Evaluation of index of cardiac electrophysiological balance in COVID-19 patients.

AIM: The aim of the current study was to evaluate the index of Cardiac Electrophysiological Balance (iCEB) in hospitalized COVID-19 patients receiving Hydroxychloroquine / azithromycin (HCQ / AZ) combination therapy to determine the susceptibility to ventricular arrhythmia among these patients. METHOD: Sixty-seven COVID-19 patients admitted to the ward were included in the study. Electrocardiograms (ECGs) were obtained from all patients before the initiation of treatment and on treatment day 5. QT/QRS (iCEB) and QTc/QRS (iCEBc) ratios were calculated. RESULTS: QRS, QT and QTc intervals were significantly prolonged on day 5 measurements compared to pre-treatment period (p <0.05). Overall, mean iCEB was 3.6±0.4 before treatment and 3.8±0.4 on day 5 in the study population (p <0.001). Considering the iCEBc values, a significant increase was observed in patients receiving HCQ/AZ treatment compared to pre-treatment period (4.1±0.5 vs 4.4±0.6; p <0.001). CONCLUSIONS: To the best of our knowledge, this was the first study to investigate iCEB and iCEBc parameters in patients with COVID-19 on HCQ/AZ therapy. In this study, we demonstrated significantly increased iCEB and iCEBc values following HCQ/AZ treatment in COVID-19 patients. iCEB and iCEBc may serve as a noninvasive, simple, and novel biomarker for detecting increased pro-arrhythmia risk in COVID-19 patients (Tab. 3, Fig. 3, Ref. 36).

Evaluation of Index of Cardio-Electrophysiological Balance (iCEB) as a New Biomarker for the Identification of Patients at Increased Arrhythmic Risk.

BACKGROUND: Recently a new risk marker for drug-induced arrhythmias called index of cardio-electrophysiological balance (iCEB), measured as QT interval divided by QRS duration, was evaluated in an animal model. It was hypothesized that iCEB is equivalent to the cardiac wavelength λ (λ = effective refractory period (ERP) x conduction velocity) and that an increased or decreased value of iCEB would potentially predict an increased susceptibility to TdP or non-TdP mediated VT/VF, respectively. METHODS: First, the correlation between QT interval and ERP was evaluated by invasively measuring ERP during a ventricular stimulation protocol in humans (N = 40). Then the effect of administration of sotalol and flecainide on iCEB was measured in 40 patients with supraventricular tachycardias. Finally iCEB was assessed in carriers of a long QT syndrome (LQTS, N = 70) or Brugada syndrome (BrS, N = 57) mutation and compared them with genotype negative family members (N = 65). RESULTS: The correlation between QT interval and ERP was established (Pearson R(2) = 0.25) which suggests that iCEB≈ERPxCV≈QT/QRS. Sotalol administration increased iCEB (+ 0.23; P = 0.01), while it decreased with the administration of flecainide (-0.21, P = 0.03). In the LQTS group iCEB was increased (5.22 ± 0.93, P < 0.0001) compared to genotype negative family members (4.24 ± 0.5), while it was decreased in the BrS group (3.52 ± 0.43, P < 0.0001). CONCLUSIONS: Our data suggest that iCEB (QT/QRS) is a simple but effective ECG surrogate of cardiac wavelength. iCEB is increased in situations that predispose to TdP and is decreased in situations that predispose to non-TdP mediated VT/VF. Therefore, iCEB might serve as a noninvasive and readily measurable marker to detect increased arrhythmic risk.

Relationship between Vitamin D Level and Index of Cardio Electrophysiological Balance in Children.

BACKGROUND: Vitamin D deficiency has been found to be associated with various cardiovascular disorders, including hypertension, coronary artery disease, heart failure, peripheral vascular diseases, and sudden cardiac death. In the literature, it has been reported that many electrocardiographic parameters have been developed to predict ventricular arrhythmias. In recent studies, it is noteworthy that the index of cardio-electrophysiological balance (iCEB) and correct cardio-electrophysiological balance (iCEBc), which are electrocardiographic parameters, can be used as new, easy, cheap and non-invasive parameters to predict ventricular arrhythmias. OBJECTIVE: This study aimed to investigate the relationship between vitamin D deficiency and iCEB and iCEBc values in children. METHODS: A total of 186 patients were included in this study. Group 1 included 114 patients with vitamin D levels below 20 ng/ml; 50 patients with vitamin D levels of 21-29 ng/ml were included in Group 2; Group 3 consisted of 36 patients with a vitamin D level above 30 ng/ml. iCEB and iCEBc values were calculated by taking 12-lead ECG from all individuals and comparing them between groups. RESULTS: A total of 186 children, 114 subjects in Group 1, 36 subjects in Group 2, and 36 subjects in Group 3, were included in the study. Demographic characteristics and height-weight values of the groups were similar. Significant differences were found between the groups in terms of QT, QTc, QT/QRS, and QTc/QRS levels (p: 0.003, 0.028, 0.001, and 0.001, respectively). In the correlation analysis, a negative correlation was found between QTc/QRS and vitamin D level (r=-0.320, p=<0.001) and between QT/QRS and vitamin D level (r=-0.268, p=<0.001). Moreover, vitamin D level (ß=0.389, p<0.001) was determined as an independent predictor of QTc/QRS in multivariate logistic regression analysis. CONCLUSION: iCEB and iCEBc parameters increase significantly in children with low vitamin D levels. These parameters are also evaluated during the follow-up of children with vitamin D deficiency in terms of the risk of ventricular arrhythmia. iCEBc can be used as an easy, inexpensive, non-invasive, and reproducible parameter.

Relationship Between Index of Cardiac Electrophysiological Balance, Frontal QRS-T Angle and Retinopathy in People with Type 2 Diabetes.

Background: Diabetic retinopathy (DR) is strongly associated with cardiovascular disease, which is a risk factor for sudden cardiac death (SCD). The index of cardiac electrophysiological balance (iCEB) and the frontal QRS-T angle are recommended to predict the risk of ventricular arrhythmias more than other ECG parameters. However, the relationships between these two markers and DR have not yet been explored. The aim of this study was to investigate the variation in the iCEB, corrected iCEB (iCEBc) and frontal QRS-T angle in different stages of DR and determine whether there are associations between these markers and DR. Methods: The sample comprised 665 patients with Type 2 diabetes mellitus (T2DM) who were classified into three groups: no DR (NDR), mild to moderate non-proliferative DR (NPDR), and vision-threatening DR (VTDR). Twelve-lead ECG was performed and the QT, QTc, QRS duration, iCEB, iCEBc and frontal QRS-T angle were recorded and compared across the groups. Results: The VTDR group had a significantly higher iCEBc and frontal QRS-T angle than the NDR and NPDR groups. After controlling for confounding variables, the correlations between the iCEBc (OR=2.217, 95% CI=1.464-3.358, P<0.001), frontal QRS-T angle (OR=1.017, 95% CI=1.008-1.025, P<0.001) and DR risk remained (P<0.05). Subjects in the fourth iCEBc quartile (adjusted OR=2.612, 95% CI=1.411-4.834, p=0.002) had a much higher chance of developing DR compared to those in the first quartile. In comparison to the first frontal QRS-T angle quartile, subjects in the third (adjusted OR=1.998, 95% CI=1.167-3.422, P=0.012) and fourth (adjusted OR=2.430, 95% CI=1.420-4.160, P=0.001) frontal QRS-T angle quartiles had significantly greater risks of DR. Conclusion: With the progression of DR, the iCEBc and frontal QRS-T angle increase. An increased iCEBc and frontal QRS-T angle are associated with an increased risk of DR.

Effect of ranolazine on Tp-e interval, Tp-e/QTc, and P-wave dispersion in patients with stable coronary artery disease.

INTRODUCTION: Ranolazine is an antianginal drug and also exhibits antiarrhythmic effect by affecting action potential time, refractory period, and repolarization reserve. We evaluated the effect of ranolazine therapy on myocardial repolarization parameters (Tp-e, QT, QTc intervals, Tp-e/QT, and Tp-e/QTc ratios), index of cardiac electrophysiological balance (iCEB) (QT/QRS, QTc/QRS) and P-wave dispersion (PWD) in patients with stable coronary artery disease (CAD). METHODS: This study included 175 patients, aged between 35 and 90 years who were followed with stable CAD for at least 3 months. Ninety patients had been receiving ranolazine for at least 1 month, and 85 patients had never received ranolazine. All patients' basic demographic data, risk factors, medications, and echocardiographic parameters recorded. Myocardial repolarization parameters, P-wave times, and PWD were analyzed from 12 lead electrodes. RESULTS: There was no variation between the groups in terms of basic demographic parameters and CAD risk factors. Tp-e interval (87.3 ± 14.4 vs. 90.8 ± 12.4 msn, P < .001), Tp-e/QT (0.22 ± 0.04 vs. 0.23 ± 0.03; P = .03), Tp-e/QTc (0.21 ± 0.04 vs. 0.22 ± 0.04 P = .001), and PWD (39.2 ± 13.7 vs. 43.5 ± 12.9 P = .028) were significantly lower in the ranolazine group. But iCEB was similar in both groups. In multivariate analysis after adjusted confounding factors such as age and BMI, Tp-e/QTc ratio, QTc, Pmax, and PWD were found significantly in ranolazine group again. CONCLUSION: Tp-e/QTc ratio, QTc, Pmax, and PWD were significantly lower in stable CAD patients under ranolazine therapy. In stable CAD patients, the prognostic significance of ranolazine for arrhythmic events requires further evaluation of these parameters through long-term follow-up and large-scale prospective studies.

Index of cardiac electrophysiological balance and transmural dispersion of the repolarization index relationships with pericardial fat volume and coronary calcification.

AIM: To assess the possible relationship between coronary atherosclerosis markers, pericardial fat volume (PFV) and coronary artery calcification, with ECG markers of index of the cardiac electrophysiological balance (iCEB) and transmural dispersion of the repolarization in patients with suspected coronary artery disease. METHODOLOGY: One hundred patients who underwent 64-slice multidetector computed tomography angiography were found to be eligible and were enrolled in the study. RESULTS: Patients with high iCEB levels tended to have a higher PFV values compared with patients with low iCEB levels (median [interquartile range]) (152 [29-206] vs 96 [14-177]; p = 0.03). No significant differences in coronary artery calcification values were observed between iCEB and transmural dispersion of the repolarization groups. CONCLUSION: A higher PFV value was observed in patients with high iCEB. Larger prospective studies are required to confirm the results.

A new biomarker--index of cardiac electrophysiological balance (iCEB)--plays an important role in drug-induced cardiac arrhythmias: beyond QT-prolongation and Torsades de Pointes (TdPs).

INTRODUCTION: In the present study, we investigated whether a new biomarker - index of cardiac electrophysiological balance (iCEB=QT/QRS) - could predict drug-induced cardiac arrhythmias (CAs), including ventricular tachycardia/ventricular fibrillation (VT/VF) and Torsades de Pointes (TdPs). METHODS: The rabbit left ventricular arterially-perfused-wedge was used to investigate whether the simple iCEB measured from the ECG is reflective of the more difficult measurement of λ (effective refractory period×conduction velocity) for predicting CAs induced by a number of drugs. RESULTS: Dofetilide concentration-dependently increased iCEB and λ, predicting potential risk of drug-induced incidence of early afterdepolarizations (EADs) starting at 0.01µM. Digoxin (1 and 5µM), encainide (5 and 20µM) and propoxyphene (10 and 100µM) markedly reduced both iCEB and λ, predicting their ability to induce non-TdP-like VT/VF. At 10µM, both NS1643 and levcromakalim significantly decreased λ and iCEB, which was preceded with presence of non-TdP-like VT/VF. Isoprenaline (0.05 to 0.5µM) significantly reduced both λ and iCEB, which was associated with a high incidence of non-TdP-like VT/VF in most preparations. Other biomarkers (i.e. transmural dispersion of T-wave and instability of the QT interval) predicted only dofetilide-induced long QT and EADs, but did not predict drug-induced risk of non-TdP-like VT/VF. DISCUSSION: Our data from 7 reference drugs of known pro-arrhythmic effects suggests that 1) this non-invasive iCEB predicts potential risk of drug-induced CAs beyond long QT and TdP; 2) iCEB is more useful than the current biomarkers (i.e. transmural dispersion and instability) in predicting potential risks for drug-induced non-TdP-like VT/VF.