Increase In QTc Interval Research Articles

Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort

BackgroundExposure to phenols has been linked in animal models and human populations to cardiac function alterations and cardiovascular diseases, although their effects on cardiac electrical properties in humans remains to be established. This study aimed to identify changes in electrocardiographic (ECG) parameters associated with environmental phenol exposure in adults of a midwestern large cohort known as the Fernald Community Cohort (FCC).MethodsDuring the day of the first comprehensive medical examination, urine samples were obtained, and electrocardiograms were recorded. Cross-sectional linear regression analyses were performed.ResultsBisphenol A (BPA) and bisphenol F (BPF) were both associated with a longer PR interval, an indication of delayed atrial-to-ventricle conduction, in females (p < 0.05) but not males. BPA combined with BPF was associated with an increase QRS duration, an indication of delayed ventricular activation, in females (P < 0.05) but not males. Higher triclocarban (TCC) level was associated with longer QTc interval, an indication of delayed ventricular repolarization, in males (P < 0.01) but not females. Body mass index (BMI) was associated with a significant increase in PR and QTc intervals and ventricular rate in females and in ventricular rate in males. In females, the combined effect of being in the top tertile for both BPA urinary concentration and BMI was an estimate of a 10% increase in PR interval. No associations were found with the other phenols.ConclusionHigher exposure to some phenols was associated with alterations of cardiac electrical properties in a sex specific manner in the Fernald cohort. Our population-based findings correlate directly with clinically relevant parameters that are associated with known pathophysiologic cardiac conditions in humans.

HIV and body mass index are associated with prolonged corrected QT interval among people with drug-resistant tuberculosis on bedaquiline-containing regimen in Uganda

ObjectivesPeople with drug-resistant tuberculosis (DR-TB) on bedaquiline-containing regimens are at risk for a prolonged corrected QT (QTc) interval but this problem is understudied in low-resource countries. We determined the magnitude and risk factors for QTc interval prolongation among people with DR-TB on bedaquiline-containing regimens at three referral hospitals in Uganda. MethodsUsing retrospectively collected data, we designed a matched case-control study, with cases as participants with prolonged QTc interval and controls as those with normal QTc interval in 1:1. QTc interval prolongation was defined as an increase in QTc interval by 60 milliseconds in electrocardiogram from the baseline or ≥500 milliseconds during follow-up for men and women. Factors associated with cases compared with controls were identified using a multivariable conditional regression analysis at a 5% significance level, reported using odds ratio (OR) and the 95% confidence interval (CI). ResultsOf 153 participants, 39 (25.5%) had a prolonged QTc interval. We matched 30 participants with prolonged QTc interval (cases) with 30 participants with normal QTc interval (controls). Cases and controls were similar in several sociodemographic and clinical characteristics but different regarding the baseline body mass index (BMI), baseline weight, and HIV infection. Increasing BMI (adjusted OR 1.29, 95% CI 1.02-1.63) and HIV infection (adjusted OR 0.27, 95% CI 0.08-0.96) were associated with the cases compared with the controls. ConclusionsWe found a relatively high prevalence of QTc interval prolongation among people with DR-TB on a bedaquiline-containing regimen compared with the prevalence in healthy individuals, with a higher likelihood in those with increasing BMI and a lower likelihood in those with HIV. We recommend routine anthropometric measurements to identify individuals with DR-TB at a high risk for QTc interval prolongation. In addition, tuberculosis/HIV treatment guidelines for people with DR-TB on bedaquiline-containing regimens should include risk assessment for prolonged QTc intervals.

Risk of corrected QT interval prolongation in patients receiving antipsychotics.

Antipsychotic (AP) use has been associated to QT interval prolongation on the surface electrocardiogram (ECG). Our study aimed to determine the incidence of corrected QT (QTc) interval prolongation among patients admitted to a psychiatric hospitalization unit requiring AP treatment and to assess the relationship between administered dose and QTc interval changes. We enrolled 179 patients admitted to the Hospital Psiquiátrico Departamental Universitario del Valle in Cali, Colombia. ECGs were conducted upon admission, and again at 3 and 7 days postadmission. The QT interval was measured, and QTc interval correction was performed using Bazzet's formula. QTc interval prolongation at time points B or C was observed in 9.5% of patients. Clozapine was the most common AP associated with QTc interval prolongation (20.59%), followed by olanzapine (15.38%). The relative risk of QT interval prolongation with clozapine compared to haloperidol was 4.17 (95% confidence interval, 1.14-15.17, P = 0.02). AP use upon hospital admission was linked to early (within 3 days) QTc interval prolongation. Clozapine and olanzapine were associated with a greater increase in QTc interval compared to haloperidol, indicating a need for rigorous electrocardiographic monitoring with their use.

A Comparative Analysis of the Effects of Haloperidol and Dexmedetomidine on QTc Interval Prolongation during Delirium Treatment in Intensive Care Units.

Haloperidol and dexmedetomidine are used to treat delirium in the intensive care unit (ICU). The effects of these drugs on the corrected QT (QTc) interval have not been compared before. It was aimed to compare the effects of haloperidol and dexmedetomidine treatment on QTc intervals in patients who developed delirium during ICU follow-up. The study is single-center, randomized, and prospective. Half of the patients diagnosed with delirium in the ICU were treated with haloperidol and the other half with dexmedetomidine. The QTc interval was measured in the treatment groups before and after drug treatment. The study's primary endpoints were maximal QT and QTc interval changes after drug administration. 90 patients were included in the study, the mean age was 75.2±12.9 years, and half were women. The mean time to delirium was 142+173.8 hours, and 53.3% of the patients died during their ICU follow-up. The most common reason for hospitalization in the ICU was sepsis (%37.8.). There was no significant change in QT and QTc interval after dexmedetomidine treatment (QT: 360.5±81.7, 352.0±67.0, p= 0.491; QTc: 409.4±63.1, 409.8±49.7, p=0.974). There was a significant increase in both QT and QTc interval after haloperidol treatment (QT: 363.2±51.1, 384.6±59.2, p=0.028; QTc: 409.4±50.9, 427.3±45.9, p=0.020). Based on the results obtained from the study, it can be concluded that the administration of haloperidol was associated with a significant increase in QT and QTc interval. In contrast, the administration of dexmedetomidine did not cause a significant change in QT and QTc interval.

Sex differences of 12 lead electrocardiographic findings of the rugby football league athlete

Cardiac electrical adaptations occur within athlete populations. Sex-related variations in the normal athlete electrocardiogram (ECG) have been observed, with males exhibiting increased QRS and PR intervals, while females have demonstrated increased QTc intervals in university-level athletes. Male athletes also maintain greater weekly training hours compared to female athletes, which is associated with increased ECG changes. The presence of these differences within Rugby Football League (RFL) athletes is unknown. This study aimed to investigate any sex-related variations in the 12-lead ECG in RFL athletes. Fifty nine RFL athletes (32 males [age = 25 ± 5 years] and 27 females [age = 24 ± 5 years]) were included in the study. One female was excluded with inferior T wave inversion and was referred for further investigation. The 12-lead ECG was collected as part of the athlete’s pre-season cardiac screening alongside completion of a health questionnaire, assessment of height and weight and brachial artery pressure. Continuous variables (i.e. heart rate, PR interval, QRS interval etc.), were analysed using an independent t-test or a Mann-Whitney U test as appropriate. For assessment of nominal data (i.e. incidence of early repolarisation and junctional rhythm etc.) a chi-squared test or Fishers exact test were used. A Spearman’s correlation coefficient was used to determine any association between training hours and ECG findings. Ethics approval was obtained from Liverpool John Moores University Ethics Committee. Height (183 ± 5 vs. 169 ± 5 cm, P &lt;0.001), weight (95 ± 11 vs. 77 ± 11 kg, P &lt;0.001) and weekly training hours (18 ± 5 vs. 12 ± 5 hrs, P = 0.001) were higher in male athletes. PR interval (156 ± 34 vs. 142 ± 19 ms, P = 0.002), QRS duration (98 ± 9 vs. 88 ± 7 ms, P &lt;0.001) and incidence of early repolarisation (47% vs. 11%, P = 0.004) were greater in males. Heart rate (57 ± 9 vs. 63 ± 11 bpm P = 0.016) and QTc interval (391 ± 20 vs. 414 ± 17 ms, P &lt;0.001) were greater in females. There was a significant negative correlation between weekly training hours and QTc interval (rs = −0.355, P = 0.009) only. In conclusion, there are significant sex-related ECG differences within RFL athletes that partially mirror previous research. These findings emphasise the importance of considering sex-related variations, during cardiac screening on RFL athletes and enhance our understanding of the normal RFL athlete ECG.

Continuous QT interval monitoring using insertable cardiac monitors during antiarrhythmic loading hospitalization: Results from the "LINQ QT" Study

Abstract Background QT interval prolongation is associated with the development of potentially lethal cardiac arrhythmias. An implantable cardiac monitor (ICM) capable of longitudinal QT monitoring may allow for mobile assessment of dynamic changes in QT and assist in predicting long term cardiotoxicity. Objective Determine feasibility of continuous QTc interval monitoring in patients with ICM hospitalized for antiarrhythmic drug loading. Methods The previously described QT detection algorithm for an ICM determines the QT interval for every beat thus providing continuous long-term QT trends. QT intervals detected from continuously collected ICM ECG data from patients enrolled in a prospective clinical study from three sites was analyzed with the primary objective of studying the long-term QT interval trends in patients undergoing antiarrhythmic drug loading in an inpatient setting. The ICM ECG was processed through the QT detection algorithm which calculates the QTc interval for every beat to generate continuous long term QTc trends. Metrics including mean and median QTc, minimum and maximum QTc, and magnitude of QTc change were studied during the hospitalization period. Continuous QTc interval trend is presented from a patient displaying increase in QTc interval following antiarrhythmic drug loading during the hospitalization period. Results 5 out of 17 patients enrolled (avg. age 71±7.3 years, 40% females) in the QT clinical study had continuous telemetered ICM ECG data available during the index antiarrhythmic loading hospitalization period. All patients were loaded with Sotalol during the hospitalization. All 5 patients had hypertension and atrial fibrillation (AF). 3 patients (60%) had a history of myocardial infarction (MI), congestive heart failure (CHF), and coronary artery disease (CAD) while 1 patient (20%) had diabetes. The magnitude of change in QTc over the hospitalization period was 139±42 msec with over 100 msec QTc change noticed in 4 of 5 patients (80%) (figure 1). Figure 2 shows continuous QTc interval trend observed from a patient (Male; Age:75; history of AF, hypertension, CHF, stroke) from this study showing a continuous increase in QTc interval. Overall, there was over 150 msec change in QTc observed for this patient during the hospitalization period. Premature ventricular complexes (PVCs) in a pattern of bigeminy were observed from ICM ECG for a 3-hr period from 12 pm-3 pm following the second antiarrhythmic dose which coupled with QT prolongation could indicate early signs of cardiotoxicity (figure 2). The five static 12-lead ECG measurements taken for this patient during the hospitalization period is also reported with the difference between these 12-lead QTc measurements and algorithm measured QTc being 22±8 msec. Conclusion ICM QT monitoring performed utilizing a QT interval detection algorithm can provide longitudinal and long-term dynamic QT trends in patients implanted with ICM.

Safety and feasibility of intravenous sotalol loading for the prevention of ventricular arrhythmias.

The use of intravenous (IV) sotalol loading following recent U.S. Food and Drug Administration (FDA) approval of a 1-day loading protocol has reduced the obligatory 3-day hospital stay for sotalol initiation when given orally. Several studies have recently demonstrated the safety and feasibility of IV loading for patients with atrial arrhythmias. However, there is a paucity of data on the feasibility and safety of IV sotalol loading for patients with ventricular arrhythmias. This study aims to assess the safety, feasibility, and length of stay (LOS) outcomes of IV sotalol loading for the prevention of ventricular arrhythmias. A retrospective analysis was performed of all patients undergoing IV sotalol loading and oral sotalol initiation for ventricular arrhythmias, or IV sotalol loading for atrial arrhythmias between August 2021 and December 2023 at Northwestern University. Baseline characteristics, success of sotalol initiation/loading, changes in heart rate (HR) and QT/QTc, safety, and LOS were compared between patients undergoing sotalol loading/initiation for ventricular arrhythmias (IV vs. PO) and between patients undergoing IV sotalol loading for ventricular arrhythmias vs. for atrial arrhythmias. A total of 28 patients underwent sotalol loading/initiation for ventricular arrhythmias (N = 15 IV and N = 13 PO) and 41 patients underwent IV sotalol loading for atrial arrhythmias. Baseline characteristics of congestive heart failure history and left ventricular ejection fraction were worse in the ventricular arrhythmias group. There was no significant difference in the successful completion of IV sotalol loading for ventricular arrhythmias compared to oral sotalol initiation for ventricular arrhythmias or IV sotalol loading for atrial arrhythmias (86.7% vs. 92.3% vs. 90.2%, p = 0.88). There was a significant increase in ΔQTc following IV sotalol infusion for ventricular arrhythmias compared to following PO sotalol initiation for ventricular arrhythmias (46.4 ± 29.2ms vs. 8.9 ± 32.6ms, p = 0.004) and following IV sotalol infusion for atrial arrhythmias (46.4 ± 29.2ms vs. 24.0 ± 25.1ms, p = 0.018). ΔHR following IV sotalol infusion for ventricular arrhythmias was similar to ΔHR following PO sotalol initiation for ventricular arrhythmias and ΔHR following IV sotalol infusion for atrial arrhythmias (- 7.5 ± 8.7bpm vs. - 8.5 ± 13.9bpm vs. - 8.3 ± 13.2bpm, p = 0.87). There were no significant differences in discontinuation for QTc prolongation (6.7% vs. 1.7% vs. 2.4%, p = 0.64) and bradycardia (13.3% vs. 7.7% vs. 9.8%, p = 0.88) between IV sotalol loading for ventricular arrhythmias, PO sotalol initiation for ventricular arrhythmias, and IV sotalol loading for atrial arrhythmias. There were no instances of hypotension, life-threatening ventricular arrhythmias, heart failure, or death. Length of stay was significantly shorter for IV sotalol loading compared to PO sotalol initiation for ventricular arrhythmias (1.1 ± 0.36days vs. 4.2 ± 1.0days, p < 0.0001). IV sotalol loading appears feasible and safe for use in ventricular arrhythmias and results in a decreased length of stay. Despite increased comorbidities and greater increase in QTc interval following IV sotalol infusion in the ventricular arrhythmias group, there were no significant differences in successful completion of loading or adverse outcomes when compared to PO sotalol initiation for ventricular arrhythmias and IV loading for atrial arrhythmias.

Comparison of QTc interval changes in drug-resistant tuberculosis patients on delamanid-containing regimens versus shorter treatment regimens.

Delamanid (DLM) is a relatively new drug for drug-resistant tuberculosis (DR-TB) that has been used in Indonesia since 2019 despite its limited safety data. DLM is known to inhibit hERG potassium channel with the potential to cause QT prolongation which eventually leads to Torsades de pointes (TdP). This study aims to analyse the changes of QTc interval in DR-TB patients on DLM regimen compared to shorter treatment regimens (STR). A retrospective cohort was implemented on secondary data obtained from two participating hospitals. The QTc interval and the changes in QTc interval from baseline (ΔQTc) were assessed every 4 weeks for 24 weeks. The maximum increased of QTc interval and ΔQTc interval were smaller in the DLM group with mean difference of 18,6 (95%CI 0.3 to 37.5) and 31.6 milliseconds (95%CI 14.1 to 49.1) respectively. The proportion of QTc interval prolongation in DLM group were smaller than STR group (RR=0.62; 95%CI 0.42 to 0.93). This study has shown that DLM regimens are less likely to increase QTc interval compared to STR. However, close monitoring of the risk of QT interval prolongation needs to be carried out upon the use of QT interval prolonging antituberculoid drugs.

The Association Between QTc-Interval and Blood Glucose with Plasma Acetylcholinesterase in Organophosphate (OP)-Poisoned Patients

Background: Organophosphate (OP) poisoning ranks among the leading causes of poisoning, morbidity, and mortality in developing countries due to its relatively high prevalence and potentially grave outcomes. Consequently, it is crucial to identify an easily accessible and cost-effective marker that can be utilized across healthcare facilities. Objectives: This study aimed to explore the relationship between the QTc interval and blood glucose levels with serum cholinesterase levels in patients poisoned by organophosphates. Methods: The sample consisted of all patients admitted with OP poisoning to a Northwest Poisoning Center in Iran during 2016 and 2017. Diagnosis of OP poisoning was confirmed through patient history, physical examination, or the measurement of acetylcholinesterase levels. Data collected were analyzed using SPSS software version 25. Results: Out of 238 patients, 104 remained after applying exclusion criteria and were included in the study. The mean age of these patients was 30.81 ± 15.04 years. A statistically significant negative correlation was found between average blood glucose and serum cholinesterase levels (P = 0.046, Pearson Correlation = -0.196). Furthermore, patients with abnormal QTc intervals exhibited significantly lower serum cholinesterase levels (P &lt; 0.001). Conclusions: The findings indicate a significant association between QTc intervals and blood glucose levels with serum cholinesterase levels. Serum cholinesterase levels decreased with an increase in QTc intervals and blood glucose levels. Specifically, patients with a QTc interval greater than 440 milliseconds or random blood glucose levels above 200 milligrams per deciliter showed significantly lower serum cholinesterase levels.

Evaluation of the Renal and Cardiovascular Effects of Long-Term Tolvaptan Treatment in Autosomal Dominant Polycystic Kidney Disease

Introduction: Cardiovascular diseases constitute a significant cause of morbidity and mortality in individuals with autosomal dominant polycystic kidney disease (ADPKD). This study aimed to assess the long-term effects of tolvaptan on the kidneys and heart in rapidly progressing ADPKD. Methods: Among 354 patients diagnosed with ADPKD, 58 meeting the eligibility criteria for tolvaptan were included in the study. The study comprised two groups with similar demographic and clinical characteristics: 29 patients receiving tolvaptan treatment and 29 in the control group. Several included genetic analysis, magnetic resonance imaging, and echocardiography. Clinical and cardiac changes were recorded in both groups after a 3-year follow-up. Results: Tolvaptan treatment demonstrated a significant reduction in the rate of eGFR decline compared to the control group. Furthermore, it was observed that tolvaptan could prevent the development of cardiac arrhythmias by inhibiting an increase in QTc interval and heart rate. Conclusion: These findings suggest that, in addition to slowing kidney progression in ADPKD management, tolvaptan may potentially benefit in preventing cardiac complications.

Incidences, risk factors, and clinical correlates of severe QT prolongation after the use of quetiapine or haloperidol

BackgroundCase reports suggest that quetiapine or haloperidol use is associated with severe QT prolongation (SQTP) and torsades de pointes. ObjectiveThe purpose of this study was to examine the incidences, risk factors, and outcomes of SQTP in quetiapine and haloperidol users. MethodsThis study accessed electronic medical records from a multicenter health-care hospital system in Taiwan and included patients who received quetiapine or haloperidol therapy and had both baseline and follow-up electrocardiograms. SQTP was defined as a posttreatment corrected QT (QTc) interval exceeding 500 ms or an increase in QTc interval of >60 ms compared with the baseline value. We analyzed the risk factors and outcomes of SQTP using multivariate logistic regression. ResultsMean increases in QTc interval were +8.3 ± 51.8 and +8.9 ± 44.0 ms after the administration of quetiapine (n = 8832) and haloperidol (n = 2341). Among these users, 1149 (13.0%) and 333 (14.2%) developed SQTP, respectively. Common risk factors for SQTP included old age, heart failure, hypokalemia, amiodarone use, and baseline QTc interval. SQTP in quetiapine users was significantly associated with ventricular arrhythmias (odds ratio 2.84; 95% confidence interval 1.95–4.13) and sudden cardiac death (odds ratio 2.29; 95% confidence interval 1.44–3.66). ConclusionMore than 10% of patients receiving quetiapine or haloperidol therapy developed SQTP, and many of them were exposed to risk factors for SQTP. SQTP in quetiapine users was significantly associated with increased risks of ventricular arrhythmias and sudden cardiac death. Clinicians should be vigilant for ventricular arrhythmias in quetiapine users who have risk factors for SQTP.

Impact of Hydroxychloroquine, on QTC Interval, in Patients with Rheumatologic Diseases

Background: Hydroxychloroquine (HCQ) has been historically used for treatment of autoimmune diseases and more recently, it is used for treatment of COVID-19 patients. Using HCQ in COVID-19 patients resulted in corrected QT(QTc) prolongation which has potential to deteriorate into Torsades de Pointes and sudden cardiac death. As it is used chronically by rheumatologic patients so this study was designed to establish effect of HCQ on QTc in rheumatic patients. Methods: A cross sectional comparative study conducted in Rheumatology Department Shaikh Zayed hospital, Lahore. Non-probability consecutive sampling technique was used. Duration of study was 169 days. 45 patients used HCQ for three months and 45 patients did not use HCQ. ECG was done at induction in the study and after three months. Serum calcium, potassium and magnesium were also checked at onset. QTc was calculated by Bazett’s formula. Results: QTc did not raise in 21(46%) patients, in both groups. QTc raised between 1- 50msec in 20(44.4%) and 23(51.1%) patients in HCQ exposed and unexposed patients, respectively. QTc rise more than 50msec in 4(8.88%) and 1(2.2%) patient in HCQ exposed and unexposed patients, respectively (p-value=0.344). The QTc change is associated with heart rate showing 75.0% chances of increased QTc among those with increased heart rate. Conclusion: HCQ did not increase QTc interval in 46% study. 8.88% of HCQ exposed population and 2.22% of HCQ unexposed population had significant change in QTc. However, no adverse cardiac events were observed in study duration

Effect of Intravenous Azithromycin on the QT Interval of ICU Patients

Background: Azithromycin is a commonly prescribed antibiotic included in many first-line regimens for pneumonia. Azithromycin also carries an FDA warning for increased risk for abnormal cardiac electrical activity, including QTc prolongation. Objective: To examine the effect of intravenous azithromycin on the QT interval in a cohort of patients receiving antibiotic therapy for community acquired pneumonia. Methods: A single-center, retrospective chart review of patients admitted to the Intensive Care Unit (ICU). The primary endpoint was change in QTc 48-72 hours after antibiotic initiation. The primary outcome was analyzed using ANOVA matched comparison. Results: Between 6/1/2019 and 3/31/2020, 241 total ICU patients received doses of either antibiotic. After application of exclusion criteria, the total number of patients included in analysis was 93, including 75 azithromycin patient and 18 doxycycline patients. The baseline QTc in the azithromycin group was 449 (95% CI 438-461) and the 72-hour QTc was 442 (95% CI 427-453) with an average change in QTc of -4 ms (P = .14). No statistically significant difference was found in QTc interval change between azithromycin and doxycycline. Conclusion: In this study, azithromycin use was not associated with a statistically significant increase in QTc interval. Based on these results, for the majority of patients receiving azithromycin, QTc prolongation is not likely a major concern. However, caution may still be warranted in patients considered high risk.

Electrocardiographic changes during sustained normobaric hypoxia in patients after myocardial infarction

The safety of prolonged high-altitude stays and exercise for physically fit post-myocardial infarction (MI) patients is unclear. Myocardial tissue hypoxia and pulmonary hypertension can affect cardiac function and electrophysiology, possibly contributing to arrhythmias. We included four non-professional male athletes, clinically stable after left ventricular MI (three with ST-segment elevation MI and one with non-ST-segment elevation MI) treated with drug-eluting stents for single-vessel coronary artery disease. Oxygen levels were reduced to a minimum of 11.8%, then restored to 20.9%. We conducted electrocardiography (ECG), ergometry, and echocardiography assessments in normoxic and hypoxic conditions. With an average age of 57.8 ± 3.3 years and MI history 37 to 104 months prior, participants experienced a significant increase in QTc intervals during hypoxia using Bazett’s (from 402 ± 13 to 417 ± 25 ms), Fridericia’s (from 409 ± 12 to 419 ± 19 ms), and Holzmann's formulas (from 103 ± 4 to 107 ± 6%) compared to normoxia. This effect partially reversed during recovery. Echocardiographic signs of pulmonary hypertension during normobaric hypoxia correlated significantly with altered QTc intervals (p < 0.001). Despite good health and complete revascularization following MI, susceptibility to hypoxia-induced QTc prolongation and ventricular ectopic beats persists, especially during physical activity. MI survivors planning high-altitude activities should consult cardiovascular specialists with high-altitude medicine expertise.

Dynamic changes in T-wave and QTc interval during tilt table testing: Innocent until proven otherwise

A16-year-old female underwent tilt table testing, which resulted positive for reflex vasodepressive syncope. 12‑lead ECG during syncope showed T-wave inversion in infero-lateral leads, along with QTc interval increase >100 msec compared to baseline. These abnormalities rapidly disappeared in supine position with resumption of consciousness. Complete cardiac evaluation excluded heart disease. T-wave changes and moderate QTc prolongation are relatively common in young (mainly female) patients undergoing tilt table testing and they appear benign in nature. However, in a minority of cases, on the basis of the clinical context and after an accurate ECG analysis, further examinations may be warranted.

Genetic variants and effect modifiers of QT interval prolongation in patients with sickle cell disease

BackgroundSickle cell disease (SCD) is a common inherited blood disorder among African Americans (AA), with premature mortality which has been associated with prolongation of the heart rate-corrected QT interval (QTc), a known risk factor for sudden cardiac death. Although numerous genetic variants have been identified as contributors to QT interval prolongation in the general population, their impact on SCD patients remains unclear. This study used an unweighted polygenic risk score (PRS) to validate the previously identified associations between SNPs and QTc interval in SCD patients, and to explore possible interactions with other factors that prolong QTc interval in AA individuals with SCD. MethodsIn SCD patients, candidate genetic variants associated with the QTc interval were genotyped. To identify any risk SNPs that may be correlated with QTc interval prolongation, linear regression was employed, and an unweighted PRS was subsequently constructed. The effect of PRS on the QTc interval was evaluated using linear regression, while stratification analysis was used to assess the influence of serum alanine transaminase (ALT), a biomarker for liver disease, on the PRS effect. We also evaluated the PRS with the two subcomponents of QTc, the QRS and JTc intervals. ResultsOut of 26 candidate SNPs, five risk SNPs were identified for QTc duration under the recessive model. For every unit increase in PRS, the QTc interval prolonged by 4.0 ms (95% CI: [2.0, 6.1]; p-value: <0.001) in the additive model and 9.4 ms in the recessive model (95% CI: [4.6, 14.1]; p-value: <0.001). Serum ALT showed a modification effect on PRS-QTc prolongation under the recessive model. In the normal ALT group, each PRS unit increased QTc interval by 11.7 ms (95% CI: [6.3, 17.1]; p-value: 2.60E-5), whereas this effect was not observed in the elevated ALT group (0.9 ms; 95% CI: [-7.0, 8.8]; p-value: 0.823). ConclusionSeveral candidate genetic variants are associated with QTc interval prolongation in SCD patients, and serum ALT acts as a modifying factor. The association of a CPS1 gene variant in both QTc and JTc duration adds to NOS1AP as evidence of involvement of the urea cycle and nitric oxide metabolism in cardiac repolarization in SCD. Larger replication studies are needed to confirm these findings and elucidate the underlying mechanisms.

Prolongation of the QTc interval is associated with an increased risk of cardiovascular diseases: The Hoorn study.

Prolonged heart rate-corrected QT interval (QTc) on the electrocardiogram (ECG) is maybe associated with the occurrence of cardiovascular diseases (CVD), but the evidence is inconsistent. Therefore, we investigated whether baseline prolongation of the QTc interval is associated with CVD morbidity and mortality and its subtypes and whether glucose tolerance modifies this association in a population-based cohort study with a mean follow-up of 10.8years. We analyzed a glucose tolerance stratified sample (N=487) from the longitudinal population-based Hoorn Study cohort (age 64±7years, 48% female). Cox regression was used to investigate the association between sex-specific baseline QTc quartiles and CVD morbidity and mortality. The risk was also estimated per 10ms increase in QTc. All analyses were adjusted for age, sex, smoking status, systolic blood pressure, prevalent CVD, glucose tolerance status, hypertension and total cholesterol. In addition, stratified analyses were conducted for glucose tolerance status. During a mean follow-up of 10.8years, 351 CVD events were observed. The adjusted hazard ratios (95% CI) for each 10ms increase in QTc interval were 1.06 (95% CI: 1.02-1.10) for CVD, 1.06 (95% CI: 0.97-1.15) for acute myocardial infarction, 1.07 (95% CI: 1.01-1.13) for stroke, 1.12 (95% CI: 1.06-1.19) for heart failure, 1.04 (95% CI: 0.96-1.12) for peripheral arterial disease and 1.01 (95% CI:0.95-1.08) for coronary heart disease. Glucose tolerance status did not modify the association (P>0.2). Prolongation of the QTc interval is associated with morbidity and mortality due to general CVD. Glucose tolerance status did not modify these associations.

Investigation of QT Dispersion and T-Peak to T-End/Corrected QT Ratio in Multisystem Inflammatory Syndrome in Children.

Introduction Multisystem inflammatory syndrome in children (MIS-C) is characterized by hyperinflammation, heart involvement, and multiorgan failure, which develop following coronavirus disease 2019. Ventricular arrhythmias have been identified during this syndrome. It is known that the risk of ventricular arrhythmia is associated with ventricular repolarization changes. The aim of this study was to investigate the corrected QT interval, QT dispersion, T wave peak-to-end interval, and T-peak to T-end/corrected QT ratio in MIS-C. Methods The study included 35 patients diagnosed with MIS-C and 35 subjects as the control group. The ventricular diameters, ejection fraction, valve insufficiency, and coronary artery were examined in both groups using echocardiography. Corrected QT interval, QT dispersion, T wave peak-to-end interval, and T-peak to T-end/corrected QT ratio were determined by 12-lead electrocardiogram. Results The patient group had increased corrected QT interval (p<0.05), QT dispersion (p = 0.001), T-peak to T-end interval (p=0.001), and T-peak to T-end/corrected QT ratio (p = 0.001) compared to the control group. Moreover, there was a correlation between increased QT dispersion, T-peak to T-end, T-peak to T-end/corrected QT ratio, and decreased ejection fraction (r = -0.51 and p = 0.001, r = -0.71 and p < 0.001, r = -0.69 and p < 0.001, r = -0.56 and p < 0.001, respectively). Conclusions Our study demonstrated increased QTc interval, QT dispersion, T-peak to T-end interval, T-peak to T-end/corrected QT ratio in MIS-C. This result may indicate an increased risk of ventricular arrhythmia for these patients.

The effect of anti-tuberculosis drug pharmacokinetics on QTc prolongation

Implementation of newer anti-tuberculosis (TB) drugs may prolong the QT interval, increasing the risk of arrythmias and sudden cardiac death. The potential for cardiac adverse events has prompted recommendations for frequent cardiac monitoring during treatment. However, unknowns remain, including the association between drug concentrations and QT interval. An observational prospective cohort study design was used. Patients undergoing treatment for drug-resistant TB in Georgia were assessed. Serial blood samples were collected at 4-6 weeks for pharmacokinetics. Electrocardiograms were recommended to be performed monthly. A generalized estimating equation spline model was used to investigate (1) the effect difference between bedaquiline and delamanid, (2) the cumulative effect of number of anti-TB drugs, and (3) the relationship between serum drug concentrations on QTc interval. Among 94 patients receiving either bedaquiline (n=64) or delamanid (n=30)-based treatment, most were male (82%), and the mean age was 39 years. The mean maximum QTc increase during the first six months was 37.5 ms (IQR: 17.8-56.8). Bedaquiline- and delamanid-based regimens displayed similar increased mean QTc change from baseline during drug administration (P=0.12). Increasing number of anti-TB drugs was associated with an increased QTc (P=0.01), but participants trended back towards baseline after drug discontinuation (P=0.25). A significant association between AUC, Cmin, Cmax, and increased QTc interval was found for bedaquiline (months 1-6) and levofloxacin (months 1-12). Bedaquiline- and delamanid-based regimens and increasing number of QT prolonging agents led to modest increases in the QTc interval with minimal clinical effect.

Dosage of the pseudoautosomal gene SLC25A6 is implicated in QTc interval duration

The genetic architecture of the QT interval, defined as the period from onset of depolarisation to completion of repolarisation of the ventricular myocardium, is incompletely understood. Only a minor part of the QT interval variation in the general population has been linked to autosomal variant loci. Altered X chromosome dosage in humans, as seen in sex chromosome aneuploidies such as Turner syndrome (TS) and Klinefelter syndrome (KS), is associated with altered QTc interval (heart rate corrected QT), indicating that genes, located in the pseudoautosomal region 1 of the X and Y chromosomes may contribute to QT interval variation. We investigate the dosage effect of the pseudoautosomal gene SLC25A6, encoding the membrane ADP/ATP translocase 3 in the inner mitochondrial membrane, on QTc interval duration. To this end we used human participants and in vivo zebrafish models. Analyses in humans, based on 44 patients with KS, 44 patients with TS, 59 male and 22 females, revealed a significant negative correlation between SLC25A6 expression level and QTc interval duration. Similarly, downregulation of slc25a6 in zebrafish increased QTc interval duration with pharmacological inhibition of KATP channels restoring the systolic duration, whereas overexpression of SLC25A6 shortened QTc, which was normalized by pharmacological activation of KATP channels. Our study demonstrate an inverse relationship between SLC25A6 dosage and QTc interval indicating that SLC25A6 contributes to QT interval variation.