nitroglicerina, n (%)</td>
                <td align="center">8 (10,4%)</td>
                <td align="center">20 (13,8%)</td>
                <td align="center">0,24</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Eventos adversos</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Infec&#231;&#227;o, n (%)</td>
                <td align="center">4 (5,2%)</td>
                <td align="center">7 (4,8%)</td>
                <td align="center">0,69</td>
              </tr>
              <tr>
                <td align="left">Acidente vascular cerebral, n (%)</td>
                <td align="center">3 (3,9%)</td>
                <td align="center">12 (8,3%)</td>
                <td align="center">0,02</td>
              </tr>
              <tr>
                <td align="left">&#211;bito intra-hospitalar, n (%)</td>
                <td align="center">6 (7,8%)</td>
                <td align="center">31 (21,5%)</td>
                <td align="center">0,001</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Cuidado domiciliar (homecare)</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Fisioterapia, n (%)</td>
                <td align="center">0</td>
                <td align="center">67 (46,5%)</td>
                <td align="center">&lt; 0,001</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5">
              <p>Valores expressos em m&#233;dia &#177; desvio padr&#227;o ou frequ&#234;ncia. Teste t de Student n&#227;o pareado foi utilizado para vari&#225;veis descritas em m&#233;dia &#177; desvio padr&#227;o; teste de &#967;<sup>2</sup> foi utilizado para avaliar diferen&#231;as de frequ&#234;ncias nas vari&#225;veis categ&#243;ricas</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>A an&#225;lise de Kaplan-Meier mostrou que eventos adversos foram significativamente maiores em pacientes com pr&#233;-fragilidade, tanto para o desfecho AVC (<xref ref-type="fig" rid="f3">Figura 1</xref>) quanto para o desfecho &#243;bito intra-hospitalar (<xref ref-type="fig" rid="f4">Figura 2</xref>). Al&#233;m disso, o OR e o HR indicaram risco aumentado para AVC e &#243;bito intra-hospitalar em pacientes com escores de fragilidade mais altos (grupo pr&#233;-fragilidade; <xref ref-type="table" rid="t7">Tabela 3</xref>).</p>
        <p>
          <fig id="f3">
            <label>Figura 1</label>
            <caption>
              <title>Sobrevida cumulativa de acidente vascular cerebral entre os grupos de pacientes com pr&#233;-fragilidade e sem fragilidade.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-109-04-0299-70131-gf01-pt.jpg"/></fig>
        </p>
        <p>
          <fig id="f4">
            <label>Figura 2</label>
            <caption>
              <title>Sobrevida cumulativa de morte intra-hospitalar entre os grupos de pacientes com pr&#233;-fragilidade e sem fragilidade.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-109-04-0299-70131-gf02-pt.jpg"/></fig>
        </p>
        <table-wrap id="t7">
          <label>Tabela 3</label>
          <caption>
            <title>Raz&#227;o de chance (Odds ratio) e raz&#227;o de risco (hazard ratio) para acidente vascular cerebral e &#243;bito intra-hospitalar no grupo pr&#233;-fragilidade</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <tbody>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="left">
								</td>
                <td align="center">
                  <bold>OR</bold>
                </td>
                <td align="center">
                  <bold>IC 95%</bold>
                </td>
                <td align="center">
                  <bold>Valor de p</bold>
                </td>
              </tr>
              <tr>
                <td align="left">AVC</td>
                <td align="center">2,139</td>
                <td align="center">0,622 - 7,351</td>
                <td align="center">0,001</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="left">&#211;bito intra-hospitalar</td>
                <td align="center">2,763</td>
                <td align="center">1,206 - 6,331</td>
                <td align="center">0,0001</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="left">
								</td>
                <td align="center">
                  <bold>HR</bold>
                </td>
                <td align="center">
                  <bold>IC 95%</bold>
                </td>
                <td align="center">
                  <bold>Valor de p</bold>
                </td>
              </tr>
              <tr>
                <td align="left">AVC</td>
                <td align="center">1,809</td>
                <td align="center">1,286 - 2,546</td>
                <td align="center">0,001</td>
              </tr>
              <tr>
                <td align="left">&#211;bito intra-hospitalar</td>
                <td align="center">1,830</td>
                <td align="center">1,476 - 2,269</td>
                <td align="center">0,0001</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN6">
              <p>AVC: acidente vascular cerebral; OR: odds ratio; HR: hazard ratio; IC: intervalo de confian&#231;a.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>No presente estudo, investigamos a rela&#231;&#227;o entre pr&#233;-fragilidade e eventos adversos no p&#243;s-operat&#243;rio de cirurgia cardiovascular. Os novos e principais achados deste estudo foram: 1) Pacientes com pr&#233;-fragilidade apresentam mais eventos adversos (AVC e &#243;bito intra-hospitalar) que pacientes sem fragilidade, e 2) Pacientes com pr&#233;-fragilidade apresentam maior tempo em ventila&#231;&#227;o mec&#226;nica e de interna&#231;&#227;o em compara&#231;&#227;o a pacientes sem fragilidade. Esses achados s&#227;o muito relevantes, uma vez que n&#227;o existem estudos pr&#233;vios que demonstraram uma rela&#231;&#227;o entre pr&#233;-fragilidade e eventos adversos no p&#243;s-operat&#243;rio de cirurgia cardiovascular.</p>
        <p>Nossos resultados contribuem para compreender o quanto as comorbidades e os d&#233;ficits pr&#233;-operat&#243;rios adicionam valor progn&#243;stico aos pacientes ap&#243;s cirurgia cardiovascular. Atualmente, mais da metade de todas as cirurgias cardiovasculares s&#227;o realizadas em pacientes com idade acima de 75 anos.<xref ref-type="bibr" rid="B12">12</xref> Recente revis&#227;o sistem&#225;tica<xref ref-type="bibr" rid="B13">13</xref> mostrou que a incid&#234;ncia de fragilidade aumenta com a idade (65-69 anos: 4%; 70-74 anos: 7%; 75-79 anos: 9%; 80-84 anos: 16%; e acima de 85 anos: 26%), como consequ&#234;ncia do decl&#237;nio relacionado &#224; idade em muitos sistemas fisiol&#243;gicos, que em geral resulta em vulnerabilidade para mudan&#231;as repentinas na sa&#250;de causadas por pequenos eventos estressores.<xref ref-type="bibr" rid="B2">2</xref> Al&#233;m disso, foi demonstrado que esses pacientes apresentam risco aumentado para quedas, interna&#231;&#227;o prolongada e mortalidade ap&#243;s a cirurgia.<xref ref-type="bibr" rid="B14">14</xref> Dados pr&#233;vios mostraram que cada ponto aumentado no escore de fragilidade est&#225; associado com maior incid&#234;ncia de limita&#231;&#227;o funcional e maior risco de mortalidade em seis meses.<xref ref-type="bibr" rid="B15">15</xref> Estudo prospectivo mostrou que 47% de uma coorte de 5210 pacientes acima de 65 anos de idade foram classificados como pr&#233;-fr&#225;geis (modelo fenot&#237;pico), com uma taxa de mortalidade elevada (23%) durante sete anos de acompanhamento.<xref ref-type="bibr" rid="B16">16</xref> Sundermann et al.,<xref ref-type="bibr" rid="B17">17</xref> relataram que pacientes com pr&#233;-fragilidade t&#234;m um desfecho intermedi&#225;rio entre pacientes fr&#225;geis e n&#227;o fr&#225;geis. Al&#233;m disso, a pr&#233;-fragilidade foi associada com um risco quatro vezes maior para se tornarem fr&#225;geis em um per&#237;odo de 4 anos de acompanhamento.<xref ref-type="bibr" rid="B16">16</xref> Sergi et al.,<xref ref-type="bibr" rid="B1">1</xref> observaram que pacientes com pr&#233;-fragilidade apresentam mais doen&#231;as cardiovasculares em compara&#231;&#227;o a pacientes n&#227;o fr&#225;geis. Contudo, a maioria dos estudos de fragilidade sobre desfechos p&#243;s-operat&#243;rios compararam somente pacientes com fragilidade versus pacientes sem fragilidade.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref> Nesse contexto, o presente estudo expande o conhecimento a respeito de pacientes com pr&#233;-fragilidade. Em um curto per&#237;odo de acompanhamento, pacientes com pr&#233;-fragilidade que se submeteram &#224; cirurgia cardiovascular apresentaram mais eventos adversos e &#243;bito intra-hospitalar que pacientes sem fragilidade. Assim, nosso estudo apresenta uma nova evid&#234;ncia de que pacientes com pr&#233;-fragilidade devem ser melhor avaliados e tratados antes da cirurgia cardiovascular.</p>
        <p>Em nosso estudo, pacientes com pr&#233;-fragilidade submetidos &#224; cirurgia cardiovascular apresentaram uma maior incid&#234;ncia de AVC. De fato, esse &#233; um achado comum na literatura cient&#237;fica e est&#225; relacionado ao envelhecimento e ao per&#237;odo intraoperat&#243;rio, apesar dos estudos pr&#233;vios n&#227;o terem avaliado a fragilidade ou pr&#233;-fragilidade.<xref ref-type="bibr" rid="B20">20</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref> Pacientes com fragilidade submetidos &#224; cirurgia (n&#227;o cardiovascular) apresentaram maior dessatura&#231;&#227;o cerebral no per&#237;odo intraoperat&#243;rio em compara&#231;&#227;o a pacientes sem fragilidade.<xref ref-type="bibr" rid="B22">22</xref> Al&#233;m disso, pacientes idosos com comorbidades tais como hipertens&#227;o e diabetes podem apresentar risco aumentado devido a altera&#231;&#245;es na autorregula&#231;&#227;o do fluxo sangu&#237;neo cerebral.<xref ref-type="bibr" rid="B23">23</xref> Nossos dados est&#227;o de acordo com a literatura atual, que sugere que pacientes com pr&#233;-fragilidade submetidos &#224; cirurgia de troca valvar apresentam maior incid&#234;ncia de AVC em compara&#231;&#227;o a pacientes submetidos a cirurgia de revasculariza&#231;&#227;o do mioc&#225;rdio. Esse fato pode ser explicado pelo maior tempo de circula&#231;&#227;o extracorp&#243;rea e de an&#243;xia durante a cirurgia. Interessante notar que 25% dos pacientes com pr&#233;-fragilidade evolu&#237;ram com &#243;bito durante a interna&#231;&#227;o, mostrando que o estado de sa&#250;de no per&#237;odo pr&#233;-operat&#243;rio &#233; um importante ponto a ser avaliado e pode influenciar o progn&#243;stico ap&#243;s um evento cr&#237;tico. Al&#233;m disso, esses pacientes t&#234;m maior probabilidade de apresentarem eventos cerebrovasculares e permanecerem em ventila&#231;&#227;o mec&#226;nica prolongada. Nesse contexto, &#233; muito prov&#225;vel que esses achados expliquem a alta incid&#234;ncia de AVC no grupo com pr&#233;-fragilidade em nosso estudo. Ainda, a maior porcentagem de hipertens&#227;o e diabetes observado nesse grupo pode estar relacionada &#224; maior incid&#234;ncia de eventos cerebrovasculares nesses pacientes.</p>
        <p>J&#225; est&#225; bem estabelecido que a ventila&#231;&#227;o mec&#226;nica prolongada est&#225; relacionada com novos d&#233;ficits ou com o agravamento de d&#233;ficits pr&#233;-existentes associados &#224; fragilidade em pacientes graves, os quais persistem mesmo ap&#243;s a resolu&#231;&#227;o da condi&#231;&#227;o cr&#237;tica,<xref ref-type="bibr" rid="B24">24</xref> independentemente do uso de ventila&#231;&#227;o invasiva ou n&#227;o invasiva.<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref> Nossos pacientes com pr&#233;-fragilidade permaneceram mais tempo em ventila&#231;&#227;o mec&#226;nica. De fato, o maior tempo em ventila&#231;&#227;o mec&#226;nica pode ser uma consequ&#234;ncia das principais complica&#231;&#245;es encontradas em nosso estudo.</p>
        <p>Al&#233;m disso, a ventila&#231;&#227;o mec&#226;nica prolongada est&#225; associada com a piora da funcionalidade, maior tempo de interna&#231;&#227;o e maior incid&#234;ncia de &#243;bito intra-hospitalar.<xref ref-type="bibr" rid="B26">26</xref> J&#225; foi demonstrado que mais de 80% desses pacientes requerem uma segunda hospitaliza&#231;&#227;o no per&#237;odo de 12 meses ap&#243;s a alta da UTI,<xref ref-type="bibr" rid="B26">26</xref> com alta incid&#234;ncia de mortalidade em seis meses.<xref ref-type="bibr" rid="B27">27</xref><sup>,</sup><xref ref-type="bibr" rid="B28">28</xref> Al&#233;m disso aqueles pacientes que sobrevivem podem ter pior capacidade funcional por quase cinco anos ap&#243;s a alta hospitalar.<xref ref-type="bibr" rid="B29">29</xref> Apesar de o seguimento dos pacientes ap&#243;s a alta hospitalar estar fora do escopo desse estudo, o grupo pr&#233;-fragilidade apresentou maior tempo de interna&#231;&#227;o, necessidade de tratamento em cl&#237;nicas ou centros especializados, incluindo fisioterapia e reabilita&#231;&#227;o ap&#243;s a alta hospitalar. Esses achados sugerem que esse grupo apresenta maior risco de reinterna&#231;&#227;o e/ou morte em um curto per&#237;odo de tempo.</p>
        <sec>
          <title>Implica&#231;&#245;es cl&#237;nicas</title>
          <p>A fragilidade &#233; reconhecida como uma s&#237;ndrome multidimensional caracterizada pela perda de reserva f&#237;sica e cognitiva que resulta em vulnerabilidade. O CFS &#233; uma escala de fragilidade de f&#225;cil aplica&#231;&#227;o usada para estratifica&#231;&#227;o de risco em idosos, que permite avaliar os desfechos relacionados &#224; fragilidade mesmo no per&#237;odo pr&#233;-operat&#243;rio, e pode melhorar tratamentos e interven&#231;&#245;es, prevenir poss&#237;veis complica&#231;&#245;es, e reduzir o tempo de interna&#231;&#227;o.</p>
          <p>Nosso estudo apresenta achados cl&#237;nicos importantes, uma vez que a fragilidade &#233; uma condi&#231;&#227;o revers&#237;vel quando tratada com interven&#231;&#245;es em est&#225;gios iniciais, tais como o exerc&#237;cio. Essas interven&#231;&#245;es s&#227;o efetivas e podem retardar a transi&#231;&#227;o de pr&#233;-fragilidade &#224; fragilidade.<xref ref-type="bibr" rid="B30">30</xref> O exerc&#237;cio antes da cirurgia cardiovascular tamb&#233;m pode contribuir para melhor recupera&#231;&#227;o na UTI.</p>
          <p>Al&#233;m disso, nosso estudo enfatiza a necessidade de se avaliar a fragilidade antes da cirurgia cardiovascular, para melhor compreender os riscos nos pacientes idosos e orientar interven&#231;&#245;es espec&#237;ficas durante o per&#237;odo pr&#233;-operat&#243;rio que minimizem o risco de eventos adversos, mesmo em pacientes em est&#225;gios precoces de fragilidade.</p>
        </sec>
        <sec>
          <title>Limita&#231;&#245;es do estudo</title>
          <p>Este estudo possui algumas limita&#231;&#245;es que devem ser consideradas. Existe uma lacuna na literatura recente em rela&#231;&#227;o ao melhor crit&#233;rio de avalia&#231;&#227;o de fragilidade. H&#225; significativa heterogeneidade nos crit&#233;rios de fragilidade utilizados em ensaios cl&#237;nicos, o que torna ainda mais dif&#237;cil o reconhecimento de fragilidade nos pacientes p&#243;s-cir&#250;rgicos.<xref ref-type="bibr" rid="B31">31</xref>
					</p>
          <p>O grupo pr&#233;-fragilidade possu&#237;a um n&#250;mero maior de pacientes que o grupo sem fragilidade. Para evitar que esse fato influenciasse nossos resultados, o poder estat&#237;stico para os principais desfechos foi calculado, resultando em um poder de 99,98% para o tempo total de interna&#231;&#227;o, e 74,22% para &#243;bito intra-hospitalar.</p>
          <p>Um estudo recente mostrou que escores amplamente utilizados (<italic>Acute Physiology Score and Acute Physiology and Chronic Health Evaluation</italic>) n&#227;o foram capazes de predizer maior risco de morte.<xref ref-type="bibr" rid="B32">32</xref> Contudo, a fragilidade, quando associada a escalas tradicionais de risco (<italic>ASA, Eagle</italic> e <italic>Lee</italic>), &#233; preditora independente de complica&#231;&#245;es no p&#243;s-operat&#243;rio, tempo de interna&#231;&#227;o, e necessidade de cuidado especializado em cl&#237;nicas ou centros especiais ap&#243;s a alta hospitalar em pacientes idosos submetidos &#224; cirurgias.<xref ref-type="bibr" rid="B8">8</xref> Nosso estudo avaliou alguns tipos de escala de risco: CFS, ASA e EuroScore, e todas estavam aumentadas nos pacientes que apresentaram piores desfechos. Al&#233;m disso, a fragilidade foi capaz de predizer eventos cardiovasculares importantes no p&#243;s-operat&#243;rio de cirurgia card&#237;aca, mesmo em pacientes em est&#225;gios iniciais de fragilidade.</p>
          <p>Existem dois modelos de fragilidade: modelos fenot&#237;picos e de d&#233;ficits acumulados (CFS). N&#243;s decidimos utilizar somente o CFS por esse ser prontamente acess&#237;vel para aplica&#231;&#227;o a beira do leito, e de uso e de compreens&#227;o mais f&#225;ceis que outros instrumentos de avalia&#231;&#227;o de fragilidade. Al&#233;m disso, o CFS foi considerado um excelente instrumento para uso na admiss&#227;o de pacientes na UTI.<xref ref-type="bibr" rid="B10">10</xref>
					</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Os pacientes com pr&#233;-fragilidade apresentaram maior tempo em ventila&#231;&#227;o mec&#226;nica, maior perman&#234;ncia na UTI e tempo de interna&#231;&#227;o hospitalar, e maior necessidade de fisioterapia domiciliar que pacientes sem fragilidade ap&#243;s cirurgia cardiovascular. Al&#233;m disso, a presen&#231;a de pr&#233;-fragilidade no per&#237;odo pr&#233;-operat&#243;rio foi preditor de eventos adversos (AVC ou &#243;bito intra-hospitalar). No entanto, ainda n&#227;o se sabe se o tratamento da fragilidade antes da cirurgia cardiovascular &#233; efetivo para prevenir eventos adversos.</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>
