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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">ijcs</journal-id>
      <journal-title-group>
        <journal-title>International Journal of Cardiovascular Sciences</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Int J Cardiovasc Sci</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">2359-4802</issn>
      <issn pub-type="epub">2359-5647</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">qgYxf57Bv6PjnFRSY8JcJvC</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S2359-56472026000100639</article-id>
      <article-id pub-id-type="other">00639</article-id>
      <article-id pub-id-type="doi">10.36660/ijcs.20250230</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>QT Prolongation Following Premature Ventricular Contractions: A Potential Marker of Concealed Long QT Syndrome</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-0122-508X</contrib-id>
          <name>
            <surname>Jalabadze</surname>
            <given-names>Khatuna</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
          <role>Conception and design of the research</role>
          <role>acquisition of data</role>
          <role>analysis and interpretation of the data</role>
          <role>writing of the manuscript</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Machavariani</surname>
            <given-names>Pavle</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <role>Conception and design of the research</role>
          <role>writing of the manuscript</role>
          <role>critical revision of the manuscript for intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tsiklauri</surname>
            <given-names>Bachuki</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
          <role>acquisition of data</role>
          <role>analysis and interpretation of the data</role>
          <role>writing of the manuscript</role>
          <role>critical revision of the manuscript for intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Garuchava</surname>
            <given-names>Natalia</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>4</sup>
          </xref>
          <role>analysis and interpretation of the data</role>
          <role>statistical analysis</role>
          <role>writing of the manuscript</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Avaliani</surname>
            <given-names>Ia</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Conception and design of the research</role>
          <role>critical revision of the manuscript for intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chigogidze</surname>
            <given-names>Maya</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>critical revision of the manuscript for intellectual content</role>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Petre Shotadze Tbilisi Medical Academy</institution>
          <addr-line>
            <named-content content-type="city">Tbilisi</named-content>
          </addr-line>
          <country country="GE">Georgia</country>
          <institution content-type="original">Petre Shotadze Tbilisi Medical Academy, Tbilisi &#8211; Georgia</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Chapidze Heart Disease Center</institution>
          <addr-line>
            <named-content content-type="city">Tbilisi</named-content>
          </addr-line>
          <country country="GE">Georgia</country>
          <institution content-type="original">Chapidze Heart Disease Center, Tbilisi &#8211; Georgia</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution content-type="orgname">Tbilisi Heart Center</institution>
          <addr-line>
            <named-content content-type="city">Tbilisi</named-content>
          </addr-line>
          <country country="GE">Georgia</country>
          <institution content-type="original">Tbilisi Heart Center, Tbilisi &#8211; Georgia</institution>
        </aff>
        <aff id="aff4">
          <label>4</label>
          <institution content-type="orgname">Tbilisi State Medical University</institution>
          <addr-line>
            <named-content content-type="city">Tbilisi</named-content>
          </addr-line>
          <country country="GE">Georgia</country>
          <institution content-type="original">Tbilisi State Medical University, Tbilisi &#8211; Georgia</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><label>Mailing Address:</label> Khatuna Jalabadze &#8226; GeoHospitals. Tsinandali st, 9/3. Postal code: <postal-code>0144</postal-code>. Tbilisi &#8211; Georgia E-mail: <email>kh.jalabadze@gmail.com</email> </corresp>
        <fn fn-type="coi-statement">
          <label>Potential Conflict of Interest</label>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor responsible for the review:</label>
          <p>Ricardo Alkmim Teixeira</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>07</day>
        <month>09</month>
        <year>2026</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <year>2026</year>
      </pub-date>
      <volume>39</volume>
      <elocation-id>e20250230</elocation-id>
      <history>
        <date date-type="received">
          <day>02</day>
          <month>11</month>
          <year>2025</year>
        </date>
        <date date-type="rev-recd">
          <day>20</day>
          <month>03</month>
          <year>2026</year>
        </date>
        <date date-type="accepted">
          <day>05</day>
          <month>05</month>
          <year>2026</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Long QT syndrome (LQTS) predisposes individuals to malignant ventricular arrhythmias and sudden cardiac death; however, diagnosis remains challenging in patients with borderline corrected QT (QTc) values. Premature Ventricular Contractions (PVCs) may unmask concealed abnormalities of ventricular repolarization.</p>
        </sec>
        <sec>
          <title>Aim:</title>
          <p>To determine whether post-PVC QTc prolongation can differentiate patients with confirmed LQTS, healthy controls, and borderline index cases.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>In this retrospective study, 24-hour electrocardiography (ECG) recordings from 84 subjects were analyzed, including 10 patients with confirmed LQTS, 72 healthy controls, and 2 index patients with borderline baseline QTc values. QTc intervals before and after PVCs were measured manually and corrected using Bazett's formula. Between-group differences were evaluated using analysis of covariance (ANCOVA) adjusted for baseline QTc, whereas within-group changes were assessed with paired t-tests. A two-tailed p &lt; 0.05 was considered statistically significant.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>Post-PVC QTc intervals were longer in patients with LQTS than in healthy controls (488 &#177; 23 ms vs 391 &#177; 37 ms; adjusted p = 0.066). Overall, PVCs were associated with a mean QTc increase of +15.7 ms (95% CI 7.1&#8211;24.3; p = 0.0005), with larger increases observed in LQTS patients (+22.3 ms; p = 0.0019) compared with healthy controls (+10.0 ms; p = 0.0098). The two index patients exhibited marked QTc prolongation, rising from borderline baseline values (360&#8211;460 ms) to 540&#8211;600 ms (&#916;&#8776;165 ms).</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>PVC-induced QTc prolongation may help distinguish healthy individuals from patients with overt or borderline LQTS. Whereas healthy controls demonstrated mild physiologic adaptation, patients with confirmed LQTS showed consistent QTc prolongation, and index patients exhibited marked post-PVC increases suggestive of concealed repolarization abnormalities. Assessment of QTc following PVCs may represent a simple bedside approach to improve diagnostic accuracy and risk stratification in LQTS; prospective studies in larger cohorts are warranted to confirm these findings.</p>
        </sec>
      </abstract>
      <abstract abstract-type="graphical">
        <p>
          <fig id="f1">
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              <graphic xlink:href="https://minio.scielo.br/documentstore/2359-5647/qgYxf57Bv6PjnFRSY8JcJvC/b475244454448c70809a419fa49ede2bf629f99e.tif"/>
              <graphic xlink:href="https://minio.scielo.br/documentstore/2359-5647/qgYxf57Bv6PjnFRSY8JcJvC/828065ccf580a4df42bb4c1b63b67ed21ed8a0d4.png" specific-use="scielo-web"/>
              <graphic xlink:href="https://minio.scielo.br/documentstore/2359-5647/qgYxf57Bv6PjnFRSY8JcJvC/bdaa8411b508b6d7b24a3f0d2aab985a4bda327c.jpg" specific-use="scielo-web" content-type="scielo-267x140"/>
            </alternatives>
          </fig>
        </p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Long QT Syndrome</kwd>
        <kwd>Ventricular Premature Complexes</kwd>
        <kwd>Cardiac Arrhythmias</kwd>
      </kwd-group>
      <funding-group>
        <funding-statement><bold>Sources of Funding</bold> There were no external funding sources for this study.</funding-statement>
      </funding-group>
      <counts>
        <fig-count count="5"/>
        <table-count count="2"/>
        <equation-count count="0"/>
        <ref-count count="5"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Long QT syndrome (LQTS) is a disorder of myocardial repolarization associated with an increased risk of malignant ventricular arrhythmias and sudden cardiac death.<sup><xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B3">3</xref></sup> It may be congenital or acquired and often remains underdiagnosed, particularly in patients with borderline or concealed QT interval prolongation. Despite established diagnostic criteria, identifying these patients remains clinically challenging and may delay appropriate risk stratification and management.</p>
      <p>Premature Ventricular Contractions (PVCs) are common ventricular arrhythmias that may influence ventricular repolarization. Previous studies suggest that PVCs can modulate QT interval dynamics and other repolarization markers; however, their effects in patients with LQTS have not been systematically evaluated.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>While PVCs have been studied in patients with uremia, frequent ectopy, and PVC-induced cardiomyopathy, little is known about their impact on QT interval behavior in patients with LQTS. Specifically, post-PVC QT prolongation has not been systematically evaluated as a potential diagnostic marker in cases of concealed or borderline LQTS. Such patients often fall below conventional QTc diagnostic thresholds yet remain at risk for malignant arrhythmias. Identifying a reliable marker in this subgroup could significantly enhance clinical diagnosis and risk assessment.</p>
      <p>This study aimed to investigate whether post-PVC QT prolongation can unmask concealed LQTS by comparing patients with confirmed LQTS, healthy controls, and borderline index patients.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>This study was conducted at Geo-Hospitals, Tbilisi, Georgia, from May 2025 to September 2025. A total of 84 patients with PVCs were enrolled.</p>
      <p>Due to the condition under investigation being relatively uncommon, an a priori sample size calculation was not feasible. Therefore, all consecutive eligible patients identified during the study period were included in the analysis. Given the sample size and study design, the findings should be considered exploratory.</p>
      <p>The study protocol was approved by the institutional ethics committee of Geo-Hospitals, and written informed consent was obtained from all participants.</p>
      <sec>
        <title>Inclusion and Exclusion Criteria</title>
        <p>Patients aged 18&#8211;67 years with PVCs confirmed by clinical evaluation and electrocardiography (ECG) findings were eligible for inclusion (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Demographic and Electrophysiological Characteristics of Study Participants</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="49%">
              <col width="1%"/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#8DC4E6">
                <th align="left" colspan="2" valign="middle">Characteristic</th>
                <th align="center" valign="middle">Value</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" colspan="2" valign="top">Study population, n</td>
                <td align="center" valign="top">84</td>
              </tr>
              <tr style="background-color:#D2E6F5">
                <td align="left" colspan="2" valign="top">
                  <bold>Study groups, n (%)</bold>
                </td>
                <td align="center" valign="top"/>
              </tr>
              <tr style="background-color:#D2E6F5">
                <td align="left" valign="top"/>
                <td align="left" valign="top">Control group</td>
                <td align="center" valign="top">72 (85.7%)</td>
              </tr>
              <tr style="background-color:#D2E6F5">
                <td align="left" valign="top"/>
                <td align="left" valign="top">Confirmed LQTS group: n (%)</td>
                <td align="center" valign="top">10 (11.9%)</td>
              </tr>
              <tr style="background-color:#D2E6F5">
                <td align="left" valign="top"/>
                <td align="left" valign="top">Index group</td>
                <td align="center" valign="top">2 (2.4%)</td>
              </tr>
              <tr style="background-color:#D2E6F5">
                <td align="left" valign="top"/>
                <td align="left" valign="top">Age (years), mean &#177; SD</td>
                <td align="center" valign="top">55.2 &#177; 14.0</td>
              </tr>
              <tr>
                <td align="left" colspan="2" valign="top">
                  <bold>Gender, n (%)</bold>
                </td>
                <td align="center" valign="top"/>
              </tr>
              <tr>
                <td align="left" valign="top"/>
                <td align="left" valign="top">Female</td>
                <td align="center" valign="top">49 (59.8%)</td>
              </tr>
              <tr>
                <td align="left" valign="top"/>
                <td align="left" valign="top">Male</td>
                <td align="center" valign="top">33 (40.2%)</td>
              </tr>
              <tr style="background-color:#D2E6F5">
                <td align="left" colspan="2" valign="top">
                  <bold>QTc before PVC (ms), mean &#177; SD</bold>
                </td>
                <td align="center" valign="top">390.6 &#177; 39.3</td>
              </tr>
              <tr>
                <td align="left" colspan="2" valign="top">
                  <bold>Post-PVC QTc (ms), mean &#177; SD</bold>
                </td>
                <td align="center" valign="top">411.2 &#177; 50.2</td>
              </tr>
              <tr style="background-color:#D2E6F5">
                <td align="left" colspan="2" valign="top">
                  <bold>&#916;QTc (QTc after &#8722; QTc before, ms), mean &#177; SD</bold>
                </td>
                <td align="center" valign="top">9.9 &#177; 22.3</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Exclusion criteria included:</p>
        <list list-type="bullet">
          <list-item>
            <p>Known congenital arrhythmias or structural heart disease;</p>
          </list-item>
          <list-item>
            <p>Severe ventricular arrhythmias;</p>
          </list-item>
          <list-item>
            <p>Active infection or significant electrolyte imbalance;</p>
          </list-item>
          <list-item>
            <p>Atrial fibrillation, ventricular bigeminy, or poor-quality ECG recordings;</p>
          </list-item>
          <list-item>
            <p>Pregnancy or lactation;</p>
          </list-item>
          <list-item>
            <p>Use of medications known to significantly affect the QT interval or arrhythmic risk (including selected antiarrhythmic agents, chemotherapeutic agents, and immunosuppressants).</p>
          </list-item>
        </list>
      </sec>
      <sec>
        <title>Data Collection</title>
        <p>Demographic and clinical data were obtained through structured patient interviews and review of medical records. Collected variables included age, sex, comorbidities (e.g., hypertension, diabetes mellitus), and medication history. Genetic testing was not routinely performed in this cohort. Therefore, the diagnosis of LQTS was established based on clinical criteria, including the Schwartz score and electrocardiographic findings.</p>
        <p>Venous blood samples were collected to assess serum electrolyte levels, including potassium, magnesium, and calcium.</p>
      </sec>
      <sec>
        <title>Electrocardiographic Assessment</title>
        <p>All participants underwent standard 12-lead ECG. QT intervals were measured manually, and the lead demonstrating the longest QT interval, most commonly lead II, was used for analysis. The corrected QT interval (QTc) was calculated using Bazett's formula (QTc = QT / &#8730;RR). QTc was calculated using the RR interval preceding the measured beat within the same cardiac cycle. No additional RR averaging was performed. QTc prolongation was defined according to established guideline thresholds as a QTc interval &gt; 450 ms in men and &gt; 470 ms in women. Values between 440&#8211;470 ms in men and 450&#8211;480 ms in women were considered borderline.</p>
        <p>Patients with prolonged QTc intervals were further evaluated for the presence of arrhythmias. ECG morphology was assessed to identify clinically significant rhythm disturbances, including atrial arrhythmias (atrial fibrillation and atrial flutter) and ventricular arrhythmias (ventricular tachycardia and torsades de pointes). Sinus arrhythmia, bradycardia, and other relevant rhythm abnormalities were also documented.</p>
        <p>Laboratory analyses were performed on the same blood samples and included renal function tests (serum creatinine and blood urea nitrogen) and electrolyte measurements.</p>
      </sec>
      <sec>
        <title>Statistical Analysis</title>
        <p>Statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were summarized as mean &#177; standard deviation (SD) and presented with corresponding 95% confidence intervals (CIs) where appropriate.</p>
        <p>The normality of continuous variables was assessed using the Shapiro&#8211;Wilk test. Homogeneity of variance was evaluated prior to group comparisons.</p>
        <p>Between-group differences in post-PVC QTc duration were evaluated using Analysis of Covariance (ANCOVA), adjusted for baseline QTc values. When the assumption of homogeneity of variance was violated, Welch's correction was applied for group comparisons.</p>
        <p>Within-group comparisons of QTc values before and after PVCs were performed using paired Student's t-tests.</p>
        <p>Because of the very small number of index cases, these patients were analyzed descriptively and excluded from formal inferential statistical testing.</p>
        <p>All statistical tests were two-tailed, and a p-value &lt; 0.05 (&#945; = 0.05) was considered statistically significant.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>A total of 84 participants were included: 10 patients with confirmed LQTS, 72 healthy controls, and two index patients with borderline baseline QTc values. Patients with LQTS demonstrated longer post-PVC QTc intervals compared with healthy controls. After adjustment for baseline QTc values, this difference approached statistical significance. Within-group analysis showed that PVCs were associated with QTc prolongation across the cohort. The magnitude of this increase was greater in patients with LQTS, whereas healthy controls demonstrated only mild QTc adaptation. The two index patients appeared as clear outliers with marked post-PVC QTc prolongation. Although formal statistical testing was not feasible due to the very small sample size, these cases illustrate how PVC-induced QTc changes may unmask concealed repolarization abnormalities. A scatter plot comparing baseline QTc before PVC with QTc after PVC is shown in <xref ref-type="fig" rid="f4">Figure 3</xref>. Healthy controls clustered close to the line of identity, reflecting minimal QT interval adaptation. In contrast, LQTS patients were consistently shifted upward, indicating systematic post-PVC QTc prolongation. The two index patients appeared as striking outliers, highlighting marked repolarization delay after PVCs.</p>
      <p><xref ref-type="fig" rid="f4">Figure 3</xref> shows scatter plot illustrating the relationship between QT interval behavior before and after a PVC. Baseline QTc before PVC is plotted on the x-axis and Post-PVC QTc on the y-axis. The dashed diagonal line represents the line of identity (y = x). Healthy controls cluster close to the identity line, indicating minimal QT interval adaptation after PVCs. In contrast, patients with LQTS demonstrate an upward shift consistent with post-PVC QTc prolongation. The two index patients appear as clear outliers with marked QTc prolongation following PVCs.</p>
      <p><xref ref-type="fig" rid="f5">Figure 4</xref> shows the group mean QTc values before and after PVCs. Patients with LQTS demonstrated higher baseline and post-PVC QTc values compared with healthy controls. The index patients showed marked QTc prolongation following PVCs with greater variability, whereas healthy controls exhibited only modest changes.</p>
      <p><xref ref-type="table" rid="t2">Table 2</xref> summarizes QTc behavior before and after PVCs across the study groups. Confirmed LQTS patients exhibited consistently prolonged QTc intervals with further prolongation after PVCs, while healthy controls showed only mild changes consistent with physiologic adaptation. The index patients demonstrated marked QTc prolongation after PVCs, suggesting concealed repolarization abnormalities.</p>
      <table-wrap id="t2">
        <label>Table 2</label>
        <caption>
          <title>Summary of QTc behavior before and after PVCs across study groups.</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="20%">
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
          </colgroup>
          <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
            <tr style="background-color:#8DC4E6">
              <th align="left" valign="middle">Group</th>
              <th align="center" valign="middle">Baseline QTc (ms)</th>
              <th align="center" valign="middle">Post-PVC QTc (ms)</th>
              <th align="center" valign="middle">&#916;QTc (ms)</th>
              <th align="left" valign="middle">Clinical Implication</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="top"><bold>Confirmed LQTS</bold> (n = 10)</td>
              <td align="center" valign="top">Prolonged (&gt; 480 ms)</td>
              <td align="center" valign="top">Markedly prolonged (&gt; 520 ms)</td>
              <td align="center" valign="top">Large (&gt; 40 ms)</td>
              <td align="left" valign="top">Consistent with abnormal repolarization and higher arrhythmic risk</td>
            </tr>
            <tr style="background-color:#D2E6F5">
              <td align="left" valign="top"><bold>Index patients</bold> (borderline QTc, n = 2)</td>
              <td align="center" valign="top">Borderline (360-460 ms)</td>
              <td align="center" valign="top">Markedly prolonged (540-600 ms)</td>
              <td align="center" valign="top">Very large (~165 ms)</td>
              <td align="left" valign="top">Suggests concealed LQTS; diagnostic clue</td>
            </tr>
            <tr>
              <td align="left" valign="top"><bold>Healthy Controls</bold> (n = 72)</td>
              <td align="center" valign="top">Normal (&lt; 440 ms)</td>
              <td align="center" valign="top">Mild prolongation (&lt; 460 ms)</td>
              <td align="center" valign="top">Small (&lt; 20 ms)</td>
              <td align="left" valign="top">Physiologic adaptation; low risk</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <p>QTc: corrected QT; LQTS: Long QT syndrome.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>This study demonstrates that PVCs reveal important differences in repolarization response across groups. As shown in the <xref ref-type="fig" rid="f1">Central Illustration</xref>, healthy controls showed only mild Post-PVC QTc prolongation (&lt; 20 ms), consistent with normal physiologic adaptation and low arrhythmic risk. In contrast, patients with confirmed LQTS exhibited larger increases (&gt; 40 ms) and markedly prolonged post-PVC QTc (&gt; 520 ms), supporting abnormal repolarization and increased susceptibility to arrhythmia (<xref ref-type="fig" rid="f2">Figures 1</xref> and <xref ref-type="fig" rid="f3">2</xref>).</p>
      <fig id="f2">
        <label>Figure 1</label>
        <caption>
          <title>Index Patient 1.</title>
        </caption>
        <graphic xlink:href="2359-5647-ijcs-39-e20250230-50230-gf01.tif"/></fig>
      <fig id="f3">
        <label>Figure 2</label>
        <caption>
          <title>Index Patient 2.</title>
        </caption>
        <graphic xlink:href="2359-5647-ijcs-39-e20250230-50230-gf02.tif"/></fig>
      <fig id="f4">
        <label>Figure 3</label>
        <caption>
          <title>Post -PVC QTc Prolongation Across Study Groups. QTc: corrected QT; PVC: Premature Ventricular Contractions.</title>
        </caption>
        <graphic xlink:href="2359-5647-ijcs-39-e20250230-50230-gf03.tif"/></fig>
      <fig id="f5">
        <label>Figure 4</label>
        <caption>
          <title>Post -PVC QTc Prolongation Across Study Groups. QTc: corrected QT; PVC: Premature Ventricular Contractions.</title>
        </caption>
        <graphic xlink:href="2359-5647-ijcs-39-e20250230-50230-gf04.tif"/></fig>
      <p>The two index patients provided the most striking illustration. Despite borderline baseline QTc values, both showed marked post-PVC prolongation (&gt; 540 ms, &#916;&#8776;165 ms) and sustained ventricular tachycardia. Their outlier position in the scatter plot and dramatic change in the summary table underscore how PVC-induced QTc measurement can unmask concealed LQTS that might remain undiagnosed on resting ECG. Although statistical inference was not possible, these cases highlight the method's potential diagnostic and clinical value.</p>
      <p>The combination of statistical results, figures, and clinical summary emphasizes a progressive spectrum of post-PVC QTc response: small and physiologic in healthy individuals, consistent and abnormal in LQTS, and marked in borderline/index patients. These findings support the concept of PVCs as a simple bedside stress test to reveal latent repolarization abnormalities.</p>
      <p>The results of this study are consistent with previous reports that dynamic repolarization markers may improve diagnostic accuracy in LQTS. The ability of PVCs to provoke measurable QTc changes could provide an additional tool in cases where baseline QTc is borderline or inconclusive. From a clinical perspective, systematic evaluation of post-PVC QTc may assist in risk stratification and guide closer monitoring or genetic testing.</p>
      <sec>
        <title>Limitations</title>
        <p>This study has several limitations. First, the retrospective design may introduce selection bias. Second, the sample size was modest, particularly in the index group, which limits statistical inference. Third, QT measurements were obtained from Holter recordings rather than standardized 12-lead ECGs, which may affect measurement precision. Finally, the absence of systematic genetic testing represents a limitation, as genotype&#8211;phenotype correlations could not be assessed.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>PVC-induced QTc prolongation may aid in differentiating healthy individuals, patients with overt LQTS, and those with borderline presentations. While healthy controls showed only mild physiologic adaptation, patients with confirmed LQTS demonstrated consistent abnormal prolongation, and index patients exhibited marked post-PVC QTc increases that unmasked concealed disease. These findings support the potential clinical utility of post-PVC QTc assessment as a simple bedside tool to enhance diagnostic accuracy and refine risk stratification in LQTS. Future prospective studies in larger, well-characterized cohorts are warranted to validate these observations and further define their clinical applicability.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure" id="fn1">
        <label>Sources of Funding</label>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other" id="fn2">
        <label>Study Association</label>
        <p>This article is part of the Doctoral thesis submitted by Khatuna Jalabadze, from Tbilisi State University.</p>
      </fn>
      <fn fn-type="other" id="fn3">
        <label>Ethics Approval and Consent to Participate</label>
        <p>This study was approved by the GeoHospitals Ethics Committee under the protocol number 25-05/404/2. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
      </fn>
      <fn fn-type="other" id="fn4">
        <label>Use of Artificial Intelligence</label>
        <p>The authors did not use any artificial intelligence tools in the development of this work.</p>
      </fn>
    </fn-group>
    <sec sec-type="data-availability" specific-use="data-in-article">
      <title>Availability of Research Data</title>
      <p>The underlying content of the research text is contained within the manuscript.</p>
    </sec>
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