QT Heart Rate Research Articles

Bivariate Entropy Analysis of Electrocardiographic RR-QT Time Series.

QT interval variability (QTV) and heart rate variability (HRV) are both accepted biomarkers for cardiovascular events. QTV characterizes the variations in ventricular depolarization and repolarization. It is a predominant element of HRV. However, QTV is also believed to accept direct inputs from upstream control system. How QTV varies along with HRV is yet to be elucidated. We studied the dynamic relationship of QTV and HRV during different physiological conditions from resting, to cycling, and to recovering. We applied several entropy-based measures to examine their bivariate relationships, including cross sample entropy (XSampEn), cross fuzzy entropy (XFuzzyEn), cross conditional entropy (XCE), and joint distribution entropy (JDistEn). Results showed no statistically significant differences in XSampEn, XFuzzyEn, and XCE across different physiological states. Interestingly, JDistEn demonstrated significant decreases during cycling as compared with that during the resting state. Besides, JDistEn also showed a progressively recovering trend from cycling to the first 3 min during recovering, and further to the second 3 min during recovering. It appeared to be fully recovered to its level in the resting state during the second 3 min during the recovering phase. The results suggest that there is certain nonlinear temporal relationship between QTV and HRV, and that the JDistEn could help unravel this nuanced property.

Protease inhibitor-contaning antiretroviral therapy effects on QT interval and heart rate: a cross-sectional study

Abstract Background HIV has been associated with QT prolongation and it is believed this is from drug interaction as well as HIV infection. In vitro studies have showed that protease inhibitors block potassium channel HERG, suggesting that these drugs can cause drug-induced QT prolongation. Few case-reports have showed that protease inhibitors can cause drug-induced bradycardia, but data is still limited. Objective To describe the correlation between HIV infection and the duration of QT interval and to evaluate the effects that protease inhibitors-containing antiretroviral regime have on the duration of QT interval and cardiac frequency. Methods A cross-sectional study was made. Participants were assigned to 3 groups: HIV positive with antiretroviral therapy which included protease inhibitors (HIV+ with treatment), treatment-naïve HIV positive and HIV negative. None of the participants had past medical history of cardiovascular disease or use of known QT prolonging medication. 12-lead ECG were made to all participants. QT interval and cardiac frequency were measured to be compared between the 3 groups and the results were analyzed by the statistical test ANOVA. Results A total of 213 participants were enrolled, 84 in the HIV+ with treatment, 45 in the HIV+ treatment-naïve, and 84 HIV-. 63% of the participants were males. The treatment-naïve HIV+ group only had 5 female participants. This study did not find a relation between HIV infection or protease inhibitor use and an increase in the duration of QT interval in males. For females, this study found an association between HIV infection and longer QT interval duration, as seen in the mean of each group: 442.8 ms for treatment-naïve HIV+ group, 422.42 ms for protease inhibitor HIV+ with treatment group and 420.34 ms HIV- group. It was found that the use of antiretroviral regime with protease inhibitor was associated with a decrease in cardiac frequency, as seen in each group's cardiac frequencies: HIV+ with treatment group: 63.34 bpm, treatment-naïve HIV positive: 79.77 bpm and control group: 69.3 bpm. Conclusion We did not find correlation between HIV infection, the use of protease inhibitor-containing antiretroviral regime and QT interval prolongation in males, as opposed to females, where it was shown that QT interval duration is longer in the HIV+ treatment-naïve group. It was also observed that the use of protease inhibitor-containing antiretroviral regime was associated with a decrease in cardiac frequency. Funding Acknowledgement Type of funding source: None

QT interval abnormalities and heart rate variability in patients with cirrhosis

Background and study aimsWe aimed to assess the relationship of the QT interval and heart rate variability with the severity and aetiology of cirrhosis and determine the effect of propranolol on them. Patients and methodsThis prospective study included 44 patients with cirrhosis categorised into three groups based on the Child–Pugh score: groups 1, 2 and 3 (with 12, 15 and 15 patients, respectively). Demographic characteristics, propranolol administration, severity of cirrhosis evaluated by the Child–Pugh score, aetiology of cirrhosis, and serum sodium, potassium and calcium levels were evaluated. All patients underwent 24 h-Holter monitoring. Corrected QT interval (QTc), average heart rate, standard deviation of normal-to-normal intervals (SDNN) and corrected SDNN (cSDNN) were evaluated. ResultsThe average QTc was significantly longer in group 3 than in groups 1 and 2 (453.4 ± 17.4 vs 422.8 ± 18.6 and 428.9 ± 17.24 ms, p < 0.001). The median SDNN was 70 ms and was significantly lower in group 3 vs groups 1 and 2 (77; interquartile range [IQR], 67–89.5 vs 57; IQR, 38–68 and 75 ms; IQR, 61–81 ms, p = 0.003). cSDNN was significantly lower in group 3 vs groups 1 and 2 (200.0 ± 42.6 vs 254.5 ± 75.3 and 277.8 ± 110.6 ms, p = 0.022). Propranolol administration resulted in a significant increase in the average SDNN value but had no effect on cSDNN or QTc. QTc was associated with the Child–Pugh class (p < 0.001), viral aetiology (p = 0.009) and sex (p = 0.010); SDNN was associated with the mean heart rate (p = 0.015) and Child–Pugh class (p = 0.024). ConclusionQTc interval prolongation and decreased SDNN are common in cirrhosis. Their prevalence is closely associated with disease severity. Propranolol has no effects on cSDNN or QTc.

QT interval variability and heart rate turbulence are associated with clinical characteristics in congenital heart disease patients with a systemic right ventricle

BackgroundQT interval variability (QTV) and heart rate turbulence (HRT) are measures of cardiac autonomic function, which, when abnormal, are correlated with ventricular arrhythmias and worse clinical outcome. This study aims to evaluate QTV and HRT in patients with a systemic right ventricle (RV) and to assess correlations with clinical characteristics. MethodsIn a retrospective cohort study, QTV and HRT were derived from 24-h Holter registrations of patients with a systemic RV and healthy controls. QTV and HRT were compared between groups. In patients, the association between QTV, HRT, and clinical characteristics was assessed. ResultsHolter recordings from 40 patients (mean age 40 years, 16 females) and 37 healthy controls (mean age 42 years, 21 females) were analyzed. Groups were comparable in terms of age and sex. QTV was increased in patients compared with controls (p < 0.001), HRT did not differ significantly between the groups. Increased QTV and decreased HRT correlated with medication use, especially of diuretics, and with clinical events, particularly supraventricular arrhythmias. Increased QTV correlated with reduced systemic RV function. Decreased HRT was independently associated with a larger number of past clinical events (estimate −0.33, 95% CI −0.63 to −0.02, p = 0.037). QTV was higher in women in both patients and controls (p = 0.041 and p = 0.034, respectively). ConclusionsQTV and HRT are associated with clinical factors and events in patients with a systemic RV. Further studies are mandatory to confirm their prognostic value.

A Randomized Placebo Controlled Clinical Trial Demonstrating Safety & Efficacy of EnXtra® in Healthy Adults

Objective: The present randomized, placebo-controlled study aimed to assess the long-term safety and perceivable mental acuity benefits of EnXtra® in healthy individuals.Methods: Study participants were administered EnXtra® with or without caffeine for a period of 12 weeks. The cardiovascular safety was evaluated by assessing change in QT interval, blood pressure and heart rate. Further, other efficacy variables evaluated were change in perceived alertness and calmness by Bond and Lader mood scales, Sleep disturbance by Pittsburgh sleep quality Index and daytime sleepiness by Epworth sleepiness scale.Results: None of the study group showed any significant change in the ECG or haemodynamic parameters as compared to baseline (p > 0.05). Post consumption, alertness and calmness scores were significantly increased in the EnXtra®, and EnXtra® plus caffeine group (p < 0.001) as compared to placebo. Daytime sleep scores decreased in the EnXtra® group however change was not significant. Sleep quality remained undisturbed in all three arms.Conclusion: The findings demonstrated the psychostimulant efficacy of EnXtra® with no safety concerns on long-term usage.

Variation of Tpeak-end, corrected Tpeak-end, QT, and corrected QT intervals, Tpeak-end/QT, Tpeak-end/corrected QT ratios and heart rate variability according to decades in the healthy male subjects aged between 30 and 79years.

BackgroundHeart rate variability (HRV) is a predictor of cardiac autonomic functions. Ventricular repolarization markers can indicate ventricular arrhythmias. We aimed to evaluate variations of HRV and these repolarization markers in five healthy male groups between age 30 and 79 years according to decades.Materials and MethodsThe study group consisted of 500 healthy male subjects between October 2018 and May 2019. The male subjects were divided into five categories according to their ages. Then, electrocardiograms (ECG), transthoracic echocardiograms (TTE), and treadmill exercise test (TET) were performed. T‐wave peak‐end (Tp‐e) interval was defined as the time between the peak point and end of T‐wave. Tp‐e, corrected Tp‐e (cTp‐e), QT, and corrected QT (QTc) were measured from the resting ECGs and HRV temporal parameters (SDNN, SDNN Index, SDANN Index, RMSSD, sNN50, and pNN50), and HRV frequency parameters (VLF, LF, HF, and LF/HF) were obtained from 24‐hour Holter monitorization recordings. One‐way ANOVA test was used for the differences between the groups. Pearson correlation test was used to determine the correlations between the values of all groups.ResultsConsidering the repolarization parameters, there are significant differences in five groups in terms of Tp‐e interval, but not Tp‐e/QT and Tp‐e/QTc ratios. Considering the HRV parameters, there were statistically significant differences between the five male healthy groups in terms of HRV temporal parameters and there are no significant differences in terms of HRV frequency parameters.ConclusionAs the age increases, basal Tp‐e interval increases and HRV temporal parameters decrease significantly in the male subjects aged between 30 and 79 years, but HRV frequency parameters do not change.

Medium-term results of cardioneuroablation for clinical bradyarrhythmias and vasovagal syncope: effects on QT interval and heart rate.

Although parasympathetic effects of cardioneuroablation (CNA) in vagally mediated bradyarrhythmias (VMB) were studied, sympathetic effects have not been elucidated, yet. We aimed to investigate the acute and medium-term outcomes of CNA as well as the impact of CNA on ventricular repolarization by using corrected QT interval (QTc) measurements. Sixty-five patients (58.5% men; age 39.4 ± 14years) undergoing CNA were included in the study. Patients who underwent CNA due to VMB were divided into two groups: (1) bi-atrial CNA and (2) right-sided CNA. QTc was calculated at 3 time points: before the procedure (time point 1); 24h post-ablation (time point 2); and at the last follow-up visit (time point 3). The mean follow-up time was 20.0 ± 20months. Acute success was achieved in 64 (98.4%) of cases. In the whole cohort, from time point 1 to 2, a significant shortening in QTcFredericia, QTcFramingham, and QTcHodges was observed which remained lower than baseline in time point 3. Although the difference between measurements in time point 1 and 2 was not statistically significant for QTcBazett, a significant shortening was detected between time point 1 and 3. There was significant difference between groups for shortening in QTcFredericia and QTcFramingham (p = 0.01). Event-free survival was detected in 90.7% (59/65) of cases. Our results demonstrate a significant shortening of QTc in addition to high acute and medium-term success rates after CNA. The most likely mechanism is the effect of CNA on the sympathetic system as well as on the parasympathetic system. Bi-atrial ablation was found related to higher QTc shortening effect.

Evaluation of electrocardiographic findings before and after hemodialysis session

Dialysis patients have higher rates of sudden cardiac death. The study of the electrocardiogram could identify patients at risk of developing rhythm disorders. The aim of this study was to evaluate the electrocardiographic findings before and after the hemodialysis (HD) session and to examine associations of clinical and serum electrolytes with electrocardiogram findings. We conducted a multicentric transversal study, including chronic HD patients during January 2018. Standard 12-lead electrocardiogram was recorded, before and after the HD session. A medical history was documented. It included age, gender, initial nephropathy, and comorbidities. Serum potassium and total serum calcium were measured before a routine HD session. Serum potassium was measured after HD session. Corrected QT for heart rate was calculated using Bazett's formula. The study included 66 patients. Nineteen patients (28.8%) had hyperkalemia before the HD session and 44 (66.7%) patients had hypokalemia after the HD session. Seventeen patients had prolonged QTc interval (25.7%). On multiple regression analysis, only the prolonged QTc interval was significantly correlated with the serum potassium (P = 0.046).When comparing the mean values of electrocardiogram parameters before and after the HD session, we noted a significant change of heart rate (P = 0.001), R wave (P = 0.016), T wave (P = 0.001), and T/R (P = 0.001) wave. Delta K+ did not correlate with the change in T wave amplitude (r = 0.23, P = 0.59), R wave amplitude (r = -0.16, P = 0.2), T/R wave (r = 0.055, P = 0.65), or QRS duration (r = 0.023, P = 0.85). Delta QTc was correlated to ΔK+. We conclude that usual electrographic manifestations of hyperkalemia are less pronounced in HD patients. Our results confirmed the unstable status of cardiac electrophysiology during HD session.

QT interval prolongation and Torsades de Pointes with donepezil, rivastigmine and galantamine.

Background:Acetylcholinesterase inhibitors (AChEis) including donepezil, galantamine and rivastigmine are used to treat Alzheimer’s disease (AD). This study aimed to evaluate evidence from the case report literature for an association between these agents and risk of QT interval prolongation and Torsades de Pointes (TdP) arrhythmia.Methods:Published literature was mined with predetermined MeSH terms for each of donepezil, galantamine and rivastigmine, to identify cases of QT interval prolongation and TdP. Case reports were analysed using causality scales and a QT interval nomogram.Results:A total of 13 case reports were found (10 for donepezil, 2 for galantamine and 1 for rivastigmine) with rate corrected QT interval (QTc) prolongation. Five cases with donepezil exhibited TdP. TdP was not reported in the cases with galantamine and rivastigmine. The use of a QT heart rate nomogram highlighted risk with donepezil compared with the other two drugs and the application of the Naranjo causality scale suggested probable or possible causation for all donepezil cases. All patients had at least two other risk factors for TdP, including modifiable risk factors such as electrolyte disturbances, bradycardia, co-administration of QT prolonging drugs. A number of recent cases involved recent changes in medication.Conclusion:Our evaluation of the case report literature suggests that there is evidence for a causal association between donepezil and QTc/TdP risk. Attention to risk factors for QTc prolongation/TdP should be exercised when prescribing donepezil and modifiable risk factors corrected. Owing to the low number of cases with galantamine and rivastigmine, further work is needed to establish whether these drugs may be more suitable than donepezil for patients with other risk factors for TdP.

The effect of transcatheter aortic valve implantation on ventricular repolarization indices and neutrophil-to-lymphocyte ratio

Aim: The electrocardiographic QT dispersion (QTd), Tpe/QT ratio and Tpeak-Tend (Tpe) interval have been known as ventricular repolarization indices. Neutrophil–to- lymphocyte ratio (NLR) is an inflammatory marker that is newly described. Increased QTd, Tpe/QT ratio, inflammation and Tpe interval are associated with ventricular arrhythmia (VA). In patients with severe aortic stenosis (AS), VA has a key role in terms of morbidity and mortality. The present study aimed at examining whether transcatheter aortic valve implantation (TAVI) affects ventricular repolarization indices and NLR. Material and Methods: Study population consisted of a total of 44 patients undergoing TAVI. Echocardiographic and laboratory parameters of patients were evaluated before TAVI and sixth month after TAVI. Comparioson of electrocardiographic QTd, Tpe/QT ratio, Tpe interval and NLR of the same petients were made before TAVI and sixth month after TAVI.Results: QT interval, corrected QT interval and heart rate were similar before and after TAVI (p>0.05 for all). There was a statistically significant decrease in QTd (26.0±9.1 vs. 21.3±7.2 ms; p=0.008), Tpe interval (88.43±12.6vs. 78.8±10.1 ms; p0.001), NLR (3.08±2.0 vs. 2.16±0.73; p=0.001) and Tpe/QT ratio ( 0.23±0.3 vs. 0.21±0.1; p=0.024) after TAVI. Morever, the reduction in the Tpe interval and Tpe / QT ratio after TAVI was found to be significantly correlated with NLR (r=0.400, p=0.007; r=0.396, p=0.008; respectively).Conclusion: TAVI does not only reduce symptoms in patients with severe AS, but may also be effective in reducing risk of VA by improving factors affecting ventricular repolarization.

Electrocardiogram and heart rate variability assessment in patients with common autoimmune diseases: a methodological review.

The aim of this article was to summarize current knowledge about the potential clinical utility of electrocardiogram (ECG) and heart rate variability (HRV) measures in patients with 4 common autoimmune diseases (ADs): rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behcet's disease (BD), and systemic sclerosis (SSc). A search was conducted of the PubMed, Embase, and Scopus databases using terms and a controlled vocabulary associated with these ADs, ECG, and HRV. The available, full-text articles published in English were considered. In all, 20 publications that examined the direct effect of these diseases on the heart were selected according to a systematic review protocol. Time-frequency domain analysis revealed that HRV parameters were lower in patients with the selected ADs in comparison with control groups. An increased QT dispersion and heart rate corrected QT, which are well-known as risk factors for sudden cardiac death, were observed in the patient group. In some studies, a correlation was seen between the duration of the disease and its activity, while others did not report such an association. Heart rate turbulence parameters were also examined. Turbulence onset was increased in SLE and SSc patients, while the turbulence slope was decreased in SLE patients. There was no significant change in these parameters in BD patients. Patients with ADs demonstrate abnormal HRV and ECG parameters, which indicates an autonomic cardiac functional impairment. Measurement of these parameters can be a useful clinical tool in the diagnosis and prediction of some disorders in patients with ADs. Both of these signals can provide helpful information for physicians to trace the efficacy of prescribed medicines.

Heart Rate Correction of the J-to-Tpeak Interval

Drug-induced changes of the J to T peak (JTp) and J to the median of area under the T wave (JT50) were reported to differentiate QT prolonging drugs that are predominant blockers of the delayed potassium rectifier current from those with multiple ion channel effects. Studies of drug-induced JTp/JT50 interval changes might therefore facilitate cardiac safety evaluation of new pharmaceuticals. It is not known whether formulas for QT heart rate correction are applicable to JTp and JT50 intervals. QT/RR, JTp/RR, and JT50/RR profiles were studied in 523 healthy subjects aged 33.5 ± 8.4 years (254 females). In individual subjects, 1,256 ± 220 electrocardiographic measurements of QT, JTp, and JT50 intervals were available including a 5-minute history of RR intervals preceding each measurement. Curvilinear, linear and log-linear regression models were used to characterize individual QT/RR, JTp/RR, and JT50/RR profiles both without and with correction for heart rate hysteresis. JTp/RR and JT50/RR hysteresis correction needs to be included but the generic universal correction for QT/RR hysteresis is also applicable to JTp/RR and JT50/RR profiles. Once this is incorporated, median regression coefficients of the investigated population suggest linear correction formulas JTpc = JTp + 0.150(1-RR) and JT50c = JT50 + 0.117(1-RR) where RR intervals of the underlying heart rate are hysteresis-corrected, and all measurements expressed in seconds. The established correction formulas can be proposed for future clinical pharmacology studies that show drug-induced heart rate changes of up to approximately 10 beats per minute.

Errors of Fixed QT Heart Rate Corrections Used in the Assessment of Drug-Induced QTc Changes.

The accuracy of studies of drug-induced QTc changes depends, among others, on the accuracy of heart rate correction of QT interval. It has been recognized that when a drug leads to substantial heart rate changes, fixed universal corrections cannot be used and that alternative methods such as subject-specific corrections established for each study participant need to be considered. Nevertheless, the maximum heart rate change that permits use of fixed correction with reasonable accuracy has not been systematically investigated. We have therefore used full QT/heart-rate profiles of 751 healthy subjects (mean age 34.2 ± 9.6, range 18–61 years, 335 females) and compared their subject-specific corrections with 6 fixed corrections, namely Bazett, Fridericia, Framingham, Hodges, Rautaharju, and Sarma formulae. The comparison was based on statistical modeling experiments which simulated clinical studies of N = 10 or N = 50 female or male subjects. The experiments compared errors of ΔQTc intervals calculated as differences between QTc intervals at an initial heart rate (in the range of 40 to 120 beats per minute, bpm) and after a heart rate change (in the range from −20 to +20 bpm). The experiments also investigated errors due to spontaneous heart rate fluctuation and due to omission of correction for QT/RR hysteresis. In each experiment, the absolute value of the single-sided 90th percentile most remote from zero was used as the error estimate. Each experiment was repeated 10,000 times with random selection of modeled study group. From these repetitions, median and upper 80th percentile was derived and graphically displayed for all different combinations of initial heart rate and heart rate change. The results showed that Fridericia formula might be reasonable (with estimated errors of ΔQTc below 8 ms) in large studies if the heart rate does not change more than ± 10 bpm and that the errors by fixed corrections and the errors due to omission of QR/RR hysteresis are additive. Additionally, the results suggest that the variability introduced into QTc data by not correcting for the underlying heart rate accurately might have a greater impact in smaller studies. The errors by Framingham formula were practically the same as with the Fridericia formula. Other investigated fixed heart rate corrections led to larger ΔQTc errors.

Assessment of QT interval in ventricular paced rhythm: Derivation of a novel formula

ObjectiveThe objective of the study was to determine the optimal formula to estimate QT interval adjusting for QRS prolongation during right ventricular (RV) pacing. MethodsThis observational study included individuals (n = 43) with a newly implanted permanent ventricular pacemaker, who had a narrow QRS complex before pacemaker insertion. QT interval with RV pacing was related to QT interval before pacemaker implantation. The validation cohort (n = 442) had permanent RV pacing in DDD mode. ResultsA new QTc formula was derived utilizing the constants from the relationship between the spline heart rate QT correction (QTcRBK) before and after pacing; specifically, QTcRBKPACED = QTcRBK × 0.86. The JT interval from paced complexes was highly heart rate (HR) dependent and was not accurate for QT assessment. Previous, QTc formula for paced complexes were not highly correlated with QT before pacing unless a robust HR correction is added. Formulae subtracting a fixed amount from QTcPACED markedly overestimated QTc before pacing. ConclusionWe proposed a new, simple formula for QT estimation in RV pacing. JT interval in paced complexes is highly HR dependent and is not accurate for QT assessment. The new spline approach for HR correction for the QT, once incorporated into some previously proposed formulae, blunts HR dependency and improves prediction of QT before pacing. QTcRBKPACED*0.86 and QTcRBKPACED – (QRS*0.5) demonstrated the best balance of relatively strong correlation to QTc before pacing and accurate QTc prolongation identification. Abnormal QT for QTcRBKPACED*0.86 as defined by the 97.5th and 99th percentile are 469 and 479 ms respectively.

Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits

Genome-wide association studies (GWAS) of quantitative electrocardiographic (ECG) traits in large consortia have identified more than 130 loci associated with QT interval, QRS duration, PR interval, and heart rate (RR interval). In the current study, we meta-analyzed genome-wide association results from 30,000 mostly Dutch samples on four ECG traits: PR interval, QRS duration, QT interval, and RR interval. SNP genotype data was imputed using the Genome of the Netherlands reference panel encompassing 19 million SNPs, including millions of rare SNPs (minor allele frequency < 5%). In addition to many known loci, we identified seven novel locus-trait associations: KCND3, NR3C1, and PLN for PR interval, KCNE1, SGIP1, and NFKB1 for QT interval, and ATP2A2 for QRS duration, of which six were successfully replicated. At these seven loci, we performed conditional analyses and annotated significant SNPs (in exons and regulatory regions), demonstrating involvement of cardiac-related pathways and regulation of nearby genes.

Correlation of QT interval and heart rate variability in type 2 diabetic patients: Possible evidence for autonomic regulation of QT interval

Objective: QT interval length in Electrocardiogram (ECG) has prognostic impact on the patients with diabetes. This interval is influenced by autonomic nervous function, which is, however, impaired in diabetic patients. Since exact mechanisms of autonomic regulation of QT interval in diabetics remains unclear, this study aimed to investigate the relationship between heartrate- corrected QT interval (QTc interval) and Heart Rate Variability (HRV) in diabetic patients. Methods: Coefficient of variance of R-R intervals (CVRR:%) in digital ECG, as a representative time-domain measure of HRV, was estimated immediately after recording 12-lead ECG in type 2 diabetic (n=60) and nondiabetic control (n=62) groups. QTc interval was obtained by BazettA¢ÂA‚€ÂA‚™s formula where QTc=QT/RR1/2. Demographic and laboratory data were extracted from medical records. Significant contributors of multiple clinical factors to the QTc interval length were analyzed by multivariate analysis. Results: Body mass index (p<0.001) and CVRR (p=0.015) contributed significantly to the QTc interval regulation in diabetic group, whereas CVRR (p=0.037) alone contributed significantly to this interval in controls. However, CVRR was correlated with the QTc interval negatively in diabetic group (standardized AA‚ÂŽ²=-0.306), whereas the opposite was found in the case of control group (standardized AA‚ÂŽ²=0.266). Conclusion: Although this allows a cross-sectional case-control study design, positive correlation of BMI and QTc interval in diabetic patients indicates cardiometabolic linkage (r=0.339, p=0.008). CVRR was considered to regulate QTc intervals. However, the details of this autonomic regulation in diabetics differed from those in controls. The mechanisms of autonomic QTc regulation in diabetics require future investigation.

Correcting QT for Heart Rate When Both are Affected by a Drug.

Correcting QT for Heart Rate When Both are Affected by a Drug.

Predicting critical drug concentrations and torsadogenic risk using a multiscale exposure-response simulator

Torsades de pointes is a serious side effect of many drugs that can trigger sudden cardiac death, even in patients with structurally normal hearts. Torsadogenic risk has traditionally been correlated with the blockage of a specific potassium channel and a prolonged recovery period in the electrocardiogram. However, the precise mechanisms by which single channel block translates into heart rhythm disorders remain incompletely understood. Here we establish a multiscale exposure-response simulator that converts block-concentration characteristics from single cell recordings into three-dimensional excitation profiles and electrocardiograms to rapidly assess torsadogenic risk. For the drug dofetilide, we characterize the QT interval and heart rate at different drug concentrations and identify the critical concentration at the onset of torsades de pointes: For dofetilide concentrations of 2x, 3x, and 4x, as multiples of the free plasma concentration Cmax = 2.1 nM, the QT interval increased by +62.0%, +71.2%, and +82.3% compared to baseline, and the heart rate changed by −21.7%, −23.3%, and +88.3%. The last number indicates that, at the critical concentration of 4x, the heart spontaneously developed an episode of a torsades-like arrhythmia. Strikingly, this critical drug concentration is higher than the concentration estimated from early afterdepolarizations in single cells and lower than in one-dimensional cable models. Our results highlight the importance of whole heart modeling and explain, at least in part, why current regulatory paradigms often fail to accurately quantify the pro-arrhythmic potential of a drug. Our exposure-response simulator could provide a more mechanistic assessment of pro-arrhythmic risk and help establish science-based guidelines to reduce rhythm disorders, design safer drugs, and accelerate drug development.

Effects of sympathetic tone in the QT interval and heart rate variability indices of beagle dogs

Effects of sympathetic tone in the QT interval and heart rate variability indices of beagle dogs

Electroencephalographic and Electrocardiographic Effect of Intravenous Lacosamide in Refractory Focal Epilepsy.

Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels to achieve seizure reduction. We studied the effect of intravenous lacosamide given as one of three single doses on EEG and electrocardiogram, as well as its tolerability in patients with drug-resistant epilepsy. This Canadian, investigator-initiated, multicenter, double-blind study recruited patients with refractory focal epilepsy admitted to a seizure monitoring unit. Participants received a loading dose of 100, 200, or 400 mg lacosamide over 30 minutes during continuous monitoring by video-EEG and 12-lead electrocardiogram. The number of interictal spikes, frequency and quantity of background EEG rhythms, corrected QT interval (QTc), PR interval, heart rate (HR), blood pressure, and respiration rate during 60 minutes before the administration were compared with 60 minutes after the infusion. We documented any adverse event during and after the infusion. Seventy-one patients completed the study. There was a significant decrease in interictal spikes (P = 0.039) and decreased frequency of the alpha rhythm (P = 0.003). No significant difference in beta, theta, and delta frequency or amount was noted. There were significant increases in PR interval (153.4-155.8 ms, P = 0.031) and HR (73.4-75.5 bpm, P = 0.022), but QTc, blood pressure, and respiration rate were not affected. Twelve patients (16.9%) experienced transient and mild adverse events, mainly dizziness and leg tingling. More adverse events occurred with 400 mg lacosamide than with the lower doses (P = 0.048). Intravenous lacosamide is effective in decreasing interictal spikes. Despite a small effect on EEG and electrocardiogram rhythms, it is well tolerated with no serious adverse events.