Heterogeneity Of Ventricular Repolarization Research Articles

Association Between Left Atrial Volume Index and Ventricular Repolarization Heterogeneity: A Cross-Sectional Study of a Healthy Chinese Population.

BackgroundElectromechanical coupling may play a significant role in the association between abnormal myocardial mechanics and heterogeneity of repolarization. This study sought to assess the potential relationship between the left atrial volume index (LAVI), which is an important marker of cardiac diastolic function, and ventricular repolarization variables, such as the QT interval, Tpeak-to-Tend (Tpe) interval and Tpe/QT ratio, in an apparently healthy Chinese population.MethodsThis was a community-based cross-sectional study conducted in Shenyang, China. A total of 414 healthy subjects aged 35–91 years, including 186 men (44.9%), were enrolled. In addition to performing clinical and laboratory measurements, all subjects underwent comprehensive echocardiography and standard 12-lead electrocardiography. Echocardiographic and electrocardiographic results were analysed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations.ResultsSubjects were divided into four groups according to quartile of LAVI levels (<16.0, 16.0–18.9, 19.0–22.5 and >22.5 mL/m2). Ventricular repolarization variables, such as QT interval and QTc interval, gradually increased with the progression from low to high LAVI levels (P<0.05). LAVI was positively and significantly correlated with the QT interval, the QTc interval, and the Tpe interval (P<0.01). After adjusting for age and other possible confounders, LAVI showed significant and independent associations with the QT interval and the QTc interval (P<0.001; P=0.003).ConclusionEchocardiographic LAVI is linearly associated with ventricular repolarization variables even in healthy people.

QT Dispersion and Drug-Induced Torsade de Pointes.

BackgroundAmiodarone causes less drug-induced torsade de pointes (TdP) compared to other class III antiarrhythmics. Two theories proposed for this finding include that amiodarone has less repolarization heterogeneity, and/or decreases early after depolarization (EADs). Corrected QT (QTc) dispersion as measured on a surface electrocardiogram (ECG) represents spatial heterogeneity of ventricular repolarization.ObjectiveThe purpose of this study was to analyze the difference in QT dispersion between amiodarone and other class III antiarrhythmics and to determine the etiology of TdP.MethodsThis was a retrospective, observational study at Montefiore Medical Center between January 2005 and January 2015. Inclusion criteria were adults >18 years on amiodarone, dofetilide, or sotalol with prolonged QT interval on 12-lead ECG. ECGs were reviewed by three blinded observers. QTc was calculated using the Bazett and Framingham formulas. QTc dispersion was calculated by subtracting the shortest from the longest QTc. Analysis of variance (ANOVA) was applied for comparison between antiarrhythmic groups with Bonferroni correction for multiple comparisons.ResultsA total of 447 ECGs were reviewed and 77 ECGs met inclusion criteria. The average QT dispersion for amiodarone, dofetilide, and sotalol was 0.050, 0.037, and 0.034, respectively (p=0.006) and the average QTc dispersion by Bazett was 0.053, 0.038, and 0.037 (p=0.008) and by Framingham was 0.049, 0.036, and 0.035 (p=0.009), respectively.ConclusionOur results show that given the increase in QT dispersion seen with amiodarone, heterogeneous ventricular repolarization as measured by QTc dispersion likely does not account for the lower incidence of drug-induced TdP seen with amiodarone. The ability of amiodarone to decrease EADs via sodium-channel blockade is more likely the explanation for its lower incidence of drug-induced TdP.

Frontal plane QRS-T angle may be a predictor for post-coronary artery bypass graft surgery atrial fibrillation

New-onset postoperative atrial fibrillation (POAF) is the most common arrhythmia following coronary artery bypass graft surgery (CABG) and is associated with prolonged hospitalization, stroke, and mortality. The frontal plane QRS-T [f(QRS-T)] angle, which is defined as the angle between the directions of ventricular depolarization (QRS-axis) and repolarization (T-axis), is a novel marker of ventricular repolarization heterogeneity. The f(QRS-T) angle is associated with adverse cardiac outcomes. In light of these findings, in this study, we aimed to investigate the potential relationship between the f(QRS-T) angle and POAF. 180 patients who underwent CABG between August 2017 and September 2018 were included in the study retrospectively. Two groups were established as patients who preserved postoperative sinus rhythm (n=130) and those who developed POAF (n=50). The f(QRS-T) angle and all other data were compared between groups. The fF(QRS-T) angle (p<0.001), SYNTAX score (p=0.039), serum high-sensitivity CRP levels (p=0.026), mean age (p<0.001), electrocardiographic left ventricular hypertrophy rate (LVH) (p=0.019), and hypertension rate (p=0.007) were higher, and the mean left ventricular ejection fraction (LVEF) (p<0.001) was lower in the POAF group. Multivariable logistic regression analyses demonstrated that lower LVEF (p=0.004), LVH (p=0.041), and higher age (p=0.008) and f(QRS-T) angle (p<0.001) were independently associated with POAF. High f(QRS-T) angle level is closely associated with the development of POAF. The f(QRS-T) angle can be a potential indicator of POAF.

Evaluation of thrombolytic treatment effect on frontal plane QRS-T angle in patients with acute pulmonary embolism : Anovel marker of successful thrombolysis.

Acute pulmonary embolism (APE) patients with hypotension and/or shock should be evaluated for thrombolytic therapy, and hemodynamics often improves after thrombolytic therapy. Frontal plane QRS‑T (f[QRS-T]) angle, which is between the directions QRS axis and Taxis, was described as anovel marker of ventricular repolarization heterogeneity. With right ventricular pressure overload, axis of heart may be affected and thrombolytic treatment may have an effect on this situation. This study aimed to investigate thrombolytic efficiency and effect on axis of heart by using f(QRS-T) angle. A total of 61APE patients treated with thrombolytics and 71APE patients treated without thrombolytics were included. Clinical findings and electrocardiogram (ECG) at diagnosis were collected. Second ECGs were included for patients with thrombolytics after 24 h, without thrombolytics after 72 h on average. No significant differences were observed with regard to gender, age, hypertension, diabetes and cardiovascular disease. In patients with thrombolytics, respiratory rate, heart rate and pulmonary artery systolic pressure were significantly higher; oxygen saturation (Sat O2) as well as systolic and diastolic pressure were significantly lower. f(QRS-T) was markedly higher in APE with right ventricular pressure overload and changed significantly after thrombolytic therapy. Right ventricular pressure overload in APE has an effect on f(QRS-T). In thrombolytic treatment, the change of f(QRS-T) angle may be amarker of successful thrombolysis.

Body Surface Mapping of Ventricular Repolarization Heterogeneity: An Ex-vivo Multiparameter Study.

BackgroundIncreased heterogeneity of ventricular repolarization is associated with life-threatening arrhythmia and sudden cardiac death (SCD). T-wave analysis through body surface potential mapping (BSPM) is a promising tool for risk stratification, but the clinical effectiveness of current electrocardiographic indices is still unclear, with limited experimental validation. This study aims to investigate performance of non-invasive state-of-the-art and novel T-wave markers for repolarization dispersion in an ex vivo model.MethodsLangendorff-perfused pig hearts (N = 7) were suspended in a human-shaped 256-electrode torso tank. Tank potentials were recorded during sinus rhythm before and after introducing repolarization inhomogeneities through local perfusion with dofetilide and/or pinacidil. Drug-induced repolarization gradients were investigated from BSPMs at different experiment phases. Dispersion of electrical recovery was quantified by duration parameters, i.e., the time interval between the peak and the offset of T-wave (TPEAK-TEND) and QT interval, and variability over time and electrodes was also assessed. The degree of T-wave symmetry to the peak was quantified by the ratio between the terminal and initial portions of T-wave area (Asy). Morphological variability between left and right BSPM electrodes was measured by dynamic time warping (DTW). Finally, T-wave organization was assessed by the complexity of repolarization index (CR), i.e., the amount of energy non-preserved by the dominant eigenvector computed by principal component analysis (PCA), and the error between each multilead T-wave and its 3D PCA approximation (NMSE). Body surface indices were compared with global measures of epicardial dispersion of repolarization, and with local gradients between adjacent ventricular sites.ResultsAfter drug intervention, both regional and global repolarization heterogeneity were significantly enhanced. On the body surface, TPEAK-TEND was significantly prolonged and less stable in time in all experiments, while QT interval showed higher variability across the interventions in terms of duration and spatial dispersion. The rising slope of the repolarization profile was steeper, and T-waves were more asymmetric than at baseline. Interventricular shape dissimilarity was enhanced by repolarization gradients according to DTW. Organized T-wave patterns were associated with abnormal repolarization, and they were properly described by the first principal components.ConclusionRepolarization heterogeneity significantly affects T-wave properties, and can be non-invasively captured by BSPM-based metrics.

Evaluation of TP-E Interval and TP-E/QT Ratio in Panic Disorder.

Background and Objectives: The autonomic nervous system (ANS) is involved in panic disorders. ANS dysfunction has been shown to be associated with ventricular arrhythmia and increased heterogeneity of ventricular repolarization. However, there remains limited evidence of the relationship between panic disorders and ventricular depolarization markers, including the Tp-e interval and Tp-e/QT ratio. This study aimed to evaluate ventricular repolarization parameters in patients with panic disorder. Materials and Methods: In total, 40 patients with panic disorder, diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, were included in the study group. The control group comprised of 50 age- and sex-matched healthy individuals. A standard 12 lead electrocardiogram was recorded on all participants, and heart rate, QT interval, QRS duration, Tp-e interval, and Tp-e/QT ratio were measured. Results: QRS durations and QT intervals were similar in the study and control groups. Compared to the control group, QTd, Tp-e, and cTp-e intervals as well as Tp-e/QT and Tp-e/QTc ratios were significantly increased in patients with panic disorder (p < 0.05 for all). In the study group, the Severity Measure for Panic Disorder—Adult score had a significant positive correlation with the Tp-e interval (r = 0.369, p < 0001), cTp-e interval (r = 0.531, p < 0.001), Tp-e/QT ratio (r = 0.358, p = 0.001), and Tp-e/QTc ratio (r = 0.351, p = 0.001). Conclusion: These findings indicate that panic disorders are associated with increased ventricular repolarization heterogeneity, which may be attributed to ANS dysregulation.

Longitudinal impact of dapagliflozin treatment on ventricular repolarization heterogeneity in patients with type 2 diabetes

Recent retrospective studies have suggested that increased ventricular repolarization heterogeneity (VRH), a predictor of poor cardiovascular prognosis, in patients with type 2 diabetes (T2DM) is reversed by treatment with an SGLT2 inhibitor, but not by other hypoglycemic agents. However, to our knowledge, no study in the literature has prospectively examined the effect of an SGLT2 inhibitor on T2DM-induced VRH.

Assessment of spatial heterogeneity of ventricular repolarization after multi-channel blocker drugs in healthy subjects

Background and ObjectivesIn contrast to potassium channel blockers, drugs affecting multiple channels seem to reduce torsadogenic risks. However, their effect on spatial heterogeneity of ventricular repolarization (SHVR) is still matter of investigation. Aim of this work is to assess the effect of four drugs blocking the human ether-à-go-go-related gene (hERG) potassium channel, alone or in combination with other ionic channel blocks, on SHVR, as estimated by the V-index on short triplicate 10 s ECG. MethodsThe V-index is an estimate of the standard deviation of the repolarization times of the myocytes across the entire myocardium, obtained from multi-lead surface electrocardiograms. Twenty-two healthy subjects received a pure hERG potassium channel blocker (dofetilide) and 3 other drugs with additional varying degrees of sodium and calcium (L‐type) channel block (quinidine, ranolazine, and verapamil), as well as placebo. A one-way repeated-measures Friedman test was performed to compare the V-index over time. ResultsComputer simulations and Bland-Altman analysis supported the reliability of the estimates of V-index on triplicate 10 s ECG. Ranolazine, verapamil and placebo did not affect the V-index. On the contrary, after quinidine and dofetilide administration, an increase of V-index from predose to its peak value was observed (ΔΔV-index values were 19 ms and 27 ms, respectively, p < 0.05). ConclusionsHigh torsadogenic drugs (dofetilide and quinidine) affected significantly the SHVR, as quantified by the V-index. The metric has therefore a potential in assessing drug arrhythmogenicity.

Akutni efekti sintetskih kanabinoida na ventrikularnu repolarizaciju

Objective: The usage of synthetic cannabinoids (SCs) has increased both in Turkey and all worldwide. Here, we evaluate if SCs cause ventricular repolarization abnormalities using initial and after 12th-hour electrocardiograms in patients with acute intoxication of SCs. We examined changes in the QTc and cTp-e parameters to demonstrate ventricular repolarization effects of the usage of SCs. Material and Methods: We used a prospective study design. Twenty patients were included who visited the emergency department, complaining of clouding of consciousness after using SCs. The QT, QTc and Tp-e intervals and several other electrocardiographic parameters were measured at baseline and 12 hours after the usage of SCs. Results: The QRS duration was significantly decreased (102.1 ± 15.5 ms vs 95.0 ± 10.7 ms; p = 0.022). We noted a significant decrease in cQT measurements at the end of the 12th hour (426.6 ± 47.2 ms vs 390.4 ± 42.9 ms; p = 0.002). Similarly, the Tp-e and cTp-e values decreased significantly when SCs lost its acute effect (93.4 ± 21.1 ms vs 77.4 ± 21.0 ms; p = 0.014, 105.3 ± 28.5 ms vs 88.1 ± 21.5 ms; p = 0.01). Conclusions: The usage of SCs affects ventricular repolarization heterogeneity based on QTc and Tp-e intervals

Assessment of ventricular repolarization instability in terms of T-wave alternans induced by head-down bed-rest immobilization

Objective: To assess the effects of different durations of simulated microgravity exposure on ventricular repolarization (VR) in terms of T-wave alternans (TWA) as well as to test whether an increase in VR heterogeneity could be detected once normal gravity was restored. Approach: A total of 63 healthy volunteers were recruited in several head-down bed-rest (HDBR) experiments in the context of the European Space Agency bed-rest strategy. TWA is evaluated during the night period using ambulatory ECG recordings, before, during and after long- (60 d), mid- (21 d) and short- (5 d) duration HDBR by the long-term averaging technique. Main results: 5–21 d of exposure to simulated microgravity by means of the HDBR model do not lead to a significant increase of cardiac electrical instability in healthy myocardial substrates up to the point of eliciting TWA on the surface ECG. However, TWA indices increased after long-term HDBR exposure, once normal gravity was re-established, indicative of incipient electrical instability on VR at the conclusion of 60 d of HDBR. Significance: The results of this work underline the importance of focusing future research on immediate effects after long-term microgravity exposure, both simulated by HDBR or from space mission scenarios, once partial gravity conditions are re-established. A deeper insight in the understanding of human body reactions in these scenarios results crucial in the design of future long-duration spaceflight missions, to mitigate any potential risk that can limit astronaut’s performance.

Cardiovascular Predictive Value and Genetic Basis of Ventricular Repolarization Dynamics.

Early prediction of cardiovascular risk in the general population remains an important issue. The T-wave morphology restitution (TMR), an ECG marker quantifying ventricular repolarization dynamics, is strongly associated with cardiovascular mortality in patients with heart failure. Our aim was to evaluate the cardiovascular prognostic value of TMR in a UK middle-aged population and identify any genetic contribution. We analyzed ECG recordings from 55 222 individuals from a UK middle-aged population undergoing an exercise stress test in UK Biobank (UKB). TMR was used to measure ventricular repolarization dynamics, exposed in this cohort by exercise (TMR during exercise, TMRex) and recovery from exercise (TMR during recovery, TMRrec). The primary end point was cardiovascular events; secondary end points were all-cause mortality, ventricular arrhythmias, and atrial fibrillation with median follow-up of 7 years. Genome-wide association studies for TMRex and TMRrec were performed, and genetic risk scores were derived and tested for association in independent samples from the full UKB cohort (N=360 631). A total of 1743 (3.2%) individuals in UKB who underwent the exercise stress test had a cardiovascular event, and TMRrec was significantly associated with cardiovascular events (hazard ratio, 1.11; P=5×10-7), independent of clinical variables and other ECG markers. TMRrec was also associated with all-cause mortality (hazard ratio, 1.10) and ventricular arrhythmias (hazard ratio, 1.16). We identified 12 genetic loci in total for TMRex and TMRrec, of which 9 are associated with another ECG marker. Individuals in the top 20% of the TMRrec genetic risk score were significantly more likely to have a cardiovascular event in the full UKB cohort (18 997, 5.3%) than individuals in the bottom 20% (hazard ratio, 1.07; P=6×10-3). TMR and TMR genetic risk scores are significantly associated with cardiovascular risk in a UK middle-aged population, supporting the hypothesis that increased spatio-temporal heterogeneity of ventricular repolarization is a substrate for cardiovascular risk and the validity of TMR as a cardiovascular risk predictor.

Diagnostic Value Of Qtc Dispersion And And Qt Dispersion Ratio Changes On Stress Test In Detecting Significance Of Coroner Lesion In Stable Angina Pectoris Patients

Background : Treadmill exercise test remains an important method and often used in the initial evaluation of patients with chest pain and can be a filter for more expensive invasive diagnostic. Increased QT dispersion (QTD) occurs because of the heterogeneity of ventricular repolarization because transient ischaemia during a treadmill stress test can be a marker of coronary artery disease (CAD) and can improve the accuracy of exercise tests to diagnose CAD, but this parameter is still controversial.&#x0D; &#x0D; Method : This is an analytic observational approach with a cross sectional study. Data was taken retrospectively at the Heart Center Installation at RSUP Dr. M. Djamil Padang, from March to April 2019, stable angina pectoris patient with a positive treadmill stress test who underwent coronary angiography as the subject. Bivariate analysis was performed on changes in QTcD (∆QTcD) and QTdR (∆QTdR) variables on the significance of coronary lesions by the chi-square method, after which a diagnostic test was based on receiver operating curve (ROC) analysis.&#x0D; &#x0D; Study Result : There were 122 subjects and found that older age, male and smoking were more common in groups with significant coronary lesions. Cut off point for ∆QTcD is ≥13 ms with a sensitivity of 87,1% and specificity 85,2% and AUC 95,1%, while ∆QTdR ≥5.5% with sensitivity 85,7% and specificity 81,9% and AUC 90,5% are related to significancy of coronary lesion. Obtained subjects with significant lesions generally had a value of ∆QTcD ≥ 13 ms (p &lt;0.001) and ∆QTdR ≥ 5.5% (p &lt;0.001).&#x0D; &#x0D; Conclusion : The use of ∆QTdR dan ∆QTdR parameters as ECG variables, which are easily obtained in evaluating stress tests, can improve the diagnostic accuracy of exercise tests. In addition, evaluation of ∆QTdR dan ∆QTdR can provide information about the incidence of CAD.&#x0D; Keywords : ∆QTcD, ∆QTdR, Treadmill Exercise Test, Coronary Lession Significancy&#x0D;

Electrophysiological remodeling of the right ventricle in experimental heart failure of different etiologies

The aim of the study was to evaluate electrophysiological remodeling of the right ventricle in rats in experimental heart failure of different etiologies. Materials and methods. Isadrin-, doxorubicin- and monocrotaline-induced heart failure models were developed. Unipolar epicardial electrograms of the ventricles (256 recording sites) were recorded using a 144-channel system. The cardiac output and pressure in both ventricles of the heart were measured. Activation-recovery intervals were used as an index of duration of local repolarization, and the general and local dispersions of activation-recovery intervals were used as an index of heterogeneity of ventricular repolarization. Results. In all models of heart failure, the following were identified: 1) non-uniform prolongation of repolarization with the greatest elongation at the apex of the right ventricle; 2) an increase in apicobasal differences of repolarization with the greatest change in the right ventricle; 3) an increase in the heterogeneity of the repolarization of the epicardial layer of the ventricles with heterogeneous changes in the local heterogeneity of repolarization and a decrease in the interregional differences in the heterogeneity of the electrophysiological properties of the myocardium; 4) more pronounced changes in the repolarization of the right ventricle than in the repolarization of the left ventricle. Conclusion. Thus, irrespective of the cause of the heart failure, the following changes occur: 1) prolongation of the right ventricular repolarization occurs non-uniformly (mostly due to the apical area), which results in an increase in the right ventricular repolarization heterogeneity; 2) an increase in the heterogeneity of right ventricular repolarization is observed, which causes an increase in the overall heterogeneity of the ventricular epicardial surface.

Insulin Resistance is Associated with Longitudinal Changes of Cardiac Repolarization Heterogeneity in Apparently Healthy Subjects.

IntroductionIncreased heterogeneity in ventricular repolarization is a risk factor of sudden cardiac death, but its natural history is unclear. Here we examined whether insulin resistance is associated with longitudinal change in ventricular repolarization heterogeneity in apparently healthy subjects.MethodsThe study subjects were participants in health checkups in cohort 1 and cohort 2, which were followed up for 6 years and 5 years, respectively. Subjects with diabetes, cardiovascular disease, or renal disease at baseline were excluded from the analyses. As indices of insulin resistance, the homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride to HDL-cholesterol ratio (TG/HDL-C) were used in cohort 1 and cohort 2, respectively. Heterogeneity in ventricular repolarization was assessed by heart rate-corrected Tpeak–Tend interval in V5 (cTpTe), QT interval, and QT dispersion. In regression analyses, parameters with a skewed distribution were normalized by logarithmic transformation or by Box–Cox transformation.ResultsIn longitudinal analyses, Box–Cox-transformed cTpTe at the end of follow-up was weakly correlated with log HOMA-IR at baseline in cohort 1 (n = 153, r = − 0.207, 95% CI − 0.354 to − 0.050, p = 0.010) and with log TG/HDL-C at baseline in cohort 2 (n = 738, r = − 0.098, 95% CI − 0.169 to − 0.026, p = 0.008). Multiple regression analysis showed that indices of insulin resistance, but not glycosylated hemoglobin (HbA1c) or plasma glucose, at baseline were significant explanatory variables for cTpTe at the end of follow-up. Neither QT interval nor QT dispersion was correlated with metabolic parameters.ConclusionInsulin resistance may be involved in the longitudinal increase of ventricular repolarization heterogeneity in apparently healthy subjects.

Abstract 4909: Whole-genome sequencing of childhood cancer survivors treated with cranial radiation therapy identifies 5p15.33 locus for stroke: A report from the St. Jude Lifetime Cohort (SJLIFE) study

Abstract Long-term survivors of childhood cancer are at increased risk of stroke, which is attributed to the well-established dose-response association with cranial radiation therapy (CRT) dose and risk. While radiation-induced vasculopathy is believed to be the likely mechanism underlying CRT-associated stroke, there is a variation in the dose-risk association, suggesting a potential contribution of genetic factors. We performed analyses of deep-coverage (36.8X) whole-genome sequencing data of 696 childhood cancer survivors of European descent [median (range): 40.4 (12.4-64.7) years old; 54% male] from the SJLIFE cohort treated with CRT, of whom 116 (17%) developed clinically-diagnosed stroke. Analyses of common variants [minor allele frequency (MAF)&amp;gt;0.05] were performed using logistic regression, adjusting for age at cancer diagnosis, sex, age at follow-up, CRT dose and top principal components derived from genotypes. Rare/low-frequency variants (MAF≤0.05) were aggregated by different functional annotations and agnostic 4-kb sliding windows and tested jointly using Burden and SKAT Tests, adjusted for the same covariates. Results identified a genome-wide significant association between a common variant on 5p15.33 locus and CRT-associated stroke [rs112896372: MAFaffected=0.27; odds ratio (OR)=2.93; P=4.66×10-8]. Stratified analyses showed that rs112896372 had the strongest association (OR=4.81; P=4.16×10-4) among survivors treated with CRT dose 25-50 Gray (Gy); survivors treated with CRT dose &amp;lt;25 Gy and those treated with CRT dose &amp;gt;50 Gy had the weaker associations (OR=2.41; P=1.01×10-3, OR=3.01; P=4.91×10-3, respectively). We replicated the association between rs112896372 and stroke in two independent SJLIFE samples: (1) 20 with and 70 without stroke of African ancestry treated with CRT (MAFaffected=0.23; OR=6.47; P=8.99×10-3) and (2) 60 with and 1581 without stroke of European ancestry not treated with CRT (MAFaffected=0.25; OR=1.58; P=0.04). SNP rs112896372 maps to an intergenic region located approximately 155 kb downstream of IRX1 (iroquois homeobox 1), a member of IRX family of transcription factors with established roles in ventricular chamber, conducting system development and heterogeneity of ventricular repolarization. Overall, we identified and independently replicated a novel locus for CRT-associated stroke among survivors of childhood cancer, with a possible CRT dose-specific effect. Considering the large effect size and the relatively high MAF, the 5p15.33 locus may have potential clinical utility for identifying high-risk CRT exposed cancer survivors and guide intervention strategies. Citation Format: Yadav Sapkota, Yin Ting Cheung, Wonjong Moon, Kyla Shelton, Carmen L. Wilson, Zhaoming Wang, Daniel A. Mulrooney, Jinghui Zhang, Gregory T. Armstrong, Melissa M. Hudson, Leslie L. Robison, Kevin R. Krull, Yutaka Yasui. Whole-genome sequencing of childhood cancer survivors treated with cranial radiation therapy identifies 5p15.33 locus for stroke: A report from the St. Jude Lifetime Cohort (SJLIFE) study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4909.

Quantification of Spatial Heterogeneity of Ventricular Repolarization During Early-Stage Cardiac Ischemia Induced by Coronary Angioplasty.

Coronary angioplasty (CA) is a surgical procedure meant to break the plaque and restore the blood flow in obstructed coronary arteries. It is based on inserting an inflatable balloon with a catheter in the clogged artery. When the balloon inflation is prolonged, it also provides an excellent model to investigate the electrophysiological changes due to early ischemia. In this work, we tested whether early cardiac ischemia induced by prolonged balloon inflations might lead to changes in spatial heterogeneity of ventricular repolarization (SHVR), as measured by the V-index on the 12-lead ECG. The metric was recently shown to significantly improve the ECG sensitivity for the diagnosis of non-ST elevation myocardial infarction, in patients presenting to the emergency department. The analysis was retrospectively performed on the data of 104 patients who underwent prolonged CA (STAFF III dataset). The V-index was estimated before, during and post-occlusion (limiting the analysis to the first inflation). Successively, it was quantified on short 90 s overlapping windows, during occlusion, to assess the time evolution of SHVR. V-index values estimated during occlusion were significantly larger (median: 6.2 ms, p <; 0.05) than baseline room values. Also, pre- and post-occlusion values did not differ (p > 0.05), suggesting a complete recovery after CA. SHVR progressively increased during the occlusion with respect to baseline (median reaching 55.6 ms vs 34.2 ms). In conclusion, the V-index detected changes in SHVR due to early-stage cardiac ischemia.

SWITCHING FROM RAMIPRIL TO SACUBITRIL/VALSARTAN FAVORABLY ALTERS ELECTROCARDIOGRAPHIC INDICES OF VENTRICULAR REPOLARIZATION IN HEART FAILURE WITH REDUCED EJECTION FRACTION

Angiotensin receptor neprilysin inhibitor (ARNI, sacubitril/valsartan) reduces sudden death in heart failure with reduced ejection fraction (HFrEF). Corrected QT (QTc), T-wave peak to T-wave end interval (Tp-e) and Tp-e/QTc are electrocardiographic indices of ventricular repolarization heterogeneity

QT Interval Dispersion Behavior in Patients With and Without Obstructive Coronary Artery Disease Undergoing Exercise Test

Abstract Background: Stress test is used to detect coronary artery disease (CAD). The QTc interval dispersion (dQTc) is an electrocardiographic index of ventricular repolarization heterogeneity. Some researchers have linked transient myocardial ischemia induced by physical exertion with increased heterogeneity of ventricular repolarization measured by dQTc. Objectives: To study the patterns of dQT in patients with and without chronic obstructive CAD and to define a reliable cutoff point for dQT that could become a diagnostic criterion for myocardial ischemia. Methods: We retrospectively analyzed the electrocardiogram in resting and in exercise of 63 patients submitted to exercise test and cardiac catheterization. We divided the patients into three groups: true negative (VN), true positive (VP) and false positive (FP). VN: patients with coronary lesion lower than 70% and exercise test without myocardial ischemia; VP: individuals with stenosis greater than 70% in coronary arteries and a test suggestive of myocardial ischemia; FP: people with stenosis lower than 70% in the coronary arteries and stress test with ischemia criteria. Values of p < 0.05 were considered statistically significant. Results: Resting dQTc was not different among the three groups. However, for the dispersion of the QTc interval in exercise was, respectively, 47 ± 17 ms, 72 ± 42 ms, and 61 ± 31 ms for VN, VP and FP (p = 0.003). Conclusions: Obstructive chronic coronary disease patients have an increase in dQTc during exercise. Measurement of dQTc may be helpful in the diagnosis of myocardial ischemia in the stress test.

Evaluation of ventricular repolarization parameters during migraine attacks

AimsMigraine is a chronic neurovascular disorder characterized by intermittent episodes of severe headache. Abnormalities in the autonomic nervous system (sympathetic and parasympathetic nervous systems) have been detected during migraine-free periods in patients with migraine. In these patients, disrupted autonomic innervations of the heart and coronary arteries may lead to electrocardiographic changes during a migraine attack. T-wave peak-to-end interval (Tp-e interval) and Tp-e/QT ratio are relatively new markers of ventricular arrhythmogenesis and repolarization heterogeneity. In the present observational study, we investigated the changes in ventricular repolarization during migraine attacks and attack-free periods by performing 12‑lead electrocardiography (ECG). MethodsThis study included 63 patients (54 [86%] women; mean age: 33.3 ± 9.9 years) with migraine. The QT and corrected QT (QTc) intervals, Tp-e interval, and Tp-e/QT ratio of the patients during migraine attacks and attack-free periods were measured by performing 12‑lead ECG. ResultsThe QT and QTc intervals, Tp-e interval, and Tp-e/QT ratio were higher during migraine attacks than during attack-free periods (P < 0.001 for all). ConclusionThese results indicate that migraine attacks are associated with an increase in ventricular repolarization parameters compared with attack-free periods possibly because of the dysregulation of the autonomic nervous system.

Switching from ramipril to sacubitril/valsartan favorably alters electrocardiographic indices of ventricular repolarization in heart failure with reduced ejection fraction

Background: Angiotensin receptor neprilysin inhibitor (ARNI, sacubitril/valsartan) reduces sudden death in heart failure with reduced ejection fraction (HFrEF). Corrected QT (QTc), T-wave peak to T-wave end interval (Tp-e) and Tp-e/QTc are electrocardiographic indices of ventricular repolarization heterogeneity. We aimed to assess the effects of switching from ramipril to ARNI on electrocardiographic indices of ventricular repolarization.Methods: A total of 48 patients with HFrEF (mean age: 63.3 ± 11.7 years; 36 males, 77.1% ischaemic etiology) were enrolled. All patients had New York Heart Association functional class II–III, left ventricular ejection fraction ≤35% and previously switched from ramipril to ARNI treatment. The standard 12-lead electrocardiograms on ramipril treatment and 1 month after ARNI treatment were analysed; heart rate, QTc, Tp-e and Tp-e/QTc were calculated. Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores and N-terminal pro-BNP (NT-proBNP) values were recorded.Results: QTc (415.2 ± 19.7 ms vs. 408.5 ± 20.8 ms, p = 0.022), Tp-e (100.7 ± 13.8 ms vs. 92.9 ± 12.1 ms, p < 0.001), Tp-e/QTc (0.242 ± 0.028 vs. 0.227 ± 0.029, p = 0.003) and heart rate (73.2 ± 4.7 bpm vs. 71.1 ± 4.9 bpm, p = 0.027) were reduced after ARNI. ARNI switch associated with improvement in MLWHFQ scores (32.4 ± 7.1 ms vs. 22.6 ± 7.0 ms, p < 0.001) and reduction of NT-proBNP (2457 ± 1879 pg/ml to 1377 ± 874 pg/ml, p < 0.001). Pearson’s correlation analysis revealed moderate correlations of MLWHFQ score with Tp-e (r = 0.543, p = 0.001) and Tp-e/QTc (r = 0.556, p = 0.001).Conclusions: Switching from ramipril to ARNI favourably alters QTc, Tp-e and Tp-e/QTc in HFREF. ARNI reduces symptoms of HFREF assessed by MLWHFQ and lowers NT-proBNP levels. Reduction in Tp-e and Tp-e/QTc correlate with clinical improvement in patients with HFrEF.