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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">Xnj3dLGLNVbB3FvjbBMvNNN</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2017000200161</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20170001</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2017005002103</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Non-Invasive Ventilation in Patients with Heart Failure: A Systematic Review and Meta-Analysis</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Bittencourt</surname>
            <given-names>Hugo Souza</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Reis</surname>
            <given-names>Helena Fran&#231;a Correia dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lima</surname>
            <given-names>Melissa Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gomes</surname>
            <given-names>Mansueto</given-names>
            <suffix>Neto</suffix>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade Federal da Bahia</institution>
        <institution content-type="orgdiv1">Curso de Fisioterapia</institution>
        <institution content-type="orgdiv2">Departamento de Fisioterapia</institution>
        <addr-line>
          <named-content content-type="city">Bahia</named-content>
          <named-content content-type="state">BA</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Programa de P&#243;s Gradua&#231;&#227;o em Medicina e Sa&#250;de, Departamento de Fisioterapia - Curso de Fisioterapia da Universidade Federal da Bahia, Bahia, BA - Brazil</institution>
        <institution content-type="normalized">Universidade Federal da Bahia</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Universidade Federal da Bahia</institution>
        <institution content-type="orgdiv1">Curso de Fisioterapia</institution>
        <institution content-type="orgdiv2">Departamento de Fisioterapia</institution>
        <addr-line>
          <named-content content-type="city">Bahia</named-content>
          <named-content content-type="state">BA</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Departamento de Fisioterapia - Curso de Fisioterapia da Universidade Federal da Bahia, Bahia, BA - Brazil</institution>
        <institution content-type="normalized">Universidade Federal da Bahia</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Hugo Souza Bittencourt</bold>, Av. Reitor Miguel Calmon s/n - Vale do Canela. Postal Code 40.110-100, Salvador, Bahia - Brazil. E-mail: <email>fisiobittencourt@hotmail.com</email>; <email>moni.chiara@globo.com</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research and Acquisition of data: Bittencourt HS, Reis HFC, Gomes Neto M; Analysis and interpretation of the data and Statistical analysis: Bittencourt HS, Gomes Neto M; Obtaining financing: Gomes Neto M; Writing of the manuscript: Bittencourt HS, Reis HFC, Lima MS; Critical revision of the manuscript for intellectual content: Reis HFC, Lima MS, Gomes Neto M.</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>16</day>
        <month>01</month>
        <year>2017</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>02</month>
        <year>2017</year>
      </pub-date>
      <volume>108</volume>
      <issue>2</issue>
      <fpage>161</fpage>
      <lpage>168</lpage>
      <history>
        <date date-type="received">
          <day>21</day>
          <month>11</month>
          <year>2015</year>
        </date>
        <date date-type="rev-recd">
          <day>15</day>
          <month>12</month>
          <year>2015</year>
        </date>
        <date date-type="accepted">
          <day>13</day>
          <month>05</month>
          <year>2016</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>
        <p>Non-invasive ventilation (NIV) may perfect respiratory and cardiac performance in patients with heart failure (HF).</p>
        <p>The objective of the study to establish, through systematic review and meta-analysis, NIV influence on functional capacity of HF patients.</p>
        <p>A systematic review with meta-analysis of randomized studies was carried out through research of databases of Cochrane Library, SciELO, Pubmed and PEDro, using the key-words: heart failure, non-invasive ventilation, exercise tolerance; and the free terms: bi-level positive airway pressure (BIPAP), continuous positive airway pressure (CPAP), and functional capacity (terms were searched for in English and Portuguese) using the Boolean operators AND and OR. Methodological quality was ensured through PEDro scale. Weighted averages and a 95% confidence interval (CI) were calculated. The meta-analysis was done thorugh the software Review Manager, version 5.3 (Cochrane Collaboration).</p>
        <p>Four randomized clinical trials were included. Individual studies suggest NIV improved functional capacity. NIV resulted in improvement in the distance of the six-minute walk test (6MWT) (68.7m 95%CI: 52.6 to 84.9) in comparison to the control group.</p>
        <p>We conclude that the NIV is an intervention that promotes important effects in the improvement of functional capacity of HF patients. However, there is a gap in literature on which are the most adequate parameters for the application of this technique.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Heart Failure</kwd>
        <kwd>Noninvasive Ventilation</kwd>
        <kwd>Exercise Tolerance</kwd>
        <kwd>Review</kwd>
        <kwd>Meta-Analysis</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>HF is a clinical syndrome in which the heart has difficulty pumping blood, generating functional limitation with important cardiovascular, hemodynamic and metabolic alterations.<xref ref-type="bibr" rid="B1">1</xref><sup>-</sup><xref ref-type="bibr" rid="B3">3</xref> HF patients have reduced FC, which may limit their performance of daily life activities (DLA) and reduce quality of life (QL).<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B6">6</xref> These alterations contribute to the increase of symptoms and to exercise intolerance, progressively reducing FC.<xref ref-type="bibr" rid="B7">7</xref>
			</p>
      <p>Cardiac rehabilitation programs are being more and more recommended for this population, with the objective of minimizing the consequences of HF and improving the patient's QL. Cardiac rehabilitation is defined as a non-pharmacological treatment with an emphasis on the practice of physical exercise.<xref ref-type="bibr" rid="B8">8</xref>
			</p>
      <p>Currently, some resources used in physical therapy are complementing a cardiac rehabilitation program for patients who initially cannot tolerate exercising. NIV with administration of CPAP is one of the utilized techniques. NIV may improve cardiac and respiratory performances of HF patients, considering it enhances oxygenation and pulmonary mechanics, so it can also improve FC.<xref ref-type="bibr" rid="B7">7</xref>
			</p>
      <p>Traditionally, NIV has been used in respiratory insufficiency situations and in HF patients with the objective of reversing pulmonary edema and respiratory failure situations. The use of NIV and its effect on exercise tolerance have only recently started to be investigated, but there are controversies surrounding its efficacy and use in clinical practice. Systematic review with meta-analysis can solve conflict issues of individual studies and provide more reliable estimates of the efficacy of NIV use in HF patients. The aim of this work was to carry out a systematic review with meta-analysis about the use of NIV to improve FC in HF patients.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>A systematic review was realized, observing the criteria established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.<xref ref-type="bibr" rid="B9">9</xref>
			</p>
      <sec>
        <title>Eligibility criteria</title>
        <p>We included random clinical trials (RCT) that tested the use of NIV in patients over 18 years old, of both genders, with HF and without associated restrictive or obstructive pulmonary disease.</p>
        <p>Evaluation measurements were: tolerance to effort; duration of exercise; perceived exertion; spirometry; lactatemia.</p>
      </sec>
      <sec>
        <title>Data source and research</title>
        <p>Article research was done with databases from PubMed, <italic>Cochrane Library</italic>, SciELO and Physiotherapy Evidence Database (PEDro). In this research we included original articles published in English, Spanish and Portuguese up to August of 2015.</p>
        <p>The initial search strategy consisted of four key-words (study design, participants, interventions, and result measurements). The utilized key-words were described from search terms Medical Subject Headings (MeSH) and Health Science Descriptors (DeCS) where, for the study design, we included: randomized clinical trial and controlled study. The group of participants used words referent to the disease such as HF, cardiac dysfunction or ventricular dysfunction. The key-words that were used for intervention were: NIV and exercise tolerance. The terms used for result measurements were: 6MWT, ergometry, ergospirometry, spirometry.</p>
        <p>An experienced reviewer carried out the search and initial selection to identify the titles and abstracts of potentially relevant studies. Each abstract was assessed independently by two reviewers. If at least one of the reviewers considered a reference to be eligible, the article was obtained in its entirety. Both reviewers would then independently analyse the articles to select the ones to be included in the review. When there was a disagreement, the decision was made by the authors' consensus. A manual tracking of citations of the selected articles was also performed.</p>
      </sec>
      <sec>
        <title>Methodological quality assessment of the studies</title>
        <p>The quality of the studies was assessed using the PEDro scale - the most widely used in the area of rehabilitation. This scale is based on the Delphi list,<xref ref-type="bibr" rid="B10">10</xref> in order to measure the internal validity through the presence or absence of methodological criteria.<xref ref-type="bibr" rid="B11">11</xref> The PEDro scale is made up of the following criteria: 1) specification of inclusion criteria (non-scored item); 2) random allocation; 3) confidential allocation; 4) group similarities in the initial or basal phase; 5) masking of subjects; 6) masking of the therapist; 7) masking of the assessor; 8) measurement of at least one primary outcome in at least 85% of the allocated subjects; 9) analysis of intention to treat; 10) comparison between groups of at least one primary outcome; 11) reports of variability measurements and parameter estimates of at least one primary variable. For each defined criterion in the scale, one point (1) is attributed to the presence of evidence quality indicator, and zero (0) is attributed to the absence of these indicators.<xref ref-type="bibr" rid="B11">11</xref>
				</p>
      </sec>
      <sec>
        <title>Statistical evaluation</title>
        <p>Meta-analysis was done due to the similarity between studies in regards to the chosen intervention, patients' characteristics, and the variable distance covered in the 6MWT. Combined effect estimates were expressed as the mean difference between the groups. Statistical heterogeneity among the studies was assessed with Cochrane's Q test, and inconsistence test I<xref ref-type="bibr" rid="B2">2</xref>, in which values above 25% and 50% were considered indicative of moderate and high heterogeneity, respectively. Calculations were done using a fixed effect model, due to the low heterogeneity. An &#945; value of 0.05 was considered significant. Analysis was done using the Review Manager, version 5.3 (<italic>Cochrane Collaboration</italic>).</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>We initially identified a total of 37 articles in the selected database research, 21 at PubMed, nine at SciELO, and seven at the Cochrane Library. After careful examination, 30 articles were excluded by title and/or abstract, and three by duplicate. The four remaining articles met the inclusion criteria and were selected, in their entirety, for reading (<xref ref-type="fig" rid="f1">Figure 1</xref>).</p>
      <p>
        <fig id="f1">
          <label>Figure 1</label>
          <caption>
            <title>Flowchart of the article selection process.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-108-02-0161-70001-gf01.jpg"/></fig>
      </p>
      <sec>
        <title>Study methodological quality analysis</title>
        <p>Methodological quality analysis of the studies that met the inclusion criteria was done by two researchers in an independent way, in which a mean value of 6.2 was found using the PEDro scale (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Quality assessment of studies through PEDro scale</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
								</th>
                <th align="center">O&#8217;Donnell et al.<xref ref-type="bibr" rid="B12">12</xref>
								</th>
                <th align="center">Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref>
								</th>
                <th align="center">Chermont et al.<xref ref-type="bibr" rid="B13">13</xref>
								</th>
                <th align="center">Lima et al.<xref ref-type="bibr" rid="B7">7</xref>
								</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">1</td>
                <td align="center">
								</td>
                <td align="center">&#10003;</td>
                <td align="center">
								</td>
                <td align="center">&#10003;</td>
              </tr>
              <tr>
                <td align="left">2</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
              </tr>
              <tr>
                <td align="left">3</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">&#10003;</td>
              </tr>
              <tr>
                <td align="left">4</td>
                <td align="center">
								</td>
                <td align="center">&#10003;</td>
                <td align="center">
								</td>
                <td align="center">&#10003;</td>
              </tr>
              <tr>
                <td align="left">5</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">6</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">7</td>
                <td align="center">
								</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">8</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
              </tr>
              <tr>
                <td align="left">9</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">10</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
              </tr>
              <tr>
                <td align="left">11</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
                <td align="center">&#10003;</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="left">Total:</td>
                <td align="center">4</td>
                <td align="center">6</td>
                <td align="center">5</td>
                <td align="center">6</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>Mean: 6,2</bold>
                </td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
      </sec>
      <sec>
        <title>Study characteristics</title>
        <p>The four studies evaluated the impact of NIV in exercise tolerance of HF patients. Participants from all selected studies suffered from HF.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> The period of study publication was from 1999 to 2011, and the studied population size varied between 12<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> and 22<xref ref-type="bibr" rid="B14">14</xref> patients, amounting to 58 studied individuals. Mean age of participants varied between 46<xref ref-type="bibr" rid="B7">7</xref> and 61<xref ref-type="bibr" rid="B12">12</xref> years of age. The four studies were done with a population made up of both genders. <xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> In three of the studies, participants belonged to functional class II to III according to the NYHA,<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> and in one study, functional class varied between II to IV.<xref ref-type="bibr" rid="B12">12</xref>
				</p>
        <p>Three of the studies used the 6MWT as an indicator of functional capacity of HF individuals,<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> and only one study used the exercise test on a cycle ergometer<xref ref-type="bibr" rid="B12">12</xref> as an evaluation tool.</p>
      </sec>
      <sec>
        <title>Non-invasive ventilation support characteristics</title>
        <p>As an interface for NIV application, two studies<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> chose the nasal mask, one study<xref ref-type="bibr" rid="B7">7</xref> used the facial mask, and another opted for the oral mask.<xref ref-type="bibr" rid="B12">12</xref>
				</p>
        <p>Three of the studies opted for CPAP,<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> and one of them used CPAP and support pressure (SP).<xref ref-type="bibr" rid="B12">12</xref> Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref> used CPAP of 8 cmH<sub>2</sub>O; Chermont et al.<xref ref-type="bibr" rid="B13">13</xref> used a pressure of 3 cmH<sub>2</sub>O for 10 minutes in the CPAP group, progressing to 4 to 6 cmH<sub>2</sub>O, while in the placebo group, a pressure of 0 to 1 cmH<sub>2</sub>O was fixed. Lima et al.<xref ref-type="bibr" rid="B7">7</xref> applied a pressure of 10 cmH<sub>2</sub>O, whereas O'Donnell et al.<xref ref-type="bibr" rid="B12">12</xref> used CPAP and SP with positive end-expiratory pressure (PEEP) of 4.8 cm of H<sub>2</sub>O, comparing it to a control that used only 1 cmH<sub>2</sub>O.</p>
        <p>The four selected articles that took part in the review used a control group and assessed the use of ventilator support in FC of HF patients.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> Two of them used CPAP in one single session before the exercises;<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> one article used CPAP for 14 days;<xref ref-type="bibr" rid="B14">14</xref> and only one article used both ventilatory support models (CPAP and SP) during the exercise.<xref ref-type="bibr" rid="B12">12</xref>
				</p>
        <p>Characteristics of the included RCTs and of the intervention are described in <xref ref-type="table" rid="t2">Tables 2</xref> and <xref ref-type="table" rid="t3">3</xref>.</p>
        <table-wrap id="t2">
          <label>Table 2</label>
          <caption>
            <title>Characteristics of studies included in the review</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
              <col width="11%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="2">Study</th>
                <th align="center" rowspan="2">Participants</th>
                <th align="center" rowspan="2">Evaluation</th>
                <th align="center" colspan="3" style="border-bottom-width:thin;border-bottom-style:solid">Methods of evaluation</th>
                <th align="center" colspan="3" style="border-bottom-width:thin;border-bottom-style:solid">Results</th>
              </tr>
              <tr>
                <th align="center">Duration of<break/> exercise</th>
                <th align="center">Aerobic<break/> capacity</th>
                <th align="center">Dyspnea</th>
                <th align="center">Duration of exercise</th>
                <th align="center">Aerobic<break/> capacity</th>
                <th align="center">Dyspnea</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">O&#8217;Donnell et al.<xref ref-type="bibr" rid="B12">12</xref>
								</td>
                <td align="center">12 patients<break/> Men (11)<break/> Women (1)<break/> LVEF 35%<break/> FC/II/IV NYHA</td>
                <td align="center">Duration of exercise dyspnea</td>
                <td align="center">Time in minutes</td>
                <td align="center">No</td>
                <td align="center">BORG Scale</td>
                <td align="center">10.1&#177;1.5 PS p &lt; 0.01 8.7&#177;1.1 CPAP p = 0.08 7.2 &#177; 1.0 control</td>
                <td align="center">No</td>
                <td align="center">p &gt; 0.005</td>
              </tr>
              <tr>
                <td align="left">Wittmer et al. <xref ref-type="bibr" rid="B14">14</xref>
								</td>
                <td align="center">22 patients<break/> Men (12)<break/> Women (10)<break/> LVEF 45%<break/> FC/II/III<break/> NYHA</td>
                <td align="center">Aerobic capacity</td>
                <td align="center">No</td>
                <td align="center">6MWT</td>
                <td align="center">No</td>
                <td align="center">No</td>
                <td align="center">&#8593;6MWT <break/>(p&lt;0.05)</td>
                <td align="center">No</td>
              </tr>
              <tr>
                <td align="left">Chermont et al.<xref ref-type="bibr" rid="B13">13</xref>
								</td>
                <td align="center">12 patients<break/> Men (8)<break/> Women (4)<break/> LVEF 45%<break/> FC/II/III<break/> NYHA</td>
                <td align="center">Aerobic capacity</td>
                <td align="center">No</td>
                <td align="center">6MWT</td>
                <td align="center">No</td>
                <td align="center">No</td>
                <td align="center">&#8593;6MWT <break/>(p&lt;0.05)</td>
                <td align="center">No</td>
              </tr>
              <tr>
                <td align="left">Lima et al.<xref ref-type="bibr" rid="B7">7</xref>
								</td>
                <td align="center">12 patients<break/> Men (8)<break/> Women (4)<break/> LVEF 35%<break/> FCII/III<break/> NYHA</td>
                <td align="center">Aerobic capacity</td>
                <td align="center">No</td>
                <td align="center">6MWT</td>
                <td align="center">BORG Scale</td>
                <td align="center">No</td>
                <td align="center">&#8593;6MWT <break/>(p&lt;0.05)</td>
                <td align="center">P: 0.009</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>6MWT: six-minute walk test; SP: support pressure; CPAP: continuous positive airway pressure; NYHA: New York Heart Association.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <title>Characteristics of interventions of studies included in the review</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="14%"/>
              <col width="14%"/>
              <col width="14%"/>
              <col width="14%"/>
              <col width="14%"/>
              <col width="14%"/>
              <col width="14%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Study</th>
                <th align="center">Intervention time</th>
                <th align="center">Application time</th>
                <th align="center">Respiratory <break/>exercises</th>
                <th align="center">PEEP</th>
                <th align="center">NIVS (CPAP) <break/>Before exercise</th>
                <th align="center">NIVS (CPAP/SP) <break/>During exercise</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">O&#8217;Donnell et al.<xref ref-type="bibr" rid="B12">12</xref>
								</td>
                <td align="center">Session (1)</td>
                <td align="center">During exercise</td>
                <td align="center">No</td>
                <td align="center">PS/CPAP 4.8 cmH<sub>2</sub>O Control 1 cmH<sub>2</sub>O</td>
                <td align="center">No</td>
                <td align="center">Yes</td>
              </tr>
              <tr>
                <td align="left">Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref>
								</td>
                <td align="center">Session (14)</td>
                <td align="center">30 minutes</td>
                <td align="center">3 x 10 repetitions SE/ DB/IH</td>
                <td align="center">CPAP 8 cmH<sub>2</sub>O</td>
                <td align="center">Yes</td>
                <td align="center">No</td>
              </tr>
              <tr>
                <td align="left">Chermont et al.<xref ref-type="bibr" rid="B13">13</xref>
								</td>
                <td align="center">Session (1)</td>
                <td align="center">30 minutes</td>
                <td align="center">No</td>
                <td align="center">CPAP 4-6 cmH<sub>2</sub>O Control 0-1 cmH<sub>2</sub>O</td>
                <td align="center">Yes</td>
                <td align="center">No</td>
              </tr>
              <tr>
                <td align="left">Lima et al.<xref ref-type="bibr" rid="B7">7</xref>
								</td>
                <td align="center">Session (1)</td>
                <td align="center">30 minutes</td>
                <td align="center">No</td>
                <td align="center">CPAP 10 cmH<sub>2</sub>O</td>
                <td align="center">Yes</td>
                <td align="center">No</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>NIVS: non-invasive ventilatory support; PEEP: positive end-expiratory pressure; SP: support pressure; CPAP: continuous positive airway pressure; SE: short expiration; DB: deep breath; IH: inspiratory hiccups.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>NIV effects on FC and pulmonary function</title>
        <p>All works evaluated NIV impact on FC of HF patients, and all studies found, after the use of NIV, <xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> an increase in exercise tolerance.</p>
        <p>Chermont et al.<xref ref-type="bibr" rid="B13">13</xref> observed an increase in tolerance to physical exercise with a longer distance covered in the 6MWT in HF patients, when they were submitted to 30 minutes of CPAP at 6 cmH<sub>2</sub>O before the test.</p>
        <p>These results confirmed the findings of Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref> in their prospective randomized blind clinical trial, in which 22 patients (12 men and 10 women) were randomly divided to do 30 minutes of treatment with CPAP, respiratory exercises, and walking exercises (CPAP group), or respiratory exercise and walking exercise (control group) for 14 days. Through the 6MWT evaluation, one day before the treatment (day 0) and on the 4<sup>th</sup>, 9<sup>th</sup>, and 14<sup>th</sup> days of treatment, the authors observed that patients in the CPAP group showed progressive improvement in the distance covered during 6MWT, reaching approximately 28% of base values at the end of the treatment, whereas the control group showed no significant changes. Despite having found an improvement in the distance covered, the authors were not able to determine with certainty if this positive outcome was due to an improvement on pulmonary function or to hemodynamic alterations.</p>
        <p>In the study by O'Donnell et al.,<xref ref-type="bibr" rid="B12">12</xref> the total time of exercise increased significantly during exercise with SP (p = 0.004), but only slightly with the use of CPAP (p = 0.079) in comparison to the control.</p>
        <p>According to Lima et al.,<xref ref-type="bibr" rid="B7">7</xref> there was significant improvement in the distance covered during 6MWT after the use of CPAP in only one application session of 30 minutes.</p>
        <p>Of the four studies we found, three evaluated pulmonary function.<xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> In the study by O'Donnell et al.<xref ref-type="bibr" rid="B12">12</xref> basal parameters of pulmonary function were within normal limits, except for a small reduction in forced vital capacity (FVC) and a reduction of the expiratory reserve volume (ERV). However, during exercise, patients presented significant increases in the end-expiratory lung volume. Even though the study by Chermont et al.<xref ref-type="bibr" rid="B13">13</xref> cites that the patients were submitted to pulmonary function tests, it did not describe the results. Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref> observed an increase in FVC in patients treated with CPAP, reaching a maximum value or 16% of the basal value on the 9<sup>th</sup> day of treatment, in comparison to the control group. In the same way, FEV1 values increased progressively, reaching a maximum value of 14% on the 14<sup>th</sup> day of treatment.</p>
      </sec>
      <sec>
        <title>NIV effects on lactate concentration</title>
        <p>Only the study by Lima et al.<xref ref-type="bibr" rid="B7">7</xref> evaluated the lactate concentration in HF patients after the 6MWT with previous application of CPAP. The patients who were submitted to NIV obtained a lower lactate concentration at the end of the test in comparison to controls.</p>
      </sec>
      <sec>
        <title>NIV effects on the duration of exercise</title>
        <p>Patients who used CPAP before the 6MWT walked a longer distance in meters than those in the control group.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> The use of CPAP, added to the respiratory exercises and walking exercises, also induced a significant increase in the covered distance during the 6MWT in comparison to a control group that did only respiratory and walking exercises.<xref ref-type="bibr" rid="B14">14</xref> The use of SP in association to exercise on a cycle ergometer, in comparison to CPAP and placebo, was more effective in the evaluation of permanence time in the exercise on a cycle ergometer, and in the evaluation of subjective perceived exertion through the BORG scale.<xref ref-type="bibr" rid="B12">12</xref> There were also differences in the use of CPAP in comparison to the placebo. CPAP mode increased the duration of the exercise, with a smaller effort rate by the BORG scale.</p>
        <p>Three studies evaluated the 6MWT. Of these, two evaluated the effect of one NIV session, while the third evaluated the effect of 14 sessions of NIV. The meta-analysis of the three showed (<xref ref-type="fig" rid="f2">Figure 2</xref>) a significant difference in the 6MWT distance (68.7 m 95% CI: 52.6 to 84.9; N=58) for participants of the NIV group compared to controls. When combining only the two studies that used NIV in one single session, meta-analysis showed (<xref ref-type="fig" rid="f2">Figure 2</xref>) a significant difference in the 6MWT distance (65.2 m 95% CI: 38.8 a 91.7; N=36) for participants in the NIV group in comparison to controls.</p>
        <p>
          <fig id="f2">
            <label>Figure 2</label>
            <caption>
              <title>CPAP versus Control: 6MWT. Review Manager (RevMan). Version 5.2 The Cochrane Collaboration, 2013.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-108-02-0161-70001-gf02.jpg"/></fig>
        </p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>This systematic review had the objective of identifying the scientific evidence on the impact of NIV on HF patients' FC. The results indicate a significant improvement on tolerance to exercise in HF patients after NIV intervention, in comparison to the control group.</p>
      <p>NIV is being used as an important tool in the treatment of HF patients for the improvement of ventilatory efficiency during exercise.<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref> This fact may be associated to factors such as improvement in oxygenation, attenuation of the metaboreflex, improvement in the ventilation/perfusion ratio (V/Q), airway patency and consequent reduction of ventilatory work and fatigue.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref>
			</p>
      <p>HF patients present decreased tolerance to effort associated to an increase of dyspnea and muscle fatigue.<xref ref-type="bibr" rid="B18">18</xref> Previous use of CPAP increased the distance patients covered during the 6MWT and prolonged duration of exercise on the cycle ergometer when used simultaneously with exercises.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref>
			</p>
      <p>Evaluation of HF patients is extremely relevant; thus, cardiopulmonary exercise testing (CPET) is the reference standard and the most specific test for ventilatory evaluation during physical exercise - it not only measures FC, which is directly linked to the severity of HF, it can also evaluate the patient's oxygen consumption (VO2). However, since the cardiopulmonary test is complex and costly, the 6MWT proves to be an efficacious tool in FC evaluation.<xref ref-type="bibr" rid="B19">19</xref>
			</p>
      <p>The 6MWT can be related to daily physical activities, and so it is a submaximal test of simple execution and low cost. The 6MWT is an excellent option, able to assess FC, and working as a predictor of mortality in this population.<xref ref-type="bibr" rid="B17">17</xref><sup>-</sup><xref ref-type="bibr" rid="B19">19</xref> Moreover, studies report that the distance covered in the test is associated to the functional classification of the NYHA.<xref ref-type="bibr" rid="B20">20</xref><sup>-</sup><xref ref-type="bibr" rid="B24">24</xref>
			</p>
      <p>The 6MWT has been used in three studies to evaluate the distance covered by the patients.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> Lima et al.<xref ref-type="bibr" rid="B7">7</xref> found significant differences in the distance covered during the 6MWT in patients submitted to NIV with CPAP, in comparison to the control group. The study's results corroborate the work done by Chermont et al.<xref ref-type="bibr" rid="B13">13</xref> in which NIV promoted an increase in the distance covered (NIV: 507 m; placebo: 446 m; p = 0.001) by patients with increased tolerance to exercise.</p>
      <p>Previous CPAP administration in HF decreases respiratory discomfort in patients, generating lower cardiac work during exercise.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref> Smaller quantities of lactate have also been attributed to the use of CPAP in patients after the 6MWT.<xref ref-type="bibr" rid="B7">7</xref>
			</p>
      <p>NIV is an important instrument used to perfect the treatment of patients, with significant improvement in the performance of physical activities.<xref ref-type="bibr" rid="B26">26</xref> Pulmonary function may be decreased in HF, having a direct relationship with the reduction in FC and in the performance of DLAs.<xref ref-type="bibr" rid="B27">27</xref><sup>,</sup><xref ref-type="bibr" rid="B28">28</xref> Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref> have demonstrated that treatment with CPAP progressively increased FVC and FEV1 in HF patients when compared to the control group. This improvement may have occurred due to the increase in functional residual capacity and opening of collapsed alveoli.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref>
			</p>
      <p>In the study by Wittimer et al.<xref ref-type="bibr" rid="B14">14</xref> a clinical implication in relation to FVC was observed as a component of the outcome associated to FC after repercussion of NIV application. The CPAP group showed progressive increase of FVC, reaching a maximum of 16% of the basal value on the 9<sup>th</sup> day of treatment, with no additional improvement on the 14<sup>th</sup> day of treatment. VEF1 values increased progressively and reached a maximum of 14% on the 14<sup>th</sup> day of treatment with CPAP, with no significant changes in the control group. The authors concluded that the treatment with CPAP, for two weeks, increased pulmonary function of HF patients, consequently improving tolerance to activities.</p>
      <p>The increase in respiratory work in HF is associated to a decreased diaphragm perfusion. Due to this event, patients who are decompensated by the disease evolve with muscle fatigue in lower limbs, caused by an increase in peripheral vascular resistance.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref> Obtainment of lower resistance to airflow in the airways with administration of positive pressure,<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref> and reduction in respiratory discomfort or fatigue in lower limbs<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> are factors that can also explain the improvement in FC with the use of NIV associated to exercise.</p>
      <p>Patients who used non-invasive ventilatory support (NIVS) increased their FC when they used a PEEP superior to 4 cmH<sub>2</sub>O. Studies that compared the use of a lower value PEEP or placebo mode proved it to be inefficacious when compared to a higher level PEEP.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B29">29</xref>
			</p>
      <p>Enlargement of the cardiac area generates a volume overload in cardiac cavities. NIV decreasesthis volume overload, momentarily, with an increase in cardiac contractility, which occurs with the advent of transmural pressure reduction.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B30">30</xref><sup>,</sup><xref ref-type="bibr" rid="B31">31</xref> Moreover, NIV favors a pressure condition, which promotes an improvement in gas exchange by simple recruitment and stabilizes alveolar units.<xref ref-type="bibr" rid="B32">32</xref>
			</p>
      <p>Despite the positive results, patient care and monitoring are necessary during NIV application. The decrease in cardiac debit and hypoperfusion seem to challenge the use of this technique. However, the positive intrathoracic pressure offered by NIV influences the patient's hemodynamic condition, with the decrease of cardiac preload and afterload due to the reduced transmural pressure.<xref ref-type="bibr" rid="B33">33</xref>
			</p>
      <p>Tkacova et al.<xref ref-type="bibr" rid="B34">34</xref> observed, after treatment with CPAP during three months, a significant decrease in atrial natriuretic peptide (ANP) in the plasma of HF patients. Patients submitted to CPAP had a decrease in pulse pressure correlated to an increase in the ejection fraction originated by the reduction of the transmural pressure.<xref ref-type="bibr" rid="B35">35</xref>
			</p>
      <p>The presence of biases in these studies leads to conclusions that systematically tend not to be completely reliable.<xref ref-type="bibr" rid="B36">36</xref> All selected studies presented high risk of biases in regards to allocation confidentiality, which is extremely important. O'Donnell et al.<xref ref-type="bibr" rid="B12">12</xref> for instance, presented uncertain risk of masking, one of the factors that may significantly alter the study's result.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>This systematic review with meta-analysis showed that NIV is an effective method for the improvement of exercise tolerance in HF patients. However, there is a gap in literature regarding which are parameters that are the most adequate for the application of this technique, and that promote the best results in FC performance. Further research is necessary to determine a standardization regarding NIV application, so that this technique can contribute, more efficiently, to the treatment of HF patients.</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 article is part of the thesis of master submitted by Hugo Souza Bittencourt, from Universidade Federal da Bahia.</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo de Revis&#227;o</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Ventila&#231;&#227;o N&#227;o Invasiva em Pacientes com Insufici&#234;ncia Card&#237;aca: Revis&#227;o Sistem&#225;tica e Meta-An&#225;lise</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Bittencourt</surname>
            <given-names>Hugo Souza</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Reis</surname>
            <given-names>Helena Fran&#231;a Correia dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lima</surname>
            <given-names>Melissa Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gomes</surname>
            <given-names>Mansueto</given-names>
            <suffix>Neto</suffix>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff3">
        <label>1</label>
        <institution content-type="original">Programa de P&#243;s Gradua&#231;&#227;o em Medicina e Sa&#250;de, Departamento de Fisioterapia - Curso de Fisioterapia da Universidade Federal da Bahia, Bahia, BA - Brasil</institution>
      </aff>
      <aff id="aff4">
        <label>2</label>
        <institution content-type="original">Departamento de Fisioterapia - Curso de Fisioterapia da Universidade Federal da Bahia, Bahia, BA - Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Hugo Souza Bittencourt</bold>, Av. Reitor Miguel Calmon s/n - Vale do Canela. CEP 40.110-100, Salvador, Bahia - Brasil. E-mail: <email>fisiobittencourt@hotmail.com</email>; <email>moni.chiara@globo.com</email></corresp>
        <fn fn-type="conflict">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa e Obten&#231;&#227;o de dados: Bittencourt HS, Reis HFC, Gomes Neto M; An&#225;lise e interpreta&#231;&#227;o dos dados e An&#225;lise estat&#237;stica: Bittencourt HS, Gomes Neto M; Obten&#231;&#227;o de financiamento: Gomes Neto M; Reda&#231;&#227;o do manuscrito: Bittencourt HS, Reis HFC, Lima MS; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Reis HFC, Lima MS, Gomes Neto M.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesse</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <p>A ventila&#231;&#227;o n&#227;o invasiva (VNI) pode aperfei&#231;oar o desempenho card&#237;aco e respirat&#243;rio dos pacientes com insufici&#234;ncia card&#237;aca (IC).</p>
        <p>O objetivo do estudo &#233; estabelecer, por meio de revis&#227;o sistem&#225;tica e meta-an&#225;lise, a influ&#234;ncia da VNI na capacidade funcional (CF) de indiv&#237;duos com IC.</p>
        <p>Foi realizada uma revis&#227;o sistem&#225;tica com meta-an&#225;lise de estudos randomizados atrav&#233;s da pesquisa nas bases de dados Biblioteca Cochrane, SciELO, Pubmed e PEDro, utilizando-se as palavras-chave: insufici&#234;ncia card&#237;aca, ventila&#231;&#227;o n&#227;o invasiva, toler&#226;ncia ao exerc&#237;cio; e os termos livres: press&#227;o positiva em dois n&#237;veis nas vias a&#233;reas (BIPAP), press&#227;o positiva cont&#237;nua em vias a&#233;reas (CPAP), CF e seus correlatos na l&#237;ngua inglesa, com a combina&#231;&#227;o dos operadores booleanos (AND e OR). A avalia&#231;&#227;o da qualidade metodol&#243;gica se deu via escala de PEDro. Foram calculadas as m&#233;dias ponderadas e o intervalo de confian&#231;a (IC) de 95%. Meta-an&#225;lise foi realizada com software Review Manager vers&#227;o 5.3 (Colabora&#231;&#227;o Cochrane).</p>
        <p>Foram inclu&#237;dos quatro ensaios cl&#237;nicos randomizados. Estudos individuais sugerem que a VNI contribuiu para melhora da CF. VNI resultou em melhora na dist&#226;ncia do teste de caminhada de seis minutos (TC6) (68,7m 95% IC: 52,6 a 84,9) comparado ao grupo controle.</p>
        <p>Concluimos que a VNI &#233; uma interven&#231;&#227;o que promove efeitos importantes na melhora da CF de pacientes com IC. No entanto, h&#225; uma lacuna na literatura de quais s&#227;o os par&#226;metros mais adequados para aplica&#231;&#227;o dessa t&#233;cnica.</p>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Insufici&#234;ncia Card&#237;aca</kwd>
        <kwd>Ventila&#231;&#227;o n&#227;o Invasiva</kwd>
        <kwd>Toler&#226;ncia ao Exerc&#237;cio</kwd>
        <kwd>Revis&#227;o</kwd>
        <kwd>Metan&#225;lise</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A IC &#233; uma s&#237;ndrome cl&#237;nica na qual o cora&#231;&#227;o tem dificuldade de bombear sangue gerando limita&#231;&#227;o funcional com importantes altera&#231;&#245;es cardiovasculares, hemodin&#226;micas e metab&#243;licas.<xref ref-type="bibr" rid="B1">1</xref><sup>-</sup><xref ref-type="bibr" rid="B3">3</xref> Pacientes com IC t&#234;m redu&#231;&#227;o da CF, o que pode gerar limita&#231;&#227;o do desempenho nas atividades da vida di&#225;ria (AVDs) e redu&#231;&#227;o da qualidade de vida (QV).<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B6">6</xref> Essas altera&#231;&#245;es contribuem para o aumento dos sintomas e intoler&#226;ncia ao exerc&#237;cio reduzindo progressivamente a CF.<xref ref-type="bibr" rid="B7">7</xref>
				</p>
        <p>A realiza&#231;&#227;o de programas de reabilita&#231;&#227;o card&#237;aca est&#225; sendo cada vez mais recomendada para essa popula&#231;&#227;o, com o objetivo de minimizar as consequ&#234;ncias da IC e melhorar a QV do paciente. A Reabilita&#231;&#227;o Card&#237;aca &#233; definida como forma de tratamento n&#227;o farmacol&#243;gico com &#234;nfase na pr&#225;tica de exerc&#237;cio f&#237;sico.<xref ref-type="bibr" rid="B8">8</xref>
				</p>
        <p>Atualmente, alguns recursos utilizados na fisioterapia v&#234;m complementando um programa de reabilita&#231;&#227;o card&#237;aca para pacientes que inicialmente n&#227;o toleram os exerc&#237;cios. A VNI com administra&#231;&#227;o de CPAP &#233; uma das t&#233;cnicas utilizadas. A VNI pode aperfei&#231;oar o desempenho card&#237;aco e respirat&#243;rio dos pacientes com IC, uma vez que melhora a oxigena&#231;&#227;o e a mec&#226;nica pulmonar, podendo melhorar tamb&#233;m a CF.<xref ref-type="bibr" rid="B7">7</xref>
				</p>
        <p>Classicamente, a VNI tem sido utilizada em situa&#231;&#245;es de insufici&#234;ncia respirat&#243;ria e em pacientes com IC com o objetivo de reverter situa&#231;&#245;es de edema pulmonar e fal&#234;ncia respirat&#243;ria. A utiliza&#231;&#227;o da VNI e seu efeito na toler&#226;ncia ao exerc&#237;cio passaram a ser investigados recentemente, mas h&#225; controv&#233;rsia sobre sua efic&#225;cia e utiliza&#231;&#227;o na pr&#225;tica cl&#237;nica. A revis&#227;o sistem&#225;tica com meta-an&#225;lise pode resolver conflitos de estudos individuais e fornecer estimativas mais confi&#225;veis da efic&#225;cia do uso da VNI em pacientes com IC. O objetivo deste trabalho foi realizar uma revis&#227;o sistem&#225;tica com meta-an&#225;lise sobre a utiliza&#231;&#227;o da VNI na melhora da CF em pacientes com IC.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Foi realizada uma revis&#227;o sistem&#225;tica observando-se os crit&#233;rios estabelecidos pelo <italic>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</italic> (PRISMA) <italic>guideline.</italic><xref ref-type="bibr" rid="B9">9</xref>
				</p>
        <sec>
          <title>Crit&#233;rios de elegibilidade</title>
          <p>Foram inclu&#237;dos ensaios cl&#237;nicos randomizados (ECR) que testaram a utiliza&#231;&#227;o da VNI em pacientes com idade superior a 18 anos, de ambos os sexos, com IC e sem doen&#231;a pulmonar obstrutiva ou restritiva associada.</p>
          <p>As medidas de avalia&#231;&#227;o inclu&#237;das foram: toler&#226;ncia ao esfor&#231;o; dura&#231;&#227;o do exerc&#237;cio; percep&#231;&#227;o do esfor&#231;o; espirometria; lactacemia.</p>
        </sec>
        <sec>
          <title>Fonte de dados e pesquisas</title>
          <p>A pesquisa dos artigos aconteceu na base de dados PubMed, <italic>Cochrane Library</italic>, SciELO e <italic>Physiotherapy Evidence Database</italic> (PEDro). Na pesquisa, foram inclu&#237;dos artigos originais publicados em ingl&#234;s, espanhol e portugu&#234;s at&#233; agosto de 2015.</p>
          <p>A estrat&#233;gia de busca inicial foi composta por quatro palavras-chave (desenho do estudo, participantes, interven&#231;&#227;o e medida dos resultados). As palavras-chave utilizadas foram descritas a partir dos termos de busca Medical Subject Headings (MeSH) e Descritores em Ci&#234;ncias da Sa&#250;de (DeCS) nas quais foram inclu&#237;das para o desenho de estudo: ensaio cl&#237;nico randomizado e estudo controlado. O grupo de participantes utilizou palavras referentes &#224; doen&#231;a como IC, disfun&#231;&#227;o card&#237;aca ou disfun&#231;&#227;o ventricular. As palavras-chave utilizadas para interven&#231;&#227;o foram: VNI e toler&#226;ncia ao exerc&#237;cio. Os termos utilizados para medidas dos resultados foram: TC6, ergometria, ergoespirometria, espirometria.</p>
          <p>Um revisor experiente realizou a busca e a sele&#231;&#227;o inicial para identificar os t&#237;tulos e resumos dos estudos potencialmente relevantes. Cada resumo foi avaliado por dois revisores de forma independente. Se ao menos um revisor considerasse uma refer&#234;ncia eleg&#237;vel, o artigo era obtido na &#237;ntegra. De forma independente, os dois autores analisaram os artigos para selecionar os que seriam inclu&#237;dos na revis&#227;o. Em caso de discord&#226;ncia, a decis&#227;o era realizada por consenso dos autores. Foi realizado, tamb&#233;m, um rastreamento manual de cita&#231;&#245;es nos artigos selecionados.</p>
        </sec>
        <sec>
          <title>Avalia&#231;&#227;o da qualidade metodol&#243;gica dos estudos</title>
          <p>A qualidade dos estudos foi avaliada utilizando-se a escala PEDro - a mais utilizada na &#225;rea da reabilita&#231;&#227;o. Essa escala &#233; baseada na lista Delphi<xref ref-type="bibr" rid="B10">10</xref> com objetivo de mensurar a validade interna por meio da presen&#231;a ou aus&#234;ncia de crit&#233;rios metodol&#243;gicos.<xref ref-type="bibr" rid="B11">11</xref> A escala de PEDro &#233; composta pelos seguintes crit&#233;rios: 1) especifica&#231;&#227;o dos crit&#233;rios de inclus&#227;o (item n&#227;o pontuado); 2) aloca&#231;&#227;o aleat&#243;ria; 3) sigilo na aloca&#231;&#227;o; 4) similaridade dos grupos na fase inicial ou basal; 5) mascaramento dos sujeitos; 6) mascaramento do terapeuta; 7) mascaramento do avaliador; 8) medida de pelo menos um desfecho prim&#225;rio em 85% dos sujeitos alocados; 9) an&#225;lise da inten&#231;&#227;o de tratar; 10) compara&#231;&#227;o entre grupos de pelo menos um desfecho prim&#225;rio; 11) relatos de medidas de variabilidade e estimativas do par&#226;metro de pelo menos uma vari&#225;vel prim&#225;ria. Para cada crit&#233;rio definido na escala, um ponto (1) &#233; atribu&#237;do &#224; presen&#231;a de indicadores da qualidade de evid&#234;ncias apresentada e zero (0) ponto &#233; atribu&#237;do &#224; aus&#234;ncia desses indicadores.<xref ref-type="bibr" rid="B11">11</xref>
					</p>
        </sec>
        <sec>
          <title>Avalia&#231;&#227;o estat&#237;stica</title>
          <p>Meta-an&#225;lise foi realizada devido &#224; similaridade entre estudos quanto &#224; interven&#231;&#227;o utilizada, as caracter&#237;sticas dos pacientes e a vari&#225;vel dist&#226;ncia percorrida no TC6. Estimativas de efeito combinados foram expressos como a diferen&#231;a da m&#233;dia entre os grupos. A heterogeneidade estat&#237;stica entre os estudos foi avaliada usando-se o teste Q de Cochran e teste de inconsist&#234;ncia I<xref ref-type="bibr" rid="B2">2</xref>, em que valores acima de 25 e 50% foram considerados indicativos de heterogeneidade moderada e alta, respectivamente. Os c&#225;lculos foram feitos usando-se um modelo de efeito fixo, devido &#224; baixa heterogeneidade. Um valor &#945; de 0,05 foi considerado significativo. A an&#225;lise foi realizada utilizando-se o <italic>Review Manager</italic> vers&#227;o 5.3 (<italic>Cochrane Collaboration</italic>).</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>Inicialmente foi identificado um total de 37 artigos nas pesquisas nas bases de dados selecionadas, sendo 21 na PubMed, nove na SciELO e sete na Biblioteca Cochrane. Ap&#243;s leitura criteriosa, 30 artigos foram exclu&#237;dos de t&#237;tulos e/ou resumos e tr&#234;s por duplicata. Os quatro artigos restantes preencheram os crit&#233;rios de inclus&#227;o e foram selecionados, na &#237;ntegra, para a leitura (<xref ref-type="fig" rid="f3">Figura 1</xref>).</p>
        <p>
          <fig id="f3">
            <label>Figura 1</label>
            <caption>
              <title>Fluxograma do processo de sele&#231;&#227;o dos artigos.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-108-02-0161-70001-gf01-pt.jpg"/></fig>
        </p>
        <sec>
          <title>An&#225;lise da qualidade metodol&#243;gica dos estudos</title>
          <p>A an&#225;lise da qualidade metodol&#243;gica dos estudos que cumpriram o crit&#233;rio de inclus&#227;o foi realizada por dois pesquisadores de forma independente, na qual o valor de m&#233;dia 6,2 foi encontrada utilizando-se a escala de PEDro (<xref ref-type="table" rid="t4">Tabela 1</xref>).</p>
          <table-wrap id="t4">
            <label>Tabela 1</label>
            <caption>
              <title>Avalia&#231;&#227;o da qualidade dos estudos atrav&#233;s da escala PEDRo</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">O&#8217;Donnell et al.<xref ref-type="bibr" rid="B12">12</xref>
									</th>
                  <th align="center">Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref>
									</th>
                  <th align="center">Chermont et al.<xref ref-type="bibr" rid="B13">13</xref>
									</th>
                  <th align="center">Lima et al.<xref ref-type="bibr" rid="B7">7</xref>
									</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">1</td>
                  <td align="center">
									</td>
                  <td align="center">&#10003;</td>
                  <td align="center">
									</td>
                  <td align="center">&#10003;</td>
                </tr>
                <tr>
                  <td align="left">2</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                </tr>
                <tr>
                  <td align="left">3</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">&#10003;</td>
                </tr>
                <tr>
                  <td align="left">4</td>
                  <td align="center">
									</td>
                  <td align="center">&#10003;</td>
                  <td align="center">
									</td>
                  <td align="center">&#10003;</td>
                </tr>
                <tr>
                  <td align="left">5</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">6</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">7</td>
                  <td align="center">
									</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">8</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                </tr>
                <tr>
                  <td align="left">9</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">10</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                </tr>
                <tr>
                  <td align="left">11</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                  <td align="center">&#10003;</td>
                </tr>
                <tr style="border-bottom-width:thin;border-bottom-style:solid">
                  <td align="left">Total:</td>
                  <td align="center">4</td>
                  <td align="center">6</td>
                  <td align="center">5</td>
                  <td align="center">6</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
                    <bold>M&#233;dia: 6,2</bold>
                  </td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
        <sec>
          <title>Caracter&#237;sticas dos estudos</title>
          <p>Os quatro estudos avaliaram o impacto da VNI na toler&#226;ncia ao exerc&#237;cio de pacientes com IC. Os participantes de todos os estudos selecionados eram indiv&#237;duos portadores de IC.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> O per&#237;odo de publica&#231;&#245;es dos estudos se deu de 1999 a 2011, e o tamanho da popula&#231;&#227;o estudada nos artigos variou de 12<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> a 22<xref ref-type="bibr" rid="B14">14</xref> pacientes, totalizando 58 indiv&#237;duos estudados. A m&#233;dia de idade dos participantes variou entre 46<xref ref-type="bibr" rid="B7">7</xref> e 61<xref ref-type="bibr" rid="B12">12</xref> anos. Os quatro estudos foram realizados com popula&#231;&#227;o de ambos os sexos.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> Em tr&#234;s dos estudos, os participantes pertenciam &#224; classe funcional II a III segundo a NYHA<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> e um estudo variou a classe funcional de II a IV.<xref ref-type="bibr" rid="B12">12</xref>
					</p>
          <p>Tr&#234;s dos estudos utilizaram o TC6 como indicador da CF de indiv&#237;duos com IC<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> sendo que um &#250;nico estudo utilizou o teste de esfor&#231;o em cicloerg&#244;metro<xref ref-type="bibr" rid="B12">12</xref> como instrumento de avalia&#231;&#227;o.</p>
        </sec>
        <sec>
          <title>Caracter&#237;sticas do suporte ventilat&#243;rio n&#227;o invasivo</title>
          <p>Dois estudos<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> escolheram como interface para aplica&#231;&#227;o da VNI a m&#225;scara nasal, um estudo<xref ref-type="bibr" rid="B7">7</xref> utilizou a m&#225;scara facial e o outro estudo optou por utilizar a bocal.<xref ref-type="bibr" rid="B12">12</xref>
					</p>
          <p>Tr&#234;s dos estudos optaram pela CPAP<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> e um estudo utilizou CPAP e a press&#227;o suporte (PS).<xref ref-type="bibr" rid="B12">12</xref> Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref> usaram CPAP de 8 cmH<sub>2</sub>O; Chermont et al.<xref ref-type="bibr" rid="B13">13</xref> utilizaram a press&#227;o de 3 cmH<sub>2</sub>O por 10 minutos no grupo CPAP progredindo para 4 a 6 cmH<sub>2</sub>O, enquanto no grupo placebo foi fixada uma press&#227;o de 0 a 1 cmH<sub>2</sub>O; Lima et al.<xref ref-type="bibr" rid="B7">7</xref> aplicaram uma press&#227;o de 10 cmH<sub>2</sub>O, j&#225; O'Donnell et al.<xref ref-type="bibr" rid="B12">12</xref> usaram CPAP e PS com press&#227;o positiva expirat&#243;ria final (PEEP) de 4,8 cm de H<sub>2</sub>O comparando com um controle que utilizou apenas 1 cmH<sub>2</sub>O.</p>
          <p>Os quatro artigos selecionados que fizeram parte da revis&#227;o utilizaram um grupo controle e avaliaram o uso do suporte ventilat&#243;rio na CF de pacientes com IC.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> Dois artigos utilizaram CPAP em uma &#250;nica sess&#227;o antes dos exerc&#237;cios,<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> um artigo utilizou CPAP durante 14 dias,<xref ref-type="bibr" rid="B14">14</xref> e apenas um artigo utilizou os dois modos de suporte ventilat&#243;rio (CPAP e PS) no decorrer do exerc&#237;cio.<xref ref-type="bibr" rid="B12">12</xref>
					</p>
          <p>As caracter&#237;sticas dos ECRs inclu&#237;dos e da interven&#231;&#227;o est&#227;o descritas nas <xref ref-type="table" rid="t5">Tabelas 2</xref> e <xref ref-type="table" rid="t6">3</xref>.</p>
          <table-wrap id="t5">
            <label>Tabela 2</label>
            <caption>
              <title>Caracter&#237;sticas dos estudos inclu&#237;dos na revis&#227;o</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
                <col width="11%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">
									</th>
                  <th align="center">
									</th>
                  <th align="center" colspan="3" style="border-bottom-width:thin;border-bottom-style:solid">M&#233;todos de avalia&#231;&#227;o</th>
                  <th align="center" colspan="3" style="border-bottom-width:thin;border-bottom-style:solid">Resultados</th>
                </tr>
                <tr>
                  <th align="left">Estudo</th>
                  <th align="center">Participantes</th>
                  <th align="center">Avalia&#231;&#227;o</th>
                  <th align="center">Dura&#231;&#227;o do<break/> exerc&#237;cio</th>
                  <th align="center">Capacidade<break/> aer&#243;bica</th>
                  <th align="center">Dispneia</th>
                  <th align="center">Dura&#231;&#227;o do<break/> exerc&#237;cio</th>
                  <th align="center">Capacidade<break/> aer&#243;bica</th>
                  <th align="center">Dispneia</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">O&#8217;Donnell et al.<xref ref-type="bibr" rid="B12">12</xref>
									</td>
                  <td align="center">12 pacientes<break/> Homens (11)<break/> Mulheres (1)<break/> FEVE 35%<break/> CF/II/IV NYHA</td>
                  <td align="center">Dura&#231;&#227;o do exerc&#237;cio dispneia</td>
                  <td align="center">Tempo em minutos</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">Escala de BORG</td>
                  <td align="center">10,1&#177;1,5 PS p &lt; 0,01 8,7&#177;1,1 CPAP p = 0,08 7,2 &#177; 1,0 controle</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">p &gt; 0,005</td>
                </tr>
                <tr>
                  <td align="left">Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref>
									</td>
                  <td align="center">22 pacientes<break/> Homens (12)<break/> Mulheres (10)<break/> FEVE 45%<break/> CF/II/III<break/> NYHA</td>
                  <td align="center">Capacidade aer&#243;bia</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">TC6</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">&#8593;TC6 (p&lt;0,05)</td>
                  <td align="center">N&#227;o</td>
                </tr>
                <tr>
                  <td align="left">Chermont et al.<xref ref-type="bibr" rid="B13">13</xref>
									</td>
                  <td align="center">12 pacientes<break/> Homens (8)<break/> Mulheres (4)<break/> FEVE 45%<break/> CF/II/III<break/> NYHA</td>
                  <td align="center">Capacidade aer&#243;bia</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">TC6</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">&#8593;TC6 (p&lt;0,05)</td>
                  <td align="center">N&#227;o</td>
                </tr>
                <tr>
                  <td align="left">Lima et al.<xref ref-type="bibr" rid="B7">7</xref>
									</td>
                  <td align="center">12 pacientes<break/> Homens (8)<break/> Mulheres (4)<break/> FEVE 35%<break/> CFII/III<break/> NYHA</td>
                  <td align="center">Capacidade aer&#243;bia</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">TC6</td>
                  <td align="center">Escala de BORG</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">&#8593;TC6 (p&lt;0,05)</td>
                  <td align="center">p: 0,009</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN3">
                <p>TC6: teste de caminhada de seis minutos; OS: press&#227;o suporte; CPAP: press&#227;o positiva cont&#237;nua em vias a&#233;reas; NYHA: New York Heart Association.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t6">
            <label>Tabela 3</label>
            <caption>
              <title>Caracter&#237;sticas das interven&#231;&#245;es dos estudos inclu&#237;dos na revis&#227;o</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="14%"/>
                <col width="14%"/>
                <col width="14%"/>
                <col width="14%"/>
                <col width="14%"/>
                <col width="14%"/>
                <col width="14%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Estudo</th>
                  <th align="center">Tempo de interven&#231;&#227;o</th>
                  <th align="center">Tempo de Aplica&#231;&#227;o</th>
                  <th align="center">Exerc&#237;cios respirat&#243;rios</th>
                  <th align="center">PEEP</th>
                  <th align="center">SVNI (CPAP) antes do exerc&#237;cio</th>
                  <th align="center">SVNI (CPAP/PS) durante o exerc&#237;cio</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">O&#8217;Donnell et al.<xref ref-type="bibr" rid="B12">12</xref>
									</td>
                  <td align="center">Sess&#227;o (1)</td>
                  <td align="center">Durante o exerc&#237;cio</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">PS/CPAP 4,8 cmH<sub>2</sub>O Controle 1 cmH<sub>2</sub>O</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">Sim</td>
                </tr>
                <tr>
                  <td align="left">Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref>
									</td>
                  <td align="center">Sess&#227;o (14)</td>
                  <td align="center">30 minutos</td>
                  <td align="center">3 x 10 repeti&#231;&#245;es EA/IP/SI</td>
                  <td align="center">CPAP 8 cmH<sub>2</sub>O</td>
                  <td align="center">Sim</td>
                  <td align="center">N&#227;o</td>
                </tr>
                <tr>
                  <td align="left">Chermont et al.<xref ref-type="bibr" rid="B13">13</xref>
									</td>
                  <td align="center">Sess&#227;o (1)</td>
                  <td align="center">30 minutos</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">CPAP 4-6 cmH<sub>2</sub>O Controle 0-1 cmH<sub>2</sub>O</td>
                  <td align="center">Sim</td>
                  <td align="center">N&#227;o</td>
                </tr>
                <tr>
                  <td align="left">Lima et al.<xref ref-type="bibr" rid="B7">7</xref>
									</td>
                  <td align="center">Sess&#227;o (1)</td>
                  <td align="center">30 minutos</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">CPAP 10 cmH<sub>2</sub>O</td>
                  <td align="center">Sim</td>
                  <td align="center">N&#227;o</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN4">
                <p>SVNI: suporte ventilat&#243;rio n&#227;o invasivo; PEEP: press&#227;o positiva expirat&#243;ria final; PS: press&#227;o suporte; CPAP: press&#227;o positiva cont&#237;nua em vias a&#233;reas; EA: expira&#231;&#227;o abreviada; IP: inspira&#231;&#227;o profunda; SI : solu&#231;os inspirat&#243;rios.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Efeitos da VNI na CF e na fun&#231;&#227;o pulmonar</title>
          <p>Todos os trabalhos avaliaram o impacto da VNI na CF de pacientes com IC, sendo que todos os estudos encontraram, ap&#243;s o uso da VNI,<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> um incremento da toler&#226;ncia ao exerc&#237;cio.</p>
          <p>O estudo de Chermont et al.<xref ref-type="bibr" rid="B13">13</xref> observou um aumento na toler&#226;ncia ao exerc&#237;cio f&#237;sico com maior dist&#226;ncia percorrida no TC6 em pacientes com IC quando submetidos a 30 minutos de CPAP a 6 cmH<sub>2</sub>O antes do teste.</p>
          <p>Esses resultados confirmam os achados de Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref> em seu estudo cl&#237;nico cego, randomizado, prospectivo em que 22 pacientes (12 homens e 10 mulheres) foram divididos aleatoriamente para realizar 30 minutos de tratamento com CPAP, exerc&#237;cios respirat&#243;rios e exerc&#237;cios de caminhada (grupo CPAP) ou exerc&#237;cio respirat&#243;rio e exerc&#237;cios de caminhada (grupo controle) por 14 dias. Por meio da avalia&#231;&#227;o do TC6 realizada um dia antes do tratamento (dia 0) e no 4&#186;, 9&#186; e 14&#186; dias de tratamento, os autores observaram que os pacientes do grupo CPAP tiveram uma melhora progressiva na dist&#226;ncia percorrida no TC6 atingindo cerca de 28% dos valores de base ao final do tratamento, mas sem altera&#231;&#245;es significativas no grupo de controle. Apesar de ter encontrado melhora na dist&#226;ncia percorrida, os autores n&#227;o identificaram ao certo, se esse desfecho positivo ocorreu devido &#224; melhora da fun&#231;&#227;o pulmonar ou por altera&#231;&#245;es hemodin&#226;micas.</p>
          <p>No estudo de O'Donnell et al.,<xref ref-type="bibr" rid="B12">12</xref> o tempo total de exerc&#237;cio aumentou significativamente durante o exerc&#237;cio com PS (p = 0,004), mas apenas modestamente com o uso do CPAP (p = 0,079) em compara&#231;&#227;o ao controle.</p>
          <p>Conforme Lima et al.,<xref ref-type="bibr" rid="B7">7</xref> houve melhora significativa na dist&#226;ncia percorrida atrav&#233;s do TC6 ap&#243;s a utiliza&#231;&#227;o do CPAP em apenas uma sess&#227;o de aplica&#231;&#227;o com o tempo de 30 minutos.</p>
          <p>Dos quatro estudos encontrados, tr&#234;s avaliaram a fun&#231;&#227;o pulmonar.<xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> No estudo de O'Donnell et al.,<xref ref-type="bibr" rid="B12">12</xref> os par&#226;metros basais da fun&#231;&#227;o pulmonar estavam dentro dos limites normais, exceto por uma discreta redu&#231;&#227;o da capacidade vital for&#231;ada (CVF) e uma redu&#231;&#227;o do volume de reserva expirat&#243;rio (VRE), contudo, durante o exerc&#237;cio, os pacientes apresentaram aumentos significativos no volume pulmonar expirat&#243;rio final. O estudo de Chermont et al.,<xref ref-type="bibr" rid="B13">13</xref> embora cite que os pacientes foram submetidos a teste de fun&#231;&#227;o pulmonar, n&#227;o descreveu os resultados. Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref> observaram um aumento na CVF dos pacientes tratados com CPAP, atingindo um valor m&#225;ximo de 16% do valor basal no nono dia de tratamento em compara&#231;&#227;o ao grupo controle. Da mesma forma, os valores de VEF1 aumentaram progressivamente atingindo um valor m&#225;ximo de 14% no 14&#176; dia de tratamento.</p>
        </sec>
        <sec>
          <title>Efeitos da VNI na concentra&#231;&#227;o de lactato</title>
          <p>Apenas o estudo de Lima et al.<xref ref-type="bibr" rid="B7">7</xref> avaliou a concentra&#231;&#227;o de lactato nos pacientes com IC ap&#243;s o TC6 com aplica&#231;&#227;o pr&#233;via do CPAP. Os pacientes que foram submetidos &#224; VNI obtiveram, comparado ao grupo controle, uma menor concentra&#231;&#227;o de lactato no final do teste.</p>
        </sec>
        <sec>
          <title>Efeitos da VNI na dura&#231;&#227;o do exerc&#237;cio</title>
          <p>Os pacientes que utilizaram CPAP antes do TC6 caminharam uma dist&#226;ncia superior em metros comparado ao grupo controle.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> O uso do CPAP, somado aos exerc&#237;cios respirat&#243;rios e de caminhada, induziu um aumento significativo tamb&#233;m na dist&#226;ncia percorrida no TC6 comparado a um grupo controle que realizou somente exerc&#237;cios respirat&#243;rios e de caminhada.<xref ref-type="bibr" rid="B14">14</xref> A utiliza&#231;&#227;o da PS associada ao exerc&#237;cio no ciclo erg&#244;metro, comparado ao CPAP e ao placebo, foi mais eficaz na avalia&#231;&#227;o do tempo de perman&#234;ncia no exerc&#237;cio no ciclo erg&#244;metro e na avalia&#231;&#227;o da percep&#231;&#227;o subjetiva de esfor&#231;o pela escala de BORG.<xref ref-type="bibr" rid="B12">12</xref> Houve tamb&#233;m diferen&#231;as na utiliza&#231;&#227;o do CPAP comparado ao placebo. O modo CPAP aumentou o tempo de dura&#231;&#227;o do exerc&#237;cio, com um menor &#237;ndice de esfor&#231;o pela de BORG.</p>
          <p>Tr&#234;s estudos avaliaram o TC6. Desses, dois avaliaram o efeito de uma sess&#227;o de VNI, enquanto o terceiro avaliou o efeito de 14 sess&#245;es de VNI. A meta-an&#225;lise dos tr&#234;s estudos mostrou (<xref ref-type="fig" rid="f4">Figura 2</xref>) uma diferen&#231;a significativa na dist&#226;ncia do TC6 (68,7 m 95% IC: 52,6 to 84,9; N=58) para participantes do grupo VNI comparado ao grupo controle. Quando combinados somente os dois estudos que utilizaram a VNI em somente uma sess&#227;o, a meta-an&#225;lise mostrou (<xref ref-type="fig" rid="f4">Figura 2</xref>) uma diferen&#231;a significativa na dist&#226;ncia do TC6 (65,2 m 95% IC: 38,8 a 91,7; N=36) para participantes do grupo VNI comparado ao grupo controle.</p>
          <p>
            <fig id="f4">
              <label>Figura 2</label>
              <caption>
                <title>CPAP versus Controle: TC6. Review Manager (RevMan). Version 5.2 The Cochrane Collaboration, 2013.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-108-02-0161-70001-gf02-pt.jpg"/></fig>
          </p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Essa revis&#227;o sistem&#225;tica teve como objetivo identificar as evid&#234;ncias cient&#237;ficas sobre o impacto da VNI na CF de pacientes com IC. Os resultados indicam uma melhora significativa na toler&#226;ncia ao exerc&#237;cio nos pacientes com IC ap&#243;s interven&#231;&#227;o com VNI, em compara&#231;&#227;o ao grupo controle.</p>
        <p>A VNI tem sido utilizada como importante ferramenta no tratamento de pacientes com IC para melhora da efici&#234;ncia ventilat&#243;ria durante o exerc&#237;cio.<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref> Esse fato pode estar associado a fatores como a melhora da oxigena&#231;&#227;o, atenua&#231;&#227;o do metaborreflexo, melhora da rela&#231;&#227;o ventila&#231;&#227;o/perfus&#227;o (V/Q), desobstru&#231;&#227;o da via a&#233;rea e consequente diminui&#231;&#227;o do trabalho ventilat&#243;rio e fadiga.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref>
				</p>
        <p>Os pacientes com IC apresentam toler&#226;ncia diminu&#237;da aos esfor&#231;os associada a um aumento da dispneia e fadiga muscular.<xref ref-type="bibr" rid="B18">18</xref> A utiliza&#231;&#227;o pr&#233;via do CPAP aumentou a dist&#226;ncia percorrida dos pacientes no TC6 e prolongou o tempo de dura&#231;&#227;o no exerc&#237;cio no ciclo erg&#244;metro, quando utilizado simultaneamente ao exerc&#237;cio.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref>
				</p>
        <p>A avalia&#231;&#227;o da CF dos pacientes &#233; de extrema relev&#226;ncia, desse modo, o teste de esfor&#231;o cardiopulmonar (TCP) &#233; o padr&#227;o de refer&#234;ncia e o mais espec&#237;fico para avalia&#231;&#227;o ventilat&#243;ria no exerc&#237;cio f&#237;sico, pois al&#233;m de mensurar a CF que est&#225; diretamente ligada &#224; gravidade da IC, tem o poder de avaliar o consumo de oxig&#234;nio (VO<sub>2</sub>) do paciente. Por&#233;m, pelo fato de o teste cardiopulmonar ser complexo e possuir alto custo, o TC6 revela-se eficaz ferramenta na avalia&#231;&#227;o da CF.<xref ref-type="bibr" rid="B19">19</xref>
				</p>
        <p>O TC6 correlaciona-se &#224;s atividades f&#237;sicas di&#225;rias, portanto &#233; um teste subm&#225;ximo de simples execu&#231;&#227;o e baixo custo. O TC6 &#233; uma excelente op&#231;&#227;o capaz de avaliar a CF, sendo tamb&#233;m um preditor de mortalidade nessa popula&#231;&#227;o.<xref ref-type="bibr" rid="B17">17</xref><sup>-</sup><xref ref-type="bibr" rid="B19">19</xref> Al&#233;m disso, estudos reportam que a dist&#226;ncia percorrida no teste est&#225; associada &#224; classifica&#231;&#227;o funcional da <italic>NYHA.</italic><xref ref-type="bibr" rid="B20">20</xref><sup>-</sup><xref ref-type="bibr" rid="B24">24</xref>
				</p>
        <p>O TC6 foi utilizado em tr&#234;s estudos para avaliar a dist&#226;ncia percorrida pelos pacientes.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref>. Lima et al.<xref ref-type="bibr" rid="B7">7</xref> encontraram diferen&#231;as significativas na dist&#226;ncia percorrida no TC6 em pacientes submetidos &#224; VNI com o CPAP, comparado ao grupo controle. Os resultados do estudo corroboram o trabalhado realizado por Chermont et al.,<xref ref-type="bibr" rid="B13">13</xref> em que VNI promoveu aumento da dist&#226;ncia percorrida (VNI: 507 m; placebo: 446 m; p = 0,001) pelos pacientes com aumento da toler&#226;ncia ao exerc&#237;cio.</p>
        <p>A administra&#231;&#227;o pr&#233;via do CPAP na IC diminui o desconforto respirat&#243;rio nos pacientes gerando um menor trabalho card&#237;aco durante o exerc&#237;cio.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref> Quantidades menores de lactato tamb&#233;m foram atribu&#237;das ao uso do CPAP em pacientes ap&#243;s TC6.<xref ref-type="bibr" rid="B7">7</xref>
				</p>
        <p>A VNI tem sido um importante instrumento utilizado para aperfei&#231;oar o tratamento de pacientes com melhora significativa no desempenho das atividades f&#237;sicas.<xref ref-type="bibr" rid="B26">26</xref> A fun&#231;&#227;o pulmonar pode estar diminu&#237;da na IC tendo uma rela&#231;&#227;o direta com a diminui&#231;&#227;o da CF e do desempenho nas AVDs.<xref ref-type="bibr" rid="B27">27</xref><sup>,</sup><xref ref-type="bibr" rid="B28">28</xref> Wittmer et al.,<xref ref-type="bibr" rid="B14">14</xref> demostraram que o tratamento com CPAP aumentou progressivamente a CVF e VEF1 em pacientes com IC quando comparados ao grupo controle. Essa melhora pode ter ocorrido em fun&#231;&#227;o do aumento da capacidade residual funcional e da abertura dos alv&#233;olos colapsados.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref>
				</p>
        <p>No estudo de Wittmer et al.<xref ref-type="bibr" rid="B14">14</xref> foi observada uma implica&#231;&#227;o cl&#237;nica em rela&#231;&#227;o &#224; CVF como componente de desfecho associada &#224; CF ap&#243;s repercuss&#227;o da aplica&#231;&#227;o da VNI. O grupo tratado com CPAP mostrou aumento progressivo da CVF atingindo um m&#225;ximo de 16% do valor basal no nono dia de tratamento, sem melhora adicional no 14&#186; dia de tratamento. Os valores de VEF1 aumentaram progressivamente e atingiram um m&#225;ximo de 14% no 14&#186; dia de tratamento com CPAP, sem altera&#231;&#227;o significativa no grupo controle. Os autores conclu&#237;ram que o tratamento com CPAP, por duas semanas, aumentou a fun&#231;&#227;o pulmonar de pacientes com IC melhorando, consequentemente, a toler&#226;ncia &#224;s atividades.</p>
        <p>O aumento do trabalho respirat&#243;rio na IC est&#225; associado a uma menor perfus&#227;o do diafragma. Por causa desse evento, pacientes descompensados pela doen&#231;a evoluem com fadiga muscular em membros inferiores ocasionada por um aumento da resist&#234;ncia vascular perif&#233;rica.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref> A obten&#231;&#227;o de uma menor resist&#234;ncia &#224; passagem de ar nas vias a&#233;reas com a administra&#231;&#227;o da press&#227;o positiva,<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref> e a redu&#231;&#227;o da sensa&#231;&#227;o de desconforto respirat&#243;rio ou fadiga em membros inferiores<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>-</sup><xref ref-type="bibr" rid="B14">14</xref> s&#227;o fatores que tamb&#233;m podem explicar a melhora da CF com o uso da VNI associado ao exerc&#237;cio.</p>
        <p>Pacientes que utilizaram o suporte ventilt&#243;rio n&#227;o-invasivo (SVNI) aumentaram a CF quando usaram uma PEEP superior a 4 cmH<sub>2</sub>O. Estudos que fizeram a compara&#231;&#227;o do uso da PEEP de um menor valor ou modo placebo demonstraram sua inefic&#225;cia quando equiparados a uma PEEP de maior valor.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B29">29</xref>
				</p>
        <p>O aumento da &#225;rea card&#237;aca gera uma sobrecarga de volume nas cavidades card&#237;acas. A VNI diminui, momentaneamente, essa sobrecarga de volume com um aumento da contratilidade card&#237;aca, que acontece com o advento da diminui&#231;&#227;o da press&#227;o transmural.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B30">30</xref><sup>,</sup><xref ref-type="bibr" rid="B31">31</xref> Al&#233;m disso, a VNI favorece a uma condi&#231;&#227;o press&#243;rica, que promove uma melhora na troca gasosa por simples recrutamento e estabiliza&#231;&#227;o das unidades alveolares.<xref ref-type="bibr" rid="B32">32</xref>
				</p>
        <p>Apesar dos resultados positivos, &#233; necess&#225;rio cuidado e monitoramento do paciente durante a aplica&#231;&#227;o da VNI. A diminui&#231;&#227;o do d&#233;bito card&#237;aco e a hipoperfus&#227;o parecem ser complicadores para a utiliza&#231;&#227;o da t&#233;cnica. Por&#233;m, a press&#227;o positiva intrator&#225;cica ofertada pela VNI influencia na condi&#231;&#227;o hemodin&#226;mica do paciente, com a diminui&#231;&#227;o da pr&#233;-carga e p&#243;s-carga card&#237;aca em consequ&#234;ncia da diminui&#231;&#227;o da press&#227;o transmural.<xref ref-type="bibr" rid="B33">33</xref>
				</p>
        <p>Tkacova et al.<xref ref-type="bibr" rid="B34">34</xref> observaram, ap&#243;s o tratamento com CPAP durante tr&#234;s meses, uma diminui&#231;&#227;o significativa do pept&#237;deo natriur&#233;tico atrial (ANP) no plasma em pacientes com IC. Pacientes submetidos ao CPAP obtiveram diminui&#231;&#227;o da press&#227;o de pulso correlacionado h&#225; um aumento da fra&#231;&#227;o de eje&#231;&#227;o originado pela diminui&#231;&#227;o da press&#227;o transmural.<xref ref-type="bibr" rid="B35">35</xref>
				</p>
        <p>A presen&#231;a de vieses nesses estudos induz a conclus&#245;es que sistematicamente tendem a n&#227;o ser totalmente fidedignas.<xref ref-type="bibr" rid="B36">36</xref> Todos os estudos selecionados apresentaram alto risco de vi&#233;s no quesito sigilo de aloca&#231;&#227;o, sendo de extrema import&#226;ncia o sigilo da lista de aloca&#231;&#227;o. O'Donnell et al.,<xref ref-type="bibr" rid="B12">12</xref> por exemplo, apresentaram risco incerto de mascaramento, um dos fatores que podem alterar de maneira significativa o resultado do estudo.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Essa revis&#227;o sistem&#225;tica com meta-an&#225;lise mostrou que a VNI &#233; um m&#233;todo eficaz para a melhora na toler&#226;ncia ao exerc&#237;cio de pacientes do IC. No entanto, h&#225; uma lacuna na literatura sobre quais os par&#226;metros que s&#227;o mais adequados para a aplica&#231;&#227;o dessa t&#233;cnica, e que promovem melhor resultado no desempenho da CF. Pesquisas futuras se tornam necess&#225;rias para determinar uma padroniza&#231;&#227;o quanto &#224; aplica&#231;&#227;o da VNI, de forma que essa t&#233;cnica contribua, de maneira mais eficiente, com o tratamento de pacientes com IC.</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>Este artigo &#233; parte de Disserta&#231;&#227;o de Mestrado de Hugo Souza Bittencourt pela Universidade Federal da Bahia.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
