Common Genetic Variants Modulate the Electrocardiographic Tpeak-to-Tend Interval.

Sudden cardiac death is responsible for half of all deaths from cardiovascular disease. The analysis of the electrophysiological substrate for arrhythmias is crucial for optimal risk stratification. A prolonged T-peak-to-Tend (Tpe) interval on the electrocardiogram is an independent predictor of increased arrhythmic risk, and Tpe changes with heart rate are even stronger predictors. However, our understanding of the electrophysiological mechanisms supporting these risk factors is limited. We conducted genome-wide association studies (GWASs) for resting Tpe and Tpe response to exercise and recovery in ∼30,000 individuals, followed by replication in independent samples (∼42,000 for resting Tpe and ∼22,000 for Tpe response to exercise and recovery), all from UK Biobank. Fifteen and one single-nucleotide variants for resting Tpe and Tpe response to exercise, respectively, were formally replicated. In a full dataset GWAS, 13 further loci for resting Tpe, 1 for Tpe response to exercise and 1 for Tpe response to exercise were genome-wide significant (p ≤ 5 × 10-8). Sex-specific analyses indicated seven additional loci. In total, we identify 32 loci for resting Tpe, 3 for Tpe response to exercise and 3 for Tpe response to recovery modulating ventricular repolarization, as well as cardiac conduction and contraction. Our findings shed light on the genetic basis of resting Tpe and Tpe response to exercise and recovery, unveiling plausible candidate genes and biological mechanisms underlying ventricular excitability.

Prolonged T-peak to T-end Interval Predicts Implantable Cardioverter Defibrillator Therapy in Patients With Cardiac Sarcoidosis.

BACKGROUND: The association between the T-peak to T-end interval (Tp-e) and ventricular arrhythmia (VA) events in cardiac sarcoidosis (CS) is unknown. The purpose of this study was to investigate whether Tp-e was associated with VA events in CS patients with implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds).Methods and Results: We retrospectively studied 50 patients (16 men; mean [±SD] age 56.3±10.5 years) with CS and ICD/CRT-D. The maximum Tp-e in the precordial leads recorded by a 12-lead electrocardiogram after ICD/CRT-D implantation was evaluated. The clinical endpoint was defined as appropriate ICD therapy. During a median follow-up period of 85.0 months, 22 patients underwent appropriate therapy and 10 patients died. Kaplan-Meier analysis revealed that the probability of the clinical endpoint was 28.3% at 2 years and 35.3% at 4 years. The optimal cut-off value of the Tp-e for the prediction of the clinical endpoint was 91 ms, with a sensitivity of 72.7% and a specificity of 87.0% (area under the curve=0.81). Multivariate Cox regression analysis showed that Tp-e ≥91 ms (hazard ratio [HR] 5.10; 95% confidence interval [CI] 1.99-13.1; P<0.001) and a histological diagnosis of CS (HR 3.84; 95% CI 1.28-11.5; P=0.016) were significantly associated with the clinical endpoint. CONCLUSIONS: Tp-e ≥91 ms was a significant predictor of VA events in patients with CS and ICD/CRT-D.

Variability of Myocardial Repolarization in Pediatric Patients with a Ventricular Septal Defect.

In patients with a ventricular septal defect, left-to-right shunting increases the left ventricular preload. This pathological change affects myocardial depolarization and repolarization and has the potential to evoke arrhythmogenic substrates. We examined the effect of ventricular septal defects on myocardial repolarization by investigating the variability in the repolarization interval. This retrospective study included 19 patients (mean age, 1.8 ± 2.1 years) who underwent surgical closure (mean left-to-right shunt ratio, 2.60 ± 0.55) and 26 age-matched healthy controls from 2008 to 2015. Using preoperative electrocardiograms, we studied two electrocardiographic parameters (heart rate-corrected repolarization and variability of repolarization) and four repolarization intervals (QT, JT, J point to T peak [JTp], and T peak to T end [Tp-e] intervals). The variability index (VI) was calculated from the logarithm of the ratio of the repolarization parameter variance to heart rate variance. The various measures were compared between the patients and controls, and significant differences were found in the corrected QT, JTp, and Tp-e intervals (p < 0.05). The VI of the four intervals also showed significant differences (patients vs. CONTROLS: QTVI, -0.55 ± 0.61 vs. -1.10 ± 0.53; JTVI, -0.33 ± 0.60 vs. -0.86 ± 0.57; JTpVI, -0.15 ± 0.78 vs. -0.73 ± 0.56; Tp-eVI, 0.75 ± 0.70 vs. 0.11 ± 0.73, respectively; p < 0.05). No correlation was found between the QTVI and corrected QT interval using linear regression analysis. These repolarization characteristics provide not only electrophysiological indices but also a new index with which to assess the pathophysiology of congenital heart disease.

The electrophysiological index can effectively predict subsequent coronary artery aneurysm in children with Kawasaki disease.

Objectives: The Gunma score is used to predict the severity of Kawasaki disease (KD), including coronary artery aneurysm (CAA) as a cardiac complication, in Japan. Additionally, the characteristic ratio of ventricular repolarization (T-peak to T-end interval to QT interval [Tp-e/QT]) on a surface electrocardiogram reflects myocardial inflammation. This study aimed to determine whether the Tp-e/QT can be used to predict CAA in children with KD. Methods: We analyzed chest surface electrocardiograms of 112 children with KD before receiving intravenous immunoglobulin therapy using available software (QTD; Fukuda Denshi, Tokyo, Japan). Results: The Tp-e/QT (lead V5) was positively correlated with the Gunma score (r=0.352, p<0.001). The Tp-e/QT was larger in patients with CAA (residual CAA at 1 month after onset) than in those without CAA (0.314±0.026 versus 0.253±0.044, p=0.003). A receiver operating characteristic curve analysis was performed to assess whether the Gunma score and Tp-e/QT could predict subsequent CAA. The area under the curve of the Gunma score was 0.719 with the cutoff set at 5 points. The area under the curve of the Tp-e/QT was 0.892 with a cutoff value of 0.299. The fit of the prediction models to the observed probability was tested by the Hosmer-Lemeshow test with calibration plots using Locally weighted scatterplot smoothing (LOESS) fit. The Gunma score (p=0.95) and Tp-e/QT (p=0.95) showed a good fit. Conclusions: The Tp-e/QT is a useful biomarker in predicting coronary aneurysm complications in KD.

Exercise-induced electrocardiographic changes after treadmill exercise testing in healthy children: A comprehensive study.

Background: Treadmill exercise testing is a crucial diagnostic tool for evaluating congenital and acquired heart disease in the pediatric population. This study aimed to perform a comprehensive evaluation of exercise-induced electrocardiographic (ECG) changes in children. Although there are numerous studies on exercise testing in various cardiac pathologies, studies on exercise-induced ECG changes in normal children with coverage of all ECG parameters of atrial and ventricular depolarization and repolarization are very scant, if any. Aims and Objectives: This study aimed to investigate the exercise-induced ECG changes in healthy children and evaluate the effects of gender and four different formulas of heart rate correction of Bazett, Fridericia, Framingham and Hodges on ventricular repolarization parameters pre-and post-exercise. Materials and Methods: Between April 2019 and April 2020, all children with normal electrocardiogram, echocardiogram and exercise test, high-quality ECG tracings and consent for participation were enrolled in this prospective study. Twenty electrocardiographic parameters were measured and 25 indices were calculated. P-value < 0.05 was considered significant. Results: Seventy-four healthy children were studied. Amplitudes of P, S, and T waves increased significantly after the exercise. All durations, except P wave time to peak and T peak -T end /QT (Tp-e/QT) interval decreased significantly with exercise. Generally, the parameters of ventricular repolarization were not statistically significant between males and females. There were significant differences among the heart-rate corrected values of intervals of QTc, QoTc, JTc, J point to peak T and Tp-e/QTc by various formulas. There was no U wave either at pre-exercise or post-exercise. QT interval was shortened by 24.6 % ± 12.1 % with exercise. The ECG-derived estimated duration of mechanical systole and diastole decreased with exercise. The percentage of decrease in diastole was more than systole (43.79 %± 13.31% versus 33.74% ±15.79 %, respectively, P-value < 0.001). Conclusion: Diastolic time decreased more than systolic time with exercise and systolic time to diastolic time increased with exercise. Hodges' and Fridericia's formulas resulted in the longest and shortest QT and QoT, JT, and JTP, respectively. Thus, using a single value as the cut-off for long QT syndrome can lead to under or over-diagnosis. Nomograms incorporating data on age, heart rate, and heart rate correction formula are indispensable for accurate long QT diagnosis. Furthermore, gender differences in ventricular repolarization parameters are not generally present in 5 to 14-year-old healthy children. The lack of U wave in this study may implicate the need for more careful investigation in the presence of U wave in the treadmill exercise testing of healthy children.

T-Peak to T-End Improvements After Beta-Blocker Administration in Peripartum Cardiomyopathy Patients.

BACKGROUND: Many studies have shown that T-peak to T-end (TPTE) interval was associated with sudden cardiac events. Peripartum cardiomyopathy (PPCM) causes reversible left ventricle systolic dysfunction which may deteriorate into sudden cardiac death. This study aimed to evaluate beta-blocker as an antiarrhythmic agent to improve TPTE interval as a prognostic value of sudden cardiac death. METHODS: A cohort experimental prospective study was performed. The PPCM was diagnosed from the emergency ward. A total of 54 cases were identified from 2014 to 2016. Thirty-four patients were followed up for further analysis. Electrocardiograms were conducted in all the patients, and TPTE interval was measured. After a follow-up of 6 months of beta-blocker treatment, the echocardiography and TPTE interval were measured again to obtain the repolarization heterogeneity. RESULTS: The mean age of subjects was 32 ± 6.4 years. The mean left ventricular ejection fraction (LVEF) was 32.24±6.3%. The mean TPTE interval was 123.7 ± 28.2 ms. After 6 months of beta-blocker administration, the mean LVEF was 58.26±4.4% and the mean TPTE was 98.7 ± 39.5 ms. The paired t-test showed a significant difference between TPTE interval pre- and post-administration of beta-blocker (P value < 0.001). CONCLUSIONS: There is an improvement of TPTE in PPCM patients after 6 months of beta-blocker administration. Administration of beta-blocker in PPCM patients is expected to prevent sudden cardiac death in PPCM populations.

Evaluation of QT dispersion and T-peak to T-end interval in patients with early-stage sarcoidosis.

INTRODUCTION AND AIM: Sarcoidosis increases inhomogeneity in ventricular repolarization due to the presence of sarcoid granuloma, which significantly correlates with ventricular fibrillation. Various studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (T-peak to T-end [Tpe] interval) may correspond to the transmural dispersion of repolarization and that increased Tpe interval and Tpe/QT ratio are associated with malignant ventricular arrhythmias. The present study hypothesized that QT and Tpe intervals are significantly prolonged in sarcoidosis patients without apparent cardiac involvement. METHODS: The study population consisted of 54 patients (37 female; mean age 43.4±10.6 years) under follow-up for sarcoidosis and 56 healthy subjects (37 female; mean age 42.4±8.6 years). RESULTS: There was no statistically significant difference between the groups in maximum QT interval, QT dispersion or corrected QT (QTc) interval, but QTc dispersion and Tpe interval were significantly prolonged in the sarcoidosis group compared to the control group (QTc dispersion 59.9±22.5 and 44.4±23.8, respectively, p=0.001; Tpe interval 79.4±9.3 and 70.7±7.03, respectively, p<0.001). We also found that the Tpe/QT ratio was significantly higher in sarcoidosis patients compared to the control group (0.21±0.02 and 0.18±0.23, respectively, p<0.001). CONCLUSION: Our study revealed that QTc dispersion, Tpe and Tpe/QT ratio were greater in sarcoidosis patients compared to the control group. To our knowledge, the present study is the first to use Tpe interval analysis in patients without cardiac involvement in sarcoidosis. Tpe interval and Tpe/QT ratio may be promising markers for cardiovascular morbidity and mortality due to ventricular arrhythmias in patients with and without cardiac involvement in sarcoidosis.

Effect of Trimetazidine on T-peak to T-end Interval in Patients With Unstable Angina Pectoris After Percutaneous Coronary Intervention / 中国循环杂志

Objective: To explore the effect of trimetazidine (TMZ) on T-peak (Tp) to T-end (Te) interval of resting ECG in patients with unstable angina pectoris (UAP) after percutaneous coronary intervention (PCI). Methods: We investigated 94 UAP patients with PCI and 76 of them ifnished the study as 2 groups. Control group,n=42, the patients received conventional treatment, and TMZ group,n=34, in addition to conventional treatment, the patients received TMZ 60 mg at 0.5 to 1 hour before PCI. The changes of Tp to Te interval before and after PCI were calculated, serum levels of creatine kinase (CK), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) at before and at 6, 24 hours after PCI were compared between 2 groups. Ventricular arrhythmia was recorded during PCI. Results: Both groups had shortened Tp to Te intervals after PCI, and TMZ group had more shortened Tp to Te interval, bothP0.05. The occurrence rate of ventricular arrhythmia in Control group was higher than that in TMZ group (12.52% vs 5.16%) during PCI,P<0.05. Compared with Control group, TMZ group had lower levels of CK, CK-MB and cTnI at 6, 24 hours after PCI, allP<0.05. Conclusion: TMZ could decrease Tp to Te interval of resting ECG, prevent ventricular arrhythmia and reduce the relevant myocardial injury in UAP patients after PCI.