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The waveform of ventricular action potential (AP) is a key determinant of the cardiac cycle, a marker of beating pathophysiology, and a target for anti‐arrhythmic drug design. The information contained in the waveform, though, is limited to the actual dynamics of the AP under consideration. By measuring quasi‐instantaneous current–voltage relationships during repolarization, I propose a three‐dimensional representation of the ventricular AP which includes potential dynamic responses that the beat can show when electrically perturbed. This representation is described in the case of a numerically reconstructed ventricular AP, but it can be, at least partially, derived in real cardiomyocytes. Simulation allows to disclose the potentialities and the limitations of the approach, that can be extended to any non‐cardiac AP. By reporting, at any AP time, the ion current available within the physiological membrane potential range at that time, the representation makes all together available: (1) refractory period, (2) thresholds for eliciting full or calcium‐driven APs, (3) threshold for all‐or‐none repolarization, (4) membrane resistance during repolarization, (5) the safety of membrane repolarization. It provides further evidence of a negative membrane resistance during the late phase of ventricular AP and a quantitative estimate of repolarization reserve (RR), key determinants of repolarization dynamics. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular diseases, arrhythmias, and sudden cardiac death (SCD). However, the acute impacts of OSA and its consequences on heart function are not yet fully elucidated. We hypothesized that desaturation events acutely destabilize ventricular repolarization, and the presence of accompanying arousals magnifies this destabilization. Ventricular repolarization lability measures, comprising heart rate corrected QT (QTc), short-time-variability of QT (STVQT), and QT variability index (QTVI), were calculated before, during, and after 20,955 desaturations from lead II electrocardiography signals of 492 patients with suspected OSA (52% men). Variations in repolarization parameters were assessed during and after desaturations, both with and without accompanying arousals, and groupwise comparisons were performed based on desaturation duration and depth. Regression analyses were used to investigate the influence of confounding factors, comorbidities, and medications. The standard deviation (SD) of QT, mean QTc, SDQTc, and STVQT increased significantly (P < 0.01), whereas QTVI decreased (P < 0.01) during and after desaturations. The changes in SDQT, mean QTc, SDQTc, and QTVI were significantly amplified (P < 0.01) in the presence of accompanying arousals. Desaturation depth was an independent predictor of increased SDQTc (β = 0.405, P < 0.01), STVQT (β = 0.151, P < 0.01), and QTVI (β = 0.009, P < 0.01) during desaturation. Desaturations cause acute changes in ventricular repolarization, with deeper desaturations and accompanying arousals independently contributing to increased ventricular repolarization lability. This may partially explain the increased risk of arrhythmias and SCD in patients with OSA, especially when the OSA phenotype includes high hypoxic load and fragmented sleep. NEW & NOTEWORTHY Nocturnal desaturations are associated with increased ventricular repolarization lability. Deeper desaturations with accompanying arousals increase the magnitude of alterations, independent of confounding factors, comorbidities, and medications. Changes associated with desaturations can partially explain the increased risk of arrhythmias and sudden cardiac death in patients with OSA, especially in patients with high hypoxic load and fragmented sleep. This highlights the importance of detailed electrocardiogram analytics for patients with OSA. [ABSTRACT FROM AUTHOR]

Sudden changes in pacing cycle length are frequently associated with repolarization abnormalities initiating cardiac arrhythmias, and physiologists have long been interested in measuring the likelihood of these events before their manifestation. A marker of repolarization stability has been found in the electrical restitution (ER), the response of the ventricular action potential duration to a pre- or post-mature stimulation, graphically represented by the so-called ER curve. According to the restitution hypothesis (ERH), the slope of this curve provides a quantitative discrimination between stable repolarization and proneness to arrhythmias. ER has been studied at the body surface, whole organ, and tissue level, and ERH has soon become a key reference point in theoretical, clinical, and pharmacological studies concerning arrhythmia development, and, despite criticisms, it is still widely adopted. The ionic mechanism of ER and cellular applications of ERH are covered in the present review. The main criticism on ERH concerns its dependence from the way ER is measured. Over the years, in fact, several different experimental protocols have been established to measure ER, which are also described in this article. In reviewing the state-of-the art on cardiac cellular ER, I have introduced a notation specifying protocols and graphical representations, with the aim of unifying a sometime confusing nomenclature, and providing a physiological tool, better defined in its scope and limitations, to meet the growing expectations of clinical and pharmacological research. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate ventricular repolarization before, at the first month, and sixth month after Sacubutril/Valsartan, an angiotensin receptor neprilysin inhibitor (ARNI) treatment in heart failure patients with reduced ejection fraction (HFrEF). Materials and Methods: We included 49 patients with HFrEF who switched to ARNI therapy. The 12-lead electrocardiography (ECG) was evaluated before ARNI therapy and also during the first and sixth months of the therapy. We evaluated demographic, clinical, and laboratory parameters, as well as medications and ECG data, including heart rate. Additionally, we examined QT, QTc, Tp-e, Tp-e calculated (Tp-ec), Tp-ec/QTc, Tpe/QT, and Tp-e/QTc. Results: After receiving ARNI treatment, ventricular repolarization indices were significantly reduced in the first and sixth months compared to before treatment. Specifically, the QTc values decreased from 457.6 ms to 443.8 ms, and the Tp-e/QT ratio decreased from 0.21±0.03 to 0.19±0.03. Additionally, the QTc values decreased from 457.6 ms to 444.9 ms, and the Tp-e/QT ratio decreased from 0.21±0.03 to 0.18±0.03. However, when the first and sixth months under ARNI treatment were compared, no significant difference was found (QTc: 443.8 ms vs. 444.9 ms, Tp-e/QT: 0.19±0.03 vs. 0.18±0.003). Conclusion: ARNI treatment in HFrEF positively affected QTc, Tp-e, and Tp-ec intervals and Tp-e/QT, Tp-e/QTc, and Tp-ec/QTc ratios, which are indicators of ventricular repolarization. Moreover, this effect started in the first month and continued in the sixth month. [ABSTRACT FROM AUTHOR]

Whether sodium–glucose cotransporter-2 inhibitors (SGLT2is) reduce ventricular arrhythmias and sudden cardiac death is controversial. Ventricular repolarization heterogeneity is associated with ventricular arrhythmias; however, the effect of SGLT2is on ventricular repolarization in patients with heart failure with reduced ejection fraction (HFrEF) has not been fully investigated. We prospectively evaluated 31 HFrEF patients in sinus rhythm who were newly started on dapagliflozin 10 mg/day. Changes in QT interval, corrected QT interval (QTc), QT dispersion (QTD), corrected QTD (QTcD), T peak to T end (TpTe), TpTe/QT ratio, and TpTe/QTc ratio were evaluated at 1-year follow-up. QT interval, QTc interval, QTD, QTcD, TpTe, and TpTe/QTc ratio decreased significantly at 1-year follow-up (427.6 ± 52.6 ms vs. 415.4 ± 35.1 ms; p = 0.047, 437.1 ± 37.3 ms vs. 425.6 ± 22.7 ms; p = 0.019, 54.1 ± 11.8 ms vs. 47.6 ± 14.7 ms; p = 0.003, 56.0 ± 11.2 ms vs. 49.4 ± 12.3 ms; p = 0.004, 98.0 ± 15.6 ms vs. 85.5 ± 20.9 ms; p = 0.018, and 0.225 ± 0.035 vs. 0.202 ± 0.051; p = 0.044, respectively). TpTe/QT ratio did not change significantly (0.231 ± 0.040 vs. 0.208 ± 0.054; p = 0.052). QT interval, QTD, and TpTe were significantly reduced 1 year after dapagliflozin treatment in patients with HFrEF. The beneficial effect of dapagliflozin on the heterogeneity of ventricular repolarization may contribute to the suppression of ventricular arrhythmias. Registry informationhttps://center6.umin.ac.jp/cgi-open-bin/ctr/ctr%5fview.cgi?recptno=R000049428. Registry number: UMIN000044902. [ABSTRACT FROM AUTHOR]

Aim: Bipolar disorder (BD) is one of the chronic psychiatric diseases. It has been reported that cardiovascular diseases are seen twice as often in patients with BD. Fragmented QRS (fQRS) has been found to be associated with myocardial scarring and is used as a marker of arrhythmia and mortality. Ventricular repolarization (VR) is often evaluated using QT interval and T wave measurement data. In our study, we aimed to evaluate fQRS, QTc interval, QT dispersion (QTd), Tp-e interval, Tp-e/QT ratio results and VR, together with blood biochemistry parameter results of cases with BD. Material and Method: Our research was conducted with 51 people diagnosed with bipolar disorder and 52 healthy people as the control group. fQRS, QTc interval, QT dispersion (QTd), Tp-e interval, Tp-e/QT ratio were measured using 12-lead electrocardiography (ECG). The results of the data obtained from ECG and blood biochemistry parameter levels were used to compare the healthy and patient groups. Results: Tp-e interval (p=0.018) and Tpe/QT ratio (p=0.036) were found to be statistically significantly higher and total cholesterol level (p=0.006) lower in patients with bipolar disorder compared to the control group. Conclusion: An increased Tpe/QT ratio, along with a prolonged Tp-e interval, may be a useful marker of ventricular arrhythmia risk in individuals with fQRS BD. [ABSTRACT FROM AUTHOR]

The index of the cardio-electrophysiological balance may be used to assess ventricular arrhythmogenesis. The index of cardio-electrophysiologic al balance has been associated with malignant ventricular arrhythmias. Ventricular arrhythmias caused by drugs have been connected to a new risk measure called the index of cardio-electrophysiological balance the interval from the beginning of the QRS complex to the end of the T wave (QT) interval divided by the deflections in an electrocardiogram (EKG) tracing that represent the ventricular activity of the heart (QRS) duration), which was recently tested in an animal model. The cardiac wavelength index of cardio-electrophysiological balance was considered to equal the effective refractory period multiplied by the conduction velocity. An increase or decrease in the index of cardio-electrophysiological balance could suggest an increased risk of ventricular tachycardia/fibrillation induced by torsades de pointes or non-torsades de pointes. The index of cardio-electrophysio logical balance is one of the most often used methods for measuring the cardiac waveform. Because it is noninvasive and simple to measure, index of cardio-electrophysiological balance may be used to predict ventricular arrhythmia risk. [ABSTRACT FROM AUTHOR]

Background: Cardiac complications due to anthracycline treatment may become evident several years after chemotherapy and are recognized as a serious cause of morbidity and mortality in cancer patients or childhood cancer survivors. Objectives: We analyzed ventricular repolarization parameters in electrocardiography for pediatric acute lymphoblastic leukemia patients during chemotherapy and in long-term follow-up. To establish the reference values of ventricular repolarization parameters in children, we retrospectively summarized the Tpe interval, QT interval, QTc interval, and Tpe/QT ratio in healthy Japanese children. Methods: Electrocardiography data recorded from students in 1st and 7th grades were randomly selected from a database maintained by the school-based screening system in the Oita city cohort, Japan. Subsequently, chronological data of the Tpe/QT ratio in 17 pediatric patients with acute lymphoblastic leukemia were analyzed over time. Results: The mean ± standard deviation of the Tpe interval in 1st and 7th graders was 70 ± 7 and 78 ± 17 ms, respectively, while the mean ± standard deviation of the Tpe/QT ratio was 0.21 ± 0.02 and 0.22 ± 0.02 ms, respectively. During the intensive phase of treatment, the Tpe/QT ratios of 3 high-risk patients among the 17 patients with acute lymphoblastic leukemia exceeded the upper limit. Conclusion: The Tpe/QT ratio has a potential clinical application in predicting the risk of long-term ventricular arrhythmia of cancer patients or childhood cancer survivors from childhood to adulthood. [ABSTRACT FROM AUTHOR]

Electronic cigarettes are often used for smoking cessation as a harm reduction strategy, but studies comparing risks of electronic cigarettes (ECs) and tobacco cigarettes (TCs) are scarce. Ventricular repolarization in people who smoke TCs is abnormal. Baseline repolarization was compared among nonusers (people who do not use TCs or ECs) and people who use ECs or TCs. The acute effects of ECs and TCs on metrics of ventricular repolarization were then compared in people who chronically smoke. A total of 110 participants (59 female), including 35 people (21 females) in the TC cohort, 34 people (17 females) in the EC cohort, and 41 people (21 females) in the nonuser cohort, were included. None of the primary outcomes, Tpeak-end (Tp-e), Tp-e/QT, and Tp-e/QTc, were different among the three cohorts at supine baseline, even when adjusted for sex. When compared with the control exposure standing after acutely using the EC but not the TC, significantly prolonged all three primary indices of ventricular repolarization in people who smoke TCs. The major new finding in this study is that in people who smoke TCs, using an EC compared with a TC significantly prolongs ventricular repolarization. Furthermore, in our subgroup analysis by sex, this adverse effect on repolarization is found only in male, not female, smokers. In summary, chronic TC smoking is the most prevalent, modifiable risk factor for cardiovascular death, including sudden cardiac death. If used for smoking cessation, ECs should only be used in the short term since they too carry their own risks; this risk appears to be greatest in males compared with females who smoke. NEW & NOTEWORTHY The major new finding in this study is that in people who smoke tobacco cigarettes, using an electronic cigarette but not a tobacco cigarette acutely and significantly prolongs several metrics of ventricular repolarization, including Tpeak-Tend, Tpeak-Tend/QT, and Tpeak-Tend/QTc. Furthermore, in our subgroup analysis by sex, this adverse effect on repolarization is found only in male, not female, smokers. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to examine the ventricular repolarization (VR) disturbances of patients operated on for acute spontaneous Achilles tendon ruptures (ATRs), by comparing them with a healthy individual control group. Materials and Methods: Between June 2014 and July 2020, a total of 29 patients (28 males, 1 female; mean age: 40 ± 9.78 years; range, 21–66 years) who presented to the emergency department within the first three weeks of injury, and were diagnosed with acute spontaneous ATRs and treated with an open Krackow suture technique, were retrospectively analyzed. Fifty-two healthy individuals (47 males, 5 females; mean age: 39 ± 11.45 years; range, 21–66 years) were recruited as a control group from the cardiology outpatient clinic. Clinical data (demographic features and laboratory parameters (serum glucose, creatinine, hemoglobin, white blood cell count, and lipid profile)) and electrocardiograms (ECGs) were collected from medical records. ECGs were evaluated for heart rate and VR parameters of QRS width, QTc interval, cQTd interval, Tp-e interval, and Tp-e/QT ratio. The clinical data and these ECG parameters were compared between groups. Results: There was no statistically significant difference between groups, regarding clinical data (all p < 0.05). Among ECG parameters, heart rate, QRS width, QTc interval, and cQTd interval were similar between groups (all p < 0.05). There were two important statistically significant findings of this research: The mean Tp-e interval was longer (ATR group: 72.4 ± 24.7, control group: 58.8 ± 14.5, p: 0.01), and the Tp-e/QT ratio was higher (ATR group: 0.2 ± 0.1, control group: 0.16 ± 0.4, p: 0.027) in the ATR group. Conclusions: According to the ventricular repolarization disturbances found in this study, patients with ATR may be at a higher risk of ventricular arrhythmia than healthy people. As a result, ATR patients should be assessed for ventricular arrhythmia risk by an expert cardiologist. [ABSTRACT FROM AUTHOR]

Objectives: T wave's peak and end interval (Tp-e), Tp-e/QT ratio and Tp-e/QTc ratio are novel markers of ventricular repolarization and are associated with ventricular arrhythmias. Increased ventricular arrhythmia incidence is reported in patients with acromegaly. The purpose of this study is to evaluate ventricular repolarization using the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio in patients with acromegaly. Methods: Thirty-five patients with acromegaly were included in the study. The control group was consisted of forty-one subjects without acromegaly that having similar age, sex ratio and comorbidities. The Tp-e interval, Tp-e/QT ratio, Tp-e/QTc ratio, and other ventricular repolarization parameters of all patients were evaluated using electrocardiography. Results: Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were significantly prolonged in patients with acromegaly compared to the control group. Furthermore, Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio showed a significant correlation with plasma GH levels and LVMI values. Conclusions: Our study revealed that Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with acromegaly. We believe that the Tp-e interval, Tp-e/QT ratio, and Tpe/QTc ratio can be used in the evaluation of increased cardiovascular risk in patients with acromegaly. [ABSTRACT FROM AUTHOR]

Late sodium current (INa,late) is an important inward current contributing to the plateau phase of the action potential (AP) in the mammalian heart. Although INa,late is considered as a possible target for antiarrhythmic agents, several aspects of this current remained hidden. In this work, the profile of INa,late, together with the respective conductance changes (GNa,late), were studied and compared in rabbit, canine, and guinea pig ventricular myocytes using the action potential voltage clamp (APVC) technique. In canine and rabbit myocytes, the density of INa,late was relatively stable during the plateau and decreased only along terminal repolarization of the AP, while GNa,late decreased monotonically. In contrast, INa,late increased monotonically, while GNa,late remained largely unchanged during the AP in guinea pig. The estimated slow inactivation of Na+ channels was much slower in guinea pig than in canine or rabbit myocytes. The characteristics of canine INa,late and GNa,late were not altered by using command APs recorded from rabbit or guinea pig myocytes, indicating that the different shapes of the current profiles are related to genuine interspecies differences in the gating of INa,late. Both INa,late and GNa,late decreased in canine myocytes when the intracellular Ca2+ concentration was reduced either by the extracellular application of 1 µM nisoldipine or by the intracellular application of BAPTA. Finally, a comparison of the INa,late and GNa,late profiles induced by the toxin of Anemonia sulcata (ATX-II) in canine and guinea pig myocytes revealed profound differences between the two species: in dog, the ATX-II induced INa,late and GNa,late showed kinetics similar to those observed with the native current, while in guinea pig, the ATX-II induced GNa,late increased during the AP. Our results show that there are notable interspecies differences in the gating kinetics of INa,late that cannot be explained by differences in AP morphology. These differences must be considered when interpreting the INa,late results obtained in guinea pig. [ABSTRACT FROM AUTHOR]

Background: Sleep is fragmented by brief arousals, and excessive arousal burden has been linked to increased cardiovascular (CV) risk, but mechanisms are poorly understood.Research Question: Do arousals trigger cardiac ventricular repolarization lability that may predispose people to long-term cardiovascular mortality?Study Design and Methods: This study analyzed 407,541 arousals in the overnight polysomnograms of 2,558 older men in the Osteoporotic Fractures in Men sleep study. QT and RR intervals were measured beat-to-beat starting 15 s prior to arousal onset until 15 s past onset. Ventricular repolarization lability was quantified by using the QT variability index (QTVi).Results: During 10.1 ± 2.5 years of follow-up, 1,000 men died of any cause, including 348 CV deaths. During arousals, QT and RR variability increased on average by 5 and 55 ms, respectively, resulting in a paradoxical transient decrease in QTVi from 0.07 ± 1.68 to -1.00 ± 1.68. Multivariable Cox proportional hazards analysis adjusted for age, BMI, cardiovascular and respiratory risk factors, sleep-disordered breathing and arousal, diabetes, and Parkinson disease indicated that excessive QTVi during arousal was independently associated with all-cause and CV mortality (all-cause hazard ratio, 1.20 [95% CI, 1.04-1.38; P = .012]; CV hazard ratio, 1.29 [95% CI, 1.01 -1.65; P = .043]).Interpretation: Arousals affect ventricular repolarization. A disproportionate increase in QT variability during arousal is associated with an increased all-cause and CV mortality and may reflect ventricular repolarization maladaptation to the arousal stimulus. Whether arousal-related QTVi can be used for more tailored risk stratification warrants further study, including evaluating whether arousal suppression attenuates ventricular repolarization lability and reduces subsequent mortality.Clinical Trial Registration: ClinicalTrials.gov; No.: NCT00070681; URL: www.Clinicaltrials: gov. [ABSTRACT FROM AUTHOR]

Approximately 30% to 70% of patients with cirrhosis have QT interval prolongation. In patients without cirrhosis, QT prolongation is associated with an increased risk of ventricular arrhythmias, such as torsade de pointes (TdP). In cirrhotic patients, there is likely a significant association between the corrected QT (QTc) interval and the severity of liver disease, and possibly with increased mortality. We present a stepwise overview of the pathophysiology and management of acquired long QT syndrome in cirrhosis. The QT interval is mainly determined by ventricular repolarization. To compare the QT interval in time it should be corrected for heart rate (QTc), preferably by the Fridericia method. A QTc interval >450 ms in males and >470 ms in females is considered prolonged. The pathophysiological mechanism remains incompletely understood, but may include metabolic, autonomic or hormonal imbalances, cirrhotic heart failure and/or genetic predisposition. Additional external risk factors for QTc prolongation include medication (IKr blockade and altered cytochrome P450 activity), bradycardia, electrolyte abnormalities, underlying cardiomyopathy and acute illness. In patients with cirrhosis, multiple hits and cardiac-hepatic interactions are often required to sufficiently erode the repolarization reserve before long QT syndrome and TdP can occur. While some risk factors are unavoidable, overall risk can be mitigated by electrocardiogram monitoring and avoiding drug interactions and electrolyte and acidbase disturbances. In cirrhotic patients with prolonged QTc interval, a joint effort by cardiologists and hepatologists may be useful and significantly improve the clinical course and outcome. [ABSTRACT FROM AUTHOR]

Objective: The clinical significance of QT interval adaptation to heart rate changes has been poorly investigated in atrial fibrillation (AF), since QT delineation in the presence of f-waves is challenging. The objective of the present study is to investigate new techniques for QT adaptation estimation in permanent AF. Methods: A multilead strategy based on periodic component analysis, to emphasize T-wave periodicity, is proposed for QT delineation. QT adaptation is modeled by a linear, time-invariant filter, which describes the dependence between the current QT interval and the preceding RR intervals, followed by a memoryless, nonlinear, function. The QT adaptation time lag is determined from the estimated impulse response. Results: Using simulated ECGs in permanent AF, the transformed lead was found to offer more accurate QT delineation and time lag estimation than did the original ECG leads for a wide range of f-wave amplitudes. In a population with chronic heart failure and permanent AF, the time lag estimated from the transformed lead was found to have the strongest, statistically significant association with sudden cardiac death (SCD) (hazard ratio = 3.49). Conclusions: Periodic component analysis provides more accurate QT delineation and improves time lag estimation in AF. A prolonged QT adaptation time lag is associated with a high risk for SCD. Significance: SCD risk markers originally developed for sinus rhythm can also be used in AF, provided that T-wave periodicity is emphasized. The time lag is a potentially useful biomarker for identifying patients at risk for SCD, guiding clinicians in adopting effective therapeutic decisions. [ABSTRACT FROM AUTHOR]

The article is focused on the evaluation of the electrical activity of the heart in rats during ventricular repolarization after a single bout of forced treadmill running until exhaustion. Electrophysiological properties of the myocardium were studied by conventional ECG and body surface potential mapping. Cardiac potentials were registered in zoletil-anesthetized rats 3–5 days before (baseline) and 5, 10, 20 and 30 min after exhaustive treadmill running. Compared with baseline, an increase in the duration of the QTII, JTII and Tpeak–TendII intervals, an earlier onset and a later completion, as well as an increase in the duration of ventricular repolarization on body surface equipotential maps (BSPMs) were revealed in rats 5 min after exhaustive exercise. Ten min following treadmill running to exhaustion, the temporal parameters of the heart electrical activity returned to pre-exercise values. Changes in the amplitude characteristics of both ECGII (ST segment depression, a decrease in the T-wave amplitude) and BSPMs (a decrease in the maximum amplitudes of positive and negative extrema during ventricular repolarization) were showed after 5–10 min and persisted up to 20–30 min after running to exhaustion. A positive correlation was found between changes in the maximum amplitude of negative extremum of BSPMs and changes in the amplitude of the TII-wave in the analyzed time periods after exhausting exercise. It is assumed that the observed changes in the electrical properties of the heart in rats during ventricular repolarization after forced treadmill running were due to ischemic myocardial damage induced by exhaustive physical exercise. [ABSTRACT FROM AUTHOR]

Introduction: Variability and prolongation of ventricular repolarization - measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality.Methods: Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each). Overnight electrocardiograms were analyzed for QTc duration and QT variability (standard deviation of QT intervals, normalized QT interval variance and the short-term interval beat-to-beat QT variability). Cox proportional hazards penalized regression modeling was used to identify predictors of mortality.Results: Eight hundred of 5600 participants were randomly selected. The participants (68 ± 10 years; 56.8% male) were followed for an average of 8.2 years during which time 222 (28.4%) died. QTc, SDQT, and QTVN were associated with the presence of SDB (p = 0.002, p = 0.014, and p = 0.024, respectively). After adjusting for covariates, the presence of sleep-disordered breathing did not moderate the association between QTc length, QT variability and mortality (p > 0.05).Conclusion: Sleep-disordered breathing was associated with some measures of ventricular repolarization. However, sleep-disordered breathing was not an effect modifier for the relationship between QTc and QT variability and mortality. [ABSTRACT FROM AUTHOR]

Background: Obesity, a rapidly increasing global health problem in all age groups, is accepted as the basis for many chronic diseases through insulin resistance mechanism. This study aimed to examine whether insulin resistance and other comorbidities of obesity have an effect on the cardiac conduction system. Methods: The study included 50 obese and 47 healthy individuals aged 6-18 years. ECGs of all cases were taken; ECG waves and intervals were measured manually. Results: Of the obese group, 19 were boys (38%) and 31 were girls (62%), 27 were children (54%) and 23 were adolescents (46%), their ages were 11.3 ± 3.5 years. These particular characteristics were similar compared to the control group. However, in the obese group, the ECG parameters QTc (p = 0.001), QTd (p < 0.001), QTdc (p < 0.001), JTc (p < 0.001), Tp-e (p < 0.001), Tp-e/QT (p < 0.001), Tp-e/QTc (p < 0.001), Tp-e/JT (p < 0.001), and Tp-e/JTc (p < 0.001) were significantly longer. Twenty-five obese subjects (50%) had insulin resistance, when ECG parameters are compared to those without it, only JTc was significantly longer (332.3 ± 16.5 vs 321.7 ± 17.7 ms, p = 0.033). JTc duration mostly affected JT (p < 0.001) and QTc (p < 0.001). The 327 ms cut-off value of JTc indicated insulin resistance in the obese patients (p = 0.044) (sensitivity 60%, specificity 60%). Conclusion: Insulin resistance and other comorbidities of obesity may cause ventricular repolarization abnormalities at an early age. JTc, an ECG parameter, can be a guide in assessing ventricular repolarization abnormality and the risk of arrhythmia in these patients. [ABSTRACT FROM AUTHOR]

Cardiac electrophysiological studies demonstrate that restricting the feeding of mice to the light cycle (time restricted feeding or TRF) causes a pronounced change in heart rate and ventricular repolarization as measured by the RR- and QT-interval, respectively. TRF slows heart rate and shifts the peak (acrophase) of the day/night rhythms in the RR- and QT-intervals from the light to the dark cycle. This study tested the hypothesis that these changes in cardiac electrophysiology are driven by the cardiomyocyte circadian clock mechanism. We determined the impact that TRF had on RR- and QT-intervals in control mice or mice that had the cardiomyocyte circadian clock mechanism disrupted by inducing the deletion of Bmal1 in adult cardiomyocytes (iCSΔBmal1−/− mice). In control and iCSΔBmal1−/− mice, TRF increased the RR-intervals measured during the dark cycle and shifted the acrophase of the day/night rhythm in the RR-interval from the light to the dark cycle. Compared to control mice, TRF caused a larger prolongation of the QT-interval measured from iCSΔBmal1−/− mice during the dark cycle. The larger QT-interval prolongation in the iCSΔBmal1−/− mice caused an increased mean and amplitude in the day/night rhythm of the QT-interval. There was not a difference in the TRF-induced shift in the day/night rhythm of the QT-interval measured from control or iCSΔBmal1−/− mice. We conclude that the cardiomyocyte circadian clock does not drive the changes in heart rate or ventricular repolarization with TRF. However, TRF unmasks an important role for the cardiomyocyte circadian clock to prevent excessive QT-interval prolongation, especially at slow heart rates. [ABSTRACT FROM AUTHOR]

Introduction: His‐bundle pacing (HBP) and left‐bundle‐area pacing (LBAP) are conduction system pacing (CSP) modalities increasingly used as alternatives to conventional biventricular pacing (BiVP). While effects of CSP on ventricular depolarization have been reported, effects on ventricular repolarization have not. Methods: QRS duration (QRSd) and validated ECG parameters of ventricular repolarization associated with arrhythmic risk (T‐peak‐to‐T‐endTransmural, T‐peak‐to‐T‐endTotal, T‐peak dispersion, QTc, QTc dispersion) were analyzed post‐implant in 107 patients: 60 with CSP (HBP: n = 35, LBAP: n = 25) and 47 with BiVP. T‐wave memory resolution and QTc shortening were analyzed on ECGs obtained ≥25 days post‐implant. Twenty blinded measurements were obtained by both authors to assess Interobserver variability. Results: Although QRSd was shorter with HBP versus LBAP (119 ± 7 ms vs. 132 ± 9 ms, p =.02), there were no significant differences in any repolarization parameters between these methods of CSP. However, when comparing CSP (HBP + LBAP) to BiVP, both QRSd (125 ± 5 ms vs. 147 ± 7 ms, p <.0001) and repolarization parameters (T‐peak‐to‐T‐endTransmural: 83 ± 5 ms vs. 107 ± 8 ms; T‐peak‐to‐T‐endTotal: 110 ± 7 ms vs. 137 ± 10 ms; QTc: 470 ± 12 ms vs. 506 ± 12 ms; all p ≤.0001) were significantly shorter with CSP. Improved T‐peak‐to‐T‐end values were unrelated to pre‐implant QRSd or LV function. Interobserver variability was 4.6 ± 1.9 ms. Frontal QRS‐T angle narrowing (132° to 104°, p =.001) and QTc shortening (483 ± 13 ms to 464 ± 12 ms, p =.008) were seen only with CSP. Conclusions: In addition to improved depolarization, CSP reduced repolarization heterogeneity and provided greater T‐wave memory resolution as compared to BiVP. Both modalities of CSP (HBP + LBAP) resulted in comparably reduced repolarization heterogeneity regardless of baseline QRSd and LV function. These observations may confer lower arrhythmogenic risk and warrant further study. [ABSTRACT FROM AUTHOR]

Objective To investigate whether the indexes of ventricular repolarization and electrical excitation conduction in sleep-disordered patients are different from those in normal people,and to provide cardiac rehabilitation basis for sleep-disordered patients with heart-related diseases. Methods We randomly selected a routine physical examination population of 130 from our hospital,and carried out a questionnaire survey on all the subjects with the Pittsburgh sleep quality index（ PSQI） scale. The subjects with a total PSQI score of 0-7 were set as normal sleep group（ 91 cases） while those with PSQI score no less than 8 were divided into sleep-disordered group（ 39 cases）.Retrospective analysis was performed on the cardiac electrophysiological indicators of all the surveyed subjects including QRS duration,heart rate,QT interval,QTc,QTd,QTcd,Tpeak-Tend interval（ Tp-Te）,Tp-Te/QT,etc. The changes of ST-T in ECG were recorded. Results Compared with the normal sleep group,QTc,QTd,QTcd,Tp-Te,Tp-Te/QT and Tp-Te/QTc are all significantly prolonged in the sleep-disordered group（ P < 0. 05）; the incidence of ST-T change is significantly increased（ P < 0. 01）. Logistic regression analysis shows that sex and sleep time are the most influential variables for ST-T change in ECG（ sex: OR = 7. 521,95% CI 2. 534-22. 325,P < 0. 05; sleep duration: OR = 2. 604,95% CI 1. 470-4. 611,P < 0. 05）. Conclusion Sleep disorders may contribute to the inhomogeneity of ventricular repolarization,and possibly serve as one of the risk factors of cardiovascular disease. Female and shortened sleep time are proved to be the independent risk factors for ST-T changes. [ABSTRACT FROM AUTHOR]

Background: Arrhythmias can be seen as a sign of cardiac autonomic neuropathy in type 1 diabetes mellitus. We aimed to evaluate pulmonary artery pressure, ventricular depolarization and repolarization variability in children with type 1 diabetes mellitus. Methods: We investigated 78 children with type 1 diabetes mellitus (mean age 11.6 ± 3.6 years) and 68 age-gender matched healthy children as control group. All type 1 diabetes mellitus patients were divided into three subgroups according to glycated hemoglobin (HbA1c) levels and the duration of disease. Electrocardiogram and transthoracic echocardiograms were performed on both groups. Results: In patients with type 1 diabetes mellitus, there was an elongation in P, Pd, PR, QTc, QTd, QTcd, JT, JTc, JTd, Tp-Te and Tp-Te/QT, Tp-Te/QTc, Tp-Te/JT, Tp-Te/JTc ratios were higher (P < 0.05). In patients with type 1 diabetes mellitus, pulmonary artery pressure was higher than control group (P = 0.001). Prolongation of QTc, thickness of left ventricle end-diastolic diameter and left ventricle posterior wall diameter were higher in the HbA1c ≥9% subgroup. When adjusted for age there was no significant correlation between left ventricle parameters and HbA1c. Conclusions: Atrial conduction delay and impairment of ventricular repolarization were significantly high and there was a predisposition for the development of pulmonary artery hypertension in children with type 1 diabetes mellitus. Poor glycemic control was not a risk factor for propensity of left ventricle hypertrophy and left ventricle dysfunction. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Low levels of vitamin D are known to increase cardiovascular mortality due to different risks. We aimed to examine whether low vitamin D levels in children and adolescents cause ventricular repolarization changes. METHODS: Sixtyseven healthy cases aged between 3.5 and 17 years were included. According to levels of vitamin D, cases were grouped as sufficient (n=44), insufficient (n=13) and deficiency (n=10). Ventricular repolarization parameters were measured manually. RESULTS: Levels of vitamin D were different for cases with insufficiency and deficiency compared to sufficiency ones (102±54.9 vs 24.4±7 ng/ml, p<0.001 and 102±54.9 vs 16.6±8.3 ng/ml, respectively, p<0.001). In the insufficient group the following parameters were different from sufficient group: QTmean (357.8±25.3 vs 332±29.9 ms, p=0.012), JTc (310.8±20.2 vs 331.6±21 ms, p=0.005) and Tpe/QT (0.2±0.02 vs 0.22±0.02, p=0.02). It was found that the level of serum vitamin D correlated with JTc (r=-0.37, p=0.002), Tp-e (r=-0.29, p=0.015) and Tp-e/QT (r=-0.24, p=0.047). In the linear regression analysis, it was found that dropping level of vitamin D below normal was an independent risk factor for prolonged duration of JTc (p=0.015). CONCLUSIONS: Decline in vitamin D levels causes ventricular repolarization anomaly. As the decrease in vitamin D levels deepens, repolarization times become longer. These results could indicate that decrease in vitamin D levels can increase sensitivity to ventricular arrhythmias. [ABSTRACT FROM AUTHOR]

Background: Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio are electrocardiographic markers and indices of ventricular arrhythmogenic events. We aimed to investigate ventricular repolarization in normal weight, overweight, obese and morbidly obese individuals by using ECG parameters including the above markers. Methods: A total of 310 obese patients with various cardiac complaints, who were admitted to our outpatient clinic between May 2020 and January 2021, were prospectively included in the study. Using the World Health Organization (WHO) body mass index (BMI) classification, patients were divided into four groups: normal weight (18.5–24.9 kg/m2, n = 48), overweight (25–29.9 kg/m2, n = 98), obese (30–39.9 kg/m2, n = 119), and morbidly obese (>40 kg/m2, n = 45). Results: The morbidly obese and normal groups were younger in age than the other two groups. The Tp-e interval values for Groups I–IV were 72.1 ± 6.9, 73.1 ± 6.2, 75.7 ± 7.3 and 81.1 ± 6.9, respectively, and significantly different (P <.001). We found that age, BMI, systolic blood pressure (BP) and diastolic BP were independent predictors of a prolonged Tp-e interval. Conclusions: The principal finding of our study was the gradual increase in Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio starting from the overweight stage and these parameters gradually increase in obese and morbidly obese patients. Additionally, systolic and diastolic blood pressure predicted Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio. [ABSTRACT FROM AUTHOR]

Ivonina, Natalya I., Andrey A. Fokin, and Irina M. Roshchevskaya. Body surface potential mapping during heart ventricular repolarization in male swimmers and untrained persons under hypoxic and hypercapnic hypoxia. High Alt Med Biol. 22:308–316, 2021. Background: In swimmers, as a result of prolonged breath-holding during swimming, first hypoxic hypoxia (HH) and then hypercapnic hypoxia (HCH) occurs, which may influence the electrical activity of the heart (EAH). What type of normobaric hypoxia more strongly affects the EAH—normocapnic HH or HCH? Methods: The electrical activity of swimmers' hearts (n = 7) and untrained persons (n = 10) was studied by using electrocardiography (ECG) and body surface potential mapping (BSPM) during the period of ventricular repolarization at baseline, at normocapnic HH, at HCH, and in the recovery period. Results: HH led to more significant changes in the EAH in all participants in comparison with HCH. There was no change in the amplitude of T waveECG at hypoxic and HCH, but a change in the amplitude of the minimum was noted in BSPM. The minimum in athletes changed by the end of the exposure (from −0.40 ± 0.12 mV to −0.26 ± 0.11 mV, p = 0.001); in the control, it decreased earlier (after 8 minutes of exposure to HH, the amplitude of the minimum was −0.24 ± 0.08 mV, p = 0.026). With HH, the duration of the QT interval in athletes was shortened due to the shortening of the J-Tpeak (from 250 to 188 ms, p = 0.001) and the Tpeak-Tend (from 98 to 86 ms) intervals. In controls, the decrease in the QT interval was due to the J-Tpeak shortening only (from 280 to 200 ms, p = 0.026). Conclusions: In the study of the effect of hypoxia on the EAH during ventricular repolarization, the use of the BSPM has proven to be more informative than the use of traditional ECG. When using potential mapping, more significant changes in ventricular repolarization at HH than at HCH were revealed, whereas the parameters changed less in swimmers compared with the baseline than in controls during both exposures. [ABSTRACT FROM AUTHOR]

The frontal plane QRS-T [f(QRS-T)] angle is an easy marker of myocardial repolarization and was associated with adverse cardiovascular outcomes like prehypertension (PHT). This study was aimed to investigate to evaluate the f(QRS-T) angle in patients with PHT. We measured f(QRS-T) angle of 70 subjects with PHT, 109 patients with hypertension (HT), and 102 normotensive healthy volunteers. The f(QRS-T) angle was calculated from 12-lead electrocardiography. The f(QRS-T) angle was significantly higher in the HT and PHT groups as compared to the control group, but there was no significant difference in the f(QRS-T) angle between the HT and PHT groups. The f(QRS-T) angle was significantly and positively correlated with age, systolic blood pressure (BP) in 24 hours, average BP in 24 hours, pulse pressure in 24 hours, hemoglobin, QT dispersion, TpE distance while was negatively correlated with left ventricular ejection fraction. In multivariable analysis, we showed that systolic BP, average BP in 24 hours, pulse pressure in 24 hours, hemoglobin, QT dispersion, Tpe distance were independent predictors of higher f(QRS-T) angle. The f(QRS-T) angle, a noninvasive measurement analyzing the dysfunction in cardiac conduction system, was increased in subjects with PHT as compared to normotensives, and the subjects with PHT had f(QRS-T) angle as higher as patients with HT did. Our findings are supportive for the hypothesis that disturbances in ventricular repolarization is present in an early stage of essential hypertension. [ABSTRACT FROM AUTHOR]

Objective: Exercise‐induced repolarization changes have not been systematically evaluated in children and young adults with congenital heart disease (CHD). We carried out this study to assess the QTc responses during exercise in children and young adults (≤ 21 years) with CHD with comparison to those with structurally normal hearts. Methods: Baseline QRS duration, calculated baseline QTc, QTc at 4 min of recovery and delta QTc was measured in 360 exercise stress tests which were performed in 360 subjects (137 stress tests in patients with CHD [CHD group] and 223 stress tests in patients with structurally normal hearts). The effects of presence of CHD and potential confounders on primary outcome measure, change in QTc (delta QTc), and secondary outcome measures (QTc at baseline and QTc at 4 min of recovery) were determined using multiple linear regression analyses. Results: The baseline QTc and the QTc at 4 min of recovery in the CHD group was longer than patients with structurally normal hearts (respective p values =.00 and.001). No significant difference was noted in delta QTc between the CHD and structurally normal heart groups. Conclusions: While patients with CHD had a longer QRS duration and QTc interval at baseline than those with structurally normal hearts, these differences did not persist or augment with exercise. [ABSTRACT FROM AUTHOR]

Savolitinib (AZD6094, HMPL‐504, volitinib) is an oral, bioavailable, selective MET‐tyrosine kinase inhibitor. This randomized, double‐blind, 3‐way, crossover phase 1 study of savolitinib versus moxifloxacin (positive control) and placebo‐evaluated effects on the QT interval after a single savolitinib dose. Healthy non‐Japanese men were randomized to 1 of 6 treatment sequences, receiving single doses of savolitinib 600 mg, moxifloxacin 400 mg, and placebo. The primary end point was time‐matched, placebo‐adjusted change from baseline in the QT interval corrected for the time between corresponding points on 2 consecutive R waves on electrocardiogram (RR) by the Fridericia formula (ΔΔQTcF). Secondary end points included 12‐lead electrocardiogram (ECG) variables, pharmacokinetics, and safety. All 3 treatment periods were completed by 44 of 45 participants (98%). Baseline demographics were balanced across treatment groups. After a single savolitinib 600‐mg dose, the highest least‐squares mean ΔΔQTcF of 12 milliseconds was observed 5 hours postdose. Upper limits of the 2‐sided 90% confidence interval for ΔΔQTcF exceeded 10 milliseconds (the prespecified International Council for Harmonisation limit) 3‐6 hours postsavolitinib but otherwise remained less than the threshold. Savolitinib showed no additional effect on PR, QRS, QT, or RR intervals. A positive ΔΔQTcF signal from the moxifloxacin group confirmed study validity. Savolitinib was well tolerated, with a low incidence of adverse events. In this thorough QT/QTc study, QTcF prolongation was observed with a single savolitinib 600‐mg dose. ECG monitoring will be implemented in ongoing and future studies of savolitinib to assess the clinical relevance of the observed QT changes from this study. [ABSTRACT FROM AUTHOR]

Objective: Tp-e, QT, and Tp-e / QT are parameters showing ventricular repolarization. The increase in these parameters causes an increase in cardiovascular mortality, mostly due to malignant arrhythmias. Our study aimed to compare the long-term changes in electrocardiographic parameters in patients with uncontrolled diabetes despite using metformin, with the addition of SGLT 2 inhibitor or sulfonylurea (SU) to the treatment. Method: This retrospective study was enrolled in 133 type 2 DM patients with uncontrolled diabetes who applied to the internal medicine outpatient clinic, using single oral antidiabetic agents. The patients were divided into two groups as SU and SGLT 2 inhibitor additive. SU was added to the treatment of 69 patients, and SGLT 2 inhibitor was added to 64 patients. 12-lead superficial ECG records of participants who received combined therapy for at least six months were analyzed and compared. RR distance, QT interval, and Tp-e intervals were measured on the ECG. QTc was calculated using Bazzet's formula. (QT/ √ RR). Tp-e / QT and Tp-e / QTc ratios were calculated. Results: Seventy-eight (58.6%) of the participants were female, and 55 (41.4) were male. The age and gender distribution of both groups were similar. The group to which SGLT 2 inhibitor was added, Tp-e, QT, and QTc distances were significantly lower than the SU group (p <0.001 for each). Also, the Tp-e / QT and Tp-e / QTc ratios were significantly greater in the SU group (0.210 ± 0.029 vs 0.190 ± 0.03; p <0.001 and 0.201 ± 0.051 vs 0.184 ± 0.032; p = 0.022 respectively). Conclusions: In our study, we showed that the addition of SGLT2 inhibitors to monotherapy in people with diabetes with poor glycemic control has a positive effect on ECG parameters, which are indicators of repolarization, compared to other oral antidiabetics. [ABSTRACT FROM AUTHOR]

Under the hypothesis that sympathetic control of ventricular repolarization may change once the second ventilatory threshold (VT2) has been reached, a novel methodology for non‐invasive VT2 estimation based on the analysis of the T wave from the electrocardiogram (ECG) is proposed, and potential underlying physiological mechanisms are suggested. 25 volunteers (33.4 ± 5.2 years) underwent an incremental power cycle ergometer test (25 W/minute). During the test, respiratory gas exchange and multi‐lead ECG were acquired. The former was employed to determine VT2, used here as a reference, whereas the latter was used to compute the temporal profiles of an index of ventricular repolarization instability (dT) and its low‐frequency (LF) oscillations (LFdT). The sudden increases observed in dT and LFdT profiles above an established heart rate threshold were employed to derive VT2 estimates, referred to as VT2dT and VT2LFdT, respectively. Estimation errors of −4.7 ± 25.2 W were obtained when considering VT2dT. Errors were lower than the one‐minute power increment of 25 W in 68% of the subjects and lower than 50 W in 89.5% of them. When using VT2LFdT, estimation error was of 15.3 ± 32.4 W. Most of the subjects shared common characteristic dT and LFdT profiles, which could be reflecting changes in the autonomic control of ventricular repolarization before and after reaching VT2. The analysis of ventricular repolarization dynamics during exercise allows non‐invasive ECG‐based estimation of VT2, possibly in relation to changes in the autonomic control of ventricular electrical activity when VT2 is reached. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) has been associated with cardiac arrhythmias. Several electrocardiographic markers have been used to predict the risk of arrhythmia in patients with COVID-19. We aim to investigate the electrocardiographic (ECG) ventricular repolarization indices in patients with COVID-19. Methodology: We performed a comprehensive systematic literature search from PubMed, EuropePMC, SCOPUS, Cochrane Central Database, and Google Scholar Preprint Servers. The primary endpoints of this search were: Tp-e (T-peak-to-T-end) interval, QTd (QT dispersion), and Tp-e/QTc ratio in patients with newly diagnosed COVID-19 from inception up until August 2020. Results: There were a total of 241 patients from 2 studies. Meta-analysis showed that Tp-e/QTc ratio was higher in COVID-19 group (mean difference 0.02 [0.01, 0.02], p < 0.001; I²: 18%,). Tp-e interval was more prolonged in COVID-19 group (mean difference 7.76 [3.11, 12.41], p < 0.001; I²: 80%) compared to control group. QT dispersion (QTd) also was increased in COVID-19 group (mean difference 1.22 [0.61, 1.83], p < 0.001; I²:30%). Conclusions: Several electrocardiographic markers including Tp-e/QTc, Tp-e interval, and QTd are significantly increased in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Adequate adaptation of ventricular repolarization (VR) duration to changes in heart rate (HR) is important for cardiac electromechanical function and electrical stability. We studied the QT and QTpeak adaptation in response to abrupt start and stop of atrial and ventricular pacing on two occasions with an interval of at least 1 mo in 25 study subjects with permanent pacemakers. Frank vectorcardiography was used for data collection. Atrial or ventricular pacing was performed for 8 min aiming at a cycle length (CL) of 500 ms. We measured the immediate response (IR), the time constant (τ) of the exponential phase, and T90 End, the time to reach 90% change of QT and QTpeak from baseline to steady state during and after pacing. During atrial pacing, the CL decreased on average 45% from mean (SD) 944 (120) to 518 (46) ms and QT decreased on average 18% from 388 (20) to 318 (17) ms. For QT, T90 End was 103 (24) s and 126 (15) s after start versus stop of atrial pacing; a difference of 24 (27) s (P = 0.006). The response pattern was similar for τ but IR did not differ significantly between pacing start and stop. The response pattern was similar for QTpeak and also for QT and QTpeak following ventricular pacing start and stop. The coefficients of variation for repeated measures were 7%-21% for T90 End and τ. In conclusion, the adaptation of VR duration was significantly more rapid following increasing than decreasing HR and intraindividually a relatively reproducible process. NEW & NOTEWORTHY We studied the duration of ventricular repolarization (VR) adaptation and its hysteresis, following increasing and decreasing heart rate by abrupt start and stop of 8-min atrial or ventricular pacing in study subjects with permanent pacemakers and repeated the protocol with ≥1 mo interval, a novel approach. VR adaptation was significantly longer following decreasing than increasing heart rate corroborating previous observations. Furthermore, VR adaptation was intraindividually a reproducible and, hence, robust phenomenon, a novel finding. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of exercise training on ventricular repolarization dynamicity and heart rate variability in chronic heart failure patients. A total of 22 chronic heart failure patients with reduced ejection fraction in sinus rhythm were included in the study. The patients were in NYHA classes II–III with an ejection fraction of 29.7 ± 7.7%. Before and after 4 weeks of aerobic exercise training, all patients performed a cardiopulmonary exercise test, a standard twelve-lead electrocardiogram and a 24 h Holter recording from which heart rate variability and ventricular repolarization dynamicity were assessed. We observed a significant decrease of QTpeak (p <.001) and QTend (p <.001) at RR intervals ranging from 600 to 1000 ms on 24 h QT/RR regressions after 4 weeks of exercise training. Our analyses revealed that short-term exercise training induced significant changes in the frequency and time domain HRV parameters on an overall time-period of 24 h. Four weeks of exercise training induced significant changes in ventricular repolarization dynamicity in chronic heart failure patients. In addition, short-term exercise training was enough to improve patients' heart rate variability. [ABSTRACT FROM AUTHOR]

Background: Biventricular (BiV) pacing increases transmural repolarization heterogeneity due to epicardial to endocardial conduction from the left ventricular (LV) lead. However, limited evidence is available on concomitant changes in ventricular depolarization and repolarization and long‐term outcomes of BiV pacing. Therefore, we investigated associations of BiV pacing‐induced concomitant changes in ventricular depolarization and repolarization with mortality (i.e., LV assist device, heart transplantation, or all‐cause mortality) and sustained ventricular arrhythmia endpoints. Methods: Consecutive BiV‐defibrillator recipients with digital preimplantation and postimplantation electrocardiograms recorded between 2006 and 2015 at Duke University Medical Center were included. We calculated changes in QRS duration and corrected JT (JTc) interval and split them by median values. For simplicity, these variables were named QRSdecreased (≤ −12 ms), QRSincreased (> –12 ms), JTcdecreased (≤22 ms), and JTcincreased (> 22 ms) and subsequently used to construct four mutually exclusive groups. Results: We included 528 patients (median age, 68 years; male, 69%). No correlation between changes in QRS duration and JTc interval was observed (P =.295). Compared to QRSdecreased/JTcincreased, increased risk of the composite mortality endpoint was associated with QRSdecreased/JTcdecreased (hazard ratio [HR] = 1.62; 95% confidence interval [CI] = 1.09‐2.43), QRSincreased/JTcdecreased (HR = 1.86; 95% CI = 1.27‐2.71), and QRSincreased/JTcincreased (HR = 2.25; 95% CI = 1.52‐3.35). No QRS/JTc group was associated with excess sustained ventricular arrhythmia risk (P =.400). Conclusion: Among BiV‐defibrillator recipients, QRSdecreased/JTcincreased was associated with the most favorable long‐term survival free of LV assist device, heart transplantation, and sustained ventricular arrhythmias. Our findings suggest that improved electrical resynchronization may be achieved by assessing concomitant changes in ventricular depolarization and repolarization. [ABSTRACT FROM AUTHOR]

Objectives: Low-flow anesthesia (LFA) gained reasonable popularity as it provides many advantages including physiological, ecological, economical issues. Desflurane is a preferable anesthetic in low-flow anesthesia practice however, the relation between QTc, QTd, and QTcd prolongation and management of anesthesia with desflurane has been previously demonstrated. We aimed to compare the effects of low-flow (LFA) and high-flow (HFA) desflurane anesthesia on hemodynamic changes and ventricular repolarization markers in gynecologic laparoscopy. Methods: 58 patients were randomized into group L (LFA, n=30) and group H (HFA, n=28). ECG was recorded before anesthesia and 60th minute of anesthesia in both groups. Results: JTc-0 values were lower than JTc-1 values within both group L and H (p=0.001 for both groups). JTcd-0 and JTd-1 values were lower than JTcd-1 within group H (p=0.042 and 0.002, respectively). QTc-0 values were lower than QTc-1 within both group L and group H (p=0.001 and 0.002, respectively). QTcd-0 values were lower than QTcd-1 within group H (p=0.021). QTd-0 values were lower than QTd-1 within-group H (p=0.026). Tpe-0 and Tpe-1 values were lower in group L (p=0.001 and 0.002 respectively). Also, JTc-0 values were lower than JTc-1 values within both group L and H (p=0.021 and 0.027, respectively). Tpe/QTc-1 ratio was significantly lower in group L (p= 0.010). The difference between Tpe/QTc-0 and Tpe/QTc-1 ratios within group H was significant (p=0.028). Conclusion: Our study showed that there was no significant difference between LFA and HFA in terms of ECG repolarization markers, which may predict the possibility of torsadogenity. [ABSTRACT FROM AUTHOR]

Aim: In patients with chronic total occlusion (CTO), negative cardiovascular outcomes (angina, more frequent ventricular arrhythmias, higher mortality) and reduced survival have been demonstrated. The association between several electrocardiogram (ECG) markers, revealing individuals at high risk for ventricular arrhythmia, and collateral has been investigated in different studies in coronary artery disease patients. In this study, we aimed to investigate the association between the electrocardiographic parameters between good coronary collateral group and poor coronary collateral group in CTO patients with PCI. Material and Methods: Patients retrospectively implemented CTO PCI to those with symptomatic symptoms of myocardial ischemia or with the exact sign of ischemia in the CTO area. The patients were divided into 2 groups according to the Rentrop class: group 1 (Rentrop 0 and 1) and group 2 (Rentrop 2 and 3). Baseline characteristics, laboratory and ECGs, procedural data, and outcome data were retrospectively collected. Results: In this study included 59 CTO patients undergoing PCI. Mean age was 61.0±10.3 years and 43 (72.9%) of patients were male, and PCI success was 69.4%. While 22 (37.2%) of the patients were poor collateral group 1 (Rentrop 0 and 1), the remaining 37 (62.3%) of them were good collateral group 2 (Rentrop 2 and 3). There was a significant difference, in poor and good collateral groups, QT dispersion (77.2±27.9 vs 66.5±22.5, p: 0.041, respectively), QTc dispersion (82.1±26.9 vs 70.4±23.9, p: 0.034, respectively), and the presence of fQRS (63.6% vs 43.2, p: 0.027, respectively). But there was no statistically difference in P wave dispersion (48.0±9.5 vs 47.2±11.3, p: 0.796). Correlation analysis reported the association between Rentrop classification and Syntax score (r: -0.397, p: 0.002), LDL-C (r: -0.198, p: 0.025), QT dispersion (r: -0.156, p: 0.045), QTc dispersion (r: -0.176, p: 0.037), and the presence of fQRS (r: 0.234, p: 0.021) were statistically significant. Conclusion: We suggest that some ECG parameters are an important, easy, simple, and cost effective tool and can be beneficial in predicting the poor or good collateral in patients with CTO. [ABSTRACT FROM AUTHOR]

Background: The electrocardiographic (ECG) effects of transcutaneous cardiac pacing (TCP) on ventricular repolarization have not been studied in detail. This study evaluated the influence of TCP on ventricular repolarization. The results were compared with those obtained by conventional transvenous right ventricular pacing (TVP). Methods: Sixty‐two patients with spontaneous bradycardia and standard indication for pacemaker or implantable cardioverter‐defibrillator implantation were enrolled. Patients were divided into two groups based on the presence or not of structural heart disease (SHD). Surface 12‐lead ECG characteristics of ventricular depolarization (QRS complex) and repolarization (QT and JT intervals, Tpeak to Tend interval [TpTe], QT dispersion [QTd], TpTe dispersion [TpTe‐d], and TpTe/QT ratio) were recorded at baseline before device implantation (45 ± 5 beats/min) and were compared with corresponding data during short periods of TCP and TVP at a similar increased heart rate (81 ± 6 beats/min). Results: Both TCP and TVP compared with baseline measures significantly increased the QRS complex and the QTc/JTc intervals regardless of SHD status (P <.001), and QTc‐d and TpTe particularly in the patients without SHD (P <.05). TCP caused greater QRS prolongation than TVP in patients without SHD (P <.05), but it was associated with lower TpTe and TpTe/QT in patients without SHD as well as lower QTc‐d in patients with SHD (P <.05). Conclusion: TCP produces greater lengthening of ventricular repolarization than TVP, but lesser increase of ECG markers of ventricular dispersion of repolarization. [ABSTRACT FROM AUTHOR]

Background: Abnormal dynamics of QT intervals in response to sympathetic nervous system stimulation are used to diagnose long‐QT syndrome (LQTS). We hypothesized that parasympathetic stimulation with cold‐water face immersion following exercise would influence QT dynamics in patients with LQTS type 3 (LQT3). Methods: Study participants (n = 42; mean age = 11.2 years) comprised 20 genotyped LQTS children and 22 healthy children. The LQTS group was divided into LQT3 (n = 12) and non‐LQT3 (n = 8) subgroups. Provocative testing for assessing QT dynamics comprised a treadmill exercise followed by cold‐water face immersion. The QT intervals were automatically measured at rest and during exercise, recovery, and cold‐water face immersion. The QT/heart rate (HR) relationship was visualized by plotting beat‐to‐beat confluence of the data. Results: The QT/HR slopes, determined by linear regression analysis, were steeper in the LQTS group than in the control group during exercise and immersion tests: −2.16 ± 0.63 versus −1.21 ± 0.28, P < 0.0001, and −2.02 ± 0.76 vs −0.75 ± 0.24, P < 0.0001, respectively. The LQT3 patients had steeper slopes in the immersion test than did non‐LQT3 and control individuals: −2.42 ± 0.52 vs −1.40 ± 0.65, P < 0.0001, and vs −0.75 ± 0.24, P < 0.0001. Conclusions: The QT dynamics of LQT3 patients differ from those of other LQTS subtypes during the post‐exercise cold‐water face immersion test in this study. Abnormal QT dynamics during the parasympathetic provocative test are concordant with the fact that cardiac events occur when HRs are lower or during sleep in LQT3 patients. [ABSTRACT FROM AUTHOR]

Purpose: Prolonged weightlessness exposure generates cardiovascular deconditioning, with potential implications on ECG circadian rhythms. Head-down (- 6°) tilt (HDT) bed rest is a ground-based analogue model for simulating the effects of reduced motor activity and fluids redistribution occurring during spaceflight. Our aim was to evaluate the impact of 60-day HDT on the circadianity of RR and ventricular repolarization (QTend) intervals extracted from 24-h Holter ECG recordings, scheduled 9 days before HDT (BDC-9), the 5th (HDT5), 21st (HDT21) and 58th (HDT58) day of HDT, the 1st (R + 0) and 8th (R + 7) day after HDT. Also, the effectiveness of a nutritional countermeasure (CM) in mitigating the HDT-related changes was tested.Methods: RR and QTend circadian rhythms were evaluated by Cosinor analysis, resulting in maximum and minimum values, MESOR (a rhythm-adjusted mean), oscillation amplitude (OA, half variation within a night-day cycle), and acrophase (φ, the time at which the fitting sinusoid's amplitude is maximal) values.Results: RR and QTend MESOR increased at HDT5, and the OA was reduced along the HDT period, mainly due to the increase of the minima. At R + 0, QTend OA increased, particularly in the control group. The φ slightly anticipated during HDT and was delayed at R + 0.Conclusion: 60-Day HDT affects the characteristics of cardiac circadian rhythm by altering the physiological daily cycle of RR and QTend intervals. Scheduled day-night cycle and feeding time were maintained during the experiment, thus inferring the role of changes in the gravitational stimulus to determine these variations. The applied nutritional countermeasure did not show effectiveness in preventing such changes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Arsenic trioxide is the first-line treatment for acute promyelocytic leukemia (APL); however, abnormalities of ventricular repolarization and QT interval prolongation are the most common adverse effects. We explore ventricular repolarization dynamic changes and the influence of clinical factors in APL patients during arsenic trioxide induction therapy. APL patients receiving arsenic trioxide induction therapy were included. Arsenic trioxide effects on ventricular repolarization-related indicators such as QTc, QT interval dispersion (QTd), heart rate-corrected J to T-peak (JTpC), and T-peak to T-end covariate (TpTec) interphase were statistically analyzed. Furthermore, logistic regression analysis was conducted to explore the correlation between various clinical factors and changes in repolarization indexes. Ninety-three patients were recruited finally. Seven patients with QTc > 500 ms after arsenic trioxide treatment were discontinued from the study. QTc, QTd and JTpC interphase prolonged on day 8; TpTec prolongation was observed at the late induction stage. The risk factors were disease risk, hemoglobin and lactate dehydrogenase for QTc; hemoglobin for QTd; disease risk and hemoglobin for JTpC and TpTec. QTc, QTd and JTpC were prolonged in the early use of arsenic trioxide and in contrast with TpTec. Hypothrombinemia was a common risk factor of ventricular repolarization prolongation and should be considered in preventing cardiac adverse effects of arsenic trioxide in APL patients. • Hypothrombinemia was a common risk factor of ventricular repolarization in APL patients. • QTc, QTd and JTpC were prolonged in the early use of arsenic trioxide and in contrast with TpTec. • QTc prolongation was significantly correlated with arsenic trioxide accumulation. [ABSTRACT FROM AUTHOR]

Tobacco cigarette smoking is associated with increased sudden death risk, perhaps through adverse effects on ventricular repolarization. The effect of electronic (e-)cigarettes on ventricular repolarization is unknown. The objective of the study was to test the hypothesis that tobacco cigarettes and e-cigarettes have similar adverse effects on electrocardiogram (ECG) indexes of ventricular repolarization and these effects are attributable to nicotine. ECG recordings were obtained in 37 chronic tobacco cigarette smokers, 43 chronic e-cigarette users, and 65 nonusers. Primary outcomes, Tpeak to Tend (Tp-e), Tp-e/QT ratio, and Tp-e/QTc ratio, were measured in tobacco cigarette smokers pre-/post-straw control and smoking one tobacco cigarette and in e-cigarette users and nonusers pre-/post-straw control and using an e-cigarette with and without nicotine (different days). Mean values of the primary outcomes were not different among the three groups at baseline. In chronic tobacco cigarette smokers, all primary outcomes, including the Tp-e (12.9 ± 5.0% vs. 1.5 ± 5%, P = 0.017), Tp-e/QT (14.9 ± 5.0% vs. 0.7 ± 5.1%, P = 0.004), and Tp-e/QTc (11.9 ± 5.0% vs. 2.1 ± 5.1%, P = 0.036), were significantly increased pre-/post-smoking one tobacco cigarette compared with pre-/post-straw control. In chronic e-cigarette users, the Tp-e/QT (6.3 ± 1.9%, P = 0.046) was increased only pre/post using an e-cigarette with nicotine but not pre/post the other exposures. The changes relative to the changes after straw control were greater after smoking the tobacco cigarette compared with using the e-cigarette with nicotine for Tp-e (11.4 ± 4.4% vs. 1.1 ± 2.5%, P < 0.05) and Tp-e/QTc (9.8 ± 4.4% vs. −1.6 ± 2.6%, P = 0.05) but not Tp-e/QT(14.2 ± 4.5% vs. 4.2 ± 2.6%, P = 0.061) . Heart rate increased similarly after the tobacco cigarette and e-cigarette with nicotine. Baseline ECG indexes of ventricular repolarization were not different among chronic tobacco cigarette smokers, electronic cigarette users and nonusers. An adverse effect of acute tobacco cigarette smoking on ECG indexes of ventricular repolarization was confirmed. In chronic e-cigarette users, an adverse effect of using an e-cigarette with nicotine, but not without nicotine, on ECG indexes of ventricular repolarization was also observed. NEW & NOTEWORTHY Abnormal ventricular repolarization, as indicated by prolonged Tpeak-end (Tp-e), is associated with increased sudden death risk. Baseline ECG indexes of repolarization, Tp-e, Tp-e/QT, and Tp-e/QTc, were not different among tobacco cigarette (TC) smokers, electronic cigarette (EC) users, and nonsmokers at baseline, but when TC smokers smoked one TC, all parameters were prolonged. Using an electronic cigarette with nicotine, but not without nicotine, increased the Tp-e/QT. Smoking induces changes in ECG indexes of ventricular repolarization associated with increased sudden death risk. [ABSTRACT FROM AUTHOR]

Although late sodium current (I Na-late) has long been known to contribute to plateau formation of mammalian cardiac action potentials, lately it was considered as possible target for antiarrhythmic drugs. However, many aspects of this current are still poorly understood. The present work was designed to study the true profile of I Na-late in canine and guinea pig ventricular cells and compare them to I Na-late recorded in undiseased human hearts. I Na-late was defined as a tetrodotoxin-sensitive current, recorded under action potential voltage clamp conditions using either canonic- or self-action potentials as command signals. Under action potential voltage clamp conditions the amplitude of canine and human I Na-late monotonically decreased during the plateau (decrescendo-profile), in contrast to guinea pig, where its amplitude increased during the plateau (crescendo profile). The decrescendo-profile of canine I Na-late could not be converted to a crescendo-morphology by application of ramp-like command voltages or command action potentials recorded from guinea pig cells. Conventional voltage clamp experiments revealed that the crescendo I Na-late profile in guinea pig was due to the slower decay of I Na-late in this species. When action potentials were recorded from multicellular ventricular preparations with sharp microelectrode, action potentials were shortened by tetrodotoxin, which effect was the largest in human, while smaller in canine, and the smallest in guinea pig preparations. It is concluded that important interspecies differences exist in the behavior of I Na-late. At present canine myocytes seem to represent the best model of human ventricular cells regarding the properties of I Na-late. These results should be taken into account when pharmacological studies with I Na-late are interpreted and extrapolated to human. Accordingly, canine ventricular tissues or myocytes are suggested for pharmacological studies with I Na-late inhibitors or modifiers. Incorporation of present data to human action potential models may yield a better understanding of the role of I Na-late in action potential morphology, arrhythmogenesis, and intracellular calcium dynamics. • Marked interspecies differences exist in the profile of cardiac I Na-late. • In human and dog I Na-late decreases, while in guinea pig increases during the AP. • This is a consequence of the slower inactivation of I Na-late in guinea pig. • The ATX-II induced current is different from the native I Na-late in dog. • Dog ventricular myocyte is the best model for studying human I Na-late. [ABSTRACT FROM AUTHOR]

Introduction: Increased 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. Methods: The 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. Results: In 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. Conclusion: Insulin resistance may be involved in the longitudinal increase of ventricular repolarization heterogeneity in apparently healthy subjects. [ABSTRACT FROM AUTHOR]

Aim: Ventricular repolarization were evaluated in patients who had POF by using novel electrocardiographic parameters including Tpe-interval and Tpe/QT and Tpe/QTc ratios. A few studies have investigated the association between premature ovarian failure (POF) and cardiovascular diseases. However, none have examined ventricular repolarization in this respect. Materials and Methods: This cross-sectional study included 60 female patients with POF (mean 32.6±4.7 years) and 54 control healthy female subjects (mean 30.9±4.6 years). All electrocardiogram (ECG) measurements were performed by a cardiologist using a computer, and the Tpe-interval, Tpe/QT, and Tpe/QTc were compared between groups. Results: There were no significant differences between groups in terms of baseline characteristics and laboratory parameters. The Tpe-interval, Tpe/QT, and Tpe/QTc were significantly prolonged in POF group than control subjects (p<0.001 for all). There was a strong and positive correlation between the serum follicle-stimulating hormone (FSH) level and Tpe-interval (r=0.681; p<0.001) and Tpe/QTc (r= 0.636; p<0.001). Furthermore, high and negative correlation was found between serum estradiol and Tpe-interval (r=- 0.531; p<0.001) and Tpe/QTc (r=-0.510). Multivariate linear regression analysis showed that that the FSH and estradiol level were independent predictors of both the Tpe-interval (B=0.541 and p<0.001, B=-0.202 and p<0.001, respectively) and Tpe/QTc (B=0.442 and p<0.001, B= -0.239 and p<0.001, respectively). Conclusion: It was concluded in the study that ECG parameters of ventricular repolarization, namely, Tpe-interval, Tpe/QT, and Tpe/QTc were significantly prolonged in patients that had POF. [ABSTRACT FROM AUTHOR]

The frontal QRS-T angle on the electrocardiogram has been described as a variable of ventricular repolarization. We evaluated how deep inspiration affected QRS axis, T-wave axis and frontal QRS-T angle. We also assessed the effects on left ventricular volume on the association using myocardial perfusion SPECT. Fifty patients undergoing ECGs both in resting state and in deep inspiration and subsequent SPECT were enrolled. Frontal QRS-T angle was defined as the absolute value of the difference between the frontal QRS axis and T-wave axis. Change in frontal QRS-T angle was calculated using (QRS-T angle in deep inspiration−QRS-T angle in resting state). In resting state, QRS axis and T-wave axis were 20.9° ± 30.0° and 40.9° ± 36.1°, respectively. Frontal QRS-T angle was 35.9° ± 36.1°. Deep inspiration caused rightward shifts of QRS axis (42.3° ± 29.5°, p < 0.001) and T-wave axis (49.5° ± 39.7°, p < 0.001). However, deep inspiration did not affect frontal QRS-T angle (33.9° ± 35.8°, p = 0.44). Frontal QRS-T angle in deep inspiration had good correlation (r = 0.87, p < 0.001) and agreement with that in resting state. Left ventricular (LV) end-diastolic volume had a significant association with change in frontal QRS-T angle (r = 0.29, p = 0.04). Our data suggest that frontal QRS-T angle in deep inspiration has a good correlation with that in resting state, and the agreement is acceptable. In patients with dilated LV, QRS-T angle in deep inspiration may be susceptible to the overestimation. [ABSTRACT FROM AUTHOR]

The frontal QRS-T angle is one of the markers of ventricular repolarization. We sought to assess the effects of myocardial perfusion defect on QRS-T angle in patients with prior anterior myocardial infarction (MI). Seventy-one patients with prior anterior MI and 71 age- and sex-matched control subjects having no myocardial perfusion defect were selected. Frontal QRS-T angle was defined as the absolute value of the difference between the frontal plane QRS axis and T-wave axis. The extent of myocardial perfusion defect was determined using myocardial perfusion single-photon emission computed tomography (SPECT). The extent of myocardial perfusion defect of patients with prior anterior MI was 21.8 ± 13.7%. Frontal QRS-T angle was significantly larger in patients with prior anterior MI than control subjects (82° ± 49° vs 30° ± 26°, p < 0.001). Prevalence of abnormal frontal QRS-T angle defined as more than 90° was significantly higher in patients with prior anterior MI than control subjects (42% vs 4%, p < 0.001). Multivariate linear regression analysis showed that age (β=0.18, p = 0.02) and myocardial perfusion defect (β = 0.46, p = 0.02) were independent determinants of frontal QRS-T angle. Our results suggest that the extent of myocardial perfusion defect is an independent determinant of frontal QRS-T angle in patients with prior anterior MI. [ABSTRACT FROM AUTHOR]

Ventricular depolarization and repolarization processes are discussed, including their differences and heterogeneity both in patients with a healthy/sick heart, a matter of ranges. Measurements expressing the characteristics of ventricular repolarization are analyzed: the QT interval and other even more reliable measurements such as the TPEAK-TEND interval, its dispersion and others. We emphasize on the existence of the long QT syndrome (and sign) and the three basic processes of arrhythmogenesis: heterogeneity, alternation and dispersion, with differences in action potentials in the three zones of the ventricular myocardium. The risk factors of long QT (common in this therapy) and ventricular arrhythmias (especially torsades de pointes, extremely rare in these cases) are highlighted. The need to assess clinical and electrical features, comorbidities, aggregate conflicts, and management of these patients is also discussed. [ABSTRACT FROM AUTHOR]

The ICH E14/S7B Questions and Answers (Q&As) guideline introduces the concept of a "double negative" nonclinical scenario (negative hERG assay and negative in vivo QTc study) to demonstrate that a drug does not produce a clinically relevant QT prolongation (i.e., no QT liability). This nonclinical "double negative" data package, along with negative Phase 1 clinical QTc data, may be sufficient to substitute for a clinical Thorough QT (TQT) study in some specific cases. While standalone GLP in vivo cardiovascular studies in non-rodent species are standard practice during nonclinical drug development for small molecule programs, a variety of approaches to the design, conduct, analysis and interpretation are utilized across pharmaceutical companies and contract research organizations (CROs) that may, in some cases, negatively impact the stringent sensitivity needed to fulfill the new Q&As. Subject matter experts from both Pharma and CROs have collaborated to recommend best practices for more robust nonclinical cardiovascular telemetry studies in non-rodent species, with input from clinical and regulatory experts. The aim was to increase consistency and harmonization across the industry and to ensure delivery of high quality nonclinical QTc data to meet the proposed sensitivities defined within the revised ICH E14/S7B Q&As guideline (Q&As 5.1 and 6.1). The detailed best practice recommendations presented here cover the design and execution of the safety pharmacology cardiovascular study, including optimal methods for acquiring, analyzing, reporting, and interpreting the resulting QTc and pharmacokinetic data to allow for direct comparison to clinical exposures and assessment of safety margin for QTc prolongation. [ABSTRACT FROM AUTHOR]

Purpose: Phase Ib study evaluating the effect of apalutamide, at therapeutic exposure, on ventricular repolarization by applying time-matched pharmacokinetics and electrocardiography (ECG) in patients with castration-resistant prostate cancer. Safety of daily apalutamide was also assessed.Methods: Patients received 240 mg oral apalutamide daily. Time-matched ECGs were collected via continuous 12-lead Holter recording before apalutamide (Day - 1) and on Days 1 and 57 (Cycle 3 Day 1). Pharmacokinetics of apalutamide were assessed on Days 1 and 57 at matched time points of ECG collection. QT interval was corrected for heart rate using Fridericia correction (QTcF). The primary endpoint was the maximum mean change in QTcF (ΔQTcF) from baseline to Cycle 3 Day 1 (steady state). Secondary endpoints were the effect of apalutamide on other ECG parameters, pharmacokinetics of apalutamide and its active metabolite, relationship between plasma concentrations of apalutamide and QTcF, and safety.Results: Forty-five men were enrolled; 82% received treatment for ≥ 3 months. At steady state, the maximum ΔQTcF was 12.4 ms and the upper bound of its associated 90% CI was 16.0 ms. No clinically meaningful effects of apalutamide were reported for heart rate or other ECG parameters. A concentration-dependent increase in QTcF was observed for apalutamide. Most adverse events (AEs) (73%) were grade 1-2 in severity. No patients discontinued due to QTc prolongation or AEs.Conclusion: The effect of apalutamide on QTc prolongation was modest and does not produce a clinically meaningful effect on ventricular repolarization. The AE profile was consistent with other studies of apalutamide. [ABSTRACT FROM AUTHOR]