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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.1" 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">HDWFwmKYXX79TzQbYrT778t</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S2359-56472018000400333</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S2359-56472018005002101</article-id>
      <article-id pub-id-type="doi">10.5935/2359-4802.20180021</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>ORIGINAL ARTICLE</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Comparison between Myocardial Ischemia Evaluation by Fractional Flow Reserve and Myocardial Perfusion Scintigraphy</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Issa</surname>
            <given-names>Aurora Felice Castro</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pittella</surname>
            <given-names>Felipe</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Leandro</surname>
            <given-names>Sergio Martins</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pa&#231;o</surname>
            <given-names>Patricia</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tadeu</surname>
            <given-names>Judas</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Felix</surname>
            <given-names>Renata</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <aff id="aff1">
          <institution content-type="orgname">Instituto Nacional de Cardiologia</institution>
          <addr-line>
            <city>Rio de Janeiro</city>
            <state>RJ</state>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto Nacional de Cardiologia, Rio de Janeiro, RJ - Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Aurora Felice Castro Issa</bold> Rua Tim&#243;teo da Costa, 623/110. Postal Code: 22450-130, Leblon, Rio de Janeiro, RJ - Brazil. E-mail: <email>auroraissa@gmail.com</email>; <email>auroraissa@cardiol.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Pittella F, Pa&#231;o P, Leandro SM, Felix R, Issa AFC. Acquisition of data: Pa&#231;o P, Leandro SM, Tadeu J, Felix R, Issa AFC. Analysis and interpretation of the data: Pittella F, Pa&#231;o P, Tadeu J, Felix R, Issa AFC. Statistical analysis: Pa&#231;o P, Issa AFC. Writing of the manuscript: Pa&#231;o P, Issa AFC. Critical revision of the manuscript for intellectual content: Pittella F, Felix R, Issa AFC. Supervision / as the major investigador: Leandro SM, Felix R, Issa AFC. Conducting examinations: Leandro SM, Felix R.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>21</day>
        <month>05</month>
        <year>2018</year>
      </pub-date>
      <pub-date pub-type="collection">
        <season>Jul-Aug</season>
        <year>2018</year>
      </pub-date>
      <volume>31</volume>
      <issue>4</issue>
      <fpage>333</fpage>
      <lpage>338</lpage>
      <history>
        <date date-type="received">
          <day>27</day>
          <month>11</month>
          <year>2016</year>
        </date>
        <date date-type="rev-recd">
          <day>18</day>
          <month>10</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>13</day>
          <month>11</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>Moderate coronary artery lesions can be, or not, responsible for myocardial ischemia. The functional analysis of these lesions can be performed by invasive and noninvasive methods.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To compare the functional analysis of moderate coronary lesions by fractional flow reserve and myocardial perfusion scintigraphy.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>47 patients with stable coronary artery disease and at least one moderate coronary artery obstruction were prospectively studied. They were submitted to fractional flow reserve and myocardial perfusion scintigraphy with a median interval of 24.5 days between January 2013 and December 2015. There was no change in clinical status or revascularization procedure between the exams. The population variables were described as medians and interquartile range. Fractional flow reserve was performed in one left main coronary artery; 37 left descending coronary arteries; 12 circumflex arteries and 4 right coronary arteries. Fractional flow reserve &lt; 0.8 was considered positive. The comparative analysis between the results of the tests was performed by two-tailed Fisher&#8217;s test and a p-value &#8804; 0.05 was considered significant.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>Fractional flow reserve &lt; 0.8 was found in the left main coronary artery (100%); 13 in the left descending coronary artery (35.14%); 6 in circumflex artery (50%) and 2 in the right coronary artery (50%). Among the patients with positive fractional flow reserve, 83% had myocardial ischemia demonstrated by the myocardial perfusion scintigraphy (p = 0.058). When analyzing specifically the left descending coronary artery, 83% of the patients with negative fractional flow reserve showed no ischemia at the myocardial perfusion scintigraphy, but 69% of the patients with positive fractional flow reserve showed no ischemia at the myocardial perfusion scintigraphy (p = 0.413).</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>Disagreements can occur between the results of the functional analysis of moderate coronary lesions by invasive and noninvasive tests.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Myocardial Ischemia</kwd>
        <kwd>Praqctional Flow Reserve, Myocardial</kwd>
        <kwd>Myocardial Perfusion / Diagnostic Imaging</kwd>
        <kwd>Microvascular Angina</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>The presence of myocardial ischemia is one of the important prognostic factors in coronary artery disease (CAD) and in the decision-making on the best treatment to be implemented. The combination of coronary anatomy and information on the hemodynamic implication of the obstructive lesion is essential to define the treatment strategy to be carried out in patients with CAD.</p>
      <p>The fractional flow reserve (FFR) measurement is a valuable tool to evaluate the functional severity of a coronary stenosis, identifying changes in coronary flow resistance. The FFR can be obtained in the hemodynamic laboratory and can be performed together with the angiography. The FFR is defined as the maximum blood flow to the myocardium in the presence of a certain stenosis, divided by this flow, if there was no such stenosis. The FFR can be determined by dividing the mean pressure distal to the coronary lesion by the mean aortic pressure during maximal adenosine-induced vasodilation. The FFR has a normal value of 1, and values &#8203;&#8203;less than 0.8 indicate myocardial ischemia. Studies have shown that coronary vessels with FFR &#8805; 0.8 can be clinically treated, with cardiovascular event rates similar to those of patients with normal noninvasive tests (&lt; 1% per year). Patients with FFR &#8804; 0.8 could benefit from percutaneous or surgical revascularization procedures.<xref ref-type="bibr" rid="B1">1</xref><sup>-</sup><xref ref-type="bibr" rid="B3">3</xref>
			</p>
      <p>Although the FFR has its defined role in moderate lesions and is not very useful in angiographically severe lesions, it helps in the decision-making regarding when to revascularize patients with multivessel disease. In these patients, it helps to define the revascularization strategy, as well as to better evaluate its extent, according to the functional evaluation of stenosis in critical coronary sites.<xref ref-type="bibr" rid="B4">4</xref>
			</p>
      <p>Myocardial perfusion scintigraphy (MPS) with tomographic images has been validated by several studies in the evaluation of diagnosis and prognosis for patients at risk of cardiovascular events. The functional repercussion of coronary lesions constitutes one of the main purposes of the method, which is based on the perfusion deficit assessment in myocardial segments irrigated by partially occluded arteries. Risk stratification is based on the ability to identify patients according to the test results. SPECT with normal or slightly altered perfusion has an excellent prognosis, with a low mortality risk (&lt; 1%) per year. The risk associated with perfusion alterations varies according to the ischemia extent and severity. The greater the perfusion defects, the higher the likelihood of future events. In those with moderate perfusion defects, the incidence of events is 1 to 3% per year, being &gt; 3% in patients with major perfusion defects.<xref ref-type="bibr" rid="B5">5</xref>
			</p>
      <p>Most percutaneous coronary interventions are performed based on angiographic criteria alone, with no objective evidence of myocardial ischemia. Coronary angiography has limitations in establishing functional severity, because the stenosis degree of a lesion does not always correlate with functional impairment in the myocardium.6 Thus, it is important to complement anatomical data with functional tests capable of adequately guiding the therapeutic approach regarding a myocardial revascularization procedure. Several studies have been carried out to evaluate the agreement between the FFR with functional methods (MPS, dobutamine stress echocardiogram and exercise testing) to define the presence of myocardial ischemia, with the FFR having the advantage of being specific for each vessel and obstruction.<xref ref-type="bibr" rid="B7">7</xref> In multi-vessel patients, MPS tends to underestimate or overestimate the functional importance of coronary stenosis when compared to FFR.<xref ref-type="bibr" rid="B8">8</xref>
			</p>
      <p>The functional tests are performed in a minority of patients referred to coronary angioplasty at Instituto Nacional de Cardiologia. In this sense, the FFR can be a useful tool in the hemodynamics room to aid in decision-making regarding whether or not to perform a percutaneous coronary intervention, saving time and costs to the health system. The objective of the present study was to compare the functional analysis between FFR and MPS in patients with moderate lesions at the coronary angiography.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>This is a prospective, observational study of patients of both genders, aged 18 years or older, admitted to the Department of Coronary Disease unit or referred to the Hemodynamic Service of Instituto Nacional de Cardiologia, who had an FFR indication after the coronary angiography by the multidisciplinary &#8220;Heart team&#8221;. The sample size of 47 patients was selected by convenience.</p>
      <p>Patients with no previous MPS were submitted to the examination. Coronary lesions were classified as moderate (between 50 and 70%) and severe (&#8805; 70%) according to visual estimation.</p>
      <p>Patients with moderate lesions and those for whom there was doubt regarding the indication of myocardial revascularization were included in the study. Patients with chronic occlusion, ST-segment elevation acute myocardial infarction, unstable patients, those with severe valvular disease or cardiomyopathies from other causes, patients with contraindications to the use of adenosine and to scintigraphy (pregnant women, infants and women with suspected pregnancy) were excluded from the study.</p>
      <p>The study was approved by the Ethics and Research Committee of Instituto Nacional de Cardiologia, and all the participants agreed to sign the Free and Informed Consent Form. The present study has no sources of funding.</p>
      <sec>
        <title>Fractional flow reserve measurement</title>
        <p>Coronary catheterization was performed with 6 and 7F guide catheters. Prior to the angiography, 10,000 u of intravenous heparin and intracoronary nitroglycerin at a dose of 0.25 to 0.5 mg were administered. Then, pressure measurements were performed in vessels with stenosis &#8805; 50% by visual estimation using a guidewire with a sensor at its tip and was positioned in the distal bed of each coronary to be analyzed. Intravenous adenosine at the dose of 140 mg/kg/minute was administered for 2 to 3 minutes to induce maximal hyperemia.</p>
        <p>The FFR was established as the ratio between the mean distal coronary pressure and the mean aortic pressure, measured by the guide catheter during maximal hyperemia. Stenoses with FFR &lt; 0.8 were considered positive for ischemia.</p>
      </sec>
      <sec>
        <title>Myocardial perfusion scintigraphy</title>
        <p>The MPS was performed using the Single-Photon Emission Computed Tomography (SPECT) technique, using technetium-99m sestamibi (Tc-99m MIBI) with the 2-day protocol at rest and exercise or dipyridamole stress test. The images were semi-quantitatively analyzed using a 17-segment model. The test was considered abnormal when it disclosed evidence of one or more ischemic areas. The percentage of ischemic area was not evaluated in all patients.</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>A descriptive analysis of the selected patients&#8217; basal characteristics was performed by calculating medians and interquartile ranges. The assessment of the association between the presence of ischemia in the MPS and FFR was assessed using the two-tailed Fisher&#8217;s exact test. A p-value &lt; 0.05 was considered statistically significant. The STATA/MP software by StatCorp LP, version 14.2, was used for data analysis.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>When characterizing the sample of assessed patients, 47 individuals with stable coronary disease and a median age of 65.4 years (interquartile range between 58.03 and 69.59 years) were selected. Most were women (66%) and had stable angina (82%); and 7% were post-acute myocardial infarction.</p>
      <p>Regarding left ventricular function, only 14% had moderate to severe dysfunction. The ejection fraction calculated by the Teichholz method showed a median of 64.5%, with an interquartile range between 45% and 71% (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
      <table-wrap id="t1">
        <label>Table 1</label>
        <caption>
          <title>Patients' characteristics</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="50%"/>
            <col width="50%"/>
          </colgroup>
          <tbody>
            <tr>
              <td align="left">Age, years</td>
              <td align="center">65.45 (58.03-69.59)</td>
            </tr>
            <tr>
              <td align="left">Female, %</td>
              <td align="center">65.96</td>
            </tr>
            <tr>
              <td align="left">Ethnicity, %</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">White</td>
              <td align="center">63.83</td>
            </tr>
            <tr>
              <td align="left">Mixed-race</td>
              <td align="center">25.53</td>
            </tr>
            <tr>
              <td align="left">Black</td>
              <td align="center">10.64</td>
            </tr>
            <tr>
              <td align="left">Diagnosis, %</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">Stable angina</td>
              <td align="center">82.98</td>
            </tr>
            <tr>
              <td align="left">Previous AMI</td>
              <td align="center">14.89</td>
            </tr>
            <tr>
              <td align="left">Others</td>
              <td align="center">2.13</td>
            </tr>
            <tr>
              <td align="left">SAH</td>
              <td align="center">91.11</td>
            </tr>
            <tr>
              <td align="left">Dyslipidemia</td>
              <td align="center">91.11</td>
            </tr>
            <tr>
              <td align="left">Diabetes Mellitus</td>
              <td align="center">42.22</td>
            </tr>
            <tr>
              <td align="left">Smoker</td>
              <td align="center">40.00</td>
            </tr>
            <tr>
              <td align="left">Cerebrovascular disease</td>
              <td align="center">8.89</td>
            </tr>
            <tr>
              <td align="left">Kidney failure</td>
              <td align="center">4.44</td>
            </tr>
            <tr>
              <td align="left">Sedentary lifestyle</td>
              <td align="center">86.67</td>
            </tr>
            <tr>
              <td align="left">Obesity</td>
              <td align="center">13.95</td>
            </tr>
            <tr>
              <td align="left">Family history</td>
              <td align="center">52.27</td>
            </tr>
            <tr>
              <td align="left">LVEF &lt; 50%</td>
              <td align="center">14.28</td>
            </tr>
            <tr>
              <td align="left">EF Teichholz</td>
              <td align="center">64.5 (45-71)</td>
            </tr>
            <tr>
              <td align="left">Three-vessel anatomy or LMCA</td>
              <td align="center">38.80</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <p>AMI: acute myocardial infarction; SAH: systemic arterial hypertension; LVEF: left ventricular ejection fraction; EF: ejection fraction; LMCA: left main coronary artery.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>The stress assessment by MPS was performed in 68% with dipyridamole and in 32% through an exercise stress test. The interval between MPS and FFR was 24.5 days between January 2013 and October 2015.</p>
      <p>In the analyzed sample of patients, 38.8% had a three-vessel lesion or had a left main coronary artery lesion. FFR was performed in the following territories: one left main coronary artery, 37 anterior descending arteries (ADA), 12 circumflex arteries and 4 right coronary arteries.</p>
      <p>In the comparative analysis of the MPS and FFR results, 83% of the patients with positive FFR also had positive MPS, but with a non-significant p value (0.058) and 53.57% of the patients with positive MPS had a negative FFR (<xref ref-type="fig" rid="f1">Figure 1</xref>).</p>
      <p>
        <fig id="f1">
          <label>Figure 1</label>
          <caption>
            <title>Myocardial scintigraphy (MS), according to the fractional flow reserve (FFR).</title>
          </caption>
          <graphic xlink:href="2359-5647-ijcs-31-04-0333-80021-gf01.jpg"/></fig>
      </p>
      <p>When discriminating the assessment of the ADA territory, 83% of patients with negative FFR also had negative MPS, but in those who obtained positive FFR results, MPS was negative in 69% &#8722; both results showed a non-significant p value (0.413) (<xref ref-type="fig" rid="f2">Figure 2</xref>).</p>
      <p>
        <fig id="f2">
          <label>Figure 2</label>
          <caption>
            <title>Myocardial scintigraphy (MS) in the anterior descending artery (ADA) according to the fractional flow reserve (FFR).</title>
          </caption>
          <graphic xlink:href="2359-5647-ijcs-31-04-0333-80021-gf02.jpg"/></fig>
      </p>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>When assessing ischemia, the agreement between MPS and FFR is a weak one.<xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B9">9</xref> In the present study, we observed the non-agreement between the methods, although 83% of patients with positive FFR had positive MPS; the <italic>p</italic> value was not significant.</p>
      <p>Such disagreement becomes more evident in patients with multivessel disease, since MPS tends to underestimate the functional importance of the lesions.<xref ref-type="bibr" rid="B8">8</xref> The FFR reflects the pressure gradient in a single vessel; on the other hand, the MS makes a comparison of the functional stenosis severity between the vessels. The perfusion defect in MPS is defined by comparison with the region of higher perfusion, considering that this region is normal, but often it is also an altered region &#8722; although less affected.<xref ref-type="bibr" rid="B10">10</xref> In the assessed sample, 38.8 % of the patients had left main coronary artery or three-vessel disease, which may have contributed to a disagreement between the results.</p>
      <p>Another factor to be considered regarding the agreement analysis is the presence of microvascular disease, which influences the FFR assessment,<xref ref-type="bibr" rid="B10">10</xref> although other invasive evaluations can be performed to better quantify the microvascular disease. The coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) improve risk stratification in patients with negative FFR, being an independent prognostic factor.<xref ref-type="bibr" rid="B11">11</xref><sup>-</sup><xref ref-type="bibr" rid="B13">13</xref> The CFR represents the vasodilation capacity of the coronary vascular bed during hyperemia, being measured by thermodilution indicators. A low CFR value (&#8804; 2) indicates microvascular dysfunction. Additionally, the microvascular resistance index also provides data on microvascular function, being measured by through the distal coronary pressure multiplied by the mean transit time of 3 mL of saline bolus during adenosine-induced hyperemia, with the normal value being &lt; 20, whereas the altered value is &gt; 30.<xref ref-type="bibr" rid="B11">11</xref><sup>-</sup><xref ref-type="bibr" rid="B13">13</xref> In the total sample, the FFR was negative in 53.57% of the patients who had a positive MPS, a result that can be explained by the presence of microvascular disease, which was confirmed by the abovementioned methods.</p>
      <p>No significant agreement was observed in the ADA-specific analysis, but 83% of the patients with negative scintigraphy also had a negative FFR.</p>
      <p>There was no significant data on agreement or disagreement in our sample, possibly due to the number of patients studied, requiring that a larger sample be assessed.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>Disagreements may occur between the functional analysis results of moderate coronary lesions by invasive and non-invasive tests. This fact can have important consequences in the use of the scintigraphy to establish the optimal revascularization strategy, mainly in multivessel patients. Therefore, fractional flow reserve is good technique to be used together with coronary angiography, especially in patients with multivessel lesions, since anatomic and functional stratifications can be obtained in a single procedure. Regarding patients with microvascular disease, the fractional flow reserve is not defined as an ideal strategy to evaluate ischemia.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Ethics approval and consent to participate</bold>
        </p>
        <p>This study was approved by the Ethics Committee of the Instituto Nacional de Cardiologia under the protocol number 5272. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>References</title>
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        <label>1</label>
        <mixed-citation>1 Sant&#8217;Anna FM, Brito MB. Fractional flow reserve: concepts and application. Rev SOCERJ. 2009;22(1):43-55.</mixed-citation>
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              <surname>Sant&#8217;Anna</surname>
              <given-names>FM</given-names>
            </name>
            <name>
              <surname>Brito</surname>
              <given-names>MB</given-names>
            </name>
          </person-group>
          <article-title>Fractional flow reserve: concepts and application</article-title>
          <source>Rev SOCERJ</source>
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              <surname>Mattos</surname>
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            <name>
              <surname>Lemos</surname>
              <given-names>PA</given-names>
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            </name>
            <name>
              <surname>Rassi</surname>
              <given-names>A</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Marin-Neto</surname>
              <given-names>JA</given-names>
            </name>
            <name>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>ARTIGO ORIGINAL</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Compara&#231;&#227;o entre Avalia&#231;&#227;o de Isquemia Mioc&#225;rdica pela Reserva de Fluxo Fracionada e Cintilografia de Perfus&#227;o Mioc&#225;rdica</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Issa</surname>
            <given-names>Aurora Felice Castro</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pittella</surname>
            <given-names>Felipe</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Leandro</surname>
            <given-names>Sergio Martins</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pa&#231;o</surname>
            <given-names>Patricia</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tadeu</surname>
            <given-names>Judas</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Felix</surname>
            <given-names>Renata</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <aff id="aff2">
          <institution content-type="original">Instituto Nacional de Cardiologia, Rio de Janeiro, RJ - Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Aurora Felice Castro Issa</bold> Rua Tim&#243;teo da Costa, 623/110. CEP: 22450-130, Leblon, Rio de Janeiro, RJ - Brasil E-mail: <email>auroraissa@gmail.com</email>; <email>auroraissa@cardiol.br</email>
				</corresp>
        <fn fn-type="con" id="fn1">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Pittella F, Pa&#231;o P, Leandro SM, Felix R, Issa AFC. Obten&#231;&#227;o de dados: Pa&#231;o P, Leandro SM, Tadeu J, Felix R, Issa AFC. An&#225;lise e interpreta&#231;&#227;o dos dados: Pittella F, Pa&#231;o P, Tadeu J, Felix R, Issa AFC. An&#225;lise estat&#237;stica: Pa&#231;o P, Issa AFC. Reda&#231;&#227;o do manuscrito: Pa&#231;o P, Issa AFC. Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Pittella F, Felix R, Issa AFC. Realiza&#231;&#227;o de Exames: Leandro SM, Felix R.</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>Les&#245;es coron&#225;rias moderadas podem ser, ou n&#227;o, respons&#225;veis pela isquemia mioc&#225;rdica. A an&#225;lise funcional das les&#245;es pode ser realizada por m&#233;todos invasivos e n&#227;o invasivos.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Comparar a an&#225;lise funcional das les&#245;es coronarianas moderadas pela reserva de fluxo fracionado e pela cintilografia de perfus&#227;o mioc&#225;rdica.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Foram estudados prospectivamente 47 pacientes com doen&#231;a arterial coron&#225;ria est&#225;vel com pelo menos uma les&#227;o coronariana moderada obstrutiva. Eles foram submetidos &#224; reserva de fluxo fracionado e &#224; cintilografia de perfus&#227;o mioc&#225;rdica com intervalo m&#233;dio de 24,5 dias, entre janeiro de 2013 e dezembro de 2015. N&#227;o houve altera&#231;&#227;o no estado cl&#237;nico e nem no procedimento de revasculariza&#231;&#227;o entre exames. As vari&#225;veis populacionais foram descritas como mediana e interquartil. A reserva de fluxo fracionado foi realizada em um de tronco de coron&#225;ria esquerda; 37 art&#233;rias coron&#225;rias descendentes; 12 art&#233;rias circunflexas e quatro art&#233;rias coron&#225;rias direitas. Reserva de fluxo fracionado &lt; 0,8 foi considerada positiva. A an&#225;lise comparativa entre os resultados dos testes foi feita pelo teste de Fisher bicaudal, sendo considerado significativo valor de p &lt; 0,05.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>A reserva de fluxo fracionado &lt; 0,8 foi encontrada no tronco de coron&#225;ria esquerda (100%); 13 na art&#233;ria coron&#225;ria descendente (35,14%); seis na art&#233;ria circunflexa (50%) e duas na art&#233;ria coron&#225;ria direita (50%). Dentre os pacientes com reserva de fluxo fracionado positiva, 83% tinham isquemia mioc&#225;rdica demonstrada na cintilografia de perfus&#227;o mioc&#225;rdica (p = 0,058). Analisando especificamente o territ&#243;rio da art&#233;ria coron&#225;ria descendente, 83% dos pacientes com reserva de fluxo fracionado negativa n&#227;o tinham isquemia na cintilografia de perfus&#227;o mioc&#225;rdica, mas 69% dos pacientes com reserva de fluxo fracionado positiva n&#227;o tinham isquemia na cintilografia de perfus&#227;o mioc&#225;rdica (p = 0,413).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>Pode ocorrer discord&#226;ncia entre os resultados de an&#225;lise funcional de les&#245;es coron&#225;rias moderadas por testes invasivos e n&#227;o invasivos.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavra-chave:</title>
        <kwd>Isquemia Mioc&#225;rdica</kwd>
        <kwd>Reserva Fracionada de Fluxo Mioc&#225;rdico</kwd>
        <kwd>Imagem de Perfus&#227;o do Mioc&#225;rdio / diagn&#243;stico por imagem</kwd>
        <kwd>Angina Microvascular</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A presen&#231;a de isquemia mioc&#225;rdica &#233; um dos fatores progn&#243;sticos importantes na doen&#231;a arterial coronariana (DAC) e na tomada de decis&#227;o sobre o melhor tratamento a ser institu&#237;do. A combina&#231;&#227;o da anatomia coron&#225;ria com a informa&#231;&#227;o do significado hemodin&#226;mico da les&#227;o obstrutiva &#233; fundamental para definir a estrat&#233;gia de tratamento a ser realizada nos pacientes com DAC.</p>
        <p>A medida da reserva de fluxo fracionada (RFF) &#233; uma ferramenta valiosa para avaliar a gravidade funcional de uma estenose coronariana, identificando-se altera&#231;&#245;es na resist&#234;ncia ao fluxo coronariano. A RFF pode ser obtida no laborat&#243;rio de hemodin&#226;mica e pode ser realizada em conjunto com a angiografia. Define-se RFF como o fluxo sangu&#237;neo m&#225;ximo para o mioc&#225;rdio na presen&#231;a de uma determinada estenose, dividido por este fluxo, se n&#227;o houvesse esta estenose. A RFF pode ser determinada dividindo-se a press&#227;o m&#233;dia distal &#224; les&#227;o coronariana pela press&#227;o m&#233;dia em aorta, durante a vasodilata&#231;&#227;o m&#225;xima induzida por adenosina. Considera-se que a RFF apresenta valor normal de 1, e que valores menores que 0,8 s&#227;o indicativos de isquemia mioc&#225;rdica. Estudos demonstram que vasos coronarianos que apresentam RFF &#8805; 0,8 podem ser tratados clinicamente, com taxas de eventos cardiovasculares semelhantes &#224;s de pacientes com testes n&#227;o invasivos normais (&lt; 1% ao ano). Pacientes com RFF &#8804; 0,8 poderiam se beneficiar de procedimentos de revasculariza&#231;&#227;o percut&#226;nea ou cir&#250;rgica.<xref ref-type="bibr" rid="B1">1</xref><sup>-</sup><xref ref-type="bibr" rid="B3">3</xref>
				</p>
        <p>Embora a RFF tenha seu papel definido em les&#245;es moderadas e seja pouco &#250;til em les&#245;es angiograficamente graves, ela ajuda na decis&#227;o sobre quando revascularizar portadores de doen&#231;a multiarterial. Nestes pacientes, ela auxilia na defini&#231;&#227;o da estrat&#233;gia de revasculariza&#231;&#227;o, al&#233;m de avaliar melhor sua extens&#227;o, de acordo com a avalia&#231;&#227;o funcional das estenoses em locais cr&#237;ticos das coron&#225;rias.<xref ref-type="bibr" rid="B4">4</xref>
				</p>
        <p>A cintilografia de perfus&#227;o mioc&#225;rdica (CPM) com imagens tomogr&#225;ficas tem sido validada por in&#250;meros estudos na avalia&#231;&#227;o do diagn&#243;stico e do progn&#243;stico para pacientes sob risco de eventos cardiovasculares. A repercuss&#227;o funcional de les&#245;es coronarianas consiste em um dos principais focos do m&#233;todo, que se baseia na avalia&#231;&#227;o do d&#233;fice de perfus&#227;o em segmentos mioc&#225;rdicos irrigados por art&#233;rias parcialmente oclu&#237;das. A estratifica&#231;&#227;o de risco &#233; baseada na capacidade de identificar pacientes, de acordo com os resultados do exame. O SPECT com perfus&#227;o normal ou discretamente alterada tem excelente progn&#243;stico, com baixo risco de mortalidade (&lt; 1%) ao ano. O risco associado &#224; altera&#231;&#227;o da perfus&#227;o varia de acordo com a extens&#227;o e a gravidade da isquemia. Quanto maiores os defeitos de perfus&#227;o, maior a probabilidade de eventos futuros. Naqueles com defeitos de perfus&#227;o moderados, a incid&#234;ncia de eventos &#233; de 1 a 3% ao ano, sendo &gt; 3% em pacientes com grandes defeitos de perfus&#227;o.<xref ref-type="bibr" rid="B5">5</xref>
				</p>
        <p>Grande parte das interven&#231;&#245;es coronarianas percut&#226;nea &#233; realizada baseada somente em crit&#233;rios angiogr&#225;ficos, sem evid&#234;ncia objetiva de isquemia mioc&#225;rdica. A angiografia coronariana mostra limita&#231;&#245;es em estabelecer a gravidade funcional, porque nem sempre o grau de estenose de uma les&#227;o correlaciona com o comprometimento funcional provocado no mioc&#225;rdio.<xref ref-type="bibr" rid="B6">6</xref> Assim, faz-se importante a complementa&#231;&#227;o de dados anat&#244;micos com testes funcionais capazes de orientar adequadamente a terap&#234;utica em rela&#231;&#227;o a um procedimento de revasculariza&#231;&#227;o mioc&#225;rdica. V&#225;rios estudos t&#234;m sido realizados com a finalidade de avaliar a concord&#226;ncia da RFF com os m&#233;todos funcionais (CPM, ecocardiograma de estresse com dobutamina e teste ergom&#233;trico) na defini&#231;&#227;o da presen&#231;a de isquemia mioc&#225;rdica, tendo a RFF a vantagem de ser espec&#237;fica para cada vaso e obstru&#231;&#227;o.<xref ref-type="bibr" rid="B7">7</xref> Em pacientes multiarteriais, a CPM tende a subestimar ou superestimar a import&#226;ncia funcional da estenose coron&#225;ria em compara&#231;&#227;o com FFR.<xref ref-type="bibr" rid="B8">8</xref>
				</p>
        <p>O testes funcionais s&#227;o realizados em uma minoria de pacientes encaminhados para angioplastia coronariana no Instituto Nacional de Cardiologia. Neste sentido, a RFF pode ser uma ferramenta &#250;til na sala de hemodin&#226;mica para auxiliar nas tomadas de decis&#227;o de realizar ou n&#227;o uma interven&#231;&#227;o coronariana percut&#226;nea, poupando tempo e custos ao sistema de sa&#250;de. O objetivo do presente trabalho foi comparar a an&#225;lise funcional entre a RFF e a CPM em pacientes com les&#245;es moderadas na coronariografia.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Trata-se de estudo prospectivo, observacional, com sele&#231;&#227;o de pacientes de ambos os sexos, com idade maior ou igual a 18 anos internados na enfermaria do Departamento de Doen&#231;a Coron&#225;ria ou encaminhados ao Servi&#231;o de Hemodin&#226;mica do Instituto Nacional de Cardiologia, que apresentavam indica&#231;&#227;o de RFF ap&#243;s a an&#225;lise da coronariografia por equipe multidisciplinar &#8220;Time do Cora&#231;&#227;o&#8221;. O tamanho amostral de 47 pacientes foi selecionado por conveni&#234;ncia.</p>
        <p>Os pacientes sem CPM pr&#233;via foram submetidos ao exame. As les&#245;es coronarianas foram classificadas em moderadas (entre 50 e 70%) e graves (&#8805; 70%) de acordo com estimativa visual.</p>
        <p>Foram inclu&#237;dos pacientes com les&#245;es moderadas e para quem existisse d&#250;vida com rela&#231;&#227;o &#224; indica&#231;&#227;o de revasculariza&#231;&#227;o mioc&#225;rdica. Foram exclu&#237;dos pacientes portadores de oclus&#227;o cr&#244;nica, com infarto agudo do mioc&#225;rdio com supradesnivelamento e os inst&#225;veis, com doen&#231;a valvar grave ou cardiomiopatias de outras causas, contraindica&#231;&#227;o ao uso de adenosina e contraindica&#231;&#227;o &#224; realiza&#231;&#227;o da cintilografia (gestantes, lactantes e mulheres com suspeita de gravidez).</p>
        <p>O estudo foi aprovado pelo Comit&#234; de &#201;tica e Pesquisa do Instituto Nacional de Cardiologia e todos os participantes concordaram com Termo de Consentimento Livre e Esclarecido. O presente estudo n&#227;o possui fontes de financiamento.</p>
        <sec>
          <title>Realiza&#231;&#227;o da medida da reserva de fluxo fracionada</title>
          <p>Foi realizado cateterismo das coron&#225;rias com cateteres guia 6 e 7 F. Antes da angiografia, foram administrado 10.000 u de heparina endovenosa e nitroglicerina intracoron&#225;ria, na dose de 0,25 a 0,5 mg. A seguir, foram feitas as medidas press&#243;ricas nos vasos com estenoses &#8805; 50% pela estimativa visual, utilizando corda guia, que tinha um sensor em sua ponta e estava posicionada no leito distal de cada coron&#225;ria a ser analisada. Foi administrado adenosina endovenosa na dose de 140 mg/kg/minuto, durante 2 a 3 minutos, para induzir hiperemia m&#225;xima.</p>
          <p>A RFF foi determinada como a raz&#227;o entre a press&#227;o m&#233;dia distal da coron&#225;ria e a press&#227;o m&#233;dia da aorta, medida pelo cateter guia durante hiperemia m&#225;xima. As estenoses com RFF &lt; 0,8 foram consideradas positivas para isquemia.</p>
        </sec>
        <sec>
          <title>Realiza&#231;&#227;o da cintilografia de perfus&#227;o mioc&#225;rdica</title>
          <p>A CPM foi realizada por meio da t&#233;cnica de Tomografia Computadorizada por Emiss&#227;o de F&#243;ton &#218;nico (SPECT, acr&#244;nimo do ingl&#234;s <italic>Single Photon Emission Computed Tomography</italic>), utilizando-se Tecn&#233;cio-99m sestamibi (Tc-99m MIBI) no protocolo de 2 dias em repouso e estresse com esfor&#231;o ou dipiridamol. A an&#225;lise das imagens foi feita de forma semiquantitativa, usando um modelo de 17 segmentos. O exame foi considerado anormal ao evidenciar um ou mais territ&#243;rios isqu&#234;micos. A porcentagem de &#225;rea isqu&#234;mica n&#227;o foi avaliada em todos os pacientes.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>Foi realizada an&#225;lise descritiva das caracter&#237;sticas basais dos pacientes selecionados por meio de c&#225;lculos de medianas e interquartis. A avalia&#231;&#227;o da associa&#231;&#227;o entre a presen&#231;a de isquemia na CPM e RFF foi avaliada por meio do teste exato de Fisher bicaudal. Valor de p &lt; 0,05 foi considerado estatisticamente significativo. Foi utilizado o <italic>software</italic> STATA/MP, vers&#227;o 14.2, da StatCorp LP para a an&#225;lise dos dados.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>Ao caracterizar a amostra de pacientes estudados, foram selecionados 47 indiv&#237;duos com doen&#231;a coronariana est&#225;vel, com mediana de idade de 65,4 anos (intervalo dos interquatis entre 58,03 e 69,59 anos). A maioria era mulheres (66%) e apresentava angina est&#225;vel (82%); e 7% eram p&#243;s-infarto agudo do mioc&#225;rdio.</p>
        <p>Em rela&#231;&#227;o &#224; fun&#231;&#227;o de ventr&#237;culo esquerdo, somente 14% apresentavam disfun&#231;&#227;o moderada &#224; grave. O valor da fra&#231;&#227;o de eje&#231;&#227;o pelo m&#233;todo de Teichholz registrou mediana foi 64,5%, e os interquatis ente 45 e 71% (<xref ref-type="table" rid="t2">Tabela 1</xref>).</p>
        <table-wrap id="t2">
          <label>Tabela 1</label>
          <caption>
            <title>Caracter&#237;sticas dos pacientes</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="50%"/>
              <col width="50%"/>
            </colgroup>
            <tbody>
              <tr>
                <td align="left">Idade, anos</td>
                <td align="center">65,45 (58,03-69,59)</td>
              </tr>
              <tr>
                <td align="left">Sexo feminino, %</td>
                <td align="center">65,96</td>
              </tr>
              <tr>
                <td align="left">Ra&#231;a, %</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Branco</td>
                <td align="center">63,83</td>
              </tr>
              <tr>
                <td align="left">Pardo</td>
                <td align="center">25,53</td>
              </tr>
              <tr>
                <td align="left">Negro</td>
                <td align="center">10,64</td>
              </tr>
              <tr>
                <td align="left">Diagn&#243;stico, %</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">Angina est&#225;vel</td>
                <td align="center">82,98</td>
              </tr>
              <tr>
                <td align="left">IAM pr&#233;vio</td>
                <td align="center">14,89</td>
              </tr>
              <tr>
                <td align="left">Outros</td>
                <td align="center">2,13</td>
              </tr>
              <tr>
                <td align="left">HAS</td>
                <td align="center">91,11</td>
              </tr>
              <tr>
                <td align="left">Dislipidemia</td>
                <td align="center">91,11</td>
              </tr>
              <tr>
                <td align="left">Diabetes melito</td>
                <td align="center">42,22</td>
              </tr>
              <tr>
                <td align="left">Tabagista</td>
                <td align="center">40,00</td>
              </tr>
              <tr>
                <td align="left">Doen&#231;a cerebrovascular</td>
                <td align="center">8,89</td>
              </tr>
              <tr>
                <td align="left">Insufici&#234;ncia renal</td>
                <td align="center">4,44</td>
              </tr>
              <tr>
                <td align="left">Sedentarismo</td>
                <td align="center">86,67</td>
              </tr>
              <tr>
                <td align="left">Obesidade</td>
                <td align="center">13,95</td>
              </tr>
              <tr>
                <td align="left">Historia familiar</td>
                <td align="center">52,27</td>
              </tr>
              <tr>
                <td align="left">FEVE &lt; 50%</td>
                <td align="center">14,28</td>
              </tr>
              <tr>
                <td align="left">FE Teichholz</td>
                <td align="center">64,5 (45-71)</td>
              </tr>
              <tr>
                <td align="left">Anatomia trivascular ou TCE</td>
                <td align="center">38,80</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>IAM: infarto agudo do mioc&#225;rdio; HAS: hipertens&#227;o arterial sist&#234;mica; FE: fra&#231;&#227;o de eje&#231;&#227;o; VE: ventr&#237;culo esquerdo; TCE: tronco de coron&#225;ria esquerda.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>A avalia&#231;&#227;o do estresse pela CPM foi feita 68% com dipiridamol e em 32% com esfor&#231;o. O intervalo entre a realiza&#231;&#227;o da CPM e a RFF foi de 24,5 dias, entre janeiro de 2013 e outubro de 2015.</p>
        <p>Na amostra analisada dos pacientes, 38,8% eram trivasculares ou com les&#227;o de tronco. O RFF foi realizado nos seguintes territ&#243;rios: um tronco da coron&#225;ria esquerda, 37 art&#233;rias descendentes anteriores (ADA), 12 circunflexas e 4 coron&#225;rias direitas.</p>
        <p>Na an&#225;lise comparativas dos resultados da CPM e RFF, 83% dos pacientes com RFF positiva tamb&#233;m possu&#237;am CPM positiva, por&#233;m com o valor de p n&#227;o significativo (0,058) e 53,57% dos pacientes com CPM positiva apresentavam RFF negativa (<xref ref-type="fig" rid="f3">Figura 1</xref>).</p>
        <p>
          <fig id="f3">
            <label>Figura 1</label>
            <caption>
              <title>Cintilografia mioc&#225;rdica (CM), de acordo com a reserva fracionada de fluxo (RFF).</title>
            </caption>
            <graphic xlink:href="2359-5647-ijcs-31-04-0333-80021-gf01-pt.jpg"/></fig>
        </p>
        <p>Ao discriminar a avalia&#231;&#227;o do territ&#243;rio da ADA, 83% dos paciente com RFF negativa tamb&#233;m apresentavam CPM negativa, mas, naqueles que obtiveram resultados positivos da RFF, a CPM foi negativa em 69% - ambos os resultados apresentaram valor de p n&#227;o significativo (0,413) (<xref ref-type="fig" rid="f4">Figura 2</xref>).</p>
        <p>
          <fig id="f4">
            <label>Figura 2</label>
            <caption>
              <title>Cintilografia mioc&#225;rdica (CM) na art&#233;ria descendente anterior (ADA) de acordo com a reserva fracionada de fluxo (RFF).</title>
            </caption>
            <graphic xlink:href="2359-5647-ijcs-31-04-0333-80021-gf02-pt.jpg"/></fig>
        </p>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Na avalia&#231;&#227;o de isquemia, a concord&#226;ncia entre a CPM e a FFR &#233; fraca.<xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B9">9</xref> No presente trabalho, observamos a n&#227;o concord&#226;ncia entre os m&#233;todos, apesar de 83% dos pacientes com RFF positiva apresentarem CPM positiva; o valor de p foi n&#227;o significativo.</p>
        <p>Tal discord&#226;ncia torna-se mais evidente em pacientes com doen&#231;a multivascular, pois a CPM tende a subestimar a import&#226;ncia funcional das les&#245;es.<xref ref-type="bibr" rid="B8">8</xref> A RFF reflete o gradiente de press&#227;o em um &#250;nico vaso; por outro lado, a CM faz a compara&#231;&#227;o da severidade funcional da estenose entre os vasos. O defeito de perfus&#227;o na CPM &#233; definido por meio da compara&#231;&#227;o com a regi&#227;o de maior perfus&#227;o, assumindo que esta regi&#227;o seja normal, mas, muitas vezes, tamb&#233;m &#233; uma regi&#227;o alterada - ainda que menos afetada.<xref ref-type="bibr" rid="B10">10</xref> Na amostra estudada, 38,8% dos pacientes possu&#237;am doen&#231;a em tronco de coron&#225;ria esquerda ou trivascular, o que pode ter contribuindo para discord&#226;ncia entre os resultados.</p>
        <p>Outro fator a ser considerado na an&#225;lise de concord&#226;ncia &#233; a presen&#231;a de doen&#231;a microvascular, que influencia na avalia&#231;&#227;o da RFF,<xref ref-type="bibr" rid="B10">10</xref> por&#233;m outras avalia&#231;&#245;es invasivas podem ser realizadas, para melhor quantificar a doen&#231;a microvascular. A reserva de fluxo coron&#225;rio (RFC) e o &#237;ndice de microrresist&#234;ncia circulat&#243;rio (IRC) melhoram a estratifica&#231;&#227;o de risco em paciente com RFF negativa, sendo um fator progn&#243;stico independente.<xref ref-type="bibr" rid="B11">11</xref><sup>-</sup><xref ref-type="bibr" rid="B13">13</xref> A RFC representa a capacidade de vasodilata&#231;&#227;o do leito vascular coronariano durante hiperemia, sendo medido por indicadores de termodilui&#231;&#227;o. Um valor baixo de CRF (&#8804; 2) indica disfun&#231;&#227;o microvascular. Adicionalmente, o &#237;ndice de resist&#234;ncia microvascular tamb&#233;m fornece dados sobre a fun&#231;&#227;o microvascular, sendo medido por meio da press&#227;o coronariana distal multiplicada pelo tempo de tr&#226;nsito m&#233;dio de 3 mL de b&#243;lus de salina durante hiperemia induzida pela adenosina, sendo menor que 20 o valor normal e maior que 30 se alterado.<xref ref-type="bibr" rid="B11">11</xref><sup>-</sup><xref ref-type="bibr" rid="B13">13</xref> Na amostra total, a RFF era negativa em 53,57% dos pacientes que apresentavam CPM positiva, resultado que pode ser explicado pela presen&#231;a de doen&#231;a microvacular, sendo sua confirma&#231;&#227;o feita pelos m&#233;todos discutidos acima.</p>
        <p>Na an&#225;lise espec&#237;fica da ADA, tamb&#233;m n&#227;o observamos concord&#226;ncia significativa, mas 83% dos pacientes com cintilografia negativa tamb&#233;m apresentaram RRF negativa.</p>
        <p>N&#227;o foram obtidos dados significantes de concord&#226;ncia ou discord&#226;ncia em nossa amostra, possivelmente por conta do n&#250;mero de pacientes estudados, sendo necess&#225;ria uma amostra maior.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Pode ocorrer discord&#226;ncia entre os resultados de an&#225;lise funcional de les&#245;es coron&#225;rias moderadas por testes invasivos e n&#227;o invasivos. Este fato pode ter consequ&#234;ncias importantes no uso da cintilografia para determinar a estrat&#233;gia de revascularizacao &#243;tima, principalmente em pacientes multivasculares. Assim, a reserva de fluxo fracionada mostra-se boa aliada &#224; coronariografia, principalmente em pacientes com les&#245;es multivasculares, uma vez que a estratifica&#231;&#227;o anat&#244;mica e funcional pode ser obtida em um &#250;nico procedimento. Tratando-se de pacientes com doen&#231;a microvascular, a reserva de fluxo fracionada n&#227;o &#233; definida com estrat&#233;gia ideal na avalia&#231;&#227;o de isquemia.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Fontes de Financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
          </p>
          <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Aprova&#231;&#227;o &#233;tica e consentimento informado</bold>
          </p>
          <p>Este estudo foi aprovado pelo Comit&#234; de &#201;tica do Instituto Nacional de Cardiologia sob o n&#250;mero de protocolo 5272. Todos os procedimentos envolvidos nesse estudo est&#227;o de acordo com a Declara&#231;&#227;o de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes inclu&#237;dos no estudo.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
