Early exposure to mercury and cardiovascular function of seven-year old children in Guadeloupe (French West Indies).

BACKGROUND: The cardiotoxicity of prenatal exposure to mercury has been suggested in populations having regular contaminated seafood intake, though replications in the literature are inconsistent. METHODS: The Timoun Mother-Child Cohort Study was set up in Guadeloupe, an island in the Caribbean Sea where seafood consumption is regular. At seven years of age, 592 children underwent a medical examination, including cardiac function assessment. Blood pressure (BP) was taken using an automated blood pressure monitor, heart rate variability (HRV, 9 parameters) and electrocardiogram (ECG) characteristics (QT, T-wave parameters) were measured using Holter cardiac monitoring during the examination. Total mercury concentrations were measured in cord blood at birth (median = 6.6 µg/L, N = 399) and in the children's blood at age 7 (median = 1.7 µg/L, N = 310). Adjusted linear and non-linear modelling was used to study the association of each cardiac parameter with prenatal and childhood exposures. Sensitivity analyses included co-exposures to lead and cadmium, adjustment for maternal seafood consumption, selenium and polyunsaturated fatty acids (n3-PUFAs), and for sporting activity. RESULTS: Higher prenatal mercury was associated with higher systolic BP at 7 years of age (ßlog2 = 1.02; 95% Confidence Interval (CI) = 0.10, 1.19). In boys, intermediate prenatal exposure was associated with reduced overall HRV and parasympathetic activity, and longer QT was observed with increasing prenatal mercury (ßlog2 = 4.02; CI = 0.48, 7.56). In girls, HRV tended to increase linearly with prenatal exposure, and no association was observed with QT-wave related parameters. Mercury exposure at 7 years was associated with decreased BP in girls (ßlog2 = -1.13; CI = -2.22, -0.004 for diastolic BP). In boys, the low/high-frequency (LF/HF) ratio increased for intermediate levels of exposure. CONCLUSION: Our study suggests sex-specific and non-monotonic modifications in some cardiac health parameters following prenatal exposure to mercury in pre-pubertal children from an insular fish-consuming population.

Abnormal Cardiac Repolarization in Thyroid Diseases: Results of an Observational Study.

Background: The relationship between thyroid function and cardiac disease is complex. Both hypothyroidism and thyrotoxicosis can predispose to ventricular arrhythmia and other major adverse cardiovascular events (MACE), so that a U-shaped relationship between thyroid signaling and the incidence of MACE has been postulated. Moreover, recently published data suggest an association between thyroid hormone concentration and the risk of sudden cardiac death (SCD) even in euthyroid populations with high-normal FT4 levels. In this study, we investigated markers of repolarization in ECGs, as predictors of cardiovascular events, in patients with a spectrum of subclinical and overt thyroid dysfunction. Methods: Resting ECGs of 100 subjects, 90 patients (LV-EF > 45%) with thyroid disease (60 overt hyperthyroid, 11 overt hypothyroid and 19 L-T4-treated and biochemically euthyroid patients after thyroidectomy or with autoimmune thyroiditis) and 10 healthy volunteers were analyzed for Tp-e interval. The Tp-e interval was measured manually and was correlated to serum concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and thyroxine (FT4). Results: The Tp-e interval significantly correlated to log-transformed concentrations of TSH (Spearman's rho = 0.30, p < 0.01), FT4 (rho = -0.26, p < 0.05), and FT3 (rho = -0.23, p < 0.05) as well as log-transformed thyroid's secretory capacity (SPINA-GT, rho = -0.33, p < 0.01). Spearman's rho of correlations of JT interval to log-transformed TSH, FT4, FT3, and SPINA-GT were 0.51 (p < 1e-7), -0.45 (p < 1e-5), -0.55 (p < 1e-8), and -0.43 (p < 1e-4), respectively. In minimal multivariable regression models, markers of thyroid homeostasis correlated to heart rate, QT, Tp-e, and JT intervals. Group-wise evaluation in hypothyroid, euthyroid and hyperthyroid subjects revealed similar correlations in all three groups. Conclusion: We observed significant inverse correlations of Tp-e and JT intervals with FT4 and FT3 over the whole spectrum of thyroid function. Our data suggest a possible mechanism of SCD in hypothyroid state by prolongation of repolarization. We do not observe a U-shaped relationship, so that the mechanism of SCD in patients with high FT4 or hyperthyroidism seems not to be driven by abnormalities in repolarization.

Effects of Antipsychotics on Arrhythmogenic Parameters in Schizophrenia Patients: Beyond Corrected QT Interval.

PURPOSE: Antipsychotic drugs have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death. However, the QT interval is considered an imperfect marker for proarrhythmic risk. Recently, improved methods, namely, QT dispersion (QTD), QTD ratio (QTDR), T wave peak-to-end interval (Tp-e), Tp-e/QT ratio and Tp-e/QTc ratio, have been regarded as proarrhythmic risk markers. We attempted to reevaluate the risk of sudden cardiac death due to antipsychotics use by measuring these improved evaluation methods. PATIENTS AND METHODS: We retrospectively evaluated QTc, QTD, QTDR, Tp-e, Tp-e/QT ratio and Tp-e/QTc ratio from the medical records of 410 patients with schizophrenia diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, or 5th Edition. Information on drugs administered was obtained from medical records. We investigated the correlation between each index on ECG and medication, such as antipsychotics, prescribed to participants with linear regression analysis. We also compared each index between 235 healthy controls and 235 patients matched for age and sex. RESULTS: Positive correlations between QTc and levomepromazine and brexpiprazole were identified. Levomepromazine and lithium were positively correlated with QTD. Levomepromazine, quetiapine, asenapine, clozapine and carbamazepine were positively correlated with QTDR. Levomepromazine, olanzapine, brexpiprazole and lithium were positively correlated with Tp-e. Olanzapine, brexpiprazole and lithium were positively correlated with the Tp-e/QT ratio. Olanzapine, brexpiprazole and lithium were positively correlated with Tp-e/QTc ratio. Significant differences in all indexes were noted between the patients and healthy controls. CONCLUSION: According to our results, the prediction of the risk of sudden cardiac death by each index was inconsistent. We should evaluate the predictive factor of ventricular arrhythmia according to various electrocardiogram indexes because QTc alone could not identify the risk of sudden cardiac death.

Accuracy of intracoronary ECG parameters for myocardial ischemia detection.

INTRODUCTION: The electrocardiogram (ECG) is a valuable diagnostic tool for the diagnosis of myocardial ischemia during acute coronary syndrome. Aside from the commonly used ST-segment shift indicative of ischemia, several other ECG parameters are pathophysiologically reasonable. Thus, the goal of this study was to assess the accuracy of different ischemia parameters as obtained by the highly susceptible intracoronary ECG (icECG). METHOD: This was a retrospective observational study in 100 patients with chronic coronary syndrome. From each patient, a non-ischemic as well as ischemic icECG at the end of a one-minute proximal coronary balloon occlusion was available, and analysed twice by three different physicians, as well as once together for consensual results. The evaluated parameters were icECG ST-segment shift (mV), ST-integral (mV*sec), T-wave-integral (mV*sec), T-peak (mV), T-peak-to-end time (TPE; msec) and QTc-time (msec). RESULTS: All six icECG parameters showed significant differences between the non-ischemic and the ischemic recording. Using the icECG recording during coronary patency or occlusion as criterion for absent or present myocardial ischemia, ROC-analysis of icECG ST-segment shift showed an area under the curve (AUC) of 0.963 ± 0.029 (p < 0.0001). AUC for ST-integral was 0.899 ± 0.044 (p < 0.0001), for T-wave integral 0.791 ± 0.059 (p < 0.0001), for T-peak 0.811 ± 0.057 (p < 0.0001), for TPE 0.667 ± 0.068 (p < 0.0001), and for QTc-time 0.770 ± 0.061 (p < 0.0001). The best cut-off point for the detection of ischemia by icECG ST-segment shift was 0.365 mV (sensitivity 90%, specificity 95%). CONCLUSION: When tested in a setting with artificially induced absolute myocardial ischemia, icECG ST-segment shift at a threshold of 0.365 mV most accurately distinguishes between absent and present ischemia.

Correlation Between T Peak to End Interval and Left Ventricular Time to Peak Longitudinal Strain in Ischemic Cardiomyopathy Patients.

BACKGROUND: Ischemic cardiomyopathy is the most frequent etiology of heart failure with reduced ejection fraction (HFrEF) and a result of ventricular structural, functional and electrical remodeling. T peak to end (Tpe) interval is an electrocardiographic parameter that represents repolarization heterogeneity and had prognostic value for ventricular arrhythmia. Patients with ischemic cardiomyopathy face a significant burden of arrhythmias. Mechanical dispersion is a functional remodeling parameter that can be measured by time to peak longitudinal strain using speckle tracking echocardiography. This study aimed to assess the relationship between Tpe interval with time to peak longitudinal strain in ischemic cardiomyopathy patients. METHODS: This study was conducted with an observational analytical cross-sectional design. Ischemic cardiomyopathy subjects were included at Dr. Hasan Sadikin General Hospital, Bandung, from August to October 2019. Tpe interval was measured manually with the tangential method. Time to peak longitudinal strain was measured using speckle tracking echocardiography. The correlation between Tpe interval and time to peak longitudinal strain was analyzed using Pearson correlation. RESULTS: A total of 30 subjects were included in this study. The average age was 58 ± 8 years old, and the average left ventricular ejection fraction was 27±5.5%. The average of Tpe interval was 83.4 ± 7.62 ms, and the average time to peak longitudinal strain was 93.13 ± 34.51 ms. The Pearson correlation test showed a significant weak positive correlation (r = 0.386, 95% confidence interval: 0.029 - 0.743, P = 0.018) between Tpe interval and time to peak longitudinal strain in ischemic cardiomyopathy patients. CONLUCIONS: There was a significant weak positive correlation between Tpe interval and time to peak longitudinal strain in ischemic cardiomyopathy patients.

Evaluation of index of cardiac-electrophysiological balance before and after hemodialysis in patients with end-stage renal disease.

BACKGROUND: Ventricular arrhythmias and sudden cardiac deaths are the most common cause of mortality in patients with end-stage renal disease (ESRD). Index of cardiac-electrophysiological balance (iCEB) (QT/QRS) may predict malignant ventricular arrhythmias. In this study, we investigated whether iCEB value is increased in ESRD patients and whether it changes before and after hemodialysis. METHODS: The study included 52 ESRD patients and 53 control subjects matched for age and comorbidities. Biochemical, electrocardiographic and echocardiographic values of all participants were recorded. QRS, QT, Tp-e were measured manually. QTC was calculated using Bazett's formula. Then, Tp-e/QT, Tp-e/QTc, QT/QRS, and QTc/QRS ratios were calculated. The changes in ECG parameters of the ESRD patients before and after HD were compared using paired t-test. RESULTS: Mean age and male sex ratio was comparable in both groups (p = 0.448 and p = 0.777, respectively). Comorbidity incidences, and biochemical parameters except eGFR (p < 0.001), albumin (p < 0.001), HDL cholesterol (p = 0.03) and platelet counts (p < 0.001) were comparable in both groups. Compared to the control group, QT, QTc, Tp-e, Tp-e/QT, Tp-e/QTc, QT/QRS, and QTc/QRS ratios were higher in the ESRD group (p < 0.05 for each). While QT and QTc intervals did not change after HD in ESRD patients, Tp-e, Tp-e/QT, Tp-e/QTc, QT/QRS, and QTc/QRS parameters increased significantly. CONCLUSION: In addition to ventricular repolarization dispersion indices in ESRD patients, iCEB elevation and increasing values after HD session indicate the increased risk of TdP-mediated ventricular arrhythmia after HD. Larger studies are needed to confirm our results.

Investigation of the Proarrhythmic Effects of Antidepressants according to QT Interval, QT Dispersion and T Wave Peak-to-End Interval in the Clinical Setting.

OBJECTIVE: Some antidepressants have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death. However, the QT interval is considered an imperfect biomarker for proarrhythmic risk. Therefore, we reevaluated the risk of sudden cardiac death due to antidepressants using improved. METHODS: , namely, QT dispersion (QTD), T wave peak-to-end interval (Tp-e), and Tp-e/QT ratio. METHODS: We compared the effects of antidepressants on QTc (QT/RR1/3), QTD, Tp-e, and Tp-e/QT ratio in 378 patients with mood disorder. We also compared each index between 165 healthy controls and 215 randomly selected age-matched patients. RESULTS: Age (p<0.01), sex (p<0.05), tricyclic antidepressant (TCA) use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly associated with a prolonged QTc. We also found that age (p<0.01), TCA use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly prolonged QTD. However, there was no correlation between each variable and Tp-e or Tp-e/QT ratio. Significant differences in QTc and QTD were found between the patients and healthy controls. CONCLUSION: From our results, prediction of risk of sudden cardiac death by QTD, Tp-e, or Tp-e/QT ratio was inconsistent. Increased QTD may be more suitable for predicting sudden cardiac death due to antidepressants.

The dispersion of myocardial repolarization in ischemic stroke and intracranial hemorrhage.

BACKGROUND: Markers of dispersion of myocardial repolarization have been proposed to identify the patients at higher risk of malignant arrhythmic events. The aim of the present study is to assess a possible association of the electrocardiografic (ECG) markers of the dispersion of repolarization with the type of stroke, involvement of insula, neurological severity (National Institutes of Health Stroke Scale, NIHSS score), and disability (modified Rankin Scale, mRS score) in patients with a cerebrovascular event. METHODS: We conducted a retrospective analysis based on data prospectively collected from consecutive patients with a cerebrovascular event who underwent 12­lead ECG at admission to the Verona Stroke Unit. RESULTS: Of the 63 patients included in the study, 55 had ischemic stroke and 8 intracranial hemorrhage. TpTe (time between the peak and the end of the T wave) and TpTe/QTc (TpTe/corrected time between the start of the Q wave and the end of the T wave) in lead V5 were higher in intracranial hemorrhage than in ischemic stroke (p = 0.03 and p = 0.04, respectively) and QT max (the longest QT calculated in the 12 leads) was higher in patients with involvement of insula (p ≤ 0.01). A correlation was found between QTc max and NIHSS score at admission (p = 0.02), QT max and NIHSS score at discharge (p = 0.05), and QT max and mRS score at discharge (p = 0.02). CONCLUSIONS: TpTe and TpTe/QTc in V5 lead were associated with intracranial hemorrhage and QT max was associated with involvement of insula. The prolongation of QT was correlated with neurological severity and disability.

Electrocardiographic P-Wave Duration, QT Interval, T Peak to End Interval and Tp-e/QT Ratio in Pregnancy with Respect to Trimesters.

BACKGROUND: P-wave duration helps to determine the risk of atrial arrhythmia, especially atrial fibrillation. QT interval, T peak to end interval (Tp-e), and Tp-e/QT ratio are electrocardiographic indices related to ventricular repolarization which are used to determine the risk of ventricular arrhythmias. We search for any alterations in electrocardiographic indices of arrhythmia in the pregnancy period with respect to trimesters. METHODS: We enrolled 154 pregnant and 62 nonpregnant, healthy women into this cross-sectional study. Maximum and minimum P-wave durations (Pmax, Pmin), and QT intervals (QTmax, QTmin) were measured from 12 leads. QT measurements were corrected using Fridericia (QTc-Fr) and Bazett's (QTc-Bz) correction. Tp-e interval was obtained from the difference between QT interval, and QT peak interval (QTp) measured from the beginning of the QRS until the peak of the T wave. Tp-e/QT ratio was calculated using these measurements. RESULTS: Pmax were 93.0 ± 9.1, 93.9 ± 8.9, 97.9 ± 5.6, 99.0 ± 6.1 in nonpregnant women, first, second, third trimesters of pregnancy, respectively (P = 0.001); whereas Pmin values were not significantly different. QTc-Fr max were 407.4 ± 14.2, 408.5 ± 16.1, 410.1 ± 13.1, 415.1 ± 10.1 (P = 0.007); Tp-e were 72.7 ± 6.2, 73.2 ± 6.5, 77.2 ± 8.9, 87.2 ± 9.6 (P < 0.001); and Tp-e/QT were 0.17 (0.14-0.20), 0.17 (0.14-0.20), 0.18 (0.15-0.23), 0.20 (0.16-0.25) in nonpregnant women, first, second, and third trimesters of pregnancy respectively (P < 0.001). None of the participants experienced any arrhythmic event. CONCLUSIONS: P-wave duration is prolonged in the second trimester, and resumes a plateau thereafter. Maximum QTc interval, Tp-e interval and Tp-e/QT ratio are increased in the late pregnancy. Although these indices are altered during the course of pregnancy, they all remain in the normal ranges.

Ibutilide and novel indexes of ventricular repolarization in persistent atrial fibrillation patients.

AIM: To examine the effect of ibutilide on novel indexes of repolarization in patients with persistent atrial fibrillation (AF). METHODS: We studied consecutive patients scheduled for elective electrical cardioversion. Intravenous ibutilide (1 + 1 mg) was administered before the electrical cardioversion while close electrocardiographic (ECG) monitoring was performed. ECG indexes such as corrected QT interval (QTc), the interval from the peak until the end of T wave (Tpe), and the Tpe/QT ratio were measured before ibutilide infusion and 10 min after the end of infusion. RESULTS: The final study population consisted of 20 patients (mean age: 67.1 ± 9.9 years, 10 men). Six patients were cardioverted pharmacologically and did not proceed to electrical cardioversion. Two patients developed short non-sustained episodes of torsades de pointes ventricular tachycardia. All but one of the aforementioned ECG indexes increased significantly after ibutilide administration. In specific, the QTc interval increased from 442 ± 29 to 471 ± 37 ms (P = 0.037), the Tpe interval in precordial leads from 96 ms (range 80-108 ms) to 101 ms (range 91-119 ms) (P = 0.021), the Tpe interval in lead II from 79 ms (range 70-88 ms) to 100 ms (range 87-104 ms) (P < 0.001), the Tpe/QT ratio in precordial leads from 0.23 ms (range 0.18-0.26 ms) to 0.26 ms (range 0.23-0.28 ms) (P = 0.028), and the Tpe interval dispersion from 25 ms (range 23-30 ms) to 35 ms (range 27-39 ms) (P = 0.012). However, the Tpe/QT ratio in lead II did not change significantly. CONCLUSION: Ibutilide increases the duration and dispersion of ventricular repolarization. The prognostic value of Tpe and Tpe/QT in the setting of drug-induced proarrhythmia needs further study.