Prolonged Heart Rate-corrected QT Interval Research Articles

Major Drug-Drug Interaction Exposure Among Medicaid-Insured Children in the Outpatient Setting.

Drug-drug interactions (DDIs) can cause adverse drug events, but little is known about DDI exposure in children in the outpatient setting. This study aimed to determine the prevalence of major DDI exposure and factors associated with higher DDI exposure rates among children in an outpatient setting. We performed a cross-sectional study of children aged 0 to 18 years with ≥1 ambulatory encounter, and ≥2 dispensed outpatient prescriptions study using the 2019 Marketscan Medicaid database. DDIs (exposure to a major DDI for ≥1 day) and the adverse physiologic effects of each DDI were identified using DrugBank's interaction database. Primary outcomes included the prevalence and rate of major DDI exposure. We used logistic regression to assess patient characteristics associated with DDI exposure. We examined the rate of DDI exposures per 100 children by adverse physiologic effects category, and organ-level effects (eg, heart rate-corrected QT interval prolongation). Of 781 019 children with ≥2 medication exposures, 21.4% experienced ≥1 major DDI exposure. The odds of DDI exposure increased with age and with medical and mental health complexity. Frequently implicated drugs included: Clonidine, psychiatric medications, and asthma medications. The highest adverse physiologic effect exposure rate per 100 children included: Increased drug concentrations (14.6), central nervous system depression (13.6), and heart rate-corrected QT interval prolongation (9.9). One in 5 Medicaid-insured children with ≥2 prescription medications were exposed to major DDIs annually, with higher exposures in those with medical or mental health complexity. DDI exposure places children at risk for negative health outcomes and adverse drug events, especially in the harder-to-monitor outpatient setting.

Corrected QTc interval combined with troponin value and mortality in acute ischemic stroke.

Cardiac biomarkers including, elevated troponin (ET) and prolonged heart rate-corrected QT (PQTc) interval on electrocardiography are known to frequent and have a prognostic significance in patients with acute ischemic stroke (AIS). However, it is still challenging to practically apply the results for appropriate risk stratification. This study evaluate whether combining ET and PQTc interval can better assess the long-term prognosis in AIS patients. In this prospectively registered observational study between May 2007 and December 2011, ET was defined as serum troponin-I ≥ 0.04 ng/ml and PQTc interval was defined as the highest tertile of sex-specific QTc interval (men ≥ 469 ms or women ≥ 487 ms). Among the 1,668 patients [1018 (61.0%) men; mean age 66.0 ± 12.4 years], patients were stratified into four groups according to the combination of ET and PQTc intervals. During a median follow-up of 33 months, ET (hazard ratio [HR]: 4.38, 95% confidence interval [CI]: 2.94-6.53) or PQTc interval (HR: 1.53, 95% CI: 1.16-2.01) alone or both (HR: 1.77, 95% CI: 1.16-2.71) was associated with increased all-cause mortality. Furthermore, ET, PQTc interval alone or both was associated with vascular death, whereas only ET alone was associated with non-vascular death. Comorbidity burden, especially atrial fibrillation and congestive heart failure, and stroke severity gradually increased both with troponin value and QTc-interval. In patients with AIS, combining ET and PQTc interval on ECG enhances risk stratification for long-term mortality while facilitating the discerning ability for the burden of comorbidities and stroke severity.

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.

Increased ventricular ectopy precedes Torsades de Pointes in patients with prolonged QT.

Torsades de Pointes (TdP) is a potentially lethal ventricular tachydysrhythmia. Prolonged heartrate corrected QT interval (QTc) predicts TdP; however, with poor specificity. We performed this study to identify other predictors of TdP among patients with prolonged QTc. We performed a retrospective case control study with 2:1 matching at an urban academic hospital. We searched our hospital electrocardiogram (ECG) database for tracings with heartrate ≤ 60, QTc≥500, and QRS<120, followed by a natural language search for electronic records with "Torsades," "polymorphic VT," or similar to identify TdP cases from 2005 to 19. We identified controls from a similar ECG database search matching for QTc, heartrate, age, and sex. We compared cardiologic and historical factors, medications, laboratory values, and ECG measurements including ectopy using univariate statistics. For those cases with saved telemetry strips that included preceding beats or TdP onset, we compared ectopy and TdP onset characteristics between the ECG and telemetry strips using mixed linear modeling. Seventy-five cases including 50 with telemetry strips and 150 controls were included. Historical, pharmacologic, laboratory, and cardiologic testing results were similar between cases and controls. The proportion of telemetry tracings with premature ventricular contractions (PVC's) preceding TdP was 0.78 compared to 0.16 for case ECG's (difference 0.62(95%CI 0.44-0.75)) and 0.10 for control ECGs (difference 0.68(95%CI 0.56-0.80)). Average telemetry heartrate was 72 and QTc 549 immediately preceding TdP, similar to the ECG values. Clinical factors don't differentiate patients with long QTc who develop TdP, however, an increase in PVC's in patients with prolonged QTc may usefully predict imminent TdP.

Diagnostic Accuracy of the Standing Test in Adults Suspected for Congenital Long-QT Syndrome.

Background An elegant bedside provocation test has been shown to aid the diagnosis of long-QT syndrome (LQTS) in a retrospective cohort by evaluation of QT intervals and T-wave morphology changes resulting from the brief tachycardia provoked by standing. We aimed to prospectively determine the potential diagnostic value of the standing test for LQTS. Methods and Results In adults suspected for LQTS who had a standing test, the QT interval was assessed manually and automated. In addition, T-wave morphology changes were determined. A total of 167 controls and 131 genetically confirmed patients with LQTS were included. A prolonged heart rate-corrected QT interval (QTc) (men ≥430 ms, women ≥450 ms) at baseline before standing yielded a sensitivity of 61% (95% CI, 47-74) in men and 54% (95% CI, 42-66) in women, with a specificity of 90% (95% CI, 80-96) and 89% (95% CI, 81-95), respectively. In both men and women, QTc≥460 ms after standing increased sensitivity (89% [95% CI, 83-94]) but decreased specificity (49% [95% CI, 41-57]). Sensitivity further increased (P<0.01) when a prolonged baseline QTc was accompanied by a QTc≥460 ms after standing in both men (93% [95% CI, 84-98]) and women (90% [95% CI, 81-96]). However, the area under the curve did not improve. T-wave abnormalities after standing did not further increase the sensitivity or the area under the curve significantly. Conclusions Despite earlier retrospective studies, a baseline ECG and the standing test in a prospective evaluation displayed a different diagnostic profile for congenital LQTS but no unequivocal synergism or advantage. This suggests that there is markedly reduced penetrance and incomplete expression in genetically confirmed LQTS with retention of repolarization reserve in response to the brief tachycardia provoked by standing.

Importance of exercise stress testing in evaluation of unexplained cardiac arrest survivor.

In sudden cardiac arrest survivors without an immediately identifiable cause, additional extensive yet individualised testing is required. We describe 3survivors of sudden cardiac arrest in whom exercise stress testing was not performed during the initial hospital admission. All 3patients were incorrectly diagnosed with long QT syndrome based on temporary sudden cardiac arrest-related heart rate-corrected QT interval prolongation, and exercise stress testing was not performed during the initial work-up. When they were subjected to exercise stress testing during follow-up, adelayed diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was made. As aresult, these patients were initially managed inappropriately, and their family members were initially not screened for CPVT. In sudden cardiac arrest survivors without an immediately identifiable cause, omission of exercise stress testing or erroneous interpretation of the results can lead to adelayed or missed diagnosis of CPVT, which may have considerable implications for survivors and their family.

Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases: Systematic review and meta-analysis

BackgroundConflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease. AimsTo identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations. MethodsA systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models. ResultsOf the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33–2.12; I2=69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08–1.50; I2=38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26–3.39; I2=78%); stroke (HR 1.59, 95% CI 1.29–1.96; I2=45%); sudden cardiac death (HR 1.60, 95% CI 1.14–2.25; I2=68%); and atrial fibrillation (HR 1.55, 95% CI 1.31–1.83; I2=0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population. ConclusionQTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population.

Heart rate-corrected QT interval prolongation is associated with decreased heart rate variability in patients with type 2 diabetes.

We investigated the association between the heart rate-corrected QT interval (QTc interval) measured by standard electrocardiography and heart rate variability (HRV) in patients with type 2 diabetes mellitus (T2DM). From March 1, 2009, to December 12, 2009, 411 patients with T2DM who underwent resting 12-lead electrocardiography and cardiovascular autonomic function testing concurrently without the exclusion criteria were consecutively recruited in this cross-sectional study. Time- and frequency-domain HRV variables were assessed for 5 minutes by beat-to-beat HRV recording. The QT interval was corrected for the heart rate using Bazett's formula. QTc interval measurements of >440 ms were considered abnormally prolonged. The mean age and diabetes duration were 56.3 ± 10.6 years and 9.6 ± 7.3 years, respectively. A total of 90 patients had QTc interval prolongation (21.9%). The participants with a prolonged QTc interval were older (59.4 ± 10.1 years vs 55.5 ± 10.6 years, P = .002), were more likely to be a woman (72.2% vs 51.7%, P = .001), had a higher prevalence of hypertension (46.7% vs 33.4%, P = .022), had a higher hemoglobin A1c level (8.8% ± 2.2% vs 8.2% ± 1.8%, P = .045), and had decreased values for the variables measuring HRV, except for the low frequency (LF)/high frequency (HF) ratio (total power [TP], 147.7 [74.1-335.9] ms vs 328.7 [185.7-721.7] ms, P = .002). After adjusting for multiple confounders, QTc interval prolongation was associated with the lowest quartile of the HRV parameters of TP (odds ratio [OR] = 3.99; 95% confidence interval [CI]: 2.29-6.96), HF (OR = 3.20; 95% CI: 1.84-5.58), LF (OR = 3.68; 95% CI: 2.10-6.43), standard deviation of the normal-to-normal interval (OR = 3.31; 95% CI: 1.89-5.77), and root-mean-square of the successive differences (OR = 1.98; 95% CI: 1.13-3.47) in patients with T2DM. Decreased values for the variables measuring HRV, except for the LF/HF ratio, might be associated with QTc interval prolongation in patients with T2DM.

QTc interval in anorexia nervosa: a systematic review and meta-analysis

Abstract Background Patients with anorexia nervosa (AN) are at higher risk of sudden cardiac death. Although the underlying aetiology for this association remains unclear. It may be related to prolongation of the QT interval, which can degenerate into fatal ventricular arrhythmias. However, the presence of prolonged heart rate-corrected QT interval (QTc) in AN remains controversial, and two previous meta-analyses on AN and QTc showed contradictory findings [1,2]. Purpose In this systematic review and meta-analysis, we aimed to evaluate if AN was associated with changes in the QTc interval and dispersion. Methods MEDLINE, EMBASE and COCHRANE databases were systematically searched from inception to January 2021. Random-effects meta-analysis and meta-regression were used. The inclusion criteria were (i) confirmed diagnosis of AN, (ii) measurement of QTc on electrocardiogram and (iii) peer-reviewed articles. The primary endpoint of the study was the duration of the QTc interval calculated using the Bazett (QTcB), Hodges (QTcH), Fridericia (QTcF) and Framingham (QTcFr) formulae. The secondary endpoints were QT dispersion (QTd) and QTc dispersion (QTcd). Results The 25 eligible studies included 5687 patients (1862 AN, 3825 control) (Figure 1: PRISMA diagram). The majority of patients were female (96.3%) with a mean age between 14.3 to 31.0 years and mean duration of disease ranging from 9.1 to 129.6 months. The mean BMI ranged from 13.7 to 18.5 kg/m2. Pooled analysis did not show significant prolongation between AN versus control in QTcB (mean difference (MD) MD 4.9ms, 95% CI −3.2, 13.1ms, p=0.23; I2=95%; n=24/25 studies; Figure 2A), QTcH (MD 1.3ms, 95% CI −8.5, 11.2ms, p=0.79; I2=71%; n=3/25 studies), and QTcF (MD 3.1ms, 95% CI −21.6, 27.7ms, p=0.81; I2=97%; n=3/25 studies). Only two studies reporting QTcFr showed a significant prolongation between AN and control (MD 15.9ms, 95% CI 0.0, 31.8ms, p=0.05, I2=65%; n=2/25 studies; Figure 2B). However, QTd and QTcd were significantly greater in AN than control (MD 21.3ms, 95% CI 10.4, 32.3ms, p=0.0001, I2=94%; Figure 2C and MD 16.9ms, 95% CI 4.5, 29.3ms, p=0.007 I2=93%; Figure 2D, respectively). Conclusion To the best of our knowledge, this is the largest meta-analysis of QTc in AN and the first meta-analysis exploring the significance of QTd and QTcd in AN. AN was not found to be associated with prolongation of QTc calculated using the Bazett, Fridericia and Hodges formulae. However, an association of AN with prolonged QTc was observed in the studies using the Framingham formula. More pronounced dispersion (QTd and QTcd) was also observed in patients with AN. Funding Acknowledgement Type of funding sources: None.

Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation.

BackgroundHeart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms.MethodsWe investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels; (2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model; and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro.ResultsIn patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (IKr).ConclusionFor the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.

Corrected QT Interval Is Associated With Stroke but Not Coronary Heart Disease: Insights From a General Chinese Population

Background: Prolonged heart rate-corrected QT (QTc) interval has been associated with incident cardiovascular diseases (CVD) in general Western populations. However, this association is unclear in Asian population. We aim to estimate the association between QTc interval and incident CVD in a general Chinese population.Methods: We analyzed 8,867 participants age ≥35 years and free of CVD at baseline in the Northeast China Rural Cardiovascular Health Study. A resting 12-lead electrocardiogram was performed on all participants, and QTc interval computed using the Framingham formula. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for associations between QTc interval and incident stroke, coronary heart disease, and combined CVD events.Results: Over a median follow-up of 4.66 years, a total of 439 CVD events occurred (298 stroke cases and 152 CHD cases). After full adjustment, prolonged QTc defined by a sex-specific cutoff was associated with increased risk of developing stroke (HR: 1.82, 95% CI 1.20–2.75, P = 0.004) and combined CVD (HR: 1.52, 95% CI 1.05–2.19, P = 0.026). Spline analyses demonstrated no clear thresholds; when modeled as a linear relationship, each 10 ms increase of QTc interval was associated with an HR of 1.12 (95% CI 1.06–1.19, P < 0.001) for stroke and an HR of 1.10 (95% CI 1.05–1.15, P < 0.001) for combined CVD. Baseline QTc interval was not associated with incident CHD with either modeling strategy.Conclusions: Baseline QTc interval is associated with incident stroke and CVD in adults without prior CVD from a general Chinese population.

Association between heart rate-corrected QT interval and severe peripheral arterial disease in patients with type 2 diabetes and foot ulcers.

BackgroundA prolonged heart rate-corrected QT interval (QTc) has been associated with peripheral artery disease (PAD) in the general population. However, no study to date has identified a link between prolonged QTc and the severity of PAD in patients with diabetes mellitus and foot ulcers (DFUs). This study aimed to investigate this relationship.MethodsThis multicenter study enrolled 281 patients with DFUs. The severity of PAD was classified into no severe PAD group (without stenosis or occlusion) and severe PAD group (with stenosis or occlusion) based on duplex ultrasonography. The association of prolonged QTc with severe PAD was evaluated in a multivariable mixed-effect logistic regression model, with the hospital as a random effect. Directed acyclic graphs were used to drive the selection of variables to fit the regression model.ResultsPatients with severe PAD had longer QTc than those without. Based on the multivariable mixed-effect logistic regression model, a prolonged QTc was positively associated with severe PAD (odds ratio (OR) = 2.61; 95% CI: 1.07–6.35) and severe DFUs (Wagner grade score ≥ 3) (OR = 2.87; 95% CI: 1.42–5.81).ConclusionsA prolonged QTc was associated with severe PAD in patients with DFUs. Further research is required to ascertain whether the association is causal.

Proton Pump Inhibitors Directly Block hERG-Potassium Channel and Independently Increase the Risk of QTc Prolongation in a Large Cohort of US Veterans

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Clinical characterization and outcome of prolonged heart rate-corrected QT interval among children with syndactyly.

Prolonged heart rate-corrected QT (QTc) interval is an independent risk factor for sudden cardiac death, which is the hallmark of Timothy syndrome (TS). There are little data on children with syndactyly and QTc prolongation.To evaluate the characteristics and long-term outcomes in children with syndactyly, and to attempt to identify TS in patients with syndactyly and QTc prolongation.This is a retrospective case-control study of children with syndactyly who visited Beijing Jishuitan Hospital between July 2003 and February 2013. The patients with prolonged QTc intervals are matched 1:4 with patients without prolongation. Genetic testing of the CACNA1C gene is routinely performed in patients with QTc prolongation.The mean age at admission is 3.4 ± 2.3 years. Compared with the normal QTc group, those with QTc prolongation showed higher frequencies of congenital heart disease (11.8% vs 1.5%, P = .042), mental retardation and facial dysmorphia (11.8% vs 0, P = .004), and T wave alternans (23.5% vs 4.4%, P = .01). In the multivariable analysis, only T wave alternans (OR = 10.61, 95%CI: 1.39–81.16, P = .023) is independently associated with QTc prolongation in patients with syndactyly. One child with QTc prolongation had a mutation in the CACNA1C gene. No patients with prolonged QTs interval met the threshold for TS.Children with syndactyly and prolonged QTc interval had more multisystem diseases and electrocardiography abnormalities. T wave alternans is independently associated with QTc prolongation in patients with syndactyly.

Corrected QT Interval-Polygenic Risk Score and Its Contribution to Type 1, Type 2, and Type 3 Long-QT Syndrome in Probands and Genotype-Positive Family Members.

Long-QT syndrome (LQTS) is characterized by a prolonged heart rate-corrected QT interval (QTc). Genome-wide association studies identified common genetic variants that collectively explain ≈8% to 10% of QTc variation in the general population. Overall, 423 patients with LQT1, LQT2, or LQT3 were genotyped for 61 QTc-associated genetic variants used in a prototype QTc-polygenic risk score (QTc-PRS). A weighted QTc-PRS (range, 0-154.8 ms) was calculated for each patient, and the FHS (Framingham Heart Study) population-based reference cohort (n=853). The average QTc-PRS in LQTS was 88.0±7.2 and explained only ≈2.0% of the QTc variability. The QTc-PRS in LQTS probands (n=137; 89.3±6.8) was significantly greater than both FHS controls (87.2±7.4, difference-in-means±SE: 2.1±0.7, P<0.002) and LQTS genotype-positive family members (87.5±7.4, difference-in-mean, 1.8±.7, P<0.009). There was no difference in QTc-PRS between symptomatic (n=156, 88.6±7.3) and asymptomatic patients (n=267; 87.7±7.2, difference-in-mean, 0.9±0.7, P=0.15). LQTS patients with a QTc≥480 ms (n=120) had a significantly higher QTc-PRS (89.3±6.7) than patients with a QTc<480 ms (n=303, 87.6±7.4, difference-in-mean, 1.7±0.8, P<0.05). There was no difference in QTc-PRS or QTc between genotypes. The QTc-PRS explained <2% of the QTc variability in our LQT1, LQT2, and LQT3 cohort, contributing 5× less to their QTc value than in the general population. This prototype QTc-PRS does not distinguish/predict the clinical outcomes of individuals with LQTS.

Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A.

Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic causes in patients with prolonged QTc intervals who were negative for pathogenic variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular genetic testing was performed using a panel including 13 LQTS-related genes and 67 additional genes implicated in other cardiac diseases. Overall, putative genetic causes of prolonged QTc interval were identified in three of the 30 patients (10%). Among the LQTS-related genes, we detected a previously reported pathogenic variant, CACNA1C c.1552C>T, responsible for cardiac-only Timothy syndrome. Among the genes related to other cardiac diseases, a likely pathogenic variant, RYR2 c.11995A>G, was identified in a patient with catecholaminergic polymorphic ventricular tachycardia. Another patient who developed dilated cardiomyopathy with prolonged QTc interval was found to carry a likely pathogenic variant, TAZ c.718G>A, associated with infantile dilated cardiomyopathy. Comprehensive screening of genetic variants using multigene panel sequencing enables detection of genetic variants with a possible involvement in QTc interval prolongation, thus uncovering unknown molecular mechanisms underlying LQTS.

The relationship between insulin sensitivity and heart rate-corrected QT interval in patients with type 2 diabetes

BackgroundReduced insulin sensitivity not only contributes to the pathogenesis of type 2 diabetes but is also linked to multiple metabolic risk factors and cardiovascular diseases (CVD). A prolonged heart rate-corrected QT interval (QTc interval) is related to ventricular arrhythmias and CVD mortality and exhibits a high prevalence among type 2 diabetes patients. The aim of the study was to investigate the relationship between insulin sensitivity and the QTc interval in patients with type 2 diabetes.MethodsThis cross-sectional observational study recruited 2927 patients with type 2 diabetes who visited the Affiliated Haian Hospital and Second Affiliated Hospital of Nantong University. The insulin sensitivity index (Matsuda index, ISIMatsuda) derived from 75-g OGTT and other metabolic risk factors were examined in all patients. The QTc interval was estimated using a resting 12-lead electrocardiogram, and an interval longer than 440 ms was considered abnormally prolonged.ResultsThe QTc interval was significantly and negatively correlated with the ISIMatsuda (r = −0.296, p < 0.001), and when the multiple linear regression analysis was adjusted for anthropometric parameters, metabolic risk factors, and current antidiabetic treatments, the QTc interval remained significantly correlated with the ISIMatsuda (β = −0.23, t = −12.63, p < 0.001). The proportion of patients with prolonged QTc interval significantly increased from 12.1% to 17.9%, 25.6% and 37.9% from the fourth to third, second and first quartile of the ISIMatsuda, respectively. After adjusting for anthropometric parameters by multiple logistic regression analysis, the corresponding odd ratios (ORs) for prolonged QTc interval of the first, second and third quartiles versus the fourth quartile of ISIMatsuda were 3.11 (95% CI 2.23–4.34), 2.09 (1.51–2.88) and 1.53 (1.09–2.14), respectively, and p for trend was <0.001.ConclusionsReduced insulin sensitivity is associated with an increase in the QTc interval in patients with type 2 diabetes.

The association of long-term glycaemic variability versus sustained chronic hyperglycaemia with heart rate-corrected QT interval in patients with type 2 diabetes.

ObjectivesProlonged heart rate-corrected QT(QTc) interval is related to ventricular arrhythmia and cardiovascular mortality, with considerably high prevalence of type 2 diabetes. Additionally, long-term glycaemic variability could be a significant risk factor for diabetic complications in addition to chronic hyperglycaemia. We compared the associations of long-term glycaemic variability versus sustained chronic hyperglycaemia with the QTc interval among type 2 diabetes patients.MethodsIn this cross-sectional study, 2904 type 2 diabetes patients were recruited who had undergone at least four fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (PPG) measurements (at least once for every 3 months, respectively) during the preceding year. Long-term glycaemic variabilities of FPG and 2-hour PPG were assessed by their standard deviations (SD-FPG and SD-PPG, respectively), and chronic fasting and postprandial hyperglycaemia were assessed by their means (M-FPG and M-PPG, respectively). HbA1c was also determined upon enrolment to assess current overall glycaemic control. QTc interval was estimated from resting 12-lead electrocardiograms, and more than 440 ms was considered abnormally prolonged.ResultsPatients with prolonged QTc interval (≥440 ms) had greater M-FPG, M-PPG, SD-PPG and HbA1c than those with normal QTc interval but comparable SD-FPG. QTc interval was correlated with M-FPG, M-PPG, SD-PPG and HbA1c (r = 0.133, 0.153, 0.245 and 0.207, respectively, p = 0.000) but not with SD-FPG (r = 0.024, p = 0.189). After adjusting for metabolic risk factors via multiple linear regression analysis, SD-PPG, M-PPG and HbA1c (t = 12.16, 2.69 and 10.16, respectively, p = 0.000) were the major independent contributors to the increased QTc interval. The proportion of prolonged QTc interval increased significantly from 10.9% to 14.2% to 26.6% for the first (T1) to second (T2) to third (T3) tertiles of SD-PPG. After adjusting via multiple logistic regression analysis, the odd ratios of prolonged QTc interval of the T2 and T3 versus the T1 of SD-PPG were 1.15 (95% CI, 0.82–1.60) and 2.62 (1.92–3.57), respectively.ConclusionsIncreased long-term variability of PPG is a strong independent risk factor for prolonged QTc interval in type 2 diabetes patients, in addition to long-term postprandial hyperglycaemia and current HbA1c.

Sex-specific association between serum uric acid and prolonged corrected QT interval: Result from a general rural Chinese population.

Recently, it has been found that high level of serum uric acid (SUA) is causally related to sudden cardiac death (SCD). We examined the sex-specific associations of SUA with prolonged heart rate-corrected QT (QTc) interval in a general Chinese population.A large sample of 11,206 Chinese research participants aged 35 years and older was recruited from rural areas of Liaoning Province during 2012 to 2013. SUA were divided into quartiles separated for males and females. Prolonged QTc interval, assessed by the Bazett formula, was defined as cut points of 460 ms or longer in females and 450 ms or longer in males. Mean (+/− standard deviation) QTc intervals were 422.1 ± 24.2 ms among 5104 males and 436.1 ± 23.5 ms among 6102 females, respectively. In both sexes, SUA showed significant correlations with QTc interval (both P < 0.001). Among male participants, the highest quartile of SUA (>379 μmol/L) was related to an increased risk for prolonged QTc interval (odds ratios: 1.402, 95% confidence interval: 1.073–1.831) compared to the lowest quartile (≤276 μmol/L) after fully adjustment. However, there were no significant relationships between SUA and prolonged QTc interval among females in all the models.Males with high SUA are prone to a higher risk for prolonged QTc interval. This study provides novel explanation for population-based findings on SUA and SCD, as well as important implications for management strategies for hyperuricemic patients in clinical practice.

Heavy Metals in Blood and Ventricular Repolarization: Modification by Sex and Smoking Status in Urban Traffic Enforcers

Introduction: Prolonged heart rate-corrected JT interval (JTc) and heart rate-corrected QT interval (QTc) have been associated with higher risk of mortality in the general population and in patient...