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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="review-article" dtd-version="1.1" specific-use="sps-1.7" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">bPTk9YtnnSZ9XyDNb4L6TnJ</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2018000200188</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2018005002105</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20180017</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>High-Intensity Interval Training in Heart Transplant Recipients: A Systematic Review with Meta-Analysis</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Perrier-Melo</surname>
            <given-names>Raphael Jos&#233;</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Figueira</surname>
            <given-names>Fernando Augusto Marinho dos Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Guimar&#227;es</surname>
            <given-names>Guilherme Veiga</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Manoel da Cunha</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade de Pernambuco</institution>
        <addr-line>
          <named-content content-type="city">Recife</named-content>
          <named-content content-type="state">PE</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade de Pernambuco (UPE), Recife, PE - Brazil</institution>
        <institution content-type="normalized">Universidade de Pernambuco</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Instituto de Medicina Integral Professor Fernando Figueira</institution>
        <addr-line>
          <named-content content-type="city">Recife</named-content>
          <named-content content-type="state">PE</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto de Medicina Integral Professor Fernando Figueira, Recife, PE - Brazil</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade de S&#227;o Paulo, S&#227;o Paulo, SP - Brazil</institution>
        <institution content-type="normalized">Universidade de S&#227;o Paulo</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Universidade de Pernambuco</institution>
        <addr-line>
          <named-content content-type="city">Recife</named-content>
          <named-content content-type="state">PE</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade de Pernambuco (UPE), Recife, PE - Brazil</institution>
        <institution content-type="normalized">Universidade de Pernambuco</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Raphael Jos&#233; Perrier-Melo,</bold> Escola Superior de Educa&#231;&#227;o F&#237;sica Rua Arn&#243;bio Marques, 310, Recife, PE - Brazil. E-mail: <email>perrierprof@gmail.com</email>, <email>rperrier2@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research and Analysis and interpretation of the data: Perrier-Melo RJ, Costa MC; Acquisition of data, Statistical analysis and Obtaining financing: Perrier-Melo RJ; Writing of the manuscript and Critical revision of the manuscript for intellectual content: Perrier-Melo RJ, Figueira FAMS, Guimar&#227;es GV, Costa MC.</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>19</day>
        <month>02</month>
        <year>2018</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>2</month>
        <year>2018</year>
      </pub-date>
      <volume>110</volume>
      <issue>2</issue>
      <fpage>188</fpage>
      <lpage>194</lpage>
      <history>
        <date date-type="received">
          <day>29</day>
          <month>05</month>
          <year>2017</year>
        </date>
        <date date-type="rev-recd">
          <day>11</day>
          <month>08</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>14</day>
          <month>09</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <p>Heart transplantation (HTx) is considered an efficient and gold-standard procedure for patients with end-stage heart failure. After surgery, patients have lower aerobic power (VO<sub>2</sub>max) and compensatory hemodynamic responses. The aim of the present study was to assess through a systematic review with meta-analysis whether high-intensity interval training (HIIT) can provide benefits for those parameters. This is a systematic review with meta-analysis, which searched the databases and data portals PubMed, Web of Science, Scopus, Science Direct and Wiley until December 2016 (pairs). The following terms and descriptors were used: &#8220;<italic>heart recipient</italic>&#8221; OR &#8220;<italic>heart transplant recipient</italic>&#8221; OR &#8221;<italic>heart transplant</italic>&#8221; OR &#8220;<italic>cardiac transplant</italic>&#8221; OR &#8220;<italic>heart graft</italic>&#8221;. Descriptors via DeCS and <italic>Mesh</italic> were: &#8220;<italic>heart transplantation</italic>&#8217;&#8217; OR &#8220;<italic>cardiac transplantation</italic>&#8221;. The words used in combination (AND) were: &#8220;<italic>exercise training</italic>&#8221; OR &#8220;<italic>interval training</italic>&#8221; OR &#8220;<italic>high intensity interval training</italic>&#8221; OR &#8220;<italic>high intensity training</italic>&#8221; OR &#8220;<italic>anaerobic training</italic>&#8221; OR &#8220;<italic>intermittent training</italic>&#8221; OR &#8220;<italic>sprint training</italic>&#8221;. The initial search identified 1064 studies. Then, only those studies assessing the influence of HIIT on the post-HTx period were added, resulting in three studies analyzed. The significance level adopted was 0.05. Heart transplant recipients showed significant improvement in VO<sub>2</sub>peak, heart rate and peak blood pressure in 8 to 12 weeks of intervention.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Exercise</kwd>
        <kwd>Heart Failure/physiopathology</kwd>
        <kwd>Life Style</kwd>
        <kwd>Cardiac Rehabilitation</kwd>
        <kwd>Meta-Analysis as Topic</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Heart transplant (HTx) is considered the gold-standard treatment for patients with heart failure refractory to clinical therapy and/or intervention procedure.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref> The bicaval technique is currently used in surgical centers, consisting in cardiac denervation via complete dissection of the right atrial appendage and interauricular septum, saving a small portion of the left atrial appendage containing the pulmonary veins.<xref ref-type="bibr" rid="B3">3</xref> The major advantage of that technique over the others is atrial geometry preservation, lower transpulmonary gradient and lower incidence of post-surgical tricuspid regurgitation.<xref ref-type="bibr" rid="B4">4</xref>
			</p>
      <p>Cardiac denervation causes cardiorespiratory (maximum oxygen uptake - VO<sub>2</sub>max) and hemodynamic (heart rate - HR, cardiac output - CO and blood pressure - BP) controls to depend initially on the Frank-Starling mechanism (the law states that preload depends on venous return) and, later, on the concentrations of circulating catecholamines and ejection fraction, because of the lack of sympathetic and parasympathetic stimulation and baroreflex.<xref ref-type="bibr" rid="B5">5</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref> Therefore, transplant recipients have a lower VO<sub>2</sub>max (70-80% of the value predicted for age as compared to healthy individuals),<xref ref-type="bibr" rid="B8">8</xref> high levels of HR, BP and vascular resistance at rest. However, physical exercise causes depressed increase in HR and BP, accompanied by an increase in vascular resistance.<xref ref-type="bibr" rid="B9">9</xref> This behavior is similar in conditions of submaximal and close-to-peak efforts, causing lower peak HR (HRpeak) and peak BP (BPpeak), with good reproducibility for VO<sub>2</sub>peak. In addition, the post-exercise recovery is slow compared to that of healthy individuals of the same age group.<xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref>
			</p>
      <p>The physiological changes previously mentioned and the immunosuppressive therapy cause cardiorespiratory and hemodynamic damage over time, and transplant recipients often develop diseases, such as systemic arterial hypertension (95%), hyperlipidemia (81%), vasculopathy (50%), kidney failure (33%) and type 2 diabetes mellitus (32%).<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> Thus, cardiac rehabilitation programs have been recommended since the first guidelines of the American Heart Association and American College of Sports Medicine. The major objective of such programs is to re-establish the patients&#8217; daily activities and to change their lifestyle, by adding activities that improve their physical, psychological and social conditions. Those activities should be structurally and continuously performed, focussing on developing the patient&#8217;s major deficient variables.<xref ref-type="bibr" rid="B14">14</xref> The current guideline recommends that cardiac rehabilitation be composed partially of physical training, consisting of three to five sessions of continuous exercise (walking, jogging, cycling) per week, at mild to moderate intensity, for at least 30 minutes daily.<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref> The sessions should begin and end with short warm-up and cool-down periods (5-10 minutes) at low intensity, respectively. Post-HTx physical exercise is safe and effective to promote significant improvement in cardiorespiratory, metabolic, hemodynamic, endothelial and morphological variables.<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref>
			</p>
      <p>However, studies of systematic review with meta-analysis conducted in patients with coronary artery disease,<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref> type 2 diabetes mellitus<xref ref-type="bibr" rid="B18">18</xref> and metabolic syndrome<xref ref-type="bibr" rid="B19">19</xref> have shown that, in contrast to moderate-intensity continuous training (MICT), high-intensity interval training (HIIT) enables patients to reach similar and/or superior benefits regarding the variables decompensated by those diseases.<xref ref-type="bibr" rid="B20">20</xref> The HIIT is characterized by sets of short- or long-lasting exertion periods (30s - 4min) at high intensity (&gt; 85% VO<sub>2</sub>max), followed by short- or long-lasting recovery periods (30s - 4 min).<xref ref-type="bibr" rid="B21">21</xref>
			</p>
      <p>Although some studies have shown greater progress with HIIT practice as compared to MICT, HIIT is still cautiously prescribed for individuals diagnosed with cardiovascular and metabolic diseases or those who underwent an organ transplantation. In addition, little is known about the dose-response ratio of the improvement in cardiorespiratory, endothelial and hemodynamic parameters caused by HIIT in HTx recipients. Thus, this study was aimed at assessing by use of a systematic review with meta-analysis whether HIIT can benefit those parameters.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>A systematic review was conducted following the recommendations and meeting the criteria determined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline (PRISMA).</p>
      <sec>
        <title>Search strategy</title>
        <p>The search for articles in English was conduct in the PubMed, Web of Science, Scopus, Science Direct e Wiley databases up to December 2016. The terms and descriptors used in the searching process were selected based on the keywords available in previous studies and via DeCS and Mesh, respectively (<xref ref-type="table" rid="t1">Table 1</xref>). The terms identified in the literature were: &#8220;<italic>heart recipient</italic>&#8221; OR &#8220;<italic>heart transplant recipient</italic>&#8221; OR &#8220;<italic>heart</italic>
					<italic>transplant</italic>&#8221; OR &#8220;<italic>cardiac transplant</italic>&#8221; OR &#8220;<italic>heart graft</italic>&#8221;. The descriptors of DeCS and Mesh were: &#8220;<italic>heart transplantation</italic>&#8217;&#8217; OR &#8220;<italic>cardiac transplantation</italic>&#8221;. The words used in combination (AND) were &#8220;<italic>exercise training</italic>&#8221; OR &#8220;<italic>interval training</italic>&#8221; OR &#8220;<italic>high intensity interval training</italic>&#8221; OR &#8220;<italic>high intensity training</italic>&#8221; OR &#8220;<italic>anaerobic training</italic>&#8221; OR &#8220;<italic>intermittent training</italic>&#8221; OR &#8220;<italic>sprint training</italic>&#8221;. Data extraction and all processes of search, selection and assessment of articles were performed in pairs.</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Strategy of the bibliographic search in data bases and portals.</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="50%"/>
              <col width="50%"/>
            </colgroup>
            <tbody>
              <tr>
                <td align="center">#1 "<italic>heart recipient</italic>"[tiab], OR "<italic>heart transplant recipient</italic>"[tiab], OR "<italic>heart transplant</italic>" [tiab], OR "<italic>cardiac transplant</italic>" [tiab], OR "<italic>heart graft</italic>" [tiab], OR"<italic>heart transplantation</italic>''[Mesh], OR "<italic>cardiac transplantation</italic>" [Mesh]</td>
                <td align="center">#2 "<italic>exercise training</italic>" [tiab], OR "<italic>interval training</italic>" [tiab], OR "<italic>high intensity interval training</italic>" [tiab], OR "<italic>high intensity training</italic>" [tiab], OR "<italic>anaerobic training</italic>" [tiab], OR "<italic>intermittent training</italic>" [tiab], OR "<italic>sprint training</italic>" [tiab]</td>
              </tr>
              <tr>
                <td align="center" colspan="2">#1 AND #2</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>Mesh: Medical Subject Headings</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Selection criteria</title>
        <p>The inclusion criteria were as follows: a) randomized studies assessing VO<sub>2</sub>peak (based on a maximum incremental test) and/or HRpeak as primary outcome; b) sample comprised exclusively of HTx recipients; c) studies assessing the HIIT effect; and d) studies with an intervention period longer than 4 weeks.</p>
        <p>The exclusion criteria were as follows: a) studies without a control group; b) studies with acute analysis; and c) case studies.</p>
      </sec>
      <sec>
        <title>Identification and selection of studies</title>
        <p>Initially the references were reviewed based on the titles and abstracts. Then, the relevant articles according to the selection criteria were fully read and assessed regarding their methodological quality by use of the Testex scale.<xref ref-type="bibr" rid="B22">22</xref>
				</p>
      </sec>
      <sec>
        <title>Data analysis</title>
        <p>The variables analyzed (VO<sub>2</sub>peak and HRpeak) were classified as continuous, and data were presented as mean and standard deviation. Data were combined to obtain the size of the general effect, 95% confidence interval (CI) and significance level, using the Review Manager (RevMan) software, version 5.3, Copenhagen: The Nordic Cochrane Centre. The HIIT group was compared with the control group (post-entrance) by use of weighted mean difference (WMD). For each result, heterogeneity (I<xref ref-type="bibr" rid="B2">2</xref>) was calculated, adopting the fixed effects model. The significance level adopted was p &lt; 0.05.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p><xref ref-type="fig" rid="f1">Figure 1</xref> shows the flowchart of the search and selection process of the articles included in this review.</p>
      <p>
        <fig id="f1">
          <label>Figure 1</label>
          <caption>
            <title>Flowchart of the search and selection process of the articles included in this review.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-110-02-0188-80017-gf01.jpg"/></fig>
      </p>
      <p>In the initial electronic search, 1064 potentially relevant studies were identified. After reading their titles, 994 articles were ruled out because they did not have a primary outcome related to the objective of the present review. Then, after reading the abstracts of the remaining studies, 14 were excluded because they did not meet the selection criteria of this study. Three articles with a mean score regarding methodological quality of 10 points, according to the Testex scale, were included in the final analysis.</p>
      <p>Major information regarding sample characteristics, methodology, qualitative analysis and results from the studies on HTx recipients are shown in chronological order in <xref ref-type="table" rid="t2">Tables 2</xref> and <xref ref-type="table" rid="t3">3</xref>. A total of 118 patients (90 men and 28 women) who had undergone HTx 5.3 &#177; 3.7 years before were included in the analysis of this systematic review, 60 in the HIIT group (49.3 &#177; 12.7 years) and 58 in the control group (53 &#177; 14.3 years), maintaining their usual activities. The HIIT sessions were conducted on cycle ergometers<xref ref-type="bibr" rid="B23">23</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref> and treadmills,<xref ref-type="bibr" rid="B25">25</xref> reaching an intensity of 80-100% of VO<sub>2</sub>peak or 85-95% of HRmax. Such training sessions were performed three to five times per week for 8 and 12 weeks.</p>
      <table-wrap id="t2">
        <label>Table 2</label>
        <caption>
          <title>Characteristics of the sample, methodological quality and major results of the studies assessing the effect of high-intensity interval training (HIIT) on heart transplant (HTx) recipients.</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
            <col width="4%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left" rowspan="2">Study</th>
              <th align="left" colspan="2">GROUPS</th>
              <th align="left" rowspan="2">HIIT protocol</th>
              <th align="left" rowspan="2">Duration<break/>(weeks)</th>
              <th align="left" rowspan="2">Major results</th>
              <th align="left" colspan="15" style="border-bottom-width:thin;border-bottom-style:solid">Testex</th>
            </tr>
            <tr>
              <th align="left">
                <bold>HIIT</bold>
              </th>
              <th align="left">
                <bold>CONTROL</bold>
              </th>
              <th align="left">
                <bold>1</bold>
              </th>
              <th align="left">
                <bold>2</bold>
              </th>
              <th align="left">
                <bold>3</bold>
              </th>
              <th align="left">
                <bold>4</bold>
              </th>
              <th align="left">
                <bold>5</bold>
              </th>
              <th align="left">
                <bold>6</bold>
              </th>
              <th align="left">
                <bold>6</bold>
              </th>
              <th align="left">
                <bold>6</bold>
              </th>
              <th align="left">
                <bold>7</bold>
              </th>
              <th align="left">
                <bold>8</bold>
              </th>
              <th align="left">
                <bold>8</bold>
              </th>
              <th align="left">
                <bold>9</bold>
              </th>
              <th align="left">
                <bold>10</bold>
              </th>
              <th align="left">
                <bold>11</bold>
              </th>
              <th align="left">
                <bold>12</bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left" rowspan="2">Haykowsky et al., 2009</td>
              <td align="left" rowspan="2">N = 2217M/5F57 &#177; 10<break/>Post-HTx time = 5.4 &#177; 4.9 years</td>
              <td align="left" rowspan="2">N = 2118M/3F59 &#177; 11<break/>Post-HTx time = 4.4 &#177; 3.3 years</td>
              <td align="left">Cycle ergometer and treadmill<bold>1-8 weeks</bold><break/>5x/week 30-45 min: 60-80%VO<sub>2</sub>peak</td>
              <td align="left" rowspan="2">5x/week<break/>12 weeks</td>
              <td align="left" rowspan="2">12 weeks of training significantly increased VO<sub>2</sub>peak (21.2 &#177; 7.3 - 24.7 &#177; 8.8 mL/kg/min, p = 0.003) of HTx recipients</td>
              <td align="left" rowspan="2">
                <bold>+</bold>
              </td>
              <td align="left" rowspan="2">
                <bold>+</bold>
              </td>
              <td align="left" rowspan="2">
                <bold>+</bold>
              </td>
              <td align="left" rowspan="2">
							</td>
              <td align="left" rowspan="2">
							</td>
              <td align="left" rowspan="2">
                <bold>+</bold>
              </td>
              <td align="left" rowspan="2">
                <bold>+</bold>
              </td>
              <td align="left" rowspan="2">
							</td>
              <td align="left" rowspan="2">
							</td>
              <td align="left" rowspan="2">
                <bold>+</bold>
              </td>
              <td align="left" rowspan="2">
                <bold>+</bold>
              </td>
              <td align="left" rowspan="2">
                <bold>+</bold>
              </td>
              <td align="left" rowspan="2">
							</td>
              <td align="left" rowspan="2">
                <bold>+</bold>
              </td>
              <td align="left" rowspan="2">
                <bold>+</bold>
              </td>
            </tr>
            <tr>
              <td align="left"><bold>9-12 weeks</bold>3x/weeks 30-45 min: 60-80%VO<sub>2</sub><break/>peak2x/weeks 20-25x (30s: 90-100% VO<sub>2</sub>peak/1 min)</td>
            </tr>
            <tr>
              <td align="left">Hermann et al., 2011</td>
              <td align="left">N = 1412M/2F53 &#177; 11Post-HTx time = 6.8 &#177; 4.0 years</td>
              <td align="left">N = 1310M/3F47 &#177; 18Post-HTx time = 7.0 &#177; 5.5 years</td>
              <td align="left">Cycle ergometer and staircase running4 min: 80% VO<sub>2</sub><break/>peak/ &#189; min2 min: 85% VO<sub>2</sub>peak/ &#189; min30 s: 90% VO<sub>2</sub>peak/ &#189; min</td>
              <td align="left">3x/week<break/>8 weeks</td>
              <td align="left">The 8-week HIIT program significantly reduced SBP (p = 0.02) and significantly increased VO<sub>2</sub>peak (p &lt; 0.001) and endothelial action</td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
							</td>
              <td align="left">
							</td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
							</td>
              <td align="left">
							</td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
							</td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
            </tr>
            <tr>
              <td align="left">Nytroen et al., 2012</td>
              <td align="left">N = 2416M/8F48 &#177; 17Post-HTx time = 4.3 &#177; 2.4 years</td>
              <td align="left">N = 2417M/7F53 &#177; 14Post-HTx time = 3.8 &#177; 2.1 years</td>
              <td align="left">Treadmill4 min (85-95% HRmax) / 3 min<break/>(11-13 Borg SEP)</td>
              <td align="left">3x/week<break/>8 weeks</td>
              <td align="left">HIIT significantly improved VO<sub>2</sub>peak (p &lt; 0.001) after 8 weeks of training</td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
							</td>
              <td align="left">
							</td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
							</td>
              <td align="left">
							</td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
							</td>
              <td align="left">
                <bold>+</bold>
              </td>
              <td align="left">
                <bold>+</bold>
              </td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN2">
            <p>N: sample; M: male; F: female; HRmax: maximum heart rate; SEP: subjective effort perception; SBP: systolic blood pressure.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <table-wrap id="t3">
        <label>Table 3</label>
        <caption>
          <title>Major results of the hemodynamic and cardiorespiratory variables found in the studies</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="16%"/>
            <col width="16%"/>
            <col width="16%"/>
            <col width="16%"/>
            <col width="16%"/>
            <col width="16%"/>
          </colgroup>
          <thead>
            <tr style="border-bottom-width:thin;border-bottom-style:solid">
              <th align="left">
							</th>
              <th align="center" colspan="2">HIIT</th>
              <th align="center" colspan="2">CON</th>
              <th align="center">
							</th>
            </tr>
            <tr>
              <th align="left">
                <bold>VARIABLES</bold>
              </th>
              <th align="center">
                <bold>Pre</bold>
              </th>
              <th align="center">
                <bold>Post</bold>
              </th>
              <th align="center">
                <bold>Pre</bold>
              </th>
              <th align="center">
                <bold>Post</bold>
              </th>
              <th align="center">
                <bold>Studies</bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left" rowspan="3">HR at rest</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">Haykowsky et al., 2009</td>
            </tr>
            <tr>
              <td align="center">76 &#177; 11</td>
              <td align="center">76 &#177; 7 (NS)</td>
              <td align="center">78 &#177; 7</td>
              <td align="center">78 &#177; 11 (NS)</td>
              <td align="center">Hermann et al., 2011</td>
            </tr>
            <tr>
              <td align="center">85 &#177; 11</td>
              <td align="center">83 &#177; 11 (NS)</td>
              <td align="center">79 &#177; 11</td>
              <td align="center">81 &#177; 13 (NS)</td>
              <td align="center">Nytroen et al., 2012</td>
            </tr>
            <tr>
              <td align="left" rowspan="3">HRpeak</td>
              <td align="center">147 &#177; 18</td>
              <td align="center">154 &#177; 15 (0.06)</td>
              <td align="center">139.6 &#177; 19</td>
              <td align="center">139 &#177; 20 (NS)</td>
              <td align="center">Haykowsky et al., 2009</td>
            </tr>
            <tr>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">Hermann et al., 2011</td>
            </tr>
            <tr>
              <td align="center">159 &#177; 14</td>
              <td align="center">163 &#177; 13 (&lt; 0.05)</td>
              <td align="center">154 &#177; 15</td>
              <td align="center">153 &#177; 17 (NS)</td>
              <td align="center">Nytroen et al., 2012</td>
            </tr>
            <tr>
              <td align="left" rowspan="3">VO<sub>2</sub>peak</td>
              <td align="center">21.2 &#177; 7.3</td>
              <td align="center">24.7 &#177; 8.8 (0.03)</td>
              <td align="center">18.2 &#177; 5.9</td>
              <td align="center">18.2 &#177; 5.3 (NS)</td>
              <td align="center">Haykowsky et al., 2009</td>
            </tr>
            <tr>
              <td align="center">23.9 &#177; 6.7</td>
              <td align="center">28.3 &#177; 6.1 (&lt; 0.001)</td>
              <td align="center">24.6 &#177; 5</td>
              <td align="center">23.4 &#177; 5.7 (NS)</td>
              <td align="center">Hermann et al., 2011</td>
            </tr>
            <tr>
              <td align="center">27.7 &#177; 5.5</td>
              <td align="center">30.9 &#177; 5.3 (&lt; 0.001)</td>
              <td align="center">28.5 &#177; 7</td>
              <td align="center">28 &#177; 6.7 (NS)</td>
              <td align="center">Nytroen et al., 2012</td>
            </tr>
            <tr>
              <td align="left" rowspan="3">FMD</td>
              <td align="center">4 &#177; 6.8</td>
              <td align="center">5.3 &#177; 4.9 (NS)</td>
              <td align="center">3.2 &#177; 4</td>
              <td align="center">3.9 &#177; 5.2 (NS)</td>
              <td align="center">Haykowsky et al., 2009</td>
            </tr>
            <tr>
              <td align="center">8.3 &#177; 1.3</td>
              <td align="center">11.4 &#177; 1.2 (0.01)</td>
              <td align="center">5.6 &#177; 1</td>
              <td align="center">5.3 &#177; 1.7 (NS)</td>
              <td align="center">Hermann et al., 2011</td>
            </tr>
            <tr>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">Nytroen et al., 2012</td>
            </tr>
            <tr>
              <td align="left" rowspan="3">SBP</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">Haykowsky et al., 2009</td>
            </tr>
            <tr>
              <td align="center">142 &#177; 17</td>
              <td align="center">127 &#177; 13 (0.02)</td>
              <td align="center">141 &#177; 15</td>
              <td align="center">142 &#177; 23 (NS)</td>
              <td align="center">Hermann et al., 2011</td>
            </tr>
            <tr>
              <td align="center">130 &#177; 17</td>
              <td align="center">136 &#177; 16 (NS)</td>
              <td align="center">131 &#177; 20</td>
              <td align="center">129 &#177; 14 (NS)</td>
              <td align="center">Nytroen et al., 2012</td>
            </tr>
            <tr>
              <td align="left" rowspan="3">DBP</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">Haykowsky et al., 2009</td>
            </tr>
            <tr>
              <td align="center">85 &#177; 7</td>
              <td align="center">82 &#177; 9 (NS)</td>
              <td align="center">82 &#177; 9</td>
              <td align="center">84 &#177; 14 (NS)</td>
              <td align="center">Hermann et al., 2011</td>
            </tr>
            <tr>
              <td align="center">80 &#177; 10</td>
              <td align="center">82 &#177; 9 (NS)</td>
              <td align="center">81 &#177; 15</td>
              <td align="center">82 &#177; 17 (NS)</td>
              <td align="center">Nytroen et al., 2012</td>
            </tr>
            <tr>
              <td align="left" rowspan="3">SBPpeak</td>
              <td align="center">175 &#177; 26</td>
              <td align="center">177 &#177; 21 (NS)</td>
              <td align="center">172 &#177; 29</td>
              <td align="center">180 &#177; 27 (NS)</td>
              <td align="center">Haykowsky et al., 2009</td>
            </tr>
            <tr>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">Hermann et al., 2011</td>
            </tr>
            <tr>
              <td align="center">181 &#177; 33</td>
              <td align="center">211 &#177; 66 (&lt; 0.05)</td>
              <td align="center">197 &#177; 22</td>
              <td align="center">191 &#177; 32 (NS)</td>
              <td align="center">Nytroen et al., 2012</td>
            </tr>
            <tr>
              <td align="left" rowspan="3">DBPpeak</td>
              <td align="center">81 &#177; 9</td>
              <td align="center">79 &#177; 9 (NS)</td>
              <td align="center">81 &#177; 8</td>
              <td align="center">80 &#177; 9 (NS)</td>
              <td align="center">Haykowsky et al., 2009</td>
            </tr>
            <tr>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">-</td>
              <td align="center">Hermann et al., 2011</td>
            </tr>
            <tr>
              <td align="center">71 &#177; 15</td>
              <td align="center">80 &#177; 14 (&lt; 0.05)</td>
              <td align="center">83 &#177; 14</td>
              <td align="center">91 &#177; 35 (NS)</td>
              <td align="center">Nytroen et al., 2012</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN3">
            <p>HIIT: high-intensity interval training; HR: heart rate; FMD: flow mediated dilation of the brachial artery; SBP: systolic blood pressure; DBP: diastolic blood pressure; NS: nonsignificant.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>All studies included had VO<sub>2</sub>peak as the major outcome of the analysis. <xref ref-type="fig" rid="f2">Figure 2</xref> shows the increased effect on VO<sub>2</sub>peak [95%CI: 4.45 (2.15 - 6.75), p = 0.0001, N = 118] of HIIT (24.3 &#177; 6.5 - 28.0 &#177; 6.7 mL/kg.min; 15%) as compared to that of the control group (23.8 &#177; 6.0 - 23.2 &#177; 5.9 mL/kg.min; -2%). Regarding HRpeak, based on the comparative analysis of the groups, two studies reported a favorable effect [95%CI: 0.74 (0.31 - 1.16) p = 0.0007, N = 46] in the HIIT group (<xref ref-type="fig" rid="f3">Figure 3</xref>).</p>
      <p>
        <fig id="f2">
          <label>Figure 2</label>
          <caption>
            <title>Forest plot (A) AND funnel plot (B) showing information about the effect of high-intensity interval training (HIIT) on VO<sub>2</sub>peak.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-110-02-0188-80017-gf02.jpg"/></fig>
      </p>
      <p>
        <fig id="f3">
          <label>Figure 3</label>
          <caption>
            <title>Forest plot (A) AND funnel plot (B) showing information about the effect of high-intensity interval training (HIIT) on peak heart rate.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-110-02-0188-80017-gf03.jpg"/></fig>
      </p>
      <p>The studies that were not statistically analyzed (forest plot) showed, in the HIIT group, a positive effect on BP at rest and BPpeak (systolic and diastolic), brachial flow velocity, maximal muscle strength (1 RM), lean mass maintenance, and inflammatory markers. Some of those results are shown in <xref ref-type="table" rid="t3">Table 3</xref>. In addition, none of the studies reported a cardiovascular event and/or mortality associated with training, showing it to be a safe practice to be included in cardiac rehabilitation programs.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>The present systematic review with meta-analysis is the first to analyze the effect of HIIT on some health-related parameters of HTx recipients. The three studies included showed that HIIT improved VO<sub>2</sub>peak by 15%. Such increase is greater than that found in two systematic reviews with meta-analysis that assessed the effect of different types of exercise<xref ref-type="bibr" rid="B26">26</xref> and of MICT<xref ref-type="bibr" rid="B27">27</xref> on the VO<sub>2</sub>peak of those patients.</p>
      <p>Although HIIT improves VO<sub>2</sub>peak, sometimes it is not indicated for HTx recipients because they have chronotropic insufficiency developed from cardiac denervation.<xref ref-type="bibr" rid="B28">28</xref> That incompetence hinders HR at rest (increase) and during close-to-peak exercise (decrease - HRpeak), decreasing the chronotropic reserve values. Thus, according to the studies assessed in this review, 8 to 12 weeks of HIIT intervention can decrease HR at rest and increase HRpeak. High-intensity exercise (&gt; 80%VO<sub>2</sub>peak or &gt; 85%HRmax) might have improved the cardiocirculatory function, stimulating the sinus node faster, facilitating faster and better responses on HR at rest and HRpeak.<xref ref-type="bibr" rid="B29">29</xref>
			</p>
      <p>Although the literature shows an insufficient number of studies on HIIT and HTx recipients, that type of training can provide significant central and peripheral benefits to improve the clinical findings after surgery.<xref ref-type="bibr" rid="B30">30</xref> In addition, recent studies comparing the contribution of HIIT and MICT to the deficient variables of HTx recipients have shown the superior effect of HIIT.<xref ref-type="bibr" rid="B31">31</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref> Such results can indicate a possible change in paradigm regarding the recommendation of exercise prescription for HTx recipients. Thus, further studies are required to identify which training protocol better improves the deficient variables of those patients.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>Our results showed that 8 to 12 weeks of cardiac rehabilitation with HIIT were sufficient to significantly increase HRpeak and aerobic power of HTx recipients (men and women).</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This article is part of the thesis of Doctoral submitted by Raphael Jos&#233; Perrier-Melo, from Universidade de Pernambuco.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Ethics approval and consent to participate</bold>
        </p>
        <p>This article does not contain any studies with human participants or animals performed by any of the authors.</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>Treinamento Intervalado de Alta Intensidade em Transplantados de Cora&#231;&#227;o: Uma Revis&#227;o Sistem&#225;tica com Meta-An&#225;lise</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Perrier-Melo</surname>
            <given-names>Raphael Jos&#233;</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Figueira</surname>
            <given-names>Fernando Augusto Marinho dos Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Guimar&#227;es</surname>
            <given-names>Guilherme Veiga</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Manoel da Cunha</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">4</xref>
        </contrib>
      </contrib-group>
      <aff id="aff5">
        <label>1</label>
        <institution content-type="original">Universidade de Pernambuco (UPE), Recife, PE - Brazil</institution>
      </aff>
      <aff id="aff6">
        <label>2</label>
        <institution content-type="original">Instituto de Medicina Integral Professor Fernando Figueira, Recife, PE - Brazil</institution>
      </aff>
      <aff id="aff7">
        <label>3</label>
        <institution content-type="original">Universidade de S&#227;o Paulo, S&#227;o Paulo, SP - Brazil</institution>
      </aff>
      <aff id="aff8">
        <label>4</label>
        <institution content-type="original">Universidade de Pernambuco (UPE), Recife, PE - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Raphael Jos&#233; Perrier-Melo,</bold> Escola Superior de Educa&#231;&#227;o F&#237;sica Rua Arn&#243;bio Marques, 310, Recife, PE - Brasil. E-mail: <email>perrierprof@gmail.com</email>, <email>rperrier2@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa e An&#225;lise e interpreta&#231;&#227;o dos dados: Perrier-Melo RJ, Costa MC; Obten&#231;&#227;o de dados, An&#225;lise estat&#237;stica e Obten&#231;&#227;o de financiamento: Perrier-Melo RJ; Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante:Perrier-Melo RJ, Figueira FAMS, Guimar&#227;es GV, Costa MC.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <p>O transplante de cora&#231;&#227;o &#233; considerado procedimento eficiente e padr&#227;o ouro para pacientes com quadro de insufici&#234;ncia card&#237;aca terminal. Verifica-se que ap&#243;s o procedimento cir&#250;rgico os pacientes apresentam menor valor de pot&#234;ncia aer&#243;bia (VO<sub>2</sub>m&#225;x) e respostas hemodin&#226;micas descompensadas. O objetivo do presente estudo foi de verificar por meio de uma revis&#227;o sistem&#225;tica com meta-an&#225;lise se o treinamento intervalado de alta intensidade &#233; capaz de proporcionar benef&#237;cios a tais capacidades. Trata-se de uma revis&#227;o sistem&#225;tica com meta-an&#225;lise, que realizou buscas em pares nas bases e portais de dados <italic>PubMed, Web of Science, Scopus, Science Direct</italic> e <italic>Wiley</italic> at&#233; dezembro de 2016. Para busca dos artigos utilizaram-se os termos e descritores: &#8220;<italic>heart recipient</italic>&#8221; OR &#8220;<italic>heart transplant recipient</italic>&#8221; OR &#8221;<italic>heart transplant</italic>&#8221; OR &#8220;<italic>cardiac transplant</italic>&#8221; OR &#8220;<italic>heart graft</italic>&#8221;. Os descritores pelo DeCS e <italic>Mesh</italic> foram: &#8220;<italic>heart transplantation</italic>&#8217;&#8217; OR &#8220;<italic>cardiac transplantation</italic>&#8221;. As palavras utilizadas em combina&#231;&#227;o (AND) foram &#8220;<italic>exercise training</italic>&#8221; OR &#8220;<italic>interval training</italic>&#8221; OR &#8220;<italic>high intensity interval training</italic>&#8221; OR &#8220;<italic>high intensity training</italic>&#8221; OR &#8220;<italic>anaerobic training</italic>&#8221; OR &#8220;<italic>intermittent training</italic>&#8221; OR &#8220;<italic>sprint training</italic>&#8221;. A busca inicial identificou 1064 estudos. Em seguida, apenas os estudos que analisaram a influ&#234;ncia do treinamento intervalado de alta intensidade no per&#237;odo p&#243;s transplante foram adicionados, sendo, assim, tr&#234;s estudos analisados. O n&#237;vel adotado nas an&#225;lises estat&#237;sticas para determinar signific&#226;ncia foi de 0,05. Verificou-se que, entre 8 e 12 semanas de interven&#231;&#227;o, os pacientes transplantados de cora&#231;&#227;o apresentaram melhoras significativas em VO<sub>2</sub>pico, frequ&#234;ncia card&#237;aca e press&#227;o arterial pico.</p>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Exerc&#237;cio</kwd>
        <kwd>Insufici&#234;ncia Card&#237;aca/fisiopatologia</kwd>
        <kwd>Estilo de Vida</kwd>
        <kwd>Reabilita&#231;&#227;o Card&#237;aca</kwd>
        <kwd>Transplante de Cora&#231;&#227;o</kwd>
        <kwd>Metanalise como Assunto</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>O transplante de cora&#231;&#227;o (TC) &#233; considerado o tratamento padr&#227;o ouro para pacientes com insufici&#234;ncia card&#237;aca refrat&#225;ria &#224; terap&#234;utica cl&#237;nica e/ou procedimento intervencionista.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref> Atualmente a t&#233;cnica em utiliza&#231;&#227;o nos centros de cirurgia &#233; a bicaval, que consiste na denerva&#231;&#227;o do cora&#231;&#227;o por meio da disseca&#231;&#227;o completa da aur&#237;cula direita e do septo interauricular, mantendo pequena por&#231;&#227;o da aur&#237;cula esquerda contendo as veias pulmonares.<xref ref-type="bibr" rid="B3">3</xref> A principal vantagem dessa t&#233;cnica em compara&#231;&#227;o &#224;s outras &#233; a preserva&#231;&#227;o da geometria atrial, menor gradiente transpulmonar e menor incid&#234;ncia de insufici&#234;ncia tric&#250;spide no momento p&#243;s-cir&#250;rgico.<xref ref-type="bibr" rid="B4">4</xref>
				</p>
        <p>A denerva&#231;&#227;o card&#237;aca faz com que o controle cardiorrespirat&#243;rio (consumo m&#225;ximo de oxig&#234;nio - VO<sub>2</sub>m&#225;x) e hemodin&#226;mico (frequ&#234;ncia card&#237;aca - FC, d&#233;bito card&#237;aco - DC e press&#227;o arterial - PA) seja dependente inicialmente do mecanismo <italic>Frank-Starling</italic> (lei da pr&#233;-carga dependente do retorno venoso) e posteriormente das concentra&#231;&#245;es de catecolaminas circulantes e da fra&#231;&#227;o de eje&#231;&#227;o, devido &#224; aus&#234;ncia da estimula&#231;&#227;o simp&#225;tica e parassimp&#225;tica e pelo barorreflexo.<xref ref-type="bibr" rid="B5">5</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref> Com isso, os pacientes transplantados apresentam menor valor de VO<sub>2</sub>m&#225;x (cerca de 70-80% do valor previsto para idade em rela&#231;&#227;o a seus pares saud&#225;veis),<xref ref-type="bibr" rid="B8">8</xref> elevados n&#237;veis de FC, PA e resist&#234;ncia vascular em repouso. J&#225; em situa&#231;&#245;es de exerc&#237;cio f&#237;sico verifica-se aumento deprimido da FC e PA, acompanhado com aumento da resist&#234;ncia vascular.<xref ref-type="bibr" rid="B9">9</xref> Tal comportamento mant&#233;m-se semelhante em condi&#231;&#245;es de esfor&#231;os subm&#225;ximos e pr&#243;ximos ao pico, causando uma FC pico (FCpico) e PA pico (PApico) menor, apresentando baixa reprodutibilidade com o VO<sub>2</sub>pico. Al&#233;m disso, h&#225; uma recupera&#231;&#227;o lenta p&#243;s-exerc&#237;cio quando comparados com indiv&#237;duos da mesma idade saud&#225;veis.<xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref>
				</p>
        <p>As altera&#231;&#245;es fisiol&#243;gicas citadas anteriormente e a terapia imunossupressora geram preju&#237;zos cardiorrespirat&#243;rios e hemodin&#226;micos ao longo do tempo, e frequentemente os receptores desenvolvem doen&#231;as como: hipertens&#227;o arterial sist&#234;mica (95%), hiperlipidemia (81%), vasculopatia (50%), insufici&#234;ncia renal (33%) e diabetes mellitus tipo 2 (32%).<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> Nesse sentido, os programas de reabilita&#231;&#227;o card&#237;aca s&#227;o recomendados desde as primeiras diretrizes desenvolvidas pelo <italic>American Heart Association</italic> e <italic>American College of Sports Medicine</italic>. O principal objetivo desses programas &#233; restaurar as atividades di&#225;rias e mudar o estilo de vida dos pacientes, a partir do somat&#243;rio de atividades capazes de melhorar a condi&#231;&#227;o f&#237;sica, psicol&#243;gica e social. Tais atividades devem ser realizadas de maneira estruturada e cont&#237;nua, focando o desenvolvimento das principais vari&#225;veis deficit&#225;rias no paciente.<xref ref-type="bibr" rid="B14">14</xref> A atual diretriz recomenda que parte da reabilita&#231;&#227;o card&#237;aca deve ser composta pelo treinamento f&#237;sico, incorporando de tr&#234;s a cinco sess&#245;es semanais de exerc&#237;cios com caracter&#237;stica cont&#237;nua (caminhada, trote, pedalada), atingindo n&#237;vel de intensidade leve a moderada, por pelo menos 30 minutos di&#225;rios.<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref> As sess&#245;es devem iniciar e finalizar com curtos per&#237;odos (5-10 minutos) de aquecimento e volta &#224; calma em baixa intensidade, respectivamente. O exerc&#237;cio f&#237;sico p&#243;s TC &#233; considerado seguro e eficaz para proporcionar melhoras significativas sobre as vari&#225;veis cardiorrespirat&#243;rias, metab&#243;licas, hemodin&#226;micas, endoteliais e morfol&#243;gicas.<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref>
				</p>
        <p>Por outro lado, em contraste com o treinamento cont&#237;nuo de moderada intensidade (TCMI), estudos de revis&#227;o sistem&#225;tica com meta-an&#225;lise realizados em pacientes com doen&#231;a arterial coronariana,<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref> diabetes mellitus tipo 2<xref ref-type="bibr" rid="B18">18</xref> e s&#237;ndrome metab&#243;lica<xref ref-type="bibr" rid="B19">19</xref> demonstram que o treinamento intervalado de alta intensidade (TIAI) possibilita que os pacientes alcancem benef&#237;cios semelhantes e/ou superiores em torno das vari&#225;veis descompensadas com tais doen&#231;as.<xref ref-type="bibr" rid="B20">20</xref> O TIAI &#233; caracterizado por envolver s&#233;ries de curtos ou longos esfor&#231;os (30s - 4min) em alta intensidade (&gt; 85% VO<sub>2</sub>m&#225;x), seguidos de breves ou longos per&#237;odos de recupera&#231;&#227;o (30s - 4 min).<xref ref-type="bibr" rid="B21">21</xref>
				</p>
        <p>Apesar de estudos apresentarem evolu&#231;&#245;es de maior magnitude com a pr&#225;tica do TIAI quando comparado ao TCMI, ainda h&#225; uma certa precau&#231;&#227;o em prescrev&#234;-lo para p&#250;blicos que apresentam diagn&#243;stico de doen&#231;as cardiovasculares, metab&#243;licas ou que passaram por algum transplante de &#243;rg&#227;o. Al&#233;m disso, pouco se sabe da rela&#231;&#227;o dose-resposta sobre o curso de melhora na capacidade cardiorrespirat&#243;ria, endotelial e hemodin&#226;mica causada pelo TIAI na popula&#231;&#227;o transplantada de cora&#231;&#227;o. Nesse sentido, o objetivo do estudo &#233; verificar por meio de uma revis&#227;o sistem&#225;tica com meta-an&#225;lise se o TIAI &#233; capaz de proporcionar benef&#237;cios em torno de tais capacidades.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Realizou-se uma revis&#227;o sistem&#225;tica seguindo as recomenda&#231;&#245;es e crit&#233;rios determinados pelo PRISMA (<italic>Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline)</italic>.</p>
        <sec>
          <title>Estrat&#233;gia de busca</title>
          <p>A busca dos artigos foi realizada na l&#237;ngua inglesa por meio das bases e portais de dados <italic>PubMed, Web of Science, Scopus, Science Direct</italic> e <italic>Wiley</italic> at&#233; dezembro de 2016. A sele&#231;&#227;o dos termos e descritores utilizados no processo de busca foi realizada a partir de palavras-chave dispon&#237;veis em estudos anteriores e por meio do DeCS e <italic>Mesh,</italic> respectivamente (<xref ref-type="table" rid="t4">Tabela 1</xref>). Os termos identificados pela literatura foram: &#8220;<italic>heart recipient</italic>&#8221; OR &#8220;<italic>heart transplant recipient</italic>&#8221; OR &#8220;<italic>heart</italic>
						<italic>transplant</italic>&#8221; OR &#8220;<italic>cardiac transplant</italic>&#8221; OR &#8220;<italic>heart graft</italic>&#8221;. J&#225; os descritores pelo DeCS e <italic>Mesh</italic> foram: &#8220;<italic>heart transplantation</italic>&#8217;&#8217; OR &#8220;<italic>cardiac transplantation</italic>&#8221;. As palavras utilizadas em combina&#231;&#227;o (AND) foram &#8220;<italic>exercise training</italic>&#8221; OR &#8220;<italic>interval training</italic>&#8221; OR &#8220;<italic>high intensity interval training</italic>&#8221; OR &#8220;<italic>high intensity training</italic>&#8221; OR &#8220;<italic>anaerobic training</italic>&#8221; OR &#8220;<italic>intermittent training</italic>&#8221; OR &#8220;<italic>sprint training</italic>&#8221;. A extra&#231;&#227;o dos dados e todos os processos de busca, sele&#231;&#227;o e avalia&#231;&#227;o dos artigos foram realizados em pares.</p>
          <table-wrap id="t4">
            <label>Tabela 1</label>
            <caption>
              <title>Estrat&#233;gia de pesquisa bibliogr&#225;fica nas bases e portais de dados</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="50%"/>
                <col width="50%"/>
              </colgroup>
              <tbody>
                <tr>
                  <td align="center">#1 "<italic>heart recipient</italic>"[tiab], OR "<italic>heart transplant recipient</italic>"[tiab], OR "<italic>heart transplant</italic>" [tiab], OR "<italic>cardiac transplant</italic>" [tiab], OR "<italic>heart graft</italic>" [tiab], OR"<italic>heart transplantation</italic>''[Mesh], OR "<italic>cardiac transplantation</italic>" [Mesh]</td>
                  <td align="center">#2 "<italic>exercise training</italic>" [tiab], OR "<italic>interval training</italic>" [tiab], OR "<italic>high intensity interval training</italic>" [tiab], OR "<italic>high intensity training</italic>" [tiab], OR "<italic>anaerobic training</italic>" [tiab], OR "<italic>intermittent training</italic>" [tiab], OR "<italic>sprint training</italic>" [tiab]</td>
                </tr>
                <tr>
                  <td align="center" colspan="2">#1 AND #2</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN4">
                <p>Mesh: Medical Subject Headings.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Crit&#233;rios de sele&#231;&#227;o</title>
          <p>Os crit&#233;rios de inclus&#227;o estabelecidos foram: a) estudos randomizados que avaliaram o VO<sub>2</sub>pico (a partir de um teste incremental m&#225;ximo) e/ou FCpico como desfecho prim&#225;rio; b) com amostra constitu&#237;da exclusivamente por pacientes que realizaram transplante de cora&#231;&#227;o; c) estudos que analisaram o efeito do TIAI; e d) estudos com per&#237;odo de interven&#231;&#227;o superior a quatro semanas. Foram exclu&#237;dos: a) estudos sem grupo controle; b) estudos com an&#225;lise aguda; e c) estudos de caso.</p>
        </sec>
        <sec>
          <title>Identifica&#231;&#227;o e sele&#231;&#227;o dos estudos</title>
          <p>Inicialmente as refer&#234;ncias foram revisadas, a partir do t&#237;tulo e resumo. Em seguida, os artigos que apresentavam relev&#226;ncia de acordo com os crit&#233;rios de sele&#231;&#227;o foram lidos na &#237;ntegra e avaliados quanto &#224; qualidade metodol&#243;gica por meio da escala <italic>Testex.</italic><xref ref-type="bibr" rid="B22">22</xref>
					</p>
        </sec>
        <sec>
          <title>An&#225;lise dos dados</title>
          <p>As vari&#225;veis analisadas (VO<sub>2</sub>pico e FCpico) foram classificadas de forma cont&#237;nua e os dados foram apresentados atrav&#233;s da m&#233;dia e desvio-padr&#227;o. Os dados foram combinados para obter o tamanho do efeito geral, intervalo de confian&#231;a (IC) de 95% e n&#237;vel de signific&#226;ncia, utilizando o <italic>software</italic>
						<italic>Review Manager</italic> (<italic>RevMan</italic>) vers&#227;o 5.3 <italic>Copenhagen: The Nordic Cochrane Centre</italic>. A compara&#231;&#227;o do grupo TIAI com o grupo controle (p&#243;s-entrada) foi realizada a partir da diferen&#231;a de m&#233;dia ponderada (WMD). Para cada resultado, a heterogeneidade (I<xref ref-type="bibr" rid="B2">2</xref>) foi calculada, adotando o modelo de efeito fixo. A signific&#226;ncia foi definida em p &lt; 0,05.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>A <xref ref-type="fig" rid="f4">Figura 1</xref> apresenta o fluxograma contendo as etapas do processo de busca e sele&#231;&#227;o dos artigos inclu&#237;dos na presente revis&#227;o.</p>
        <p>Na busca eletr&#244;nica inicial foram identificados 1064 estudos potencialmente relevantes. A partir da leitura dos t&#237;tulos, 994 manuscritos foram descartados por n&#227;o apresentarem desfecho prim&#225;rio relacionado ao objetivo da presente revis&#227;o. Posteriormente, a partir da leitura dos resumos dos estudos, 14 foram exclu&#237;dos por n&#227;o se adequarem aos crit&#233;rios de sele&#231;&#227;o do estudo. Assim, tr&#234;s artigos foram inclu&#237;dos para an&#225;lise final, os quais apresentaram m&#233;dia dos escores referentes a qualidade metodol&#243;gica de 10 pontos, de acordo com a escala <italic>Testex</italic>.</p>
        <p>
          <fig id="f4">
            <label>Figura 1</label>
            <caption>
              <title>Fluxograma do processo de sele&#231;&#227;o dos artigos inclu&#237;dos na revis&#227;o sistem&#225;tica.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-02-0188-80017-gf01-pt.jpg"/></fig>
        </p>
        <p>As principais informa&#231;&#245;es referentes &#224;s caracter&#237;sticas da amostra, os procedimentos metodol&#243;gicos, a an&#225;lise qualitativa e os principais resultados encontrados nos estudos realizados com pacientes p&#243;s TC est&#227;o detalhadas em ordem cronol&#243;gica crescente nas <xref ref-type="table" rid="t5">tabelas 2</xref> e <xref ref-type="table" rid="t6">3</xref>. Um total de 118 pacientes (90 homens e 28 mulheres), transplantados h&#225; 5,3 &#177; 3,7 anos foram inclu&#237;dos na an&#225;lise da revis&#227;o sistem&#225;tica, 60 pertencentes ao grupo TIAI (49,3 &#177; 12,7 anos) e 58 ao grupo controle (53 &#177; 14,3 anos), os quais mantiveram suas atividades habituais. As sess&#245;es de TIAI foram feitas em cicloerg&#244;metros<xref ref-type="bibr" rid="B23">23</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref> e esteiras,<xref ref-type="bibr" rid="B25">25</xref> atingindo intensidade que variaram entre 80-100% VO<sub>2</sub>pico ou 85-95% FCm&#225;x. Tais est&#237;mulos foram realizados de tr&#234;s a cinco vezes (sess&#245;es) semanais ao longo de 8 e 12 semanas de treinamento.</p>
        <table-wrap id="t5">
          <label>Tabela 2</label>
          <caption>
            <title>Caracter&#237;sticas da amostra, qualidade metodol&#243;gica e principais resultados dos estudos que analisaram o efeito do treinamento intervalado de alta intensidade (TIAI) em pacientes p&#243;s transplante card&#237;aco (TC)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
              <col width="4%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="2">Estudo</th>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">GRUPOS</th>
                <th align="center" rowspan="2">Protocolo TIAI</th>
                <th align="center" rowspan="2">Dura&#231;&#227;o<break/>(semanas)</th>
                <th align="center" rowspan="2">Principais resultados</th>
                <th align="center" colspan="15" style="border-bottom-width:thin;border-bottom-style:solid">Testex</th>
              </tr>
              <tr>
                <th align="center">
                  <bold>TIAI</bold>
                </th>
                <th align="center">
                  <bold>CONTROLE</bold>
                </th>
                <th align="center">
                  <bold>1</bold>
                </th>
                <th align="center">
                  <bold>2</bold>
                </th>
                <th align="center">
                  <bold>3</bold>
                </th>
                <th align="center">
                  <bold>4</bold>
                </th>
                <th align="center">
                  <bold>5</bold>
                </th>
                <th align="center">
                  <bold>6</bold>
                </th>
                <th align="center">
                  <bold>6</bold>
                </th>
                <th align="center">
                  <bold>6</bold>
                </th>
                <th align="center">
                  <bold>7</bold>
                </th>
                <th align="center">
                  <bold>8</bold>
                </th>
                <th align="center">
                  <bold>8</bold>
                </th>
                <th align="center">
                  <bold>9</bold>
                </th>
                <th align="center">
                  <bold>10</bold>
                </th>
                <th align="center">
                  <bold>11</bold>
                </th>
                <th align="center">
                  <bold>12</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" rowspan="2">Haykowsky et al.,<xref ref-type="bibr" rid="B23">23</xref> 2009</td>
                <td align="center" rowspan="2">N = 22<break/>17H/5M<break/>57 &#177; 10<break/>Tempo p&#243;s TC = 5,4&#177;4,9 anos</td>
                <td align="center" rowspan="2">N = 21<break/>18H/3M<break/>59 &#177; 11<break/>Tempo p&#243;s TC = 4,4&#177;3,3 anos</td>
                <td align="center">Ciclo erg&#244;metro e esteira<bold>1-8 semanas</bold><break/>5x/semana 30-45 min: 60-80%<break/>VO<sub>2</sub>pico</td>
                <td align="center" rowspan="2">5x/semana<break/>12 semanas</td>
                <td align="center" rowspan="2">12 semanas de treinamento foram eficientes para incrementar de forma significativa o VO<sub>2</sub>pico (21.2 &#177; 7,3 - 24,7 &#177; 8,8 ml/kg/min, p = 0,003) dos pacientes transplantados</td>
                <td align="center" rowspan="2">
                  <bold>+</bold>
                </td>
                <td align="center" rowspan="2">
                  <bold>+</bold>
                </td>
                <td align="center" rowspan="2">
                  <bold>+</bold>
                </td>
                <td align="center" rowspan="2">
								</td>
                <td align="center" rowspan="2">
								</td>
                <td align="center" rowspan="2">
                  <bold>+</bold>
                </td>
                <td align="center" rowspan="2">
                  <bold>+</bold>
                </td>
                <td align="center" rowspan="2">
								</td>
                <td align="center" rowspan="2">
								</td>
                <td align="center" rowspan="2">
                  <bold>+</bold>
                </td>
                <td align="center" rowspan="2">
                  <bold>+</bold>
                </td>
                <td align="center" rowspan="2">
                  <bold>+</bold>
                </td>
                <td align="center" rowspan="2">
								</td>
                <td align="center" rowspan="2">
                  <bold>+</bold>
                </td>
                <td align="center" rowspan="2">
                  <bold>+</bold>
                </td>
              </tr>
              <tr>
                <td align="center"><bold>9-12 semanas</bold><break/>3x/semana 30-45 min: 60-80%VO<sub>2</sub>pico2<break/>x/semana 20-25x (30s 90-100% VO<sub>2</sub>pico/1 min)</td>
              </tr>
              <tr>
                <td align="left">Hermann et al.,<xref ref-type="bibr" rid="B24">24</xref> 2011</td>
                <td align="center">N = 14<break/>12H/2M<break/>53 &#177; 11<break/>Tempo p&#243;s TC = 6,8 &#177; 4,0 anos</td>
                <td align="center">N = 13<break/>10H/3M<break/>47 &#177; 18<break/>Tempo p&#243;s TC = 7,0 &#177; 5,5 anos</td>
                <td align="center">Ciclo erg&#244;metro e corrida em escada<break/>4 min: 80% VO<sub>2</sub>pico/ &#189; min<break/>2 min: 85% VO<sub>2</sub>pico/ &#189; min<break/>30 s: 90% VO<sub>2</sub>pico/ &#189; min</td>
                <td align="center">3x/semana<break/>8 semanas</td>
                <td align="center">O programa de treinamento (8 semanas) TIAI foi eficiente em diminuir significativamente a PAS (p = 0,02), al&#233;m de aumentar significativamente o VO<sub>2</sub>pico (p &lt; 0,001) e a a&#231;&#227;o endotelial</td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
              </tr>
              <tr>
                <td align="left">Nytroen et al.,<xref ref-type="bibr" rid="B25">25</xref> 2012</td>
                <td align="center">N = 24<break/>16H/8M<break/>48 &#177; 17<break/>Tempo p&#243;s TC = 4,3 &#177; 2,4 anos</td>
                <td align="center">N = 24<break/>17H/7M<break/>53 &#177; 14<break/>Tempo p&#243;s TC = 3,8 &#177; 2,1 anos</td>
                <td align="center">Esteira4 min (85-95% FCm&#225;x) / 3 min<break/>(11-13 PSE BORG)</td>
                <td align="center">3x/semana<break/>8 semanas</td>
                <td align="center">O TIAI apresentou benef&#237;cios significativamente superiores quanto ao VO<sub>2</sub>pico (p &lt; 0,001) ap&#243;s 8 semanas de treinamento</td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
                  <bold>+</bold>
                </td>
                <td align="center">
                  <bold>+</bold>
                </td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5">
              <p>N: amostra; H: homens; M: mulheres; FCm&#225;x: frequ&#234;ncia card&#237;aca m&#225;xima; PSE: percep&#231;&#227;o subjetiva de esfor&#231;o; TC: transplante.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t6">
          <label>Tabela 3</label>
          <caption>
            <title>Principais resultados encontrados nos estudos em torno das vari&#225;veis hemodin&#226;mica e cardiorrespirat&#243;ria</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
            </colgroup>
            <thead>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <th align="left">
								</th>
                <th align="center" colspan="2">TIAI</th>
                <th align="center" colspan="2">CON</th>
                <th align="center">
								</th>
              </tr>
              <tr>
                <th align="left">
                  <bold>VARI&#193;VEIS</bold>
                </th>
                <th align="center">
                  <bold>Pr&#233;</bold>
                </th>
                <th align="center">
                  <bold>P&#243;s</bold>
                </th>
                <th align="center">
                  <bold>Pr&#233;</bold>
                </th>
                <th align="center">
                  <bold>P&#243;s</bold>
                </th>
                <th align="center">
                  <bold>Estudos</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" rowspan="3">FC repouso</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">Haykowsky et al., 2009</td>
              </tr>
              <tr>
                <td align="center">76 &#177; 11</td>
                <td align="center">76 &#177; 7 (NS)</td>
                <td align="center">78 &#177; 7</td>
                <td align="center">78 &#177; 11 (NS)</td>
                <td align="center">Hermann et al., 2011</td>
              </tr>
              <tr>
                <td align="center">85 &#177; 11</td>
                <td align="center">83 &#177; 11 (NS)</td>
                <td align="center">79 &#177; 11</td>
                <td align="center">81 &#177; 13 (NS)</td>
                <td align="center">Nytroen et al., 2012</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">FC pico</td>
                <td align="center">147 &#177; 18</td>
                <td align="center">154 &#177; 15 (0,06)</td>
                <td align="center">139,6 &#177; 19</td>
                <td align="center">139 &#177; 20 (NS)</td>
                <td align="center">Haykowsky et al., 2009</td>
              </tr>
              <tr>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">Hermann et al., 2011</td>
              </tr>
              <tr>
                <td align="center">159 &#177; 14</td>
                <td align="center">163 &#177; 13 (&lt; 0,05)</td>
                <td align="center">154 &#177; 15</td>
                <td align="center">153 &#177; 17 (NS)</td>
                <td align="center">Nytroen et al., 2012</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">VO<sub>2</sub>pico</td>
                <td align="center">21,2 &#177; 7,3</td>
                <td align="center">24,7 &#177; 8,8 (0,03)</td>
                <td align="center">18,2 &#177; 5,9</td>
                <td align="center">18,2 &#177; 5,3 (NS)</td>
                <td align="center">Haykowsky et al., 2009</td>
              </tr>
              <tr>
                <td align="center">23,9 &#177; 6,7</td>
                <td align="center">28,3 &#177; 6,1 (&lt; 0,001)</td>
                <td align="center">24,6 &#177; 5</td>
                <td align="center">23,4 &#177; 5,7 (NS)</td>
                <td align="center">Hermann et al., 2011</td>
              </tr>
              <tr>
                <td align="center">27,7 &#177; 5,5</td>
                <td align="center">30,9 &#177; 5,3 (&lt; 0,001)</td>
                <td align="center">28,5 &#177; 7</td>
                <td align="center">28 &#177; 6,7 (NS)</td>
                <td align="center">Nytroen et al., 2012</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">FMD</td>
                <td align="center">4 &#177; 6,8</td>
                <td align="center">5,3 &#177; 4,9 (NS)</td>
                <td align="center">3,2 &#177; 4</td>
                <td align="center">3,9 &#177; 5,2 (NS)</td>
                <td align="center">Haykowsky et al., 2009</td>
              </tr>
              <tr>
                <td align="center">8,3 &#177; 1,3</td>
                <td align="center">11,4 &#177; 1,2 (0,01)</td>
                <td align="center">5,6 &#177; 1</td>
                <td align="center">5,3 &#177; 1,7 (NS)</td>
                <td align="center">Hermann et al., 2011</td>
              </tr>
              <tr>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">Nytroen et al., 2012</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">PAS</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">Haykowsky et al., 2009</td>
              </tr>
              <tr>
                <td align="center">142 &#177; 17</td>
                <td align="center">127 &#177; 13 (0,02)</td>
                <td align="center">141 &#177; 15</td>
                <td align="center">142 &#177; 23 (NS)</td>
                <td align="center">Hermann et al., 2011</td>
              </tr>
              <tr>
                <td align="center">130 &#177; 17</td>
                <td align="center">136 &#177; 16 (NS)</td>
                <td align="center">131 &#177; 20</td>
                <td align="center">129 &#177; 14 (NS)</td>
                <td align="center">Nytroen et al., 2012</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">PAD</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">Haykowsky et al., 2009</td>
              </tr>
              <tr>
                <td align="center">85 &#177; 7</td>
                <td align="center">82 &#177; 9 (NS)</td>
                <td align="center">82 &#177; 9</td>
                <td align="center">84 &#177; 14 (NS)</td>
                <td align="center">Hermann et al., 2011</td>
              </tr>
              <tr>
                <td align="center">80 &#177; 10</td>
                <td align="center">82 &#177; 9 (NS)</td>
                <td align="center">81 &#177; 15</td>
                <td align="center">82 &#177; 17 (NS)</td>
                <td align="center">Nytroen et al., 2012</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">PASpico</td>
                <td align="center">175 &#177; 26</td>
                <td align="center">177 &#177; 21 (NS)</td>
                <td align="center">172 &#177; 29</td>
                <td align="center">180 &#177; 27 (NS)</td>
                <td align="center">Haykowsky et al., 2009</td>
              </tr>
              <tr>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">Hermann et al., 2011</td>
              </tr>
              <tr>
                <td align="center">181 &#177; 33</td>
                <td align="center">211 &#177; 66 (&lt; 0,05)</td>
                <td align="center">197 &#177; 22</td>
                <td align="center">191 &#177; 32 (NS)</td>
                <td align="center">Nytroen et al., 2012</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">PADpico</td>
                <td align="center">81 &#177; 9</td>
                <td align="center">79 &#177; 9 (NS)</td>
                <td align="center">81 &#177; 8</td>
                <td align="center">80 &#177; 9 (NS)</td>
                <td align="center">Haykowsky et al., 2009</td>
              </tr>
              <tr>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">Hermann et al., 2011</td>
              </tr>
              <tr>
                <td align="center">71 &#177; 15</td>
                <td align="center">80 &#177; 14 (&lt; 0,05)</td>
                <td align="center">83 &#177; 14</td>
                <td align="center">91 &#177; 35 (NS)</td>
                <td align="center">Nytroen et al., 2012</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN6">
              <p>TIAI: treinamento intervalado de alta intensidade; FC: frequ&#234;ncia card&#237;aca; FMD: dilata&#231;&#227;o da art&#233;ria braquial mediada pelo fluxo; PAS: press&#227;o arterial sist&#243;lica: PAD: press&#227;o arterial diast&#243;lica: NS: n&#227;o significativo.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Todos os estudos inclu&#237;dos tiveram a vari&#225;vel VO<sub>2</sub>pico como desfecho principal de an&#225;lise. Nesse sentido, a <xref ref-type="fig" rid="f5">Figura 2</xref> apresenta o efeito sum&#225;rio aumentado [IC 95%: 4,45 (2,15 - 6,75), p = 0,0001, N = 118] da contribui&#231;&#227;o do TIAI (24,3 &#177; 6,5 - 28,0 &#177; 6,7 ml/kg.min; 15%) em rela&#231;&#227;o ao grupo controle (23,8 &#177; 6,0 - 23,2 &#177; 5,9 ml/kg.min; -2%) sobre o VO<sub>2</sub>pico. J&#225; para a vari&#225;vel FCpico, a partir da an&#225;lise comparativa entre os grupos foi poss&#237;vel identificar em dois estudos inclu&#237;dos na revis&#227;o efeito favor&#225;vel [IC 95%: 0,74 (0,31 - 1,16) p = 0,0007, N = 46] ao grupo TIAI, conforme a <xref ref-type="fig" rid="f6">Figura 3</xref>.</p>
        <p>
          <fig id="f5">
            <label>Figura 2</label>
            <caption>
              <title>Forest plot (A) e funnel plot (B) apresentando informa&#231;&#245;es relacionadas ao treinamento intervalado de alta intensidade (TIAI) sobre o VO<sub>2</sub>pico.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-02-0188-80017-gf02-pt.jpg"/></fig>
        </p>
        <p>
          <fig id="f6">
            <label>Figura 3</label>
            <caption>
              <title>Forest plot (A) e funnel plot (B) apresentando informa&#231;&#245;es relacionadas ao treinamento intervalado de alta intensidade (TIAI) sobre a frequ&#234;ncia card&#237;aca pico.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-02-0188-80017-gf03-pt.jpg"/></fig>
        </p>
        <p>Outros resultados reportados pelos estudos que n&#227;o foram analisados estatisticamente (<italic>forest plot</italic>) demonstraram que o grupo TIAI apresentou efeito positivo sobre a PA (sist&#243;lica e diast&#243;lica) de repouso e pico, velocidade de fluxo braquial, for&#231;a muscular m&#225;xima (1 RM), manuten&#231;&#227;o da massa magra e biomarcadores inflamat&#243;rios. Alguns desses resultados est&#227;o apresentados na <xref ref-type="table" rid="t3">Tabela 3</xref>. Al&#233;m disso, nenhum dos estudos relatou a ocorr&#234;ncia de evento e/ou mortalidade cardiovascular associado ao treinamento, mostrando que &#233; uma pr&#225;tica segura a ser inclu&#237;da nos programas de reabilita&#231;&#227;o card&#237;aca.</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>A presente revis&#227;o sistem&#225;tica com meta-an&#225;lise &#233; a primeira a analisar o efeito do TIAI sobre alguns par&#226;metros relacionados &#224; sa&#250;de dos pacientes p&#243;s TC. De acordo com os tr&#234;s estudos inclu&#237;dos, foi poss&#237;vel verificar que o TIAI proporcionou melhora de 15% sobre o VO<sub>2</sub>pico. Tal aumento &#233; superior ao encontrado em duas revis&#245;es sistem&#225;ticas com meta-an&#225;lise que avaliaram o efeito de diferentes formas de exerc&#237;cio<xref ref-type="bibr" rid="B26">26</xref> e do TCMI<xref ref-type="bibr" rid="B27">27</xref> sobre o VO<sub>2</sub>pico desses pacientes.</p>
        <p>Apesar de o TIAI proporcionar benef&#237;cios em torno do VO<sub>2</sub>pico, muitas vezes o mesmo n&#227;o &#233; indicado para o p&#250;blico p&#243;s TC pelo fato de esses pacientes apresentarem insufici&#234;ncia cronotr&#243;pica desenvolvida a partir da denerva&#231;&#227;o card&#237;aca.<xref ref-type="bibr" rid="B28">28</xref> Essa incompet&#234;ncia causa preju&#237;zo na FC de repouso (aumento) e durante (diminui&#231;&#227;o) a realiza&#231;&#227;o de exerc&#237;cios pr&#243;ximos &#224; intensidade pico (FCpico), diminuindo os valores da reserva cronotr&#243;pica. Nesse sentido, de acordo com os estudos analisados na presente revis&#227;o, pode-se notar que 8 a 12 semanas de interven&#231;&#227;o com TIAI podem causar diminui&#231;&#245;es nos valores de FC repouso e aumentos na FCpico. Provavelmente os est&#237;mulos em alta intensidade (&gt; 80%VO<sub>2</sub>pico ou &gt; 85%FCm&#225;x) causaram melhora na fun&#231;&#227;o cardiocirculat&#243;ria, estimulando mais rapidamente o n&#243; sinusal, o que de fato facilita respostas mais r&#225;pidas e melhores sobre a FC de repouso e pico.<xref ref-type="bibr" rid="B29">29</xref>
				</p>
        <p>Mesmo que a literatura apresente um n&#250;mero insuficiente de pesquisas relacionadas ao TIAI e pacientes p&#243;s TC, &#233; poss&#237;vel verificar que esse tipo de treinamento possibilita benef&#237;cios centrais e perif&#233;ricos importantes para melhorar o quadro cl&#237;nico ap&#243;s o procedimento cir&#250;rgico.<xref ref-type="bibr" rid="B30">30</xref> Al&#233;m disso, recentes estudos que compararam a contribui&#231;&#227;o do TIAI e TCMI sobre as vari&#225;veis deficit&#225;rias dos transplantados de cora&#231;&#227;o demonstraram efeito superior do TIAI.<xref ref-type="bibr" rid="B31">31</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref> Tais resultados podem indicar uma poss&#237;vel mudan&#231;a de paradigma no que tange &#224;s recomenda&#231;&#245;es da prescri&#231;&#227;o de exerc&#237;cio para pacientes transplantados. Assim, torna-se necess&#225;rio a realiza&#231;&#227;o de pesquisas futuras com o intuito de identificar qual protocolo de treinamento possibilita melhoras de maior magnitude sobre as vari&#225;veis deficit&#225;rias desses pacientes.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Nossos resultados demonstraram que 8 a 12 semanas de reabilita&#231;&#227;o card&#237;aca com TIAI foram suficientes para provocar aumentos significativos na FCpico e pot&#234;ncia aer&#243;bia de pacientes (homens e mulheres) transplantados de cora&#231;&#227;o.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <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 faz parte da tese de doutorado de Raphael Jos&#233; Perrier-Melo da Universidade de Pernambuco.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Aprova&#231;&#227;o &#201;tica e consentimento informado</bold>
          </p>
          <p>Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
