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In children with hypertrophic cardiomyopathy (HCM), the genotype–phenotype association of abnormal electrocardiographic (ECG) features in the backdrop of gene positivity has not been well described. This study aimed to describe the abnormal ECG findings in children with HCM harboring who have genetic variants and determine the association with major adverse cardiac events (MACE). We retrospectively analyzed 81 variants-positive, phenotype-positive (V+P+), 66 variant-positive, phenotype-negative (V+P−), and 85 non-sarcomeric subjects. We analyzed ECG findings and clinical outcomes in the three groups of subjects. Repolarization abnormalities (ST and T wave changes) and pathologic Q waves were the most common abnormalities in variant and non-sarcomeric subjects. The V+P+ group showed higher occurrence of ST segment changes and T wave abnormalities compared to V+P− group. Independent predictors of MACE included ST segment changes (OR 3.54, CI 1.20–10.47, p = 0.022). T wave changes alone did not predict outcome (OR 2.13, CI 0.75–6.07, p = 0.157), but combined repolarization abnormalities (ST+T changes) were strong predictors of MACE (OR 5.84, CI 1.43–23.7, p = 0.014) than ST segment changes alone. Maximal wall z score by echocardiography was a predictor of MACE (OR 1.21, CI 1.07–1.37, p = 0.002). Despite the presence of significant myocardial hypertrophy (z score > 4.7), voltage criteria for LVH were much less predictive. In the non-sarcomeric group, RVH was significantly associated with MACE (OR 3.85, CI 1.08–13.73, p = 0.038). These abnormal ECG findings described on the platform of known genetic status and known myocardial hypertrophy may add incremental value to the diagnosis and surveillance of disease progression in children with HCM. Select ECG findings, particularly repolarization abnormalities, may serve as predictors of MACE in children. [ABSTRACT FROM AUTHOR]

Background: Populations of in silico electrophysiological models of human cardiomyocytes represent natural variability in cell activity and are thoroughly calibrated and validated using experimental data from the human heart. The models have been shown to predict the effects of drugs and their pro-arrhythmic risks. However, excitation and contraction are known to be tightly coupled in the myocardium, with mechanical loads and stretching affecting both mechanics and excitation through mechanisms of mechano-calcium-electrical feedback. However, these couplings are not currently a focus of populations of cell models. Aim: We investigated the role of cardiomyocyte mechanical activity under different mechanical conditions in the generation, calibration, and validation of a population of electro-mechanical models of human cardiomyocytes. Methods: To generate a population, we assumed 11 input parameters of ionic currents and calcium dynamics in our recently developed TP + M model as varying within a wide range. A History matching algorithm was used to generate a non-implausible parameter space by calibrating the action potential and calcium transient biomarkers against experimental data and rejecting models with excitation abnormalities. The population was further calibrated using experimental data on human myocardial force characteristics and mechanical tests involving variations in preload and afterload. Models that passed the mechanical tests were validated with additional experimental data, including the effects of drugs with high or low pro-arrhythmic risk. Results: More than 10% of the models calibrated on electrophysiological data failed mechanical tests and were rejected from the population due to excitation abnormalities at reduced preload or afterload for cell contraction. The final population of accepted models yielded action potential, calcium transient, and force/shortening outputs consistent with experimental data. In agreement with experimental and clinical data, the models demonstrated a high frequency of excitation abnormalities in simulations of Dofetilide action on the ionic currents, in contrast to Verapamil. However, Verapamil showed a high frequency of failed contractions at high concentrations. Conclusion: Our results highlight the importance of considering mechanoelectric coupling in silico cardiomyocyte models. Mechanical tests allow a more thorough assessment of the effects of interventions on cardiac function, including drug testing. [ABSTRACT FROM AUTHOR]

Background: In post-ST-segment elevation myocardial infarction (STEMI) patients, the indices of repolarization on electrocardiogram (ECG) have shown promise for the prediction of death and malignant arrhythmias. In our study, we analyzed prospectively, in patients with STEMI undergoing reperfusion therapy, the acute effects of the reperfusion on the Tpeak-Tend (TpTe) and its predictive value for 30-day mortality, ventricular arrhythmias, and heart failure. Materials and Methods: We studied 75 STEMI patients aged 18-80 years admitted to Nizam's Institute of Medical Sciences, Hyderabad, over 6 months. ECGs were taken before and 90 min after reperfusion. TpTe interval was measured before (pre-TpTe) and after reperfusion (post-TpTe). 24-h Holter monitoring was recorded within 72 h of reperfusion to look for any arrhythmias. Patients were followed up for a period of 30 days, and all the major adverse cardiac events (MACE) if any, were noted. Results: In the primary percutaneous transluminal coronary angioplasty (PTCA) group, the mean change in TpTe after intervention was 19.7 ± 16.7 ms, whereas in thrombolysis group, it was 10.7 ± 13.8; and the difference was statistically significant (P < 0.05), suggesting the superiority of primary PTCA compared to thrombolysis. When pre-TpTe interval was compared between who survived (69) and who succumbed (09), higher values were seen in patients who succumbed to death (115 ± 5.48) versus (88 ± 16.5) (P < 0.05). Pre-TpTe value of 105 had 100% sensitivity and 83% specificity in predicting mortality. Conclusion: Primary PTCA was superior to thrombolysis in reducing the TpTe interval and MACE events. The pre-TpTe interval could predict 30-day mortality and ventricular arrhythmias in the immediate and late period after revascularization in STEMI. [ABSTRACT FROM AUTHOR]

The aim of present study is to evaluate the predictive value of QTc dispersion, Tp-Te interval and Tp-Te/QT ratio for idiopathic monomorphic outflow tract ventricular tachycardia (VT) occurrence in patients with frequent idiopathic outflow tract premature ventricular complexes (PVCs). A total of 180 patients (49.2 ± 13.6 years, 74 male) who had undergone outflow tract PVC ablation between 01 January 2015 and 01 November 2018 constituted our study population. Patients with isolated outflow tract PVC without any VT recording on Holter recordings and without any inducible VT at EPS were classified as isolated PVC group. Patients with any episode of VT that has the same morphology with outflow tract PVC were classified as nonsustained or sustained VT groups based on the duration of VT episode. QTc dispersion, Tp-Te and Tp-Te/QT ratio values were calculated and compared between groups. There were 116 patients with isolated PVC, 35 patients with nonsustained VT and 29 patients with sustained VT. QTc dispersion, Tp-Te and Tp-Te/QT ratio values were significantly lower in patients with isolated PVC compared to patients with nonsustained or sustained VT episodes. Tpeak to Tend interval greater than 110.5 msec on derivation V6 predicted VT occurrence with 93.8% sensitivity and 82.8% specificity. Tpeak to Tend/QT interval greater than 0.27 on derivation V6 predicted VT occurrence with 93.8% sensitivity and 0.81% specificity. Tp-Te interval and Tp-Te/QT ratio on derivation V6 may aid in prediction of presence of outflow tract VT in clinical practice. [ABSTRACT FROM AUTHOR]

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Aims: Significant T wave inversion in young asymptomatic athletes is rare but poses a significant clinical challenge. Pre-participation sports screening programs identify such subjects. Clinical concern that such ECG changes represent an occult cardiomyopathy or forme fruste hypertrophic cardiomyopathy leads to diagnostic and therapeutic dilemma. We sought to genotype a cohort of such subjects with a normal cardiac phenotype identified in our unit over a 3-year period. Methods: Ten athletes were referred from external screening. All exhibited deep T wave inversion inferolaterally. All had negative family history for sudden death and had a normal phenotype. A panel of 133 cardiac genes were screened. Results: Ten male subjects with mean age of 39 years were screened. Seven had no evidence of mutations. Three subjects demonstrated variants of uncertain significance in 5 different genes: alpha-2-actinin (ACTN2), myopalladin (MYPN), the calcium channel genes CACNA1C and TRPM4 and potassium channel gene KCNQ1. The variants found have not been described in cardiomyopathies or channelopathies. At 3-year follow-up, one patient had undergone detraining, and his ECG showed complete resolution of all T wave changes. He did not have any demonstrated variants. Conclusions: The absence of mutations in target genes and heterogeneous sequence variations identified in this study suggest that inferolateral T wave inversion in athletes without a phenotype may potentially represent a benign repolarization syndrome related to athletic adaptation. This was the first study to assess a phenotype-genotype correlation in this population. Further genetic studies need to be undertaken in this area. [ABSTRACT FROM AUTHOR]

Objective: In recent years, there has been worldwide recognition of the problems associated with Human Immunodeficiency Virus (HIV) infection and Acquired Immune Deficiency Syndrome (AIDS). The prevalence of cardiovascular disease in the HIV-infected population is increasing. Repolarization abnormalities, the significant contributor to life-threatening arrhythmias and mortality, are the most frequent electrocardiographic changes in this population. This study aimed to evaluate the changes in Tp-e interval, Tp-e/QT and Tp-e/corrected QT (QTc) ratios, and traditional electrocardiographic features of electrical dispersion in adults infected with HIV.Subjects and Methods: A total of 235 participants were selected in the current study. The HIV group consisted of 85 subjects (median age 36 years [25-48], and the control group included 150 individuals (median age 39 years [27-51]). Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were measured by the 12-lead electrocardiogram.Results: Tp-e interval, cTp-e interval, and Tp-e/QT and Tp-e/QTc ratios were significantly higher in HIV patients compared to the control group (p = 0.006, p = 0.004, p = 0.003, and p = 0.002, respectively). In correlation analysis, there was inverse correlation between the mean cTp-e interval and CD4 count and Tp-e/QTc ratios and CD4 count (r = - 0.407, p < 0.001, r = - 0.416, p < 0.001, respectively). Besides, there was correlation between the mean cTp-e interval and high-sensitivity C-reactive protein (hsCRP) and Tp-e/QTc ratios and hsCRP (r = 0.403, p = 0.001, r = 0.406, p = 0.001, respectively).Conclusion: Our study revealed that the cTp-e interval, Tp-e/QT and cTp-e/QT ratios were prolonged and correlated to the severity of the disease in HIV-infected patients. Our findings may shed light on the cTp-e interval and Tp-e/QTc ratio and lead to further studies showing a relationship with ventricular arrhythmias and mortality in HIV-infected individuals. [ABSTRACT FROM AUTHOR]

Prompt diagnosis of acute ST segment elevation myocardial infarction (STEMI) by the initial ECG is important in order to perform an urgent coronary angiography as soon as possible and achieve successful revascularization, therewith improving mortality and morbidity. Several diseases and conditions can mimic an acute myocardial infarction (AMI) but may not benefit from a (percutaneous) revascularization strategy. This narrative clinical review will discuss the ECG features of some of the causes of nonischemic ST segment elevation to facilitate early recognition, prevent wrongful diagnosis and improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective: Recent studies utilizing fetal magnetocardiography have demonstrated the efficacy of corrected QT interval (QTc) measurement for in utero diagnosis and prognosis of long QT syndrome, a leading cause of sudden death in early life. The objective of the study was to formulate and test a novel statistical estimation method to detect the end of the fetal T-wave and thereby improve the accuracy of fetal QT interval measurement. Methods: To detect the end of the T-wave, we apply a sequential composite hypothesis test to decide when the T-wave has returned to baseline. The method uses the generalized likelihood ratio test in conjunction with a low-rank spatiotemporal model that exploits the repetitive nature of cardiac signals. The unknown model parameters are determined using maximum likelihood estimation. Results: In realistic simulations, the detector was shown to be accurate to within 10 ms (95% prediction interval), even at noise-to-signal ratios as high as 6. When applied to real data from normal fetuses, the detector agreed well with measurements made by cardiologists ( $-$1.4 $\pm$ 6.9 ms). Conclusions: The method was effective and practical. Detector performance was excellent despite the continual presence of strong maternal interference. Significance: This detector serves as a valuable adjunct to traditional measurement based on subjective assessment. [ABSTRACT FROM PUBLISHER]

Background/aim: Myocarditis in the acute phase usually presents with sinus tachycardia but many other arrhythmias might be seen as well. In this study we aimed to investigate repolarization abnormalities in baseline ECG of patients with myocarditis for the first time. Materials and methods: Thirty patients diagnosed with myocarditis and 25 healthy age-matched controls were included. Two different cardiologists measured corrected QT (QTc), QT dispersion (QTd), QT peak (QTp), T wave peak to T wave end (TpTe), TpTe/QT ratio, and TpTe/QTc ratio in 12-lead ECG. Results: When compared with the control group, QTp (P: 0.021), QT (P: 0.003), TpTe (P < 0.001), TpTe/QTc ratio (P < 0.001), and TpTe/QT ratio (P: 0.005) were significantly higher in patients with myocarditis. A comparison of receiver operating characteristic (ROC) curves was conducted using the Hanley and McNeil method. The area under the curve (AUC) of the electrocardiographic characteristics QT (AUC: 0.736; 95% CI [0.600-0.846]), QTP (AUC: 0.680; 95% CI [0.540-0.799]), and TpTe (AUC: 0.771; 95% CI [0.638-873]) and TpTe/QTc (AUC: 0.774; 95% CI [0.641-0.876]) and TpTe/QT (AUC: 0.726; 95% CI [0.589-0.838]) in myocarditis were not significantly different from each other but all of them were different from 0.5. Conclusion: Baseline ECGs of patients with myocarditis were associated with repolarization abnormalities. These novel findings may be one of the reasons underlying arrhythmic events in patients with myocarditis. [ABSTRACT FROM AUTHOR]

Objective This study analyses dynamic changes in dispersion of ventricular repolarization over the time course of takotsubo cardiomyopathy (TC), and their relationships with clinical features and life-threatening arrhythmias. Methods and results All consecutive patients admitted to our division between January 2008 and December 2011 with a diagnosis of TC were analysed. Patients with prior myocardial infarction, symptoms-onset-to-admission time greater than 12 hours, an implanted pacemaker, or under treatment with drugs affecting QT interval, were excluded. Standard 12-lead ECG recordings during the acute, subacute and chronic phases were collected for each patient. Twentyfour patients (23 women, 63 ± 14 years) were included in our analysis. Only one patient experienced ventricular arrhythmias (4.2%). Significant increases were observed in QT and QTc intervals (from 420 ± 423 to 505 ± 66 ms, P < 0.00001, and from 479 ± 33 to 551 ± 51 ms, P < 0.00001, respectively), QT dispersion (from 59 ± 18 to 100 ± 44 ms, P = 0.0006), Tpeak-to-Tend (from 82 ± 20 to 123 ± 39 ms, P = 0.00006) and Tpeak-to-Tend/QT (from 0.20 ± 0.33 to 0.26 ± 0.57, P = 0.0003) during the subacute phase. All these parameters returned to baseline values in the chronic phase and did not show any significant differences between the acute and chronic phases. Conclusions A marked increase in QTc, QT dispersion, Tpeak-to-Tend and Tpeak-to-Tend/QT was observed during the subacute phase; this increase was transient and reverted in all patients before hospital discharge. Of note, these findings were not associated with an increased risk of life-threatening arrhythmias. [ABSTRACT FROM AUTHOR]

T-wave alternans (TWA) is an indicator of cardiac instability and is associated with life-threatening ventricular arrhythmias. Detection of TWA in the adult has been widely investigated and is used routinely for cardiac risk assessment. Detection of TWA in the fetus, however, is much more difficult due to the low amplitude and variable configuration of the signal, the presence of strong interferences, and the brevity of fetal TWA episodes. In this paper, we present a statistical detector based on the generalized likelihood ratio test that is designed for detection of TWA in the fetus. The performance of the detector is evaluated by constructing receiver-operator characteristic curves, using simulated data and real data from subjects with macroscopic TWA. The detector is capable of detecting TWA episodes as brief as 20 beats. The detection performance is improved significantly by modeling the fetal T-wave as a low-rank, low bandwidth signal, and using maximum likelihood estimation to estimate the model parameters. This approach enables all of the data to be used to estimate the noise statistics, providing highly effective suppression of interference, including maternal interference. The method is suitable for routine use because it can be applied to raw, unprocessed recordings, allowing automated analysis of extended fetal magnetocardiography recordings. [ABSTRACT FROM PUBLISHER]

We examined whether there is a relationship between repolarization abnormalities on electrocardiography (EKG) and deformation abnormalities by echocardiography. Analysis of baseline EKGs and mechanical (echo-based deformation) changes was performed in 128 patients with a clinical diagnosis of hypertrophic cardiomyopathy (HCM). Patients with left ventricular hypertrophy (LVH) or repolarization abnormalities had higher septal thickness when compared to patients with normal EKG. Patients with EKG evidence of LVH or QT prolongation had lower systolic velocity, systolic strain, systolic strain rate, late diastolic velocity, and late diastolic strain rate than patients with a normal EKG. Patients with strain pattern or ST depression/T-wave inversion had lower systolic velocity, systolic strain, systolic strain rate, early diastolic velocity, and late diastolic velocity when compared to patients with normal EKGs. LVH and repolarization abnormalities on surface EKG are markers of impaired systolic and diastolic mechanics in HCM. [ABSTRACT FROM AUTHOR]

In the failing heart general specific (e.g., Q-waves after acute myocardial infarction, persistentST-elevations in post-myocardial infarction left ventricular aneurysm) and unspecific ECG changes (e.g.,left bundle branch block, right bundle branch block, ST-T-alterations due to digitalis glycosides or antiarrhythmicdrugs) may be seen in the conventional 12-lead ECG. In addition, atrial and ventricular tachy-arrhythmias maybe detected and quantified by 24-hour-Holter ECG recordings, that may be relevant for a worse prognosis of patientswith congestive heart failure. Heart rate variability as the most relevant derived ECG parameter of sympathetictone fluctuations may be of important prognostic significance in congestive heart failure patients. An abnormalsignal averaged P-wave duration may predict the incidence of atrial fibrillation, as may apply to QRS-prolongationand/or ventricular late potentials in the signal averaged ECG for the incidence of serious life-threateningventricular tachy-arrhythmias or death from pump failure. Last but not least, cardiac repolarization abnormalitiesmay be detected by QT dispersion-, QT-/QTc-fluctuation- or T-wave alternans studies, but the true prognosticsignificance of these parameters for predicting sudden cardiac death or death from pump failure in patients withcongestive heart failure remains unclear. [ABSTRACT FROM AUTHOR]

Introduction: Abnormalities of ventricular repolarization leading to ventricular arrhythmias place children with long QT syndrome at high risk for sodden death. Dispersion of the QT (QTd) and JT (JTd) intervals, as markers of cardiac electrical heterogeneity, may be helpful in evaluating children with long QT syndrome and Identifying a subset of patients at high risk for development of critical ventricular arrhythmias (ventricular tachycardia, torsades de pointes, and/or cardiac arrest). Methods and Results: The QTd and JTd intervals in 39 children with long QT syndrome were compared to those of 50 normal age-matched children. In the long QT syndrome group, QTd measured 81 ± 70 msec compared to 28 ± 14 msec in the control group (P < 0.05), and JTd in the long QT syndrome group was 80 ± 69 msec compared to 25 ± 15 msec in the control group (P < 0.05). Conclusion: Children with long QT syndrome have an Increased QTd and JTd when compared to normal controls. A QTd or JTd ≥ 55 msec correlates with the presence of critical ventricular arrhythmias. These ECG measures of dispersion can be useful in stratifying children with the long QT syndrome who are at higher risk for developing critical ventricular arrhythmias. [ABSTRACT FROM AUTHOR]