<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.1" specific-use="sps-1.7" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">ijcs</journal-id>
      <journal-title-group>
        <journal-title>International Journal of Cardiovascular Sciences</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Int. J. Cardiovasc. Sci.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">2359-4802</issn>
      <issn pub-type="epub">2359-5647</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">VcQSmrQmvh3p39QMhBdTWnR</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S2359-56472018000200143</article-id>
      <article-id pub-id-type="doi">10.5935/2359-4802.20180001</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Study with a Portable Gas Analyzer of the 6-Minute Walk Test in Heart Failure with Normal Ejection Fraction</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Teixeira</surname>
            <given-names>Jos&#233; Ant&#244;nio Caldas</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Messias</surname>
            <given-names>Leandro Rocha</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Dias</surname>
            <given-names>K&#225;tia Pedreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Washington Luiz Batista da</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cascon</surname>
            <given-names>Roberto Macedo</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Miranda</surname>
            <given-names>Sandra Marina Ribeiro de</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Teixeira</surname>
            <given-names>Pedro Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Jorge</surname>
            <given-names>Juliana Grael</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nobrega</surname>
            <given-names>Antonio Claudio Lucas da</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Araujo</surname>
            <given-names>Denizar V</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">5</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade Federal Fluminense</institution>
        <addr-line>
          <city>Rio de Janeiro</city>
          <state>RJ</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal Fluminense (UFF), Rio de Janeiro, RJ &#8211; Brazil</institution>
        <institution content-type="normalized">Universidade Federal Fluminense</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Cl&#237;nica Fit Center</institution>
        <addr-line>
          <city>Rio de Janeiro</city>
          <state>RJ</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Cl&#237;nica Fit Center</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Complexo Hospitalar de Niter&#243;i</institution>
        <addr-line>
          <city>Rio de Janeiro</city>
          <state>RJ</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Complexo Hospitalar de Niter&#243;i, Rio de Janeiro, RJ &#8211; Brazil</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Rede Dor</institution>
        <institution content-type="orgdiv1">Servi&#231;o de Arritmia</institution>
        <addr-line>
          <city>Rio de Janeiro</city>
          <state>RJ</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Servi&#231;o de Arritmia da Rede Dor, Rio de Janeiro, RJ &#8211; Brazil</institution>
      </aff>
      <aff id="aff5">
        <label>5</label>
        <institution content-type="orgname">Universidade do Estado do Rio de Janeiro</institution>
        <addr-line>
          <city>Rio de Janeiro</city>
          <state>RJ</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ &#8211; Brazil</institution>
        <institution content-type="normalized">Universidade do Estado do Rio de Janeiro</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Jos&#233; Ant&#244;nio Caldas Teixeira</bold>, Rua Presidente Jo&#227;o Pessoa, 248. Postal Code: 24220-331, Icara&#237;, Niter&#243;i, RJ &#8211; Brazil. E-mail: <email>jacaldas_@hotmail.com</email>, <email>jacaldas@uninet.com.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Teixeira JAC, Nobrega ACL, Araujo DV. Acquisition of data: Teixeira JAC, Messias LR, Dias KP, Costa WLB, Cascon RM, Miranda SMR, Teixeira PS, Jorge JG. Analysis and interpretation of the data: Teixeira JAC, Messias LR, Dias KP, Costa WLB, Teixeira PS, Nobrega ACL, Araujo DV. Writing of the manuscript: Teixeira JAC, Teixeira PS, Jorge JG. Critical revision of the manuscript for intellectual content: Teixeira JAC, Nobrega ACL, Araujo DV. Bibliographic Survey: Teixeira JAC, Messias LR, Miranda SMR. Bibliographic Review: Costa WLB, Cascon RM.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <season>Mar-Apr</season>
        <year>2018</year>
      </pub-date>
      <volume>31</volume>
      <issue>2</issue>
      <fpage>143</fpage>
      <lpage>151</lpage>
      <history>
        <date date-type="received">
          <day>6</day>
          <month>2</month>
          <year>2017</year>
        </date>
        <date date-type="rev-recd">
          <day>1</day>
          <month>6</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>31</day>
          <month>7</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Few studies have used portable gas analyzers during the 6-minute walk test (6MWT) in patients with heart failure and normal ejection fraction (HFNEF).</p>
        </sec>
        <sec>
          <title>Objectives:</title>
          <p>To analyze the kinetics of hemodynamic, ventilatory, and metabolic variables in patients with HFNEF during the T6m using a portable gas analyzer.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>Prospective, analytical study with an intentional, non-probabilistic, convenience sample. In total, 24 patients with HFNEF and past hospital admissions due to a clinical diagnosis of heart failure (HF) were included using the 2007 criteria established by the European Society of Cardiology. Three assessments were performed: 6MWT familiarization, 6MWT with the portable gas analyzer, and cardiopulmonary exercise test (CPET).</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>The heart rates (HRs) and the peak VO<sub>2</sub> at the end of the 6MWT corresponded to 85.7% and 86.45% of the values obtained during the CPET. The final HRs after the T6m were equivalent to those obtained at the CPET anaerobic threshold (AT), with relative VO<sub>2</sub> values at the end of the 6MWT above the VO<sub>2</sub> of the CPET AT. There was no difference between the maximum respiratory quotient (RQ) values in these two tests, which were both above 1.0. The VE/VO<sub>2</sub> slope descended initially and then ascended significantly after the fifth minute of the test, estimating the identification of the AT.</p>
          <p>Conclusions: In patients with HFNEF, the 6MWT represents an almost maximum effort, and is performed above the CPET AT and 85% above the maximum HR and the CPET peak VO<sub>2</sub>, with a maximum RQ similar to that in the CPET.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Heart Failure</kwd>
        <kwd>Blood Gas Analysis</kwd>
        <kwd>Stroke Volume</kwd>
        <kwd>Exercise</kwd>
        <kwd>Walk Test</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Heart failure (HF) evokes the image of a dilated heart with reduced systolic function and ejection fraction (HF with reduced ejection fraction, HFREF). However, the study by Burkhoff et al.,<xref ref-type="bibr" rid="B1">1</xref> has shown that a large proportion of patients with HF symptoms has an ejection fraction within the normal range, and are then classified as having HF with normal ejection fraction (HFNEF).<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref> The limited tolerance to physical effort in HF is often the first and main clinical characteristic of the disease.<xref ref-type="bibr" rid="B4">4</xref> In the identification of this exercise intolerance, the 6-minute walk test (6MWT) has been used as an instrument to evaluate the progression after different interventions.<xref ref-type="bibr" rid="B5">5</xref>
			</p>
      <p>Only a few studies have been conducted using portable gas analyzers to describe and analyze the behavior of variables in the 6MWT and possible characteristics or markers that may help guide the therapy and improve the prognosis in HF,<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B10">10</xref> particularly in patients with HFNEF.</p>
      <p>The aim of this study was to describe and analyze the kinetic behavior at each minute of hemodynamic, ventilatory, and metabolic variables in patients with HFNEF during the 6MWT using a portable gas analyzer, and to compare the findings with those obtained during a cardiopulmonary exercise test (CPET).</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>Prospective, analytical study with a non-probabilistic, intentional, and convenience sample, as set by the adopted criteria, carried out at the <italic>Hospital Universit&#225;rio Ant&#244;nio Pedro</italic> (HUAP) of the <italic>Universidade Federal Fluminense</italic> (UFF) between March 2010 and July 2013. The study project was approved by the Ethics Research Committee at HUAP under the number 152A/2010, and all participants signed an informed consent form.</p>
      <p>The inclusion criteria adopted to characterize HFNEF were those described by Paulus et al., <xref ref-type="bibr" rid="B11">11</xref> in addition to the following factors: (A) complaints suggestive of HF (dyspnea, fatigue, and/or edema); (B) report of prior hospitalization due to decompensated heart disease, but at the moment of the test presenting with a functional class II to III according to the New York Heart Association (NYHA); (c) age &gt; 18 years; (d) disease duration greater than 6 months; (e) use of medication; and (F) stable disease.</p>
      <p>The exclusion criteria adopted were: (A) chronic obstructive pulmonary disease (COPD) based on clinical criteria, (B) functional class IV or other criteria contraindicating the CPET,<xref ref-type="bibr" rid="B12">12</xref> and (C) participation in supervised cardiac rehabilitation programs.</p>
      <p>The patients were instructed to maintain the current medications. The tests comprised three moments: conventional 6MWT (6MWT1), 6MWT coupled to a portable gas analyzer (6MWT2), and CPET on a treadmill. Due to a matter related to the hospital's flow, some patients were first assigned randomly to the 6MWT and others to the CPET.</p>
      <p>The 6MWT was performed in a hallway with an extension of 30 meters. The first 6MWT (6MWT1) had a learning effect as objective, as recommended in the literature.<xref ref-type="bibr" rid="B6">6</xref> The second 6MWT (6MWT2) was performed at least 3 days and no more than 3 weeks after the first, when the patients repeated the 6MWT, but this time they were connected to a portable gas analyzer. The maximum interval between the 6MWT and the CPET was also 3 weeks. Both the 6MWT and the CPET were scheduled by the same evaluator and applied by the same team to avoid application variability.</p>
      <p>We used for the assessments the metabolic analyzer MedGraphics (MGC) VO2000 (Imbrasport, Porto Alegre, RS, Brazil), the system Ergo PC Elite 13, and the treadmill Centurion 300 (MicroMed<italic>,</italic> Bras&#237;lia, DF, Brazil). The gas analyzer was calibrated before each test by the autocalibration system in a ventilated environment. The biological control of the calibration was performed monthly and the control by the equipment's representative (CAEL, Rio de Janeiro, RJ, Brazil) was conducted every 3 months.</p>
      <p>In the CPET, each patient underwent a 2-minute baseline collection followed by a 1-minute warm-up at 1 km/h and 0&#186; slope before starting the ramp protocol. In order to analyze and assess the CPET variables, we used the software ErgoPCElite for Windows 13W (MicroMed, Bras&#237;lia, DF, Brazil). The perceived exertion (PE), assessed by the Borg scale (variation 0-10), and the hemodynamic and electrocardiographic variables were recorded at every minute. During the recovery phase, the patient remained seated. Two referees analyzed the report of the test to obtain the following information: VE/VCO<sub>2</sub> slope value, presence of oscillatory breathing (OB), and establishment of the ventilatory threshold I, referred from now on as the anaerobic threshold (AT). In order to determine the AT, we used the curves of the ventilatory equivalents of the VO<sub>2</sub> and VCO<sub>2</sub>, in addition to the curves of VO<sub>2</sub> and VCO<sub>2</sub> expired fractions, as recommended by the CPET guideline of the American Heart Association (AHA).<xref ref-type="bibr" rid="B13">13</xref>
			</p>
      <p>The evaluations were performed while the patients maintained the use of their usual medications, during the same time of the day, and at least 2 hours after the last meal. Peak VO<sub>2</sub> was defined as the highest VO<sub>2</sub> value obtained up to the final 30 seconds or 10 seconds into the immediate recovery. In order to determine the occurrence of OB and the value of the VE/VCO<sub>2</sub> slope, we followed the AHA guideline<xref ref-type="bibr" rid="B13">13</xref> and the recommendations by Guazzi et al.,<xref ref-type="bibr" rid="B14">14</xref> Since spirometry was not performed, the ventilatory reserve was not considered in the analysis. Only one CPET was performed, as recommended by Scott et al.,<xref ref-type="bibr" rid="B15">15</xref>
			</p>
      <p>The maximum estimated heart rate (HR) was obtained using the formula by Tanaka et al., <xref ref-type="bibr" rid="B16">16</xref> and was used to calculate the chronotropic index.</p>
      <p>During the 6MWT, we recorded the HR (Polar monitor, model T31, Oulu, Finland) at each minute, along with the PE according to the Borg scale and the capillary O<sub>2</sub> saturation using a pulse oximeter (Onyx, Minneapolis, MN<italic>,</italic> USA<italic>).</italic></p>
      <p>In order to analyze the gases expired during the 6MWT and obtain the values of the variables, we used the same VO2000 in a portable mode connected wirelessly to a computer. We used the software Aerograph, version 4.3 <italic>(</italic>Imbrasport, Porto Alegre, RS, Brazil), which organized the data for later analysis.</p>
      <p>During the 6MWT, the patient connected to the gas analyzer remained seated for 4 minutes and 30 seconds. After the values of the variables were collected during this resting period, the patient stood up for 30 seconds before initiating the 6MWT, which was performed according to the guidelines of the American Thoracic Society (ATS).<xref ref-type="bibr" rid="B5">5</xref>
			</p>
      <p>All patients completed the 6 minutes of walk. The gas analysis ended after the fifth minute of recovery. The maximum blood pressure (BP) considered in the analysis was the one obtained immediately after the effort, <italic>i.e.</italic>, after the sixth minute of the walk when the patient sat down and the BP was then measured between 30-40 seconds during recovery.</p>
      <sec>
        <title>Statistical analysis</title>
        <p>The numerical data are expressed as mean &#177; standard deviation (SD) since all the variables included had an approximately normal distribution (p value of the Kolmogorov-Smirnov test &gt; 0.05). Categorical data are expressed as frequency (n) and percentage (%).</p>
        <p>The variation of the hemodynamic, metabolic, and ventilatory measurements between the tests (assessments) CPET and 6MWT were analyzed by Student's <italic>t</italic> test for paired samples.</p>
        <p>A descriptive graphic analysis was performed, presenting the mean and SD values of the measurements obtained at each minute of the variables HR and VO<sub>2</sub>, indicating, for each one of these variables, the maximum CPET values and values equivalent to the AT.</p>
        <p>In order to evaluate the correlation levels between the 6MWT distance and the peak VO<sub>2</sub> and CPET peak VO<sub>2</sub>, we used Pearson's correlation coefficient (r).</p>
        <p>We adopted a significance level of 5%. The statistical analysis was performed using the software SAS 6.11 (SAS Institute, Inc. Cary, NC, USA).</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>A total of 24 patients were evaluated. Of these, 22 underwent both tests (CPET and 6MWT) while two underwent only the CPET; thus, the comparison between the CPET and 6MWT included only data of 22 patients. <xref ref-type="table" rid="t1">Table 1</xref> shows the baseline characteristics of the study population. There was a predominance of the female gender (70.8%) and obesity (58.3%). Hypertension was present in 100.0% of the patients.</p>
      <table-wrap id="t1">
        <label>Table 1</label>
        <caption>
          <title>Clinical characteristics of the study population</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="20%"/>
            <col width="20%"/>
            <col width="20%"/>
            <col width="20%"/>
            <col width="20%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="center" style="background-color:#C5C6C8">Variables</th>
              <th align="center" style="background-color:#C5C6C8">
							</th>
              <th align="center" style="background-color:#C5C6C8">
							</th>
              <th align="center" style="background-color:#C5C6C8">n = 24</th>
              <th align="center" style="background-color:#C5C6C8">%</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left" rowspan="2">Sex</td>
              <td align="center">male</td>
              <td align="center">
							</td>
              <td align="center">7</td>
              <td align="center">29.2</td>
            </tr>
            <tr>
              <td align="left">female</td>
              <td align="center">
							</td>
              <td align="center">17</td>
              <td align="center">70.8</td>
            </tr>
            <tr style="border-bottom-width:thin;border-bottom-style:solid;border-top-width:thin;border-top-style:solid">
              <td align="center" style="background-color:#C5C6C8">
							</td>
              <td align="center" style="background-color:#C5C6C8">
							</td>
              <td align="center" style="background-color:#C5C6C8">
                <bold>Mean</bold>
              </td>
              <td align="center" style="background-color:#C5C6C8">
							</td>
              <td align="center" style="background-color:#C5C6C8">
                <bold>SD</bold>
              </td>
            </tr>
            <tr>
              <td align="left">EF (%)</td>
              <td align="center">
							</td>
              <td align="center">64.7</td>
              <td align="center">
							</td>
              <td align="center">8.2</td>
            </tr>
            <tr>
              <td align="left">Weight (kg)</td>
              <td align="center">
							</td>
              <td align="center">84.3</td>
              <td align="center">
							</td>
              <td align="center">16.6</td>
            </tr>
            <tr>
              <td align="left">Height (cm)</td>
              <td align="center">
							</td>
              <td align="center">160.2</td>
              <td align="center">
							</td>
              <td align="center">7.4</td>
            </tr>
            <tr>
              <td align="left">BMI</td>
              <td align="center">
							</td>
              <td align="center">32.9</td>
              <td align="center">
							</td>
              <td align="center">6.7</td>
            </tr>
            <tr>
              <td align="left">Waist (cm)</td>
              <td align="center">
							</td>
              <td align="center">104.4</td>
              <td align="center">
							</td>
              <td align="center">13.3</td>
            </tr>
            <tr>
              <td align="left">Hip (cm)</td>
              <td align="center">
							</td>
              <td align="center">110.8</td>
              <td align="center">
							</td>
              <td align="center">11.6</td>
            </tr>
            <tr>
              <td align="left">W/H</td>
              <td align="center">
							</td>
              <td align="center">0.944</td>
              <td align="center">
							</td>
              <td align="center">0.086</td>
            </tr>
            <tr>
              <td align="left">Age (years)</td>
              <td align="center">
							</td>
              <td align="center">59.6</td>
              <td align="center">
							</td>
              <td align="center">10.2</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <p>Abbreviations: EF: ejection fraction; BMI: body mass index; W/H: waist-to-hip ratio; SD: standard deviation.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Most patients (70.8%) used beta-blockers. The profile of the medications used by the patients showed the usual therapeutic approach for hypertension: beta-blockers, angiotensin-converting enzyme inhibitors (25.0%) or angiotensin receptor blockers (54.1%), calcium channel blockers (37.5%), thiazides (29.1%), and vasodilators (48.5%).</p>
      <p>A stratification of the patients according to the results of the CEPT and following the classification by Weber<xref ref-type="bibr" rid="B17">17</xref> showed a higher percentage of patients categorized as class B (30.4%).</p>
      <p>The patients had a mean E/E' of 15.9 &#177; 4.3, which fulfilled one of the criteria for diagnosis of HFNEF.<xref ref-type="bibr" rid="B11">11</xref>
			</p>
      <p>The mean walked distance was 419.2 &#177; 76.5 meters during the 6MWT1 and 446.2 &#177; 67.7 meters during the 6MWT2, with a significant difference between both groups (p = 0.002).</p>
      <p><xref ref-type="table" rid="t2">Table 2</xref> shows the maximum values of the variables obtained in the 6MWT2 and in the CPET. There was no difference between the maximum respiratory quotient (RQ) values of the two tests, and their maximum values were greater than 1.0. The results showed increased values at the end of the 6MWT2 (1.04), and of 22 patients who underwent the 6MWT2, 11 had an RQ &#8805; 1.0 (50% of the group). Of these 11 patients, 7 obtained an RQ &#8805; 1.10 (31.8% of the sample).</p>
      <table-wrap id="t2">
        <label>Table 2</label>
        <caption>
          <title>Maximum variables obtained in the 6-minute walk test (6MWT) and the cardiopulmonary exercise test (CPET) (n = 22)</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" colspan="6" style="background-color:#C5C6C8">Mean values - 6MWTversus CPET</th>
            </tr>
            <tr>
              <th align="center" style="background-color:#C5C6C8">
							</th>
              <th align="center" style="background-color:#C5C6C8">6MWT</th>
              <th align="center" style="background-color:#C5C6C8">SD</th>
              <th align="center" style="background-color:#C5C6C8">CPET</th>
              <th align="center" style="background-color:#C5C6C8">SD</th>
              <th align="center" style="background-color:#C5C6C8">p &lt; 0.05</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Max SBP</td>
              <td align="center">187.04</td>
              <td align="center">26.60</td>
              <td align="center">215.3</td>
              <td align="center">27.4</td>
              <td align="center">0.002</td>
            </tr>
            <tr>
              <td align="left">Max DBP</td>
              <td align="center">97.80</td>
              <td align="center">13.7</td>
              <td align="center">104.1</td>
              <td align="center">16.0</td>
              <td align="center">0.09</td>
            </tr>
            <tr>
              <td align="left">Max DP</td>
              <td align="center">20951</td>
              <td align="center">5497</td>
              <td align="center">27524</td>
              <td align="center">6130</td>
              <td align="center">0.0004</td>
            </tr>
            <tr>
              <td align="left">CircPot</td>
              <td align="center">2533</td>
              <td align="center">957</td>
              <td align="center">3462</td>
              <td align="center">1266</td>
              <td align="center">0.002</td>
            </tr>
            <tr>
              <td align="left">Max HR</td>
              <td align="center">110.9</td>
              <td align="center">18.1</td>
              <td align="center">125.4</td>
              <td align="center">19.6</td>
              <td align="center">0.004</td>
            </tr>
            <tr>
              <td align="left">HR1Rec</td>
              <td align="center">23.1</td>
              <td align="center">10.1</td>
              <td align="center">17.2</td>
              <td align="center">10.1</td>
              <td align="center">0.035</td>
            </tr>
            <tr>
              <td align="left">ChronI</td>
              <td align="center">0.42</td>
              <td align="center">0.2</td>
              <td align="center">0.57</td>
              <td align="center">0.1</td>
              <td align="center">0.002</td>
            </tr>
            <tr>
              <td align="left">O<sub>2</sub> pulse</td>
              <td align="center">10.5</td>
              <td align="center">3.6</td>
              <td align="center">10.5</td>
              <td align="center">3.5</td>
              <td align="center">0.95</td>
            </tr>
            <tr>
              <td align="left">Max RQ</td>
              <td align="center">1.06</td>
              <td align="center">0.24</td>
              <td align="center">1.08</td>
              <td align="center">0.09</td>
              <td align="center">0.47</td>
            </tr>
            <tr>
              <td align="left">VE/VCO<sub>2</sub> slope</td>
              <td align="center">22.3</td>
              <td align="center">4.8</td>
              <td align="center">23.2</td>
              <td align="center">4.4</td>
              <td align="center">0.10</td>
            </tr>
            <tr>
              <td align="left">VP</td>
              <td align="center">8.31</td>
              <td align="center">1.92</td>
              <td align="center">9.59</td>
              <td align="center">2.11</td>
              <td align="center">0.0002</td>
            </tr>
            <tr>
              <td align="left">Peak VO<sub>2</sub> (mL.kg<sup>-1</sup>. min<sup>-1</sup>)</td>
              <td align="center">13.8</td>
              <td align="center">4.1</td>
              <td align="center">15.9</td>
              <td align="center">5.4</td>
              <td align="center">0.025</td>
            </tr>
            <tr>
              <td align="left">T1/2</td>
              <td align="center">61.4</td>
              <td align="center">16.5</td>
              <td align="center">111.2</td>
              <td align="center">25.7</td>
              <td align="center">0.0001</td>
            </tr>
            <tr>
              <td align="left">OUES</td>
              <td align="center">1.26</td>
              <td align="center">0.74</td>
              <td align="center">1.34</td>
              <td align="center">0.59</td>
              <td align="center">0.10</td>
            </tr>
            <tr>
              <td align="left">AT VO<sub>2</sub></td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">11.76</td>
              <td align="center">3.79</td>
              <td align="center">
							</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN2">
            <p>Max SBP: maximum systolic blood pressure; Max DBP: maximum diastolic blood pressure; Max DP: maximum double product; CircPot: circulatory power; Max HR: maximum heart rate; HR1Rec: heart rate in the first minute of recovery; ChronoI: chronotropic index; O<sub>2</sub>pulse: oxygen pulse (mL.kg<sup>-1</sup>.min<sup>-1</sup>/bpm); Max RQ: maximum respiratory quotient; VE/VCO<sub>2</sub> slope: ventilation minute to carbon dioxide production ratio; VP: ventilatory power; peak VO<sub>2</sub> (mL.kg<sup>-1</sup>. min<sup>-1</sup>): oxygen consumption peak; T1/2: time (in seconds) of the recovery kinetics of oxygen consumption up to half of the value of peak effort; OUES: oxygen uptake efficiency slope; AT: anaerobic threshold; 6MWT2: second 6-minute walk test; CPET: cardiopulmonary exercise test; SD: standard deviation. All heart rate values are represented in beats per minute.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Since BP measurement during the 6MWT was not feasible, BP was only measured in the baseline condition and immediately after the 6MWT. Considering that prior spirometry was not performed, other ventilatory parameters were not assessed.</p>
      <p>The longitudinal analysis of the HR during the 6MWT2 showed that the group reached stable HR values after the second minute of the 6MWT2 (T3). The maximum HR during the 6MWT2 (108.9 bpm) was similar to the HR at the CPET AT (108 bpm), shown by the dashed line (<xref ref-type="fig" rid="f1">Figure 1</xref>), and 85.7% compared with the CPET maximum HR (126 bpm), highlighted in the Figure.</p>
      <p>
        <fig id="f1">
          <label>Figure 1</label>
          <caption>
            <title>Longitudinal progression of the heart rate (HR) during the second 6-minute walk test (6MWT2) in the study participants. HFNEF: heart failure with normal ejection fraction; CPET: cardiopulmonary exercise test; maxHR: maximum heart rate; AT: CPET anaerobic threshold; T1: time zero of the 6MWT (baseline conditions); T2, T3, T4, T5, T6, T7: first, second, third, fourth, fifth, and sixth minutes of the 6MWT, respectively.</title>
          </caption>
          <graphic xlink:href="2359-5647-ijcs-31-02-0143-80001-gf01.jpg"/></fig>
      </p>
      <p>The longitudinal progression of the relative VO<sub>2</sub> (mL.kg<sup>-1</sup>.min<sup>-1</sup>) during the 6MWT2 in the study participants is shown in <xref ref-type="fig" rid="f2">Figure 2</xref>. Note in the dashed line the VO<sub>2</sub> value of the CPET AT (11.76 mL.kg<sup>-1</sup>. min<sup>-1</sup>) and in the highlighted area, the value of 15.9 mL.kg<sup>-1</sup>. min<sup>-1</sup> of the CPET peak VO<sub>2</sub> (<xref ref-type="fig" rid="f2">Figure 2</xref>).</p>
      <p>
        <fig id="f2">
          <label>Figure 2</label>
          <caption>
            <title>Longitudinal progression of the relative VO<sub>2</sub> (mL/kg/min<sup>-1</sup>) during the 6MWT2. HFNEF: heart failure with normal ejection fraction; CPET: cardiopulmonary exercise test; VO<sub>2</sub>: oxygen consumption (mL.kg<sup>-1</sup>.min<sup>-1</sup>); T1: time zero of the 6MWT (baseline conditions); T2, T3, T4, T5, T6, T7: first, second, third, fourth, fifth, and sixth minutes of the 6MWT, respectively, AT: anaerobic threshold.</title>
          </caption>
          <graphic xlink:href="2359-5647-ijcs-31-02-0143-80001-gf02.jpg"/></fig>
      </p>
      <p>The longitudinal progression of the production of carbon dioxide (VCO<sub>2</sub>) during the 6MWT2 occurred in a similar way to that of the VO<sub>2</sub>, reaching maximum values in the 6MWT2 of 11.5 mL.kg<sup>-1</sup>.min<sup>-1</sup> (not displayed).</p>
      <p>Pearson's correlation (r) levels found between the maximum walked distance in the 6MWT2 with the peak VO<sub>2</sub> obtained in the same test and between the walked distance with the CPET peak VO<sub>2</sub> were r = 0.528 (p = 0.014) and r = 0.532 (p = 0.013), respectively.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>A review of the literature on the subject of this study &#8211; 6MWT and HFNEF &#8211; has shown that most studies in this area are focused on HFREF. Therefore, it became difficult to compare the results found in the present study, which included patients with HFNEF, with data from the literature. Due to that, the discussion below will be based on similar results found in studies with HFREF.</p>
      <p>Riley et al.,<xref ref-type="bibr" rid="B6">6</xref> Foray et al.,<xref ref-type="bibr" rid="B7">7</xref> Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> and Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> analyzed the kinetics of variables using a portable gas analyzer and demonstrated that the kinetics and other cardiovascular parameters are decreased in HFREF in response to the effort imposed by the 6MWT. However, no studies have described how the kinetics of patients with HFREF respond during this test.</p>
      <p>Among the study patients, there was a predominance of patients of the female gender, with hypertension, and with an increased body mass index (BMI),<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref> characteristics that confirm the typical clinical profile of patients with HFNEF.</p>
      <p>The average distance walked is within the values that indicate a good prognosis, <italic>i.e.</italic>, above 300 meters.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref> A significant percentage (81.81%) equaled or increased in the 6MWT2 the distance walked during the 6MWT1 but did not obtain values of clinical significance, <italic>i.e.</italic>, above 50 meters.<xref ref-type="bibr" rid="B5">5</xref> This reinforces the importance of conducting at least one learning and familiarization test due to a potential influence on the results of the 6MWT.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref>
			</p>
      <p>The distances obtained are aligned with the average values found in studies with patients with HFREF, such as those by Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> (452.6 &#177; 18.7 meters), Faggiano et al., <xref ref-type="bibr" rid="B8">8</xref> (419 &#177; 120 meters), and Guimar&#227;es et al.,<xref ref-type="bibr" rid="B9">9</xref> (470 &#177; 48 meters).</p>
      <p>The correlation levels found between the 6MWT2 and the peak VO<sub>2</sub> in the 6MWT1 and with the CPET peak VO<sub>2</sub> are aligned with findings in the literature, despite some discrepancies. Some authors report a good correlation between the distance of the 6MWT and the peak VO<sub>2</sub>, with an average of 0.73 in patients with HF<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref> (all with HFREF). Riley et al.,<xref ref-type="bibr" rid="B6">6</xref> found a high correlation (r = 0.63), whereas Lucas et al.,<xref ref-type="bibr" rid="B20">20</xref> and Roul et al.,<xref ref-type="bibr" rid="B21">21</xref> found a low correlation with the walked distance in the 6MWT (r = 0.28 and r = 0.24, respectively). Such discrepancies could be attributed to different methodologies of the 6MWT and the type of ergometers used.</p>
      <p>The HFREF studies found in the literature assessing the 6MWT with portable gas analyzers and performed in a hallway were: Riley et al.,<xref ref-type="bibr" rid="B6">6</xref> Foray et al.,<xref ref-type="bibr" rid="B7">7</xref> Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> and Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> Guimar&#227;es et al., <xref ref-type="bibr" rid="B9">9</xref>, in turn, used the gas analyzer during two 6MWT tests performed on a treadmill, also in patients with HFREF.</p>
      <p>In regards to HR parameters, the study group showed more stable values after the second minute of the 6MWT (T3). Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> highlight that earlier achievement of a stable state reflect better clinical conditions and, therefore, less severe ones.</p>
      <p>The HR at the end of the 6MWT was 85.7% of the CPET maximum HR, which is similar to the percentage values of the peak VO<sub>2</sub> in the 6MWT in relation to the CPET peak VO<sub>2</sub>.</p>
      <p>It is noteworthy that the final HR in the 6MWT was similar to the HR in the CPET AT, reinforcing that the 6MWT represents an intense effort, carried out at the level of or above the CPET AT in patients with HF.<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref>
			</p>
      <p>Despite the authors&#8217; claim that patients with HFNEF present HR alterations in the first minute of recovery (HR1Rec)<xref ref-type="bibr" rid="B22">22</xref> and the fact that there are no data in the literature related to the 6MWT, if we consider the recommended value of 12 bpm, this value was within the normal limits both in the T6M as well as in the CPET.<xref ref-type="bibr" rid="B23">23</xref>
			</p>
      <p>The chronotropic index analysis demonstrated a chronotropic incompetence, even if we consider the use of beta-blockers (normal &gt; 0.60), both in relation to the 6MWT as well as to the CPET, as found in the literature.<xref ref-type="bibr" rid="B24">24</xref>
			</p>
      <p>The maximum O<sub>2</sub> pulse in the 6MWT and the CPET showed no difference between the two tests, yielding reduced pulse O<sub>2</sub> values in relation to the predicted one (&lt; 85%), around 70%, and with absolute values below 12 mL.kg<sup>-1</sup>.min<sup>-1</sup>/bpm, which is considered of poor prognosis.<xref ref-type="bibr" rid="B25">25</xref>
			</p>
      <p>In relation to the two ventilatory variables analyzed, no difference in the VE/VCO<sub>2</sub> slope was observed. The VE/VCO<sub>2</sub> slope values are within the values cited as indicative of good prognosis (&lt; 30),<xref ref-type="bibr" rid="B13">13</xref> and this fact associated with the lack of difference between the two tests can reinforce the prognostic ability of the 6MWT. The ventilatory power (VP) analysis also showed a difference between the two tests, with higher values for the CPET. The VP, which combines the response of the SBP with the VE/VCO<sub>2</sub> slope (VP = SBP x VE/VCO<sub>2</sub> slope)<xref ref-type="bibr" rid="B26">26</xref> showed a difference probably due to the higher SBP in the CPET. However, good prognosis values (&gt; 3.5) were observed for both tests.<xref ref-type="bibr" rid="B26">26</xref>
			</p>
      <p>The RQ is a criterion to obtain intense (&gt; 1.0) or maximum effort in exercises of increasing intensity (&gt; 1.15).<xref ref-type="bibr" rid="B13">13</xref> There was no difference between the maximum RQ values between the two tests. The data found here are in agreement with those found by Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> who consider the RQ in the 6MWT as reflecting intense effort. Both in the population with HFREF<xref ref-type="bibr" rid="B10">10</xref> and in patients with HFNEF in the study, 50% of each sample obtained an RQ &gt; 1.0. Other authors agree and claim that the greater the functional deficiency of the studied cohort, the more the 6MWT would be executed close to the maximum.<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref>
			</p>
      <p>In the analysis of the VE/VO<sub>2</sub>, the curve first descended and then ascended, which became significant after the fifth minute of the test (T6 and T7). Such progression is one of the criteria used to identify the CPET AT.<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref> When this concept is transferred to the 6MWT, it confirms that it represents an effort similar to or slightly above the AT.</p>
      <p>In regards to the VE/VCO<sub>2</sub>, the values stabilized after the second minute of effort (T3), with peak values slightly above those of the CPET AT (24.5 &#177; 3.1 in the 6MWT <italic>versus</italic> 23.6 of the CPET AT).The VE/VCO<sub>2</sub> stabilized in values that do not reflect ventilatory inefficiency.</p>
      <p>The relative VO<sub>2</sub> in the 6MWT showed stable values and its progression in patients with HFNEF did not differ from that found in similar studies in patients with HFREF, both in terms of progression during the 6MWT as well as in regards to the percentages obtained in relation to the CPET:<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref> it reached values above the VO<sub>2</sub> corresponding to the CPET AT and of significant percentages of the CPET peak VO<sub>2</sub> (86.45%).</p>
      <p>The variable VCO<sub>2</sub> tended to stabilize after T5 (the fourth minute of the 6MWT), which contrasts with the data presented by Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> in which this variable did not reach a stable state until the end of the 6MWT in patients with HFREF.</p>
      <p>The patients with HFREF in the study by Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> performed their 6MWT above the relative VO<sub>2</sub> of the CPET AT, which is aligned with findings in patients with HFNEF in this study. The VO<sub>2</sub> at the CPET AT obtained by Kervio et al., <xref ref-type="bibr" rid="B10">10</xref> (11.7 &#177; 0.6 mL.kg<sup>-1</sup>.min<sup>-1</sup>) is also very similar to that found in this study (11.76 mL.kg<sup>-1</sup>.min<sup>-1</sup>).</p>
      <p>It is interesting to note that 7 out of 22 patients in the present study had peak VO<sub>2</sub> in the 6MWT equal to or greater than the CPET peak VO<sub>2</sub>, representing 31.8% of the total sample. This percentage value is aligned and supersedes those by Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> (27.0%) in a HFREF population.</p>
      <p>The high intensity of the 6MWT for patients with HF is reinforced by findings from the study by Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> and Foray et al., <xref ref-type="bibr" rid="B7">7</xref> which demonstrated that the 6MWT leads to a demand above 85% of the values of the CPET relative peak VO<sub>2</sub>.</p>
      <p>Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> found a peak VO<sub>2</sub> at 86% of the CPET, which represented 73.0% of the VO<sub>2</sub> of the CPET AT. The present study showed similar percentages in relation to the CPET, but the VO<sub>2</sub> at the CPET AT presented higher percentages, corresponding to 85.03% of the peak VO<sub>2</sub> in the 6MWT in patients with HFNEF. Guimar&#227;es et al.,<xref ref-type="bibr" rid="B9">9</xref> analyzed the results of a single CPET and 6MWT on a treadmill, with the participants connected to a gas analyzer and, using an incentive, found a peak VO<sub>2</sub> at 90% of the CPET.</p>
      <p>The values of the CPET relative peak VO<sub>2</sub> are aligned with the findings by Guazzi et al.,<xref ref-type="bibr" rid="B27">27</xref> These authors found CPET peak VO<sub>2</sub> values of 15 mL.kg<sup>-1</sup>.min<sup>-1</sup> in HFNEF patients.</p>
      <p>The oxygen uptake efficiency slope (OUES) showed lower values in the 6MWT, but no difference in values was observed between the 6MWT and the CPET. Although the literature indicates that reduced values in both HFREF and HFNEF,<xref ref-type="bibr" rid="B13">13</xref> the HFNEF patients evaluated obtained values above 1.2, which are considered to be of poor prognosis.<xref ref-type="bibr" rid="B28">28</xref>
			</p>
      <p>The metabolic variable with the most difference was the kinetics of oxygen consumption during recovery (T1/2), which showed a significantly greater recovery time in the CPET. The T1/2 values in the 6MWT did not fulfill the criteria of poor prognosis.<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref><sup>,</sup><xref ref-type="bibr" rid="B29">29</xref> Considering that the value of 90 seconds<xref ref-type="bibr" rid="B29">29</xref> in the CPET, the study participants exceeded this value.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>There is an actual possibility of patients with HFNEF to be are able to perform a 6MWT at maximum or almost maximum intensity. This estimate is based on the following observations: high percentages obtained in peak values in the 6MWT in relation to the maximum value of the variables HR (85.7%) and relative VO<sub>2</sub> (86.4%) in the CPET, similar RQ values, similar peak VO<sub>2</sub> values in the 6MWT and at the CPET AT, and the progression of the VE/VO<sub>2</sub>, which after reaching a nadir, showed a trend to curve upward.</p>
      <p>It should be noted that in relation to the reviewed studies, all conducted in patients with HFREF, the assessed variables in HFNEF showed, on average, an equal profile during the 6MWT.</p>
      <sec>
        <title>Study limitations</title>
        <p>Some limitations in this study are identified:</p>
        <list list-type="bullet">
          <list-item>
            <p>Reduced size of the study sample. Further studies with an increased number of patients are suggested to validate some of the conclusions.</p>
          </list-item>
          <list-item>
            <p>The predominance of the female gender and overweight/obesity, characteristic of HFNEF, may have influenced the variables related to functional capacity in both 6MWT and CPET.</p>
          </list-item>
          <list-item>
            <p>The peripheral determinants of peak VO<sub>2</sub>, such as the oxygen transportation system or changes in peripheral muscles, were not considered in the functional assessment.</p>
          </list-item>
          <list-item>
            <p>The use of beta-blockers and other medications may have influenced the interpretation of variables that integrate HR or BP in their calculation.</p>
          </list-item>
        </list>
      </sec>
    </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 associate professor submitted by Jos&#233; Ant&#244;nio Caldas Teixeira, from Universidade Federal Fluminense.</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>
    <ref-list>
      <title>References</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1 Burkhoff D, Maurer MS, Packer M. Heart failure with a normal ejection fraction. is it really a disorder of diastolic function? Circulation. 2003;107(5):656-8. PMID: 12578861.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Burkhoff</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Maurer</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Packer</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Heart failure with a normal ejection fraction. is it really a disorder of diastolic function?</article-title>
          <source>Circulation</source>
          <year>2003</year>
          <volume>107</volume>
          <issue>5</issue>
          <fpage>656</fpage>
          <lpage>658</lpage>
          <pub-id pub-id-type="pmid">12578861</pub-id>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2 Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol. 1995;26(7):1565-74. doi: 10.1016/0735-1097(95)00381-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Vasan</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Benjamin</surname>
              <given-names>EJ</given-names>
            </name>
            <name>
              <surname>Levy</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective</article-title>
          <source>J Am Coll Cardiol</source>
          <year>1995</year>
          <volume>26</volume>
          <issue>7</issue>
          <fpage>1565</fpage>
          <lpage>1574</lpage>
          <pub-id pub-id-type="doi">10.1016/0735-1097(95)00381-9</pub-id>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3 Zile MR, Kjellstrom B, Bennett T, Cho Y, Baicu CF, Aaron MF, et al. Effects of exercise on left ventricular systolic and diastolic properties in patients with heart failure and a preserved ejection fraction versus heart failure and a reduced ejection fraction. Circ Heart Fail. 2013;6(3):508-16. doi: 10.1161/CIRCHEARTFAILURE.112.000216.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Zile</surname>
              <given-names>MR</given-names>
            </name>
            <name>
              <surname>Kjellstrom</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Bennett</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Cho</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Baicu</surname>
              <given-names>CF</given-names>
            </name>
            <name>
              <surname>Aaron</surname>
              <given-names>MF</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Effects of exercise on left ventricular systolic and diastolic properties in patients with heart failure and a preserved ejection fraction versus heart failure and a reduced ejection fraction</article-title>
          <source>Circ Heart Fail</source>
          <year>2013</year>
          <volume>6</volume>
          <issue>3</issue>
          <fpage>508</fpage>
          <lpage>516</lpage>
          <pub-id pub-id-type="doi">10.1161/CIRCHEARTFAILURE.112.000216</pub-id>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4 Downing J, Balady GJ. The role of exercise training in heart failure. J Am Coll Cardiol. 2011;58(6):561-9. doi: 10.1016/j.jacc.2011.04.020.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Downing</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Balady</surname>
              <given-names>GJ</given-names>
            </name>
          </person-group>
          <article-title>The role of exercise training in heart failure</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2011</year>
          <volume>58</volume>
          <issue>6</issue>
          <fpage>561</fpage>
          <lpage>569</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2011.04.020</pub-id>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5 ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <collab>ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories</collab>
          </person-group>
          <article-title>ATS statement: guidelines for the six-minute walk test</article-title>
          <source>Am J Respir Crit Care Med</source>
          <year>2002</year>
          <volume>166</volume>
          <issue>1</issue>
          <fpage>111</fpage>
          <lpage>117</lpage>
          <pub-id pub-id-type="doi">10.1164/ajrccm.166.1.at1102</pub-id>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6 Riley M, McParland J, Stanford CF, Nicholls DP. Oxygen consumption during corridor walk testing in chronic cardiac failure. Eur Heart J.1992;13(6):789-93. PMID: 1623869.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Riley</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>McParland</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Stanford</surname>
              <given-names>CF</given-names>
            </name>
            <name>
              <surname>Nicholls</surname>
              <given-names>DP</given-names>
            </name>
          </person-group>
          <article-title>Oxygen consumption during corridor walk testing in chronic cardiac failure</article-title>
          <source>Eur Heart J</source>
          <year>1992</year>
          <volume>13</volume>
          <issue>6</issue>
          <fpage>789</fpage>
          <lpage>793</lpage>
          <pub-id pub-id-type="pmid">1623869</pub-id>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7 Foray A, Williams D, Reemtsma K, Oz M, Mancini D. Assessment of submaximal exercise capacity in patients with left ventricular assist devices. Circulation. 1996;94(9 Suppl):II-222-6. PMID: 8901750.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Foray</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Williams</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Reemtsma</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Oz</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Mancini</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Assessment of submaximal exercise capacity in patients with left ventricular assist devices</article-title>
          <source>Circulation</source>
          <year>1996</year>
          <volume>94</volume>
          <supplement>9</supplement>
          <issue>II</issue>
          <fpage>222</fpage>
          <lpage>226</lpage>
          <pub-id pub-id-type="pmid">8901750</pub-id>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8 Faggiano P, D'Aloia A, Gualeni A, Lavatelli A, Giordano A. Assessment of oxygen uptake during the 6-minute walking test in patients with heart failure: preliminary experience with a portable device. Am Heart J. 1997;134(2 Pt 1):203-6. PMID: 9313598.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Faggiano</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>D'Aloia</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Gualeni</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Lavatelli</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Giordano</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Assessment of oxygen uptake during the 6-minute walking test in patients with heart failure: preliminary experience with a portable device</article-title>
          <source>Am Heart J.</source>
          <year>1997</year>
          <volume>134</volume>
          <issue>2</issue>
          <comment>Pt 1</comment>
          <fpage>203</fpage>
          <lpage>206</lpage>
          <pub-id pub-id-type="pmid">9313598</pub-id>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9 Guimar&#227;es GV, Bellotti G, Bacal F, Mocelin A, Bocchi EA. Can the cardiopulmonary 6-minute walk test reproduce the usual activities of patients with heart failure? Arq Bras Cardiol. 2002;78(6):553-60. <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1590/S0066-782X2002000600003">http://dx.doi.org/10.1590/S0066-782X2002000600003</ext-link>.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Guimar&#227;es</surname>
              <given-names>GV</given-names>
            </name>
            <name>
              <surname>Bellotti</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Bacal</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Mocelin</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Bocchi</surname>
              <given-names>EA</given-names>
            </name>
          </person-group>
          <article-title>Can the cardiopulmonary 6-minute walk test reproduce the usual activities of patients with heart failure?</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2002</year>
          <volume>78</volume>
          <issue>6</issue>
          <fpage>553</fpage>
          <lpage>560</lpage>
          <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1590/S0066-782X2002000600003">http://dx.doi.org/10.1590/S0066-782X2002000600003</ext-link>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10 Kervio G, Ville NS, Leclercq C, Daubert JC, Carre F. Cardiorespiratory adaptations during the six-minute walk test in chronic heart failure patients. Eur J Cardiovasc Prev Rehabil. 2004;11(2):171-7. PMID: 15187823.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kervio</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Ville</surname>
              <given-names>NS</given-names>
            </name>
            <name>
              <surname>Leclercq</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Daubert</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Carre</surname>
              <given-names>F</given-names>
            </name>
          </person-group>
          <article-title>Cardiorespiratory adaptations during the six-minute walk test in chronic heart failure patients</article-title>
          <source>Eur J Cardiovasc Prev Rehabil</source>
          <year>2004</year>
          <volume>11</volume>
          <issue>2</issue>
          <fpage>171</fpage>
          <lpage>177</lpage>
          <pub-id pub-id-type="pmid">15187823</pub-id>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11 Paulus WJ, Tsch&#246;pe C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J.2007;28(20):2539-50. doi: 10.1093/eurheartj/ehm037.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Paulus</surname>
              <given-names>WJ</given-names>
            </name>
            <name>
              <surname>Tsch&#246;pe</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Sanderson</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Rusconi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Flachskampf</surname>
              <given-names>FA</given-names>
            </name>
            <name>
              <surname>Rademakers</surname>
              <given-names>FE</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology</article-title>
          <source>Eur Heart J</source>
          <year>2007</year>
          <volume>28</volume>
          <issue>20</issue>
          <fpage>2539</fpage>
          <lpage>2550</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehm037</pub-id>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12 Fletcher GF, Ades PA, KligfieldP, Arena R, Balady GF, Bittner VA, et al; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology, Council on Nutrition, Physical Activity and Metabolism, Council on Cardiovascular and Stroke Nursing, and Council on Epidemiology and Prevention. Exercise standards for testing and training: a scientific statement from the American Heart Association. Circulation. 2013;128(8):873-934. doi: 10.1161/CIR.0b013e31829b5b44.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fletcher</surname>
              <given-names>GF</given-names>
            </name>
            <name>
              <surname>Ades</surname>
              <given-names>PA</given-names>
            </name>
            <name>
              <surname>Kligfield</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Arena</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Balady</surname>
              <given-names>GF</given-names>
            </name>
            <name>
              <surname>Bittner</surname>
              <given-names>VA</given-names>
            </name>
            <etal/>
            <collab>American Heart Association Exercise</collab>
            <collab>Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology</collab>
            <collab>Council on Nutrition, Physical Activity and Metabolism</collab>
            <collab>Council on Cardiovascular and Stroke Nursing, and Council on Epidemiology and Prevention</collab>
          </person-group>
          <article-title>Exercise standards for testing and training: a scientific statement from the American Heart Association</article-title>
          <source>Circulation</source>
          <year>2013</year>
          <volume>128</volume>
          <issue>8</issue>
          <fpage>873</fpage>
          <lpage>934</lpage>
          <pub-id pub-id-type="doi">10.1161/CIR.0b013e31829b5b44</pub-id>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13 Balady GJ, Arena R,Sietsema K, Myers J, Coke L, Fletcher, GF, et al; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Peripheral Vascular Disease; Interdisciplinary Council on Quality of Care and Outcomes Research. Clinician's Guide to cardiopulmonary exercise testing in adults a scientific statement from the American Heart Association. Circulation. 2010;122(2):191-225. doi: 10.1161/CIR.0b013e3181e52e69.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Balady</surname>
              <given-names>GJ</given-names>
            </name>
            <name>
              <surname>Arena</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Sietsema</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Myers</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Coke</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Fletcher</surname>
              <given-names>GF</given-names>
            </name>
            <etal/>
            <collab>American Heart Association Exercise.Cardiac Rehabilitation.and Prevention Committee of the Council on Clinical CardiologyCouncil on Epidemiology and PreventionCouncil on Peripheral Vascular DiseaseInterdisciplinary Council on Quality of Care and Outcomes Research</collab>
          </person-group>
          <article-title>Clinician's Guide to cardiopulmonary exercise testing in adults a scientific statement from the American Heart Association</article-title>
          <source>Circulation</source>
          <year>2010</year>
          <volume>122</volume>
          <issue>2</issue>
          <fpage>191</fpage>
          <lpage>225</lpage>
          <pub-id pub-id-type="doi">10.1161/CIR.0b013e3181e52e69</pub-id>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14 Guazzi M, Raimondo R, Vicenzi M, Arena R, Proserpio C, Sarzi Braga S, et al. Exercise oscillatory ventilation may predict sudden cardiac death in heart failure patients. J Am Coll Cardiol. 2007;50(4):299-308. doi: 10.1016/j.jacc.2007.03.042.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Guazzi</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Raimondo</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Vicenzi</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Arena</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Proserpio</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Sarzi Braga</surname>
              <given-names>S</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Exercise oscillatory ventilation may predict sudden cardiac death in heart failure patients</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2007</year>
          <volume>50</volume>
          <issue>4</issue>
          <fpage>299</fpage>
          <lpage>308</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2007.03.042</pub-id>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15 Scott JM, Haykowsky MJ, Eggebeen J, Morgan TM, Brubaker PH, Kitzman DW. Reliability of peak exercise testing in patients with heart failure with preserved ejection fraction. Am J Cardiol. 2012;110(12):1809-13. doi: 10.1016/j.amjcard.2012.08.015.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Scott</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Haykowsky</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Eggebeen</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Morgan</surname>
              <given-names>TM</given-names>
            </name>
            <name>
              <surname>Brubaker</surname>
              <given-names>PH</given-names>
            </name>
            <name>
              <surname>Kitzman</surname>
              <given-names>DW</given-names>
            </name>
          </person-group>
          <article-title>Reliability of peak exercise testing in patients with heart failure with preserved ejection fraction</article-title>
          <source>Am J Cardiol</source>
          <year>2012</year>
          <volume>110</volume>
          <issue>12</issue>
          <fpage>1809</fpage>
          <lpage>1813</lpage>
          <pub-id pub-id-type="doi">10.1016/j.amjcard.2012.08.015</pub-id>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16 Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. J Am Coll Cardiol. 2001;37(1):153-6. PMID: 11153730.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tanaka</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Monahan</surname>
              <given-names>KD</given-names>
            </name>
            <name>
              <surname>Seals</surname>
              <given-names>DR</given-names>
            </name>
          </person-group>
          <article-title>Age-predicted maximal heart rate revisited.</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2001</year>
          <volume>37</volume>
          <issue>1</issue>
          <fpage>153</fpage>
          <lpage>156</lpage>
          <pub-id pub-id-type="pmid">11153730</pub-id>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>17 Task Force of the Italian Working Group on Cardiac Rehabilitation and Prevention (Gruppo Italiano di Cardiologia Riabilitativa e Prevenzione, GICR), Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology. Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part III: Interpretation of cardiopulmonary exercise testing in chronic heart failure and future applications. Eur J Cardiovasc Prev Rehabil. 2006;13(4):485-94. doi: 10.1097/01.hjr.0000201518.43837.bc.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <collab>Task Force of the Italian Working Group on Cardiac Rehabilitation and Prevention (Gruppo Italiano di Cardiologia Riabilitativa e Prevenzione, GICR)</collab>
            <collab>Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology</collab>
          </person-group>
          <article-title>Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part III: Interpretation of cardiopulmonary exercise testing in chronic heart failure and future applications</article-title>
          <source>Eur J Cardiovasc Prev Rehabil</source>
          <year>2006</year>
          <volume>13</volume>
          <issue>4</issue>
          <fpage>485</fpage>
          <lpage>494</lpage>
          <pub-id pub-id-type="doi">10.1097/01.hjr.0000201518.43837.bc</pub-id>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>18 Arslan S, Erol MK, GundogduF, Sevimli S, Aksakal E, Senocak H, et al. Prognostic value of 6-minute walk test in stable outpatients with heart failure. Tex Heart Inst J. 2007;34(2):166-9. PMID: 17622362.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Arslan</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Erol</surname>
              <given-names>MK</given-names>
            </name>
            <name>
              <surname>Gundogdu</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Sevimli</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Aksakal</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Senocak</surname>
              <given-names>H</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prognostic value of 6-minute walk test in stable outpatients with heart failure</article-title>
          <source>Tex Heart Inst J.</source>
          <year>2007</year>
          <volume>34</volume>
          <issue>2</issue>
          <fpage>166</fpage>
          <lpage>169</lpage>
          <pub-id pub-id-type="pmid">17622362</pub-id>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>19 Faggiano P, D'Aloia A, Gualeni A, Brentana L, Dei Cas L. The 6 minute walking test in chronic heart failure: indications, interpretation and limitations from a review of the literature. Eur J Heart Fail. 2004;6(6):687-91. doi: 10.1016/j.ejheart.2003.11.024.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Faggiano</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>D'Aloia</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Gualeni</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Brentana</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Dei Cas</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>The 6 minute walking test in chronic heart failure: indications, interpretation and limitations from a review of the literature</article-title>
          <source>Eur J Heart Fail</source>
          <year>2004</year>
          <volume>6</volume>
          <issue>6</issue>
          <fpage>687</fpage>
          <lpage>691</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ejheart.2003.11.024</pub-id>
        </element-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <mixed-citation>20 Lucas C, Stevenson LW, Johnson W, Hartley H, Hamilton MA, Walden J, et al. The 6-min walk and peak oxygen consumption in advanced heart failure: aerobic capacity and survival. Am Heart J. 1999;138(4 Pt 1):618-24. PMID: 10502205.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lucas</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Stevenson</surname>
              <given-names>LW</given-names>
            </name>
            <name>
              <surname>Johnson</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Hartley</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Hamilton</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Walden</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>The 6-min walk and peak oxygen consumption in advanced heart failure: aerobic capacity and survival</article-title>
          <source>Am Heart J.</source>
          <year>1999</year>
          <volume>138</volume>
          <issue>4</issue>
          <comment>Pt 1</comment>
          <fpage>618</fpage>
          <lpage>624</lpage>
          <pub-id pub-id-type="pmid">10502205</pub-id>
        </element-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <mixed-citation>21 Roul G, Germain P, Bareiss P. Does the 6-min walk test predict the prognosis in patients with NYHA class II or III chronic heart failure? Am Heart J. 1998;136(3):449-57. PMID: 9736136.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Roul</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Germain</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Bareiss</surname>
              <given-names>P</given-names>
            </name>
          </person-group>
          <article-title>Does the 6-min walk test predict the prognosis in patients with NYHA class II or III chronic heart failure?</article-title>
          <source>Am Heart J</source>
          <year>1998</year>
          <volume>136</volume>
          <issue>3</issue>
          <fpage>449</fpage>
          <lpage>457</lpage>
          <pub-id pub-id-type="pmid">9736136</pub-id>
        </element-citation>
      </ref>
      <ref id="B22">
        <label>22</label>
        <mixed-citation>22 Guazzi M, Myers J, Peberdy MA, Bensimhon D, Chase P, Arena R. Cardiopulmonary exercise testing variables reflect the degree of diastolic dysfunction in patients with heart failure-normal ejection fraction. J Cardiopulm Rehabil Prev. 2010;30(3):165-72. doi: 10.1097/HCR.0b013e3181d0c1ad.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Guazzi</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Myers</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Peberdy</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Bensimhon</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Chase</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Arena</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>Cardiopulmonary exercise testing variables reflect the degree of diastolic dysfunction in patients with heart failure-normal ejection fraction</article-title>
          <source>J Cardiopulm Rehabil Prev</source>
          <year>2010</year>
          <volume>30</volume>
          <issue>3</issue>
          <fpage>165</fpage>
          <lpage>172</lpage>
          <pub-id pub-id-type="doi">10.1097/HCR.0b013e3181d0c1ad</pub-id>
        </element-citation>
      </ref>
      <ref id="B23">
        <label>23</label>
        <mixed-citation>23 Cole CR, Foody JM, Blackstone EH, Lauer MS. Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort. Ann Intern Med. 2000;132(7):552-5. PMID: 10744592.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Cole</surname>
              <given-names>CR</given-names>
            </name>
            <name>
              <surname>Foody</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Blackstone</surname>
              <given-names>EH</given-names>
            </name>
            <name>
              <surname>Lauer</surname>
              <given-names>MS</given-names>
            </name>
          </person-group>
          <article-title>Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort</article-title>
          <source>Ann Intern Med</source>
          <year>2000</year>
          <volume>132</volume>
          <issue>7</issue>
          <fpage>552</fpage>
          <lpage>555</lpage>
          <pub-id pub-id-type="pmid">10744592</pub-id>
        </element-citation>
      </ref>
      <ref id="B24">
        <label>24</label>
        <mixed-citation>24 Meneghelo RS, Ara&#250;jo CG, Stein R, Mastrocolla LE, Albuquerque PF, Serra SM, et al; Sociedade Brasileira de Cardiologia. [;III Guidelines of Sociedade Brasileira de Cardiologia on the exercise test];. Arq Bras Cardiol. 2010;95(5 supl. 1):1-26. doi: <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1590/S0066-782X2010000800001">http://dx.doi.org/10.1590/S0066-782X2010000800001</ext-link>.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Meneghelo</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Ara&#250;jo</surname>
              <given-names>CG</given-names>
            </name>
            <name>
              <surname>Stein</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Mastrocolla</surname>
              <given-names>LE</given-names>
            </name>
            <name>
              <surname>Albuquerque</surname>
              <given-names>PF</given-names>
            </name>
            <name>
              <surname>Serra</surname>
              <given-names>SM</given-names>
            </name>
            <etal/>
            <collab>Sociedade Brasileira de Cardiologia</collab>
          </person-group>
          <article-title>III Guidelines of Sociedade Brasileira de Cardiologia on the exercise test</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2010</year>
          <volume>95</volume>
          <issue>5</issue>
          <supplement>supl. 1</supplement>
          <fpage>1</fpage>
          <lpage>26</lpage>
          <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1590/S0066-782X2010000800001">http://dx.doi.org/10.1590/S0066-782X2010000800001</ext-link>
        </element-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <mixed-citation>25 Oliveira RB, Myers J, Ara&#250;jo CG, Abella J, Mandic S, Froelicher V. Maximal exercise oxygen pulse as a predictor of mortality among male veterans referred for exercise testing. Eur J Cardiovasc Prev Rehab. 2009;16(3):358-64. doi: 10.1097/HJR.0b013e3283292fe8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Oliveira</surname>
              <given-names>RB</given-names>
            </name>
            <name>
              <surname>Myers</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Ara&#250;jo</surname>
              <given-names>CG</given-names>
            </name>
            <name>
              <surname>Abella</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Mandic</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Froelicher</surname>
              <given-names>V</given-names>
            </name>
          </person-group>
          <article-title>Maximal exercise oxygen pulse as a predictor of mortality among male veterans referred for exercise testing</article-title>
          <source>Eur J Cardiovasc Prev Rehab</source>
          <year>2009</year>
          <volume>16</volume>
          <issue>3</issue>
          <fpage>358</fpage>
          <lpage>364</lpage>
          <pub-id pub-id-type="doi">10.1097/HJR.0b013e3283292fe8</pub-id>
        </element-citation>
      </ref>
      <ref id="B26">
        <label>26</label>
        <mixed-citation>26 Forman DE, Guazzi M, Myers J, Chase P, Bensimhon D, Cahalin LP, et al. Ventilatory power: a novel index that enhances prognostic assessment of patients with heart failure. Circ Heart Fail. 2012;5(5):621-6. doi: 10.1161/CIRCHEARTFAILURE.112.968529.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Forman</surname>
              <given-names>DE</given-names>
            </name>
            <name>
              <surname>Guazzi</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Myers</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Chase</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Bensimhon</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Cahalin</surname>
              <given-names>LP</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Ventilatory power: a novel index that enhances prognostic assessment of patients with heart failure</article-title>
          <source>Circ Heart Fail</source>
          <year>2012</year>
          <volume>5</volume>
          <issue>5</issue>
          <fpage>621</fpage>
          <lpage>626</lpage>
          <pub-id pub-id-type="doi">10.1161/CIRCHEARTFAILURE.112.968529</pub-id>
        </element-citation>
      </ref>
      <ref id="B27">
        <label>27</label>
        <mixed-citation>27 Guazzi M, Dickstein K, Vicenzi M, Arena R. Six-minute walk test and cardiopulmonary exercise testing in patients with chronic heart failure: a comparative analysis on clinical and prognostic insights. Circ Heart Fail. 2009;2(6):549-55. doi: 10.1161/CIRCHEARTFAILURE.109.881326.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Guazzi</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Dickstein</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Vicenzi</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Arena</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>Six-minute walk test and cardiopulmonary exercise testing in patients with chronic heart failure: a comparative analysis on clinical and prognostic insights</article-title>
          <source>Circ Heart Fail</source>
          <year>2009</year>
          <volume>2</volume>
          <issue>6</issue>
          <fpage>549</fpage>
          <lpage>555</lpage>
          <pub-id pub-id-type="doi">10.1161/CIRCHEARTFAILURE.109.881326</pub-id>
        </element-citation>
      </ref>
      <ref id="B28">
        <label>28</label>
        <mixed-citation>28 Hollenberg M, Tager IB. Oxygen uptake efficiency slope: an index of exercise performance and cardiopulmonary reserve requiring only submaximal exercise. J Am Coll Cardiol. 2000;36(1):194-201. PMID: 10898434.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hollenberg</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Tager</surname>
              <given-names>IB</given-names>
            </name>
          </person-group>
          <article-title>Oxygen uptake efficiency slope: an index of exercise performance and cardiopulmonary reserve requiring only submaximal exercise</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2000</year>
          <volume>36</volume>
          <issue>1</issue>
          <fpage>194</fpage>
          <lpage>201</lpage>
          <pub-id pub-id-type="pmid">10898434</pub-id>
        </element-citation>
      </ref>
      <ref id="B29">
        <label>29</label>
        <mixed-citation>29 Cohen-Solal A, Tabot JY, Logeart D, Bourgoin P, Tokmakova M, Dahan M. A non-invasively determined surrogate of cardiac power ('circulatory power') at peak exercise is a powerful prognostic factor in chronic heart failure. Eur Heart J. 2002;23(10):806-14. doi: 10.1053/euhj.2001.2966.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Cohen-Solal</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Tabot</surname>
              <given-names>JY</given-names>
            </name>
            <name>
              <surname>Logeart</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Bourgoin</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Tokmakova</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Dahan</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>A non-invasively determined surrogate of cardiac power ('circulatory power') at peak exercise is a powerful prognostic factor in chronic heart failure</article-title>
          <source>Eur Heart J</source>
          <year>2002</year>
          <volume>23</volume>
          <issue>10</issue>
          <fpage>806</fpage>
          <lpage>814</lpage>
          <pub-id pub-id-type="doi">10.1053/euhj.2001.2966</pub-id>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Estudo por Analisador de Gases do Teste de Caminhada de Seis Minutos na Insufici&#234;ncia Card&#237;aca com Fra&#231;&#227;o de Eje&#231;&#227;o Normal</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Teixeira</surname>
            <given-names>Jos&#233; Ant&#244;nio Caldas</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Messias</surname>
            <given-names>Leandro Rocha</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Dias</surname>
            <given-names>K&#225;tia Pedreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Washington Luiz Batista da</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cascon</surname>
            <given-names>Roberto Macedo</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Miranda</surname>
            <given-names>Sandra Marina Ribeiro de</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Teixeira</surname>
            <given-names>Pedro Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Jorge</surname>
            <given-names>Juliana Grael</given-names>
          </name>
          <xref ref-type="aff" rid="aff9">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nobrega</surname>
            <given-names>Antonio Claudio Lucas da</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Araujo</surname>
            <given-names>Denizar V</given-names>
          </name>
          <xref ref-type="aff" rid="aff10">5</xref>
        </contrib>
      </contrib-group>
      <aff id="aff6">
        <label>1</label>
        <institution content-type="original">Universidade Federal Fluminense (UFF), Rio de Janeiro, RJ &#8211; Brasil</institution>
      </aff>
      <aff id="aff7">
        <label>2</label>
        <institution content-type="original">Cl&#237;nica Fit Center, Rio de Janeiro, RJ &#8211; Brasil</institution>
      </aff>
      <aff id="aff8">
        <label>3</label>
        <institution content-type="original">Complexo Hospitalar de Niter&#243;i, Rio de Janeiro, RJ &#8211; Brasil</institution>
      </aff>
      <aff id="aff9">
        <label>4</label>
        <institution content-type="original">Servi&#231;o de Arritmia da Rede Dor, Rio de Janeiro, RJ &#8211; Brasil</institution>
      </aff>
      <aff id="aff10">
        <label>5</label>
        <institution content-type="original">Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Jos&#233; Ant&#244;nio Caldas Teixeira</bold>, Rua Presidente Jo&#227;o Pessoa, 248. CEP: 24220-331, Icara&#237;, Niter&#243;i, RJ &#8211; Brasil. E-mail: <email>jacaldas_@hotmail.com</email>, <email>jacaldas@uninet.com.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Teixeira JAC, Nobrega ACL, Araujo DV. Obten&#231;&#227;o de dados: Teixeira JAC, Messias LR, Dias KP, Costa WLB, Cascon RM, Miranda SMR, Teixeira PS, Jorge JG. An&#225;lise e interpreta&#231;&#227;o dos dados: Teixeira JAC, Messias LR, Dias KP, Costa WLB, Teixeira PS, Nobrega ACL, Araujo DV. Reda&#231;&#227;o do manuscrito: Teixeira JAC, Teixeira PS, Jorge JG. Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Teixeira JAC, Nobrega ACL, Araujo DV. Levantamento bibliogr&#225;fico: Teixeira JAC, Messias LR, Miranda SMR. Revis&#227;o Bibliogr&#225;fica: Costa WLB, Cascon RM.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial Conflito de Interesse</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamentos:</title>
          <p> Poucos estudos utilizaram analisadores de gases port&#225;teis no teste da caminhada de seis minutos (T6m) em portadores de insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o normal (ICFEN).</p>
        </sec>
        <sec>
          <title>Objetivos:</title>
          <p> Analisar a cin&#233;tica das vari&#225;veis hemodin&#226;micas, ventilat&#243;rias e metab&#243;licas utilizando analisador de gases port&#225;til em portadores de ICFEN durante o T6m.</p>
        </sec>
        <sec>
          <title>M&#233;todos: </title>
          <p>Estudo prospectivo, anal&#237;tico, com amostra n&#227;o probabil&#237;stica, intencional e por conveni&#234;ncia. Foram estudados 24 pacientes portadores de ICFEN com passado de interna&#231;&#227;o por cl&#237;nica de insufici&#234;ncia card&#237;aca (IC), inclu&#237;dos pelos crit&#233;rios da <italic>European Society of Cardiology</italic> 2007. Realizaram-se tr&#234;s avalia&#231;&#245;es: T6m de aprendizado, T6m com o analisador de gases port&#225;til e teste de esfor&#231;o cardiopulmonar (TECP).</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p> As frequ&#234;ncias card&#237;acas (FC) e o consumo de oxig&#234;nio (VO<sub>2</sub>) pico ao final do T6m corresponderam a 85,7% e 86,45% dos valores obtidos no TECP. As FC finais no T6m foram equivalentes &#224;s obtidas no limiar anaer&#243;bio (LA) do TECP, com valores de VO<sub>2</sub> relativo ao final do T6m acima do VO<sub>2</sub> no LA do TECP. N&#227;o houve diferen&#231;a entre os valores m&#225;ximos do quociente respirat&#243;rio (QR) entre os dois testes, ambos acima de 1,0. A curva de VE/VO<sub>2</sub> demonstrou descenso com posterior ascens&#227;o significativa ap&#243;s o quinto minuto de teste, estimando-se a identifica&#231;&#227;o do LA.</p>
          <p>Conclus&#245;es: Para pacientes com ICFEN, o T6m representa um esfor&#231;o quase m&#225;ximo, sendo executado acima do LA do TECP e acima dos 85% da FC m&#225;xima e do VO<sub>2</sub> pico do TECP, com QR m&#225;ximo semelhante ao do TECP.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Insufici&#234;ncia Card&#237;aca</kwd>
        <kwd>Gasometria</kwd>
        <kwd>Volume Sist&#243;lico</kwd>
        <kwd>Exerc&#237;cio</kwd>
        <kwd>Teste de Caminhada</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A insufici&#234;ncia card&#237;aca (IC) evoca a imagem de um cora&#231;&#227;o dilatado, com fun&#231;&#227;o sist&#243;lica e fra&#231;&#227;o de eje&#231;&#227;o reduzidas (IC com fra&#231;&#227;o de eje&#231;&#227;o reduzida, ICFER). Por&#233;m, o estudo de Burkhoff et al.,<xref ref-type="bibr" rid="B1">1</xref> mostrou que uma grande propor&#231;&#227;o de pacientes com sintomas de IC tem fra&#231;&#227;o de eje&#231;&#227;o dentro da faixa normal, sendo ent&#227;o classificados como portadores de IC com fra&#231;&#227;o de eje&#231;&#227;o normal (ICFEN).<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref> A limitada toler&#226;ncia aos esfor&#231;os na IC &#233; frequentemente a primeira e principal caracter&#237;stica cl&#237;nica da doen&#231;a.<xref ref-type="bibr" rid="B4">4</xref> Na identifica&#231;&#227;o dessa intoler&#226;ncia ao esfor&#231;o, o teste de caminhada de seis minutos (T6m) tem sido utilizado como instrumento para avaliar a evolu&#231;&#227;o ap&#243;s diferentes interven&#231;&#245;es.<xref ref-type="bibr" rid="B5">5</xref>
				</p>
        <p>H&#225; poucos estudos realizados com utiliza&#231;&#227;o de analisadores de gases port&#225;teis para descrever e analisar o comportamento de vari&#225;veis no T6m e poss&#237;veis caracter&#237;sticas ou marcadores que auxiliem na orienta&#231;&#227;o terap&#234;utica e na melhora progn&#243;stica na IC,<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B10">10</xref> especialmente em portadores de ICFEN.</p>
        <p>O objetivo deste estudo foi descrever e analisar o comportamento cin&#233;tico a cada minuto de vari&#225;veis hemodin&#226;micas, ventilat&#243;rias e metab&#243;licas em portadores de ICFEN durante o T6m com a utiliza&#231;&#227;o de um analisador de gases port&#225;til e comparar os resultados com os obtidos durante o teste de esfor&#231;o cardiopulmonar (TECP).</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Estudo prospectivo, anal&#237;tico, com amostra n&#227;o probabil&#237;stica, intencional e por conveni&#234;ncia, conforme crit&#233;rios adotados, realizado no Hospital Universit&#225;rio Ant&#244;nio Pedro (HUAP) da Universidade Federal Fluminense (UFF) no per&#237;odo de mar&#231;o de 2010 a julho de 2013. O projeto deste estudo foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa (CEP) do HUAP sob o n&#186; 152A/2010, e todos os participantes assinaram o Termo de Consentimento Livre e Esclarecido. Todos os procedimentos envolvidos nesse estudo est&#227;o de acordo com a Declara&#231;&#227;o de Helsinki de 1975, atualizada em 2013.</p>
        <p>Os crit&#233;rios de inclus&#227;o adotados para caracterizar a ICFEN foram os descritos por Paulus et al.,<xref ref-type="bibr" rid="B11">11</xref> al&#233;m dos seguintes fatores: (A) queixas sugestivas de IC (dispneia e/ou fadiga e/ou edema); (B) relato de hospitaliza&#231;&#227;o pr&#233;via por doen&#231;a card&#237;aca descompensada, por&#233;m no momento do teste em classe funcional II a III pela <italic>New York Heart Association</italic> (NYHA); (C) idade &gt; 18 anos; (D) dura&#231;&#227;o da doen&#231;a maior que 6 meses; (E) uso de medica&#231;&#227;o e (F) doen&#231;a est&#225;vel.</p>
        <p>Os crit&#233;rios de exclus&#227;o adotados foram: (A) doen&#231;a pulmonar obstrutiva cr&#244;nica (DPOC) por crit&#233;rios cl&#237;nicos, (B) classe funcional IV ou outros crit&#233;rios de contraindica&#231;&#227;o para a realiza&#231;&#227;o do TECP<xref ref-type="bibr" rid="B12">12</xref> e (C) participa&#231;&#227;o em programas de reabilita&#231;&#227;o card&#237;aca supervisionada.</p>
        <p>Os pacientes foram orientados a manter os medicamentos em uso. Os testes compreenderam tr&#234;s momentos: T6m convencional (T6m1), T6m acoplado a um analisador de gases port&#225;til (T6m2) e TECP em esteira. Por quest&#227;o de fluxo do hospital, alguns pacientes realizaram de forma aleat&#243;ria primeiro o T6m e outros o TECP.</p>
        <p>O T6m foi realizado em um corredor com 30 metros de extens&#227;o. O primeiro T6m (T6m1) tinha por objetivo um efeito de aprendizagem, conforme recomendado pela literatura.<xref ref-type="bibr" rid="B6">6</xref> O segundo T6m (T6m2) foi realizado no m&#237;nimo 3 dias e no m&#225;ximo 3 semanas ap&#243;s o primeiro, quando o paciente repetia o T6m, agora acoplado ao analisador de gases port&#225;til. O intervalo m&#225;ximo entre o T6m e o TECP foi tamb&#233;m de 3 semanas. O T6m e o TECP foram coordenados pelo mesmo avaliador e aplicados pela mesma equipe para evitar variabilidade na sua aplica&#231;&#227;o.</p>
        <p>Utilizou-se para as avalia&#231;&#245;es o analisador metab&#243;lico MedGraphics (MGC) VO2000 (Imbrasport, Porto Alegre, RS, Brasil), sistema Ergo PC Elite 13 e esteira Centurion 300 (MicroMed<italic>,</italic> Bras&#237;lia, DF, Brasil). O analisador de gases foi calibrado antes de cada teste pelo sistema de autocalibra&#231;&#227;o em ambiente ventilado. O controle biol&#243;gico da calibra&#231;&#227;o ocorreu a cada m&#234;s e o controle pelo representante do equipamento (CAEL, Rio de Janeiro, RJ, Brasil) foi realizado a cada 3 meses.</p>
        <p>No TECP, cada paciente passava por 2 minutos de coleta basal e realizava 1 minuto de aquecimento a 1 km/h e 0&#186; de inclina&#231;&#227;o, para ent&#227;o iniciar o protocolo de rampa. Para a an&#225;lise e obten&#231;&#227;o das vari&#225;veis do TECP, utilizou-se o programa ErgoPCElite para Windows 13W (MicroMed, Bras&#237;lia, DF, Brasil). A percep&#231;&#227;o de esfor&#231;o (PE), avaliada pela escala de Borg (varia&#231;&#227;o de 0-10), e as vari&#225;veis hemodin&#226;micas e eletrocardiogr&#225;ficas eram registradas a cada minuto. Durante a fase de recupera&#231;&#227;o o paciente permanecia sentado. Dois &#225;rbitros analisaram o laudo do teste para obten&#231;&#227;o das seguintes informa&#231;&#245;es: valor da inclina&#231;&#227;o VE/VCO<sub>2</sub>, presen&#231;a de ventila&#231;&#227;o peri&#243;dica (VP) e estabelecimento do limiar ventilat&#243;rio I, a partir desse momento denominado limiar anaer&#243;bio (LA). Para determinar o LA, foram consideradas as curvas dos equivalentes ventilat&#243;rios do VO<sub>2</sub> e VCO<sub>2</sub>, al&#233;m das curvas das fra&#231;&#245;es expiradas do VO<sub>2</sub> e VCO<sub>2</sub>, conforme recomenda a diretriz para TECP da <italic>American Heart Association</italic> (AHA).<xref ref-type="bibr" rid="B13">13</xref>
				</p>
        <p>As avalia&#231;&#245;es foram realizadas durante vig&#234;ncia dos medicamentos usuais utilizados pelos pacientes, durante o mesmo hor&#225;rio do dia e pelo menos 2 horas ap&#243;s a &#250;ltima refei&#231;&#227;o. O VO<sub>2</sub> pico foi definido como o maior valor de VO<sub>2</sub> obtido at&#233; os 30 segundos finais ou 10 segundos na recupera&#231;&#227;o imediata. A avalia&#231;&#227;o da ocorr&#234;ncia de VP e a determina&#231;&#227;o do valor da inclina&#231;&#227;o VE/VCO<sub>2</sub> foram realizadas com base na diretriz da AHA<xref ref-type="bibr" rid="B13">13</xref> e nas recomenda&#231;&#245;es de Guazzi et al.,<xref ref-type="bibr" rid="B14">14</xref> Como n&#227;o foi realizada espirometria, a reserva ventilat&#243;ria n&#227;o foi considerada na an&#225;lise. Foi realizado somente um TECP, conforme recomendado por Scott et al.,<xref ref-type="bibr" rid="B15">15</xref>
				</p>
        <p>A frequ&#234;ncia card&#237;aca (FC) m&#225;xima estimada foi obtida pela f&#243;rmula de Tanaka et al., <xref ref-type="bibr" rid="B16">16</xref> e utilizada para o c&#225;lculo do &#237;ndice cronotr&#243;pico.</p>
        <p>Durante o T6m, foi registrada a FC (monitor Polar modelo T31, Oulu, Finl&#226;ndia) a cada minuto, juntamente com a PE pela escala de Borg e a satura&#231;&#227;o capilar de O<sub>2</sub> por ox&#237;metro de pulso marca Onyx (Minneapolis, MN<italic>,</italic> EUA<italic>).</italic></p>
        <p>Para a an&#225;lise dos gases expirados durante o T6m e obten&#231;&#227;o dos valores das vari&#225;veis, utilizou-se o mesmo VO2000 no modo port&#225;til, conectado a um computador por um sistema de telemetria sem fio. Utilizou-se o programa Aerograph, vers&#227;o 4.3 <italic>(</italic>Imbrasport, Porto Alegre, RS, Brasil), que organizou os dados para posterior an&#225;lise.</p>
        <p>Na realiza&#231;&#227;o do T6m2, o paciente acoplado ao analisador de gases permanecia sentado por 4 minutos e 30 segundos. Ap&#243;s a coleta das vari&#225;veis nesse per&#237;odo de repouso, o paciente permanecia em p&#233; por 30 segundos antes de iniciar o T6m2, que foi realizado de acordo com as orienta&#231;&#245;es da American Thoracic Society (ATS).<xref ref-type="bibr" rid="B5">5</xref>
				</p>
        <p>Todos os pacientes conclu&#237;ram os 6 minutos de caminhada. A an&#225;lise dos gases se encerrava ap&#243;s o 5&#186;. minuto de recupera&#231;&#227;o. A press&#227;o arterial (PA) m&#225;xima considerada foi a obtida imediatamente ap&#243;s o esfor&#231;o, ou seja, terminado o 6&#186;. minuto de caminhada, o paciente se sentava e ent&#227;o era realizada a medida da PA, entre 30-40 segundos durante a recupera&#231;&#227;o.</p>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>Os dados num&#233;ricos est&#227;o expressos como m&#233;dia &#177; desvio padr&#227;o (DP), uma vez que todas as vari&#225;veis inclu&#237;das apresentaram distribui&#231;&#227;o aproximadamente normal (valor de p do teste de Kolmogorov-Smirnov &gt; 0,05). Os dados categ&#243;ricos est&#227;o expressos como frequ&#234;ncia (n) e percentual (%).</p>
          <p>A varia&#231;&#227;o das medidas hemodin&#226;micas, metab&#243;licas e ventilat&#243;rias entre os testes (exames) TECP e T6m foram analisadas pelo teste <italic>t</italic> de Student para amostras pareadas.</p>
          <p>Realizou-se uma an&#225;lise descritiva gr&#225;fica apresentando a m&#233;dia e o DP das medidas obtidas a cada minuto das vari&#225;veis FC e VO<sub>2</sub>, indicando-se, para cada uma delas, os valores m&#225;ximos do TECP e os valores equivalentes aos do LA.</p>
          <p>Para avaliar os n&#237;veis de correla&#231;&#227;o entre a dist&#226;ncia do T6m2 com o VO<sub>2</sub> pico e com o VO<sub>2</sub> pico do TECP, utilizou-se o teste de correla&#231;&#227;o de Pearson (r).</p>
          <p>Foi adotado o n&#237;vel de signific&#226;ncia de 5%. A an&#225;lise estat&#237;stica foi realizada com o programa SAS 6.11 (SAS Institute, Inc. Cary, NC, EUA).</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>Foram estudados 24 pacientes. Destes, 22 realizaram ambos os testes (TECP e T6m) e dois realizaram apenas o TECP; assim, a compara&#231;&#227;o entre o TECP e o T6m incluiu somente os dados de 22 pacientes. As caracter&#237;sticas cl&#237;nicas da popula&#231;&#227;o estudada podem ser observadas na <xref ref-type="table" rid="t3">Tabela 1</xref>. Observou-se predom&#237;nio do sexo feminino (70,8%) e de obesidade (58,3%). A hipertens&#227;o arterial sist&#234;mica (HAS) esteve presente em 100,0% dos pacientes.</p>
        <table-wrap id="t3">
          <label>Tabela 1</label>
          <caption>
            <title>Caracter&#237;sticas cl&#237;nicas da popula&#231;&#227;o estudada</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="center" style="background-color:#C5C6C8">Vari&#225;veis</th>
                <th align="center" style="background-color:#C5C6C8">
								</th>
                <th align="center" style="background-color:#C5C6C8">
								</th>
                <th align="center" style="background-color:#C5C6C8">n = 24</th>
                <th align="center" style="background-color:#C5C6C8">%</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" rowspan="2">Sexo</td>
                <td align="center">masculino</td>
                <td align="center">
								</td>
                <td align="center">7</td>
                <td align="center">29,2</td>
              </tr>
              <tr>
                <td align="center">feminino</td>
                <td align="center">
								</td>
                <td align="center">17</td>
                <td align="center">70,8</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid;border-top-width:thin;border-top-style:solid">
                <td align="center" style="background-color:#C5C6C8">
								</td>
                <td align="center" style="background-color:#C5C6C8">
								</td>
                <td align="center" style="background-color:#C5C6C8">
                  <bold>M&#233;dia</bold>
                </td>
                <td align="center" style="background-color:#C5C6C8">
								</td>
                <td align="center" style="background-color:#C5C6C8">
                  <bold>DP</bold>
                </td>
              </tr>
              <tr>
                <td align="left">FE (%)</td>
                <td align="center">
								</td>
                <td align="center">64,7</td>
                <td align="center">
								</td>
                <td align="center">8,2</td>
              </tr>
              <tr>
                <td align="left">Peso (kg)</td>
                <td align="center">
								</td>
                <td align="center">84,3</td>
                <td align="center">
								</td>
                <td align="center">16,6</td>
              </tr>
              <tr>
                <td align="left">Estatura (cm)</td>
                <td align="center">
								</td>
                <td align="center">160,2</td>
                <td align="center">
								</td>
                <td align="center">7,4</td>
              </tr>
              <tr>
                <td align="left">IMC</td>
                <td align="center">
								</td>
                <td align="center">32,9</td>
                <td align="center">
								</td>
                <td align="center">6,7</td>
              </tr>
              <tr>
                <td align="left">Cintura (cm)</td>
                <td align="center">
								</td>
                <td align="center">104,4</td>
                <td align="center">
								</td>
                <td align="center">13,3</td>
              </tr>
              <tr>
                <td align="left">Quadril (cm)</td>
                <td align="center">
								</td>
                <td align="center">110,8</td>
                <td align="center">
								</td>
                <td align="center">11,6</td>
              </tr>
              <tr>
                <td align="left">C/Q</td>
                <td align="center">
								</td>
                <td align="center">0,944</td>
                <td align="center">
								</td>
                <td align="center">0,086</td>
              </tr>
              <tr>
                <td align="left">Idade (anos)</td>
                <td align="center">
								</td>
                <td align="center">59,6</td>
                <td align="center">
								</td>
                <td align="center">10,2</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3">
              <p>Abreviaturas: FE: fra&#231;&#227;o de eje&#231;&#227;o; IMC: &#237;ndice de massa corporal; C/Q: rela&#231;&#227;o cintura quadril; DP: desvio padr&#227;o.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>A maioria dos pacientes (70,8%) estava em uso de betabloqueadores. O perfil de medicamentos utilizados pelos pacientes evidenciou a abordagem terap&#234;utica usual para HAS: betabloqueadores, inibidores da enzima de convers&#227;o da angiotensina (25,0%) ou bloqueadores dos receptores da angiotensina (54,1%), bloqueador de canal de c&#225;lcio (37,5%), tiaz&#237;dicos (29,1%) e vasodilatadores (48,5%).</p>
        <p>Uma estratifica&#231;&#227;o dos pacientes de acordo com os resultados ao TECP e seguindo a classifica&#231;&#227;o de Weber,<xref ref-type="bibr" rid="B17">17</xref> mostrou um maior percentual de pacientes categorizados na classe B (30,4%).</p>
        <p>Os pacientes apresentaram um E/E&#8217; m&#233;dio de 15,9 &#177; 4,3, caracterizando um dos crit&#233;rios para o diagn&#243;stico de ICFEN.<xref ref-type="bibr" rid="B11">11</xref>
				</p>
        <p>A dist&#226;ncia m&#233;dia percorrida no T6m1 foi de 419,2 &#177; 76,5 metros e no T6m2 foi de 446,2 &#177; 67,7 metros, com diferen&#231;a significativa entre ambos (p = 0,002).</p>
        <p>A <xref ref-type="table" rid="t4">Tabela 2</xref> apresenta os valores m&#225;ximos das vari&#225;veis obtidas no T6m2 e no TECP. N&#227;o houve diferen&#231;a entre os valores m&#225;ximos do quociente respirat&#243;rio (QR) entre os dois testes, e seus valores m&#225;ximos foram superiores a 1,0. Os resultados mostram valores elevados ao final do T6m2 (1,04), sendo que dos 22 pacientes que realizaram o T6m2, 11 obtiveram um QR &#8805; 1,0 (50% do grupo). Destes 11 pacientes, 7 obtiveram um QR &#8805; 1,10 (31,8% da amostra).</p>
        <table-wrap id="t4">
          <label>Tabela 2</label>
          <caption>
            <title>Valores m&#225;ximos das vari&#225;veis obtidas no segundo teste de caminhada de seis minutos (T6m2) e no teste de esfor&#231;o cardiopulmonar (TECP; n = 22)</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" colspan="6" style="background-color:#C5C6C8">Valores m&#233;dios - T6m2 versus TECP</th>
              </tr>
              <tr>
                <th align="center" style="background-color:#C5C6C8">
								</th>
                <th align="center" style="background-color:#C5C6C8">T6m2</th>
                <th align="center" style="background-color:#C5C6C8">DP</th>
                <th align="center" style="background-color:#C5C6C8">TECP</th>
                <th align="center" style="background-color:#C5C6C8">DP</th>
                <th align="center" style="background-color:#C5C6C8">p &lt; 0,05</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">PAS max</td>
                <td align="center">187,04</td>
                <td align="center">26,60</td>
                <td align="center">215,3</td>
                <td align="center">27,4</td>
                <td align="center">0,002</td>
              </tr>
              <tr>
                <td align="left">PAD max</td>
                <td align="center">97,80</td>
                <td align="center">13,7</td>
                <td align="center">104,1</td>
                <td align="center">16,0</td>
                <td align="center">0,09</td>
              </tr>
              <tr>
                <td align="left">DP Max</td>
                <td align="center">20951</td>
                <td align="center">5497</td>
                <td align="center">27524</td>
                <td align="center">6130</td>
                <td align="center">0,0004</td>
              </tr>
              <tr>
                <td align="left">PotCirc</td>
                <td align="center">2533</td>
                <td align="center">957</td>
                <td align="center">3462</td>
                <td align="center">1266</td>
                <td align="center">0,002</td>
              </tr>
              <tr>
                <td align="left">FCmax</td>
                <td align="center">110,9</td>
                <td align="center">18,1</td>
                <td align="center">125,4</td>
                <td align="center">19,6</td>
                <td align="center">0,004</td>
              </tr>
              <tr>
                <td align="left">FC1Rec</td>
                <td align="center">23,1</td>
                <td align="center">10,1</td>
                <td align="center">17,2</td>
                <td align="center">10,1</td>
                <td align="center">0,035</td>
              </tr>
              <tr>
                <td align="left">ICrono</td>
                <td align="center">0,42</td>
                <td align="center">0,2</td>
                <td align="center">0,57</td>
                <td align="center">0,1</td>
                <td align="center">0,002</td>
              </tr>
              <tr>
                <td align="left">Pulso O<sub>2</sub></td>
                <td align="center">10,5</td>
                <td align="center">3,6</td>
                <td align="center">10,5</td>
                <td align="center">3,5</td>
                <td align="center">0,95</td>
              </tr>
              <tr>
                <td align="left">QRmax</td>
                <td align="center">1,06</td>
                <td align="center">0,24</td>
                <td align="center">1,08</td>
                <td align="center">0,09</td>
                <td align="center">0,47</td>
              </tr>
              <tr>
                <td align="left">Inclina&#231;&#227;o VE/VCO<sub>2</sub></td>
                <td align="center">22,3</td>
                <td align="center">4,8</td>
                <td align="center">23,2</td>
                <td align="center">4,4</td>
                <td align="center">0,10</td>
              </tr>
              <tr>
                <td align="left">PV</td>
                <td align="center">8,31</td>
                <td align="center">1,92</td>
                <td align="center">9,59</td>
                <td align="center">2,11</td>
                <td align="center">0,0002</td>
              </tr>
              <tr>
                <td align="left">VO<sub>2</sub> pico (mL.kg<sup>-1</sup>. min<sup>-1</sup>)</td>
                <td align="center">13,8</td>
                <td align="center">4,1</td>
                <td align="center">15,9</td>
                <td align="center">5,4</td>
                <td align="center">0,025</td>
              </tr>
              <tr>
                <td align="left">T1/2</td>
                <td align="center">61,4</td>
                <td align="center">16,5</td>
                <td align="center">111,2</td>
                <td align="center">25,7</td>
                <td align="center">0,0001</td>
              </tr>
              <tr>
                <td align="left">OUES</td>
                <td align="center">1,26</td>
                <td align="center">0,74</td>
                <td align="center">1,34</td>
                <td align="center">0,59</td>
                <td align="center">0,10</td>
              </tr>
              <tr>
                <td align="left">VO<sub>2</sub> do LA</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">11,76</td>
                <td align="center">3,79</td>
                <td align="center">
								</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN4">
              <p>Abreviaturas: PAS max: press&#227;o arterial sist&#243;lica m&#225;xima; PAD max: press&#227;o arterial diast&#243;lica m&#225;xima; DP max: duplo-produto m&#225;ximo; PotCirc: pot&#234;ncia circulat&#243;ria; FCmax: frequ&#234;ncia card&#237;aca m&#225;xima; FC1Rec: frequ&#234;ncia card&#237;aca no primeiro minuto da recupera&#231;&#227;o; ICrono: &#237;ndice cronotr&#243;pico; Pulso O<sub>2</sub>: pulso de oxig&#234;nio (mL.kg<sup>-1</sup>.min<sup>-1</sup>/bpm); QRmax: quociente respirat&#243;rio m&#225;ximo; Inclina&#231;&#227;o VE/VCO<sub>2</sub>: rela&#231;&#227;o da ventila&#231;&#227;o minuto com a produ&#231;&#227;o de di&#243;xido de carbono; PV: pot&#234;ncia ventilat&#243;ria; VO<sub>2</sub> pico (mL.kg<sup>-1</sup>. min<sup>-1</sup>): consumo de oxig&#234;nio pico; T1/2: tempo (em segundos) da cin&#233;tica de recupera&#231;&#227;o do consumo de oxig&#234;nio at&#233; a metade do valor do pico de esfor&#231;o; OUES (oxygen uptake efficiency slope): inclina&#231;&#227;o da efici&#234;ncia do consumo de oxig&#234;nio; LA: limiar anaer&#243;bio; T6m2: segundo teste de caminhada de seis minutos; TECP: teste de esfor&#231;o cardiopulmonar; DP: desvio padr&#227;o. Todas as frequ&#234;ncias card&#237;acas est&#227;o representadas em batimentos por minuto.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Devido &#224; impossibilidade de se medir a PA durante o T6m, esta s&#243; foi obtida na situa&#231;&#227;o basal e no p&#243;s-esfor&#231;o imediato ao T6m. Como n&#227;o era realizada espirometria pr&#233;via, n&#227;o foram avaliados outros par&#226;metros ventilat&#243;rios.</p>
        <p>A an&#225;lise longitudinal da FC durante o T6m2 mostrou que o grupo atingiu valores est&#225;veis de FC ap&#243;s o segundo minuto do T6m2 (T3). A FC m&#225;xima durante o T6m2 (108,9 bpm) foi semelhante &#224; FC do LA no TECP (108 bpm), demonstrado na linha tracejada (<xref ref-type="fig" rid="f3">Figura 1</xref>), e 85,7 % em rela&#231;&#227;o &#224; FC m&#225;xima do TECP (126 bpm), mostrado em destaque na Figura.</p>
        <p>
          <fig id="f3">
            <label>Figura 1</label>
            <caption>
              <title>Comportamento longitudinal da frequ&#234;ncia card&#237;aca (FC) durante o segundo teste da caminhada de 6 minutos (T6m2) no grupo estudado. Abreviaturas: ICFEN: insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o normal; TECP: teste de esfor&#231;o cardiopulmonar; FC: frequ&#234;ncia card&#237;aca; FCmax: frequ&#234;ncia card&#237;aca m&#225;xima; LA: limiar anaer&#243;bio no TECP; T1: tempo zero do T6m (situa&#231;&#227;o basal); T2, T3, T4, T5, T6, T7 - respectivamente: primeiro, segundo, terceiro, quarto, quinto e sexto minutos do T6m.</title>
            </caption>
            <graphic xlink:href="2359-5647-ijcs-31-02-0143-80001-gf01-pt.jpg"/></fig>
        </p>
        <p>O comportamento longitudinal do VO<sub>2</sub> relativo (mL.kg<sup>-1</sup>.min<sup>-1</sup>) durante o T6m2 no grupo estudado encontra-se na <xref ref-type="fig" rid="f4">Figura 2</xref>. Observa-se na linha tracejada o valor do VO<sub>2</sub> do LA do TECP (11,76 mL.kg<sup>-1</sup>.min<sup>-1</sup>) e o valor de 15,9 mL.kg<sup>-1</sup>.min<sup>-1</sup> do VO<sub>2</sub> pico do TECP em destaque (<xref ref-type="fig" rid="f4">Figura 2</xref>).</p>
        <p>
          <fig id="f4">
            <label>Figura 2</label>
            <caption>
              <title>Comportamento longitudinal do consumo de oxig&#234;nio (VO<sub>2</sub>) relativo (mL/kg/min<sup>-1</sup>) durante o segundo teste da caminhada de 6 minutos (T6m2). Abreviaturas: T6m: segundo teste de caminhada de seis minutos; TECP: teste de esfor&#231;o cardiopulmonar; VO<sub>2</sub>: consumo de oxig&#234;nio (mL.kg<sup>-1</sup>.min<sup>-1</sup>); T1: tempo zero do T6m (situa&#231;&#227;o basal); T2, T3, T4, T5, T6, T7 - respectivamente: primeiro, segundo, terceiro, quarto, quinto e sexto minutos do T6m; LA: limiar anaer&#243;bio.</title>
            </caption>
            <graphic xlink:href="2359-5647-ijcs-31-02-0143-80001-gf02-pt.jpg"/></fig>
        </p>
        <p>O comportamento longitudinal da produ&#231;&#227;o de di&#243;xido de carbono (VCO<sub>2</sub>) relativo durante o T6m2 evoluiu de forma semelhante &#224; do VO<sub>2</sub>, atingindo valores m&#225;ximos no T6m2 de 11,5 mL.kg<sup>-1</sup>.min<sup>-1</sup> (Figura n&#227;o apresentada).</p>
        <p>Os n&#237;veis de correla&#231;&#227;o de Pearson (r) encontrados entre a dist&#226;ncia m&#225;xima percorrida no T6m2 com o VO<sub>2</sub> pico obtido neste mesmo teste, e desta dist&#226;ncia percorrida com o VO<sub>2</sub> pico do TECP foram, respectivamente, r = 0,528 (p = 0,014) e r = 0,532 (p = 0,013).</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Uma revis&#227;o de literatura realizada sobre o tema deste estudo &#8211; T6m e ICFEN &#8211; evidenciou que a quase totalidade dos trabalhos sobre este tema est&#225; voltada para a ICFER. Tornou-se dif&#237;cil, ent&#227;o, comparar os resultados encontrados neste estudo, que incluiu pacientes com ICFEN, com os achados da literatura. Por isso, a discuss&#227;o abaixo ser&#225; realizada com base em resultados similares encontrados em estudos com ICFER.</p>
        <p>Riley et al.,<xref ref-type="bibr" rid="B6">6</xref> Foray et al.,<xref ref-type="bibr" rid="B7">7</xref> Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> e Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> analisaram a cin&#233;tica de vari&#225;veis utilizando analisador de g&#225;s port&#225;til e demonstraram que a cin&#233;tica e outros par&#226;metros cardiovasculares est&#227;o alentecidos na popula&#231;&#227;o de ICFER, em resposta ao esfor&#231;o representado pelo T6m. Entretanto, n&#227;o se encontram estudos que descrevam como a cin&#233;tica de um grupo de portadores de ICFEN se comporta durante esse teste.</p>
        <p>No grupo de pacientes estudados, predominou o sexo feminino, portador de HAS e &#237;ndice de massa corporal (IMC) elevado,<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref> caracter&#237;sticas que confirmam o perfil cl&#237;nico t&#237;pico da ICFEN.</p>
        <p>A dist&#226;ncia m&#233;dia percorrida encontra-se dentro de valores que indicam bom progn&#243;stico, ou seja, acima dos 300 metros.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref> Um percentual significativo (81,81%) igualou ou elevou no T6m2 a dist&#226;ncia percorrida no T6m1, mas n&#227;o obteve valores para ter significado cl&#237;nico, ou seja, acima dos 50 metros.<xref ref-type="bibr" rid="B5">5</xref> Isto refor&#231;a a import&#226;ncia da realiza&#231;&#227;o de pelo menos um teste de aprendizagem e de familiariza&#231;&#227;o, por potencial influ&#234;ncia nos resultados do T6m.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref>
				</p>
        <p>As dist&#226;ncias obtidas est&#227;o de acordo com as m&#233;dias encontradas em estudos com grupos de ICFER, tais como os de Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> (452,6 &#177; 18,7 metros), Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> (419 &#177; 120 metros) e Guimar&#227;es et al.,<xref ref-type="bibr" rid="B9">9</xref> (470 &#177; 48 metros).</p>
        <p>Os n&#237;veis de correla&#231;&#227;o encontrados entre T6m2 com o VO<sub>2</sub> pico do T6m1 e com o VO<sub>2</sub> pico do TECP est&#227;o de acordo com achados da literatura, apesar das diverg&#234;ncias. Alguns autores citam uma boa correla&#231;&#227;o entre a dist&#226;ncia do T6m e VO<sub>2</sub> pico, com uma m&#233;dia de 0,73 em pacientes com IC<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref> (todos com ICFER). Riley et al.,<xref ref-type="bibr" rid="B6">6</xref> encontraram uma correla&#231;&#227;o alta (r = 0,63), j&#225; Lucas et al., <xref ref-type="bibr" rid="B20">20</xref> e Roul et al.,<xref ref-type="bibr" rid="B21">21</xref> encontraram baixa correla&#231;&#227;o com a dist&#226;ncia percorrida no T6m (r = 0,28 e r = 0,24, respectivamente). Tais diverg&#234;ncias poderiam ser atribu&#237;das a diferentes metodologias do T6m e tipos de erg&#244;metros utilizados.</p>
        <p>Os estudos em ICFER encontrados na literatura que avaliam o T6m realizados em um corredor e com analisadores de gases port&#225;teis acoplados foram os de Riley et al.,<xref ref-type="bibr" rid="B6">6</xref> Foray et al.,<xref ref-type="bibr" rid="B7">7</xref> Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> e Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> J&#225; Guimar&#227;es et al.,<xref ref-type="bibr" rid="B9">9</xref> utilizaram o analisador de gases durante dois testes T6m realizados em esteira, tamb&#233;m em portadores de ICFER.</p>
        <p>No comportamento da FC, observa-se que o grupo estudado mostra valores mais est&#225;veis a partir do segundo minuto do T6m (T3). Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> destacam que a obten&#231;&#227;o de um estado est&#225;vel mais precoce reflete melhores condi&#231;&#245;es cl&#237;nicas e, portanto, condi&#231;&#245;es menos graves.</p>
        <p>As FC ao final do T6m situaram-se em 85,7% em rela&#231;&#227;o &#224; FC m&#225;xima do TECP, assemelhando-se aos valores percentuais do VO<sub>2</sub> pico do T6m em rela&#231;&#227;o ao VO<sub>2</sub> pico do TECP.</p>
        <p>Destaca-se que as FC finais do T6m s&#227;o semelhantes &#224;s FC do LA do TECP, refor&#231;ando que o T6m representa um esfor&#231;o intenso, realizado a n&#237;vel ou acima do LA do TECP para portadores de IC.<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref>
				</p>
        <p>Apesar dos autores afirmarem que pacientes com ICFEN apresentam altera&#231;&#245;es na recupera&#231;&#227;o da FC no primeiro minuto da recupera&#231;&#227;o (FC1Rec)<xref ref-type="bibr" rid="B22">22</xref> e de n&#227;o haver dados na literatura em rela&#231;&#227;o ao T6m, se considerarmos o valor preconizado de 12 bpm, este dado ficou dentro da normalidade tanto no T6m quanto no TECP.<xref ref-type="bibr" rid="B23">23</xref>
				</p>
        <p>Pela an&#225;lise do &#237;ndice cronotr&#243;pico, demonstrou-se incompet&#234;ncia cronotr&#243;pica, mesmo se considerarmos o uso do betabloqueadores (normal &gt; 0,60), tanto em rela&#231;&#227;o ao T6m quanto para o TECP, conforme encontrado na literatura.<xref ref-type="bibr" rid="B24">24</xref>
				</p>
        <p>O pulso O<sub>2</sub> m&#225;ximo do T6m e TECP n&#227;o evidenciou diferen&#231;a entre os dois testes, obtendo-se valores de pulso O<sub>2</sub> reduzidos em rela&#231;&#227;o ao previsto (&lt; 85%), em torno de 70%, e com valores absolutos abaixo de 12 mL.kg<sup>-1</sup>.min<sup>-1</sup>/bpm, considerado de mau progn&#243;stico.<xref ref-type="bibr" rid="B25">25</xref>
				</p>
        <p>Em rela&#231;&#227;o &#224;s duas vari&#225;veis ventilat&#243;rias analisadas, n&#227;o foi observada diferen&#231;a para a inclina&#231;&#227;o VE/VCO<sub>2</sub>. Os valores da inclina&#231;&#227;o VE/VCO<sub>2</sub> se encontraram dentro dos citados como de bom progn&#243;stico (&lt; 30),<xref ref-type="bibr" rid="B13">13</xref> e tal fato associado &#224; falta de diferen&#231;a entre os dois testes pode refor&#231;ar a capacidade progn&#243;stica do T6m. A an&#225;lise da pot&#234;ncia ventilat&#243;ria (PV) tamb&#233;m demonstrou diferen&#231;a entre os dois testes, com maiores valores para o TECP. A PV, que conjuga a reposta da PAS com a inclina&#231;&#227;o VE/VCO<sub>2</sub> (PV = PAS x inclina&#231;&#227;o VE/VCO<sub>2</sub>)<xref ref-type="bibr" rid="B26">26</xref> apresentou diferen&#231;a provavelmente devido &#224; maior PAS no TECP. Entretanto, para ambos os testes, observaram-se valores de bom progn&#243;stico (&gt;3,5).<xref ref-type="bibr" rid="B26">26</xref>
				</p>
        <p>O QR &#233; crit&#233;rio para se obter esfor&#231;os intensos (&gt; 1,0) ou m&#225;ximos em exerc&#237;cios de intensidade crescente (&gt; 1,15).<xref ref-type="bibr" rid="B13">13</xref> N&#227;o houve diferen&#231;a entre os valores m&#225;ximos do QR entre os dois testes. Os dados aqui encontrados concordam com os de Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> que consideram o QR do T6m como de esfor&#231;o intenso. Tanto na popula&#231;&#227;o com ICFER<xref ref-type="bibr" rid="B10">10</xref> quanto nos pacientes com ICFEN no presente estudo, 50% de cada amostra obteve QR &gt; 1,0. Outros autores concordam e afirmam que quanto maior ao defici&#234;ncia funcional do grupo estudado, mais o T6m seria executado pr&#243;ximo ao m&#225;ximo.<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref>
				</p>
        <p>A an&#225;lise da VE/VO<sub>2</sub> demonstrou que a curva apresentou descenso e posterior ascens&#227;o, que se tornou significativa ap&#243;s o quinto minuto de teste (T6 e T7). Tal comportamento &#233; um dos crit&#233;rios utilizados na identifica&#231;&#227;o do LA em um TECP.<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref> Ao se transferir este conceito para o T6m, confirma-se que ele representou esfor&#231;o equivalente ao LA ou pouco acima.</p>
        <p>Em rela&#231;&#227;o a VE/VCO<sub>2</sub>, observou-se estabiliza&#231;&#227;o dos valores ap&#243;s o segundo minuto de esfor&#231;o (T3), com valores de pico pouco superiores aos do LA obtido no TECP (24,5 &#177; 3,1 no T6m <italic>versus</italic> 23,6 do LA no TECP). O VE/VCO<sub>2</sub> se estabilizou em valores que n&#227;o traduzem inefici&#234;ncia ventilat&#243;ria.</p>
        <p>O VO<sub>2</sub> relativo no T6m demonstrou valores est&#225;veis. Seu comportamento nos pacientes com ICFEN n&#227;o diferiu do encontrado em estudos semelhantes em pacientes com ICFER, tanto em termos de evolu&#231;&#227;o durante todo o T6m quanto em rela&#231;&#227;o aos percentuais obtidos em rela&#231;&#227;o ao TECP:<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref> atingem valores acima do VO<sub>2</sub> correspondente ao LA do TECP e de percentuais significativos do VO<sub>2</sub> pico do TECP (86,45%).</p>
        <p>A vari&#225;vel VCO<sub>2</sub> tendeu a se estabilizar a partir do T5 (quarto minuto do T6m), discordando dos dados de Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> que, para portadores de ICFER, n&#227;o observaram estado est&#225;vel nesta vari&#225;vel at&#233; o final do T6m.</p>
        <p>Os pacientes com ICFER no estudo de Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> realizaram o T6m acima do VO<sub>2</sub> relativo do LA no TECP, concordando com os achados para pacientes com ICFEN no presente estudo. Os VO<sub>2</sub> do LA no TECP obtidos por Kervio et al., <xref ref-type="bibr" rid="B10">10</xref> (11,7 &#177; 0,6 mL.kg<sup>-1</sup>.min<sup>-1</sup>) tamb&#233;m se encontram bem semelhantes aos encontrados neste estudo (11,76 mL.kg<sup>-1</sup>.min<sup>-1</sup>).</p>
        <p>Interessante notar que 7 dos 22 pacientes no presente estudo obtiveram VO<sub>2</sub> pico do T6m igual ou acima do VO<sub>2</sub> pico do TECP, representando 31,8% do total da amostra. Este valor percentual concorda e supera os de Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> (27,0%) para uma popula&#231;&#227;o de ICFER.</p>
        <p>A alta intensidade do T6m para os portadores de IC &#233; refor&#231;ada por achados do estudo de Kervio et al.,<xref ref-type="bibr" rid="B10">10</xref> Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> e Foray et al.,<xref ref-type="bibr" rid="B7">7</xref> que demonstraram que o T6m causa uma demanda acima de 85% dos valores do VO<sub>2</sub> relativo de pico do TECP.</p>
        <p>Faggiano et al.,<xref ref-type="bibr" rid="B8">8</xref> encontraram VO<sub>2</sub> pico a 86% do TECP, que representava 73,0% do VO<sub>2</sub> do LA do TECP. O presente estudo mostrou percentuais semelhantes em rela&#231;&#227;o ao TECP, mas o VO<sub>2</sub> do LA no TECP apresentou percentuais mais elevados, correspondendo a 85,03% do VO<sub>2</sub> pico do T6m para o grupo ICFEN. Guimar&#227;es et al.,<xref ref-type="bibr" rid="B9">9</xref> realizaram um TECP e um T6m, tamb&#233;m em esteira, com os participantes acoplados a um analisador de g&#225;s e, utilizando incentivo, encontraram um VO<sub>2</sub> pico a 90% do TECP.</p>
        <p>Os valores do VO<sub>2</sub> pico relativo encontrados no TECP concordam com os achados de Guazzi et al.,<xref ref-type="bibr" rid="B27">27</xref> Esses autores encontraram valores de VO<sub>2</sub> pico de 15 mL.kg<sup>-1</sup>.min<sup>-1</sup> no TECP em pacientes com ICFEN.</p>
        <p>Na inclina&#231;&#227;o da efici&#234;ncia do consumo de oxig&#234;nio (<italic>oxygen uptake efficiency slope</italic>, OUES), apesar de valores mais baixos para o T6m, n&#227;o houve diferen&#231;a entre o T6m e o TECP. Apesar da literatura indicar que tanto a ICFER quanto a ICFEN podem obter valores reduzidos,<xref ref-type="bibr" rid="B13">13</xref> os pacientes com ICFEN avaliados obtiveram valores acima de 1,2, considerados de mau progn&#243;stico.<xref ref-type="bibr" rid="B28">28</xref>
				</p>
        <p>A vari&#225;vel metab&#243;lica que mais mostrou diferen&#231;a foi a cin&#233;tica do consumo de oxig&#234;nio na recupera&#231;&#227;o (T1/2), que mostrou diferen&#231;a significativa entre os dois testes, com um tempo de recupera&#231;&#227;o significativamente maior no TECP. Os valores do T1/2 no T6m n&#227;o chegaram a preencher crit&#233;rios de mau progn&#243;stico.<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref><sup>,</sup><xref ref-type="bibr" rid="B29">29</xref> Considerando o valor de 90 segundos<xref ref-type="bibr" rid="B29">29</xref> no TECP, os participantes estudados ultrapassaram este valor.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>H&#225; uma real possibilidade dos pacientes portadores de ICFEN realizarem um T6m em intensidade m&#225;xima ou quase m&#225;xima. Tal estimativa &#233; embasada nas seguintes observa&#231;&#245;es: altos percentuais obtidos nos valores de pico do T6m em rela&#231;&#227;o aos valores m&#225;ximos das vari&#225;veis FC (85,7%) e VO<sub>2</sub> relativo (86,4%) no TECP, valores de QR semelhantes, valores do VO<sub>2</sub> pico do T6m semelhantes aos do LA no TECP e pela observa&#231;&#227;o do comportamento do VE/VO<sub>2</sub> que, ap&#243;s atingir seu nadir, mostrou tend&#234;ncia &#224; curva ascendente.</p>
        <p>Observa-se que em rela&#231;&#227;o aos estudos revisados, todos em pacientes com ICFER, a ICFEN mostra em m&#233;dia igual perfil de comportamento das vari&#225;veis avaliadas durante o T6m.</p>
        <sec>
          <title>Limita&#231;&#245;es do estudo</title>
          <p>S&#227;o identificadas algumas limita&#231;&#245;es neste estudo:</p>
          <list list-type="bullet">
            <list-item>
              <p>Tamanho reduzido da amostra estudada. Sugerem-se estudos adicionais com um n&#250;mero maior de pacientes para validar algumas das conclus&#245;es.</p>
            </list-item>
            <list-item>
              <p>A predomin&#226;ncia do sexo feminino e do sobrepeso/obesidade, caracter&#237;sticos da ICFEN, pode ter influenciado as vari&#225;veis referentes &#224; capacidade funcional tanto no T6m quanto no TECP.</p>
            </list-item>
            <list-item>
              <p>Os determinantes perif&#233;ricos do VO<sub>2</sub> pico, como o sistema de transporte de oxig&#234;nio ou altera&#231;&#245;es da musculatura perif&#233;rica, n&#227;o foram considerados na avalia&#231;&#227;o funcional.</p>
            </list-item>
            <list-item>
              <p>O uso de betabloqueadores e de outros f&#225;rmacos pode ter influenciado a interpreta&#231;&#227;o das vari&#225;veis que integram a FC ou PA no seu c&#225;lculo.</p>
            </list-item>
          </list>
        </sec>
      </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 &#233; parte de tese de professor associado de Jos&#233; Ant&#244;nio Caldas Teixeira pela Universidade Federal Fluminense.</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>
