Evaluation of Differences in Automated QT/QTc Measurements between Fukuda Denshi and Nihon Koden Systems

<div><p>Background</p><p>Automatic measurement becomes a preference, and indeed a necessity, when analyzing 1000 s of ECGs in the setting of either drug-inducing QT prolongation screening or genome-wide association studies of QT interval. The problem is that individual manufacturers apply different computerized algorithms to measure QT interval. We conducted a comparative study to assess the outcomes with different automated measurements of QT interval between ECG machine manufacturers and validated the related heart rate correction methods.</p><p>Methods and Results</p><p>Herein, we directly compared these different commercial systems using 10,529 Fukuda Denshi ECGs and 72,754 Nihon Kohden ECGs taken in healthy Japanese volunteers. Log-transformed data revealed an equal optimal heart rate correction formula of QT interval for Fukuda Denshi and Nihon Kohden, in the form of QTc = QT/RR^−0.347. However, with the raw data, the optimal heart rate correction formula of QT interval was in the form of QTc = QT+0.156×(1-RR) for Fukuda Denshi and QTc = QT+0.152×(1-RR) for Nihon Kohden. After optimization of heart rate correction of QT interval by the linear regression model using either log-transformed data or raw data, QTc interval was ∼10 ms longer in Nihon Kohden ECGs than in those recorded on Fukuda Denshi machines. Indeed, regression analysis revealed that differences in the ECG machine used had up to a two-fold larger impact on QT variation than gender difference. Such an impact is likely to be of considerable importance when ECGs for a given individual are recorded on different machines in the setting of multi-institutional joint research.</p><p>Conclusions</p><p>We recommend that ECG machines of the same manufacturer should be used to measure QT and RR intervals in the setting of multi-institutional joint research. It is desirable to unify the computer algorithm for automatic QT and RR measurements from an ECG.</p></div

Analysis of resting Fukuda Denshi ECGs.

<p>(A) Histograms of QT, log-transformed QT, RR, and log-transformed RR intervals. (B) Scatter plots of log QT versus log RR and log QTc_ours log versus log RR. (C) QT versus RR and QTc_ours raw versus RR. Units of all variables are ms.</p

Analysis of resting Nihon Kohden ECGs.

<p>(A) Histograms of QT, log-transformed QT, RR, and log-transformed RR intervals. (B) Scatter plots of log QT versus log RR and log QTc_ours log versus log RR. (C) QT versus RR and QTc_ours raw versus RR. Units of all variables are ms.</p

Comparison of automatic QT measurements in adult resting ECGs between Fukuda Denshi and Nihon Kohden.

<p>Units of RR, QT and all corrected forms of QT in this table are ms.</p><p>The results of the tests of differences in QT, RR, QTc(ours_log), Fredericia, Bazett, QTc(ours_raw), Framingham and ECAPs12 between Nihon Koden and Fukuda Denshi for each gender were all P<2.2×10⁻¹⁶ (Student t-test).</p><p>Comparison of automatic QT measurements in adult resting ECGs between Fukuda Denshi and Nihon Kohden.</p

Negative legacy of obesity

<div><p>Obesity promotes excessive inflammation, which is associated with senescence-like changes in visceral adipose tissue (VAT) and the development of type 2 diabetes (T2DM) and cardiovascular diseases. We have reported that a unique population of CD44^hi CD62L^lo CD4⁺ T cells that constitutively express PD-1 and CD153 exhibit cellular senescence and cause VAT inflammation by producing large amounts of osteopontin. Weight loss improves glycemic control and reduces cardiovascular disease risk factors, but its long-term effects on cardiovascular events and longevity in obese individuals with T2DM are somewhat disappointing and not well understood. High-fat diet (HFD)-fed obese mice were subjected to weight reduction through a switch to a control diet. They lost body weight and visceral fat mass, reaching the same levels as lean mice fed a control diet. However, the VAT of weight reduction mice exhibited denser infiltration of macrophages, which formed more crown-like structures compared to the VAT of obese mice kept on the HFD. Mechanistically, CD153⁺ PD-1⁺ CD4⁺ T cells are long-lived and not easily eliminated, even after weight reduction. Their continued presence maintains a self-sustaining chronic inflammatory loop via production of large amounts of osteopontin. Thus, we concluded that T-cell senescence is essentially a negative legacy effect of obesity.</p></div

Effect of weight reduction on adipose tissue inflammation in obese mice.

<p>Mice were fed either a high-fat diet (HFD) or a control diet (CD). The HFD was introduced at 4 weeks of age. Half of the HFD mice were switched to control diet at 30 weeks of age (HFD to CD). The other half of the HFD mice were continuously kept on the HFD. These mice were evaluated at 38 weeks of age. <b>a, b</b> Body and eVAT weights were analyzed (n = 6 mice per group). <b>c, d</b> Effect of HFD or weight reduction on oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) (n = 6 mice per group). *: CD vs HFD → CD, ^#: CD vs HFD. <b>e</b> Serum insulin levels of mice fed CD, HFD, and HFD to CD (n = 3–9 mice per group). <b>f</b> Adipose tissue of indicated mice were analyzed for the expression of <i>Spp1</i>, <i>Tnf</i>, <i>Il1b</i>, and <i>Col1a1</i> by real-time PCR analysis (n = 6 mice per group). *P < 0.05, **P < 0.01, and ***P < 0.001, ^##P < 0.01, and ^###P < 0.001; n.s., not significant. Data are represented as mean ± SEM.</p

Effect of weight reduction on T lymphocytes in VAT of obese mice.

<p><b>a–d</b> Flow cytometric analysis of SA-β-gal activity on CD4⁺ T cells and CD8⁺ T cells from VAT. (n = 5 mice per group). <b>a, c</b> Expression of SA-β-gal on CD4⁺ T cells and CD8⁺ T cells in the VAT of mice fed CD, HFD, and HFD to CD. <b>b, d</b> Results are expressed as cell number per gram of SA-β-gal⁺ cells. <b>e–g</b> Flow cytometric analysis of VAT CD153⁺ PD-1⁺ CD4⁺ T cells obtained from mice fed CD, HFD, and HFD to CD. <b>e</b> A representative flow cytometric analysis of VAT CD153⁺ PD-1⁺ CD4⁺ T cells. <b>f</b> Expression of CD153⁺ on CD4⁺ T cells. <b>g</b> Results are expressed as cell number per gram of CD153⁺ PD-1⁺ CD4⁺ T cells (n = 5–10 mice per group). <b>h, i</b> Serum osteopontin (<b>h</b>) and total IgG (<b>i</b>) from mice fed CD, HFD, and HFD to CD were assessed by ELISA (n = 5–8 mice per group). <b>j, k</b> PD-1⁻, CD153^- PD-1⁺, CD153⁺ PD-1⁺ CD4⁺ T cells were separately isolated from the spleens of obese mice. Indicated cells were cultured with IL-2 for 15 days and analyzed for live and dead cells (n = 3–4 mice per group). *P < 0.05, **P < 0.01, and ***P < 0.001. Data are represented as mean ± SEM.</p

Negative legacy of obesity - Fig 4

<p><b>Visceral fat accumulation promotes senescence-like changes in VAT, a, b</b> Histochemical identification of adipocytes (BODIPY, red), SA-β-gal (yellow), and nuclei (DAPI, blue) in VAT. Scale bars, 100 μm. Original magnification: ×10 (a), ×40 (b). <b>c</b> A representative flow cytometric analysis demonstrating SA-β-gal activity of CD45⁺ T cells in the VAT of mice fed CD or HFD (n = 3 mice per group). <b>d–g</b> Flow cytometric analysis of SA-β-gal activity on CD4⁺ T cells, CD8⁺ T cells, B cells, and macrophages from VAT (n = 3–5 mice per group). ***P < 0.001; n.s., not significant. Data are represented as mean ± SEM.</p