Dispersion Of Ventricular Repolarization Research Articles

Exercise-induced regional heterogeneity of myocardial left ventricular contraction in hereditary long QT syndrome

Abstract Background Hereditary long QT syndrome (LQTS) is characterized by prolonged ventricular repolarization and an increased risk for ventricular arrhythmias (VA) and sudden cardiac death. Dispersion of ventricular repolarization in LQTS may be more pronounced during exercise and not only impacts the heart’s electrical functions but also the pattern of mechanical contraction. Little is known about the intraventricular heterogeneity of wall motion abnormalities in LQTS patients. Methods In this cross-sectional study we quantify regional, transmural, and longitudinal alterations in left ventricular (LV) contraction at rest, during exercise, and recovery in genetically confirmed LQTS patients and healthy controls to evaluate their value in differentiating high risk patients as defined by a history of VA. ECG and echocardiographic assessments were conducted during rest, peak ergometer activity (105 to 125 bpm), and four minutes into recovery phases. Longitudinal strain (LStr) parameters were measured for each LV segment separately. We differentiated LStr variations as heterogeneity of LStr amplitude (hetLStr; standard deviation [SD] or mean range) and dispersion of time-to-peak LStr (disLStr; SD or mean range). Here, we present the analyses of disLStr. Results At present, 15 patients with genetically confirmed LQTS (LQT1: 8, LQTS 2: 7; mean QTc 475 ± 46 ms) have been included of which 9 had a history of VA. In addition, we collected data from 8 age- and gender-matched control patients (mean QTc 401 ± 18 ms). LV ejection fraction and LStr were not significantly different between the LQTS and control groups. However, LQTS patients exhibited a significantly lower mean LStr in both the endocardial and epicardial layers across all phases compared to control. We observed a significantly more pronounced disLStr across all segments in the LQTS group during the rest and recovery phases in the endocardial layer and during all phases in the epicardial layer. Regional differences (apical vs. basal) were found in all LQTS patients only endocardially at rest. Globally, disLStr showed transmural differences (epicardial vs. endocardial) in both asymptomatic and symptomatic LQTS patients during peak exercise and recovery. Upon segmental analysis, it was observed that symptomatic patients exhibited these transmural differences apically already at rest (p=.004), as well as in the basal region during peak exercise (p=.01), and in the apical region during recovery (p=.02). Conclusion LQTS patients show regional (base to apex) and transmural (endocardial to epicardial) heterogeneities in myocardial contraction at rest, during exercise, and recovery as compared to healthy patients. These regional variations in myocardial contraction patterns may be more pronounced in high risk LQTS patients. Ongoing analyses of hetLStr are in progress to corroborate our findings.

Time-Warping Analysis of the T-Wave Peak-to-End Interval to Quantify Ventricular Repolarization Dispersion During Ischemia.

The presence of myocardial ischemia can increase ventricular arrhythmic risk due to a raised dispersion of ventricular repolarization. This is reflected on the morphology of the T-wave on the electrocardiogram (ECG), and can be quantified by time-warping based indexes, like dw. However, T-wave morphology can also be affected by ischemia-induced ST segment changes, impacting the accuracy of dw. We hypothesize that ischemia-induced repolarization dispersion can be better quantified by restricting dw to the T-wave peak-to-end (T pe) interval. 101 ECG recordings from patients undergoing a percutaneous coronary intervention (PCI) were analyzed together with their control ECG recordings, acquired before the intervention. A series of dw values was calculated by quantifying the T pe morphological variations between the T-waves from the PCI and a reference derived from the control ECG recordings. We proposed a normalized version of dw, Rd, reflecting relative variations of dw during PCI to control recordings, and compare it with traditional indices behaviour. Values of dw followed a gradually increasing trend as PCI inflation time progressed, reaching a median[range] Rd value of 9.44 [1.01, 80.74] at the occlusion end. During control recordings, dw remained stable, with a low intra-patient standard deviation, range [0.02, 2.09] ms and a median[range] Rd of 1.00 [0.03, 2.93]. Rd at oclussion end was significantly higher than threshold values of 1, 2, 5, and 10 in 94.1%, 85.11%, 64.4% and 48.5% of patients, respectively. The spatial lead-wise analysis of dw showed distinct distributions depending on the occluded artery, suggesting a relation with the ischemia location. The relative variation R with ischemia of index dw (9.4) is greater than for traditional T wave amplitude (7.7), T peak-to-end interval (2.7) and T width (3.0). The index dw, quantifying T pe morphology variations, allows to follow the ischemia induced variations in repolarization in a more robust manner than classical indexes, avoiding ST segment and early T wave distortions not related to repolarization dispersion, and warranting further clinical studies to evaluate its ventricular arrhythmia risk predictive value during ischemia.

Action potential morphology affects T-wave symmetry (simulation study)

BackgroundAssessing T-wave symmetry in addition to QT subintervals measurements can provide novel independent data about ventricular repolarization abnormalities linked with arrhythmogenesis. However, the causes of the changes of T-wave symmetry are not completely understood. In silico studies showed that the more symmetrical T-waves were associated with shorter action potential duration (APD) and larger dispersion of ventricular repolarization (DOR). The aim of present simulation was to study the association between T-wave symmetry and action potential (AP) shape. MethodsECGs were simulated using a cellular automata model shaped as a ventricular wall segment, and two biophysically-detailed models of ventricular AP – the rabbit and the human. The symmetry ratio (SR) was calculated as a T-wave onset-peak to peak-end area ratio. The individual and combined effects of APD, DOR and AP shape on SR were simulated. To study the effect of AP shape, different APs from triangulated to rectangular were simulated. ResultsThe simulations showed that AP shape along with APD and DOR contributes much to T-wave symmetry. APs with a flat phase 3 (triangulated) produced asymmetrical T-waves (SR ≥ 1.5) in all simulations, except the shortest APD range. APs with a rapid phase 3 (rectangular) were associated with more symmetrical T-waves (SR ≤ =1) both at the short and the long APDs. ConclusionSR marker in combination with the standard ECG parameters (QT interval, Tpeak-Tend interval) may be useful to identify the proarrhythmic triangulated AP shape.

Increased Dispersion of Ventricular Repolarization as an Arrhythmic Risk Marker in Drug-free Patients With Major Depressive Disorder: A Preliminary Comparative Study.

Drug-free patients with major depressive disorder (MDD) are understudied in terms of increased risk for arrhythmias. In this study, we compared changes in corrected QT interval (QTc), QTc dispersion (QTcd), Tpeak-Tend (Tp-e), Tp-e/QT ratio, corrected JT interval (JTc), and JTc dispersion (JTcd), which are considered to be among the risk factors for the emergence of ventricular arrhythmias in patients with MDD. The study involved 50 patients with MDD who had been free of psychotropic medications for at least 1 month and 52 age-matched and sex-matched healthy controls. Illness-related characteristics, including duration of illness and Beck Depression Inventory scores, were recorded. Electrocardiography recordings made under a standardized procedure were performed for all participants, and arrhythmia risk markers were calculated from the electrocardiograms. The patient group had significantly higher QTcd, JTc, and JTcd values compared with the controls. Among electrocardiogram markers, only Tp-e/QTc was significantly and inversely correlated with the duration of illness, while none of the markers was associated with Beck Depression Inventory scores. Alterations in electrocardiogram-derived markers of ventricular arrhythmia, which can be obtained easily and inexpensively, can be evaluated for the prediction and prevention of severe cardiac conditions in patients with MDD and considered in selecting the safest antidepressant options available.

Relationship of the T-wave Tpeak-Tend interval with conduction system disorders in arterial hypertension.

The Tpeak-Tend interval of the T wave has emerged as a new electrocardiographic marker of increased transmural dispersion of ventricular repolarization. We aimed to determine the presence of cardiac conduction system disorders in patients with systemic arterial hypertension (SAH) who have altered Tpeak-Tend interval of the T wave. The 67 patients with SAH were divided into two groups. Those with prolonged (≥ 77 ms) Tpeak-Tend intervals, 21 (31%) patients were in the study group. Those with normal (< 77 ms) Tpeak-Tend intervals, 46 (69%) patients were in the control group. Alteration of ventricular repolarization manifested as a prolongation of the Tpeak-Tend interval was detected by computerized electrocardiographic analysis tools. The median value of QRS complex duration was significantly wider in the study group as compared to the control group (110 ± 12 ms vs. 94 ± 8 ms p < 0.001). There was a significantly greater incidence of left anterior hemiblock in the study group (14% vs. 0% p < 0.04). The median value of the QTc interval was significantly greater in the study group (440 ± 26 vs. 422 ± 15 p < 0.01). There was a significantly greater incidence of patients with prolonged QTc interval in the study group (33% vs. 11% p < 0.02). The median value of the Tpeak-Tend interval was significantly greater in the study group (84 ± 5 ms vs. 65 ± 4 ms p < 0.001), as well as, the Tpeak-Tend/QTc ratio in the study group (0.19 ± 0.1 vs. 0.16 ± 0.1 p < 0.001). There is a significantly greater ventricular repolarization disorders and abnormalities of the cardiac conduction system in SAH patients who possess altered Tpeak-Tend interval of the T wave.

Comparison of immediate changes of repolarization parameters after left bundle branch area pacing and traditional biventricular pacing in heart failure patients.

Comparison of immediate changes of repolarization parameters after left bundle branch area pacing and traditional biventricular pacing in heart failure patients.

Changes of repolarization parameters after left bundle branch area pacing and the association with echocardiographic response in heart failure patients.

Background: Left bundle branch area pacing (LBBAP) has become a safe and effective option for heart failure (HF) patients indicated for cardiac resynchronization therapy (CRT) and/or ventricular pacing, yet the response rate was only 70%. Repolarization parameters were demonstrated to be associated with cardiac mechanics and systolic function. This study aimed to investigate the effects of LBBAP on repolarization parameters and the potential association between those parameters and echocardiographic response. Methods and results: A total of 59 HF patients undergoing successful LBBAP were consecutively included. QTc, Tpeak-Tend (TpTe), and TpTe/QTc were measured before and after the implantation. The results turned out that the dispersion of ventricular repolarization (DVR) improved after LBBAP among the total population. Although trends of repolarization parameters varied according to different QRS configurations at baseline, the post-implant parameters showed no significant difference between groups. The association between repolarization parameters and LBBAP response was then evaluated among patients with wide QRS. Multivariate analysis demonstrated that post-implant TpTe was the independent predictor of LBBAP response (p < 0.05). Receiver operating characteristic analysis indicated an area under the curve of 0.77 (95% CI, 0.60–0.93) with a cutoff value of 81.2 ms (p < 0.01). Patients with post-implant TpTe<81.2 ms had a significantly higher rate of echocardiographic response (93.3 vs. 44.4%, p < 0.01). Further subgroup analysis indicated that the predictive value of post-implant TpTe for LBBAP response was more significant in non-left bundle branch block (LBBB) patients than in LBBB patients. Conclusion: LBBAP improved DVR significantly in HF patients. Post-implant TpTe was associated with the echocardiographic response after LBBAP among patients with wide QRS, especially for non-LBBB patients.

Synchronization of repolarization after cardiac resynchronization therapy: time course and relation to reverse remodeling

Abstract Funding Acknowledgements Type of funding sources: None. Background The changes in ventricular repolarization after cardiac resynchronization therapy (CRT) are poorly understood. Objective Address this knowledge gap using a multimodality approach including electrocardiographic and echocardiographic measurements in patients and patient-specific computational modeling. Methods In a cohort of consecutive CRT patients, electrocardiographic and echocardiographic measurements were performed before and at various intervals after CRT, both during CRT-ON and temporary CRT-OFF. T-wave area was calculated from vectorcardiograms, reconstructed from the 12-lead ECG. Computer simulations were performed using a patient-specific eikonal model of cardiac activation with spatially varying action potential duration (APD) and repolarization rate, based on a patient’s ECG and MRI-based chest and cardiac anatomy. Results In 33 patients T-wave area during CRT-OFF doubled within 5 days of CRT (left figure) while other repolarization markers like QT-interval and peak-to-end T-wave interval hardly changed. Patients with T-wave area increase above the median increase showed a significantly larger increase in left ventricular ejection fraction than those with smaller T-wave area increase (+11±8% vs. +6±6%, respectively; p&amp;lt;0.05, n=76). Computer simulations (figure, right) show the sequence of depolarization and repolarization before CRT, obtained by the patient-specific model (BL LBBB) and following Acute CRT. Repolarization after chronic CRT-OFF was obtained by matching the measured CRT-OFF ECG with that provided by the model. The best match was obtained by changes in APD following chronic CRT that are opposite to the change in CRT-induced activation time. Such APD changes were associated with a reduction in right and left ventricular dispersion in repolarization during chronic CRT-ON compared with acute CRT-ON. Conclusions T-wave area during CRT-OFF is a sensitive marker for adaptations in ventricular repolarization after CRT that are related to CRT-induced reverse remodeling and may involve an inverse relation between activation time and APD, coinciding with lower right and left ventricular dispersion of repolarization and with larger increases in LV ejection fraction during chronic CRT.

Ventricular Repolarization Dispersion is a Potential Risk for the Development of Life-Threatening Arrhythmia in Children with Hypertrophic Cardiomyopathy.

The risk stratification and early interventions are necessary in patients with hypertrophic cardiomyopathy (HCM), as life-threatening arrhythmia (LTA) is a leading cause of death. This study aimed to explore whether an interval between the peak of the T wave to the end terminal of the T wave (Tp-e), which represents ventricular repolarization dispersion, could predict the risk for LTA in children with HCM. We analyzed electrocardiography at the first and last visits in children (aged < 15years) with HCM, and compared Tp-e interval and theratio of Tp-e interval to QT interval (Tp-e/QT) between children with and without LTA. We studied 25 children with HCM. During the follow-up of 85 (38-146) months, there were 7 children with LTA. The 5-year sudden cardiac death (SCD) risk was 1.4 (1.1-2.5) %, which suggested that our cohort consisted of patients at a lower risk for SCD. Age was significantly older in children with LTA compared to those without it (12.5 vs.1.0years, P = 0.037), although sex, the presence of family history and symptoms at diagnosis, the maximum left ventricular wall thickness Z-score did not differ between the groups. At the last electrocardiography before LTA, corrected Tp-e interval and Tp-e/QT ratio were significantly greater in patients with LTA compared to those in patients without LTA (corrected Tp-e: 103 vs. 78ms, P = 0.020; Tp-e/QT: 0.28 vs. 0.22, P = 0.046). Corrected Tp-e and Tp-e/QT ratio cutoff values of 91ms and 0.28 yielded as the predictors for LTA with sensitivity of 85% and 72%, specificity of 71% and 89%, respectively. Prolonged absolute and corrected Tp-e intervals and an increase in the Tp-e/QT ratio can be useful predictors for LTA in children with HCM. We offer temporal assessments of ventricular repolarization dispersion to stratify the risk for the development of LTA/SCD among children with HCM.

Abstract EP29: Sex Differences In Anxiety Associated With Left Ventricular Hypertrophy And Transmural Dispersion Of Repolarization In Hypertensive Patients

Background: Previous studies showed that hypertensive with anxiety have a higher mean left ventricular mass index (LVMI) and QTc dispersion. This study explores the associations between anxiety and left ventricular hypertrophy (LVH) as well as transmural dispersion of repolarization (TDR) (as detected by T peak-T end interval/QT interval, Tp-Te/QT ratio) in hypertensive patients. Methods: A total of 353 uncomplicated hypertensive patients were enrolled at Shaanxi Provincial People’s Hospital from 2017 to 2021. All enrolled subjects completed the Hamilton Anxiety Scale (HAMA). HAM-A score ≥14 was defined as the presence of anxiety. The association between HAM-A and hypertensive LVH was estimated with logistic regression models. The association between HAM-A score and Tp-Te/QT was estimated with linear regression model (adjusted for age, sex, body mass index, smoking, creatinine, uric acid, triglyceride, total cholesterol, low density lipoprotein cholesterol, and high-density lipoprotein cholesterol). This study was approved by the Ethics Committee of Shaanxi Provincial People’s Hospital and performed in keeping with the requirements of the Declaration of Helsinki. Results: Participants were divided into two groups according to anxiety or not. The LVMI was significantly higher in hypertensive patients with anxiety than hypertensive patients without anxiety (no anxiety: 84.36±23.82, anxiety: 105.75±25.45, g/m 2 , P &lt;0.001). The HAM-A score was positive correlated with LVMI (r=0.578, P &lt;0.001) and Tp-Te/QT (r=0.252, P &lt;0.001). In logistic regression models, hypertensive patients with anxiety had a higher risk of hypertensive LVH than hypertensive patients without anxiety (unadjusted OR, 2.86, 95% CI, 1.65-4.93, P &lt;0.001; adjusted OR, 2.62, 95% CI, 1.49-4.64, P &lt;0.001). Linear regression analysis also showed that HAM-A score was associated with Tp-Te/QT ratio (unadjusted β, 0.002, 95% CI, 0.001-0.002, P &lt;0.001; adjusted β, 0.002, 95% CI, 0.001-0.002, P &lt;0.001). There was an interaction between sex and anxiety in regard to LVH risk ( P for interaction = 0.035) and increased Tp-Te/QT ( P for interaction = 0.014). After stratification by sex, the anxiety group had a higher risk of hypertensive LVH than no anxiety group in male (unadjusted OR, 5.73, 95% CI, 2.43-13.50, P &lt;0.001; adjusted OR, 5.39, 95% CI, 2.13-13.66, P &lt;0.001) but not in female (unadjusted OR, 1.70, 95% CI, 0.82-3.53, P =0.152; adjusted: OR, 1.62, 95% CI, 0.76-3.45, P =0.209) hypertensive patients. HAM-A score was also associated with Tp-Te/QT ratio in male (unadjusted β, 0.003, 95% CI, 0.002-0.004, P &lt;0.001; adjusted β, 0.003, 95% CI, 0.001-0.004, P &lt;0.001) but not in female (unadjusted β, 0.001, 95% CI, -0.0001-0.002, P =0.061; adjusted β, 0.001, 95% CI, -0.0001-0.002, P =0.086). Conclusion: Our data indicated that anxiety is associated with LVH and increased TDR in male but not female hypertensive patients.

Plasma potassium concentration and cardiac repolarisation markers, Tpeak–Tend and Tpeak–Tend/QT, during and after exercise in healthy participants and in end-stage renal disease

The cardiac T-wave peak-to-end interval (Tpe) is thought to reflect dispersion in ventricular repolarisation, with abnormalities in Tpe associated with increased risk of arrhythmia. Extracellular K+ modulates cardiac repolarisation, and since arterial plasma K+ concentration ([K+]) rapidly increases during and declines following exercise, we investigated the relationship between [K+] and Tpe with exercise. Serial ECGs (Tpe, Tpe/QT ratio) and [K+] were obtained from 8 healthy, normokalaemic volunteers and 22 patients with end-stage renal disease (ESRD), at rest, during, and after exhaustive exercise. Post-exercise [K+] nadir was 3.1 ± 0.1, 5.0 ± 0.2 and 4.0 ± 0.1mmol.L-1 (mean ± SEM) for healthy participants and ESRD patients before and after haemodialysis, respectively. In healthy participants, compared to pre-exercise, recovery-induced low [K+] was associated with a prolongation of Tpe (110 ± 8 vs. 87 ± 5ms, respectively, p = 0.03) and an increase in Tpe/QT ratio (0.28 ± 0.01 vs. 0.23 ± 0.01, respectively, p = 0.01). Analyses of serial data revealed [K+] as a predictor of Tpe in healthy participants (β = -0.54 ±0.05, p < 0.0001), in ESRD patients (β = -0.75 ± 0.06, p < 0.0001) and for all data pooled (β = -0.61 ± 0.04, p < 0.0001). The [K+] was also a predictor of Tpe/QT ratio in healthy participants and ESRD patients. Tpe and Tpe/QT ratio are predicted by [K+] during exercise. Low [K+] during recovery from exercise was associated with increased Tpe and Tpe/QT, indicating accentuated dispersion of ventricular repolarisation. The findings suggest that variations in [K+] with physical exertion may unmask electrophysiological vulnerabilities to arrhythmia.

OR11. Association between T peak-T end interval and mortality in patient with complex coronary lesion scheduled for Coronary Artery Bypass Graft procedure

Abstract Aim Patient with complex coronary lesion face a mortality risk caused by sudden cardiac death (SCD). The Tpeak-Tend (TpTe) interval is a measure of dispersion of ventricular repolarization. Our aim is to investigate the relationship between the TpTe interval in patient’s resting 12-lead electrocardiogram (ECG) and the mortality incidence of patient waiting for Coronary Artery Bypass Graft (CABG) procedure. Methods and result Total of 175 patient scheduled for CABG procedure between January 2018 to December 2020. ECG was taken from medical record, interval of TpTe is calculated in V2 lead with tangent method ECG analysis. Association between variables analysed with Pearson chi-square test. Baseline characteristic showed age 58.7 ± 6.8 years old, syntax score 30.66 ± 4.0 and left ventricle ejection fraction 47.8% ±14.4. There is significant association between prolonged TpTe interval (&amp;gt;85 ms) and mortality incidence before CABG with odds ratio 3.821 (95% CI 1.727 – 8.454; p = 0.001). Conclusion TpTe interval is a feasible parameter that associate with the mortality in patient with complex coronary disease.

Refractory Angina Confounded by Preexcitation Syndrome.

Scenario: This 12-lead electrocardiogram (ECG) was obtained on a 48-year-old man who came to the emergency department with progressively worsening left lateral crushing chest pain and dyspnea of 3 hours’ duration. The patient drinks 9 beers daily, is an active smoker, and is treated for hypertension and hypercholesterolemia. His initial vital signs during prehospital transport showed a heart rate of ~110/minute and blood pressure of 151/100 mm Hg. Paramedics administered aspirin and sublingual nitroglycerin during ambulance transport, and this ECG was obtained upon arrival in the emergency department.Sinus rhythm with Wolff-Parkinson-White (WPW) syndrome type A.In the normal electrical conduction system, the atrioventricular (AV) node serves as a gatekeeper to regulate the propagation of signals from the atria into the ventricles. When an accessory pathway exists, ventricular activation occurs through both the AV node and the extra anatomical pathway, yielding a shorter PR interval and a slurred upstroke of the QRS complex (ie, delta wave). When the accessory pathway connects to the left ventricle, the preexcitation starts in the left ventricle first before it proceeds normally through the bundle of His and bundle branches (called WPW type A). This syndrome manifests as a wide QRS complex with pseudo right bundle branch block pattern (ie, tall R wave in right precordial leads). Because of the temporal heterogeneity in ventricular activation, repolarization abnormalities (or non-specific ST-segment and T-wave changes) are common, including early repolarization pattern (eg, J-point elevation best seen in lead V3 in this example). Such dispersion in ventricular depolarization and repolarization might lead to back propagation of the signal to the atria either through the bundle of His or through the accessory pathway. This back propagation may create an atrioventricular reentry circuit and sustained tachycardia. Although WPW syndrome is usually benign, curative catheter ablation is considered in symptomatic or hemodynamically unstable patients.Although secondary repolarization changes are common in WPW syndrome, the ST-segment elevation in the anterior wall that is accompanied with reciprocal changes in the inferolateral walls, coupled with the highly suspicious presenting symptoms and history, are worrisome for acute myocardial infarction. In this specific patient, the initial cardiac workup was negative, and the patient was admitted to the telemetry unit for serial ECGs and troponin assays. Owing to persistent refractory angina, the patient was referred for cardiac angiography the following morning, which revealed normal left ventricular function and mild atherosclerotic disease in the right coronary artery at 20% to 30% occlusion. The patient was discharged home on oral anti-ischemic therapy (eg, aspirin, nitroglycerin) with a referral to cardiac electrophysiology for further management of the underlying WPW syndrome. Long-term ambulatory monitoring (eg, Holter ECG) is warranted to rule out reentry tachyarrhythmias.

QT interval and repolarization dispersion changes during the administration of hydroxychloroquine/chloroquine with/without azithromycin in early COVID 19 pandemic: A prospective observational study from two academic hospitals in Indonesia.

BackgroundHydroxychloroquine/chloroquine (HCQ/CQ) treatment for COVID‐19 was associated with QT interval prolongation and arrhythmia risks. This study aimed to investigate QTc interval and ventricular repolarization dispersion changes, as markers of arrhythmia risks, after HCQ/CQ administration with/without azithromycin (AZT) during COVID‐19 pandemic.MethodsA prospective observational study was performed in two academic hospitals in Indonesia. Adult patients who received HCQ/CQ alone and HCQ/CQ + AZT concomitant treatments for COVID‐19 infection were enrolled. Baseline and post HCQ/CQ treatment electrocardiograms were obtained. Baseline and post HCQ/CQ treatment QT interval by Bazett (B‐QTc) and Fridericia (F‐QTc) formulas and ventricular repolarization dispersion indices by Tpeak‐Tend (Tp‐e) interval and Tpeak‐Tend/QT (Tp‐e/QT) ratio were calculated and analyzed.ResultsThe study enrolled 55 (HCQ/CQ alone) and 77 subjects (HCQ/CQ + AZT concomitant). F‐QTc interval significantly lengthened in subjects with HCQ/CQ + AZT (mean difference 11.89 ms [P = .028]). The incidences of severe B‐QTc and F‐QTc lengthening were 13.1% and 12.3%, B‐QTc and F‐QTc prolongation were 25.4% and 12.3%, and severe B‐QTc and F‐QTc prolongation were 6.2% and 3.2%. Tp‐e interval lengthened significantly from baseline to posttreatment in HCQ/CQ alone and HCQ/CQ + AZT (mean difference 10.83 ms [P = .006] and 18.73 ms [P < .001], respectively). Tp‐e/QT ratio increased significantly from baseline to posttreatment in HCQ/CQ + AZT concomitant (mean difference 0.035 [P < .001]). No fatal arrhytmia occurred.ConclusionsDuring COVID‐19 pandemic, HCQ/CQ + AZT concomitant treatment caused significant F‐QTc lengthening, significantly increased Tp‐e interval and increased Tp‐e/QT ratio. HCQ/CQ alone only caused significant increase of Tp‐e interval. Incidences of severe QTc lengthening and prolongation were low in both HCQ/CQ alone and HCQ/CQ + AZT concomitant.

Adaptation of ventricular repolarization dispersion during heart rate increase in humans: A roller coaster process

BackgroundRegional differences in ventricular activation sequence and action potential duration and morphology result in dispersion in ventricular repolarization (VR). VR dispersion is a key factor in arrhythmogenesis. We studied the adaptation of global VR dispersion in humans during normal and abnormal ventricular activation, and the relation to the QT adaptation (hysteresis). MethodsWe measured global VR dispersion as T amplitude, T area, and ventricular gradient (VG), using continuous Frank vectorcardiography, in response to abrupt and sustained atrial (AP) or ventricular pacing (VP) aiming at 120 bpm, in 21 subjects with permanent pacemakers. ResultsFollowing pacing start, VR adaptation showed an initially rapid and complex tri-phasic pattern, most pronounced for T amplitude. There were major differences in the patterns of VR dispersion adaptation following abrupt AP vs VP, confirming that the adaptation pattern is activation dependent. In response to AP, an instantaneous decrease in VR dispersion occurred, followed by an increase and then a slow decrease, all at a lower level than baseline. In contrast, following VP there was an immediate increase to ~4× baseline in T amplitude and T area (but not in VG), with a subsequent biphasic adaptation lasting longer during VP than AP. The initial rapid changes occurred within the time for QT adaptation to reach steady-state. ConclusionsOur results corroborate and expand data from animal and invasive human studies, showing similarities of the adaptation pattern on different scales. The initial rapidly changing VR adaptation phase presumably reflects a window of increased vulnerability to arrhythmias.

Myocardial repolarization is affected in patients with diabetic retinopathy

Background/Aim: Diabetes Mellitus (DM), considered the equivalent of coronary artery disease, is one cause of ventricular repolarization (VR) dispersion. Retinopathy is one of the vascular consequences of diabetes. The association between myocardial repolarization dispersion and diabetic retinopathy is not fully elucidated. We aimed to evaluate ventricular repolarization using Tp-e interval and corrected (c) Tp-e/QT ratio in DM patients with and without retinopathy. Methods: A total of 124 diabetic subjects were included in this retrospective cohort study. All medical data were obtained from the electronic database of our university hospital. The subjects were divided into the no diabetic retinopathy (NDR) group (n=45), and the diabetic retinopathy (DR) group (n=79), which were compared in terms of demographic features, clinic and laboratory findings, and electrocardiographic findings such as QT, QTc, Tp-e, Tp-e/QT, Tp-e/QTc. Results: The groups were similar in terms of demographic features (P>0.05). Both Tp-e interval and Tp-e/QTc were significantly prolonged in the DR group compared to the NDR group. There were significant correlations between Tp-e, Tp-e/QTc, DM duration, and age. In multivariate logistic regression analysis, Tp-e (OR=6.01, %95 CI=4.17-7.52, P=0.012), Tp-e/QTc (OR=1.215, 95% CI=0.874-1.612, P=0.029), and DM duration (OR=1.422, 95% CI= 1.146–1.712, P<0.001) were independent predictors of DR. Conclusion: We showed that DM patients with retinopathy may also have an increased risk for sudden cardiac death due to ventricular arrhythmogenesis.

Long-Term Prognostic Significance of Ventricular Repolarization Dispersion in Patients with Cardiac Sarcoidosis

Cardiac sarcoidosis (CS) is frequently complicated by fatal ventricular arrhythmias. T-peak to T-end interval to QT interval ratio (TpTe/QT) on electrocardiograms (ECG) was proposed as a marker of ventricular repolarization dispersion. Although this ratio could be associated with the incidence of ventricular arrhythmias in cardiovascular diseases, its prognostic implication in patients with CS is unclear. We sought to investigate whether TpTe/QT was associated with long-term clinical outcomes in patients with CS. Ninety consecutive patients with CS in 2 tertiary hospitals who had ECG data before initiation of immunosuppressive therapy between November 1995 and March 2019 were examined. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation (VT/VF), heart failure hospitalization, and all-cause death. During a median follow-up period of 4.70 (interquartile range 2.06-7.23) years, the primary outcome occurred in 21 patients (23.3%). Survival analyses revealed that the primary outcome (p < 0.001), especially VT/VF or sudden cardiac death (p=0.002), occurred more frequently in patients with higher TpTe/QT (≥ 0.242, the median) than in those with lower TpTe/QT. Multivariable Cox regression analysis showed that a higher TpTe/QT was independently associated with increased subsequent risk of adverse events (hazard ratio1.11, 95% confidence interval 1.03-1.20, p=0.008) even after adjustment for the significant covariates. In conclusion, a higher TpTe/QT was associated with worse long-term clinical outcomes, especially fatal ventricular arrhythmic events, in patients with cardiac sarcoidosis, suggesting the importance of assessing TpTe/QT as a surrogate for risk stratification in these patients.

When Manual Analysis of 12-Lead ECG Holter Plays a Critical Role in Discovering Unknown Patterns of Increased Arrhythmogenic Risk: A Case Report of a Patient Treated with Tamoxifen and Subsequent Pneumonia in COVID-19

Several medicines, including cancer therapies, are known to alter the electrophysiological function of ventricular myocytes resulting in abnormal prolongation and dispersion of ventricular repolarization (quantified by multi-lead QTc measurement). This effect could be amplified by other concomitant factors (e.g., combination with other drugs affecting the QT, and/or electrolyte abnormalities, such as especially hypokalemia, hypomagnesaemia, and hypocalcemia). Usually, this condition results in higher risk of torsade de point and other life-threatening arrhythmias, related to unrecognized unpaired cardiac ventricular repolarization reserve (VRR). Being VRR a dynamic phenomenon, QT prolongation might often not be identified during the 10-s standard 12-lead ECG recording at rest, leaving the patient at increased risk for life-threatening event. We report the case of a 49-year woman, undergoing tamoxifen therapy for breast cancer, which alteration of ventricular repolarization reserve, persisting also after correction of concomitant recurrent hypokalemia, was evidenced only after manual measurements of the corrected QT (QTc) interval from selected intervals of the 12-lead ECG Holter monitoring. This otherwise missed finding was fundamental to drive the discontinuation of tamoxifen, shifting to another “safer” therapeutic option, and to avoid the use of potentially arrhythmogenic antibiotics when treating a bilateral pneumonia in recent COVID-19.

The ECG Characteristics of Patients With Isolated Hypomagnesemia.

BackgroundElectrocardiographic (ECG) characteristics of patients with isolated hypomagnesemia are not well defined. We aimed to investigate these ECG characteristics in order to define clearly the features of isolated hypomagnesemia.HypothesisLower serum magnesium could affect ECG parameters after excluding potential confounders.MethodsThis retrospective study was of patients with low serum magnesium <0.65 mmol/L compared with the same patients after restoration to normal serum magnesium. Patients with hypokalemia, hypocalcemia and other electrolyte disturbances were excluded. ECG parameters manually determined and analyzed were P wave dispersion, PR interval, QRS duration, ST-T changes, T wave amplitude, T peak-to-end interval (Tpe), corrected Tpe (Tpec), QT, corrected QT (QTc), QT peak corrected (QTpc) and Tpe dispersion, Tpe/QT ratio.ResultsTwo-hundred-and-fourteen patients with isolated hypomagnesemia were identified with 50 of them (56.9 ± 13.6 years; 25 males) being eligible for final analysis from 270,997 patients presenting April 2011–October 2017. In the period of isolated hypomagnesemia, P wave duration was found prolonged (p ≤ 0.02); as was QTc (439 ± 27 vs. 433 ± 22, p = 0.01). Tpec (122 ± 24vs. 111 ± 22, p = 0.000) and Tpe/QT ratio (0.29 ± 0.05 vs. 0.27 ± 0.05, p = 0.000) were increased. QTpc decreased during hypomagnesemia (334 ± 28 vs. 342 ± 21, p = 0.02). However, no significant differences were found in PR interval, QRS duration (85 ± 12 ms vs. 86 ± 12 ms, p = 0.122) and ST-T segments between the patients and their own controls.ConclusionsIn patients with isolated hypomagnesemia, P wave duration, QTc, Tpec, and Tpe/QT ratio suggesting atrial depolarization and ventricular repolarization dispersion were significantly increased compared with normal magnesium levels in the same patients after restoration to normal levels.

Exercise Induced Worsening of Mechanical Heterogeneity and Diastolic Impairment in Long QT Syndrome.

Background: Electromechanical heterogeneities due to marked dispersion of ventricular repolarisation and mechanical function have been associated with symptoms in long QT syndrome (LQTS) patients; Aim: To examine the exercise response of longitudinal LV systolic and diastolic myocardial function and synchronicity in LQTS patients and its relationship with symptoms; Methods: Forty seven (age 45 ± 15 yrs, 25 female, 20 symptomatic) LQTS patients and 35 healthy individuals underwent an exercise test (Bruce protocol). ECG and echo parameters were recorded at rest, peak exercise (p.e.), and recovery; Results: LQTS patients had prolonged and markedly dispersed myocardial contraction, delayed early relaxation phase, and significantly decreased filling time at all exercise phases. Unlike controls, these electromechanical disturbances deteriorated further with exercise, during which additional decrease of the LV diastolic myocardial function and attenuated LV stroke volume were noted. Such abnormal responses to exercise were seen to a greater degree in symptomatic patients and in the LQT1 subgroup and improved with B-blocker therapy. Worsening myocardial contraction dispersion at p.e. was the strongest discriminator for previous clinical events, and its discriminating power excelled further by adding early relaxation delay; Conclusions: Electromechanical disturbances were shown to worsen during exercise in LQTS patients and were more pronounced in those with previous arrhythmic events.