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<article article-type="editorial" dtd-version="1.1" specific-use="sps-1.9" xml:lang="en" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">
	<front>
		<journal-meta>
			<journal-id journal-id-type="publisher-id">dic</journal-id>
			<journal-title-group>
				<journal-title>ABC Imagem Cardiovascular</journal-title>
				<abbrev-journal-title abbrev-type="publisher">Arq Bras Cardiol: Imagem cardiovasc.</abbrev-journal-title>
			</journal-title-group>
			<issn pub-type="epub">2675-312X</issn>
			<publisher>
				<publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
			</publisher>
		</journal-meta>
		<article-meta>
			<article-id pub-id-type="doi">10.36660/abcimg.2023363i</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Editorial</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>How Can the Assessment of Myocardial Flow Reserve by Nuclear Medicine Change the Interpretation of Myocardial Perfusion Scintigraphy?</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<name>
						<surname>Lima</surname>
						<given-names>Ronaldo de Souza Leão</given-names>
					</name>
					<role>Writing of the manuscript</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1">
				<label> 1 </label>
				<institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
				<addr-line>
					<named-content content-type="city">Rio de Janeiro</named-content>
					<named-content content-type="state">RJ</named-content>
				</addr-line>
				<country country="BR">Brazil</country>
				<institution content-type="original"> Universidade Federal do Rio de Janeiro , Rio de Janeiro , RJ – Brazil </institution>
			</aff>
			<author-notes>
				<corresp id="c01">Mailing Address: Ronaldo de Souza Leão Lima • Rua Paissandu, 329/303, Flamengo, Rio de Janeiro, RJ – Brazil Email: <email>ronlima@hotmail.com</email>
				</corresp>
				<fn fn-type="conflict">
					<p>Potential Conflict of Interest</p>
					<p>No potential conflict of interest relevant to this article was reported.</p>
				</fn>
			</author-notes>
			<pub-date date-type="pub" publication-format="electronic">
				<day>06</day>
				<month>03</month>
				<year>2023</year>
			</pub-date>
			<pub-date date-type="collection" publication-format="electronic">
				<year>2023</year>
			</pub-date>
			<volume>36</volume>
			<issue>1</issue>
			<elocation-id>e363</elocation-id>
			<permissions>
				<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by-nc/4.0/">
					<license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
				</license>
			</permissions>
			<kwd-group xml:lang="en">
				<kwd>Coronary artery disease</kwd>
				<kwd>Scintigraphy</kwd>
				<kwd>Diagnosis</kwd>
			</kwd-group>
			<counts>
				<fig-count count="0"/>
				<table-count count="2"/>
				<equation-count count="0"/>
				<ref-count count="23"/>
			</counts>
		</article-meta>
	</front>
	<body>
		<p>Myocardial perfusion scintigraphy (MPS) with single-photon emission computed tomography (SPECT) is important for the diagnosis and prognostic evaluation in patients with coronary artery disease (CAD). <sup><xref ref-type="bibr" rid="B1">1</xref></sup> MPS evaluates the presence, extent and degree of myocardial ischemia and/or infarction, usually through visual observation or semi-quantitative parameters. Despite its proven diagnostic and prognostic values, the relative nature of perfusion imaging may limit SPECT ability to identify patients with high-risk multivessel CAD. <sup><xref ref-type="bibr" rid="B2">2</xref></sup> Limitations regarding visual or semi-quantitative assessment of regional myocardial perfusion defects may result in underestimation or misdiagnosis due to “balanced” ischemia.</p>
		<p>This limitation can be addressed by quantifying myocardial blood flow (MBF) or myocardial flow reserve (MFR) using tracer kinetics in positron emission tomography (PET). <sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B4">4</xref></sup> PET is a well-validated non-invasive method for quantification of myocardial perfusion, demonstrating an incremental diagnostic and prognostic power compared to MPS in patients with suspected or known CAD. <sup><xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B6">6</xref></sup> PET then is considered the gold standard for non-invasive quantification of MBF and MFR. <sup><xref ref-type="bibr" rid="B7">7</xref> - <xref ref-type="bibr" rid="B9">9</xref></sup> However, the production of PET tracers is costly and the technology is not yet available in many countries.</p>
		<p>The introduction of high-sensitivity cadmium-zinc-teluride (CZT) cameras for cardiology tests allows the dynamic acquisition of tomographic images to evaluate radiotracer kinetics, and opens a new era for measuring MBF and MFR. <sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
		<p>Quantification of MBF and MFR using dynamic CZT-SPECT in list mode is technically feasible and clinically useful. <sup><xref ref-type="bibr" rid="B11">11</xref> , <xref ref-type="bibr" rid="B12">12</xref></sup> The WATERDAY study <sup><xref ref-type="bibr" rid="B13">13</xref></sup> compared MBF and MFR obtained with 99mTc-sestamibi in CZT-SPECT with those obtained in a <sup><xref ref-type="bibr" rid="B15">15</xref></sup> O-water PET and fractional flow reserve (FFR). While stress and rest MBF were significantly overestimated with CZT-SPECT compared to PET, MFR was similar between the two techniques, which means that the quantification of MBF and MFR by dynamic 99mTc-sestamibi CZT-SPECT is clinically useful. <sup><xref ref-type="bibr" rid="B13">13</xref></sup> Acampa et al. <sup><xref ref-type="bibr" rid="B14">14</xref></sup> demonstrated that CZT-SPECT values are higher than those measured by 82Rb-PET imaging, with a moderate correlation between the two methods. CZT-SPECT showed good diagnostic accuracy for identifying obstructive CAD. Different studies have outlined the incremental value of MFR measurements in different categories of patients for diagnosis or prognosis. <sup><xref ref-type="bibr" rid="B14">14</xref></sup> In patients with multivessel CAD, where normal myocardial perfusion imaging (MPI) may not necessarily identify truly low-risk subgroups among high-risk cohorts, they often show reduced MFR. <sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
		<p>Despite the excellent diagnostic value of FFR, which quantifies pressure gradient through stenosis, it does not reflect microcirculation abnormalities. Unlike FFR, myocardial perfusion reserve (MPR) reflects flow in epicardial arteries and microvasculature. Therefore, FFR and MPR are not equivalent. <sup><xref ref-type="bibr" rid="B16">16</xref></sup></p>
		<p>It should be noted that several factors can affect the hemodynamic flow response to luminal stenosis, including lesion geometry and location and the presence of collateral vessels, impacting overall regional flow. In a study by our group, De Souza et al. <sup><xref ref-type="bibr" rid="B17">17</xref></sup> showed that both global MPR and MBF stress were reduced in patients with abnormal perfusion. In addition to assessing perfusion, this study demonstrated that overall MPR is inversely associated with CAD prognostic index (CADPI), a hierarchical index that includes the entire epicardial coronary tree and is related to overall cardiovascular risk. <sup><xref ref-type="bibr" rid="B17">17</xref></sup></p>
		<p>In this scenario, Panjer et al. <sup><xref ref-type="bibr" rid="B18">18</xref></sup> performed a systematic review and meta-analysis with the objective of evaluating the diagnostic accuracy of dynamic CZT-SPECT in coronary artery disease (CAD) compared to FFR and PET as a reference. To assess CZT-SPECT, the analysis yielded 0.79 sensitivity (95% CI 0.73–0.85) and 0.85 specificity (95% CI 0.74–0.92). Diagnostic odds ratio was 17.82 (95% CI 8.80–36.08, P \ 0.001). Positive likelihood ratio and negative likelihood ratio were 3.86 (95% CI 2.76–5.38, P&lt;0.001) and 0.21 (95% CI 0.13–0.33, P&lt;0.001), respectively. The results of this systematic review and meta-analysis emphasize the role of dynamic CZT-SPECT MPI with good sensitivity and specificity for diagnosing CAD compared to gold standards. The use of CZT-SPECT systems for measuring MPR is very attractive considering that in just one scan it is possible to obtain perfusion and functional parameters with results comparable to PET. However, what emerges from this meta-analysis is that the protocol used in different centers should be better standardized. The included studies use different methodologies in terms of dose administration, acquisition protocol, CZT cameras, radiotracers and software package used. Furthermore, in each study a different cutoff value was defined for the dynamic SPECT MPI. Seven studies compared with FFR and two used PET. To measure acquisition, MPI was performed with different types of CZT-SPECT cameras. Six studies used Discovery NM 530c (GE Healthcare, Chicago, IL, USA), one study (11.1%) used Discovery NM/CT 570c (Alcyone technology, GE Healthcare, Haifa, Israel) and two studies (22.2%) used D-SPECT (Spectrum Dynamics, Palo Alto, California). Dual isotope administration was used in one study. Two studies used 201Tl as a radiotracer, and six studies (66.7%) used 99mTc-labeled markers. Different software was used for MBF quantification and MFR measurement, including internal software, with 4DM Corridor (INVIA, Ann Arbor, MI, USA) applied more often than others. Furthermore, the main limitation of this systematic review and meta-analysis, in addition to the typical limitations for this type of analysis, is the relatively small number of included studies and patients and inter-comparison heterogeneity. <sup><xref ref-type="bibr" rid="B19">19</xref></sup> In this regard, studies with a larger population and smaller variability between methodologies, such as different thresholds for MFR, myocardial radiotracer distribution, different reconstruction algorithms and applied flow models will be necessary to clearly demonstrate the additional clinical impact of MBF with CZT.</p>
		<p>Myocardial flow reserve assessment using CZT can be useful in many clinical situations, as shown by PET ( <xref ref-type="table" rid="t1"> Table 1 </xref> ).</p>
		<p>
			<table-wrap id="t1">
				<label>Table 1</label>
				<caption>
					<title>– In which situations can myocardial flow reserve make a difference?</title>
				</caption>
				<table frame="hsides" rules="groups">
					<colgroup width="100%">
						<col/>
					</colgroup>
					<tbody>
						<tr>
							<td>1) Patients with little ischemia who may have multivessel CAD.</td>
						</tr>
						<tr>
							<td>2) Perfusion defects, but with artifact.</td>
						</tr>
						<tr>
							<td>3) Normal perfusion but at high risk for CAD.</td>
						</tr>
						<tr>
							<td>4) Identification of microvascular disease.</td>
						</tr>
						<tr>
							<td>5) Determine vaso-stressor effectiveness.</td>
						</tr>
					</tbody>
				</table>
			</table-wrap>
		</p>
		<p>One of the main uses was demonstrated in the extremely high sensitivity to detect multivascular disease, as in the study by DiCarli et al., where normal MFR on PET virtually excluded the possibility of this event. <sup><xref ref-type="bibr" rid="B20">20</xref></sup> MFR evaluation by CZT-SPECT also allows for this increase in accuracy. <sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
		<p>The possibility of identifying microvascular disease as the cause of angina is useful for reducing investigation costs but also very important as a determinant of prognosis. MFR, both on PET and on CZT-SPECT, is a non-invasive modality for confirming this phenomenon. <sup><xref ref-type="bibr" rid="B22">22</xref></sup></p>
		<p>In preparation for pharmacological stress with dipyridamole or adenosine, abstinence from caffeine for at least 24 hours is recommended. However, when this preparation is not carried out properly, vasodilator response may be compromised and, consequently, induction of flow disparity. In traditional scintigraphy, this cannot be identified and may result in a “false-negative” result, but this inadequate response is detected by MFR evaluation. <sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
		<p>As more studies are published, leading to better standardization of MBF and MFR quantification by CZT-SPECT, it will become an important tool in the clinical practice of ischemic cardiomyopathies, adding to our understanding of this disease.</p>
	</body>
	<back>
		<ref-list>
			<title>References</title>
			<ref id="B1">
				<label>1</label>
				<mixed-citation>1. Mastrocola LE, Amorim BJ, Vitola JV, Brandão SCS, Grossman GB, Lima RSL, et al. Update of the Brazilian Guideline on Nuclear Cardiology - 2020. Arq Bras Cardiol. 2020;114(2):325-29. doi: 10.36660/abc.20200087.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Mastrocola</surname>
							<given-names>LE</given-names>
						</name>
						<name>
							<surname>Amorim</surname>
							<given-names>BJ</given-names>
						</name>
						<name>
							<surname>Vitola</surname>
							<given-names>JV</given-names>
						</name>
						<name>
							<surname>Brandão</surname>
							<given-names>SCS</given-names>
						</name>
						<name>
							<surname>Grossman</surname>
							<given-names>GB</given-names>
						</name>
						<name>
							<surname>Lima</surname>
							<given-names>RSL</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Update of the Brazilian Guideline on Nuclear Cardiology - 2020</article-title>
					<source>Arq Bras Cardiol</source>
					<year>2020</year>
					<volume>114</volume>
					<issue>2</issue>
					<fpage>325</fpage>
					<lpage>329</lpage>
					<issue-id pub-id-type="doi">10.36660/abc.20200087</issue-id>
				</element-citation>
			</ref>
			<ref id="B2">
				<label>2</label>
				<mixed-citation>2. Lima RS, Watson DD, Goode AR, Siadaty MS, Ragosta M, Beller GA, et al. Incremental Value of Combined Perfusion and Function Over Perfusion Alone by Gated SPECT Myocardial Perfusion Imaging for Detection of Severe Three-Vessel Coronary Artery Disease. J Am Coll Cardiol. 2003;42(1):64-70. doi: 10.1016/s0735-1097(03)00562-x.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lima</surname>
							<given-names>RS</given-names>
						</name>
						<name>
							<surname>Watson</surname>
							<given-names>DD</given-names>
						</name>
						<name>
							<surname>Goode</surname>
							<given-names>AR</given-names>
						</name>
						<name>
							<surname>Siadaty</surname>
							<given-names>MS</given-names>
						</name>
						<name>
							<surname>Ragosta</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Beller</surname>
							<given-names>GA</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Incremental Value of Combined Perfusion and Function Over Perfusion Alone by Gated SPECT Myocardial Perfusion Imaging for Detection of Severe Three-Vessel Coronary Artery Disease</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2003</year>
					<volume>42</volume>
					<issue>1</issue>
					<fpage>64</fpage>
					<lpage>70</lpage>
					<issue-id pub-id-type="doi">10.1016/s0735-1097(03)00562-x</issue-id>
				</element-citation>
			</ref>
			<ref id="B3">
				<label>3</label>
				<mixed-citation>3. Muzik O, Duvernoy C, Beanlands RS, Sawada S, Dayanikli F, Wolfe ER Jr, et al. Assessment of Diagnostic Performance of Quantitative Flow Measurements in Normal Subjects and Patients with Angiographically Documented Coronary Artery Disease by Means of Nitrogen-13 Ammonia and Positron Emission Tomography. J Am Coll Cardiol. 1998;31(3):534-40. doi: 10.1016/s0735-1097(97)00526-3.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Muzik</surname>
							<given-names>O</given-names>
						</name>
						<name>
							<surname>Duvernoy</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Beanlands</surname>
							<given-names>RS</given-names>
						</name>
						<name>
							<surname>Sawada</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Dayanikli</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Wolfe</surname>
							<given-names>ER</given-names>
							<suffix>Jr</suffix>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Assessment of Diagnostic Performance of Quantitative Flow Measurements in Normal Subjects and Patients with Angiographically Documented Coronary Artery Disease by Means of Nitrogen-13 Ammonia and Positron Emission Tomography</article-title>
					<source>J Am Coll Cardiol</source>
					<year>1998</year>
					<volume>31</volume>
					<issue>3</issue>
					<fpage>534</fpage>
					<lpage>540</lpage>
					<issue-id pub-id-type="doi">10.1016/s0735-1097(97)00526-3</issue-id>
				</element-citation>
			</ref>
			<ref id="B4">
				<label>4</label>
				<mixed-citation>4. Parkash R, de Kemp RA, Ruddy TD, Kitsikis A, Hart R, Beauchesne L, et al. Potential Utility of Rubidium 82 PET Quantification in Patients with 3-Vessel Coronary Artery Disease. J Nucl Cardiol. 2004;11(4):440-9. doi: 10.1016/j.nuclcard.2004.04.005.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Parkash</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Kemp</surname>
							<given-names>RA</given-names>
						</name>
						<name>
							<surname>Ruddy</surname>
							<given-names>TD</given-names>
						</name>
						<name>
							<surname>Kitsikis</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Hart</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Beauchesne</surname>
							<given-names>L</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Potential Utility of Rubidium 82 PET Quantification in Patients with 3-Vessel Coronary Artery Disease</article-title>
					<source>J Nucl Cardiol</source>
					<year>2004</year>
					<volume>11</volume>
					<issue>4</issue>
					<fpage>440</fpage>
					<lpage>449</lpage>
					<issue-id pub-id-type="doi">10.1016/j.nuclcard.2004.04.005</issue-id>
				</element-citation>
			</ref>
			<ref id="B5">
				<label>5</label>
				<mixed-citation>5. Zampella E, Acampa W, Assante R, Nappi C, Gaudieri V, Mainolfi CG, et al. Combined Evaluation of Regional Coronary Artery Calcium and Myocardial Perfusion by 82Rb PET/CT in the Identification of Obstructive Coronary Artery Disease. Eur J Nucl Med Mol Imaging. 2018;45(4):521-29. doi: 10.1007/s00259-018-3935-1.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Zampella</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Acampa</surname>
							<given-names>W</given-names>
						</name>
						<name>
							<surname>Assante</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Nappi</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Gaudieri</surname>
							<given-names>V</given-names>
						</name>
						<name>
							<surname>Mainolfi</surname>
							<given-names>CG</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Combined Evaluation of Regional Coronary Artery Calcium and Myocardial Perfusion by 82Rb PET/CT in the Identification of Obstructive Coronary Artery Disease</article-title>
					<source>Eur J Nucl Med Mol Imaging</source>
					<year>2018</year>
					<volume>45</volume>
					<issue>4</issue>
					<fpage>521</fpage>
					<lpage>529</lpage>
					<issue-id pub-id-type="doi">10.1007/s00259-018-3935-1</issue-id>
				</element-citation>
			</ref>
			<ref id="B6">
				<label>6</label>
				<mixed-citation>6. Assante R, Acampa W, Zampella E, Arumugam P, Nappi C, Gaudieri V, et al. Prognostic Value of Atherosclerotic Burden and Coronary Vascular Function in Patients with Suspected Coronary Artery Disease. Eur J Nucl Med Mol Imaging. 2017;44(13):2290-98. doi: 10.1007/s00259-017-3800-7.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Assante</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Acampa</surname>
							<given-names>W</given-names>
						</name>
						<name>
							<surname>Zampella</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Arumugam</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Nappi</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Gaudieri</surname>
							<given-names>V</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Prognostic Value of Atherosclerotic Burden and Coronary Vascular Function in Patients with Suspected Coronary Artery Disease</article-title>
					<source>Eur J Nucl Med Mol Imaging</source>
					<year>2017</year>
					<volume>44</volume>
					<issue>13</issue>
					<fpage>2290</fpage>
					<lpage>2298</lpage>
					<issue-id pub-id-type="doi">10.1007/s00259-017-3800-7</issue-id>
				</element-citation>
			</ref>
			<ref id="B7">
				<label>7</label>
				<mixed-citation>7. Johnson NP, Gould KL, Di Carli MF, Taqueti VR. Invasive FFR and Noninvasive CFR in the Evaluation of Ischemia: What Is the Future? J Am Coll Cardiol. 2016;67(23):2772-88. doi: 10.1016/j.jacc.2016.03.584.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Johnson</surname>
							<given-names>NP</given-names>
						</name>
						<name>
							<surname>Gould</surname>
							<given-names>KL</given-names>
						</name>
						<name>
							<surname>Di Carli</surname>
							<given-names>MF</given-names>
						</name>
						<name>
							<surname>Taqueti</surname>
							<given-names>VR</given-names>
						</name>
					</person-group>
					<article-title>Invasive FFR and Noninvasive CFR in the Evaluation of Ischemia: What Is the Future?</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2016</year>
					<volume>67</volume>
					<issue>23</issue>
					<fpage>2772</fpage>
					<lpage>2788</lpage>
					<issue-id pub-id-type="doi">10.1016/j.jacc.2016.03.584</issue-id>
				</element-citation>
			</ref>
			<ref id="B8">
				<label>8</label>
				<mixed-citation>8. Danad I, Uusitalo V, Kero T, Saraste A, Raijmakers PG, Lammertsma AA, et al. Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease: Cutoff Values and Diagnostic Accuracy of Quantitative [(15)O]H2O PET Imaging. J Am Coll Cardiol. 2014;64(14):1464-75. doi: 10.1016/j.jacc.2014.05.069.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Danad</surname>
							<given-names>I</given-names>
						</name>
						<name>
							<surname>Uusitalo</surname>
							<given-names>V</given-names>
						</name>
						<name>
							<surname>Kero</surname>
							<given-names>T</given-names>
						</name>
						<name>
							<surname>Saraste</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Raijmakers</surname>
							<given-names>PG</given-names>
						</name>
						<name>
							<surname>Lammertsma</surname>
							<given-names>AA</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease: Cutoff Values and Diagnostic Accuracy of Quantitative [(15)O]H2O PET Imaging</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2014</year>
					<volume>64</volume>
					<issue>14</issue>
					<fpage>1464</fpage>
					<lpage>1475</lpage>
					<issue-id pub-id-type="doi">10.1016/j.jacc.2014.05.069</issue-id>
				</element-citation>
			</ref>
			<ref id="B9">
				<label>9</label>
				<mixed-citation>9. Kajander SA, Joutsiniemi E, Saraste M, Pietilä M, Ukkonen H, Saraste A, et al. Clinical Value of Absolute Quantification of Myocardial Perfusion with (15)O-Water in Coronary Artery Disease. Circ Cardiovasc Imaging. 2011;4(6):678-84. doi: 10.1161/CIRCIMAGING.110.960732.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Kajander</surname>
							<given-names>SA</given-names>
						</name>
						<name>
							<surname>Joutsiniemi</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Saraste</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Pietilä</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Ukkonen</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Saraste</surname>
							<given-names>A</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Clinical Value of Absolute Quantification of Myocardial Perfusion with (15)O-Water in Coronary Artery Disease</article-title>
					<source>Circ Cardiovasc Imaging</source>
					<year>2011</year>
					<volume>4</volume>
					<issue>6</issue>
					<fpage>678</fpage>
					<lpage>684</lpage>
					<issue-id pub-id-type="doi">10.1161/CIRCIMAGING.110.960732</issue-id>
				</element-citation>
			</ref>
			<ref id="B10">
				<label>10</label>
				<mixed-citation>10. Wells RG, Timmins R, Klein R, Lockwood J, Marvin B, deKemp RA, et al. Dynamic SPECT Measurement of Absolute Myocardial Blood Flow in a Porcine Model. J Nucl Med. 2014;55(10):1685-91. doi: 10.2967/jnumed.114.139782.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Wells</surname>
							<given-names>RG</given-names>
						</name>
						<name>
							<surname>Timmins</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Klein</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Lockwood</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Marvin</surname>
							<given-names>B</given-names>
						</name>
						<name>
							<surname>deKemp</surname>
							<given-names>RA</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Dynamic SPECT Measurement of Absolute Myocardial Blood Flow in a Porcine Model</article-title>
					<source>J Nucl Med</source>
					<year>2014</year>
					<volume>55</volume>
					<issue>10</issue>
					<fpage>1685</fpage>
					<lpage>1691</lpage>
					<issue-id pub-id-type="doi">10.2967/jnumed.114.139782</issue-id>
				</element-citation>
			</ref>
			<ref id="B11">
				<label>11</label>
				<mixed-citation>11. Esteves FP, Raggi P, Folks RD, Keidar Z, Askew JW, Rispler S, et al. Novel Solid-State-Detector Dedicated Cardiac Camera for Fast Myocardial Perfusion Imaging: Multicenter Comparison with Standard Dual Detector Cameras. J Nucl Cardiol. 2009;16(6):927-34. doi: 10.1007/s12350-009-9137-2.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Esteves</surname>
							<given-names>FP</given-names>
						</name>
						<name>
							<surname>Raggi</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Folks</surname>
							<given-names>RD</given-names>
						</name>
						<name>
							<surname>Keidar</surname>
							<given-names>Z</given-names>
						</name>
						<name>
							<surname>Askew</surname>
							<given-names>JW</given-names>
						</name>
						<name>
							<surname>Rispler</surname>
							<given-names>S</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Novel Solid-State-Detector Dedicated Cardiac Camera for Fast Myocardial Perfusion Imaging: Multicenter Comparison with Standard Dual Detector Cameras</article-title>
					<source>J Nucl Cardiol</source>
					<year>2009</year>
					<volume>16</volume>
					<issue>6</issue>
					<fpage>927</fpage>
					<lpage>934</lpage>
					<issue-id pub-id-type="doi">10.1007/s12350-009-9137-2</issue-id>
				</element-citation>
			</ref>
			<ref id="B12">
				<label>12</label>
				<mixed-citation>12. Bocher M, Blevis IM, Tsukerman L, Shrem Y, Kovalski G, Volokh L. A Fast Cardiac Gamma Camera with Dynamic SPECT Capabilities: Design, System Validation and Future Potential. Eur J Nucl Med Mol Imaging. 2010;37(10):1887-902. doi: 10.1007/s00259-010-1488-z.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Bocher</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Blevis</surname>
							<given-names>IM</given-names>
						</name>
						<name>
							<surname>Tsukerman</surname>
							<given-names>L</given-names>
						</name>
						<name>
							<surname>Shrem</surname>
							<given-names>Y</given-names>
						</name>
						<name>
							<surname>Kovalski</surname>
							<given-names>G</given-names>
						</name>
						<name>
							<surname>Volokh</surname>
							<given-names>L</given-names>
						</name>
					</person-group>
					<article-title>A Fast Cardiac Gamma Camera with Dynamic SPECT Capabilities: Design, System Validation and Future Potential</article-title>
					<source>Eur J Nucl Med Mol Imaging</source>
					<year>2010</year>
					<volume>37</volume>
					<issue>10</issue>
					<fpage>1887</fpage>
					<lpage>1902</lpage>
					<issue-id pub-id-type="doi">10.1007/s00259-010-1488-z</issue-id>
				</element-citation>
			</ref>
			<ref id="B13">
				<label>13</label>
				<mixed-citation>13. Agostini D, Roule V, Nganoa C, Roth N, Baavour R, Parienti JJ, et al. First Validation of Myocardial Flow Reserve Assessed by Dynamic 99mTc-Sestamibi CZT-SPECT Camera: Head to Head Comparison with 15O-Water PET and Fractional Flow Reserve in Patients with Suspected Coronary Artery Disease. The WATERDAY study. Eur J Nucl Med Mol Imaging. 2018;45(7):1079-90. doi: 10.1007/s00259-018-3958-7.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Agostini</surname>
							<given-names>D</given-names>
						</name>
						<name>
							<surname>Roule</surname>
							<given-names>V</given-names>
						</name>
						<name>
							<surname>Nganoa</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Roth</surname>
							<given-names>N</given-names>
						</name>
						<name>
							<surname>Baavour</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Parienti</surname>
							<given-names>JJ</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>First Validation of Myocardial Flow Reserve Assessed by Dynamic 99mTc-Sestamibi CZT-SPECT Camera: Head to Head Comparison with 15O-Water PET and Fractional Flow Reserve in Patients with Suspected Coronary Artery Disease. The WATERDAY study</article-title>
					<source>Eur J Nucl Med Mol Imaging</source>
					<year>2018</year>
					<volume>45</volume>
					<issue>7</issue>
					<fpage>1079</fpage>
					<lpage>1090</lpage>
					<issue-id pub-id-type="doi">10.1007/s00259-018-3958-7</issue-id>
				</element-citation>
			</ref>
			<ref id="B14">
				<label>14</label>
				<mixed-citation>14. Murthy VL, Naya M, Foster CR, Hainer J, Gaber M, Di Carli G, et al. Improved Cardiac Risk Assessment with Noninvasive Measures of Coronary Flow Reserve. Circulation. 2011;124(20):2215-24. doi: 10.1161/CIRCULATIONAHA.111.050427.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Murthy</surname>
							<given-names>VL</given-names>
						</name>
						<name>
							<surname>Naya</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Foster</surname>
							<given-names>CR</given-names>
						</name>
						<name>
							<surname>Hainer</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Gaber</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Di Carli</surname>
							<given-names>G</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Improved Cardiac Risk Assessment with Noninvasive Measures of Coronary Flow Reserve</article-title>
					<source>Circulation</source>
					<year>2011</year>
					<volume>124</volume>
					<issue>20</issue>
					<fpage>2215</fpage>
					<lpage>2224</lpage>
					<issue-id pub-id-type="doi">10.1161/CIRCULATIONAHA.111.050427</issue-id>
				</element-citation>
			</ref>
			<ref id="B15">
				<label>15</label>
				<mixed-citation>15. Acampa W, Zampella E, Assante R, Genova A, De Simini G, Mannarino T, et al. Quantification of Myocardial Perfusion Reserve by CZT-SPECT: A Head to Head Comparison with 82Rubidium PET Imaging. J Nucl Cardiol. 2021;28(6):2827-39. doi: 10.1007/s12350-020-02129-w</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Acampa</surname>
							<given-names>W</given-names>
						</name>
						<name>
							<surname>Zampella</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Assante</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Genova</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>De Simini</surname>
							<given-names>G</given-names>
						</name>
						<name>
							<surname>Mannarino</surname>
							<given-names>T</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Quantification of Myocardial Perfusion Reserve by CZT-SPECT: A Head to Head Comparison with 82Rubidium PET Imaging</article-title>
					<source>J Nucl Cardiol</source>
					<year>2021</year>
					<volume>28</volume>
					<issue>6</issue>
					<fpage>2827</fpage>
					<lpage>2839</lpage>
					<issue-id pub-id-type="doi">10.1007/s12350-020-02129-w</issue-id>
				</element-citation>
			</ref>
			<ref id="B16">
				<label>16</label>
				<mixed-citation>16. Zavadovsky KV, Mochula AV, Boshchenko AA, Vrublevsky AV, Baev AE, Krylov AL, et al. Absolute Myocardial Blood Flows Derived by Dynamic CZT Scan vs Invasive Fractional Flow Reserve: Correlation and accuracy. J Nucl Cardiol. 2021;28(1):249-59. doi: 10.1007/s12350-019-01678-z.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Zavadovsky</surname>
							<given-names>KV</given-names>
						</name>
						<name>
							<surname>Mochula</surname>
							<given-names>AV</given-names>
						</name>
						<name>
							<surname>Boshchenko</surname>
							<given-names>AA</given-names>
						</name>
						<name>
							<surname>Vrublevsky</surname>
							<given-names>AV</given-names>
						</name>
						<name>
							<surname>Baev</surname>
							<given-names>AE</given-names>
						</name>
						<name>
							<surname>Krylov</surname>
							<given-names>AL</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Absolute Myocardial Blood Flows Derived by Dynamic CZT Scan vs Invasive Fractional Flow Reserve: Correlation and accuracy</article-title>
					<source>J Nucl Cardiol</source>
					<year>2021</year>
					<volume>28</volume>
					<issue>1</issue>
					<fpage>249</fpage>
					<lpage>259</lpage>
					<issue-id pub-id-type="doi">10.1007/s12350-019-01678-z</issue-id>
				</element-citation>
			</ref>
			<ref id="B17">
				<label>17</label>
				<mixed-citation>17. Souza ACDAH, Gonçalves BKD, Tedeschi AL, Lima RSL. Quantification of Myocardial Flow Reserve Using a Gamma Camera with Solid-State Cadmium-Zinc-Telluride Detectors: Relation to Angiographic Coronary Artery Disease. J Nucl Cardiol. 2021;28(3):876-84. doi: 10.1007/s12350-019-01775-z.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Souza</surname>
							<given-names>ACDAH</given-names>
						</name>
						<name>
							<surname>Gonçalves</surname>
							<given-names>BKD</given-names>
						</name>
						<name>
							<surname>Tedeschi</surname>
							<given-names>AL</given-names>
						</name>
						<name>
							<surname>Lima</surname>
							<given-names>RSL</given-names>
						</name>
					</person-group>
					<article-title>Quantification of Myocardial Flow Reserve Using a Gamma Camera with Solid-State Cadmium-Zinc-Telluride Detectors: Relation to Angiographic Coronary Artery Disease</article-title>
					<source>J Nucl Cardiol</source>
					<year>2021</year>
					<volume>28</volume>
					<issue>3</issue>
					<fpage>876</fpage>
					<lpage>884</lpage>
					<issue-id pub-id-type="doi">10.1007/s12350-019-01775-z</issue-id>
				</element-citation>
			</ref>
			<ref id="B18">
				<label>18</label>
				<mixed-citation>18. Panjer M, Dobrolinska M, Wagenaar NRL, Slart RHJA. Diagnostic Accuracy of Dynamic CZT-SPECT in Coronary Artery Disease. A Systematic Review and Meta-Analysis. J Nucl Cardiol. 2022;29(4):1686-97. doi: 10.1007/s12350-021-02721-8.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Panjer</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Dobrolinska</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Wagenaar</surname>
							<given-names>NRL</given-names>
						</name>
						<name>
							<surname>Slart</surname>
							<given-names>RHJA</given-names>
						</name>
					</person-group>
					<article-title>Diagnostic Accuracy of Dynamic CZT-SPECT in Coronary Artery Disease. A Systematic Review and Meta-Analysis</article-title>
					<source>J Nucl Cardiol</source>
					<year>2022</year>
					<volume>29</volume>
					<issue>4</issue>
					<fpage>1686</fpage>
					<lpage>1697</lpage>
					<issue-id pub-id-type="doi">10.1007/s12350-021-02721-8</issue-id>
				</element-citation>
			</ref>
			<ref id="B19">
				<label>19</label>
				<mixed-citation>19. Cantoni V, Green R, D’Antonio A, Cuocolo A. Dynamic CZT-SPECT in Coronary Artery Disease: Where are we Now? J Nucl Cardiol. 2022;29(4):1698-701. doi: 10.1007/s12350-021-02752-1.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Cantoni</surname>
							<given-names>V</given-names>
						</name>
						<name>
							<surname>Green</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>D’Antonio</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Cuocolo</surname>
							<given-names>A</given-names>
						</name>
					</person-group>
					<article-title>Dynamic CZT-SPECT in Coronary Artery Disease: Where are we Now?</article-title>
					<source>J Nucl Cardiol</source>
					<year>2022</year>
					<volume>29</volume>
					<issue>4</issue>
					<fpage>1698</fpage>
					<lpage>1701</lpage>
					<issue-id pub-id-type="doi">10.1007/s12350-021-02752-1</issue-id>
				</element-citation>
			</ref>
			<ref id="B20">
				<label>20</label>
				<mixed-citation>20. Naya M, Murthy VL, Taqueti VR, Foster CR, Klein J, Garber M, et al. Preserved Coronary Flow Reserve Effectively Excludes High-Risk Coronary Artery Disease on Angiography. J Nucl Med. 2014;55(2):248-55. doi: 10.2967/jnumed.113.121442.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Naya</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Murthy</surname>
							<given-names>VL</given-names>
						</name>
						<name>
							<surname>Taqueti</surname>
							<given-names>VR</given-names>
						</name>
						<name>
							<surname>Foster</surname>
							<given-names>CR</given-names>
						</name>
						<name>
							<surname>Klein</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Garber</surname>
							<given-names>M</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Preserved Coronary Flow Reserve Effectively Excludes High-Risk Coronary Artery Disease on Angiography</article-title>
					<source>J Nucl Med</source>
					<year>2014</year>
					<volume>55</volume>
					<issue>2</issue>
					<fpage>248</fpage>
					<lpage>255</lpage>
					<issue-id pub-id-type="doi">10.2967/jnumed.113.121442</issue-id>
				</element-citation>
			</ref>
			<ref id="B21">
				<label>21</label>
				<mixed-citation>21. Souza ACDAH, Gonçalves BKD, Tedeschi A, Lima RSL. Quantification of Coronary Flow Reserve with CZT Gamma Camera in the Evaluation of Multivessel Coronary Disease. Arq Bras Cardiol. 2018;111(4):635-37. doi: 10.5935/abc.20180196.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Souza</surname>
							<given-names>ACDAH</given-names>
						</name>
						<name>
							<surname>Gonçalves</surname>
							<given-names>BKD</given-names>
						</name>
						<name>
							<surname>Tedeschi</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Lima</surname>
							<given-names>RSL</given-names>
						</name>
					</person-group>
					<article-title>Quantification of Coronary Flow Reserve with CZT Gamma Camera in the Evaluation of Multivessel Coronary Disease</article-title>
					<source>Arq Bras Cardiol</source>
					<year>2018</year>
					<volume>111</volume>
					<issue>4</issue>
					<fpage>635</fpage>
					<lpage>637</lpage>
					<issue-id pub-id-type="doi">10.5935/abc.20180196</issue-id>
				</element-citation>
			</ref>
			<ref id="B22">
				<label>22</label>
				<mixed-citation>22. Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U, et al. International Standardization of Diagnostic Criteria for Microvascular Angina. Int J Cardiol. 2018;250:16-20. doi: 10.1016/j.ijcard.2017.08.068.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Ong</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Camici</surname>
							<given-names>PG</given-names>
						</name>
						<name>
							<surname>Beltrame</surname>
							<given-names>JF</given-names>
						</name>
						<name>
							<surname>Crea</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Shimokawa</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Sechtem</surname>
							<given-names>U</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>International Standardization of Diagnostic Criteria for Microvascular Angina</article-title>
					<source>Int J Cardiol</source>
					<year>2018</year>
					<volume>250</volume>
					<fpage>16</fpage>
					<lpage>20</lpage>
					<issue-id pub-id-type="doi">10.1016/j.ijcard.2017.08.068</issue-id>
				</element-citation>
			</ref>
			<ref id="B23">
				<label>23</label>
				<mixed-citation>23. Bateman TM, Heller GV, Beanlands R, Calnon DA, Case J, deKemp R, et al. Practical Guide for Interpreting and Reporting Cardiac PET Measurements of Myocardial Blood Flow: An Information Statement from the American Society of Nuclear Cardiology, and the Society of Nuclear Medicine and Molecular Imaging. J Nucl Med. 2021;62(11):1599-615. doi: 10.2967/jnumed.121.261989.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Bateman</surname>
							<given-names>TM</given-names>
						</name>
						<name>
							<surname>Heller</surname>
							<given-names>GV</given-names>
						</name>
						<name>
							<surname>Beanlands</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Calnon</surname>
							<given-names>DA</given-names>
						</name>
						<name>
							<surname>Case</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>deKemp</surname>
							<given-names>R</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Practical Guide for Interpreting and Reporting Cardiac PET Measurements of Myocardial Blood Flow: An Information Statement from the American Society of Nuclear Cardiology, and the Society of Nuclear Medicine and Molecular Imaging</article-title>
					<source>J Nucl Med</source>
					<year>2021</year>
					<volume>62</volume>
					<issue>11</issue>
					<fpage>1599</fpage>
					<lpage>1615</lpage>
					<issue-id pub-id-type="doi">10.2967/jnumed.121.261989</issue-id>
				</element-citation>
			</ref>
		</ref-list>
		<fn-group>
			<fn fn-type="other">
				<p>Study Association</p>
				<p>This study is not associated with any thesis or dissertation work.</p>
			</fn>
			<fn fn-type="other">
				<p>Ethics Approval and Consent to Participate</p>
				<p>This article does not contain any studies with human participants or animals performed by any of the authors.</p>
			</fn>
		</fn-group>
		<fn-group>
			<fn fn-type="supported-by">
				<p>Sources of Funding: There were no external funding sources for this study.</p>
			</fn>
		</fn-group>
	</back>
	<sub-article article-type="translation" id="TRpt" xml:lang="pt">
		<front-stub>
			<article-id pub-id-type="doi">10.36660/abcimg.2023363</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Editorial</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Como a Avaliação da Reserva de Fluxo Miocárdico pela Medicina Nuclear Pode Mudar a Interpretação da Cintilografia Miocárdica de Perfusão?</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<name>
						<surname>Lima</surname>
						<given-names>Ronaldo de Souza Leão</given-names>
					</name>
					<role>Redação do manuscrito</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1002">
				<label> 1 </label>
				<country country="BR">Brasil</country>
				<institution content-type="original"> Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ – Brasil </institution>
			</aff>
			<author-notes>
				<corresp id="c01002">Correspondência: Ronaldo de Souza Leão Lima • Rua Paissandu, 329/303, Flamengo, Rio de Janeiro, RJ – Brasil Email: ronlima@hotmail.com</corresp>
				<fn fn-type="conflict">
					<p>Potencial Conflito de Interesse</p>
					<p>Declaro não haver conflito de interesses pertinentes.</p>
				</fn>
			</author-notes>
			<kwd-group xml:lang="pt">
				<kwd>Doença das coronarias</kwd>
				<kwd>Cintilografia</kwd>
				<kwd>Diagnóstico</kwd>
			</kwd-group>
		</front-stub>
		<body>
			<p>A cintilografia de perfusão miocárdica (CPM) com tomografia computadorizada por emissão de fóton único (SPECT) é importante para o diagnóstico e avaliação prognóstica em pacientes com doença arterial coronariana (DAC). <sup><xref ref-type="bibr" rid="B1">1</xref></sup> A CPM avalia a presença, extensão e grau de isquemia miocárdica e/ou infarto geralmente por meio de observação visual ou parâmetros semiquantitativos. Apesar de seus valores diagnóstico e prognóstico comprovados, a natureza relativa das imagens de perfusão pode limitar a capacidade da SPECT de identificar pacientes com DAC multiarterial de alto risco. <sup><xref ref-type="bibr" rid="B2">2</xref></sup> Essas limitações, que dizem respeito à avaliação visual ou semiquantitativa de defeitos regionais de perfusão miocárdica, podem resultar em subestimação ou diagnóstico errôneo devido a isquemia “balanceada”.</p>
			<p>Essa limitação pode ser superada pela quantificação do fluxo sanguíneo miocárdico (FSM) ou a reserva de fluxo miocárdico (RFM) usando a cinética dos traçadores na tomografia por emissão de pósitrons (PET). <sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B4">4</xref></sup> A PET é um método não invasivo bem validado para quantificação da perfusão miocárdica, demonstrando um poder incremental de diagnóstico e prognóstico quando comparada à CPMem pacientes com suspeita ou DAC conhecida. <sup><xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B6">6</xref></sup> Assim, a PET é considerada padrão-ouro para quantificação não invasiva de FSM e RFM. <sup><xref ref-type="bibr" rid="B7">7</xref> - <xref ref-type="bibr" rid="B9">9</xref></sup> No entanto, a produção de traçadores próprios para a PET tem custos elevados e a tecnologia ainda não está disponível em muitos países.</p>
			<p>Câmeras de cádmio-zinco-telureto (CZT) de alta sensibilidade dedicadas a exames cardiológicos permitem a aquisição dinâmica de imagens tomográficas adequadas para avaliação da cinética do radio traçador e abrem uma nova era para medição de FSM e RFM. <sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
			<p>Quantificação de MBF e RFM por CZT-SPECT dinâmica em <italic>list mode</italic> é tecnicamente viável e clinicamente útil. <sup><xref ref-type="bibr" rid="B11">11</xref> , <xref ref-type="bibr" rid="B12">12</xref></sup> O estudo WATERDAY <sup><xref ref-type="bibr" rid="B13">13</xref></sup> comparou o FSM e a RFM obtidos com 99mTc-sestamibi em CZT-SPECT com aqueles obtidos em <sup><xref ref-type="bibr" rid="B15">15</xref></sup> O-água PET e fluxo fracionado de reserva (FFR). Enquanto MBF de estresse e de repouso foram significativamente superestimados com CZT-SPECT em comparação com PET, a RFM foi semelhante entre as duas técnicas, destacando-se que a quantificação de FSM e RFM por 99mTc-sestamibi CZT-SPECT dinâmica é clinicamente útil. <sup><xref ref-type="bibr" rid="B13">13</xref></sup> Acampa et al. <sup><xref ref-type="bibr" rid="B14">14</xref></sup> demonstraram que os valores obtidos pela CZT-SPECT são superiores aos medidos por imagem 82Rb-PET, com uma correlação moderada entre os dois métodos. CZT-SPECT mostrou boa acurácia diagnóstica para a identificação de DAC obstrutiva. Diferentes estudos delinearam o valor incremental das medidas de RFM em diferentes categorias de pacientes para diagnóstico ou prognóstico. <sup><xref ref-type="bibr" rid="B14">14</xref></sup> Pacientes com DAC multiarterial, nos quais uma cintilografia de perfusão miocárdica ( <italic>myocardial perfusion imaging</italic> — MPI) normal pode não necessariamente identificar subgrupos verdadeiramente de baixo risco entre coortes de alto risco, geralmente mostram RFM reduzido. <sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
			<p>Apesar do excelente valor diagnóstico do FFR, que quantifica o gradiente de pressão por meio da estenose, o FFR não reflete alterações de microcirculação. Ao contrário do FFR, a reserva de perfusão miocárdica (RPM) reflete o fluxo nas artérias epicárdicas e na microvasculatura. Portanto, FFR e MPR não são equivalentes. <sup><xref ref-type="bibr" rid="B16">16</xref></sup></p>
			<p>Deve-se notar que vários fatores podem afetar a resposta hemodinâmica do fluxo à estenose luminal, incluindo a geometria e a localização da lesão e a presença de vasos colaterais, impactando o fluxo regional geral. Em estudo do nosso grupo, Souza et al. <sup><xref ref-type="bibr" rid="B17">17</xref></sup> mostraram que tanto a RPM global quanto o estresse MBF foram reduzidos em pacientes com perfusão anormal. Além de avaliar a perfusão, o estudo demonstrou que a RPM global está inversamente associada ao índice de prognóstico de doença arterial coronariana (IPDAC), um índice hierárquico que abrange toda a árvore coronária epicárdica e está relacionado ao risco cardiovascular geral. <sup><xref ref-type="bibr" rid="B17">17</xref></sup></p>
			<p>Nesse cenário, Panjer et al. <sup><xref ref-type="bibr" rid="B18">18</xref></sup> realizaram uma revisão sistemática e meta-análise com o objetivo de avaliar a acurácia diagnóstica da CZT-SPECT dinâmica em doença arterial coronariana (DAC) em comparação com FFR e PET como referência. Para a avaliação da CZT-SPECT, a análise produziu uma sensibilidade de 0,79 (IC 95% 0,73–0,85) e uma especificidade de 0,85 (IC 95% 0,74–0,92). A razão de chances diagnóstica foi 17,82 (IC 95% 8,80–36,08, P &lt; 0,001). Razão de verossimilhança positiva e razão de verossimilhança negativa foram 3,86 (IC 95% 2,76–5,38, P&lt;0,001) e 0,21 (95% CI 0,13–0,33, P&lt;0,001), respectivamente. Os resultados dessa revisão sistemática e meta-análise enfatizam o papel da CZT-SPECT MPI dinâmica com boa sensibilidade e especificidade para diagnosticar DAC em comparação a padrões-ouro. O uso dos sistemas CZT-SPECT para a medição de RPM é muito atraente, considerando que em um exame é possível obter parâmetros de perfusão e funcionais com resultados comparáveis à PET. No entanto, o que emerge desta meta-análise é que o protocolo utilizado nos diferentes centros deveria ser mais padronizado. Os estudos incluídos usam metodologias diferentes em termos de administração de dose, protocolo de aquisição, câmeras CZT, radio traçadores e pacote de software usado. Além disso, em cada estudo foi definido um valor de corte diferente para a SPECT MPI dinâmica. Sete estudos comparam com o FFR e dois utilizaram PET. A medição da aquisição MPI foi realizada com diferentes tipos de câmeras CZT-SPECT. Seis estudos usaram o Discovery NM 530c (GE Healthcare, Chicago, IL, EUA), um estudo (11,1%) usou Discovery NM/CT 570c (tecnologia Alcyone, GE Healthcare, Haifa, Israel) e dois estudos (22,2%) usaram D-SPECT (Spectrum Dynamics, Palo Alto, Califórnia). A administração de isótopos duplos foi usada em um estudo, dois estudos usaram 201Tl como radio traçador, e seis estudos (66,7%) utilizaram marcadores marcados com 99mTc. É importante ressaltar que um software diferente foi usado para a quantificação de FSM e medição de RFM, incluindo software interno, com Corridor 4DM (INVIA, Ann Arbor, MI, EUA), aplicado com mais frequência do que outros. Além disso, a principal limitação dessa revisão sistemática e meta-análise, além das limitações típicas para esse tipo de análise, é um número relativamente pequeno de estudos e pacientes e heterogeneidade entrecomparadores. <sup><xref ref-type="bibr" rid="B19">19</xref></sup> Nessa visão, estudos com uma população maior e menor variabilidade entre as metodologias, como diferentes limites para RFM, distribuição do radiotraçador miocárdico, diferentes algoritmos de reconstrução e modelos de fluxo aplicados serão necessários para demonstrar claramente o impacto clínico aditivo do MBF com CZT.</p>
			<p>O emprego da avaliação de reserva de fluxo miocárdico pelo CZT pode ter utilidade em diversas situações clínicas, assim como ficou claro com PET ( <xref ref-type="table" rid="t1002">Tabela 1</xref> ).</p>
			<p>
				<table-wrap id="t1002">
					<label>Tabela 1</label>
					<caption>
						<title>– Em quais situações a reserva de fluxo miocárdico pode fazer a diferença?</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup width="100%">
							<col/>
						</colgroup>
						<tbody>
							<tr>
								<td>1) Pacientes com pouca isquemia, mas que podem ter DAC multivascular.</td>
							</tr>
							<tr>
								<td>2) Defeitos de perfusão, mas com artefato.</td>
							</tr>
							<tr>
								<td>3) Perfusão normal, mas com alto risco para DAC.</td>
							</tr>
							<tr>
								<td>4) Identificação de doença microvascular.</td>
							</tr>
							<tr>
								<td>5) Determinar a eficácia do vasoestressor.</td>
							</tr>
						</tbody>
					</table>
				</table-wrap>
			</p>
			<p>Uma das principais utilidades foi demonstrada na sensibilidade extremamente elevada para detectar doença multivascular como o estudo de DiCarli et al., onde uma RFM normal no PET praticamente excluiu a possibilidade dessa ocorrência. <sup><xref ref-type="bibr" rid="B20">20</xref></sup> A avaliação da RFM pela CZT-SPECT também permite esse incremento de acurácia. <sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
			<p>A possibilidade de identificar a doença microvascular como causa de angina é útil para redução dos custos na investigação, mas também muito importante como determinante de prognóstico. A RFM, tanto pela PET quanto pela CZT-SPECT, é uma modalidade não invasiva para confirmação desse fenômeno. <sup><xref ref-type="bibr" rid="B22">22</xref></sup></p>
			<p>No preparo para realização de estresse farmacológico com dipiridamol ou adenosina, recomenda-se a abstinência de cafeína por no mínimo 24 horas. Entretanto, quando esse preparo não é cumprido adequadamente, podemos comprometer a resposta vasodilatadora e, consequentemente, a indução da disparidade de fluxo. Em uma cintilografia tradicional, não há como isso ser identificado, podendo resultar em um exame “falso-negativo”. Porém, essa resposta inadequada é detectada pela avaliação da RFM. <sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
			<p>À medida que mais estudos forem publicados, levando a uma maior padronização da quantificação de FSM e RFM pela CZT-SPECT, a tornará uma importante ferramenta na prática clínica das cardiomiopatias isquêmicas, aumentando nosso entendimento sobre essa doença.</p>
		</body>
		<back>
			<fn-group>
				<fn fn-type="other">
					<p>Vinculação Acadêmica</p>
					<p>Não há vinculação deste estudo a programas de pós-graduação.</p>
				</fn>
				<fn fn-type="other">
					<p>Aprovação Ética e Consentimento Informado</p>
					<p>Este artigo não contém estudos com humanos ou animais realizados por nenhum dos autores.</p>
				</fn>
			</fn-group>
			<fn-group>
				<fn fn-type="supported-by">
					<p>Fontes de Financiamento: O presente estudo não teve fontes de financiamento externas.</p>
				</fn>
			</fn-group>
		</back>
	</sub-article>
</article>