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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Cardiovasc. Med.</journal-id>
<journal-title>Frontiers in Cardiovascular Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Cardiovasc. Med.</abbrev-journal-title>
<issn pub-type="epub">2297-055X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fcvm.2023.1242215</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Cardiovascular Medicine</subject>
<subj-group>
<subject>Mini Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Magnetocardiography for the detection of myocardial ischemia</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author"><name><surname>Her</surname><given-names>Ae-Young</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="fn001"><sup>&#x2020;</sup></xref></contrib>
<contrib contrib-type="author"><name><surname>Dischl</surname><given-names>Dominic</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="author-notes" rid="fn001"><sup>&#x2020;</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/1919761/overview" /></contrib>
<contrib contrib-type="author"><name><surname>Kim</surname><given-names>Yong Hoon</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="fn001"><sup>&#x2020;</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/1465397/overview"/></contrib>
<contrib contrib-type="author"><name><surname>Kim</surname><given-names>Sang-Wook</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="author-notes" rid="fn001"><sup>&#x2020;</sup></xref></contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Shin</surname><given-names>Eun-Seok</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<xref ref-type="corresp" rid="cor1">&#x002A;</xref>
<xref ref-type="author-notes" rid="fn001"><sup>&#x2020;</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/1348811/overview" /></contrib>
</contrib-group>
<aff id="aff1"><label><sup>1</sup></label><addr-line>Department of Internal Medicine, Division of Cardiology</addr-line>, <institution>Kangwon National University College of Medicine, Kangwon National University School of Medicine</institution>, <addr-line>Chuncheon</addr-line>, <country>Republic of Korea</country></aff>
<aff id="aff2"><label><sup>2</sup></label><addr-line>Department of Cardiology, Deutsches Herzzentrum der Charit&#x00E9; (DHZC)</addr-line>, <institution>Angiology and Intensive Care Medicine</institution>, <addr-line>Berlin</addr-line>, <country>Germany</country></aff>
<aff id="aff3"><label><sup>3</sup></label><addr-line>Heart Research Institute, Cardiovascular-Arrhythmia Center, College of Medicine</addr-line>, <institution>Chung-Ang University Hospital</institution>, <addr-line>Seoul</addr-line>, <country>Republic of Korea</country></aff>
<aff id="aff4"><label><sup>4</sup></label><addr-line>Department of Cardiology</addr-line>, <institution>Ulsan University Hospital, University of Ulsan College of Medicine</institution>, <addr-line>Ulsan</addr-line>, <country>Republic of Korea</country></aff>
<author-notes>
<fn fn-type="edited-by"><p><bold>Edited by:</bold> Jai-Wun Park, Charit&#x00E9; University Medicine Berlin, Germany</p></fn>
<fn fn-type="edited-by"><p><bold>Reviewed by:</bold> Friedrich Jung, Helmholtz Centre for Materials and Coastal Research (HZG), Germany Niels Wessel, Humboldt University of Berlin, Germany</p></fn>
<corresp id="cor1"><label>&#x002A;</label><bold>Correspondence:</bold> Eun-Seok Shin <email>sesim1989@gmail.com</email></corresp>
<fn fn-type="other" id="fn001"><label><sup>&#x2020;</sup></label><p>ORCID Ae-Young Her <ext-link ext-link-type="uri" xlink:href="http://orcid.org/0000-0002-9990-6843">orcid.org/0000-0002-9990-6843</ext-link> Dominic Dischl <ext-link ext-link-type="uri" xlink:href="http://orcid.org/0000-0001-8382-765X">orcid.org/0000-0001-8382-765X</ext-link> Yong Hoon Kim <ext-link ext-link-type="uri" xlink:href="http://orcid.org/0000-0002-9669-3598">orcid.org/0000-0002-9669-3598</ext-link> Sang-Wook Kim <ext-link ext-link-type="uri" xlink:href="http://orcid.org/0000-0002-7208-8596">orcid.org/0000-0002-7208-8596</ext-link> Eun-Seok Shin <ext-link ext-link-type="uri" xlink:href="http://orcid.org/0000-0002-9169-6968">orcid.org/0000-0002-9169-6968</ext-link></p></fn>
</author-notes>
<pub-date pub-type="epub"><day>07</day><month>07</month><year>2023</year></pub-date>
<pub-date pub-type="collection"><year>2023</year></pub-date>
<volume>10</volume><elocation-id>1242215</elocation-id>
<history>
<date date-type="received"><day>18</day><month>06</month><year>2023</year></date>
<date date-type="accepted"><day>28</day><month>06</month><year>2023</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2023 Her, Dischl, Kim, Kim and Shin.</copyright-statement>
<copyright-year>2023</copyright-year><copyright-holder>Her, Dischl, Kim, Kim and Shin</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<abstract>
<p>Ischemic heart disease (IHD) continues to be a significant global public health concern and ranks among the leading causes of mortality worldwide. However, the identification of myocardial ischemia in patients suspected of having coronary artery disease (CAD) remains a challenging issue. Functional or stress testing is widely recognized as the gold standard method for diagnosing myocardial ischemia, but it is hindered by low diagnostic accuracy and limitations such as radiation exposure. Magnetocardiography (MCG) is a non-contact, non-invasive method that records magnetic fields produced by the electrical activity of the heart. Unlike electrocardiography (EKG) and other functional or stress testing, MCG offers numerous advantages. It is highly sensitive and can detect early signs of myocardial ischemia that may be missed by other diagnostic tools. This review aims to provide an extensive overview of the available evidence that establishes the utility of MCG as a valuable diagnostic tool for identifying myocardial ischemia, accompanied by a discussion of potential future research directions in this domain.</p>
</abstract>
<kwd-group>
<kwd>magnetocardiography</kwd>
<kwd>myocardial ischemia</kwd>
<kwd>coronary artery disease</kwd>
<kwd>electrocardiography</kwd>
<kwd>acute coronary syndrome</kwd>
</kwd-group>
<counts>
<fig-count count="0"/>
<table-count count="2"/><equation-count count="0"/><ref-count count="58"/><page-count count="0"/><word-count count="0"/></counts><custom-meta-wrap><custom-meta><meta-name>section-at-acceptance</meta-name><meta-value>General Cardiovascular Medicine</meta-value></custom-meta></custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro"><title>Introduction</title>
<p>Ischemic heart disease (IHD) remains a significant global public health issue, and its prevalence has been increasing over the years. According to the 2023 report from the National Center for Biotechnology Information (NCBI), IHD is responsible for 17.8 million deaths annually, positioning it as the third most common cause of mortality worldwide (<xref ref-type="bibr" rid="B1">1</xref>). However, identifying myocardial ischemia in patients with suspected coronary artery disease (CAD) remains a challenging aspect of routine cardiological diagnostics with its diverse manifestation and the complexities involved in distinguishing non-IHD. Functional or stress testing, which aims to detect inducible myocardial ischemia, has traditionally been considered the &#x201C;gold standard&#x201D; and is the most commonly used as a non-invasive method for diagnosing CAD (<xref ref-type="bibr" rid="B2">2</xref>). However, a non-invasive evaluation is performed on less than half of the patients before percutaneous coronary intervention (PCI) (<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>). This is primarily due to limitations in testing, which include low diagnostic accuracy and the potential radiation risks associated with coronary computed tomography (CT) or single-photon emission computed tomography (SPECT) (<xref ref-type="bibr" rid="B5">5</xref>).</p>
<p>Magnetocardiography (MCG) is a non-contact, non-invasive, radiation and contrast-free method that enables the recording of magnetic fields generated by the electrical activity of the heart (<xref ref-type="bibr" rid="B6">6</xref>&#x2013;<xref ref-type="bibr" rid="B9">9</xref>). Although electrocardiography (EKG) and MCG provide information about the same electrical activities of the heart, MCG presents several advantages. Cardiac magnetic fields remain unaffected by variations in the conductivity of body tissues or fluids, without attenuation or distortion (<xref ref-type="bibr" rid="B10">10</xref>). Additionally, its high sensitivity and non-invasive, contactless procedure make it a valuable tool for early diagnosis of myocardial ischemia that may otherwise go undetected by EKG (<xref ref-type="bibr" rid="B11">11</xref>). Several clinical studies have already demonstrated the superior sensitivity of MCG compared to EKG in detecting ischemic myocardium both at rest and during stress (<xref ref-type="bibr" rid="B11">11</xref>&#x2013;<xref ref-type="bibr" rid="B17">17</xref>). The remarkable ability of MCG to identify patients with CAD has been widely recognized (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B17">17</xref>&#x2013;<xref ref-type="bibr" rid="B20">20</xref>). Various MCG investigations have employed a variety of devices, including cryogenic superconducting quantum interference devices (SQUIDs) (<xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B22">22</xref>). These devices have primarily been utilized in magnetically shielded rooms (MSR) to eliminate background environmental noise, for instance, noise emanating from nearby instruments. However, they can also yield reliable outcomes in unshielded environments by incorporating a second (or higher order) gradiometer configuration of the pick-up coils and/or utilizing real-time electronic noise subtraction (<xref ref-type="bibr" rid="B10">10</xref>). Recently, advancements have been made in non-cryogenic MCG devices, offering alternative options (<xref ref-type="bibr" rid="B23">23</xref>). Furthermore, a variety of quantitative methods and computer algorithms have been devised to facilitate the interpretation of diverse magnetic field patterns (<xref ref-type="bibr" rid="B24">24</xref>&#x2013;<xref ref-type="bibr" rid="B27">27</xref>).</p>
<p>This review will provide an overview of the evidence supporting the utility of MCG, a valuable tool for diagnosing myocardial ischemia that is currently available, and discuss the potential impact of these findings on the future integration of MCG into clinical practice.</p>
</sec>
<sec id="s2"><title>Evidence on the efficacy of MCG for the diagnosis of ischemic heart disease</title>
<p>Previous studies have explored the application of MCG for the diagnosis or ruling out of stable CAD in <xref ref-type="table" rid="T1">Table&#x00A0;1</xref>. Other studies have investigated its use for the detection or ruling out of acute coronary syndrome (ACS) in <xref ref-type="table" rid="T2">Table&#x00A0;2</xref>. These studies have utilized a range of techniques to qualitatively and quantitatively analyze the magnetic field throughout the cardiac cycle. In most of the studies, the quantitative analysis has been focused on evaluating changes in the magnetic field during ventricular repolarization, typically occurring at the end of the ST segment (prior to the T wave) and/or the T wave. These methods encompass the analysis of various aspects, such as the extrema and dynamics of the magnetic field angle, as well as the dynamics of distance and ratio involving the minimum and maximum poles. These measurements are typically taken during the ascending T wave, specifically from one-third of the peak intensity (Tmax/3) to the peak intensity (Tmax) (<xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B28">28</xref>&#x2013;<xref ref-type="bibr" rid="B32">32</xref>, <xref ref-type="bibr" rid="B42">42</xref>, <xref ref-type="bibr" rid="B49">49</xref>). Additionally, other studies have also investigated different parameters related to the ST segment and T wave, particularly during or after exercise (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B33">33</xref>). Due to the typically higher magnetic field and signal-to-noise (S/N) ratio during rest, many subsequent studies have focused on utilizing variations of parameters measured during the T wave, initially described by Park et al. (<xref ref-type="bibr" rid="B42">42</xref>). Additionally, other MCG parameters have been investigated during the QT and QRS intervals (<xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B34">34</xref>&#x2013;<xref ref-type="bibr" rid="B39">39</xref>), and there have been reports on the application of machine-learning approaches for interpreting MCG signals (<xref ref-type="bibr" rid="B24">24</xref>&#x2013;<xref ref-type="bibr" rid="B26">26</xref>).</p>
<table-wrap id="T1" position="float"><label>Table 1</label>
<caption><p>Studies of MCG in patients with stable CAD.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="left"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Study</th>
<th valign="top" align="center">Diagnostic criteria of MCG</th>
<th valign="top" align="center">Indication/Test population (n)/Control (n)</th>
<th valign="top" align="center">Testing conditions</th>
<th valign="top" align="center">Specificity/Sensitivity (ROC AUC)</th>
<th valign="top" align="center">PPV/NPV (ROC AUC)</th>
<th valign="top" align="center">Reference</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Park et al. (<xref ref-type="bibr" rid="B5">5</xref>)</td>
<td valign="top" align="left">Change in ST-segment fluctuation score between rest and stress with a cut-off of &#x2212;39.0&#x0025;<break/>Bulls-eye mapping of current between beginning of T wave and T<sub>max</sub> at rest vs. stress</td>
<td valign="top" align="left">Anatomic CAD/Patients with suspected CAD with subsequent angiographically proven &#x2265;50&#x0025; stenosis of a vessel without acute MI in previous 3 months (42) and patients with angiographically proven non-obstructive CAD (5)/-</td>
<td valign="top" align="left">Shielded<break/>64-channel<break/>Rest and exercise (bicycle ergometry test)/dobutamine stress</td>
<td valign="top" align="center">74&#x0025;/87&#x0025;<break/>(0.84)<break/>(ST fluctuation score)<break/>92&#x0025;/91&#x0025;<break/>(0.91) (mapping)</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="left">Fractional flow reserve</td>
</tr>
<tr>
<td valign="top" align="left">Fenici et al. (<xref ref-type="bibr" rid="B6">6</xref>)</td>
<td valign="top" align="left">Angle (A), distance (D), and ratio (R) dynamics of the dipoles during the T wave interval and ST angle as prespecified criteria</td>
<td valign="top" align="left">Anatomic CAD<break/>Patients with IHD and angiographically proven &#x003E;70&#x0025; coronary stenosis and positive stress/SPECT (19)<break/>Healthy volunteers (20)</td>
<td valign="top" align="left">Unshielded,<break/>36-channel<break/>Rest</td>
<td valign="top" align="center">20&#x2005;Hz low pass filtering:<break/>100&#x0025;/32&#x0025; (A)<break/>90&#x0025;/42&#x0025; (D)<break/>80&#x0025;/42&#x0025; (R)<break/>70&#x0025;/79&#x0025; (ST&#x03B1;)<break/>50&#x2005;Hz adaptive filtering:<break/>100&#x0025;/47&#x0025; (A)<break/>65&#x0025;/74&#x0025; (D)<break/>50&#x0025;/63&#x0025; (R)<break/>75&#x0025;/79&#x0025; (ST&#x03B1;)</td>
<td valign="top" align="center">20&#x2005;Hz low pass filtering:<break/>100&#x0025;/60&#x0025; (A)<break/>80&#x0025;/62&#x0025; (D)<break/>67&#x0025;/59&#x0025; (R)<break/>71&#x0025;/79&#x0025; (ST&#x03B1;)<break/>50&#x2005;Hz adaptive filtering:<break/>100&#x0025;/66&#x0025; (A)<break/>67&#x0025;/72&#x0025; (D)<break/>55&#x0025;/59&#x0025; (R)<break/>75&#x0025;/79&#x0025; (ST&#x03B1;)</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Park et al. (<xref ref-type="bibr" rid="B9">9</xref>)</td>
<td valign="top" align="left">Reduction of epicardial current density and strength at QRS<sub>max</sub> between rest and stress used as diagnostic for ischemia</td>
<td valign="top" align="left">Functional ischemia/<break/>Patients with intermediate pre-test probability of CAD with subsequent angiographically proven &#x2265;70&#x0025; stenosis of a vessel (42) or with angiographically proven non-obstructive CAD (58)/-</td>
<td valign="top" align="left">Shielded<break/>55-channel<break/>Rest and pharmacologic (dobutamine) stress</td>
<td valign="top" align="center">83&#x0025;/98&#x0025;</td>
<td valign="top" align="center">80&#x0025;/98&#x0025;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">H&#x00E4;nninen et al. (<xref ref-type="bibr" rid="B13">13</xref>)</td>
<td valign="top" align="left">ST slope increase and peak gradient orientation of the ST segment at cessation of stress, T-wave amplitude increase at two minutes recovery</td>
<td valign="top" align="left">Functional ischemia/<break/>Patients with CAD with anginal pain, and a positive EKG stress test and either single-vessel disease<break/>(&#x003E;50&#x0025; luminal diameter stenosis in one of the main coronary arteries) with no history of MI (27) or triple-vessel disease (stenosis &#x2265;70&#x0025; luminal diameter) and &#x2265;1 previous MI (17)/Healthy volunteers (26)</td>
<td valign="top" align="left">Shielded<break/>67-channel<break/>Exercise (supine bicycle ergometry test)</td>
<td valign="top" align="center">&#x2013;<break/>(0.83) (ST slope)<break/>(0.83) (ST peak gradient)<break/>(0.86) (T-wave increase)</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Shin et al. (<xref ref-type="bibr" rid="B18">18</xref>)</td>
<td valign="top" align="left">Quantitative and qualitative analysis of the change in<break/>ST-segment fluctuation score<break/>(&#x2013;51&#x0025; cut-off selected as best cut-off) and the non-dipole phenomenon during the interval from the beginning of the T wave to the T<sub>max</sub></td>
<td valign="top" align="left">Anatomic CAD and functional ischemia/<break/>Patients with suspected CAD without acute MI in previous 3 months, with subsequent angiographically confirmed CAD (&#x2265;70&#x0025; stenosis in<break/>&#x2265;1 proximal epicardial coronary artery) and objective evidence of myocardial ischemia or<break/>&#x2265;1 coronary stenosis of &#x2265;80&#x0025; and classic angina without provocative testing (71)/Asymptomatic patients without angiographically proven CAD (25)</td>
<td valign="top" align="left">Shielded<break/>64-channel<break/>Rest and exercise (bicycle ergometry test)</td>
<td valign="top" align="center">82&#x0025;/74&#x0025;<break/>(0.79)<break/>(rST segment-fluctuation score)<break/>88&#x0025;/85&#x0025;<break/>(0.86)<break/>(non-dipole)<break/>ROC AUC for combination 0.93</td>
<td valign="top" align="center">79&#x0025;/77&#x0025;<break/>(rST segment-fluctuation score)<break/>87&#x0025;/86&#x0025;<break/>(non-dipole)</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Shin et al. (<xref ref-type="bibr" rid="B20">20</xref>)</td>
<td valign="top" align="left">Scoring system based on five MCG parameters (T wave score at stress; T wave dispersion at stress; T wave vector MCG at rest; &#x0025; change in half RT interval vector MCG; and &#x0025; change in<break/>T wave vector MCG) with cut-off of &#x2013;0.27 shown as best discriminant of significant stenosis</td>
<td valign="top" align="left">Anatomic CAD/<break/>Training set: patients with indication for angiography due to chest pain or suspected CAD with<break/>&#x2265;1 vessel with 70&#x0025; stenosis, and without ACS or history of MI within 3 months (35)<break/>Internal cross-validation set: patients with indication for angiography due to chest pain or suspected CAD [45; Park et al. (<xref ref-type="bibr" rid="B5">5</xref>)]/Training set: patients with indication for angiography due to chest pain or suspected CAD without significant stenosis (73)</td>
<td valign="top" align="left">Shielded<break/>64-channel<break/>Rest and exercise (bicycle ergometry test)</td>
<td valign="top" align="center">77&#x0025;/89&#x0025;<break/>(0.91)</td>
<td valign="top" align="center">74&#x0025;/91&#x0025;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Huang et al. (<xref ref-type="bibr" rid="B24">24</xref>)</td>
<td valign="top" align="left">Machine learning approach to analysis of multilayer perceptron neural network as best model</td>
<td valign="top" align="left">Anatomic CAD/<break/>Patients with chest pain and suspected CAD and underwent coronary angiography (209)/-</td>
<td valign="top" align="left">Unshielded<break/>4-channel<break/>Rest</td>
<td valign="top" align="center">89&#x0025;/90&#x0025; for M10<break/>92&#x0025;/88&#x0025; for M11</td>
<td valign="top" align="center">93&#x0025;/85&#x0025; for M10<break/>92&#x0025;/87&#x0025; for M11</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Tao et al. (<xref ref-type="bibr" rid="B25">25</xref>)</td>
<td valign="top" align="left">Machine learning classification (SVM-XGBoost model) of 164 MCG features measured during segments of the T wave and categorized as time domain, frequency domain, or information theory features</td>
<td valign="top" align="left">Anatomic CAD/Patients with IHD with clinically identified stenosis (227), including NSTEMI (16)/Healthy subjects (347)</td>
<td valign="top" align="left">Unshielded<break/>4-channel<break/>Rest</td>
<td valign="top" align="center">NR/97.8&#x0025; (0.98)</td>
<td valign="top" align="center">86.6&#x0025;/NR</td>
<td valign="top" align="left">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">Kangwanariyakul et al. (<xref ref-type="bibr" rid="B26">26</xref>)</td>
<td valign="top" align="left">Machine-learning approach to analysis of the JT interval using algorithms of neural network, with BNN identified as best model</td>
<td valign="top" align="left">IHD/Patients with IHD (29)/Healthy subjects with no evidence of cardiac abnormal symptoms (22)</td>
<td valign="top" align="left">Not stated<break/>9-channel<break/>Rest</td>
<td valign="top" align="center">55&#x0025;/97&#x0025;<break/>(0.85)</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="left">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">Steinberg et al. (<xref ref-type="bibr" rid="B28">28</xref>)</td>
<td valign="top" align="left">Algorithm-generated score of a scale of 0&#x2013;100 based on<break/>four MCG parameters during T<sub>max/3</sub> and T<sub>max</sub>: (1) Direction of the main vector from the plus to minus pole (&#x03B1;) between &#x2013;20&#x00B0; and &#x002B;110&#x00B0;; (2) Change in the angle of the main vector &#x2265;45&#x00B0; in a time interval of 30 msec; (3) Change in the distance separating the plus and minus poles &#x2265;20&#x00A0;mm in a time interval of 30 msec;<break/>(4) Change in the ratio of the pole strengths &#x2265;0.3 in a time interval of 30&#x00A0;msec. Score cut-off of &#x003E;49 applied based on a previous cohort</td>
<td valign="top" align="left">Anatomic CAD<break/>Patients with suspected CAD and angiographically proven &#x003E;50&#x0025; stenosis (36)<break/>Patients with angiographically proven non-obstructive CAD (10)</td>
<td valign="top" align="left">Unshielded<break/>9-channel<break/>Rest</td>
<td valign="top" align="center">40&#x0025;/84&#x0025;</td>
<td valign="top" align="center">73&#x0025;/57&#x0025;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Ramesh et al. (<xref ref-type="bibr" rid="B29">29</xref>)</td>
<td valign="top" align="left">The presence of an abnormal MFM and an abnormal magnetic field angle</td>
<td valign="top" align="left">Anatomic CAD/Patients with chest pain with normal EKG, positive TMT (12) and negative TMT (17)/-</td>
<td valign="top" align="left">Shielded<break/>37-channel</td>
<td valign="top" align="center">94&#x0025;/91&#x0025;</td>
<td valign="top" align="center">-</td>
<td valign="top" align="left">Treadmill test</td>
</tr>
<tr>
<td valign="top" align="left">Huang et al. (<xref ref-type="bibr" rid="B30">30</xref>)</td>
<td valign="top" align="left">Pearson&#x2019;s correlation coefficient by comparing each two T-waves by bivariate correlation analysis &#x003E;0.55</td>
<td valign="top" align="left">Anatomic CAD/Patients with an indication for coronary angiography due to angina-like symptoms and without a prior history of CAD; not requiring PCI (85) or requiring PCI (118)/-</td>
<td valign="top" align="left">Unshielded<break/>4-channel</td>
<td valign="top" align="center">66&#x0025;/73&#x0025;<break/>(0.75)</td>
<td valign="top" align="center">75&#x0025;/64&#x0025;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Brisinda et al. (<xref ref-type="bibr" rid="B31">31</xref>)</td>
<td valign="top" align="left">ST&#x03B1; and T&#x03B1;, or one of the following:<break/>(1) Pattern with &#x2265;2 dipoles in the time interval between 100 msec at the end of S wave (S<sub>100</sub>) and T<sub>max</sub>;<break/>(2) Direction of the current vector between &#x2013;20&#x00B0; and &#x002B;110&#x00B0; for the same time interval; (3) If the current vector direction lies between &#x002B;110&#x00B0; and &#x2013;20&#x00B0;, one of three parameters had to be satisfactory: (a) Change in the angle of the current vector &#x003E;60 in 30 msec of the change of angle of S<sub>100</sub>&#x2013;T<sub>max</sub>; (b) Change in the pole distance &#x003E;20&#x2005;mm (in 30 msec of S<sub>100</sub>&#x2013;T<sub>max</sub>); c) Ratio magnetic field poles strength &#x003E;&#x2009;&#x00B1;&#x2009;0.3 (in 30 msec of S<sub>100</sub>&#x2013;T<sub>max</sub>)</td>
<td valign="top" align="left">Anatomic CAD and functional ischemia<break/>Patients with documented CAD by angiography (four by SPECT and exercise bicycle ergometry test) (21)<break/>Healthy subjects (13)</td>
<td valign="top" align="left">Unshielded, 36-channel<break/>Rest and exercise (bicycle ergometry test)</td>
<td valign="top" align="center">92&#x0025;/93&#x0025;</td>
<td valign="top" align="center">92&#x0025;/NR</td>
<td valign="top" align="left">Stress EKG<break/>SPECT</td>
</tr>
<tr>
<td valign="top" align="left">Fenici et al. (<xref ref-type="bibr" rid="B32">32</xref>)</td>
<td valign="top" align="left">Machine learning classification based on scores for the dipoles (&#x003E;0) and T wave extrema (angle [&#x003E;45&#x00B0;], distance [&#x003E;20&#x2005;mm], ratio [&#x003E;0.3]) of the MFM in 30 msec intervals during the T<sub>max/3</sub> to T<sub>max</sub>, and ST<italic>&#x03B1;</italic> and T&#x03B1; (0&#x2013;90&#x00B0; normal) as prespecified discriminatory criteria</td>
<td valign="top" align="left">Anatomic CAD<break/>Subgroup of patients classified as ischemic on the basis of clinical criteria and diagnostic tests, and who did not receive PCI (32)<break/>Healthy subjects with no evidence of CAD at clinical history, normal physical examination, and echocardiography (33)</td>
<td valign="top" align="left">Unshielded, 36-channel<break/>Rest</td>
<td valign="top" align="center">85&#x0025;/75&#x0025;</td>
<td valign="top" align="center">83&#x0025;/78&#x0025;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">H&#x00E4;nninen et al. (<xref ref-type="bibr" rid="B33">33</xref>)</td>
<td valign="top" align="left">Abnormalities in the orientation of the peak gradient of the precordial ST-segment and T-wave magnetic field</td>
<td valign="top" align="left">Functional ischemia/Patients with single-vessel CAD with angiographically proven stenosis (&#x003E;50&#x0025; luminal diameter) in one of the main coronary branches, anginal pain, and a positive EKG stress test, with no prior MI (27)/Healthy volunteers (17)</td>
<td valign="top" align="left">Shielded<break/>67-channel<break/>Exercise (bicycle ergometry test)</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Van Leeuwen et al. (<xref ref-type="bibr" rid="B34">34</xref>)</td>
<td valign="top" align="left">Spatial distribution of the QT interval with SI cut-off of 3.18 selected as best discriminator</td>
<td valign="top" align="left">Anatomic CAD/Patients with CAD and angiographically proven &#x2265;75&#x0025; stenosis with prior MI (31) or without prior MI (23)<break/>Healthy subjects proven angiographically or volunteers with no history of CAD (20)</td>
<td valign="top" align="left">Shielded<break/>37-channel</td>
<td valign="top" align="center">80&#x0025;/74&#x0025;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Van Leeuwen et al. (<xref ref-type="bibr" rid="B35">35</xref>)</td>
<td valign="top" align="left">&#x003E;10&#x0025; deviation from the normal course of the MFM orientation during QT interval selected as a discriminator</td>
<td valign="top" align="left">Anatomic CAD/<break/>Patients with CAD with angiographically proven &#x2265;75&#x0025; stenosis of a vessel without evidence of MI (43) or with previous MI (36)/Patients with angiographically proven non-obstructive CAD and healthy volunteers (50)</td>
<td valign="top" align="left">Shielded<break/>37 or 61-channel<break/>Rest</td>
<td valign="top" align="center">90&#x0025;/68&#x0025;<break/>(in patients without prior MI)<break/>90&#x0025;/85&#x0025;<break/>(in patients with prior MI)</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="left">EKG<break/>TTE<break/>Angiography</td>
</tr>
<tr>
<td valign="top" align="left">On et al. (<xref ref-type="bibr" rid="B36">36</xref>)</td>
<td valign="top" align="left">Sum of the integral values of the QRS (QRSi) or JT (JTi) intervals with JTi/QRSi &#x003C;1.0 prespecified as discriminant</td>
<td valign="top" align="left">Anatomic CAD/Patients with angina pectoris and angiographically proven &#x003E;75&#x0025; stenosis of a vessel (14) with no (11) or previous (3) MI/Healthy volunteers (30)</td>
<td valign="top" align="left">Shielded<break/>64-channel<break/>Rest</td>
<td valign="top" align="center">80&#x0025;/71&#x0025;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Goernig et al. (<xref ref-type="bibr" rid="B37">37</xref>)</td>
<td valign="top" align="left">Spatiotemporal correlation analysis of 11 MCG parameters. Analysis combining three parameters (mean value correlation QRS at T, STDEV correlation T at QRS and QRS form) was identified as best discriminant</td>
<td valign="top" align="left">Anatomic CAD/<break/>Patients who experienced MI 6&#x2013;64 (mean 28) days earlier with angiographically proven &#x003E;70&#x0025; stenosis (108)/Subjects without known CAD and with echocardiographic proven normal LVEF (70)</td>
<td valign="top" align="left">Shielded<break/>31-channel<break/>Rest</td>
<td valign="top" align="center">64&#x0025;/73&#x0025;</td>
<td valign="top" align="center">86&#x0025;/73&#x0025;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Gapelyuk et al. (<xref ref-type="bibr" rid="B38">38</xref>)</td>
<td valign="top" align="left">Combination of Kullback-Leibler entropy at ST-T and normalized residual magnetic field strength at QRS selected as best discriminant index</td>
<td valign="top" align="left">Anatomic CAD/<break/>Patients with symptomatic stable CAD and angiographically proven &#x003E;50&#x0025; stenosis in main coronary arteries without previous MI (101)/Healthy subjects with normal findings in EKG, echocardiography, and bicycle ergometry, and no history of cardiac symptoms (59)</td>
<td valign="top" align="left">Shielded<break/>7-channel<break/>Rest</td>
<td valign="top" align="center">88&#x0025;/88&#x0025;<break/>(0.94)</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Wu et al. (<xref ref-type="bibr" rid="B39">39</xref>)</td>
<td valign="top" align="left">QT<sub>c</sub>&#x00A0;dispersion (from the difference between the longest and shortest QT<sub>C</sub> interval on the QT<sub>c</sub> contour map)&#x2009;&#x2265;&#x2009;79&#x2005;ms or spatial smoothness index of QT<sub>c</sub> (SI-QT<sub>c</sub>)&#x2009;&#x2265;&#x2009;9.1&#x2005;ms</td>
<td valign="top" align="left">Anatomic CAD/Patients with stable angina and CAD (55)/-</td>
<td valign="top" align="left">Shielded<break/>64-channel<break/>Rest</td>
<td valign="top" align="center">68&#x0025;/86&#x0025;<break/>(0.77)</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="left">Stress SPECT<break/>Treadmill test</td>
</tr>
<tr>
<td valign="top" align="left">Gapelyuk et al. (<xref ref-type="bibr" rid="B40">40</xref>)</td>
<td valign="top" align="left">Three-parameter index (based on ST slope at measurement positions A4 and A6, and the deviation in the MFM orientation) identified by LDA as best discriminant index</td>
<td valign="top" align="left">Anatomic CAD/<break/>Patients with stable CAD<break/>and angiographically proven &#x003E;50&#x0025; stenosis without previous MI (101)/Healthy subjects with normal findings in EKG, echocardiography, and bicycle ergometry test, and no history of cardiac symptoms (59)</td>
<td valign="top" align="left">Shielded<break/>7-channel<break/>Rest</td>
<td valign="top" align="center">83&#x0025;/84&#x0025;<break/>(0.91)</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Fenici et al. (<xref ref-type="bibr" rid="B41">41</xref>)</td>
<td valign="top" align="left">Automated analysis of the dynamic motion of the effective magnetic vector during the<break/>T wave identified as best discriminator</td>
<td valign="top" align="left">Anatomic CAD/<break/>Patients with stable angina and CAD (51), of whom<break/>35 had prior MI/Healthy subjects (52)</td>
<td valign="top" align="left">Unshielded<break/>36-channel<break/>Rest</td>
<td valign="top" align="center">96&#x0025;/56&#x0025;</td>
<td valign="top" align="center">94&#x0025;/69&#x0025;</td>
<td valign="top" align="left">EKG</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table-fn1"><p>&#x03B1;&#x2009;&#x003D;&#x2009;average angle of direction for the abnormal current vector during ventricle repolarization period.</p></fn>
<fn id="table-fn2"><p>MCG, magnetocardiography; CAD, coronary artery disease; ROC, receiver operating curve; AUC, area under the curve; PPV, positive predictive value; NPV, negative predictive value; CAD, coronary artery disease; EKG, electrocardiography; MI, myocardial infarction; SI, smoothness index; MFM, magnetic field map; TTE, transthoracic echocardiography; LDA, linear discriminant analysis; STDEV, standard deviation; LVEF, left ventricular ejection fraction; QTc, corrected QT; T<sub>max</sub>, peak intensity of the T wave; ACS, acute coronary syndrome; ST&#x03B1;, magnetic field map angle &#x03B1; for the ST segment; T&#x03B1;, magnetic field map angle &#x03B1; for the T wave apex; SPECT, single-photon emission computed tomography; IHD, ischemic heart disease; T<sub>max/3</sub>, one-third of peak intensity; PCI, percutaneous coronary intervention; NR, not reported; BNN, Bayesian neural network; NSTEMI, non-ST segment elevation myocardial infarction.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="T2" position="float"><label>Table 2</label>
<caption><p>Studies of MCG in patients with ACS.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Study</th>
<th valign="top" align="center">Diagnostic criteria of MCG</th>
<th valign="top" align="center">Indication/Test population (n)/Control (n)</th>
<th valign="top" align="center">Testing conditions</th>
<th valign="top" align="center">Specificity/Sensitivity (ROC AUC)</th>
<th valign="top" align="center">PPV/NPV (ROC AUC)</th>
<th valign="top" align="center">Reference</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Park et al. (<xref ref-type="bibr" rid="B8">8</xref>)</td>
<td valign="top" align="left">&#x2265;1 of the following MCG parameters prespecified as defining ischemia: direction of the main vector from plus to minus pole between &#x2212;20&#x00B0; and &#x002B;110&#x00B0;; change in the angle of the main vector &#x2265;45&#x00B0; in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub>; change in the distance separating the plus and minus poles &#x2265;20&#x2005;mm in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub>; change in the ratio of the pole strengths &#x2265;0.3 in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub></td>
<td valign="top" align="left">NSTEMI/Patients presenting with chest pain for whom the criteria for Group 2 according to the ESC guidelines for ACS were applicable, who had coronary angiogram performed within 36&#x2005;h after admission, were NSTEMI, were hemodynamically stable and had LVEF &#x2265;40&#x0025;, and who had an abnormal MCG at admission meeting the criteria for ischemia (249)/Patients presenting with chest pain for whom the criteria for Group 2 according to the ESC guidelines for ACS were applicable, who had coronary angiogram performed within<break/>36&#x2005;h after admission, were NSTEMI, were hemodynamically stable and had LVEF &#x2265;40&#x0025;, and who had a normal MCG at admission (106)</td>
<td valign="top" align="left">Unshielded<break/>9-channel<break/>Rest</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
</tr>
<tr>
<td valign="top" align="left">Tolstrup et al. (<xref ref-type="bibr" rid="B14">14</xref>)</td>
<td valign="top" align="left">Effective magnetic dipole vector analysis, based on an automated analysis of pre-peak (3 parameters) and post-peak (4 parameters) ventricular repolarization</td>
<td valign="top" align="left">ACS/Patients with acute chest pain with a diagnosis of IHD by gold standard criteria (55)/Patients with acute chest pain without IHD (70)</td>
<td valign="top" align="left">Unshielded<break/>9-channel<break/>Rest</td>
<td valign="top" align="left">74&#x0025;/76&#x0025;</td>
<td valign="top" align="left">70&#x0025;/80&#x0025;</td>
<td valign="top" align="left">Stress testing<break/>Troponin<break/>Angiography</td>
</tr>
<tr>
<td valign="top" align="left">Lim et al. (<xref ref-type="bibr" rid="B15">15</xref>)</td>
<td valign="top" align="left">Field map angle of T wave peak and angle of maximum current of T wave peak identified as best diagnostic discriminators vs. age-matched and young controls, respectively</td>
<td valign="top" align="left">NSTEMI/Patients with NSTEMI (83)/Age-matched subjects presenting with chest pain, but no clinical evidence to indicate MI (57)
Young subjects (165)</td>
<td valign="top" align="left">Shielded<break/>64-channel<break/><break/></td>
<td valign="top" align="left">75&#x0025;/86&#x0025; (0.87)<break/>(field map angle)<break/>92&#x0025;/76&#x0025; (0.93) (angle of maximum current)</td>
<td valign="top" align="left">84&#x0025;/78&#x0025;<break/>84&#x0025;/93&#x0025;</td>
<td valign="top" align="left">Angiography<break/>Troponin T</td>
</tr>
<tr>
<td valign="top" align="left">Ghasemi-Roudsari et al. (<xref ref-type="bibr" rid="B23">23</xref>)</td>
<td valign="top" align="left">Logistic regression model based on 10 parameters measuring depolarization (QR_MMR, QR_interval, QR_angle, RS_MMR, RS_interval, RS_angle, QR_peak, QR_pd, RS_peak, and RS_pd) with a cut-off of 0.2 determined and internally cross-validated as best discriminant for IHD</td>
<td valign="top" align="left">NSTEMI/Patients with suspected IHD (55) and patients with NSTEMI requiring admission for chest pain (15)/Healthy age-matched subjects (51) and non-IHD patients with chest pain (18)</td>
<td valign="top" align="left">Unshielded<break/>15-channel<break/>Rest</td>
<td valign="top" align="left">35&#x0025;/95&#x0025;<break/>(rule-out)</td>
<td valign="top" align="left">NR/98&#x0025;<break/>(0.78)</td>
<td valign="top" align="center">&#x2013;</td>
</tr>
<tr>
<td valign="top" align="left">Park et al. (<xref ref-type="bibr" rid="B42">42</xref>)</td>
<td valign="top" align="left">&#x2265;1 of the following MCG parameters prespecified as defining ischemia: direction of the main vector from plus to minus pole between &#x2212;20&#x00B0; and &#x002B;110&#x00B0;; change in the angle of the main vector &#x2265;45&#x00B0; in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub>; change in the distance separating the plus and minus poles &#x2265;20&#x2005;mm in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub>; change in the ratio of the pole strengths &#x2265;0.3 in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub></td>
<td valign="top" align="left">NSTEMI/Patients presenting with acute chest pain diagnosed as CAD by coronary angiography and without persistent<break/>ST segment elevation on EKG (143)/Subjects presenting with chest pain with normal EKG, troponins, or coronary angiography (42)</td>
<td valign="top" align="left">Unshielded<break/>9-channel<break/>Rest</td>
<td valign="top" align="left">93&#x0025;/95&#x0025; (visual)<break/>82.5&#x0025;/86.4&#x0025; (automated)</td>
<td valign="top" align="left">98&#x0025;/85&#x0025; (visual)<break/>94.5&#x0025;/63.5&#x0025; (automated)</td>
<td valign="top" align="left">EKG<break/>TTE<break/>Troponin</td>
</tr>
<tr>
<td valign="top" align="left">Lant et al. (<xref ref-type="bibr" rid="B43">43</xref>)</td>
<td valign="top" align="left">Abnormalities of the mean time isointegral MFM</td>
<td valign="top" align="left">Acute MI/ Patients with MI with a history of prolonged cardiac pain and diagnostic enzyme level elevations who were either previously diagnosed using standard 12-lead EKG, as having anterior (4) or inferior (7) Q wave MI or non-Q wave MI (11)/Normal controls (9)</td>
<td valign="top" align="left">Shielded<break/>NR<break/>Rest</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="left">Body surface potential mapping</td>
</tr>
<tr>
<td valign="top" align="left">Kwon et al. (<xref ref-type="bibr" rid="B44">44</xref>)</td>
<td valign="top" align="left">Algorithm of weighted maximum of posteriori as a function of<break/>five prespecified MCG variables, T_FMA, T_FMA&#x2014;R_FMA, TT_CAMx, TT_CAMx&#x2014;R_FMA, and TT_CMD</td>
<td valign="top" align="left">ACS and non-ACS CAD/Patients admitted to hospital with suspected ACS diagnosed as CAD with angiographically proven &#x2265;50&#x0025; stenosis of a vessel (237)<break/>Subgroup of patients with chest pain and angiographically proven CAD, but with no abnormality of EKG or troponin (102)/Patients with angiographically proven non-obstructive CAD (127)<break/>Healthy subjects (89)</td>
<td valign="top" align="left">Shielded<break/>64-channel<break/>Rest</td>
<td valign="top" align="left">85&#x0025;/84&#x0025;</td>
<td valign="top" align="left">91&#x0025;/74&#x0025;</td>
<td valign="top" align="center">&#x2013;</td>
</tr>
<tr>
<td valign="top" align="left">Park et al. (<xref ref-type="bibr" rid="B45">45</xref>)</td>
<td valign="top" align="left">&#x2265;1 of the following MCG parameters prespecified as defining ischemia: direction of the main vector from plus to minus pole between &#x2212;20&#x00B0; and &#x002B;110&#x00B0;; change in the angle of the main vector &#x2265;45&#x00B0; in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub>; change in the distance separating the plus and minus poles &#x2265;20&#x2005;mm in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub>; change in the ratio of the pole strengths &#x2265;0.3 in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub></td>
<td valign="top" align="left">Unstable angina/Patients with symptoms of unstable angina, who were diagnosed with CAD angiographically (53)/Patients with normal troponin levels in whom CAD could be ruled out (33)</td>
<td valign="top" align="left">Unshielded<break/>9-channel<break/>Rest</td>
<td valign="top" align="left">94&#x0025;/94&#x0025;</td>
<td valign="top" align="left">91&#x0025;/96&#x0025;</td>
<td valign="top" align="left">EKG<break/>Troponin</td>
</tr>
<tr>
<td valign="top" align="left">Lin et al. (<xref ref-type="bibr" rid="B46">46</xref>)</td>
<td valign="top" align="left">Analysis based on three MCG parameters (pre-peak repolarization [angle, trajectory, and angular deviation], post-peak repolarization [angle, trajectory, and angular deviation] and the pre-post angle change) and map morphology</td>
<td valign="top" align="left">ACS/Patients presenting with chest pain, and diagnosed CAD with angiographically proven &#x2265;70&#x0025; stenosis (190)/Patients with angiographically proven non-obstructive CAD (97)</td>
<td valign="top" align="left">Shielded<break/>9-channel<break/>Rest</td>
<td valign="top" align="left">73&#x0025;/89&#x0025;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="left">EKG</td>
</tr>
<tr>
<td valign="top" align="left">Leith&#x00E4;user et al. (<xref ref-type="bibr" rid="B47">47</xref>)</td>
<td valign="top" align="left">&#x2265;1 of the following MCG parameters prespecified as defining ischemia: direction of the main vector from plus to minus pole between &#x2212;20&#x00B0; and &#x002B;110&#x00B0;; change in the angle of the main vector &#x2265;45&#x00B0; in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub>; change in the distance separating the plus and minus poles &#x2265;20&#x2005;mm in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub>; change in the ratio of the pole strengths &#x2265;0.3 in a time interval of 30 msec between T<sub>max/3</sub> and T<sub>max</sub></td>
<td valign="top" align="left">NSTEMI with BBB/Patients presenting with ACS without ST-segment elevation who have BBB-EKG (QRS duration &#x003E;120 msec) (62; four with prior MI)/NR</td>
<td valign="top" align="left">Unshielded<break/>NR<break/>Rest</td>
<td valign="top" align="left">97&#x0025;/88&#x0025;</td>
<td valign="top" align="left">99&#x0025;/71&#x0025;</td>
<td valign="top" align="left">TTE<break/>Troponin</td>
</tr>
<tr>
<td valign="top" align="left">Park et al. (<xref ref-type="bibr" rid="B48">48</xref>)</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NSTEMI/Patients with acute chest pain with NSTEMI and with angiographically proven CAD (264; 62 with BBB)/-</td>
<td valign="top" align="left">NR<break/>Rest</td>
<td valign="top" align="left">94&#x0025;/87&#x0025;</td>
<td valign="top" align="left">98&#x0025;/71&#x0025;</td>
<td valign="top" align="left">TTE<break/>Troponin</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table-fn3"><p>&#x03B1;&#x2009;&#x003D;&#x2009;average angle of direction for the abnormal current vector during ventricle repolarization period.</p></fn>
<fn id="table-fn4"><p>MCG, magnetocardiography; ACS, acute coronary syndrome; ROC, receiver operating curve; AUC, area under the curve; PPV, positive predictive value; NPV, negative predictive value; T<sub>max</sub>, peak intensity of the T wave; T<sub>max/3</sub>, one-third of peak intensity; NSTEMI, non-ST segment elevation myocardial infarction; ESC, European society of cardiology; LVEF, left ventricular ejection fraction; IHD, ischemic heart disease; MI, myocardial infarction; CAD, coronary artery disease; EKG, electrocardiography; TTE, transthoracic echocardiography; MFM, magnetic field map; NR, not reported; BBB, bundle branch block.</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3"><title>Stable CAD</title>
<p>Numerous studies have provided evidence that MCG, whether conducted in a shielded or unshielded environment, at rest, or under conditions of exercise or pharmacologic stress, can effectively differentiate between patients with angiographically confirmed stable CAD and healthy individuals (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B34">34</xref>, <xref ref-type="bibr" rid="B36">36</xref>&#x2013;<xref ref-type="bibr" rid="B38">38</xref>, <xref ref-type="bibr" rid="B40">40</xref>, <xref ref-type="bibr" rid="B41">41</xref>). Additionally, MCG has shown potential in distinguishing patients with chest pain but without evidence of CAD on angiography or other diagnostic tests (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B9">9</xref>, <xref ref-type="bibr" rid="B18">18</xref>, <xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B39">39</xref>). However, it is important to proceed with caution when interpreting these results, as many of the studies enrolled small populations and included highly selected patient cohorts with or without the disease, which may not fully represent the broader population encountered in clinical practice.</p>
<p>Several studies have subsequently examined the patterns of resting magnetic fields in individuals with CAD. These studies have evaluated different parameters of MCG and have endeavored to enhance diagnostic accuracy and minimize background noise by employing various analytical approaches and algorithms. The earlier study revealed significant differences in multiple MCG parameters such as ST slope, ST shift, T peak amplitude, ST-T integral, and magnetic field map (MFM) orientation between patients with CAD (<italic>n</italic>&#x2009;&#x003D;&#x2009;101) and a control group of healthy subjects (<italic>n</italic>&#x2009;&#x003D;&#x2009;59) (<xref ref-type="bibr" rid="B40">40</xref>). They yielded a specificity and sensitivity of 83&#x0025; and 84&#x0025; respectively [with an area under the curve (AUC) of 91.2&#x0025; for the receiver operating curve (ROC)], and the accuracy of CAD classification at 84&#x0025; remained consistent regardless of the number of affected vessels or the severity of stenosis. In addition, various quantitative methods have been employed to differentiate CAD. These methods include binary classification approaches utilizing threshold values for MCG indices (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B36">36</xref>), integrated indices derived from MCG parameter values (<xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B50">50</xref>&#x2013;<xref ref-type="bibr" rid="B52">52</xref>), the assessment of the number of abnormal MCG parameters (<xref ref-type="bibr" rid="B31">31</xref>), spatial distribution analysis of the QT interval (<xref ref-type="bibr" rid="B34">34</xref>), and the utilization of automated machine learning algorithms (<xref ref-type="bibr" rid="B25">25</xref>&#x2013;<xref ref-type="bibr" rid="B27">27</xref>). In a recent study, a combination of quantitative (change in ST-segment fluctuation score) and qualitative (non-dipole phenomenon) parameters was utilized to improve the diagnostic accuracy of shielded MCG in distinguishing patients with stable angina from asymptomatic individuals without CAD (<xref ref-type="bibr" rid="B18">18</xref>). The inclusion of the non-dipole phenomenon resulted in an increased AUC of the ROC curve, elevating it from 0.79 to 0.93.</p>
<p>Initial investigations on MCG in patients with CAD demonstrated its capacity to identify alterations in multiple MCG parameters during stress induced by exercise or drugs. The analysis indicated that ST segment MCG parameters exhibited greater sensitivity to exercise-induced ischemia in patients without a history of MI (<italic>n</italic>&#x2009;&#x003D;&#x2009;27), whereas T wave MCG parameters were most sensitive to changes in patients with prior MI (<italic>n</italic>&#x2009;&#x003D;&#x2009;17) (<xref ref-type="bibr" rid="B13">13</xref>). For the assessment of 42 patients with CAD following a dobutamine-stress test, an analytical approach centered on the epicardial current distribution at the point of maximum amplitude of the QRS complex (QRSmax) was employed (<xref ref-type="bibr" rid="B9">9</xref>). MCG demonstrated a sensitivity of over 90&#x0025; for detecting CAD, irrespective of the location of stenosis or the number of affected vessels.</p>
<p>Several studies have directly compared the diagnostic efficacy of MCG with other tests. In a study by Park et al., MCG exhibited superior sensitivity compared to 12-lead EKG in detecting CAD using a conventional dobutamine stress protocol (<xref ref-type="bibr" rid="B9">9</xref>). Another study demonstrated higher sensitivity, along with comparable specificity, and similar positive predictive value (PPV) and negative predictive value (NPV) for MCG compared to EKG in the diagnosis of stable angina (<xref ref-type="bibr" rid="B41">41</xref>). In another study, MCG showed higher specificity and comparable sensitivity, PPV, and NPV when compared to single photon emission computed tomography (SPECT) for discriminating patients with angina (<xref ref-type="bibr" rid="B39">39</xref>).</p>
</sec>
<sec id="s4"><title>Acute coronary syndrome</title>
<p>In studies involving patients experiencing acute chest pain and suspected ACS, the analysis of MCG data, measured either at rest or after exercise, in shielded or unshielded environments, has revealed qualitative and quantitative distinctions that facilitate differentiation between patients with ACS and healthy individuals (<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B44">44</xref>, <xref ref-type="bibr" rid="B53">53</xref>, <xref ref-type="bibr" rid="B54">54</xref>). Moreover, MCG has been successful in distinguishing patients without definitive evidence of ACS or CAD in diagnostic examinations (<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B42">42</xref>, <xref ref-type="bibr" rid="B44">44</xref>&#x2013;<xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B55">55</xref>, <xref ref-type="bibr" rid="B56">56</xref>). A previous study utilizing a shielded, 64-channel MCG system showed the capability of 15 MCG parameters to discriminate between patients diagnosed with non-ST segment elevation myocardial infarction (NSTEMI) (<italic>n</italic>&#x2009;&#x003D;&#x2009;83) and age-matched individuals presenting with chest pain but without clinical indications of CAD (<xref ref-type="bibr" rid="B15">15</xref>). Among these parameters, the field map angle of the T wave peak exhibited the highest diagnostic accuracy, with a sensitivity of 86&#x0025; and a specificity of 75&#x0025;. In a prospective study involving 402 patients experiencing acute chest pain without ST-segment elevation in the EKG, it was observed that abnormalities in the MFM between the onset and peak of the T wave at admission were predictive of an elevated risk of mortality over a 3-year period. The relative risk for MCG abnormalities was 4.58, compared to 1.69 for EKG, and 2.58 for elevated troponin levels (<xref ref-type="bibr" rid="B8">8</xref>). Another study found that MCG has the potential to differentiate patients with ACS and bundle branch block, a condition that can complicate the diagnosis of ACS when using EKG (<xref ref-type="bibr" rid="B47">47</xref>, <xref ref-type="bibr" rid="B48">48</xref>). MCG has also shown promise in discriminating patients with reduced left ventricular ejection fraction (<xref ref-type="bibr" rid="B37">37</xref>) and those with a history of previous MI (<xref ref-type="bibr" rid="B57">57</xref>). However, further studies with larger patient populations are necessary to explore the full potential of MCG in these particular conditions. Additionally, a direct comparison between MCG, utilizing either visual or automated analysis, and other diagnostic tests such as EKG, cardiac troponin I, and echocardiography, revealed that MCG showed higher sensitivity, comparable specificity, comparable positive predictive value (PPV), and higher negative predictive value (NPV) in distinguishing patients with CAD and acute chest pain from patients with chest pain but normal results on diagnostic tests (<xref ref-type="bibr" rid="B42">42</xref>).</p>
</sec>
<sec id="s5"><title>Perspectives for the clinical application of MCG in the detection of myocardial ischemia</title>
<p>Previous studies evaluated various MCG parameters to improve the detection of stable CAD or ACS in patients with different clinical presentations. MCG proved effective in identifying ischemia, even in patients with normal EKG and cardiac biomarker results. Initial evidence suggests acceptable sensitivity and specificity for detecting IHD in selected cohorts with stable CAD or ACS, with MCG outperforming EKG, echocardiography, and cardiac troponin assays. MCG could be a valuable initial test for suspected CAD or ACS, but more research is needed to determine the best parameters and validate its diagnostic performance across diverse patient populations. Further studies should focus on integrating MCG into clinical practice and assessing its incremental value in existing diagnostic pathways, potentially leading to the development of MCG criteria for early exclusion of non-ischemic or non-CAD patients, reducing unnecessary testing and hospital resource utilization. In addition, to address the challenges posed by the evolving nature of MCG technology and diagnostic criteria in CAD studies conducted over several decades, a meta-analysis of current data or the following approaches are needed. Although significant progress has been made in MCG device technology and machine-learning analysis techniques, further validation of potential diagnostic parameters is necessary, particularly in large patient cohorts that represent a diverse range of cases.</p>
<p>The use of MCG has the potential to benefit the assessment of patients with suspected ACS, particularly in the field of emergency medicine. Chest pain is a common reason for emergency department visits, but a significant portion of patients (60&#x0025;&#x2013;90&#x0025;) do not have an acute cardiac cause for their pain. Current diagnosis of ACS in patients with acute undifferentiated chest pain involves a resting 12-lead EKG, multiple measurements of cardiac troponin levels over several hours, and clinical judgment. Integrating MCG into the diagnostic pathway could help reduce the time to diagnosis and the costs associated with serial troponin testing. Another challenge in emergency medicine is the risk of missed diagnoses of patients with NSTEMI or unstable angina, which can lead to adverse outcomes after discharge. MCG has the potential to decrease the likelihood of missed diagnoses and improve clinical outcomes. The benefits of early identification of patients with non-cardiac chest pain have been demonstrated through accelerated risk algorithms that incorporate high-sensitivity cardiac troponin assays, resulting in significant improvements in time to discharge, cardiac outcomes, and hospital resource utilization. Further evaluation through prospective observational studies involving unselected cohorts of patients presenting to the emergency department with acute chest pain will provide insights into whether MCG could be used prior to cardiac troponin testing to expedite patient assessment. Most of the original multichannel MCG devices have specific operational requirements and high running costs, primarily due to the need for external electromagnetic shielding (EMS) or liquid helium cooling. However, the recent development of portable MCG devices holds the potential for bedside assessment of patients with acute chest pain upon their initial presentation to the emergency department (<xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B58">58</xref>). Enhancements in the practical aspects of MCG devices such as device footprint, ease of use, operator training requirements, and the need for a shielded operating environment will play a crucial role in determining their ease of implementation in clinical practice.</p>
<p>Finally, validation studies are necessary to determine the diagnostic accuracy of MCG parameters compared to current diagnostic pathways in undifferentiated patient populations. Validated MCG diagnostic criteria should be evaluated in well-defined cohorts including patients with stable CAD, ACS, inducible ischemia, and non-ischemic chest pain. Furthermore, there are indications in the literature that MCG may have broader clinical applications in CAD beyond diagnosis. For instance, its use in stress testing to detect functional ischemia could provide valuable prognostic information for risk stratification. Future clinical studies should explore other endpoints such as infarction location and severity, as well as the prediction of major adverse cardiac events and post-MI arrhythmias.</p>
</sec>
<sec id="s6" sec-type="conclusions"><title>Conclusions</title>
<p>MCG presents a non-invasive and non-contact imaging modality that is free from emissions, offering potential improvements in the management of patients with CAD. It has demonstrated the ability to detect myocardial ischemia in patients with stable CAD and ACS. However, further clinical studies are necessary to evaluate the use of MCG in undifferentiated patient cohorts. It is also important to validate and standardize MCG analytical techniques and parameters. Prospective, multicenter observational studies are currently needed to investigate the effectiveness of MCG in ruling out ACS in emergency settings. These studies will help determine the utility of newer MCG devices and their potential integration into routine clinical practice as complementary diagnostic tools.</p>
</sec>
</body>
<back>
<sec id="s7" sec-type="author-contributions"><title>Author contributions</title>
<p>Conceptualization: AH, YK, and ES. Supervision: YK, SK, and ES. Visualization: AH, DD, YK, SK, and ES. Writing-original draft: AH. Writing-review &#x0026; editing: AH, DD, YK, SK, and ES. All authors contributed to the article and approved the submitted version.</p>
</sec>
<sec id="s8" sec-type="COI-statement"><title>Conflict of interests</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
<p>The handling editor JP declared a shared affiliation with the author DD at the time of review.</p>
</sec>
<sec id="s9" sec-type="disclaimer"><title>Publisher&#x0027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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