Interpretable machine learning of action potential duration restitution kinetics in single-cell models of atrial cardiomyocytes

Song, Euijun; Lee, Young-Seon

doi:10.1016/j.jelectrocard.2022.09.010

Cited by 4 publications

(8 citation statements)

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“…Britton et al developed a coupled model of experimental measurements and mathematical modeling to calibrate the myocyte model according to inter-individual physiological variability [ 28 ]. Song et al investigated how I NaK plays a significant role in the maximal slope of APD restitution curves through sensitivity analysis using the atrial myocyte population model and the interpretable machine learning model [ 29 ]. Llopis–Lorente suggested that the population model could improve the assessment accuracy of drug-induced torsadogenic risk by choosing different biomarkers depending on individuality [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…APD alternans can occur at the tissue level, and anisotropy plays an important role in the development of APD alternans by affecting the occurrence of APD alternans [ 31 , 32 , 33 ]. In addition, the ventricular tissue has heterogeneous characteristics: the myocyte of each tissue, such as the endocardium, mid-myocardium, and epicardium; and different conductances of ion channels [ 29 , 33 ]. However, it was impossible to consider the heterogeneity of ventricular tissue through the single-cell model.…”

Section: Discussionmentioning

confidence: 99%

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Sensitivity Analysis of Cardiac Alternans and Tachyarrhythmia to Ion Channel Conductance Using Population Modeling

2022

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Action potential duration (APD) alternans, an alternating phenomenon between action potentials in cardiomyocytes, causes heart arrhythmia when the heart rate is high. However, some of the APD alternans observed in clinical trials occurs under slow heart rate conditions of 100 to 120 bpm, increasing the likelihood of heart arrhythmias such as atrial fibrillation. Advanced studies have identified the occurrence of this type of APD alternans in terms of electrophysiological ion channel currents in cells. However, they only identified physiological phenomena, such as action potential due to random changes in a particular ion channel’s conductivity through ion models specializing in specific ion channel currents. In this study, we performed parameter sensitivity analysis via population modeling using a validated human ventricular physiology model to check the sensitivity of APD alternans to ion channel conductances. Through population modeling, we expressed the changes in alternans onset cycle length (AOCL) and mean APD in AOCL (AO meanAPD) according to the variations in ion channel conductance. Finally, we identified the ion channel that maximally affected the occurrence of APD alternans. AOCL and AO meanAPD were sensitive to changes in the plateau Ca2+ current. Accordingly, it was expected that APD alternans would be vulnerable to changes in intracellular calcium concentration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sensitivity Analysis of Cardiac Alternans and Tachyarrhythmia to Ion Channel Conductance Using Population Modeling

2022

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“…At a pacing cycling length (PCL) of 1000 ms (=1 Hz), we measured the APD at 90% of repolarization (APD 90 ), APD at 50% of repolarization (APD 50 ), resting membrane potential (RMP), maximum upstroke velocity (V max ), and calcium transient amplitude (∆CaT; [ 31 , 32 ]). A steady state was achieved by stimulating the cells for 60 s. The ∆CaT was defined as the difference between the maximum and minimum intracellular Ca 2+ concentrations [ 31 – 33 ].…”

Section: Methodsmentioning

confidence: 99%

“…A steady state was achieved by stimulating the cells for 60 s. The ∆CaT was defined as the difference between the maximum and minimum intracellular Ca 2+ concentrations [ 31 – 33 ]. We also estimated the refractory period and APD (or ∆CaT) alternans threshold cycle lengths using a dynamic ramp pacing protocol as previously described [ 32 ]: PCLs of 1000, 600, and 500 ms were used, and the PCL was decreased to 300 ms in steps of 50 ms and further decreased in steps of 10 ms until failure of 1:1 capture. For each PCL, the cell was stimulated for 16 beats.…”

Section: Methodsmentioning

confidence: 99%

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Wirkung von Hydroxychloroquin auf die Vorhofelektrophysiologie bei In-silico-Wildtyp- und PITX2+/--Vorhofkardiomyozyten

Song

2023

Herz

Self Cite

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Background Hydroxychloroquine (HCQ) is commonly used in the treatment of autoimmune diseases and increases the risk of QT interval prolongation. However, it is unclear how HCQ affects atrial electrophysiology and the risk of atrial fibrillation (AF). Methods We quantitatively examined the potential atrial arrhythmogenic effects of HCQ on AF using a computational model of human atrial cardiomyocytes. We measured atrial electrophysiological markers after systematically varying HCQ concentrations. Results The HCQ concentrations were positively correlated with the action potential duration (APD), resting membrane potential, refractory period, APD alternans threshold, and calcium transient alternans threshold ( p < 0.05). By contrast, HCQ concentrations were inversely correlated with the maximum upstroke velocity and calcium transient amplitude ( p < 0.05). When the therapeutic concentration (C max ) of HCQ was applied, HCQ increased APD 90 by 1.4% in normal sinus rhythm, 1.8% in wild-type AF, and 2.6% in paired-like homeodomain transcription factor 2 (PITX2) +/- AF, but did not affect the alternans thresholds. The overall in silico results suggest no significant atrial arrhythmogenic effects of HCQ at C max , instead implying a potential antiarrhythmic role of low-dose HCQ in AF. However, at an HCQ concentration of fourfold C max , a rapid pacing rate of 4 Hz induced prominent APD alternans, particularly in the PITX2 +/- AF model. Conclusion Our in silico analysis suggests a potential antiarrhythmic role of low-dose HCQ in AF. Concomitant PITX2 mutations and high-dose HCQ treatments may increase the risk of AF, and this potential genotype/dose-dependent arrhythmogenic effect of HCQ should be investigated further. Supplementary Information The online version of this article (10.1007/s00059-023-05162-w) contains supplementary material, which is available to authorized users.

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Vaginal microbiota molecular profiling and diagnostic performance of artificial intelligence-assisted multiplex PCR testing in women with bacterial vaginosis: a single-center experience

Lu,

Li,

Chen

et al. 2024

Front. Cell. Infect. Microbiol.

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BackgroundBacterial vaginosis (BV) is a most common microbiological syndrome. The use of molecular methods, such as multiplex real-time PCR (mPCR) and next-generation sequencing, has revolutionized our understanding of microbial communities. Here, we aimed to use a novel multiplex PCR test to evaluate the microbial composition and dominant lactobacilli in non-pregnant women with BV, and combined with machine learning algorithms to determine its diagnostic significance.MethodsResidual material of 288 samples of vaginal secretions derived from the vagina from healthy women and BV patients that were sent for routine diagnostics was collected and subjected to the mPCR test. Subsequently, Decision tree (DT), random forest (RF), and support vector machine (SVM) hybrid diagnostic models were constructed and validated in a cohort of 99 women that included 74 BV patients and 25 healthy controls, and a separate cohort of 189 women comprising 75 BV patients, 30 intermediate vaginal microbiota subjects and 84 healthy controls, respectively.ResultsThe rate or abundance of Lactobacillus crispatus and Lactobacillus jensenii were significantly reduced in BV-affected patients when compared with healthy women, while Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae, BVAB2, Megasphaera type 2, Prevotella bivia, and Mycoplasma hominis were significantly increased. Then the hybrid diagnostic models were constructed and validated by an independent cohort. The model constructed with support vector machine algorithm achieved excellent prediction performance (Area under curve: 0.969, sensitivity: 90.4%, specificity: 96.1%). Moreover, for subjects with a Nugent score of 4 to 6, the SVM-BV model might be more robust and sensitive than the Nugent scoring method.ConclusionThe application of this mPCR test can be effectively used in key vaginal microbiota evaluation in women with BV, intermediate vaginal microbiota, and healthy women. In addition, this test may be used as an alternative to the clinical examination and Nugent scoring method in diagnosing BV.

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Interpretable machine learning of action potential duration restitution kinetics in single-cell models of atrial cardiomyocytes

Cited by 4 publications

References 49 publications

Sensitivity Analysis of Cardiac Alternans and Tachyarrhythmia to Ion Channel Conductance Using Population Modeling

Sensitivity Analysis of Cardiac Alternans and Tachyarrhythmia to Ion Channel Conductance Using Population Modeling

Wirkung von Hydroxychloroquin auf die Vorhofelektrophysiologie bei In-silico-Wildtyp- und PITX2+/--Vorhofkardiomyozyten

Vaginal microbiota molecular profiling and diagnostic performance of artificial intelligence-assisted multiplex PCR testing in women with bacterial vaginosis: a single-center experience

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