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<article article-type="research-article" dtd-version="1.0" specific-use="sps-1.7" 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="nlm-ta">Braz J Cardiovasc Surg</journal-id>
			<journal-id journal-id-type="publisher-id">rbccv</journal-id>
			<journal-title-group>
				<journal-title>Brazilian Journal of Cardiovascular Surgery</journal-title>
				<abbrev-journal-title abbrev-type="publisher">Braz. J. Cardiovasc.
					Surg.</abbrev-journal-title>
			</journal-title-group>
			<issn pub-type="ppub">0102-7638</issn>
			<issn pub-type="epub">1678-9741</issn>
			<publisher>
				<publisher-name>Sociedade Brasileira de Cirurgia Cardiovascular</publisher-name>
			</publisher>
		</journal-meta>
		<article-meta>
			<article-id pub-id-type="doi">10.21470/1678-9741-2018-0001</article-id>
			<article-id pub-id-type="publisher-id">00008</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>ORIGINAL ARTICLE</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Does Moderate Coronary Stenosis Affect the Fate of the Left Internal
					Thoracic Artery Graft?</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<name>
						<surname>Caliskan</surname>
						<given-names>Aytac</given-names>
					</name>
					<xref ref-type="aff" rid="aff1">1</xref>
					<xref ref-type="corresp" rid="c1"/>
					<role>MD</role>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Unal</surname>
						<given-names>Ertekin Utku</given-names>
					</name>
					<xref ref-type="aff" rid="aff2">2</xref>
					<role>MD</role>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Kubat</surname>
						<given-names>Emre</given-names>
					</name>
					<xref ref-type="aff" rid="aff3">3</xref>
					<role>MD</role>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Aytekin</surname>
						<given-names>Bahadir</given-names>
					</name>
					<xref ref-type="aff" rid="aff2">2</xref>
					<role>MD</role>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Turkcan</surname>
						<given-names>Basak Soran</given-names>
					</name>
					<xref ref-type="aff" rid="aff2">2</xref>
					<role>MD</role>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Kiris</surname>
						<given-names>Erman Sureyya</given-names>
					</name>
					<xref ref-type="aff" rid="aff2">2</xref>
					<role>MD</role>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Tola</surname>
						<given-names>Muharrem</given-names>
					</name>
					<xref ref-type="aff" rid="aff4">4</xref>
					<role>MD</role>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Iscan</surname>
						<given-names>Hakki Zafer</given-names>
					</name>
					<xref ref-type="aff" rid="aff2">2</xref>
					<role>MD</role>
				</contrib>
			</contrib-group>
			<aff id="aff1">
				<label>1</label>
				<institution content-type="orgname">Cigli District Training Hospital</institution>
				<addr-line>
        <named-content content-type="city">Izmir</named-content>
				</addr-line>
				<country country="TR">Turkey</country>
				<institution content-type="original">Cigli District Training Hospital,
					Cardiovascular Surgery, Izmir, Turkey.</institution>
			</aff>
			<aff id="aff2">
				<label>2</label>
				<institution content-type="orgname">Turkey Yuksek Ihtisas Training and Research
					Hospital</institution>
				<addr-line>
        <named-content content-type="city">Ankara</named-content>
				</addr-line>
				<country country="TR">Turkey</country>
				<institution content-type="original">Turkey Yuksek Ihtisas Training and Research
					Hospital, Cardiovascular Surgery Ankara, Turkey.</institution>
			</aff>
			<aff id="aff3">
				<label>3</label>
				<institution content-type="orgname">Karabuk Training and Research
					Hospital</institution>
				<addr-line>
        <named-content content-type="city">Karabuk</named-content>
				</addr-line>
				<country country="TR">Turkey</country>
				<institution content-type="original">Karabuk Training and Research Hospital,
					Cardiovascular Surgery, Karabuk, Turkey.</institution>
			</aff>
			<aff id="aff4">
				<label>4</label>
				<institution content-type="orgname">Turkey Yuksek Ihtisas Training and Research
					Hospital</institution>
				<addr-line>
        <named-content content-type="city">Ankara</named-content>
				</addr-line>
				<country country="TR">Turkey</country>
				<institution content-type="original">Turkey Yuksek Ihtisas Training and Research
					Hospital, Radiology, Ankara,Turkey.</institution>
			</aff>
			<author-notes>
				<corresp id="c1">Correspondence Address: Aytac Caliskan, Cigli Training Hospital,
					Cardiovascular Surgery, Yenimahalle Mahallesi, 8780/1 Sokak, no18, Cigli, Izmir,
					TR 35620. E-mail: <email>aytac.caliskan@gmail.com</email></corresp>
				<fn fn-type="conflict">
					<p>No conflict of interest.</p>
				</fn>
			</author-notes>
			<pub-date pub-type="epub-ppub">
				<season>Nov-Dec</season>
				<year>2018</year>
			</pub-date>
			<volume>33</volume>
			<issue>6</issue>
			<fpage>567</fpage>
			<lpage>572</lpage>
			<history>
				<date date-type="received">
					<day>02</day>
					<month>01</month>
					<year>2018</year>
				</date>
				<date date-type="accepted">
					<day>28</day>
					<month>06</month>
					<year>2018</year>
				</date>
			</history>
			<permissions>
				<license license-type="open-access"
					xlink:href="http://creativecommons.org/licenses/by/4.0/" xml:lang="en">
					<license-p>This is an Open Access article distributed under the terms of the
						Creative Commons Attribution License, which permits unrestricted use,
						distribution, and reproduction in any medium, provided the original work is
						properly cited.</license-p>
				</license>
			</permissions>
			<abstract>
				<title>Abstract</title>
				<sec>
					<title>Introduction:</title>
					<p>In this study we try to observe the fate of the left internal thoracic artery
						grafts that were bypassed to left anterior descending artery with moderate
						stenosis identified with fractional flow reserve (FFR) technique. Doppler
						ultrasonography was chosen as a noninvasive screening method.</p>
				</sec>
				<sec>
					<title>Methods:</title>
					<p>A total of 30 patients who underwent coronary artery bypass grafting
						depending on results of the fractional flow reserve between January 2007 and
						January 2012, were subjected to transthoracic color Doppler ultrasonographic
						evaluation irrespective of the presence of symptoms, and the presence of a
						systolic-diastolic flow pattern was investigated using the supraclavicular
						approach.</p>
				</sec>
				<sec>
					<title>Results:</title>
					<p>The left internal thoracic artery graft was found to be functional in 63.3%
						of patients within a mean period of 35.1&#x00b1;19.7 months between coronary
						bypass and color Doppler ultrasonography. This period was found to be
						29.4&#x00b1;19.6 months in the functional graft group, and 44.7&#x00b1;16.6
						months in the dysfunctional graft group (<italic>P</italic>=0.046).
						Preoperative complaints of angina were reported to fall from 88.9% to 16.7%
						in the functional graft group, when compared to the postoperative period
							(<italic>P</italic>&lt;0.001), but fell from 90.9% to 36.4% in the
						dysfunctional graft group (<italic>P</italic>=0.034).</p>
				</sec>
				<sec>
					<title>Conclusion:</title>
					<p>Functional left internal thoracic artery graft rates of the study population
						were found to be lower than the studies reported in the literature.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="en">
				<title>Keywords:</title>
				<kwd>Coronary Angiography</kwd>
				<kwd>Coronary Artery Bypass</kwd>
				<kwd>Ultrasonography</kwd>
				<kwd>Internal Mammary-Coronary Artery Anastomosis</kwd>
				<kwd>Coronary Stenosis</kwd>
			</kwd-group>
		</article-meta>
	</front>
	<body>
		<table-wrap id="t4">
						<alternatives>
							<graphic xlink:href="t0.jpg"/>
			<table frame="hsides" rules="groups">
				<colgroup>
					<col width="25%"/>
					<col width="75%"/>
				</colgroup>
				<thead>
					<tr style="background-color:#eaeaea">
						<th align="left" colspan="2">Abbreviations, acronyms &amp; symbols</th>
					</tr>
				</thead>
				<tbody>
					<tr style="background-color:#eaeaea">
						<td align="left"><bold>CABG</bold></td>
						<td align="left"><bold>= Coronary artery bypass grafting</bold></td>
					</tr>
					<tr style="background-color:#eaeaea">
						<td align="left"><bold>CAG</bold></td>
						<td align="left"><bold>= Coronary angiography</bold></td>
					</tr>
					<tr style="background-color:#eaeaea">
						<td align="left"><bold>CDUS</bold></td>
						<td align="left"><bold>= Color Doppler ultrasonography</bold></td>
					</tr>
					<tr style="background-color:#eaeaea">
						<td align="left"><bold>FFR</bold></td>
						<td align="left"><bold>= Fractional flow reserve</bold></td>
					</tr>
					<tr style="background-color:#eaeaea">
						<td align="left"><bold>ITAG</bold></td>
						<td align="left"><bold>= Internal thoracic artery grafts</bold></td>
					</tr>
					<tr style="background-color:#eaeaea">
						<td align="left"><bold>LAD</bold></td>
						<td align="left"><bold>= Left anterior descending artery</bold></td>
					</tr>
					<tr style="background-color:#eaeaea">
						<td align="left"><bold>NYHA</bold></td>
						<td align="left"><bold>= New York Heart Association</bold></td>
					</tr>
					<tr style="background-color:#eaeaea">
						<td align="left"><bold>PCI</bold></td>
						<td align="left"><bold>= Percutaneous coronary interventions</bold></td>
					</tr>
				</tbody>
			</table>
		</alternatives>
		</table-wrap>
		<sec sec-type="intro">
			<title>INTRODUCTION</title>
			<p>Results of the interventions to severe coronary artery stenoses are mostly
				predictable. However, controversy still exists concerning moderate stenoses. Rapid
				increase in plaque sizes of borderline lesions have been reported, and long periods
				of nonintervention with these lesions can lead to undesirable cardiac
					events<sup>[</sup><xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref
					ref-type="bibr" rid="B2">2</xref><sup>]</sup>. Coronary artery bypass grafting
				(CABG) to moderately stenotic coronary vessels that were diagnosed by qualitative
				coronary angiography (CAG), is associated with lower long-term
					mortality<sup>[</sup><xref ref-type="bibr" rid="B3">3</xref><sup>]</sup>. But
				the success of surgical intervention in moderate stenoses is suggested to be
				associated with the functional importance of the lesion. Fractional flow reserve
				(FFR) is the suggested technique to decide the functional importance of a moderate
				coronary stenosis<sup>[</sup><xref ref-type="bibr" rid="B4">4</xref><sup>]</sup>.
				FFR has a very critical role in a surgeon's decision because a graft that was
				bypassed to a coronary artery with a functionally insignificant stenosis may be
				dysfunctional as a result of the competitive flow<sup>[</sup><xref ref-type="bibr"
					rid="B5">5</xref><sup>]</sup>. In this study we try to observe the fate of the
				left internal thoracic artery grafts (ITAG) that were bypassed to left anterior
				descending artery (LAD) with moderate stenoses that were identified with FFR
				technique. The patients were included in the study regardless of their symptom
				status so we chose color Doppler ultrasonography (CDUS) as a noninvasive screening
				method. The studies, which have demonstrated that CDUS could detect ITAG patency at
				a rate of over 90%, had encouraged us to choose CDUS as a screening
					method<sup>[</sup><xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref
					ref-type="bibr" rid="B7">7</xref><sup>]</sup>.</p>
		</sec>
		<sec sec-type="methods">
			<title>METHODS</title>
			<sec>
				<title>Study Patients</title>
				<p>A cross-sectional examination, from the data of 494 patients who were subjected
					to FFR for LAD between January 2007 and January 2012, was conducted. In our
					institution, experienced interventional cardiologists and surgeons decide the
					severity of the lesion mostly by visual assessment, but FFR is performed in case
					of suspected moderate stenosis. The decision to perform CABG has been made for
					patients with a FFR value &#x2264;0.80. Patients needing associated valve
					surgery and emergent CABG (defined as within 24 hours of the index procedure)
					were excluded. The 128 patients who underwent CABG at our hospital and who could
					be contacted by phone or by mail were invited for outpatient follow-ups; 30 of
					these invited patients responded to the calls and came for follow-up controls.
					Data concerning the variables were obtained from patients' medical records in
					the automation system, and from patient files. Patients were also examined
					according to the New York Heart Association (NYHA) functional capacity and the
					presence of angina, on arrival at the hospital for follow-up. Evaluation of
					angina was made according to standard guidelines recommendations as 'definite
					angina', 'probable angina', 'probably not angina' and 'definitely not angina';
					and patients in the 'definite angina' and 'probable angina' group were
					considered as having angina<sup>[</sup><xref ref-type="bibr" rid="B8"
						>8</xref><sup>]</sup>. All the patients were subjected to transthoracic
					echocardiography. Transthoracic CDUS was also performed in all the patients for
					the assessment of ITAG irrespective of the presence of symptoms. CAG was
					recommended to all patients who reported postoperative angina complaints during
					their outpatient follow-up visits.</p>
			</sec>
			<sec>
				<title>Surgical Technique</title>
				<p>While preparing the ITAG after median sternotomy in all patients, the great
					saphenous vein was used as a graft in all patients who were scheduled for bypass
					in more than one vessel. The ITAG was prepared from the origin of the subclavian
					artery to the superior epigastric and musculophrenic branches in the sixth
					intercostal space, using low-current electrocautery and hemoclips in the side
					branches, releasing it together with the pedicle and wrapping it with papaverine
					gas tampon. ITAG was harvested in all cases by senior residents.</p>
				<p>Standard cannulation was made from the ascending aorta and the right atrium
					(two-stage venous cannula). The targeted heparinization was accomplished at
					300-400 IU/kg and a target activated clotting time is 480 seconds. Surgery was
					performed under mild hypothermia (34-35ºC). We did not observe any off-pump
					operation in study population.</p>
				<p>The ITAG of all patients in the study population was anastomosed to the LAD. No
					medication was administered to the patients after surgery to prevent bleeding.
					All patients were transferred to the postoperative intensive care unit and
					placed on a mechanical ventilator for a few hours for follow-up.</p>
			</sec>
			<sec>
				<title>CDUS Technique</title>
				<p>All CDUS conducted for the visualization of the ITAG was performed using the
					Logiq 7 (Medical Systems, Milwaukee, WI, USA) Doppler ultrasonographic device
					and the 3-7 MHz multi-frequency linear probe. Examination of the ITAG was made
					using the CDUS by the supraclavicular approach, to visualize the subclavian
					artery towards the origin of the vertebral artery in the vertical plane. The
					presence of a cystolo-diastolic flow pattern was then investigated by
					visualizing the origin of the internal thoracic artery in the form of a tubular
					structure with the probe rotated caudally 90 degrees clockwise. Patients, whose
					cystolo-diastolic flow pattern in ITAG could not be examined, were considered to
					have dysfunctional grafts.</p>
			</sec>
			<sec>
				<title>Statistical Analysis</title>
				<p>Continuous numerical variables are expressed as "mean &#x00b1; standard deviation
					(SD)" of descriptive statistical analysis. On the other hand, the cut-off and
					categorized data are expressed as "number" and "percentage (%)". The "Chi-square
					test" and the "Fisher test" were used to compare categorized variables.
					Independent variables which were inconsistent with normal distribution were
					analyzed using the nonparametric "Mann-Whitney U test". The difference between
					inter-group preoperative and postoperative variables was obtained using the
					"Wilcoxon test". On the other hand, the time-dependent functional ITAG rate was
					evaluated using "Kaplan-Meier analysis". The "<italic>P</italic> value" was
					determined as "&#x03b1;=0.05" in all data analyses for the assessment of
					statistical significance level. Data were analyzed using the "IBM SPSS
					Statistics Version 15.0" packet program.</p>
			</sec>
		</sec>
		<sec sec-type="results">
			<title>RESULTS</title>
			<p>Basic demographic and clinical characteristics of the 30 patients who form the study
				population are shown in <xref ref-type="table" rid="t1">Table 1</xref>.</p>
			<table-wrap id="t1">
				<label>Table 1</label>
				<caption>
					<title>Basic demographic and intraoperative characteristics of the
						patients.</title>
				</caption>
						<alternatives>
							<graphic xlink:href="t1.jpg"/>
				<table frame="hsides" rules="all">
					<colgroup>
						<col width="28%"/>
						<col width="18%"/>
						<col width="18%"/>
						<col width="18%"/>
						<col width="18%"/>
					</colgroup>
					<thead>
						<tr>
							<th align="left" colspan="2">Characteristics of the patients</th>
							<th align="center">n</th>
							<th align="center">%</th>
							<th align="center">Mean &#x00b1; SD</th>
						</tr>
					</thead>
					<tbody>
						<tr>
							<td align="left" rowspan="2">Gender           </td>
							<td align="left">Female</td>
							<td align="center">5</td>
							<td align="center">16.7</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left">Male</td>
							<td align="center">25</td>
							<td align="center">83.3</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Age (years)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">&#x00A0;</td>
							<td align="center">63.6&#x00b1;9.6</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Diabetes mellitus</td>
							<td align="center">4</td>
							<td align="center">13.3</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Hypertension</td>
							<td align="center">21</td>
							<td align="center">70.0</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Peripheral artery disease</td>
							<td align="center">2</td>
							<td align="center">6.7</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Hyperlipidemia</td>
							<td align="center">14</td>
							<td align="center">46.7</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Smoking</td>
							<td align="center">10</td>
							<td align="center">33.3</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Carotid stenosis</td>
							<td align="center">1</td>
							<td align="center">3.3</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">CKD</td>
							<td align="center">3</td>
							<td align="center">10.0</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">SVE</td>
							<td align="center">__</td>
							<td align="center">__</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">COPD</td>
							<td align="center">1</td>
							<td align="center">3.3</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">FFR value</td>
							<td align="center">&#x00A0;</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.69&#x00b1;0.06</td>
						</tr>
						<tr>
							<td align="left" colspan="2">EF (%)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">&#x00A0;</td>
							<td align="center">54.4&#x00b1;7.9</td>
						</tr>
						<tr>
							<td align="left" colspan="2">CPB</td>
							<td align="center">30</td>
							<td align="center">100.0</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">The number of distal coronary bypasses</td>
							<td align="center">&#x00A0;</td>
							<td align="center">&#x00A0;</td>
							<td align="center">2.10&#x00b1;0.88</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Patients who underwent single vessel
								coronary artery bypass</td>
							<td align="center">10</td>
							<td align="center">33.3</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Patients who underwent two or more vessel
								coronary artery bypass</td>
							<td align="center">20</td>
							<td align="center">66.7</td>
							<td align="center">&#x00A0;</td>
						</tr>
					</tbody>
				</table>
			</alternatives>
				<table-wrap-foot>
					<fn id="TFN01">
						<p>CKD=chronic kidney disease; COPD=chronic obstructive pulmonary disease;
							CPB=cardiopulmonary bypass; EF=ejection fraction; FFR=fractional flow
							reserve; SD=standard deviation; SVE=cerebrovascular event</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<p>Preoperative and postoperative distribution and comparison of symptoms and functional
				capacities of patients are seen in <xref ref-type="table" rid="t2">Table 2</xref>.
				No statistically significant difference was found between the preoperative and
				postoperative functional capacities of the patients (<italic>P</italic>=0.059).
				However, patients were reported to have improved from their angina during the
				postoperative follow-ups (<italic>P</italic>&lt;0.001). Angina complaints have been
				reduced significantly in patients with single-vessel bypass, as well as in those who
				underwent coronary artery bypass grafting in two or more vessels
				(<italic>P</italic>=0.008 and <italic>P</italic>=0.001, respectively).</p>
			<table-wrap id="t2">
				<label>Table 2</label>
				<caption>
					<title>Preoperative and postoperative distribution and comparison of patient
						symptoms and functional capacity values.</title>
				</caption>
						<alternatives>
							<graphic xlink:href="t2.jpg"/>
				<table frame="hsides" rules="all">
					<colgroup>
						<col width="24%"/>
						<col width="19%"/>
						<col width="19%"/>
						<col width="19%"/>
						<col width="19%"/>
					</colgroup>
					<thead>
						<tr>
							<th align="left">Characteristics</th>
							<th align="center">&#x00A0;</th>
							<th align="center">n</th>
							<th align="center">%</th>
							<th align="center"><italic>P</italic> value</th>
						</tr>
					</thead>
					<tbody>
						<tr>
							<td align="left">Preoperative FC   </td>
							<td align="center">NYHA 1</td>
							<td align="center">18</td>
							<td align="center">60.0</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left">&#x00A0;</td>
							<td align="center">NYHA 2</td>
							<td align="center">7</td>
							<td align="center">23.3</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left">&#x00A0;</td>
							<td align="center">NYHA 3</td>
							<td align="center">5</td>
							<td align="center">16.7</td>
							<td align="center">0.059</td>
						</tr>
						<tr>
							<td align="left">Postoperative FC </td>
							<td align="center">NYHA 1</td>
							<td align="center">21</td>
							<td align="center">70.0</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left">&#x00A0;</td>
							<td align="center">NYHA 2</td>
							<td align="center">9</td>
							<td align="center">30.0</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left">Preoperative angina</td>
							<td align="center">&#x00A0;</td>
							<td align="center">26</td>
							<td align="center">89.7</td>
							<td align="center">            </td>
						</tr>
						<tr>
							<td align="left">Postoperative angina</td>
							<td align="center">&#x00A0;</td>
							<td align="center">7</td>
							<td align="center">24.1</td>
							<td align="center">&lt;0.001</td>
						</tr>
					</tbody>
				</table>
			</alternatives>
				<table-wrap-foot>
					<fn id="TFN02">
						<p>FC=functional capacity; NYHA=New York Heart Association</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<p>Apart from the CABG, three (10%) patients were subjected to additional intervention
				with one patient undergoing septal myectomy, one patient carotid endarterectomy,
				while one patient also underwent repair of femoral artery pseudoaneurysm.</p>
			<p>The median FFR value was found to be 0.70 (range: 0.56-0.80). Only two patients were
				found to be in the 0.75-0.80 range.</p>
			<p>The mean period of postoperative stay in the intensive care unit was found to be
				1.8&#x00b1;3.1 days for all patients, whereas the postoperative period for
				hospitalization was reported as 6.3&#x00b1;4.1 days. The mean period between CABG
				and CDUS was found to be 35.1&#x00b1;19.7 months.</p>
			<p>Results from CDUS conducted during outpatient follow-up visits demonstrated that the
				ITAG was functional in 63.3% of the patients (19 patients). Patients were then
				divided into two groups (functional and dysfunctional) according to assessment of
				ITAG, and the statistically significant difference between the groups evaluated
					(<xref ref-type="table" rid="t3">Table 3</xref>). A significant difference was
				reported between the two groups with regards only to the duration between CABG and
				CDUS. This duration was found to be 29.4&#x00b1;19.6 months in the group with
				functional ITAG, and 44.7&#x00b1;16.6 months in the dysfunctional group
					(<italic>P</italic>=0.046).</p>
			<table-wrap id="t3">
				<label>Table 3</label>
				<caption>
					<title>Comparison of demographic and clinical characteristics of patients with
						functional and dysfunctional ITAG on color CDUS.</title>
				</caption>
						<alternatives>
							<graphic xlink:href="t3.jpg"/>
				<table frame="hsides" rules="all">
					<colgroup>
						<col width="20%"/>
						<col width="18%"/>
						<col width="12%"/>
						<col width="12%"/>
						<col width="12%"/>
						<col width="12%"/>
						<col width="12%"/>
					</colgroup>
					<thead>
						<tr>
							<th align="left" colspan="2">&#x00A0;</th>
							<th align="center" colspan="2">Functional</th>
							<th align="center" colspan="3">Dysfunctional</th>
						</tr>
						<tr>
							<th align="left" colspan="2">Characteristics</th>
							<th align="center">n (%)</th>
							<th align="center">Mean &#x00b1; SS</th>
							<th align="center">n (%)</th>
							<th align="center">Mean&#x00b1; SD</th>
							<th align="center"><italic>P</italic> value</th>
						</tr>
					</thead>
					<tbody>
						<tr>
							<td align="left" rowspan="2">Gender             </td>
							<td align="left">Female</td>
							<td align="center">2 (10.5)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">3 (27.3)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.327</td>
						</tr>
						<tr>
							<td align="left">Male</td>
							<td align="center">17 (89.5)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">8 (72.7)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">&#x00A0;</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Age (years)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">63.4&#x00b1;10.4</td>
							<td align="center">&#x00A0;</td>
							<td align="center">64&#x00b1;8.6</td>
							<td align="center">0.800</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Diabetes mellitus</td>
							<td align="center">4 (21.1)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">__</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.268</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Hypertension</td>
							<td align="center">13 (68.4)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">8 (72.7)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.804</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Peripheral artery disease</td>
							<td align="center">1 (5.3)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1 (9.1)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1.000</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Hyperlipidemia</td>
							<td align="center">8 (42.1)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">6 (54.5)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.510</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Smoking</td>
							<td align="center">7 (36.8)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">3 (27.3)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.592</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Carotid stenosis</td>
							<td align="center">1 (5.3)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">__</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1.000</td>
						</tr>
						<tr>
							<td align="left" colspan="2">CKD</td>
							<td align="center">2 (10.5)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1 (9.1)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1.000</td>
						</tr>
						<tr>
							<td align="left" colspan="2">COPD</td>
							<td align="center">1 (5.3)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">__</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1.000</td>
						</tr>
						<tr>
							<td align="left" colspan="2">FFR value</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.68&#x00b1;0.06</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.72&#x00b1;0.04</td>
							<td align="center">0.310</td>
						</tr>
						<tr>
							<td align="left" colspan="2">EF (%)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">53.8&#x00b1;9.3</td>
							<td align="center">&#x00A0;</td>
							<td align="center">55.4&#x00b1;4.7</td>
							<td align="center">0.767</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Additional procedure</td>
							<td align="center">3 (15.3)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">__</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.279</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Coronary bypass number</td>
							<td align="center">&#x00A0;</td>
							<td align="center">2.05&#x00b1;0.97</td>
							<td align="center">&#x00A0;</td>
							<td align="center">2.18&#x00b1;0.75</td>
							<td align="center">0.800</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Preoperative angina</td>
							<td align="center">16 (88.9)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">10 (90.9)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1.000</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Postoperative angina</td>
							<td align="center">3 (16.7)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">4 (36.4)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.375</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Postoperative CKD</td>
							<td align="center">1 (5.3)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">__</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1.000</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Postoperative MI</td>
							<td align="center">1 (5.3)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">__</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1.000</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Postoperative low cardiac output</td>
							<td align="center">1 (5.3)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">__</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1.000</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Postoperative others</td>
							<td align="center">2 (10.5)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">__</td>
							<td align="center">&#x00A0;</td>
							<td align="center">0.520</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Postoperative stay in ICU (days)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">2.1&#x00b1;3.8</td>
							<td align="center">&#x00A0;</td>
							<td align="center">1.4&#x00b1;0.9</td>
							<td align="center">0.902</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Postoperative hospitalization (days)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">6.5&#x00b1;5.1</td>
							<td align="center">&#x00A0;</td>
							<td align="center">6.0&#x00b1;1.2</td>
							<td align="center">0.359</td>
						</tr>
						<tr>
							<td align="left" colspan="2">Duration between CABG and CDUS
								(months)</td>
							<td align="center">&#x00A0;</td>
							<td align="center">29.4&#x00b1;19.6</td>
							<td align="center">&#x00A0;</td>
							<td align="center">44.7&#x00b1;16.6</td>
							<td align="center">0.046</td>
						</tr>
					</tbody>
				</table>
			</alternatives>
				<table-wrap-foot>
					<fn id="TFN03">
						<p>CABG=coronary artery bypass grafting; CDUS=color Doppler ultrasonography;
							CKD=chronic kidney disease; COPD=chronic obstructive pulmonary disease,
							EF=ejection fraction; FC=functional capacity; FFR=fractional flow
							reserve; ICU=intensive care unit, ITAG: internal thoracic artery graft;
							MI=myocardial infarction; NYHA=New York Heart Association; SD=standard
							deviation</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<p>There was no significant difference between the two groups with regards to the
				preoperative and postoperative functional capacities (ITAG functional group
					<italic>P</italic>=0.053; ITAG dysfunctional group
				<italic>P=</italic>0.655).</p>
			<p>Four of the patients who were found to be consistent with postoperative angina
				accepted to undergo CAG. As a result, no statistically significant comparison was
				performed.</p>
			<p>Preoperative complaints of angina were reported to fall from 88.9% to 16.7% in the
				functional ITAG group, when compared to the postoperative period
				(<italic>P</italic>&lt;0.001), whereas the complaints fell from 90.9% to 36.4% in
				the dysfunctional ITAG group (<italic>P</italic>=0.034).</p>
			<p>The functional ITAG rates of the patients according to CDUS are shown in <xref
					ref-type="fig" rid="f1">Figure 1</xref>. Accordingly, the two-year functional
				graft rates were found to be 90.8%, whereas the three-year functional graft rates
				were 76.6%.</p>
			<p>
				<fig id="f1">
					<label>Fig. 1</label>
					<caption>
						<title>5 year functional left ITAG rates with 95% CI and patients at risk
							according to Kaplan Meier analysis.</title>
					</caption>
					<graphic xlink:href="0102-7638-rbccv-33-06-0567-gf01.jpg"/>
				</fig>
			</p>
		</sec>
		<sec sec-type="discussion">
			<title>DISCUSSION</title>
			<p>About 63.3% of the ITAG of the patients who underwent CABG according to FFR values,
				were found to be functional during a mean postoperative period of 35.1&#x00b1;19.7
				months. Functional graft rates were found to be lower than the known patency rates
				of the ITAG. In the dysfunctional ITAG group the period between CABG and CDUS was
				found to be significantly longer than that observed in the functional ITAG
				group.</p>
			<p>Moderate coronary stenoses are currently being treated according to their functional
				significance. Non-intervention for moderate stenoses, considered to be functionally
				insignificant, has demonstrated to alter survival and the incidence of
					angina<sup>[</sup><xref ref-type="bibr" rid="B9">9</xref><sup>]</sup>.
				Uneventful survival rate in cases with percutaneous coronary interventions (PCI)
				performed according to FFR guidance has shown to be higher than in procedures
				determined by CAG alone, and that FFR reduces the number of vessels involved with,
				and the cost of PCI<sup>[</sup><xref ref-type="bibr" rid="B10"
				>10</xref><sup>]</sup>. These findings are in line with another study which shows
				that surgical revascularization of moderate lesions according to their functional
				significance does not increase unwanted cardiac events despite reducing the number
				of anastomoses<sup>[</sup><xref ref-type="bibr" rid="B11">11</xref><sup>]</sup>.
				These results may be due to the fact that the patency of grafts for coronary
				stenoses, considered as functionally severe, is higher than that of those considered
				to be non-severe<sup>[</sup><xref ref-type="bibr" rid="B12"
				>12</xref><sup>]</sup>.</p>
			<p>ITAG is normally a conduit with a 10-year patency rate of 95%<sup>[</sup><xref
					ref-type="bibr" rid="B13">13</xref><sup>]</sup>. The fact that our study
				population consisted of patients with moderate stenosis suggests that the low
				functional ITAG rates (63.3%) may be due to native coronary blood flow. This flow in
				native vessels is more pronounced in vessels with moderate stenosis than in those
				with severe stenosis. Moderate target vessel stenoses have shown to be an
				independent risk factor for arterial graft dysfunction and can particularly cause
				grafts to become dysfunctional due to competitive flow, reducing the three-year
				patency rates to less than 90%<sup>[</sup><xref ref-type="bibr" rid="B14"
					>14</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref><sup>]</sup>. Due
				to the fact that arterial grafts reduce disease progression and also ensure
				regression of existing stenosis<sup>[</sup><xref ref-type="bibr" rid="B16"
					>16</xref><sup>]</sup>, improvement in native coronary flow may be another
				reason for dysfunctional ITAG in patients with moderate LAD stenosis as observed in
				our study population. The flow in the native coronary artery may prevent graft
				function when it is providing adequate perfusion to the myocardium distal to the
				stenosis. This sufficient flow in the native vasculature may have rendered patients
				to remain asymptomatic.</p>
			<p>ITAG which could not be assessed with CDUS in our study were considered as being
				dysfunctional. Literature studies show that the grafts of approximately 10% of
				patients could not be evaluated with CDUS, and at least 60% of these grafts were
				detected as being patent on CAG<sup>[</sup><xref ref-type="bibr" rid="B6"
					>6</xref><sup>]</sup>. Similarly, one of the reasons why the functional ITAG
				rate was below the expected level can be attributed to such limitations in the
				imaging procedure.</p>
			<p>The small sample size of our study may be the most important limiting factor. The
				period between CABG and CDUS are not homogeneous in the study population. Also study
				results could be affected by the heterogeneity of surgical technique or even
				surgeons, the diameter of coronary arteries as well as the severity of FFR values.
				The FFR values in the grey zone, which is considered to be within the range of
				0.75-0.80, were reported in only two patients; hence, a comparison could not be
				performed according to lesion severity. There is another heterogeneity in the number
				of diseased and bypassed vessels. Results obtained show that there was a significant
				decrease in postoperative angina complaints in patients with single-vessel bypass,
				as well as in those who were subjected to bypass grafting in two or more vessels
					(<italic>P</italic>=0.008 and <italic>P</italic>=0.001). The ITAG was used only
				at the LAD position in all of the patients and CDUS was used for visualizing only
				the functional status of the ITAG. Occlusion of saphenous venous grafts of coronary
				stenosis other than LAD may cause ischemia in some parts of the myocardium, leading
				to observable symptoms, while saphenous grafts of vessels which are a source of
				preoperative pain may remain patent, leading to asymptomatic features in the
				patients. Finally, evaluation of graft function was performed with CDUS; however,
				results could not be compared to CAG which is considered to be the golden
				standard.</p>
		</sec>
		<sec sec-type="conclusions">
			<title>CONCLUSION</title>
			<p>This study may give us an idea that grafting of moderate coronary stenoses may
				negatively affect graft patency rates. In order to assess the safety of determining
				the hemodynamic importance of moderate lesions by the FFR technique, studies with
				adequate and homogenous follow-up periods, involving a larger study population, and
				whose CDUS results can be confirmed by CAG, are required so as to obtain more
				definite results.</p>
			<table-wrap id="t5">
						<alternatives>
							<graphic xlink:href="t00.jpg"/>
				<table frame="hsides" rules="groups">
					<colgroup>
						<col width="5%"/>
						<col width="95%"/>
					</colgroup>
					<thead>
						<tr>
							<th align="left" colspan="2"><bold>Authors’ roles &amp;
									responsibilities</bold></th>
						</tr>
					</thead>
					<tbody>
						<tr>
							<td align="left">AC</td>
							<td align="left">Substantial contributions to the conception or design
								of the work; or the acquisition, analysis, or interpretation of data
								for the work; final approval of the version to be published</td>
						</tr>
						<tr>
							<td align="left">EUU</td>
							<td align="left">Substantial contributions to the conception or design
								of the work; or the acquisition, analysis, or interpretation of data
								for the work; final approval of the version to be published</td>
						</tr>
						<tr>
							<td align="left">EK</td>
							<td align="left">Drafting the work or revising it critically for
								important intellectual content; final approval of the version to be
								published</td>
						</tr>
						<tr>
							<td align="left">BA</td>
							<td align="left">Final approval of the version to be published</td>
						</tr>
						<tr>
							<td align="left">BST</td>
							<td align="left">Substantial contributions to the conception or design
								of the work; or the acquisition, analysis, or interpretation of data
								for the work; final approval of the version to be published</td>
						</tr>
						<tr>
							<td align="left">ESK</td>
							<td align="left">Substantial contributions to the conception or design
								of the work; or the acquisition, analysis, or interpretation of data
								for the work; final approval of the version to be published</td>
						</tr>
						<tr>
							<td align="left">MT</td>
							<td align="left">Performed the echocardiographic evaluation; final
								approval of the version to be published</td>
						</tr>
						<tr>
							<td align="left">HZI</td>
							<td align="left">Drafting the work or revising it critically for
								important intellectual content; final approval of the version to be
								published</td>
						</tr>
					</tbody>
				</table>
			</alternatives>
			</table-wrap>
		</sec>
	</body>
	<back>
		<fn-group>
			<fn fn-type="other">
				<p>This study was carried out at Cigli District Training Hospital, Cardiovascular
					Surgery, Izmir, Turkey.</p>
			</fn>
			<fn fn-type="supported-by">
				<p>No financial support.</p>
			</fn>
		</fn-group>
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					<issue>2</issue>
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					<lpage>481</lpage>
				</element-citation>
			</ref>
		</ref-list>
	</back>
</article>
